Favorable Partitioning Research Articles

Squalene-Conjugated Drugs Exploit Endogenous Low-Density Lipoproteins for Enhanced Targeting for Cancer Therapy

Cancer is a major global health threat and a leading cause of mortality worldwide. Nucleotide analog chemodrugs are commonly used in the treatment of various solid tumors, but their clinical efficacy is often limited by rapid blood metabolization, poor intracellular diffusion and significant side effects due to non-selectivity targeting. To address these challenges, this study investigates the potential of conjugating squalenea natural triterpene and cholesterol biosynthesis precursorto two model chemodrugs to enhance the drug's incorporation into endogenous low-density lipoproteins (LDLs) for targeted cancer delivery. By leveraging the natural affinity of lipoproteins for cancer cells with overexpressed lipoprotein receptors, this approach can potentially improve the drugs specificity to cancer cells and accumulation at tumor sites. Using molecular dynamics (MD) simulations, we found that squalene-conjugated drugs have favorable partitioning into LDL interior with a deep negative free energy well. It confirms that squalene-drug conjugates possess the significantly higher affinity to LDL and the potential to exploit LDL for targeting cancer cells. The improved drug behaviors are expected to improve drug circulation and tumor accumulation. The findings provide valuable insights into the potential of squalene-conjugated chemodrugs as a novel strategy for improving the therapeutic efficacy of nucleoside analogs in cancer treatment

Enhancing remediation of residual DNAPL in multilayer aquifers: Post-injection of alcohol-surfactant-polymer mixtures

Although polymer-surfactant injection is an effective remediation technology for multilayer aquifers contaminated by Dense Non-Aqueous Phase Liquids (DNAPL), the existence of residual DNAPL after treatment is inevitable. This study evaluates the efficiency of the post-injection of alcohol-surfactant-polymer (ASP) mixtures containing 1-propanol/1-hexanol, sodium dodecylbenzenesulfonate (SDBS), and xanthan in enhancing remediation of residual DNAPL in layered systems. A range of experimental devices, including batch, rheological measurements, centimetric 1D column, and decametric 2D tank experiments, were employed. Batch experiments revealed that the inclusion of 1-hexanol swelled the DNAPL volume due to alcohol partitioning. Conversely, with only 1-propanol present in the alcohol-surfactant (AS) mixture, DNAPL dissolved in the aqueous phase. The co-presence of 1-hexanol along with 1-propanol in AS mixture favored 1-propanol's partitioning into the DNAPL phase. Column experiments, following primary xanthan-SDBS (XS) injections, demonstrated that ASP mixtures with 1-hexanol (regardless of presence of 1-propanol) underwent a mobilization mechanism. DNAPL appeared in the effluent as an organic phase after the post-injection of 0.3 pore-volumes (PV), by a reduction trend in its density. In contrast, mixtures with solely 1-propanol exhibited a solubilization mechanism, with DNAPL dissolving in the aqueous phase and emerging in the effluent after approximately 1 PV. 2D tank experiments visualized mobilization and solubilization mechanisms in multilayered systems. Post-injection of the ASP mixture with solely 1-propanol led to DNAPL solubilization, demonstrated by a dark zone of varied DNAPL concentrations, followed by a clearer white zone indicating significant DNAPL dissolution. Injecting ASP mixture containing both 1-propanol and 1-hexanol mobilized swollen DNAPL ganglia throughout layers, with these droplets coalescing and migrating to the recovery point. The darkness of mobilized droplets was faded as more DNAPL was recovered. The solubilization ASP mixture enhanced the recovery factor by 0.02 while the mobilization ASP mixture led to a 0.08 increase in the recovery factor.

Transport and Energetics of Carbon Dioxide in Ionic Liquids at Aqueous Interfaces.

