Scaling-Up Techniques for the Nanofabrication of Cell Culture Substrates via Two-Photo Polymerization for Industrial-Scale Expansion of Stem Cells

Stem-cell-based therapies require a high number (106–109) of cells, therefore in vitro expansion is needed because of the initially low amount of stem cells obtainable from human tissues. Standard protocols for stem cell expansion are currently based on chemically-defined culture media and animal-derived feeder-cell layers, which expose cells to additives and to xenogeneic compounds, resulting in potential issues when used in clinics. The two-photon laser polymerization technique enables three-dimensional micro-structures to be fabricated, which we named synthetic nichoids. Here we review our activity on the technological improvements in manufacturing biomimetic synthetic nichoids and, in particular on the optimization of the laser-material interaction to increase the patterned area and the percentage of cell culture surface covered by such synthetic nichoids, from a low initial value of 10% up to 88% with an optimized micromachining time. These results establish two-photon laser polymerization as a promising tool to fabricate substrates for stem cell expansion, without any chemical supplement and in feeder-free conditions for potential therapeutic uses

SCN1B gene variants in Brugada Syndrome: a study of 145 SCN5A-negative patients.

Brugada syndrome is characterised by a typical ECG with ST segment elevation in the right precordial leads. Individuals with this condition are susceptible to ventricular arrhythmias and sudden cardiac death. The principal gene responsible for this syndrome is SCN5A, which encodes the α-subunit of the Nav1.5 voltage-gated sodium channel. Mutations involving other genes have been increasingly reported, but their contribution to Brugada syndrome has been poorly investigated. Here we focused on the SCN1B gene, which encodes the β1-subunit of the voltage-gated sodium channel and its soluble β1b isoform. SCN1B mutations have been associated with Brugada syndrome as well as with other cardiac arrhythmias and familial epilepsy. In this study, we have analysed SCN1B exons (including the alternatively-spliced exon 3A) and 3′UTR in 145 unrelated SCN5A-negative patients from a single centre. We took special care to report all identified variants (including polymorphisms), following the current nomenclature guidelines and considering both isoforms. We found two known and two novel (and likely deleterious) SCN1B variants. We also found two novel changes with low evidence of pathogenicity. Our findings contribute more evidence regarding the occurrence of SCN1B variants in Brugada syndrome, albeit with a low prevalence, which is in agreement with previous reports

AntRS: Recommending Lists through a Multi-Objective Ant Colony System

International audienceWhen people use recommender systems, they generally expect coherent lists of items. Depending on the application domain, it can be a playlist of songs they are likely to enjoy in their favorite online music service, a set of educational resources to acquire new competencies through an intelligent tutoring system, or a sequence of exhibits to discover from an adaptive mobile museum guide. To make these lists coherent from the users' perspective, recommendations must find the best compromise between multiple objectives (best possible precision, need for diversity and novelty). We propose to achieve that goal through a multi-agent recommender system, called AntRS. We evaluated our approach with a music dataset with about 500 users and more than 13,000 sessions. The experiments show that we obtain good results as regards to precision, novelty and coverage in comparison with typical state-of-the-art single and multi-objective algorithms

On duality symmetry in perturbative quantum theory

Non-compact symmetries of extended 4d supergravities involve duality rotations of vectors and thus are not manifest off-shell invariances in standard "second-order" formulation. To study how such symmetries are realised in the quantum theory we consider examples in 2 dimensions where vector-vector duality is replaced by scalar-scalar one. Using a "doubled" formulation, where fields and their momenta are treated on an equal footing and the duality becomes a manifest symmetry of the action (at the expense of Lorentz symmetry), we argue that the corresponding on-shell quantum effective action or S-matrix are duality symmetric as well as Lorentz invariant. The simplest case of discrete Z_2 duality corresponds to a symmetry of the S-matrix under flipping the sign of the negative-chirality scalars in 2 dimensions or phase rotations of chiral (definite-helicity) parts of vectors in 4 dimensions. We also briefly discuss some 4d models and comment on implications of our analysis for extended supergravities.Comment: 21 pages, Latex v2: comments and references added v3: references and minor comments adde

A manifestly MHV Lagrangian for N=4 Yang-Mills

We derive a manifestly MHV Lagrangian for the N=4 supersymmetric Yang-Mills theory in light-cone superspace. This is achieved by constructing a canonical redefinition which maps the N=4 superfield and its conjugate to a new pair of superfields. In terms of these new superfields the N=4 Lagrangian takes a (non-polynomial) manifestly MHV form, containing vertices involving two superfields of negative helicity and an arbitrary number of superfields of positive helicity. We also discuss constraints satisfied by the new superfields, which ensure that they describe the correct degrees of freedom in the N=4 supermultiplet. We test our derivation by showing that an expansion of our superspace Lagrangian in component fields reproduces the correct gluon MHV vertices.Comment: 37 pages, 1 figure. v2: minor changes, references adde

