Time-dependent oral absorption models
NASA Technical Reports Server (NTRS)
Higaki, K.; Yamashita, S.; Amidon, G. L.
2001-01-01
The plasma concentration-time profiles following oral administration of drugs are often irregular and cannot be interpreted easily with conventional models based on first- or zero-order absorption kinetics and lag time. Six new models were developed using a time-dependent absorption rate coefficient, ka(t), wherein the time dependency was varied to account for the dynamic processes such as changes in fluid absorption or secretion, in absorption surface area, and in motility with time, in the gastrointestinal tract. In the present study, the plasma concentration profiles of propranolol obtained in human subjects following oral dosing were analyzed using the newly derived models based on mass balance and compared with the conventional models. Nonlinear regression analysis indicated that the conventional compartment model including lag time (CLAG model) could not predict the rapid initial increase in plasma concentration after dosing and the predicted Cmax values were much lower than that observed. On the other hand, all models with the time-dependent absorption rate coefficient, ka(t), were superior to the CLAG model in predicting plasma concentration profiles. Based on Akaike's Information Criterion (AIC), the fluid absorption model without lag time (FA model) exhibited the best overall fit to the data. The two-phase model including lag time, TPLAG model was also found to be a good model judging from the values of sum of squares. This model also described the irregular profiles of plasma concentration with time and frequently predicted Cmax values satisfactorily. A comparison of the absorption rate profiles also suggested that the TPLAG model is better at prediction of irregular absorption kinetics than the FA model. In conclusion, the incorporation of a time-dependent absorption rate coefficient ka(t) allows the prediction of nonlinear absorption characteristics in a more reliable manner.
Miles, Lisa; Hall, Jessica; Jenner, Bartosz; Addis, Richard; Hutchings, Simon
2018-04-27
This study evaluated the early absorption characteristics of ibuprofen salt formulations and standard ibuprofen acid (the reference). In this open-label, crossover, single-center study (NCT02452450) in 32 healthy, fasted adults receiving single oral doses (400 mg ibuprofen) of ibuprofen lysine, ibuprofen liquid capsule, ibuprofen sodium, ibuprofen acid, and paracetamol, intensive blood sampling was conducted for up to 6 h. Time between dosing and the start of absorption (T lag ); a novel parameter, time at which the test formulations (ibuprofen salts) reached the observed maximum plasma concentration (C max ) of the reference (standard ibuprofen acid) (T C maxRef ); and time to achieve therapeutic plasma concentration were measured. Ibuprofen was absorbed more rapidly from the salt formulations than the reference; T lag was 3.3-6.4 min for salt formulations compared with 10.9 min for the reference, and 100% of subjects had a T lag ≤ 5 min for ibuprofen lysine, compared with 61% for ibuprofen liquid capsule, 21% for ibuprofen sodium, and 7% for the reference. T C maxRef was 3.22-5.74-times shorter for salt formulations than for the reference (all p < .0001). The salt formulations reached therapeutic levels earlier than the reference (all p < .0001). All formulations were well tolerated. This study shows that ibuprofen salts are absorbed faster than ibuprofen acid. T lag and T C maxRef demonstrated early start and increased speed of absorption of salts compared with the reference, and may predict more rapid onset of analgesia.
NASA Astrophysics Data System (ADS)
Saturni, F. G.; Trevese, D.; Vagnetti, F.; Perna, M.; Dadina, M.
2016-03-01
Context. The study of high-redshift bright quasars is crucial to gather information about the history of galaxy assembly and evolution. Variability analyses can provide useful data on the physics of quasar processes and their relation with the host galaxy. Aims: In this study, we aim to measure the black hole mass of the bright lensed BAL QSO APM 08279+5255 at z = 3.911 through reverberation mapping, and to update and extend the monitoring of its C IV absorption line variability. Methods: We perform the first reverberation mapping of the Si IV and C IV emission lines for a high-luminosity quasar at high redshift with the use of 138 R-band photometric data and 30 spectra available over 16 years of observations. We also cross-correlate the C IV absorption equivalent width variations with the continuum light curve to estimate the recombination time lags of the various absorbers and infer the physical conditions of the ionised gas. Results: We find a reverberation-mapping time lag of ~900 rest-frame days for both Si IV and C IV emission lines. This is consistent with an extension of the BLR size-to-luminosity relation for active galactic nuclei up to a luminosity of ~1048 erg s-1, and implies a black hole mass of 1010 M⊙. Additionally, we measure a recombination time lag of ~160 days in the rest frame for the C IV narrow absorption system, which implies an electron density of the absorbing gas of ~2.5 × 104 cm-3. Conclusions: The measured black hole mass of APM 08279+5255 indicates that the quasar resides in an under-massive host-galaxy bulge with Mbulge ~ 7.5MBH, and that the lens magnification is lower than ~8. Finally, the inferred electron density of the narrow-line absorber implies a distance of the order of 10 kpc of the absorbing gas from the quasar, placing it within the host galaxy.
Ueda, S; Ibuki, R; Kawamura, A; Murata, S; Takahashi, T; Kimura, S; Hata, T
1994-01-01
Time-Controlled Explosion System (TES) has the time-controlled drug release property with a pre-designed lag time. The drug release from the system is initiated by destruction of the membrane. In this study, metoprolol tartrate was used as a model drug. After five types of TES with different in vitro lag times were orally administrated to dogs, plasma metoprolol concentration was monitored. There existed a good correlation between in vitro and in vivo lag time, while the extent of absorbed metoprolol decreased with prolongation of lag time. Next, the in vivo drug release behavior was directly investigated using five different colored TES with a lag time of two hours. Each TES was consecutively administrated to the fasted dogs at predetermined intervals. The amount of metoprolol released was monitored by recovering the administered TES from the gastrointestinal trace. The in vivo release profile corresponded with the in vitro one. It is demonstrated that TES can release the drug in in vivo conditions similarly to in vitro. Based on these results, the decrease of the absorption is suggested to be caused by increased hepatic first-pass metabolism of the drug due to the retarded release rate with longer lag time.
Fundamental understanding of drug absorption from a parenteral oil depot.
Kalicharan, Raween W; Schot, Peter; Vromans, Herman
2016-02-15
Oil depots are parenteral drug formulations meant for sustained release of lipophilic compounds. Until now, a comprehensive understanding of the mechanism of drug absorption from oil depots is lacking. The aim of this paper was to fill this gap. A clinical study with healthy volunteers was conducted. An oil depot with nandrolone decanoate and benzyl alcohol was subcutaneously administered in the upper arm of female volunteers. Pharmacokinetic profiles of both substances were related to each other and to literature data. Benzyl alcohol absorbs much more rapidly than nandrolone. In detail, it appears that benzyl alcohol enters the central compartment directly, while nandrolone decanoate is recovered in serum after a lag time. This lag time is also seen in literature data, although not reported explicitly. The absorption of nandrolone is enhanced by the presence of benzyl alcohol. This is most likely an effect of altered oil viscosity and partition coefficient between the oil and aqueous phase. The absorption rate constant of compounds is found to be related to the logP of the solubilized prodrug. The absorption rate is however not only determined by the physico-chemical properties of the formulation but also by the tissue properties. Here, it is argued that lymphatic flow must be considered as a relevant parameter. Copyright © 2015 Elsevier B.V. All rights reserved.
Conjugate observation of electron microburst groups by Bremsstrahlung X-ray and riometer techniques
DOE Office of Scientific and Technical Information (OSTI.GOV)
Siren, J.C.; Rosenberg, T.J.; Detrick, D.
1980-12-01
The first evidence is reported of simultaneous conjugate electron microburst group precipitation. Groups of bremsstrahlung X ray microbursts (E>25 keV) were observed during a substorm recovery phase by a balloon-borne scintillation counter over Roberval, Quebec, Canada. The microburst groups were accompanied one-to-one by time-delayed and broadened pulses of ionospheric absorption measured by a high sensitivity 30-MHz riometer at Siple Station, Antarctica (Lapprox. =4.1). For the interval of highest correlation, the absolute lag between the two data sets was 4 +- 1 s, to the limit of the relative timing accuracy. Approximately 2 s of the observed lag had been introducesmore » by a low-pass filter in the riometer data acquistion unit. The remainder (2 s) was due to the ionospheric recombination process, which evidently had a response time (tauapprox.5 s) during this event much shorter than that ordinarily associated with the D region of the ionosphere. Model calculations of the ionspheric response to time-varying precipitation, derived from the profile of the measurement X ray flux, provide a consistent picture of simultaneous microburst group precipitation at conjugate points, absolute absorption and the electron spectrum derived from X rays, the degree of variation in absorption and X ray fluxes, and the characteristic ionospheric time constant at the altitude of maximum energy deposition.« less
Cawello, Willi; Braun, Marina; Andreas, Jens-Otto
2018-01-13
Pharmacokinetic studies using deconvolution methods and non-compartmental analysis to model clinical absorption of drugs are not well represented in the literature. The purpose of this research was (1) to define the system of equations for description of rotigotine (a dopamine receptor agonist delivered via a transdermal patch) absorption based on a pharmacokinetic model and (2) to describe the kinetics of rotigotine disposition after single and multiple dosing. The kinetics of drug disposition was evaluated based on rotigotine plasma concentration data from three phase 1 trials. In two trials, rotigotine was administered via a single patch over 24 h in healthy subjects. In a third trial, rotigotine was administered once daily over 1 month in subjects with early-stage Parkinson's disease (PD). A pharmacokinetic model utilizing deconvolution methods was developed to describe the relationship between drug release from the patch and plasma concentrations. Plasma-concentration over time profiles were modeled based on a one-compartment model with a time lag, a zero-order input (describing a constant absorption via skin into central circulation) and first-order elimination. Corresponding mathematical models for single- and multiple-dose administration were developed. After single-dose administration of rotigotine patches (using 2, 4 or 8 mg/day) in healthy subjects, a constant in vivo absorption was present after a minor time lag (2-3 h). On days 27 and 30 of the multiple-dose study in patients with PD, absorption was constant during patch-on periods and resembled zero-order kinetics. Deconvolution based on rotigotine pharmacokinetic profiles after single- or multiple-dose administration of the once-daily patch demonstrated that in vivo absorption of rotigotine showed constant input through the skin into the central circulation (resembling zero-order kinetics). Continuous absorption through the skin is a basis for stable drug exposure.
Shah, Sunny; Patel, Romik; Soniwala, Moinuddin; Chavda, Jayant
2015-01-01
The present work is aimed to develop and optimize pulsatile delivery during dissolution of an improved formulation of valsartan to coordinate the drug release with circadian rhythm. Preliminary studies suggested that β cyclodextrin could improve the solubility of valsartan and showed AL type solubility curve. A 1:1 stoichiometric ratio of valsartan to β cyclodextrin was revealed from phase solubility studies and Job's plot. The prepared complex showed significantly better dissolution efficiency (p < 0.05) compared to pure drug, which could be due to the formation of inclusion complex as revealed from FTIR and DSC studies. Continuous dissolution-absorption studies revealed that absorption of drug from valsartan β cyclodextrin complex was significantly higher (p < 0.05) compared to pure drug, in second part press-coated tablets of valsartan β cyclodextrin complex were subsequently prepared and application of the Plackett-Burman screening design revealed that HPMC K4M and EC showed significant effect on lag time. A 3(2) full factorial design was used to measure the response of HPMC K4M and EC on lag time and time taken for 90% drug release (T90). The optimized batch prepared according to the levels obtained from the desirability function had a lag time of 6 h and consisted of HPMC K4M:ethylcellulose in a 1:1.5 ratio with 180 mg of coating and revealed a close agreement between observed and predicted value (R(2 )= 0.9694).
Ex-Vivo percutaneous absorption of enrofloxacin: Comparison of LMOG organogel vs. pentravan cream.
Kirilov, Plamen; Tran, Van Hung; Ducrotté-Tassel, Alban; Salvi, Jean-Paul; Perrot, Sébastien; Haftek, Marek; Boulieu, Roselyne; Pirot, Fabrice
2016-02-10
The objective of this study was to investigate the percutaneous absorption of enrofloxacin from two base formulations, Pentravan cream and LMOG organogel. Ex-vivo experiments were carried out on pig ear skin. The percutaneous permeation through pig skin of two formulations containing 5 wt% of enrofloxacin was measured and compared using Franz diffusion cells. At appropriate intervals up to 120 h, diffusion samples were taken and analyzed using HPLC assays. Permeation profiles were established and the parameters Tlag and flux values were calculated. In this ex-vivo study, the flux values were 0.35 μgcm(-2)h(-1) for Pentravan and 1.22 μgcm(-2)h(-1) for LMOG organogel, corresponding respectively to 7.9 % and 29.3 % of enrofloxacin absorbed after 120 h by these formulations. The lag time (T lag) of Pentravan and organogel were 6.32 and 0.015 h respectively. The absorption time to reach the antibiotic concentration of enrofloxacin (2 μgmL(-1)) in the receptor was 60 h with Pentravan and 30 h with the organogel, suggesting more effective treatment by the latter. Enrofloxacin contained in organogel could be absorbed through pig ear skin 3.7 times greater than that in Pentravan (commercial formulation). This study demonstrates the perspective of organogel formulations as potential drug delivery systems. Copyright © 2015 Elsevier B.V. All rights reserved.
Bioavailability of a Lipidic Formulation of Curcumin in Healthy Human Volunteers
Pawar, Yogesh B.; Munjal, Bhushan; Arora, Saurabh; Karwa, Manoj; Kohli, Gunjan; Paliwal, Jyoti K.; Bansal, Arvind K.
2012-01-01
Numerous publications have reported the significant pharmacodynamic activity of Curcumin (CRM) despite low or undetectable levels in plasma. The objective of the present study was to perform a detailed pharmacokinetic evaluation of CRM after the oral administration of a highly bioavailable lipidic formulation of CRM (CRM-LF) in human subjects. Cmax, Tmax and AUC0–∞ were found to be 183.35 ± 37.54 ng/mL, 0.60 ± 0.05 h and 321.12 ± 25.55 ng/mL respectively, at a dose of 750 mg. The plasma profile clearly showed three distinct phases, viz., absorption, distribution and elimination. A close evaluation of the primary pharmacokinetic parameters provided valuable insight into the behavior of the CRM after absorption by CRM-LF. CRM-LF showed a lag time (Tlag) of 0.18 h (around 12 min). Pharmacokinetic modeling revealed that CRM-LF followed a two-compartment model with first order absorption, lag time and first order elimination. A high absorption rate constant (K01, 4.51/h) signifies that CRM-LF ensured rapid absorption of the CRM into the central compartment. This was followed by the distribution of CRM from the central to peripheral compartment (K12, 2.69/h). The rate of CRM transfer from the peripheral to central compartment (K21, 0.15/h) was slow. This encourages higher tissue levels of CRM as compared with plasma levels. The study provides an explanation of the therapeutic efficacy of CRM, despite very low/undetectable levels in the plasma. PMID:24300368
The effect of Beta-cyclodextrin on percutaneous absorption of commonly used Eusolex® sunscreens.
Shokri, J; Hasanzadeh, D; Ghanbarzadeh, S; Dizadji-Ilkhchi, M; Adibkia, K
2013-11-01
There is a serious concern about the topical and systemic absorption of organic ultraviolet filters in sunscreen formulations and subsequent phototoxic and photo allergic reactions. Ideally, a sunscreen should localize in the surface of stratum corneum and create a barrier against UV radiation, but not penetrate into the underlying viable tissues and systemic circulation. The objective of the present study was to determine the effects of β-cyclodextrin (β-CDX) complexation on the transdermal penetration of 3 commonly used sun blocking agents, Eusolex ® 4360 (avobenzone), Eusolex ® 9020 (Oxybenzone) and Eusolex ® 232 (Ensulizole). The complexation of the sunscreen agents with β-CDX was performed by 3 methods and confirmed by differential scanning calorimetry (DSC). Sunscreens, and their physical mixtures and complexes with β-CDX were introduced into a model cream base (o/w emulsion). To find out the influence of β-CDX, sunscreen creams were applied to the rat skin in vitro in standard Franz diffusion cells and the amount of sunscreen permeated after 6 h was assessed by HPLC. The skin penetration flux of the UV filters was significantly reduced (4–15 fold) by complexation with β-CDX. Complexation also could prolong absorption lag time of sun blocking agents to more than 150 min. Considering the ability of β-CDX complexation in the reduction of flux and enhancement ratio as well as prolongation of absorption lag time, this technique could be very helpful for reducing systemic absorption of the UV filters and subsequent toxicity and allergic reaction.
[Pharmacokinetics of controlled-release oxycodone in patients with cancer pain].
Nakamura, Kazuyo; Kokubun, Hideya; Komatsu, Toshiaki; Matoba, Motohiro; Hoka, Sumio; Yago, Kazuo
2007-09-01
Oxycodone is a useful analgesic for cancer patients in pain. However, its pharmacokinetics have not been sufficiently examined and there is a lack of information, with very few reports on pharmacokinetics concerning the absorption process in particular. With this in mind, we studied the pharmacokinetics of controlled-release oxycodone (Oxy contin). We measured its serum concentration in patients with cancer pain, and calculated parameters derived using the nonlinear least-squared method program (MULTI). In the result, pharmacokinetic parameters calculated at CL/F were: 45.6+/-22.0 L/hr (Mean+/-SD), Vd/F: 473.0+/-19 6.7 L, t(1/2): 7.2+/- 6.2 hr, kel: 0.103+/-0.034, kal: 1.082+/-0.604, Lag time: 0.9 9+/-0.40 hr. In addition, the serum oxycodone concentration hardly rose until 1 hour after and just before medication, whereupon a rapid increase was evident after 1 hour. The pharmacokinetics of controlled-release oxycodone in patients with cancer pain were clarified in this study. Especially during the absorption process, the lag time was calculated specifically at about 1 hour, making it approximately equal to MS contin.
NASA Astrophysics Data System (ADS)
Kriss, G.; Storm Team
2015-07-01
The Space Telescope and Optical Reverberation Mapping (STORM) project monitored the Seyfert 1 galaxy NGC 5548 over a six-month period, obtaining 171 far-ultraviolet HST/COS spectra at approximately daily intervals. We find significant correlated variability in the continuum and broad emission lines, with amplitudes ranging from a factor of two in the emission lines to a factor of three in the continuum. The variations of all the strong emission lines lag behind those of the continuum, with He II lagging by ˜ 2.5 days and Ly&alpha,; C IV, and Si IV lagging by 5 to 6 days. The broad UV absorption lines discovered by Kaastra et al. (2014) and associated with the new soft X-ray obscurer are continuously present in the STORM campaign COS spectra. Their strength varies with the degree of soft X-ray obscuration as revealed by the Swift X-ray spectra. The narrow absorption lines associated with the historical warm absorber varied in response to the changing UV flux on a daily basis with lags of 3 to 8 days. The ionization response allows precise determinations of the locations, mass flux, and kinetic luminosities of the absorbers.
Design of Chronomodulated Drug Delivery System of Valsartan: In Vitro Characterization.
Sokar, M; Hanafy, A; Elkamel, A; El-Gamal, S
2015-01-01
The aim of the present study was to design and evaluate a chronomodulated time-clock pulsatile tablets of valsartan to release it after a certain lag time, independent of the gastrointestinal pH, in its absorption window to cope with the circadian rhythm of human body for blood pressure elevation. Core tablets were prepared by direct compression of a homogenous mixture of valsartan, Avicel PH101, croscarmellose sodium, magnesium stearate and Aerosil. The core tablets were then sprayed coated with a sealing layer formed of ethyl cellulose that was subsequently coated with a release-controlling layer. Three different aqueous dispersions namely; carnauba wax or beeswax or a mixture in a ratio of 2.5:1, respectively, were used to form five time-clock tablet formulations having the release controlling layer with different thickness {B5, B10, B20, BW5 and CW5}. Quality control testing were carried out to the core tablets. Differential scanning calorimetry was also performed to detect the possible drug excipient interaction in the core tablet formulation. The release was carried out, for the prepared time-clock tablet formulations, in 0.1 N hydrochloric acid for the first 2 h, followed by phosphate buffer (pH 6.8) for 4.5 h. The effect of pH on valsartan release was studied through a release study in 0.1 N hydrochloric acid for 6.5 h. Two phase dissolution study was performed to the selected time-clock tablet formulation to predict the drug permeation through the gastrointestinal tract. Stability study of the selected formula was performed at 25°/60% RH and at 40°/75% RH for 3 months. Results showed that a release-controlling layer composed of a mixture of carnauba wax and beeswax in a ratio of 2.5:1 showed a reasonable release lag time. The release lag time of the tablets increased with the increase of the coat thickness, thus B20>B10>B5 with corresponding lag time values of 4.5, 3 and 2.5 h, respectively. Selected B5 tablet formula exhibited a reasonable lag time after which the highest, complete % drug release at pH 6.8 was obtained. In addition, a good partitioning of valsartan, between the aqueous and organic phases in a ratio of 1:7, was observed. The selected formula was stable for at least 3 months under standard long-term and accelerated storage conditions. In conclusion, in vitro studies revealed that the novel time-clock system could be used successfully to deliver valsartan in a pulsatile pH-independent manner. It provided a desirable lag time followed by a rapid and complete drug release accompanied by an expected effective permeation through the biological membranes upon release in the duodenum; the window of absorption, as indicated by the two phase release study.
Design of Chronomodulated Drug Delivery System of Valsartan: In Vitro Characterization
Sokar, M.; Hanafy, A.; Elkamel, A.; El-Gamal, S.
2015-01-01
The aim of the present study was to design and evaluate a chronomodulated time-clock pulsatile tablets of valsartan to release it after a certain lag time, independent of the gastrointestinal pH, in its absorption window to cope with the circadian rhythm of human body for blood pressure elevation. Core tablets were prepared by direct compression of a homogenous mixture of valsartan, Avicel PH101, croscarmellose sodium, magnesium stearate and Aerosil. The core tablets were then sprayed coated with a sealing layer formed of ethyl cellulose that was subsequently coated with a release-controlling layer. Three different aqueous dispersions namely; carnauba wax or beeswax or a mixture in a ratio of 2.5:1, respectively, were used to form five time-clock tablet formulations having the release controlling layer with different thickness {B5, B10, B20, BW5 and CW5}. Quality control testing were carried out to the core tablets. Differential scanning calorimetry was also performed to detect the possible drug excipient interaction in the core tablet formulation. The release was carried out, for the prepared time-clock tablet formulations, in 0.1 N hydrochloric acid for the first 2 h, followed by phosphate buffer (pH 6.8) for 4.5 h. The effect of pH on valsartan release was studied through a release study in 0.1 N hydrochloric acid for 6.5 h. Two phase dissolution study was performed to the selected time-clock tablet formulation to predict the drug permeation through the gastrointestinal tract. Stability study of the selected formula was performed at 25°/60% RH and at 40°/75% RH for 3 months. Results showed that a release-controlling layer composed of a mixture of carnauba wax and beeswax in a ratio of 2.5:1 showed a reasonable release lag time. The release lag time of the tablets increased with the increase of the coat thickness, thus B20>B10>B5 with corresponding lag time values of 4.5, 3 and 2.5 h, respectively. Selected B5 tablet formula exhibited a reasonable lag time after which the highest, complete % drug release at pH 6.8 was obtained. In addition, a good partitioning of valsartan, between the aqueous and organic phases in a ratio of 1:7, was observed. The selected formula was stable for at least 3 months under standard long-term and accelerated storage conditions. In conclusion, in vitro studies revealed that the novel time-clock system could be used successfully to deliver valsartan in a pulsatile pH-independent manner. It provided a desirable lag time followed by a rapid and complete drug release accompanied by an expected effective permeation through the biological membranes upon release in the duodenum; the window of absorption, as indicated by the two phase release study. PMID:26664064
Monomeric insulins and their experimental and clinical implications.
Brange, J; Owens, D R; Kang, S; Vølund, A
1990-09-01
Due to the inherent pharmacokinetic properties of available insulins, normoglycemia is rarely, if ever, achieved in insulin-dependent diabetic patients without compromising their quality of life. Subcutaneous insulin absorption is influenced by many factors, among which the associated state of insulin (hexameric) in pharmaceutical formulation may be of importance. This review describes the development of a series of human insulin analogues with reduced tendency to self-association that, because of more rapid absorption, are better suited to meal-related therapy. DNA technology has made it possible to prepare insulins that remain dimeric or even monomeric at high concentration by introducing one or a few amino acid substitutions into human insulin. These analogues were characterized and used for elucidating the mechanisms involved in subcutaneous absorption and were investigated in preliminary clinical studies. Their relative receptor binding and in vitro potency (free-fat cell assay), ranging from 0.05 to 600% relative to human insulin, were strongly correlated (r = 0.97). In vivo, most of the analogues exhibited approximately 100% activity, explainable by a dominating receptor-mediated clearance. This was confirmed by clamp studies in which correlation between receptor binding and clearance was observed. Thus, an analogue with reduced binding and clearance gives higher circulating concentrations, counterbalancing the reduced potency at the cellular level. Absorption studies in pigs revealed a strong inverse correlation (r = 0.96) between the rate of subcutaneous absorption and the mean association state of the insulin analogues. These studies also demonstrated that monomeric insulins were absorbed three times faster than human insulin. In healthy subjects, rates of disappearance from subcutis were two to three times faster for dimeric and monomeric analogues than for human insulin. Concomitantly, a more rapid rise in plasma insulin concentration and an earlier hypoglycemic response with the analogues were observed. The monomeric insulin had no lag phase and followed a monoexponential course throughout the absorption process. In contrast, two phases in rate of absorption were identified for the dimer and three for the normal hexameric human insulin. The initial lag phase and the subsequent accelerated absorption of soluble insulin can now be explained by the associated state of native insulin in pharmaceutical formulation and its progressive dissociation into smaller units during the absorption process. In the light of these results, the effects of insulin concentration, injected volume, temperature, and massage on the absorption process are now also understood.(ABSTRACT TRUNCATED AT 400 WORDS)
Effect of antioxidant oxidation potential in the oxygen radical absorption capacity (ORAC) assay.
Bisby, Roger H; Brooke, Rachel; Navaratnam, Suppiah
2008-06-01
The "oxygen radical absorption capacity" (ORAC) assay (Ou, B., Hampsch-Woodill, M., Prior, R.L. (2001). Development and validation of an improved oxygen radical absorbance capacity assay using fluorescein as the fluorescent probe. Journal of Agricultural and Food Chemistry 49, 4619-4626) is widely employed to determine antioxidant content of foods and uses fluorescein as a probe for oxidation by peroxyl radicals. Kinetic modeling of the ORAC assay suggests that the lag phase for loss of fluorescence results from equilibrium between antioxidant and fluorescein radicals and the value of the equilibrium constant determines the shape of the lag phase. For an efficient antioxidant this constitutes a "repair" reaction for fluoresceinyl radicals and produces a well defined lag phase. The lag phase becomes less marked with increasing oxidation potential of the antioxidant. Pulse radiolysis confirms that fluoresceinyl radicals are rapidly (k∼10(9)dm(3)mol(-1)s(-1)) reduced by Trolox C, a water soluble vitamin E analogue. ORAC assays of phenols with varying oxidation potentials suggest that it might be employed to obtain an estimate of the redox potential of antioxidants within food materials. Copyright © 2007 Elsevier Ltd. All rights reserved.
NASA Astrophysics Data System (ADS)
Sasaki, Hiroaki; Miyamura, Tsuyoshi; Saitoh, Sei-ichi; Ishizaka, Joji
2005-08-01
Between November 2000 and October 2001, the seasonal variation in absorption by particles (phytoplankton and detritus) and colored dissolved organic matter (CDOM) was measured in Funka Bay (a subarctic coastal region of Japan). In autumn-winter, chlorophyll a concentration (Chl a) near the euphotic zone remained very low (<1.0 mg m -3) but markedly increased in spring (16.8 mg m -3). Chlorophyll-specific absorption coefficient for phytoplankton ( a∗ph( λ)) was high during summer and low during the spring bloom. This is because the package effect was greater during the spring bloom due to the presence of large diatoms, while small phytoplankton dominated during summer. Absorption at 440 nm by CDOM was higher than that of phytoplankton and detritus, except during the spring bloom, and the relative contribution of CDOM absorption to the total absorption coefficient was >50%. CDOM and detritus absorption did not increase with increasing Chl a, but it showed a time lag between the spring bloom. It is suggested that phytoplankton degradation started after the spring bloom; detritus absorption increased and, then, CDOM absorption increased. River runoff was not a significant influence in Funka Bay, therefore, CDOM production may be mainly related to microbial activity.
Tran, Phuong; Yoo, Hee-Doo; Ngo, Lien; Cho, Hea-Young; Lee, Yong-Bok
2017-12-01
The objective of this study was to perform population pharmacokinetic (PK) analysis of gabapentin in healthy Korean subjects and to investigate the possible effect of genetic polymorphisms (1236C > T, 2677G > T/A, and 3435C > T) of ABCB1 gene on PK parameters of gabapentin. Data were collected from bioequivalence studies, in which 173 subjects orally received three different doses of gabapentin (300, 400, and 800 mg). Only data from reference formulation were used. Population pharmacokinetics (PKs) of gabapentin was estimated using a nonlinear mixed-effects model (NONMEM). Gabapentin showed considerable inter-individual variability (from 5.2- to 8.7-fold) in PK parameters. Serum concentration of gabapentin was well fitted by a one-compartment model with first-order absorption and lag time. An inhibitory Emax model was applied to describe the effect of dose on bioavailability. The oral clearance was estimated to be 11.1 L/h. The volume of distribution was characterized as 81.0 L. The absorption rate constant was estimated at 0.860 h -1 , and the lag time was predicted at 0.311 h. Oral bioavailability was estimated to be 68.8% at dose of 300 mg, 62.7% at dose of 400 mg, and 47.1% at dose of 800 mg. The creatinine clearance significantly influenced on the oral clearance (P < 0.005) and ABCB1 2677G > T/A genotypes significantly influenced on the absorption rate constant (P < 0.05) of gabapentin. However, ABCB1 1236C > T and 3435C > T genotypes showed no significant effect on gabapentin PK parameters. The results of the present study indicate that the oral bioavailability of gabapentin is decreased when its dosage is increased. In addition, ABCB1 2677G > T/A polymorphism can explain the substantial inter-individual variability in the absorption of gabapentin.
Yoshihara, Kazutaka; Gao, Yuying; Shiga, Hiroshi; Wada, D Russell; Hisaoka, Masafumi
2005-01-01
Olmesartan medoxomil (CS-866) is a new orally active angiotensin II receptor antagonist that is highly selective for the AT1 receptor subtype. To develop a population pharmacokinetic model for olmesartan (RNH-6270), the active metabolite of olmesartan medoxomil, in healthy volunteers and hypertensive patients, and to evaluate effects of covariates on the apparent oral clearance (CL/F), with particular emphasis on the effect of race. Retrospective analysis of data from 12 phase I-III trials in the US, Europe and Japan. Eighty-nine healthy volunteers and 383 hypertensive patients. Nonlinear mixed-effects modelling was used to evaluate 7911 olmesartan plasma sample concentrations. The covariates included age, bodyweight, sex, race (Westerners [including Caucasians and Hispanics] versus Japanese), patient status (hypertensive patients versus healthy volunteers), serum creatinine level as an index of renal function and serum chemistry data as indices of hepatic function. The pharmacokinetic data of olmesartan were well described by a two-compartment linear model with first-order absorption and an absorption lag-time, parameterised in terms of CL/F (6.66 L/h for a typical male Western hypertensive patient), absorption rate constant (1.46h-1), elimination rate constant (0.193h-1), rate constant from the central to peripheral compartment (0.061h-1), rate constant from the peripheral to central compartment (0.079h-1) and absorption lag-time (0.427h). Analysis of covariates showed that age, bodyweight, sex, patient status and renal function were factors influencing the clearance of olmesartan. The population pharmacokinetic analysis of olmesartan showed that: (i) severe renal impairment (serum creatinine >265 micromol/L [approximately 3 mg/dL]) could cause a clearance decrease of > or =30%; (ii) older age, lower bodyweight and being female were determinants of lower clearance but their effects on olmesartan clearance were within 20%; (iii) no statistically significant difference in clearance was found between Westerners and Japanese.
NASA Astrophysics Data System (ADS)
Loubet, Benjamin; Buysse, Pauline; Lafouge, Florence; Ciuraru, Raluca; Decuq, Céline; Zurfluh, Olivier
2017-04-01
Field scale flux measurements of volatile organic compounds (VOC) are essential for improving our knowledge of VOC emissions from ecosystems. Many VOCs are emitted from and deposited to ecosystems. Especially less known, are crops which represent more than 50% of French terrestrial surfaces. In this study, we evaluate a new on-line methodology for measuring VOC fluxes by Eddy Covariance with a PTR-Qi-TOF-MS. Measurements were performed at the ICOS FR-GRI site over a crop using a 30 m long high flow rate sampling line and an ultrasonic anemometer. A Labview program was specially designed for acquisition and on-line covariance calculation: Whole mass spectra ( 240000 channels) were acquired on-line at 10 Hz and stored in a temporary memory. Every 5 minutes, the spectra were mass-calibrated and normalized by the primary ion peak integral at 10 Hz. The mass spectra peaks were then retrieved from the 5-min averaged spectra by withdrawing the baseline, determining the resolution and using a multiple-peak detection algorithm. In order to optimize the peak detection algorithm for the covariance, we determined the covariances as the integrals of the peaks of the vertical-air-velocity-fluctuation weighed-averaged-spectra. In other terms, we calculate
The Transient Dermal Exposure II: Post-Exposure Absorption and Evaporation of Volatile Compounds
FRASCH, H. FREDERICK; BUNGE, ANNETTE L.
2016-01-01
The transient dermal exposure is one where the skin is exposed to chemical for a finite duration, after which the chemical is removed and no residue remains on the skin’s surface. Chemical within the skin at the end of the exposure period can still enter the systemic circulation. If it has some volatility, a portion of it will evaporate from the surface before it has a chance to be absorbed by the body. The fate of this post-exposure “skin depot” is the focus of this theoretical study. Laplace domain solutions for concentration distribution, flux, and cumulative mass absorption and evaporation are presented, and time domain results are obtained through numerical inversion. The Final Value Theorem is applied to obtain the analytical solutions for the total fractional absorption by the body and evaporation from skin at infinite time following a transient exposure. The solutions depend on two dimensionless variables: χ, the ratio of evaporation rate to steady-state dermal permeation rate; and the ratio of exposure time to membrane lag time. Simple closed form algebraic equations are presented that closely approximate the complete analytical solutions. Applications of the theory to the dermal risk assessment of pharmaceutical, occupational, and environmental exposures are presented for four example chemicals. PMID:25611182
Effect of different penetration enhancers on diclofenac permeation across horse skin.
Ferrante, M; Andreeta, A; Landoni, M F
2010-12-01
Diclofenac is a hydrophilic non-steroidal anti-inflammatory drug widely used in humans and animals. Previous reports have shown that this compound has low percutaneous absorption in horses. The effect of five penetration enhancers (10% urea, 15% and 20% oleic acid and 5% and 10% d-limonene) on the percutaneous absorption of diclofenac diethylamine through horse skin was evaluated in vitro using Franz-type diffusion cells. All tested penetration enhancers induced a significant increase in diclofenac diethylamine permeation, with limonene showing the highest enhancing effect at the lowest concentration (5%) applied. The presence of the permeation enhancers did not affect lag-time. This is the first in vitro study of the effects of penetration enhancers on transdermal permeation of diclofenac diethylamine across horse skin. The results suggested that urea, limonene and 5% oleic acid were useful for enhancing the transdermal absorption of diclofenac diethylamine and may assist in the development of a transdermal formulation of diclofenac diethylamine for use in horses. Copyright © 2009. Published by Elsevier Ltd.
Nanoflare vs Footpoint Heating : Observational Signatures
NASA Technical Reports Server (NTRS)
Winebarger, Amy; Alexander, Caroline; Lionello, Roberto; Linker, Jon; Mikic, Zoran; Downs, Cooper
2015-01-01
Time lag analysis shows very long time lags between all channel pairs. Impulsive heating cannot address these long time lags. 3D Simulations of footpoint heating shows a similar pattern of time lags (magnitude and distribution) to observations. Time lags and relative peak intensities may be able to differentiate between TNE and impulsive heating solutions. Adding a high temperature channel (like XRT Be-thin) may improve diagnostics.
Wada, Yoshiro; Nishiike, Suetaka; Kitahara, Tadashi; Yamanaka, Toshiaki; Imai, Takao; Ito, Taeko; Sato, Go; Matsuda, Kazunori; Kitamura, Yoshiaki; Takeda, Noriaki
2016-11-01
After repeated snowboard exercises in the virtual reality (VR) world with increasing time lags in trials 3-8, it is suggested that the adaptation to repeated visual-vestibulosomatosensory conflict in the VR world improved dynamic posture control and motor performance in the real world without the development of motion sickness. The VR technology was used and the effects of repeated snowboard exercise examined in the VR world with time lags between visual scene and body rotation on the head stability and slalom run performance during exercise in healthy subjects. Forty-two healthy young subjects participated in the study. After trials 1 and 2 of snowboard exercise in the VR world without time lag, trials 3-8 were conducted with 0.1, 0.2, 0.3, 0.4, 0.5, and 0.6 s time lags of the visual scene that the computer creates behind board rotation, respectively. Finally, trial 9 was conducted without time lag. Head linear accelerations and subjective slalom run performance were evaluated. The standard deviations of head linear accelerations in inter-aural direction were significantly increased in trial 8, with a time lag of 0.6 s, but significantly decreased in trial 9 without a time lag, compared with those in trial 2 without a time lag. The subjective scores of slalom run performance were significantly decreased in trial 8, with a time lag of 0.6 s, but significantly increased in trial 9 without a time lag, compared with those in trial 2 without a time lag. Motion sickness was not induced in any subjects.
Lag Times and Peak Coefficients for Rural Watersheds in Kansas
DOT National Transportation Integrated Search
1999-10-01
Lag time is an essential input to the most common synthetic unit-hydrograph models. The lag time for an ungaged stream must be estimated from the physical characteristics of the stream and its watershed. In this study, a lag-time formula for small ru...
NASA Astrophysics Data System (ADS)
Ayres, Thomas R.; Brault, James W.
1990-11-01
Time series of the 2100/cm Delta v = 1 absorption bands of CO at the center of the solar disk and at the extreme limb have been recorded by Fourier transform spectrometer. The photospheric 5-min oscillation appears prominently at sun center. The peak-to-peak brightness temperature amplitude is roughly 300 K, and the peak-to-peak Doppler shift is roughly 1100 m/s. The 70 deg phase lag of maximum core intensity with respect to maximum redshift for the strongest Delta v = 1 absorptions is less than the 90 deg expected in the adiabatic limit. No dominant four-minute signal in the line intensity like that reported by Deming et al. (1984, 1986, and 1987) is found, nor is evidence for extreme fluctuations on short time scales like those proposed by Kalkofen et al. (1984). The strong Delta v = 1 lines exhibit systematic Doppler shifts of less than about 1 km/s, contrary to the predictions of transonic redshifts if the CO 'clouds' are associated with a dynamic cooling phase of the Ca II 'cell flashes.'
Code of Federal Regulations, 2010 CFR
2010-10-01
... 47 Telecommunication 3 2010-10-01 2010-10-01 false Lag times. 52.103 Section 52.103... Free Numbers § 52.103 Lag times. (a) Definitions. As used in this section, the following definitions... and an exchange carrier intercept recording is being provided. (3) Lag Time. The interval between a...
Code of Federal Regulations, 2012 CFR
2012-10-01
... 47 Telecommunication 3 2012-10-01 2012-10-01 false Lag times. 52.103 Section 52.103... Free Numbers § 52.103 Lag times. (a) Definitions. As used in this section, the following definitions... and an exchange carrier intercept recording is being provided. (3) Lag Time. The interval between a...
Code of Federal Regulations, 2011 CFR
2011-10-01
... 47 Telecommunication 3 2011-10-01 2011-10-01 false Lag times. 52.103 Section 52.103... Free Numbers § 52.103 Lag times. (a) Definitions. As used in this section, the following definitions... and an exchange carrier intercept recording is being provided. (3) Lag Time. The interval between a...
Code of Federal Regulations, 2013 CFR
2013-10-01
... 47 Telecommunication 3 2013-10-01 2013-10-01 false Lag times. 52.103 Section 52.103... Free Numbers § 52.103 Lag times. (a) Definitions. As used in this section, the following definitions... and an exchange carrier intercept recording is being provided. (3) Lag Time. The interval between a...
[In vitro percutaneous absorption of chromium powder and the effect of skin cleanser].
D'Agostin, F; Crosera, M; Adami, G; Malvestio, A; Rosani, R; Bovenzi, M; Maina, G; Filon, F Larese
2007-01-01
Occupational chromium dermatitis occurs frequently among cement and metal workers, workers dealing with leather tanning and employees in the ceramic industry. The present study, using an in-vitro system, evaluated percutaneous absorption of chromium powder and the effect of rapid skin decontamination with a common detergent. Experiments were performed using the Franz diffusion cell method with human skin. Physiological solution was used as receiving phase and a suspension of chromium powder in synthetic sweat was used as donor phase. The tests were performed without or with decontamination using the cleanser 30 minutes after the start of exposure. The amount of chromium permeated through the skin was analysed by Inductively Coupled Plasma Atomic Emission Spectroscopy and Electro Thermal Atomic Absorption Spectroscopy. Speciation analysis and measurements of chromium skin content were also performed. We calculated a permeation flux of 0.843 +/- 0.25 ng cm(-2) h(-1) and a lag time of 1.1 +/- 0.7 h. The cleaning procedure significantly increased chromium skin content, whereas skin passage was not increased. These results showed that chromium powder can pass through the skin and that skin decontamination did not decrease skin absorption. Therefore, it is necessary to prevent skin contamination when using toxic agents.
Molecular Chemistry of Atmospheric Brown Carbon Inferred from a Nationwide Biomass Burning Event
DOE Office of Scientific and Technical Information (OSTI.GOV)
Lin, Peng; Bluvshtein, Nir; Rudich, Yinon
Lag Ba'Omer, a nationwide bonfire festival in Israel, was chosen as a case study to investigate the influence of a major biomass burning event on the light absorption properties of atmospheric brown carbon (BrC). The chemical composition and optical properties of BrC chromophores were investigated using a high performance liquid chromatography (HPLC) platform coupled to photo diode array (PDA) and high resolution mass spectrometry (HRMS) detectors. Substantial increase of BrC light absorption coefficient was observed during the night-long biomass burning event. Most chromophores observed during the event were attributed to nitroaromatic compounds, comprising 28 elemental formulas of at least 63more » structural isomers. The NAC, in combination, accounted for 50-80% of the total visible light absorption (> 400 nm) by solvent extractable BrC. The results highlight that NAC, particular nitrophenols, are important light absorption contributors of biomass burning organic aerosol (BBOA), suggesting that night time chemistry of ·NO 3 and N 2O 5 with particles may play a significant role in atmospheric transformations of BrC. Nitrophenols and related compounds were especially important chromophores of BBOA. The absorption spectra of the BrC chromophores are influenced by the extraction solvent and solution pH, implying that the aerosol acidity is an important factor controlling the light absorption properties of BrC.« less
Molecular Chemistry of Atmospheric Brown Carbon Inferred from a Nationwide Biomass Burning Event
Lin, Peng; Bluvshtein, Nir; Rudich, Yinon; ...
2017-08-26
Lag Ba'Omer, a nationwide bonfire festival in Israel, was chosen as a case study to investigate the influence of a major biomass burning event on the light absorption properties of atmospheric brown carbon (BrC). The chemical composition and optical properties of BrC chromophores were investigated using a high performance liquid chromatography (HPLC) platform coupled to photo diode array (PDA) and high resolution mass spectrometry (HRMS) detectors. Substantial increase of BrC light absorption coefficient was observed during the night-long biomass burning event. Most chromophores observed during the event were attributed to nitroaromatic compounds, comprising 28 elemental formulas of at least 63more » structural isomers. The NAC, in combination, accounted for 50-80% of the total visible light absorption (> 400 nm) by solvent extractable BrC. The results highlight that NAC, particular nitrophenols, are important light absorption contributors of biomass burning organic aerosol (BBOA), suggesting that night time chemistry of ·NO 3 and N 2O 5 with particles may play a significant role in atmospheric transformations of BrC. Nitrophenols and related compounds were especially important chromophores of BBOA. The absorption spectra of the BrC chromophores are influenced by the extraction solvent and solution pH, implying that the aerosol acidity is an important factor controlling the light absorption properties of BrC.« less
Single-dose pharmacokinetic study of 13-cis-retinoic acid in man.
Besner, J G; Leclaire, R; Band, P; Meloche, S; Deschamps, M; Mailhot, S; Moisan, R; Diorio, G
1985-03-01
A pharmacokinetic study of 13-cis-retinoic acid was performed in nine patients following administration of a single oral dose of 80 mg. An average lag time of 1.2 hours was observed, followed by fast absorption, with a mean half-life of 0.5 hour. Peak plasmatic concentration of 733 ng/ml occurred at 2.3 hours. The disposition profile showed a rapid distribution half-life of 1.3 hours and a terminal elimination half-life of 24.7 hours. No 13-cis-retinoic acid was detected unchanged in urine. An important interpatient variability was noted.
DOT National Transportation Integrated Search
2016-04-01
The new lag-time equation for the Kansas City area performs better than the 2001 KU-KDOT equation for urban lag time, which was developed from a study of 14 gaged watersheds in Johnson County (McEnroe & Zhao, 2001). The main advantage of the new lag-...
Wang, Hui-Mei; Sun, Wei; Zu, Yuan-Gang; Wang, Wen-Jie
2011-12-01
Based on the one-year (2005) observations with a frequency of half hour on the stem sap flow of Larix gmelinii plantation trees planted in 1969 and the related environmental factors air humidity (RH), air temperature (T(air)), photosynthetic components active radiation (PAR), soil temperature (T(soil)), and soil moisture (TDR), principal analysis (PCA) and correction analysis were made on the time lag effect of the stem flow in different seasons (26 days of each season) and in a year via dislocation analysis, with the complexity and its integrative effects of the time lags of environment factors affecting the stem sap flow approached. The results showed that in different seasons and for different environmental factors, the time lag effect varied obviously. In general, the time lag of PAR was 0.5-1 hour ahead of sap flow, that of T(air) and RH was 0-2 hours ahead of or behind the sap flow, and the time lags of T(soil) and TDR were much longer or sometimes undetectable. Because of the complexity of the time lags, no evident improvements were observed in the linear correlations (R2, slope, and intercept) when the time lags based on short-term (20 days) data were used to correct the time lags based on whole year data. However, obvious improvements were found in the standardized and non-standardized correlation coefficients in stepwise multiple regressions, i.e., the time lag corrections could improve the effects of RH, but decreased the effects of PAR, T(air), and T(soil). PCA could be used to simplify the complexity. The first and the second principal components could stand for over 75% information of all the environmental factors in different seasons and in whole year. The time lags of both the first and the second principal components were 1-1.5 hours in advance of the sap flow, except in winter (no time lag effect).
Effective Iterated Greedy Algorithm for Flow-Shop Scheduling Problems with Time lags
NASA Astrophysics Data System (ADS)
ZHAO, Ning; YE, Song; LI, Kaidian; CHEN, Siyu
2017-05-01
Flow shop scheduling problem with time lags is a practical scheduling problem and attracts many studies. Permutation problem(PFSP with time lags) is concentrated but non-permutation problem(non-PFSP with time lags) seems to be neglected. With the aim to minimize the makespan and satisfy time lag constraints, efficient algorithms corresponding to PFSP and non-PFSP problems are proposed, which consist of iterated greedy algorithm for permutation(IGTLP) and iterated greedy algorithm for non-permutation (IGTLNP). The proposed algorithms are verified using well-known simple and complex instances of permutation and non-permutation problems with various time lag ranges. The permutation results indicate that the proposed IGTLP can reach near optimal solution within nearly 11% computational time of traditional GA approach. The non-permutation results indicate that the proposed IG can reach nearly same solution within less than 1% computational time compared with traditional GA approach. The proposed research combines PFSP and non-PFSP together with minimal and maximal time lag consideration, which provides an interesting viewpoint for industrial implementation.
Pharmacokinetics of brotizolam in healthy subjects following intravenous and oral administration
Jochemsen, Roeline; Wesselman, J. G. J.; Hermans, J.; van Boxtel, C. J.; Breimer, D. D.
1983-01-01
1 Pharmacokinetics and bioavailability of brotizolam after i.v. and oral administration were studied in healthy young volunteers. 2 Kinetic parameters after i.v. administration were: volume of distribution 0.66 ± 0.19 1/kg, total plasma clearance 113 ± 28 ml/min, distribution half-life 11 ± 6 min, and elimination half-life 4.8 ± 1.4 h (mean values ± s.d.). 3 Kinetic parameters after oral administration were: absorption lag-time 8 ± 12 min, absorption half-life 10 ± 11 min, and elimination half-life 5.1 ± 1.2 h (mean values ± s.d.). 4 Bioavailability of brotizolam was 70 ± 22% when calculated by comparing oral and intravenous area-under-curve values, corrected for intra-individual half-life differences. An alternative calculation method, which is relatively independent of large clearance variations, provided a bioavailability of 70 ± 24% (range: 47-117%). PMID:6661374
Statistical properties of Fourier-based time-lag estimates
NASA Astrophysics Data System (ADS)
Epitropakis, A.; Papadakis, I. E.
2016-06-01
Context. The study of X-ray time-lag spectra in active galactic nuclei (AGN) is currently an active research area, since it has the potential to illuminate the physics and geometry of the innermost region (I.e. close to the putative super-massive black hole) in these objects. To obtain reliable information from these studies, the statistical properties of time-lags estimated from data must be known as accurately as possible. Aims: We investigated the statistical properties of Fourier-based time-lag estimates (I.e. based on the cross-periodogram), using evenly sampled time series with no missing points. Our aim is to provide practical "guidelines" on estimating time-lags that are minimally biased (I.e. whose mean is close to their intrinsic value) and have known errors. Methods: Our investigation is based on both analytical work and extensive numerical simulations. The latter consisted of generating artificial time series with various signal-to-noise ratios and sampling patterns/durations similar to those offered by AGN observations with present and past X-ray satellites. We also considered a range of different model time-lag spectra commonly assumed in X-ray analyses of compact accreting systems. Results: Discrete sampling, binning and finite light curve duration cause the mean of the time-lag estimates to have a smaller magnitude than their intrinsic values. Smoothing (I.e. binning over consecutive frequencies) of the cross-periodogram can add extra bias at low frequencies. The use of light curves with low signal-to-noise ratio reduces the intrinsic coherence, and can introduce a bias to the sample coherence, time-lag estimates, and their predicted error. Conclusions: Our results have direct implications for X-ray time-lag studies in AGN, but can also be applied to similar studies in other research fields. We find that: a) time-lags should be estimated at frequencies lower than ≈ 1/2 the Nyquist frequency to minimise the effects of discrete binning of the observed time series; b) smoothing of the cross-periodogram should be avoided, as this may introduce significant bias to the time-lag estimates, which can be taken into account by assuming a model cross-spectrum (and not just a model time-lag spectrum); c) time-lags should be estimated by dividing observed time series into a number, say m, of shorter data segments and averaging the resulting cross-periodograms; d) if the data segments have a duration ≳ 20 ks, the time-lag bias is ≲15% of its intrinsic value for the model cross-spectra and power-spectra considered in this work. This bias should be estimated in practise (by considering possible intrinsic cross-spectra that may be applicable to the time-lag spectra at hand) to assess the reliability of any time-lag analysis; e) the effects of experimental noise can be minimised by only estimating time-lags in the frequency range where the sample coherence is larger than 1.2/(1 + 0.2m). In this range, the amplitude of noise variations caused by measurement errors is smaller than the amplitude of the signal's intrinsic variations. As long as m ≳ 20, time-lags estimated by averaging over individual data segments have analytical error estimates that are within 95% of the true scatter around their mean, and their distribution is similar, albeit not identical, to a Gaussian.
[Evaluation of Dissolution Profiles of Famotidine from Over-the-counter Drugs].
Saito, Yuji; Adachi, Naoki; Kato, Miki; Nadai, Masayuki
2018-03-27
In recent years, self-medication has started to receive more attention in Japan owing to increasing medical costs and health awareness among people. One of the main roles of pharmacists in self-medication is to provide appropriate information regarding over-the-counter (OTC) drugs. However, pharmacists promoting the proper use of OTC drugs have little information on their formulation properties. In this study, we performed dissolution tests on both OTC drugs and ethical drug (ED) containing famotidine, and evaluated the differences in their dissolution profiles. Marked differences in dissolution profiles of OTC drugs were observed in test solutions at pH 1.2, 4.0, and 6.8 and in water. To evaluate the differences quantitatively, we calculated the lag time and dissolution rate constant from the dissolution profiles. Significant differences in lag times and dissolution rate constants between some OTC drugs and ED were observed. We also used similarity factor (f2), to quantify the similarity between dissolution profiles of OTC drugs and ED. f2 values less than 42 were observed in some OTC drugs, suggesting that these differences might influence absorption in vivo resulting in differences in their onset time and efficacy. The findings of this study will provide useful information for the promotion of proper use of OTC drugs.
Signatures of Steady Heating in Time Lag Analysis of Coronal Emission
NASA Technical Reports Server (NTRS)
Viall, Nicholeen M.; Klimchuk, James A.
2016-01-01
Among the multitude of methods used to investigate coronal heating, the time lag method of Viall Klimchuk is becoming increasingly prevalent as an analysis technique that is complementary to those that are traditionally used.The time lag method cross correlates light curves at a given spatial location obtained in spectral bands that sample different temperature plasmas. It has been used most extensively with data from the Atmospheric Imaging Assembly on the Solar Dynamics Observatory. We have previously applied the time lag method to entire active regions and surrounding the quiet Sun and created maps of the results. We find that the majority of time lags are consistent with the cooling of coronal plasma that has been impulsively heated. Additionally, a significant fraction of the map area has a time lag of zero. This does not indicate a lack of variability. Rather, strong variability must be present, and it must occur in phase between the different channels. We have previously shown that these zero time lags are consistent with the transition region response to coronal nanoflares, although other explanations are possible. A common misconception is that the zero time lag indicates steady emission resulting from steady heating. Using simulated and observed light curves, we demonstrate here that highly correlated light curves at zero time lag are not compatible with equilibrium solutions. Such light curves can only be created by evolution
The effect of premilking udder preparation on Holstein cows milked 3 times daily.
Watters, R D; Schuring, N; Erb, H N; Schukken, Y H; Galton, D M
2012-03-01
Premilking udder preparation (including forestripping and duration of lag time-the time between first tactile stimulation and attachment of milking unit) might influence milking measures such as milking unit on-time, incidence of bimodality, and milk flow rates in Holstein cows milked 3 times daily. Holstein cows (n=786) from an 1,800-cow commercial dairy herd were enrolled under a restricted randomized design to determine the effect of 9 different premilking routines. Lag times were 0, 60, 90, 120, and 240s and included forestripping or no forestripping for a total of 9 treatments (no forestripping for 0 lag time); the study was conducted from February to November 2008. All cow-treatment combinations were compared with the control: predipping plus forestripping and drying with 90s of lag time. Cows were initially assigned to 1 of 3 treatments for a period of 7d and upon completion of the first 7-d period were reassigned to a different treatment until all treatments had been completed. From one treatment period to the next, cows had to switch stimulation method with no restriction on lag time. Cows did not receive all treatments during the duration of the trial. Early- to mid-lactation cows (EML; 17-167 DIM) and late-lactation cows (LL; 174-428 DIM) were housed in 2 different pens. Milk yield was significantly different between dip + forestrip and dip+dry for 2 of the treatments for EML cows compared with dip + forestrip and 90 s of lag-time (DF90); however, this was not thought to be due to treatment because the significant lag times were very different (60 and 240 s) and neither was an extreme value. Milk yield did not differ with treatment for the LL cows. Milking unit on-time did not differ when comparing all treatments for EML with treatment DF90; however, an increase in milking unit on-time occurred when lag time was 60s or less for LL cows. The highest incidence of bimodal milk curves was when lag time = 0 and this was independent of stage of lactation; a lag time of 240 s had the second-highest incidence of bimodal milk curves for EML and LL cows. Milk harvested in the first 2 min was lower for lag times of 0 and 240 s when compared with DF90. Increasing the lag time for all cows appeared to improve overall milking time efficiency (although lag time had no effect on EML cows). Copyright © 2012 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.
Effect of lag time distribution on the lag phase of bacterial growth - a Monte Carlo analysis
USDA-ARS?s Scientific Manuscript database
The objective of this study is to use Monte Carlo simulation to evaluate the effect of lag time distribution of individual bacterial cells incubated under isothermal conditions on the development of lag phase. The growth of bacterial cells of the same initial concentration and mean lag phase durati...
NASA Astrophysics Data System (ADS)
DeWalle, David R.; Boyer, Elizabeth W.; Buda, Anthony R.
2016-12-01
Forecasts of ecosystem changes due to variations in atmospheric emissions policies require a fundamental understanding of lag times between changes in chemical inputs and watershed response. Impacts of changes in atmospheric deposition in the United States have been documented using national and regional long-term environmental monitoring programs beginning several decades ago. Consequently, time series of weekly NADP atmospheric wet deposition and monthly EPA-Long Term Monitoring stream chemistry now exist for much of the Northeast which may provide insights into lag times. In this study of Appalachian forest basins, we estimated lag times for S, N and Cl by cross-correlating monthly data from four pairs of stream and deposition monitoring sites during the period from 1978 to 2012. A systems or impulse response function approach to cross-correlation was used to estimate lag times where the input deposition time series was pre-whitened using regression modeling and the stream response time series was filtered using the deposition regression model prior to cross-correlation. Cross-correlations for S were greatest at annual intervals over a relatively well-defined range of lags with the maximum correlations occurring at mean lags of 48 months. Chloride results were similar but more erratic with a mean lag of 57 months. Few high-correlation lags for N were indicated. Given the growing availability of atmospheric deposition and surface water chemistry monitoring data and our results for four Appalachian basins, further testing of cross-correlation as a method of estimating lag times on other basins appears justified.
Wilkins, Nicolas J; Rawson, Katherine A
2013-10-01
In Rickard, Lau, and Pashler's (2008) investigation of the lag effect on memory-based automaticity, response times were faster and proportion of trials retrieved was higher at the end of practice for short lag items than for long lag items. However, during testing after a delay, response times were slower and proportion of trials retrieved was lower for short lag items than for long lag items. The current study investigated the extent to which the lag effect on the durability of memory-based automaticity is due to interference or to the loss of memory strength with time. Participants repeatedly practiced alphabet subtraction items in short lag and long lag conditions. After practice, half of the participants were immediately tested and the other half were tested after a 7-day delay. Results indicate that the lag effect on the durability of memory-based automaticity is primarily due to interference. We discuss potential modification of current memory-based processing theories to account for these effects. © 2013.
AN INVESTIGATION OF TIME LAG MAPS USING THREE-DIMENSIONAL SIMULATIONS OF HIGHLY STRATIFIED HEATING
DOE Office of Scientific and Technical Information (OSTI.GOV)
Winebarger, Amy R.; Lionello, Roberto; Downs, Cooper
2016-11-10
The location and frequency of coronal energy release provide a significant constraint on the coronal heating mechanism. The evolution of the intensity observed in coronal structures found from time lag analysis of Atmospheric Imaging Assembly (AIA) data has been used to argue that heating must occur sporadically. Recently, we have demonstrated that quasi-steady, highly stratified (footpoint) heating can produce results qualitatively consistent with the evolution of observed coronal structures. The goals of this paper are to demonstrate that time lag analysis of 3D simulations of footpoint heating are qualitatively consistent with time lag analysis of observations and to use themore » 3D simulations to further understand whether time lag analysis is a useful tool in defining the evolution of coronal structures. We find the time lag maps generated from simulated data are consistent with the observed time lag maps. We next investigate several example points. In some cases, the calculated time lag reflects the evolution of a unique loop along the line of sight, though there may be additional evolving structures along the line of sight. We confirm that using the multi-peak AIA channels can produce time lags that are difficult to interpret. We suggest using a different high temperature channel, such as an X-ray channel. Finally, we find that multiple evolving structures along the line of sight can produce time lags that do not represent the physical properties of any structure along the line of sight, although the cross-correlation coefficient of the lightcurves is high. Considering the projected geometry of the loops may reduce some of the line-of-sight confusion.« less
Priestley, Tony; Chappa, Arvind K; Mould, Diane R; Upton, Richard N; Shusterman, Neil; Passik, Steven; Tormo, Vicente J; Camper, Stephen
2017-09-29
To develop a model to predict buprenorphine plasma concentrations during transition from transdermal to buccal administration. Population pharmacokinetic model-based meta-analysis of published data. A model-based meta-analysis of available buprenorphine pharmacokinetic data in healthy adults, extracted as aggregate (mean) data from published literature, was performed to explore potential conversion from transdermal to buccal buprenorphine. The time course of mean buprenorphine plasma concentrations following application of transdermal patch or buccal film was digitized from available literature, and a meta-model was developed using specific pharmacokinetic parameters (e.g., absorption rate, apparent clearance, and volumes of distribution) derived from analysis of pharmacokinetic data for intravenously, transdermally, and buccally administered buprenorphine. Data from six studies were included in this analysis. The final transdermal absorption model employed a zero-order input rate that was scaled to reflect a nominal patch delivery rate and time after patch application (with decline in rate over time). The transdermal absorption rate constant became zero following patch removal. Buccal absorption was a first-order process with a time lag and bioavailability term. Simulations of conversion from transdermal 20 mcg/h and 10 mcg/h to buccal administration suggest that transition can be made rapidly (beginning 12 hours after patch removal) using the recommended buccal formulation titration increments (75-150 mcg) and schedule (every four days) described in the product labeling. Computer modeling and simulations using a meta-model built from data extracted from publications suggest that rapid and straightforward conversion from transdermal to buccal buprenorphine is feasible. © 2017 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Shepard, Dale R; Mani, Sridhar; Kastrissios, Helen; Learned-Coughlin, Susan; Smith, Deborah; Ertel, Phillip; Magnum, Steve; Janisch, Linda; Fleming, Gini F; Schilsky, Richard L; Ratain, Mark J
2002-05-01
To determine the effect of food on the pharmacokinetics of 5-fluoruracil (5-FU) taken orally with eniluracil and to compare the performance of different pharmacokinetic analysis methods in the detection a potential food-drug interaction. In a randomized, open-label, two-way crossover study, 12 patients received eniluracil (50 mg, orally) on days 1 and 2 and 5-FU (20 mg/m(2), orally) on day 2 following either a 2-h fast or 20 min after a standard meal. Treatments were separated by 7 days. Timed blood samples were collected during the first two treatment periods and 5-FU concentrations determined by GC/MS. Data were analyzed and pharmacokinetic parameter estimates were obtained using a noncompartmental, two-stage and population analysis methods. In fasted individuals, the clearance/bioavailability of 5-FU was estimated to be 5.6 l/h. The mean absorption lag-time was 0.24 h and was followed by rapid absorption of 5-FU. Administration of 5-FU and eniluracil with food resulted in a decrease in the 5-FU absorption rate constant by 90%. As a result, the peak plasma concentration (C(max)) of 5-FU was decreased by 21% and the time to C(max) was increased 2.9-fold. Clearance of 5-FU, relative bioavailability, and area under the plasma concentration vs time curve (AUC) remained unchanged with coadministration of food. Similar results were obtained using all three data analysis methods. Administration of food with oral 5-FU and eniluracil slowed absorption of 5-FU and decreased 5-FU C(max), but did not effect AUC. Further investigation of the incorporation of population pharmacokinetic approaches in food effect studies is warranted.
NASA Astrophysics Data System (ADS)
Bucher, François-Xavier; Cao, Frédéric; Viard, Clément; Guichard, Frédéric
2014-03-01
We present in this paper a novel capacitive device that stimulates the touchscreen interface of a smartphone (or of any imaging device equipped with a capacitive touchscreen) and synchronizes triggering with the DxO LED Universal Timer to measure shooting time lag and shutter lag according to ISO 15781:2013. The device and protocol extend the time lag measurement beyond the standard by including negative shutter lag, a phenomenon that is more and more commonly found in smartphones. The device is computer-controlled, and this feature, combined with measurement algorithms, makes it possible to automatize a large series of captures so as to provide more refined statistical analyses when, for example, the shutter lag of "zero shutter lag" devices is limited by the frame time as our measurements confirm.
Frasch, H Frederick; Barbero, Ana M
2017-11-01
Nicotine plus flavorings in a propylene glycol (PG) vehicle are the components of electronic cigarette liquids (e-liquids), which are vaporized and inhaled by the user. Dermal exposure to nicotine and e-liquids may occur among workers in mixing and filling of e-cigarettes in the manufacturing process. Inadvertent skin contact among consumers is also a concern. In vitro nicotine permeation studies using heat-separated human epidermis were performed with surrogate and two commercial e-liquids, neat and aqueous nicotine donor formulations. Steady-state fluxes (J ss ), and lag times (t lag ) were measured for each formulation. In addition, transient (4 h) exposure and finite dose (1-10 μl/cm 2 ) experiments were undertaken using one commercial e-liquid. Average J ss (μg/cm 2 /h) from formulations were: nicotine in PG (24 mg/ml): 3.97; commercial e-liquid containing menthol (25 mg/ml nicotine): 10.2; commercial e-liquid containing limonene (25 mg/ml nicotine): 23.7; neat nicotine: 175. E-liquid lag times ranged from 5 to 10 h. Absorbed fraction of nicotine from finite doses was ≈0.3 at 48 h. The data were applied to transient exposure and finite dose dermal exposure assessment models and to a simple pharmacokinetic model. Three illustrative exposure scenarios demonstrate use of the data to predict systemic uptake and plasma concentrations from dermal exposure. The data demonstrate the potential for significant nicotine absorption through skin contact with e-cigarette refill solutions and the neat nicotine used to mix them.
SUPERGRANULES AS PROBES OF THE SUN'S MERIDIONAL CIRCULATION
DOE Office of Scientific and Technical Information (OSTI.GOV)
Hathaway, David H., E-mail: david.hathaway@nasa.gov
2012-11-20
Recent analysis revealed that supergranules (convection cells seen at the Sun's surface) are advected by the zonal flows at depths equal to the widths of the cells themselves. Here we probe the structure of the meridional circulation by cross-correlating maps of the Doppler velocity signal using a series of successively longer time lags between maps. We find that the poleward meridional flow decreases in amplitude with time lag and reverses direction to become an equatorward return flow at time lags >24 hr. These cross-correlation results are dominated by larger and deeper cells at longer time lags. (The smaller cells havemore » shorter lifetimes and do not contribute to the correlated signal at longer time lags.) We determine the characteristic cell size associated with each time lag by comparing the equatorial zonal flows measured at different time lags with the zonal flows associated with different cell sizes from a Fourier analysis. This association gives a characteristic cell size of {approx}50 Mm at a 24 hr time lag. This indicates that the poleward meridional flow returns equatorward at depths >50 Mm-just below the base of the surface shear layer. A substantial and highly significant equatorward flow (4.6 {+-} 0.4 m s{sup -1}) is found at a time lag of 28 hr corresponding to a depth of {approx}70 Mm. This represents one of the first positive detections of the Sun's meridional return flow and illustrates the power of using supergranules to probe the Sun's internal dynamics.« less
Patadia, Riddhish; Vora, Chintan; Mittal, Karan; Mashru, Rajashree
2016-01-01
The research envisaged focuses on vital impacts of variegated lubricants, glidants and hydrophilic additives on lag time of press coated ethylcellulose (EC) tablets using prednisone as a model drug. Several lubricants and glidants such as magnesium stearate, colloidal SiO2, sodium stearyl fumarate, talc, stearic acid, polyethylene glycol (6000) and glyceryl behenate were investigated to understand their effects on lag time by changing their concentrations in outer coat. Further, the effects of hydrophilic additives on lag time were examined for hydroxypropylmethylcellulose (E5), hydroxypropylcellulose (EF and SSL), povidone (K30), copovidone, polyethylene glycol (4000), lactose and mannitol. In vitro drug release testing revealed that each selected lubricant/glidant, if present even at concentration of 0.25% w/w, significantly reduced the lag time of press coated tablets. Specifically, colloidal SiO2 and/or magnesium stearate were detrimental while other lubricants/glidants were relatively less injurious. Among hydrophilic additives, freely water soluble fillers had utmost influence in lag time, whereas, comparatively less impact was observed with polymeric binders. Concisely, glidant and lubricant should be chosen to have minimal impact on lag time and further judicious selection of hydrophilic additives should be exercised for modulating lag time of pulsatile release formulations.
Miled, Rabeb Bennour; Guillier, Laurent; Neves, Sandra; Augustin, Jean-Christophe; Colin, Pierre; Besse, Nathalie Gnanou
2011-06-01
Cells of six strains of Cronobacter were subjected to dry stress and stored for 2.5 months at ambient temperature. The individual cell lag time distributions of recovered cells were characterized at 25 °C and 37 °C in non-selective broth. The individual cell lag times were deduced from the times taken by cultures from individual cells to reach an optical density threshold. In parallel, growth curves for each strain at high contamination levels were determined in the same growth conditions. In general, the extreme value type II distribution with a shape parameter fixed to 5 (EVIIb) was the most effective at describing the 12 observed distributions of individual cell lag times. Recently, a model for characterizing individual cell lag time distribution from population growth parameters was developed for other food-borne pathogenic bacteria such as Listeria monocytogenes. We confirmed this model's applicability to Cronobacter by comparing the mean and the standard deviation of individual cell lag times to populational lag times observed with high initial concentration experiments. We also validated the model in realistic conditions by studying growth in powdered infant formula decimally diluted in Buffered Peptone Water, which represents the first enrichment step of the standard detection method for Cronobacter. Individual lag times and the pooling of samples significantly affect detection performances. Copyright © 2010 Elsevier Ltd. All rights reserved.
Estimation of watershed lag times and times of concentration for the Kansas City Area.
DOT National Transportation Integrated Search
2016-04-01
Lag time (TL) and time of concentration (TC) are two related measures of how quickly a stream responds to : runoff-producing rainfall over its watershed. In this report, a general relationship for lag time is derived from the : Manning equation for f...
Analysis of Quasi-periodic Oscillations and Time Lag in Ultraluminous X-Ray Sources with XMM-Newton
DOE Office of Scientific and Technical Information (OSTI.GOV)
Li, Zi-Jian; Xiao, Guang-Cheng; Zhang, Shu
We investigated the power density spectrum (PDS) and time lag of ultraluminous X-ray sources (ULXs) observed by XMM-Newton . We determined the PDSs for each ULX and found that five of them show intrinsic variability due to obvious quasi-periodic oscillations (QPOs) of mHz–1 Hz, consistent with previous reports. We further investigated these five ULXs to determine their possible time lag. The ULX QPOs exhibit a soft time lag that is linearly related to the QPO frequency. We discuss the likelihood of the ULX QPOs being type-C QPO analogs, and the time lag models. The ULXs might harbor intermediate-mass black holesmore » if their QPOs are type-C QPO analogs. We suggest that the soft lag and the linearity may be due to reverberation.« less
Population Pharmacokinetic Model of Doxycycline Plasma Concentrations Using Pooled Study Data
Wojciechowski, Jessica; Mudge, Stuart; Upton, Richard N.; Foster, David J. R.
2017-01-01
ABSTRACT The literature presently lacks a population pharmacokinetic analysis of doxycycline. This study aimed to develop a population pharmacokinetic model of doxycycline plasma concentrations that could be used to assess the power of bioequivalence between Doryx delayed-release tablets and Doryx MPC. Doxycycline pharmacokinetic data were available from eight phase 1 clinical trials following single/multiple doses of conventional-release doxycycline capsules, Doryx delayed-release tablets, and Doryx MPC under fed and fasted conditions. A population pharmacokinetic model was developed in a stepwise manner using NONMEM, version 7.3. The final covariate model was developed according to a forward inclusion (P < 0.01) and then backward deletion (P < 0.001) procedure. The final model was a two-compartment model with two-transit absorption compartments. Structural covariates in the base model included formulation effects on relative bioavailability (F), absorption lag (ALAG), and the transit absorption rate (KTR) under the fed status. An absorption delay (lag) for the fed status (FTLAG2 = 0.203 h) was also included in the model as a structural covariate. The fed status was observed to decrease F by 10.5%, and the effect of female sex was a 14.4% increase in clearance. The manuscript presents the first population pharmacokinetic model of doxycycline plasma concentrations following oral doxycycline administration. The model was used to assess the power of bioequivalence between Doryx delayed-release tablets and Doryx MPC, and it could potentially be used to critically examine and optimize doxycycline dose regimens. PMID:28052851
Population Pharmacokinetic Model of Doxycycline Plasma Concentrations Using Pooled Study Data.
Hopkins, Ashley M; Wojciechowski, Jessica; Abuhelwa, Ahmad Y; Mudge, Stuart; Upton, Richard N; Foster, David J R
2017-03-01
The literature presently lacks a population pharmacokinetic analysis of doxycycline. This study aimed to develop a population pharmacokinetic model of doxycycline plasma concentrations that could be used to assess the power of bioequivalence between Doryx delayed-release tablets and Doryx MPC. Doxycycline pharmacokinetic data were available from eight phase 1 clinical trials following single/multiple doses of conventional-release doxycycline capsules, Doryx delayed-release tablets, and Doryx MPC under fed and fasted conditions. A population pharmacokinetic model was developed in a stepwise manner using NONMEM, version 7.3. The final covariate model was developed according to a forward inclusion ( P < 0.01) and then backward deletion ( P < 0.001) procedure. The final model was a two-compartment model with two-transit absorption compartments. Structural covariates in the base model included formulation effects on relative bioavailability ( F ), absorption lag (ALAG), and the transit absorption rate (KTR) under the fed status. An absorption delay (lag) for the fed status (FTLAG2 = 0.203 h) was also included in the model as a structural covariate. The fed status was observed to decrease F by 10.5%, and the effect of female sex was a 14.4% increase in clearance. The manuscript presents the first population pharmacokinetic model of doxycycline plasma concentrations following oral doxycycline administration. The model was used to assess the power of bioequivalence between Doryx delayed-release tablets and Doryx MPC, and it could potentially be used to critically examine and optimize doxycycline dose regimens. Copyright © 2017 American Society for Microbiology.
A generalized expression for lag-time in the gas-phase permeation of hollow tubes
NASA Technical Reports Server (NTRS)
Shah, K. K.; Nelson, H. G.; Johnson, D. L.; Hamaker, F. M.
1975-01-01
A generalized expression for the nonsteady-state parameter, lag-time, has been obtained from Fick's second law for gas-phase transport through hollow, cylindrical membranes. This generalized expression is simplified for three limiting cases of practical interest: (1) diffusion controlled transport, (2) phase boundary reaction control at the inlet surface, and (3) phase boundary reaction control at the outlet surface. In all three cases the lag-time expressions were found to be inversely proportional only to the diffusion coefficient and functionally dependent on the membrane radii. Finally, the lag-time expressions were applied to experimentally obtained lag-time data for alpha-phase titanium and alpha-phase iron.
Regmi, Rajesh; Lovelock, D Michael; Zhang, Pengpeng; Pham, Hai; Xiong, Jianping; Yorke, Ellen D; Goodman, Karyn A; Wu, Abraham J; Mageras, Gig S
2015-06-01
To investigate constancy, within a treatment session, of the time lag relationship between implanted markers in abdominal tumors and an external motion surrogate. Six gastroesophageal junction and three pancreatic cancer patients (IRB-approved protocol) received two cone-beam CTs (CBCT), one before and one after treatment. Time between scans was less than 30 min. Each patient had at least one implanted fiducial marker near the tumor. In all scans, abdominal displacement (Varian RPM) was recorded as the external motion signal. Purpose-built software tracked fiducials, representing internal signal, in CBCT projection images. Time lag between superior-inferior (SI) internal and anterior-posterior external signals was found by maximizing the correlation coefficient in each breathing cycle and averaging over all cycles. Time-lag-induced discrepancy between internal SI position and that predicted from the external signal (external prediction error) was also calculated. Mean ± standard deviation time lag, over all scans and patients, was 0.10 ± 0.07 s (range 0.01-0.36 s). External signal lagged the internal in 17/18 scans. Change in time lag between pre- and post-treatment CBCT was 0.06 ± 0.07 s (range 0.01-0.22 s), corresponding to 3.1% ± 3.7% (range 0.6%-10.8%) of gate width (range 1.6-3.1 s). In only one patient, change in time lag exceeded 10% of the gate width. External prediction error over all scans of all patients varied from 0.1 ± 0.1 to 1.6 ± 0.4 mm. Time lag between internal motion along SI and external signals is small compared to the treatment gate width of abdominal patients examined in this study. Change in time lag within a treatment session, inferred from pre- to post-treatment measurements is also small, suggesting that a single measurement of time lag at the session start is adequate. These findings require confirmation in a larger number of patients.
Regmi, Rajesh; Lovelock, D. Michael; Zhang, Pengpeng; Pham, Hai; Xiong, Jianping; Yorke, Ellen D.; Goodman, Karyn A.; Wu, Abraham J.; Mageras, Gig S.
2015-01-01
Purpose: To investigate constancy, within a treatment session, of the time lag relationship between implanted markers in abdominal tumors and an external motion surrogate. Methods: Six gastroesophageal junction and three pancreatic cancer patients (IRB-approved protocol) received two cone-beam CTs (CBCT), one before and one after treatment. Time between scans was less than 30 min. Each patient had at least one implanted fiducial marker near the tumor. In all scans, abdominal displacement (Varian RPM) was recorded as the external motion signal. Purpose-built software tracked fiducials, representing internal signal, in CBCT projection images. Time lag between superior–inferior (SI) internal and anterior–posterior external signals was found by maximizing the correlation coefficient in each breathing cycle and averaging over all cycles. Time-lag-induced discrepancy between internal SI position and that predicted from the external signal (external prediction error) was also calculated. Results: Mean ± standard deviation time lag, over all scans and patients, was 0.10 ± 0.07 s (range 0.01–0.36 s). External signal lagged the internal in 17/18 scans. Change in time lag between pre- and post-treatment CBCT was 0.06 ± 0.07 s (range 0.01–0.22 s), corresponding to 3.1% ± 3.7% (range 0.6%–10.8%) of gate width (range 1.6–3.1 s). In only one patient, change in time lag exceeded 10% of the gate width. External prediction error over all scans of all patients varied from 0.1 ± 0.1 to 1.6 ± 0.4 mm. Conclusions: Time lag between internal motion along SI and external signals is small compared to the treatment gate width of abdominal patients examined in this study. Change in time lag within a treatment session, inferred from pre- to post-treatment measurements is also small, suggesting that a single measurement of time lag at the session start is adequate. These findings require confirmation in a larger number of patients. PMID:26127033
Fungal mycelia show lag time before re-growth on endogenous carbon.