A major hurdle in utilizing carbon dioxide (CO2) lies in separating it from industrial flue gas mixtures and finding suitable storage methods that enable its application in various industries. To address this issue, we utilized a combination of molecular dynamics simulations and experiments to investigate the behavior of CO2 in common room-temperature ionic liquids (RTIL) when in contact with aqueous interfaces. Our investigation of RTILs, [EMIM][TFSI] and [OMIM][TFSI], and their interaction with a pure water layer mimics the environment of a previously developed ultrathin enzymatic liquid membrane for CO2 separation. We analyzed diffusion constants and viscosity, which reveals that CO2 molecules exhibit faster mobility within the selected ILs compared to what would be predicted solely based on the viscosity of the liquids using the standard Einstein-Stokes relation. Moreover, we calculated the free energy of translocation for various species across the aqueous-IL interface, including CO2 and HCO3-. Free energy profiles demonstrate that CO2 exhibits a more favorable partitioning behavior in the RTILs compared to that in pure water, while a significant barrier hinders the movement of HCO3- from the aqueous layer. Experimental measurement of the CO2 transport in the RTILs corroborates the model. These findings strongly suggest that hydrophobic RTILs could serve as a promising option for selectively transporting CO2 from aqueous media and concentrating it as a preliminary step toward storage.

Synthesis and Evaluation of [18F]SiFA-Conjugated Ligands for Fibroblast Activation Protein Imaging.

In recent years, fibroblast activation protein (FAP) has emerged as an important target for the diagnosis and therapy of various tumors due to its high expression on the cell surface of cancer-associated fibroblasts, which are the major components of the tumor stroma. In this study, we synthesized and evaluated 18F-labeled FAP inhibitors (FAPIs) for FAP imaging. Two silicon fluoride acceptor (SiFA)-conjugated FAPIs were synthesized: one containing a γ-carboxy-l-glutamic acid (Gla) residue (1) and another containing two Gla residues (2). Both ligands exhibited high binding affinities for FAP. 18F/19F exchange reactions on both ligands were performed in the presence of 2% water. This resulted in the formation of radioligands [18F]1 and [18F]2 in high radiochemical yields. Radioligand [18F]2, with a more favorable partition coefficient, was selected for the U87MG cell binding study, and the results showed FAP-specific binding of the radioligand to the cells. An ex vivo biodistribution study in U87MG tumor-bearing mice 60 min after injection demonstrated a 5.8-fold higher tumor accumulation of [18F]2 than that of [18F]1. Furthermore, PET and ex vivo biodistribution studies of [18F]2 in U87MG tumor-bearing mice showed high and persistent tumor uptake over time, which was significantly blocked by the preinjection of FAPI-04. Our results indicate that [18F]SiFA-(Gla)2-conjugated FAPI ([18F]2) has the potential for FAP imaging.

An Optimized Framework for Matrix Factorization on the New Sunway Many-core Platform

Matrix factorization functions are used in many areas and often play an important role in the overall performance of the applications. In the LAPACK library, matrix factorization functions are implemented with blocked factorization algorithm, shifting most of the workload to the high-performance Level-3 BLAS functions. But the non-blocked part, the panel factorization, becomes the performance bottleneck, especially for small- and medium-size matrices that are the common cases in many real applications. On the new Sunway many-core platform, the performance bottleneck of panel factorization can be alleviated by keeping the panel in the LDM for the panel factorization. Therefore, we propose a new framework for implementing matrix factorization functions on the new Sunway many-core platform, facilitating the in-LDM panel factorization. The framework provides a template class with wrapper functions, which integrates inter-CPE communication for the Level-1 and Level-2 BLAS functions with flexible interfaces and can accommodate different partitioning schemes. With the framework, writing panel factorization code with data residing in the LDM space can be done with much higher productivity. We implemented three functions ( dgetrf , dgeqrf , and dpotrf ) based on the framework and compared our work with a CPE_BLAS version, which uses the original LAPACK implementation linked with optimized BLAS library that runs on the CPE mesh. Using the most favorable partitioning, the panel factorization part achieves speedup of up to 26.3, 19.1, and 18.2 for the three matrix factorization functions. For the whole function, our implementation is based on a carefully tuned recursion framework, and we added specific optimization to some subroutines used in the factorization functions. Overall, we obtained average speedup of 9.76 on dgetrf , 10.12 on dgeqrf , and 4.16 on dpotrf , compared to the CPE_BLAS version. Based on the current template class, our work can be extended to support more categories of linear algebra functions.

