Single-cell analysis of patient-derived PDAC organoids reveals cell state heterogeneity and a conserved developmental hierarchy

Pancreatic tumors are frequently divided into basal and classical subtypes. Here, the authors use single cell sequencing to investigate organoids derived from pancreatic cancer tissue and find a hierarchy of distinct cell states, and classical and basal cells existing within the same tumor. Pancreatic ductal adenocarcinoma (PDAC) is projected to be the second leading cause of cancer mortality by 2030. Bulk transcriptomic analyses have distinguished 'classical' from 'basal-like' tumors with more aggressive clinical behavior. We derive PDAC organoids from 18 primary tumors and two matched liver metastases, and show that 'classical' and 'basal-like' cells coexist in individual organoids. By single-cell transcriptome analysis of PDAC organoids and primary PDAC, we identify distinct tumor cell states shared across patients, including a cycling progenitor cell state and a differentiated secretory state. Cell states are connected by a differentiation hierarchy, with 'classical' cells concentrated at the endpoint. In an imaging-based drug screen, expression of 'classical' subtype genes correlates with better drug response. Our results thus uncover a functional hierarchy of PDAC cell states linked to transcriptional tumor subtypes, and support the use of PDAC organoids as a clinically relevant model for in vitro studies of tumor heterogeneity

Gravity, antimatter and the Dirac-Milne universe

We review the main arguments against antigravity, a different acceleration of antimatter relative to matter in a gravitational field, discussing and challenging Morrison's, Good's and Schiff's arguments. Following Price, we show that, very surprisingly, the usual expression of the Equivalence Principle is violated by General Relativity when particles of negative mass are supposed to exist, which may provide a fundamental explanation of MOND phenomenology, obviating the need for Dark Matter. Motivated by the observation of repulsive gravity under the form of Dark Energy, and by the fact that our universe looks very similar to a coasting (neither decelerating nor accelerating) universe, we study the Dirac-Milne cosmology, a symmetric matter-antimatter cosmology where antiparticles have the same gravitational properties as holes in a semiconductor. Noting the similarities with our universe (age, SN1a luminosity distance, nucleosynthesis, CMB angular scale), we focus our attention on structure formation mechanisms, finding strong similarities with our universe. Additional tests of the Dirac-Milne cosmology are briefly reviewed, and we finally note that a crucial test of the Dirac-Milne cosmology will be soon realized at CERN next to the ELENA antiproton decelerator, possibly as early as fall 2018, with the AEgIS, ALPHA-g and Gbar antihydrogen gravity experiments.Comment: Proceedings of the Low Energy Antiproton Physics Conference (LEAP), Sorbonne University, Paris, March 12th to 16th, 201

Termoestables híbridos organo-inorgánicos: síntesis, caracterización y propiedades