Pollack, Judith K; Li, Zheng Jian; Marten, Mark R
2008-06-15
Nutrient starvation is a common occurrence for filamentous fungi. To better understand the effects of starvation, we used a parallel plate flow chamber to study individual fungal mycelia when subjected to a step change in glucose concentration. We report the presence of a finite "lag time" in starved mycelia during which they ceased to grow/extend while switching from growth on exogenous carbon to re-growth on endogenous carbon. This lag time precedes other morphological or physiological changes such as change in growth rate (50-70% reduction), vacuolation (up to 16%), and decreased hyphal diameter (almost 50% reduction). Data suggests that during lag time, vacuolar degradation produces sufficient endogenous carbon to support survival and restart hyphal extension. Lag time is inversely related to the size of the mycelium at the time of starvation, which suggests a critical flow of endogenous carbon to the apical tip. We present a mathematical model consistent with our experimental observations that relate lag time, area, and flow of endogenous carbon. (c) 2008 Wiley Periodicals, Inc.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Regmi, Rajesh; Lovelock, D. Michael; Zhang, Pengpeng
Purpose: To investigate constancy, within a treatment session, of the time lag relationship between implanted markers in abdominal tumors and an external motion surrogate. Methods: Six gastroesophageal junction and three pancreatic cancer patients (IRB-approved protocol) received two cone-beam CTs (CBCT), one before and one after treatment. Time between scans was less than 30 min. Each patient had at least one implanted fiducial marker near the tumor. In all scans, abdominal displacement (Varian RPM) was recorded as the external motion signal. Purpose-built software tracked fiducials, representing internal signal, in CBCT projection images. Time lag between superior–inferior (SI) internal and anterior–posterior externalmore » signals was found by maximizing the correlation coefficient in each breathing cycle and averaging over all cycles. Time-lag-induced discrepancy between internal SI position and that predicted from the external signal (external prediction error) was also calculated. Results: Mean ± standard deviation time lag, over all scans and patients, was 0.10 ± 0.07 s (range 0.01–0.36 s). External signal lagged the internal in 17/18 scans. Change in time lag between pre- and post-treatment CBCT was 0.06 ± 0.07 s (range 0.01–0.22 s), corresponding to 3.1% ± 3.7% (range 0.6%–10.8%) of gate width (range 1.6–3.1 s). In only one patient, change in time lag exceeded 10% of the gate width. External prediction error over all scans of all patients varied from 0.1 ± 0.1 to 1.6 ± 0.4 mm. Conclusions: Time lag between internal motion along SI and external signals is small compared to the treatment gate width of abdominal patients examined in this study. Change in time lag within a treatment session, inferred from pre- to post-treatment measurements is also small, suggesting that a single measurement of time lag at the session start is adequate. These findings require confirmation in a larger number of patients.« less
Time Resolved Spectroscopy, High Sensitivity Power Spectrum & a Search for the X-Ray QPO in NGC 5548
NASA Astrophysics Data System (ADS)
Yaqoob, Tahir
1999-09-01
Controversy surrounds the EXOSAT discovery of a QPO (period ~500 s) in NGC 5548 due to the data being plagued by high background and instrumental systematics. If the NGC 5548 QPO is real, the implications for the physics of the X-ray emission mechanism and inner-most disk/black-hole system are enormous. AXAF provides the first opportunity to settle the issue, capable of yielding power spectra with unprecedented sensitivity, pushing the limit on finding new features. Using HETG/ACIS we will also perform time-resolved spectroscopy of the ionized absorption features and Fe-K emission line, search for energy-dependent time lags in the continuum, between the continuum and spectral features, and between the spectral features. These data will provide powerful constraints on models of AGN.
Temporal evolution of photon energy emitted from two-component advective flows: origin of time lag
NASA Astrophysics Data System (ADS)
Chatterjee, Arka; Chakrabarti, Sandip K.; Ghosh, Himadri
2017-12-01
X-ray time lag of black hole candidates contains important information regarding the emission geometry. Recently, study of time lags from observational data revealed very intriguing properties. To investigate the real cause of this lag behavior with energy and spectral states, we study photon paths inside a two-component advective flow (TCAF) which appears to be a satisfactory model to explain the spectral and timing properties. We employ the Monte Carlo simulation technique to carry out the Comptonization process. We use a relativistic thick disk in Schwarzschild geometry as the CENtrifugal pressure supported BOundary Layer (CENBOL) which is the Compton cloud. In TCAF, this is the post-shock region of the advective component. Keplerian disk on the equatorial plane which is truncated at the inner edge i.e. at the outer boundary of the CENBOL, acts as the soft photon source. Ray-tracing code is employed to track the photons to a distantly located observer. We compute the cumulative time taken by a photon during Comptonization, reflection and following the curved geometry on the way to the observer. Time lags between various hard and soft bands have been calculated. We study the variation of time lags with accretion rates, CENBOL size and inclination angle. Time lags for different energy channels are plotted for different inclination angles. The general trend of variation of time lag with QPO frequency and energy as observed in satellite data is reproduced.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kroon, John J.; Becker, Peter A., E-mail: jkroon@gmu.edu, E-mail: pbecker@gmu.edu
2016-04-20
Many accreting black holes manifest time lags during outbursts, in which the hard Fourier component typically lags behind the soft component. Despite decades of observations of this phenomenon, the underlying physical explanation for the time lags has remained elusive, although there are suggestions that Compton reverberation plays an important role. However, the lack of analytical solutions has hindered the interpretation of the available data. In this paper, we investigate the generation of X-ray time lags in Compton scattering coronae using a new mathematical approach based on analysis of the Fourier-transformed transport equation. By solving this equation, we obtain the Fouriermore » transform of the radiation Green’s function, which allows us to calculate the exact dependence of the time lags on the Fourier frequency, for both homogeneous and inhomogeneous coronal clouds. We use the new formalism to explore a variety of injection scenarios, including both monochromatic and broadband (bremsstrahlung) seed photon injection. We show that our model can successfully reproduce both the observed time lags and the time-averaged (quiescent) X-ray spectra for Cyg X-1 and GX 339-04, using a single set of coronal parameters for each source. The time lags are the result of impulsive bremsstrahlung injection occurring near the outer edge of the corona, while the time-averaged spectra are the result of continual distributed injection of soft photons throughout the cloud.« less
Diclofenac and metabolite pharmacokinetics in children.
van der Marel, Caroline D; Anderson, Brian J; Rømsing, Janne; Jacqz-Aigrain, Evelyne; Tibboel, Dick
2004-06-01
Data concerning metabolism of diclofenac in children are limited to intravenous and enteric coated oral formulations. There are no data examining diclofenac or its hydroxyl metabolite pharmacokinetics after rectal administration in children. Infants (n = 26) undergoing tonsillectomy were given diclofenac 2 mg.kg(-1) followed by 1 mg.kg(-1) 8 h as suppository formulation for postoperative analgesia. Serum was assayed for diclofenac, 4'-hydroxydiclofenac and 5'-hydroxydiclofenac concentrations during the procedure and 1, 2 and 4 h postoperatively. The formation clearances of diclofenac to hydroxyl metabolites were estimated using nonlinear mixed effects models. A single compartment, first order absorption and first order elimination model was used to describe diclofenac pharmacokinetics. Published data from 11 children given enteric-coated diclofenac tablets were used to assess relative bioavailability. Mean (sd) age and weight of the patients were 4.5 (1.5) years and 20.5 (4.1) kg. The formation clearance to 4'-hydroxydiclofenac (% CV) and to 5'-hydroxydiclofenac were 8.41 (8.1) and 3.41 (113) l.h(-1) respectively, standardized to a 70 kg person using allometric '1/4 power' models. Clearance by other routes contributed 33.0 (64) l.h(-1) 70 kg(-1). Elimination clearance of hydroxyl metabolites was fixed at 27.5 l.h(-1) 70 kg(-1). The volumes of distribution of parent diclofenac and its hydroxyl metabolite were 22.8 (19.0) and 45.3 (l.70) kg(-1). The suppository formulation had an absorption half-life of 0.613 (33.2) h with a lag time of 0.188 (24.9) h. Interoccasion variability of formation clearance to 4'-hydroxydiclofenac, diclofenac volume of distribution, absorption half-time and lag time for the suppository was 36%, 55%, 14% and 119%, respectively. The relative bioavailability of the suppository compared with an enteric-coated tablet was 1.26. The formation clearance of the active metabolite 4'-hydroxydiclofenac contributed 19% of total clearance (44.82 l.h(-1) 70 kg(-1)). The rectum is a suitable route for administration of diclofenac in children 2-8 year of age and was associated with a higher relative bioavailabilty than enteric-coated tablets and an earlier maximum concentration (50 vs. 108 min). This pharmacokinetic profile renders diclofenac suppository a suitable formulation for short duration surgery.
Patadia, Riddhish; Vora, Chintan; Mittal, Karan; Mashru, Rajashree
2016-11-01
The research undertaken exemplifies the effects of hydroxypropyl methylcellulose (HPMC) molecular weight (MW) grades of on lag time of press-coated ethylcellulose (EC) tablets. The formulation comprised an immediate release core (containing prednisone as a model drug) surrounded by compression coating with variegated EC-HPMC blends. Five selected HPMC grades (E5, E15, E50, K100LV and K4M) were explored at three different concentrations (10% w/w, 20% w/w and 30% w/w in outer coat) to understand their effects on lag time and drug release. In vitro drug release testing demonstrated that, with increase in concentration of E5 and E15, up to 30% w/w, the mean lag time decreased progressively; whereas with remaining grades, the mean lag time initially decreased up to 20% w/w level and thereafter increased for 30% w/w level. Importantly, with increase in HPMC concentration in the outer coat, the variability in lag time (%RSD; n = 6) was decreased for each of E5, E15 and E50, whereas increased for K100LV and K4M. In general, the variability in lag time was increased with increase in HPMC MW at studied concentration levels. Markedly, tablets with 30% w/w K4M in outer coat exhibited slight premature release (before the rupture of outer coat) along with high variability in lag time. Overall, the study concluded that low MW HPMCs (E5, E15 and E50) were found rather efficient than higher MW HPMCs for developing robust EC-based press-coated pulsatile release formulations where precise lag time followed by sharp burst release is desired.
Hydrophilic excipients modulate the time lag of time-controlled disintegrating press-coated tablets.
Lin, Shan-Yang; Li, Mei-Jane; Lin, Kung-Hsu
2004-08-16
An oral press-coated tablet was developed by means of direct compression to achieve the time-controlled disintegrating or rupturing function with a distinct predetermined lag time. This press-coated tablet containing sodium diclofenac in the inner core was formulated with an outer shell by different weight ratios of hydrophobic polymer of micronized ethylcellulose (EC) powder and hydrophilic excipients such as spray-dried lactose (SDL) or hydroxypropyl methylcellulose (HPMC). The effect of the formulation of an outer shell comprising both hydrophobic polymer and hydrophilic excipients on the time lag of drug release was investigated. The release profile of the press-coated tablet exhibited a time period without drug release (time lag) followed by a rapid and complete release phase, in which the outer shell ruptured or broke into 2 halves. The lag phase was markedly dependent on the weight ratios of EC/SDL or EC/HPMC in the outer shell. Different time lags of the press-coated tablets from 1.0 to 16.3 hours could be modulated by changing the type and amount of the excipients. A semilogarithmic plot of the time lag of the tablet against the weight ratios of EC/SDL or EC/HPMC in the outer shell demonstrated a good linear relationship, with r = 0.976 and r = 0.982, respectively. The predetermined time lag prior to the drug release from a press-coated tablet prepared by using a micronized EC as a retarding coating shell can be adequately scheduled with the addition of hydrophilic excipients according to the time or site requirements.
Effects of timber harvesting on the lag time of Caspar Creek watershed
Karen Hardison Sendek
1985-01-01
Abstract - Hydrograph lag time was analyzed to determine changes after road construction and after selective, tractor-yarded logging in a Caspar Creek watershed, Mendocino County, California. The paired watershed technique was used. Hydrograph lag time for each storm was the time separation between the midpoint of precipitation and the time coordinate of the runoff...
Okano, Daisuke
2013-02-01
In this study of corona streamer discharges from an impulse generator using a dc power supply, the relationship of the discharge time-lag with the dc bias voltage between the sphere-to-needle electrodes under atmospheric conditions is investigated. Devices utilizing corona discharges have been used to purify air or water, destroy bacteria, and to remove undesirable substances, and in order to achieve fast response times and high power efficiencies in such devices, it is important to minimize the time-lag of the corona discharge. Our experimental results show that (a) the discharge path of a negatively biased needle electrode will be straighter than that of a positively biased needle and (b) the discharge threshold voltage in both the positive and the negative needle electrodes is nearly equal to 33 kV. By expressing the discharge voltage as a power function of time-lag, the extent of corona generation can be quantitatively specified using the exponent of this power function. The observed behavior of a corona streamer discharge between the negative spherical and the positive needle electrodes indicates that the largest power exponent is associated with the shortest time-lag, owing to the reduction in the statistical time-lag in the absence of a formative time-lag.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kroon, John J.; Becker, Peter A., E-mail: jkroon@gmu.edu, E-mail: pbecker@gmu.edu
Accreting black hole sources show a wide variety of rapid time variability, including the manifestation of time lags during X-ray transients, in which a delay (phase shift) is observed between the Fourier components of the hard and soft spectra. Despite a large body of observational evidence for time lags, no fundamental physical explanation for the origin of this phenomenon has been presented. We develop a new theoretical model for the production of X-ray time lags based on an exact analytical solution for the Fourier transform describing the diffusion and Comptonization of seed photons propagating through a spherical corona. The resultingmore » Green's function can be convolved with any source distribution to compute the associated Fourier transform and time lags, hence allowing us to explore a wide variety of injection scenarios. We show that thermal Comptonization is able to self-consistently explain both the X-ray time lags and the steady-state (quiescent) X-ray spectrum observed in the low-hard state of Cyg X-1. The reprocessing of bremsstrahlung seed photons produces X-ray time lags that diminish with increasing Fourier frequency, in agreement with the observations for a wide range of sources.« less
NASA Astrophysics Data System (ADS)
Okano, Daisuke
2013-02-01
In this study of corona streamer discharges from an impulse generator using a dc power supply, the relationship of the discharge time-lag with the dc bias voltage between the sphere-to-needle electrodes under atmospheric conditions is investigated. Devices utilizing corona discharges have been used to purify air or water, destroy bacteria, and to remove undesirable substances, and in order to achieve fast response times and high power efficiencies in such devices, it is important to minimize the time-lag of the corona discharge. Our experimental results show that (a) the discharge path of a negatively biased needle electrode will be straighter than that of a positively biased needle and (b) the discharge threshold voltage in both the positive and the negative needle electrodes is nearly equal to 33 kV. By expressing the discharge voltage as a power function of time-lag, the extent of corona generation can be quantitatively specified using the exponent of this power function. The observed behavior of a corona streamer discharge between the negative spherical and the positive needle electrodes indicates that the largest power exponent is associated with the shortest time-lag, owing to the reduction in the statistical time-lag in the absence of a formative time-lag.
Fukui, E; Uemura, K; Kobayashi, M
2000-08-10
Press-coated tablets, containing diltiazem hydrochloride (DIL) in the core tablet and coated with hydroxypropylcellulose (HPC) as the outer shell, were examined for applicability as timed-release tablets with a predetermined lag time and subsequent rapid drug release phase. Various types of press-coated tablets were prepared using a rotary tabletting machine and their DIL dissolution behavior was evaluated by the JP paddle method. The results indicated that tablets with the timed-release function could be prepared, and that the lag times were prolonged as the viscosity of HPC and the amount of the outer shell were increased. The lag times could be controlled widely by the above method, however, the compression load had little effect. Two different kinds of timed-release press-coated tablets that showed lag times of 3 and 6 h in the in vitro test (denoted PCT(L3) and PCT(L6), respectively) were administered to beagle dogs. DIL was first detected in the plasma more than 3 h after administration, and both tablets showed timed-release. The lag times showed a good agreement between the in vivo and in vitro tests in PCT(L3). However, the in vivo lag times were about 4 h in PCT(L6) and were much shorter than the in vitro lag time. The dissolution test was performed at different paddle rotation speeds, and good agreement was obtained between the in vivo and in vitro lag times at 150 rpm. This suggested that the effects of gastrointestinal peristalsis and contraction should also be taken into consideration for the further development of drug delivery systems.
NASA Astrophysics Data System (ADS)
Mizumoto, Misaki; Done, Chris; Hagino, Kouichi; Ebisawa, Ken; Tsujimoto, Masahiro; Odaka, Hirokazu
2018-07-01
X-rays illuminating the accretion disc in active galactic nuclei give rise to an iron K line and its associated reflection spectrum that are lagged behind the continuum variability by the light-travel time from the source to the disc. The measured lag time-scales in the iron band can be as short as ˜Rg/c, where Rg is the gravitational radius, which is often interpreted as evidence for a very small continuum source close to the event horizon of a rapidly spinning black hole. However, the short lags can also be produced by reflection from more distant material, because the primary photons with no time-delay dilute the time-lags caused by the reprocessed photons. We perform a Monte Carlo simulation to calculate the dilution effect in the X-ray reverberation lags from a half-shell of neutral material placed at 100 Rg from the central source. This gives lags of ˜2 Rg/c, but the iron line is a distinctly narrow feature in the lag-energy plot, whereas the data often show a broader line. We show that both the short lag and the line broadening can be reproduced, if the scattering material is outflowing at ˜0.1c. The velocity structure in the wind can also give shifts in the line profile in the lag-energy plot calculated at different frequencies. Hence we propose that the observed broad iron reverberation lags and shifts in profile as a function of frequency of variability can arise from a disc wind at fairly large distances from the X-ray source.
Nielsen, L; Khurana, R; Coats, A; Frokjaer, S; Brange, J; Vyas, S; Uversky, V N; Fink, A L
2001-05-22
In the search for the molecular mechanism of insulin fibrillation, the kinetics of insulin fibril formation were studied under different conditions using the fluorescent dye thioflavin T (ThT). The effect of insulin concentration, agitation, pH, ionic strength, anions, seeding, and addition of 1-anilinonaphthalene-8-sulfonic acid (ANS), urea, TMAO, sucrose, and ThT on the kinetics of fibrillation was investigated. The kinetics of the fibrillation process could be described by the lag time for formation of stable nuclei (nucleation) and the apparent rate constant for the growth of fibrils (elongation). The addition of seeds eliminated the lag phase. An increase in insulin concentration resulted in shorter lag times and faster growth of fibrils. Shorter lag times and faster growth of fibrils were seen at acidic pH versus neutral pH, whereas an increase in ionic strength resulted in shorter lag times and slower growth of fibrils. There was no clear correlation between the rate of fibril elongation and ionic strength. Agitation during fibril formation attenuated the effects of insulin concentration and ionic strength on both lag times and fibril growth. The addition of ANS increased the lag time and decreased the apparent growth rate for insulin fibril formation. The ANS-induced inhibition appears to reflect the formation of amorphous aggregates. The denaturant, urea, decreased the lag time, whereas the stabilizers, trimethylamine N-oxide dihydrate (TMAO) and sucrose, increased the lag times. The results indicated that both nucleation and fibril growth were controlled by hydrophobic and electrostatic interactions. A kinetic model, involving the association of monomeric partially folded intermediates, whose concentration is stimulated by the air-water interface, leading to formation of the critical nucleus and thence fibrils, is proposed.
Yamamoto, Syunsuke; Karashima, Masatoshi; Arai, Yuta; Tohyama, Kimio; Amano, Nobuyuki
2017-09-01
Although several mathematical models have been reported for the estimation of human plasma concentration profiles of drug substances after dermal application, the successful cases that can predict human pharmacokinetic profiles are limited. Therefore, the aim of this study is to investigate the prediction of human plasma concentrations after dermal application using in vitro permeation parameters obtained from excised human skin. The in vitro skin permeability of 7 marketed drug products was evaluated. The plasma concentration-time profiles of the drug substances in humans after their dermal application were simulated using compartment models and the clinical pharmacokinetic parameters. The transdermal process was simulated using the in vitro skin permeation rate and lag time assuming a zero-order absorption. These simulated plasma concentration profiles were compared with the clinical data. The result revealed that the steady-state plasma concentration of diclofenac and the maximum concentrations of nicotine, bisoprolol, rivastigmine, and lidocaine after topical application were within 2-fold of the clinical data. Furthermore, the simulated concentration profiles of bisoprolol, nicotine, and rivastigmine reproduced the decrease in absorption due to drug depletion from the formulation. In conclusion, this simple compartment model using in vitro human skin permeation parameters as zero-order absorption predicted the human plasma concentrations accurately. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.
NASA Astrophysics Data System (ADS)
Nazarieh, F.; Ansari, H.; Ziaei, A. N.; Izady, A.; Davari, K.; Brunner, P.
2018-05-01
The time required for deep percolating water to reach the water table can be considerable in areas with a thick vadose zone. Sustainable groundwater management, therefore, has to consider the spatial and temporal dynamics of groundwater recharge. The key parameters that control the lag time have been widely examined in soil physics using small-scale lysimeters and modeling studies. However, only a small number of studies have analyzed how deep-percolation rates affect groundwater recharge dynamics over large spatial scales. This study examined how the parameters influencing lag time affect groundwater recharge in a semi-arid catchment under irrigation (in northeastern Iran) using a numerical modeling approach. Flow simulations were performed by the MODFLOW-NWT code with the Vadose-Zone Flow (UZF) Package. Calibration of the groundwater model was based on data from 48 observation wells. Flow simulations showed that lag times vary from 1 to more than 100 months. A sensitivity analysis demonstrated that during drought conditions, the lag time was highly sensitive to the rate of deep percolation. The study illustrated two critical points: (1) the importance of providing estimates of the lag time as a basis for sustainable groundwater management, and (2) lag time not only depends on factors such as soil hydraulic conductivity or vadose zone depth but also depends on the deep-percolation rates and the antecedent soil-moisture condition. Therefore, estimates of the lag time have to be associated with specific percolation rates, in addition to depth to groundwater and soil properties.
X-ray time lags in PG 1211+143
NASA Astrophysics Data System (ADS)
Lobban, A. P.; Vaughan, S.; Pounds, K.; Reeves, J. N.
2018-05-01
We investigate the X-ray time lags of a recent ˜630 ks XMM-Newton observation of PG 1211+143. We find well-correlated variations across the XMM-Newton EPIC bandpass, with the first detection of a hard lag in this source with a mean time delay of up to ˜3 ks at the lowest frequencies. We find that the energy-dependence of the low-frequency hard lag scales approximately linearly with log(E) when averaged over all orbits, consistent with the propagating fluctuations model. However, we find that the low-frequency lag behaviour becomes more complex on time-scales longer than a single orbit, suggestive of additional modes of variability. We also detect a high-frequency soft lag at ˜10-4 Hz with the magnitude of the delay peaking at ≲ 0.8 ks, consistent with previous observations, which we discuss in terms of small-scale reverberation.
Wang, Fang; Wang, Lin; Chen, Yuming
2017-08-31
In order to investigate the time-dependent cross-correlations of fine particulate (PM2.5) series among neighboring cities in Northern China, in this paper, we propose a new cross-correlation coefficient, the time-lagged q-L dependent height crosscorrelation coefficient (denoted by p q (τ, L)), which incorporates the time-lag factor and the fluctuation amplitude information into the analogous height cross-correlation analysis coefficient. Numerical tests are performed to illustrate that the newly proposed coefficient ρ q (τ, L) can be used to detect cross-correlations between two series with time lags and to identify different range of fluctuations at which two series possess cross-correlations. Applying the new coefficient to analyze the time-dependent cross-correlations of PM2.5 series between Beijing and the three neighboring cities of Tianjin, Zhangjiakou, and Baoding, we find that time lags between the PM2.5 series with larger fluctuations are longer than those between PM2.5 series withsmaller fluctuations. Our analysis also shows that cross-correlations between the PM2.5 series of two neighboring cities are significant and the time lags between two PM2.5 series of neighboring cities are significantly non-zero. These findings providenew scientific support on the view that air pollution in neighboring cities can affect one another not simultaneously but with a time lag.
Dagnas, Stéphane; Gougouli, Maria; Onno, Bernard; Koutsoumanis, Konstantinos P; Membré, Jeanne-Marie
2017-01-02
The inhibitory effect of water activity (a w ) and storage temperature on single spore lag times of Aspergillus niger, Eurotium repens (Aspergillus pseudoglaucus) and Penicillium corylophilum strains isolated from spoiled bakery products, was quantified. A full factorial design was set up for each strain. Data were collected at levels of a w varying from 0.80 to 0.98 and temperature from 15 to 35°C. Experiments were performed on malt agar, at pH5.5. When growth was observed, ca 20 individual growth kinetics per condition were recorded up to 35days. Radius of the colony vs time was then fitted with the Buchanan primary model. For each experimental condition, a lag time variability was observed, it was characterized by its mean, standard deviation (sd) and 5 th percentile, after a Normal distribution fit. As the environmental conditions became stressful (e.g. storage temperature and a w lower), mean and sd of single spore lag time distribution increased, indicating longer lag times and higher variability. The relationship between mean and sd followed a monotonous but not linear pattern, identical whatever the species. Next, secondary models were deployed to estimate the cardinal values (minimal, optimal and maximal temperatures, minimal water activity where no growth is observed anymore) for the three species. That enabled to confirm the observation made based on raw data analysis: concerning the temperature effect, A. niger behaviour was significantly different from E. repens and P. corylophilum: T opt of 37.4°C (standard deviation 1.4°C) instead of 27.1°C (1.4°C) and 25.2°C (1.2°C), respectively. Concerning the a w effect, from the three mould species, E. repens was the species able to grow at the lowest a w (aw min estimated to 0.74 (0.02)). Finally, results obtained with single spores were compared to findings from a previous study carried out at the population level (Dagnas et al., 2014). For short lag times (≤5days), there was no difference between lag time of the population (ca 2000 spores inoculated in one spot) and mean (nor 5 th percentile) of single spore lag time distribution. In contrast, when lag time was longer, i.e. under more stressful conditions, there was a discrepancy between individual and population lag times (population lag times shorter than 5 th percentiles of single spore lag time distribution), confirming a stochastic process. Finally, the temperature cardinal values estimated with single spores were found to be similar to those obtained at the population level, whatever the species. All these findings will be used to describe better mould spore lag time variability and then to predict more accurately bakery product shelf-life. Copyright © 2016 Elsevier B.V. All rights reserved.
Do subjective symptoms predict our perception of jet-lag?
Waterhouse, J; Edwards, B; Nevill, A; Atkinson, G; Reilly, T; Davies, P; Godfrey, R
2000-10-01
A total of 39 subjects were studied after a flight from the UK to either Sydney or Brisbane (10 time-zones to the east). Subjects varied widely in their age, their athletic ability, whether or not they were taking melatonin, and in their objectives when in Australia. For the first 6 days after arrival, subjects scored their jet-lag five times per day and other subjective variables up to five times per day, using visual analogue scales. For jet-lag, the scale was labelled 0 = no jet-lag to 10 = very bad jet-lag; the extremes of the other scales were labelled - 5 and + 5, indicating marked changes compared with normal, and the centrepoint was labelled 0 indicating 'normal'. Mean daily values for jet-lag and fatigue were initially high (+ 3.65 +/- 0.35 and + 1.55 +/- 0.22 on day 1, respectively) and fell progressively on subsequent days, but were still raised significantly (p < 0.05) on day 5 (fatigue) or day 6 (jet-lag). In addition, times of waking were earlier on all days. By contrast, falls in concentration and motivation, and rises in irritability and nocturnal wakings, had recovered by day 4 or earlier, and bowel activity was less frequent, with harder stools, on days 1 and 2 only. Also, on day 1, there was a decrease in the ease of getting to sleep (- 1.33 +/- 0.55), but this changed to an increase from day 2 onwards (for example, + 0.75 +/- 0.25 on day 6). Stepwise regression analysis was used to investigate predictors of jet-lag. The severity of jet-lag at all the times that were measured was strongly predicted by fatigue ratings made at the same time. Its severity at 08:00 h was predicted by an earlier time of waking, by feeling less alert 30 min after waking and, marginally, by the number of waking episodes. Jet-lag at 12:00 and 16:00 h was strongly predicted by a fall of concentration at these times; jet-lag at mealtimes (12:00, 16:00 and 20:00 h) was predicted by the amount of feeling bloated. Such results complicate an exact interpretation that can be placed on an assessment of a global term such as jet-lag, particularly if the assessment is made only once per day.
Time-lag effects of global vegetation responses to climate change.
Wu, Donghai; Zhao, Xiang; Liang, Shunlin; Zhou, Tao; Huang, Kaicheng; Tang, Bijian; Zhao, Wenqian
2015-09-01
Climate conditions significantly affect vegetation growth in terrestrial ecosystems. Due to the spatial heterogeneity of ecosystems, the vegetation responses to climate vary considerably with the diverse spatial patterns and the time-lag effects, which are the most important mechanism of climate-vegetation interactive effects. Extensive studies focused on large-scale vegetation-climate interactions use the simultaneous meteorological and vegetation indicators to develop models; however, the time-lag effects are less considered, which tends to increase uncertainty. In this study, we aim to quantitatively determine the time-lag effects of global vegetation responses to different climatic factors using the GIMMS3g NDVI time series and the CRU temperature, precipitation, and solar radiation datasets. First, this study analyzed the time-lag effects of global vegetation responses to different climatic factors. Then, a multiple linear regression model and partial correlation model were established to statistically analyze the roles of different climatic factors on vegetation responses, from which the primary climate-driving factors for different vegetation types were determined. The results showed that (i) both the time-lag effects of the vegetation responses and the major climate-driving factors that significantly affect vegetation growth varied significantly at the global scale, which was related to the diverse vegetation and climate characteristics; (ii) regarding the time-lag effects, the climatic factors explained 64% variation of the global vegetation growth, which was 11% relatively higher than the model ignoring the time-lag effects; (iii) for the area with a significant change trend (for the period 1982-2008) in the global GIMMS3g NDVI (P < 0.05), the primary driving factor was temperature; and (iv) at the regional scale, the variation in vegetation growth was also related to human activities and natural disturbances. Considering the time-lag effects is quite important for better predicting and evaluating the vegetation dynamics under the background of global climate change. © 2015 John Wiley & Sons Ltd.
Constraining Anisotropic Lorentz Violation via the Spectral-lag Transition of GRB 160625B
DOE Office of Scientific and Technical Information (OSTI.GOV)
Wei, Jun-Jie; Wu, Xue-Feng; Shao, Lang
Violations of Lorentz invariance can lead to an energy-dependent vacuum dispersion of light, which results in arrival-time differences of photons with different energies arising from a given transient source. In this work, direction-dependent dispersion constraints are obtained on nonbirefringent Lorentz-violating effects using the observed spectral lags of the gamma-ray burst GRB 160625B. This burst has unusually large high-energy photon statistics, so we can obtain constraints from the true spectral time lags of bunches of high-energy photons rather than from the rough time lag of a single highest-energy photon. Also, GRB 160625B is the only burst to date having a well-definedmore » transition from positive lags to negative lags, providing a unique opportunity to distinguish Lorentz-violating effects from any source-intrinsic time lag in the emission of photons of different energy bands. Our results place comparatively robust two-sided constraints on a variety of isotropic and anisotropic coefficients for Lorentz violation, including the first bounds on Lorentz-violating effects from operators of mass dimension 10 in the photon sector.« less
NASA Astrophysics Data System (ADS)
Vero, Sara E.; Basu, Nandita B.; Van Meter, Kimberly; Richards, Karl G.; Mellander, Per-Erik; Healy, Mark G.; Fenton, Owen
2018-02-01
The efficacy of water quality policies aiming to reduce or prevent nitrate contamination of waterbodies may be constrained by the inherent delay or "time lag" of water and solute transport through unsaturated (soil) and saturated (groundwater) pathways. These delays must be quantified in order to establish realistic deadlines, thresholds and policy expectations, and to design effective best management practices. The objective of this review is to synthesise the current state of research on nitrate-related time lags in both the European and North American environmental and legislative contexts. The durations of time lags have been found to differ according to climatic, pedological, landscape and management scenarios. Elucidation of these driving factors at a watershed scale is essential where water quality is impaired or at risk. Finally, the existence of time lags is increasingly being acknowledged at a policy level and incorporated into the development of environmental legislation. However, the full impact of these time lags is not yet fully understood or appreciated, and continued outreach and education in scientific, public and policy venues is still required.
The Weighted-Average Lagged Ensemble.
DelSole, T; Trenary, L; Tippett, M K
2017-11-01
A lagged ensemble is an ensemble of forecasts from the same model initialized at different times but verifying at the same time. The skill of a lagged ensemble mean can be improved by assigning weights to different forecasts in such a way as to maximize skill. If the forecasts are bias corrected, then an unbiased weighted lagged ensemble requires the weights to sum to one. Such a scheme is called a weighted-average lagged ensemble. In the limit of uncorrelated errors, the optimal weights are positive and decay monotonically with lead time, so that the least skillful forecasts have the least weight. In more realistic applications, the optimal weights do not always behave this way. This paper presents a series of analytic examples designed to illuminate conditions under which the weights of an optimal weighted-average lagged ensemble become negative or depend nonmonotonically on lead time. It is shown that negative weights are most likely to occur when the errors grow rapidly and are highly correlated across lead time. The weights are most likely to behave nonmonotonically when the mean square error is approximately constant over the range forecasts included in the lagged ensemble. An extreme example of the latter behavior is presented in which the optimal weights vanish everywhere except at the shortest and longest lead times.
Current Status of Biomedical Book Reviewing: Part II. Time Lag in Biomedical Book Reviewing
Chen, Ching-Chih
1974-01-01
This part of the study explores the effectiveness of the review media in terms of speed of reviewing, comprehensiveness of review treatment, and authority. The time lags for the fifty-four journals varied widely, the mean ranging from 5.8 months to forty-two months. The time lags for all 3,347 reviews varied even more widely, ranging from less than a month to 108 months after a book was off the press. The 3,347 reviews had a mean time lag of 10.43 months and a standard deviation of 6.63 months. PMID:4826480
How to induce multiple delays in coupled chaotic oscillators?
NASA Astrophysics Data System (ADS)
Bhowmick, Sourav K.; Ghosh, Dibakar; Roy, Prodyot K.; Kurths, Jürgen; Dana, Syamal K.
2013-12-01
Lag synchronization is a basic phenomenon in mismatched coupled systems, delay coupled systems, and time-delayed systems. It is characterized by a lag configuration that identifies a unique time shift between all pairs of similar state variables of the coupled systems. In this report, an attempt is made how to induce multiple lag configurations in coupled systems when different pairs of state variables attain different time shift. A design of coupling is presented to realize this multiple lag synchronization. Numerical illustration is given using examples of the Rössler system and the slow-fast Hindmarsh-Rose neuron model. The multiple lag scenario is physically realized in an electronic circuit of two Sprott systems.
NASA Astrophysics Data System (ADS)
Mizumoto, Misaki; Done, Chris; Hagino, Kouichi; Ebisawa, Ken; Tsujimoto, Masahiro; Odaka, Hirokazu
2018-05-01
X-rays illuminating the accretion disc in active galactic nuclei give rise to an iron K line and its associated reflection spectrum which are lagged behind the continuum variability by the light-travel time from the source to the disc. The measured lag timescales in the iron band can be as short as ˜Rg/c, where Rg is the gravitational radius, which is often interpreted as evidence for a very small continuum source close to the event horizon of a rapidly spinning black hole. However, the short lags can also be produced by reflection from more distant material, because the primary photons with no time-delay dilute the time-lags caused by the reprocessed photons. We perform a Monte-Carlo simulation to calculate the dilution effect in the X-ray reverberation lags from a half-shell of neutral material placed at 100 Rg from the central source. This gives lags of ˜2 Rg/c, but the iron line is a distinctly narrow feature in the lag-energy plot, whereas the data often show a broader line. We show that both the short lag and the line broadening can be reproduced if the scattering material is outflowing at ˜0.1c. The velocity structure in the wind can also give shifts in the line profile in the lag-energy plot calculated at different frequencies. Hence we propose that the observed broad iron reverberation lags and shifts in profile as a function of frequency of variability can arise from a disc wind at fairly large distances from the X-ray source.
ERIC Educational Resources Information Center
Greene, Monica R.; Pasnak, Robert; Romero, Sandy L.
2009-01-01
Research Findings: The present study employed a time lag design to assess temporal relationships between motivation, academic achievement, and cognitive development. Eighty-one children from 2 preschool programs were measured twice, with an 11-week time lag, on 2 measures of motivation (marble drop task, bean bag toss task), 2 measures of…
Sintov, Amnon C; Levy, Haim V; Botner, Shafir
2010-12-01
The main purpose of this study was to investigate the nasal absorption of insulin from a new microemulsion spray preparation in rabbits. The bioavailability of insulin lispro via the nasal route using a W/O microemulsion was found to reach 21.5% relative to subcutaneous administration, whereas the use of an inverse microemulsion as well as a plain solution yielded less than 1% bioavailability. The profile of plasma glucose levels obtained after nasal spray application of the microemulsion (1IU/kg lispro) was similar to the subcutaneous profile of 0.5IU/kg at the first 90min after application and resulted in a 30-40% drop in glucose levels. The microemulsion system was characterized by DLS, TEM, viscosity measurements, and by construction of pseudo-ternary phase diagram. The average droplet size of an insulin-unloaded and insulin-loaded microemulsions containing 20% aqueous phase (surfactants-to-oil ratio=87:13) was 2nm and 2.26nm in diameter, respectively. In addition, the effect of the microemulsion on FITC-labeled insulin permeation was examined across the porcine nasal mucosa in vitro. The permeability coefficient of FITC-insulin via the microemulsion was 0.210±0.048cm/h with a lag time of 10.9±6.5min, whereas the permeability coefficient from a plain solution was 0.082±0.043cm/h with a lag time of 36.3±10.1min. In view of the absorption differences of insulin between 20%, 50% water-containing microemulsions and an aqueous solution obtained in vitro and in vivo, it has been concluded that the acceleration in the intramucosal transport process is the result of encapsulating insulin within the nano-droplet clusters of a W/O microemulsion, while the microemulsion ingredients seems to have no direct role. Copyright © 2010 Elsevier B.V. All rights reserved.
van Aart, C; Boshuizen, H; Dekkers, A; Korthals Altes, H
2017-05-01
In low-incidence countries, most tuberculosis (TB) cases are foreign-born. We explored the temporal relationship between immigration and TB in first-generation immigrants between 1995 and 2012 to assess whether immigration can be a predictor for TB in immigrants from high-incidence countries. We obtained monthly data on immigrant TB cases and immigration for the three countries of origin most frequently represented among TB cases in the Netherlands: Morocco, Somalia and Turkey. The best-fit seasonal autoregressive integrated moving average (SARIMA) model to the immigration time-series was used to prewhiten the TB time series. The cross-correlation function (CCF) was then computed on the residual time series to detect time lags between immigration and TB rates. We identified a 17-month lag between Somali immigration and Somali immigrant TB cases, but no time lag for immigrants from Morocco and Turkey. The absence of a lag in the Moroccan and Turkish population may be attributed to the relatively low TB prevalence in the countries of origin and an increased likelihood of reactivation TB in an ageing immigrant population. Understanding the time lag between Somali immigration and TB disease would benefit from a closer epidemiological analysis of cohorts of Somali cases diagnosed within the first years after entry.
Heisig, M; Lieckfeldt, R; Wittum, G; Mazurkevich, G; Lee, G
1996-03-01
The diffusion equation should be solved for the non-steady-state problem of drug diffusion within a two-dimensional, biphasic stratum corneum membrane having homogeneous lipid and corneocyte phases. A numerical method was developed for a brick-and-mortar SC-geometry, enabling an explicit solution for time-dependent drug concentration within both phases. The lag time and permeability were calculated. It is shown how the barrier property of this model membrane depends on relative phase permeability, corneocyte alignment, and corneocyte-lipid partition coefficient. Additionally, the time-dependent drug concentration profiles within the membrane can be observed during the lag and steady-state phases. The model SC-membrane predicts, from purely morphological principles, lag times and permeabilities that are in good agreement with experimental values. The long lag times and very small permeabilities reported for human SC can only be predicted for a highly-staggered corneocyte geometry and corneocytes that are 1000 times less permeable than the lipid phase. Although the former conclusion is reasonable, the latter is questionable. The elongated, flattened corneocyte shape renders lag time and permeability insensitive to large changes in their alignment within the SC. Corneocyte/lipid partitioning is found to be fundamentally different to SC/donor partitioning, since increasing drug lipophilicity always reduces both lag time and permeability.
Vero, S E; Ibrahim, T G; Creamer, R E; Grant, J; Healy, M G; Henry, T; Kramers, G; Richards, K G; Fenton, O
2014-12-01
The true efficacy of a programme of agricultural mitigation measures within a catchment to improve water quality can be determined only after a certain hydrologic time lag period (subsequent to implementation) has elapsed. As the biophysical response to policy is not synchronous, accurate estimates of total time lag (unsaturated and saturated) become critical to manage the expectations of policy makers. The estimation of the vertical unsaturated zone component of time lag is vital as it indicates early trends (initial breakthrough), bulk (centre of mass) and total (Exit) travel times. Typically, estimation of time lag through the unsaturated zone is poor, due to the lack of site specific soil physical data, or by assuming saturated conditions. Numerical models (e.g. Hydrus 1D) enable estimates of time lag with varied levels of input data. The current study examines the consequences of varied soil hydraulic and meteorological complexity on unsaturated zone time lag estimates using simulated and actual soil profiles. Results indicated that: greater temporal resolution (from daily to hourly) of meteorological data was more critical as the saturated hydraulic conductivity of the soil decreased; high clay content soils failed to converge reflecting prevalence of lateral component as a contaminant pathway; elucidation of soil hydraulic properties was influenced by the complexity of soil physical data employed (textural menu, ROSETTA, full and partial soil water characteristic curves), which consequently affected time lag ranges; as the importance of the unsaturated zone increases with respect to total travel times the requirements for high complexity/resolution input data become greater. The methodology presented herein demonstrates that decisions made regarding input data and landscape position will have consequences for the estimated range of vertical travel times. Insufficiencies or inaccuracies regarding such input data can therefore mislead policy makers regarding the achievability of water quality targets. Copyright © 2014 Elsevier B.V. All rights reserved.
A Race Against Time: Time Lags in Terrestrial-Aquatic Linkages
NASA Astrophysics Data System (ADS)
Basu, N. B.
2017-12-01
Unprecedented decreases in atmospheric nitrogen (N) deposition together with increases in agricultural N-use efficiency have led to decreases in net anthropogenic N inputs in many eastern U.S. and Canadian watersheds as well as in Europe. Despite such decreases, N concentrations in streams and rivers continue to increase, and problems of coastal eutrophication remain acute. Such a mismatch between N inputs and outputs can arise due to legacy N accumulation and subsequent lag times between implementation of conservation measures and improvements in water quality. In the present study, we quantified such lag times by pairing long-term N input trajectories with stream N concentration data in multiple watersheds in North America. Results show significant nonlinearity between N inputs and outputs, with a strong hysteresis effect indicative of decadal-scale lag times. Lag times were found to be negatively correlated with both tile drainage and watershed slope, with tile drainage being a dominant control in fall and watershed slope being significant during the spring snowmelt period. Quantification of such lags will be crucial to policy-makers as they struggle to set appropriate goals for water quality improvement in human-impacted watersheds.
Relation between germination and mycelium growth of individual fungal spores.
Gougouli, Maria; Koutsoumanis, Konstantinos P
2013-02-15
The relation between germination time and lag time of mycelium growth of individual spores was studied by combining microscopic and macroscopic techniques. The radial growth of a large number (100-200) of Penicillium expansum and Aspergillus niger mycelia originating from single spores was monitored macroscopically at isothermal conditions ranging from 0 to 30°C and 10 to 41.5°C, respectively. The radial growth curve for each mycelium was fitted to a linear model for the estimation of mycelium lag time. The results showed that the lag time varied significantly among single spores. The cumulative frequency distributions of the lag times were fitted to the modified Gompertz model and compared with the respective distributions for the germination time, which were obtained microscopically. The distributions of the measured mycelium lag time were found to be similar to the germination time distributions under the same conditions but shifted in time with the lag times showing a significant delay compared to germination times. A numerical comparison was also performed based on the distribution parameters λ(m) and λ(g), which indicate the time required from the spores to start the germination process and the completion of the lag phase, respectively. The relative differences %(λ(m)-λ(g))/λ(m) were not found to be significantly affected by temperatures tested with mean values of 72.5±5.1 and 60.7±2.1 for P. expansum for A. niger, respectively. In order to investigate the source of the above difference, a time-lapse microscopy method was developed providing videos with the behavior of single fungal spore from germination until mycelium formation. The distances of the apexes of the first germ tubes that emerged from the swollen spore were measured in each frame of the videos and these data were expressed as a function of time. The results showed that in the early hyphal development, the measured radii appear to increase exponentially, until a certain time, where growth becomes linear. The two phases of hyphal development can explain the difference between germination and lag time. Since the lag time is estimated from the extrapolation of the regression line of the linear part of the graph only, its value is significantly higher than the germination time, t(G). The relation of germination and lag time was further investigated by comparing their temperature dependence using the Cardinal Model with Inflection. The estimated values of the cardinal parameters (T(min), T(opt), and T(max)) for 1/λ(g) were found to be very close to the respective values for 1/λ(m), indicating similar temperature dependence between them. Copyright © 2012 Elsevier B.V. All rights reserved.
Inacio, R; Barlow, D; Kong, X; Keeble, J; Jones, S A
2016-05-01
Relatively little is known about how drug self-association influences absorption into the human body. This study presented two hydrophobic membranes with a series of solutions containing different types of tetracaine aggregates with the aim of understanding how the attributes of supramolecular aggregate formation influenced passive membrane transport. The data showed that aqueous solutions of the unprotonated form of tetracaine displayed a significantly higher (p<0.05) passive membrane transport compared to solutions with mixtures of the unprotonated and protonated drug microspecies (e.g. transport through the skin was 0.96±0.31μgcm(-2)min(-1) and 1.59±0.26μgcm(-2)min(-1) respectively). However, despite an enhanced rate of drug transport and a better membrane partitioning the unionised molecules showed a significantly longer (p<0.05) lag time to membrane penetration compared solutions rich in the ionised microspecies. Analytical characterisation of the solutions applied to the apical surface of the membranes in the transport studies showed that larger tetracaine aggregates with smaller surface charge gave rise to the longer lag times. These large aggregates demonstrated more extensive intermolecular bonding and therefore, it was suggest that it was the enhanced propensity of the unionised species to form tightly bound drug aggregates that caused the delay in the membrane penetration. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.
NASA Astrophysics Data System (ADS)
Cipriano, F. R.; Lagmay, A. M. A.; Horritt, M.; Mendoza, J.; Sabio, G.; Punay, K. N.; Taniza, H. J.; Uichanco, C.
2015-12-01
Widespread flooding is a major problem in the Philippines. The country experiences heavy amount of rainfall throughout the year and several areas are prone to flood hazards because of its unique topography. Human casualties and destruction of infrastructure are just some of the damages caused by flooding and the Philippine government has undertaken various efforts to mitigate these hazards. One of the solutions was to create flood hazard maps of different floodplains and use them to predict the possible catastrophic results of different rain scenarios. To produce these maps with accurate output, different input parameters were needed and one of those is calculating hydrological components from topographical data. This paper presents how a calibrated lag time (TL) equation was obtained using measurable catchment parameters. Lag time is an essential input in flood mapping and is defined as the duration between the peak rainfall and peak discharge of the watershed. The lag time equation involves three measurable parameters, namely, watershed length (L), maximum potential retention (S) derived from the curve number, and watershed slope (Y), all of which were available from RADARSAT Digital Elevation Models (DEM). This approach was based on a similar method developed by CH2M Hill and Horritt for Taiwan, which has a similar set of meteorological and hydrological parameters with the Philippines. Rainfall data from fourteen water level sensors covering 67 storms from all the regions in the country were used to estimate the actual lag time. These sensors were chosen by using a screening process that considers the distance of the sensors from the sea, the availability of recorded data, and the catchment size. The actual lag time values were plotted against the values obtained from the Natural Resource Conservation Management handbook lag time equation. Regression analysis was used to obtain the final calibrated equation that would be used to calculate the lag time specifically for rivers in the Philippine setting. The calculated lag time values could then be used as a parameter for modeling different flood scenarios in the country.
NASA Astrophysics Data System (ADS)
Wang, Yuanbing; Min, Jinzhong; Chen, Yaodeng; Huang, Xiang-Yu; Zeng, Mingjian; Li, Xin
2017-01-01
This study evaluates the performance of three-dimensional variational (3DVar) and a hybrid data assimilation system using time-lagged ensembles in a heavy rainfall event. The time-lagged ensembles are constructed by sampling from a moving time window of 3 h along a model trajectory, which is economical and easy to implement. The proposed hybrid data assimilation system introduces flow-dependent error covariance derived from time-lagged ensemble into variational cost function without significantly increasing computational cost. Single observation tests are performed to document characteristic of the hybrid system. The sensitivity of precipitation forecasts to ensemble covariance weight and localization scale is investigated. Additionally, the TLEn-Var is evaluated and compared to the ETKF(ensemble transformed Kalman filter)-based hybrid assimilation within a continuously cycling framework, through which new hybrid analyses are produced every 3 h over 10 days. The 24 h accumulated precipitation, moisture, wind are analyzed between 3DVar and the hybrid assimilation using time-lagged ensembles. Results show that model states and precipitation forecast skill are improved by the hybrid assimilation using time-lagged ensembles compared with 3DVar. Simulation of the precipitable water and structure of the wind are also improved. Cyclonic wind increments are generated near the rainfall center, leading to an improved precipitation forecast. This study indicates that the hybrid data assimilation using time-lagged ensembles seems like a viable alternative or supplement in the complex models for some weather service agencies that have limited computing resources to conduct large size of ensembles.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Jiang, Yan-Fei; Green, Paul J.; Pancoast, Anna
We study the time lags between the continuum emission of quasars at different wavelengths, based on more than four years of multi-band ( g , r , i , z ) light curves in the Pan-STARRS Medium Deep Fields. As photons from different bands emerge from different radial ranges in the accretion disk, the lags constrain the sizes of the accretion disks. We select 240 quasars with redshifts of z ≈ 1 or z ≈ 0.3 that are relatively emission-line free. The light curves are sampled from day to month timescales, which makes it possible to detect lags on themore » scale of the light crossing time of the accretion disks. With the code JAVELIN , we detect typical lags of several days in the rest frame between the g band and the riz bands. The detected lags are ∼2–3 times larger than the light crossing time estimated from the standard thin disk model, consistent with the recently measured lag in NGC 5548 and microlensing measurements of quasars. The lags in our sample are found to increase with increasing luminosity. Furthermore, the increase in lags going from g − r to g − i and then to g − z is slower than predicted in the thin disk model, particularly for high-luminosity quasars. The radial temperature profile in the disk must be different from what is assumed. We also find evidence that the lags decrease with increasing line ratios between ultraviolet Fe ii lines and Mg ii, which may point to changes in the accretion disk structure at higher metallicity.« less
Determine if analysis of lag structure from time series epidemiology, using gases, particles, and source factor time series, can contribute to understanding the relationships among various air pollution indicators. Methods: Analyze lag structure from an epidemiologic study of ca...
Schug, B S; Brendel, E; Chantraine, E; Wolf, D; Martin, W; Schall, R; Blume, H H
2002-06-01
The aim of this study was to investigate the effect of concomitant food intake on the bioavailability of two nifedipine containing modified release dosage forms for once daily administration. The clinical study was performed to investigate the in vivo relevance of pH-dependent differences in the in vitro release properties of the two dosage forms. This was a randomized, open, 4-way crossover study in 24 healthy, male subjects. Following an overnight fast of 12 h single doses of Adalat OROS or Slofedipine XL were administered either in the fasted state or immediately after a high fat American breakfast. Nifedipine plasma concentrations in samples obtained until 48 h after drug administration were determined using a validated LC-MS/MS method. Calculation of pharmacokinetic parameters was conducted model-independently. The two dosage forms as well as the two administration conditions were compared by calculating point estimates and 90% confidence intervals for the relevant pharmacokinetic parameters. In vitro dissolution tests were performed using a paddle apparatus 3 acc. USP, a pharmacopoeial dissolution system consisting of reciprocating cylinders in flat-bottomed glass vessels, with various buffer systems covering the entire physiological pH-range of the gastrointestinal tract. After fasted administration the extent of bioavailability of nifedipine as characterized by AUC(0,infinity) was slightly lower for Slofedipine XL compared with Adalat OROS with a point estimate of 82.3% primarily resulting from pronounced differences in nifedipine concentrations during the first 15 h after administration. Accordingly, maximum plasma concentrations were lower after administration of Slofedipine XL compared with Adalat OROS (point estimate: 84.3%). Under fed conditions the differences in bioavailability between the two products as characterized by the pharmacokinetic parameters AUC(0,tn) and Cmax were greater than after fasting conditions with point estimates of 69.6% and 81.0%, respectively. However, most striking was a pronounced delay in nifedipine absorption observed under fed conditions after administration of Slofedipine XL which resulted in lag-times of more than 15 h in 15 out of 24 subjects. Owing to this lag-time under fed conditions the relative bioavailability of nifedipine from Slofedipine XL compared with Adalat OROS was only 28% over the intended dosing interval of 24 h. In this study a dosage form-dependent food interaction was observed which, under fed conditions, resulted in pronounced differences in the relative bioavailability of nifedipine between Slofedipine XL and Adalat OROS over the intended dosing interval of 24 h. The delay in nifedipine absorption when Slofedipine XL is administered after a high-fat breakfast may be explained by the formulation properties. Slofedipine XL is an erosive tablet with an acid resistant coating whereas Adalat OROS is designed with an osmotic push-pull system. Under fed conditions drug from the single unit enteric coated dosage form exhibits a delayed absorption probably due to an extensively prolonged gastric residence time which does not allow drug release, on the other hand the osmotically driven push-pull system is not sensitive to concomitant food intake. The observed phenomenon might be of therapeutic relevance. For example a change from taking Slofedipine XL in the fed to the fasted state might result in increased systemic concentrations of nifedipine.
Formulation and evaluation of buccal patches for delivery of atenolol.
Adhikari, Surya N Ratha; Nayak, Bhabani S; Nayak, Amit K; Mohanty, Biswaranjan
2010-09-01
Buccal patches for the delivery of atenolol using sodium alginate with various hydrophilic polymers like carbopol 934 P, sodium carboxymethyl cellulose, and hydroxypropyl methylcellulose in various proportions and combinations were fabricated by solvent casting technique. Various physicomechanical parameters like weight variation, thickness, folding endurance, drug content, moisture content, moisture absorption, and various ex vivo mucoadhesion parameters like mucoadhesive strength, force of adhesion, and bond strength were evaluated. An in vitro drug release study was designed, and it was carried out using commercial semipermeable membrane. All these fabricated patches were sustained for 24 h and obeyed first-order release kinetics. Ex vivo drug permeation study was also performed using porcine buccal mucosa, and various drug permeation parameters like flux and lag time were determined.
Lee, Nuri; Kim, Ji-Eun; Gu, Ja-Yoon; Yoo, Hyun Ju; Kim, Inho; Yoon, Sung-Soo; Park, Seonyang; Han, Kyou-Sup; Kim, Hyun Kyung
2016-01-01
Disseminated intravascular coagulation (DIC) is characterized by consumption of coagulation factors and anticoagulants. Thrombin generation assay (TGA) gives useful information about global hemostatic status. We developed a new TGA system that anticoagulant addition can deplete thrombin generation in plasma, which may reflect defective anticoagulant system in DIC. TGAs were measured on the calibrated automated thrombogram with and without thrombomodulin or protein Z in 152 patients who were suspected of having DIC, yielding four parameters including lag time, endogenous thrombin potential, peak thrombin and time-to-peak in each experiment. Nonsurvivors showed significantly prolonged lag time and time-to-peak in TGA-protein Z system, which was performed with added protein Z. In multivariate Cox regression analysis, lag time and time-to-peak in TGA system were significant independent prognostic factors. In TGA-protein Z system, lag time and time-to-peak were revealed as independent prognostic factors of DIC. Protein Z addition could potentiate its anticoagulant effect in DIC with poor prognosis, suggesting the presence of defective protein Z system. The prolonged lag time and time-to-peak in both TGA and TGA-protein Z systems are expected to be used as independent prognostic factors of DIC.
Di, Sun; Guan, De-xin; Yuan, Feng-hui; Wang, An-zhi; Wu, Jia-bing
2010-11-01
By using Granier's thermal dissipation probe, the sap flow velocity of the poplars in agroforestry system in west Liaoning was continuously measured, and the microclimate factors were measured synchronously. Dislocation contrast method was applied to analyze the sap flow velocity and corresponding air temperature, air humidity, net radiation, and vapor pressure deficit to discuss the time lag effect between poplar' s sap flow velocity and microclimate factors on sunny days. It was found that the poplar's sap flow velocity advanced of air temperature, air humidity, and vapor pressure deficit, and lagged behind net radiation. The sap flow velocity in June, July, August, and September was advanced of 70, 30, 50, and 90 min to air temperature, of 80, 30, 40, and 90 min to air humidity, and of 90, 50, 70, and 120 min to vapor pressure deficit, but lagged behind 10, 10, 40, and 40 min to net radiation, respectively. The time lag time of net radiation was shorter than that of air temperature, air humidity, and vapor pressure. The regression analysis showed that in the cases the time lag effect was contained and not, the determination coefficients between comprehensive microclimate factor and poplar's sap flow velocity were 0.903 and 0.855, respectively, indicating that when the time lag effect was contained, the determination coefficient was ascended by 2.04%, and thus, the simulation accuracy of poplar's sap flow velocity was improved.
A Comparison of Several Methods of Measuring Ignition Lag in a Compression-ignition Engine
NASA Technical Reports Server (NTRS)
Spanogle, J A
1934-01-01
The ignition lag of a fuel oil in the combustion chamber of a high speed compression-ignition engine was measured by three different methods. The start of injection of the fuel as observed with a Stoborama was taken as the start of the period of ignition lag in all cases. The end of the period of ignition lag was determined by observation of the appearance of incandescence in the combustion chamber, by inspection of a pressure-time card for evidence of pressure rise, and by analysis of the indicator card for evidence of the combustion of a small but definite quantity of fuel. A comparison of the values for ignition lags obtained by these three methods indicates that the appearance of incandescence is later than other evidences of the start of combustion, that visual inspection of a pressure-time diagram gives consistent and usable values with a minimum requirement of time and/or apparatus, and that analysis of the indicator card is not worth while for ignition lag alone.
A comparison of alternative variants of the lead and lag time TTO.
Devlin, Nancy; Buckingham, Ken; Shah, Koonal; Tsuchiya, Aki; Tilling, Carl; Wilkinson, Grahame; van Hout, Ben
2013-05-01
'Lead Time' TTO improves upon conventional TTO by providing a uniform method for eliciting positive and negative values. This research investigates (i) the values generated from different combinations of time in poor health and in full health; and the order in which these appear (lead vs. lag); (ii) whether values concur with participants' views about states; (iii) methods for handling extreme preferences. n = 208 participants valued five EQ-5D states, using two of four variants. Combinations of lead time and health state duration were: 10 years and 20 years; 5 years and 1 year; 5 years and 10 years; and a health state duration of 5 years with a lag time of 10 years. Longer lead times capture more preferences, but may involve a framing effect. Lag time results in less non-trading for mild states, and less time being traded for severe states. Negative values broadly agree with participants' stated opinion that the state is worse than dead. The values are sensitive to the ratio of lead time to duration of poor health, and the order in which these appear (lead vs. lag). It is feasible to handle extreme preferences though challenges remain. Copyright © 2012 John Wiley & Sons, Ltd.
Time lags between crown and basal sap flows in tropical lianas and co-occurring trees.
Chen, Ya-Jun; Bongers, Frans; Tomlinson, Kyle; Fan, Ze-Xin; Lin, Hua; Zhang, Shu-Bin; Zheng, Yu-Long; Li, Yang-Ping; Cao, Kun-Fang; Zhang, Jiao-Lin
2016-06-01
Water storage in the stems of woody plants contributes to their responses to short-term water shortages. To estimate the contribution of water storage to the daily water budget of trees, time lags of sap flow between different positions of trunk are used as a proxy of stem water storage. In lianas, another large group of woody species, it has rarely been studied whether stored water functions in their daily water use, despite their increasing roles in the carbon and water dynamics of tropical forests caused by their increasing abundance. We hypothesized that lianas would exhibit large time lags due to their extremely long stems, wide vessels and large volume of parenchyma in the stem. We examined time lags in sap flow, diel changes of stem volumetric water content (VWC) and biophysical properties of sapwood of 19 lianas and 26 co-occurring trees from 27 species in 4 forests (karst, tropical seasonal, flood plain and savanna) during a wet season. The plants varied in height/length from <5 to >60 m. The results showed that lianas had significantly higher saturated water content (SWC) and much lower wood density than trees. Seven of 19 liana individuals had no time lags; in contrast, only 3 of 26 tree individuals had no time lags. In general, lianas had shorter time lags than trees in our data set, but this difference was not significant for our most conservative analyses. Across trees and lianas, time lag duration increased with diurnal maximum changeable VWC but was independent of the body size, path length, wood density and SWC. The results suggest that in most lianas, internal stem water storage contributes little to daily water budget, while trees may rely more on stored water in the stem. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
Transport and time lag of chlorofluorocarbon gases in the unsaturated zone, Rabis Creek, Denmark
Engesgaard, Peter; Højberg, Anker L.; Hinsby, Klaus; Jensen, Karsten H.; Laier, Troels; Larsen, Flemming; Busenberg, Eurybiades; Plummer, Niel
2004-01-01
Transport of chlorofluorocarbon (CFC) gases through the unsaturated zone to the water table is affected by gas diffusion, air–water exchange (solubility), sorption to the soil matrix, advective–dispersive transport in the water phase, and, in some cases, anaerobic degradation. In deep unsaturated zones, this may lead to a time lag between entry of gases at the land surface and recharge to groundwater. Data from a Danish field site were used to investigate how time lag is affected by variations in water content and to explore the use of simple analytical solutions to calculate time lag. Numerical simulations demonstrate that either degradation or sorption of CFC-11 takes place, whereas CFC-12 and CFC-113 are nonreactive. Water flow did not appreciably affect transport. An analytical solution for the period with a linear increase in atmospheric CFC concentrations (approximately early 1970s to early 1990s) was used to calculate CFC profiles and time lags. We compared the analytical results with numerical simulations. The time lags in the 15-m-deep unsaturated zone increase from 4.2 to between 5.2 and 6.1 yr and from 3.4 to 3.9 yr for CFC-11 and CFC-12, respectively, when simulations change from use of an exponential to a linear increase in atmospheric concentrations. The CFC concentrations at the water table before the early 1990s can be estimated by displacing the atmospheric input function by these fixed time lags. A sensitivity study demonstrates conditions under which a time lag in the unsaturated zone becomes important. The most critical parameter is the tortuosity coefficient. The analytical approach is valid for the low range of tortuosity coefficients (τ = 0.1–0.4) and unsaturated zones greater than approximately 20 m in thickness. In these cases the CFC distribution may still be from either the exponential or linear phase. In other cases, the use of numerical models, as described in our work and elsewhere, is an option.
D'Elia, Riccardo; Allen, Patricia L; Johanson, Kelly; Nickerson, Cheryl A; Hammond, Timothy G
2005-06-01
This study identifies genes that determine length of lag phase, using the model eukaryotic organism, Saccharomyces cerevisiae. We report growth of a yeast deletion series following variations in the lag phase induced by variable storage times after drying-down yeast on filters. Using a homozygous diploid deletion pool, lag times ranging from 0 h to 90 h were associated with increased drop-out of mitochondrial genes and increased survival of nuclear genes. Simple linear regression (R2 analysis) shows that there are over 500 genes for which > 70% of the variation can be explained by lag alone. In the genes with a positive correlation, such that the gene abundance increases with lag and hence the deletion strain is suitable for survival during prolonged storage, there is a strong predominance of nucleonic genes. In the genes with a negative correlation, such that the gene abundance decreases with lag and hence the strain may be critical for getting yeast out of the lag phase, there is a strong predominance of glycoproteins and transmembrane proteins. This study identifies yeast deletion strains with survival advantage on prolonged storage and amplifies our understanding of the genes critical for getting out of the lag phase.
NASA Technical Reports Server (NTRS)
D'Elia, Riccardo; Allen, Patricia L.; Johanson, Kelly; Nickerson, Cheryl A.; Hammond, Timothy G.
2005-01-01
This study identifies genes that determine length of lag phase, using the model eukaryotic organism, Saccharomyces cerevisiae. We report growth of a yeast deletion series following variations in the lag phase induced by variable storage times after drying-down yeast on filters. Using a homozygous diploid deletion pool, lag times ranging from 0 h to 90 h were associated with increased drop-out of mitochondrial genes and increased survival of nuclear genes. Simple linear regression (R2 analysis) shows that there are over 500 genes for which > 70% of the variation can be explained by lag alone. In the genes with a positive correlation, such that the gene abundance increases with lag and hence the deletion strain is suitable for survival during prolonged storage, there is a strong predominance of nucleonic genes. In the genes with a negative correlation, such that the gene abundance decreases with lag and hence the strain may be critical for getting yeast out of the lag phase, there is a strong predominance of glycoproteins and transmembrane proteins. This study identifies yeast deletion strains with survival advantage on prolonged storage and amplifies our understanding of the genes critical for getting out of the lag phase.
An improved measurement system for FOG pure lag time with no changing of FOG work status
NASA Astrophysics Data System (ADS)
Chen, X.; Yang, J. H.; Zhou, Y. L.; Shu, X. W.
2018-05-01
The minimum pure lag time is an important factor for characterizing the dynamic performance of fiber optical gyroscope. It is defined as the time duration from the reception of velocity-shock signal to the output of corresponding fiber-optic gyroscope data. Many engineering projects have required for this index specifically, so the measurement of the minimum pure lag time is highly demanded. In typically measurement system, the work status of tested FOG has to be changed. In this work, a FOG pure lag time measurement system without changing the work status of the FOG has been demonstrated. During the operation of this test system, the impact structure generated a shock towards the FOG, and the pure lag time was measured through data processing analysis. The design scheme and test principle have been researched and analyzed in detail. And a prototype has been developed and used for experiment successfully. This measurement system can realize a measurement accuracy of better than ±3 μs and a system resolution of 108.6ns.
A study of the cross-correlation and time lag in black hole X-ray binary XTE J1859+226
NASA Astrophysics Data System (ADS)
Pei, Songpeng; Ding, Guoqiang; Li, Zhibing; Lei, Yajuan; Yuen, Rai; Qu, Jinlu
2017-07-01
With Rossi X-ray Timing Explorer (RXTE) data, we systematically study the cross-correlation and time lag in all spectral states of black hole X-ray binary (BHXB) XTE J1859+226 in detail during its entire 1999-2000 outburst that lasted for 166 days. Anti-correlations and positive correlations and their respective soft and hard X-ray lags are only detected in the first 100 days of the outburst when the luminosity is high. This suggests that the cross-correlations may be related to high luminosity. Positive correlations are detected in every state of XTE J1859+226, viz., hard state, hard-intermediate state (HIMS), soft-intermediate state (SIMS) and soft state. However, anti-correlations are only detected in HIMS and SIMS, anti-correlated hard lags are only detected in SIMS, while anti-correlated soft lags are detected in both HIMS and SIMS. Moreover, the ratio of the observations with anti-correlated soft lags to hard lags detected in XTE J1859+226 is significantly different from that in neutron star low-mass X-ray binaries (NS LMXBs). So far, anti-correlations are never detected in the soft state of BHXBs but detected in every branch or state of NS LMXBs. This may be due to the origin of soft seed photons in BHXBs is confined to the accretion disk and, for NS LMXBs, from both accretion disk and the surface of the NS. We notice that the timescale of anti-correlated time lags detected in XTE J1859+226 is similar with that of other BHXBs and NS LMXBs. We suggest that anti-correlated soft lag detected in BHXB may result from fluctuation in the accretion disk as well as NS LMXB.
NASA Astrophysics Data System (ADS)
Lin, Ye-Chen; Yeh, Hund-Der
2017-10-01
This study proposes a generalized Darcy's law with considering phase lags in both the water flux and drawdown gradient to develop a lagging flow model for describing drawdown induced by constant-rate pumping (CRP) in a leaky confined aquifer. The present model has a mathematical formulation similar to the dual-porosity model. The Laplace-domain solution of the model with the effect of wellbore storage is derived by the Laplace transform method. The time-domain solution for the case of neglecting the wellbore storage and well radius is developed by the use of Laplace transform and Weber transform. The results of sensitivity analysis based on the solution indicate that the drawdown is very sensitive to the change in each of the transmissivity and storativity. Also, a study for the lagging effect on the drawdown indicates that its influence is significant associated with the lag times. The present solution is also employed to analyze a data set taken from a CRP test conducted in a fractured aquifer in South Dakota, USA. The results show the prediction of this new solution with considering the phase lags has very good fit to the field data, especially at early pumping time. In addition, the phase lags seem to have a scale effect as indicated in the results. In other words, the lagging behavior is positively correlated with the observed distance in the Madison aquifer.
Umemoto, Ayaka; Yagi, Hisashi; So, Masatomo; Goto, Yuji
2014-01-01
Amyloid fibrils form in supersaturated solutions of precursor proteins by a nucleation and growth mechanism characterized by a lag time. Although the lag time provides a clue to understanding the complexity of nucleation events, its long period and low reproducibility have been obstacles for exact analysis. Ultrasonication is known to effectively break supersaturation and force fibrillation. By constructing a Handai amyloid burst inducer, which combines a water bath-type ultrasonicator and a microplate reader, we examined the ultrasonication-forced fibrillation of several proteins, with a focus on the fluctuation in the lag time. Amyloid fibrillation of hen egg white lysozyme was examined at pH 2.0 in the presence of 1.0–5.0 M guanidine hydrochloride (GdnHCl), in which the dominant species varied from the native to denatured conformations. Although fibrillation occurred at various concentrations of GdnHCl, the lag time varied largely, with a minimum being observed at ∼3.0 m, the concentration at which GdnHCl-dependent denaturation ended. The coefficient of variation of the lag time did not depend significantly on the GdnHCl concentration and was 2-fold larger than that of the ultrasonication-dependent oxidation of iodide, a simple model reaction. These results suggest that the large fluctuation observed in the lag time for amyloid fibrillation originated from a process associated with a common amyloidogenic intermediate, which may have been a relatively compact denatured conformation. We also suggest that the Handai amyloid burst inducer system will be useful for studying the mechanism of crystallization of proteins because proteins form crystals by the same mechanism as amyloid fibrils under supersaturation. PMID:25118286
Response variables for evaluation of the effectiveness of conservation corridors.
Gregory, Andrew J; Beier, Paul
2014-06-01
Many studies have evaluated effectiveness of corridors by measuring species presence in and movement through small structural corridors. However, few studies have assessed whether these response variables are adequate for assessing whether the conservation goals of the corridors have been achieved or considered the costs or lag times involved in measuring the response variables. We examined 4 response variables-presence of the focal species in the corridor, interpatch movement via the corridor, gene flow, and patch occupancy--with respect to 3 criteria--relevance to conservation goals, lag time (fewest generations at which a positive response to the corridor might be evident with a particular variable), and the cost of a study when applying a particular variable. The presence variable had the least relevance to conservation goals, no lag time advantage compared with interpatch movement, and only a moderate cost advantage over interpatch movement or gene flow. Movement of individual animals between patches was the most appropriate response variable for a corridor intended to provide seasonal migration, but it was not an appropriate response variable for corridor dwellers, and for passage species it was only moderately relevant to the goals of gene flow, demographic rescue, and recolonization. Response variables related to gene flow provided a good trade-off among cost, relevance to conservation goals, and lag time. Nonetheless, the lag time of 10-20 generations means that evaluation of conservation corridors cannot occur until a few decades after a corridor has been established. Response variables related to occupancy were most relevant to conservation goals, but the lag time and costs to detect corridor effects on occupancy were much greater than the lag time and costs to detect corridor effects on gene flow. © 2014 Society for Conservation Biology.
Kerri T. Vierling; Charles E. Swift; Andrew T. Hudak; Jody C. Vogeler; Lee A. Vierling
2014-01-01
Vegetation structure quantified by light detection and ranging (LiDAR) can improve understanding of wildlife occupancy and species-richness patterns. However, there is often a time lag between the collection of LiDAR data and wildlife data. We investigated whether a time lag between the LiDAR acquisition and field-data acquisition affected mapped wildlife distributions...
Halbach, Udo; Burkhardt, Heinz Jürgen
1972-09-01
Laboratory populations of the rotifer Brachionus calyciflorus were cultured at different temperatures (25, 20, 15°C) but otherwise at constant conditions. The population densities showed relatively constant oscillations (Figs. 1 to 3A-C). Amplitudes and frequencies of the oscillations were positively correlated with temperature (Table 1). A test was made, whether the logistic growth function with simple time lag is able to describe the population curves. There are strong similarities between the simulations (Figs. 1-3E) and the real population dynamics if minor adjustments of the empirically determined parameters are made. There-fore it is suggested that time lags are responsible for the observed oscillations. However, the actual time lags probably do not act in the simple manner of the model, because birth and death rates react with different time lags, and both parameters are dependent on individual age and population density. A more complex model, which incorporates these modifications, should lead to a more realistic description of the observed oscillations.
Feng, Cun-Fang; Xu, Xin-Jian; Wang, Sheng-Jun; Wang, Ying-Hai
2008-06-01
We study projective-anticipating, projective, and projective-lag synchronization of time-delayed chaotic systems on random networks. We relax some limitations of previous work, where projective-anticipating and projective-lag synchronization can be achieved only on two coupled chaotic systems. In this paper, we realize projective-anticipating and projective-lag synchronization on complex dynamical networks composed of a large number of interconnected components. At the same time, although previous work studied projective synchronization on complex dynamical networks, the dynamics of the nodes are coupled partially linear chaotic systems. In this paper, the dynamics of the nodes of the complex networks are time-delayed chaotic systems without the limitation of the partial linearity. Based on the Lyapunov stability theory, we suggest a generic method to achieve the projective-anticipating, projective, and projective-lag synchronization of time-delayed chaotic systems on random dynamical networks, and we find both its existence and sufficient stability conditions. The validity of the proposed method is demonstrated and verified by examining specific examples using Ikeda and Mackey-Glass systems on Erdos-Renyi networks.
To lag or not to lag? How to compare indices of stock markets that operate on different times
NASA Astrophysics Data System (ADS)
Sandoval, Leonidas
2014-06-01
Financial markets worldwide do not have the same working hours. As a consequence, the study of correlation or causality between financial market indices becomes dependent on whether we should use all indices on the same day or lagged indices in computations of correlation matrices. The answer this article proposes is that we should consider both, by representing original and lagged indices in the same network. We then obtain a better understanding of how indices that operate on different hours relate to each other. We use a diverse range of 79 stock market indices from around the world and study their correlation structure, the eigenvalues and eigenvectors of their correlations under different time periods and volatility, as well as the differences between the working hours of the stock exchanges in order to analyze the possible time zone effects and suggest ways to remove them. We also analyze the enlarged correlation matrix obtained from original and lagged indices and examine a network structure derived from it, thus showing connections between lagged and original indices that could not be well represented before.
Facile synthesis of Fe3O4/C composites for broadband microwave absorption properties
NASA Astrophysics Data System (ADS)
Liu, Xiang; Ma, Yating; Zhang, Qinfu; Zheng, Zhiming; Wang, Lai-Sen; Peng, Dong-Liang
2018-07-01
Rod-like and flower-like Fe3O4/C composites were successfully synthesized via a facile approach in aqueous phase. The morphologies, structures and static magnetic properties of as-prepared rod-like and flower-like Fe3O4/C composites were characterized thoroughly. The relative complex permittivity and permeability of Fe3O4/C/paraffin composites were recorded by a vector network analyzer (VNA) in the range of 1-18 GHz. The resonant-antiresonant electromagnetic behavior was observed simultaneously in both rod-like and flower-like Fe3O4/C composites. Moreover, the resonant-antiresonant behavior was explained using displacement current lag at the "core/shell" interface. The flower-like Fe3O4/C/paraffin composites show superior microwave absorption performance with minimum reflection loss (RL) of up to -18.73 dB at 15.37 GHz. Comparatively, the rod-like Fe3O4/C/paraffin composites have uncommon continuous trinal absorption peaks at a thickness of 2.5 mm that effectively broadens the absorption bandwidth which is from 8.0 to 13.4 GHz. Furthermore, the microwave absorption mechanism has been discussed to provide a novel design for microwave absorption materials.
Riva, Antonella; Morazzoni, Paolo; Artaria, Christian; Allegrini, Pietro; Meins, Jürgen; Savio, Daniele; Appendino, Giovanni; Schubert-Zsilavecz, Manfred; Abdel-Tawab, Mona
2016-11-15
The oral administration of the gum resin extracts of Indian frankincense (Boswellia serrata Roxb. ex Colebr) results in very low plasma concentrations of boswellic acids (BAs), being far below the pharmacologically active concentrations required in vitro for anti-inflammatory activity. For that reason the use of Indian frankincense in clinical practice and pharmaceutical development has substantially lagged behind. Recently the application of new formulation technologies resulted in a formulation of frankincense extract with lecithin, which revealed improved absorption and tissue penetration of BAs in a rodent study, leading for the first time to plasma concentrations of BAs in the range of their anti-inflammatory activity. In order to verify these encouraging results in humans, the absorption of a standardized Boswellia serrata extract (BE) and its lecithin formulation (CSP) was comparatively investigated in healthy volunteers. According to a randomized cross-over design with two treatments, two sequences and two periods, 12 volunteers alternatively received the lecithin-formulated Boswellia extract (CSP) or the non-formulated Boswellia extract (BE) at a dosage of 2×250mg capsules. The plasma concentrations of the six major BAs (KBA, AKBA, βBA, αBA, AβBA, AαBA) were determined using LC/MS. With the exception of KBA, a significantly higher (both in terms of weight-to-weight and molar comparison) and quicker absorption of BAs from the lecithin formulation was observed, leading to C max in the range required for the interaction with their molecular targets. These findings pave the way to further studies evaluating the clinical potential of BAs, and verify the beneficial effect of lecithin formulation to improve the absorption of poorly soluble phytochemicals. Copyright © 2016 The Authors. Published by Elsevier GmbH.. All rights reserved.
Van Meter, Kimberly J.; Basu, Nandita B.
2015-01-01
Nutrient legacies in anthropogenic landscapes, accumulated over decades of fertilizer application, lead to time lags between implementation of conservation measures and improvements in water quality. Quantification of such time lags has remained difficult, however, due to an incomplete understanding of controls on nutrient depletion trajectories after changes in land-use or management practices. In this study, we have developed a parsimonious watershed model for quantifying catchment-scale time lags based on both soil nutrient accumulations (biogeochemical legacy) and groundwater travel time distributions (hydrologic legacy). The model accurately predicted the time lags observed in an Iowa watershed that had undergone a 41% conversion of area from row crop to native prairie. We explored the time scales of change for stream nutrient concentrations as a function of both natural and anthropogenic controls, from topography to spatial patterns of land-use change. Our results demonstrate that the existence of biogeochemical nutrient legacies increases time lags beyond those due to hydrologic legacy alone. In addition, we show that the maximum concentration reduction benefits vary according to the spatial pattern of intervention, with preferential conversion of land parcels having the shortest catchment-scale travel times providing proportionally greater concentration reductions as well as faster response times. In contrast, a random pattern of conversion results in a 1:1 relationship between percent land conversion and percent concentration reduction, irrespective of denitrification rates within the landscape. Our modeling framework allows for the quantification of tradeoffs between costs associated with implementation of conservation measures and the time needed to see the desired concentration reductions, making it of great value to decision makers regarding optimal implementation of watershed conservation measures. PMID:25985290
Van Meter, Kimberly J; Basu, Nandita B
2015-01-01
Nutrient legacies in anthropogenic landscapes, accumulated over decades of fertilizer application, lead to time lags between implementation of conservation measures and improvements in water quality. Quantification of such time lags has remained difficult, however, due to an incomplete understanding of controls on nutrient depletion trajectories after changes in land-use or management practices. In this study, we have developed a parsimonious watershed model for quantifying catchment-scale time lags based on both soil nutrient accumulations (biogeochemical legacy) and groundwater travel time distributions (hydrologic legacy). The model accurately predicted the time lags observed in an Iowa watershed that had undergone a 41% conversion of area from row crop to native prairie. We explored the time scales of change for stream nutrient concentrations as a function of both natural and anthropogenic controls, from topography to spatial patterns of land-use change. Our results demonstrate that the existence of biogeochemical nutrient legacies increases time lags beyond those due to hydrologic legacy alone. In addition, we show that the maximum concentration reduction benefits vary according to the spatial pattern of intervention, with preferential conversion of land parcels having the shortest catchment-scale travel times providing proportionally greater concentration reductions as well as faster response times. In contrast, a random pattern of conversion results in a 1:1 relationship between percent land conversion and percent concentration reduction, irrespective of denitrification rates within the landscape. Our modeling framework allows for the quantification of tradeoffs between costs associated with implementation of conservation measures and the time needed to see the desired concentration reductions, making it of great value to decision makers regarding optimal implementation of watershed conservation measures.