Natural crystalline fibers of (E)-(R)-4-thujanol: green kilogram production from a selected wild thyme. X-ray and NMR characterization of a spiral structure

(E)-(R)-4-Thujanol present in thyme essential oils is an important aromatic ingredient for food, cosmetic and pharmaceutical applications. Until now, its extraction was challenging due to its low content in classical aromatic plants such as thyme or marjoram. Although this molecule is synthetically available, there is no production on an industrial scale because of very time-consuming and expensive chemical processes. We report here for the first time a new eco-responsible method to produce (E)-(R)-4-thujanol crystals on a kilogram scale. This new milestone is based on 2 fundamental research gaps: i) the selection of a wild thyme (Thymus vulgaris) for its high content of (E)-(R)-4-thujanol and its careful harvesting in the hills of French Provence and ii) a steam distillation producing an organic aromatic oil which aggregates spontaneously due to a favorable amphipathic partition at the air-water interface. Gas chromatography revealed a composition made of (E)-(R)-4-thujanol (76%), thymol (5%), β-myrcene (2,8%) and other minor monoterpenes. The white aggregate submitted to a cycle of sublimation/crystallization, led to accumulating translucent fibers made of (E)-(R)-4-thujanol (98%). X-ray diffraction unambiguously demonstrated that crystals of (E)-(R)-4-thujanol form a trimer (monoclinic asymmetric (C2)) unit composed of three independent (E)-(R)-4-thujanol molecules. The trimer is further organized into a chiral P-type supramolecular helix of trimers through a network of intermolecular hydrogen bonds. This study is based on the cheap, easy and eco-responsible kilogram production of (E)-(R)-4-thujanol crystals may open up new opportunities for the flavor, fragrance and pharmaceutical industries. Fibers of (E)-(R)-4-thujanol may also have applications as bio-active fibrous assemblies.

Ca2+ and Mg2+ Influence the Thermodynamics of Peptide-Membrane Interactions

Accurate quantitative estimates of protein-membrane interactions are critical to studies of membrane proteins. Here, we demonstrate that thermodynamic analyses based on current hydropathy scales do not account for the significant and experimentally determined effects that Ca2+ or Mg2+ have on protein-membrane interactions. We examined distinct modes of interaction (interfacial partitioning and folding and transmembrane insertion) by studying three highly divergent peptides: Bid-BH3 (derived from apoptotic regulator Bid), peripherin-2-derived prph2-CTER, and the cancer-targeting pH-Low-Insertion-Peptide (pHLIP). Fluorescence experiments demonstrate that adding 1-2mM of divalent cations led to a substantially more favorable bilayer partitioning and insertion, with free energy differences of 5-15kcal/mol.

Toward revealing the role of the cation in the phytotoxicity of the betaine-based esterquats comprising dicamba herbicide

In this study, two homologous series of esterquats comprising alkyl (from ethyl to octadecyl) betainate cations and bromide as well as dicamba anions were successfully synthesized, starting from a renewable raw material - glycine betaine. Due to the favorable octanol-water partition coefficient and utilization of biodegradable cations of natural origin, synthesized esterquats can be considered promising alternatives to currently applied dicamba-based formulations. In addition, the obtained results allowed us to verify whether the organic cations in quaternary ammonium salts containing herbicidally active anions (such as dicamba) play the role of biologically inactive adjuvants that only enhance the efficiency of the active ingredient or if they simultaneously exhibit a significant degree of phytotoxicity. Analysis of the influence of alkyl betainate esterquats containing nonherbicidal (bromide) anions on seedlings of white mustard revealed that alkyl betainate cations promote the germination of white mustard seeds; however, the subsequent growth of the seedlings was significantly inhibited. Further studies performed on white mustard and cornflower plants in a stage of 4-6 leaves allowed us to conclude that in the case of sensitive plants, the high phytotoxicity can be attributed to the presence of the dicamba anion, whereas for more resistant plants the additional influence of the cation on the phytotoxic effect is visible. Esterquats comprising a dodecyl substituent or longer had high surface active properties. Nonetheless, their contact angle values were not correlated with phytotoxicity data, indicating an additional influence of the cation on this stage of plant development. Interestingly, subsequent dose-response experiments conducted for two selected dicamba-based products confirmed that the greatest phytotoxicity was expressed by compounds containing a decyl substituent.

