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We develop strategies to improve the crystallinity and mechanical properties of PLA, without compromising its hydrolytic degradation behaviour. These include reactive extrusion, and addition of a novel type of cross-linked PLA-based nucleating agent (biofiller, BF). The crystallinity is further increased by annealing at temperatures between 80 and 120 °C. Maximum crystallinities of 55% were achieved in the presence of 7 wt% of the BF at 100 °C. The increases in crystallinity upon annealing translated to a 42% increase in the flexural modulus relative to the base PLA, while impact strength was maintained. Annealing temperatures of 100 °C are optimum, because of thermal degradation taking place above this temperature. Annealing also results in increases in the glass transition temperatures followed by improvements in the heat deflection temperature by as much as 7 °C. The nucleated and annealed PLA degraded to the same extent as the untreated PLA, when subjected to hydrolysis over a 12-week period. Image 1 • Reactive extrusion and nucleating agents were used in combination with annealing to improve the properties of PLA. • A cross-linked PLA-based biofiller acts as a very effective nucleating agent. • Significant improvements in crystallinity and flexural modulus were achieved. • Annealing resulted in an increase in the glass transition temperature, followed by an increase in HDT. • The modified PLA maintained its degradability under hydrolysis. [ABSTRACT FROM AUTHOR]

Abstract The chemical modification of polylactic acid (PLA) and related polyesters by peroxide-initiated grafting of multifunctional allylic and acrylic monomers is described. Solvent-free, melt-state reactions of PLA and triallyl trimesate (TAM) are shown to be remarkably efficient compared to analogous reactions of polyolefins such as poly(ethylene-co-octene) (EOC), requiring very low reagent loadings to produce a long chain branched (LCB) architecture. A systematic study of potential transesterification chemistry confirms that ionic reactions do not contribute significantly to PLA reactivity under typical grafting conditions. Further explorations of H-atom abstraction and monomer addition yields demonstrate that PLA is relatively unreactive toward the radical reactions that support LCB production. Careful examination of the solubility of coagent intermediates reveal dramatic differences in oligomer solubility between a hydrocarbon system and an ester-based matrix. Whereas TAM conversion in hydrocarbon leads to a precipitation polymerization that removes coagent from solution, reactions conducted in the polyester do not incur losses of oligomeric intermediates, indicating that the ability of PLA to retain multi-functional intermediates is the underlying cause of its remarkable LCB grafting yields. Graphical abstract Image 1 Highlights • Coagent branching processes are more efficient for PLA than polyolefins. • PLA is a poor H-atom donor and a low-yield grafting substrate. • PLA's ability to solvate coagent oligomers underlies its branching reactivity. [ABSTRACT FROM AUTHOR]

Abstract Reactive extrusion using dicumyl peroxide (DCP) and a tri-functional coagent, triallyl trimesate (TAM) is implemented to introduce long-chain branching (LCB) in poly(lactic acid) (PLA). The effects of this modification on the long-term hydrolysis of PLA are assessed by monitoring the mass, molar mass distributions, and thermal properties of specimens exposed to hydrolytic degradation at a temperature of 60 °C. A slow initial rate of mass loss coupled with an immediate and rapid loss in molar mass are characteristic of a bulk erosion mechanism. Significant loss is observed in all molar mass averages within the first 20 days. In LCB PLA the most drastic decrease was observed in the z-average molar mass, M z , as a result of the cleavage of the LCB segments from the polymer chain. Degradation induced crystallinity is observed in all formulations, attributed to the combined influence of annealing and the plasticizing effect of water. Although the hydrolysis profile is altered, reactive modification does not affect negatively the degradability of LCB PLA over a 12-week period, suggesting that these modified PLAs can be used in commodity applications that require degradable polymers. Highlights • The hydrolysis of long chain branched poly(lactic acid) (LCB PLA) is investigated. • Preferential degradation of low and high molar mass segments is observed in LCB PLA. • Specimen mass loss and molar mass loss profiles confirm a bulk erosion mechanism. • Increased crystallinity results from a combined annealing and plasticizing effect. • The presence of LCB in PLA does not negatively affect its degradability. [ABSTRACT FROM AUTHOR]

Charles Franklin Kettering (1876e1958) was an inventor well-known during his lifetime, earning 186 US patents. His most notable invention was the automobile electric starter which put an end to the difficult and dangerous practice of hand cranking. Some of his later workdleaded gasoline and Freondwas controversial and had unintended environmental consequences. He led both the National Inventors' Council and the National Patent Planning Commission. Kettering characterized himself as "just a plain old inventor," but he was a shrewd businessman. He is still remembered fondly by scientists and staff at the General Motors R&D Center he founded in 1920. [ABSTRACT FROM AUTHOR]