Extreme AGN Captured in a Low State by XMM-Newton and NuSTAR
NASA Astrophysics Data System (ADS)
Frederick, Sara; Kara, Erin; Reynolds, Christopher S.
2018-01-01
The most variable active galactic nuclei (AGN), taken together, are a compelling wellspring of interesting accretion-related phenomena and can exhibit dramatic variability in the X-ray band down to timescales of a few minutes. We present the exemplifying case study of 1H 1934-063 (z = 0.0102), a narrow-line Seyfert I (NLS1) that is among the most variable AGN ever observed with XMM-Newton. We present spectroscopic and temporal analyses of a concurrent XMM-Newton and NuSTAR 120 ks observation, during which the source exhibited a steep (factor of 1.5) plummet and subsequent full recovery of flux that we explore in detail. Combined spectral and timing results point to a dramatic change in the continuum on timescales as short as a few ks. Similar to other highly variable Seyfert 1s, this AGN is X-ray bright and displays strong reflection spectral features. We find agreement with a change in the continuum, and we rule out absorption as the cause for this dramatic variability that is observed even at NuSTAR energies. We compare measurements from detailed time-resolved spectral fitting with Fourier-based timing results to constrain coronal geometry, dynamics, and emission/absorption processes dictating the nature of this variability. We also announce the discovery of a Fe-K time lag between the hard X-ray continuum emission (1-4 keV) and relativistically-blurred reprocessing by the inner accretion flow (0.3-1 keV).
Diekman, Casey O; Bose, Amitabha
2018-01-21
The normal alignment of circadian rhythms with the 24-h light-dark cycle is disrupted after rapid travel between home and destination time zones, leading to sleep problems, indigestion, and other symptoms collectively known as jet lag. Using mathematical and computational analysis, we study the process of reentrainment to the light-dark cycle of the destination time zone in a model of the human circadian pacemaker. We calculate the reentrainment time for travel between any two points on the globe at any time of the day and year. We construct one-dimensional entrainment maps to explain several properties of jet lag, such as why most people experience worse jet lag after traveling east than west. We show that this east-west asymmetry depends on the endogenous period of the traveler's circadian clock as well as daylength. Thus the critical factor is not simply whether the endogenous period is greater than or less than 24 h as is commonly assumed. We show that the unstable fixed point of an entrainment map determines whether a traveler reentrains through phase advances or phase delays, providing an understanding of the threshold that separates orthodromic and antidromic modes of reentrainment. Contrary to the conventional wisdom that jet lag only occurs after east-west travel across multiple time zones, we predict that the change in daylength encountered during north-south travel can cause jet lag even when no time zones are crossed. Our techniques could be used to provide advice to travelers on how to minimize jet lag on trips involving multiple destinations and a combination of transmeridian and translatitudinal travel. Copyright © 2017 Elsevier Ltd. All rights reserved.
Technical Note: High temporal resolution characterization of gating response time.
Wiersma, Rodney D; McCabe, Bradley P; Belcher, Andrew H; Jensen, Patrick J; Smith, Brett; Aydogan, Bulent
2016-06-01
Low temporal latency between a gating ON/OFF signal and the LINAC beam ON/OFF during respiratory gating is critical for patient safety. Here the authors describe a novel method to precisely measure gating lag times at high temporal resolutions. A respiratory gating simulator with an oscillating platform was modified to include a linear potentiometer for position measurement. A photon diode was placed at linear accelerator isocenter for beam output measurement. The output signals of the potentiometer and diode were recorded simultaneously at 2500 Hz with an analog to digital converter for four different commercial respiratory gating systems. The ON and OFF of the beam signal were located and compared to the expected gating window for both phase and position based gating and the temporal lag times extracted. For phase based gating, a real-time position management (RPM) infrared marker tracking system with a single camera and a RPM system with a stereoscopic camera were measured to have mean gate ON/OFF lag times of 98/90 and 86/44 ms, respectively. For position based gating, an AlignRT 3D surface system and a Calypso magnetic fiducial tracking system were measured to have mean gate ON/OFF lag times of 356/529 and 209/60 ms, respectively. Temporal resolution of the method was high enough to allow characterization of individual gate cycles and was primary limited by the sampling speed of the data recording device. Significant variation of mean gate ON/OFF lag time was found between different gating systems. For certain gating devices, individual gating cycle lag times can vary significantly.
Technical Note: High temporal resolution characterization of gating response time
Wiersma, Rodney D.; McCabe, Bradley P.; Belcher, Andrew H.; Jensen, Patrick J.; Smith, Brett; Aydogan, Bulent
2016-01-01
Purpose: Low temporal latency between a gating ON/OFF signal and the LINAC beam ON/OFF during respiratory gating is critical for patient safety. Here the authors describe a novel method to precisely measure gating lag times at high temporal resolutions. Methods: A respiratory gating simulator with an oscillating platform was modified to include a linear potentiometer for position measurement. A photon diode was placed at linear accelerator isocenter for beam output measurement. The output signals of the potentiometer and diode were recorded simultaneously at 2500 Hz with an analog to digital converter for four different commercial respiratory gating systems. The ON and OFF of the beam signal were located and compared to the expected gating window for both phase and position based gating and the temporal lag times extracted. Results: For phase based gating, a real-time position management (RPM) infrared marker tracking system with a single camera and a RPM system with a stereoscopic camera were measured to have mean gate ON/OFF lag times of 98/90 and 86/44 ms, respectively. For position based gating, an AlignRT 3D surface system and a Calypso magnetic fiducial tracking system were measured to have mean gate ON/OFF lag times of 356/529 and 209/60 ms, respectively. Conclusions: Temporal resolution of the method was high enough to allow characterization of individual gate cycles and was primary limited by the sampling speed of the data recording device. Significant variation of mean gate ON/OFF lag time was found between different gating systems. For certain gating devices, individual gating cycle lag times can vary significantly. PMID:27277028
Inacio, R.; Barlow, D.; Kong, X.; Keeble, J.; Jones, S.A.
2016-01-01
Relatively little is known about how drug self-association influences absorption into the human body. This study presented two hydrophobic membranes with a series of solutions containing different types of tetracaine aggregates with the aim of understanding how the attributes of supramolecular aggregate formation influenced passive membrane transport. The data showed that aqueous solutions of the unprotonated form of tetracaine displayed a significantly higher (p < 0.05) passive membrane transport compared to solutions with mixtures of the unprotonated and protonated drug microspecies (e.g. transport through the skin was 0.96 ± 0.31 μg cm−2 min−1 and 1.59 ± 0.26 μg cm−2 min−1 respectively). However, despite an enhanced rate of drug transport and a better membrane partitioning the unionised molecules showed a significantly longer (p < 0.05) lag time to membrane penetration compared solutions rich in the ionised microspecies. Analytical characterisation of the solutions applied to the apical surface of the membranes in the transport studies showed that larger tetracaine aggregates with smaller surface charge gave rise to the longer lag times. These large aggregates demonstrated more extensive intermolecular bonding and therefore, it was suggest that it was the enhanced propensity of the unionised species to form tightly bound drug aggregates that caused the delay in the membrane penetration. PMID:26965142
Kalicharan, R W; Bout, M R; Oussoren, C; Vromans, H
2016-12-30
Long-term therapy of nandrolone (N) is recommended to increase mineral density and muscle strength. Using a parenteral sustained release drug formulation with nandrolone decanoate (ND), therapeutic N levels can be achieved and maintained. Until now, it is unknown if hydrolysis of ND into N occurs in tissue at the injection site or after systemic absorption. Therefore, hydrolysis studies were conducted to investigate the location and rate of ND hydrolysis after its release from the oil depot. ND hydrolysis was studied in porcine tissues, to mimic the human muscular and subcutaneous tissues. Additionally, the ND hydrolysis was studied in human whole blood, plasma and serum at a concentration range of 23.3-233.3μM. ND hydrolysis only occurred in human whole blood. The hydrolysis did not start immediately, but after a lag time. The mean lag time for all studied concentrations was 34.9±2.5min. Because of a slow penetration into tissue, hydrolysis of ND is found to be very low in surrounding tissue. Therefore the local generation of the active compound is clinically irrelevant. It is argued that after injection of the oil depot, ND molecules will be transported via the lymphatic system towards lymph nodes. From here, it will enter the central circulation and within half an hour it will hydrolyse to the active N compound. Copyright © 2016 Elsevier B.V. All rights reserved.
Egelund, E F; Isaza, R; Brock, A P; Alsultan, A; An, G; Peloquin, C A
2015-04-01
The objective of this study was to develop a population pharmacokinetic model for rifampin in elephants. Rifampin concentration data from three sources were pooled to provide a total of 233 oral concentrations from 37 Asian elephants. The population pharmacokinetic models were created using Monolix (version 4.2). Simulations were conducted using ModelRisk. We examined the influence of age, food, sex, and weight as model covariates. We further optimized the dosing of rifampin based upon simulations using the population pharmacokinetic model. Rifampin pharmacokinetics were best described by a one-compartment open model including first-order absorption with a lag time and first-order elimination. Body weight was a significant covariate for volume of distribution, and food intake was a significant covariate for lag time. The median Cmax of 6.07 μg/mL was below the target range of 8-24 μg/mL. Monte Carlo simulations predicted the highest treatable MIC of 0.25 μg/mL with the current initial dosing recommendation of 10 mg/kg, based upon a previously published target AUC0-24/MIC > 271 (fAUC > 41). Simulations from the population model indicate that the current dose of 10 mg/kg may be adequate for MICs up to 0.25 μg/mL. While the targeted AUC/MIC may be adequate for most MICs, the median Cmax for all elephants is below the human and elephant targeted ranges. © 2014 John Wiley & Sons Ltd.
Payne, O J; Graham, S J; Dalton, C H; Spencer, P M; Mansson, R; Jenner, J; Azeke, J; Braue, E
2013-02-01
The percutaneous absorption of tritiated water ((3)H(2)O) through sulfur mustard (SM) exposed abdominal pig skin was measured using in vitro Franz-type static diffusion cells. The barrier function to water permeation following exposure to liquid SM for 8 min and excision 3h later did not change significantly. A small, but statistically significant difference (P<0.05) in steady state penetration (Jss), permeability coefficient (Kp) and lag time (t(L)) of (3)H(2)O was observed between fresh skin and skin stored frozen (-20 °C) for up to two weeks. Steady-state penetration and Kp values were significantly higher (P < 0.05) in skin stored frozen compared with fresh skin. Fresh naïve skin had an average Kp of 1.65 × 10(-3) cm h(-1), whereas frozen naïve skin was 2.04 × 10(-3) cm h(-1). Fresh SM exposed skin had a mean Kp of 1.72 × 10(-3) cm h(-1), whereas frozen SM exposed skin was 2.31 × 10(-3) cm h(-1). Lag times were also shorter (P<0.05) in skin that had been stored frozen. Frozen, SM-exposed porcine abdominal skin may be used for in vitro penetration studies, but effects of treatment and storage on the barrier layer should be taken into account. Copyright © 2012 Elsevier Ltd. All rights reserved.
Recent Shift in Climate Relationship Enables Prediction of the Timing of Bird Breeding
Bellamy, Paul E.; Hill, Ross A.; Ferns, Peter N.
2016-01-01
Large-scale climate processes influence many aspects of ecology including breeding phenology, reproductive success and survival across a wide range of taxa. Some effects are direct, for example, in temperate-zone birds, ambient temperature is an important cue enabling breeding effort to coincide with maximum food availability, and earlier breeding in response to warmer springs has been documented in many species. In other cases, time-lags of up to several years in ecological responses have been reported, with effects mediated through biotic mechanisms such as growth rates or abundance of food supplies. Here we use 23 years of data for a temperate woodland bird species, the great tit (Parus major), breeding in deciduous woodland in eastern England to demonstrate a time-lagged linear relationship between the on-set of egg laying and the winter index of the North Atlantic Oscillation such that timing can be predicted from the winter index for the previous year. Thus the timing of bird breeding (and, by inference, the timing of spring events in general) can be predicted one year in advance. We also show that the relationship with the winter index appears to arise through an abiotic time-lag with local spring warmth in our study area. Examining this link between local conditions and larger-scale processes in the longer-term showed that, in the past, significant relationships with the immediately preceding winter index were more common than those with the time-lagged index, and especially so from the late 1930s to the early 1970s. However, from the mid 1970s onwards, the time-lagged relationship has become the most significant, suggesting a recent change in climate patterns. The strength of the current time-lagged relationship suggests that it might have relevance for other temperature-dependent ecological relationships. PMID:27182711
Patterns of Activity in A Global Model of A Solar Active Region
NASA Technical Reports Server (NTRS)
Bradshaw, S. J.; Viall, N. M.
2016-01-01
In this work we investigate the global activity patterns predicted from a model active region heated by distributions of nanoflares that have a range of frequencies. What differs is the average frequency of the distributions. The activity patterns are manifested in time lag maps of narrow-band instrument channel pairs. We combine hydrodynamic and forward modeling codes with a magnetic field extrapolation to create a model active region and apply the time lag method to synthetic observations. Our aim is not to reproduce a particular set of observations in detail, but to recover some typical properties and patterns observed in active regions. Our key findings are the following. (1) Cooling dominates the time lag signature and the time lags between the channel pairs are generally consistent with observed values. (2) Shorter coronal loops in the core cool more quickly than longer loops at the periphery. (3) All channel pairs show zero time lag when the line of sight passes through coronal loop footpoints. (4) There is strong evidence that plasma must be re-energized on a timescale comparable to the cooling timescale to reproduce the observed coronal activity, but it is likely that a relatively broad spectrum of heating frequencies are operating across active regions. (5) Due to their highly dynamic nature, we find nanoflare trains produce zero time lags along entire flux tubes in our model active region that are seen between the same channel pairs in observed active regions.
NASA Astrophysics Data System (ADS)
Langford, B.; Acton, W.; Ammann, C.; Valach, A.; Nemitz, E.
2015-10-01
All eddy-covariance flux measurements are associated with random uncertainties which are a combination of sampling error due to natural variability in turbulence and sensor noise. The former is the principal error for systems where the signal-to-noise ratio of the analyser is high, as is usually the case when measuring fluxes of heat, CO2 or H2O. Where signal is limited, which is often the case for measurements of other trace gases and aerosols, instrument uncertainties dominate. Here, we are applying a consistent approach based on auto- and cross-covariance functions to quantify the total random flux error and the random error due to instrument noise separately. As with previous approaches, the random error quantification assumes that the time lag between wind and concentration measurement is known. However, if combined with commonly used automated methods that identify the individual time lag by looking for the maximum in the cross-covariance function of the two entities, analyser noise additionally leads to a systematic bias in the fluxes. Combining data sets from several analysers and using simulations, we show that the method of time-lag determination becomes increasingly important as the magnitude of the instrument error approaches that of the sampling error. The flux bias can be particularly significant for disjunct data, whereas using a prescribed time lag eliminates these effects (provided the time lag does not fluctuate unduly over time). We also demonstrate that when sampling at higher elevations, where low frequency turbulence dominates and covariance peaks are broader, both the probability and magnitude of bias are magnified. We show that the statistical significance of noisy flux data can be increased (limit of detection can be decreased) by appropriate averaging of individual fluxes, but only if systematic biases are avoided by using a prescribed time lag. Finally, we make recommendations for the analysis and reporting of data with low signal-to-noise and their associated errors.
NASA Astrophysics Data System (ADS)
Langford, B.; Acton, W.; Ammann, C.; Valach, A.; Nemitz, E.
2015-03-01
All eddy-covariance flux measurements are associated with random uncertainties which are a combination of sampling error due to natural variability in turbulence and sensor noise. The former is the principal error for systems where the signal-to-noise ratio of the analyser is high, as is usually the case when measuring fluxes of heat, CO2 or H2O. Where signal is limited, which is often the case for measurements of other trace gases and aerosols, instrument uncertainties dominate. We are here applying a consistent approach based on auto- and cross-covariance functions to quantifying the total random flux error and the random error due to instrument noise separately. As with previous approaches, the random error quantification assumes that the time-lag between wind and concentration measurement is known. However, if combined with commonly used automated methods that identify the individual time-lag by looking for the maximum in the cross-covariance function of the two entities, analyser noise additionally leads to a systematic bias in the fluxes. Combining datasets from several analysers and using simulations we show that the method of time-lag determination becomes increasingly important as the magnitude of the instrument error approaches that of the sampling error. The flux bias can be particularly significant for disjunct data, whereas using a prescribed time-lag eliminates these effects (provided the time-lag does not fluctuate unduly over time). We also demonstrate that when sampling at higher elevations, where low frequency turbulence dominates and covariance peaks are broader, both the probability and magnitude of bias are magnified. We show that the statistical significance of noisy flux data can be increased (limit of detection can be decreased) by appropriate averaging of individual fluxes, but only if systematic biases are avoided by using a prescribed time-lag. Finally, we make recommendations for the analysis and reporting of data with low signal-to-noise and their associated errors.
Transdermal nicotine absorption handling e-cigarette refill liquids.
Maina, Giovanni; Castagnoli, Carlotta; Passini, Valter; Crosera, Matteo; Adami, Gianpiero; Mauro, Marcella; Filon, Francesca Larese
2016-02-01
The concentrated nicotine in e-cigarette refill liquids can be toxic if inadvertently ingested or absorbed through the skin. Reports of poisonings due to accidental ingestion of nicotine on refill liquids are rapidly increasing, while the evaluation of nicotine dermally absorbed still lacks. For that reason we studied transdermal nicotine absorption after the skin contamination with e-liquid. Donor chambers of eight Franz diffusion cells were filled with 1 mL of 0.8 mg/mL nicotine e-liquid for 24 h. The concentration of nicotine in the receiving phase was determined by high-performance liquid chromatography (LOD:0.1 μg/mL). Nicotine was detectable in receiving solution 2 h after the start of exposure and increased progressively. The medium flux calculated was 4.82 ± 1.05 μg/cm(2)/h with a lag time of 3.9 ± 0.1 h. After 24 h, the nicotine concentration in the receiving compartment was 101.02 ± 22.35 μg/cm(2) corresponding to 3.04 mg of absorbed nicotine after contamination of a skin surface of 100 cm(2). Skin contamination with e-liquid can cause nicotine skin absorption: caution must be paid when handling refill e-liquids. Copyright © 2015 Elsevier Inc. All rights reserved.
Zhang, Feifei; Liu, Zhidong; Zhang, Caixia; Jiang, Baofa
2016-09-01
This time-stratified case-crossover study aimed to quantify the impact of floods on daily Japanese encephalitis (JE) cases from 2007 to 2012 in Nanchong city of Sichuan Province, China. Using conditional logistic regression analysis, we calculated the odds ratios (ORs) and 95% confidence intervals (CIs) at different lagged days, adjusting for daily average temperature (AT) and daily average relative humidity (ARH). A total of 370 JE cases were notified during the study period, with the median patient age being 4.2years. The seasonal pattern of JE cases clustered in July and August during the study period. Floods were significantly associated with an increased number of JE cases from lag 23 to lag 24, with the strongest lag effect at lag 23 (OR=2.00, 95% CI: 1.14-3.52). Similarly, AT and ARH were positively associated with daily JE cases from lag 0 to lag 8 and from lag 0 to lag 9, respectively. Floods, with AT and ARH, can be used to forecast JE outbreaks in the study area. Based on the results of this study, recommendations include undertaking control measures before the number of cases increases, especially for regions with similar geographic, climatic, and socio-economic conditions as those in the study area. Copyright © 2016 Elsevier B.V. All rights reserved.
The Measurement of Pressure Through Tubes in Pressure Distribution Tests
NASA Technical Reports Server (NTRS)
Hemke, Paul E
1928-01-01
The tests described in this report were made to determine the error caused by using small tubes to connect orifices on the surface of aircraft to central pressure capsules in making pressure distribution tests. Aluminum tubes of 3/16-inch inside diameter were used to determine this error. Lengths from 20 feet to 226 feet and pressures whose maxima varied from 2 inches to 140 inches of water were used. Single-pressure impulses for which the time of rise of pressure from zero to a maximum varied from 0.25 second to 3 seconds were investigated. The results show that the pressure recorded at the capsule on the far end of the tube lags behind the pressure at the orifice end and experiences also a change in magnitude. For the values used in these tests the time lag and pressure change vary principally with the time of rise of pressure from zero to a maximum and the tube length. Curves are constructed showing the time lag and pressure change. Empirical formulas are also given for computing the time lag. Analysis of pressure distribution tests made on airplanes in flight shows that the recorded pressures are slightly higher than the pressures at the orifice and that the time lag is negligible. The apparent increase in pressure is usually within the experimental error, but in the case of the modern pursuit type of airplane the pressure increase may be 5 per cent. For pressure-distribution tests on airships the analysis shows that the time lag and pressure change may be neglected.
Lennernäs, Hans
2009-01-01
Generally, gastric emptying of a drug to the small intestine is controlled by gastric motor activity and is the main factor affecting the onset of absorption. Accordingly, the emptying rate from the stomach is mainly affected by the digestive state, the properties of the pharmaceutical formulation and the effect of drugs, posture and circadian rhythm. Variability in the gastric emptying of drugs is reflected in variability in the absorption rate and the shape of the plasma pharmacokinetic profile. When ethanol interacts with an oral controlled release product, such that the mechanism controlling drug release is impaired, the delivery of the dissolved dose into the small intestine and the consequent absorption may result in dangerously high plasma concentrations. For example, the maximal plasma concentration of hydromorphone has individually been shown to be increased as much as 16 times through in vivo testing as a result of this specific pharmacokinetic ethanol-drug formulation interaction. Thus, a pharmacokinetic ethanol-drug interaction is a very serious safety concern when substantially the entire dose from a controlled release product is rapidly emptied into the small intestine (dose dumping), having been largely dissolved in a strong alcoholic beverage in the stomach during a sufficient lag-time in gastric emptying. Based on the literature, a two hour time frame for screening the in vitro dissolution profile of a controlled release product in ethanol concentrations of up to 40% is strongly supported and may be considered as the absolute minimum standard. It is also evident that the dilution, absorption and metabolism of ethanol in the stomach are processes with a minor effect on the local ethanol concentration and that ethanol exposure will be highly dependent on the volume and ethanol concentration of the fluid ingested, together with the rate of intake and gastric emptying. When and in which patients a clinically significant dose dumping will happen is almost impossible to predict and will depend on drinking behavior and the highly variable gastrointestinal factors of importance for dissolution, transit and absorption. Therefore, controlled release products which show a vulnerability to ethanol during two hours in vitro should be required to demonstrate clinical safety by going through in vivo testing with an alcoholic beverage of up to 40% ethanol and of a sufficient volume (probably 120 mL or more), consumed in a relatively short period of time. Alternatively, such preparations should be reformulated in accordance with quality-by-design principles.
Time-lagged response of the Antarctic atmosphere to tropical MJO convection
NASA Astrophysics Data System (ADS)
Henderson, G. R.; Barrett, B.
2017-12-01
Intraseasonal tropical climate variability has important implications on mid- and high- latitude climate, and in recent studies has been shown to modulate a number of weather processes in the Northern Hemisphere, such as snow depth, sea ice concentration, precipitation, atmospheric rivers, and air temperature. In such studies, the leading mode of tropical intraseasonal variability, the Madden-Julian Oscillation (MJO), has tended to lag tropical convection by approximately 7 days. However, no such consensus exists when considering the relationship and lag between the MJO and the Antarctic atmosphere. This study builds on previous work by further examining the time-lagged response of Southern Hemisphere tropospheric circulation to tropical MJO forcing, with specific focus on the latitude belt associated with the Antarctic Oscillation, during the months of June (Austral winter) and December (Austral summer) using NCEP-DOE Reanalysis 2 data for the years 1970-2016. Principal findings indicate that the time lag with strongest height anomalies depends on both the location of the MJO convection (e.g., the MJO phase) and the season, and that the lagged height anomalies in the Antarctic atmosphere are fairly consistent across different vertical levels and latitudinal bands. In addition, certain MJO phases in December displayed lagged height anomalies indicative of blocking-type atmospheric patterns, with an approximate wavenumber of 4, whereas in June most phases were associated with progressive height anomaly centers displaying a wavenumber-3 type pattern.
NASA Astrophysics Data System (ADS)
Shanmugasundaram, Jothiganesh; Lee, Eungul
2018-03-01
The association of North-East Indian Monsoon rainfall (NEIMR) over the southeastern peninsular India with the oceanic and atmospheric conditions over the adjacent ocean regions at pentad time step (five days period) was investigated during the months of October to December for the period 1985-2014. The non-parametric correlation and composite analyses were carried out for the simultaneous and lagged time steps (up to four lags) of oceanic and atmospheric variables with pentad NEIMR. The results indicated that NEIMR was significantly correlated: 1) positively with both sea surface temperature (SST) led by 1-4 pentads (lag 1-4 time steps) and latent heat flux (LHF) during the simultaneous, lag 1 and 2 time steps over the equatorial western Indian Ocean, 2) positively with SST but negatively with LHF (less heat flux from ocean to atmosphere) during the same and all the lagged time steps over the Bay of Bengal. Consistently, during the wet NEIMR pentads over the southeastern peninsular India, SST significantly increased over the Bay of Bengal during all the time steps and the equatorial western Indian Ocean during the lag 2-4 time steps, while the LHF decreased over the Bay of Bengal (all time steps) and increased over the Indian Ocean (same, lag 1 and 2). The investigation on ocean-atmospheric interaction revealed that the enhanced LHF over the equatorial western Indian Ocean was related to increased atmospheric moisture demand and increased wind speed, whereas the reduced LHF over the Bay of Bengal was associated with decreased atmospheric moisture demand and decreased wind speed. The vertically integrated moisture flux and moisture transport vectors from 1000 to 850 hPa exhibited that the moisture was carried away from the equatorial western Indian Ocean to the strong moisture convergence regions of the Bay of Bengal during the same and lag 1 time steps of wet NEIMR pentads. Further, the moisture over the Bay of Bengal was transported to the southeastern peninsular India through stronger cyclonic circulations, which were confirmed by the moisture transport vectors and positive vorticity. The identified ocean and atmosphere processes, associated with the wet NEIMR conditions, could be a valuable scientific input for enhancing the rainfall predictability, which has a huge socioeconomic value to agriculture and water resource management sectors in the southeastern peninsular India.
Technical Note: High temporal resolution characterization of gating response time
DOE Office of Scientific and Technical Information (OSTI.GOV)
Wiersma, Rodney D., E-mail: rwiersma@uchicago.edu; McCabe, Bradley P.; Belcher, Andrew H.
2016-06-15
Purpose: Low temporal latency between a gating ON/OFF signal and the LINAC beam ON/OFF during respiratory gating is critical for patient safety. Here the authors describe a novel method to precisely measure gating lag times at high temporal resolutions. Methods: A respiratory gating simulator with an oscillating platform was modified to include a linear potentiometer for position measurement. A photon diode was placed at linear accelerator isocenter for beam output measurement. The output signals of the potentiometer and diode were recorded simultaneously at 2500 Hz with an analog to digital converter for four different commercial respiratory gating systems. The ONmore » and OFF of the beam signal were located and compared to the expected gating window for both phase and position based gating and the temporal lag times extracted. Results: For phase based gating, a real-time position management (RPM) infrared marker tracking system with a single camera and a RPM system with a stereoscopic camera were measured to have mean gate ON/OFF lag times of 98/90 and 86/44 ms, respectively. For position based gating, an AlignRT 3D surface system and a Calypso magnetic fiducial tracking system were measured to have mean gate ON/OFF lag times of 356/529 and 209/60 ms, respectively. Conclusions: Temporal resolution of the method was high enough to allow characterization of individual gate cycles and was primary limited by the sampling speed of the data recording device. Significant variation of mean gate ON/OFF lag time was found between different gating systems. For certain gating devices, individual gating cycle lag times can vary significantly.« less
Theory for Transitions Between Exponential and Stationary Phases: Universal Laws for Lag Time
NASA Astrophysics Data System (ADS)
Himeoka, Yusuke; Kaneko, Kunihiko
2017-04-01
The quantitative characterization of bacterial growth has attracted substantial attention since Monod's pioneering study. Theoretical and experimental works have uncovered several laws for describing the exponential growth phase, in which the number of cells grows exponentially. However, microorganism growth also exhibits lag, stationary, and death phases under starvation conditions, in which cell growth is highly suppressed, for which quantitative laws or theories are markedly underdeveloped. In fact, the models commonly adopted for the exponential phase that consist of autocatalytic chemical components, including ribosomes, can only show exponential growth or decay in a population; thus, phases that halt growth are not realized. Here, we propose a simple, coarse-grained cell model that includes an extra class of macromolecular components in addition to the autocatalytic active components that facilitate cellular growth. These extra components form a complex with the active components to inhibit the catalytic process. Depending on the nutrient condition, the model exhibits typical transitions among the lag, exponential, stationary, and death phases. Furthermore, the lag time needed for growth recovery after starvation follows the square root of the starvation time and is inversely related to the maximal growth rate. This is in agreement with experimental observations, in which the length of time of cell starvation is memorized in the slow accumulation of molecules. Moreover, the lag time distributed among cells is skewed with a long time tail. If the starvation time is longer, an exponential tail appears, which is also consistent with experimental data. Our theory further predicts a strong dependence of lag time on the speed of substrate depletion, which can be tested experimentally. The present model and theoretical analysis provide universal growth laws beyond the exponential phase, offering insight into how cells halt growth without entering the death phase.
Matthews, Russell A; Toumbeva, Tatiana H
2015-07-01
In the present study, grounded in organizational support and social exchange theory, the dynamic lagged interplay between family supportive supervision (FSS), family supportive organization perceptions (FSOP), perceived organizational support (POS), and leader-member exchange (LMX) was examined. Data were collected from 435 respondents over 3 time points with 6-week lags between assessments. Consistent with theory, FSS had a significant lagged effect on FSOP, whereas the reverse relationship was not supported. Interestingly, contrary to conservation of resources theory, we did not find significant lagged effects between POS and FSOP. Results further indicated that LMX and FSS were reciprocally related over time, suggesting the potential for a dynamic, mutually beneficial exchange relationship between subordinates and supervisors. Theoretical implications and considerations for research and practice are discussed. (PsycINFO Database Record (c) 2015 APA, all rights reserved).
Dynamic characteristics of heart rate control by the autonomic nervous system in rats.
Mizuno, Masaki; Kawada, Toru; Kamiya, Atsunori; Miyamoto, Tadayoshi; Shimizu, Shuji; Shishido, Toshiaki; Smith, Scott A; Sugimachi, Masaru
2010-09-01
We estimated the transfer function of autonomic heart rate (HR) control by using random binary sympathetic or vagal nerve stimulation in anaesthetized rats. The transfer function from sympathetic stimulation to HR response approximated a second-order, low-pass filter with a lag time (gain, 4.29 +/- 1.55 beats min(1) Hz(1); natural frequency, 0.07 +/- 0.03 Hz; damping coefficient, 1.96 +/- 0.64; and lag time, 0.73 +/- 0.12 s). The transfer function from vagal stimulation to HR response approximated a first-order, low-pass filter with a lag time (gain, 8.84 +/- 4.51 beats min(1) Hz(1); corner frequency, 0.12 +/- 0.06 Hz; and lag time, 0.12 +/- 0.08 s). These results suggest that the dynamic characteristics of HR control by the autonomic nervous system in rats are similar to those of larger mammals.
The Causal Connection Between Disc and Power-Law Variability in Hard State Black Hole X-Ray Binaries
NASA Technical Reports Server (NTRS)
Uttley, P.; Wilkinson, T.; Cassatella, P.; Wilms, J.; Pottschimdt, K.; Hanke, M.; Boeck, M.
2010-01-01
We use the XMM-Newton EPIC-pn instrument in timing mode to extend spectral time-lag studies of hard state black hole X-ray binaries into the soft X-ray band. \\Ve show that variations of the disc blackbody emission substantially lead variations in the power-law emission, by tenths of a second on variability time-scales of seconds or longer. The large lags cannot be explained by Compton scattering but are consistent with time-delays due to viscous propagation of mass accretion fluctuations in the disc. However, on time-scales less than a second the disc lags the power-law variations by a few ms, consistent with the disc variations being dominated by X-ray heating by the power-law, with the short lag corresponding to the light-travel time between the power-law emitting region and the disc. Our results indicate that instabilities in the accretion disc are responsible for continuum variability on time-scales of seconds or longer and probably also on shorter time-scales.
LAG-3 Represents a Marker of CD4+ T Cells with Regulatory Activity in Patients with Bone Fracture.
Wang, Jun; Ti, Yunfan; Wang, Yicun; Guo, Guodong; Jiang, Hui; Chang, Menghan; Qian, Hongbo; Zhao, Jianning; Sun, Guojing
2018-04-19
The lymphocyte activation gene 3 (LAG-3) is a CD4 homolog with binding affinity to MHC class II molecules. It is thought that LAG-3 exerts a bimodal function, such that co-ligation of LAG-3 and CD3 could deliver an inhibitory signal in conventional T cells, whereas, on regulatory T cells, LAG-3 expression could promote their inhibitory function. In this study, we investigated the role of LAG-3 expression on CD4 + T cells in patients with long bone fracture. We found that LAG-3 + cells represented approximately 13% of peripheral blood CD4 + T cells on average. Compared to LAG-3 - CD4 + T cells, LAG-3 + CD4 + T cells presented significantly higher Foxp3 and CTLA-4 expression. Directly ex vivo or with TCR stimulation, LAG-3 + CD4 + T cells expressed significantly higher levels of IL-10 and TGF-β than LAG-3 - CD4 + T cells. Interestingly, blocking the LAG-3-MHC class II interaction actually increased the IL-10 expression by LAG-3 + CD4 + T cells. The frequency of LAG-3 + CD4 + T cell was positively correlated with restoration of healthy bone function in long bone fracture patients. These results together suggested that LAG-3 is a marker of CD4 + T cells with regulatory function; at the same time, LAG-3 might have limited the full suppressive potential of Treg cells.
Competition between Primary Nucleation and Autocatalysis in Amyloid Fibril Self-Assembly
Eden, Kym; Morris, Ryan; Gillam, Jay; MacPhee, Cait E.; Allen, Rosalind J.
2015-01-01
Kinetic measurements of the self-assembly of proteins into amyloid fibrils are often used to make inferences about molecular mechanisms. In particular, the lag time—the quiescent period before aggregates are detected—is often found to scale with the protein concentration as a power law, whose exponent has been used to infer the presence or absence of autocatalytic growth processes such as fibril fragmentation. Here we show that experimental data for lag time versus protein concentration can show signs of kinks: clear changes in scaling exponent, indicating changes in the dominant molecular mechanism determining the lag time. Classical models for the kinetics of fibril assembly suggest that at least two mechanisms are at play during the lag time: primary nucleation and autocatalytic growth. Using computer simulations and theoretical calculations, we investigate whether the competition between these two processes can account for the kinks which we observe in our and others’ experimental data. We derive theoretical conditions for the crossover between nucleation-dominated and growth-dominated regimes, and analyze their dependence on system volume and autocatalysis mechanism. Comparing these predictions to the data, we find that the experimentally observed kinks cannot be explained by a simple crossover between nucleation-dominated and autocatalytic growth regimes. Our results show that existing kinetic models fail to explain detailed features of lag time versus concentration curves, suggesting that new mechanistic understanding is needed. More broadly, our work demonstrates that care is needed in interpreting lag-time scaling exponents from protein assembly data. PMID:25650930
SPECTRAL-TIMING ANALYSIS OF THE LOWER kHz QPO IN THE LOW-MASS X-RAY BINARY AQUILA X-1
DOE Office of Scientific and Technical Information (OSTI.GOV)
Troyer, Jon S.; Cackett, Edward M., E-mail: jon.troyer@wayne.edu
2017-01-10
Spectral-timing products of kilohertz quasi-periodic oscillations (kHz QPOs) in low-mass X-ray binary (LMXB) systems, including energy- and frequency-dependent lags, have been analyzed previously in 4U 1608-52, 4U 1636-53, and 4U 1728-34. Here, we study the spectral-timing properties of the lower kHz QPO of the neutron star LMXB Aquila X-1 for the first time. We compute broadband energy lags as well as energy-dependent lags and the covariance spectrum using data from the Rossi X-ray Timing Explorer . We find characteristics similar to those of previously studied systems, including soft lags of ∼30 μ s between the 3.0–8.0 keV and 8.0–20.0 keVmore » energy bands at the average QPO frequency. We also find lags that show a nearly monotonic trend with energy, with the highest-energy photons arriving first. The covariance spectrum of the lower kHz QPO is well fit by a thermal Comptonization model, though we find a seed photon temperature higher than that of the mean spectrum, which was also seen in Peille et al. and indicates the possibility of a composite boundary layer emitting region. Lastly, we see in one set of observations an Fe K component in the covariance spectrum at 2.4- σ confidence, which may raise questions about the role of reverberation in the production of lags.« less
Waterhouse, J; Edwards, B; Nevill, A; Carvalho, S; Atkinson, G; Buckley, P; Reilly, T; Godfrey, R; Ramsay, R
2002-02-01
Travelling across multiple time zones disrupts normal circadian rhythms and induces "jet lag". Possible effects of this on training and performance in athletes were concerns before the Sydney Olympic Games. To identify some determinants of jet lag and its symptoms. A mixture of athletes, their coaches, and academics attending a conference (n = 85) was studied during their flights from the United Kingdom to Australia (two flights with a one hour stopover in Singapore), and for the first six days in Australia. Subjects differed in age, sex, chronotype, flexibility of sleeping habits, feelings of languor, fitness, time of arrival in Australia, and whether or not they had previous experience of travel to Australia. These variables and whether the body clock adjusted to new local time by phase advance or delay were tested as predictors for jet lag and some of its symptoms by stepwise multiple regression analyses. The amount of sleep in the first flight was significantly greater in those who had left the United Kingdom in the evening than the morning (medians of 5.5 hours and 1.5 hours respectively; p = 0.0002, Mann-Whitney), whereas there was no significant difference on the second flight (2.5 hours v 2.8 hours; p = 0.72). Only the severity of jet lag and assessments of sleep and fatigue were commonly predicted significantly (p<0.05) by regression analysis, and then by only some of the variables. Thus increasing age and a later time of arrival in Australia were associated with less jet lag and fatigue, and previous experience of travel to Australia was associated with an earlier time of getting to sleep. Subjects who had adjusted by phase advance suffered worse jet lag during the 5th and 6th days in Australia. These results indicate the importance of an appropriate choice of itinerary and lifestyle for reducing the negative effects of jet lag in athletes and others who wish to perform optimally in the new time zone.
Effect of Repetition Lag on Priming of Unfamiliar Visual Objects in Young and Older Adults
Gordon, Leamarie T.; Soldan, Anja; Thomas, Ayanna K.; Stern, Yaakov
2013-01-01
Across three experiments, we examined the effect of repetition lag on priming of unfamiliar visual objects in healthy young and older adults. Multiple levels of lag were examined, ranging from short (one to four intervening stimuli) to long (50+ intervening stimuli). In each experiment, subjects viewed a series of new and repeated line drawings of objects and decided whether they depicted structurally possible or impossible figures. Experiment 1 and 2 found similar levels of priming in young and older adults at short and medium lags. At the longer repetition lags (∼20+ intervening stimuli), older adults showed less overall priming, as measured by reaction time facilitation, than young adults. This indicates that older adults can rapidly encode unfamiliar three-dimensional objects to support priming at shorter lags; however, they cannot maintain these representations over longer intervals. In addition to repetition lag, we also explored the relationship between priming and cognitive reserve, as measured by education and verbal intelligence. In the older adults, higher levels of cognitive reserve were associated with greater reaction time priming, suggesting that cognitive reserve may mediate the relationship between aging and priming. PMID:23276220
Time-dependent Electron Acceleration in Blazar Transients: X-Ray Time Lags and Spectral Formation
NASA Astrophysics Data System (ADS)
Lewis, Tiffany R.; Becker, Peter A.; Finke, Justin D.
2016-06-01
Electromagnetic radiation from blazar jets often displays strong variability, extending from radio to γ-ray frequencies. In a few cases, this variability has been characterized using Fourier time lags, such as those detected in the X-rays from Mrk 421 using BeppoSAX. The lack of a theoretical framework to interpret the data has motivated us to develop a new model for the formation of the X-ray spectrum and the time lags in blazar jets based on a transport equation including terms describing stochastic Fermi acceleration, synchrotron losses, shock acceleration, adiabatic expansion, and spatial diffusion. We derive the exact solution for the Fourier transform of the electron distribution and use it to compute the Fourier transform of the synchrotron radiation spectrum and the associated X-ray time lags. The same theoretical framework is also used to compute the peak flare X-ray spectrum, assuming that a steady-state electron distribution is achieved during the peak of the flare. The model parameters are constrained by comparing the theoretical predictions with the observational data for Mrk 421. The resulting integrated model yields, for the first time, a complete first-principles physical explanation for both the formation of the observed time lags and the shape of the peak flare X-ray spectrum. It also yields direct estimates of the strength of the shock and the stochastic magnetohydrodynamical wave acceleration components in the Mrk 421 jet.
Paploski, Igor A.D.; Prates, Ana Paula P.B.; Cardoso, Cristiane W.; Kikuti, Mariana; Silva, Monaise M. O.; Waller, Lance A.; Reis, Mitermayer G.; Kitron, Uriel
2016-01-01
Zika virus infection emerged as a public health emergency after increasing evidence for its association with neurologic disorders and congenital malformations. In Salvador, Brazil, outbreaks of acute exanthematous illness (AEI) attributed to Zika virus, Guillain-Barré syndrome (GBS), and microcephaly occurred in 2015. We investigated temporal correlations and time lags between these outbreaks to identify a common link between them by using epidemic curves and time series cross-correlations. Number of GBS cases peaked after a lag of 5–9 weeks from the AEI peak. Number of suspected cases of microcephaly peaked after a lag of 30–33 weeks from the AEI peak, which corresponded to time of potential infections of pregnant mothers during the first trimester. These findings support the association of GBS and microcephaly with Zika virus infection and provide evidence for a temporal relationship between timing of arboviral infection of pregnant women during the first trimester and birth outcome. PMID:27144515
Lag and anticipating synchronization without time-delay coupling.
Corron, Ned J; Blakely, Jonathan N; Pethel, Shawn D
2005-06-01
We describe a new method for achieving approximate lag and anticipating synchronization in unidirectionally coupled chaotic oscillators. The method uses a specific parameter mismatch between the drive and response that is a first-order approximation to true time-delay coupling. As a result, an adjustable lag or anticipation effect can be achieved without the need for a variable delay line, making the method simpler and more economical to implement in many physical systems. We present a stability analysis, demonstrate the method numerically, and report experimental observation of the effect in radio-frequency electronic oscillators. In the circuit experiments, both lag and anticipation are controlled by tuning a single capacitor in the response oscillator.
Air pollutants and atmospheric pressure increased risk of ED visit for spontaneous pneumothorax.
Park, Joo Hyung; Lee, Sun Hwa; Yun, Seong Jong; Ryu, Seokyong; Choi, Seung Woon; Kim, Hye Jin; Kang, Tae Kyung; Oh, Sung Chan; Cho, Suk Jin
2018-04-14
To investigate the impact of short-term exposure to air pollutants and meteorological variation on ED visits for primary spontaneous pneumothorax (PSP). We retrospectively identified PSP cases that presented at the ED of our tertiary center between January 2015 and September 2016. We classified the days into three types: no PSP day (0 case/day), sporadic days (1-2 cases/day), and cluster days (PSP, ≥3 cases/day). Association between the daily incidence of PSP with air pollutants and meteorological data were determined using Poisson generalized-linear-model to calculate incidence rate ratio (IRRs) and the use of time-series (lag-1 [the cumulative air pollution level on the previous day of PSP], lag-2 [two days ago], and lag-3 [three days ago]). Using multivariate logistic regression analysis, O 3 (p = 0.010), NO 2 (p = 0.047), particulate matters (PM) 10 (p = 0.021), and PM 2.5 (p = 0.008) were significant factors of PSP occurrence. When the concentration of O 3 , NO 2 , PM 10 , and PM 2.5 were increased, PSP IRRs increased approximately 15, 16, 3, and 5-fold, respectively. With the time-series analyses, atmospheric pressure in lag-3 was significantly lower and in lag-2, was significantly higher in PSP days compared with no PSP days. Among air pollutant concentrations, O 3 in lag-1 (p = 0.017) and lag-2 (p = 0.038), NO 2 in lag-1 (p = 0.015) and lag-2 (p = 0.009), PM 10 in lag-1 (p = 0.012), and PM 2.5 in lag-1 (p = 0.021) and lag-2 (p = 0.032) were significantly different between no PSP and PSP days. Increased concentrations of air pollutants and abrupt change in atmospheric pressure were significantly associated with increased IRR of PSP. Copyright © 2018 Elsevier Inc. All rights reserved.
NASA Astrophysics Data System (ADS)
Xu, Beibei; Chen, Diyi; Zhang, Hao; Wang, Feifei; Zhang, Xinguang; Wu, Yonghong
2017-06-01
This paper focus on a Hamiltonian mathematical modeling for a hydro-turbine governing system including fractional item and time-lag. With regards to hydraulic pressure servo system, a universal dynamical model is proposed, taking into account the viscoelastic properties and low-temperature impact toughness of constitutive materials as well as the occurrence of time-lag in the signal transmissions. The Hamiltonian model of the hydro-turbine governing system is presented using the method of orthogonal decomposition. Furthermore, a novel Hamiltonian function that provides more detailed energy information is presented, since the choice of the Hamiltonian function is the key issue by putting the whole dynamical system to the theory framework of the generalized Hamiltonian system. From the numerical experiments based on a real large hydropower station, we prove that the Hamiltonian function can describe the energy variation of the hydro-turbine suitably during operation. Moreover, the effect of the fractional α and the time-lag τ on the dynamic variables of the hydro-turbine governing system are explored and their change laws identified, respectively. The physical meaning between fractional calculus and time-lag are also discussed in nature. All of the above theories and numerical results are expected to provide a robust background for the safe operation and control of large hydropower stations.
Drug Lag and Key Regulatory Barriers in the Emerging Markets
Wileman, Harriet; Mishra, Arun
2010-01-01
There have been numerous investigations targeted at identifying whether a drug lag exists in the mature markets of the US, EU and Japan. This work focuses on the emerging markets because of the potential they hold for the future of the pharmaceutical industry as a consequence of rapid economic and political development. The aims of this work are to ascertain whether a drug lag exists in the emerging markets and how it has changed over time from the 1960s to the 2000s. It will also highlight key regulatory barriers which may contribute to drug lag. The date of the marketing authorisation (MA) approval by the US Food and Drug Administration (FDA) was used as a reference point. A comparison against the company database regarding emerging market specific approval enabled the difference in time and thus the drug lag for that particular market to be calculated. This work concludes that the overall relative drug lag in the emerging markets has decreased over time and that there are seven key regulatory barriers which need to be targeted in order to make further improvements; ‘Western Approval’, local clinical development (LCD), Certificate of Pharmaceutical Product (CPP), Good Manufacturing Practice (GMP), pricing approval, document authentication and harmonisation. PMID:21829782
Long-Term Outcome and Complications Following Prophylactic Laparoscopic-Assisted Gastropexy in Dogs.
Loy Son, Natasha K; Singh, Ameet; Amsellem, Pierre; Kilkenny, Jessica; Brisson, Brigitte A; Oblak, Michelle L; Ogilvie, Adam T
2016-11-01
To characterize the short- and long-term outcome (>12 months), complications, and owner satisfaction following prophylactic laparoscopic-assisted gastropexy (LAG) in dogs. Retrospective study. Client-owned dogs (n = 49). Dogs that underwent prophylactic LAG at 2 veterinary academic hospitals were studied. Surgical time, anesthesia time, concurrent intra- and extra-abdominal procedures, and intraoperative and postoperative complications were recorded following review of medical records. Veterinarian and/or owner follow-up was obtained to determine outcome and satisfaction with LAG. Five of 49 dogs (10%) experienced complications related to abdominal access during LAG. Four percent (2/49) of dogs experienced an intraoperative complication. Follow-up information was available for 89% of dogs (44/49). Four dogs died of causes unrelated to LAG or gastric dilatation volvulus (GDV) in the follow-up period. Two dogs experienced major postoperative complications requiring additional veterinary intervention. Thirty percent (13 dogs) experienced a minor postoperative self-limiting wound-related complication. Median follow-up time was 698 days (range, 411-1825). No dogs experienced GDV. One hundred percent of dog owners were satisfied with LAG, would repeat the procedure in a future pet, and would recommend the procedure to a friend or family member. LAG was an effective procedure for prevention of GDV and was associated with high client satisfaction in this cohort of dogs. A moderate rate of postoperative wound complications occurred that were minor and self-limiting in nature. © Copyright 2016 by The American College of Veterinary Surgeons.
Nath, Bipul; Nath, Lila Kanta
2013-01-01
The purpose of this study is to explore the possible applicability of Sterculia urens gum as a novel carrier for colonic delivery system of a sparingly soluble drug, azathioprine. The study involves designing a microflora triggered colon-targeted drug delivery system (MCDDS) which consists of a central polysaccharide core and is coated to different film thicknesses with blends of chitosan/Eudragit RLPO, and is overcoated with Eudragit L00 to provide acid and intestinal resistance. The microflora degradation property of gum was investigated in rat caecal medium. Drug release study in simulated colonic fluid revealed that swelling force of the gum could concurrently drive the drug out of the polysaccharide core due to the rupture of the chitosan/Eudargit coating in microflora-activated environment. Chitosan in the mixed film coat was found to be degraded by enzymatic action of the microflora in the colon. Release kinetic data revealed that the optimized MCDDS was fitted well into first-order model, and apparent lag time was found to be 6 hours, followed by Higuchi release kinetics. In vivo study in rabbits shows delayed T max, prolonged absorption time, decreased C max, and absorption rate constant (Ka), indicating a reduced systemic toxicity of the drug as compared to other dosage forms. PMID:26555985
Pharmacokinetics of isotretinoin during repetitive dosing to patients.
Brazzell, R K; Vane, F M; Ehmann, C W; Colburn, W A
1983-01-01
The multiple dose pharmacokinetics of isotretinoin and its major blood metabolite, 4-oxo-isotretinoin, were studied in 10 patients with cystic acne and 11 patients with various keratinization disorders. Blood samples were obtained at predetermined times following the first dose, interim doses and the final dose. Blood concentrations of isotretinoin and 4-oxo-isotretinoin were measured by a specific and sensitive HPLC method. A lag time was usually observed prior to the onset of absorption following oral administration of the drug in a soft elastic gelatin capsule. Absorption then proceeded rapidly and maximum blood concentrations usually occurred within 4 h of drug administration. The harmonic mean half-life for the elimination of isotretinoin by the cystic acne patients was approximately 10 h after the initial dose and did not change significantly following 25 days of 40 mg b.i.d. dosing. Steady-state blood concentrations remained relatively constant after the fifth day of dosing. The harmonic mean elimination half-life in the patients with various disorders of keratinization was about 16 h. The results of the 2 studies suggest that no significant changes in the pharmacokinetics of isotretinoin occur during multiple dosing and that the multiple dose pharmacokinetic profile is predictable and can be described using a linear pharmacokinetic model. This suggests that the steady-state concentrations of isotretinoin can be predicted from single dose data.
He, Shuang; Li, Feng; Zhou, Dan; Du, Junrong; Huang, Yuan
2012-10-01
A novel coated gastric floating drug-delivery system (GFDDS) of bergenin (BN) and cetirizine dihydrochloride (CET) was developed. First, the pharmacodynamic studies were performed and the results revealed that the new compounds of bergenin/cetirizine dihydrochloride had comparative efficacy as commercial products (bergenin/chlorphenamine maleate) but with fewer side effects on central nervous system (CNS). Subsequently, bergenin was formulated as an extended-release core tablet while cetirizine dihydrochloride was incorporated into the gastric coating film for immediate release. The formulation of GFDDS was optimized by CET content uniformity test, in vitro buoyancy and drug release. Herein, the effects of sodium bicarbonate (effervescent), hydroxypropyl methylcellulose (HPMC, matrix polymer) and coating weight gain were investigated respectively. The optimized GFDDS exhibited good floating properties (buoyancy lag time < 2 min; floating duration > 10 h) and satisfactory drug-release profiles (immediate release of CET in 10 min and sustained release of BN for 12 h). In vivo gamma scintigraphy proved that the optimized GFDDS could retain in the stomach with a prolonged gastric retention time (GRT) of 5 h, and the coating layer showed no side effect for gastric retention. The novel coated gastric floating drug-delivery system offers a new approach to enhance BN's absorption at its absorption site and the efficacy of both CET and BN.
Monthly ENSO Forecast Skill and Lagged Ensemble Size
DelSole, T.; Tippett, M.K.; Pegion, K.
2018-01-01
Abstract The mean square error (MSE) of a lagged ensemble of monthly forecasts of the Niño 3.4 index from the Climate Forecast System (CFSv2) is examined with respect to ensemble size and configuration. Although the real‐time forecast is initialized 4 times per day, it is possible to infer the MSE for arbitrary initialization frequency and for burst ensembles by fitting error covariances to a parametric model and then extrapolating to arbitrary ensemble size and initialization frequency. Applying this method to real‐time forecasts, we find that the MSE consistently reaches a minimum for a lagged ensemble size between one and eight days, when four initializations per day are included. This ensemble size is consistent with the 8–10 day lagged ensemble configuration used operationally. Interestingly, the skill of both ensemble configurations is close to the estimated skill of the infinite ensemble. The skill of the weighted, lagged, and burst ensembles are found to be comparable. Certain unphysical features of the estimated error growth were tracked down to problems with the climatology and data discontinuities. PMID:29937973
Monthly ENSO Forecast Skill and Lagged Ensemble Size
NASA Astrophysics Data System (ADS)
Trenary, L.; DelSole, T.; Tippett, M. K.; Pegion, K.
2018-04-01
The mean square error (MSE) of a lagged ensemble of monthly forecasts of the Niño 3.4 index from the Climate Forecast System (CFSv2) is examined with respect to ensemble size and configuration. Although the real-time forecast is initialized 4 times per day, it is possible to infer the MSE for arbitrary initialization frequency and for burst ensembles by fitting error covariances to a parametric model and then extrapolating to arbitrary ensemble size and initialization frequency. Applying this method to real-time forecasts, we find that the MSE consistently reaches a minimum for a lagged ensemble size between one and eight days, when four initializations per day are included. This ensemble size is consistent with the 8-10 day lagged ensemble configuration used operationally. Interestingly, the skill of both ensemble configurations is close to the estimated skill of the infinite ensemble. The skill of the weighted, lagged, and burst ensembles are found to be comparable. Certain unphysical features of the estimated error growth were tracked down to problems with the climatology and data discontinuities.
Mutagenic analysis of the nucleation propensity of oxidized Alzheimer's beta-amyloid peptide.
Christopeit, Tony; Hortschansky, Peter; Schroeckh, Volker; Gührs, Karlheinz; Zandomeneghi, Giorgia; Fändrich, Marcus
2005-08-01
The formation of polypeptide aggregates represents a nucleated polymerization reaction in which an initial nucleation event (lag phase) is followed by the extension of newly formed nuclei into larger aggregates, including fibrils (growth phase). The efficiencies of these reactions relate to the lag time (lag phase) and to the rate of aggregation (growth phase), which can be determined from experimental aggregation curves. Here we present a mutagenic analysis in which we replace valine 18 of the Alzheimer's Abeta (1-40) peptide with 17 different amino acids and determine its effect on the lag time, and therefore, on the propensity of nucleation. Comparison with various physico-chemical properties shows that nucleation is affected in a predictable manner depending on the beta-sheet propensity and hydrophobicity of residue 18. In addition, we observe a direct proportionality between the lag time and the rate of aggregation. These data imply that the two reactions, nucleation and polymerization, are governed by very similar physicochemical principles and that they involve the formation of the same types of noncovalent interactions.
SOFT LAGS IN NEUTRON STAR kHz QUASI-PERIODIC OSCILLATIONS: EVIDENCE FOR REVERBERATION?
DOE Office of Scientific and Technical Information (OSTI.GOV)
Barret, Didier, E-mail: didier.barret@irap.omp.eu; CNRS, Institut de Recherche en Astrophysique et Planetologie, 9 Av. colonel Roche, BP 44346, F-31028 Toulouse cedex 4
2013-06-10
High frequency soft reverberation lags have now been detected from stellar mass and supermassive black holes. Their interpretation involves reflection of a hard source of photons onto an accretion disk, producing a delayed reflected emission, with a time lag consistent with the light travel time between the irradiating source and the disk. Independently of the location of the clock, the kHz quasi-periodic oscillation (QPO) emission is thought to arise from the neutron star boundary layer. Here, we search for the signature of reverberation of the kHz QPO emission, by measuring the soft lags and the lag energy spectrum of themore » lower kHz QPOs from 4U1608-522. Soft lags, ranging from {approx}15 to {approx}40 {mu}s, between the 3-8 keV and 8-30 keV modulated emissions are detected between 565 and 890 Hz. The soft lags are not constant with frequency and show a smooth decrease between 680 Hz and 890 Hz. The broad band X-ray spectrum is modeled as the sum of a disk and a thermal Comptonized component, plus a broad iron line, expected from reflection. The spectral parameters follow a smooth relationship with the QPO frequency, in particular the fitted inner disk radius decreases steadily with frequency. Both the bump around the iron line in the lag energy spectrum and the consistency between the lag changes and the inferred changes of the inner disk radius, from either spectral fitting or the QPO frequency, suggest that the soft lags may indeed involve reverberation of the hard pulsating QPO source on the disk.« less
Sleep Disorders and Complementary Health Approaches : What the Science Says
... symptoms of jet lag and improve sleep following travel across multiple time zones. A 2009 Cochrane review supporting this recommendation ... oral melatonin for alleviating jet lag after air travel across several time zones, and concluded that melatonin is remarkably effective ...
A Falling Corona Model for the Anomalous Behavior of the Broad Emission Lines in NGC 5548
NASA Astrophysics Data System (ADS)
Sun, Mouyuan; Xue, Yongquan; Cai, Zhenyi; Guo, Hengxiao
2018-04-01
NGC 5548 has been intensively monitored by the AGN Space Telescope and Optical Reverberation Mapping collaboration. Approximately after half of the light curves, the correlation between the broad emission lines and the lag-corrected ultraviolet (UV) continua becomes weak. This anomalous behavior is accompanied by an increase of soft X-ray emission. We propose a simple model to understand this anomalous behavior, i.e., the corona might fall down, thereby increasing the covering fraction of the inner disk. Therefore, X-ray and extreme-UV emission suffer from spectral variations. The UV continua variations are driven by both X-ray and extreme-UV variations. Consequently, the spectral variability induced by the falling corona would dilute the correlation between the broad emission lines and the UV continua. Our model can explain many additional observational facts, including the dependence of the anomalous behavior on velocity and ionization energy. We also show that the time lag and correlation between the X-ray and the UV variations change as NGC 5548 displays the anomalous behavior. The time lag is dramatically longer than the expectation from disk reprocessing if the anomalous behavior is properly excluded. During the anomalous state, the time lag approaches the light-travel timescale of disk reprocessing albeit with a much weaker correlation. We speculate that the time lag in the normal state is caused by reprocessing of the broad line region gas. As NGC 5548 enters the abnormal state, the contribution of the broad line region gas is smaller; the time lag reflects disk reprocessing. We also discuss alternative scenarios.
TEMPORAL VARIABILITY FROM THE TWO-COMPONENT ADVECTIVE FLOW SOLUTION AND ITS OBSERVATIONAL EVIDENCE
DOE Office of Scientific and Technical Information (OSTI.GOV)
Dutta, Broja G.; Chakrabarti, Sandip K.
2016-09-10
In the propagating oscillatory shock model, the oscillation of the post-shock region, i.e., the Compton cloud, causes the observed low-frequency quasi-periodic oscillations (QPOs). The evolution of QPO frequency is explained by the systematic variation of the Compton cloud size, i.e., the steady radial movement of the shock front, which is triggered by the cooling of the post-shock region. Thus, analysis of the energy-dependent temporal properties in different variability timescales can diagnose the dynamics and geometry of accretion flows around black holes. We study these properties for the high-inclination black hole source XTE J1550-564 during its 1998 outburst and the low-inclinationmore » black hole source GX 339-4 during its 2006–07 outburst using RXTE /PCA data, and we find that they can satisfactorily explain the time lags associated with the QPOs from these systems. We find a smooth decrease of the time lag as a function of time in the rising phase of both sources. In the declining phase, the time lag increases with time. We find a systematic evolution of QPO frequency and hard lags in these outbursts. In XTE J1550-564, the lag changes from hard to soft (i.e., from a positive to a negative value) at a crossing frequency (ν {sub c}) of ∼3.4 Hz. We present possible mechanisms to explain the lag behavior of high and low-inclination sources within the framework of a single two-component advective flow model.« less
NASA Astrophysics Data System (ADS)
Gaskell, C. Martin; Harrington, Peter Z.
2018-04-01
The profiles of the broad emission lines of active galactic nuclei (AGNs) and the time delays in their response to changes in the ionizing continuum ("lags") give information about the structure and kinematics of the inner regions of AGNs. Line profiles are also our main way of estimating the masses of the supermassive black holes (SMBHs). However, the profiles often show ill-understood, asymmetric structure and velocity-dependent lags vary with time. Here we show that partial obscuration of the broad-line region (BLR) by outflowing, compact, dusty clumps produces asymmetries and velocity-dependent lags similar to those observed. Our model explains previously inexplicable changes in the ratios of the hydrogen lines with time and velocity, the lack of correlation of changes in line profiles with variability of the central engine, the velocity dependence of lags, and the change of lags with time. We propose that changes on timescales longer than the light-crossing time do not come from dynamical changes in the BLR, but are a natural result of the effect of outflowing dusty clumps driven by radiation pressure acting on the dust. The motion of these clumps offers an explanation of long-term changes in polarization. The effects of the dust complicate the study of the structure and kinematics of the BLR and the search for sub-parsec SMBH binaries. Partial obscuration of the accretion disc can also provide the local fluctuations in luminosity that can explain sizes deduced from microlensing.
Observing the Fast X-ray Spectral Variability of NLS1 1H1934-063 with XMM-Newton and NuSTAR
NASA Astrophysics Data System (ADS)
Frederick, Sara; Kara, Erin; Reynolds, Christopher S.
2017-08-01
The most variable active galactic nuclei (AGN), taken together, are a compelling wellspring of interesting accretion-related phenomena. They can exhibit dramatic variability in the X-ray band on a range of timescales down to a few minutes. We present the exemplifying case study of 1H1934-063 (z = 0.0102), a narrow-line Seyfert I (NLS1) that is among the most variable AGN ever observed with XMM-Newton. We present spectral and temporal analyses of a concurrent XMM-Newton and NuSTAR observation taken in 2015 and lasting 120 ks, during which the source exhibited a steep (factor of 1.5) plummet and subsequent full recovery of flux that we explore in detail here. Combined spectral and timing results point to a dramatic change in the continuum on timescales as short as a few ks. Similar to other highly variable Seyfert 1s, this AGN is quite X-ray bright and displays strong reflection spectral features. We find agreement with a change in the continuum, and we rule out absorption as the cause for this dramatic variability observed even at NuSTAR energies. We compare detailed time-resolved spectral fitting with Fourier-based timing analysis in order to constrain coronal geometry, dynamics, and emission/absorption processes dictating the nature of this variability. We also announce the discovery of a Fe-K time lag between the hard X-ray continuum emission (1 - 4 keV) and its relativistically-blurred reflection off the inner accretion flow (0.3 - 1 keV).
Uezu, Alexandre; Metzger, Jean Paul
2016-01-01
There are few opportunities to evaluate the relative importance of landscape structure and dynamics upon biodiversity, especially in highly fragmented tropical landscapes. Conservation strategies and species risk evaluations often rely exclusively on current aspects of landscape structure, although such limited assumptions are known to be misleading when time-lag responses occur. By relating bird functional-group richness to forest patch size and isolation in ten-year intervals (1956, 1965, 1978, 1984, 1993 and 2003), we revealed that birds with different sensitivity to fragmentation display contrasting responses to landscape dynamics in the Brazilian Atlantic Forest. For non-sensitive groups, there was no time-lag in response: the recent degree of isolation best explains their variation in richness, which likely relates to these species' flexibility to adapt to changes in landscape structure. However, for sensitive bird groups, the 1978 patch area was the best explanatory variable, providing evidence for a 25-year time-lag in response to habitat reduction. Time-lag was more likely in landscapes that encompass large patches, which can support temporarily the presence of some sensitive species, even when habitat cover is relatively low. These landscapes potentially support the most threatened populations and should be priorities for restoration efforts to avoid further species loss. Although time-lags provide an opportunity to counteract the negative consequences of fragmentation, it also reinforces the urgency of restoration actions. Fragmented landscapes will be depleted of biodiversity if landscape structure is only maintained, and not improved. The urgency of restoration action may be even higher in landscapes where habitat loss and fragmentation history is older and where no large fragment remained to act temporarily as a refuge.
Observation and modeling of compressional Pi 3 magnetic pulsations
NASA Technical Reports Server (NTRS)
Matsuoka, Hitoshi; Takahashi, K.; Yumoto, K.; Anderson, B. J.; Sibeck, D. G.
1995-01-01
Compressional magnetic pulsations with irregular waveforms and periods longer than 150 s (here termed Pi 3) have been studied by using data from Active Magnetospheric Particle Tracer Explorers Charge Composition Explorer (AMPTE/CCE) and GOES 5 and 6 in the dayside magnetosphere and compared with signatures on the ground at low latitudes by using data from Kakioka station (L = 1.25). On the ground, the pulsations appear in the horizontal component. A study of 17 such concurrent events during a 2-month period in 1986 reveals the following pulsation characteristics. (1) The peak-to-peak amplitudes in space (delta B(sub T)) and on the ground (delta H) are comparable and are in the range of 0.5-7 nT. (2) On the ground the pulsations can be seen at all local times, even at midnight, while at geostationary orbit they are observed only on the dayside with a clear amplitude maximum at noon. (3) The pulsations on the ground lag those observed by CCE near local noon, and the lag increases as the local time separation between CCE and the ground station increases. The time lag is 1-2 min longer when the ground station is on the nightside than when it is on the dayside. (4) The time lag between pulsations observed at geostationary orbit and near noon by CCE varies systematically with local time and is about 2 min per 6 hours of local time separation. These observations indicate that some nightside pulsations in the Pi 3 band have dayside origins. The position dependence of the pulsation amplitude can be explained well by changes in the magnetopause current, which are in turn presumably caused by changes in the solar wind dynamic pressure. The time lags observed in space are consistent with signal propagation in the MHD fast mode, but the variation in space-ground time lags with ground station local time must be attributed to another mechanism.
Gougouli, Maria; Koutsoumanis, Konstantinos P
2010-06-15
The growth of Penicillium expansum and Aspergillus niger, isolated from yogurt production environment, was investigated on malt extract agar with pH=4.2 and a(w)=0.997, simulating yogurt, at isothermal conditions ranging from -1.3 to 35 degrees C and from 5 to 42.3 degrees C, respectively. The growth rate (mu) and (apparent) lag time (lambda) of the mycelium growth were modelled as a function of temperature using a Cardinal Model with Inflection (CMI). The results showed that the CMI can describe successfully the effect of temperature on fungal growth within the entire biokinetic range for both isolates. The estimated values of the CMI for mu were T(min)=-5.74 degrees C, T(max)=30.97 degrees C, T(opt)=22.08 degrees C and mu(opt)=0.221 mm/h for P. expansum and T(min)=10.13 degrees C, T(max)=43.13 degrees C, T(opt)=31.44 degrees C, and mu(opt)=0.840 mm/h for A. niger. The cardinal values for lambda were very close to the respective values for mu indicating similar temperature dependence of the growth rate and the lag time of the mycelium growth. The developed models were further validated under fluctuating temperature conditions using various dynamic temperature scenarios. The time-temperature conditions studied included single temperature shifts before or after the end of the lag time and continuous periodic temperature fluctuations. The prediction of growth at changing temperature was based on the assumption that after a temperature shift the growth rate is adopted instantaneously to the new temperature, while the lag time was predicted using a cumulative lag approach. The results showed that when the temperature shifts occurred before the end of the lag, they did not cause any significant additional lag and the observed total lag was very close to the cumulative lag predicted by the model. In experiments with temperature shifts after the end of the lag time, accurate predictions were obtained when the temperature profile included temperatures which were inside the region of growth, showing that the assumption that mu is adopted instantaneously to the current temperature is concrete. In contrast, for scenarios with temperatures close or outside the growth region the models overestimated growth, indicating that fungi were stressed by this type of temperature shifts. The present study provides useful data for understanding the behavior of P. expansum and A. niger at dynamic temperature conditions while the developed models can be used as effective tools in assessing the risk of fungal spoilage and predicting shelf life of foods. Copyright 2010. Published by Elsevier B.V.
Diverse Responses of Global Vegetation to Climate Changes: Spatial Patterns and Time-lag Effects
NASA Astrophysics Data System (ADS)
Wu, D.; Zhao, X.; Zhou, T.; Huang, K.; Xu, W.
2014-12-01
Global climate changes have enormous influences on vegetation growth, meanwhile, response of vegetation to climate express space diversity and time-lag effects, which account for spatial-temporal disparities of climate change and spatial heterogeneity of ecosystem. Revelation of this phenomenon will help us further understanding the impact of climate change on vegetation. Assessment and forecast of global environmental change can be also improved under further climate change. Here we present space diversity and time-lag effects patterns of global vegetation respond to three climate factors (temperature, precipitation and solar radiation) based on quantitative analysis of satellite data (NDVI) and Climate data (Climate Research Unit). We assessed the time-lag effects of global vegetation to main climate factors based on the great correlation fitness between NDVI and the three climate factors respectively among 0-12 months' temporal lags. On this basis, integrated response model of NDVI and the three climate factors was built to analyze contribution of different climate factors to vegetation growth with multiple regression model and partial correlation model. In the result, different vegetation types have distinct temporal lags to the three climate factors. For the precipitation, temporal lags of grasslands are the shortest while the evergreen broad-leaf forests are the longest, which means that grasslands are more sensitive to precipitation than evergreen broad-leaf forests. Analysis of different climate factors' contribution to vegetation reveal that vegetation are dominated by temperature in the high northern latitudes; they are mainly restricted by precipitation in arid and semi-arid areas (Australia, Western America); in humid areas of low and intermediate latitudes (Amazon, Eastern America), vegetation are mainly influenced by solar radiation. Our results reveal the time-lag effects and major driving factors of global vegetation growth and explain the spatiotemporal variations of global vegetation in last 30 years. Significantly, it is as well as in forecasting and assessing the influences of future climate change on the vegetation dynamics. This work was supported by the High Technology Research and Development Program of China (Grant NO.2013AA122801).
Emergence and temporal structure of Lead-Lag correlations in collective stock dynamics
NASA Astrophysics Data System (ADS)
Xia, Lisi; You, Daming; Jiang, Xin; Chen, Wei
2018-07-01
Understanding the correlations among stock returns is crucial for reducing the risk of investment in stock markets. As an important stylized correlation, lead-lag effect plays a major role in analyzing market volatility and deriving trading strategies. Here, we explore historical lead-lag relationships among stocks in the Chinese stock market. Strongly positive lagged correlations can be empirically observed. We demonstrate this lead-lag phenomenon is not constant but temporally emerges during certain periods. By introducing moving time window method, we transform the lead-lag dynamics into a series of asymmetric lagged correlation matrices. Dynamic lead-lag structures are uncovered in the form of temporal network structures. We find that the size of lead-lag group experienced a rapid drop during the year 2012, which signaled a re-balance of the stock market. On the daily timescale, we find the lead-lag structure exhibits several persistent patterns, which can be characterized by the Jaccard matrix. We show significant market events can be distinguished in the Jaccard matrix diagram. Taken together, we study an integration of all the temporal networks and identify several leading stock sectors, which are in accordance with the common Chinese economic fundamentals.
Microbial detection method based on sensing molecular hydrogen
NASA Technical Reports Server (NTRS)
Wilkins, J. R.; Stoner, G. E.; Boykin, E. H.
1974-01-01
A simple method for detecting bacteria, based on the time of hydrogen evolution, was developed and tested against various members of the Enterobacteriaceae group. The test system consisted of (1) two electrodes, platinum and a reference electrode, (2) a buffer amplifier, and (3) a strip-chart recorder. Hydrogen evolution was measured by an increase in voltage in the negative (cathodic) direction. A linear relationship was established between inoculum size and the time hydrogen was detected (lag period). Lag times ranged from 1 h for 1 million cells/ml to 7 h for 1 cell/ml. For each 10-fold decrease in inoculum, length of the lag period increased 60 to 70 min. Based on the linear relationship between inoculum and lag period, these results indicate the potential application of the hydrogen-sensing method for rapidly detecting coliforms and other gas-producing microorganisms in a variety of clinical, food, and other samples.
Time lag and communication in changing unpopular norms.
Gërxhani, Klarita; Bruggeman, Jeroen
2015-01-01
Humans often coordinate their social lives through norms. When a large majority of people are dissatisfied with an existing norm, it seems obvious that they will change it. Often, however, this does not occur. We investigate how a time lag between individual support of a norm change and the change itself hinders such change, related to the critical mass of supporters needed to effectuate the change, and the (im)possibility of communicating about it. To isolate these factors, we utilize a laboratory experiment. As predicted, we find unambiguous effects of time lag on precluding norm change; a higher threshold for a critical mass does so as well. Communication facilitates choosing superior norms but it does not necessarily lead to norm change when the uncertainty on whether there will be a norm change in the future is high. Communication seems to help coordination on actions at the present but not the future. Hence, the uncertainty driven by time lag makes individuals choose the status quo, here the unpopular norm.
Time Lag and Communication in Changing Unpopular Norms
Gërxhani, Klarita; Bruggeman, Jeroen
2015-01-01
Humans often coordinate their social lives through norms. When a large majority of people are dissatisfied with an existing norm, it seems obvious that they will change it. Often, however, this does not occur. We investigate how a time lag between individual support of a norm change and the change itself hinders such change, related to the critical mass of supporters needed to effectuate the change, and the (im)possibility of communicating about it. To isolate these factors, we utilize a laboratory experiment. As predicted, we find unambiguous effects of time lag on precluding norm change; a higher threshold for a critical mass does so as well. Communication facilitates choosing superior norms but it does not necessarily lead to norm change when the uncertainty on whether there will be a norm change in the future is high. Communication seems to help coordination on actions at the present but not the future. Hence, the uncertainty driven by time lag makes individuals choose the status quo, here the unpopular norm. PMID:25880200
Calculation of power spectrums from digital time series with missing data points
NASA Technical Reports Server (NTRS)
Murray, C. W., Jr.
1980-01-01
Two algorithms are developed for calculating power spectrums from the autocorrelation function when there are missing data points in the time series. Both methods use an average sampling interval to compute lagged products. One method, the correlation function power spectrum, takes the discrete Fourier transform of the lagged products directly to obtain the spectrum, while the other, the modified Blackman-Tukey power spectrum, takes the Fourier transform of the mean lagged products. Both techniques require fewer calculations than other procedures since only 50% to 80% of the maximum lags need be calculated. The algorithms are compared with the Fourier transform power spectrum and two least squares procedures (all for an arbitrary data spacing). Examples are given showing recovery of frequency components from simulated periodic data where portions of the time series are missing and random noise has been added to both the time points and to values of the function. In addition the methods are compared using real data. All procedures performed equally well in detecting periodicities in the data.
Song, Hong-Tao; Zhang, Qian; Jiang, Peng; Guo, Tao; Chen, Da-Wei; He, Zhong-Gui
2006-09-01
To prepare a sustained-release formulation of traditional Chinese medicine compound recipe by adopting time-controlled release techniques. Shuxiong tablets were chosen as model drug. The prescription and technique of core tablets were formulated with selecting disintegrating time and swelling volume of core tablets in water as index. The time-controlled release tablets were prepared by adopting press-coated techniques, using PEG6000, HCO and EVA as coating materials. The influences of compositions, preparation process and dissolution conditions in vitro on the lag time (T(lag)) of drug release were investigated. The composition of core tablets was as follow: 30% of drug, 50% MCC and 20% CMS-Na. The T(lag) of time-controlled release tablets was altered remarkably by PEG6000 content of the outer layer, the amount of outer layer and hardness of tablet. The viscosity of dissolution media and basket rotation had less influence on the T(lag) but more on rate of drug release. The core tablets pressed with the optimized composition had preferable swelling and disintegrating properties. The shuxiong sustained-release formulations which contained core tablet and two kinds of time-controlled release tablets with 3 h and 6 h of T(lag) could release drug successively at 0 h, 3 h and 6 h in vitro. The technique made it possible that various components with extremely different physicochemical properties in these preparations could release synchronously.
TIME-DEPENDENT ELECTRON ACCELERATION IN BLAZAR TRANSIENTS: X-RAY TIME LAGS AND SPECTRAL FORMATION
DOE Office of Scientific and Technical Information (OSTI.GOV)
Lewis, Tiffany R.; Becker, Peter A.; Finke, Justin D., E-mail: pbecker@gmu.edu, E-mail: tlewis13@gmu.edu, E-mail: justin.finke@nrl.navy.mil
2016-06-20
Electromagnetic radiation from blazar jets often displays strong variability, extending from radio to γ -ray frequencies. In a few cases, this variability has been characterized using Fourier time lags, such as those detected in the X-rays from Mrk 421 using Beppo SAX. The lack of a theoretical framework to interpret the data has motivated us to develop a new model for the formation of the X-ray spectrum and the time lags in blazar jets based on a transport equation including terms describing stochastic Fermi acceleration, synchrotron losses, shock acceleration, adiabatic expansion, and spatial diffusion. We derive the exact solution formore » the Fourier transform of the electron distribution and use it to compute the Fourier transform of the synchrotron radiation spectrum and the associated X-ray time lags. The same theoretical framework is also used to compute the peak flare X-ray spectrum, assuming that a steady-state electron distribution is achieved during the peak of the flare. The model parameters are constrained by comparing the theoretical predictions with the observational data for Mrk 421. The resulting integrated model yields, for the first time, a complete first-principles physical explanation for both the formation of the observed time lags and the shape of the peak flare X-ray spectrum. It also yields direct estimates of the strength of the shock and the stochastic magnetohydrodynamical wave acceleration components in the Mrk 421 jet.« less
Cloud-to-ground lightning and surface rainfall in warm-season Florida thunderstorms
Gungle, B.; Krider, E.P.
