Average Diffusion Time Research Articles

Drug polymer conjugates: Average release time from thin films

The reaction–diffusion problem describing the release of drugs conjugated through labile bonds to polymeric thin films has a known analytical solution, when the reaction kinetics is of first order. Using this solution, an exact formula is derived for the average release time of the system. This simple expression provides the characteristic time of release tav as the sum of the corresponding average diffusion time plus the inverse reaction rate constant: tav=(1/12)⋅(L2/D)+(1/k), where L is the slab thickness, D the diffusion coefficient, and k the reaction rate constant. The former term dominates in a diffusion-controlled release, while the latter one in a reaction-controlled delivery. The crossover regime is exactly described by their sum. The obtained result for the average release time is verified by direct numerical integration through the drug release profiles of the analytical solution. The value of fractional drug release at the characteristic average time is between 60–64%. These results can be used for the design of polymer-drug conjugates with a desired delivery time scale, as well as for the experimental determination of the values of microscopic parameters D and k in a conjugated system of interest.

Determination of the Electrical Parameters of Iodine-Doped Polymer Solar Cells at the Macro- and Nanoscale for Indoor Applications

In this work, macro- and nanodiagnostic procedures for working, third-generation photovoltaic devices based on a modified polymer:fullerene (P3HT:PCBM) absorber were conducted using atomic force microscopy (AFM) and impedance spectroscopy (IS) equipment. All experiments were performed both in the dark and under irradiation with a specific light wavelength. Photoactive Kelvin probe force microscopy (p-KPFM) and impedance spectroscopy (p-IS) experiments were conducted on half- and whole-solar cell devices. Based on the p-KPFM measurements, the surface potential (SP) and surface photovoltage (SPV) on top of the active layer at the micro/nanoscale were estimated for various light wavelengths (red, green, blue, and white). For light in the red spectrum range, which was associated with an optical absorption edge and acceptor states that occurred in the band gap of the P3HT material after doping the donor polymer with iodine, the SPV was measured at levels of 183 mV, 199 mV, and 187 mV for the samples with 0%, 5% and 10% iodine doping, respectively. In addition, a macroscale investigation enabling the determination of the electrical parameters of the studied organic solar cells (OSCs) was carried out using p-IS. Based on the data obtained during p-IS experiments, it was possible to propose a series electrical equivalent circuit to define and describe the charge transfer phenomenon in the OSCs. Estimations of data obtained from the fitting of the experimental results of p-IS under white light allowed us to evaluate the average diffusion time of electric charges at 8.15 µs, 16.66 µs, and 24.15 µs as a function of organic layer thickness for the device without doping and with 5% and 10% iodine doping. In this study, we demonstrated that correlating information obtained at the macro- and nanoscale enabled a better understanding of the electrical charge distribution of OSCs for indoor applications.

A design-driven creation of an innovative and environment-friendly nature-based yarn with moisture wicking and fast-drying effect

Wicking in textiles is a key property of fabric moisture permeability, which has been found to be dominant in the comfort-maintaining mechanism of apparel products, especially for sportswear that has high requirements for sweat transfer. Various methods have been given in order to improve moisture transfer behavior of fabrics, among which fiber modification is the most direct and ideal way. In this article, a design-driven yarn structure spinning model for moisture wicking improvement is established by using a helically shaped covering material to limit the inter-fiber spacings of the staple core yarn so that an improvement in effective capillary channels with better continuity can be achieved. The developed yarn constructions combine the advantages of natural and synthetic fibers, showing significant improvements on moisture wicking performance, fast-drying effects as well as commercial values. Experiments on the fabrics made in accordance achieved excellent results both before and after washing. For the most efficient fabric 5 with cotton-linen as the core material, the average diffusion time was decreased by 86.4% and 66.5% before and after washing, compared with the core yarn. Excessively large water absorption rates of the control fabrics were limited and decreased by 22.1% and 32.4%. The evaporation rates of the fabric were increased by 25.6% and 18.5%, indicating obvious improvements in fast drying effects. Through various experiments, the optimal spinning parameters were investigated which provided methods and established foundations for subsequent research. The finding in this study offer the possibility of fiber moisture performance modification with high efficiency, low cost, and environmental sustainability.

