The future of mesenchymal stem cell-based therapeutic approaches for cancer – From cells to ghosts

Mesenchymal stem cells (MSCs) are multipotent stromal cells which can differentiate into a variety of cell types including osteoblasts, adipocytes and chondrocytes. They are normally resident in adipose tissue, bone marrow and the umbilical cord, but can also be found in other tissues and are known to be recruited to sites of wound healing as well as growing tumours. The therapeutic potential of MSCs has been explored in a number of phase I/II and III clinical trials, of which several were targeted against graft-versus-host disease and to support engraftment of haematopoietic stem cells (HSCs), but currently only very few in the oncology field. There are now three clinical trials either ongoing or recruiting patients that use MSCs to treat tumour disease. In these, MSCs target gastrointestinal, lung and ovarian cancer, respectively. The first study uses MSCs loaded with a HSV-TK expression construct under the control of the CCL5 promoter, and has recently reported successful completion of Phase I/II. While no adverse side effects were seen during this study, no outcomes with respect to therapeutic benefits have been published. The other clinical trials targeting lung and ovarian cancer will be using MSCs expressing cytokines as therapeutic payload. Despite these encouraging early steps towards their clinical use, many questions are still unanswered regarding the biology of MSCs in normal and pathophysiological settings. In this review, in addition to summarising the current state of MSC-based therapeutic approaches for cancer, we will describe the remaining questions, obstacles and risks, as well as novel developments such as MSC-derived nanoghosts

The Journal of Undergraduate Research: Volume 13

This is the complete issue of the South Dakota State University Journal of Undergraduate Research, Volume 13

Food-Borne Chemical Carcinogens and the Evidence for Human Cancer Risk

Commonly consumed foods and beverages can contain chemicals with reported carcinogenic activity in rodent models. Moreover, exposures to some of these substances have been associated with increased cancer risks in humans. Food-borne carcinogens span a range of chemical classes and can arise from natural or anthropogenic sources, as well as form endogenously. Important considerations include the mechanism(s) of action (MoA), their relevance to human biology, and the level of exposure in diet. The MoAs of carcinogens have been classified as either DNA-reactive (genotoxic), involving covalent reaction with nuclear DNA, or epigenetic, involving molecular and cellular effects other than DNA reactivity. Carcinogens are generally present in food at low levels, resulting in low daily intakes, although there are some exceptions. Carcinogens of the DNA-reactive type produce effects at lower dosages than epigenetic carcinogens. Several food-related DNA-reactive carcinogens, including aflatoxins, aristolochic acid, benzene, benzo[a]pyrene and ethylene oxide, are recognized by the International Agency for Research on Cancer (IARC) as causes of human cancer. Of the epigenetic type, the only carcinogen considered to be associated with increased cancer in humans, although not from low-level food exposure, is dioxin (TCDD). Thus, DNA-reactive carcinogens in food represent a much greater risk than epigenetic carcinogens

Synthesis and Pharmacological Properties of Heterocyclic Analogs

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Extractives from six species of Lamiaceae

In continuation of the phytochemical studies of plants belonging to the Lamiaceae (formerly Labiatae) the acetone extractives of six Southern African species from this family have been examined. The genus Syncolostemon has not been investigated before and a new 6- substituted-5 ,6-dihydro-a-pyrone , synrotolide was isolated from S. rotundifolius. The structure of synrotolide was fully elucidated as 6fixii [3'R, 61S-(diacetyloxy)-4 1R, 5 1 8-(dihydroxy)-1~-hepteny~ -5,6-dihydro-2H-pyran- 2-one. Oleanolic acid is the major component of both~ rotundifolius and S. densifloris. The flavonol quercetin was isolated from S. densifloris as its 3, 3', 4' , 7 tetramethyl ether. A further 6-substituted-5,6-dihydro-a-pyrone, boronolide, was obtained from Tetradenia barberae. The structure of boronolide was known but the absolute stereochemistry was unassigned. Chemical degradation established the total structure of this compound as 6R- [1 'R, 2'R, 3's -(trisacetyloxy)heptyl] -5,6-dihydro-2H-pyran-2-one. The chemistry of naturally occuring 6-substituted-5,6-dihydro-apyrones has not as such been previously reviewed and a comprehensive review covering the literature up to June 1987 is presented here. Three known labdane diterpenoids nepetaefuran, hispanalone and dubiin were iso lated from Leonotis nepetaefolia, Ballota africana and L. ocymifolia var. ocymifolia (formerly~ dubia). Both~ nepetaefolia and L. dubia have been examined before. An X-ray analysis of saponified dubiin and a circular dichroism study of 6-deacetyldehydrodubiin and related compounds corroborated the structure of dubiin as 48, 5R, 6R, 8R, 9R, 10R-[6-acetoxy-15,16-epoxy-9-hydroxylabda-13 (16), 14-dien-19, 20- olactoneJ. The chemotaxonomic relationships of the genera Ballota and Leonotis are discussed

Narrative Finance - The use of narrative to inform investment judgement. How stories move markets - the system behind the Boeing 737 MAX shock news.