Paleodiet of Lamini camelids (Mammalia: Artiodactyla) from the Pleistocene of southern Brazil: insights from stable isotope analysis (δ13C, δ18O)

AbstractCamelids (Camelidae) were a diverse and widely distributed group in South America during the Pleistocene. According to the fossil record, three species inhabited southern Brazil in the recent past: Hemiauchenia paradoxa, Lama guanicoe, and Vicugna vicugna. The analysis of carbon and oxygen stable isotope ratios in bioapatite provides insight into the paleobiology of nonliving animals and the environment they used to inhabit. We applied this tool to investigate the diet of camelids from two geological localities in southern Brazil: Touro Passo and Santa Vitória Formations (H. paradoxa, n = 7; L. guanicoe, n = 6; V. vicugna, n = 4). Carbon stable isotopes from enamel, dentin, and bone indicated that H. paradoxa and L. guanicoe had diets comprising mostly C3 grasses, but the latter showed a broader diet due to one individual with a mixed diet, whereas V. vicugna had a mixed C3–C4 diet. These different foraging behaviors may have minimized interspecific competition and favored niche partitioning and the coexistence of related species. Combined oxygen and carbon isotope data showed a consistent diet according to climate, probably due to the greater availability in glacial periods of cool-season grasses, which mainly use the C3 photosynthetic pathway. Given their adaptations to grazing, the climate amelioration, followed by the loss of grasslands, likely had a great impact on camelid populations, leading to their extinction in southern Brazil. These results, therefore, contribute to the understanding of the dynamics of paleocommunities in this region.

Effects of aqueous systems and stabilization membranes on the separation of an antibiotic precursor in a microextractor

• a tube-in-a-shell membrane microextractor is developed. • the microextractor is tested for the separation of 7-ADCA – an antibiotic precursor. • a counter-current arrangement provides an almost 100 % yield of 7-ADCA. • the contribution of the membrane to the overall mass transport resistance is low. • the use of ATPS and identical aqueous phases for extraction is critically evaluated. Small-scale, continuous separation and purification of fine chemicals of pharmaceutical value represent a challenging engineering task. Currently available slug-flow and parallel-flow microfluidic extractors suffer from instabilities of the liquid–liquid interface and difficult realization of the counter-current arrangement. To tackle this challenge, we constructed a robust microfluidic membrane extractor, which was realized as a membrane tube-in-a-shell system operating in a wide range of extraction conditions. We tested the microextractor performance on separating 7-aminodeacetoxycephalosporanic acid (7-ADCA), an essential precursor of β-lactam antibiotics. Aqueous two-phase system (ATPS) and a system of identical aqueous phases were used in a series of extraction experiments. Expectedly, we found that the counter-current arrangement provides an almost 100 % yield of 7-ADCA. The enhanced 7-ADCA enrichment anticipated in the selected ATPS thanks to favorable 7-ADCA partitioning was only reached at longer residence times. Lower mass transport resistances occurring in low-viscous aqueous phases turned out to have a primary effect on the extraction characteristics. A detailed analysis of transport resistances also revealed that the contribution of the tubular membrane to the overall mass transport resistance is low. This important finding indicates that microcontactors with thin integrated membranes are a promising option for micro- or milli-plants when fine chemicals are continuously produced.

Arene Ru(II) Complexes with Difluorinated Ligands Act as Potential Inducers of S-Phase Arrest via the Stabilization of c-myc G-Quadruplex DNA.

Here, a series of half-sandwich arene Ru(II) complexes with difluorinated ligands [Ru(η6-arene)(L)Cl] (L1 = 2-(2,3-difluorophenyl)imidazole[4,5f][1,10]-phenanthroline; L2 = 2-(2,4-difluorophenyl)imidazole[4,5f][1,10]-phenanthroline; arene = benzene, toluene, and p-cymene) were synthesized and characterized. Molecular docking analysis showed that these complexes bind to c-myc G-quadruplex DNA through either groove binding or π–π stacking, and the relative difluorinated site in the main ligand plays a role in regulating the binding mode. The binding behavior of these complexes with c-myc G-quadruplex DNA was evaluated using ultraviolet–visible spectroscopy, fluorescence intercalator displacement assay, fluorescence resonance energy transfer melting assay, and polymerase chain reaction. The comprehensive analysis indicated that complex 1 exhibited a better affinity and stability in relation to c-myc G-quadruplex DNA with a DC50 of 6.6 μM and ΔTm values of 13.09 °C, than other molecules. Further activity evaluation results displayed that this class of complexes can also inhibit the growth of various tumor cells, especially complexes 3 and 6, which exhibited a better inhibitory effect against human U87 glioblastoma cells (51.61 and 23.75 μM) than other complexes, even superior to cisplatin (32.59 μM). Owing to a befitting lipophilicity associated with the high intake of drugs by tumor cells, complexes 3 and 6 had favorable lipid-water partition coefficients of −0.6615 and −0.8077, respectively. Moreover, it was found that complex 6 suppressed the proliferation of U87 cells mainly through an induced obvious S phase arrest and slight apoptosis, which may have resulted from the stabilization of c-myc G-quadruplex DNA to block the transcription and expression of c-myc. In brief, these types of arene Ru(II) complexes with difluorinated ligands can be developed as potential inducers of S-phase arrest and apoptosis through the binding and stabilization of c-myc G-quadruplex DNA, and could be used in clinical applications in the future.