Long-term Dynamical Stability in the Outer Solar System. I. The Regular and Chaotic Evolution of the 34 Largest Trans-Neptunian Objects

Abstract We carried out an extensive analysis of the stability of the outer solar system, making use of the frequency analysis technique over short-term integrations of nearly 100,000 test particles, as well as a statistical analysis of 200 1 Gyr long numerical simulations, which consider the mutual perturbations of the giant planets and the 34 largest trans-Neptunian objects (we have called all 34 objects “dwarf planets,” DPs, even if probably only the largest of them are true DPs). From the frequency analysis, we produced statistical diffusion maps for a wide region of the a–e phase-space plane; we also present the average diffusion time for orbits as a function of perihelion. We later turned our attention to the 34 DPs, making an individualized analysis for each of them and producing a first approximation of their future stability. From the 200 distinct realizations of the orbital evolution of the 34 DPs, we classified the sample into three categories, including 17 stable, 11 unstable, and 6 resonant objects; we also found that, statistically, two objects from the sample will leave the trans-Neptunian region within the next gigayear, most likely being ejected from the solar system, but with a nonnegligible probability of going inside the orbit of Neptune, either to collide with a giant planet or even falling to the inner solar system, where our simulations are no longer able to resolve their continuous evolution.

Random neighborhood graphs as models of fracture networks on rocks: Structural and dynamical analysis

We propose a new model to account for the main structural characteristics of rock fracture networks (RFNs). The model is based on a generalization of the random neighborhood graphs to consider fractures embedded into rectangular spaces. We study a series of 29 real-world RFNs and find the best fit with the random rectangular neighborhood graphs (RRNGs) proposed here. We show that this model captures most of the structural characteristics of the RFNs and allows a distinction between small and more spherical rocks and large and more elongated ones. We use a diffusion equation on the graphs in order to model diffusive processes taking place through the channels of the RFNs. We find a small set of structural parameters that highly correlates with the average diffusion time in the RFNs. We found analytically some bounds for the diameter and the algebraic connectivity of these graphs that allow to bound the diffusion time in these networks. We also show that the RRNGs can be used as a suitable model to replace the RFNs in the study of diffusion-like processes. Indeed, the diffusion time in RFNs can be predicted by using structural and dynamical parameters of the RRNGs. Finally, we also explore some potential extensions of our model to include variable fracture apertures, the possibility of long-range hops of the diffusive particles as a way to account for heterogeneities in the medium and possible superdiffusive processes, and the extension of the model to 3-dimensional space.

A comparative study on the effect of Curcumin and Chlorin-p6 on the diffusion of two organic cations across a negatively charged lipid bilayer probed by second harmonic spectroscopy

The influence of Curcumin and Chlorin-p6 (Cp6) on the real time diffusion kinetics of two organic cations, LDS (LDS-698) and Malachite Green (MG) across a negatively charged phospholipid bilayer is investigated by Second Harmonic (SH) spectroscopy. The diffusion time constant of LDS at neutral pH in liposomes containing either Curcumin or Cp6 is significantly reduced, the effect being more pronounced with Curcumin. At acidic pH, the quantum of reduction in the diffusion time constant of MG by both the drugs was observed to be similar. The relative changes in the average diffusion time constants of the cations with increasing drug concentration at pH 5.0 and 7.4 shows a substantial pH effect for Curcumin induced membrane permeability, while a modest pH effect was observed for Cp6 induced membrane permeability. Based on available evidence this can be attributed to the increased interaction between the drug and the polar head groups of the lipid at pH 7.4 where the drug resides closer to the lipid–water interface.

