Crooks' fluctuation theorem for the fluctuating lattice-Boltzmann model

We probe the validity of Crooks' fluctuation relation on the fluctuating lattice-Boltzmann model (FLBM), a highly simplified lattice model for a thermal ideal gas. We drive the system between two thermodynamic equilibrium states and compute the distribution of the work performed. By comparing the distributions of the work performed during the forward driving and time reversed driving, we show that the system satisfies Crooks' relation. The results of the numerical experiment suggest that the temperature and the free energy of the system are well defined.Comment: To be published in J. Stat. Mec

Fluctuations of 1/f1/f noise and the low frequency cutoff paradox

Recent experiments on blinking quantum dots and weak turbulence in liquid crystals reveal the fundamental connection between $1/f$ noise and power law intermittency. The non-stationarity of the process implies that the power spectrum is random -- a manifestation of weak ergodicity breaking. Here we obtain the universal distribution of the power spectrum, which can be used to identify intermittency as the source of the noise. We solve an outstanding paradox on the non integrability of $1/f$ noise and the violation of Parseval's theorem. We explain why there is no physical low frequency cutoff and therefore cannot be found in experiments.Comment: 5 pages, 2 figures, supplementary material (4 pages

Rapid intensification of an established CHO cell fed-batch process

Currently, the mammalian biomanufacturing industry explores process intensification (PI) to meet upcoming demands of biotherapeutics while keeping production flexible but, more importantly, as economic as possible. However, intensified processes often require more development time compared with conventional fed-batches (FBs) preventing their implementation. Hence, rapid and efficient, yet straightforward strategies for PI are needed. In this study we demonstrate such a strategy for the intensification of an N-stage FB by implementing N-1 perfusion cell culture and high inoculum cell densities resulting in a robust intensified FB (iFB). Furthermore, we show successful combination of such an iFB with the addition of productivity enhancers, which has not been reported so far. The conventional CHO cell FB process was step-wise improved and intensified rapidly in multi-parallel small-scale bioreactors using N-1 perfusion. The iFBs were performed in 15 and 250 ml bioreactors and allowed to evaluate the impact on key process indicators (KPI): the space–time yield (STY) was successfully doubled from 0.28 to 0.55 g/L d, while product quality was maintained. This gain was generated by initially increasing the inoculation density, thus shrinking process time, and second supplementation with butyric acid (BA), which reduced cell growth and enhanced cell-specific productivity from ~25 to 37 pg/(cell d). Potential impacts of PI on cell metabolism were evaluated using flux balance analysis. Initial metabolic differences between the standard and intensified process were observed but disappeared quickly. This shows that PI can be achieved rapidly for new as well as existing processes without introducing sustained changes in cellular and metabolic behavior.publishedVersio

1/f^beta noise in a model for weak ergodicity breaking

In systems with weak ergodicity breaking, the equivalence of time averages and ensemble averages is known to be broken. We study here the computation of the power spectrum from realizations of a specific process exhibiting 1/f^beta noise, the Rebenshtok-Barkai model. We show that even the binned power spectrum does not converge in the limit of infinite time, but that instead the resulting value is a random variable stemming from a distribution with finite variance. However, due to the strong correlations in neighboring frequency bins of the spectrum, the exponent beta can be safely estimated by time averages of this type. Analytical calculations are illustrated by numerical simulations.Comment: 10 pages, 7 figures; extended references and summary, smaller corrections; final versio

Right ventricular involvement in left ventricular non-compaction cardiomyopathy

Background: Left ventricular non-compaction cardiomyopathy (LVNC) features extensive trabeculations. Involvement of the right ventricle (RV) has been reported; however, distinction from normal RV trabeculation is difficult. This study aimed at assessing RV morphology and function in LVNC by cardiac magnetic resonance (CMR) and transthoracic echocardiography (TTE).Methods: Dimensional and functional parameters were assessed according to guidelines. Novel CMR parameters were RV end-diastolic (ED) trabeculated area, RV ED trabeculated volume, and RV ED non-compacted to compacted (NC/N) ratio in short axis (SAX) as well as in four-chamber view (4CH).Results: Twenty patients with LVNC and 20 controls were included. RV size and function were comparable in LVNC and controls and exhibited a good correlation between TTE and CMR. Although RV trabeculated area, RV trabeculated volume, and RV ED NC/C ratio in SAX as well as in 4CH were larger in LVNC, there was a major overlap with values in controls. RV ED NC/C ratio in SAX correlated with LV ED NC/C ratio (not in 4CH). Quantitative assessment of RV non-compaction was not feasible in TTE.Conclusions: Right ventricle size and function in LVNC can be measured by CMR and TTE, while RV trabeculation can only be quantified by CMR. RV myocardium displays more trabeculations in LVNC; however, overlap with normal individuals is extensive, not allowing separation of patients with LVNC from controls