Evaluating phospholipid− and protein−water partitioning of two groups of chemicals of emerging concern: Diastereo- and enantioselectivity

The partitioning between phospholipids/proteins and water can be used to predict the bioaccumulation potential of chemicals with better accuracy compared with n-octanol-water partition coefficient. However, such partitioning is poorly understood for chiral chemicals, many of which exhibit differential bioaccumulation and toxicity potential between enantiomers. In this study, the enantiospecific liposome-water and bovine serum albumin (BSA)-water partition coefficients (Klip/w and KBSA/w, determined at 25 ℃ and 37 ℃, respectively) were measured by equilibrium dialysis for α-, β-, and γ-hexabromocyclododecane (HBCD) and three β-blockers (propranolol, metoprolol, and sotalol). Raman and fluorescence analyses and molecular docking were conducted to provide additional insights into the partitioning process. Results showed α- and β-HBCD displayed stronger enantioselective partitioning to liposomes with the (-)-form, while (-)-α-HBCD, R-(+)-propranolol, R-(+)-metoprolol, and E2-sotalol favored partitioning to BSA compared with their antipodes. Raman spectra revealed α- and γ-HBCD enhanced and reduced the organization of liposome acyl chains, respectively, and polar interactions enhanced the liposome partitioning of β-blockers. Fluorescence spectra indicated the changed tryptophan microenvironment might influence the BSA steric effect toward HBCD, and electrostatic interactions dominated the formation of BSA-β-blocker complexes. Molecular docking results supported the difference in the thermodynamic nature of interaction between the studied enantiomers and BSA.

2-(4-Hydroxyphenyl)benzothiazole dicarboxylate ester TACN chelators for 64Cu PET imaging in Alzheimer's disease.

Herein we report a new series of bifunctional chelators (BFCs) with high affinity for amyloid β aggregates, strong binding affinity towards Cu(II), and favorable lipophilicity for potential blood-brain barrier (BBB) penetration. The alkyl carboxylate ester pendant arms show high binding affinity towards Cu(II). The BFCs form stable 64Cu-radiolabeled complexes and exhibit favorable partition coefficient (log D) values of 0.75-0.95. Among the five compounds tested, 64Cu-YW-1 and 64Cu-YW-13 complexes exhibit significant staining of amyloid plaques in ex vivo autoradiography studies.

The importance of sesquiterpene oxidation products for secondary organic aerosol formation in a springtime hemiboreal forest