2006-01-01
Relationships between cloud-to-ground (CG) lightning and surface rainfall have been examined in nine isolated, warm-season thunderstorms on the east coast of central Florida. CG flashes and the associated rain volumes were measured as a function of time in storm-centered reference frames that followed each storm over a network of rain gauges. Values of the storm-average rain volume per CG flash ranged from 0.70 ?? 104 to 6.4 ?? 104 m3/CG flash, with a mean (and standard deviation) of 2.6 ?? 104 ?? 2.1 ?? 104 m3/CG flash. Values of the rain volume concurrent with CG flashes ranged from 0.11 ?? 104 to 4.9 ?? 104 m3/CG flash with a mean of 2.1 ?? 104 ?? 2.0 ?? 104 m3/CG flash. The lag-time between the peak CG flash rate and the peak rainfall rate (using 5 min bins), and the results of a lag correlation analysis, show that surface rainfall tends to follow the lightning (positive lag) by up to 20 min in six storms. In one storm the rainfall preceded the lightning by 5 min, and two storms had nonsignificant lags. Values of the lagged rain volume concurrent with CG flashes ranged from 0.43 ?? 104 to 4.9 ?? 104 m3/CG flash, and the mean was 1.9 ?? 104 ?? 1.7 ?? 104 m3/CG flash. For the five storms that produced 12 or more flashes and had significant lags, a plot of the optimum lag time versus the total number of CG flashes shows a linear trend (R2 = 0.56). The number of storms is limited, but the lag results do indicate that large storms tend to have longer lags. A linear fit to the lagged rain volume vs. the number of concurrent CG flashes has a slope of 1.9 ?? 104 m3/CG flash (R2 = 0.83). We conclude that warm-season Florida thunderstorms produce a roughly constant rain volume per CG flash and that CG lightning can be used to estimate the location and intensity of convective rainfall in that weather regime. Copyright 2006 by the American Geophysical Union.
Population pharmacokinetics of oxycodone in patients with cancer-related pain.
Komatsu, Toshiaki; Kokubun, Hideya; Suzuki, Ai; Takayanagi, Risa; Yamada, Yasuhiko; Matoba, Motohiro; Yago, Kazuo
2012-09-01
Oxycodone is an opioid widely prescribed to cancer patients for pain relief. However, the pharmacokinetics of oxycodone has not been sufficiently examined. Therefore the aim of this work was to study population pharmacokinetics of oxycodone in patients with cancer pain. The authors analyzed 108 serum oxycodone samples of 33 individuals with nonlinear mixed-effects model (NONMEM). Population pharmacokinetics was calculated using the one-compartment model of clearance, volume of distribution, bioavailability, absorption constant rate, and lag time. An exponential error model was used to determine interindividual variability and a relative error model was applied to assess residual variability. Population pharmacokinetics of oxycodone at the end point were as follows: CL(L/h) = 10.7 × [1 + (2 - Child-Pugh Classification)] (Class: A = 0, B = 1, C = 2); V(d) (L) = 193; k(a) (h(-1)) = 0.336; T(lag) (h) = 0.859; F (%) = 63.9. Interindividual variability was CL: 30.5%, V(d): 44.6%, and F: 37.0%, and residual variability was 16.2%. As the total clearance in patients with liver dysfunction (Child-Pugh class B) was reduced to 33.3%, serum concentration of oxycodone increased by 1.5. Therefore, it became clear that dose adjustments are essential when treating patients with liver dysfunction. These findings suggest that population parameters are useful for evaluating pharmacokinetics of oxycodone in patients with cancer pain.
Response of spectral vegetation indices to soil moisture in grasslands and shrublands
Zhang, Li; Ji, Lei; Wylie, Bruce K.
2011-01-01
The relationships between satellite-derived vegetation indices (VIs) and soil moisture are complicated because of the time lag of the vegetation response to soil moisture. In this study, we used a distributed lag regression model to evaluate the lag responses of VIs to soil moisture for grasslands and shrublands at Soil Climate Analysis Network sites in the central and western United States. We examined the relationships between Moderate Resolution Imaging Spectroradiometer (MODIS)-derived VIs and soil moisture measurements. The Normalized Difference Vegetation Index (NDVI) and Normalized Difference Water Index (NDWI) showed significant lag responses to soil moisture. The lag length varies from 8 to 56 days for NDVI and from 16 to 56 days for NDWI. However, the lag response of NDVI and NDWI to soil moisture varied among the sites. Our study suggests that the lag effect needs to be taken into consideration when the VIs are used to estimate soil moisture.
Van Batavia, Jason P; Combs, Andrew J; Hyun, Grace; Bayer, Agnes; Medina-Kreppein, Daisy; Schlussel, Richard N; Glassberg, Kenneth I
2011-10-01
Noninvasive uroflowmetry with simultaneous electromyography is useful to triage cases of lower urinary tract symptoms into 4 urodynamically defined conditions, especially when incorporating short and long electromyography lag times in the analysis. We determined the prevalence of these 4 conditions at a single referral institution and the usefulness of uroflowmetry with simultaneous electromyography and electromyography lag time to confirm the diagnosis, guide treatment and monitor response. We retrospectively reviewed the records of 100 consecutive normal children who presented with persistent lower urinary tract symptoms, underwent uroflowmetry with electromyography as part of the initial evaluation and were diagnosed with 1 of 4 conditions based on certain uroflowmetry/electromyography features. The conditions included 1) dysfunctional voiding--active pelvic floor electromyography during voiding with or without staccato flow, 2a) idiopathic detrusor overactivity disorder-A--a quiet pelvic floor during voiding and shortened lag time (less than 2 seconds), 2b) idiopathic detrusor overactivity disorder-B--a quiet pelvic floor with a normal lag time, 3) detrusor underutilization disorder--volitionally deferred voiding with expanded bladder capacity but a quiet pelvic floor, and 4) primary bladder neck dysfunction--prolonged lag time (greater than 6 seconds) and a depressed, right shifted uroflowmetry curve with a quiet pelvic floor during voiding. Treatment was tailored to the underlying condition in each patient. The group consisted of 50 males and 50 females with a mean age of 8 years (range 3 to 18). Dysfunctional voiding was more common in females (p <0.05) while idiopathic detrusor overactivity disorder-B and primary bladder neck dysfunction were more common in males (p <0.01). With treatment uroflowmetry parameters normalized for all types. Electromyography lag time increased in idiopathic detrusor overactivity disorder-A cases and decreased in primary bladder neck dysfunction cases. Noninvasive uroflowmetry with simultaneous electromyography offers an excellent alternative to invasive urodynamics to diagnose 4 urodynamically defined conditions. It identifies the most appropriate therapy for the specific condition and objectively monitors the treatment response. Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Bentz, Misty C.; Walsh, Jonelle L.; Barth, Aaron J.
2009-11-01
We have recently completed a 64-night spectroscopic monitoring campaign at the Lick Observatory 3-m Shane telescope with the aim of measuring the masses of the black holes in 12 nearby (z < 0.05) Seyfert 1 galaxies with expected masses in the range approx10{sup 6}-10{sup 7} M {sub sun} and also the well-studied nearby active galactic nucleus (AGN) NGC 5548. Nine of the objects in the sample (including NGC 5548) showed optical variability of sufficient strength during the monitoring campaign to allow for a time lag to be measured between the continuum fluctuations and the response to these fluctuations in themore » broad Hbeta emission. We present here the light curves for all the objects in this sample and the subsequent Hbeta time lags for the nine objects where these measurements were possible. The Hbeta lag time is directly related to the size of the broad-line region (BLR) in AGNs, and by combining the Hbeta lag time with the measured width of the Hbeta emission line in the variable part of the spectrum, we determine the virial mass of the central supermassive black hole in these nine AGNs. The absolute calibration of the black hole masses is based on the normalization derived by Onken et al., which brings the masses determined by reverberation mapping into agreement with the local M {sub BH}-sigma{sub *}relationship for quiescent galaxies. We also examine the time lag response as a function of velocity across the Hbeta line profile for six of the AGNs. The analysis of four leads to rather ambiguous results with relatively flat time lags as a function of velocity. However, SBS 1116+583A exhibits a symmetric time lag response around the line center reminiscent of simple models for circularly orbiting BLR clouds, and Arp 151 shows an asymmetric profile that is most easily explained by a simple gravitational infall model. Further investigation will be necessary to fully understand the constraints placed on the physical models of the BLR by the velocity-resolved response in these objects.« less
ERIC Educational Resources Information Center
Hays, Ron D.; And Others
1994-01-01
Applied structural equation modeling to evaluation of cross-lagged panel models. Self-reports of physical and mental health at three time points spanning four-year interval were analyzed to illustrate cross-lagged analysis methodology. Data were analyzed from 856 patients with hypertension, diabetes, heart disease, or depression. Cross-lagged…
Limits on an energy dependence of the speed of light from a flare of the active galaxy PKS 2155-304.
Aharonian, F; Akhperjanian, A G; Barres de Almeida, U; Bazer-Bachi, A R; Becherini, Y; Behera, B; Beilicke, M; Benbow, W; Bernlöhr, K; Boisson, C; Bochow, A; Borrel, V; Braun, I; Brion, E; Brucker, J; Brun, P; Bühler, R; Bulik, T; Büsching, I; Boutelier, T; Carrigan, S; Chadwick, P M; Charbonnier, A; Chaves, R C G; Chounet, L-M; Clapson, A C; Coignet, G; Costamante, L; Dalton, M; Degrange, B; Deil, C; Dickinson, H J; Djannati-Ataï, A; Domainko, W; Drury, L O'C; Dubois, F; Dubus, G; Dyks, J; Egberts, K; Emmanoulopoulos, D; Espigat, P; Farnier, C; Feinstein, F; Fiasson, A; Förster, A; Fontaine, G; Füssling, M; Gabici, S; Gallant, Y A; Gérard, L; Giebels, B; Glicenstein, J F; Glück, B; Goret, P; Hadjichristidis, C; Hauser, D; Hauser, M; Heinz, S; Heinzelmann, G; Henri, G; Hermann, G; Hinton, J A; Hoffmann, A; Hofmann, W; Holleran, M; Hoppe, S; Horns, D; Jacholkowska, A; de Jager, O C; Jung, I; Katarzyński, K; Kaufmann, S; Kendziorra, E; Kerschhaggl, M; Khangulyan, D; Khélifi, B; Keogh, D; Komin, Nu; Kosack, K; Lamanna, G; Lenain, J-P; Lohse, T; Marandon, V; Martin, J M; Martineau-Huynh, O; Marcowith, A; Maurin, D; McComb, T J L; Medina, C; Moderski, R; Moulin, E; Naumann-Godo, M; de Naurois, M; Nedbal, D; Nekrassov, D; Niemiec, J; Nolan, S J; Ohm, S; Olive, J-F; de Oña Wilhelmi, E; Orford, K J; Osborne, J L; Ostrowski, M; Panter, M; Pedaletti, G; Pelletier, G; Petrucci, P-O; Pita, S; Pühlhofer, G; Punch, M; Quirrenbach, A; Raubenheimer, B C; Raue, M; Rayner, S M; Renaud, M; Rieger, F; Ripken, J; Rob, L; Rosier-Lees, S; Rowell, G; Rudak, B; Ruppel, J; Sahakian, V; Santangelo, A; Schlickeiser, R; Schöck, F M; Schröder, R; Schwanke, U; Schwarzburg, S; Schwemmer, S; Shalchi, A; Skilton, J L; Sol, H; Spangler, D; Stawarz, Ł; Steenkamp, R; Stegmann, C; Superina, G; Tam, P H; Tavernet, J-P; Terrier, R; Tibolla, O; van Eldik, C; Vasileiadis, G; Venter, C; Vialle, J P; Vincent, P; Vivier, M; Völk, H J; Volpe, F; Wagner, S J; Ward, M; Zdziarski, A A; Zech, A
2008-10-24
In the past few decades, several models have predicted an energy dependence of the speed of light in the context of quantum gravity. For cosmological sources such as active galaxies, this minuscule effect can add up to measurable photon-energy dependent time lags. In this Letter a search for such time lags during the High Energy Stereoscopic System observations of the exceptional very high energy flare of the active galaxy PKS 2155-304 on 28 July 2006 is presented. Since no significant time lag is found, lower limits on the energy scale of speed of light modifications are derived.
Effectiveness of Circadian countermeasures in simulated transmeridian flight schedules
NASA Technical Reports Server (NTRS)
Moline, Margaret L.; Monk, Timothy H.
1989-01-01
The symptoms of jet-lag commonly afflict travelers who cross time zones. Insomnia during the new night, daytime fatigue, malaise, sleepiness, and gastrointestinal disturbances can occur for as long as 3 weeks after jet travel across even a few time zones. These symptoms are largely due to the slow rate of adjustment of the internal circadian timing system to the new time zone. Since business (or pleasure) can be seriously interrupted by such symptoms, it is important to determine ways to speed up the adjustment process to ameliorate the symptoms. Airline pilots have reported that they frequently nap to counter jet lag symptoms, and that they view this as a useful technique. Napping as a countermeasure would be attractive since it is practical and would take advantage of a naturally occurring phase of sleepiness after lunch. Napping also makes sense since insomnia is a common jet lag symptom. Thus, a laboratory simulation of jet lag was designed to test the ability of napping to increase the rate of adjustment following a time zone shift in a population of middle-aged men.
Throwing Pattern: Changes in Timing of Joint Lag According to Age between and within Skill Level
ERIC Educational Resources Information Center
Southard, Dan
2009-01-01
Accomplished throwers conserve angular momentum when distal joints of the throwing arm reach peak velocity at a later time than their proximal neighbors. The result is an increase in velocity of the most distal segment--the hand. Past research indicates that skill level varies by the number of joints experiencing distal timing lag (time to peak…
Sega, Emanuela I.; Leveson-Gower, Dennis B.; Florek, Mareike; Schneidawind, Dominik; Luong, Richard H.; Negrin, Robert S.
2014-01-01
Lag-3 has emerged as an important molecule in T cell biology. We investigated the role of Lag-3 in conventional T cell (Tcon) and regulatory T cell (Treg) function in murine GVHD with the hypothesis that Lag-3 engagement diminishes alloreactive T cell responses after bone marrow transplantation. We demonstrate that Lag-3 deficient Tcon (Lag-3−/− Tcon) induce significantly more severe GVHD than wild type (WT) Tcon and that the absence of Lag-3 on CD4 but not CD8 T cells is responsible for exacerbating GVHD. Lag-3−/− Tcon exhibited increased activation and proliferation as indicated by CFSE and bioluminescence imaging analyses and higher levels of activation markers such as CD69, CD107a, granzyme B, and Ki-67 as well as production of IL-10 and IFN-g early after transplantation. Lag-3−/− Tcon were less responsive to suppression by WT Treg as compared to WT Tcon. The absence of Lag-3, however, did not impair Treg function as both Lag-3−/− and WT Treg equally suppress the proliferation of Tcon in vitro and in vivo and protect against GVHD. Further, we demonstrate that allogeneic Treg acquire recipient MHC class II molecules through a process termed trogocytosis. As MHC class II is a ligand for Lag-3, we propose a novel suppression mechanism employed by Treg involving the acquisition of host MHC-II followed by the engagement of Lag-3 on T cells. These studies demonstrate for the first time the biologic function of Lag-3 expression on conventional and regulatory T cells in GVHD and identify Lag-3 as an important regulatory molecule involved in alloreactive T cell proliferation and activation after bone marrow transplantation. PMID:24475140
NASA Astrophysics Data System (ADS)
Basu, N. B.; Van Meter, K. J.
2012-12-01
Increased nutrient loads delivered from watersheds due to agricultural intensification, industrialization, and urbanization have contributed globally to the persistence of large hypoxic zones in inland and coastal waters. Watershed management practices targeting these non-point source pollutants often lead to little or no improvement in water quality, even after extensive implementation of conservation measures or Best Management Practices (BMPs). The lag time between implementation of a conservation measure and resultant water quality benefits has recently been recognized as an important factor in the "apparent" failure of these BMPs. When conservation measures are implemented without explicit consideration of the lag time and with expectations that they will lead to immediate benefits, the resulting failure to meet such expectations can discourage vital restoration efforts. It is therefore important to quantify the lag times associated with watershed management efforts a priori and to implement restoration strategies targeted specifically at minimizing lag times and maximizing restoration benefits. The focus of this research is to develop a framework for understanding the time lags between land-use changes and stream water quality benefits. We hypothesize that such time lags arise from nutrient legacies building over decades of fertilizer application. For nitrogen (N), one can conceptualize this as either hydrologic legacy, in the form of dissolved nitrate that is delayed due to slow groundwater transport, or as biogeochemical legacy, in the form of organic N, possibly in dissolved or readily mineralizable forms. Indeed, mass-balance studies across the Mississippi and Thames river basins indicate the possibility of missing N mass in these landscapes, with inputs being consistently greater than the outputs even when accounting for all possible pathways of nitrogen transformation. Historical soil data within the upper Mississippi River Basin (MRB) indicate that agriculture depletes organic N in surface soil, but leads to N accumulations deeper in the profile. Nitrogen accumulation estimates (approximately 2 million Mt/yr) based on the historical data are startlingly close to the deficit suggested by mass-balance studies of the MRB (3 million Mt/yr). Understanding the lag times associated with such biogeochemical legacies requires quantification of this accumulation as a function of landscape attributes, climate, and management controls, as well as the rate of mineralization of accumulated N after implementation of management practices. Understanding hydrologic legacy requires a partitioning of flow along various pathways (e.g., overland flow, tile flow, or groundwater pathways), and the distribution of travel times along the pathways. Based on this framework, we developed a coupled hydrologic and biogeochemical model to quantify these legacies and predict landscape recovery times as a function of natural and anthropogenic controls.
USDA-ARS?s Scientific Manuscript database
The performance of conventional filtering methods can be degraded by ignoring the time lag between soil moisture and discharge response when discharge observations are assimilated into streamflow modelling. This has led to the ongoing development of more optimal ways to implement sequential data ass...
R Jivani, Rishad; N Patel, Chhagan; M Patel, Dashrath; P Jivani, Nurudin
2010-01-01
The present study deals with development of a floating in-situ gel of the narrow absorption window drug baclofen. Sodium alginate-based in-situ gelling systems were prepared by dissolving various concentrations of sodium alginate in deionized water, to which varying concentrations of drug and calcium bicarbonate were added. Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) were used to check the presence of any interaction between the drug and the excipients. A 3(2) full factorial design was used for optimization. The concentrations of sodium alginate (X1) and calcium bicarbonate (X2) were selected as the independent variables. The amount of the drug released after 1 h (Q1) and 10 h (Q10) and the viscosity of the solution were selected as the dependent variables. The gels were studied for their viscosity, in-vitro buoyancy and drug release. Contour plots were drawn for each dependent variable and check-point batches were prepared in order to get desirable release profiles. The drug release profiles were fitted into different kinetic models. The floating lag time and floating time found to be 2 min and 12 h respectively. A decreasing trend in drug release was observed with increasing concentrations of CaCO3. The computed values of Q1 and Q10 for the check-point batch were 25% and 86% respectively, compared to the experimental values of 27.1% and 88.34%. The similarity factor (f 2) for the check-point batch being 80.25 showed that the two dissolution profiles were similar. The drug release from the in-situ gel follows the Higuchi model, which indicates a diffusion-controlled release. A stomach specific in-situ gel of baclofen could be prepared using floating mechanism to increase the residence time of the drug in stomach and thereby increase the absorption.
Evolution of Accretion Disc Geometry of GRS 1915+105 during its χ state as revealed by TCAF solution
NASA Astrophysics Data System (ADS)
Dutta, Broja G.; Pal, Partha Sarathi; Chakrabarti, Sandip K.
2018-06-01
The evolution of the C-type low frequency quasi-periodic oscillations (LFQPOs) and associated time lag in transient black hole sources as a function of time can be explained by variation of the Compton cloud size in a Two Component Advective Flow solution (TCAF). A similar study of a persistent source, GRS 1915+105, has not been attempted. We fit the evolution of QPOs with propagatory oscillating shock (POS) solution for two sets of so-called χ-state observations and find that the shock steadily recedes with almost constant velocity when QPO frequency is decreasing and the spectrum is hardening. The shock moves inward with a constant velocity v0 = 473.0 cm s-1 and v0 = 400.0 cm s-1 respectively in these two cases, when the QPO frequency is increasing and the spectrum softens. This behavior is similar to what was observed in XTE J1550-564 during the 1998 outburst. The time lag measured at the QPO frequency varies in a similar way as the size of the Compton cloud. Most interestingly, in both the cases, the lag switches sign (hard lag to soft lag) at a QPO frequency of ˜2.3 - 2.5 Hz irrespective of the energy of photons. We find, at very low frequencies <1 Hz, the Comptonizing Efficiency (CE) increases with QPO frequency and at higher QPO frequencies the trend is opposite. The time lags become mostly positive at all energies when CE is larger than ˜0.85% for both the sources.
THE SPECTRAL-TIMING PROPERTIES OF UPPER AND LOWER kHz QPOs
DOE Office of Scientific and Technical Information (OSTI.GOV)
Peille, Philippe; Barret, Didier; Uttley, Phil, E-mail: philippe.peille@irap.omp.eu
2015-10-01
Soft lags from the emission of the lower kilohertz quasi-periodic oscillations (kHz QPOs) of neutron star low-mass X-ray binaries have been reported from 4U1608-522 and 4U1636-536. Those lags hold prospects for constraining the origin of the QPO emission. In this paper, we investigate the spectral-timing properties of both the lower and upper kHz QPOs from the neutron star binary 4U1728-34, using the entire Rossi X-Ray Timing Explorer archive on this source. We show that the lag-energy spectra of the two QPOs are systematically different: while the lower kHz QPO shows soft lags, the upper kHz QPO shows either a flatmore » lag-energy spectrum or hard variations lagging softer variations. This suggests two different QPO-generation mechanisms. We also performed the first spectral deconvolution of the covariance spectra of both kHz QPOs. The QPO spectra are consistent with Comptonized blackbody emission, similar to the one found in the time-averaged spectrum, but with a higher seed-photon temperature, suggesting that a more compact inner region of the Comptonization layer (boundary/spreading layer, corona) is responsible for the QPO emission. Considering our results together with other recent findings, this leads us to the hypothesis that the lower kHz QPO signal is generated by coherent oscillations of the compact boundary layer region itself. The upper kHz QPO signal may then be linked to less-coherent accretion-rate variations produced in the inner accretion disk, and is then detected when they reach the boundary layer.« less
On the phase lag of turbulent dissipation in rotating tidal flows
NASA Astrophysics Data System (ADS)
Zhang, Qianjiang; Wu, Jiaxue
2018-03-01
Field observations of rotating tidal flows in a shallow tidally swept sea reveal that a notable phase lag of both shear production and turbulent dissipation increases with height above the seafloor. These vertical delays of turbulent quantities are approximately equivalent in magnitude to that of squared mean shear. The shear production approximately equals turbulent dissipation over the phase-lag column, and thus a main mechanism of phase lag of dissipation is mean shear, rather than vertical diffusion of turbulent kinetic energy. By relating the phase lag of dissipation to that of the mean shear, a simple formulation with constant eddy viscosity is developed to describe the phase lag in rotating tidal flows. An analytical solution indicates that the phase lag increases linearly with height subjected to a combined effect of tidal frequency, Coriolis parameter and eddy viscosity. The vertical diffusion of momentum associated with eddy viscosity produces the phase lag of squared mean shear, and resultant delay of turbulent quantities. Its magnitude is inhibited by Earth's rotation. Furthermore, a theoretical formulation of the phase lag with a parabolic eddy viscosity profile can be constructed. A first-order approximation of this formulation is still a linear function of height, and its magnitude is approximately 0.8 times that with constant viscosity. Finally, the theoretical solutions of phase lag with realistic viscosity can be satisfactorily justified by realistic phase lags of dissipation.
Determination of the Time-Space Magnetic Correlation Functions in the Solar Wind
NASA Astrophysics Data System (ADS)
Weygand, J. M.; Matthaeus, W. H.; Kivelson, M.; Dasso, S.
2013-12-01
Magnetic field data from many different intervals and 7 different solar wind spacecraft are employed to estimate the scale-dependent time decorrelation function in the interplanetary magnetic field in both the slow and fast solar wind. This estimation requires correlations varying with both space and time lags. The two point correlation function with no time lag is determined by correlating time series data from multiple spacecraft separated in space and for complete coverage of length scales relies on many intervals with different spacecraft spatial separations. In addition we employ single spacecraft time-lagged correlations, and two spacecraft time lagged correlations to access different spatial and temporal correlation data. Combining these data sets gives estimates of the scale-dependent time decorrelation function, which in principle tells us how rapidly time decorrelation occurs at a given wavelength. For static fields the scale-dependent time decorrelation function is trivially unity, but in turbulence the nonlinear cascade process induces time-decorrelation at a given length scale that occurs more rapidly with decreasing scale. The scale-dependent time decorrelation function is valuable input to theories as well as various applications such as scattering, transport, and study of predictability. It is also a fundamental element of formal turbulence theory. Our results are extension of the Eulerian correlation functions estimated in Matthaeus et al. [2010], Weygand et al [2012; 2013].
Modeling eye gaze patterns in clinician-patient interaction with lag sequential analysis.
Montague, Enid; Xu, Jie; Chen, Ping-Yu; Asan, Onur; Barrett, Bruce P; Chewning, Betty
2011-10-01
The aim of this study was to examine whether lag sequential analysis could be used to describe eye gaze orientation between clinicians and patients in the medical encounter. This topic is particularly important as new technologies are implemented into multiuser health care settings in which trust is critical and nonverbal cues are integral to achieving trust. This analysis method could lead to design guidelines for technologies and more effective assessments of interventions. Nonverbal communication patterns are important aspects of clinician-patient interactions and may affect patient outcomes. The eye gaze behaviors of clinicians and patients in 110 videotaped medical encounters were analyzed using the lag sequential method to identify significant behavior sequences. Lag sequential analysis included both event-based lag and time-based lag. Results from event-based lag analysis showed that the patient's gaze followed that of the clinician, whereas the clinician's gaze did not follow the patient's. Time-based sequential analysis showed that responses from the patient usually occurred within 2 s after the initial behavior of the clinician. Our data suggest that the clinician's gaze significantly affects the medical encounter but that the converse is not true. Findings from this research have implications for the design of clinical work systems and modeling interactions. Similar research methods could be used to identify different behavior patterns in clinical settings (physical layout, technology, etc.) to facilitate and evaluate clinical work system designs.
Modeling Eye Gaze Patterns in Clinician-Patient Interaction with Lag Sequential Analysis
Montague, E; Xu, J; Asan, O; Chen, P; Chewning, B; Barrett, B
2011-01-01
Objective The aim of this study was to examine whether lag-sequential analysis could be used to describe eye gaze orientation between clinicians and patients in the medical encounter. This topic is particularly important as new technologies are implemented into multi-user health care settings where trust is critical and nonverbal cues are integral to achieving trust. This analysis method could lead to design guidelines for technologies and more effective assessments of interventions. Background Nonverbal communication patterns are important aspects of clinician-patient interactions and may impact patient outcomes. Method Eye gaze behaviors of clinicians and patients in 110-videotaped medical encounters were analyzed using the lag-sequential method to identify significant behavior sequences. Lag-sequential analysis included both event-based lag and time-based lag. Results Results from event-based lag analysis showed that the patients’ gaze followed that of clinicians, while clinicians did not follow patients. Time-based sequential analysis showed that responses from the patient usually occurred within two seconds after the initial behavior of the clinician. Conclusion Our data suggest that the clinician’s gaze significantly affects the medical encounter but not the converse. Application Findings from this research have implications for the design of clinical work systems and modeling interactions. Similar research methods could be used to identify different behavior patterns in clinical settings (physical layout, technology, etc.) to facilitate and evaluate clinical work system designs. PMID:22046723
A critique of the cross-lagged panel model.
Hamaker, Ellen L; Kuiper, Rebecca M; Grasman, Raoul P P P
2015-03-01
The cross-lagged panel model (CLPM) is believed by many to overcome the problems associated with the use of cross-lagged correlations as a way to study causal influences in longitudinal panel data. The current article, however, shows that if stability of constructs is to some extent of a trait-like, time-invariant nature, the autoregressive relationships of the CLPM fail to adequately account for this. As a result, the lagged parameters that are obtained with the CLPM do not represent the actual within-person relationships over time, and this may lead to erroneous conclusions regarding the presence, predominance, and sign of causal influences. In this article we present an alternative model that separates the within-person process from stable between-person differences through the inclusion of random intercepts, and we discuss how this model is related to existing structural equation models that include cross-lagged relationships. We derive the analytical relationship between the cross-lagged parameters from the CLPM and the alternative model, and use simulations to demonstrate the spurious results that may arise when using the CLPM to analyze data that include stable, trait-like individual differences. We also present a modeling strategy to avoid this pitfall and illustrate this using an empirical data set. The implications for both existing and future cross-lagged panel research are discussed. (c) 2015 APA, all rights reserved).
The Lag-Luminosity Relation in the GRB Source-Frame: An Investigation with Swift BAT Bursts
NASA Technical Reports Server (NTRS)
Ukwatta, T. N.; Dhuga, K. S.; Stamatikos, M.; Dermer, C. D.; Sakamoto, T.; Sonbas, E.; Parke, W. C.; Maximon, L. C.; Linnemann, J. T.; Bhat, P. N.;
2012-01-01
Spectral lag, which is defined as the difference in time of arrival of high and low energy photons, is a common feature in Gamma-ray Bursts (GRBs). Previous investigations have shown a correlation between this lag and the isotropic peak luminosity for long duration bursts. However, most of the previous investigations used lags extracted in the observer-frame only. In this work (based on a sample of 43 Swift long GRBs with known redshifts), we present an analysis of the lag-luminosity relation in the GRB source-frame. Our analysis indicates a higher degree of correlation -0.82+/-0.05 (chance probability of approx 5.5 X 10(exp -5) between the spectral lag and the isotropic peak luminosity, L(sub iso), with a best-fit power-law index of -1.2 +/- 0.2, such that L(sub iso) varies as lag(exp -1.2). In addition, there is an anti-correlation between the source-frame spectral lag and the source-frame peak energy of the burst spectrum, E(sub pk)(1 + z).
NASA Astrophysics Data System (ADS)
Penland, C.
2017-12-01
One way to test for the linearity of a multivariate system is to perform Linear Inverse Modeling (LIM) to a multivariate time series. LIM yields an estimated operator by combining a lagged covariance matrix with the contemporaneous covariance matrix. If the underlying dynamics is linear, the resulting dynamical description should not depend on the particular lag at which the lagged covariance matrix is estimated. This test is known as the "tau test." The tau test will be severely compromised if the lag at which the analysis is performed is approximately half the period of an internal oscillation frequency. In this case, the tau test will fail even though the dynamics are actually linear. Thus, until now, the tau test has only been possible for lags smaller than this "Nyquist lag." In this poster, we investigate the use of Hilbert transforms as a way to avoid the problems associated with Nyquist lags. By augmenting the data with dimensions orthogonal to those spanning the original system, information that would be inaccessible to LIM in its original form may be sampled.
Miller, Jeff; Sproesser, Gudrun; Ulrich, Rolf
2008-07-01
In two experiments, we used response signals (RSs) to control processing time and trace out speed--accuracy trade-off(SAT) functions in a difficult perceptual discrimination task. Each experiment compared performance in blocks of trials with constant and, hence, temporally predictable RS lags against performance in blocks with variable, unpredictable RS lags. In both experiments, essentially equivalent SAT functions were observed with constant and variable RS lags. We conclude that there is little effect of advance preparation for a given processing time, suggesting that the discrimination mechanisms underlying SAT functions are driven solely by bottom-up information processing in perceptual discrimination tasks.
Science, technology, and application of THz air photonics
NASA Astrophysics Data System (ADS)
Lu, X. F.; Clough, B.; Ho, I.-C.; Kaur, G.; Liu, J.; Karpowicz, N.; Dai, J. M.; Zhang, X.-C.
2010-11-01
The significant scientific and technological potential of terahertz (THz) wave sensing and imaging has been attracted considerable attention within many fields of research. However, the development of remote, broadband THz wave sensing technology is lagging behind the compelling needs that exist in the areas of astronomy, global environmental monitoring, and homeland security. This is due to the challenge posed by high absorption of ambient moisture in the THz range. Although various time-domain THz detection techniques have recently been demonstrated, the requirement for an on-site bias or forward collection of the optical signal inevitably prohibits their applications for remote sensing. The objective of this paper is to report updated THz air-plasma technology to meet this great challenge of remote sensing. A focused optical pulse (mJ pulse energy and femtosecond pulse duration) in gas creates a plasma, which can serve to generate intense, broadband, and directional THz waves in the far field.
Temperature and humidity profiles in the atmosphere from spaceborne lasers: A feasibility study
NASA Technical Reports Server (NTRS)
Grassl, H.; Schluessel, P.
1984-01-01
Computer simulations of the differential absorption lidar technique in a space craft for the purpose of temperature and humidity profiling indicate: (1) Current technology applied to O2 and H2O lines in the .7 to .8 micrometers wavelength band gives sufficiently high signal-to-noise ratios (up to 50 for a single pulse pair) if backscattering by aerosol particles is high, i.e. profiling accurate to 2 K for temperature and 10% for humidity should be feasible within the turbid lower troposphere in 1 km layers and with an averaging over approximately 100 pulses. (2) The impact of short term fluctuations in aerosol particle concentration is too big for a one laser system. Only a two laser system firing at a time lag of about 1 millisecond can surmount these difficulties. (3) The finite width of the laser line and the quasi-random shift of this line introduce tolerable, partly systematic errors.
Temporal studies of black hole X-ray transients during outburst decay
NASA Astrophysics Data System (ADS)
Kalemci, Emrah
Galactic black holes (GBH) are a class of astrophysical sources with X-ray emission that is powered by accretion from a companion star. An important goal of GBH research is to understand the accretion structure and the nature of the variability of these systems. The GBHs sometimes show significant changes in the X-ray emission properties, and these changes are called state transitions. The transitions are believed to be caused by variation of the mass accretion rate and changes in accretion geometry. Thus, their study provides valuable information on the nature of the accretion structure. In this thesis work, I present results from studying the spectral and temporal evolution of all GBH transients that have been observed with NASA's Rossi X-ray Timing Explorer during outburst decay. I explore the physical conditions before, during and after the state transition, characterize the quasi-periodic oscillations (QPO) and continuum of power spectral density (PSD) in different energy bands, and study the correlations between spectral and temporal fit parameters. I also analyze the evolution of the cross- spectral parameters during and after the transition. I show that the appearance of the broad band variability is coincident with an increase of power-law flux. The evolution of the characteristic frequencies and the spectral parameters after the transition are consistent with retreating of the inner accretion disk. The energy dependent PSD analysis shows that the level of variability increases with energy when there is significant soft flux from the optically thick accretion disk. The variability level also increases with energy if the absorption column density to the source is high. This may be a result of small angle scatterings of lower energy X-ray photons with the ISM dust around these sources. I find global correlations between the spectral index and three temporal fit parameters: the QPO frequency, the overall level of variability and the integrated time lag. The relation between the spectral index and the time lags are interpreted within the context of the average number of Compton scatterings and the temperature of the scattering medium. During the transitions, the average lag is higher and average coherence is lower. I discuss whether a hybrid accretion model, for which the hot electron corona is the base of an optically thin outflow or a jet, can explain the physical properties during the transition.
The Lag-Luminosity Relation in the GRB Source Frame: An Investigation with Swift BAT Bursts
NASA Technical Reports Server (NTRS)
Ukwatta, T. N.; Dhuga, K. S.; Stamatikos, M.; Dermer, C. D.; Sakamoto, T.; Sonbas, E.; Parke, W. C.; Maximon, L. C.; Linnemann, J. T.; Bhat, P. N.;
2011-01-01
Spectral lag. which is defined as the difference in time of arrival of high- and low-energy photons. is a common feature in gamma-ray bursts (GRBs). Previous investigations have shown a correlation between this lag and the isotropic peak luminosity for long duration bursts. However. most of the previous investigations used lags extracted in the observer frame only. In this work (based on a sample of 43 Swift long GRBs with known redshifts). we present an analysis of the lag-luminosity relation in the GRB source frame. Our analysis indicates a higher degree of correlation -0.82 +/- 0.05 (chance probability of approx. 5.5 x 10(exp -5) between the spectral lag and the isotropic peak luminosity, L(sub iso). with a best-fitting power-law index of -1.2 +/- 0.2. In addition, there is an anticorrelation between the source-frame spectral lag and the source-frame peak energy of the burst spectrum.
Ward, W K; Engle, J M; Branigan, D; El Youssef, J; Massoud, R G; Castle, J R
2012-08-01
Because declining glucose levels should be detected quickly in persons with Type 1 diabetes, a lag between blood glucose and subcutaneous sensor glucose can be problematic. It is unclear whether the magnitude of sensor lag is lower during falling glucose than during rising glucose. Initially, we analysed 95 data segments during which glucose changed and during which very frequent reference blood glucose monitoring was performed. However, to minimize confounding effects of noise and calibration error, we excluded data segments in which there was substantial sensor error. After these exclusions, and combination of data from duplicate sensors, there were 72 analysable data segments (36 for rising glucose, 36 for falling). We measured lag in two ways: (1) the time delay at the vertical mid-point of the glucose change (regression delay); and (2) determination of the optimal time shift required to minimize the difference between glucose sensor signals and blood glucose values drawn concurrently. Using the regression delay method, the mean sensor lag for rising vs. falling glucose segments was 8.9 min (95%CI 6.1-11.6) vs. 1.5 min (95%CI -2.6 to 5.5, P<0.005). Using the time shift optimization method, results were similar, with a lag that was higher for rising than for falling segments [8.3 (95%CI 5.8-10.7) vs. 1.5 min (95% CI -2.2 to 5.2), P<0.001]. Commensurate with the lag results, sensor accuracy was greater during falling than during rising glucose segments. In Type 1 diabetes, when noise and calibration error are minimized to reduce effects that confound delay measurement, subcutaneous glucose sensors demonstrate a shorter lag duration and greater accuracy when glucose is falling than when rising. © 2011 The Authors. Diabetic Medicine © 2011 Diabetes UK.
Testing Under Fire: Chicago's Problem.
ERIC Educational Resources Information Center
Byrd, Manford, Jr.
The history and development of city-wide testing programs in Chicago since 1936 are reviewed and placed in context with the impact on testing of Sputnik and the passage of the National Defense Education Act of 1958. Current testing problems include the time lag between events and curricular changes and new test construction, the time lag between…
Modeling Time-Dependent Association in Longitudinal Data: A Lag as Moderator Approach
ERIC Educational Resources Information Center
Selig, James P.; Preacher, Kristopher J.; Little, Todd D.
2012-01-01
We describe a straightforward, yet novel, approach to examine time-dependent association between variables. The approach relies on a measurement-lag research design in conjunction with statistical interaction models. We base arguments in favor of this approach on the potential for better understanding the associations between variables by…
Summer Travel: Plan Ahead To Stay Healthy
... Twery says. “It’s especially important before and during travel to consciously schedule time to sleep.” Too little sleep leads to poor ... and their ability to meet the challenges of travel.” Jet lag is another sleep concern for travelers crossing multiple time zones. Jet lag is often more severe for ...
Erdeljić, Viktorija; Francetić, Igor; Bošnjak, Zrinka; Budimir, Ana; Kalenić, Smilja; Bielen, Luka; Makar-Aušperger, Ksenija; Likić, Robert
2011-05-01
The relationship between antibiotic consumption and selection of resistant strains has been studied mainly by employing conventional statistical methods. A time delay in effect must be anticipated and this has rarely been taken into account in previous studies. Therefore, distributed lags time series analysis and simple linear correlation were compared in their ability to evaluate this relationship. Data on monthly antibiotic consumption for ciprofloxacin, piperacillin/tazobactam, carbapenems and cefepime as well as Pseudomonas aeruginosa susceptibility were retrospectively collected for the period April 2006 to July 2007. Using distributed lags analysis, a significant temporal relationship was identified between ciprofloxacin, meropenem and cefepime consumption and the resistance rates of P. aeruginosa isolates to these antibiotics. This effect was lagged for ciprofloxacin and cefepime [1 month (R=0.827, P=0.039) and 2 months (R=0.962, P=0.001), respectively] and was simultaneous for meropenem (lag 0, R=0.876, P=0.002). Furthermore, a significant concomitant effect of meropenem consumption on the appearance of multidrug-resistant P. aeruginosa strains (resistant to three or more representatives of classes of antibiotics) was identified (lag 0, R=0.992, P<0.001). This effect was not delayed and it was therefore identified both by distributed lags analysis and the Pearson's correlation coefficient. Correlation coefficient analysis was not able to identify relationships between antibiotic consumption and bacterial resistance when the effect was delayed. These results indicate that the use of diverse statistical methods can yield significantly different results, thus leading to the introduction of possibly inappropriate infection control measures. Copyright © 2010 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.
Chromatic induction in space and time.
Coia, Andrew J; Shevell, Steven K
2018-04-01
The color appearance of a light depends on variation in the complete visual field over both space and time. In the spatial domain, a chromatic stimulus within a patterned chromatic surround can appear a different hue than the same stimulus within a uniform surround. In the temporal domain, a stimulus presented as an element of a continuously changing chromaticity can appear a different color compared to the identical stimulus, presented simultaneously but viewed alone. This is the flash-lag effect for color, which has an analog in the domain of motion: a pulsed object seen alone can appear to lag behind an identical pulsed object that is an element of a motion sequence. Studies of the flash-lag effect for motion have considered whether it is mediated by a neural representation for the moving physical stimulus or, alternatively, for the perceived motion. The current study addresses this question for the flash-lag effect for color by testing whether the color flash lag depends on a representation of only the changing chromatic stimulus or, alternatively, its color percept, which can be altered by chromatic induction. baseline measurements for spatial chromatic induction determined the chromaticity of a flashed ring within a uniform surround that matched a flashed ring within a patterned surround. Baseline measurements for the color flash-lag effect determined the chromaticity of a pulsed ring presented alone (within a uniform surround) that matched a pulsed ring presented in a sequence of changing chromaticity over time (also within a uniform surround). Finally, the main experiments combined chromatic induction from a patterned surround and the flash-lag effect, in three conditions: (1) both the changing and pulsed rings were within a patterned chromatic surround; (2) the changing ring was within a patterned surround and the pulsed ring within a uniform surround; and (3) the changing ring was within a uniform surround and the pulsed ring within a patterned surround. the flash-lag measurements for a changing chromaticity were affected by perceptual changes induced by the surrounding chromatic pattern. Thus, the color shifts induced by a chromatic surround are incorporated in the neural representation mediating the flash-lag effect for color.
Thomsen, Maria; Rosenkilde, Mette Marie
2018-01-01
Insulin is a vital part of diabetes treatment, whereas glucagon is primarily used to treat insulin-induced hypoglycemia. However, glucagon is suggested to have a central role in the regulation of body weight, which would be beneficial for diabetic patients. Since the glucagon effect on blood glucose is known to be transient, it is relevant to investigate the pharmacodynamics of glucagon after repeated dosing. In the present study, we used telemetry to continuously measure blood glucose in streptozotocin induced diabetic Sprague-Dawley rats. This allowed for a more detailed analysis of glucose regulation compared to intermittent blood sampling. In particular, we evaluated the blood glucose-lowering effect of different insulin doses alone, and in combination with a long acting glucagon analog (LAG). We showed how the effect of the LAG accumulated and persisted over time. Furthermore, we found that addition of the LAG decreased body weight without affecting food intake. In a subsequent study, we focused on the glucagon effect on body weight and food intake during equal glycemic control. In order to obtain comparable maximum blood glucose lowering effect to insulin alone, the insulin dose had to be increased four times in combination with 1 nmol/kg of the LAG. In this set-up the LAG prevented further increase in body weight despite the four times higher insulin-dose. However, the body composition was changed. The insulin group increased both lean and fat mass, whereas the group receiving four times insulin in combination with the LAG only significantly increased the fat mass. No differences were observed in food intake, suggesting a direct effect on energy expenditure by glucagon. Surprisingly, we observed decreased levels of FGF21 in plasma compared to insulin treatment alone. With the combination of insulin and the LAG the blood glucose-lowering effect of insulin was prolonged, which could potentially be beneficial in diabetes treatment. PMID:29558502
Sleep and Alertness Management during Military Operations: Review and Plan of Action.
1999-11-01
1996 Suhneretal. 1998b 17 pax across 8 time zones eastwards 52 pax across 9 time zones west- and eastwards 20 aircrew across 11 time zones west...and eastwards 30 pax across 6 time zones eastwards 52 aircrew across 11 time zones west- and eastwards 29 Army personnel across 7- 9 time...Jet Lag De missie-effectiviteit heeft in de eerste dagen na verplaatsing over meerdere tijdzones te lijden onder de gevolgen van jet lag, zoals
Time-Lag Bias in Trials of Pediatric Antidepressants: A Systematic Review and Meta-Analysis
Reyes, Magdalena M.; Panza, Kaitlyn E.; Martin, Andrés; Bloch, Michael H.
2013-01-01
Objective To determine if there is evidence of a time-lag bias in the publication of pediatric antidepressant trials. Method We conducted a meta-analysis of published and unpublished randomized, placebo-controlled trials of serotonin reuptake inhibitors (SRIs) in subjects less than 18 years old with major depressive disorder. Our main outcomes were (1) time to publication of positive versus negative trials, and (2) proportion of treatment responders in trials with standard (< 3 years after study completion) versus delayed publication. Results We identified 15 randomized, placebo-controlled trials of SRIs for pediatric depression. Trials with negative findings had a significantly longer time to publication (median years ± standard deviation = 4.2 ±1.9) than trials with positive findings (2.2 ±0.9; log-rank χ2 = 4.35, p = 0.037). The estimated efficacy in trials with standard publication time (number needed to treat = 7, 95% CI: 5 – 11) was significantly greater than those with delayed publication (17, 95% CI: 9 – ∞; χ2 = 4.98, p = 0.025). The inflation-adjusted impact factor of journals for published trials with positive (15.33 ±11.01) and negative results (7.54 ±7.90) did not statistically differ (t = 1.4, df = 10, p = 0.17). Conclusions Despite a small number of trials of SRIs for pediatric antidepressants we found a significant evidence of time-lag bias in the publication of findings. This time-lag bias altered the perceived efficacy of pediatric antidepressants in the medical literature. Time-lag bias is not unique to child psychiatry and reflects a larger problem in scientific publishing. PMID:21156271
Modeling of Engine Parameters for Condition-Based Maintenance of the MTU Series 2000 Diesel Engine
2016-09-01
are suitable. To model the behavior of the engine, an autoregressive distributed lag (ARDL) time series model of engine speed and exhaust gas... time series model of engine speed and exhaust gas temperature is derived. The lag length for ARDL is determined by whitening of residuals using the...15 B. REGRESSION ANALYSIS ....................................................................15 1. Time Series Analysis
NASA Astrophysics Data System (ADS)
Gutowska, Dorota; Piskozub, Jacek
2017-04-01
There is a vast literature body on the climate indices and processes they represent. A large part of it deals with "teleconnections" or causal relations between them. However until recently time lagged correlations was the best tool of studying causation. However no correlation (even lagged) proves causation. We use a recently developed method of studying casual relations between short time series, Convergent Cross Mapping (CCM), to search for causation between the atmospheric (AO and NAO) and oceanic (AMO) indices. The version we have chosen (available as an R language package rEDM) allows for comparing time series with time lags. This work builds on previous one, showing with time-lagged correlations that AO/NAO precedes AMO by about 15 years and at the same time is preceded by AMO (but with an inverted sign) also by the same amount of time. This behaviour is identical to the relationship of a sine and cosine with the same period. This may suggest that the multidecadal oscillatory parts of the atmospheric and oceanic indices represent the same global-scale set of processes. In other words they may be symptoms of the same oscillation. The aim of present study is to test this hypothesis with a tool created specially for discovering causal relationships in dynamic systems.
Time-lagged intraspecific competition in temporally separated cohorts of a generalist insect.
Barnes, Elizabeth E; Murphy, Shannon M
2018-03-01
Competition can have far-reaching consequences for insect fitness and dispersion. Time-lagged interspecific competition is known to negatively affect fitness, yet time-lagged intraspecific competition is rarely studied outside of outbreak conditions. We tested the impact of competition between larval cohorts of the western tent caterpillar (Malacosoma californicum) feeding on chokecherry (Prunus virginiana). We reared larvae on host plants that either had or did not have feeding damage from tent caterpillars the previous season to test the bottom-up fitness effects of intraspecific competition. We measured host-plant quality to test potential mechanisms for bottom-up effects and conducted field oviposition surveys to determine if female adult tent caterpillars avoided host plants with evidence of prior tent caterpillar presence. We found that time-lagged intraspecific competition impacted tent caterpillar fitness by reducing female pupal mass, which is a predictor of lifetime fitness. We found that plants that had been fed upon by tent caterpillars the previous season had leaves that were significantly tougher than plants that had not been fed upon by tent caterpillars, which may explain why female tent caterpillars suffered reduced fitness on these plants. Finally, we found that there were fewer tent caterpillar egg masses on plants that had tent caterpillars earlier in the season than plants without tent caterpillars, which suggests that adult females avoid these plants for oviposition. Our results confirm that intraspecific competition occurs among tent caterpillars and suggests that time-lagged intraspecific competition has been overlooked as an important component of insect fitness.
Staying Healthy While You Travel (For Parents)
... ear discomfort , travel (or motion) sickness, and diarrhea . Jet Lag When you fly across time zones, it ... for longer than usual. In addition to tiredness, jet lag can also cause an upset stomach and ...
Aggregation of model amyloid insulin protein in crowding environments and under ac-electric fields
NASA Astrophysics Data System (ADS)
Zheng, Zhongli; Jing, Benxin; Murray, Brian; Sorci, Mirco; Belfort, Georges; Zhu, Y.
2013-03-01
In vitro experiments have been widely used to characterize the misfolding/unfolding pathway characteristic of amylodogenic proteins. Conversion from natively folded amyloidogenic proteins to oligomers via nucleation is the accepted path to fibril formation upon heating over a certain lag time period. In this work, we investigate the effect of crowing environment and external electric fields on the pathway and kinetics of insulin, a well-established amyloid model protein by single fluorescence spectroscopy and imaging. With added co-solutes, such as glycerol and polyvinylpyrrolidone (PVP), to mimic the cellular crowding environments, we have observed that the lag time can be significantly prolonged. The lag time increases with increasing co-solute concentration, yet showing little dependence on solution viscosity. Conversely, applied ac-electric fields can considerably shorten the lag timewhen a critical ac-voltage is exceeded. The strong dependence of lag time on ac-frequency over a narrow range of 500 Hz-5 kHz indicates the effect of ac-electroosmosis on the diffusion controlled process of insulin nucleation. Yet, no conformational structure is detected with insulin under applied ac-fields, suggesting the equivalence of ac-polarization to the conventional thermal activation process for insulin aggregation. These finding suggest that at least the aggregation kinetics of insulin can be altered by local solution condition or external stimuli, which gives new insight to the treatment of amyloid related diseases.
A Correlated Optical and Gamma Emission from GRB 081126A
DOE Office of Scientific and Technical Information (OSTI.GOV)
Gendre, B.; Klotz, A.; CESR, Observatoire Midi-Pyrenees, CNRS, Universite de Toulouse, BP 4346, F-31028-Toulouse Cedex 04
2010-10-15
We present an analysis of time-resolved optical emissions observed from the gamma-ray burst GRB 081126 during the prompt phase. The analysis employed time-resolved photometry using optical data obtained by the TAROT telescope, BAT data from the Swift spacecraft and time-resolved spectroscopy at high energies from the GBM instrument onboard the Fermi spacecraft. The optical emission of GRB 081126 is found to be compatible with the second gamma emission pulse shifted by a positive time-lag of 8.4{+-}3.9 sec. This is the first well resolved observation of a time lag between optical and gamma emissions during a gamma-ray burst. Our observations couldmore » potentially provide new constraints on the fireball model for gamma ray burst early emissions. Furthermore, observations of time-lags between optical and gamma ray photons provides an exciting opportunity to constrain quantum gravity theories.« less
Smith, M. G.
1985-01-01
The growth of coliform organisms on meat tissue from sheep carcasses processed in a commercial abattoir was investigated. The results indicated that for practical purposes the minimum temperature of growth of these organisms on meat may be taken as 8 degrees C. Equations were derived relating the generation time and the lag time of coliform organisms in raw blended mutton to the temperature at which the meat is held. Estimates of growth obtained with these equations were found to agree closely with the experimental results, especially at temperatures above 10 degrees C, and allowed the generation times and the lag times for all temperatures up to 40 degrees C to be calculated. These times were also found to agree closely with the times determined using a strain of Escherichia coli inoculated into blended mutton tissue. A strain of Salmonella typhimurium inoculated in the same way into blended mutton tissue gave longer generation and lag times at temperatures below 15 degrees C. Therefore, it is believed that the calculated tables of lag and generation times included in this paper can be used to determine the length of time raw chilled meat may be held afterwards at temperatures above the minimum temperature of growth without an increase in the number of any salmonella organisms present, and these times include a safety margin at each temperature. The study indicates that the mandatory codes of practice presently applied in commercial abattoirs are too stringent. Maintaining the temperature of boning rooms at 10 degrees C or less does not appear to be necessary providing the meat is processed within the calculated time limits. A relaxation of the restrictions on boning room temperatures would decrease costs, increase worker comfort and safety and would not compromise the bacteriological safety of the meat produced. PMID:3891847
A Disposable Tear Glucose Biosensor—Part 4
Engelschall, Erica; Lan, Kenneth; Shah, Pankti; Saez, Neil; Maxwell, Stephanie; Adamson, Teagan; Abou-Eid, Michelle; McAferty, Kenyon; Patel, Dharmendra R.; Cook, Curtiss B.
2014-01-01
Objective: A prototype tear glucose (TG) sensor was tested in New Zealand white rabbits to assess eye irritation, blood glucose (BG) and TG lag time, and correlation with BG. Methods: A total of 4 animals were used. Eye irritation was monitored by Lissamine green dye and analyzed using image analysis software. Lag time was correlated with an oral glucose load while recording TG and BG readings. Correlation between TG and BG were plotted against one another to form a correlation diagram, using a Yellow Springs Instrument (YSI) and self-monitoring of blood glucose as the reference measurements. Finally, TG levels were calculated using analytically derived expressions. Results: From repeated testing carried over the course of 12 months, little to no eye irritation was detected. TG fluctuations over time visually appeared to trace the same pattern as BG with an average lag times of 13 minutes. TG levels calculated from the device current measurements ranged from 4 to 20 mg/dL and correlated linearly with BG levels of 75-160 mg/dL (TG = 0.1723 BG = 7.9448 mg/dL; R2 = .7544). Conclusion: The first steps were taken toward preliminary development of a sensor for self-monitoring of tear glucose (SMTG). No conjunctival irritation in any of the animals was noted. Lag time between TG and BG was found to be noticeable, but a quantitative modeling to correlate lag time in this study is unnecessary. Measured currents from the sensors and the calculated TG showed promising correlation to BG levels. Previous analytical bench marking showed BG and TG levels consistent with other literature. PMID:24876546
Abdallah, Mohamed Abou-Elwafa; Pawar, Gopal; Harrad, Stuart
2015-11-01
Ethical and technical difficulties inherent to studies in human tissues are impeding assessment of the dermal bioavailability of brominated flame retardants (BFRs). This is further complicated by increasing restrictions on the use of animals in toxicity testing, and the uncertainties associated with extrapolating data from animal studies to humans due to inter-species variations. To overcome these difficulties, we evaluate 3D-human skin equivalents (3D-HSE) as a novel in vitro alternative to human and animal testing for assessment of dermal absorption of BFRs. The percutaneous penetration of hexabromocyclododecanes (HBCD) and tetrabromobisphenol-A (TBBP-A) through two commercially available 3D-HSE models was studied and compared to data obtained for human ex vivo skin according to a standard protocol. No statistically significant differences were observed between the results obtained using 3D-HSE and human ex vivo skin at two exposure levels. The absorbed dose was low (less than 7%) and was significantly correlated with log Kow of the tested BFR. Permeability coefficient values showed increasing dermal resistance to the penetration of γ-HBCD>β-HBCD>α-HBCD>TBBPA. The estimated long lag times (>30 min) suggests that frequent hand washing may reduce human exposure to HBCDs and TBBPA via dermal contact. Copyright © 2015 Elsevier Ltd. All rights reserved.
Yousef, A M; Melhem, M; Xue, B; Arafat, T; Reynolds, D K; Van Wart, S A
2013-05-01
Clopidogrel is metabolized primarily into an inactive carboxyl metabolite (clopidogrel-IM) or to a lesser extent an active thiol metabolite. A population pharmacokinetic (PK) model was developed using NONMEM(®) to describe the time course of clopidogrel-IM in plasma and to design a sparse-sampling strategy to predict clopidogrel-IM exposures for use in characterizing anti-platelet activity. Serial blood samples from 76 healthy Jordanian subjects administered a single 75 mg oral dose of clopidogrel were collected and assayed for clopidogrel-IM using reverse phase high performance liquid chromatography. A two-compartment (2-CMT) PK model with first-order absorption and elimination plus an absorption lag-time was evaluated, as well as a variation of this model designed to mimic enterohepatic recycling (EHC). Optimal PK sampling strategies (OSS) were determined using WinPOPT based upon collection of 3-12 post-dose samples. A two-compartment model with EHC provided the best fit and reduced bias in C(max) (median prediction error (PE%) of 9.58% versus 12.2%) relative to the basic two-compartment model, AUC(0-24) was similar for both models (median PE% = 1.39%). The OSS for fitting the two-compartment model with EHC required the collection of seven samples (0.25, 1, 2, 4, 5, 6 and 12 h). Reasonably unbiased and precise exposures were obtained when re-fitting this model to a reduced dataset considering only these sampling times. A two-compartment model considering EHC best characterized the time course of clopidogrel-IM in plasma. Use of the suggested OSS will allow for the collection of fewer PK samples when assessing clopidogrel-IM exposures. Copyright © 2013 John Wiley & Sons, Ltd.
Sheng, Yu-Cheng; Wang, Kun; He, Ying-Chun; Yang, Juan; Zheng, Qing-Shan
2010-11-01
To explore the pharmacokinetic/pharmacodynamic relationship of rabeprazole and the role of CYP2C19 genotypes after a single oral dose in healthy Chinese volunteers by a population approach. Plasma concentration time profile data and intragastric pH values of 19 genotyped healthy male adults after a single oral dose of rabeprazole in an open label randomized fashion were used for this population analysis. Simulation technology was performed to examine the rabeprazole response in subjects with different CYP2C19 genotypes to further investigate the effect of acid inhibition. The pharmacokinetics of rabeprazole was characterized by a two-compartment model with first order absorption and with an absorption lag-time. The results show that clearance of rabeprazole was affected by CYP2C19 genotypes (average clearances of homEM, hetEM, and PM were 13.9, 11.5, and 8.74 L·h(-1) respectively). An effect compartment with a sigmoidal Emax model was considered more rational for analyzing the relationship between rabeprazole concentrations and intragastric pH values. Simulated results suggest that rabeprazole 20 mg once daily for PMs is sufficient, but might be administered more frequently for other genotypes in treating gastro-esophageal reflux disease. The CYP2C19 genotype played a considerable role in the pharmacokinetic characteristics of rabeprazole, and this might need to be taken into account for clinical use.
Hagihara, Akihito; Onozuka, Daisuke; Miyazaki, Shougo; Abe, Takeru
2015-12-30
We examined whether the weekly number of newspaper articles reporting on influenza was related to the incidence of influenza in a large city. Prospective, non-randomised, observational study. Registry data of influenza cases in Fukuoka City, Japan. A total of 83,613 cases of influenza cases that occurred between October 1999 and March 2007 in Fukuoka City, Japan. A linear model with autoregressive time series errors was fitted to time series data on the incidence of influenza and the accumulated number of influenza-related newspaper articles with different time lags in Fukuoka City, Japan. In order to obtain further evidence that the number of newspaper articles a week with specific time lags is related to the incidence of influenza, Granger causality was also tested. Of the 16 models including 'number of newspaper articles' with different time lags between 2 and 17 weeks (xt-2 to t-17), the β coefficients of 'number of newspaper articles' at time lags between t-5 and t-13 were significant. However, the β coefficients of 'number of newspaper articles' that are significant with respect to the Granger causality tests (p<0.05) were the weekly number of newspaper articles at time lags between t-6 and t-10 (time shift of 10 weeks, β=-0.301, p<0.01; time shift of 9 weeks, β=-0.200, p<0.01; time shift of 8 weeks, β=-0.156, p<0.01; time shift of 7 weeks, β=-0.122, p<0.05; time shift of 6 weeks, β=-0.113, p<0.05). We found that the number of newspaper articles reporting on influenza in a week was related to the incidence of influenza 6-10 weeks after media coverage in a large city in Japan. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
Hagihara, Akihito; Onozuka, Daisuke; Miyazaki, Shougo; Abe, Takeru
2015-01-01
Objectives We examined whether the weekly number of newspaper articles reporting on influenza was related to the incidence of influenza in a large city. Design Prospective, non-randomised, observational study. Setting Registry data of influenza cases in Fukuoka City, Japan. Participants A total of 83 613 cases of influenza cases that occurred between October 1999 and March 2007 in Fukuoka City, Japan. Main outcome measure A linear model with autoregressive time series errors was fitted to time series data on the incidence of influenza and the accumulated number of influenza-related newspaper articles with different time lags in Fukuoka City, Japan. In order to obtain further evidence that the number of newspaper articles a week with specific time lags is related to the incidence of influenza, Granger causality was also tested. Results Of the 16 models including ‘number of newspaper articles’ with different time lags between 2 and 17 weeks (xt-2 to t-17), the β coefficients of ‘number of newspaper articles’ at time lags between t-5 and t-13 were significant. However, the β coefficients of ‘number of newspaper articles’ that are significant with respect to the Granger causality tests (p<0.05) were the weekly number of newspaper articles at time lags between t-6 and t-10 (time shift of 10 weeks, β=−0.301, p<0.01; time shift of 9 weeks, β=−0.200, p<0.01; time shift of 8 weeks, β=−0.156, p<0.01; time shift of 7 weeks, β=−0.122, p<0.05; time shift of 6 weeks, β=−0.113, p<0.05). Conclusions We found that the number of newspaper articles reporting on influenza in a week was related to the incidence of influenza 6–10 weeks after media coverage in a large city in Japan. PMID:26719323
ERIC Educational Resources Information Center
Rantanen, Johanna; Kinnunen, Ulla; Feldt, Taru; Pulkkinen, Lea
2008-01-01
The rank-order stability and cross-lagged relations between work-to-family conflict (WFC), family-to-work conflict (FWC), and psychological well-being were examined in two longitudinal studies with full two-wave panel designs. In Study 1 (n = 365), the time lag was one year, and in Study 2 (n = 153), six years. The Structural Equation Modeling…
DOE Office of Scientific and Technical Information (OSTI.GOV)
Shao, Lang; Wang, Fu-Ri; Cheng, Ye-Hao
We carry out a systematical study of the spectral lag properties of 50 single-pulsed gamma-ray bursts (GRBs) detected by the Fermi Gamma-Ray Burst Monitor. By dividing the light curves into multiple consecutive energy channels, we provide a new measurement of the spectral lag that is independent of energy channel selections. We perform a detailed statistical study of our new measurements. We find two similar power-law energy dependencies of both the pulse arrival time and pulse width. Our new results on the power-law indices would favor the relativistic geometric effects for the origin of spectral lag. However, a complete theoretical frameworkmore » that can fully account for the diverse energy dependencies of both arrival time and pulse width revealed in this work is still lacking. We also study the spectral evolution behaviors of the GRB pulses. We find that a GRB pulse with negligible spectral lag would usually have a shorter pulse duration and would appear to have a “hardness-intensity tracking” behavior, and a GRB pulse with a significant spectral lag would usually have a longer pulse duration and would appear to have a “hard-to-soft” behavior.« less
Nutrient pressures and legacies in a small agricultural karst catchment
NASA Astrophysics Data System (ADS)
Fenton, Owen; Mellander, Per-Erik; Daly, Karen; Wall, David P.; Jahangir, Mohammad M.; Jordan, Phil; Hennessey, Deirdre; Huebsch, Manuela; Blum, Philipp; Vero, Sara; Richards, Karl G.
2017-04-01
Catchments with short subsurface hydrologic time lags are commonly at risk for leached losses of nitrogen (N) and phosphorus (P). Such catchments are suitable for testing the efficacy of mitigation measures as management changes. In some sites, however, N and P may be retained in the soil and subsoil layers, and then leached, mobilised or attenuated over time. This biogeochemical time lag may therefore have enduring effects on the water quality. The aim of this study was to improve the understanding of N and P retention, attenuation and distribution of subsurface pathway in an intensively managed agricultural karst catchment with an oxidised aquifer setting, and also to inform how similar sites can be managed in the future. Results showed that in the years pre-2000 slurry from an on-site integrated pig production unit had been applied at rates of 33 t/ha annually, which supplied approximately 136 kg/ha total N and approximately 26 kg/ha total P annually. This practice contributed to large quantities of N (total N and NH4-N) and elevated soil test P (Morgan extractable P), present to a depth of 1 m. This store was augmented by recent surpluses of 263 kg N/ha, with leached N to groundwater of 82.5 kg N/ha and only 2.5 kg N/ha denitrified in the aquifer thereafter. Sub hourly spring data showed the largest proportion of N loss from small (54-88%) and medium fissure pathways (7- 21%) with longer hydrologic time lags, with smallest loads from either large fissure (1-13%) or conduit (1-10%) pathways with short hydrologic time lags (reaction time at the spring from onset of a rainfall event is within hours). Although soils were saturated in P and in mobile forms to 0.5 m, dissolved reactive P concentrations in groundwater remained low due to Ca and Mg limestone chemistry. Under these conditions a depletion of the legacy store, with no further inputs, would take approximately 50 years and with NO3-N concentrations in the source area dropping to levels that could sustain groundwater NO3-N concentrations below admissible levels within 9 years. Biogeochemical time lags (decades) are longer than hydrologic time lags on this site (months to years). Future management should target farm surpluses that maintain a legacy store at or below a soil organic N mass of ca. 20 kg N/ha. Incorporation of biogeochemical and hydrologic time lag principles into future water quality regulations will provide regulators with realistic expectations when implementing policies.
Lag and seasonality considerations in evaluating AVHRR NDVI response to precipitation
Ji, Lei; Peters, Albert J.
2005-01-01
Assessment of the relationship between the normalized difference vegetation index (NDVI) and precipitation is important in understanding vegetation and climate interaction at a large scale. NDVI response to precipitation, however, is difficult to quantify due to the lag and seasonality effects, which will vary due to vegetation cover type, soils and climate. A time series analysis was performed on biweekly NDVI and precipitation around weather stations in the northern and central U.S. Great Plains. Regression models that incorporate lag and seasonality effects were used to quantify the relationship between NDVI and lagged precipitation in grasslands and croplands. It was found that the time lag was shorter in the early growing season, but longer in the mid- to late-growing season for most locations. The regression models with seasonal adjustment indicate that the relationship between NDVI and precipitation over the entire growing season was strong, with R2 values of 0.69 and 0.72 for grasslands and croplands, respectively. We conclude that vegetation greenness can be predicted using current and antecedent precipitation, if seasonal effects are taken into account.
The growth of Listeria monocytogenes in cheese packed under a modified atmosphere.
Whitley, E; Muir, D; Waites, W M
2000-01-01
The effect of modified atmosphere Packaging (MAP) on the growth of Listeria monocytogenes in mould ripened cheeses was studied at refrigeration temperatures (2-8.3 degrees C) over a storage period of 6 weeks. Control experiments in cling film with no atmospheric modification produced a lag time before growth of up to 1 week and rapid subsequent growth. MAP with a CO2 concentration of less than 20% allowed growth to occur but when O2 was incorporated; the lag time was reduced from 3 to 2 weeks and subsequent growth was also faster, producing an increase in cell numbers of 1.4 log cycles over the incubation period. N2-MAP in the absence of O2 increased the lag time to 3 weeks and slowed growth, while the inclusion of CO2 extended the lag to 3 weeks and slowed subsequent growth even more. In MAP with 80:10:10 (v/v/v) N2:CO2:O2, there was a lag period of 2-3 weeks before growth of L. monocytogenes occurred, while the total viable aerobic count (TVAC) decreased by 2-3 log cycles and the total Lactobacillus count showed little change. It was concluded that MAP was not suitable for preventing the growth of L. monocytogenes in such cheeses.
Time-Lag Bias in Trials of Pediatric Antidepressants: A Systematic Review and Meta-Analysis
ERIC Educational Resources Information Center
Reyes, Magdalena M.; Panza, Kaitlyn E.; Martin, Andres; Bloch, Michael H.
2011-01-01
Objective: To determine whether there is evidence of a time-lag bias in the publication of pediatric antidepressant trials. Method: We conducted a meta-analysis of published and unpublished randomized placebo-controlled trials of serotonin reuptake inhibitors (SRIs) in subjects less than 18 years of age with major depressive disorder. Our main…
Heat conduction errors and time lag in cryogenic thermometer installations
NASA Technical Reports Server (NTRS)
Warshawsky, I.
1973-01-01
Installation practices are recommended that will increase rate of heat exchange between the thermometric sensing element and the cryogenic fluid and that will reduce the rate of undesired heat transfer to higher-temperature objects. Formulas and numerical data are given that help to estimate the magnitude of heat-conduction errors and of time lag in response.
A Voice Onset Time Analysis of Apical Stop Production in 3-Year-Olds
ERIC Educational Resources Information Center
Gilbert, John H. V.
1977-01-01
This paper reports data for voice onset time (VOT) for /d/ and /t/, from six children at average age 3;0. Values for /d/ clearly achieve the short voicing lag category of adults, reported previously. Values for /t/, however, are much more varied, although falling within the category long voicing lag. (CHK)
Individual Differences in Working-Memory Capacity and Task Resumption Following Interruptions
ERIC Educational Resources Information Center
Foroughi, Cyrus K.; Werner, Nicole E.; McKendrick, Ryan; Cades, David M.; Boehm-Davis, Deborah A.
2016-01-01
Previous research has shown that there is a time cost (i.e., a resumption lag) associated with resuming a task following an interruption and that the longer the duration of the interruption, the greater the time cost (i.e., resumption lag increases as interruption duration increases). The memory-for-goals model (Altmann & Trafton, 2002)…
Yoo, Hee-Doo; Cho, Hea-Young; Lee, Yong-Bok
2010-01-01
AIMS To investigate the influence of genetic polymorphisms in the CYP3A5, CYP2C19 and ABCB1 genes on the population pharmacokinetics of cilostazol in healthy subjects. METHODS Subjects who participated in four separate cilostazol bioequivalence studies with the same protocols were included in this retrospective analysis. One hundred and four healthy Korean volunteers were orally administered a single 50- or 100-mg dose of cilostazol. We estimated the population pharmacokinetics of cilostazol using a nonlinear mixed effects modelling (nonmem) method and explored the possible influence of genetic polymorphisms in CYP3A (CYP3A5*3), CYP2C19 (CYP2C19*2 and CYP2C19*3) and ABCB1 (C1236T, G2677T/A and C3435T) on the population pharmacokinetics of cilostazol. RESULTS A two-compartment model with a first-order absorption and lag time described the cilostazol serum concentrations well. The apparent oral clearance (CL/F) was estimated to be 12.8 l h−1. The volumes of the central and the peripheral compartment were characterized as 20.5 l and 73.1 l, respectively. Intercompartmental clearance was estimated at 5.6 l h−1. Absorption rate constant was estimated at 0.24 h−1 and lag time was predicted at 0.57 h. The genetic polymorphisms of CYP3A5 had a significant (P < 0.001) influence on the CL/F of cilostazol. When CYP2C19 was evaluated, a significant difference (P < 0.01) was observed among the three genotypes (extensive metabolizers, intermediate metabolizers and poor metabolizers) for the CL/F. In addition, a combination of CYP3A5 and CYP2C19 genotypes was found to be associated with a significant difference (P < 0.005) in the CL/F. When including these genotypes, the interindividual variability of the CL/F was reduced from 34.1% in the base model to 27.3% in the final model. However, no significant differences between the ABCB1 genotypes and cilostazol pharmacokinetic parameters were observed. CONCLUSIONS The results of the present study indicate that CYP3A5 and CYP2C19 polymorphisms explain the substantial interindividual variability that occurs in the metabolism of cilostazol. PMID:20078610
Delay time correction of the gas analyzer in the calculation of anatomical dead space of the lung.
Okubo, T; Shibata, H; Takishima, T
1983-07-01
By means of a mathematical model, we have studied a way to correct the delay time of the gas analyzer in order to calculate the anatomical dead space using Fowler's graphical method. The mathematical model was constructed of ten tubes of equal diameter but unequal length, so that the amount of dead space varied from tube to tube; the tubes were emptied sequentially. The gas analyzer responds with a time lag from the input of the gas signal to the beginning of the response, followed by an exponential response output. The single breath expired volume-concentration relationship was examined with three types of expired flow patterns of which were constant, exponential and sinusoidal. The results indicate that the time correction by the lag time plus time constant of the exponential response of the gas analyzer gives an accurate estimation of anatomical dead space. Time correction less inclusive than this, e.g. lag time only or lag time plus 50% response time, gives an overestimation, and a correction larger than this results in underestimation. The magnitude of error is dependent on the flow pattern and flow rate. The time correction in this study is only for the calculation of dead space, as the corrected volume-concentration curves does not coincide with the true curve. Such correction of the output of the gas analyzer is extremely important when one needs to compare the dead spaces of different gas species at a rather faster flow rate.
Sousa, Marcelo R; Jones, Jon P; Frind, Emil O; Rudolph, David L
2013-01-01
In contaminant travel from ground surface to groundwater receptors, the time taken in travelling through the unsaturated zone is known as the unsaturated zone time lag. Depending on the situation, this time lag may or may not be significant within the context of the overall problem. A method is presented for assessing the importance of the unsaturated zone in the travel time from source to receptor in terms of estimates of both the absolute and the relative advective times. A choice of different techniques for both unsaturated and saturated travel time estimation is provided. This method may be useful for practitioners to decide whether to incorporate unsaturated processes in conceptual and numerical models and can also be used to roughly estimate the total travel time between points near ground surface and a groundwater receptor. This method was applied to a field site located in a glacial aquifer system in Ontario, Canada. Advective travel times were estimated using techniques with different levels of sophistication. The application of the proposed method indicates that the time lag in the unsaturated zone is significant at this field site and should be taken into account. For this case, sophisticated and simplified techniques lead to similar assessments when the same knowledge of the hydraulic conductivity field is assumed. When there is significant uncertainty regarding the hydraulic conductivity, simplified calculations did not lead to a conclusive decision. Copyright © 2012 Elsevier B.V. All rights reserved.
TRACING THE REVERBERATION LAG IN THE HARD STATE OF BLACK HOLE X-RAY BINARIES
DOE Office of Scientific and Technical Information (OSTI.GOV)
De Marco, B.; Ponti, G.; Nandra, K.
2015-11-20
We report results obtained from a systematic analysis of X-ray lags in a sample of black hole X-ray binaries, with the aim of assessing the presence of reverberation lags and studying their evolution during outburst. We used XMM-Newton and simultaneous Rossi X-ray Timing Explorer (RXTE) observations to obtain broadband energy coverage of both the disk and the hard X-ray Comptonization components. In most cases the detection of reverberation lags is hampered by low levels of variability-power signal-to-noise ratio (typically when the source is in a soft state) and/or short exposure times. The most detailed study was possible for GX 339-4more » in the hard state, which allowed us to characterize the evolution of X-ray lags as a function of luminosity in a single source. Over all the sampled frequencies (∼0.05–9 Hz), we observe the hard lags intrinsic to the power-law component, already well known from previous RXTE studies. The XMM-Newton soft X-ray response allows us to detail the disk variability. At low frequencies (long timescales) the disk component always leads the power-law component. On the other hand, a soft reverberation lag (ascribable to thermal reprocessing) is always detected at high frequencies (short timescales). The intrinsic amplitude of the reverberation lag decreases as the source luminosity and the disk fraction increase. This suggests that the distance between the X-ray source and the region of the optically thick disk where reprocessing occurs gradually decreases as GX 339-4 rises in luminosity through the hard state, possibly as a consequence of reduced disk truncation.« less
Time-lag of the earthquake energy release between three seismic regions
NASA Astrophysics Data System (ADS)
Tsapanos, Theodoros M.; Liritzis, Ioannis
1992-06-01
Three complete data sets of strong earthquakes ( M≥5.5), which occurred in the seismic regions of Chile, Mexico and Kamchatka during the time period 1899 1985, have been used to test the existence of a time-lag in the seismic energy release between these regions. These data sets were cross-correlated in order to determine whether any pair of the sets are correlated. For this purpose statistical tests, such as the T-test, the Fisher's transformation and probability distribution have been applied to determine the significance of the obtained correlation coefficients. The results show that the time-lag between Chile and Kamchatka is -2, which means that Kamchatka precedes Chile by 2 years, with a correlation coefficient significant at 99.80% level, a weak correlation between Kamchatka-Mexico and noncorrelation for Mexico-Chile.
Brouwers, Joachim; Anneveld, Bart; Goudappel, Gert-Jan; Duchateau, Guus; Annaert, Pieter; Augustijns, Patrick; Zeijdner, Evelijn
2011-02-01
In the present study, we demonstrated the value of two advanced tools, the TNO gastric and small Intestinal Model (TIM-1) and magnetic resonance imaging (MRI), for the in vitro evaluation of food-dependent disintegration of immediate release fosamprenavir tablets. Upon introduction of a tablet with the nutritional drink Scandishake Mix® in the stomach compartment of TIM-1, simulating the fed state, disintegration and fosamprenavir dissolution were significantly postponed compared to the fasted state (lag time 80 ± 23 min). This resulted in a lag in the appearance of bioaccessible fosamprenavir (<5% during the first 2h), even though the nutritional state did not significantly alter the cumulative bioaccessibility after 5h. These results were in agreement with the previously observed postprandial delay in gastric fosamprenavir tablet disintegration and subsequent amprenavir absorption in healthy volunteers. Therefore, TIM-1 can be used in tablet development to identify food-induced disintegration issues causing unexpected clinical behavior. From a mechanistic perspective, we applied MRI to illustrate impaired water ingress in fosamprenavir tablets immersed in the nutritional drink compared to simulated gastric fluid. This effect may be attributed to both competition between nutritional components and the tablet for the available water (indicated by reduced rotational and translational diffusion) as well as the possible formation of a food-dependent precipitation layer on the HPMC-coated tablet. Copyright © 2010 Elsevier B.V. All rights reserved.
Anderson, Brian J; Woollard, Gerald A; Holford, Nicholas H G
2000-01-01
Aims The aims of this study were to describe paracetamol pharmacokinetics in neonates and infants. Methods Infants in their first 3 months of life (n = 30) were randomised to sequentially receive one of three paracetamol formulations (dose 30–40 mg kg−1) over a 2 day period. The formulations were (a) elixir, (b) glycogelatin capsule suppository and (c) triglyceride base suppository. Approximately six blood samples were taken after each dose over the subsequent 10–16 h. Data were analysed using a nonlinear mixed effect model. These neonatal and infant data were then included with data from four published studies of paracetamol pharmacokinetics (n = 221) and age-related pharmacokinetic changes investigated. Results Population pharmacokinetic parameter estimates and their coefficients of variation (CV%) for a one compartment model with first order input, lag time and first order elimination were volume of distribution 69.9 (18%) l and clearance 13.0 (41%) l h−1 (standardized to a 70 kg person). The volume of distribution decreased exponentially with a half-life of 1.9 days from 120 l 70 kg−1 at birth to 69.9 l 70 kg−1 by 14 days. Clearance increased from birth (4.9 l h−1 70 kg−1) with a half-life of 3.25 months to reach 12.4 l h−1 70 kg−1 by 12 months. The absorption half-life (tabs) for the oral preparation was 0.13 (154%) h with a lag time (tlag) of 0.39 h (31%). Absorption parameters for the triglyceride base and capsule suppositories were tabs 1.34 (90%) h, tlag 0.14 h (31%) and tabs 0.65 (63%) h, tlag 0.54 h (31%), respectively. The tabs for elixir and capsule suppository in children under 3 months were 3.68 and 1.51 times greater than children over 3 months. The relative bioavailability of rectal formulations compared with elixir were 0.67 (30%) and 0.61 (23%) for the triglyceride base and capsule suppositories, respectively. Conclusions Total body clearance of paracetamol at birth is 62% and volume of distribution 174% that of older children. A target concentration above 10 mg l−1 in approximately 50% subjects can be achieved by a dose from 45 mg kg−1 day−1 at birth and up to 90 mg kg−1 day−1 in 5-year-old children. A reduced dose of 75 mg kg−1 day−1 in an 8-year-old child is sufficient because clearance is a nonlinear function of weight. PMID:10930964
Collective Dynamics of Oscillator Networks: Why do we suffer from heavy jet lag?
