Kinematic reduction of reaction-diffusion fronts with multiplicative noise. Derivation of stochastic sharp-interface equations

We study the dynamics of generic reaction-diffusion fronts, including pulses and chemical waves, in the presence of multiplicative noise. We discuss the connection between the reaction-diffusion Langevin-like field equations and the kinematic (eikonal) description in terms of a stochastic moving-boundary or sharp-interface approximation. We find that the effective noise is additive and we relate its strength to the noise parameters in the original field equations, to first order in noise strength, but including a partial resummation to all orders which captures the singular dependence on the microscopic cutoff associated with the spatial correlation of the noise. This dependence is essential for a quantitative and qualitative understanding of fluctuating fronts, affecting both scaling properties and nonuniversal quantities. Our results predict phenomena such as the shift of the transition point between the pushed and pulled regimes of front propagation, in terms of the noise parameters, and the corresponding transition to a non-Kardar-Parisi-Zhang universality class. We assess the quantitative validity of the results in several examples including equilibrium fluctuations and kinetic roughening. We also predict and observe a noise-induced pushed-pulled transition. The analytical predictions are successfully tested against rigorous results and show excellent agreement with numerical simulations of reaction-diffusion field equations with multiplicative noise.

Identification of secretory IgA, free secretory piece and serum IgA in the ovine and caprine species.

Caprine and ovine IgA were identified by cross-reaction with anti-human and anti-bovine IgA sera in colostrum, mature milk, saliva, urine and serum. Secretory component (SC) was shown in the free form and associated with polymeric serum IgA in secretions. Mean molecular weights were determined for the IgA and the free secretory components. The high IgA content of saliva suggested that it was a major secretory immunoglobulin in these species. Traces of secretory IgA were also found in normal sera but most of the serum IgA had no secretory determinant. Secretory IgA, serum IgA and free secretory component were purified. Levels of the sheep and goat immunoglobulins were measured in various fluids.

hMMP9 as predictive factor for response and progression free survival in breast cancer patients treated with bevacizumab and pegylated liposomal doxorubicin (PLD)

Background: The anti-angiogenic drug, bevacizumab (Bv), is currently used in the treatment of different malignancies including breast cancer. Many angiogenesis-associated molecules are found in the circulation of cancer patients. Until now, there are no prognostic or predictive factors identified in breast cancer patients treated with Bv. We present here the first results of the prospective monitoring of 6 angiogenesis-related molecules in the peripheral blood of breast cancer patients treated with a combination of Bv and PLD in the phase II trial, SAKK 24/06. Methods: Patients were treated with PLD (20 mg/m2) and Bv (10 mg/kg) on days 1 and 15 of each 4-week cycle for a maximum of 6 cycles, followed by Bv monotherapy maintenance (10 mg/m2 q2 weeks) until progression or severe toxicity. Plasma and serum samples were collected at baseline, after 2 months of therapy, then every 3 months and at treatment discontinuation. Enzyme-linked immunosorbent assays (Quantikine, R&D Systems and Reliatech) were used to measure the expression levels of human vascular endothelial growth factor (hVEGF), placental growth factor (hPlGF), matrix metalloproteinase 9 (hMMP9) and soluble VEGF receptors hsVEGFR-1, hsVEGFR-2 and hsVEGFR-3. The log-transformed data (to reduce the skewness) for each marker was analyzed using an analysis of variance (ANOVA) model to determine if there was a difference between the mean of the subgroups of interest (where α = 0.05). The untransformed data was also analyzed in the same manner as a "sensitivity" check. Results: 132 blood samples were collected in 41 out of 43 enrolled patients. Baseline levels of the molecules were compared to disease status according to RECIST. There was a statistically significant difference in the mean of the log-transformed levels of hMMP9 between responders [CR+PR] versus the mean in patients with PD (p-value=0.0004, log fold change=0.7536), and between patients with disease control [CR+PR+SD] and those with PD (p-value=<0.0001, log fold change=0.81559), with the log-transformed level of hMMP9 being higher for the responder group. The mean of the log-transformed levels of hsVEGFR-1 was statistically significantly different between patients with disease control [CR+PR+SD] and those with PD (p-value=0.0068, log fold change=-0.6089), where the log-transformed level of hsVEGFR-1 was lower for the responder group. The log-transformed level of hMMP9 at baseline was identified as a significant prognostic factor in terms of progression free survival (PFS): p-value=0.0417, hazard ratio (HR)=0.574 with a corresponding 95% confidence interval (0.336 - 0.979)). No strong correlation was shown either between the log-transformed levels of hsVEGF, hPlGF, hsVEGFR-2 or hsVEGFR-3 and clinical response or the occurrence of severe toxicity, or between the levels of the different molecules. Conclusions: Our results suggest that baseline plasma level of the matrix metalloproteinase, hMMP9, could predict tumor response and PFS in patients treated with a combination of Bv and PLD. These data justify further investigation in breast cancer patients treated with anti-angiogenic therapy.

