Thermal, mechanical and chemical analysis of poly(vinyl alcohol) multifilament and braided yarns

Poly(vinyl alcohol) (PVA) in multifilament and braided yarns (BY) forms presents great potential for the design of numerous applications. However, such solutions fail to accomplish their requirements if the chemical and thermomechanical behaviour is not sufficiently known. Hence, a comprehensive characterisation of PVA multifilament and three BY architectures (6, 8, and 10 yarns) was performed involving the application of several techniques to evaluate the morphological, chem- ical, thermal, and mechanical features of those structures. Scanning electron microscopy (SEM) was used to reveal structural and morphological information. Differential thermal analysis (DTA) pointed out the glass transition temperature of PVA at 76 °C and the corresponding crystalline melt- ing point at 210 °C. PVA BY exhibited higher tensile strength under monotonic quasi-static loading in comparison to their multifilament forms. Creep tests demonstrated that 6BY structures present the most deformable behaviour, while 8BY structures are the least deformable. Relaxation tests showed that 8BY architecture presents a more expressive variation of tensile stress, while 10BY of- fered the least. Dynamic mechanical analysis (DMA) revealed storage and loss moduli curves with similar transition peaks for the tested structures, except for the 10BY. Storage modulus is always four to six times higher than the loss modulus.This work was funded by European Regional Development funds (FEDER) through the Competitiveness and Internationalization Operational Program (POCI)—COMPETE andby Na-tional Funds through Portuguese Fundação para a Ciência e Tecnologia (FCT) under the project UID/EMS/50022/2020, UID/EEA/04436/2019 andUID/ CTM/00264/2019. Andrea Zille acknowledges financial support of the FCT through the project PTDC/CTM-TEX/28295/2017,and Nuno Dourado acknowledges financial support of the FCT through the project PTDC/EME-SIS/28225/2017. M.F.S.M. de Moura acknowledges the ‘Laboratório Associado de Energia, Transportes e Aeronáutica’ (LAETA) for the financial support

Osteosynthesis metal plate system for bone fixation using bicortical screws: numerical–experimental characterization

This study reports the numerical and experimental characterization of a standard immobilization system currently being used to treat simple oblique bone fractures of femoral diaphyses. The procedure focuses on the assessment of the mechanical behavior of a bone stabilized with a dynamic compression plate (DCP) in a neutralization function, associated to a lag screw, fastened with surgical screws. The non-linear behavior of cortical bone tissue was revealed through four-point bending tests, from which damage initiation and propagation occurred. Since screw loosening was visible during the loading process, damage parameters were measured experimentally in independent pull-out tests. A realistic numerical model of the DCP-femur setup was constructed, combining the evaluated damage parameters and contact pairs. A mixed-mode (I+II) trapezoidal damage law was employed to mimic the mechanical behavior of both the screw–bone interface and bone fractures. The numerical model replicated the global behavior observed experimentally, which was visible by the initial stiffness and the ability to preview the first loading peak, and bone crack satisfactorily.This research was funded by the Portuguese Foundation for Science and Technology (FCT), grant numbers SFRH/BD/143736/2019, UIDB/CVT/00772/2020, LA/P/0059/2020, UIDB/04033/2020, PTDC/EME-SIS/28225/2017, UID/EEA/04436/2019 and Laboratório Associado de Energia, Transportes e Aeronáutica (LAETA), grant number UID/EMS/50022/2020

Autologous humanized PDX modeling for immuno-oncology recapitulates features of the human tumor microenvironment.