NASA Astrophysics Data System (ADS)
Kori, Hiroshi
The circadian rhythm of the entire body in mammals is orchestrated by a small tissue in the brain called the suprachiamatic nucleus (SCN). The SCN consists of a population of neurons, each of which exhibit circadian (i.e., approximately 24 h) gene expression. Neurons form a complex network and interact with each other using various types of neurotransmitters. The rhythmic gene expressions of individual cells in the SCN synchronize through such interaction. Jet-lag symptoms arise from temporal mismatch between the internal circadian clock orchestrated by the SCN and external solar time. It may take about one week or even longer to recover from jet lag after a long-distance trip. We recently found that recovery from jet lag is considerably accelerated in the knocked-out (KO) mice lacking the receptors of a certain neurotransmitter in the SCN. Importantly, all other properties of mice including sleep-awake rhythms and breeding seem to be intact. Only the response to the jet lag changes. It was also found that after a few days of jet lag, cells in the SCN desynchronize in the wild type (WT) mice, whereas they do not in KO mice. This desynchrony might be a main reason for heavy jet lag symptoms. To understand the mechanism underlying jet lag, we propose a simple model of the SCN, which is a network of phase oscillators. Despite its simplicity, this model can reproduce important dynamical properties of the SCN. For example, this model reproduces the desynchrony of oscillators after jet lag. Moreover, when intercellular interaction is weaker, this desynchrony is suppressed and the recover from jet lag is considerably accelerated. Our mathematical study provides a deeper understanding of jet lag and an idea how to circumvent heavy jet lag symptoms
Evolutionary lag times and recent origin of the biota of an ancient desert (Atacama-Sechura).
Guerrero, Pablo C; Rosas, Marcelo; Arroyo, Mary T K; Wiens, John J
2013-07-09
The assembly of regional biotas and organismal responses to anthropogenic climate change both depend on the capacity of organisms to adapt to novel ecological conditions. Here we demonstrate the concept of evolutionary lag time, the time between when a climatic regime or habitat develops in a region and when it is colonized by a given clade. We analyzed the time of colonization of four clades (three plant genera and one lizard genus) into the Atacama-Sechura Desert of South America, one of Earth's driest and oldest deserts. We reconstructed time-calibrated phylogenies for each clade and analyzed the timing of shifts in climatic distributions and biogeography and compared these estimates to independent geological estimates of the time of origin of these deserts. Chaetanthera and Malesherbia (plants) and Liolaemus (animal) invaded arid regions of the Atacama-Sechura Desert in the last 10 million years, some 20 million years after the initial onset of aridity in the region. There are also major lag times between when these clades colonized the region and when they invaded arid habitats within the region (typically 4-14 million years). Similarly, hyperarid climates developed ∼8 million years ago, but the most diverse plant clade in these habitats (Nolana) only colonized them ∼2 million years ago. Similar evolutionary lag times may occur in other organisms and habitats, but these results are important in suggesting that many lineages may require very long time scales to adapt to modern desertification and climatic change.
Faes, Luca; Nollo, Giandomenico
2010-11-01
The Partial Directed Coherence (PDC) and its generalized formulation (gPDC) are popular tools for investigating, in the frequency domain, the concept of Granger causality among multivariate (MV) time series. PDC and gPDC are formalized in terms of the coefficients of an MV autoregressive (MVAR) model which describes only the lagged effects among the time series and forsakes instantaneous effects. However, instantaneous effects are known to affect linear parametric modeling, and are likely to occur in experimental time series. In this study, we investigate the impact on the assessment of frequency domain causality of excluding instantaneous effects from the model underlying PDC evaluation. Moreover, we propose the utilization of an extended MVAR model including both instantaneous and lagged effects. This model is used to assess PDC either in accordance with the definition of Granger causality when considering only lagged effects (iPDC), or with an extended form of causality, when we consider both instantaneous and lagged effects (ePDC). The approach is first evaluated on three theoretical examples of MVAR processes, which show that the presence of instantaneous correlations may produce misleading profiles of PDC and gPDC, while ePDC and iPDC derived from the extended model provide here a correct interpretation of extended and lagged causality. It is then applied to representative examples of cardiorespiratory and EEG MV time series. They suggest that ePDC and iPDC are better interpretable than PDC and gPDC in terms of the known cardiovascular and neural physiologies.
Epps, Clinton W; Keyghobadi, Nusha
2015-12-01
Landscape genetics seeks to determine the effect of landscape features on gene flow and genetic structure. Often, such analyses are intended to inform conservation and management. However, depending on the many factors that influence the time to reach equilibrium, genetic structure may more strongly represent past rather than contemporary landscapes. This well-known lag between current demographic processes and population genetic structure often makes it challenging to interpret how contemporary landscapes and anthropogenic activity shape gene flow. Here, we review the theoretical framework for factors that influence time lags, summarize approaches to address this temporal disconnect in landscape genetic studies, and evaluate ways to make inferences about landscape change and its effects on species using genetic data alone or in combination with other data. Those approaches include comparing correlation of genetic structure with historical versus contemporary landscapes, using molecular markers with different rates of evolution, contrasting metrics of genetic structure and gene flow that reflect population genetic processes operating at different temporal scales, comparing historical and contemporary samples, combining genetic data with contemporary estimates of species distribution or movement, and controlling for phylogeographic history. We recommend using simulated data sets to explore time lags in genetic structure, and argue that time lags should be explicitly considered both when designing and interpreting landscape genetic studies. We conclude that the time lag problem can be exploited to strengthen inferences about recent landscape changes and to establish conservation baselines, particularly when genetic data are combined with other data. © 2015 John Wiley & Sons Ltd.
Burri, Susanne; Sturm, Patrick; Baur, Thomas; Barthel, Matti; Knohl, Alexander; Buchmann, Nina
2014-01-01
Pulse labelling experiments provide a common tool to study short-term processes in the plant-soil system and investigate below-ground carbon allocation as well as the coupling of soil CO(2) efflux to photosynthesis. During the first hours after pulse labelling, the measured isotopic signal of soil CO(2) efflux is a combination of both physical tracer diffusion into and out of the soil as well as biological tracer release via root and microbial respiration. Neglecting physical back-diffusion can lead to misinterpretation regarding time lags between photosynthesis and soil CO(2) efflux in grassland or any ecosystem type where the above-ground plant parts cannot be labelled in gas-tight chambers separated from the soil. We studied the effects of physical (13)CO(2) tracer back-diffusion in pulse labelling experiments in grassland, focusing on the isotopic signature of soil CO(2) efflux. Having accounted for back-diffusion, the estimated time lag for first tracer appearance in soil CO(2) efflux changed from 0 to 1.81±0.56 h (mean±SD) and the time lag for maximum tracer appearance from 2.67±0.39 to 9.63±3.32 h (mean±SD). Thus, time lags were considerably longer when physical tracer diffusion was considered. Using these time lags after accounting for physical back-diffusion, high nocturnal soil CO(2) efflux rates could be related to daytime rates of gross primary productivity (R(2)=0.84). Moreover, pronounced diurnal patterns in the δ(13)C of soil CO(2) efflux were found during the decline of the tracer over 3 weeks. Possible mechanisms include diurnal changes in the relative contributions of autotrophic and heterotrophic soil respiration as well as their respective δ(13)C values. Thus, after accounting for physical back-diffusion, we were able to quantify biological time lags in the coupling of photosynthesis and soil CO(2) efflux in grassland at the diurnal time scale.
Clegg, Miriam E; Shafat, Amir
2010-08-01
The (13)C octanoic acid breath test (OBT) was first developed as an alternative method of measuring gastric emptying (GE) to scintigraphy. There has been much debate about the test duration and how often measurements need to be taken. This study aims to address these issues. For 78 GE tests using the (13)C OBT, GE lag phase (T(lag)) was calculated while sampling more frequently than the recommended every 15 min. Comparisons between T(lag) were completed using Bland-Altman plots. Similarly, 4 or 6 h test durations were assessed to establish if they yield the same GE half time (T(half)). From one volunteer, samples were taken every 1 min for the first 30 min and then every 15 min until 6 h. GE times were then calculated using different combinations of sampling times. Evidence of a visible T(lag) was also explored from this data. Findings indicated that taking samples every 5 min for the first 30 min instead of every 15 min did not change the GE T(lag) based on Bland-Altman plots. The correlation between these two methods was also high (r(2) = 0.9957). The findings showed that the difference between the two sampling durations 4 and 6 h was large and the correlation between the methods was low (r(2) = 0.8335). Samples taken at a rate of one breath per min indicated lack of a visible T(lag). Sampling for the (13)C OBT should be completed every 15 min for 6 h.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Efroimsky, Michael; Makarov, Valeri V., E-mail: michael.efroimsky@usno.navy.mil, E-mail: vvm@usno.navy.mil
Tidal torques play a key role in rotational dynamics of celestial bodies. They govern these bodies' tidal despinning and also participate in the subtle process of entrapment of these bodies into spin-orbit resonances. This makes tidal torques directly relevant to the studies of habitability of planets and their moons. Our work begins with an explanation of how friction and lagging should be built into the theory of bodily tides. Although much of this material can be found in various publications, a short but self-consistent summary on the topic has been lacking in the hitherto literature, and we are filling themore » gap. After these preparations, we address a popular concise formula for the tidal torque, which is often used in the literature, for planets or stars. We explain why the derivation of this expression, offered in the paper by Goldreich and in the books by Kaula (Equation (4.5.29)) and Murray and Dermott (Equation (4.159)), implicitly sets the time lag to be frequency independent. Accordingly, the ensuing expression for the torque can be applied only to bodies having a very special (and very hypothetical) rheology which makes the time lag frequency independent, i.e., the same for all Fourier modes in the spectrum of tide. This expression for the torque should not be used for bodies of other rheologies. Specifically, the expression cannot be combined with an extra assertion of the geometric lag being constant, because at finite eccentricities the said assumption is incompatible with the constant-time-lag condition.« less
Assessing delay and lag in sagittal trunk control using a tracking task.
Reeves, N Peter; Luis, Abraham; Chan, Elizabeth C; Sal Y Rosas, Victor G; Tanaka, Martin L
2018-05-17
Slower trunk muscle responses are linked to back pain and injury. Unfortunately, clinical assessments of spine function do not objectively evaluate this important attribute, which reflects speed of trunk control. Speed of trunk control can be parsed into two components: (1) delay, the time it takes to initiate a movement, and (2) lag, the time it takes to execute a movement once initiated. The goal of this study is to demonstrate a new approach to assess delay and lag in trunk control using a simple tracking task. Ten healthy subjects performed four blocks of six trials of trunk tracking in the sagittal plane. Delay and lag were estimated by modeling trunk control for predictable and unpredictable (control mode) trunk movements in flexion and extension (control direction) at movement amplitudes of 2°, 4°, and 6° (control amplitude). The main effect of control mode, direction, and amplitude of movement were compared between trial blocks to assess secondary influencers (e.g., fatigue). Only control mode was consistent across trial blocks with predictable movements being faster than unpredictable for both delay and lag. Control direction and amplitude effects on delay and lag were consistent across the first two trial blocks and less consistent in later blocks. Given the heterogeneity in the presentation of back pain, clinical assessment of trunk control should include different control modes, directions, and amplitudes. To reduce testing time and the influence of fatigue, we recommend six trials to assess trunk control. Copyright © 2018 Elsevier Ltd. All rights reserved.
Optical/UV-to-X-Ray Echoes from the Tidal Disruption Flare ASASSN-14li
DOE Office of Scientific and Technical Information (OSTI.GOV)
Pasham, Dheeraj R.; Sadowski, Aleksander; Cenko, S. Bradley
We carried out the first multi-wavelength (optical/UV and X-ray) photometric reverberation mapping of a tidal disruption flare (TDF) ASASSN-14li. We find that its X-ray variations are correlated with and lag the optical/UV fluctuations by 32 ± 4 days. Based on the direction and the magnitude of the X-ray time lag, we rule out X-ray reprocessing and direct emission from a standard circular thin disk as the dominant source of its optical/UV emission. The lag magnitude also rules out an AGN disk-driven instability as the origin of ASASSN-14li and thus strongly supports the tidal disruption picture for this event and similarmore » objects. We suggest that the majority of the optical/UV emission likely originates from debris stream self-interactions. Perturbations at the self-interaction sites produce optical/UV variability and travel down to the black hole where they modulate the X-rays. The time lag between the optical/UV and the X-rays variations thus correspond to the time taken by these fluctuations to travel from the self-interaction site to close to the black hole. We further discuss these time lags within the context of the three variants of the self-interaction model. High-cadence monitoring observations of future TDFs will be sensitive enough to detect these echoes and would allow us to establish the origin of optical/UV emission in TDFs in general.« less
Design and evaluation of a dry coated drug delivery system with floating-pulsatile release.
Zou, Hao; Jiang, Xuetao; Kong, Lingshan; Gao, Shen
2008-01-01
The objective of this work was to develop and evaluate a floating-pulsatile drug delivery system intended for chronopharmacotherapy. Floating-pulsatile concept was applied to increase the gastric residence of the dosage form having lag phase followed by a burst release. To overcome limitations of various approaches for imparting buoyancy, we generated the system which consisted of three different parts, a core tablet, containing the active ingredient, an erodible outer shell and a top cover buoyant layer. The dry coated tablet consists in a drug-containing core, coated by a hydrophilic erodible polymer which is responsible for a lag phase in the onset of pulsatile release. The buoyant layer, prepared with Methocel K4M, Carbopol 934P and sodium bicarbonate, provides buoyancy to increase the retention of the oral dosage form in the stomach. The effect of the hydrophilic erodible polymer characteristics on the lag time and drug release was investigated. Developed formulations were evaluated for their buoyancy, dissolution and pharmacokinetic, as well gamma-scintigraphically. The results showed that a certain lag time before the drug released generally due to the erosion of the dry coated layer. Floating time was controlled by the quantity and composition of the buoyant layer. Both pharmacokinetic and gamma-scintigraphic data point out the capability of the system of prolonged residence of the tablets in the stomach and releasing drugs after a programmed lag time. (c) 2007 Wiley-Liss, Inc.
ERIC Educational Resources Information Center
Huang, Tien-Chi; Huang, Yueh-Min; Yu, Fu-Yun
2011-01-01
This paper examines the effects of using weblog technologies to support cooperative learning in higher education. The study focused on the effects of features embedded in weblogs on social interactions, time lags, and cognitive loads. A quasi-experimental control-group research design was adopted. The participants were 115 undergraduates who were…
Heat conduction errors and time lag in cryogenic thermometer installations
NASA Technical Reports Server (NTRS)
Warshawsky, I.
1973-01-01
Installation practices are recommended that will increase rate of heat exchange between the thermometric sensing element and the cryogenic fluid, in addition to bringing about a reduction in the rate of undesired heat transfer to higher temperature objects. Formulas and numerical data are given that help to estimate the magnitude of heat conduction errors and of time lag in response.
El-Maradny, Hoda A
2007-11-01
Diclofenac sodium tablets consisting of core coated with two layers of swelling and rupturable coatings were prepared and evaluated as a pulsatile drug delivery system. Cores containing the drug were prepared by direct compression using microcrystalline cellulose and Ludipress as hydrophilic excipients with the ratio of 1:1. Cores were then coated sequentially with an inner swelling layer of different swellable materials; either Explotab, Croscarmellose sodium, or Starch RX 1500, and an outer rupturable layer of different levels of ethylcellulose. The effect of the nature of the swelling layer and the level of the rupturable coating on the lag time and the water uptake were investigated. Drug release rate studies were performed using USP paddle method. Results showed the dependence of the lag time and water uptake prior to tablet rupture on the nature of the swelling layer and the coating levels. Explotab showed a significant decrease in the lag time, followed by Croscarmellose sodium and finally by Starch RX 1500. Increasing the level of ethylcellulose coating retarded the diffusion of the release medium to the swelling layer and the rupture of the coat, thus prolonging the lag time.
Aerosol Plume Detection Algorithm Based on Image Segmentation of Scanning Atmospheric Lidar Data
Weekley, R. Andrew; Goodrich, R. Kent; Cornman, Larry B.
2016-04-06
An image-processing algorithm has been developed to identify aerosol plumes in scanning lidar backscatter data. The images in this case consist of lidar data in a polar coordinate system. Each full lidar scan is taken as a fixed image in time, and sequences of such scans are considered functions of time. The data are analyzed in both the original backscatter polar coordinate system and a lagged coordinate system. The lagged coordinate system is a scatterplot of two datasets, such as subregions taken from the same lidar scan (spatial delay), or two sequential scans in time (time delay). The lagged coordinatemore » system processing allows for finding and classifying clusters of data. The classification step is important in determining which clusters are valid aerosol plumes and which are from artifacts such as noise, hard targets, or background fields. These cluster classification techniques have skill since both local and global properties are used. Furthermore, more information is available since both the original data and the lag data are used. Performance statistics are presented for a limited set of data processed by the algorithm, where results from the algorithm were compared to subjective truth data identified by a human.« less
Tank, David C; Eastman, Jonathan M; Pennell, Matthew W; Soltis, Pamela S; Soltis, Douglas E; Hinchliff, Cody E; Brown, Joseph W; Sessa, Emily B; Harmon, Luke J
2015-07-01
Our growing understanding of the plant tree of life provides a novel opportunity to uncover the major drivers of angiosperm diversity. Using a time-calibrated phylogeny, we characterized hot and cold spots of lineage diversification across the angiosperm tree of life by modeling evolutionary diversification using stepwise AIC (MEDUSA). We also tested the whole-genome duplication (WGD) radiation lag-time model, which postulates that increases in diversification tend to lag behind established WGD events. Diversification rates have been incredibly heterogeneous throughout the evolutionary history of angiosperms and reveal a pattern of 'nested radiations' - increases in net diversification nested within other radiations. This pattern in turn generates a negative relationship between clade age and diversity across both families and orders. We suggest that stochastically changing diversification rates across the phylogeny explain these patterns. Finally, we demonstrate significant statistical support for the WGD radiation lag-time model. Across angiosperms, nested shifts in diversification led to an overall increasing rate of net diversification and declining relative extinction rates through time. These diversification shifts are only rarely perfectly associated with WGD events, but commonly follow them after a lag period. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.
Romberg-Camps, Mariëlle J L; Hesselink-van de Kruijs, Martine A M; Schouten, Leo J; Dagnelie, Pieter C; Limonard, Charles B; Kester, Arnold D M; Bos, Laurens P; Goedhard, Jelle; Hameeteman, Wim H A; Wolters, Frank L; Russel, Maurice G V M; Stockbrügger, Reinhold W
2009-06-01
Increasing incidence in Inflammatory Bowel Disease (IBD) has been suggested. Recent data on population based incidence rates within Europe are however scarce. Primary aim was to investigate prospectively the incidence of IBD within a well-defined geographical and administrative area of the Netherlands, the South Limburg IBD registry. Secondary aims were to study the duration of symptoms before diagnosis (lag time) and seasonal influences on the incidence of IBD. The incidence was examined using standardized registration of all newly diagnosed IBD patients, between 1-1-1991 and 1-1-2003. Medical records were reviewed to verify the diagnosis. At inclusion, diagnostic lag time was registered in months. Age standardized incidence rates per 100,000 person-years (p-y) were: Crohn's Disease, male 4.84, female 7.58; Ulcerative Colitis, male 8.51, female 6.92; and Indeterminate Colitis, male 1.05, female 0.93. Incidence rates did not significantly changes over time in either Crohn's Disease, Ulcerative Colitis or Indeterminate Colitis. Lag time was 5 (0-360) months in Crohn's Disease, 3.0 (0-480) months in Ulcerative Colitis and 3.0 (0-180) months in Indeterminate Colitis. Lag time was not significantly different between the periods 1991-1993 and 2000-2002, and no statistical differences in the onset of symptoms per calendar month or season were found. Our results, from the South Limburg region (the Netherlands), show no significant change in incidence rates of IBD. The incidence found is relatively high compared to other European countries. Lag time did not change during the study period, and seasonal influence of incidence rates could not be confirmed.
La Belle, Jeffrey T; Engelschall, Erica; Lan, Kenneth; Shah, Pankti; Saez, Neil; Maxwell, Stephanie; Adamson, Teagan; Abou-Eid, Michelle; McAferty, Kenyon; Patel, Dharmendra R; Cook, Curtiss B
2014-01-01
A prototype tear glucose (TG) sensor was tested in New Zealand white rabbits to assess eye irritation, blood glucose (BG) and TG lag time, and correlation with BG. A total of 4 animals were used. Eye irritation was monitored by Lissamine green dye and analyzed using image analysis software. Lag time was correlated with an oral glucose load while recording TG and BG readings. Correlation between TG and BG were plotted against one another to form a correlation diagram, using a Yellow Springs Instrument (YSI) and self-monitoring of blood glucose as the reference measurements. Finally, TG levels were calculated using analytically derived expressions. From repeated testing carried over the course of 12 months, little to no eye irritation was detected. TG fluctuations over time visually appeared to trace the same pattern as BG with an average lag times of 13 minutes. TG levels calculated from the device current measurements ranged from 4 to 20 mg/dL and correlated linearly with BG levels of 75-160 mg/dL (TG = 0.1723 BG = 7.9448 mg/dL; R 2 = .7544). The first steps were taken toward preliminary development of a sensor for self-monitoring of tear glucose (SMTG). No conjunctival irritation in any of the animals was noted. Lag time between TG and BG was found to be noticeable, but a quantitative modeling to correlate lag time in this study is unnecessary. Measured currents from the sensors and the calculated TG showed promising correlation to BG levels. Previous analytical bench marking showed BG and TG levels consistent with other literature. © 2014 Diabetes Technology Society.
Hou, Yu; Yao, Qi; Zhang, Gen'ai; Ding, Lixiang
2018-01-01
To confirm the association between tail femur distance (TFD) and lag screw migration or cutting-out in the treatment of intertrochanteric fracture with the third generation of Gamma nail (TGN). The clinical data of 124 cases of intertrochanteric fracture treated with TGN internal fixation and followed up more than 18 months between January 2012 and December 2015 were reviewed and analyzed. There were 52 males and 72 females, with an age of 46-93 years (mean, 78.5 years). According to AO/Association for the Study of Internal Fixation (AO/ASIF) classification, 43 cases were type 31-A1, 69 cases were type 31-A2, and 12 cases were type 31-A3. The time from injury to operation was 1-10 days (mean, 2.9 days). According to the fracture healing of the patients, the patients were divided into the healing group and failure group. The age, gender, height, bone mineral density (BMD), fracture AO/ASIF classification, the time from injury to operation, and the TFD value at 1 day after operation were recorded and compared. The risk factors for the migration or cutting-out of lag screw were analyzed by logistic regression. There were 111 cases in healing group, the healing time was 80-110 days (mean, 95.5 days). There were 13 cases in failure group, including 2 cases of lag screw cutting-out and 11 cases of significant migration. Except for the TFD value at 1 day after operation in failure group was significantly higher than that in the healing group( t =5.14, P =0.00), there was no significant difference in gender, age, height, BMD, fracture of AO/ASIF classification, and the time from injury to operation ( P >0.05) between 2 groups. logistic regression analysis showed that TFD value was a risk factor for the migration or cutting-out of lag screw (B=1.22, standardized coefficient=0.32, Wald χ 2 =14.66, P =0.00, OR=3.37). The patients with higher TFD value had higher risk of postoperative lag screw migration or cutting-out. This result indicates that the appropriate length of the lag screw is helpful to reduce TFD value and prevent postoperative lag screw migration or cutting-out.
Time-varying mixed logit model for vehicle merging behavior in work zone merging areas.
Weng, Jinxian; Du, Gang; Li, Dan; Yu, Yao
2018-08-01
This study aims to develop a time-varying mixed logit model for the vehicle merging behavior in work zone merging areas during the merging implementation period from the time of starting a merging maneuver to that of completing the maneuver. From the safety perspective, vehicle crash probability and severity between the merging vehicle and its surrounding vehicles are regarded as major factors influencing vehicle merging decisions. Model results show that the model with the use of vehicle crash risk probability and severity could provide higher prediction accuracy than previous models with the use of vehicle speeds and gap sizes. It is found that lead vehicle type, through lead vehicle type, through lag vehicle type, crash probability of the merging vehicle with respect to the through lag vehicle, crash severities of the merging vehicle with respect to the through lead and lag vehicles could exhibit time-varying effects on the merging behavior. One important finding is that the merging vehicle could become more and more aggressive in order to complete the merging maneuver as quickly as possible over the elapsed time, even if it has high vehicle crash risk with respect to the through lead and lag vehicles. Copyright © 2018 Elsevier Ltd. All rights reserved.
Levine, Matthew E; Albers, David J; Hripcsak, George
2016-01-01
Time series analysis methods have been shown to reveal clinical and biological associations in data collected in the electronic health record. We wish to develop reliable high-throughput methods for identifying adverse drug effects that are easy to implement and produce readily interpretable results. To move toward this goal, we used univariate and multivariate lagged regression models to investigate associations between twenty pairs of drug orders and laboratory measurements. Multivariate lagged regression models exhibited higher sensitivity and specificity than univariate lagged regression in the 20 examples, and incorporating autoregressive terms for labs and drugs produced more robust signals in cases of known associations among the 20 example pairings. Moreover, including inpatient admission terms in the model attenuated the signals for some cases of unlikely associations, demonstrating how multivariate lagged regression models' explicit handling of context-based variables can provide a simple way to probe for health-care processes that confound analyses of EHR data.
Analysis and IbM simulation of the stages in bacterial lag phase: basis for an updated definition.
Prats, Clara; Giró, Antoni; Ferrer, Jordi; López, Daniel; Vives-Rego, Josep
2008-05-07
The lag phase is the initial phase of a culture that precedes exponential growth and occurs when the conditions of the culture medium differ from the pre-inoculation conditions. It is usually defined by means of cell density because the number of individuals remains approximately constant or slowly increases, and it is quantified with the lag parameter lambda. The lag phase has been studied through mathematical modelling and by means of specific experiments. In recent years, Individual-based Modelling (IbM) has provided helpful insights into lag phase studies. In this paper, the definition of lag phase is thoroughly examined. Evolution of the total biomass and the total number of bacteria during lag phase is tackled separately. The lag phase lasts until the culture reaches a maximum growth rate both in biomass and cell density. Once in the exponential phase, both rates are constant over time and equal to each other. Both evolutions are split into an initial phase and a transition phase, according to their growth rates. A population-level mathematical model is presented to describe the transitional phase in cell density. INDividual DIScrete SIMulation (INDISIM) is used to check the outcomes of this analysis. Simulations allow the separate study of the evolution of cell density and total biomass in a batch culture, they provide a depiction of different observed cases in lag evolution at the individual-cell level, and are used to test the population-level model. The results show that the geometrical lag parameter lambda is not appropriate as a universal definition for the lag phase. Moreover, the lag phase cannot be characterized by a single parameter. For the studied cases, the lag phases of both the total biomass and the population are required to fully characterize the evolution of bacterial cultures. The results presented prove once more that the lag phase is a complex process that requires a more complete definition. This will be possible only after the phenomena governing the population dynamics at an individual level of description, and occurring during the lag and exponential growth phases, are well understood.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Bentz, Misty C.; Walsh, Jonelle L.; Barth, Aaron J.
2010-06-20
We have recently completed a 64-night spectroscopic monitoring campaign at the Lick Observatory 3 m Shane telescope with the aim of measuring the masses of the black holes in 12 nearby (z < 0.05) Seyfert 1 galaxies with expected masses in the range {approx}10{sup 6}-10{sup 7} M{sub sun} and also the well-studied nearby active galactic nucleus (AGN) NGC 5548. Nine of the objects in the sample (including NGC 5548) showed optical variability of sufficient strength during the monitoring campaign to allow for a time lag to be measured between the continuum fluctuations and the response to these fluctuations in themore » broad H{beta} emission, which we have previously reported. We present here the light curves for the H{alpha}, H{gamma}, He II {lambda}4686, and He I {lambda}5876 emission lines and the time lags for the emission-line responses relative to changes in the continuum flux. Combining each emission-line time lag with the measured width of the line in the variable part of the spectrum, we determine a virial mass of the central supermassive black hole from several independent emission lines. We find that the masses are generally consistent within the uncertainties. The time-lag response as a function of velocity across the Balmer line profiles is examined for six of the AGNs. We find similar responses across all three Balmer lines for Arp 151, which shows a strongly asymmetric profile, and for SBS 1116+583A and NGC 6814, which show a symmetric response about zero velocity. For the other three AGNs, the data quality is somewhat lower and the velocity-resolved time-lag response is less clear. Finally, we compare several trends seen in the data set against the predictions from photoionization calculations as presented by Korista and Goad. We confirm several of their predictions, including an increase in responsivity and a decrease in the mean time lag as the excitation and ionization level for the species increases. Specifically, we find the time lags of the optical recombination lines to have weighted mean ratios of {tau}(H{alpha}):{tau}(H{beta}):{tau}(H{gamma}):{tau}(He I):{tau}(He II) = 1.54:1.00:0.61:0.36:0.25. Further confirmation of photoionization predictions for broad-line gas behavior will require additional monitoring programs for these AGNs while they are in different luminosity states.« less
A new method for determining the optimal lagged ensemble
DelSole, T.; Tippett, M. K.; Pegion, K.
2017-01-01
Abstract We propose a general methodology for determining the lagged ensemble that minimizes the mean square forecast error. The MSE of a lagged ensemble is shown to depend only on a quantity called the cross‐lead error covariance matrix, which can be estimated from a short hindcast data set and parameterized in terms of analytic functions of time. The resulting parameterization allows the skill of forecasts to be evaluated for an arbitrary ensemble size and initialization frequency. Remarkably, the parameterization also can estimate the MSE of a burst ensemble simply by taking the limit of an infinitely small interval between initialization times. This methodology is applied to forecasts of the Madden Julian Oscillation (MJO) from version 2 of the Climate Forecast System version 2 (CFSv2). For leads greater than a week, little improvement is found in the MJO forecast skill when ensembles larger than 5 days are used or initializations greater than 4 times per day. We find that if the initialization frequency is too infrequent, important structures of the lagged error covariance matrix are lost. Lastly, we demonstrate that the forecast error at leads ≥10 days can be reduced by optimally weighting the lagged ensemble members. The weights are shown to depend only on the cross‐lead error covariance matrix. While the methodology developed here is applied to CFSv2, the technique can be easily adapted to other forecast systems. PMID:28580050
SIMULATION OF FLOOD HYDROGRAPHS FOR GEORGIA STREAMS.
Inman, E.J.; Armbruster, J.T.
1986-01-01
Flood hydrographs are needed for the design of many highway drainage structures and embankments. A method for simulating these flood hydrographs at urban and rural ungauged sites in Georgia is presented. The O'Donnell method was used to compute unit hydrographs from 355 flood events from 80 stations. An average unit hydrograph and an average lag time were computed for each station. These average unit hydrographs were transformed to unit hydrographs having durations of one-fourth, one-third, one-half, and three-fourths lag time and then reduced to dimensionless terms by dividing the time by lag time and the discharge by peak discharge. Hydrographs were simulated for these 355 flood events and their widths were compared with the widths of the observed hydrographs at 50 and 75 percent of peak flow. For simulating hydrographs at sites larger than 500 mi**2, the U. S. Geological Survey computer model CONROUT can be used.
An approach to the determination of aircraft handling qualities using pilot transfer functions
NASA Technical Reports Server (NTRS)
Adams, J. J.; Hatch, H. G., Jr.
1978-01-01
It was shown that a correlation exists between pilot-aircraft system closed-loop characteristics, determined by using analytical expressions for pilot response along with the analytical expression for the aircraft response, and pilot ratings obtained in many previous flight and simulation studies. Two different levels of preferred pilot response were used. These levels were: (1) a static gain and a second-order lag function with a lag time constant of 0.2 second; and (2) a static gain, a lead time constant of 1 second, and a 0.2-second lag time constant. If a system response with a pitch-angle time constant of 2.6 seconds and a stable oscillatory mode of motion with a period of 2.5 seconds could be achieved with the first-level pilot model, it was shown that the pilot rating will be satisfactory for that vehicle.
Statistical models and time series forecasting of sulfur dioxide: a case study Tehran.
Hassanzadeh, S; Hosseinibalam, F; Alizadeh, R
2009-08-01
This study performed a time-series analysis, frequency distribution and prediction of SO(2) levels for five stations (Pardisan, Vila, Azadi, Gholhak and Bahman) in Tehran for the period of 2000-2005. Most sites show a quite similar characteristic with highest pollution in autumn-winter time and least pollution in spring-summer. The frequency distributions show higher peaks at two residential sites. The potential for SO(2) problems is high because of high emissions and the close geographical proximity of the major industrial and urban centers. The ACF and PACF are nonzero for several lags, indicating a mixed (ARMA) model, then at Bahman station an ARMA model was used for forecasting SO(2). The partial autocorrelations become close to 0 after about 5 lags while the autocorrelations remain strong through all the lags shown. The results proved that ARMA (2,2) model can provides reliable, satisfactory predictions for time series.
Cellini, Cristiano; Scocchia, Lisa; Drewing, Knut
2016-10-01
In the flash-lag illusion, a brief visual flash and a moving object presented at the same location appear to be offset with the flash trailing the moving object. A considerable amount of studies investigated the visual flash-lag effect, and flash-lag-like effects have also been observed in audition, and cross-modally between vision and audition. In the present study, we investigate whether a similar effect can also be observed when using only haptic stimuli. A fast vibration (or buzz, lasting less than 20 ms) was applied to the moving finger of the observers and employed as a "haptic flash." Participants performed a two-alternative forced-choice (2AFC) task where they had to judge whether the moving finger was located to the right or to the left of the stationary finger at the time of the buzz. We used two different movement velocities (Slow and Fast conditions). We found that the moving finger was systematically misperceived to be ahead of the stationary finger when the two were physically aligned. This result can be interpreted as a purely haptic analogue of the flash-lag effect, which we refer to as "buzz-lag effect." The buzz-lag effect can be well accounted for by the temporal-sampling explanation of flash-lag-like effects.
Time Delays of Blazar Flares Observed at Different Wavebands
NASA Technical Reports Server (NTRS)
Marscher, Alan P.
2000-01-01
Correlated variability at different frequencies can probe the structure and physics of the jet of a blazar on size scales much smaller than can be resolved by telescopes and interferometers. I discuss some observations of frequency dependent time lags and how these place constraints on models for the nonthermal emission in blazars. The time lags can be either positive (high frequency variations leading those at lower frequencies) or negative, while simultaneous flares are also possible.
Vithani, Kapilkumar; Hawley, Adrian; Jannin, Vincent; Pouton, Colin; Boyd, Ben J
2017-05-01
Solid self-microemulsifying drug delivery systems (SMEDDS) have received considerable attention in recent times attempting to overcome the drawbacks of liquid SMEDDS. Earlier literature reports on solid SMEDDS have focussed on formulation development; however, the digestibility and propensity for self-assembly of the digested components with endogenous bile salts and phospholipids are unknown. Therefore, as a starting point, previously reported solid SMEDDS containing Gelucire® 44/14 (GEL) and the non-digestible surfactants, Vitamin E TPGS (TPGS) and Lutrol® F 127 (F 127), were prepared, and their dispersion and digestion behaviours were studied using an in vitro lipolysis model, coupled with small-angle X-ray scattering (SAXS) to determine the formed colloidal structures during digestion in real time. GEL alone was digested (89%) and formed a lamellar phase (Lα). When surfactants were added at a 40:60% w/w lipid to surfactants ratio, digestion was inhibited with a significant lag time being evident. However, increasing the fraction of GEL to 50% w/w enabled digestion with reduced lag time. The substitution of the non-digestible surfactants with digestible surfactants, sucrose esters S-1670 (S-1670) and Span® 60 (S-60), eliminated the digestion lag time, and the formation of colloidal structures was more similar to that of GEL alone.
Design and In Vitro Evaluation of Compression-coated Pulsatile Release Tablets of Losartan Potassium
Bajpai, M.; Singh, D. C. P.; Bhattacharya, A.; Singh, A.
2012-01-01
In majority of individuals blood pressure rises in the early morning hours, which lead to serious cardiovascular complications. Formulation of pulsatile system makes it possible to deliver drug at definite period of time when symptoms of the disease condition are most critical. The purpose of the present work was to develop pulsatile release tablet of losartan potassium for chronotherapy in hypertension. The prepared system consisted of a core tablet coated with versatile and safe hydrophilic cellulosic ethers such as, hydroxypropyl methylcellulose, hydroxypropyl cellulose and sodium carboxy methylcellulose to produce burst release after predetermined lag time. Various formulation factors were studied through series of test and in vitro dissolution study. It was found that core tablets containing superdisintegrant failed to produce burst drug release pattern while effervescent agent was able to do so. Results also reveal that coating composition and coating level affects lag time. Formulation containing effervescent agent in core and coated with 200 mg hydroxypropyl cellulose provide lag time of 4.5 h with 73% drug release in 6 h that followed a sigmoidal release pattern. These values were close to the desired objective of producing lag time of 5-6 h followed by fast drug release. This approach can thus provide a useful means for timed release of losartan and is helpful for patients with morning surge. PMID:23325989
Modeling the response of a standard accretion disc to stochastic viscous fluctuations
NASA Astrophysics Data System (ADS)
Ahmad, Naveel; Misra, Ranjeev; Iqbal, Naseer; Maqbool, Bari; Hamid, Mubashir
2018-01-01
The observed variability of X-ray binaries over a wide range of time-scales can be understood in the framework of a stochastic propagation model, where viscous fluctuations at different radii induce accretion rate variability that propagate inwards to the X-ray producing region. The scenario successfully explains the power spectra, the linear rms-flux relation as well as the time-lag between different energy photons. The predictions of this model have been obtained using approximate analytical solutions or empirically motivated models which take into account the effect of these propagating variability on the radiative process of complex accretion flows. Here, we study the variation of the accretion rate due to such viscous fluctuations using a hydro-dynamical code for the standard geometrically thin, gas pressure dominated α-disc with a zero torque boundary condition. Our results confirm earlier findings that the time-lag between a perturbation and the resultant inner accretion rate variation depends on the frequency (or time-period) of the perturbation. Here we have quantified that the time-lag tlag ∝f-0.54 , for time-periods less than the viscous time-scale of the perturbation radius and is nearly constant otherwise. This, coupled with radiative process would produce the observed frequency dependent time-lag between different energy bands. We also confirm that if there are random Gaussian fluctuations of the α-parameter at different radii, the resultant inner accretion rate has a power spectrum which is a power-law.
REJEKI, Dwi Sarwani Sri; NURHAYATI, Nunung; AJI, Budi; MURHANDARWATI, E. Elsa Herdiana; KUSNANTO, Hari
2018-01-01
Background: Climatic and weather factors become important determinants of vector-borne diseases transmission like malaria. This study aimed to prove relationships between weather factors with considering human migration and previous case findings and malaria cases in endemic areas in Purworejo during 2005–2014. Methods: This study employed ecological time series analysis by using monthly data. The independent variables were the maximum temperature, minimum temperature, maximum humidity, minimum humidity, precipitation, human migration, and previous malaria cases, while the dependent variable was positive malaria cases. Three models of count data regression analysis i.e. Poisson model, quasi-Poisson model, and negative binomial model were applied to measure the relationship. The least Akaike Information Criteria (AIC) value was also performed to find the best model. Negative binomial regression analysis was considered as the best model. Results: The model showed that humidity (lag 2), precipitation (lag 3), precipitation (lag 12), migration (lag1) and previous malaria cases (lag 12) had a significant relationship with malaria cases. Conclusion: Weather, migration and previous malaria cases factors need to be considered as prominent indicators for the increase of malaria case projection. PMID:29900134
Demonstration of an Enhanced Vertical Magnetic Gradient System for UXO
2008-04-01
flights were conducted and results evaluated. The cesium magnetometers , GPS systems (positioning and attitude), fluxgate magnetometers , data...makes a measurement and when it is time-stamped and recorded. This applies to the magnetometers , fluxgate and the GPS. Accurate positioning...requires a correction for this lag. Time lags between the magnetometers , fluxgate and GPS signals were measured by a proprietary utility. This utility
ERIC Educational Resources Information Center
Yingling, Marissa E.; Hock, Robert M.; Bell, Bethany A.
2018-01-01
Health coverage of early intensive behavioral intervention (EIBI) for children with autism spectrum disorder (ASD) is rapidly expanding across the United States. Yet we know little about the time-lag between diagnosis and treatment onset. We integrated administrative, Medicaid claims, and Census data for children in an EIBI Medicaid waiver (n =…
Effects of timber harvesting on the lag time of a Caspar Creek watershed...a study in progress
Karen D. Hardison
1982-01-01
Researchers are not agreed on the effects of logging on lag time. Numerous studies have shown that the use of heavy equipment in logging operations can cause soil compaction. Also, associated roads alter natural drainage patterns by concentrating runoff and interrupting subsurface flow. As a result these researchers say, less infiltration into the soil takes place...
ERIC Educational Resources Information Center
Fujiwara, Takeo; Okuyama, Makiko; Funahashi, Keiichi
2011-01-01
The early assessment of autism spectrum disorders (ASDs) is important to improving patient outcomes, allowing family members to prepare for and cope with symptoms, and assisting in plans for appropriate educational opportunities. However, little is known about factors that influence the time lag between the parents' first concerns and the first…
Gleason, Jessie A; Fagliano, Jerald A
2015-10-01
Asthma is one of the most common chronic diseases affecting children. This study assesses the associations of ozone and fine particulate matter (PM2.5) with pediatric emergency department visits in the urban environment of Newark, NJ. Two study designs were utilized and evaluated for usability. We obtained daily emergency department visits among children aged 3-17 years with a primary diagnosis of asthma during April to September for 2004-2007. Both a time-stratified case-crossover study design with bi-directional control sampling and a time-series study design were utilized. Lagged effects (1-d through 5-d lag, 3-d average, and 5-d average) of ozone and PM2.5 were explored and a dose-response analysis comparing the bottom 5th percentile of 3-d average lag ozone with each 5 percentile increase was performed. Associations of interquartile range increase in same-day ozone were similar between the time-series and case-crossover study designs (RR = 1.08, 95% CI 1.04-1.12) and (OR = 1.10, 95% CI 1.06-1.14), respectively. Similar associations were seen for 1-day lag and 3-day average lag ozone levels. PM2.5 was not associated with the outcome in either study design. Dose-response assessment indicated a statistically significant and increasing association around 50-55 ppb consistent for both study designs. Ozone was statistically positively associated with pediatric asthma ED visits in Newark, NJ. Our results were generally comparable across the time-series and case-crossover study designs, indicating both are useful to assess local air pollution impacts.
Development of press-coated, floating-pulsatile drug delivery of lisinopril.
Jagdale, Swati C; Suryawanshi, Vishnu M; Pandya, Sudhir V; Kuchekar, Bhanudas S; Chabukswar, Aniruddha R
2014-01-01
Lisinopril is an angiotensin-converting enzyme (ACE) inhibitor, primarily used for the treatment of hypertension, congestive heart failure, and heart attack. It belongs to BCS class III having a half-life of 12 hrs and 25% bioavailability. The purpose of the present work was to develop a press-coated, floating-pulsatile drug delivery system. The core tablet was formulated using the super-disintegrants crosprovidone and croscarmellose sodium. A press-coated tablet (barrier layer) contained the polymer carrageenan, xanthan gum, HPMC K4M, and HPMC K15M. The buoyant layer was optimized with HPMC K100M, sodium bicarbonate, and citric acid. The tablets were evaluated for physical characteristics, floating lag time, swelling index, FTIR, DSC, and in vitro and in vivo behavior. The 5% superdisintgrant showed good results. The FTIR and DSC study predicted no chemical interactions between the drug and excipients. The formulation containing xanthan gum showed drug retaining abilities, but failed to float. The tablet containing HPMC K15M showed a high swelling index. The lag time for the tablet coated with 200 mg carrageenan was 3±0.1 hrs with 99.99±1.5% drug release; with 140 mg HPMC K4M, the lag time was 3±0.1 hrs with 99.71±1.2% drug release; and with 120 mg HPMC K15M, the lag time was 3±0.2 hrs with 99.98±1.7% drug release. The release mechanism of the tablet followed the Korsmeyer-Peppas equation and a first-order release pattern. Floating and lag time behavior have shown good in vitro and in vivo correlations.
Fowler, Peter; Duffield, Rob; Howle, Kieran; Waterson, Adam; Vaile, Joanna
2015-07-01
The current study examined the effects of 10-h northbound air travel across 1 time zone on sleep quantity, together with subjective jet lag and wellness ratings, in 16 male professional Australian football (soccer) players. Player wellness was measured throughout the week before (home training week) and the week of (away travel week) travel from Australia to Japan for a preseason tour. Sleep quantity and subjective jet lag were measured 2 d before (Pre 1 and 2), the day of, and for 5 d after travel (Post 1-5). Sleep duration was significantly reduced during the night before travel (Pre 1; 4.9 [4.2-5.6] h) and night of competition (Post 2; 4.2 [3.7-4.7] h) compared with every other night (P<.01, d>0.90). Moreover, compared with the day before travel, subjective jet lag was significantly greater for the 5 d after travel (P<.05, d>0.90), and player wellness was significantly lower 1 d post-match (Post 3) than at all other time points (P<.05, d>0.90). Results from the current study suggest that sleep disruption, as a result of an early travel departure time (8 PM) and evening match (7:30 PM), and fatigue induced by competition had a greater effect on wellness ratings than long-haul air travel with a minimal time-zone change. Furthermore, subjective jet lag may have been misinterpreted as fatigue from sleep disruption and competition, especially by the less experienced players. Therefore, northbound air travel across 1 time zone from Australia to Asia appears to have negligible effects on player preparedness for subsequent training and competition.
Kamgar-Parsi, Kian; Hong, Liu; Naito, Akira; Brooks, Charles L; Ramamoorthy, Ayyalusamy
2017-09-08
The role of the peptide hormone calcitonin in skeletal protection has led to its use as a therapeutic for osteoporosis. However, calcitonin aggregation into amyloid fibrils limits its therapeutic efficacy, necessitating a modification of calcitonin's aggregation kinetics. Here, we report a direct relationship between human calcitonin (hCT) concentration and aggregation lag time. This kinetic trend was contrary to the conventional understanding of amyloid aggregation and persisted over a range of aggregation conditions, as confirmed by thioflavin-T kinetics assays, CD spectroscopy, and transmission EM. Dynamic light scattering, 1 H NMR experiments, and seeded thioflavin-T assay results indicated that differences in initial peptide species contribute to this trend more than variations in the primary nucleus formation rate. On the basis of kinetics modeling results, we propose a mechanism whereby a structural conversion of hCT monomers is needed before incorporation into the fibril. Our kinetic mechanism recapitulates the experimentally observed relationship between peptide concentration and lag time and represents a novel mechanism in amyloid aggregation. Interestingly, hCT at low pH and salmon calcitonin (sCT) exhibited the canonical inverse relationship between concentration and lag time. Comparative studies of hCT and sCT with molecular dynamics simulations and CD indicated an increased α-helical structure in sCT and low-pH hCT monomers compared with neutral-pH hCT, suggesting that α-helical monomers represent a growth-competent species, whereas unstructured random coil monomers represent a growth-incompetent species. Our finding that initial monomer concentration is positively correlated with lag time in hCT aggregation could help inform future efforts for improving therapeutic applications of CT. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.
Development of Press-Coated, Floating-Pulsatile Drug Delivery of Lisinopril
Jagdale, Swati C.; Suryawanshi, Vishnu M.; Pandya, Sudhir V.; Kuchekar, Bhanudas S.; Chabukswar, Aniruddha R.
2014-01-01
Lisinopril is an angiotensin-converting enzyme (ACE) inhibitor, primarily used for the treatment of hypertension, congestive heart failure, and heart attack. It belongs to BCS class III having a half-life of 12 hrs and 25% bioavailability. The purpose of the present work was to develop a press-coated, floating-pulsatile drug delivery system. The core tablet was formulated using the super-disintegrants crosprovidone and croscarmellose sodium. A press-coated tablet (barrier layer) contained the polymer carrageenan, xanthan gum, HPMC K4M, and HPMC K15M. The buoyant layer was optimized with HPMC K100M, sodium bicarbonate, and citric acid. The tablets were evaluated for physical characteristics, floating lag time, swelling index, FTIR, DSC, and in vitro and in vivo behavior. The 5% superdisintgrant showed good results. The FTIR and DSC study predicted no chemical interactions between the drug and excipients. The formulation containing xanthan gum showed drug retaining abilities, but failed to float. The tablet containing HPMC K15M showed a high swelling index. The lag time for the tablet coated with 200 mg carrageenan was 3±0.1 hrs with 99.99±1.5% drug release; with 140 mg HPMC K4M, the lag time was 3±0.1 hrs with 99.71±1.2% drug release; and with 120 mg HPMC K15M, the lag time was 3±0.2 hrs with 99.98±1.7% drug release. The release mechanism of the tablet followed the Korsmeyer-Peppas equation and a first-order release pattern. Floating and lag time behavior have shown good in vitro and in vivo correlations. PMID:24959410
Watanabe, Yukari; Watanabe, Takamitsu
2017-10-01
Head injury is considered as a potential risk factor for amyotrophic lateral sclerosis (ALS). However, several recent studies have suggested that head injury is not a cause, but a consequence of latent ALS. We aimed to evaluate such a possibility of reverse causation with meta-analyses considering time lags between the incidence of head injuries and the occurrence of ALS. We searched Medline and Web of Science for case-control, cross-sectional, or cohort studies that quantitatively investigated the head-injury-related risk of ALS and were published until 1 December 2016. After selecting appropriate publications based on PRISMA statement, we performed random-effects meta-analyses to calculate odds ratios (ORs) and 95% confidence intervals (CI). Sixteen of 825 studies fulfilled the eligibility criteria. The association between head injuries and ALS was statistically significant when the meta-analysis included all the 16 studies (OR 1.45, 95% CI 1.21-1.74). However, in the meta-analyses considering the time lags between the experience of head injuries and diagnosis of ALS, the association was weaker (OR 1.21, 95% CI 1.01-1.46, time lag ≥ 1 year) or not significant (e.g. OR 1.16, 95% CI 0.84-1.59, time lag ≥ 3 years). Although it did not deny associations between head injuries and ALS, the current study suggests a possibility that such a head-injury-oriented risk of ALS has been somewhat overestimated. For more accurate evaluation, it would be necessary to conduct more epidemiological studies that consider the time lags between the occurrence of head injuries and the diagnosis of ALS.
Radio pulsar glitches as a state-dependent Poisson process
NASA Astrophysics Data System (ADS)
Fulgenzi, W.; Melatos, A.; Hughes, B. D.
2017-10-01
Gross-Pitaevskii simulations of vortex avalanches in a neutron star superfluid are limited computationally to ≲102 vortices and ≲102 avalanches, making it hard to study the long-term statistics of radio pulsar glitches in realistically sized systems. Here, an idealized, mean-field model of the observed Gross-Pitaevskii dynamics is presented, in which vortex unpinning is approximated as a state-dependent, compound Poisson process in a single random variable, the spatially averaged crust-superfluid lag. Both the lag-dependent Poisson rate and the conditional distribution of avalanche-driven lag decrements are inputs into the model, which is solved numerically (via Monte Carlo simulations) and analytically (via a master equation). The output statistics are controlled by two dimensionless free parameters: α, the glitch rate at a reference lag, multiplied by the critical lag for unpinning, divided by the spin-down rate; and β, the minimum fraction of the lag that can be restored by a glitch. The system evolves naturally to a self-regulated stationary state, whose properties are determined by α/αc(β), where αc(β) ≈ β-1/2 is a transition value. In the regime α ≳ αc(β), one recovers qualitatively the power-law size and exponential waiting-time distributions observed in many radio pulsars and Gross-Pitaevskii simulations. For α ≪ αc(β), the size and waiting-time distributions are both power-law-like, and a correlation emerges between size and waiting time until the next glitch, contrary to what is observed in most pulsars. Comparisons with astrophysical data are restricted by the small sample sizes available at present, with ≤35 events observed per pulsar.
Simple and flexible SAS and SPSS programs for analyzing lag-sequential categorical data.
O'Connor, B P
1999-11-01
This paper describes simple and flexible programs for analyzing lag-sequential categorical data, using SAS and SPSS. The programs read a stream of codes and produce a variety of lag-sequential statistics, including transitional frequencies, expected transitional frequencies, transitional probabilities, adjusted residuals, z values, Yule's Q values, likelihood ratio tests of stationarity across time and homogeneity across groups or segments, transformed kappas for unidirectional dependence, bidirectional dependence, parallel and nonparallel dominance, and significance levels based on both parametric and randomization tests.
Information theoretical approach to discovering solar wind drivers of the outer radiation belt
Wing, Simon; Johnson, Jay R.; Camporeale, Enrico; ...
2016-07-29
The solar wind-magnetosphere system is nonlinear. The solar wind drivers of geosynchronous electrons with energy range of 1.8–3.5 MeV are investigated using mutual information, conditional mutual information (CMI), and transfer entropy (TE). These information theoretical tools can establish linear and nonlinear relationships as well as information transfer. The information transfer from solar wind velocity ( Vsw) to geosynchronous MeV electron flux ( Je) peaks with a lag time of 2 days. As previously reported, Je is anticorrelated with solar wind density ( nsw) with a lag of 1 day. However, this lag time and anticorrelation can be attributed at leastmore » partly to the Je( t + 2 days) correlation with Vsw( t) and nsw( t + 1 day) anticorrelation with Vsw( t). Analyses of solar wind driving of the magnetosphere need to consider the large lag times, up to 3 days, in the ( Vsw, nsw) anticorrelation. Using CMI to remove the effects of Vsw, the response of Je to nsw is 30% smaller and has a lag time < 24 h, suggesting that the MeV electron loss mechanism due to nsw or solar wind dynamic pressure has to start operating in < 24 h. nsw transfers about 36% as much information as Vsw (the primary driver) to Je. Nonstationarity in the system dynamics is investigated using windowed TE. Here, when the data are ordered according to transfer entropy value, it is possible to understand details of the triangle distribution that has been identified between Je( t + 2 days) versus Vsw( t).« less
Information theoretical approach to discovering solar wind drivers of the outer radiation belt
DOE Office of Scientific and Technical Information (OSTI.GOV)
Wing, Simon; Johnson, Jay R.; Camporeale, Enrico
The solar wind-magnetosphere system is nonlinear. The solar wind drivers of geosynchronous electrons with energy range of 1.8–3.5 MeV are investigated using mutual information, conditional mutual information (CMI), and transfer entropy (TE). These information theoretical tools can establish linear and nonlinear relationships as well as information transfer. The information transfer from solar wind velocity ( Vsw) to geosynchronous MeV electron flux ( Je) peaks with a lag time of 2 days. As previously reported, Je is anticorrelated with solar wind density ( nsw) with a lag of 1 day. However, this lag time and anticorrelation can be attributed at leastmore » partly to the Je( t + 2 days) correlation with Vsw( t) and nsw( t + 1 day) anticorrelation with Vsw( t). Analyses of solar wind driving of the magnetosphere need to consider the large lag times, up to 3 days, in the ( Vsw, nsw) anticorrelation. Using CMI to remove the effects of Vsw, the response of Je to nsw is 30% smaller and has a lag time < 24 h, suggesting that the MeV electron loss mechanism due to nsw or solar wind dynamic pressure has to start operating in < 24 h. nsw transfers about 36% as much information as Vsw (the primary driver) to Je. Nonstationarity in the system dynamics is investigated using windowed TE. Here, when the data are ordered according to transfer entropy value, it is possible to understand details of the triangle distribution that has been identified between Je( t + 2 days) versus Vsw( t).« less
Gadalla, Tahany M; Fuller-Thomson, Esme
2008-12-01
State-level income inequality has been found to have an effect on individual health outcomes, even when controlled for important individual-level variables such as income, education, age, and gender. The effect of income inequality on health may not be immediate and may, in fact, have a substantial lag time between exposure to inequality and eventual health outcome. We used the 2006 American Community Survey to examine the association of state-level income inequality and 2 types of physical disabilities. We used 6 different lag times, ranging between 0 and 25 years, on the total sample and on those who resided in their state of birth. Income inequality in 1986 had the strongest correlation with 2006 disability levels. Odds ratios were consistently 10% higher for those born in the same state compared with the total population.
What time-lag for a retraction search on PubMed?
Decullier, Evelyne; Huot, Laure; Maisonneuve, Hervé
2014-06-25
To investigate fraud and errors, scientists have studied cohorts of retraction notices. These researches have been performed using a PubMed search on publication type "retraction of publication" which retrieves the notices of the retractions. We assessed the stability of the indexation of retraction notices over a 15-month period and what was the time-lag to get stability. A search on notices of retraction issued in 2008 was repeated every 3 months during 15 months from February 2011. The first search resulted in 237 notices of retraction. Throughout the study period, 14 discrepancies with the initial search were observed (6%). We found that the number of retraction notices became stable 35 months after the retraction. The time-lag observed in this study has to be taken into account when performing a PubMed search.
A Dynamic Attitude Measurement System Based on LINS
Li, Hanzhou; Pan, Quan; Wang, Xiaoxu; Zhang, Juanni; Li, Jiang; Jiang, Xiangjun
2014-01-01
A dynamic attitude measurement system (DAMS) is developed based on a laser inertial navigation system (LINS). Three factors of the dynamic attitude measurement error using LINS are analyzed: dynamic error, time synchronization and phase lag. An optimal coning errors compensation algorithm is used to reduce coning errors, and two-axis wobbling verification experiments are presented in the paper. The tests indicate that the attitude accuracy is improved 2-fold by the algorithm. In order to decrease coning errors further, the attitude updating frequency is improved from 200 Hz to 2000 Hz. At the same time, a novel finite impulse response (FIR) filter with three notches is designed to filter the dither frequency of the ring laser gyro (RLG). The comparison tests suggest that the new filter is five times more effective than the old one. The paper indicates that phase-frequency characteristics of FIR filter and first-order holder of navigation computer constitute the main sources of phase lag in LINS. A formula to calculate the LINS attitude phase lag is introduced in the paper. The expressions of dynamic attitude errors induced by phase lag are derived. The paper proposes a novel synchronization mechanism that is able to simultaneously solve the problems of dynamic test synchronization and phase compensation. A single-axis turntable and a laser interferometer are applied to verify the synchronization mechanism. The experiments results show that the theoretically calculated values of phase lag and attitude error induced by phase lag can both match perfectly with testing data. The block diagram of DAMS and physical photos are presented in the paper. The final experiments demonstrate that the real-time attitude measurement accuracy of DAMS can reach up to 20″ (1σ) and the synchronization error is less than 0.2 ms on the condition of three axes wobbling for 10 min. PMID:25177802
Ghimire, Manish; McInnes, Fiona J; Watson, David G; Mullen, Alexander B; Stevens, Howard N E
2007-09-01
The aim of the current study was to investigate the in-vitro and in-vivo performance of a press-coated tablet (PCT) intended for time delayed drug release, consisting of a rapidly disintegrating theophylline core tablet, press-coated with barrier granules containing glyceryl behenate (GB) and low-substituted hydroxypropylcellulose (L-HPC). The PCTs showed pulsatile release with a lag time dependent upon the GB and L-HPC composition of the barrier layer. In-vivo gamma-scintigraphic studies were carried out for PCTs containing GB:L-HPC at 65:35 w/w and 75:25 w/w in the barrier layer in four beagle dogs, in either the fed or fasted state. The in-vivo lag time in both the fed and fasted states did not differ significantly (p>0.05) from the in-vitro lag time. Additionally, no significant difference (p<0.05) between in-vivo fed and fasted disintegration times was observed, demonstrating that in-vivo performance of the PCT was not influenced by the presence or absence of food in the gastrointestinal tract. A distinct lag time was obtained prior to the appearance of drug in plasma and correlated (R2=0.98) with disintegration time observed from scintigraphic images. However, following disintegration, no difference in pharmacokinetic parameters (AUC(0-6 dis), K(el), Cmax) was observed. The current study highlighted the potential use of these formulations for chronopharmaceutical drug delivery.
NASA Technical Reports Server (NTRS)
Bhattacharya, K.; Ghil, M.
1979-01-01
A slightly modified version of the one-dimensional time-dependent energy-balance climate model of Ghil and Bhattacharya (1978) is presented. The albedo-temperature parameterization has been reformulated and the smoothing of the temperature distribution in the tropics has been eliminated. The model albedo depends on time-lagged temperature in order to account for finite growth and decay time of continental ice sheets. Two distinct regimes of oscillatory behavior which depend on the value of the albedo-temperature time lag are considered.
A Novel Connectionist Network for Solving Long Time-Lag Prediction Tasks
NASA Astrophysics Data System (ADS)
Johnson, Keith; MacNish, Cara
Traditional Recurrent Neural Networks (RNNs) perform poorly on learning tasks involving long time-lag dependencies. More recent approaches such as LSTM and its variants significantly improve on RNNs ability to learn this type of problem. We present an alternative approach to encoding temporal dependencies that associates temporal features with nodes rather than state values, where the nodes explicitly encode dependencies over variable time delays. We show promising results comparing the network's performance to LSTM variants on an extended Reber grammar task.
Solar oscillations: time analysis of the GOLF p-mode signal
NASA Astrophysics Data System (ADS)
Renaud, C.; Grec, G.; Boumier, P.; Gabriel, A. H.; Robillot, J. M.; Cortés, T. Roca; Turck-Chièze, S.; Ulrich, R. K.
1999-05-01
We determine the intrinsic phase lag of the GOLF data for the solar p-mode velocity deduced either from one of the narrow band photometers working alternatively on blue and red wing of the sodium lines. The timing of the ``blue wing'' velocity coming from the current GOLF data is given in respect to the ground-based observations. The phase lag for the ``blue'' velocity is 6 s in advance relatively to a velocity coming from a differential device. For individual p modes, the phase lag from the ``blue'' velocity to the ``red'' velocity are not in opposition of phase, as expected in a very simple solar model, but differs from 8(o) to 18(o) from the opposition, depending on the degree and the radial order of the acoustic mode. The measurement of the differential lag between the blue and red wings of the D lines may open a new way to monitor the temperature oscillations with the optical depth.
Liu, Zhi-Hua; Chang, Yu; Chen, Hong-Wei; Zhou, Rui; Jing, Guo-Zhi; Zhang, Hong-Xin; Zhang, Chang-Meng
2008-03-01
By using geo-statistics and based on time-lag classification standard, a comparative study was made on the land surface dead combustible fuels in Huzhong forest area in Great Xing'an Mountains. The results indicated that the first level land surface dead combustible fuel, i. e., 1 h time-lag dead fuel, presented stronger spatial auto-correlation, with an average of 762.35 g x m(-2) and contributing to 55.54% of the total load. Its determining factors were species composition and stand age. The second and third levels land surface dead combustible fuel, i. e., 10 h and 100 h time-lag dead fuels, had a sum of 610.26 g x m(-2), and presented weaker spatial auto-correlation than 1 h time-lag dead fuel. Their determining factor was the disturbance history of forest stand. The complexity and heterogeneity of the factors determining the quality and quantity of forest land surface dead combustible fuels were the main reasons for the relatively inaccurate interpolation. However, the utilization of field survey data coupled with geo-statistics could easily and accurately interpolate the spatial pattern of forest land surface dead combustible fuel loads, and indirectly provide a practical basis for forest management.
Barbero, Ana M.; Frasch, H. Frederick
2015-01-01
Skin is commonly stored frozen and then thawed prior to use for in-vitro permeation experiments. Does frozen storage of skin alter its barrier property? Numerous studies have found contradictory answers to this question. In this study, the steady state flux and lag time of diethyl phthalate (DEP) were measured for fresh human skin and skin frozen at −85 °C for 1, 2, 3, 6, 9, 12, and 18 months, with 10% glycerol as cryoprotective agent. No significant differences in steady state flux were found between fresh and previously frozen samples (P = 0.6). For lag time, a significant (P = 0.002) difference was found among all groups but comparisons with fresh skin were not significant. Does glycerol have a cryoprotective effect? The steady state flux and lag time of DEP and caffeine were measured through human skin stored at −85 °C for up to 12 months with and without 10 % glycerol. No significant differences in steady state flux or lag time were found between samples stored with or without glycerol for either DEP or caffeine (P ≥ 0.17). These findings support the use of frozen skin to measure the passive permeation of chemicals in studies unconcerned with viability and metabolism. PMID:26606593
Development of a gastroretentive pulsatile drug delivery platform.
Thitinan, Sumalee; McConville, Jason T
2012-04-01
To develop a novel gastroretentive pulsatile drug delivery platform by combining the advantages of floating dosage forms for the stomach and pulsatile drug delivery systems. A gastric fluid impermeable capsule body was used as a vessel to contain one or more drug layer(s) as well as one or more lag-time controlling layer(s). A controlled amount of air was sealed in the innermost portion of the capsule body to reduce the overall density of the drug delivery platform, enabling gastric floatation. An optimal mass fill inside the gastric fluid impermeable capsule body enabled buoyancy in a vertical orientation to provide a constant surface area for controlled erosion of the lag-time controlling layer. The lag-time controlling layer consisted of a swellable polymer, which rapidly formed a gel to seal the mouth of capsule body and act as a barrier to gastric fluid ingress. By varying the composition of the lag-time controlling layer, it was possible to selectively program the onset of the pulsatile delivery of a drug. This new delivery platform offers a new method of delivery for a variety of suitable drugs targeted in chronopharmaceutical therapy. This strategy could ultimately improve drug efficacy and patient compliance, and reduce harmful side effects by scaling back doses of drug administered. © 2012 The Authors. JPP © 2012 Royal Pharmaceutical Society.
Formulation and evaluation of floating tablet of H2-receptor antagonist.
Kesarla, Rajesh S; Vora, Pratik Ashwinbhai; Sridhar, B K; Patel, Gunvant; Omri, Abdelwahab
2015-01-01
Conventional sustained dosage form of ranitidine hydrochloride (HCl) does not prevent frequent administration due to its degradation in colonic media and limited absorption in the upper part of GIT. Ranitidine HCl floating tablet was formulated with sublimation method to overcome the stated problem. Compatibility study for screening potential excipients was carried out using Fourier transform infrared spectroscopy (FT-IR) and differential scanning chromatography (DSC). Selected excipients were further evaluated for optimizing the formulation. Preliminary screening of binder, polymer and sublimating material was based on hardness and drug release, drug release with release kinetics and floating lag time with total floatation time, respectively. Selected excipients were subjected to 3(2) factorial design with polymer and sublimating material as independent factors. Matrix tablets were obtained by using 16/32" flat-faced beveled edges punches followed by sublimation. FT-IR and DSC indicated no significant incompatibility with selected excipients. Klucel-LF, POLYOX WSR N 60 K and l-menthol were selected as binder, polymer and sublimating material, respectively, for factorial design batches after preliminary screening. From the factorial design batches, optimum concentration to release the drug within 12 h was found to be 420 mg of POLYOX and 40 mg of l-menthol. Stability studies indicated the formulation as stable. Ranitidine HCl matrix floating tablets were formulated to release 90% of drug in stomach within 12 h. Hence, release of the drug could be sustained within narrow absorption site. Moreover, the dosage form was found to be floating within a fraction of second independent of the pH of media ensuring a robust formulation.
Jagdale, Swati C; Pawar, Chandrakala R
2014-01-01
Migraine follows circadian rhythm in which headache is more painful at the awakening time. This needs administration of dosage form at night time to release drug after lag period when pain gets worse. Sumatriptan succinate is a drug of choice for migraine. Sumatriptan succinate has bitter taste, low oral bioavailability, and shorter half-life. Present work deals with application of design of experiment for polyox and xanthan gum in development of press coated floating pulsatile tablet. Floating pulsatile concept was applied to increase gastric residence of the dosage form. Burst release was achieved through immediate release tablet using crospovidone as superdisintegrant (10%). Pulse lag time was achieved using swellable polymer polyox WSR 205 and xanthan gum. 3(2) experimental design was applied. Optimized formulation was evaluated for physical characteristics and in-vitro and in-vivo study. From results, it can be concluded that optimized batch F8 containing polyox WSR205 (72.72%) and xanthan gum (27.27%) of total weight of polymer has shown floating lag time of 55 ± 2 sec, drug content of 100.35 ± 0.4%, hardness of 6 ± 0.1 Kg/cm(2), and 98.69 ± 2% drug release in pulse manner with lag time of 7 ± 0.1 h. Optimized batch showed prolong gastric residence which was confirmed by in-vivo X-ray study.
Jagdale, Swati C; Pawar, Chandrakala R
2014-01-01
Floating pulsatile is combined approach designed according to circadian rhythm to deliver the drug at right time, in right quantity and at right site as per pathophysiological need of disease with prolong gastric residence and lag phase followed by burst release. As the migraine follows circadian rhythm in which headache is more painful at the awakening time, the dosage form should be given during night time to release drug when pain get worsen. Present work deals with formulation and optimization of floating pulsatile tablet of sumatriptan succinate. Core tablet containing crospovidone as superdisintegrant (10%) showed burst release. Lag time was maintained using swellable polymer as polyoxN12K and xanthum gum. 3(2) experimental design was carried out. Developed formulations were evaluated for physical characteristics, in vitro and in vivo study. Optimized batch F2 with concentration of polyox N12K (73.43%) and xanthum gum (26.56%) of total polymer weight showed floating lag time 15±2 sec, drug content 99.58±0.2 %, hardness 6±0.2 Kg/cm(2) and drug release 99.54±2% with pulsatile manner followed lag period of 7±0.1h. In vivo x-ray study confirms prolong gastric residence of system. Programmable pulsatile release has been achieved by formulation F2 which meet demand of chronotherapeutic objective of migraine.
Layered Ensemble Architecture for Time Series Forecasting.
Rahman, Md Mustafizur; Islam, Md Monirul; Murase, Kazuyuki; Yao, Xin
2016-01-01
Time series forecasting (TSF) has been widely used in many application areas such as science, engineering, and finance. The phenomena generating time series are usually unknown and information available for forecasting is only limited to the past values of the series. It is, therefore, necessary to use an appropriate number of past values, termed lag, for forecasting. This paper proposes a layered ensemble architecture (LEA) for TSF problems. Our LEA consists of two layers, each of which uses an ensemble of multilayer perceptron (MLP) networks. While the first ensemble layer tries to find an appropriate lag, the second ensemble layer employs the obtained lag for forecasting. Unlike most previous work on TSF, the proposed architecture considers both accuracy and diversity of the individual networks in constructing an ensemble. LEA trains different networks in the ensemble by using different training sets with an aim of maintaining diversity among the networks. However, it uses the appropriate lag and combines the best trained networks to construct the ensemble. This indicates LEAs emphasis on accuracy of the networks. The proposed architecture has been tested extensively on time series data of neural network (NN)3 and NN5 competitions. It has also been tested on several standard benchmark time series data. In terms of forecasting accuracy, our experimental results have revealed clearly that LEA is better than other ensemble and nonensemble methods.
LAG3 Expression in Active Mycobacterium tuberculosis Infections
Phillips, Bonnie L.; Mehra, Smriti; Ahsan, Muhammad H.; Selman, Moises; Khader, Shabaana A.; Kaushal, Deepak
2016-01-01
Mycobacterium tuberculosis (MTB) is a highly successful pathogen because of its ability to persist in human lungs for long periods of time. MTB modulates several aspects of the host immune response. Lymphocyte-activation gene 3 (LAG3) is a protein with a high affinity for the CD4 receptor and is expressed mainly by regulatory T cells with immunomodulatory functions. To understand the function of LAG3 during MTB infection, a nonhuman primate model of tuberculosis, which recapitulates key aspects of natural human infection in rhesus macaques (Macaca mulatta), was used. We show that the expression of LAG3 is highly induced in the lungs and particularly in the granulomatous lesions of macaques experimentally infected with MTB. Furthermore, we show that LAG3 expression is not induced in the lungs and lung granulomas of animals exhibiting latent tuberculosis infection. However, simian immunodeficiency virus–induced reactivation of latent tuberculosis infection results in an increased expression of LAG3 in the lungs. This response is not observed in nonhuman primates infected with non-MTB bacterial pathogens, nor with simian immunodeficiency virus alone. Our data show that LAG3 was expressed primarily on CD4+ T cells, presumably by regulatory T cells but also by natural killer cells. The expression of LAG3 coincides with high bacterial burdens and changes in the host type 1 helper T-cell response. PMID:25549835
Santaniello, G; Ferré, P; Rodríguez-Gómez, P; Poch, C; Eva, M Moreno; Hinojosa, J A
2018-06-15
Evidence from prior studies has shown an advantage in recognition memory for emotional compared to neutral words. Whether this advantage is short-lived or rather extends over longer periods, as well as whether the effect depends on words' valence (i.e., positive or negative), remains unknown. In the present ERP/EEG study, we investigated this issue by manipulating the lag distance (LAG-2, LAG-8 and LAG-16) between the presentation of old and new words in an online recognition memory task. LAG differences were observed at behavior, ERPs and in the theta frequency band. In line with previous studies, negative words were associated with faster reaction times, higher hit rates and increased amplitude in a positive ERP component between 386 and 564 ms compared to positive and neutral words. Remarkably, the interaction of LAG by EMOTION revealed that negative words were associated with better performance and larger ERPs amplitudes only at LAG-2. Also in the LAG-2 condition, emotional words (i.e., positive and negative words) induced a stronger desynchronization in the beta band between 386 and 542 ms compared to neutral words. These early enhanced memory effects for emotional words are discussed in terms of the Negative Emotional Valence Enhances Recapitulation (NEVER) model and the mobilization-minimization hypothesis. Copyright © 2018 Elsevier Ltd. All rights reserved.
Kodati, Devender; Yellu, Narsimhareddy
2017-06-01
Furosemide is a loop diuretic drug frequently indicated in hypertension and fluid overload conditions such as congestive heart failure and hepatic cirrhosis. The purpose of the study was to establish a population pharmacokinetic model for furosemide in Indian hypertensive and fluid overload patients, and to evaluate effects of covariates on the volume of distribution (V/F) and oral clearance (CL/F) of furosemide. A total of 188 furosemide plasma sample concentrations from 63 patients with hypertension or fluid overload conditions were collected in this study. The population pharmacokinetic model for furosemide was built using Phoenix NLME 1.3 software. The covariates included age, sex, body surface area, bodyweight, height and creatinine clearance (CRCL). The pharmacokinetic data of furosemide was adequately explained by a two-compartment linear pharmacokinetic model with first-order absorption and an absorption lag-time. The mean values of CL/F and Vd/F of furosemide in the patients were 15.054Lh -1 and 4.419L, respectively. Analysis of covariates showed that CRCL was significantly influencing the clearance of furosemide. The final population pharmacokinetic model was demonstrated to be appropriate and effective and it can be used to assess the pharmacokinetic parameters of furosemide in Indian patients with hypertension and fluid overload conditions. Copyright © 2017. Published by Elsevier Urban & Partner Sp. z o.o.
Formulation and evaluation of atenolol floating bioadhesive system using optimized polymer blends
Siddam, Haritha; Kotla, Niranjan G.; Maddiboyina, Balaji; Singh, Sima; Sunnapu, Omprakash; Kumar, Anil; Sharma, Dinesh
2016-01-01
Introduction: Oral sustained release gastro retentive dosage forms offer several advantages for drugs having absorption from the upper gastrointestinal tract to improve the bioavailability of medications which have narrow absorption window. The aim of the study was to develop a floating bioadhesive drug delivery system exhibiting a unique combination of floatation and bioadhesion to prolong the residence in the stomach using atenolol as a model drug. Methods: Prior to compression, polymeric blend(s) were evaluated for flow properties. The tablets were prepared by direct compression method using bioadhesive polymer like Carbopol 934P and hydrophilic polymers like HPMC K4M, HPMC K15M, and HPMC K100M. The prepared tablets were evaluated for physical characteristics, bioadhesive strength, buoyancy lag time, swelling index and in vitro drug release studies. Results: The mean bioadhesive strength was found to be in the range of 16.2 to 52.1 gm. The optimized blend (F11) showed 92.3% drug releases after 24 hrs. Whilst, increase in concentration of carbopol 934P, bioadhesive strength and swelling index was increased with slow release. The n values of optimized formulations were found in the range of 0.631-0.719 indicating non-fickian anomalous type transport mechanism. Conclusion: The study aided in developing an ideal once-a-day gastro retentive floating drug delivery system with improved floating, swelling and bioadhesive characteristics with better bioavailability. PMID:27051631
Jaffe, B.E.; Rubin, D.M.
1996-01-01
The time-dependent response of sediment suspension to flow velocity was explored by modeling field measurements collected in the surf zone during a large storm. Linear and nonlinear models were created and tested using flow velocity as input and suspended-sediment concentration as output. A sequence of past velocities (velocity history), as well as velocity from the same instant as the suspended-sediment concentration, was used as input; this velocity history length was allowed to vary. The models also allowed for a lag between input (instantaneous velocity or end of velocity sequence) and output (suspended-sediment concentration). Predictions of concentration from instantaneous velocity or instantaneous velocity raised to a power (up to 8) using linear models were poor (correlation coefficients between predicted and observed concentrations were less than 0.10). Allowing a lag between velocity and concentration improved linear models (correlation coefficient of 0.30), with optimum lag time increasing with elevation above the seabed (from 1.5 s at 13 cm to 8.5 s at 60 cm). These lags are largely due to the time for an observed flow event to effect the bed and mix sediment upward. Using a velocity history further improved linear models (correlation coefficient of 0.43). The best linear model used 12.5 s of velocity history (approximately one wave period) to predict concentration. Nonlinear models gave better predictions than linear models, and, as with linear models, nonlinear models using a velocity history performed better than models using only instantaneous velocity as input. Including a lag time between the velocity and concentration also improved the predictions. The best model (correlation coefficient of 0.58) used 3 s (approximately a quarter wave period) of the cross-shore velocity squared, starting at 4.5 s before the observed concentration, to predict concentration. Using a velocity history increases the performance of the models by specifying a more complete description of the dynamical forcing of the flow (including accelerations and wave phase and shape) responsible for sediment suspension. Incorporating such a velocity history and a lag time into the formulation of the forcing for time-dependent models for sediment suspension in the surf zone will greatly increase our ability to predict suspended-sediment transport.
von Biela, Vanessa R.; Zimmerman, Christian E.; Moulton, L. L.
2011-01-01
Arctic cisco Coregonus autumnalis young-of-year (YOY) growth was used as a proxy to examine the long-term response of a high-latitude fish population to changing climate from 1978 to 2004. YOY growth increased over time (r2 = 0·29) and was correlated with monthly averages of the Arctic oscillation index, air temperature, east wind speed, sea-ice concentration and river discharge with and without time lags. Overall, the most prevalent correlates to YOY growth were sea-ice concentration lagged 1 year (significant correlations in 7 months; r2 = 0·14-0·31) and Mackenzie River discharge lagged 2 years (significant correlations in 8 months; r2 = 0·13-0·50). The results suggest that decreased sea-ice concentrations and increased river discharge fuel primary production and that life cycles of prey species linking increased primary production to fish growth are responsible for the time lag. Oceanographic studies also suggest that sea ice concentration and fluvial inputs from the Mackenzie River are key factors influencing productivity in the Beaufort Sea. Future research should assess the possible mechanism relating sea ice concentration and river discharge to productivity at upper trophic levels.
