Titanium based cranial reconstruction using incremental sheet forming

In this paper, we report recent work in cranial plate manufacturing using incremental sheet forming (ISF) process. With a typical cranial shape, the ISF process was used to manufacture the titanium cranial shape by using different ISF tooling solutions with and without backing plates. Detailed evaluation of the ISF process including material deformation and thinning, geometric accuracy and surface finish was conducted by using a combination of experimental testing and Finite Element (FE) simulation. The results show that satisfactory cranial shape can be achieved with sufficient accuracy and surface finish by using a feature based tool path generation method and new ISF tooling design. The results also demonstrate that the ISF based cranial reconstruction has the potential to achieve considerable lead time reduction as compared to conventional methods for cranial plate manufacturing. This outcome indicates that there is a potential for the ISF process to achieve technological advances and economic benefits as well as improvement to quality of life

Schistosomes Induce Regulatory Features in Human and Mouse CD1dhi B Cells: Inhibition of Allergic Inflammation by IL-10 and Regulatory T Cells

Chronic helminth infections, such as schistosomes, are negatively associated with allergic disorders. Here, using B cell IL-10-deficient mice, Schistosoma mansoni-mediated protection against experimental ovalbumin-induced allergic airway inflammation (AAI) was shown to be specifically dependent on IL-10-producing B cells. To study the organs involved, we transferred B cells from lungs, mesenteric lymph nodes or spleen of OVA-infected mice to recipient OVA-sensitized mice, and showed that both lung and splenic B cells reduced AAI, but only splenic B cells in an IL-10-dependent manner. Although splenic B cell protection was accompanied by elevated levels of pulmonary FoxP3+ regulatory T cells, in vivo ablation of FoxP3+ T cells only moderately restored AAI, indicating an important role for the direct suppressory effect of regulatory B cells. Splenic marginal zone CD1d+ B cells proved to be the responsible splenic B cell subset as they produced high levels of IL-10 and induced FoxP3+ T cells in vitro. Indeed, transfer of CD1d+ MZ-depleted splenic B cells from infected mice restored AAI. Markedly, we found a similarly elevated population of CD1dhi B cells in peripheral blood of Schistosoma haematobium-infected Gabonese children compared to uninfected children and these cells produced elevated levels of IL-10. Importantly, the number of IL-10-producing CD1dhi B cells was reduced after anti-schistosome treatment. This study points out that in both mice and men schistosomes have the capacity to drive the development of IL-10-producing regulatory CD1dhi B cells and furthermore, these are instrumental in reducing experimental allergic inflammation in mice

Low Enzymatic Activity Haplotypes of the Human Catechol-O-Methyltransferase Gene: Enrichment for Marker SNPs

Catechol-O-methyltransferase (COMT) is an enzyme that plays a key role in the modulation of catechol-dependent functions such as cognition, cardiovascular function, and pain processing. Three common haplotypes of the human COMT gene, divergent in two synonymous and one nonsynonymous (val158met) position, designated as low (LPS), average (APS), and high pain sensitive (HPS), are associated with experimental pain sensitivity and risk of developing chronic musculoskeletal pain conditions. APS and HPS haplotypes produce significant functional effects, coding for 3- and 20-fold reductions in COMT enzymatic activity, respectively. In the present study, we investigated whether additional minor single nucleotide polymorphisms (SNPs), accruing in 1 to 5% of the population, situated in the COMT transcript region contribute to haplotype-dependent enzymatic activity. Computer analysis of COMT ESTs showed that one synonymous minor SNP (rs769224) is linked to the APS haplotype and three minor SNPs (two synonymous: rs6267, rs740602 and one nonsynonymous: rs8192488) are linked to the HPS haplotype. Results from in silico and in vitro experiments revealed that inclusion of allelic variants of these minor SNPs in APS or HPS haplotypes did not modify COMT function at the level of mRNA folding, RNA transcription, protein translation, or enzymatic activity. These data suggest that neutral variants are carried with APS and HPS haplotypes, while the high activity LPS haplotype displays less linked variation. Thus, both minor synonymous and nonsynonymous SNPs in the coding region are markers of functional APS and HPS haplotypes rather than independent contributors to COMT activity