Belghitar, Yacine - Associate SupervisorNARRATIVE FINANCE: The use of narrative to inform investment judgement Narrative Finance is the term coined for research into this new sub-discipline of financial economics - for it is the “voice of the market.” The information embedded within text and speech is pervasive in determining asset prices. This contribution to financial research highlights ways to use financial narratives to inform investment judgement. Financial narrative is modelled as a disruptive force by uniquely applying General System Theory to illustrate the complex architecture of the financial system. The energy budget of a material narrative is seen to be expended in the work carried out to adjust asset prices. Investors can use the departure and recovery of prices from the dynamic equilibrium upon the receipt of news as an investment indicator; described herein as Decoupling Theory. The signal of a narrative is mapped as it travels through the non- linear financial system (and back as feedback). Narrative nomenclature is devised to describe dominant, dormant, and legacy narratives, the Narrative Cycle, Narrative Signal, Narrative Phases, and the Narrative Tree. This theory was tested against the shock news of the two Boeing 737 MAX 8 accidents, which provided two proxy narrative signals and investment outcomes from a single event cause. The empirical output includes the proof of theory for the narrative morphology and phases, the extraction of fast and frugal investment narrative indicators, the importance of feedback, and the matching of narrative frequency to market movements. These metrics can help investors make better judgements and decisions by narrowing the probabilities in nowcasting and forecasting models. Narrative Finance is an intellectual descendant of classical finance and behavioural economics and contributes an alternative method of valuing investments to the toolbox of investors, academics, and securities regulators.PhD in Leadership and Managemen

Über die Hemmung des Flavivirins Makrocyclische Peptidderivate als Inhibitoren der NS2B-NS3-Protease des Zika-Virus und des West-Nil-Virus

Das Flavivirin oder die NS2B-NS3-Protease ist ein Enzym, das essentiell für die Vermehrung aller Flavivirus-Spezies ist. In dieser Arbeit wurden die Möglichkeiten zur Hemmung des Flavivirins des Zika-Virus (ZIKV) und des West-Nil-Virus (WNV) durch cyclische Peptidderivate untersucht. Dazu wurden über 100 Verbindungen hergestellt, die in enzymkinetischen Assays, Röntgenstrukturanalysen und Zellkulturexperimenten umfassend untersucht wurden. Die dabei gewonnen Erkenntnisse zur Struktur-Wirkungs-Beziehung liefern neue Ansatzpunkte zur Entwicklung antiviraler Wirkstoffe

INVESTIGACIÓN DE LAS MODIFICACIONES MICROESTRUCTURALES Y PROPIEDADES MECÁNICAS EN UNA ALEACIÓN DE ALUMINIO AA6082-T6 SOLDADA CON LA TÉCNICA DE FRICCIÓN-AGITACIÓN (FSW)