On the Nature of QPO Phase Lags in Black Hole Candidates
NASA Technical Reports Server (NTRS)
Shaposhnikov, Nikolai
2012-01-01
Observations of quasi-periodic oscillations (QPOs) in X-ray binaries hold a key to understanding many aspects of these enigmatic systems. Complex appearance of the Fourier phase lags related to QPOs is one of the most puzzling observational effects in accreting black holes. In this Letter we show that QPO properties, including phase lags, can be explained in a framework of a simple scenario, where the oscillating media provides a feedback on the emerging spectrum. We demonstrate that the QPO waveform is presented by the product of a perturbation and a time delayed response factors, where the response is energy dependent. The essential property of this effect is its non-linear and multiplicative nature. Our multiplicative reverberation model successfully describes the QPO components in energy dependent power spectra as well as the appearance of the phase lags between signal in different energy bands. We apply our model to QPOs observed by Rossi X-ray Timing Explorer in BH candidate XTE J1550-564. We briefly discuss the implications of the observed energy dependence of the QPO reverberation times and amplitudes to the nature of the power law spectral component and its variability.
Urbanization and Income Inequality in Post-Reform China: A Causal Analysis Based on Time Series Data
Chen, Guo; Glasmeier, Amy K.; Zhang, Min; Shao, Yang
2016-01-01
This paper investigates the potential causal relationship(s) between China’s urbanization and income inequality since the start of the economic reform. Based on the economic theory of urbanization and income distribution, we analyze the annual time series of China’s urbanization rate and Gini index from 1978 to 2014. The results show that urbanization has an immediate alleviating effect on income inequality, as indicated by the negative relationship between the two time series at the same year (lag = 0). However, urbanization also seems to have a lagged aggravating effect on income inequality, as indicated by positive relationship between urbanization and the Gini index series at lag 1. Although the link between urbanization and income inequality is not surprising, the lagged aggravating effect of urbanization on the Gini index challenges the popular belief that urbanization in post-reform China generally helps reduce income inequality. At deeper levels, our results suggest an urgent need to focus on the social dimension of urbanization as China transitions to the next stage of modernization. Comprehensive social reforms must be prioritized to avoid a long-term economic dichotomy and permanent social segregation. PMID:27433966
Chen, Guo; Glasmeier, Amy K; Zhang, Min; Shao, Yang
2016-01-01
This paper investigates the potential causal relationship(s) between China's urbanization and income inequality since the start of the economic reform. Based on the economic theory of urbanization and income distribution, we analyze the annual time series of China's urbanization rate and Gini index from 1978 to 2014. The results show that urbanization has an immediate alleviating effect on income inequality, as indicated by the negative relationship between the two time series at the same year (lag = 0). However, urbanization also seems to have a lagged aggravating effect on income inequality, as indicated by positive relationship between urbanization and the Gini index series at lag 1. Although the link between urbanization and income inequality is not surprising, the lagged aggravating effect of urbanization on the Gini index challenges the popular belief that urbanization in post-reform China generally helps reduce income inequality. At deeper levels, our results suggest an urgent need to focus on the social dimension of urbanization as China transitions to the next stage of modernization. Comprehensive social reforms must be prioritized to avoid a long-term economic dichotomy and permanent social segregation.
NASA Astrophysics Data System (ADS)
Grover, D.; Seth, R. K.
2018-05-01
Analysis and numerical results are presented for the thermoelastic dissipation of a homogeneous isotropic, thermally conducting, Kelvin-Voigt type circular micro-plate based on Kirchhoff's Love plate theory utilizing generalized viscothermoelasticity theory of dual-phase-lagging model. The analytical expressions for thermoelastic damping of vibration and frequency shift are obtained for generalized dual-phase-lagging model and coupled viscothermoelastic plates. The scaled thermoelastic damping has been illustrated in case of circular plate and axisymmetric circular plate for fixed aspect ratio for clamped and simply supported boundary conditions. It is observed that the damping of vibrations significantly depend on time delay and mechanical relaxation times in addition to thermo-mechanical coupling in circular plate under resonance conditions and plate dimensions.
Analysis of munitions constituents in groundwater using a field-portable GC-MS.
Bednar, A J; Russell, A L; Hayes, C A; Jones, W T; Tackett, P; Splichal, D E; Georgian, T; Parker, L V; Kirgan, R A; MacMillan, D K
2012-05-01
The use of munitions constituents (MCs) at military installations can produce soil and groundwater contamination that requires periodic monitoring even after training or manufacturing activities have ceased. Traditional groundwater monitoring methods require large volumes of aqueous samples (e.g., 2-4 L) to be shipped under chain of custody, to fixed laboratories for analysis. The samples must also be packed on ice and shielded from light to minimize degradation that may occur during transport and storage. The laboratory's turn-around time for sample analysis and reporting can be as long as 45 d. This process hinders the reporting of data to customers in a timely manner; yields data that are not necessarily representative of current site conditions owing to the lag time between sample collection and reporting; and incurs significant shipping costs for samples. The current work compares a field portable Gas Chromatograph-Mass Spectrometer (GC-MS) for analysis of MCs on-site with traditional laboratory-based analysis using High Performance Liquid Chromatography with UV absorption detection. The field method provides near real-time (within ~1 h of sampling) concentrations of MCs in groundwater samples. Mass spectrometry provides reliable confirmation of MCs and a means to identify unknown compounds that are potential false positives for methods with UV and other non-selective detectors. Published by Elsevier Ltd.
Milutinović, Suzana; Nikić, Dragana; Stosić, Ljiljana; Stanković, Aleksandra; Bogdanović, Dragan
2009-03-01
The present study assesses the short-term association between black smoke (BS) and sulphur dioxide (SO2) levels in urban air and the daily number of emergency room admissions for chronic obstructive pulmonary disease (COPD) in Nis, Serbia. Generalised linear models extending Poisson regression were fitted controlling for time trend, seasonal variations, days of the week, temperature, relative humidity, air pressure, precipitation, rainfall, snowfall, overcast, and wind velocity. The emergency room admissions for all ages for COPD were significantly associated with previous-day level of BS and lag 0-2 (1,60% and 2,26% increase per 10 microg/m3, respectively). After controlling for SO2, single lagged (lag 1 and lag 2) as well as mean lagged values of BS (up to lag 0-3) were significantly associated with COPD emergencies. No effect was found for SO2, even after controlling for black smoke. The present findings support the conclusion that current levels of ambient BS may have an effect on the respiratory health of susceptible persons.
Visualizing the quality of partially accruing data for use in decision making.
Eaton, Julia; Painter, Ian; Olson, Don; Lober, William B
2015-01-01
Secondary use of clinical health data for near real-time public health surveillance presents challenges surrounding its utility due to data quality issues. Data used for real-time surveillance must be timely, accurate and complete if it is to be useful; if incomplete data are used for surveillance, understanding the structure of the incompleteness is necessary. Such data are commonly aggregated due to privacy concerns. The Distribute project was a near real-time influenza-like-illness (ILI) surveillance system that relied on aggregated secondary clinical health data. The goal of this work is to disseminate the data quality tools developed to gain insight into the data quality problems associated with these data. These tools apply in general to any system where aggregate data are accrued over time and were created through the end-user-as-developer paradigm. Each tool was developed during the exploratory analysis to gain insight into structural aspects of data quality. Our key finding is that data quality of partially accruing data must be studied in the context of accrual lag-the difference between the time an event occurs and the time data for that event are received, i.e. the time at which data become available to the surveillance system. Our visualization methods therefore revolve around visualizing dimensions of data quality affected by accrual lag, in particular the tradeoff between timeliness and completion, and the effects of accrual lag on accuracy. Accounting for accrual lag in partially accruing data is necessary to avoid misleading or biased conclusions about trends in indicator values and data quality.
Multi-time-scale X-ray reverberation mapping of accreting black holes
NASA Astrophysics Data System (ADS)
Mastroserio, Guglielmo; Ingram, Adam; van der Klis, Michiel
2018-04-01
Accreting black holes show characteristic reflection features in their X-ray spectrum, including an iron Kα line, resulting from hard X-ray continuum photons illuminating the accretion disc. The reverberation lag resulting from the path-length difference between direct and reflected emission provides a powerful tool to probe the innermost regions around both stellar-mass and supermassive black holes. Here, we present for the first time a reverberation mapping formalism that enables modelling of energy-dependent time lags and variability amplitude for a wide range of variability time-scales, taking the complete information of the cross-spectrum into account. We use a pivoting power-law model to account for the spectral variability of the continuum that dominates over the reverberation lags for longer time-scale variability. We use an analytic approximation to self-consistently account for the non-linear effects caused by this continuum spectral variability, which have been ignored by all previous reverberation studies. We find that ignoring these non-linear effects can bias measurements of the reverberation lags, particularly at low frequencies. Since our model is analytic, we are able to fit simultaneously for a wide range of Fourier frequencies without prohibitive computational expense. We also introduce a formalism of fitting to real and imaginary parts of our cross-spectrum statistic, which naturally avoids some mistakes/inaccuracies previously common in the literature. We perform proof-of-principle fits to Rossi X-ray Timing Explorer data of Cygnus X-1.
A global study of type B quasi-periodic oscillation in black hole X-ray binaries
NASA Astrophysics Data System (ADS)
Gao, H. Q.; Zhang, Liang; Chen, Yupeng; Zhang, Zhen; Chen, Li; Zhang, Shuang-Nan; Zhang, Shu; Ma, Xiang; Li, Zi-Jian; Bu, Qing-Cui; Qu, JinLu
2017-04-01
We performed a global study on the timing and spectral properties of type-B quasi-periodic oscillations (QPOs) in the outbursts of black hole X-ray binaries. The sample is built based on the observations of Rossi X-ray Timing Explorer (RXTE), via searching in the literature in RXTE era for all the identified type-B QPOs. To enlarge the sample, we also investigated some type-B QPOs that are reported but not yet fully identified. Regarding to the time lag and hard/soft flux ratio, we found that the sources with type-B QPOs behave in two subgroups. In one subgroup, type-B QPO shows a hard time lag that first decreases and then reverse into a soft time lag along with softening of the energy spectrum. In the other subgroup, type-B QPOs distribute only in a small region with hard time lag and relatively soft hardness. These findings may be understood with a diversity of the homogeneity showing up for the hot inner flow of different sources. We confirm the universality of a positive relation between the type-B QPO frequency and the hard component luminosity in different sources. We explain the results by considering that the type-B QPO photons are produced in the inner accretion flow around the central black hole, under a local Eddington limit. Using this relationship, we derived a mass estimation of 9.3-27.1 M⊙ for the black hole in H 1743-322.
Jeon, Sangil; Han, Seunghoon; Lee, Jongtae; Hong, Taegon; Yim, Dong-Seok
2012-08-01
We analyzed the pharmacokinetics of C3G on data from twelve subjects, after 2-week multiple dosing of black bean (Phaseolus vulgaris, Cheongjakong-3-ho) seed coat extract, using the mixed effect analysis method (NONMEM, Ver. 6.2), as well as the conventional non-compartmental method. We also examined the safety and tolerability. The PK analysis used plasma concentrations of the C3G on day 1 and 14. There was no observed accumulation of C3G after 2-week multiple dosing of black bean seed coat extract. The typical point estimates of PK were CL (clearance)=3,420 l/h, V (volume)=7,280 L, Ka (absorption constant)=9.94 h(-1), ALAG (lag time)=0.217 h. The black bean seed coat extract was well tolerated and there were no serious adverse events. In this study, we confirmed that a significant amount of C3G was absorbed in human after given the black bean seed coat extract.
Yom-Tov, Ortal; Seliktar, Dror; Bianco-Peled, Havazelet
2015-10-01
The use of buoyant or floating hydrogel tablets is of particular interest in the sustained release of drugs to the stomach. They have an ability to slow the release rates of drugs by prolonging their absorption window in the upper part of the gastrointestinal (GI) tract. In this study we synthesized bioactive hydrogels that have sustainable release rates for drugs in the stomach based on a hydrogel preparation technique that employs emulsifying surfactants. The emulsion gelation technique, which encapsulates oil droplets within the hydrogels during crosslinking, was used to decrease their specific gravity in aqueous environments, resulting in floating drug release depots. Properties such as swelling, buoyancy, density and drug release were manipulated by changing the polymer concentrations, surfactant percentages and the oil:polymer ratios. The relationship between these properties and the hydrogel's floating lag time was documented. The potential for this material to be used as a floating drug delivery system was demonstrated. Copyright © 2015 Elsevier B.V. All rights reserved.
Bilirubin-a potential marker of drug exposure in atazanavir-based antiretroviral therapy.
Rekić, Dinko; Clewe, Oskar; Röshammar, Daniel; Flamholc, Leo; Sönnerborg, Anders; Ormaasen, Vidar; Gisslén, Magnus; Abelö, Angela; Ashton, Michael
2011-12-01
The objective of this work was to examine the atazanavir-bilirubin relationship using a population-based approach and to assess the possible application of bilirubin as a readily available marker of atazanavir exposure. A model of atazanavir exposure and its concentration-dependent effect on bilirubin levels was developed based on 200 atazanavir and 361 bilirubin samples from 82 patients receiving atazanavir in the NORTHIV trial. The pharmacokinetics was adequately described by a one-compartment model with first-order absorption and lag-time. The maximum inhibition of bilirubin elimination rate constant (I(max)) was estimated at 91% (95% CI, 87-94) and the atazanavir concentration resulting in half of I(max) (IC50) was 0.30 μmol/L (95% CI, 0.24-0.37). At an atazanavir/ritonavir dose of 300/100 mg given once daily, the bilirubin half-life was on average increased from 1.6 to 8.1 h. A nomogram, which can be used to indicate suboptimal atazanavir exposure and non-adherence, was constructed based on model simulations.
Internet and free press are associated with reduced lags in global outbreak reporting.
McAlarnen, Lindsey; Smith, Katherine; Brownstein, John S; Jerde, Christopher
2014-10-30
Global outbreak detection and reporting have generally improved for a variety of infectious diseases and geographic regions in recent decades. Nevertheless, lags in outbreak reporting remain a threat to the global human health and economy. In the time between first occurrence of a novel disease incident and public notification of an outbreak, infected individuals have a greater possibility of traveling and spreading the pathogen to other nations. Shortening outbreak reporting lags has the potential to improve global health by preventing local outbreaks from escalating into global epidemics. Reporting lags between the first record and the first public report of an event were calculated for 318 outbreaks occurring 1996-2009. The influence of freedom of the press, Internet usage, per capita health expenditure, and cell phone subscriptions, on the timeliness of outbreak reporting was evaluated. Freer presses and increasing Internet usage correlate with reduced time between the first record of an outbreak and the public report. Increasing Internet usage reduced the expected reporting lag from more than one month in nations without Internet users to one day in those where 75 of 100 people use the Internet. Advances in technology and the emergence of more open and free governments are associated with to improved global infectious disease surveillance.
Delays in new drug applications in Japan and industrial R&D strategies.
Hirai, Y; Kinoshita, H; Kusama, M; Yasuda, K; Sugiyama, Y; Ono, S
2010-02-01
The gap between Japan and both the United States (US) and the European Union (EU) with regard to access to new drugs is becoming a major issue in Japan. We analyzed the time lags involved in new drug application (NDA) and biological license application submissions in Japan, the US, and the EU in order to identify the causes of delayed access. The time lag related to submission of applications ("submission lag") was longer for in-licensed products and for non-Japanese companies. Factors related to costs of clinical studies and potential volumes of sales were not associated with the submission lag. A bridging strategy (extrapolative use of foreign clinical data in the clinical data package based on International Conference on Harmonisation guideline E5) seemed to reduce submission lag, but the association between the two diminished when the cause-and-effect relationship was specifically investigated. These results suggest that multinational companies are likely to place more emphasis on the choice of development strategies that successfully lead to their goal rather than on direct costs and expected sales when deciding to introduce their pharmaceutical products in Japan. Our findings indicate that the clinical development guidances that helps pharmaceutical companies decide on investment and strategies are also the key to narrowing the gap in access to new drugs.
A Fixed-Lag Kalman Smoother to Filter Power Line Interference in Electrocardiogram Recordings.
Warmerdam, G J J; Vullings, R; Schmitt, L; Van Laar, J O E H; Bergmans, J W M
2017-08-01
Filtering power line interference (PLI) from electrocardiogram (ECG) recordings can lead to significant distortions of the ECG and mask clinically relevant features in ECG waveform morphology. The objective of this study is to filter PLI from ECG recordings with minimal distortion of the ECG waveform. In this paper, we propose a fixed-lag Kalman smoother with adaptive noise estimation. The performance of this Kalman smoother in filtering PLI is compared to that of a fixed-bandwidth notch filter and several adaptive PLI filters that have been proposed in the literature. To evaluate the performance, we corrupted clean neonatal ECG recordings with various simulated PLI. Furthermore, examples are shown of filtering real PLI from an adult and a fetal ECG recording. The fixed-lag Kalman smoother outperforms other PLI filters in terms of step response settling time (improvements that range from 0.1 to 1 s) and signal-to-noise ratio (improvements that range from 17 to 23 dB). Our fixed-lag Kalman smoother can be used for semi real-time applications with a limited delay of 0.4 s. The fixed-lag Kalman smoother presented in this study outperforms other methods for filtering PLI and leads to minimal distortion of the ECG waveform.
Short-term memory for pictures seen once or twice.
Martini, Paolo; Maljkovic, Vera
2009-06-01
The present study is concerned with the effects of exposure time, repetition, spacing and lag on old/new recognition memory for generic visual scenes presented in a RSVP paradigm. Early memory studies with verbal material found that knowledge of total exposure time at study is sufficient to accurately predict memory performance at test (the Total Time Hypothesis), irrespective of number of repetitions, spacing or lag. However, other studies have disputed such simple dependence of memory strength on total study time, demonstrating super-additive facilitatory effects of spacing and lag, as well as inhibitory effects, such as the Ranschburg effect, Repetition Blindness and the Attentional Blink. In the experimental conditions of the present study we find no evidence of either facilitatory or inhibitory effects: recognition memory for pictures in RSVP supports the Total Time Hypothesis. The data are consistent with an Unequal-Variance Signal Detection Theory model of memory that assumes the average strength and the variance of the familiarity of pictures both increase with total study time. The main conclusion is that the growth of visual scene familiarity with temporal exposure and repetition is a stochastically independent process.
Sornborger, Andrew T; Lauderdale, James D
2016-11-01
Neural data analysis has increasingly incorporated causal information to study circuit connectivity. Dimensional reduction forms the basis of most analyses of large multivariate time series. Here, we present a new, multitaper-based decomposition for stochastic, multivariate time series that acts on the covariance of the time series at all lags, C ( τ ), as opposed to standard methods that decompose the time series, X ( t ), using only information at zero-lag. In both simulated and neural imaging examples, we demonstrate that methods that neglect the full causal structure may be discarding important dynamical information in a time series.
Lagged PM2.5 effects in mortality time series: Critical impact of covariate model
The two most common approaches to modeling the effects of air pollution on mortality are the Harvard and the Johns Hopkins (NMMAPS) approaches. These two approaches, which use different sets of covariates, result in dissimilar estimates of the effect of lagged fine particulate ma...
18 CFR 154.312 - Composition of Statements.
Code of Federal Regulations, 2012 CFR
2012-04-01
... the time of filing. Give the docket number of the certificate proceeding. (2) Schedule C-2. Show, for... requested must be based on a fully-developed and reliable lead-lag study. The components of the lead-lag study must include actual total company revenues, purchased gas costs, storage expense, transportation...
18 CFR 154.312 - Composition of Statements.
Code of Federal Regulations, 2014 CFR
2014-04-01
... the time of filing. Give the docket number of the certificate proceeding. (2) Schedule C-2. Show, for... requested must be based on a fully-developed and reliable lead-lag study. The components of the lead-lag study must include actual total company revenues, purchased gas costs, storage expense, transportation...
18 CFR 154.312 - Composition of Statements.
Code of Federal Regulations, 2010 CFR
2010-04-01
... the time of filing. Give the docket number of the certificate proceeding. (2) Schedule C-2. Show, for... requested must be based on a fully-developed and reliable lead-lag study. The components of the lead-lag study must include actual total company revenues, purchased gas costs, storage expense, transportation...
18 CFR 154.312 - Composition of Statements.
Code of Federal Regulations, 2011 CFR
2011-04-01
... the time of filing. Give the docket number of the certificate proceeding. (2) Schedule C-2. Show, for... requested must be based on a fully-developed and reliable lead-lag study. The components of the lead-lag study must include actual total company revenues, purchased gas costs, storage expense, transportation...
Time-lagged autoencoders: Deep learning of slow collective variables for molecular kinetics
NASA Astrophysics Data System (ADS)
Wehmeyer, Christoph; Noé, Frank
2018-06-01
Inspired by the success of deep learning techniques in the physical and chemical sciences, we apply a modification of an autoencoder type deep neural network to the task of dimension reduction of molecular dynamics data. We can show that our time-lagged autoencoder reliably finds low-dimensional embeddings for high-dimensional feature spaces which capture the slow dynamics of the underlying stochastic processes—beyond the capabilities of linear dimension reduction techniques.
Interpretation of link fluctuations in climate networks during El Niño periods
NASA Astrophysics Data System (ADS)
Martin, E. A.; Paczuski, M.; Davidsen, J.
2013-05-01
Recent work has shown that the topologies of functional climate networks are sensitive to El Niño events. One important interpretation of the findings was that parts of the globe act in correlated relationships which become weaker, on average, during El Niño periods (this was shown using monthly averaged data where no time lag is required, and with daily averaged data where time lags were utilized). In contrast to this, we show that El Niño periods actually exhibit higher correlations than “Normal” climate conditions, while typically having lower correlations than La Niña periods. We also show that it is crucial to establish the sensitivity and the robustness of a given method used to extract functional climate networks —parameters such as time lags can significantly influence and even totally alter the outcome.
NASA Astrophysics Data System (ADS)
Stange, P.; Bach, L. T.; Le Moigne, F. A. C.; Taucher, J.; Boxhammer, T.; Riebesell, U.
2017-01-01
The ocean's potential to export carbon to depth partly depends on the fraction of primary production (PP) sinking out of the euphotic zone (i.e., the e-ratio). Measurements of PP and export flux are often performed simultaneously in the field, although there is a temporal delay between those parameters. Thus, resulting e-ratio estimates often incorrectly assume an instantaneous downward export of PP to export flux. Evaluating results from four mesocosm studies, we find that peaks in organic matter sedimentation lag chlorophyll a peaks by 2 to 15 days. We discuss the implications of these time lags (TLs) for current e-ratio estimates and evaluate potential controls of TL. Our analysis reveals a strong correlation between TL and the duration of chlorophyll a buildup, indicating a dependency of TL on plankton food web dynamics. This study is one step further toward time-corrected e-ratio estimates.
NASA Astrophysics Data System (ADS)
Lobban, A. P.; Porquet, D.; Reeves, J. N.; Markowitz, A.; Nardini, E.; Grosso, N.
2018-03-01
We present the spectral/timing properties of the bare Seyfert galaxy Ark 120 through a deep ˜420 ks XMM-Newton campaign plus recent NuSTAR observations and a ˜6-month Swift monitoring campaign. We investigate the spectral decomposition through fractional rms, covariance and difference spectra, finding the mid- to long-time-scale (˜day-year) variability to be dominated by a relatively smooth, steep component, peaking in the soft X-ray band. Additionally, we find evidence for variable Fe K emission redward of the Fe Kα core on long time-scales, consistent with previous findings. We detect a clearly defined power spectrum which we model with a power law with a slope of α ˜ 1.9. By extending the power spectrum to lower frequencies through the inclusion of Swift and Rossi X-ray Timing Explorer data, we find tentative evidence of a high-frequency break, consistent with existing scaling relations. We also explore frequency-dependent Fourier time lags, detecting a negative (`soft') lag for the first time in this source with the 0.3-1 keV band lagging behind the 1-4 keV band with a time delay, τ, of ˜900 s. Finally, we analyse the variability in the optical and ultraviolet (UV) bands using the Optical/UV Monitor onboard XMM-Newton and the Ultra-Violet/Optical Telescope onboard Swift and search for time-dependent correlations between the optical/UV/X-ray bands. We find tentative evidence for the U-band emission lagging behind the X-rays with a time delay of τ = 2.4 ± 1.8 d, which we discuss in the context of disc reprocessing.
Long-Lag, Wide-pulse Gamma-Ray Bursts
NASA Technical Reports Server (NTRS)
Norris, J. P.; Bonnell, J. T.; Kazanas, D.; Scargle, . D.; Hakkila, J.; Giblin, T. W.
2004-01-01
Currently, the best available probe of the early phase of gamma-ray burst (GRB) jet attributes is the prompt gamma-ray emission, in which several intrinsic and extrinsic variables determine GRB pulse evolution. Bright, usually complex bursts have many narrow pulses that are difficult to model due to overlap. However, the relatively simple, long spectral lag, wide-pulse bursts may have simpler physics and are easier to model. In this work we analyze the temporal and spectral behavior of wide pulses in 24 long-lag bursts, using a pulse model with two shape parameters - width and asymmetry - and the Band spectral model with three shape parameters. We find that pulses in long-lag bursts are distinguished both temporally and spectrally from those in bright bursts: the pulses in long spectral lag bursts are few in number, and approximately 100 times wider (10s of seconds), have systematically lower peaks in vF(v), harder low-energy spectra and softer high-energy spectra. We find that these five pulse descriptors are essentially uncorrelated for our long-lag sample, suggesting that at least approximately 5 parameters are needed to model burst temporal and spectral behavior. However, pulse width is strongly correlated with spectral lag; hence these two parameters may be viewed as mutual surrogates. We infer that accurate formulations for estimating GRB luminosity and total energy will depend on several gamma-ray attributes, at least for long-lag bursts. The prevalence of long-lag bursts near the BATSE trigger threshold, their predominantly low vF(v) spectral peaks, and relatively steep upper power-law spectral indices indicate that Swift will detect many such bursts.
Modelling the perennial energy crop market: the role of spatial diffusion
Alexander, Peter; Moran, Dominic; Rounsevell, Mark D. A.; Smith, Pete
2013-01-01
Biomass produced from energy crops, such as Miscanthus and short rotation coppice is expected to contribute to renewable energy targets, but the slower than anticipated development of the UK market implies the need for greater understanding of the factors that govern adoption. Here, we apply an agent-based model of the UK perennial energy crop market, including the contingent interaction of supply and demand, to understand the spatial and temporal dynamics of energy crop adoption. Results indicate that perennial energy crop supply will be between six and nine times lower than previously published, because of time lags in adoption arising from a spatial diffusion process. The model simulates time lags of at least 20 years, which is supported empirically by the analogue of oilseed rape adoption in the UK from the 1970s. This implies the need to account for time lags arising from spatial diffusion in evaluating land-use change, climate change (mitigation or adaptation) or the adoption of novel technologies. PMID:24026474
Observations of hysteresis in solar cycle variations among seven solar activity indicators
NASA Technical Reports Server (NTRS)
Bachmann, Kurt T.; White, Oran R.
1994-01-01
We show that smoothed time series of 7 indices of solar activity exhibit significant solar cycle dependent differences in their relative variations during the past 20 years. In some cases these observed hysteresis patterns start to repeat over more than one solar cycle, giving evidence that this is a normal feature of solar variability. Among the indices we study, we find that the hysteresis effects are approximately simple phase shifts, and we quantify these phase shifts in terms of lag times behind the leading index, the International Sunspot Number. Our measured lag times range from less than one month to greater than four months and can be much larger than lag times estimated from short-term variations of these same activity indices during the emergence and decay of major active regions. We argue that hysteresis represents a real delay in the onset and decline of solar activity and is an important clue in the search for physical processes responsible for changing solar emission at various wavelengths.
Modelling the perennial energy crop market: the role of spatial diffusion.
Alexander, Peter; Moran, Dominic; Rounsevell, Mark D A; Smith, Pete
2013-11-06
Biomass produced from energy crops, such as Miscanthus and short rotation coppice is expected to contribute to renewable energy targets, but the slower than anticipated development of the UK market implies the need for greater understanding of the factors that govern adoption. Here, we apply an agent-based model of the UK perennial energy crop market, including the contingent interaction of supply and demand, to understand the spatial and temporal dynamics of energy crop adoption. Results indicate that perennial energy crop supply will be between six and nine times lower than previously published, because of time lags in adoption arising from a spatial diffusion process. The model simulates time lags of at least 20 years, which is supported empirically by the analogue of oilseed rape adoption in the UK from the 1970s. This implies the need to account for time lags arising from spatial diffusion in evaluating land-use change, climate change (mitigation or adaptation) or the adoption of novel technologies.
Haraguchi, Tomoya; Kimura, Shiho; Itoh, Harumichi; Nishikawa, Shimpei; Hiyama, Masato; Tani, Kenji; Iseri, Toshie; Itoh, Yoshiki; Nakaichi, Munekazu; Taura, Yasuho; Itamoto, Kazuhito
2017-09-12
This study compared the effects of postoperative pain and inflammation reaction after preventive laparoscopic-assisted gastropexy (LAG) and incisional gastropexy (IG) in 10 clinically normal Beagles. Surgical time, incision length, visual analog scale (VAS) score, University of Melbourne Pain Scale (UMPS) score, and plasma C-reactive protein (CRP), plasma cortisol (COR), and serum interleukin-6 (IL-6) levels were evaluated. The VAS and UMPS scores and COR and IL-6 levels were recorded at 0.5, 1, 2, 4, 8, 12, 18 and 24 hr after surgery. CRP level was recorded at 12, 24 and 48 hr after surgery. The VAS and UMPS scores showed no significant intergroup differences. Compared to IG, LAG had significantly lower surgical time (45 ± 9.91 min vs 64 ± 5.30 min; P<0.05), incision length (46 ± 8.21 mm vs 129 ± 19.49 mm; P<0.05), CRP level (12 hr after surgery; 4.58 ± 1.58 mg/dl vs 12.4 ± 1.34 mg/dl; P<0.01), and COR level (1 hr after surgery; 10.79 ± 3.07 µg/dl vs 15.9 ± 3.77 µg/dl; P<0.05). IL-6 levels showed no significant intergroup differences at any time point. However, LAG resulted in lower IL-6 levels than did IG at all postoperative time points. Neither procedure resulted in significant surgical complications. LAG produced lower surgical stress than did IG, suggesting that LAG is a safe, minimally invasive, and highly useful technique for preventing canine gastric dilatation-volvulus. Nevertheless, since this study used experimental models, its usefulness should be evaluated in future cases.
HARAGUCHI, Tomoya; KIMURA, Shiho; ITOH, Harumichi; NISHIKAWA, Shimpei; HIYAMA, Masato; TANI, Kenji; ISERI, Toshie; ITOH, Yoshiki; NAKAICHI, Munekazu; TAURA, Yasuho; ITAMOTO, Kazuhito
2017-01-01
This study compared the effects of postoperative pain and inflammation reaction after preventive laparoscopic-assisted gastropexy (LAG) and incisional gastropexy (IG) in 10 clinically normal Beagles. Surgical time, incision length, visual analog scale (VAS) score, University of Melbourne Pain Scale (UMPS) score, and plasma C-reactive protein (CRP), plasma cortisol (COR), and serum interleukin-6 (IL-6) levels were evaluated. The VAS and UMPS scores and COR and IL-6 levels were recorded at 0.5, 1, 2, 4, 8, 12, 18 and 24 hr after surgery. CRP level was recorded at 12, 24 and 48 hr after surgery. The VAS and UMPS scores showed no significant intergroup differences. Compared to IG, LAG had significantly lower surgical time (45 ± 9.91 min vs 64 ± 5.30 min; P<0.05), incision length (46 ± 8.21 mm vs 129 ± 19.49 mm; P<0.05), CRP level (12 hr after surgery; 4.58 ± 1.58 mg/dl vs 12.4 ± 1.34 mg/dl; P<0.01), and COR level (1 hr after surgery; 10.79 ± 3.07 µg/dl vs 15.9 ± 3.77 µg/dl; P<0.05). IL-6 levels showed no significant intergroup differences at any time point. However, LAG resulted in lower IL-6 levels than did IG at all postoperative time points. Neither procedure resulted in significant surgical complications. LAG produced lower surgical stress than did IG, suggesting that LAG is a safe, minimally invasive, and highly useful technique for preventing canine gastric dilatation-volvulus. Nevertheless, since this study used experimental models, its usefulness should be evaluated in future cases. PMID:28717065
Revealing structure and evolution within the corona of the Seyfert galaxy I Zw 1
NASA Astrophysics Data System (ADS)
Wilkins, D. R.; Gallo, L. C.; Silva, C. V.; Costantini, E.; Brandt, W. N.; Kriss, G. A.
2017-11-01
X-ray spectral timing analysis is presented of XMM-Newton observations of the narrow-line Seyfert 1 galaxy I Zwicky 1 taken in 2015 January. After exploring the effect of background flaring on timing analyses, X-ray time lags between the reflection-dominated 0.3-1.0 keV energy and continuum-dominated 1.0-4.0 keV band are measured, indicative of reverberation off the inner accretion disc. The reverberation lag time is seen to vary as a step function in frequency; across lower frequency components of the variability, 3 × 10-4-1.2 × 10-3 Hz a lag of 160 s is measured, but the lag shortens to (59 ± 4) s above 1.2 × 10-3 Hz. The lag-energy spectrum reveals differing profiles between these ranges with a change in the dip showing the earliest arriving photons. The low-frequency signal indicates reverberation of X-rays emitted from a corona extended at low height over the disc, while at high frequencies, variability is generated in a collimated core of the corona through which luminosity fluctuations propagate upwards. Principal component analysis of the variability supports this interpretation, showing uncorrelated variation in the spectral slope of two power-law continuum components. The distinct evolution of the two components of the corona is seen as a flare passes inwards from the extended to the collimated portion. An increase in variability in the extended corona was found preceding the initial increase in X-ray flux. Variability from the extended corona was seen to die away as the flare passed into the collimated core leading to a second sharper increase in the X-ray count rate.
Fowler, Peter M; Duffield, Rob; Lu, Donna; Hickmans, Jeremy A; Scott, Tannath J
2016-10-01
To examine the effects of 24-h travel west across 11 time zones on subjective jet-lag and wellness responses together with self-reported sleep and upper respiratory symptoms in 18 professional rugby league players. Measures were obtained 1 or 2 d before (pretravel) and 2, 6, and 8 d after travel (post-2, post-6, and post-8) from Australia to the United Kingdom (UK) for the 2015 World Club Series. Compared with pretravel, subjective jet-lag remained significantly elevated on post-8 (3.1 ± 2.3, P < .05, d > 0.90), although it was greatest on post-2 (4.1 ± 1.4). Self-reported sleep-onset times were significantly earlier on post-2 than at all other time points (P < .05, d > 0.90), and large effect sizes suggested that wake times were earlier on post-2 than on post-6 and post-8 (d > 0.90). Although significantly more upper respiratory symptoms were reported on post-6 than at pretravel (P < .05, d ˃ 0.90), no incidence of injury and negligible changes in wellness and muscle strength and range of motion (P > .05, d < 0.90) were evident after travel. Results suggest that westward long-haul travel between Australia and the UK exacerbates subjective jet-lag and sleep responses, along with upper respiratory symptoms, in professional rugby league players. Of note, the increase in self-reported upper respiratory symptoms is a reminder that the demands of long-haul travel may be an additional concern in jet-lag for traveling athletes. However, due to the lack of sport-specific performance measures, it is still unclear whether international travel interferes with training to the extent that subsequent competition performance is impaired.
Hamabe, Atsushi; Omori, Takeshi; Tanaka, Koji; Nishida, Toshirou
2012-06-01
Laparoscopy-assisted gastrectomy (LAG) has been established as a low-invasive surgery for early gastric cancer. However, it remains unknown whether it is applicable also for advanced gastric cancer, mainly because the long-term results of LAG with D2 lymph node dissection for advanced gastric cancer have not been well validated compared with open gastrectomy (OG). A retrospective cohort study was performed to compare LAG and OG with D2 lymph node dissection. For this study, 167 patients (66 LAG and 101 OG patients) who underwent gastrectomy with D2 lymph node dissection for advanced gastric cancer were reviewed. Recurrence-free survival and overall survival time were estimated using Kaplan-Meier curves. Stratified log-rank statistical evaluation was used to compare the difference between the LAG and OG groups stratified by histologic type, pathologic T status, N status, and postoperative adjuvant chemotherapy. The adjusted Cox proportional hazards regression models were used to calculate the hazard ratios (HRs) of LAG. The 5-year recurrence-free survival rate was 89.6% in the LAG group and 75.8% in the OG group (nonsignificant difference; stratified log-rank statistic, 3.11; P = 0.0777). The adjusted HR of recurrence for LAG compared with OG was 0.389 [95% confidence interval (CI) 0.131-1.151]. The 5-year overall survival rate was 94.4% in the LAG group and 78.5% in the OG group (nonsignificant difference; stratified log-rank statistic, 0.4817; P = 0.4877). The adjusted HR of death for LAG compared with OG was 0.633 (95% CI 0.172-2.325). The findings show that LAG with D2 lymph node dissection is acceptable in terms of long-term results for advanced gastric cancer cases and may be applicable for advanced gastric cancer treatment.
Implications of Lag-Luminosity Relationship for Unified GRB Paradigms
NASA Technical Reports Server (NTRS)
Norris, J. P.; White, Nicholas E. (Technical Monitor)
2002-01-01
Spectral lags (tau(sub lag)) are deduced for 1437 long (T(sub 90) greater than 2 s) BATSE gamma-ray bursts (GRBs) with peak flux F(sub p) greater than 0.25 photons cm(sup -2)/s, near to the BATSE trigger threshold. The lags are modeled to approximate the observed distribution in the F(sub p)-T(sub lag) plane, realizing a noise-free representation. Assuming a two-branch lag-luminosity relationship, the lags are self-consistently corrected for cosmological effects to yield distributions in luminosity, distance, and redshift. The results have several consequences for GRB populations and for unified gamma-ray/afterglow scenarios which would account for afterglow break times and gamma-ray spectral evolution in terms of jet opening angle, viewing angle, or a profiled jet with variable Lorentz factor: A component of the burst sample is identified - those with few, wide pulses, lags of a few tenths to several seconds, and soft spectra - whose Log[N]-Log[F(sub p)] distribution approximates a -3/2 power-law, suggesting homogeneity and thus relatively nearby sources. The proportion of these long-lag bursts increases from negligible among bright BATSE bursts to approx. 50% at trigger threshold. Bursts with very long lags, approx. 1-2 less than tau(sub lag) (S) less than 10, show a tendency to concentrate near the Supergalactic Plane with a quadrupole moment of approx. -0.10 +/- 0.04. GRB 980425 (SN 1998bw) is a member of this subsample of approx. 90 bursts with estimated distances less than 100 Mpc. The frequency of the observed ultra-low luminosity bursts is approx. 1/4 that of SNe Ib/c within the same volume. If truly nearby, the core-collapse events associated with these GRBs might produce gravitational radiation detectable by LIGO-II. Such nearby bursts might also help explain flattening of the cosmic ray spectrum at ultra-high energies, as observed by AGASA.
The time lag and interval of discharge with a spring actuated fuel injection pump
NASA Technical Reports Server (NTRS)
Matthews, Robertson; Gardiner, A W
1923-01-01
Discussed here is research on a spring activated fuel pump for solid or airless injection with small, high speed internal combustion engines. The pump characteristics under investigation were the interval of fuel injection in terms of degrees of crank travel and in absolute time, the lag between the time the injection pump plunger begins its stroke and the appearance of the jet at the orifice, and the manner in which the fuel spray builds up to a maximum when the fuel valve is opened, and then diminishes.
Untangling the drivers of nonlinear systems with information theory
NASA Astrophysics Data System (ADS)
Wing, S.; Johnson, J.
2017-12-01
Many systems found in nature are nonlinear. The drivers of the system are often nonlinearly correlated with one another, which makes it a challenge to understand the effects of an individual driver. For example, solar wind velocity (Vsw) and density (nsw) are both found to correlate well with radiation belt fluxes and are thought to be drivers of the magnetospheric dynamics; however, the Vsw is anti-correlated with nsw, which can potentially confuse interpretation of these relationships as causal or coincidental. Information theory can untangle the drivers of these systems, describe the underlying dynamics, and offer constraints to modelers and theorists, leading to better understanding of the systems. Two examples are presented. In the first example, the solar wind drivers of geosynchronous electrons with energy range of 1.8-3.5 MeV are investigated using mutual information (MI), conditional mutual information (CMI), and transfer entropy (TE). The information transfer from Vsw to geosynchronous MeV electron flux (Je) peaks with a lag time (t) of 2 days. As previously reported, Je is anticorrelated with nsw with a lag of 1 day. However, this lag time and anticorrelation can be attributed mainly to the Je(t + 2 days) correlation with Vsw(t) and nsw(t + 1 day) anticorrelation with Vsw(t). Analyses of solar wind driving of the magnetosphere need to consider the large lag times, up to 3 days, in the (Vsw, nsw) anticorrelation. Using CMI to remove the effects of Vsw, the response of Je to nsw is 30% smaller and has a lag time < 24 hr, suggesting that the loss mechanism due to nsw or solar wind dynamic pressure has to start operating in < 24 hr. nsw transfers about 36% as much information as Vsw (the primary driver) to Je. Nonstationarity in the system dynamics are investigated using windowed TE. When the data is ordered according to high or low transfer entropy it is possible to understand details of the triangle distribution that has been identified between Je(t + 2 days) vs. Vsw(t). In the second example, the previously identified causal parameters of the solar cycle such as the solar polar field, meridional flow, polar faculae (proxy for polar field), dipole axis strength, are investigated. We discuss the response lag times of the sunspot numbers and information transferred to the sunspot numbers from the dynamic time series of these parameters.
Decision tree for accurate infection timing in individuals newly diagnosed with HIV-1 infection.
Verhofstede, Chris; Fransen, Katrien; Van Den Heuvel, Annelies; Van Laethem, Kristel; Ruelle, Jean; Vancutsem, Ellen; Stoffels, Karolien; Van den Wijngaert, Sigi; Delforge, Marie-Luce; Vaira, Dolores; Hebberecht, Laura; Schauvliege, Marlies; Mortier, Virginie; Dauwe, Kenny; Callens, Steven
2017-11-29
There is today no gold standard method to accurately define the time passed since infection at HIV diagnosis. Infection timing and incidence measurement is however essential to better monitor the dynamics of local epidemics and the effect of prevention initiatives. Three methods for infection timing were evaluated using 237 serial samples from documented seroconversions and 566 cross sectional samples from newly diagnosed patients: identification of antibodies against the HIV p31 protein in INNO-LIA, SediaTM BED CEIA and SediaTM LAg-Avidity EIA. A multi-assay decision tree for infection timing was developed. Clear differences in recency window between BED CEIA, LAg-Avidity EIA and p31 antibody presence were observed with a switch from recent to long term infection a median of 169.5, 108.0 and 64.5 days after collection of the pre-seroconversion sample respectively. BED showed high reliability for identification of long term infections while LAg-Avidity is highly accurate for identification of recent infections. Using BED as initial assay to identify the long term infections and LAg-Avidity as a confirmatory assay for those classified as recent infection by BED, explores the strengths of both while reduces the workload. The short recency window of p31 antibodies allows to discriminate very early from early infections based on this marker. BED recent infection results not confirmed by LAg-Avidity are considered to reflect a period more distant from the infection time. False recency predictions in this group can be minimized by elimination of patients with a CD4 count of less than 100 cells/mm3 or without no p31 antibodies. For 566 cross sectional sample the outcome of the decision tree confirmed the infection timing based on the results of all 3 markers but reduced the overall cost from 13.2 USD to 5.2 USD per sample. A step-wise multi assay decision tree allows accurate timing of the HIV infection at diagnosis at affordable effort and cost and can be an important new tool in studies analyzing the dynamics of local epidemics or the effects of prevention strategies.
LAG3 expression in active Mycobacterium tuberculosis infections.
Phillips, Bonnie L; Mehra, Smriti; Ahsan, Muhammad H; Selman, Moises; Khader, Shabaana A; Kaushal, Deepak
2015-03-01
Mycobacterium tuberculosis (MTB) is a highly successful pathogen because of its ability to persist in human lungs for long periods of time. MTB modulates several aspects of the host immune response. Lymphocyte-activation gene 3 (LAG3) is a protein with a high affinity for the CD4 receptor and is expressed mainly by regulatory T cells with immunomodulatory functions. To understand the function of LAG3 during MTB infection, a nonhuman primate model of tuberculosis, which recapitulates key aspects of natural human infection in rhesus macaques (Macaca mulatta), was used. We show that the expression of LAG3 is highly induced in the lungs and particularly in the granulomatous lesions of macaques experimentally infected with MTB. Furthermore, we show that LAG3 expression is not induced in the lungs and lung granulomas of animals exhibiting latent tuberculosis infection. However, simian immunodeficiency virus-induced reactivation of latent tuberculosis infection results in an increased expression of LAG3 in the lungs. This response is not observed in nonhuman primates infected with non-MTB bacterial pathogens, nor with simian immunodeficiency virus alone. Our data show that LAG3 was expressed primarily on CD4(+) T cells, presumably by regulatory T cells but also by natural killer cells. The expression of LAG3 coincides with high bacterial burdens and changes in the host type 1 helper T-cell response. Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
Carbon allocation belowground in Pinus pinaster using stable carbon isotope pulse labeling technique
NASA Astrophysics Data System (ADS)
Dannoura, M.; Bosc, A.; Chipeaux, C.; Sartore, M.; Lambrot, C.; Trichet, P.; Bakker, M.; Loustau, D.; Epron, D.
2010-12-01
Carbon allocation belowground competes with aboveground growth and biomass production. In the other hand, it contributes to resource acquisition such as nutrient, water and carbon sequestration in soil. Thus, a better characterization of carbon flow from plant to soil and its residence time within each compartment is an important issue for understanding and modeling forest ecosystem carbon budget. 13C pulse labeling of whole crown was conducted at 4 seasons to study the fate of assimilated carbon by photosynthesis into the root on 12 year old Pinus pinaster planted in the INRA domain of Pierroton. Maritime pine is the most widely planted species in South-West Europe. Stem, root and soil CO2 effluxes and their isotope composition were measured continuously by tunable diode laser absorption spectroscopy with a trace gas analyzer (TGA 100A; Campbell Scientific) coupled to flow-through chambers. 13CO2 recovery and peak were observed in respiration of each compartment after labeling. It appeared sequentially from top of stem to bottom, and to coarse root. The maximum velocity of carbon transfer was calculated as the difference in time lag of recovery between two positions on the trunk or on the root. It ranged between 0.08-0.2 m h-1 in stem and between 0.04-0.12 m h-1 in coarse root. This velocity was higher in warmer season, and the difference between time lag of recovery and peak increased after first frost. Photosynthates arrived underground 1.5 to 5 days after labeling, at similar time in soil CO2 effluxes and coarse root respiration. 0.08-1.4 g of carbon was respired per tree during first 20 days following labeling. It presented 0.6 -10% of 13C used for labeling and it is strongly related to seasons. The isotope signal was detected in fine root organs and microbial biomass by periodical core sampling. The peak was observed 6 days after labeling in early summer while it was delayed more than 10 days in autumn and winter with less amount of carbon allocated belowground.
The Spheroplast Lysis Assay for Yeast in Microtiter Plate Format
Ovalle, Rafael; Spencer, Moyah; Thiwanont, Monthiwa; Lipke, Peter N.
1999-01-01
A yeast lysis assay in the microtiter plate format improved precision and throughput and led to an improved algorithm for estimating lag time. The assay reproducibly revealed differences of 10% or greater in the maximal lysis rate and 50% or greater in the lag time. Clonal differences were determined to be the major source of variation. Microtiter-based assays should be useful for screening for drug susceptibility and for analyzing mutant phenotypes. PMID:10427014
Climate variability and increase in intensity and magnitude of dengue incidence in Singapore.
Hii, Yien Ling; Rocklöv, Joacim; Ng, Nawi; Tang, Choon Siang; Pang, Fung Yin; Sauerborn, Rainer
2009-11-11
Dengue is currently a major public health burden in Asia Pacific Region. This study aims to establish an association between dengue incidence, mean temperature and precipitation, and further discuss how weather predictors influence the increase in intensity and magnitude of dengue in Singapore during the period 2000-2007. Weekly dengue incidence data, daily mean temperature and precipitation and the midyear population data in Singapore during 2000-2007 were retrieved and analysed. We employed a time series Poisson regression model including time factors such as time trends, lagged terms of weather predictors, considered autocorrelation, and accounted for changes in population size by offsetting. The weekly mean temperature and cumulative precipitation were statistically significant related to the increases of dengue incidence in Singapore. Our findings showed that dengue incidence increased linearly at time lag of 5-16 and 5-20 weeks succeeding elevated temperature and precipitation, respectively. However, negative association occurred at lag week 17-20 with low weekly mean temperature as well as lag week 1-4 and 17-20 with low cumulative precipitation. As Singapore experienced higher weekly mean temperature and cumulative precipitation in the years 2004-2007, our results signified hazardous impacts of climate factors on the increase in intensity and magnitude of dengue cases. The ongoing global climate change might potentially increase the burden of dengue fever infection in near future.
FOURIER ANALYSIS OF BLAZAR VARIABILITY: KLEIN–NISHINA EFFECTS AND THE JET SCATTERING ENVIRONMENT
DOE Office of Scientific and Technical Information (OSTI.GOV)
Finke, Justin D.; Becker, Peter A., E-mail: justin.finke@nrl.navy.mil, E-mail: pbecker@gmu.edu
The strong variability of blazars can be characterized by power spectral densities (PSDs) and Fourier frequency-dependent time lags. In previous work, we created a new theoretical formalism for describing the PSDs and time lags produced via a combination of stochastic particle injection and emission via the synchrotron, synchrotron self-Compton, and external Compton (EC) processes. This formalism used the Thomson cross section and simple δ-function approximations to model the synchrotron and Compton emissivities. Here we expand upon this work, using the full Compton cross section and detailed and accurate emissivities. Our results indicate good agreement between the PSDs computed using themore » δ-function approximations and those computed using the accurate expressions, provided the observed photons are produced primarily by electrons with energies exceeding the lower limit of the injected particle population. Breaks are found in the PSDs at frequencies corresponding to the cooling timescales of the electrons primarily responsible for the observed emission, and the associated time lags are related to the difference in electron cooling timescales between the two energy channels, as expected. If the electron cooling timescales can be determined from the observed time lags and/or the observed EC PSDs, then one could in principle use the method developed here to determine the energy of the external seed photon source for EC, which is an important unsolved problem in blazar physics.« less
Zhang, Fengying; Li, Liping; Krafft, Thomas; Lv, Jinmei; Wang, Wuyi; Pei, Desheng
2011-06-01
The association between daily cardiovascular/respiratory mortality and air pollution in an urban district of Beijing was investigated over a 6-year period (January 2003 to December 2008). The purpose of this study was to evaluate the relative importance of the major air pollutants [particulate matter (PM), SO2, NO2] as predictors of daily cardiovascular/respiratory mortality. The time-series studied comprises years with lower level interventions to control air pollution (2003-2006) and years with high level interventions in preparation for and during the Olympics/Paralympics (2007-2008). Concentrations of PM10, SO2, and NO2, were measured daily during the study period. A generalized additive model was used to evaluate daily numbers of cardiovascular/respiratory deaths in relation to each air pollutant, controlling for time trends and meteorological influences such as temperature and relative humidity. The results show that the daily cardiovascular/respiratory death rates were significantly associated with the concentration air pollutants, especially deaths related to cardiovascular disease. The current day effects of PM10 and NO2 were higher than that of single lags (distributed lags) and moving average lags for respiratory disease mortality. The largest RR of SO2 for respiratory disease mortality was in Lag02. For cardiovascular disease mortality, the largest RR was in Lag01 for PM10, and in current day (Lag0) for SO2 and NO2. NO2 was associated with the largest RRs for deaths from both cardiovascular disease and respiratory disease.
Jagdale, Swati C.; Pawar, Chandrakala R.
2014-01-01
Migraine follows circadian rhythm in which headache is more painful at the awakening time. This needs administration of dosage form at night time to release drug after lag period when pain gets worse. Sumatriptan succinate is a drug of choice for migraine. Sumatriptan succinate has bitter taste, low oral bioavailability, and shorter half-life. Present work deals with application of design of experiment for polyox and xanthan gum in development of press coated floating pulsatile tablet. Floating pulsatile concept was applied to increase gastric residence of the dosage form. Burst release was achieved through immediate release tablet using crospovidone as superdisintegrant (10%). Pulse lag time was achieved using swellable polymer polyox WSR 205 and xanthan gum. 32 experimental design was applied. Optimized formulation was evaluated for physical characteristics and in-vitro and in-vivo study. From results, it can be concluded that optimized batch F8 containing polyox WSR205 (72.72%) and xanthan gum (27.27%) of total weight of polymer has shown floating lag time of 55 ± 2 sec, drug content of 100.35 ± 0.4%, hardness of 6 ± 0.1 Kg/cm2, and 98.69 ± 2% drug release in pulse manner with lag time of 7 ± 0.1 h. Optimized batch showed prolong gastric residence which was confirmed by in-vivo X-ray study. PMID:25530963
Tibayrenc, Pierre; Preziosi-Belloy, Laurence; Ghommidh, Charles
2011-06-01
Interest in bioethanol production has experienced a resurgence in the last few years. Poor temperature control in industrial fermentation tanks exposes the yeast cells used for this production to intermittent heat stress which impairs fermentation efficiency. Therefore, there is a need for yeast strains with improved tolerance, able to recover from such temperature variations. Accordingly, this paper reports the development of methods for the characterization of Saccharomyces cerevisiae growth recovery after a sublethal heat stress. Single-cell measurements were carried out in order to detect cell-to-cell variability. Alcoholic batch fermentations were performed on a defined medium in a 2 l instrumented bioreactor. A rapid temperature shift from 33 to 43 °C was applied when ethanol concentration reached 50 g l⁻¹. Samples were collected at different times after the temperature shift. Single cell growth capability, lag-time and initial growth rate were determined by monitoring the growth of a statistically significant number of cells after agar medium plating. The rapid temperature shift resulted in an immediate arrest of growth and triggered a progressive loss of cultivability from 100 to 0.0001% within 8 h. Heat-injured cells were able to recover their growth capability on agar medium after a lag phase. Lag-time was longer and more widely distributed as the time of heat exposure increased. Thus, lag-time distribution gives an insight into strain sensitivity to heat-stress, and could be helpful for the selection of yeast strains of technological interest.
Lankin, V Z; Ivanova, M V; Konovalova, G G; Tikhaze, A K; Kaminnyi, A I; Kukharchuk, V V
2007-04-01
We studied the effects of two inhibitors of beta-hydroxy-beta-methylglutaryl coenzyme A reductase, simvastatin and lovastatin, on the lag phase of ascorbate-dependent lipid oxidation in rat liver. Oxidizability of liver biological membranes significantly increased in intact animals and rats with induced hypercholesterolemia after peroral administration of these statins. The lag phase of ascorbate-dependent lipid oxidation in liver biomembranes decreased by 2.1 times in hypercholesterolemic rats. In animals of the lovastatin group this parameter decreased by 4.4 times compared to the control. In intact rats receiving simvastatin, the lag phase of oxidation in biomembranes from the liver decreased practically by 2 times. At the same time, in animals receiving simvastatin in combination with antioxidant vitamins (vitamins E and C, provitamin A) and selenium, the period of induction of oxidation increased by 3.3 times. Our results indicate that beta-hydroxy-beta-methylglutaryl coenzyme A reductase inhibitors produce a prooxidant effect on the liver, which can be prevented by administration of antioxidant agents.
Aaltonen, Sari; Latvala, Antti; Rose, Richard J.; Kujala, Urho M.; Kaprio, Jaakko; Silventoinen, Karri
2016-01-01
Physical activity and academic performance are positively associated, but the direction of the association is poorly understood. This longitudinal study examined the direction and magnitude of the associations between leisure-time physical activity and academic performance throughout adolescence and young adulthood. The participants were Finnish twins (from 2,859 to 4,190 individuals/study wave) and their families. In a cross-lagged path model, higher academic performance at ages 12, 14 and 17 predicted higher leisure-time physical activity at subsequent time-points (standardized path coefficient at age 14: 0.07 (p < 0.001), age 17: 0.12 (p < 0.001) and age 24: 0.06 (p < 0.05)), whereas physical activity did not predict future academic performance. A cross-lagged model of co-twin differences suggested that academic performance and subsequent physical activity were not associated due to the environmental factors shared by co-twins. Our findings suggest that better academic performance in adolescence modestly predicts more frequent leisure-time physical activity in late adolescence and young adulthood. PMID:27976699
Aaltonen, Sari; Latvala, Antti; Rose, Richard J; Kujala, Urho M; Kaprio, Jaakko; Silventoinen, Karri
2016-12-15
Physical activity and academic performance are positively associated, but the direction of the association is poorly understood. This longitudinal study examined the direction and magnitude of the associations between leisure-time physical activity and academic performance throughout adolescence and young adulthood. The participants were Finnish twins (from 2,859 to 4,190 individuals/study wave) and their families. In a cross-lagged path model, higher academic performance at ages 12, 14 and 17 predicted higher leisure-time physical activity at subsequent time-points (standardized path coefficient at age 14: 0.07 (p < 0.001), age 17: 0.12 (p < 0.001) and age 24: 0.06 (p < 0.05)), whereas physical activity did not predict future academic performance. A cross-lagged model of co-twin differences suggested that academic performance and subsequent physical activity were not associated due to the environmental factors shared by co-twins. Our findings suggest that better academic performance in adolescence modestly predicts more frequent leisure-time physical activity in late adolescence and young adulthood.
Ueda, S; Hata, T; Asakura, S; Yamaguchi, H; Kotani, M; Ueda, Y
1994-01-01
A novel controlled drug release system. Time-Controlled Explosion System (TES) has been developed. TES has a four-layered spherical structure, which consists of core, drug, swelling agent and water insoluble polymer membrane. TES is characterized by a rapid drug release with a precisely programmed lag time; i.e. expansion of the swelling agent by water penetrating through the outer membrane, destruction of the membrane by stress due to swelling force and subsequent rapid drug release. For establishing the concept and development strategy, TES was designed using metoprolol and polystyrene balls (size: 3.2 mm in diameter) as a model drug and core particles. Among the polymers screened, low-substituted hydroxypropylcellulose (L-HPC) and ethylcellulose (EC) were selected for a swelling agent and an outer water insoluble membrane, respectively. The release profiles of metoprolol from the system were not affected by the pH of the dissolution media. Lag time was controlled by the thickness of the outer EC membrane; thus, a combination of TES particles possessing different lag times could offer any desired release profile of the model compound, metoprolol.
ERIC Educational Resources Information Center
Burkholder, Gary J.; Harlow, Lisa L.
2003-01-01
Tested a model of HIV behavior risk, using a fully cross-lagged, longitudinal design to illustrate the analysis of larger structural equation models. Data from 527 women who completed a survey at three time points show excellent fit of the model to the data. (SLD)
ERIC Educational Resources Information Center
Palmu, Iines R.; Närhi, Vesa M.; Savolainen, Hannu K.
2018-01-01
The current study examined the over-time association between externalizing behaviour problems and academic performance during school transition in a cross-lagged design. The main focus was to reveal whether the externalizing behaviour composite and its components separately, including symptoms of CD and ADHD, differ in their relationship with…
Single molecular biology: coming of age in DNA replication.
Liu, Xiao-Jing; Lou, Hui-Qiang
2017-09-20
DNA replication is an essential process of the living organisms. To achieve precise and reliable replication, DNA polymerases play a central role in DNA synthesis. Previous investigations have shown that the average rates of DNA synthesis on the leading and lagging strands in a replisome must be similar to avoid the formation of significant gaps in the nascent strands. The underlying mechanism has been assumed to be coordination between leading- and lagging-strand polymerases. However, Kowalczykowski's lab members recently performed single molecule techniques in E. coli and showed the real-time behavior of a replisome. The leading- and lagging-strand polymerases function stochastically and independently. Furthermore, when a DNA polymerase is paused, the helicase slows down in a self-regulating fail-safe mechanism, akin to a ''dead-man's switch''. Based on the real-time single-molecular observation, the authors propose that leading- and lagging-strand polymerases synthesize DNA stochastically within a Gaussian distribution. Along with the development and application of single-molecule techniques, we will witness a new age of DNA replication and other biological researches.
Moutsopoulou, Karolina; Waszak, Florian
2013-05-01
It has been shown that in associative learning it is possible to disentangle the effects caused on behaviour by the associations between a stimulus and a classification (S-C) and the associations between a stimulus and the action performed towards it (S-A). Such evidence has been provided using ex-Gaussian distribution analysis to show that different parameters of the reaction time distribution reflect the different processes. Here, using this method, we investigate another difference between these two types of associations: What is the relative durability of these associations across time? Using a task-switching paradigm and by manipulating the lag between the point of the creation of the associations and the test phase, we show that S-A associations have stronger effects on behaviour when the lag between the two repetitions of a stimulus is short. However, classification learning affects behaviour not only in short-term lags but also (and equally so) when the lag between prime and probe is long and the same stimuli are repeatedly presented within a different classification task, demonstrating a remarkable durability of S-C associations.
Information-theoretic approach to lead-lag effect on financial markets
NASA Astrophysics Data System (ADS)
Fiedor, Paweł
2014-08-01
Recently the interest of researchers has shifted from the analysis of synchronous relationships of financial instruments to the analysis of more meaningful asynchronous relationships. Both types of analysis are concentrated mostly on Pearson's correlation coefficient and consequently intraday lead-lag relationships (where one of the variables in a pair is time-lagged) are also associated with them. Under the Efficient-Market Hypothesis such relationships are not possible as all information is embedded in the prices, but in real markets we find such dependencies. In this paper we analyse lead-lag relationships of financial instruments and extend known methodology by using mutual information instead of Pearson's correlation coefficient. Mutual information is not only a more general measure, sensitive to non-linear dependencies, but also can lead to a simpler procedure of statistical validation of links between financial instruments. We analyse lagged relationships using New York Stock Exchange 100 data not only on an intraday level, but also for daily stock returns, which have usually been ignored.
Changing response of the North Atlantic/European winter climate to the 11 year solar cycle
NASA Astrophysics Data System (ADS)
Ma, Hedi; Chen, Haishan; Gray, Lesley; Zhou, Liming; Li, Xing; Wang, Ruili; Zhu, Siguang
2018-03-01
Recent studies have presented conflicting results regarding the 11 year solar cycle (SC) influences on winter climate over the North Atlantic/European region. Analyses of only the most recent decades suggest a synchronized North Atlantic Oscillation (NAO)-like response pattern to the SC. Analyses of long-term climate data sets dating back to the late 19th century, however, suggest a mean sea level pressure (mslp) response that lags the SC by 2-4 years in the southern node of the NAO (i.e. Azores region). To understand the conflicting nature and cause of these time dependencies in the SC surface response, the present study employs a lead/lag multi-linear regression technique with a sliding window of 44 years over the period 1751-2016. Results confirm previous analyses, in which the average response for the whole time period features a statistically significant 2-4 year lagged mslp response centered over the Azores region. Overall, the lagged nature of Azores mslp response is generally consistent in time. Stronger and statistically significant SC signals tend to appear in the periods when the SC forcing amplitudes are relatively larger. Individual month analysis indicates the consistent lagged response in December-January-February average arises primarily from early winter months (i.e. December and January), which has been associated with ocean feedback processes that involve reinforcement by anomalies from the previous winter. Additional analysis suggests that the synchronous NAO-like response in recent decades arises primarily from late winter (February), possibly reflecting a result of strong internal noise.
NASA Technical Reports Server (NTRS)
Fausnaugh, M. M.; Denney, K. D.; Barth, A.J.; Bentz, M.C.; Bottorff, M.C.; Carini, M.T.; Croxall, K. V.; Rosa, G. De; Goad, M.R.; Gehrels, Cornelis;
2016-01-01
We present ground-based optical photometric monitoring data for NGC 5548, part of an extended multiwavelength reverberation mapping campaign. The light curves have nearly daily cadence from 2014 January to July in ninefilters (BVRI and ugriz). Combined with ultraviolet data from the Hubble Space Telescope and Swift, we confirm significant time delays between the continuum bands as a function of wavelength, extending the wavelength coverage from 1158 Angstrom to the z band (approximately 9160 angstrom). We find that the lags at wavelengths longer than the V band are equal to or greater than the lags of high-ionization-state emission lines (such as He pi lambdal1640 and lambda 4686), suggesting that the continuum-emitting source is of a physical size comparable to the inner broad-line region (BLR). The trend of lag with wavelength is broadly consistent with the prediction for continuum reprocessing by an accretion disk with (tau varies as lambda(exp 4/3)). However, the lags also imply a disk radius that is 3 times larger than the prediction from standardthin-disk theory, assuming that the bolometric luminosity is 10 percent of the Eddington luminosity (L 0.1L(sub Edd)).Using optical spectra from the Large Binocular Telescope, we estimate the bias of the interband continuum lagsdue to BLR emission observed in the filters. We find that the bias for filters with high levels of BLR contamination(20 percent) can be important for the shortest continuum lags and likely has a significant impact on the u and U bandsowing to Balmer continuum emission.
EVOLUTION OF THE CROSS-CORRELATION AND TIME LAG OF 4U 1735-44 ALONG THE BRANCHES
DOE Office of Scientific and Technical Information (OSTI.GOV)
Lei Yajuan; Zhang Haotong; Zhang Chengmin
We analyze the cross-correlation function between the soft and hard X-rays of atoll source 4U 1735-44 with RXTE data, and find anti-correlated soft and hard time lags of about a hecto-second. In the island state, the observations do not show any obvious correlations, and most observations of the banana branch show a positive correlation. However, anti-correlations are detected in the upper banana branch. These results are different from those of Z-sources (Cyg X-2, GX 5-1), where anti-correlations are detected in the horizontal branch and upper normal branch. In this case, the lag timescales of both this atoll and Z-sources aremore » found to be similar, at a magnitude of several tens to hundreds of seconds. As a comparison, it is noted that anti-correlated lags lasting thousands of seconds have been reported from several black hole candidates in their intermediate states. In addition, for an observation containing four segments that show positive or anti-correlation, we analyze the spectral evolution with the hybrid model. In the observation, the anti-correlation is detected at the highest flux. The fitting results show that the Comptonized component is not the lowest at the highest flux, which suggests that the anti-correlation corresponds to the transition between the soft and hard states. Finally, we compare the corresponding results of atoll source 4U 1735-44 with those observed in Z-sources and black hole candidates, and the possible origins of the anti-correlated time lags are discussed.« less
Shi, Li-Hong; Luo, Fei; Woodward, Donald J.; McIntyre, Dan C.; Chang, Jing-Yu
2007-01-01
We used a multiple channel, single unit recording technique to investigate the neural activity in different corticolimbic and basal ganglia regions in freely moving rats before and during generalized amygdala kindled seizures. Neural activity was recorded simultaneously in the sensorimotor cortex (Ctx), hippocampus, amygdala, substantia nigra pars reticulata (SNr) and the subthalamic nucleus (STN). We observed massive synchronized activity among neurons of different brain regions during seizure episodes. Neurons in the kindled amygdala led other regions in synchronized firing, revealed by time lags of neurons in other regions in crosscorrelogram analysis. While there was no obvious time lag between Ctx and SNr, the STN and hippocampus did lag behind the Ctx and SNr in correlated firing. Activity in the amygdala and SNr contralateral to the kindling stimulation site lagged behind their ipsilateral counterparts. However no time lag was found between the kindling and contralateral sides of Ctx, hippocampus and STN. Our data confirm that the amygdala is an epileptic focus that emits ictal discharges to other brain regions. The observed temporal pattern indicates that ictal discharges from the amygdala arrive first at Ctx and SNr, and then spread to the hippocampus and STN. The simultaneous activation of both sides of the Ctx suggests that the neocortex participates in kindled seizures as a unisonant entity to provoke the clonic motor seizures. Early activation of the SNr (before the STN and hippocampus) points to an important role of the SNr in amygdala kindled seizures and supports the view that different SNr manipulations may be effective ways to control seizures. PMID:17049434
NASA Astrophysics Data System (ADS)
Wouden, Alex; Cimbala, John; Lewis, Bryan
2014-11-01
While the periodic boundary condition is useful for handling rotational symmetry in many axisymmetric geometries, its application fails for analysis of rotor-stator interaction (RSI) in multi-stage turbomachinery flow. The inadequacy arises from the underlying geometry where the blade counts per row differ, since the blade counts are crafted to deter the destructive harmonic forces of synchronous blade passing. Therefore, to achieve the computational advantage of modeling a single blade passage per row while preserving the integrity of the RSI, a phase-lag boundary condition is adapted to OpenFOAM® software's incompressible pressure-based solver. The phase-lag construct is accomplished through restating the implicit periodic boundary condition as a constant boundary condition that is updated at each time step with phase-shifted data from the coupled cells adjacent to the boundary. Its effectiveness is demonstrated using a typical Francis hydroturbine modeled as single- and double-passages with phase-lag boundary conditions. The evaluation of the phase-lag condition is based on the correspondence of the overall computational performance and the calculated flow parameters of the phase-lag simulations with those of a baseline full-wheel simulation. Funded in part by DOE Award Number: DE-EE0002667.
Viotti, Sara; Essenmacher, Lynnette; Hamblin, Lydia E.; Arnetz, Judith E.
2018-01-01
In spite of the considerable number of studies on co-worker incivility, knowledge on this topic needs to be further enhanced. In particular, no studies have focused on the reciprocal nature of the relationship of incivility with other important aspects of working life, i.e. employee well-being and the quality of the working process. The aim of the present study was to examine the cross-lagged associations among co-worker incivility, work-related exhaustion, and organisational efficiency in a sample of healthcare workers. Based on the conservation of resource theory, we hypothesised that those three variables affect each other reciprocally over the time. Data from a two-wave study design (with a one-year time lag) were utilised, and cross-lagged structural equation models were performed. Results confirmed that incivility and efficiency affected each other reciprocally over time. On the other hand, whereas incivility positively predicted exhaustion and exhaustion at inversely predicted organisational efficiency, the opposite paths were found to be not significant. The study suggests that efficiency is crucial for understanding incivility because it operates both as its cause and as its outcome. Interventions aimed at promoting civility and respect in the workplace may help prevent co-worker incivility, work-related exhaustion, and enhance organisational efficiency.
Viotti, Sara; Essenmacher, Lynnette; Hamblin, Lydia E; Arnetz, Judith E
2018-01-01
In spite of the considerable number of studies on co-worker incivility, knowledge on this topic needs to be further enhanced. In particular, no studies have focused on the reciprocal nature of the relationship of incivility with other important aspects of working life, i.e. employee well-being and the quality of the working process. The aim of the present study was to examine the cross-lagged associations among co-worker incivility, work-related exhaustion, and organisational efficiency in a sample of healthcare workers. Based on the conservation of resource theory, we hypothesised that those three variables affect each other reciprocally over the time. Data from a two-wave study design (with a one-year time lag) were utilised, and cross-lagged structural equation models were performed. Results confirmed that incivility and efficiency affected each other reciprocally over time. On the other hand, whereas incivility positively predicted exhaustion and exhaustion at inversely predicted organisational efficiency, the opposite paths were found to be not significant. The study suggests that efficiency is crucial for understanding incivility because it operates both as its cause and as its outcome. Interventions aimed at promoting civility and respect in the workplace may help prevent co-worker incivility, work-related exhaustion, and enhance organisational efficiency.
Von Biela, V.R.; Zimmerman, C.E.; Moulton, L.L.
2011-01-01
Arctic cisco Coregonus autumnalis young-of-year (YOY) growth was used as a proxy to examine the long-term response of a high-latitude fish population to changing climate from 1978 to 2004. YOY growth increased over time (r2 = 0??29) and was correlated with monthly averages of the Arctic oscillation index, air temperature, east wind speed, sea-ice concentration and river discharge with and without time lags. Overall, the most prevalent correlates to YOY growth were sea-ice concentration lagged 1 year (significant correlations in 7 months; r2 = 0??14-0??31) and Mackenzie River discharge lagged 2 years (significant correlations in 8 months; r2 = 0??13-0??50). The results suggest that decreased sea-ice concentrations and increased river discharge fuel primary production and that life cycles of prey species linking increased primary production to fish growth are responsible for the time lag. Oceanographic studies also suggest that sea ice concentration and fluvial inputs from the Mackenzie River are key factors influencing productivity in the Beaufort Sea. Future research should assess the possible mechanism relating sea ice concentration and river discharge to productivity at upper trophic levels. Journal of Fish Biology ?? 2010 The Fisheries Society of the British Isles. No claim to original US government works.
From neurons to circuits: linear estimation of local field potentials.
Rasch, Malte; Logothetis, Nikos K; Kreiman, Gabriel
2009-11-04
Extracellular physiological recordings are typically separated into two frequency bands: local field potentials (LFPs) (a circuit property) and spiking multiunit activity (MUA). Recently, there has been increased interest in LFPs because of their correlation with functional magnetic resonance imaging blood oxygenation level-dependent measurements and the possibility of studying local processing and neuronal synchrony. To further understand the biophysical origin of LFPs, we asked whether it is possible to estimate their time course based on the spiking activity from the same electrode or nearby electrodes. We used "signal estimation theory" to show that a linear filter operation on the activity of one or a few neurons can explain a significant fraction of the LFP time course in the macaque monkey primary visual cortex. The linear filter used to estimate the LFPs had a stereotypical shape characterized by a sharp downstroke at negative time lags and a slower positive upstroke for positive time lags. The filter was similar across different neocortical regions and behavioral conditions, including spontaneous activity and visual stimulation. The estimations had a spatial resolution of approximately 1 mm and a temporal resolution of approximately 200 ms. By considering a causal filter, we observed a temporal asymmetry such that the positive time lags in the filter contributed more to the LFP estimation than the negative time lags. Additionally, we showed that spikes occurring within approximately 10 ms of spikes from nearby neurons yielded better estimation accuracies than nonsynchronous spikes. In summary, our results suggest that at least some circuit-level local properties of the field potentials can be predicted from the activity of one or a few neurons.
From neurons to circuits: linear estimation of local field potentials
Rasch, Malte; Logthetis, Nikos K.; Kreiman, Gabriel
2010-01-01
Extracellular physiological recordings are typically separated into two frequency bands: local field potentials (LFPs, a circuit property) and spiking multi-unit activity (MUA). There has been increased interest in LFPs due to their correlation with fMRI measurements and the possibility of studying local processing and neuronal synchrony. To further understand the biophysical origin of LFPs, we asked whether it is possible to estimate their time course based on the spiking activity from the same or nearby electrodes. We used Signal Estimation Theory to show that a linear filter operation on the activity of one/few neurons can explain a significant fraction of the LFP time course in the macaque primary visual cortex. The linear filter used to estimate the LFPs had a stereotypical shape characterized by a sharp downstroke at negative time lags and a slower positive upstroke for positve time lags. The filter was similar across neocortical regions and behavioral conditions including spontaneous activity and visual stimulation. The estimations had a spatial resolution of ~1 mm and a temporal resolution of ~200 ms. By considering a causal filter, we observed a temporal asymmetry such that the positive time lags in the filter contributed more to the LFP estimation than negative time lags. Additionally, we showed that spikes occurring within ~10 ms of spikes from nearby neurons yielded better estimation accuracies than nonsynchronous spikes. In sum, our results suggest that at least some circuit-level local properties of the field potentials can be predicted from the activity of one or a few neurons. PMID:19889990
Chen, Dingjiang; Guo, Yi; Hu, Minpeng; Dahlgren, Randy A
2015-08-01
Legacy nitrogen (N) sources originating from anthropogenic N inputs (NANI) may be a major cause of increasing riverine N exports in many regions, despite a significant decline in NANI. However, little quantitative knowledge exists concerning the lag effect of NANI on riverine N export. As a result, the N leaching lag effect is not well represented in most current watershed models. This study developed a lagged variable model (LVM) to address temporally dynamic export of watershed NANI to rivers. Employing a Koyck transformation approach used in economic analyses, the LVM expresses the indefinite number of lag terms from previous years' NANI with a lag term that incorporates the previous year's riverine N flux, enabling us to inversely calibrate model parameters from measurable variables using Bayesian statistics. Applying the LVM to the upper Jiaojiang watershed in eastern China for 1980-2010 indicated that ~97% of riverine export of annual NANI occurred in the current year and succeeding 10 years (~11 years lag time) and ~72% of annual riverine N flux was derived from previous years' NANI. Existing NANI over the 1993-2010 period would have required a 22% reduction to attain the target TN level (1.0 mg N L(-1)), guiding watershed N source controls considering the lag effect. The LVM was developed with parsimony of model structure and parameters (only four parameters in this study); thus, it is easy to develop and apply in other watersheds. The LVM provides a simple and effective tool for quantifying the lag effect of anthropogenic N input on riverine export in support of efficient development and evaluation of watershed N control strategies.
When Long-Range Zero-Lag Synchronization is Feasible in Cortical Networks
Viriyopase, Atthaphon; Bojak, Ingo; Zeitler, Magteld; Gielen, Stan
2012-01-01
Many studies have reported long-range synchronization of neuronal activity between brain areas, in particular in the beta and gamma bands with frequencies in the range of 14–30 and 40–80 Hz, respectively. Several studies have reported synchrony with zero phase lag, which is remarkable considering the synaptic and conduction delays inherent in the connections between distant brain areas. This result has led to many speculations about the possible functional role of zero-lag synchrony, such as for neuronal communication, attention, memory, and feature binding. However, recent studies using recordings of single-unit activity and local field potentials report that neuronal synchronization may occur with non-zero phase lags. This raises the questions whether zero-lag synchrony can occur in the brain and, if so, under which conditions. We used analytical methods and computer simulations to investigate which connectivity between neuronal populations allows or prohibits zero-lag synchrony. We did so for a model where two oscillators interact via a relay oscillator. Analytical results and computer simulations were obtained for both type I Mirollo–Strogatz neurons and type II Hodgkin–Huxley neurons. We have investigated the dynamics of the model for various types of synaptic coupling and importantly considered the potential impact of Spike-Timing Dependent Plasticity (STDP) and its learning window. We confirm previous results that zero-lag synchrony can be achieved in this configuration. This is much easier to achieve with Hodgkin–Huxley neurons, which have a biphasic phase response curve, than for type I neurons. STDP facilitates zero-lag synchrony as it adjusts the synaptic strengths such that zero-lag synchrony is feasible for a much larger range of parameters than without STDP. PMID:22866034
Costa, Amine Farias; Hoek, Gerard; Brunekreef, Bert; Ponce de Leon, Antônio C M
2017-03-01
Evaluation of short-term mortality displacement is essential to accurately estimate the impact of short-term air pollution exposure on public health. We quantified mortality displacement by estimating single-day lag effects and cumulative effects of air pollutants on mortality using distributed lag models. We performed a daily time series of nonaccidental and cause-specific mortality among elderly residents of São Paulo, Brazil, between 2000 and 2011. Effects of particulate matter smaller than 10 μm (PM 10 ), nitrogen dioxide (NO 2 ) and carbon monoxide (CO) were estimated in Poisson generalized additive models. Single-day lag effects of air pollutant exposure were estimated for 0-, 1- and 2-day lags. Distributed lag models with lags of 0-10, 0-20 and 0-30 days were used to assess mortality displacement and potential cumulative exposure effects. PM 10 , NO 2 and CO were significantly associated with nonaccidental and cause-specific deaths in both single-day lag and cumulative lag models. Cumulative effect estimates for 0-10 days were larger than estimates for single-day lags. Cumulative effect estimates for 0-30 days were essentially zero for nonaccidental and circulatory deaths but remained elevated for respiratory and cancer deaths. We found evidence of mortality displacement within 30 days for nonaccidental and circulatory deaths in elderly residents of São Paulo. We did not find evidence of mortality displacement within 30 days for respiratory or cancer deaths. Citation: Costa AF, Hoek G, Brunekreef B, Ponce de Leon AC. 2017. Air pollution and deaths among elderly residents of São Paulo, Brazil: an analysis of mortality displacement. Environ Health Perspect 125:349-354; http://dx.doi.org/10.1289/EHP98.