Dual-Phase Cardiac Diffusion Tensor Imaging with Strain Correction

Purpose In this work we present a dual-phase diffusion tensor imaging (DTI) technique that incorporates a correction scheme for the cardiac material strain, based on 3D myocardial tagging. Methods: In vivo dual-phase cardiac DTI with a stimulated echo approach and 3D tagging was performed in 10 healthy volunteers. The time course of material strain was estimated from the tagging data and used to correct for strain effects in the diffusion weighted acquisition. Mean diffusivity, fractional anisotropy, helix, transverse and sheet angles were calculated and compared between systole and diastole, with and without strain correction. Data acquired at the systolic sweet spot, where the effects of strain are eliminated, served as a reference. Results: The impact of strain correction on helix angle was small. However, large differences were observed in the transverse and sheet angle values, with and without strain correction. The standard deviation of systolic transverse angles was significantly reduced from 35.9±3.9° to 27.8°±3.5° (p<0.001) upon strain-correction indicating more coherent fiber tracks after correction. Myocyte aggregate structure was aligned more longitudinally in systole compared to diastole as reflected by an increased transmural range of helix angles (71.8°±3.9° systole vs. 55.6°±5.6°, p<0.001 diastole). While diastolic sheet angle histograms had dominant counts at high sheet angle values, systolic histograms showed lower sheet angle values indicating a reorientation of myocyte sheets during contraction. Conclusion: An approach for dual-phase cardiac DTI with correction for material strain has been successfully implemented. This technique allows assessing dynamic changes in myofiber architecture between systole and diastole, and emphasizes the need for strain correction when sheet architecture in the heart is imaged with a stimulated echo approach

Differences in Fabry Cardiomyopathy Between Female and Male Patients Consequences for Diagnostic Assessment

ObjectivesWe hypothesized that Fabry cardiomyopathy in female patients might differ substantially from that in male patients and sought to prove this hypothesis in a large cohort consisting of 104 patients with Fabry disease.BackgroundFabry cardiomyopathy in male patients is characterized by left ventricular (LV) hypertrophy, impaired myocardial function, and subsequent progressive myocardial fibrosis. In contrast, the occurrence of these 3 cardiomyopathic hallmarks in female patients remains unknown.MethodsIn 104 patients (58 females, age 42 ± 16 years; 46 males, age 42 ± 13 years) with genetically proven Fabry disease, LV hypertrophy, regional myocardial deformation and myocardial fibrosis were assessed by standard echocardiography, strain rate imaging, and cardiac magnetic resonance (CMR) imaging–guided late enhancement (LE).ResultsIn men, end-diastolic left ventricular wall thickness (LVWT) ranged from 6 to 19.5 mm (LV mass CMR 55 to 200 g/m2), and LE was never seen with LVWT <12 mm (LV mass <99 g/m2). In contrast in female patients, LVWT ranged from 5 to 15.5 mm, LV mass ranged from 39 to 146 g/m2, and LE was already detectable with an LVWT of 9 mm (LV mass 56 g/m2). When LV mass was examined in CMR, LE was detected in 23% of the female patients without hypertrophy (n = 9), whereas LE was never seen in male patients with normal LV mass. LE was always associated with low systolic strain rate, but the severity of impairment was independent of LVWT in female patients (lateral strain rate in patients with LV hypertrophy with LE −0.7 ± 0.2 s−1; patients without LV hypertrophy with LE −0.8 ± 0.2 s−1; p = 0.45).ConclusionsIn contrast to male patients, the loss of myocardial function and the development of fibrosis do not necessarily require myocardial hypertrophy in female patients with Fabry disease. Thus, in contrast to actual recommendations, initial cardiac staging and monitoring should be based on LV hypertrophy and on replacement fibrosis in female patients with Fabry disease