Material selection for a new type of fire extinguisher

Nowadays safety is a hot topic, damage inflicted to human beings is intolerable. Fire safety is a big concern in industrial areas, but in residential areas a lot less precautions are in place. Therefore a new type of fire extinguisher should be developed that should encourage the installation of fire extinguishers in commercial environments and at home. The design of this fire extinguisher has to answer to a lot of demands. From a legal point of view, the extinguisher has to comply with the PED regulations and the EN 3 standard. Extra demands are, given the purpose, superb performance, great ergonomics and an attractive visual design. One of the steps in the design process is to make a material selection based on needed and desired properties of materials. Also the possible processes for manufacturing are an important parameter

Genetic Variability Study in a Wide Germplasm of Domesticated Peach Through High Throughput

Peach (Prunus persica (L.) Batsch) is one of the most economically important fruit crops in temperate areas. Classical fruit tree breeding is generally slow and inefficient. Molecular markers could improve its efficiency but, although nowadays many Mendelian traits are mapped in peach and SSR markers have been found to be linked to some of the key major genes, its use in breeding programs is still limited. Main reasons for that are insufficient linkage between the markers and the genes and the lack of markers suitable for medium-high degree of multiplexing. To address this limitation, about 1,300 peach cultivars were genotyped with the 9K peach SNP chip (Verde et al. 2012) in the frame of FruitBreedomics project. This germplasm was chosen to be representative of the genetic diversity present in five germplasm collection in Europe and in China. Out of the 8144SNPs present in the chip, about 4300 were positively genotyped and used for the further analysis. The average number of heterozygous loci in the genotyped accessions was 1186 (spanning from 13 to 2775). The preliminary results of the population structure reveal three main subpopulations and the presence of high number of admixed individuals. LD seems to decay at distance longer than ca. 1 Mb. These results will be instrumental for implementing LD-based mapping of QTLs and genes in peach

Evasion of anti-growth signaling: a key step in tumorigenesis and potential target for treatment and prophylaxis by natural compounds

The evasion of anti-growth signaling is an important characteristic of cancer cells. In order to continue to proliferate, cancer cells must somehow uncouple themselves from the many signals that exist to slow down cell growth. Here, we define the anti-growth signaling process, and review several important pathways involved in growth signaling: p53, phosphatase and tensin homolog (PTEN), retinoblastoma protein (Rb), Hippo, growth differentiation factor 15 (GDF15), AT-rich interactive domain 1A (ARID1A), Notch, insulin-like growth factor (IGF), and Krüppel-like factor 5 (KLF5) pathways. Aberrations in these processes in cancer cells involve mutations and thus the suppression of genes that prevent growth, as well as mutation and activation of genes involved in driving cell growth. Using these pathways as examples, we prioritize molecular targets that might be leveraged to promote anti-growth signaling in cancer cells. Interestingly, naturally-occurring phytochemicals found in human diets (either singly or as mixtures) may promote anti-growth signaling, and do so without the potentially adverse effects associated with synthetic chemicals. We review examples of naturally-occurring phytochemicals that may be applied to prevent cancer by antagonizing growth signaling, and propose one phytochemical for each pathway. These are: epigallocatechin-3-gallate (EGCG) for the Rb pathway, luteolin for p53, curcumin for PTEN, porphyrins for Hippo, genistein for GDF15, resveratrol for ARID1A, withaferin A for Notch and diguelin for the IGF1-receptor pathway. The coordination of anti-growth signaling and natural compound studies will provide insight into the future application of these compounds in the clinical setting

Super-heavy fermion material as metallic refrigerant for adiabatic demagnetization cooling

Low-temperature refrigeration is of crucial importance in fundamental research of condensed matter physics, as the investigations of fascinating quantum phenomena, such as superconductivity, superfluidity and quantum criticality, often require refrigeration down to very low temperatures. Currently, cryogenic refrigerators with $^3$He gas are widely used for cooling below 1 Kelvin. However, usage of the gas is being increasingly difficult due to the current world-wide shortage. Therefore, it is important to consider alternative methods of refrigeration. Here, we show that a new type of refrigerant, super-heavy electron metal, YbCo$_2$Zn$_{20}$, can be used for adiabatic demagnetization refrigeration, which does not require 3He gas. A number of advantages includes much better metallic thermal conductivity compared to the conventional insulating refrigerants. We also demonstrate that the cooling performance is optimized in Yb$_{1-x}$Sc$_x$Co$_2$Zn$_{20}$ by partial Sc substitution with $x\sim$0.19. The substitution induces chemical pressure which drives the materials close to a zero-field quantum critical point. This leads to an additional enhancement of the magnetocaloric effect in low fields and low temperatures enabling final temperatures well below 100 mK. Such performance has up to now been restricted to insulators. Since nearly a century the same principle of using local magnetic moments has been applied for adiabatic demagnetization cooling. This study opens new possibilities of using itinerant magnetic moments for the cryogen-free refrigeration