El-Kattan, A F; Asbill, C S; Michniak, B B
2000-04-05
The percutaneous permeation of hydrocortisone (HC) was investigated in hairless mouse skin after application of an alcoholic hydrogel using a diffusion cell technique. The formulations contained one of 12 terpenes, the selection of which was based on an increase in their lipophilicity (log P 1.06-5.36). Flux, cumulative receptor concentrations, skin content, and lag time of HC were measured over 24 h and compared with control gels (containing no terpene). Furthermore, HC skin content and the solubility of HC in the alcoholic hydrogel solvent mixture in the presence of terpene were determined, and correlated to the enhancing activity of terpenes. The in vitro permeation experiments with hairless mouse skin revealed that the terpene enhancers varied in their ability to enhance the flux of HC. Nerolidol which possessed the highest lipophilicity (log P = 5.36+/-0.38) provided the greatest enhancement for HC flux (35.3-fold over control). Fenchone (log P = 2.13+/-0.30) exhibited the lowest enhancement of HC flux (10.1-fold over control). In addition, a linear relationship was established between the log P of terpenes and the cumulative amount of HC in the receptor after 24 h (Q(24)). Nerolidol, provided the highest Q(24) (1733+/-93 microg/cm(2)), whereas verbenone produced the lowest Q(24) (653+/-105 microg/cm(2)). Thymol provided the lowest HC skin content (1151+/-293 microg/g), while cineole produced the highest HC skin content (18999+/-5666 microg/g). No correlation was established between the log P of enhancers and HC skin content. A correlation however, existed between the log P of terpenes and the lag time. As log P increased, a linear decrease in lag time was observed. Cymene yielded the shortest HC lag time, while fenchone produced the longest lag time. Also, the increase in the log P of terpenes resulted in a proportional increase in HC solubility in the formulation solvent mixture.
Hydraulic responses to environmental perturbations in Tsuga canadensis and Betula lenta.
Daley, Michael J; Phillips, Nathan G; Pettijohn, Justin C; Hadley, Julian
2008-09-01
Eastern hemlock (Tsuga canadensis (L). Carr.) is a late-successional species found across the northeastern United States of America that is currently threatened by the exotic pest, hemlock woolly adelgid (Adelges tsugae Annand). Because whole-tree physiological characteristics may scale to influence ecosystem processes, we considered whole-tree hydraulic controls in eastern hemlock and the replacement species black birch (Betula lenta L.). Through a series of misting perturbations, whole-tree resistances (R), capacitances (C) and time constants (tau) were determined from time series sap flux data in eastern hemlock and black birch. Black birch trees responded more rapidly to environmental perturbations than eastern hemlock. Utilizing the step function after applied treatments, whole-tree tau ranged between 9.4 and 24.8 min in eastern hemlock trees compared with 5.9 to 10.5 min in black birch. Species was not a significant predictor of R or C when controlling for tree size. In both species, R decreased with sapwood area and C increased. Our tau results indicate that the loss and replacement of eastern hemlock by black birch will decrease the lag between transpiration and absorption of water from the soil and potentially alter the diurnal pattern of carbon and water uptake.
Study of controlled-release floating tablets of dipyridamole using the dry-coated method.
Chen, Kai; Wen, Haoyang; Yang, Feifei; Yu, Yibin; Gai, Xiumei; Wang, Haiying; Li, Pingfei; Pan, Weisan; Yang, Xinggang
2018-01-01
Dipyridamole (DIP), having a short biological half-life, has a narrow absorption window and is primarily absorbed in the stomach. So, the purpose of this study was to prepare controlled-release floating (CRF) tablets of dipyridamole by the dry-coated method. The influence of agents with different viscosity, hydroxypropylmethylcellulose (HPMC) and polyvinylpyrollidon K30 (PVP K30) in the core tablet and low-viscosity HPMC and PVP K30 in the coating layer on drug release, were investigated. Then, a study with a three-factor, three-level orthogonal experimental design was used to optimize the formulation of the CRF tablets. After data processing, the optimized formulation was found to be: 80 mg HPMC K4M in the core tablet, 80 mg HPMC E15 in core tablet and 40 mg PVP K30 in the coating layer. Moreover, an in vitro buoyancy study showed that the optimized formulation had an excellent floating ability and could immediately float without a lag time and this lasted more than 12 h. Furthermore, an in vivo gamma scintigraphic study showed that the gastric residence time of the CRF tablet was about 8 h.
NASA Astrophysics Data System (ADS)
Iny, David
2007-09-01
This paper addresses the out-of-sequence measurement (OOSM) problem associated with multiple platform tracking systems. The problem arises due to different transmission delays in communication of detection reports across platforms. Much of the literature focuses on the improvement to the state estimate by incorporating the OOSM. As the time lag increases, there is diminishing improvement to the state estimate. However, this paper shows that optimal processing of OOSMs may still be beneficial by improving data association as part of a multi-target tracker. This paper derives exact multi-lag algorithms with the property that the standard log likelihood track scoring is independent of the order in which the measurements are processed. The orthogonality principle is applied to generalize the method of Bar- Shalom in deriving the exact A1 algorithm for 1-lag estimation. Theory is also developed for optimal filtering of time averaged measurements and measurements correlated through periodic updates of a target aim-point. An alternative derivation of the multi-lag algorithms is also achieved using an efficient variant of the augmented state Kalman filter (AS-KF). This results in practical and reasonably efficient multi-lag algorithms. Results are compared to a well known ad hoc algorithm for incorporating OOSMs. Finally, the paper presents some simulated multi-target multi-static scenarios where there is a benefit to processing the data out of sequence in order to improve pruning efficiency.
Modeling optical and UV polarization of AGNs. IV. Polarization timing
NASA Astrophysics Data System (ADS)
Rojas Lobos, P. A.; Goosmann, R. W.; Marin, F.; Savić, D.
2018-03-01
Context. Optical observations cannot resolve the structure of active galactic nuclei (AGN), and a unified model for AGN was inferred mostly from indirect methods, such as spectroscopy and variability studies. Optical reverberation mapping allowed us to constrain the spatial dimension of the broad emission line region and thereby to measure the mass of supermassive black holes. Recently, reverberation was also applied to the polarized signal emerging from different AGN components. In principle, this should allow us to measure the spatial dimensions of the sub-parsec reprocessing media. Aim. We conduct numerical modeling of polarization reverberation and provide theoretical predictions for the polarization time lag induced by different AGN components. The model parameters are adjusted to the observational appearance of the Seyfert 1 galaxy NGC 4151. Methods: We modeled scattering-induced polarization and tested different geometries for the circumnuclear dust component. Our tests included the effects of clumpiness and different dust prescriptions. To further extend the model, we also explored the effects of additional ionized winds stretched along the polar direction, and of an equatorial scattering ring that is responsible for the polarization angle observed in pole-on AGN. The simulations were run using a time-dependent version of the STOKES code. Results: Our modeling confirms the previously found polarization characteristics as a function of the observer`s viewing angle. When the dust adopts a flared-disk geometry, the lags reveal a clear difference between type 1 and type 2 AGN. This distinction is less clear for a torus geometry where the time lag is more sensitive to the geometry and optical depth of the inner surface layers of the funnel. The presence of a scattering equatorial ring and ionized outflows increased the recorded polarization time lags, and the polar outflows smooths out dependence on viewing angle, especially for the higher optical depth of the wind (τ = 0.3). Conclusions: Together with other AGN observables, the polarization time lag places new, independent "seismological" constraints on the inner geometry of AGN. If we conduct time-dependent spectropolarimetric observing campaigns of AGN, this method has a high potential for a census of supermassive black holes.
Aguinaga Ontoso, I; Guillén Grima, F; Oviedo de Sola, P J; Floristan Floristan, M Y; Laborda Santesteban, M S; Martínez Ramírez, M T; Martínez González, M A
1999-01-01
To assess the short-term impact of air pollution on the daily death rate in the city of Pamplona. Ecological study with a population of 212,000 inhabitants. A time series data analysis is conducted by means of multiple linear regression and Poisson regression, with the daily death rate data, air pollution levels for Particles and SO2, weather parameters of average relative humidity and temperature daily and number of cases weekly of flu for the 1991-1995 period. The average number of deaths daily for non-external causes is that of 4.15 deaths, with a range from zero to 13 deaths. The city of Pamplona has a mean annual temperature of 12.7 degrees C (-2.3 degrees C to 31.6 degrees C) and a relative humidity of 68.5%. In the model, the temperature (with a one-day time lag and a six-day time lag temperature squared) and the humidity (with a one-day time lag) is related to the death rate for all causes. But the death rate for non-external causes is only related in the model with the temperature (one-day time lag, P: 0.035) and five-day time lag with temperature squared (p: 0.028). The timely estimates of the relative particle-related risk show that the highest risk of dying stems from respiratory causes with a relative risk of 1.13. However, none of these relationships is statistically significant. In the case of Sulfur Dioxide, the estimates closely near the zero figure, and none of them is significant. The Temperature has an impact of the death rate for all causes, both external and non-external, and the relative humidity solely has an impact on the death rate for non-external causes. It has not been possible to prove any influence of the daily environmental pollution levels on the daily death rate.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Bizyaev, D.; Pan, K.; Brinkmann, J.
2017-04-20
We present a study of the kinematics of the extraplanar ionized gas around several dozen galaxies observed by the Mapping of Nearby Galaxies at the Apache Point Observatory (MaNGA) survey. We considered a sample of 67 edge-on galaxies out of more than 1400 extragalactic targets observed by MaNGA, in which we found 25 galaxies (or 37%) with regular lagging of the rotation curve at large distances from the galactic midplane. We model the observed H α emission velocity fields in the galaxies, taking projection effects and a simple model for the dust extinction into account. We show that the verticalmore » lag of the rotation curve is necessary in the modeling, and estimate the lag amplitude in the galaxies. We find no correlation between the lag and the star formation rate in the galaxies. At the same time, we report a correlation between the lag and the galactic stellar mass, central stellar velocity dispersion, and axial ratio of the light distribution. These correlations suggest a possible higher ratio of infalling-to-local gas in early-type disk galaxies or a connection between lags and the possible presence of hot gaseous halos, which may be more prevalent in more massive galaxies. These results again demonstrate that observations of extraplanar gas can serve as a potential probe for accretion of gas.« less
NASA Astrophysics Data System (ADS)
Bizyaev, D.; Walterbos, R. A. M.; Yoachim, P.; Riffel, R. A.; Fernández-Trincado, J. G.; Pan, K.; Diamond-Stanic, A. M.; Jones, A.; Thomas, D.; Cleary, J.; Brinkmann, J.
2017-04-01
We present a study of the kinematics of the extraplanar ionized gas around several dozen galaxies observed by the Mapping of Nearby Galaxies at the Apache Point Observatory (MaNGA) survey. We considered a sample of 67 edge-on galaxies out of more than 1400 extragalactic targets observed by MaNGA, in which we found 25 galaxies (or 37%) with regular lagging of the rotation curve at large distances from the galactic midplane. We model the observed Hα emission velocity fields in the galaxies, taking projection effects and a simple model for the dust extinction into account. We show that the vertical lag of the rotation curve is necessary in the modeling, and estimate the lag amplitude in the galaxies. We find no correlation between the lag and the star formation rate in the galaxies. At the same time, we report a correlation between the lag and the galactic stellar mass, central stellar velocity dispersion, and axial ratio of the light distribution. These correlations suggest a possible higher ratio of infalling-to-local gas in early-type disk galaxies or a connection between lags and the possible presence of hot gaseous halos, which may be more prevalent in more massive galaxies. These results again demonstrate that observations of extraplanar gas can serve as a potential probe for accretion of gas.
Influence of several factors on ignition lag in a compression-ignition engine
NASA Technical Reports Server (NTRS)
Gerrish, Harold C; Voss, Fred
1932-01-01
This investigation was made to determine the influence of fuel quality, injection advance angle, injection valve-opening pressure, inlet-air pressure, compression ratio, and engine speed on the time lag of auto-ignition of a Diesel fuel oil in a single-cylinder compression-ignition engine as obtained from an analysis of indicator diagrams. Three cam-operated fuel-injection pumps, two pumps cams, and an automatic injection valve with two different nozzles were used. Ignition lag was considered to be the interval between the start of injection of the fuel as determined with a Stroborama and the start of effective combustion as determined from the indicator diagram, the latter being the point where 4.0 x 10(exp-6) pound of fuel had been effectively burned. For this particular engine and fuel it was found that: (1) for a constant start and the same rate of fuel injection up the point of cut-off, a variation in fuel quantity from 1.2 x 10(exp-4) to 4.1 x 10(exp-4) pound per cycle has no appreciable effect on the ignition lag; (2) injection advance angle increases or decreases the lag according to whether density, temperature, or turbulence has the controlling influence; (3) increase in valve-opening pressure slightly increases the lag; and (4) increase of inlet-air pressure, compression ratio, and engine speed reduces the lag.
Evolution of stimulants to treat ADHD: transdermal methylphenidate
Patrick, Kennerly S.; Straughn, Arthur B.; Perkins, Jeb S.; González, Mario A.
2009-01-01
Objective The following comprehensive review describes the evolution of stimulant drug formulations used in the treatment of attention-deficit/hyperactivity disorder (ADHD). Emphasis is placed on the basic and clinical pharmacology of the dl-methylphenidate (MPH) transdermal system (MTS). Methods The pharmacokinetic and pharmacodynamic literature pertaining to MPH and amphetamine enantiomers was reviewed in the context of ADHD therapy and MTS as a treatment option. Results MTS incorporates MPH into an adhesive monolithic matrix, using the free base form of the drug to facilitate transdermal absorption. MTS technology minimizes contact dermatitis by eliminating to need for percutaneous penetration enhancers. After a lag time of approximately 2 h, plasma concentrations of the therapeutic d-MPH isomer become detectable, then continuously rise over the course of the recommended 9 h wear time. Concentrations of l-MPH typically attain 40−50% that of d-MPH (vs. 1−2% following oral MPH). Unauthorized MTS removal poses some misuse liability and over 50% of MTS drug content remains in the discarded system. Conclusions While liquid or chewable MPH formulations overcome potential swallowing difficulties, as do sprinkled once-daily extended-release (ER) MPH products, only MTS addresses swallowing difficulties while also offering a flexible individualized MPH exposure time in a once-daily MPH regimen. PMID:19051222
Warm Season Temperatures and Emergency Department Visits in Atlanta, Georgia
Winquist, Andrea; Grundstein, Andrew; Chang, Howard H.; Hess, Jeremy; Sarnat, Stefanie Ebelt
2016-01-01
Purpose Extreme heat events will likely increase in frequency with climate change. Heat-related health effects are better documented among the elderly than among younger age groups. We assessed associations between warm-season ambient temperature and emergency department (ED) visits across ages in Atlanta during 1993-2012. Methods We examined daily counts of ED visits with primary diagnoses of heat illness, fluid/electrolyte imbalances, renal disease, cardiorespiratory diseases, and intestinal infections by age group (0-4, 5-18, 19-64, 65+ years) in relation to daily maximum temperature (TMX) using Poisson time series models that included cubic terms for TMX at single-day lags of 0-6 days, controlling for maximum dew-point temperature, time trends, week day, holidays, and hospital participation periods. We estimated rate ratios (RRs) and 95% confidence intervals (CI) for TMX changes from 27 °C to 32 °C (25th to 75th percentile) and conducted extensive sensitivity analyses. Results We observed associations between TMX and ED visits for all internal causes, heat illness, fluid/electrolyte imbalances, renal diseases, asthma/wheeze, diabetes, and intestinal infections. Age groups with the strongest observed associations were 65+ years for all internal causes [lag 0 RR (CI)=1.022 (1.016-1.028)] and diabetes [lag 0 RR=1.050 (1.008-1.095)]; 19-64 years for fluid/electrolyte imbalances [lag 0 RR=1.170 (1.136-1.205)] and renal disease [lag 1 RR=1.082 (1.065-1.099)]; and 5-18 years for asthma/wheeze [lag 2 RR=1.059 (1.030-1.088)] and intestinal infections [lag 1 RR=1.120 (1.041-1.205)]. Conclusions Varying strengths of associations between TMX and ED visits by age suggest that optimal interventions and health-impact projections would account for varying heat health impacts across ages. PMID:26922412
Practical limitations on the use of diurnal temperature signals to quantify groundwater upwelling
Briggs, Martin A.; Lautz, Laura K.; Buckley, Sean F.; Lane, John W.
2014-01-01
Groundwater upwelling to streams creates unique habitat by influencing stream water quality and temperature; upwelling zones also serve as vectors for contamination when groundwater is degraded. Temperature time series data acquired along vertical profiles in the streambed have been applied to simple analytical models to determine rates of vertical fluid flux. These models are based on the downward propagation characteristics (amplitude attenuation and phase-lag) of the surface diurnal signal. Despite the popularity of these models, there are few published characterizations of moderate-to-strong upwelling. We attribute this limitation to the thermodynamics of upwelling, under which the downward conductive signal transport from the streambed interface occurs opposite the upward advective fluid flux. Governing equations describing the advection–diffusion of heat within the streambed predict that under upwelling conditions, signal amplitude attenuation will increase, but, counterintuitively, phase-lag will decrease. Therefore the extinction (measurable) depth of the diurnal signal is very shallow, but phase lag is also short, yielding low signal to noise ratio and poor model sensitivity. Conversely, amplitude attenuation over similar sensor spacing is strong, yielding greater potential model sensitivity. Here we present streambed thermal time series over a range of moderate to strong upwelling sites in the Quashnet River, Cape Cod, Massachusetts. The predicted inverse relationship between phase-lag and rate of upwelling was observed in the field data over a range of conditions, but the observed phase-lags were consistently shorter than predicted. Analytical solutions for fluid flux based on signal amplitude attenuation return results consistent with numerical models and physical seepage meters, but the phase-lag analytical model results are generally unreasonable. Through numerical modeling we explore reasons why phase-lag may have been over-predicted by the analytical models, and develop guiding relations of diurnal temperature signal extinction depth based on stream diurnal signal amplitude, upwelling magnitude, and streambed thermal properties that will be useful in designing future experiments.
Kawabata-Shoda, E; Masuda, S; Kimura, H
2012-10-01
Concern about the drug lag, the delay in marketing approval between one country and another, for anticancer drugs has increased in Japan. Although a number of studies have investigated the drug lag, none has investigated it in relation to the transition of anticancer therapy from traditional cytotoxic drugs to molecularly targeted agents. Our aim was to investigate current trend in oncology drug lag between the US and Japan and identify oncology drugs approved in only one of the two countries. Publicly and commercially available data sources were used to identify drugs approved in the US and Japan as of 31 December 2010 and the data used to calculate the drug lag for individual drugs. Fifty-one drugs were approved in both the US and Japan, whereas 34 and 19 drugs were approved only in the US or Japan, respectively. Of the 19 drugs approved only in Japan, 12 had not been subject to development for a cancer indication in the US, and all were approved before 1996 in Japan. Of the 34 drugs approved only in the US, 20 had not been subject to development in Japan, and none was in the top 25 by annual US anticancer drug-class sales. For drugs approved in both countries, the mean approval lag of the molecularly targeted drugs (MTDs) was significantly shorter than that of the non-molecularly targeted drugs (non-MTDs) (3·3 vs. 5·4 years). Further, mean R&D time of the MTDs was significantly shorter than that of non-MTDs (10·0 vs. 13·7 years). The price of MTDs had increased on average by 6·6% annually in the US, whereas it had decreased on average by 4·3% biyearly in Japan. The emergence of new molecularly targeted agents has contributed to reducing the approval lag, most likely due to improvements in R&D strategy. © 2012 Blackwell Publishing Ltd.
Localization of marine mammals near Hawaii using an acoustic propagation model
NASA Astrophysics Data System (ADS)
Tiemann, Christopher O.; Porter, Michael B.; Frazer, L. Neil
2004-06-01
Humpback whale songs were recorded on six widely spaced receivers of the Pacific Missile Range Facility (PMRF) hydrophone network near Hawaii during March of 2001. These recordings were used to test a new approach to localizing the whales that exploits the time-difference of arrival (time lag) of their calls as measured between receiver pairs in the PMRF network. The usual technique for estimating source position uses the intersection of hyperbolic curves of constant time lag, but a drawback of this approach is its assumption of a constant wave speed and straight-line propagation to associate acoustic travel time with range. In contrast to hyperbolic fixing, the algorithm described here uses an acoustic propagation model to account for waveguide and multipath effects when estimating travel time from hypothesized source positions. A comparison between predicted and measured time lags forms an ambiguity surface, or visual representation of the most probable whale position in a horizontal plane around the array. This is an important benefit because it allows for automated peak extraction to provide a location estimate. Examples of whale localizations using real and simulated data in algorithms of increasing complexity are provided.
LateBiclustering: Efficient Heuristic Algorithm for Time-Lagged Bicluster Identification.
Gonçalves, Joana P; Madeira, Sara C
2014-01-01
Identifying patterns in temporal data is key to uncover meaningful relationships in diverse domains, from stock trading to social interactions. Also of great interest are clinical and biological applications, namely monitoring patient response to treatment or characterizing activity at the molecular level. In biology, researchers seek to gain insight into gene functions and dynamics of biological processes, as well as potential perturbations of these leading to disease, through the study of patterns emerging from gene expression time series. Clustering can group genes exhibiting similar expression profiles, but focuses on global patterns denoting rather broad, unspecific responses. Biclustering reveals local patterns, which more naturally capture the intricate collaboration between biological players, particularly under a temporal setting. Despite the general biclustering formulation being NP-hard, considering specific properties of time series has led to efficient solutions for the discovery of temporally aligned patterns. Notably, the identification of biclusters with time-lagged patterns, suggestive of transcriptional cascades, remains a challenge due to the combinatorial explosion of delayed occurrences. Herein, we propose LateBiclustering, a sensible heuristic algorithm enabling a polynomial rather than exponential time solution for the problem. We show that it identifies meaningful time-lagged biclusters relevant to the response of Saccharomyces cerevisiae to heat stress.
Analytical determination of the lag phase in grapes by remote measurement of trellis tension
USDA-ARS?s Scientific Manuscript database
The lag phase (L) of grape berry growth is used to determine the timing of hand sampling for yield estimation. In commercial practice, growers apply scalars to measurements of berry of cluster masses under the assumption that fruit was assessed during L, which is the short period of slowest increase...
NASA Astrophysics Data System (ADS)
Green, Rebecca E.; Gould, Richard W., Jr.; Ko, Dong S.
2008-06-01
We developed statistically-based, optical models to estimate tripton (sediment/detrital) and colored dissolved organic matter (CDOM) absorption coefficients ( a sd, a g) from physical hydrographic and atmospheric properties. The models were developed for northern Gulf of Mexico shelf waters using multi-year satellite and physical data. First, empirical algorithms for satellite-derived a sd and a g were developed, based on comparison with a large data set of cruise measurements from northern Gulf shelf waters; these algorithms were then applied to a time series of ocean color (SeaWiFS) satellite imagery for 2002-2005. Unique seasonal timing was observed in satellite-derived optical properties, with a sd peaking most often in fall/winter on the shelf, in contrast to summertime peaks observed in a g. Next, the satellite-derived values were coupled with the physical data to form multiple regression models. A suite of physical forcing variables were tested for inclusion in the models: discharge from the Mississippi River and Mobile Bay, Alabama; gridded fields for winds, precipitation, solar radiation, sea surface temperature and height (SST, SSH); and modeled surface salinity and currents (Navy Coastal Ocean Model, NCOM). For satellite-derived a sd and a g time series (2002-2004), correlation and stepwise regression analyses revealed the most important physical forcing variables. Over our region of interest, the best predictors of tripton absorption were wind speed, river discharge, and SST, whereas dissolved absorption was best predicted by east-west wind speed, river discharge, and river discharge lagged by 1 month. These results suggest the importance of vertical mixing (as a function of winds and thermal stratification) in controlling a sd distribution patterns over large regions of the shelf, in comparison to advection as the most important control on a g. The multiple linear regression models for estimating a sd and a g were applied on a pixel-by-pixel basis and results were compared to monthly SeaWiFS composite imagery. The models performed well in resolving seasonal and interannual optical variability in model development years (2002-2004) (mean error of 32% for a sd and 29% for a g) and in predicting shelfwide optical patterns in a year independent of model development (2005; mean error of 41% for a sd and 46% for a g). The models provide insight into the dominant processes controlling optical distributions in this region, and they can be used to predict the optical fields from the physical properties at monthly timescales.
Pseudo-random bit generator based on lag time series
NASA Astrophysics Data System (ADS)
García-Martínez, M.; Campos-Cantón, E.
2014-12-01
In this paper, we present a pseudo-random bit generator (PRBG) based on two lag time series of the logistic map using positive and negative values in the bifurcation parameter. In order to hidden the map used to build the pseudo-random series we have used a delay in the generation of time series. These new series when they are mapped xn against xn+1 present a cloud of points unrelated to the logistic map. Finally, the pseudo-random sequences have been tested with the suite of NIST giving satisfactory results for use in stream ciphers.
NASA Astrophysics Data System (ADS)
Becker, Martin Andrew
1997-11-01
Unconformities and fossil rich layers are common elements in the stratigraphic architecture of upper Cretaceous sediments exposed on both the Atlantic and Eastern Gulf Coastal Plains. Contacts between the Eutaw Formation and Tombigbee Sands Member in Alabama, the Blufftown Formation and Cusseta Sands in Georgia and the Wenonah- Mt. Laurel and Navesink Formations in New Jersey are marked by erosional surfaces with overlying blankets and lenses of macrofossil residuum. These contacts correspond to bounding unconformities and transgressive lags separating Santonian-Campanian, lower Campanian-upper Campanian and Campanian-Maastrichtian depositional sequences. Regression and subsequent transgression of sea level at the top of these depositional sequences resulted in hydrodynamic sorting of sediments and fossils that had previously accumulated in shelf and lower shoreface paleoenvironments. Remobilization of sediments by shoreface retreat reworked fossil hard-parts which became concentrated above erosional surfaces as sea level rose. Because of the abundance of chondrichthyan, pelecypod and ammonite fossils, these lags have great biostratigraphic significance and provide a basis for examining time averaging in macrofossil zonation. Chondrichthyan teeth are composed of extremely durable and highly insoluble, biogenic apatite. This tooth apatite accurately records the Sr87/Sr86 isotopic signature of seawater, from which the numerical age of the teeth can be calculated using published age/concentration data. Teeth (e.g. Squalicorax kaupi, Scapanorhynchus texanus) from Santonian-Campanian lag deposits at the contact of the Eutaw Formation and Tombigbee Sands Member in Alabama yield approximate ages of 85-81 Ma. Teeth from lower-upper Campanian lag deposits at the contact of the Blufftown Formation and Cusseta Sands in Georgia yield approximate ages of 83-75 Ma. Teeth from Campanian-Maastrichtian lag deposits at the contact of the Wenonah-Mt. Laurel and Navesink Formations in New Jersey yield approximate ages of 80-76 Ma. Isotopic age determination from these chondrichthyan teeth indicate average hiatus of approximately 3-7 million years occur during the development of lag accumulations and transgressive unconformities. Santonian, Campanian and Maastrichtian macrofossils analyzed in this study are hydrodynamically stable components representing time-averaged fossil assemblages sorted together by physical processes and are not life cohorts. Abrupt appearance and disappearance of organisms found in upper Cretaceous lag deposits of the Atlantic and Eastern Gulf Coastal Plains are artifacts of a physical sorting processes associated with sea-level cyclicity.
Predictability in community dynamics.
Blonder, Benjamin; Moulton, Derek E; Blois, Jessica; Enquist, Brian J; Graae, Bente J; Macias-Fauria, Marc; McGill, Brian; Nogué, Sandra; Ordonez, Alejandro; Sandel, Brody; Svenning, Jens-Christian
2017-03-01
The coupling between community composition and climate change spans a gradient from no lags to strong lags. The no-lag hypothesis is the foundation of many ecophysiological models, correlative species distribution modelling and climate reconstruction approaches. Simple lag hypotheses have become prominent in disequilibrium ecology, proposing that communities track climate change following a fixed function or with a time delay. However, more complex dynamics are possible and may lead to memory effects and alternate unstable states. We develop graphical and analytic methods for assessing these scenarios and show that these dynamics can appear in even simple models. The overall implications are that (1) complex community dynamics may be common and (2) detailed knowledge of past climate change and community states will often be necessary yet sometimes insufficient to make predictions of a community's future state. © 2017 John Wiley & Sons Ltd/CNRS.
[The effects of exposure to ozone on sperm quality in Wuhan].
Tian, X J; Wang, X C; Ye, B; Li, C L; Zhang, Y; Ma, L
2017-03-06
Objective: To evaluate the effects of exposure to ozone (O(3)) on sperm quality during different stages of spermatogenesis. Methods: All 1 780 subjects attending to the Reproductive Medicine Center in Renmin Hospital of Wuhan University were recruited from April, 4, 2013 to June, 30, 2015. The subjects were living in Wuhan more than 3 months before attending to the program, aged 20 to 40 years. Semen quality (sperm concentration and sperm count) were measured according to standardized protocols. Corresponding daily 8 hours average concentration of O(3), other polluted concentration, average temperature and relative humidity were collected in different time, including lag 0, 10, 70 and 90 d, and lag 0-9 d, lag 10-14 d, lag 70-90 d and lag 0-90 d. After controlling the age, BMI, education level and other confounders, generalized linear Model was used to investigate the association between O(3) and sperm quality during different stages of spermatogenesis. Results: Average daily concentration of O(3) during the study period was (114.20±74.88) μg/m(3) and the mean values of sperm concentration and count were (76.32±50.17) millions/ml and (164.77 ± 133.05) millions/sample, respectively. Exposure to O(3) was associated with decreasing sperm concentration and count. For every 1 μg/m(3) increase of O(3), the decrease of sperm concentration during lag 10, lag 0-9 and lag 10-14 days exposure windows were 0.040 (95% CI: 0.004-0.077) millions/ml, 0.081 (95% CI: 0.003-0.158) millions/ml and 0.059 (95% CI: 0.001-0.116) millions/ml, respectively. And the decrease of sperm count during lag 10, lag 0-9 days exposure windows were 0.105 (95% CI: 0.008-0.202) millions/sample and 0.221 (95% CI: 0.016-0.426) millions/sample. After stratification, in the ozone concentration
Nath, Bipul; Nath, Lila Kanta
2013-11-01
The present study was aimed at designing a microflora triggered colon-targeted drug delivery system (MCDDS) based on swellable polysaccharide, Sterculia gum in combination with biodegradable polymers with a view to target azathioprine (AZA) in the colon for the treatment of IBD with reduced systemic toxicity. The microflora degradation study of gum was investigated in rat cecal medium. The polysaccharide tablet was coated to different film thicknesses with blends of chitosan/Eudragit RLPO and over coated with Eudragit L00 to provide acid and intestinal resistance. Swelling and drug release studies were carried out in simulated gastric fluid (SGF) (pH 1.2), simulated intestinal fluid (SIF) (pH 6.8) and simulated colonic fluid (SCF) (pH 7.4 under anaerobic environment), respectively. Drug release study in SCF revealed that swelling force of the gum could concurrently drive the drug out of the polysaccharide core due to the rupture of the chitosan/Eudragit coating in microflora-activated environment. Chitosan in the mixed film coat was found to be degraded by enzymatic action of the microflora in the colon. Release kinetic data revealed that, the optimized MCDDS was fitted well into first order model and apparent lag time was found to be 6 h, followed by Higuchi spherical matrix release. The degradation of chitosan was the rate-limiting factor for drug release in the colon. In-vivo study in rabbit shows delayed T(max), prolonged absorption time, decreased C(max) and absorption rate constant (Ka) indicating reduced systemic toxicity of the drug as compared to other dosage forms.
NASA Astrophysics Data System (ADS)
Lamolda, Héctor; Felpeto, Alicia; Bethencourt, Abelardo
2017-07-01
Between 2011 and 2014 there were at least seven episodes of magmatic intrusion in El Hierro Island, but only the first one led to a submarine eruption in 2011-2012. In order to study the relationship between GPS deformation and seismicity during these episodes, we compare the temporal evolution of the deformation with the cumulative seismic energy released. In some of the episodes both deformation and seismicity evolve in a very similar way, but in others a time lag appears between them, in which the deformation precedes the seismicity. Furthermore, a linear correlation between decimal logarithm of intruded magma volume and decimal logarithm of total seismic energy released along the different episodes has been observed. Therefore, if a future magmatic intrusion in El Hierro Island follows this behavior with a proper time lag, we could have an a priori estimate on the order of magnitude the seismic energy released would reach.
Balaev, Mikhail
2014-07-01
The author examines how time delayed effects of economic development, education, and gender equality influence political democracy. Literature review shows inadequate understanding of lagged effects, which raises methodological and theoretical issues with the current quantitative studies of democracy. Using country-years as a unit of analysis, the author estimates a series of OLS PCSE models for each predictor with a systematic analysis of the distributions of the lagged effects. The second set of multiple OLS PCSE regressions are estimated including all three independent variables. The results show that economic development, education, and gender have three unique trajectories of the time-delayed effects: Economic development has long-term effects, education produces continuous effects regardless of the timing, and gender equality has the most prominent immediate and short term effects. The results call for the reassessment of model specifications and theoretical setups in the quantitative studies of democracy. Copyright © 2014 Elsevier Inc. All rights reserved.
No evidence for the radiation time lag model after whole genome duplications in Teleostei
Laurent, Sacha; Salamin, Nicolas
2017-01-01
The short and long term effects of polyploidization on the evolutionary fate of lineages is still unclear despite much interest. First recognized in land plants, it has become clear that polyploidization is widespread in eukaryotes, notably at the origin of vertebrates and teleost fishes. Many hypotheses have been proposed to link the species richness of lineages and whole genome duplications. For instance, the radiation time lag model suggests that paleopolyploidy would favour the apparition of new phenotypic traits, although the radiation of the lineage would not occur before a later dispersion event. Some results indicate that this model may be observed during land plant evolution. In this work, we test predictions of the radiation time lag model using both fossil data and molecular phylogenies in ancient and more recent teleost whole genome duplications. We fail to find any evidence of delayed increase of the species number after any of these events and conclude that paleopolyploidization still remains to be unambiguously linked to taxonomic diversity in teleosts. PMID:28426792
Polyamine-Induced Rapid Root Abscission in Azolla pinnata
Gurung, Sushma; Cohen, Michael F.; Fukuto, Jon; Yamasaki, Hideo
2012-01-01
Floating ferns of the genus Azolla detach their roots under stress conditions, a unique adaptive response termed rapid root abscission. We found that Azolla pinnata plants exhibited dose-dependent rapid root abscission in response to the polyamines spermidine and spermine after a substantial time lag (>20 min). The duration of the time lag decreased in response to high pH and high temperature whereas high light intensity increased the time lag and markedly lowered the rate of abscission. The oxidation products of polyamines, 1,3-diaminopropane, β-alanine and hydrogen peroxide all failed to initiate root abscission, and hydroxyethyl hydrazine, an inhibitor of polyamine oxidase, did not inhibit spermine-induced root abscission. Exposure of A. pinnata to the polyamines did not result in detectable release of NO and did not affect nitrite-dependent NO production. The finding of polyamine-induced rapid root abscission provides a facile assay for further study of the mode of action of polyamines in plant stress responses. PMID:22997568
Polyamine-Induced Rapid Root Abscission in Azolla pinnata.
Gurung, Sushma; Cohen, Michael F; Fukuto, Jon; Yamasaki, Hideo
2012-01-01
Floating ferns of the genus Azolla detach their roots under stress conditions, a unique adaptive response termed rapid root abscission. We found that Azolla pinnata plants exhibited dose-dependent rapid root abscission in response to the polyamines spermidine and spermine after a substantial time lag (>20 min). The duration of the time lag decreased in response to high pH and high temperature whereas high light intensity increased the time lag and markedly lowered the rate of abscission. The oxidation products of polyamines, 1,3-diaminopropane, β-alanine and hydrogen peroxide all failed to initiate root abscission, and hydroxyethyl hydrazine, an inhibitor of polyamine oxidase, did not inhibit spermine-induced root abscission. Exposure of A. pinnata to the polyamines did not result in detectable release of NO and did not affect nitrite-dependent NO production. The finding of polyamine-induced rapid root abscission provides a facile assay for further study of the mode of action of polyamines in plant stress responses.
NASA Astrophysics Data System (ADS)
Vogel, H.; Förstner, J.; Vogel, B.; Hanisch, T.; Mühr, B.; Schättler, U.; Schad, T.
2014-08-01
An extended version of the German operational weather forecast model was used to simulate the ash dispersion during the eruption of the Eyjafjallajökull. As an operational forecast was launched every 6 hours, a time-lagged ensemble was obtained. Sensitivity runs show the ability of the model to simulate thin ash layers when an increased vertical resolution is used. Calibration of the model results with measured data allows for a quantitative forecast of the ash concentration. After this calibration an independent comparison of the simulated number concentration of 3 μm particles and observations at Hohenpeißenberg gives a correlation coefficient of 0.79. However, this agreement could only be reached after additional modifications of the emissions. Based on the time lagged ensemble the conditional probability of violation of a certain threshold is calculated. Improving the ensemble technique used in our study such probabilities could become valuable information for the forecasters advising the organizations responsible for the closing of the airspace.
Kumar, Dinesh; Rai, K N
2017-07-01
In this paper, we investigated the thermal behavior in living biological tissues using time fractional dual-phase-lag bioheat transfer (DPLBHT) model subjected to Dirichelt boundary condition in presence of metabolic and electromagnetic heat sources during thermal therapy. We solved this bioheat transfer model using finite element Legendre wavelet Galerkin method (FELWGM) with help of block pulse function in sense of Caputo fractional order derivative. We compared the obtained results from FELWGM and exact method in a specific case, and found a high accuracy. Results are interpreted in the form of standard and anomalous cases for taking different order of time fractional DPLBHT model. The time to achieve hyperthermia position is discussed in both cases as standard and time fractional order derivative. The success of thermal therapy in the treatment of metastatic cancerous cell depends on time fractional order derivative to precise prediction and control of temperature. The effect of variability of parameters such as time fractional derivative, lagging times, blood perfusion coefficient, metabolic heat source and transmitted power on dimensionless temperature distribution in skin tissue is discussed in detail. The physiological parameters has been estimated, corresponding to the value of fractional order derivative for hyperthermia treatment therapy. Copyright © 2017 Elsevier Ltd. All rights reserved.
NASA Astrophysics Data System (ADS)
Du, Pu; Zhang, Zhi-Xiang; Wang, Kai; Huang, Ying-Ke; Zhang, Yue; Lu, Kai-Xing; Hu, Chen; Li, Yan-Rong; Bai, Jin-Ming; Bian, Wei-Hao; Yuan, Ye-Fei; Ho, Luis C.; Wang, Jian-Min; SEAMBH collaboration
2018-03-01
As one paper in a series reporting on a large reverberation mapping campaign of super-Eddington accreting massive black holes (SEAMBHs) in active galactic nuclei (AGNs), we present the results of 10 SEAMBHs monitored spectroscopically during 2015–2017. Six of them are observed for the first time, and have generally higher 5100 Å luminosities than the SEAMBHs monitored in our campaign from 2012 to 2015; the remaining four are repeat observations to check if their previous lags change. Similar to the previous SEAMBHs, the Hβ time lags of the newly observed objects are shorter than the values predicted by the canonical R Hβ –L 5100 relation of sub-Eddington AGNs, by factors of ∼2–6, depending on the accretion rate. The four previously observed objects have lags consistent with previous measurements. We provide linear regressions for the R Hβ –L 5100 relation, solely for the SEAMBH sample and for low-accretion AGNs. We find that the relative strength of Fe II and the profile of the Hβ emission line can be used as proxies of accretion rate, showing that the shortening of Hβ lags depends on accretion rates. The recent SDSS-RM discovery of shortened Hβ lags in AGNs with low accretion rates provides compelling evidence for retrograde accretion onto the black hole. These evidences show that the canonical R Hβ –L 5100 relation holds only in AGNs with moderate accretion rates. At low accretion rates, it should be revised to include the effects of black hole spin, whereas the accretion rate itself becomes a key factor in the regime of high accretion rates.
NASA Astrophysics Data System (ADS)
Schneider, Kai; Kadoch, Benjamin; Bos, Wouter
2017-11-01
The angle between two subsequent particle displacement increments is evaluated as a function of the time lag. The directional change of particles can thus be quantified at different scales and multiscale statistics can be performed. Flow dependent and geometry dependent features can be distinguished. The mean angle satisfies scaling behaviors for short time lags based on the smoothness of the trajectories. For intermediate time lags a power law behavior can be observed for some turbulent flows, which can be related to Kolmogorov scaling. The long time behavior depends on the confinement geometry of the flow. We show that the shape of the probability distribution function of the directional change can be well described by a Fischer distribution. Results for two-dimensional (direct and inverse cascade) and three-dimensional turbulence with and without confinement, illustrate the properties of the proposed multiscale statistics. The presented Monte-Carlo simulations allow disentangling geometry dependent and flow independent features. Finally, we also analyze trajectories of football players, which are, in general, not randomly spaced on a field.
Relationships among abilities in elderly adults: a time lag analysis.
Hayslip, B; Brookshire, R G
1985-11-01
Previous research has suggested that relationships among primary abilities said to measure crystallized (Gc) and fluid (Gf) intelligences remain the same across cohorts if age is held constant, despite generational changes in the levels of abilities. The present study assessed differences in relationship among several components of Gf/Gc in two independent samples of elderly adults, tested in 1975 and 1979 by the same investigator. The 1975 sample consisted of 54 elderly adults aged 59 to 76 years (M = 67.7); the 1979 sample of 50 elderly adults was aged 55 to 82 (M = 69.4). Time-lagged differences in relationships among abilities measuring Gf and Gc (induction, figural relations, and verbal comprehension) were investigated using confirmatory factor analytic procedures. Although a two factor (Gf, Gc) model was common to both the 1975 and 1979 samples, significant differences in unique variances were observed across samples. Some, albeit weaker, evidence was found suggesting time-lagged differences in factor covariances. These data, for the most part, support previous research with younger individuals, suggesting consistency in factor structure across time and cohort.
NASA Astrophysics Data System (ADS)
Marin, F.; Rojas Lobos, P. A.; Hameury, J. M.; Goosmann, R. W.
2018-05-01
Context. From stars to active galactic nuclei, many astrophysical systems are surrounded by an equatorial distribution of dusty material that is, in a number of cases, spatially unresolved even with cutting edge facilities. Aims: In this paper, we investigate if and how one can determine the unresolved and heterogeneous morphology of dust distribution around a central bright source using time-resolved polarimetric observations. Methods: We used polarized radiative transfer simulations to study a sample of circumnuclear dusty morphologies. We explored a grid of geometrically variable models that are uniform, fragmented, and density stratified in the near-infrared, optical, and ultraviolet bands, and we present their distinctive time-dependent polarimetric signatures. Results: As expected, varying the structure of the obscuring equatorial disk has a deep impact on the inclination-dependent flux, polarization degree and angle, and time lags we observe. We find that stratified media are distinguishable by time-resolved polarimetric observations, and that the expected polarization is much higher in the infrared band than in the ultraviolet. However, because of the physical scales imposed by dust sublimation, the average time lags of months to years between the total and polarized fluxes are important; these time lags lengthens the observational campaigns necessary to break more sophisticated, and therefore also more degenerated, models. In the ultraviolet band, time lags are slightly shorter than in the infrared or optical bands, and, coupled to lower diluting starlight fluxes, time-resolved polarimetry in the UV appears more promising for future campaigns. Conclusions: Equatorial dusty disks differ in terms of inclination-dependent photometric, polarimetric, and timing observables, but only the coupling of these different markers can lead to inclination-independent constraints on the unresolved structures. Even though it is complex and time consuming, polarized reverberation mapping in the ultraviolet-blue band is probably the best technique to rely on in this field.
Effect of Asian dust storms on mortality in three Asian cities
NASA Astrophysics Data System (ADS)
Lee, Hyewon; Honda, Yasushi; Lim, Youn-Hee; Guo, Yue Leon; Hashizume, Masahiro; Kim, Ho
2014-06-01
Asian dust storms (ADS) have affected several Asian countries and have been a major concern due to adverse effects on public health. The occurrence of ADS differs in each country based on geographical features and distance from the storms' origin. Many studies have reported significant associations between ADS and morbidity. However, regarding the association between ADS and mortality, only a few studies have found statistically significant ADS effects in Korea, Taiwan and Japan. Accordingly, this study aimed to examine the effects of ADS on daily mortality in three Asian cities (Seoul, South Korea; Taipei, Taiwan; and Kitakyushu, Japan) and to explore the differences in the extent of effects in each city. We performed time-series analyses using a generalized additive model (GAM) with Quasi-Poisson regressions. Deaths due to accidents or external causes were excluded. We used a dummy variable as an indicator of ADS and considered lag effects of ADS. Stratified analyses by disease and age and sensitivity analyses controlling for NO2, SO2, and PM10 were also conducted respectively. Additionally, influenza epidemics were adjusted for considering seasonal patterns, and a meta-analysis was performed. We reported results as excess mortality by percentage due to Asian dust storms. We found significant excess mortality in Seoul and Kitakyushu as follows. In Seoul, ADS showed adverse effects on mortality under 65 years old (lag 2: 4.44%, lag 3: 5%, lag 4: 4.39%). In Kitakyushu, ADS had adverse effects on respiratory mortality (lag 2: 18.82%). Contradictory to results in Seoul and Kitakyushu, ADS seemed to have a protective effect in Taipei: total non-accidental mortality (lag 0: -2.77%, lag 1: -3.24%), mortality over 65 years old (lag 0: -3.35%, lag 1: -3.29%) and respiratory mortality (lag 0: -10.62%, lag 1: -9.67%). Sensitivity analyses showed similar findings as the main results. Our findings suggest that ADS may affect mortality in several Asian cities, and that a dust storm warning system could help protect people from dust storms.
Time series regression model for infectious disease and weather.
Imai, Chisato; Armstrong, Ben; Chalabi, Zaid; Mangtani, Punam; Hashizume, Masahiro
2015-10-01
Time series regression has been developed and long used to evaluate the short-term associations of air pollution and weather with mortality or morbidity of non-infectious diseases. The application of the regression approaches from this tradition to infectious diseases, however, is less well explored and raises some new issues. We discuss and present potential solutions for five issues often arising in such analyses: changes in immune population, strong autocorrelations, a wide range of plausible lag structures and association patterns, seasonality adjustments, and large overdispersion. The potential approaches are illustrated with datasets of cholera cases and rainfall from Bangladesh and influenza and temperature in Tokyo. Though this article focuses on the application of the traditional time series regression to infectious diseases and weather factors, we also briefly introduce alternative approaches, including mathematical modeling, wavelet analysis, and autoregressive integrated moving average (ARIMA) models. Modifications proposed to standard time series regression practice include using sums of past cases as proxies for the immune population, and using the logarithm of lagged disease counts to control autocorrelation due to true contagion, both of which are motivated from "susceptible-infectious-recovered" (SIR) models. The complexity of lag structures and association patterns can often be informed by biological mechanisms and explored by using distributed lag non-linear models. For overdispersed models, alternative distribution models such as quasi-Poisson and negative binomial should be considered. Time series regression can be used to investigate dependence of infectious diseases on weather, but may need modifying to allow for features specific to this context. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
Climate variability and increase in intensity and magnitude of dengue incidence in Singapore
Hii, Yien Ling; Rocklöv, Joacim; Ng, Nawi; Tang, Choon Siang; Pang, Fung Yin; Sauerborn, Rainer
2009-01-01
Introduction Dengue is currently a major public health burden in Asia Pacific Region. This study aims to establish an association between dengue incidence, mean temperature and precipitation, and further discuss how weather predictors influence the increase in intensity and magnitude of dengue in Singapore during the period 2000–2007. Materials and methods Weekly dengue incidence data, daily mean temperature and precipitation and the midyear population data in Singapore during 2000–2007 were retrieved and analysed. We employed a time series Poisson regression model including time factors such as time trends, lagged terms of weather predictors, considered autocorrelation, and accounted for changes in population size by offsetting. Results The weekly mean temperature and cumulative precipitation were statistically significant related to the increases of dengue incidence in Singapore. Our findings showed that dengue incidence increased linearly at time lag of 5–16 and 5–20 weeks succeeding elevated temperature and precipitation, respectively. However, negative association occurred at lag week 17–20 with low weekly mean temperature as well as lag week 1–4 and 17–20 with low cumulative precipitation. Discussion As Singapore experienced higher weekly mean temperature and cumulative precipitation in the years 2004–2007, our results signified hazardous impacts of climate factors on the increase in intensity and magnitude of dengue cases. The ongoing global climate change might potentially increase the burden of dengue fever infection in near future. PMID:20052380
Senjoti, Faria Gias; Mahmood, Syed; Jaffri, Juliana Md; Mandal, Uttam Kumar
2016-01-01
An oral sustained-release floating tablet formulation of metformin HCl was designed and developed. Effervescence and swelling properties were attributed on the developed tablets by sodium bicarbonate and HPMC-PEO polymer combination, respectively. Tablet composition was optimized by response surface methodology (RSM). Seventeen (17) trial formulations were analyzed according to Box-Behnken design of experiment where polymer content of HPMC and PEO at 1: 4 ratio (A), amount of sodium bi-carbonate (B), and amount of SSG (C) were adopted as independent variables. Floating lag time in sec (Y1), cumulative percent drug released at 1 h (Y2) and 12 h (Y3) were chosen as response variables. Tablets from the optimized formulation were also stored at accelerated stability condition (40°C and 75% RH) for 3 months to assess their stability profile. RSM could efficiently optimize the tablet composition with excellent prediction ability. In-vitro drug release until 12 h, floating lag time, and duration of floating were dependent on the amount of three selected independent variables. Optimized tablets remained floating for more than 24 h with a floating lag time of less than 4 min. Based on best fitting method, optimized formulation was found to follow Korsmeyer-Peppas release kinetic. Accelerated stability study revealed that optimized formulation was stable for three months without any major changes in assay, dissolution profile, floating lag time and other physical properties. PMID:27610147
Chen, Dong; Yao, Jia; Chen, Lie; Yin, Jingping; Lv, Ruizhi; Huang, Bin; Liu, Siqi; Zhang, Zhi-Guo; Yang, Chunhe; Chen, Yiwang; Li, Yongfang
2018-04-16
All-polymer solar cells (all-PSCs) can offer unique advantages for applications in flexible devices, and naphthalene diimide (NDI)-based polymer acceptors are the widely used polymer acceptors. However, their power conversion efficiency (PCE) still lags behind that of state-of-the-art polymer solar cells, due to low light absorption, suboptimal energy levels and the strong aggregation of the NDI-based polymer acceptor. Herein, a rhodanine-based dye molecule was introduced into the NDI-based polymer acceptor by simple random copolymerization and showed an improved light absorption coefficient, an up-shifted lowest unoccupied molecular orbital level and reduced crystallization. Consequently, additive-free all-PSCs demonstrated a high PCE of 8.13 %, which is one of the highest performance characteristics reported for all-PSCs to date. These results indicate that incorporating a dye into the n-type polymer gives insight into the precise design of high-performance polymer acceptors for all-PSCs. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
Time-averaged fluxes of lead and fallout radionuclides to sediments in Florida Bay
Robbins, J.A.; Holmes, C.; Halley, R.; Bothner, Michael H.; Shinn, E.; Graney, J.; Keeler, G.; TenBrink, M.; Orlandini, K.A.; Rudnick, D.
2000-01-01
Recent, unmixed sediments from mud banks of central Florida Bay were dated using 210Pb/226Ra, and chronologies were verified by comparing sediment lead temporal records with Pb/Ca ratios in annual layers of coral (Montastrea annularis) located on the ocean side of the Florida Keys. Dates of sediment lead peaks (1978±2) accord with prior observations of a 6 year lag between the occurrence of maximum atmospheric lead in 1972 and peak coral lead in 1978. Smaller lags of 1–2 years occur between the maximum atmospheric radionuclide fallout and peaks in sediment temporal records of 137Cs and Pu. Such lags are consequences of system time averaging (STA) in which atmospherically delivered particle-associated constituents accumulate and mix in a (sedimentary?) reservoir before transferring to permanent sediments and coral. STA model calculations, using time-dependent atmospheric inputs, produced optimized profiles in excellent accord with measured sediment 137Cs, Pu, lead, and coral lead distributions. Derived residence times of these particle tracers (16±1, 15.7±0.7, 19±3, and 16±2 years, respectively) are comparable despite differences in sampling locations, in accumulating media, and in element loading histories and geochemical properties. For a 16 year weighted mean residence time, STA generates the observed 6 year lead peak lag. Evidently, significant levels of nondegradable, particle-associated contaminants can persist in Florida Bay for many decades following elimination of external inputs. Present results, in combination with STA model analysis of previously reported radionuclide profiles, suggest that decade-scale time averaging may occur widely in recent coastal marine sedimentary environments.
Forbes-Robertson, Sarah; Dudley, Edward; Vadgama, Pankaj; Cook, Christian; Drawer, Scott; Kilduff, Liam
2012-03-01
Jet lag has potentially serious deleterious effects on performance in athletes following transmeridian travel, where time zones are crossed eastwards or westwards; as such, travel causes specific effects related to desynchronization of the athlete's internal body clock or circadian clock. Athletes are particularly sensitive to the effects of jet lag, as many intrinsic aspects of sporting performance show a circadian rhythm, and optimum competitive results require all aspects of the athlete's mind and body to be working in tandem at their peak efficiency. International competition often requires transmeridian travel, and competition timings cannot be adjusted to suit individual athletes. It is therefore in the interest of the individual athlete and team to understand the effects of jet lag and the potential adaptation strategies that can be adopted. In this review, we describe the underlying genetic and physiological mechanisms controlling the circadian clock and its inherent ability to adapt to external conditions on a daily basis. We then examine the fundamentals of the various adaptation stimuli, such as light, chronobiotics (e.g. melatonin), exercise, and diet and meal timing, with particular emphasis on their suitability as strategies for competing athletes on the international circuit. These stimuli can be artificially manipulated to produce phase shifts in the circadian rhythm to promote adaptation in the optimum direction, but care must be taken to apply them at the correct time and dose, as the effects produced on the circadian rhythm follow a phase-response curve, with pronounced shifts in direction at different times. Light is the strongest realigning stimulus and careful timing of light exposure and avoidance can promote adjustment. Chronobiotics such as melatonin can also be used to realign the circadian clock but, as well as timing and dosage issues, there are also concerns as to its legal status in different countries and with the World Anti-Doping Agency. Experimental data concerning the effects of food intake and exercise timing on jet lag is limited to date in humans, and more research is required before firm guidelines can be stated. All these stimuli can also be used in pre-flight adaptation strategies to promote adjustment in the required direction, and implementation of these is described. In addition, the effects of individual variability at the behavioural and genetic levels are also discussed, along with the current limitations in assessment of these factors, and we then put forward three case studies, as examples of practical applications of these strategies, focusing on adaptations to travel involving competition in the Rugby Sevens World Cup and the 2016 Summer Olympics in Rio de Janeiro, Brazil. Finally, we provide a list of practice points for optimal adaptation of athletes to jet lag.
Paracetamol plasma and cerebrospinal fluid pharmacokinetics in children
Anderson, B J; Holford, N H G; Woollard, G A; Chan, P L S
1998-01-01
Aims Paracetamol has a central action for both antipyresis and analgesia. Maximum temperature decrease and peak analgesia are reported at 1–2 h after peak plasma paracetamol concentration. We wished to determine the relationship between plasma and cerebrospinal fluid (CSF) pharmacokinetics in children. Methods Concentration-time profiles in plasma and CSF after nasogastric paracetamol 40 mg kg−1 were measured in nine children who had indwelling ventricular drains. Estimation of population pharmacokinetic parameters was made using both a standard two-stage population approach (MKMODEL) and a nonlinear mixed effect model (NONMEM). Results were standardized to a 70 kg person using an allometric power model. Results Both approaches gave similar estimates. NONMEM parameter estimates were clearance 10.2 l h−1 (CV 47%), volume of distribution 67.1 l (CV 58%) and absorption rate constant 0.77 h−1 (CV 49%). Cerebrospinal fluid concentrations lagged behind those of plasma. The equilibration half time was 0.72 h (CV 117%). The CSF/plasma partition coefficient was 1.18 (CV 8%). Conclusions Higher concentrations in the CSF probably reflect the lower free water volume of plasma. The CSF equilibration half time suggests that CSF kinetics approximate more closely to the effect compartment than plasma, but further time is required for paracetamol to exert its effects. Effect site concentrations equilibrate slowly with plasma. Paracetamol should be given 1–2 h before anticipated pain or fever in children. PMID:9764964
Predicting depressed patients with suicidal ideation from ECG recordings.
Khandoker, A H; Luthra, V; Abouallaban, Y; Saha, S; Ahmed, K I; Mostafa, R; Chowdhury, N; Jelinek, H F
2017-05-01
Globally suicidal behavior is the third most common cause of death among patients with major depressive disorder (MDD). This study presents multi-lag tone-entropy (T-E) analysis of heart rate variability (HRV) as a screening tool for identifying MDD patients with suicidal ideation. Sixty-one ECG recordings (10 min) were acquired and analyzed from control subjects (29 CONT), 16 MDD subjects with (MDDSI+) and 16 without suicidal ideation (MDDSI-). After ECG preprocessing, tone and entropy values were calculated for multiple lags (m: 1-10). The MDDSI+ group was found to have a higher mean tone value compared to that of the MDDSI- group for lags 1-8, whereas the mean entropy value was lower in MDDSI+ than that in CONT group at all lags (1-10). Leave-one-out cross-validation tests, using a classification and regression tree (CART), obtained 94.83 % accuracy in predicting MDDSI+ subjects by using a combination of tone and entropy values at all lags and including demographic factors (age, BMI and waist circumference) compared to results with time and frequency domain HRV analysis. The results of this pilot study demonstrate the usefulness of multi-lag T-E analysis in identifying MDD patients with suicidal ideation and highlight the change in autonomic nervous system modulation of the heart rate associated with depression and suicidal ideation.
Failure of the precedence effect with a noise-band vocoder
Seeber, Bernhard U.; Hafter, Ervin R.
2011-01-01
The precedence effect (PE) describes the ability to localize a direct, leading sound correctly when its delayed copy (lag) is present, though not separately audible. The relative contribution of binaural cues in the temporal fine structure (TFS) of lead–lag signals was compared to that of interaural level differences (ILDs) and interaural time differences (ITDs) carried in the envelope. In a localization dominance paradigm participants indicated the spatial location of lead–lag stimuli processed with a binaural noise-band vocoder whose noise carriers introduced random TFS. The PE appeared for noise bursts of 10 ms duration, indicating dominance of envelope information. However, for three test words the PE often failed even at short lead–lag delays, producing two images, one toward the lead and one toward the lag. When interaural correlation in the carrier was increased, the images appeared more centered, but often remained split. Although previous studies suggest dominance of TFS cues, no image is lateralized in accord with the ITD in the TFS. An interpretation in the context of auditory scene analysis is proposed: By replacing the TFS with that of noise the auditory system loses the ability to fuse lead and lag into one object, and thus to show the PE. PMID:21428515
[Influence of humidex on incidence of bacillary dysentery in Hefei: a time-series study].
Zhang, H; Zhao, K F; He, R X; Zhao, D S; Xie, M Y; Wang, S S; Bai, L J; Cheng, Q; Zhang, Y W; Su, H
2017-11-10
Objective: To investigate the effect of humidex combined with mean temperature and relative humidity on the incidence of bacillary dysentery in Hefei. Methods: Daily counts of bacillary dysentery cases and weather data in Hefei were collected from January 1, 2006 to December 31, 2013. Then, the humidex was calculated from temperature and relative humidity. A Poisson generalized linear regression combined with distributed lag non-linear model was applied to analyze the relationship between humidex and the incidence of bacillary dysentery, after adjusting for long-term and seasonal trends, day of week and other weather confounders. Stratified analyses by gender, age and address were also conducted. Results: The risk of bacillary dysentery increased with the rise of humidex. The adverse effect of high humidex (90 percentile of humidex) appeared in 2-days lag and it was the largest at 4-days lag ( RR =1.063, 95 %CI : 1.037-1.090). Subgroup analyses indicated that all groups were affected by high humidex at lag 2-5 days. Conclusion: High humidex could significantly increase the risk of bacillary dysentery, and the lagged effects were observed.
Skeldon, Anne C; Phillips, Andrew J K; Dijk, Derk-Jan
2017-03-27
Why do we go to sleep late and struggle to wake up on time? Historically, light-dark cycles were dictated by the solar day, but now humans can extend light exposure by switching on artificial lights. We use a mathematical model incorporating effects of light, circadian rhythmicity and sleep homeostasis to provide a quantitative theoretical framework to understand effects of modern patterns of light consumption on the human circadian system. The model shows that without artificial light humans wakeup at dawn. Artificial light delays circadian rhythmicity and preferred sleep timing and compromises synchronisation to the solar day when wake-times are not enforced. When wake-times are enforced by social constraints, such as work or school, artificial light induces a mismatch between sleep timing and circadian rhythmicity ('social jet-lag'). The model implies that developmental changes in sleep homeostasis and circadian amplitude make adolescents particularly sensitive to effects of light consumption. The model predicts that ameliorating social jet-lag is more effectively achieved by reducing evening light consumption than by delaying social constraints, particularly in individuals with slow circadian clocks or when imposed wake-times occur after sunrise. These theory-informed predictions may aid design of interventions to prevent and treat circadian rhythm-sleep disorders and social jet-lag.
Predictable pulsatile release of tramadol hydrochloride for chronotherapeutics of arthritis.
Dabhi, Chandu; Randale, Shivsagar; Belgamwar, Veena; Gattani, Surendra; Tekade, Avinash
2010-07-01
The present investigation deals with the development of a pH and time-dependent press-coated pulsatile drug delivery system for delivering drugs into the colon. The system consists of a drug containing core, coated by a combination of natural polymer Delonix regia gum (DRG) and hydroxypropyl methylcellulose (HPMC K4M) in various proportions, which controls the onset of release. The whole system was coated with methacrylic acid copolymers, which not only prevents the drug release in the stomach, but also prolongs the lag time. Tramadol HCl was used as a model drug and varying combinations of DRG and HPMC K4M were used to achieve the desired lag time before rapid and complete release of the drug in the colon. It was observed that the lag time depends on the coating ratio of DRG to HPMC and also on press coating weight. Drug release was found to be increased by 15-30% in the presence of colonic microbial flora. The results showed the capability of the system in achieving pulsatile release for a programmable period of time and pH-dependent release to attain colon-targeted delivery.
Dynein-ADP as a force-generating intermediate revealed by a rapid reactivation of flagellar axoneme.
Tani, T; Kamimura, S
1999-01-01
Fragmented flagellar axonemes of sand dollar spermatozoa were reactivated by rapid photolysis of caged ATP. After a time lag of 10 ms, axonemes treated with protease started sliding disintegration. Axonemes without protease digestion started nanometer-scale high-frequency oscillation after a similar time lag. Force development in the sliding disintegration was measured with a flexible glass needle and its time course was corresponded well to that of the dynein-ADP intermediate production estimated using kinetic rates previously reported. However, with a high concentration ( approximately 80 microM) of vanadate, which binds to the dynein-ADP intermediate and forms a stable complex of dynein-ADP-vanadate, the time course of force development in sliding disintegration was not affected at all. In the case of high frequency oscillation, the time lag to start the oscillation, the initial amplitude, and the initial frequency were not affected by vanadate, though the oscillation once started was damped more quickly at higher concentrations of vanadate. These results suggest that during the initial turnover of ATP hydrolysis, force generation of dynein is not blocked by vanadate. A vanadate-insensitive dynein-ADP is postulated as a force-generating intermediate. PMID:10465762
NASA Astrophysics Data System (ADS)
Kahn, Amanda S.; Ruhl, Henry A.; Smith, Kenneth L.
2012-12-01
Density and average size of two species of abyssal sponges were analyzed at Station M (∼4100 m depth) over an 18-year time-series (1989-2006) using camera sled transects. Both sponge taxa share a similar plate-like morphology despite being within different families, and both showed similar variations in density and average body size over time, suggesting that the same factors may control the demographics of both species. Peaks in significant cross correlations between increases in particulate organic carbon flux and corresponding increases in sponge density occurred with a time lag of 13 months. Sponge density also fluctuated with changes in two climate indices: the NOI with a time lag of 18 months and NPGO with a time lag of 15 months. The results support previous suggestions that increased particulate organic carbon flux may induce recruitment or regeneration in deep-sea sponges. It is unknown whether the appearance of young individuals results from recruitment, regeneration, or both, but the population responses to seasonal and inter-annual changes in food supply demonstrate that sponge populations are dynamic and are capable of responding to inter-annual changes despite being sessile and presumably slow-growing.
ERIC Educational Resources Information Center
East, Patricia L.; Chien, Nina C.; Barber, Jennifer S.
2012-01-01
The authors used cross-lagged analyses to examine the across-time influences on and consequences of adolescents' pregnancy intentions, wantedness, and regret. One hundred pregnant Latina adolescents were studied during pregnancy and at 6 and 12 months postpartum. The results revealed 4 main findings: (a) similar to what has been found in adult…
ERIC Educational Resources Information Center
Benbenishty, Rami; Astor, Ron Avi; Roziner, Ilan; Wrabel, Stephani L.
2016-01-01
The present study explores the causal link between school climate, school violence, and a school's general academic performance over time using a school-level, cross-lagged panel autoregressive modeling design. We hypothesized that reductions in school violence and climate improvement would lead to schools' overall improved academic performance.…
Analysis of inadvertent microprocessor lag time on eddy covariance results
Karl Zeller; Gary Zimmerman; Ted Hehn; Evgeny Donev; Diane Denny; Jeff Welker
2001-01-01
Researchers using the eddy covariance approach to measuring trace gas fluxes are often hoping to measure carbon dioxide and energy fluxes for ecosystem intercomparisons. This paper demonstrates a systematic microprocessor- caused lag of 20.1 to 20.2 s in a commercial sonic anemometer-analog-to-digital datapacker system operated at 10 Hz. The result of the inadvertent...
Negative Input for Grammatical Errors: Effects after a Lag of 12 Weeks
ERIC Educational Resources Information Center
Saxton, Matthew; Backley, Phillip; Gallaway, Clare
2005-01-01
Effects of negative input for 13 categories of grammatical error were assessed in a longitudinal study of naturalistic adult-child discourse. Two-hour samples of conversational interaction were obtained at two points in time, separated by a lag of 12 weeks, for 12 children (mean age 2;0 at the start). The data were interpreted within the framework…
Using lagged dependence to identify (de)coupled surface and subsurface soil moisture values
NASA Astrophysics Data System (ADS)
Carranza, Coleen D. U.; van der Ploeg, Martine J.; Torfs, Paul J. J. F.
2018-04-01
Recent advances in radar remote sensing popularized the mapping of surface soil moisture at different spatial scales. Surface soil moisture measurements are used in combination with hydrological models to determine subsurface soil moisture values. However, variability of soil moisture across the soil column is important for estimating depth-integrated values, as decoupling between surface and subsurface can occur. In this study, we employ new methods to investigate the occurrence of (de)coupling between surface and subsurface soil moisture. Using time series datasets, lagged dependence was incorporated in assessing (de)coupling with the idea that surface soil moisture conditions will be reflected at the subsurface after a certain delay. The main approach involves the application of a distributed-lag nonlinear model (DLNM) to simultaneously represent both the functional relation and the lag structure in the time series. The results of an exploratory analysis using residuals from a fitted loess function serve as a posteriori information to determine (de)coupled values. Both methods allow for a range of (de)coupled soil moisture values to be quantified. Results provide new insights into the decoupled range as its occurrence among the sites investigated is not limited to dry conditions.
Chi, Peilian; Li, Xiaoming; Zhao, Junfeng; Zhao, Guoxiang
2014-06-01
Previous research has found a deleterious impact of stigma on the mental health of children affected by HIV/AIDS. Little is known about the longitudinal relationship of stigma and children's mental health. This study explores the longitudinal reciprocal effects of depressive symptoms and stigma, specifically enacted stigma and perceived stigma, among children affected by HIV/AIDS aged 6-12. Longitudinal data were collected from 272 children orphaned by AIDS and 249 children of HIV-positive parents in rural China. Cross-lagged panel analysis was conducted in the study. Results showed that the autoregressive effects were stable for depressive symptoms, perceived stigma and enacted stigma suggesting the substantially stable individual differences over time. The cross-lagged effects indicated a vicious circle among the three variables in an order of enacted stigma → depressive symptom → perceived stigma → enacted stigma. The possibility of employing equal constraints on cross-lagged paths suggested that the cross-lagged effects were repeatable over time. The dynamic interplay of enacted stigma, perceived stigma and depressive symptoms suggests the need of a multilevel intervention in stigma reduction programming to promote mental health of children affected by HIV/AIDS.
Chi, Peilian; Li, Xiaoming; Zhao, Junfeng; Zhao, Guoxiang
2013-01-01
Previous research has found a deleterious impact of stigma on the mental health of children affected by HIV/AIDS. Little is known about the longitudinal relationship of stigma and children’s mental health. This study explores the longitudinal reciprocal effects of depressive symptoms and stigma, specifically enacted stigma and perceived stigma, among children affected by HIV/AIDS aged 6 to 12. Longitudinal data were collected from 272 children orphaned by AIDS and 249 children of HIV-positive parents in rural China. Cross-lagged panel analysis was conducted in the study. Results showed that the autoregressive effects were stable for depressive symptoms, perceived stigma and enacted stigma suggesting the substantially stable individual differences over time. The cross-lagged effects indicated a vicious circle among the three variables in an order of enacted stigma→depressive symptom→perceived stigma→enacted stigma. The possibility of employing equal constraints on cross-lagged paths suggested that the cross-lagged effects were repeatable over time. The dynamic interplay of enacted stigma, perceived stigma and depressive symptoms suggests the need of a multilevel intervention in stigma reduction programming to promote mental health of children affected by HIV/AIDS. PMID:24158487
Flap-Lag-Torsion Stability in Forward Flight
NASA Technical Reports Server (NTRS)
Panda, B.; Chopra, I.
1985-01-01
An aeroelastic stability of three-degree flap-lag-torsion blade in forward flight is examined. Quasisteady aerodynamics with a dynamic inflow model is used. The nonlinear time dependent periodic blade response is calculated using an iterative procedure based on Floquet theory. The periodic perturbation equations are solved for stability using Floquet transition matrix theory as well as constant coefficient approximation in the fixed reference frame. Results are presented for both stiff-inplane and soft-inplane blade configurations. The effects of several parameters on blade stability are examined, including structural coupling, pitch-flap and pitch-lag coupling, torsion stiffness, steady inflow distribution, dynamic inflow, blade response solution and constant coefficient approximation.
Effects of Air Pollutant Exposure on Acute Myocardial Infarction, According to Gender.
Tuan, Tássia Soldi; Venâncio, Taís Siqueira; Nascimento, Luiz Fernando Costa
2016-09-01
There is evidence of the effects of air pollution on hospital admissions due to cardiovascular diseases, including myocardial infarction. To estimate the association between exposure to air pollutants and hospital admissions due to myocardial infarction according to gender, between January 1st 2012 and December 31st 2013, in São Jose dos Campos-SP. An ecological time series study was carried out with daily data of admissions due to AMI, pollutants CO, O3, PM10, SO2, and NO2, according to gender. We used the Poisson regression generalized linear model to estimate the relative risks of hospital admissions with lags of 0-5 days, adjusted for temperature, humidity, seasonality and days of the week. There were 1837 admissions for ischemic heart diseases, with 636 women and 1201 men. For females, the risks were significant for CO in lag 0 (RR = 1,09), lag1 (RR = 1,08) and lag 5 (RR = 1,10) and SO2 in lag 0 (RR = 1,10) and 3 (RR = 1,09). For men there was significance of the CO in, lag 3 and lag 5 (RR = 1,05). There was significance, regardless of gender, for CO at lag 1 (RR = 1,05) and lag 5 (RR = 1,07) and lag 0 for SO2 (RR = 1,06). The data presented show the important role of CO and SO2 in the genesis of myocardial infarction admissions, and responses to pollutant exposure are different if analyzed by gender and together - hence the importance of a stratified analyses. Existem evidências sobre os efeitos da poluição do ar nas internações por doenças cardiovasculares, entre elas o infarto do miocárdio. Estimar a associação entre exposição a poluentes do ar e internações por infarto segundo gêneros, entre 01 de Janeiro de 2012 e 31 de Dezembro de 2013, em São José dos Campos - SP. Estudo ecológico de série temporal com dados diários de internações por IAM dos poluentes CO, O3, PM10, SO2, NO2, segundo gêneros. Utilizou-se modelo linear generalizado da Regressão de Poisson para estimar os riscos relativos para internações com defasagens de 0 a 5 dias, ajustados por temperatura, umidade, sazonalidade e dias da semana. Foram 1837 internações por doenças isquêmicas do coração, sendo 636 mulheres e 1201 homens. Para o gênero feminino, os riscos foram significativos para o CO nos lag 0 (RR = 1,09), lag1 (RR = 1,08) e lag 5 (RR = 1,10) e para o SO2 no lag 0 (RR = 1,10) e 3 (RR = 1,09). Para o gênero masculino houve significância para o CO no lag 3 e lag 5 (RR = 1,05). Sem distinção de gênero houve significância para o CO no lag 1 (RR = 1,05) e lag 5 (RR = 1,07) e no lag 0 para o SO2 (RR = 1,06). Os dados apresentados mostram o importante papel do CO e do SO2 na gênese das internações por infarto e que as respostas à exposição aos poluentes são diferentes se analisadas por sexo e em conjunto, daí a importância de se estratificarem as análises.
NASA Astrophysics Data System (ADS)
Andrews, Allen H.; Asami, Ryuji; Iryu, Yasufumi; Kobayashi, Donald R.; Camacho, Frank
2016-08-01
High-resolution radiocarbon (14C) analyses on a coral core extracted from Guam, a western tropical Pacific island, revealed a series of early bomb-produced 14C spikes. The typical marine bomb 14C signal—phase lagged and attenuated relative to atmospheric records—is present in the coral and is consistent with other regional coral records. However, 14C levels well above what can be attributed to air-sea diffusion alone punctuate this pattern. This anomaly was observed in other Indo-Pacific coral records, but the Guam record is unmatched in magnitude and temporal resolution. The Guam coral Δ14C record provided three spikes in 1954-1955, 1956-1957, and 1958-1959 that are superimposed on a normal 14C record. Relative to mean prebomb levels, the first peak rises an incredible ˜700‰ and remained elevated for ˜1.2 years. A follow up assay with finer resolution increased the peak by ˜300‰. Subsequent spikes were less intense with a rise of ˜35 and ˜70‰. Each can be linked to thermonuclear testing in the Pacific Proving Grounds at Bikini and Enewetak atolls in Operations Castle (1954), Redwing (1956), and Hardtack I (1958). These 14C signals can be explained by vaporization of coral reef material in the nuclear fireball, coupled with neutron activation of atmospheric nitrogen (14C production), and subsequent absorption of 14CO2 to form particulate carbonates of close-in fallout. The lag time in reaching Guam and other coral records abroad was tied to ocean surface currents and modeling provided validation of 14C arrival observations.
Emotion Modulation of Visual Attention: Categorical and Temporal Characteristics
Ciesielski, Bethany G.; Armstrong, Thomas; Zald, David H.; Olatunji, Bunmi O.
2010-01-01
Background Experimental research has shown that emotional stimuli can either enhance or impair attentional performance. However, the relative effects of specific emotional stimuli and the specific time course of these differential effects are unclear. Methodology/Principal Findings In the present study, participants (n = 50) searched for a single target within a rapid serial visual presentation of images. Irrelevant fear, disgust, erotic or neutral images preceded the target by two, four, six, or eight items. At lag 2, erotic images induced the greatest deficits in subsequent target processing compared to other images, consistent with a large emotional attentional blink. Fear and disgust images also produced a larger attentional blinks at lag 2 than neutral images. Erotic, fear, and disgust images continued to induce greater deficits than neutral images at lag 4 and 6. However, target processing deficits induced by erotic, fear, and disgust images at intermediate lags (lag 4 and 6) did not consistently differ from each other. In contrast to performance at lag 2, 4, and 6, enhancement in target processing for emotional stimuli was observed in comparison to neutral stimuli at lag 8. Conclusions/Significance These findings suggest that task-irrelevant emotion information, particularly erotica, impairs intentional allocation of attention at early temporal stages, but at later temporal stages, emotional stimuli can have an enhancing effect on directed attention. These data suggest that the effects of emotional stimuli on attention can be both positive and negative depending upon temporal factors. PMID:21079773
Vigotti, Maria Angela; Serinelli, Maria; Marchini, Laura
2010-01-01
we evaluated the association of daily pollutants' concentrations with daily hospital admissions for respiratory causes in children residents in Pisa during 1998-2002. We compared the results obtained with two methods of statistical analyses. A total of 657 children under ten years and admitted to local hospitals for respiratory diseases (ICD 9: 460-469, 480- 519) were included in the study. both time-series and case-crossover analysis were applied, controlling for temperature, holidays, influenza epidemics,rain and relative humidity. Pollutants' effects are expressed as percentage increase (and 95% CI) of hospital admissions for an increase of 10 μg/m³ of pollutants (1 mg/m³ for CO). with both analyses, children's hospital admissions for respiratory conditions were significantly associated to increasing daily levels of PM10 and CO at different time lags, while no association was found for NO₂ and O₃. In the case-crossover analysis, for a daily increase of 10 μg/m³ in PM10, a significant increment of 8.5% (CI 95% 0.02; 17.6) in children respiratory admissions was observed at lag 0-3. Results were stronger for males and during the warm season. A 1 mg/m³ increment in daily CO levels was associated with an increase of respiratory admissions at lag 0 (20.2%, CI 95% 5.3; 37.2) and at all cumulative lags: the maximum value was observed at lag 0-3 (32.6%, CI 95%8.3; 62.2). Time series analyses provides similar results, although the estimates were lower than with the other method, in terms of percentage increment and length of confidence intervals. this study indicates adverse effects of air pollution on respiratory health of children living in urban environment. The results of both analyses were consistent.
Greater Effect of East versus West Travel on Jet Lag, Sleep, and Team Sport Performance.