Abstract. Secondary organic aerosols (SOAs) formed from biogenic volatile organic compounds (BVOCs) constitute a significant fraction of atmospheric particulate matter and have been recognized to significantly affect the climate and air quality. Atmospheric SOA particulate mass yields and chemical composition result from a complex mixture of oxidation products originating from a diversity of BVOCs. Many laboratory and field experiments have studied SOA particle formation and growth in the recent years. However, a large uncertainty still remains regarding the contribution of BVOCs to SOA. In particular, organic compounds formed from sesquiterpenes have not been thoroughly investigated, and their contribution to SOA remains poorly characterized. In this study, a Filter Inlet for Gases and Aerosols (FIGAERO) combined with a high-resolution time-of-flight chemical ionization mass spectrometer (CIMS), with iodide ionization, was used for the simultaneous measurement of gas-phase and particle-phase oxygenated compounds. The aim of the study was to evaluate the relative contribution of sesquiterpene oxidation products to SOA in a springtime hemiboreal forest environment. Our results revealed that monoterpene and sesquiterpene oxidation products were the main contributors to SOA particles. The chemical composition of SOA particles was compared for times when either monoterpene or sesquiterpene oxidation products were dominant and possible key oxidation products for SOA particle formation were identified for both situations. Surprisingly, sesquiterpene oxidation products were the predominant fraction in the particle phase in some periods, while their gas-phase concentrations remained much lower than those of monoterpene products. This can be explained by favorable and effective partitioning of sesquiterpene products into the particle phase. The SOA particle volatility determined from measured thermograms increased when the concentration of sesquiterpene oxidation products in SOA particles was higher than that of monoterpenes. Overall, this study demonstrates that sesquiterpenes may have an important role in atmospheric SOA formation and oxidation chemistry, in particular during the spring recovery period.

Synchrotron x-ray diffraction and crystal plasticity modeling study of martensitic transformation, texture development, and stress partitioning in deep-drawn TRIP steels

The micromechanics of the formability of a lean duplex TRIP steel was investigated using Synchrotron X-Ray Diffraction (S-XRD) measurements and Crystal Plasticity Finite Element Modeling (CPFEM). Specifically, the effect of the ferrite phase on the reduction of stress concentrations in the martensite phase and the influence of the austenite texture on the distribution of the martensite phase in the deep-drawn duplex TRIP steel were studied in comparison to a TRIP steel case. A series of deep-drawing processes were carried out to examine the sheet formability at ambient temperature, followed by S-XRD evaluations of the phase fraction, texture, and the residual-stress distributions in the deep-drawn cups. The macroscopic residual stress and its partitioning among constituent phases were studied using both S-XRD and CPFEM. In the deep-drawn TRIP steel, large tensile hoop residual stresses concentrated in the strain-induced α’ martensite phase, correlating well with the cracking phenomenon observed. Furthermore, the initial austenite texture influenced the martensite transformation kinetics during the deep-drawing process, resulting in a heterogeneous distribution of the martensite phase fractions around the circumference of the deep-drawn cups, which, in turn, caused an orientation-dependent cracking behavior. In the deep-drawn duplex TRIP steel, the tensile hoop residual stresses in the α’ martensite phase were significantly reduced due to a favorable load partitioning to the ferrite phase, resulting in a better formability.

Identification of quantitative trait loci (QTL) controlling fibre content of sugarcane (Saccharum hybrids spp.)

AbstractThe fibre content (FC) of sugarcane millable stalks is important for both sugar and bioenergy production. Higher FC favours the energy producer while lower FC facilitates the efficient sugar extraction. A molecular marker for FC helps select improved sugarcane cultivars with favourable partitioning of FC for both sugar and energy production industries. A quantitative trait loci (QTL) study was conducted using an enriched linkage map of LCP 85‐384 and FC data from two crop cycles (plant cane and first ratoon) of its self‐progeny population. A total of five unique QTL were identified across both crop cycles and combined, of which three QTL (qFC020, qFC044 and qFC053) were common explained a total of 22.46%, 23.93% and 25.14% of the phenotypic variances for plant cane, first ratoon and combined data, respectively. As FC values increased gradually, the QTL allele combination effect also increased. Using markers linked to these putative common QTL alleles would benefit the breeders to select sugarcane lines for sugar and bioenergy production.

Preferred penetration of active nano-rods into narrow channels and their clustering.

In a channel connected to a reservoir, passive particles prefer staying in the reservoir than the channel due to the entropic effect, as the size of the particles is comparable to that of the channel. Self-propelled rods can exhibit out-of-equilibrium phenomena, and their partition behavior may differ from that of passive rods due to their persistent swimming ability. In this work, the distribution of active nano-rods between the nanoscale channel and reservoir is explored using dissipative particle dynamics. The ratio of the nano-rod concentration in the slit to that in the reservoir, defined as the partition ratio Ψ, is a function of active force, channel width, and rod length. Although passive nano-rods prefer staying in bulk (Ψ < 1), active rods can overcome the entropic barrier and show favorable partition toward narrow channels (Ψ > 1). As the slit width decreases to about the rod's width, active rods entering the slit behave like a quasi-two-dimensional system dynamically. At sufficiently high concentrations and Peclet numbers, nano-rods tend to align and move together in the same direction for a certain time. The distribution (PM) of the cluster size (M) follows a power law, PM ∝ M-2, for small clusters.