[EN] The friction stir welding (FSW) is a joining process that uses a non-consumable tool generates frictional heat (without reaching the melting point) and plastic deformation in the weld line as it rotates and moves the tool, so that a welded joint is obtained in solid state. This technique is capable to join many engineering materials but was initially focused on high strength aluminum alloys (series 2XXX, 6XXX and 7XXX) due to two main approaches: because they are difficult to weld by conventional welding processes fusion for their applications in key sectors such as automotive, aviation, aerospace, shipbuilding and other manufacturing industries due to high strength/weight ratio. FSW parameters as rotational speed, welding speed, weld pitch ratio (WPR), tool profile, among others, are responsible for obtaining sound welds (flawless), of the microstructural changes, of the mechanical and technological properties of welded joints. Therefore, it is important to study the parameters-microstructure-property relationship to maintain the quality of welded joints. In this work we have studied the influence of some FSW processing parameters (rotation speed, welding speed, weld pitch ratio and joint configuration) on the microstructural changes, mechanical and technological properties to a rolling sheet of aluminum alloy AA6082-T6 of 5mm thick. For the four configurations obtained it has been characterized the microstructure with various techniques, such as optical microscopy (OM), scanning electron microscopy (SEM), transmission electron microscopy (TEM), electron backscatter diffraction (EBSD) and differential scanning calorimetry (DSC) to identify major phases, dispersoids, second phases, dissolution, precipitation, and re-precipitation of phases, sub-structure, crystallographic texture, etc. in each welding zone and for each configuration. Also it has been obtained mechanical properties through microhardness tests, tensile and fatigue tests, and technological properties through accelerated corrosion tests. The results of the experiments indicate that it can to obtain sound welds, i.e. defect-free with different processing parameters, and they greatly influence in the microstructure and therefore on the mechanical and technological properties. Similarly, it found that it can get better mechanical properties (tensile strength and hardness) with a low weld pitch ratio (WPR [mm/rev]4 "hot condition") and single-pass butt joint. In comparison, the base metal has better mechanical properties and worse corrosion properties than the four configurations studied and in any case the double-pass butt joint never were one revulsive option to single-pass butt joint.[ES] La soldadura por fricción-agitación (FSW) es proceso de unión que utiliza una herramienta no consumible que genera calor por fricción (sin llegar al punto de fusión) y deformación plástica en la línea de soldeo a medida que rota y avanza la herramienta, con lo que se obtiene una unión soldada en estado sólido. Esta técnica es capaz de unir muchos materiales de ingeniería pero se ha centrado inicialmente en las aleaciones de aluminio de alta resistencia (series 2XXX, 6XXX y 7XXX) debido a dos enfoques principales: porque son difíciles de soldar por procesos de soldadura por fusión convencionales y por sus aplicaciones en sectores claves como automoción, aeronáutico, aeroespacial, construcción naval y otras industrias de fabricación, debido a la alta relación resistencia/peso. Los parámetros de FSW como velocidad de rotación, velocidad de avance, relación de soldeo (WPR), perfil de la herramienta, entre otros, son responsables de la obtención de soldadas sanas (sin defectos), de las transformaciones microestructurales, de las propiedades mecánicas y tecnológicas de las uniones soldadas. Por lo tanto, es importante estudiar la relación parámetros-microestructura-propiedades para mantener la calidad de las juntas soldadas. En este trabajo se ha estudiado la influencia de algunos parámetros de procesado FSW (velocidad de avance, velocidad de rotación, relación de soldeo, configuración de junta) en las modificaciones microestructurales, propiedades mecánicas y tecnológicas para una chapa laminada de aleación de aluminio AA6082-T6 de 5 mm de espesor. Para las cuatro configuraciones obtenidas se han caracterizado a profundidad la microestructura con varias técnicas, tales como, microscopia óptica (MO), microscopía electrónica de barrido (MEB), microscopía electrónica de transmisión (MET), difracción de electrones retrodispersados (EBSD) y calorimetría diferencia de barrido (DSC) para identificar fases, dispersoides, segundas fases, disolución y precipitación de fases, sub-estructura, textura cristalográfica, etc., en cada zona de soldadura y para cada configuración. También se han obtenido las propiedades mecánicas a través de ensayos de microdureza, tracción y fatiga, y propiedades tecnológicas a través de ensayos de corrosión acelerada. Los resultados de la experimentación indican que se pueden obtener cordones sanos, es decir, libres de defectos con diferentes parámetros de procesado, y que éstos influyen en gran medida en la microestructura y por ende en las propiedades mecánicas y tecnológicas. Igualmente, encontramos que se pueden obtener mejores propiedades mecánicas de tracción y dureza para una relación de soldeo (WPR) con bajo aporte térmico y soldadura por una cara, mientras que las mejores propiedades a fatiga se obtienen para la configuración con alto aporte térmico y soldadura por una cara. En comparación, el metal base tiene mejores propiedades mecánicas y bajas propiedades a corrosión con respecto a las cuatro configuraciones estudiadas y, en ningún caso las soldaduras por ambas caras fueron una opción revulsiva de las soldaduras por una cara.[CA] La soldadura per fricció-agitació (FSW) és un procés d'unió que utilitza una eina noconsumible que genera calor per fricció (sense arribar al punt de fusió) i deformació plàstica en la línia de soldadura a mesura que gira i avança l'eina, amb el que s'obté una unió soldada en estat sòlid. Aquesta tècnica és capaç d'unir molts materials d'enginyeria però s'ha centrat inicialment en els aliatges d'alumini d'alta resistència (sèries 2xxx, 6xxx i 7XXX) a causa de dos enfocaments principals: perquè són difícils de soldar per processos de soldadura per fusió convencionals i per les seves aplicacions en sectors claus com automoció, aeronàutic, aeroespacial, construcció naval i altres indústries de fabricació, degut a l'alta relació resistència/pes. Els paràmetres de FSW com velocitat de rotació, velocitat d'avanç, relació de soldadura (WPR), perfil de l'eina, entre d'altres, són responsables de l'obtenció de soldadures sanes (sense defectes), de les transformacions microestructurals, de les propietats mecàniques i tecnològiques de les unions soldades. Per tant, és important estudiar la relació paràmetres-microestructura-propietats per mantenir la qualitat de les juntes soldades. En aquest treball s'ha estudiat la influència d'alguns paràmetres de processat FSW (velocitat d'avanç, velocitat de rotació, relació de soldadura, configuració de les juntes) en les modificacions microestructurals, propietats mecàniques i tecnològiques per a una xapa laminada d'aliatge d'alumini AA6082- T6 de 5 mm de gruix. Per a les quatre configuracions obtingudes s'han caracteritzat a profunditat la microestructura amb diverses tècniques, com ara, microscòpia òptica (MO), microscòpia electrònica de rastreig (MER), microscòpia electrònica de transmissió (MET), difracció d'electrons retrodispersats (EBSD) i calorimetria diferèncial d'escombrat (DSC) per identificar fases, dispersoides, segones fases, dissolució i precipitació de fases, sub-estructures, textura cristal-logràfica, etc., a cada zona de soldadura i per a cada configuració. També s'han obtingut les propietats mecàniques a través d'assajos de microduresa, tracció i fatiga, i propietats tecnològiques a través d'assaigs de corrosió accelerada. Els resultats de l'experimentació indiquen que es poden obtenir cordons sans, és a dir lliures de defectes, amb diferents paràmetres de processat, i que aquests influeixen en gran mesura en la microestructura i per tant en les propietats mecàniques i tecnològiques. Igualment, trobem que es poden obtindre millors propietats mecàniques de tracció i duresa per una relació de soldadura (WPR) amb baix contingut tèrmic i soldadura per una cara, mentre que les millors propietats a fatiga s'obtenen per a la configuració amb alta aportació tèrmica i soldadura per una cara. En comparació, el metall base té millors propietats mecàniques i baixes propietats a corrosió pel que fa a les quatre configuracions estudiades i, en cap cas les soldadures per ambdues cares van ser una opció revulsiva de les soldadures.Martínez Díaz, E. (2016). INVESTIGACIÓN DE LAS MODIFICACIONES MICROESTRUCTURALES Y PROPIEDADES MECÁNICAS EN UNA ALEACIÓN DE ALUMINIO AA6082-T6 SOLDADA CON LA TÉCNICA DE FRICCIÓN-AGITACIÓN (FSW) [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/62161TESI