BACKGROUND: Interactions between immune and tumor cells are critical to determining cancer progression and response. In addition, preclinical prediction of immune-related drug efficacy is limited by interspecies differences between human and mouse, as well as inter-person germline and somatic variation. To address these gaps, we developed an autologous system that models the tumor microenvironment (TME) from individual patients with solid tumors. METHOD: With patient-derived bone marrow hematopoietic stem and progenitor cells (HSPCs), we engrafted a patient\u27s hematopoietic system in MISTRG6 mice, followed by transfer of patient-derived xenograft (PDX) tissue, providing a fully genetically matched model to recapitulate the individual\u27s TME. We used this system to prospectively study tumor-immune interactions in patients with solid tumor. RESULTS: Autologous PDX mice generated innate and adaptive immune populations; these cells populated the TME; and tumors from autologously engrafted mice grew larger than tumors from non-engrafted littermate controls. Single-cell transcriptomics revealed a prominent vascular endothelial growth factor A (VEGFA) signature in TME myeloid cells, and inhibition of human VEGF-A abrogated enhanced growth. CONCLUSIONS: Humanization of the interleukin 6 locus in MISTRG6 mice enhances HSPC engraftment, making it feasible to model tumor-immune interactions in an autologous manner from a bedside bone marrow aspirate. The TME from these autologous tumors display hallmarks of the human TME including innate and adaptive immune activation and provide a platform for preclinical drug testing

Laminar and columnar development of barrel cortex relies on thalamocortical neurotransmission

A dynamic interplay between intrinsic regional molecular cues and extrinsic factors from the thalamus shape multiple features of early cortical development. It remains uncertain and controversial, however, whether the initial formation of cortical columns depends on neuronal activity, and there is little evidence that cortical lamination or neuronal differentiation is influenced by extrinsic activity. We examined the role of thalamic-derived factors in cortical development by selectively eliminating glutamatergic synaptic transmission from thalamocortical neurons in mice and found that eliminating thalamocortical neurotransmission prevented the formation of "barrel" columns in somatosensory cortex. Interestingly, based on cytoarchitectonic criteria and genetic markers, blocking thalamocortical neurotransmission also perturbed the development of superficial cortical lamina and the morphologic development of neurons. These experiments demonstrate that barrels and aspects of the layer-dependent pattern of cortical cytoarchitecture, gene expression, and neuronal differentiation depend on thalamocortical neurotransmission, extending the apparent influence of extrinsic, presumably activity-dependent factors, on cortical developmen

Osteosynthesis Metal Plate System for Bone Fixation Using Bicortical Screws: Numerical–Experimental Characterization

This study reports the numerical and experimental characterization of a standard immobilization system currently being used to treat simple oblique bone fractures of femoral diaphyses. The procedure focuses on the assessment of the mechanical behavior of a bone stabilized with a dynamic compression plate (DCP) in a neutralization function, associated to a lag screw, fastened with surgical screws. The non-linear behavior of cortical bone tissue was revealed through four-point bending tests, from which damage initiation and propagation occurred. Since screw loosening was visible during the loading process, damage parameters were measured experimentally in independent pull-out tests. A realistic numerical model of the DCP-femur setup was constructed, combining the evaluated damage parameters and contact pairs. A mixed-mode (I+II) trapezoidal damage law was employed to mimic the mechanical behavior of both the screw–bone interface and bone fractures. The numerical model replicated the global behavior observed experimentally, which was visible by the initial stiffness and the ability to preview the first loading peak, and bone crack satisfactorily

Non-epithelial stem cells and cortical interneuron production in the human ganglionic eminences

GABAergic cortical interneurons underlie the complexity of neural circuits and are particularly numerous and diverse in humans. In rodents, cortical interneurons originate in the subpallial ganglionic eminences, but their developmental origins in humans are controversial. We characterized the developing human ganglionic eminences and found that the subventricular zone (SVZ) expanded massively during the early second trimester, becoming densely populated with neural stem cells and intermediate progenitor cells. In contrast with the cortex, most stem cells in the ganglionic eminence SVZ did not maintain radial fibers or orientation. The medial ganglionic eminence exhibited unique patterns of progenitor cell organization and clustering, and markers revealed that the caudal ganglionic eminence generated a greater proportion of cortical interneurons in humans than in rodents. On the basis of labeling of newborn neurons in slice culture and mapping of proliferating interneuron progenitors, we conclude that the vast majority of human cortical interneurons are produced in the ganglionic eminences, including an enormous contribution from non-epithelial SVZ stem cells