Se han preparado varios poliorganosiloxanos basados en el poli(3-aminopropilmetilsiloxano) (PAMS), mediante hidrólisis y condensación del monómero3-aminopropilmetildietoxisilano (APDES). La modificación de su funcionalidad se hallevado a cabo por reacción con pequeñas cantidades de fenilglicidil éter (PGE),formando aductos PAMS:PGE. Se ha analizado la miscibilidad de los polisiloxanossintetizados con una resma epoxídica base, el diglicidil éter del bisfenol-A (DGEBA).Las mezclas resultantes son inmiscibles inicialmente, aunque el avance de la reacciónepoxi/amina provoca su homogeneización parcial.Se ha estudiado el curado de los diferentes endurecedores poliaminosiloxánicos, PAMSy PAMS:PGE, con DGEBA. Se ha analizado el efecto que ejerce la presencia de gruposamina secundarios en la mezcla inicial, así como la influencia de la concentracióninicial de grupos hidroxilo, capaces de catalizar la reacción epoxi/amina. La reacción seajusta a un modelo autocatalítico, presentando una autoaceleración a relativas bajasconversiones. Al aumentar la proporción de aminas secundarias en la mezcla inicial, lareacción no-catalizada pierde importancia respecto a la autocatalizada. Por otra parte, elcalor de reacción y la energía de activación obtenidos son comparables a los reportadospara el curado de resinas epoxi con diaminas convencionales.Mediante diversas técnicas microscópicas, se ha analizado la morfología de los sistemascurados, observándose cierto grado de heterogeneidad composicional provocado por lainmiscibilidad inicial de los componentes. Se han encontrado “pseudodominios” ricosen silano distribuidos homogéneamente por la matriz epoxi. Dichos dominios estánconstituidos por gradientes de concentración en forma de capas concéntricas. Se hacomprobado que dicha heterogeneidad afecta a las propiedades mecánicas y quedisminuye a medida que aumenta el grado de entrecruzamiento.También se ha estudiado la capacidad de absorción de agua de la resmaDGEBA/PAMS. La máxima cantidad de agua absorbida es del 3% en peso. Se hapropuesto un nuevo procedimiento para el estudio del hinchamiento producido por laentrada de agua a través de n-FTIR. ------------------------------------------------------------------------------------------------------------------------------------------------------------------------Several polyorganosiloxanes were prepared. The synthesis of poly(3-aminopropylmethylsiloxane) (PAMS) was carried out by hydrolysis and condensation of 3-aminopropyl methyldiethoxysilane monomer (APDES). The ftinctionality modificationof PAMS was done by subsequent reaction with phenylglycidyl ether (PGE), formingPAMS:PGE adducts. The miscibility of the synthesised polysiloxanes with an epoxyresin, bisphenol A diglycidyl ether (DGEBA) was analysed. The initial mixtures areinmiscible, but the epoxy/amine reaction induces a partial compatibilisation.The curing reaction of DGEBA with the different polysiloxane hardeners, PAMS orPAMS:PGE, was studied. The influence of initial hydroxyl groups concentration, ableto catalyse the epoxy/amine reaction, and also, the presence of secondary amines in theinitial mixture, were analysed. Reaction foliows an autocatalytic model, showingautoacceleration at low conversion. When the secondary amine and hydroxyl groupsconcentrations are high in the initial mixture, the curing process occurs mainly by thecatalytic reaction. The non-catalytic path becomes almost negligible. The obtainedreaction heat and activation energy are similar to the reported for DGEBA curing withconventional diamines.The morphology of the cured products has been analysed by severa! microscopytechniques. A compositional heterogeneity was observed, caused by the initialinmiscibility of the components. The siloxane is concentrated in “pseudodomains”distributed homogeneous!y in the epoxy matrix. Concentric layers of gradientconcentration constitute these domains. This heterogeneity affects to the mechanicalproperties and decreases with crosslinking degree.Water absorption capacity of DGEBAIPAMS system has been also studied. Themaximum water absorption is 3% w/w. A novel procedure has been proposed forstudying the swelling phenomena by n-FTIR

DESIGNING OF A RT REAL TIME PCR ASSAY BASED ON NS1 GENE FOR RAPID DETECTION OF USUTU VIRUS (USUV)

Introduction: Usutu virus belongs to the Japanese encephalitis virus group (the isolates exhibited 97% identity) within the family Flaviviridae closely related to West Nile virus (WNV). Both share in nature an enzootic infectious cycle between avian hosts and mosquito vectors (i.e. Culex spp.). The distribution areal is expanding in several European countries, including Italy; the simultaneous spatial and temporal co-circulation of new flaviviruses require a new approaches in the laboratory diagnosis for Flaviviridae infection in humans

Avaliação das incertezas associadas à determinação do parâmetro de solubilidade de Hildebrand de petróleos

Asphaltenes are fractions of crude oils that can precipitate and one of the parameters used in the prediction of the conditions in which this phenomenon occurs is the Hildebrand solubility parameter. In this work, it was evaluated the uncertainty propagation in the experimental determination of the solubility parameter of different crude oils, calculated from data of the asphaltenes precipitation by the addition of n-heptane, identified by optical microscopy. It was verified that the solubility parameter of an oil and the associated uncertainty are specific, being recommended that, whenever viable, it is determined parallel both, conferring higher credibility to the results