Molecular Classification and Pharmacogenetics of Primary Plasma Cell Leukemia: An Initial Approach toward Precision Medicine

Primary plasma cell leukemia (pPCL) is a rare and aggressive variant of multiple myeloma (MM) which may represent a valid model for high-risk MM. This disease is associated with a very poor prognosis, and unfortunately, it has not significantly improved during the last three decades. New high-throughput technologies have allowed a better understanding of the molecular basis of this disease and moved toward risk stratification, providing insights for targeted therapy studies. This knowledge, added to the pharmacogenetic profile of new and old agents in the analysis of efficacy and safety, could contribute to help clinical decisions move toward a precision medicine and a better clinical outcome for these patients. In this review, we describe the available literature concerning the genomic characterization and pharmacogenetics of plasma cell leukemia (PCL).     

Comprehensive Profiling of Secretome Formulations from Fetal- and Perinatal Human Amniotic Fluid Stem Cells

We previously reported that c-KIT+ human amniotic-fluid derived stem cells obtained from leftover samples of routine II trimester prenatal diagnosis (fetal hAFS) are endowed with regenerative paracrine potential driving pro-survival, anti-fibrotic and proliferative effects. hAFS may also be isolated from III trimester clinical waste samples during scheduled C-sections (perinatal hAFS), thus offering a more easily accessible alternative when compared to fetal hAFS. Nonetheless, little is known about the paracrine profile of perinatal hAFS. Here we provide a detailed characterization of the hAFS total secretome (i.e., the entirety of soluble paracrine factors released by cells in the conditioned medium, hAFS-CM) and the extracellular vesicles (hAFS-EVs) within it, from II trimester fetal- versus III trimester perinatal cells. Fetal- and perinatal hAFS were characterized and subject to hypoxic preconditioning to enhance their paracrine potential. hAFS-CM and hAFS-EV formulations were analyzed for protein and chemokine/cytokine content, and the EV cargo was further investigated by RNA sequencing. The phenotype of fetal- and perinatal hAFS, along with their corresponding secretome formulations, overlapped; yet, fetal hAFS showed immature oxidative phosphorylation activity when compared to perinatal ones. The profiling of their paracrine cargo revealed some differences according to gestational stage and hypoxic preconditioning. Both cell sources provided formulations enriched with neurotrophic, immunomodulatory, anti-fibrotic and endothelial stimulating factors, and the immature fetal hAFS secretome was defined by a more pronounced pro-vasculogenic, regenerative, pro-resolving and anti-aging profile. Small RNA profiling showed microRNA enrichment in both fetal- and perinatal hAFS-EV cargo, with a stably- expressed pro-resolving core as a reference molecular signature. Here we confirm that hAFS represents an appealing source of regenerative paracrine factors; the selection of either fetal or perinatal hAFS secretome formulations for future paracrine therapy should be evaluated considering the specific clinical scenario.     

Extension of the Terpene Chemical Space: the Very First Biosynthetic Steps

The structural diversity of terpenes is particularly notable and many studies are carried out to increase it further. In the terpene biosynthetic pathway this diversity is accessible from only two common precursors, i. e. isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP). Methods recently developed (e. g. the Terpene Mini Path) have allowed DMAPP and IPP to be obtained from a two-step enzymatic conversion of industrially available isopentenol (IOH) and dimethylallyl alcohol (DMAOH) into their corresponding diphosphates. Easily available IOH and DMAOH analogues then offer quick access to modified terpenoids thus avoiding the tedious chemical synthesis of unnatural diphosphates. The aim of this minireview is to cover the literature devoted to the use of these analogues for widening the accessible terpene chemical space.     

Adding security and trust to multiagent systems

Multiagent systems (MASs) are societies whose individuals are software delegatees (agents) acting on behalf of their owners or delegators (people or organizations). When deployed in an open network such as the Internet, MASs face some trust and security issues. Agents comeand go, and interact with strangers. Assumptions about security and general trustworthiness of agents and their deployers are inadequate in this context. In this paper, the design of a security infrastructure is presented applicable to MASs in general. This design addresses both security threats and trust issues. In this design, there are mechanisms for ensuring secure communication among agents and secure naming and resource location services. And two types of trusts are addressed: trust that agents will not misbehave and trust that agents are really delegatees of whom they claim to be. To establish the first type of trust, deployers of agents are made liable for the actions of their agents; to establish the second type of trust, it is proposed that agents prove that they know secrets that only their delegators know.     

Conditional neural sequence learners for generating drums’ rhythms

Neural Computing and Applications - Machine learning has shown a successful component of methods for automatic music composition. Considering music as a sequence of events with multiple complex...     

Maintenance resources optimization applied to a manufacturing system

This paper presents an availability optimization of an engineering system assembled in a series configuration, with redundancy of units and corrective maintenance resources as optimization parameters. The aim is to reach maximum availability, considering as constraints installation and corrective maintenance costs, weight and volume. The optimization method uses a Genetic Algorithm based on biological concepts of species evolution. It is a robust method, as it does not converge to a local optimum. It does not require the use of differential calculus, thus facilitating computational implementation. Results indicate that the methodology is suitable to solve a wide range of engineering design problems involving allocation of redundancies and maintenance resources.     

An enhanced Lemaitre model formulation for materials processing damage computation

The Lemaitre damage model is now widely used to deal with coupled damage analyses for various mechanical applications. In this article, different extensions of the model are presented and discussed to deal with complex multiaxial configurations—such as multi-stages bulk forming processes. A specific treatment is done to account for compressive damage growth, and a stress triaxiality cut-off value is considered to avoid any damage evolution below a critical negative triaxiality. The damage potential is also modified to deal with highly ductile materials, and the plastic strain is split into a negative part and a positive part to differentiate damage growth for compressive states of stress and for tensile states of stress. Finally, an anisotropic damage approach based on the comparison between grain flow orientation and principal loading directions is defined. A combination of these extensions is achieved within a single Lemaitre formulation. Application on different examples show the robustness and accuracy of the model defined in this paper.     

A Markov chain model to describe fluidization of particles with time-varying properties

A one-dimensional mathematical model of particulate solids thermal treatment in a fluidized bed based on the theory of Markov chains is proposed. A feature of the model takes into account the variation of particle properties that takes place during the fluidization. This variation occurs due to thermo-physical and chemical processes that take place during particulate solids treatment in the fluidized bed. These variations affect the particle settling velocity which is the main parameter that forms the bed expansion and local velocity of flow around the particles that strongly influences the thermo-physical and chemical processes in the bed. A generalized correlation for the drag force coefficient is proposed and tested for various materials. It was necessary to have more precise calculation of the particle settling velocity in the model. The model was developed to describe the drying process in the bed. A good correlation between computed and experimental data was achieved.