Fowler, Peter M; Knez, Wade; Crowcroft, Stephen; Mendham, Amy E; Miller, Joanna; Sargent, Charlie; Halson, Shona; Duffield, Rob
2017-12-01
This study aimed to determine the recovery timeline of sleep, subjective jet lag and fatigue, and team sport physical performance after east and west long-haul travel. Ten physically trained men underwent testing at 0900 h and 1700 h local time on four consecutive days 2 wk before outbound travel (BASE), and the first 4 d after 21 h of outbound (WEST) and return (EAST) air travel across eight time zones between Australia and Qatar. Data collection included performance (countermovement jump, 20-m sprint, and Yo-Yo intermittent recovery level 1 [YYIR1] test) and perceptual (jet lag, motivation, perceived exertion, and physical feeling) measures. In addition, sleep was measured via wrist activity monitors and self-report diaries throughout the aforementioned data collection periods. Compared with the corresponding day at BASE, the reduction in YYIR1 distance after EAST was significantly different from the increase in WEST on day 1 after travel (P < 0.001). On day 2, significantly slower 20-m sprint times were detected in EAST compared with WEST (P = 0.03), with large effect sizes (ES) also indicating a greater reduction in YYIR1 distance in EAST compared with WEST (d = 1.06). Mean sleep onset and offset were significantly later and mean time in bed and sleep duration were significantly reduced across the 4 d in EAST compared with BASE and WEST (P < 0.05). Lastly, mean jet lag, fatigue, and motivation ratings across the 4 d were significantly worse in EAST compared with BASE and WEST (P < 0.05) and WEST compared with BASE (P < 0.05). Long-haul transmeridian travel can impede team sport physical performance. Specifically, east travel has a greater detrimental effect on sleep, subjective jet lag, fatigue, and motivation. Consequently, maximal and intermittent sprint performance is also reduced after east travel, particularly within 72 h after arrival.
Fredman, Lisa; Lyons, Jennifer G; Cauley, Jane A; Hochberg, Marc; Applebaum, Katie M
2015-09-01
Previous studies have shown inconsistent associations between caregiving and mortality. This may be due to analyzing caregiver status at baseline only, and that better health is probably related to taking on caregiving responsibilities and continuing in that role. The latter is termed The Healthy Caregiver Hypothesis, similar to the Healthy Worker Effect in occupational epidemiology. We applied common approaches from occupational epidemiology to evaluate the association between caregiving and mortality, including treating caregiving as time-varying and lagging exposure up to 5 years. Caregiving status among 1,068 women (baseline mean age = 81.0 years; 35% caregivers) participating in the Caregiver-Study of Osteoporotic Fractures study was assessed at five interviews conducted between 1999 and 2009. Mortality was determined through January 2012. Cox proportional hazards models were used to estimate adjusted hazard ratios and 95% confidence intervals adjusted for sociodemographics, perceived stress, and functional limitations. A total of 483 participants died during follow-up (38.8% and 48.7% of baseline caregivers and noncaregivers, respectively). Using baseline caregiving status, the association with mortality was 0.77, 0.62-0.95. Models of time-varying caregiving status showed a more pronounced reduction in mortality in current caregivers (hazard ratios = 0.54, 0.38-0.75), which diminished with longer lag periods (3-year lag hazard ratio = 0.68, 0.52-0.88, 5-year lag hazard ratios = 0.76, 0.60-0.95). Overall, caregivers had lower mortality rates than noncaregivers in all analyses. These associations were sensitive to the lagged period, indicating that the timing of leaving caregiving does influence this relationship and should be considered in future investigations. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Reducing the Disruptive Effects of Interruptions With Noninvasive Brain Stimulation.
Blumberg, Eric J; Foroughi, Cyrus K; Scheldrup, Melissa R; Peterson, Matthew S; Boehm-Davis, Debbie A; Parasuraman, Raja
2015-09-01
The authors determine whether transcranial direct current stimulation (tDCS) can reduce resumption time when an ongoing task is interrupted. Interruptions are common and disruptive. Working memory capacity has been shown to predict resumption lag (i.e., time to successfully resume a task after interruption). Given that tDCS applied to brain areas associated with working memory can enhance performance, tDCS has the potential to improve resumption lag when a task is interrupted. Participants were randomly assigned to one of four groups that received anodal (active) stimulation of 2 mA tDCS to one of two target brain regions, left and right dorsolateral prefrontal cortex (DLPFC), or to one of two control areas, active stimulation of the left primary motor cortex or sham stimulation of the right DLPFC, while completing a financial management task that was intermittently interrupted with math problem solving. Anodal stimulation to the right and left DLPFC significantly reduced resumption lags compared to the control conditions (sham and left motor cortex stimulation). Additionally, there was no speed-accuracy tradeoff (i.e., the improvement in resumption time was not accompanied by an increased error rate). Noninvasive brain stimulation can significantly decrease resumption lag (improve performance) after a task is interrupted. Noninvasive brain stimulation offers an easy-to-apply tool that can significantly improve interrupted task performance. © 2014, Human Factors and Ergonomics Society.
von Biela, V R; Zimmerman, C E; Moulton, L L
2011-01-01
Arctic cisco Coregonus autumnalis young-of-year (YOY) growth was used as a proxy to examine the long-term response of a high-latitude fish population to changing climate from 1978 to 2004. YOY growth increased over time (r² = 0·29) and was correlated with monthly averages of the Arctic oscillation index, air temperature, east wind speed, sea-ice concentration and river discharge with and without time lags. Overall, the most prevalent correlates to YOY growth were sea-ice concentration lagged 1 year (significant correlations in 7 months; r² = 0·14-0·31) and Mackenzie River discharge lagged 2 years (significant correlations in 8 months; r² = 0·13-0·50). The results suggest that decreased sea-ice concentrations and increased river discharge fuel primary production and that life cycles of prey species linking increased primary production to fish growth are responsible for the time lag. Oceanographic studies also suggest that sea ice concentration and fluvial inputs from the Mackenzie River are key factors influencing productivity in the Beaufort Sea. Future research should assess the possible mechanism relating sea ice concentration and river discharge to productivity at upper trophic levels. Journal of Fish Biology © 2010 The Fisheries Society of the British Isles. No claim to original US government works.
NASA Technical Reports Server (NTRS)
1974-01-01
An X-ray observation of the Norma-Lupus region, charge and isotope measurements of heavy cosmic ray nuclei and their role in the determination of cosmic ray age, and the possibility of a contribution to primary cosmic ray spectra from pulsars are among the topics covered in papers concerned with some of the results of recent cosmic ray research. Other topics covered include multiple scattering of charged particles in magnetic fields, absorption of primary cosmic rays in the atmosphere, and phase lag effects on cosmic ray modulation during a recent solar cycle. Individual items are announced in this issue.
Design considerations of manipulator and feel system characteristics in roll tracking
NASA Technical Reports Server (NTRS)
Johnston, Donald E.; Aponso, Bimal L.
1988-01-01
A fixed-base simulation was performed to identify and quantify interactions between the pilot's hand/arm neuromuscular subsystem and such control system features of typical modern fighter aircraft roll rate command mechanizations as: (1) force versus displacement sensing side-stick type manipulator, (2) feel force/displacement gradient, (3) feel system versus command prefilter dynamic lag, and (4) flight control system effective time delay. The experiment encompassed some 48 manipulator/filter/aircraft configurations. Displacement side-stick experiment results are given and compared with the previous force sidestick experiment results. Attention is focused on control bandwidth, excitement (peaking) of the neuromuscular mode, feel force/displacement gradient effects, time delay effects, etc. Section 5 is devoted to experiments with a center-stick in which force versus displacement sensing, feel system lag, and command prefilter lag influences on tracking performance and pilot preference are investigated.
Dynamic correlations at different time-scales with empirical mode decomposition
NASA Astrophysics Data System (ADS)
Nava, Noemi; Di Matteo, T.; Aste, Tomaso
2018-07-01
We introduce a simple approach which combines Empirical Mode Decomposition (EMD) and Pearson's cross-correlations over rolling windows to quantify dynamic dependency at different time scales. The EMD is a tool to separate time series into implicit components which oscillate at different time-scales. We apply this decomposition to intraday time series of the following three financial indices: the S&P 500 (USA), the IPC (Mexico) and the VIX (volatility index USA), obtaining time-varying multidimensional cross-correlations at different time-scales. The correlations computed over a rolling window are compared across the three indices, across the components at different time-scales and across different time lags. We uncover a rich heterogeneity of interactions, which depends on the time-scale and has important lead-lag relations that could have practical use for portfolio management, risk estimation and investment decisions.
Liao, Duanping; Shaffer, Michele L.; He, Fan; Rodriguez-Colon, Sol; Wu, Rongling; Whitsel, Eric A.; Bixler, Edward O.; Cascio, Wayne E.
2011-01-01
The acute effects and the time course of fine particulate pollution (PM2.5) on atrial fibrillation/flutter (AF) predictors, including P-wave duration, PR interval duration, and P-wave complexity, were investigated in a community-dwelling sample of 106 nonsmokers. Individual-level 24-h beat-to-beat electrocardiogram (ECG) data were visually examined. After identifying and removing artifacts and arrhythmic beats, the 30-min averages of the AF predictors were calculated. A personal PM2.5 monitor was used to measure individual-level, real-time PM2.5 exposures during the same 24-h period, and corresponding 30-min average PM2.5 concentration were calculated. Under a linear mixed-effects modeling framework, distributed lag models were used to estimate regression coefficients (βs) associating PM2.5 with AF predictors. Most of the adverse effects on AF predictors occurred within 1.5–2 h after PM2.5 exposure. The multivariable adjusted βs per 10-µg/m3 rise in PM2.5 at lag 1 and lag 2 were significantly associated with P-wave complexity. PM2.5 exposure was also significantly associated with prolonged PR duration at lag 3 and lag 4. Higher PM2.5 was found to be associated with increases in P-wave complexity and PR duration. Maximal effects were observed within 2 h. These findings suggest that PM2.5 adversely affects AF predictors; thus, PM2.5 may be indicative of greater susceptibility to AF. PMID:21480044
ANALYSES OF RESPONSE–STIMULUS SEQUENCES IN DESCRIPTIVE OBSERVATIONS
Samaha, Andrew L; Vollmer, Timothy R; Borrero, Carrie; Sloman, Kimberly; Pipkin, Claire St. Peter; Bourret, Jason
2009-01-01
Descriptive observations were conducted to record problem behavior displayed by participants and to record antecedents and consequences delivered by caregivers. Next, functional analyses were conducted to identify reinforcers for problem behavior. Then, using data from the descriptive observations, lag-sequential analyses were conducted to examine changes in the probability of environmental events across time in relation to occurrences of problem behavior. The results of the lag-sequential analyses were interpreted in light of the results of functional analyses. Results suggested that events identified as reinforcers in a functional analysis followed behavior in idiosyncratic ways: after a range of delays and frequencies. Thus, it is possible that naturally occurring reinforcement contingencies are arranged in ways different from those typically evaluated in applied research. Further, these complex response–stimulus relations can be represented by lag-sequential analyses. However, limitations to the lag-sequential analysis are evident. PMID:19949537
Kinetics of Bacteriophage λ Deoxyribonucleic Acid Infection of Escherichia coli
Barnhart, Benjamin J.
1965-01-01
Barnhart, Benjamin J. (Los Alamos Scientific Laboratory, University of California, Los Alamos, N.M.). Kinetics of bacteriophage λ deoxyribonucleic acid infection of Escherichia coli. J. Bacteriol. 90:1617–1623. 1965.—The kinetics of Escherichia coli K-12 infection by phage λ deoxyribonucleic acid (DNA) were determined. An initial lag of 55 to 80 sec was found to be the time required for infecting DNA to become deoxyribonuclease-insensitive at 33 C. When cell-DNA interactions were stopped by washing away unbound DNA, the already bound DNA continued to infect the cell at rates described by linear kinetics with no apparent lag. Whereas the lag period was relatively insensitive to DNA and cell concentrations, both the lag and the subsequent linear portions of the rate curves were temperature-sensitive. Cell and DNA dose-response curves prescribed hyperbolic functions. Similarities between λ DNA infection of E. coli and bacterial transformation systems are discussed. PMID:5322721
Evidence for a physical linkage between galactic cosmic rays and regional climate time series
Perry, C.A.
2007-01-01
The effects of solar variability on regional climate time series were examined using a sequence of physical connections between total solar irradiance (TSI) modulated by galactic cosmic rays (GCRs), and ocean and atmospheric patterns that affect precipitation and streamflow. The solar energy reaching the Earth's surface and its oceans is thought to be controlled through an interaction between TSI and GCRs, which are theorized to ionize the atmosphere and increase cloud formation and its resultant albedo. High (low) GCR flux may promote cloudiness (clear skies) and higher (lower) albedo at the same time that TSI is lowest (highest) in the solar cycle which in turn creates cooler (warmer) ocean temperature anomalies. These anomalies have been shown to affect atmospheric flow patterns and ultimately affect precipitation over the Midwestern United States. This investigation identified a relation among TSI and geomagnetic index aa (GI-AA), and streamflow in the Mississippi River Basin for the period 1878-2004. The GI-AA was used as a proxy for GCRs. The lag time between the solar signal and streamflow in the Mississippi River at St. Louis, Missouri is approximately 34 years. The current drought (1999-2007) in the Mississippi River Basin appears to be caused by a period of lower solar activity that occurred between 1963 and 1977. There appears to be a solar "fingerprint" that can be detected in climatic time series in other regions of the world, with each series having a unique lag time between the solar signal and the hydroclimatic response. A progression of increasing lag times can be spatially linked to the ocean conveyor belt, which may transport the solar signal over a time span of several decades. The lag times for any one region vary slightly and may be linked to the fluctuations in the velocity of the ocean conveyor belt.
Long-Lag, Wide-pulse Gamma-Ray Bursts
NASA Technical Reports Server (NTRS)
Norris, J. P.; Bonnell, J. T.; Kazanas, D.; Scargie, J. D.; Hakkila, J.; Giblin, T. W.
2005-01-01
The best available probe of the early phase of gamma-ray burst (GRB) jet attributes is the prompt gamma-ray emission, in which several intrinsic and extrinsic variables determine observed GRB pulse evolution, including at least: jet opening angle, profiles of Lorentz factor and matter/field density, distance of emission region from central source, and viewing angle. Bright, usually complex bursts have many narrow pulses that are difficult to model due to overlap. However, the relatively simple, long spectral lag, wide-pulse bursts may have simpler physics and are easier to model. We have analyzed the temporal and spectral behavior of wide pulses in 24 long-lag bursts from the BATSE sample, using a pulse model with two shape parameters - width and asymmetry - and the Band spectral model with three shape parameters. We find that pulses in long-lag bursts are distinguished both temporally and spectrally from those in bright bursts: the pulses in long spectral lag bursts are few in number, and approximately 100 times wider (10s of seconds), have systemtically lower peaks in nu*F(nu), harder low-energy spectra and softer high-energy spectra. These five pulse descriptors are essentially uncorrelated for our long-lag sample, suggesting that at least approximately 5 parameters are needed to model burst temporal and spectral behavior, roughly commensurate with the theoretical phase space. However, we do find that pulse width is strongly correlated with spectral lag; hence these two parameters may be viewed as mutual surrogates. The prevalence of long-lag bursts near the BATSE trigger threshold, their predominantly low nu*F(nu) spectral peaks, and relatively steep upper power-law spectral indices indicate that Swiift will detect many such bursts.
Sewe, Maquins Odhiambo; Ahlm, Clas; Rocklöv, Joacim
2016-01-01
Malaria is an important cause of morbidity and mortality in malaria endemic countries. The malaria mosquito vectors depend on environmental conditions, such as temperature and rainfall, for reproduction and survival. To investigate the potential for weather driven early warning systems to prevent disease occurrence, the disease relationship to weather conditions need to be carefully investigated. Where meteorological observations are scarce, satellite derived products provide new opportunities to study the disease patterns depending on remotely sensed variables. In this study, we explored the lagged association of Normalized Difference Vegetation Index (NVDI), day Land Surface Temperature (LST) and precipitation on malaria mortality in three areas in Western Kenya. The lagged effect of each environmental variable on weekly malaria mortality was modeled using a Distributed Lag Non Linear Modeling approach. For each variable we constructed a natural spline basis with 3 degrees of freedom for both the lag dimension and the variable. Lag periods up to 12 weeks were considered. The effect of day LST varied between the areas with longer lags. In all the three areas, malaria mortality was associated with precipitation. The risk increased with increasing weekly total precipitation above 20 mm and peaking at 80 mm. The NDVI threshold for increased mortality risk was between 0.3 and 0.4 at shorter lags. This study identified lag patterns and association of remote- sensing environmental factors and malaria mortality in three malaria endemic regions in Western Kenya. Our results show that rainfall has the most consistent predictive pattern to malaria transmission in the endemic study area. Results highlight a potential for development of locally based early warning forecasts that could potentially reduce the disease burden by enabling timely control actions.
Ambient ozone concentration and emergency department visits for panic attacks.
Cho, Jaelim; Choi, Yoon Jung; Sohn, Jungwoo; Suh, Mina; Cho, Seong-Kyung; Ha, Kyoung Hwa; Kim, Changsoo; Shin, Dong Chun
2015-03-01
The effect of ambient air pollution on panic disorder in the general population has not yet been thoroughly elucidated, although the occurrence of panic disorder in workers exposed to organic solvents has been reported previously. We investigated the association of ambient air pollution with the risk of panic attack-related emergency department visits. Using health insurance claims, we collected data from emergency department visits for panic attacks in Seoul, Republic of Korea (2005-2009). Daily air pollutant concentrations were obtained using automatic monitoring system data. We conducted a time-series study using a generalized additive model with Poisson distribution, which included spline variables (date of visit, daily mean temperature, and relative humidity) and parametric variables (daily mean air pollutant concentration, national holiday, and day of the week). In addition to single lag models (lag1 to lag3), cumulative lag models (lag0-1 to lag0-3) were constructed using moving-average concentrations on the days leading up to the visit. The risk was expressed as relative risk (RR) per one standard deviation of each air pollutant and its 95% confidence interval (95% CI). A total of 2320 emergency department visits for panic attacks were observed during the study period. The adjusted RR of panic attack-related emergency department visits was 1.051 (95% CI, 1.014-1.090) for same-day exposure to ozone. In cumulative models, adjusted RRs were 1.068 (1.029-1.107) in lag0-2 and 1.074 (1.035-1.114) in lag0-3. The ambient ozone concentration was significantly associated with emergency department visits for panic attacks. Copyright © 2015 Elsevier Ltd. All rights reserved.
Reverberation Mapping of the Continuum Source in Active Galactic Nuclei
NASA Astrophysics Data System (ADS)
Fausnaugh, Michael Martin
I present results from a monitoring campaign of 11 active galactic nuclei (AGN) conducted in Spring of 2014. I use the reverberation mapping method to probe the interior structures of the AGN, specifically the broad line regions (BLRs) and accretion disks. One of these AGN, NGC 5548, was also subject to multi-wavelength (X-ray, UV, optical, and near-IR) monitoring using 25 ground-based telescopes and four space-based facilities. For NGC 5548, I detect lags between the continuum emission at different wavelengths that follow a trend consistent with the prediction for continuum reprocessing by an accretion disk with temperature profile T ∝ R -3/4. However, the lags imply a disk radius that is 3 times larger than the prediction from standard thin-disk models. The lags at wavelengths longer than the Vband are also equal to or greater than the lags of high-ionization-state emission lines (such as HeII lambda1640 and lambda4686), suggesting that the continuum-emitting source is of a physical size comparable to the inner broad-line region. Using optical spectra from the Large Binocular Telescope, I estimate the bias of the interband continuum lags due to BLR emission observed in the filters, and I find that the bias for filters with high levels of BLR contamination (˜20%) can be important for the shortest continuum lags. This likely has a significant impact on the u and U bands owing to Balmer continuum emission. I then develop a new procedure for the internal (night-to-night) calibration of time series spectra that can reach precisions of ˜1 millimagnitude and improves traditional techniques by up to a factor of 5. At this level, other systematic issues (e.g., the nightly sensitivity functions and Fe II contamination) limit the final precision of the observed light curves. Using the new calibration method, I next present the data and first results from the optical spectroscopic monitoring component of the reverberation mapping campaign. Five AGN were sufficiently variable to measure continuum-Hbeta lags and super-massive black hole masses: MCG+08-11-011, NGC 2617, NGC 4051, 3C 382, and Mrk 374. I also obtain Hgamma and HeII lags for all objects except 3C 382. The HeII lags indicate radial stratification of the BLR, and the masses derived from different emission lines are in general agreement. The relative responsivities of these lines to continuum variations are also in qualitative agreement with photoionization models. Finally, I measure optical continuum lags for the two most variable targets, MCG+08-11-011 and NGC 2617. I again find lags consistent with geometrically thin accretion-disk models that have temperature profiles T ∝ R-3/4. The observed lags are larger than predictions based on standard thin-disk theory by factors of 3.3 for MCG+08-11-011 and 2.3 for NGC 2617. Using a physical model, these differences can be explained if the mass accretion rates are larger than inferred from the optical continuum luminosity by a factor of 4.3 in MCG+08-11-011 and a factor of 1.3 in NGC 2617. While the X-ray variability in NGC 2617 precedes the UV/optical variability, the long 2.6 day lag is problematic for coronal reprocessing models.
The Chaotic Light Curves of Accreting Black Holes
NASA Technical Reports Server (NTRS)
Kazanas, Demosthenes
2007-01-01
We present model light curves for accreting Black Hole Candidates (BHC) based on a recently developed model of these sources. According to this model, the observed light curves and aperiodic variability of BHC are due to a series of soft photon injections at random (Poisson) intervals and the stochastic nature of the Comptonization process in converting these soft photons to the observed high energy radiation. The additional assumption of our model is that the Comptonization process takes place in an extended but non-uniform hot plasma corona surrounding the compact object. We compute the corresponding Power Spectral Densities (PSD), autocorrelation functions, time skewness of the light curves and time lags between the light curves of the sources at different photon energies and compare our results to observation. Our model reproduces the observed light curves well, in that it provides good fits to their overall morphology (as manifest by the autocorrelation and time skewness) and also to their PSDs and time lags, by producing most of the variability power at time scales 2 a few seconds, while at the same time allowing for shots of a few msec in duration, in accordance with observation. We suggest that refinement of this type of model along with spectral and phase lag information can be used to probe the structure of this class of high energy sources.
Melatonin for the prevention and treatment of jet lag.
Herxheimer, A; Petrie, K J
2002-01-01
: Jet-lag commonly affects air travellers who cross several time zones. It results from the body's internal rhythms being out of step with the day-night cycle at the destination. Melatonin is a pineal hormone that plays a central part in regulating bodily rhythms and has been used as a drug to re-align them with the outside world. : To assess the effectiveness of oral melatonin taken in different dosage regimens for alleviating jet-lag after air travel across several time zones. : We searched the Cochrane Controlled Trials Register, MEDLINE, EMBASE, PsychLit and Science Citation Index electronically, and the journals 'Aviation, Space and Environmental Medicine' and 'Sleep' by hand. We searched citation lists of relevant studies for other relevant trials. We asked principal authors of relevant studies to tell us about unpublished trials. Reports of adverse events linked to melatonin use outside randomised trials were searched for systematically in 'Side Effects of Drugs' (SED) and SED Annuals, 'Reactions Weekly', MEDLINE, and the adverse drug reactions databases of the WHO Uppsala Monitoring Centre (UMC) and the US Food & Drug Administration. : Randomised trials in airline passengers, airline staff or military personnel given oral melatonin, compared with placebo or other medication. Outcome measures should consist of subjective rating of jet-lag or related components, such as subjective wellbeing, daytime tiredness, onset and quality of sleep, psychological functioning, duration of return to normal, or indicators of circadian rhythms. : Ten trials met the inclusion criteria. All compared melatonin with placebo; one in addition compared it with a hypnotic, zolpidem. Nine of the trials were of adequate quality to contribute to the assessment, one had a design fault and could not be used in the assessment. Reports of adverse events outside trials were found through MEDLINE, 'Reactions Weekly', and in the WHO UMC database. : Nine of the ten trials found that melatonin, taken close to the target bedtime at the destination (10pm to midnight), decreased jet-lag from flights crossing five or more time zones. Daily doses of melatonin between 0.5 and 5mg are similarly effective, except that people fall asleep faster and sleep better after 5mg than 0.5mg. Doses above 5mg appear to be no more effective. The relative ineffectiveness of 2mg slow-release melatonin suggests that a short-lived higher peak concentration of melatonin works better. Based on the review, the number needed to treat (NNT) is 2. The benefit is likely to be greater the more time zones are crossed, and less for westward flights. The timing of the melatonin dose is important: if it is taken at the wrong time, early in the day, it is liable to cause sleepiness and delay adaptation to local time. The incidence of other side effects is low. Case reports suggest that people with epilepsy, and patients taking warfarin may come to harm from melatonin. : Melatonin is remarkably effective in preventing or reducing jet-lag, and occasional short-term use appears to be safe. It should be recommended to adult travellers flying across five or more time zones, particularly in an easterly direction, and especially if they have experienced jet-lag on previous journeys. Travellers crossing 2-4 time zones can also use it if need be. The pharmacology and toxicology of melatonin needs systematic study, and routine pharmaceutical quality control of melatonin products must be established. The effects of melatonin in people with epilepsy, and a possible interaction with warfarin, need investigation.
Melatonin for preventing and treating jet lag.
Herxheimer, A; Petrie, K J
2001-01-01
Jet-lag commonly affects air travellers who cross several time zones. It results from the body's internal rhythms being out of step with the day-night cycle at the destination. Melatonin is a pineal hormone that plays a central part in regulating bodily rhythms and has been used as a drug to re-align them with the outside world. To assess the effectiveness of oral melatonin taken in different dosage regimens for alleviating jet-lag after air travel across several time zones. We searched the Cochrane Controlled Trials Register, MEDLINE, EMBASE, PsychLit and Science Citation Index electronically, and the journals 'Aviation, Space and Environmental Medicine' and 'Sleep' by hand. We searched citation lists of relevant studies for other relevant trials. We asked principal authors of relevant studies to tell us about unpublished trials. Reports of adverse events linked to melatonin use outside randomised trials were searched for systematically in 'Side Effects of Drugs' (SED) and SED Annuals, 'Reactions Weekly', MEDLINE, and the adverse drug reactions databases of the WHO Uppsala Monitoring Centre (UMC) and the US Food & Drug Administration. Randomised trials in airline passengers, airline staff or military personnel given oral melatonin, compared with placebo or other medication. Outcome measures should consist of subjective rating of jet-lag or related components, such as subjective wellbeing, daytime tiredness, onset and quality of sleep, psychological functioning, duration of return to normal, or indicators of circadian rhythms. : Ten trials met the inclusion criteria. All compared melatonin with placebo; one in addition compared it with a hypnotic, zolpidem. Nine of the trials were of adequate quality to contribute to the assessment, one had a design fault and could not be used in the assessment. Reports of adverse events outside trials were found through MEDLINE, 'Reactions Weekly', and in the WHO UMC database. : Nine of the ten trials found that melatonin, taken close to the target bedtime at the destination (10pm to midnight), decreased jet-lag from flights crossing five or more time zones. Daily doses of melatonin between 0.5 and 5mg are similarly effective, except that people fall asleep faster and sleep better after 5mg than 0.5mg. Doses above 5mg appear to be no more effective. The relative ineffectiveness of 2mg slow-release melatonin suggests that a short-lived higher peak concentration of melatonin works better. Based on the review, the number needed to treat (NNT) is 2. The benefit is likely to be greater the more time zones are crossed, and less for westward flights. The timing of the melatonin dose is important: if it is taken at the wrong time, early in the day, it is liable to cause sleepiness and delay adaptation to local time. The incidence of other side effects is low. Case reports suggest that people with epilepsy, and patients taking warfarin may come to harm from melatonin. Melatonin is remarkably effective in preventing or reducing jet-lag, and occasional short-term use appears to be safe. It should be recommended to adult travellers flying across five or more time zones, particularly in an easterly direction, and especially if they have experienced jet-lag on previous journeys. Travellers crossing 2-4 time zones can also use it if need be. The pharmacology and toxicology of melatonin needs systematic study, and routine pharmaceutical quality control of melatonin products must be established. The effects of melatonin in people with epilepsy, and a possible interaction with warfarin, need investigation.
2002 Airborne Geophysical Survey at Pueblo of Laguna Bombing Targets, New Mexico. Revision 3
2005-10-01
conducted and results evaluated. The eight cesium magnetometers , GPS systems (positioning and attitude), fluxgate magnetometers , data recording...Accurate positioning requires a correction for this lag. Time lags between the magnetometers , fluxgate magnetometer , and GPS signals were measured by...between magnetometers and fluxgate ); An initial check flight after installation. Under the category of data QA/QC: An extensive test flight to
The nonlinear instability in flap-lag of rotor blades in forward flight
NASA Technical Reports Server (NTRS)
Tong, P.
1971-01-01
The nonlinear flap-lag coupled oscillation of torsionally rigid rotor blades in forward flight is examined using a set of consistently derived equations by the asymptotic expansion procedure of multiple time scales. The regions of stability and limit cycle oscillation are presented. The roles of parametric excitation, nonlinear oscillation, and forced excitation played in the response of the blade are determined.
Effects of air pollution on respiratory hospital admissions in İstanbul, Turkey, 2013 to 2015.
Çapraz, Özkan; Deniz, Ali; Doğan, Nida
2017-08-01
We examined the associations between the daily variations of air pollutants and hospital admissions for respiratory diseases in İstanbul, the largest city of Turkey. A time series analysis of counts of daily hospital admissions and outdoor air pollutants was performed using single-pollutant Poisson generalized linear model (GLM) while controlling for time trends and meteorological factors over a 3-year period (2013-2015) at different time lags (0-9 days). Effects of the pollutants (Excess Risk, ER) on current-day (lag 0) hospital admissions to the first ten days (lag 9) were determined. Data on hospital admissions, daily mean concentrations of air pollutants of PM 10 , PM 2.5 and NO 2 and daily mean concentrations of temperature and humidity of İstanbul were used in the study. The analysis was conducted among people of all ages, but also focused on different sexes and different age groups including children (0-14 years), adults (35-44 years) and elderly (≥65 years). We found significant associations between air pollution and respiratory related hospital admissions in the city. Our findings showed that the relative magnitude of risks for an association of the pollutants with the total respiratory hospital admissions was in the order of: PM 2.5 , NO 2 , and PM 10 . The highest association of each pollutant with total hospital admission was observed with PM 2.5 at lag 4 (ER = 1.50; 95% CI = 1.09-1.99), NO 2 at lag 4 (ER = 1.27; 95% CI = 1.02-1.53) and PM 10 at lag 0 (ER = 0.61; 95% CI = 0.33-0.89) for an increase of 10 μg/m3 in concentrations of the pollutants. In conclusion, our study showed that short-term exposure to air pollution was positively associated with increased respiratory hospital admissions in İstanbul during 2013-2015. As the first air pollution hospital admission study using GLM in İstanbul, these findings may have implications for local environmental and social policies. Copyright © 2017 Elsevier Ltd. All rights reserved.
Temporal performance of amorphous selenium mammography detectors
DOE Office of Scientific and Technical Information (OSTI.GOV)
Zhao Bo; Zhao Wei
2005-01-01
We investigated temporal performance of amorphous selenium (a-Se) detectors specifically designed for mammographic imaging. Our goal is to quantify the inherent lag and ghosting of a-Se photoconductor as a function of imaging conditions. Two small area electroded a-Se samples, one positively and the other negatively biased on the entrance side of x rays, were used in the experiments. The study of lag and ghosting was performed by delivering a number of raw exposures as experienced in screening mammography to the samples at different electric field strength E{sub Se} while measuring the current through the a-Se sample. Ghosting at different operationalmore » conditions was quantified as the percentage x-ray sensitivity (x-ray generated photocurrent measured from the sample) reduction compared to before irradiation. Lag was determined by measuring the residual current of a-Se at a given time after the end of each x-ray exposure. Both lag and ghosting were measured as a function of E{sub Se} and cumulative exposure. The values of E{sub Se} used in our experiments ranged from 1 to 20 V/{mu}m. It was found that ghosting increases with exposure and decreases with E{sub Se} for both samples because of the dominant effect of recombination between trapped electrons and x-ray generated holes. Lag on the other hand has different dependence on E{sub Se} and cumulative exposure. At E{sub Se}{<=}10 V/{mu}m, the first frame lag for both samples changed slowly with cumulative exposure, with a range of 0.2%-1.7% for the positively biased sample and 0.5%-8% for the negatively biased sample. Overall the positively biased sample has better temporal performance than the negatively biased sample due to the lower density of trapped electrons. The impact of time interval between exposures on the temporal performance was also investigated. Recovery of ghosting with longer time interval was observed, which was attributed to the neutralization of trapped electrons by injected holes through dark current.« less
NASA Astrophysics Data System (ADS)
Gerdel, Katharina; Spielmann, Felix M.; Hammerle, Albin; Wohlfahrt, Georg
2016-04-01
Carbonyl sulfide (COS) is the most abundant sulfur containing trace gas present in the troposphere at concentrations of around 500 ppt. Recent interest in COS by the ecosystem-physiological community has been sparked by the fact that COS co-diffuses into plant leaves pretty much the same way as carbon dioxide (CO2) does, but in contrast to CO2, COS is not known to be emitted by plants. Thus uptake of COS by vegetation has the potential to be used as a tracer for canopy gross photosynthesis, which cannot be measured directly, however represents a key term in the global carbon cycle. Since a few years, quantum cascade laser absorption spectrometers (QCLAS) are commercially available with the precision, sensitivity and time response suitable for eddy covariance (EC) flux measurements. While there exist a handful of published reports on EC flux measurements in the recent literature, no rigorous investigation of the applicability of QCLAS for EC COS flux measurements has been carried out so far, nor have been EC processing and QA/QC steps developed for carbon dioxide and water vapor flux measurements within FLUXNET been assessed for COS. The aim of this study is to close this knowledge gap, to discuss critical steps in the post-processing chain of COS EC flux measurements and to devise best-practice guidelines for COS EC flux data processing. To this end we collected EC COS (and CO2, H2O and CO) flux measurements above a temperate mountain grassland in Austria over the vegetation period 2015 with a commercially available QCLAS. We discuss various aspects of EC data post-processing, in particular issues with the time-lag estimation between sonic anemometer and QCLAS signals and QCLAS time series detrending, as well as QA/QC, in particular flux detection limits, random flux uncertainty, the interaction of various processing steps with common EC QA/QC filters (e.g. detrending and stationarity tests), u*-filtering, etc.
NASA Astrophysics Data System (ADS)
Hwang, James Ho-Jin; Duran, Adam
2016-08-01
Most of the times pyrotechnic shock design and test requirements for space systems are provided in Shock Response Spectrum (SRS) without the input time history. Since the SRS does not describe the input or the environment, a decomposition method is used to obtain the source time history. The main objective of this paper is to develop a decomposition method producing input time histories that can satisfy the SRS requirement based on the pyrotechnic shock test data measured from a mechanical impact test apparatus. At the heart of this decomposition method is the statistical representation of the pyrotechnic shock test data measured from the MIT Lincoln Laboratory (LL) designed Universal Pyrotechnic Shock Simulator (UPSS). Each pyrotechnic shock test data measured at the interface of a test unit has been analyzed to produce the temporal peak acceleration, Root Mean Square (RMS) acceleration, and the phase lag at each band center frequency. Maximum SRS of each filtered time history has been calculated to produce a relationship between the input and the response. Two new definitions are proposed as a result. The Peak Ratio (PR) is defined as the ratio between the maximum SRS and the temporal peak acceleration at each band center frequency. The ratio between the maximum SRS and the RMS acceleration is defined as the Energy Ratio (ER) at each band center frequency. Phase lag is estimated based on the time delay between the temporal peak acceleration at each band center frequency and the peak acceleration at the lowest band center frequency. This stochastic process has been applied to more than one hundred pyrotechnic shock test data to produce probabilistic definitions of the PR, ER, and the phase lag. The SRS is decomposed at each band center frequency using damped sinusoids with the PR and the decays obtained by matching the ER of the damped sinusoids to the ER of the test data. The final step in this stochastic SRS decomposition process is the Monte Carlo (MC) simulation. The MC simulation identifies combinations of the PR and decays that can meet the SRS requirement at each band center frequency. Decomposed input time histories are produced by summing the converged damped sinusoids with the MC simulation of the phase lag distribution.
Monitoring Insulin Aggregation via Capillary Electrophoresis
Pryor, Elizabeth; Kotarek, Joseph A.; Moss, Melissa A.; Hestekin, Christa N.
2011-01-01
Early stages of insulin aggregation, which involve the transient formation of oligomeric aggregates, are an important aspect in the progression of Type II diabetes and in the quality control of pharmaceutical insulin production. This study is the first to utilize capillary electrophoresis (CE) with ultraviolet (UV) detection to monitor insulin oligomer formation at pH 8.0 and physiological ionic strength. The lag time to formation of the first detected species in the aggregation process was evaluated by UV-CE and thioflavin T (ThT) binding for salt concentrations from 100 mM to 250 mM. UV-CE had a significantly shorter (5–8 h) lag time than ThT binding (15–19 h). In addition, the lag time to detection of the first aggregated species via UV-CE was unaffected by salt concentration, while a trend toward an increased lag time with increased salt concentration was observed with ThT binding. This result indicates that solution ionic strength impacts early stages of aggregation and β-sheet aggregate formation differently. To observe whether CE may be applied for the analysis of biological samples containing low insulin concentrations, the limit of detection using UV and laser induced fluorescence (LIF) detection modes was determined. The limit of detection using LIF-CE, 48.4 pM, was lower than the physiological insulin concentration, verifying the utility of this technique for monitoring biological samples. LIF-CE was subsequently used to analyze the time course for fluorescein isothiocyanate (FITC)-labeled insulin oligomer formation. This study is the first to report that the FITC label prevented incorporation of insulin into oligomers, cautioning against the use of this fluorescent label as a tag for following early stages of insulin aggregation. PMID:22272138
NASA Astrophysics Data System (ADS)
Ghosh, Arindam; Chakrabarti, Sandip K.
2018-05-01
We study several Galactic black hole candidates using long-time RXTE/ASM X-ray data to search for telltale signatures of differences in viscous timescales in the two components used in the Two-Component Advective Flow (TCAF) paradigm. In high-mass X-ray binaries (HMXBs) mainly winds are accreted. This nearly inviscid and dominant sub-Keplerian flow falls almost freely towards the black hole. A standard Keplerian disc can form out of this sub-Keplerian matter in presence of a significant viscosity and could be small in size. However, in low-mass X-ray binaries (LMXBs), highly viscous and larger Keplerian accretion disc is expected to form inside the sub-Keplerian disc due to the Roche-lobe overflow. Due to two viscous timescales in these two components, it is expected to have a larger lag between the times-of-arrival of these components in LMXBs than that in HMXBs. Direct cross-correlation between the photon fluxes will not reveal this lag since they lack linear dependence; however, they are coupled through the viscous processes which bring in both matter. To quantify the aforesaid time lag, we introduce an index (Θ), which is a proxy of the usual photon index (Γ). Thus, when Θ, being dynamically responsive to both fluxes, is considered as a reference, the arrival time lag between the two fluxes in LMXBs is found to be much larger than that in HMXBs. Our result establishes the presence of two dynamical components in accretion and shows that the Keplerian disc size indeed is smaller in HMXBs as compared to that in LMXBs.
Kong, Lin; Yang, Jia-xiang; Li, Sheng-li; Zhang, Qiong; Xue, Zhao-ming; Zhou, Hong-ping; Wu, Jie-ying; Jin, Bao-kang; Tian, Yu-peng
2013-12-02
A fluorophore-phenylamine derivative (L) has been coupled with silver nanocrystals (NCs) to construct an L-Ag nanohybrid. Owing to synergic effects of the L and Ag components, the exciton-plasmon interactions between L and Ag increase the strength of the donor-acceptor interaction within the nanohybrid, a fact that results in an energy-transfer process and further brings about a dramatic redshift of single-photon absorption and fluorescence, and a decreased fluorescence FL lifetime. The coupling effect also leads to enhancement of a series of nonlinear optical properties, including two-photon-excited fluorescence (TPEF), two-photon-absorption (TPA) cross section (δ), two-photon-absorption coefficient (β), nonlinear refractive index (γ), and third order nonlinear optical susceptibility (χ((3))). The enhanced two-photon fluorescence of the nanohybrid is proven to be potentially useful for two-photon microscopy of live cells, such as HepG2. Moreover, cytotoxicity tests show that the low-micromolar concentrations of the nanohybrid do not cause significant reduction in cell viability over a period of at least 24 h and should be safe for further biological studies. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Distinctive time-lagged resting-state networks revealed by simultaneous EEG-fMRI.
Feige, Bernd; Spiegelhalder, Kai; Kiemen, Andrea; Bosch, Oliver G; Tebartz van Elst, Ludger; Hennig, Jürgen; Seifritz, Erich; Riemann, Dieter
2017-01-15
Functional activation as evidenced by blood oxygen level-dependent (BOLD) functional MRI changes or event-related EEG is known to closely follow patterns of stimulation or self-paced action. Any lags are compatible with axonal conduction velocities and neural integration times. The important analysis of resting state networks is generally based on the assumption that these principles also hold for spontaneous fluctuations in brain activity. Previous observations using simultaneous EEG and fMRI indicate that slower processes, with delays in the seconds range, determine at least part of the relationship between spontaneous EEG and fMRI. To assess this relationship systematically, we used deconvolution analysis of EEG-fMRI during the resting state, assessing the relationship between EEG frequency bands and fMRI BOLD across the whole brain while allowing for time lags of up to 10.5s. Cluster analysis, identifying similar BOLD time courses in relation to EEG band power peaks, showed a clear segregation of functional subsystems of the brain. Our analysis shows that fMRI BOLD increases commonly precede EEG power increases by seconds. Most zero-lag correlations, on the other hand, were negative. This indicates two main distinct neuromodulatory mechanisms: an "idling" mechanism of simultaneous electric and metabolic network anticorrelation and a "regulatory" mechanism in which metabolic network activity precedes increased EEG power by some seconds. This has to be taken into consideration in further studies which address the causal and functional relationship of metabolic and electric brain activity patterns. Copyright © 2016 Elsevier Inc. All rights reserved.
Effect of climatic variability on malaria trends in Baringo County, Kenya.
Kipruto, Edwin K; Ochieng, Alfred O; Anyona, Douglas N; Mbalanya, Macrae; Mutua, Edna N; Onguru, Daniel; Nyamongo, Isaac K; Estambale, Benson B A
2017-05-25
Malaria transmission in arid and semi-arid regions of Kenya such as Baringo County, is seasonal and often influenced by climatic factors. Unravelling the relationship between climate variables and malaria transmission dynamics is therefore instrumental in developing effective malaria control strategies. The main aim of this study was to describe the effects of variability of rainfall, maximum temperature and vegetation indices on seasonal trends of malaria in selected health facilities within Baringo County, Kenya. Climate variables sourced from the International Research Institute (IRI)/Lamont-Doherty Earth Observatory (LDEO) climate database and malaria cases reported in 10 health facilities spread across four ecological zones (riverine, lowland, mid-altitude and highland) between 2004 and 2014 were subjected to a time series analysis. A negative binomial regression model with lagged climate variables was used to model long-term monthly malaria cases. The seasonal Mann-Kendall trend test was then used to detect overall monotonic trends in malaria cases. Malaria cases increased significantly in the highland and midland zones over the study period. Changes in malaria prevalence corresponded to variations in rainfall and maximum temperature. Rainfall at a time lag of 2 months resulted in an increase in malaria transmission across the four zones while an increase in temperature at time lags of 0 and 1 month resulted in an increase in malaria cases in the riverine and highland zones, respectively. Given the existence of a time lag between climatic variables more so rainfall and peak malaria transmission, appropriate control measures can be initiated at the onset of short and after long rains seasons.
A forward bias method for lag correction of an a-Si flat panel detector
DOE Office of Scientific and Technical Information (OSTI.GOV)
Starman, Jared; Tognina, Carlo; Partain, Larry
2012-01-15
Purpose: Digital a-Si flat panel (FP) x-ray detectors can exhibit detector lag, or residual signal, of several percent that can cause ghosting in projection images or severe shading artifacts, known as the radar artifact, in cone-beam computed tomography (CBCT) reconstructions. A major contributor to detector lag is believed to be defect states, or traps, in the a-Si layer of the FP. Software methods to characterize and correct for the detector lag exist, but they may make assumptions such as system linearity and time invariance, which may not be true. The purpose of this work is to investigate a new hardwaremore » based method to reduce lag in an a-Si FP and to evaluate its effectiveness at removing shading artifacts in CBCT reconstructions. The feasibility of a novel, partially hardware based solution is also examined. Methods: The proposed hardware solution for lag reduction requires only a minor change to the FP. For pulsed irradiation, the proposed method inserts a new operation step between the readout and data collection stages. During this new stage the photodiode is operated in a forward bias mode, which fills the defect states with charge. A Varian 4030CB panel was modified to allow for operation in the forward bias mode. The contrast of residual lag ghosts was measured for lag frames 2 and 100 after irradiation ceased for standard and forward bias modes. Detector step response, lag, SNR, modulation transfer function (MTF), and detective quantum efficiency (DQE) measurements were made with standard and forward bias firmware. CBCT data of pelvic and head phantoms were also collected. Results: Overall, the 2nd and 100th detector lag frame residual signals were reduced 70%-88% using the new method. SNR, MTF, and DQE measurements show a small decrease in collected signal and a small increase in noise. The forward bias hardware successfully reduced the radar artifact in the CBCT reconstruction of the pelvic and head phantoms by 48%-81%. Conclusions: Overall, the forward bias method has been found to greatly reduce detector lag ghosts in projection data and the radar artifact in CBCT reconstructions. The method is limited to improvements of the a-Si photodiode response only. A future hybrid mode may overcome any limitations of this method.« less
A Survey of Nanoflare Properties in Solar Active Regions
NASA Astrophysics Data System (ADS)
Viall, N. M.; Klimchuk, J. A.
2013-12-01
We investigate coronal heating using a systematic technique to analyze the properties of nanoflares in active regions (AR). Our technique computes cooling times, or time-lags, on a pixel-by-pixel basis using data taken with the Atmospheric Imaging Assembly onboard the Solar Dynamics Observatory. Our technique has the advantage that it allows us to analyze all of the coronal AR emission, including the so-called diffuse emission. We recently presented results using this time-lag analysis on NOAA AR 11082 (Viall & Klimchuk 2012) and found that the majority of the pixels contained cooling plasma along their line of sight, consistent with impulsive coronal nanoflare heating. Additionally, our results showed that the nanoflare energy is stronger in the AR core and weaker in the active region periphery. Are these results representative of the nanoflare properties exhibited in the majority of ARs, or is AR 11082 unique? Here we present the time-lag results for a survey of ARs and show that these nanoflare patterns are born out in other active regions, for a range of ages, magnetic complexity, and total unsigned magnetic flux. Other aspects of the nanoflare properties, however, turn out to be dependent on certain AR characteristics.
Wang, Wen-Jie; Cui, Song; Liu, Wei; Zu, Yuan-Gang; Sun, Wei; Wang, Hui-Min
2008-10-01
Based on a 3-year (2003-2005) observation of soil heat flux (SHF) in a larch (Larix gmelinii) plantation, the characteristics of soil heat conduction in the plantation and their relationships with environment factors were analyzed. The results showed that there was an obvious seasonal variation of SHF in different years and sampling sites. The SHF was positive from April to August and mostly negative from September to next March, with an almost balance between heat income and outcome at annual scale. Solar net radiation had significant effects on the SHF and soil heat conductance (k), and an obvious time-lag effect was found, with 4-5 hours' time-lag in winter and 2-3 hours' time-lag in summer. Based on the real-time measurement of SHF and soil temperature difference at the study sites, the k value was significantly higher in early spring (P < 0.05), but no significant difference was observed in other seasons (P > 0.05). Therefore, when we use the observation data of soil temperature from weather stations to estimate soil heat flux, the k value in spring (from March to May) could induce a bias estimation.
Reverberation Mapping of AGN Accretion Disks
NASA Astrophysics Data System (ADS)
Fausnaugh, Michael; AGN STORM Collaboration
2017-01-01
I will discuss new reverberation mapping results that allow us to investigate the temperature structure of AGN accretion disks. By measuring time-delays between broad-band continuum light curves, we can determine the size of the disk as a function of wavelength. I will discuss the detection of continuum lags in NGC 5548 reported by the AGN STORM project and implications for the accretion disk. I will also present evidence for continuum lags in two other AGN for which we recently measured black hole masses from continuum-Hbeta reverberations. The mass measurements allow us to compare the continuum lags to predictions from standard thin disk theory, and our results indicate that the accretion disks are larger than the simplest expectations.
Quasar Accretion Disk Sizes With Continuum Reverberation Mapping From the Dark Energy Survey
DOE Office of Scientific and Technical Information (OSTI.GOV)
Mudd, D.; et al.
We present accretion disk size measurements for 15 luminous quasars atmore » $$0.7 \\leq z \\leq 1.9$$ derived from $griz$ light curves from the Dark Energy Survey. We measure the disk sizes with continuum reverberation mapping using two methods, both of which are derived from the expectation that accretion disks have a radial temperature gradient and the continuum emission at a given radius is well-described by a single blackbody. In the first method we measure the relative lags between the multiband light curves, which provides the relative time lag between shorter and longer wavelength variations. The second method fits the model parameters for the canonical Shakura-Sunyaev thin disk directly rather than solving for the individual time lags between the light curves. Our measurements demonstrate good agreement with the sizes predicted by this model for accretion rates between 0.3-1 times the Eddington rate. These results are also in reasonable agreement with disk size measurements from gravitational microlensing studies of strongly lensed quasars, as well as other photometric reverberation mapping results.« less
Large plasma-membrane depolarization precedes rapid blue-light-induced growth inhibition in cucumber
NASA Technical Reports Server (NTRS)
Spalding, E. P.; Cosgrove, D. J.
1989-01-01
Blue-light (BL)-induced suppression of elongation of etiolated Cucumis sativus L. hypocotyls began after a 30-s lag time, which was halved by increasing the fluence rate from 10 to 100 micromoles m-2 s-1. Prior to the growth suppression, the plasma-membrane of the irradiated cells depolarized by as much as 100 mV, then returned within 2-3 min to near its initial value. The potential difference measured with surface electrodes changed with an identical time course but opposite polarity. The lag time for the change in surface potential showed an inverse dependence on fluence rate, similar to the lag for the growth inhibition. Green light and red light caused neither the electrical response nor the rapid inhibition of growth. The depolarization by BL did not propagate to nonirradiated regions and exhibited a refractory period of about 10 min following a BL pulse. Fluence-response relationships for the electrical and growth responses provide correlational evidence that the plasma-membrane depolarization reflects an event in the transduction chain of this light-growth response.
NASA Astrophysics Data System (ADS)
Bolea, J.; Almeida, R.; Pueyo, E.; Laguna, P.; Caiani, E. G.
2013-02-01
Microgravity exposure for long periods of time leads to body deconditioning and it increases the risk of experiencing life-threatening arrhythmias. The study of ventricular repolarization dependence on heart rate has been used to stratify patients according to their arrhythmic risk. The QTp adaptation to HR changes is characterized by M90 (90% of the adaptation). The QTp=HR , after compensation for the adaptation lag, is modeled using a set of regression functions (a , kind of slope of relationship). Subjects with lower orthostatic tolerance time showed a non significant decrease in the adaptation lag (M90 from 148 to 108 beats), which may be due to an extra deconditioning in the sympathovagal response. Nevertheless an increase in the QTp=HR adaptation lag (M90 from 108 to 117 beats with a p = 0.06) and a significant reduction in the slope (a from 0.53 to 0.35 with a p < 0.005), which in previous studies have been correlated with an increased arrhytimic risk, were observed for subjects with higher orthostatic tolerance time.
Matias, Fernanda S.; Carelli, Pedro V.; Mirasso, Claudio R.; Copelli, Mauro
2015-01-01
Several cognitive tasks related to learning and memory exhibit synchronization of macroscopic cortical areas together with synaptic plasticity at neuronal level. Therefore, there is a growing effort among computational neuroscientists to understand the underlying mechanisms relating synchrony and plasticity in the brain. Here we numerically study the interplay between spike-timing dependent plasticity (STDP) and anticipated synchronization (AS). AS emerges when a dominant flux of information from one area to another is accompanied by a negative time lag (or phase). This means that the receiver region pulses before the sender does. In this paper we study the interplay between different synchronization regimes and STDP at the level of three-neuron microcircuits as well as cortical populations. We show that STDP can promote auto-organized zero-lag synchronization in unidirectionally coupled neuronal populations. We also find synchronization regimes with negative phase difference (AS) that are stable against plasticity. Finally, we show that the interplay between negative phase difference and STDP provides limited synaptic weight distribution without the need of imposing artificial boundaries. PMID:26474165
Influence of Permeant Lipophilicity on Permeation Across Human Sclera
Wen, He; Li, S. Kevin
2010-01-01
Purpose The objectives of this study were to determine the effects of permeant lipophilicity on permeant uptake into and transport across human sclera for transscleral delivery. Methods Model permeants with a wide range of lipophilicities were selected and studied with human sclera. Uptake experiments were carried out to measure permeant partitioning into the sclera. Transport experiments were performed in side-by-side diffusion cells, and the permeability coefficients and transport lag times of the permeants across the sclera were evaluated. Results Permeants with higher lipophilicity showed higher partition coefficients to human sclera, and the apparent transport lag time also increased significantly as the permeant lipophilicity increased. No correlation between the permeability coefficients and lipophilicity of the model permeants was observed in this study with human sclera. A hypothesis on the different findings between the present and previous studies was proposed. Conclusions Permeants with higher lipophilicity exhibited stronger binding to human sclera and would therefore lead to larger permeant partitioning to the sclera and longer transport lag time. The steady-state permeability coefficients of the permeants were not significantly affected by permeant lipophilicity. PMID:20734114
Neophytou, Andreas M; Picciotto, Sally; Brown, Daniel M; Gallagher, Lisa E; Checkoway, Harvey; Eisen, Ellen A; Costello, Sadie
2018-02-13
Prolonged exposures can have complex relationships with health outcomes, as timing, duration, and intensity of exposure are all potentially relevant. Summary measures such as cumulative exposure or average intensity of exposure may not fully capture these relationships. We applied penalized and unpenalized distributed lag non-linear models (DLNMs) with flexible exposure-response and lag-response functions in order to examine the association between crystalline silica exposure and mortality from lung cancer and non-malignant respiratory disease in a cohort study of 2,342 California diatomaceous earth workers, followed 1942-2011. We also assessed associations using simple measures of cumulative exposure assuming linear exposure-response and constant lag-response. Measures of association from DLNMs were generally higher than from simpler models. Rate ratios from penalized DLNMs corresponding to average daily exposures of 0.4 mg/m3 during lag years 31-50 prior to the age of observed cases were 1.47 (95% confidence interval (CI) 0.92, 2.35) for lung cancer and 1.80 (95% CI: 1.14, 2.85) for non-malignant respiratory disease. Rate ratios from the simpler models for the same exposure scenario were 1.15 (95% CI: 0.89-1.48) and 1.23 (95% CI: 1.03-1.46) respectively. Longitudinal cohort studies of prolonged exposures and chronic health outcomes should explore methods allowing for flexibility and non-linearities in the exposure-lag-response. © The Author(s) 2018. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.
The drug lag: an interpretive review of the literature.
Schifrin, L G; Tayan, J R
1977-01-01
This articel reviews the literature pertinent to the "drug lag" issue, in order to evaluate the evidence underlying the thesis that the U.S. has suffered from a slow-down in the rate and timing of new drug introductions, to the detriment of patients, because of the stricter requirements since 1962 regarding proof of safety and efficacy for new drugs. Comparing the post-1962 record in the U.S. with (a) the U.S. record before 1962 and (b) the post-1962 record in other, mainly Western European, countries, the weight of evidence and argument falls on the side of those who see a lag existing in the U.S. Other evidence, more subjective, supports the view that this lag imposes net positive costs on U.S. patients. However, it is not clear that the 1962 Drug Act is the sole, or even the main, cause of the lag. Instead, the drug information system and its inefficiencies emerge as the fundamental reason for the existence of a lag; hence, changes in the administration of the law by the Food and Drug Administration and greater efficiency by companies in supporting New Drug Applications can help close the gap, but probably only in minor degree. The solution to the lag problem lies in formulating and implementing a drug information system that quickly and accurately gathers, interprets, and disseminates information on the positive and negative effects of newly introduced drugs; with such a system, protection of drug users from undue risk is compatible with a greater rate and more rapid appearance of new drug discoveries.
NASA Astrophysics Data System (ADS)
Kori, Hiroshi; Yamaguchi, Yoshiaki; Okamura, Hitoshi
2017-04-01
The endogenous circadian clock drives oscillations that are completely synchronized with the environmental day-night rhythms with a period of approximately 24 hours. Temporal misalignment between one’s internal circadian clock and the external solar time often occurs in shift workers and long-distance travelers; such misalignments are accompanied by sleep disturbances and gastrointestinal distress. Repeated exposure to jet lag and rotating shift work increases the risk of lifestyle-related diseases, such as cardiovascular complaints and metabolic insufficiencies. However, the mechanism behind the disruption of one’s internal clock is not well understood. In this paper, we therefore present a new theoretical concept called “jet lag separatrix” to understand circadian clock disruption and slow recovery from jet lag based on the mathematical model describing the hierarchical structure of the circadian clock. To demonstrate the utility of our theoretical study, we applied it to predict that re-entrainment via a two-step jet lag in which a four-hour shift of the light-dark cycle is given in the span of two successive days requires fewer days than when given as a single eight-hour shift. We experimentally verified the feasibility of our theory in C57BL/6 strain mice, with results indicating that this pre-exposure of jet lag is indeed beneficial.
Development and evaluation of a prototype tracking system using the treatment couch
DOE Office of Scientific and Technical Information (OSTI.GOV)
Lang, Stephanie, E-mail: stephanie.lang@usz.ch; Riesterer, Oliver; Klöck, Stephan
2014-02-15
Purpose: Tumor motion increases safety margins around the clinical target volume and leads to an increased dose to the surrounding healthy tissue. The authors have developed and evaluated a one-dimensional treatment couch tracking system to counter steer respiratory tumor motion. Three different motion detection sensors with different lag times were evaluated. Methods: The couch tracking system consists of a motion detection sensor, which can be the topometrical system Topos (Cyber Technologies, Germany), the respiratory gating system RPM (Varian Medical Systems) or a laser triangulation system (Micro Epsilon), and the Protura treatment couch (Civco Medical Systems). The control of the treatmentmore » couch was implemented in the block diagram environment Simulink (MathWorks). To achieve real time performance, the Simulink models were executed on a real time engine, provided by Real-Time Windows Target (MathWorks). A proportional-integral control system was implemented. The lag time of the couch tracking system using the three different motion detection sensors was measured. The geometrical accuracy of the system was evaluated by measuring the mean absolute deviation from the reference (static position) during motion tracking. This deviation was compared to the mean absolute deviation without tracking and a reduction factor was defined. A hexapod system was moving according to seven respiration patterns previously acquired with the RPM system as well as according to a sin{sup 6} function with two different frequencies (0.33 and 0.17 Hz) and the treatment table compensated the motion. Results: A prototype system for treatment couch tracking of respiratory motion was developed. The laser based tracking system with a small lag time of 57 ms reduced the residual motion by a factor of 11.9 ± 5.5 (mean value ± standard deviation). An increase in delay time from 57 to 130 ms (RPM based system) resulted in a reduction by a factor of 4.7 ± 2.6. The Topos based tracking system with the largest lag time of 300 ms achieved a mean reduction by a factor of 3.4 ± 2.3. The increase in the penumbra of a profile (1 × 1 cm{sup 2}) for a motion of 6 mm was 1.4 mm. With tracking applied there was no increase in the penumbra. Conclusions: Couch tracking with the Protura treatment couch is achievable. To reliably track all possible respiration patterns without prediction filters a short lag time below 100 ms is needed. More scientific work is necessary to extend our prototype to tracking of internal motion.« less
Suárez-García, Inés; Jarrín, Inmaculada; Iribarren, José Antonio; López-Cortés, Luis Fernando; Lacruz-Rodrigo, José; Masiá, Mar; Gómez-Sirvent, Juan Luis; Hernández-Quero, José; Vidal, Francesc; Alejos-Ferreras, Belén; Moreno, Santiago; Del Amo, Julia
2013-05-01
The aim of this study was to investigate the incidence and risk factors for the development of AIDS-defining cancers (ADCs); and to investigate the effect of making different assumptions on the definition of incident cases. A multicentre cohort study was designed. Poisson regression was used to assess incidence and risk factors. To account for misclassification, incident cases were defined using lag-times of 0, 14 and 30 days after enrolment. A total of 6393 HIV-positive subjects were included in the study. The incidences of ADCs changed as the lag periods were varied from 0 to 30 days. Different risk factors emerged as the definition of incident cases was changed. For a lag time of 0, the risk of Kaposi sarcoma [KS] and non-Hodgkin lymphoma [NHL] increased at CD4 counts <200/ml. HAART was associated with lower risk of NHL and KS. Men who had sex with men had a higher risk of KS. KS and NHL were not associated with viral load, gender, or hepatitis B or C. The results were similar for a lag-time of 14 and 30 days; however, hepatitis C was significantly associated with NHL. This analysis shows the importance of the definition of incident cases in cohort studies. Alternative definitions gave different incidence estimates, and may have implications for the analysis of risk factors. Copyright © 2011 Elsevier España, S.L. All rights reserved.
Kölling, Sarah; Treff, Gunnar; Winkert, Kay; Ferrauti, Alexander; Meyer, Tim; Pfeiffer, Mark; Kellmann, Michael
2017-11-01
This study examined sleep-wake habits and subjective jet-lag ratings of 55 German junior rowers (n = 30 male, 17.8 ± 0.5 years) before and during the World Rowing Junior Championships 2015 in Rio de Janeiro, Brazil. Athletes answered sleep logs every morning, and Liverpool John Moore's University Jet-Lag Questionnaires each evening and morning. Following an 11-h westward flight with 5-h time shift, advanced bedtimes (-1 h, P < .001, η p 2 = 0.68), reduced sleep onset latency (P = .002, η p 2 = 0.53) and increased sleep duration (P < .001, η p 2 = 0.60) were reported for the first two nights. Jet-lag symptoms peaked upon arrival but were still present after 6 days. Sleep quality improved (P < .001, η p 2 = 0.31) as well as some scales of the Recovery-Stress Questionnaire for Athletes. Participation was successful as indicated by 11 of 13 top 3 placings. Overall, the initial desynchronisation did not indicate negative impacts on competition performance. As travel fatigue probably had a major effect on perceptual decrements, sleep during travel and time to recover upon arrival should be emphasised. Coaches and practitioners should consider higher sleep propensity in the early evening by scheduling training sessions and meetings until the late afternoon.
PHAGE FORMATION IN STAPHYLOCOCCUS MUSCAE CULTURES
Price, Winston H.
1949-01-01
1. The total nucleic acid synthesized by normal and by infected S. muscae suspensions is approximately the same. This is true for either lag phase cells or log phase cells. 2. The amount of nucleic acid synthesized per cell in normal cultures increases during the lag period and remains fairly constant during log growth. 3. The amount of nucleic acid synthesized per cell by infected cells increases during the whole course of the infection. 4. Infected cells synthesize less RNA and more DNA than normal cells. The ratio of RNA/DNA is larger in lag phase cells than in log phase cells. 5. Normal cells release neither ribonucleic acid nor desoxyribonucleic acid into the medium. 6. Infected cells release both ribonucleic acid and desoxyribonucleic acid into the medium. The time and extent of release depend upon the physiological state of the cells. 7. Infected lag phase cells may or may not show an increased RNA content. They release RNA, but not DNA, into the medium well before observable cellular lysis and before any virus is liberated. At virus liberation, the cell RNA content falls to a value below that initially present, while DNA, which increased during infection falls to approximately the original value. 8. Infected log cells show a continuous loss of cell RNA and a loss of DNA a short time after infection. At the time of virus liberation the cell RNA value is well below that initially present and the cells begin to lyse. PMID:18139006
Simultaneous Monitoring of X-Ray and Radio Variability in Sagittarius A*
NASA Astrophysics Data System (ADS)
Capellupo, Daniel M.; Haggard, Daryl; Choux, Nicolas; Baganoff, Fred; Bower, Geoffrey C.; Cotton, Bill; Degenaar, Nathalie; Dexter, Jason; Falcke, Heino; Fragile, P. Chris; Heinke, Craig O.; Law, Casey J.; Markoff, Sera; Neilsen, Joey; Ponti, Gabriele; Rea, Nanda; Yusef-Zadeh, Farhad
2017-08-01
Monitoring of Sagittarius A* from X-ray to radio wavelengths has revealed structured variability—including X-ray flares—but it is challenging to establish correlations between them. Most studies have focused on variability in the X-ray and infrared, where variations are often simultaneous, and because long time series at submillimeter and radio wavelengths are limited. Previous work on submillimeter and radio variability hints at a lag between X-ray flares and their candidate submillimeter or radio counterparts, with the long wavelength data lagging the X-ray. However, there is only one published time lag between an X-ray flare and a possible radio counterpart. Here we report nine contemporaneous X-ray and radio observations of Sgr A*. We detect significant radio variability peaking ≳ 176 minutes after the brightest X-ray flare ever detected from Sgr A*. We also report other potentially associated X-ray and radio variability, with the radio peaks appearing ≲ 80 minutes after these weaker X-ray flares. Taken at face value, these results suggest that stronger X-ray flares lead to longer time lags in the radio. However, we also test the possibility that the variability at X-ray and radio wavelengths is not temporally correlated. We cross-correlate data from mismatched X-ray and radio epochs and obtain comparable correlations to the matched data. Hence, we find no overall statistical evidence that X-ray flares and radio variability are correlated, underscoring a need for more simultaneous, long duration X-ray-radio monitoring of Sgr A*.
Evaluation of a nationally funded state-based programme to reduce fatal occupational injuries
Menendez, Cammie Chaumont; Castillo, Dawn; Rosenman, Kenneth; Harrison, Robert; Hendricks, Scott
2015-01-01
Background The Fatality Assessment and Control Evaluation (FACE) programme was established by the National Institute for Occupational Safety and Health to help prevent occupational traumatic fatalities by funding states to conduct targeted fatality investigations within cause-specific focus areas and associated prevention efforts. Purpose To investigate the impact of the state-based FACE programme on two previous focus areas. Methods A longitudinal time-series analysis spanning 22 years compared state fatality rates for occupational falls and electrocutions before and after FACE programme funding with states not receiving FACE programme funding. Lag periods were utilised to allow time for the programme to have an effect, and rates were adjusted for a variety of covariates. Separate analyses were conducted for each injury outcome. Results A reduction in fall fatality rates that was of borderline significance (1-year lag adjRR=0.92 (0.84 to 1.00)) and a non-significant reduction in electrocution fatality rates (3-year lag adjRR=0.92 (0.82 to 1.03)) were observed in states with FACE programme funding, Best-fit models presented two separate lag periods. Conclusions While it is challenging to quantitatively evaluate effectiveness of programmes such as FACE, the data suggest the FACE programme may be effective in preventing occupational injury deaths within its outcome focus areas throughout the state. It is important to look for ways to measure intermediate effects more precisely, as well as ways to maintain effects over time. PMID:22864251
Díaz, Julio; Martínez-Martín, Pablo; Rodríguez-Blázquez, Carmen; Vázquez, Blanca; Forjaz, Maria João; Ortiz, Cristina; Carmona, Rocío; Linares, Cristina
2017-03-23
To analyse whether there is a short-term association between road traffic noise in the city of Madrid and Parkinson's disease (PD)-related demand for healthcare. Time-series analysis (2008-2009) using variables of analysis linked to emergency and daily PD-related demand for healthcare (ICD-10: G20-G21), namely, PD-hospital admissions (HAs), PD-outpatient visits (OVs) and PD-emergency medical calls in Madrid. The noise pollution measurements used were Leqd, equivalent sound level for the daytime hours (from 8 a.m. to 10 p.m.), and Leqn, equivalent sound level for night time hours (from 10 p.m. to 8 a.m.) in dB(A). We controlled for temperature, pollution, trends and seasons, and used the Poisson regression model to calculate relative risk (RR). The association between Leqd and HAs was found to be linear. Leqd and Leqn at lag 0.1 and temperature at lags 1 and 5 were the only environmental variables associated with increased PD-related healthcare demand. The RR (lag 0) for Leqd and HA was 1.07 (1.04-1.09), the RR (lag 0) for Leqd and OV was 1.28 (1.12-1.45), and the RR (lags 0.1) for Leqn and emergency medical calls was 1.46 (1.06-2.01). The above results indicate that road traffic noise is a risk factor for PD exacerbation. Measures to reduce noise-exposure levels could result in a lower PD-related healthcare demand. Copyright © 2017 SESPAS. Publicado por Elsevier España, S.L.U. All rights reserved.
Chin, Wei-Chien-Benny; Wen, Tzai-Hung; Sabel, Clive E; Wang, I-Hsiang
2017-10-03
A diffusion process can be considered as the movement of linked events through space and time. Therefore, space-time locations of events are key to identify any diffusion process. However, previous clustering analysis methods have focused only on space-time proximity characteristics, neglecting the temporal lag of the movement of events. We argue that the temporal lag between events is a key to understand the process of diffusion movement. Using the temporal lag could help to clarify the types of close relationships. This study aims to develop a data exploration algorithm, namely the TrAcking Progression In Time And Space (TaPiTaS) algorithm, for understanding diffusion processes. Based on the spatial distance and temporal interval between cases, TaPiTaS detects sub-clusters, a group of events that have high probability of having common sources, identifies progression links, the relationships between sub-clusters, and tracks progression chains, the connected components of sub-clusters. Dengue Fever cases data was used as an illustrative case study. The location and temporal range of sub-clusters are presented, along with the progression links. TaPiTaS algorithm contributes a more detailed and in-depth understanding of the development of progression chains, namely the geographic diffusion process.
Pashaei, S; Ghoorchi, T; Yamchi, A
2016-04-01
An experiment was conducted to study disappearance of C14 to C18 fatty acids, lag times and biohydrogenation (BH) rates of C18 fatty acids of ground soya bean and canola seeds in situ. Three ruminally fistulated Dallagh sheep were used to determine ruminal BH of unsaturated fatty acids (UFAs). Differences in the disappearance of fatty acids through the bags and lag times were observed between the oilseeds. We saw that the longer the incubation time of the oilseeds in the rumen, the lower the content of C18:2 and C18:3. Significantly higher lag times for both C18:2 and C18:3 were observed in ground canola compared to ground soya bean. BH rates of C18:2 and C18:3 fatty acids in soya bean were three times higher than those of canola. These results suggest that the fatty acid profile of fat source can affect the BH of UFAs by rumen micro-organisms. So that UFAs of canola had higher ability to escape from ruminal BH. It seems that fatty acid profile of ruminant products is more affected by canola seed compared to soya bean seed. Journal of Animal Physiology and Animal Nutrition © 2015 Blackwell Verlag GmbH.
Goldsmith, K A; Chalder, T; White, P D; Sharpe, M; Pickles, A
2018-06-01
Clinical trials are expensive and time-consuming and so should also be used to study how treatments work, allowing for the evaluation of theoretical treatment models and refinement and improvement of treatments. These treatment processes can be studied using mediation analysis. Randomised treatment makes some of the assumptions of mediation models plausible, but the mediator-outcome relationship could remain subject to bias. In addition, mediation is assumed to be a temporally ordered longitudinal process, but estimation in most mediation studies to date has been cross-sectional and unable to explore this assumption. This study used longitudinal structural equation modelling of mediator and outcome measurements from the PACE trial of rehabilitative treatments for chronic fatigue syndrome (ISRCTN 54285094) to address these issues. In particular, autoregressive and simplex models were used to study measurement error in the mediator, different time lags in the mediator-outcome relationship, unmeasured confounding of the mediator and outcome, and the assumption of a constant mediator-outcome relationship over time. Results showed that allowing for measurement error and unmeasured confounding were important. Contemporaneous rather than lagged mediator-outcome effects were more consistent with the data, possibly due to the wide spacing of measurements. Assuming a constant mediator-outcome relationship over time increased precision.
Goldsmith, KA; Chalder, T; White, PD; Sharpe, M; Pickles, A
2016-01-01
Clinical trials are expensive and time-consuming and so should also be used to study how treatments work, allowing for the evaluation of theoretical treatment models and refinement and improvement of treatments. These treatment processes can be studied using mediation analysis. Randomised treatment makes some of the assumptions of mediation models plausible, but the mediator–outcome relationship could remain subject to bias. In addition, mediation is assumed to be a temporally ordered longitudinal process, but estimation in most mediation studies to date has been cross-sectional and unable to explore this assumption. This study used longitudinal structural equation modelling of mediator and outcome measurements from the PACE trial of rehabilitative treatments for chronic fatigue syndrome (ISRCTN 54285094) to address these issues. In particular, autoregressive and simplex models were used to study measurement error in the mediator, different time lags in the mediator–outcome relationship, unmeasured confounding of the mediator and outcome, and the assumption of a constant mediator–outcome relationship over time. Results showed that allowing for measurement error and unmeasured confounding were important. Contemporaneous rather than lagged mediator–outcome effects were more consistent with the data, possibly due to the wide spacing of measurements. Assuming a constant mediator–outcome relationship over time increased precision. PMID:27647810
NASA Technical Reports Server (NTRS)
Wardwell, Douglas A.; Corsiglia, Victor R.; Kuhn, Richard E.
1992-01-01
NASA Ames Research Center has been conducting a program to improve the methods for predicting the jet-induced lift loss (suckdown) and hot gas ingestion on jet Short Takeoff and Vertical Landing (STOVL) aircraft during hover near the ground. As part of that program, small-scale hover tests were conducted to expand the current data base and to improve upon the current empirical methods for predicting jet-induced lift loss and hot gas ingestion (HGI) effects. This report is one of three data reports covering data obtained from hover tests conducted at Lockheed Aeronautical Systems, Rye Canyon Facility. It will include dynamic (time dependent) test data for both lift loss and HGI parameters (height, nozzle temperature, nozzle pressure ratio, and inlet location). The flat plate models tested were tandem jet configurations with three planform variations and variable position side-by-side sucking inlets mounted above the planform. Temperature time lags from 8-15 seconds were observed before the model temperatures stabilize. This was larger than the expected 1.5-second lag calculated from literature. Several possible explanations for the flow temperatures to stabilize may include some, or all, of the following: thermocouple lag, radiation to the model surface, and heat loss to the ground board. Further investigations are required to understand the reasons for this temperature lag.
State-dependent resource harvesting with lagged information about system states
Johnson, Fred A.; Fackler, Paul L.; Boomer, G Scott; Zimmerman, Guthrie S.; Williams, Byron K.; Nichols, James D.; Dorazio, Robert
2016-01-01
Markov decision processes (MDPs), which involve a temporal sequence of actions conditioned on the state of the managed system, are increasingly being applied in natural resource management. This study focuses on the modification of a traditional MDP to account for those cases in which an action must be chosen after a significant time lag in observing system state, but just prior to a new observation. In order to calculate an optimal decision policy under these conditions, possible actions must be conditioned on the previous observed system state and action taken. We show how to solve these problems when the state transition structure is known and when it is uncertain. Our focus is on the latter case, and we show how actions must be conditioned not only on the previous system state and action, but on the probabilities associated with alternative models of system dynamics. To demonstrate this framework, we calculated and simulated optimal, adaptive policies for MDPs with lagged states for the problem of deciding annual harvest regulations for mallards (Anas platyrhynchos) in the United States. In this particular example, changes in harvest policy induced by the use of lagged information about system state were sufficient to maintain expected management performance (e.g. population size, harvest) even in the face of an uncertain system state at the time of a decision.
Voss, Andreas; Fischer, Claudia; Schroeder, Rico; Figulla, Hans R; Goernig, Matthias
2012-07-01
The objectives of this study were to introduce a new type of heart-rate variability analysis improving risk stratification in patients with idiopathic dilated cardiomyopathy (DCM) and to provide additional information about impaired heart beat generation in these patients. Beat-to-beat intervals (BBI) of 30-min ECGs recorded from 91 DCM patients and 21 healthy subjects were analyzed applying the lagged segmented Poincaré plot analysis (LSPPA) method. LSPPA includes the Poincaré plot reconstruction with lags of 1-100, rotating the cloud of points, its normalized segmentation adapted to their standard deviations, and finally, a frequency-dependent clustering. The lags were combined into eight different clusters representing specific frequency bands within 0.012-1.153 Hz. Statistical differences between low- and high-risk DCM could be found within the clusters II-VIII (e.g., cluster IV: 0.033-0.038 Hz; p = 0.0002; sensitivity = 85.7 %; specificity = 71.4 %). The multivariate statistics led to a sensitivity of 92.9 %, specificity of 85.7 % and an area under the curve of 92.1 % discriminating these patient groups. We introduced the LSPPA method to investigate time correlations in BBI time series. We found that LSPPA contributes considerably to risk stratification in DCM and yields the highest discriminant power in the low and very low-frequency bands.
Kutsch, Miriam; Hortmann, Pascal; Herrmann, Christian; Weibels, Sebastian; Weingärtner, Hermann
2016-03-03
Diseases like Alzheimer, type II diabetes mellitus, and others go back to fibril formation of partially unfolded proteins. The impact of sodium, potassium, choline, guanidinium, and 1-ethyl-3-methylimidazolium chloride on the fibrillation kinetics of insulin in an acid-denaturing solvent environment is studied by fluorescence spectroscopy using thioflavin T as a fibril-specific stain. The fibrillation kinetics reveal a sigmoidal behavior, characterized by the lag time τlag and the maximum elongation rate k of the fibrils. Up to ionic strengths of about 70 mM, the elongation rate increases with salt concentration. This increase is nonspecific with regard to the salts. Below ionic strengths of ∼50 mM, it can be explained by a Debye-Hückel type model, indicating a dominant role of Coulomb interactions between the charged reactants and products screened by the ionic environment. At higher ionic strength, the elongation rates pass maxima, followed by a Hofmeister type ion-specific decrease. There is a correlation between the lag time τlag and the inverse elongation rate k, which can be described by a power law of the form τlag ∝ aτ(α) with a sublinear exponent α ≅ 1/2.
Xu, Y Zh; Métris, A; Stasinopoulos, D M; Forsythe, S J; Sutherland, J P
2015-02-01
The effect of heat stress and subsequent recovery temperature on the individual cellular lag of Cronobacter turicensis was analysed using optical density measurements. Low numbers of cells were obtained through serial dilution and the time to reach an optical density of 0.035 was determined. Assuming the lag of a single cell follows a shifted Gamma distribution with a fixed shape parameter, the effect of recovery temperature on the individual lag of untreated and sublethally heat treated cells of Cr. turicensis were modelled. It was found that the shift parameter (Tshift) increased asymptotically as the temperature decreased while the logarithm of the scale parameter (θ) decreased linearly with recovery temperature. To test the validity of the model in food, growth of low numbers of untreated and heat treated Cr. turicensis in artificially contaminated infant first milk was measured experimentally and compared with predictions obtained by Monte Carlo simulations. Although the model for untreated cells slightly underestimated the actual growth in first milk at low temperatures, the model for heat treated cells was in agreement with the data derived from the challenge tests and provides a basis for reliable quantitative microbiological risk assessments for Cronobacter spp. in infant milk. Copyright © 2014 Elsevier Ltd. All rights reserved.
Lag-driven motion in front propagation
NASA Astrophysics Data System (ADS)
Amor, Daniel R.; Fort, Joaquim
2013-10-01
Front propagation is a ubiquitous phenomenon. It arises in physical, biological and cross-disciplinary systems as diverse as flame propagation, superconductors, virus infections, cancer spread or transitions in human prehistory. Here we derive a single, approximate front speed from three rather different time-delayed reaction-diffusion models, suggesting a general law. According to our approximate speed, fronts are crucially driven by the lag times (periods during which individuals or particles do not move). Rather surprisingly, the approximate speed is able to explain the observed spread rates of completely different biophysical systems such as virus infections, the Neolithic transition in Europe, and postglacial tree recolonizations.