Discerning Membrane Steady-State Oxygen Flux by Monte Carlo Markov Chain Modeling.

Molecular oxygen (O2) permeability coefficients for lipid bilayers have previously been estimated using both electron paramagnetic resonance (EPR) oximetry and molecular dynamics simulation data. Yet, neither technique captures the fluxes that exist physiologically. Here, the dynamic steady state is modeled using a stochastic approach built on atomic resolution molecular dynamics simulation data. A Monte Carlo Markov chain technique is used to examine membrane-level fluxes of oxygen in lipid-water systems. At steady state, the concentration of oxygen is found to be higher inside the model membranes than in surrounding water, consistent with the known favorable partitioning of O2 toward the lipid phase. Pure phospholipid 1-palmitoyl,2-oleoyl-phosphatidylcholine (POPC) bilayers accrue ~40% more O2 molecules at steady state than POPC/cholesterol bilayers (1:1 molecular ratio) mimicking the red blood cell membrane. Steady-state levels of oxygen were reached inside both bilayer types within the same timeframe, but depletion of oxygen from the bilayer interior occurred 17% faster for POPC than for POPC/cholesterol. Likewise, first-order rate constants estimated for accrual to steady state were the same for POPC and POPC/cholesterol, at 190μs-1, while first-order rate constants for depletion of the accrued O2 from the bilayers differed, at 95μs-1 for POPC and 81μs-1 for POPC/cholesterol (lower by 15%). These results are consistent with prior experiments in red blood cells (RBCs) with varying membrane cholesterol content, in which additional cholesterol slowed oxygen uptake and release. Further work is needed to understand whether differences in RBC membrane cholesterol content would affect the delivery of oxygen to tissues.

Strain partitioning and back-stress evaluation in harmonic-structure materials

Abstract Heterogenous bimodal harmonic-structure (HS) materials are interesting because of excellent structural efficiency. In this work, we present a simple yet powerful analytical model allowing to evaluate strain partitioning between coarse- and ultrafine- grain (CG and UFG, respectively) structure components in HS materials and to estimate the magnitude of back-stress forming at their interphases. The analysis of experimental results on pure nickel using this model shows that HS promotes a favourable strain partitioning between CG and UFG components and the build-up of back-stress in the vicinity of their interfaces allowing the material performance to exceed expectations from the rule of mixtures.

Deformation mechanics in inclined, brittle-ductile transpression zones: Insights from 3D finite element modelling

Most natural examples of transpression zones developed at oblique convergence regime are inherently 3D and have inclined boundaries. A 3D finite element model with an elasto-plastic rheology is used to investigate the structural and mechanical evolution of inclined transpression zones in a rock sequence above a frictional basal detachment. Inelastic constitutive relationships allow permanent strains to develop in response to the applied loads. FE-modelling results show that oblique convergence is accommodated by discrete deformation at the main pre-existing inclined faults (=70°) and by distributed brittle and ductile deformation at active blocks. Oblique contraction at the active blocks resulted mainly in layer-parallel shortening, orthogonal to the model outer boundaries, whereas thickening in the horizontal and vertical directions was accommodated via layer-parallel, fault strike-parallel extension and up-dip extrusion (i.e., inclined extrusion). Lateral extrusion should have compensated the rest and/or volume loss took place. Folding and thickening of the mobile backstop produced a non-cylindrical, asymmetric, bi-vergent anticline where permanent strains developed principally in the steep forelimb. Secondary, conjugate fault zones also accommodate oblique slip and contribute to uplift. Displacement vectors within the transpression zone are rotated counter-clockwise (ca. 20°–30°) with respect to vectors in the fixed backstop. Areas with higher rotation values seem to correlate with those showing higher ellipticity values. The presence of pre-existing faults favored strain partitioning from the onset of deformation. FE-modelling results compared with analytical, natural example, and analogue modelling results show that our mechanical modelling can overall match inclined transpression zones geometry that present different modes of strain partitioning and localisation.