Structural Reconstitution in Polymer Matrix Composites and its Significance for Performance and Functionality

Using a combination of inelastic light scattering and atomic scale simulations, we investigated the structure and properties of thermoset polymeric materials, while reversibly removed from their thermodynamic ground state. In one set of experiments we measured the adiabatic elastic modulus of epoxy in situ, while undergoing polymerization and cross-linking reactions. Throughout the experiment, the degree of cure was monitored using Raman light scattering (RLS), while the adiabatic modulus was measured using Brillouin light scattering (BLS). Since these are both inelastic light scattering techniques, RLS and BLS are carried out concurrently, i.e., the respective spectra were collected from the same location in the specimen and at the same time, allowing us to directly compare the modulus with the degree. As illustrate in Fig. 1, we find that the adiabatic modulus of the polymer evolves non-uniquely as a function of cure degree; it strongly depends on the cure rate.1 We can explain the observed behavior by taking into account that two mechanisms contribute to the increase in the elastic modulus of the material during curing. First, there is the formation of covalent bonds in the network during the curing process. While the formation of these bonds lowers the electronic structure energy of the system, atoms are still somewhat removed from their ground state positions. Hence, in a second process the structure undergoes structural reconstitution toward a more optimally packed configuration of the network, which enhances non-bonding interactions. Both contributions are apparent in the adiabatic modulus derived from Brillouin scattering, as it reflects the elastic response of the polymer network in thermodynamic equilibrium. To further ascertain the notion of structural reconstitution, which is affecting only non-bonding interactions, we subject a fully cured epoxy to various degrees of strain, well within the elastic regime, using a miniature tensile tester mounted in the beam path of the light scattering setup, while simultaneously measuring the adiabatic and isothermal elastic moduli as a function of the applied strain. We find that straining this polymer network is equivalent to forming the bonds between its atoms while these are in locations displaced from the structural ground state. The fact that the polymer structure can reconstitute after undergoing appreciable deformation opens new ways of thinking about its applicability in terms of functionality and performance. Molecular simulations provide additional insights into the underlying mechanisms, and delineate the blueprints for materials design.2 Please click Additional Files below to see the full abstract

Cure kinetics and interfacial phenomena in polymer matrix composites

Polymer matrix composites with textile reinforcement are used in a wide range of aerospace and industrial applications. Continuum mechanical predictions of the composite behaviors have been inaccurate, possibly because of the lack of information with regard to polymer materials properties, especially near the interfaces with the reinforcing fibers. Concurrent micro-Brillouin and Raman light scattering provides sufficiently high spatial resolution to probe the mechanical properties and chemical composition of the interphase regions of the matrix, without interfering with the thermo-mechanical equilibrium of the material. Using this technique, we mapped the elastic properties of epoxy resin in between and within the fiber tows of a composite, revealing that the modulus exhibits a marked spatial inhomogeneity in proximity of fibers, with a decrease of up to 5% compared to that of bulk epoxy resin in the regions of highest fiber density (see Fig. 1).1 We estimate that it would take a deformation of four times the failure strain to cause such a change in modulus based on residual stresses. Hence, the origin must lie elsewhere. Using the same methodology, we then monitored the elastic properties in situ, during epoxy cure under different thermal and chemical conditions. We find that depending on the reaction rate, the elastic modulus evolves differently as a function of the degree of cure: the faster the rate, the more the modulus lags behind of what would be expected from the amount of cross-links that have formed according to the degree of cure. This is because the overall modulus is based on the stiffness resulting from bonded and non-boned network connections, the latter arising the optimization of network packing that ensues after a slow structural relaxation.2 Provided enough time, the same final modulus is reached, unless network formation is impeded by the under-supply of hardener. To interpret and enhance these results, experiments are complemented with molecular dynamics simulations of the interface. Accordingly, the one-sided confinement of polymer adjacent to a fiber surface results in clearly detectable structural features, e.g., layering and densification, as well as changes in the elastic properties within a spatial extent that reaches significantly beyond the region of distinguishable structural features. In conclusion, we attribute the inhomogeneity in mechanical properties to a combination of hardener depletion and an impediment of structural relaxation due to unilateral confinement that lowers the extent and effectiveness of non-bonded interaction

Extending HIV/AIDS-prevention efforts in Kenya: primary schools as community-based organizations

The question of whether primary schools in Kenya can take on community-based activities beyond their day-to-day functioning, emerged from a larger HIV/AIDS education and prevention program—Primary School Action for Better Health (PSABH). The methodology involved both quantitative and qualitative approaches. The quantitative component was based on 163 schools, which were involved in the larger PSABH program. Qualitative analysis was based on consultative meetings with twenty key informants and follow-up focus-group discussions with representatives from eight schools involved in community-based activities. The results suggest that in this context schools have strong community ties, with most of them willing to take up community-based organization (CBO)-related activities beyond their day-to-day functioning. Schools were more likely to take on CBO-related activities, such as support for orphans, if they had a higher proportion of female teachers, a school sponsor that was involved in the selection of the head teacher, more Parent Teacher Association meetings, and if HIV/AIDS was incorporated into community festivals. A school’s involvement was reinforced if it performed well in the Kenya Certificate of Primary Education examination, if the school’s head teacher was committed, and if most of the teachers were from the local community. Despite several challenges, the findings point to the need to take schools seriously in their duty as CBOs which can have a positive impact in mitigating not only the effects of HIV/AIDS, but also other community-development activities in ravaged sub-Saharan African countries. The proposed expansion of PSABH further puts Kenyan schools in a stronger position to be involved in their communities through CBO-related activities.