Functional COMT Val158Met Polymorphism, Risk of Acute Coronary Events and Serum Homocysteine: The Kuopio Ischaemic Heart Disease Risk Factor Study

http://deepblue.lib.umich.edu/bitstream/2027.42/55410/1/Voutilainen S, Functional COMT Val158Met polymorphism, 2007.pd

Socio-semiotics and the symbiosis of humans, horses, and objects in later Iron Age Britain

This is an Accepted Manuscript of an article published by Taylor & Francis in Archaeological Journal on 14/03/2018, available online: https://www.tandfonline.com/doi/full/10.1080/00665983.2018.1441105Using an approach derived from material culture studies and semiotics, this paper addresses possible relationships between humans and horses in the British Iron Age.Through a study of the dominance of horse imagery found on Iron Age British coinage, specifically the Western coinage traditionally attributed to the 'Dobunni', the author explores how it may reflect possible relationships between humans and horses and their personhood therein. Drawing on wider faunal and metalwork evidence it is argued that these coins could be interpreted as a manifestation of the complex perspectives surrounding a symbiotic relationship between humans and horses

Verbi sintagmatici in italiano antico e moderno: un\u2019analisi corpus-based

Il presente contributo analizza un tipo particolare di polirematica verbale dell\u2019italiano in due diversi stati di lingua, in italiano moderno (it. mod.) e in italiano antico (it. ant.). Le polirematiche in questione sono costruzioni come saltare fuori, mettere sotto, che verranno qui chiamate, col termine proposto da Raffaele Simone (1997, ripreso in Simone 2008), verbi sintagmatici (VS). Lo studio trae spunto da un lavoro di individuazione e datazione della prima attestazione di tali forme che \ue8 stato svolto ai fini di un trattamento lessicografico in un dizionario monolingue, il Sabatini Coletti (2007). Qui ci si propone di capire in che misura i VS sono presenti in it. ant.1 (cf. Masini 2006a), e soprattutto se si rilevano differenze sintattiche e semantiche fra i VS dell\u2019it. mod. e quelli dell\u2019it. ant. L\u2019analisi \ue8 stata svolta con l\u2019ausilio di corpora (cf. \ua72.1). I sensi dei verbi sono stati individuati empiricamente attraverso l\u2019analisi delle concordanze, secondo un approccio \u2039costruzionale\u203a alla definizione del senso in base al quale il significato degli elementi lessicali \ue8 modulato in contesto (Pustejovsky 1995)

Large-scale engineering of hiPSC-derived nephron sheets and cryopreservation of their progenitors

Background: The generation of human induced pluripotent stem cells (hiPSCs) has opened a world of opportunities for stem cell-based therapies in regenerative medicine. Currently, several human kidney organoid protocols are available that generate organoids containing kidney structures. However, these kidney organoids are relatively small ranging up to 0.13 cm(2) and therefore contain a small number of nephrons compared to an adult kidney, thus defying the exploration of future use for therapy.Method: We have developed a scalable, easily accessible, and reproducible protocol to increase the size of the organoid up to a nephron sheet of 2.5 cm(2) up to a maximum of 12.6 cm(2) containing a magnitude of nephrons.Results: Confocal microscopy showed that the subunits of the nephrons remain evenly distributed throughout the entire sheet and that these tissue sheets can attain similar to 30,000-40,000 glomerular structures. Upon transplantation in immunodeficient mice, such nephron sheets became vascularized and matured. They also show reuptake of injected low-molecular mass dextran molecules in the tubular structures, indicative of glomerular filtration. Furthermore, we developed a protocol for the cryopreservation of intermediate mesoderm cells during the differentiation and demonstrate that these cells can be successfully thawed and recovered to create such tissue sheets.Conclusion: The scalability of the procedures, and the ability to cryopreserve the cells during differentiation are important steps forward in the translation of these differentiation protocols to future clinical applications such as transplantable auxiliary kidney tissue.Nephrolog