Whole-Genome Analysis of Diversity and SNP-Major Gene Association in Peach Germplasm

Peach was domesticated in China more than four millennia ago and from there it spread world-wide. Since the middle of the last century, peach breeding programs have been very dynamic generating hundreds of new commercial varieties, however, in most cases such varieties derive from a limited collection of parental lines (founders). This is one reason for the observed low levels of variability of the commercial gene pool, implying that knowledge of the extent and distribution of genetic variability in peach is critical to allow the choice of adequate parents to confer enhanced productivity, adaptation and quality to improved varieties. With this aim we genotyped 1,580 peach accessions (including a few closely related Prunus species) maintained and phenotyped in five germplasm collections (four European and one Chinese) with the International Peach SNP Consortium 9K SNP peach array. The study of population structure revealed the subdivision of the panel in three main populations, one mainly made up of Occidental varieties from breeding programs (POP1OCB), one of Occidental landraces (POP2OCT) and the third of Oriental accessions (POP3OR). Analysis of linkage disequilibrium (LD) identified differential patterns of genome-wide LD blocks in each of the populations. Phenotypic data for seven monogenic traits were integrated in a genome-wide association study (GWAS). The significantly associated SNPs were always in the regions predicted by linkage analysis, forming haplotypes of markers. These diagnostic haplotypes could be used for marker-assisted selection (MAS) in modern breeding programs

Development and characterization of immunogenic genetically engineered mouse models of pancreatic cancer

Thesis: Ph. D., Massachusetts Institute of Technology, Department of Biology, 2020Cataloged from student-submitted PDF of thesis. Vita. Page 191 blank.Includes bibliographical references.Insights into mechanisms of immune escape have fueled the clinical success of immunotherapy in many cancers. However, pancreatic cancer has remained largely refractory to checkpoint immunotherapy. To uncover mechanisms of immune escape, we have characterized two preclinical models of immunogenic pancreatic ductal adenocarcinoma (PDAC). In order to dissect the endogenous antigen-specific T cell response in PDAC, lentivirus encoding the Cre recombinase and a tumor specific antigen (SIINFEKL, OVA[subscript 257-264]) was delivered to Kras[superscript LSL-G12D/+]; Trp[superscript 53flox/flox] (KP) mice. We demonstrate that KP tumors show distinct antigenic outcomes: a subset of PDAC tumors undergoes clearance or editing by a robust antigen-specific CD8+ T cell response, while a fraction undergo immune escape. Subsequently, we have developed an immunogenic pancreatic tumor organoid orthotopic transplant model.In this model, immunogenic pancreatic tumors manifest divergent tumor phenotypes; 40% of tumor organoids do not form tumors ("non-progressors"), whereas 50% of organoids form aggressive tumors despite maintaining antigen expression and a demonstrable T cell response ("progressors"). Additionally, a subset (10%) of tumors show an intermediate phenotype, possibly reflective of an immune equilibrium state. We have further phenotypically and transcriptionally characterized the CD8+ T cell response to understand immune escape in this model. Our analyses reveal unexpected T cell heterogeneity, and acquisition of T cell dysfunctionality. Therapeutic combinatorial targeting of co-inhibitory receptors identified on dysfunctional antigen-specific CD8+ T cells led to dramatic regression of aggressive pancreatic tumors.Finally, we demonstrate that human CD8+ T cells isolated from pancreatic tumors co-express co-inhibitory receptors, suggesting that T cell dysfunction may be operational in human disease. This is the first demonstration of immunoediting in an autochthonous and organoid-based model of pancreatic cancer. Further characterization of these preclinical model systems will enable rational design of novel clinical immunotherapeutic strategies for treatment of this devastating disease.by Laurens J. Lambert.Ph. D.Ph.D. Massachusetts Institute of Technology, Department of Biolog

La sélection assistée par marqueurs (SAM) chez les arbres fruitiers: une approche prometteuse au service de l’innovation variétale

