Average viral kinetics and symptom dynamics.

<p>The solid line represents influenza viral kinetics and the dashed line the systemic symptom dynamics without antiviral therapy.</p

Average oseltamivir carboxylate kinetics (red line: 75 mg, blue line: 150 mg, green: 300 mg).

<p>Panel A shows the pharmacokinetics for twice-a-day intake for 5 days and the panel B once a day intake for 10 days. The black line represents the for drug-sensitive virus and the dashed line the for resistant virus. The s were converted from to ng/mL for this figure.</p

A. Graphical presentation of the PK model of oseltamivir.

<p>Oseltamivir phosphate (OP) is absorbed at rate and converted into oseltamivir carboxylate (OC) at rate . OC is eliminated at rate . B. Graphical presentation of the viral kinetic symptom dynamic (VKSD) model with the effect of emerging resistance and oseltamivir therapy. Free virus infects target epithelial cells, which become infected cells not yet producing virus, and , which transition at rate into productively infected cells, and . These latter cells produce free virus and lead to the production of pro-inflammatory cytokines, either directly or via activation of macrophages or dendritic cells. Pro-inflammatory cytokines reduce the virus production rate, activate natural killer (NK) cells, and induce systemic symptoms. NK cells kill infected cells. Resistant virus can emerge during replication, infect target cells and induce the VKSD cycle. Oseltamivir acts by blocking the release of free viruses. is the target cell infection rate, is the transition rate from to , is the mortality rate of infected cells, is the effect of NK cells on infected cells, is the cytokine clearance, is the mortality rate of NK cells, is the rate of virus production by , is the effect of cytokines on , and is the virus clearance. , the initial number of target cells in the upper respiratory tract, was set to 4×10⁸. We set the cytokine and NK cell production rates to 1, as it changes only the units in which the early immune response is measured and does not lead to a loss of generality.</p

Median virological efficacy for different therapy initiation times and drug regimens.

<p>The inter-quartile range (IQR) is given between brackets.</p><p>* currently approved regimens.</p

Stochastic model for resistant virus.

<p> and represent the effectiveness of oseltamivir on drug-sensitive and drug-resistant virus, respectively, with and where OC is oseltamivir carboxylate concentration, is the concentration necessary to observe 50% of the maximal effect on drug-sensitive virus and is the concentration necessary to observe 50% of the maximal effect on drug-resistant virus. represents the absence of any element.</p

Oseltamivir efficacy measured in terms of virological and symptom efficacy.

<p>Each panel represents the variation of efficacy depending on the therapy initiation time relative to the time of infection. 0 indicates the time of inoculation and the grey rectangle the incubation period. Comparison of the effect of three possible doses (red: 75 mg bid for 5 days, blue: 150 mg bid 5 days, green: 300 mg bid 5 days) used to treat influenza on (A) virological efficacy and (B) symptom efficacy; Comparison of the effect on (C) virological efficacy and (D) symptom efficacy of three intake frequency (red: 75 mg bid for 5 days, purple: 75 mg qd for 5 days, turquoise: 75 mg tid for 5 days) used to treat influenza; Comparison of the effect on (E) virological efficacy and (F) symptom efficacy of three therapy durations (red: 75 mg bid for 5 days, pink: 75 mg bid for 10 days, black: 75 mg bid for 15 days) used to treat influenza.</p

Viral kinetics, model fits and projected time to cure.

<p><b>(A)</b> Time (days) to reach HCV <15 IU/ml or target not detected, TND, during therapy. At end of treatment (w24) all patients but one were TND. <b>(B)</b> Observed viral kinetics and model curves in 4 representative patients (P). Filled triangles: observed HCV viral load above the limit of quantification, LOQ (>15 IU/mL); stars, observed HCV < 15 IU/mL but still detected; crossed squares, TND (arbitrary set to 1 IU/mL); solid lines, biphasic model (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0187409#pone.0187409.e001" target="_blank">Eq 1</a>) best fit curves (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0187409#pone.0187409.s004" target="_blank">S3 Table</a> for individual parameters). HCV viral load and fit curves of the remaining subjects are shown in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0187409#pone.0187409.s009" target="_blank">S1 Fig</a>. <b>(C)</b> Predicted treatment duration (weeks) to reach cure based on a viral cure defined as <1 virus copy in entire patient extracellular fluid (~13.5L).</p

Detection of the voice fundamental frequency

This bachelor thesis deals with the detection of the pitch man. The frequency of the basic tone is one of the basic parameters of speech signal in the frequency domain. In this thesis we describe several methods for pitch detection and practical application of correlation method and cepstral analysis