Second harmonic generation correlation spectroscopy for single molecule experiments

We demonstrate a single molecule detection approach to further extend the detection limit of correlation spectroscopic techniques through the Second Harmonic Generation Correlation Spectroscopy (SHGCS). SHG signals with high signal-to-noise ratio (SNR) were obtained from Barium titanium oxide, BaTiO(3) (BTO) nanocrystals (NCs) upon excitation by a femto-second laser fitted to the scanning confocal bench. The fluctuation of SHG signals from BTO NCs in transparent and turbid media was examined and their diffusion time and particle concentration were evaluated by autocorrelation. Proof-of-concept measurements indicate that water-dispersed BTO NCs at different concentrations yield an average diffusion time of 6.43 ± 0.68 ms and the detection limit of SHGCS was found to be at 814 ± 41 fM, approximately 100 folds below the detection limit of fluorescence correlation spectroscopy (FCS). The dynamics of BTO NCs was demonstrated in serum with high SNR and selectivity to show its potential applicability in biomedicine. High SNR and the sub-picomolar detection limit positions SHGCS as an excellent technique for ultralow single particle or single molecule experimentation in a complex medium.

Chemical and physical aggregation of small-functionality particles

The number of potentially relevant materials resulting from the aggregation of elementary units with a finite functionality continues to increase. The growth of branched clusters and networks may proceed through the formation of reversible (physical) or irreversible (chemical) bonds. The kinetics of bond formation is sensitive both to the intrinsic rate of the bonding process, controlled by the chemistry of the system, and to the encounter rate of clusters, controlled by cluster diffusion. In this Highlight we review a series of our recent numerical simulation studies designed to investigate the connections between chemical and physical aggregation and the crossover from a chemically controlled to diffusion-controlled regime. It is shown that in the chemically controlled limit, it is possible to formally correlate elapsed time during irreversible aggregation with equilibrium temperature in reversible aggregation. The diffusion-controlled regime sets in well-beyond percolation and the effect of diffusion can be described by introducing a single additional time scale, related to the average diffusion time. This concept can be readily generalized to interpret the experimental data.

Two Distinct Amyloid β-Protein (Aβ) Assembly Pathways Leading to Oligomers and Fibrils Identified by Combined Fluorescence Correlation Spectroscopy, Morphology, and Toxicity Analyses

Nonfibrillar assemblies of amyloid β-protein (Aβ) are considered to play primary roles in Alzheimer disease (AD). Elucidating the assembly pathways of these specific aggregates is essential for understanding disease pathogenesis and developing knowledge-based therapies. However, these assemblies cannot be monitored in vivo, and there has been no reliable in vitro monitoring method at low protein concentration. We have developed a highly sensitive in vitro monitoring method using fluorescence correlation spectroscopy (FCS) combined with transmission electron microscopy (TEM) and toxicity assays. Using Aβ labeled at the N terminus or Lys(16), we uncovered two distinct assembly pathways. One leads to highly toxic 10-15-nm spherical Aβ assemblies, termed amylospheroids (ASPDs). The other leads to fibrils. The first step in ASPD formation is trimerization. ASPDs of ∼330 kDa in mass form from these trimers after 5 h of slow rotation. Up to at least 24 h, ASPDs remain the dominant structures in assembly reactions. Neurotoxicity studies reveal that the most toxic ASPDs are ∼128 kDa (∼32-mers). In contrast, fibrillogenesis begins with dimer formation and then proceeds to formation of 15-40-nm spherical intermediates, from which fibrils originate after 15 h. Unlike ASPD formation, the Lys(16)-labeled peptide disturbed fibril formation because the Aβ(16-20) region is critical for this final step. These differences in the assembly pathways clearly indicated that ASPDs are not fibril precursors. The method we have developed should facilitate identifying Aβ assembly steps at which inhibition may be beneficial.

Modeling the Crossover between Chemically and Diffusion-Controlled Irreversible Aggregation in a Small-Functionality Gel-Forming System

The analysis of realistic numerical simulations of a gel-forming irreversible aggregation process provides information on the role of cluster diffusion in controlling the late stages of the aggregation kinetics. Interestingly, the crossover from chemically controlled to diffusion-controlled aggregation takes place well beyond percolation, after most of the particles have aggregated in the spanning network and only small clusters remain in the sol. The simulation data are scrutinized to gain insight into the origin of this crossover. We show that a single additional time scale (related to the average diffusion time) is sufficient to provide an accurate description of the evolution of the extent of reaction at all times.