National audienceFruit tree breeding has to face numerous constraints which strongly slow down development and release of new varieties. The breeding methods are often empirical, as a result of the low genetic knowledge on the main agronomic traits, to which is added the influence of environment. Thus, breeders are looking for new methods to speed up selection process to release new cultivars. In the last ten years, significant development have been made in molecular biology applied to perennial crops in particular in genetic mapping of major genes and QTLs. This technical improvement makes it possible to develop a new approach: the marker assisted breeding or MAB. It is based on the researches from upstream and on the techniques allowing the high throughput genotyping of large numbers of individuals. It is already exploited for traits showing simple heredity in several fruit breeding programs, in particular in peach tree. Even if it is less obvious and more complex to implement on quantitative inherited traits, it is a real improvement compared to traditional breeding methods. MAB thus appears a promising approach to fruit tree breedingChez les arbres fruitiers, la sélection classique doit faire face à des contraintes nombreuses qui ralentissent fortement le développement et l’édition de nouvelles variétés. Les méthodes de sélection sont souvent empiriques, par suite de la faible connaissance des facteurs génétiques impliqués, à laquelle s’ajoute l’influence de l’environnement. C’est pourquoi une demande forte des sélectionneurs pour de nouveaux outils qui permettraient une sélection plus rapide, est apparue. Depuis une dizaine d’années, le développement important de la biologie moléculaire chez les plantes pérennes et en particulier celui de la cartographie génétique et des techniques d’analyse des caractères quantitatifs, a permis de développer une nouvelle approche: la sélection assistée par marqueurs ou SAM. Celle-ci s’appuie sur les recherches d’amont et sur des techniques permettant le génotypage à haut débit d’un grand nombre d’individus. Elle est déjà exploitée pour des caractères à hérédité simple dans plusieurs programmes de sélection variétale, notamment pour le pêcher. Cependant, bien que son développement et sa mise en oeuvre soient plus complexes lorsqu’il s’agit de caractères à effet quantitatif ou lorsque l’on désire cumuler plusieurs caractères d’intérêt, elle permet une réelle amélioration de la sélection classique. La SAM apparaît donc une approche prometteuse pour l’innovation variétale chez les arbres fruitiers

La sélection assistée par marqueurs (SAM) chez les arbres fruitiers: une approche prometteuse au service de l’innovation variétale

Chez les arbres fruitiers, la sélection classique doit faire face à des contraintes nombreuses qui ralentissent fortement le développement et l’édition de nouvelles variétés. Les méthodes de sélection sont souvent empiriques, par suite de la faible connaissance des facteurs génétiques impliqués, à laquelle s’ajoute l’influence de l’environnement. C’est pourquoi une demande forte des sélectionneurs pour de nouveaux outils qui permettraient une sélection plus rapide, est apparue. Depuis une dizaine d’années, le développement important de la biologie moléculaire chez les plantes pérennes et en particulier celui de la cartographie génétique et des techniques d’analyse des caractères quantitatifs, a permis de développer une nouvelle approche: la sélection assistée par marqueurs ou SAM. Celle-ci s’appuie sur les recherches d’amont et sur des techniques permettant le génotypage à haut débit d’un grand nombre d’individus. Elle est déjà exploitée pour des caractères à hérédité simple dans plusieurs programmes de sélection variétale, notamment pour le pêcher. Cependant, bien que son développement et sa mise en oeuvre soient plus complexes lorsqu’il s’agit de caractères à effet quantitatif ou lorsque l’on désire cumuler plusieurs caractères d’intérêt, elle permet une réelle amélioration de la sélection classique. La SAM apparaît donc une approche prometteuse pour l’innovation variétale chez les arbres fruitiers.Fruit tree breeding has to face numerous constraints which strongly slow down development and release of new varieties. The breeding methods are often empirical, as a result of the low genetic knowledge on the main agronomic traits, to which is added the influence of environment. Thus, breeders are looking for new methods to speed up selection process to release new cultivars. In the last ten years, significant development have been made in molecular biology applied to perennial crops in particular in genetic mapping of major genes and QTLs. This technical improvement makes it possible to develop a new approach: the marker assisted breeding or MAB. It is based on the researches from upstream and on the techniques allowing the high throughput genotyping of large numbers of individuals. It is already exploited for traits showing simple heredity in several fruit breeding programs, in particular in peach tree. Even if it is less obvious and more complex to implement on quantitative inherited traits, it is a real improvement compared to traditional breeding methods. MAB thus appears a promising approach to fruit tree breedin