100% Renewable Energy Transition: Pathways and Implementation

Energy markets are already undergoing considerable transitions to accommodate new (renewable) energy forms, new (decentral) energy players, and new system requirements, e.g. flexibility and resilience. Traditional energy markets for fossil fuels are therefore under pressure, while not-yet-mature (renewable) energy markets are emerging. As a consequence, investments in large-scale and capital intensive (traditional) energy production projects are surrounded by high uncertainty, and are difficult to hedge by private entities. Traditional energy production companies are transforming into energy service suppliers and companies aggregating numerous potential market players are emerging, while regulation and system management are playing an increasing role. To address these increasing uncertainties and complexities, economic analysis, forecasting, modeling and investment assessment require fresh approaches and views. Novel research is thus required to simulate multiple actor interplays and idiosyncratic behavior. The required approaches cannot deal only with energy supply, but need to include active demand and cover systemic aspects. Energy market transitions challenge policy-making. Market coordination failure, the removal of barriers hindering restructuring and the combination of market signals with command-and-control policy measures are some of the new aims of policies.The aim of this Special Issue is to collect research papers that address the above issues using novel methods from any adequate perspective, including economic analysis, modeling of systems, behavioral forecasting, and policy assessment.The issue will include, but is not be limited to: Local control schemes and algorithms for distributed generation systems; Centralized and decentralized sustainable energy management strategies; Communication architectures, protocols and properties of practical applications; Topologies of distributed generation systems improving flexibility, efficiency and power quality; Practical issues in the control design and implementation of distributed generation systems; Energy transition studies for optimized pathway options aiming for high levels of sustainabilit