Abstract: Objective: to explore women’s experience of living with a ‘high-risk’ pregnancy following a perinatal loss. Design: a feminist phenomenological methodology provided the framework for the research study. Participants and setting: the experience of ‘high-risk’ pregnancy following perinatal loss of seven women receiving care at a tertiary health centre in Atlantic Canada was explored by way of conversational interviews and reflective journaling. Findings: four themes emerged through thematic analysis and researcher interpretation: (1) understanding the meaning in the label of ‘high-risk’ pregnancy, (2) relational engagement with the unborn infant, (3) insight and acceptance of the influence of previous loss, and (4) essentiality of information. Taken together, these four themes represent the storied text embedded in the research study. The focus of attention in this article is based solely on the first theme, understanding the meaning in the label of ‘high-risk’ pregnancy, in so far as this fosters an ability to attend to the interpretive text in the methodological manner appropriate to phenomenological inquiry. Conclusions and implications: although previous research indicates that the label of ‘high-risk’ in pregnancy is often associated with increased anxiety and fear, findings from this study suggest that a ‘high-risk’ pregnancy following perinatal loss results in women embracing the ‘high-risk’ label. By recognising the possibility that women experiencing ‘high-risk’ pregnancy following perinatal loss may perceive the label of ‘high-risk’ pregnancy in a positive way, nurses, midwives and other health-care providers may begin to alter their practices when caring for these women in current health-care environments. [ABSTRACT FROM AUTHOR]

• TCRα/β depletion and sirolimus do not prevent GvHD after MHC-matched alloHSCT in Mauritian cynomolgus macaques. • Cyclophosphamide allows mixed chimerism without GvHD after TCRα/β-depleted MHC-matched alloHSCT. • The Mauritian macaque model allows for alloHSCT across reproducible MHC barriers. Allogeneic hematopoietic stem cell transplantation (alloHSCT) is a potentially curative treatment for hematologic cancers and chronic infections such as human immunodeficiency virus (HIV). Its success in these settings is attributed to the ability of engrafting immune cells to eliminate cancer cells or deplete the HIV reservoir (graft-versus-host effect [GvHE]). However, alloHSCT is commonly associated with graft-versus-host diseases (GvHDs) causing significant morbidity and mortality, thereby requiring development of novel allogeneic HSCT protocols and therapies promoting GvHE without GvHD using physiologically relevant preclinical models. Here we evaluated the outcomes of major histocompatibility complex-matched T-cell receptor α/β-depleted alloHSCT in Mauritian cynomolgus macaques (MCMs). Following T-cell receptor α/β depletion, bone marrow cells were transplanted into major histocompatibility complex-identical MCMs conditioned with total body irradiation. GvHD prophylaxis included sirolimus alone in two animals or tacrolimus with cyclophosphamide in another two animals. Posttransplant chimerism was determined by sequencing diagnostic single-nucleotide polymorphisms to quantify the amounts of donor and recipient cells present in blood. Animals treated posttransplant with sirolimus developed nearly complete chimerism with acute GvHD. In the cyclophosphamide and tacrolimus treatment group, animals developed mixed chimerism without GvHD, with long-term engraftment observed in one animal. None of the animals developed cytomegalovirus infection. These studies indicate the feasibility of alloHSCT engraftment without GvHD in an MHC-identical MCM model following complete myeloablative conditioning and anti-GvHD prophylaxis with posttransplant cyclophosphamide and tacrolimus. Further exploration of this model will provide a platform for elucidating the mechanisms of GvHD and GvHE and for testing novel alloHSCT modalities for HIV infection. [ABSTRACT FROM AUTHOR]

Shear wave elasticity imaging has shown promise in evaluation of the pregnant cervix. Changes in shear wave group velocity have been attributed exclusively to changes in stiffness. This assumes homogeneity within the region of interest and purely elastic tissue behavior. However, the cervix is structurally/microstructurally heterogeneous and viscoelastic. We therefore developed strategies to investigate these complex tissue properties. Shear wave elasticity imaging was performed ex vivo on 14 unripened and 13 misoprostol-ripened cervix specimens from rhesus macaques. After tests of significant and uniform shear wave displacement, as well as reliability of estimates, group velocity decreased significantly from the distal (vaginal) to proximal (uterine) end of unripened, but not ripened, specimens. Viscosity was quantified by the slope of the phase velocity versus frequency. Dispersion was observed in both groups (median: 5.5 m/s/kHz, interquartile range: 1.5-12.0 m/s/kHz), also decreasing toward the proximal cervix. This work suggests that comprehensive assessment of complex tissues such as cervix requires consideration of structural heterogeneity and viscosity. [ABSTRACT FROM AUTHOR]

Genome editing of somatic cells via clustered regularly interspaced short palindromic repeats (CRISPR) offers promise for new therapeutics to treat a variety of genetic disorders, including neurological diseases. However, the dense and complex parenchyma of the brain and the post-mitotic state of neurons make efficient genome editing challenging. In vivo delivery systems for CRISPR-Cas proteins and single guide RNA (sgRNA) include both viral vectors and non-viral strategies, each presenting different advantages and disadvantages for clinical application. We developed non-viral and biodegradable PEGylated nanocapsules (NCs) that deliver preassembled Cas9-sgRNA ribonucleoproteins (RNPs). Here, we show that the RNP NCs led to robust genome editing in neurons following intracerebral injection into the healthy mouse striatum. Genome editing was predominantly observed in medium spiny neurons (>80%), with occasional editing in cholinergic, calretinin, and parvalbumin interneurons. Glial activation was minimal and was localized along the needle tract. Our results demonstrate that the RNP NCs are capable of safe and efficient neuronal genome editing in vivo. [ABSTRACT FROM AUTHOR]