Interface dynamics in Hele-Shaw flows with centrifugal forces. Preventing cusp singularities with rotation

A class of exact solutions of Hele-Shaw flows without surface tension in a rotating cell is reported. We show that the interplay between injection and rotation modifies the scenario of formation of finite-time cusp singularities. For a subclass of solutions, we show that, for any given initial condition, there exists a critical rotation rate above which cusp formation is suppressed. We also find an exact sufficient condition to avoid cusps simultaneously for all initial conditions within the above subclass.

Rationale for consolidation to improve progression-free survival in patients with non-Hodgkin's lymphoma: a review of the evidence.

Non-Hodgkin's lymphoma (NHL) comprises both indolent forms, including follicular lymphoma (FL) and marginal zone lymphoma (MZL), and aggressive forms, including diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma (MCL). FL and DLBCL are the most common subtypes of indolent and aggressive NHL, respectively. Although these lymphomas exhibit different clinical behaviors and outcomes, the prognosis is negatively affected in both DLBCL and FL by the lack of a complete response (CR) with standard treatment options. The aim of therapy should therefore be achievement of a CR, which is not only associated with longer progression-free survival (PFS) and overall survival times, but is also a prerequisite for a cure, particularly in DLBCL. Consolidation treatment with radioimmunotherapy (RIT) is an innovative treatment approach to increase CR rates. Phase II studies have indicated promising results with yttrium-90 ((90)Y)-ibritumomab tiuxetan and iodine-131 ((131)I)-tositumomab as consolidation following induction therapy for previously untreated patients with advanced FL. More recently, investigators reported a marked increase in CR rates and significant improvements in PFS using standard chemotherapy regimens followed by (90)Y-ibritumomab tiuxetan in a phase III randomized trial in patients with previously untreated FL. Data also suggest that RIT may play a role in the treatment of high-risk DLBCL, with encouraging PFS results from a phase II trial of (90)Y-ibritumomab tiuxetan consolidation following induction with rituximab plus chemotherapy in elderly patients with previously untreated DLBCL. With the higher CR rates and longer PFS times observed in patients with FL and DLBCL, as well as encouraging early data from MZL and MCL consolidation trials, RIT appears to have an important role in the treatment of patients with NHL.

Model-Free Reconstruction of Excitatory Neuronal Connectivity from Calcium Imaging Signals