Thermal Conductance in Cross-linked Polymers: Effects of Non-Bonding Interactions

Weak interchain interactions have been considered to be a bottleneck for heat transfer in polymers, while covalent bonds are believed to give a high thermal conductivity to polymer chains. For this reason, cross-linkers have been explored as a means to enhance polymer thermal conductivity; however, results have been inconsistent. Some studies show an enhancement in the thermal conductivity for polymers upon cross-linking, while others show the opposite trend. In this work we study the mechanisms of heat transfer in cross-linked polymers in order to understand the reasons for these discrepancies, in particular examining the relative contributions of covalent (referred to here as “bonding”) and nonbonding (e.g., van der Waals and electrostatic) interactions. Our results indicate cross-linkers enhance thermal conductivity primarily when they are short in length and thereby bring polymer chains closer to each other, leading to increased interchain heat transfer by enhanced nonbonding interactions between the chains (nonbonding interactions being highly dependent on interchain distance). This suggests that enhanced nonbonding interactions, rather than thermal pathways through cross-linker covalent bonds, are the primary transport mechanism by which thermal conductivity is increased. We further illustrate this by showing that energy from THz acoustic waves travels significantly faster in polymers when nonbonding interactions are included versus when only covalent interactions are present. These results help to explain prior studies that measure differing trends in thermal conductivity for polymers upon cross-linking with various species

A CRUK First-in-human Phase I Trial of LY3143921, a Novel CDC7 Inhibitor, in OPatients with Advanced Solid Tumors

Background: CDC7, a protein with key roles in regulating cell-cycle progression is often over-expressed in malignant cells, particularly those with TP53 mutations. LY3143921, an orally administered ATP-competitive CDC7 inhibitor, demonstrated favorable pre-clinical anti-cancer activity in colorectal cancer (CRC) and squamous non-small cell lung cancer (sqNSCLC), particularly in TP53 mutant models. Methods: Phase Ia (dose escalation) recruited patients (pts) with advanced solid tumors enriched for malignancies associated with TP53 mutation. Pts received LY3143921 OD or BD continuously on a 21-day schedule, using an accelerated 3+3 escalation design, starting at 30 mg OD. Phase Ib recruited pts with CRC or sqNSCLC treated continuously at RP2D, or pts with other advanced tumors treated at RP2D on days 1-3 every 7 days. Radiological assessment was performed every 2 cycles initially. Pts in phase Ib could consent to pre- and on-treatment skin +/- tumor biopsies. Primary objectives: assess safety/tolerability and determine MTD and RP2D of LY3143921. Secondary objectives: evaluate preliminary efficacy and pharmacokinetic (PK) profile of LY3143921. Exploratory objective: correlate efficacy to baseline molecular/genetic alterations, including TP53 mutation and measure markers including pMCM2 in pre- and on- treatment tumor and skin samples. Results: 68 pts were recruited and 67 treated (38 phase Ia, 29 phase Ib). Most frequent drug-related CTCAEs (all grades): nausea (75%), orthostatic hypotension (50%), vomiting (47%), fatigue (45%) & diarrhea (44%). Grade 3-4 LY3143921 related AEs occurred in 17 pts. In phase Ia 8 DLTs occurred in 5 pts (G3 nausea, vomiting, fatigue & hyponatraemia and G2 diarrhea, anorexia & lethargy). RP2D was 360 mg BD (continuous non-fasted dosing schedule). 37 pts were evaluable for radiological response with no complete or partial responses seen, and stable disease (SD) was observed in 24 pts (65%). In phase Ia 3 pts achieved long term SD of 1, 2.5 and 3+ years duration. For evaluable pts treated in phase Ib, SD was seen in 8/12 CRC pts, 1/2 sqNSCLC pts and 2/2 pts treated with the intermittent schedule (median duration 15 weeks, range 6-18+). 2 pts remain on-study. Recruitment ceased due to lack of radiological response according to RECIST. Dose-dependent increases in LY3143921 exposure (Cmax & AUC0-24) were seen. IHC analyses of skin biopsies demonstrated reductions in pMCM2, indicating on-target activity of LY3143921. Pre-clinical testing of combination with standard of care agents is ongoing. Additional PD and PK data will be presented. Conclusions: LY3143921 is well tolerated, exhibits dose-dependent increases in plasma exposure and demonstrates evidence of target inhibition. Significant monotherapy clinical activity was not observed; further analyses should investigate potential predictive response biomarkers and rational combination approaches. Clinical trial information: NCT03096054