Kinesin-1/Hsc70-dependent mechanism of slow axonal transport and its relation to fast axonal transport

Cytoplasmic protein transport in axons ('slow axonal transport') is essential for neuronal homeostasis, and involves Kinesin-1, the same motor for membranous organelle transport ('fast axonal transport'). However, both molecular mechanisms of slow axonal transport and difference in usage of Kinesin-1 between slow and fast axonal transport have been elusive. Here, we show that slow axonal transport depends on the interaction between the DnaJ-like domain of the kinesin light chain in the Kinesin-1 motor complex and Hsc70, scaffolding between cytoplasmic proteins and Kinesin-1. The domain is within the tetratricopeptide repeat, which can bind to membranous organelles, and competitive perturbation of the domain in squid giant axons disrupted cytoplasmic protein transport and reinforced membranous organelle transport, indicating that this domain might have a function as a switchover system between slow and fast transport by Hsc70. Transgenic mice overexpressing a dominant-negative form of the domain showed delayed slow transport, accelerated fast transport and optic axonopathy. These findings provide a basis for the regulatory mechanism of intracellular transport and its intriguing implication in neuronal dysfunction.

Imaging Diffusion in Living Cells Using Time-Correlated Single-Photon Counting

Current efforts to monitor the diffusion of proteins in living cells are based on either fluorescence correlation spectroscopy (FCS), fluorescence recovery after photobleaching, or image correlation spectroscopy. However, these methods cannot generate a map of diffusion times. Here, we introduce a new method termed diffusion imaging microscopy that combines scanning confocal microscopy, time-correlated single-photon counting, and FCS and thus allows us to measure spatially resolved diffusion times. In our approach, we record scan images with time-resolved photon streams within each individual pixel. By extending the pixel dwell time to 25-100 ms, a software correlation of individual photons within each pixel yields the average diffusion time. Additionally, information on fluorescence intensity (number of photons) and fluorescence lifetime is available and can be used to sort fluorescence photons and to discriminate from autofluorescence. We evaluated our method by measuring diffusion times of dT20-TMR in solutions of different viscosity. We further demonstrate the applicability of the method to living cells and recorded a diffusion map of a living 3T3 mouse fibroblast incubated with dT20-ATTO488.

In vivo fluorescence correlation microscopy (FCM) reveals accumulation and immobilization of Nod factors in root hair cell walls.

Fluorescence correlation microscopy (FCM) is a new single-molecule detection technique based on the confocal principle to quantify molecular diffusion and concentration of fluorescent molecules (particles) with sub-micron resolution. In this study, FCM is applied to examine the diffusional behaviour of fluorescent Nod factor analogues on living Vicia sativa root hairs. Three recently described Nod factors with a fluorescent acyl chain (Goedhart et al. Biochemistry 1999, 38, 10898-10907) were used. Plasmolysis of fluorescently labelled root hairs showed that the Nod factors are predominantly located in the cell wall, as hardly any fluorescence could be detected in the plasma membrane. After Nod factor-induced root hair deformation, the new outgrowth was not labelled, indicating a lack of migration of Nod factors to the newly synthesized cell wall. In agreement, FCM showed a > 1,000-fold reduction of molecular mobility of the fluorescence Nod factors upon binding to the cell wall. In addition, FCM demonstrated that Nod factors, when exogenously applied in aqueous solution at 10 nM, markedly concentrate in the cell wall of root hairs (up to 50-fold). The feasibility of applying FCM for the study of living plant cells as well as the implications of our results for the perception of Nod factors are discussed.

Quantitative analysis by the polymerase chain reaction using fluorescence correlation spectroscopy

DNA amplification by the polymerase chain reaction (PCR) was monitored at the level of single molecules. The technique used consisted of a direct fluorescent labeling method using the PCR and measurement of fluorescence fluctuation by fluorescence correlation spectroscopy (FCS). An increasing number of target DNA molecules during amplification resulted in a decrease of the number fluctuations, and also an increase of the average diffusion time. Fluorescein-11-dUTP was incorporated into the DNA strand with a length of 4000 bp using Taq DNA polymerase. Increasing the apparent labeling density according to concentration of fluorescein-11-dUTP was evaluated from the fluorescence intensity per DNA molecule. The number of amplified DNA molecules could be detected quantitatively after 10 PCR cycles even when the initial template number was 3750 copies; however, a linear relationship between the initial template number and amplified DNA number was shown at 20 cycles in PCR.