A systematic assessment of global neural network connectivity through direct electrophysiological assays has remained technically infeasible, even in simpler systems like dissociated neuronal cultures. We introduce an improved algorithmic approach based on Transfer Entropy to reconstruct structural connectivity from network activity monitored through calcium imaging. We focus in this study on the inference of excitatory synaptic links. Based on information theory, our method requires no prior assumptions on the statistics of neuronal firing and neuronal connections. The performance of our algorithm is benchmarked on surrogate time series of calcium fluorescence generated by the simulated dynamics of a network with known ground-truth topology. We find that the functional network topology revealed by Transfer Entropy depends qualitatively on the time-dependent dynamic state of the network (bursting or non-bursting). Thus by conditioning with respect to the global mean activity, we improve the performance of our method. This allows us to focus the analysis to specific dynamical regimes of the network in which the inferred functional connectivity is shaped by monosynaptic excitatory connections, rather than by collective synchrony. Our method can discriminate between actual causal influences between neurons and spurious non-causal correlations due to light scattering artifacts, which inherently affect the quality of fluorescence imaging. Compared to other reconstruction strategies such as cross-correlation or Granger Causality methods, our method based on improved Transfer Entropy is remarkably more accurate. In particular, it provides a good estimation of the excitatory network clustering coefficient, allowing for discrimination between weakly and strongly clustered topologies. Finally, we demonstrate the applicability of our method to analyses of real recordings of in vitro disinhibited cortical cultures where we suggest that excitatory connections are characterized by an elevated level of clustering compared to a random graph (although not extreme) and can be markedly non-local.

Protein-binding microarrays: probing disease markers at the interface of proteomics and genomics.

DNA-binding proteins mediate a variety of crucial molecular functions, such as transcriptional regulation and chromosome maintenance, replication and repair, which in turn control cell division and differentiation. The roles of these proteins in disease are currently being investigated using microarray-based approaches. However, these assays can be difficult to adapt to routine diagnosis of complex diseases such as cancer. Here, we review promising alternative approaches involving protein-binding microarrays (PBMs) that probe the interaction of proteins from crude cell or tissue extracts with large collections of synthetic or natural DNA sequences. Recent studies have demonstrated the use of these novel PBM approaches to provide rapid and unbiased characterization of DNA-binding proteins as molecular markers of disease, for example cancer progression or infectious diseases.

Physical activity under confinement and free-living conditions.

The objective of this study was to investigate the relationship between the physical activity (PA) and its related variables under confinement and in free-living conditions in Asian individuals, where no such information presently exists. The subjects consisted of eighty-six Japanese individuals with a mean age of 38+/-12 years. Under confinement in a large respiratory chamber, the energy expenditure (EE) was measured for 24h. In addition, two moderate walking exercises of 30 min each on a horizontal treadmill were assigned. Free-living measurements of 7 days were also performed using a validated accelerometer. The PA level in the chamber (1.47+/-0.11), expressed as a multiple of the basal EE, was lower than that in free-living conditions (1.53+/-0.12) (p<0.001). However, the two values were closely correlated (r=0.744, p<0.001). Conversely, a residual analysis showed a wide variation in the mean difference for both conditions and revealed a significant systematic error (r=-0.548, p<0.001), thus indicating an increased gap with increasing PA levels in free-living conditions. Similar results were obtained following the exclusion of the imposed exercise sessions. In contrast, the daily step counts under both conditions did not show any correlation. The PA level in the chamber (including and excluding imposed walking exercises) is compatible with the PA level in free-living conditions at the group level, although the daily step counts are unrelated. Thus, the PA level in the chamber may provide valuable information to help us achieve a better understanding of human PA in daily life as it is related to behavioral research.

On the determination of the interface density of states in a-Si:H/a-SiC:H multilayers

This paper deals with the determination of the interface density of states in amorphous silicon-based multilayers. Photothermal deflection spectroscopy is used to characterize two series of aSi:H/aSi1-xCx:H multilayers, and a new approach in the treatment of experimental dada is used in order to obtain accurate results. From this approach, an upper limit of 10^10 cm-2 is determined for the interface density of states.

Film-free laser forward printing of transparent and weakly absorbing liquids

A laser-based technique for printing transparent and weakly absorbing liquids is developed. Its principle of operation relies in the tight focusing of short laser pulses inside the liquid and close to its free surface, in such a way that the laser radiation is absorbed in a tiny volume around the beam waist, with practically no absorption in any other location along the beam path. If the absorbed energy overcomes the optical breakdown threshold, a cavitation bubble is generated, and its expansion results in the propulsion of a small fraction of liquid which can be collected on a substrate, leading to the printing of a microdroplet for each laser pulse. The technique does not require the preparation of the liquid in thin film form, and its forward mode of operation imposes no restriction concerning the optical properties of the substrate. These characteristics make it well suited for printing a wide variety of materials of interest in diverse applications. We demonstrate that the film-free laser forward printing technique is capable of printing microdroplets with good resolution, reproducibility and control, and analyze the influence of the main process parameter, laser pulse energy. The mechanisms of liquid printing are also investigated: time-resolved imaging provides a clear picture of the dynamics of liquid transfer which allows understanding the main features observed in the printed droplets.

Real-time motion correction in navigator-gated free-breathing double-oblique submillimeter 3D right coronary artery magnetic resonance angiography.

RATIONALE AND OBJECTIVES: The purpose of this study was the investigation of the impact of real-time adaptive motion correction on image quality in navigator-gated, free-breathing, double-oblique three-dimensional (3D) submillimeter right coronary magnetic resonance angiography (MRA). MATERIALS AND METHODS: Free-breathing 3D right coronary MRA with real-time navigator technology was performed in 10 healthy adult subjects with an in-plane spatial resolution of 700 x 700 microm. Identical double-oblique coronary MR-angiograms were performed with navigator gating alone and combined navigator gating and real-time adaptive motion correction. Quantitative objective parameters of contrast-to-noise ratio (CNR) and vessel sharpness and subjective image quality scores were compared. RESULTS: Superior vessel sharpness, increased CNR, and superior image quality scores were found with combined navigator gating and real-time adaptive motion correction (vs. navigator gating alone; P < 0.01 for all comparisons). CONCLUSION: Real-time adaptive motion correction objectively and subjectively improves image quality in 3D navigator-gated free-breathing double-oblique submillimeter right coronary MRA.

Synthesis, structural order and magnetic behavior of self-assembled epsilon-Co nanocrystal arrays

The synthesis of magnetic nanoparticles with monodispere size distributions, their self assembly into ordered arrays and their magnetic behavior as a function of structural order (ferrofluids and 2D assemblies) are presented. Magnetic colloids of monodispersed, passivated, cobalt nanocrystals were produced by the rapid pyrolysis of cobalt carbonyl in solution. The size, size distribution (std. dev.< 5%) and the shape of the nanocrystals were controlled by varying the surfactant, its concentration, the reaction rate and the reaction temperature. The Co particles are defect-free single crystals with a complex cubic structure related to the beta phase of manganese (epsilon-Co). In the 2D assembly, a collective behavior was observed in the low-field susceptibility measurements where the magnetization of the zero field cooled process increases steadily and the magnetization of the field cooling process is independent the temperature. This was different from the observed behavior in a sample comprised of disordered interacting particles. A strong paramagnetic contribution appears at very low temperatures where the magnetization increases drastically after field cooling the sample. This has been attributed to the Co surfactant-particle interface since no magnetic atomic impurities are present in these samples.

First-passage times for non-Markovian processes: Correlated impacts on a free process

We develop a method to obtain first-passage-time statistics for non-Markovian processes driven by dichotomous fluctuations. The fluctuations themselves need not be Markovian. We calculate analytic first-passage-time distributions and mean first-passage times for exponential, rectangular, and long-tail temporal distributions of the fluctuations.

Singularity-free space-time

We show that the solution published in the paper by Senovilla [Phys. Rev. Lett. 64, 2219 (1990)] is geodesically complete and singularity-free. We also prove that the solution satisfies the stronger energy and causality conditions, such as global hyperbolicity, the strong energy condition, causal symmetry, and causal stability. A detailed discussion about which assumptions in the singularity theorems are not satisfied is performed, and we show explicitly that the solution is in accordance with those theorems. A brief discussion of the results is given.