The Moore-Penrose Pseudoinverse. A Tutorial Review of the Theory

In the last decades the Moore-Penrose pseudoinverse has found a wide range of applications in many areas of Science and became a useful tool for physicists dealing, for instance, with optimization problems, with data analysis, with the solution of linear integral equations, etc. The existence of such applications alone should attract the interest of students and researchers in the Moore-Penrose pseudoinverse and in related sub jects, like the singular values decomposition theorem for matrices. In this note we present a tutorial review of the theory of the Moore-Penrose pseudoinverse. We present the first definitions and some motivations and, after obtaining some basic results, we center our discussion on the Spectral Theorem and present an algorithmically simple expression for the computation of the Moore-Penrose pseudoinverse of a given matrix. We do not claim originality of the results. We rather intend to present a complete and self-contained tutorial review, useful for those more devoted to applications, for those more theoretically oriented and for those who already have some working knowledge of the sub ject.Comment: 23 page

Inhibition of the Intrinsic but Not the Extrinsic Apoptosis Pathway Accelerates and Drives Myc-Driven Tumorigenesis Towards Acute Myeloid Leukemia

Myc plays an important role in tumor development, including acute myeloid leukemia (AML). However, MYC is also a powerful inducer of apoptosis, which is one of the major failsafe programs to prevent cancer development. To clarify the relative importance of the extrinsic (death receptor-mediated) versus the intrinsic (mitochondrial) pathway of apoptosis in MYC-driven AML, we coexpressed MYC together with anti-apoptotic proteins of relevance for AML; BCL-XL/BCL-2 (inhibiting the intrinsic pathway) or FLIPL (inhibiting the extrinsic pathway), in hematopoietic stems cells (HSCs). Transplantation of HSCs expressing MYC into syngeneic recipient mice resulted in development of AML and T-cell lymphomas within 7–9 weeks as expected. Importantly, coexpression of MYC together with BCL-XL/BCL-2 resulted in strongly accelerated kinetics and favored tumor development towards aggressive AML. In contrast, coexpression of MYC and FLIPL did neither accelerate tumorigenesis nor change the ratio of AML versus T-cell lymphoma. However, a change in distribution of immature CD4+CD8+ versus mature CD4+ T-cell lymphoma was observed in MYC/FLIPL mice, possibly as a result of increased survival of the CD4+ population, but this did not significantly affect the outcome of the disease. In conclusion, our findings provide direct evidence that BCL-XL and BCL-2 but not FLIPL acts in synergy with MYC to drive AML development

The Evolution of Compact Binary Star Systems

We review the formation and evolution of compact binary stars consisting of white dwarfs (WDs), neutron stars (NSs), and black holes (BHs). Binary NSs and BHs are thought to be the primary astrophysical sources of gravitational waves (GWs) within the frequency band of ground-based detectors, while compact binaries of WDs are important sources of GWs at lower frequencies to be covered by space interferometers (LISA). Major uncertainties in the current understanding of properties of NSs and BHs most relevant to the GW studies are discussed, including the treatment of the natal kicks which compact stellar remnants acquire during the core collapse of massive stars and the common envelope phase of binary evolution. We discuss the coalescence rates of binary NSs and BHs and prospects for their detections, the formation and evolution of binary WDs and their observational manifestations. Special attention is given to AM CVn-stars -- compact binaries in which the Roche lobe is filled by another WD or a low-mass partially degenerate helium-star, as these stars are thought to be the best LISA verification binary GW sources.Comment: 105 pages, 18 figure

Identification and Characterization of Two Functionally Unknown Genes Involved in Butanol Tolerance of Clostridium acetobutylicum

Solvents toxicity is a major limiting factor hampering the cost-effective biotechnological production of chemicals. In Clostridium acetobutylicum, a functionally unknown protein (encoded by SMB_G1518) with a hypothetical alcohol interacting domain was identified. Disruption of SMB_G1518 and/or its downstream gene SMB_G1519 resulted in increased butanol tolerance, while overexpression of SMB_G1518-1519 decreased butanol tolerance. In addition, SMB_G1518-1519 also influences the production of pyruvate:ferredoxin oxidoreductase (PFOR) and flagellar protein hag, the maintenance of cell motility. We conclude that the system of SMB_G1518-1519 protein plays a role in the butanol sensitivity/tolerance phenotype of C. acetobutylicum, and can be considered as potential targets for engineering alcohol tolerance

Compressed representation of a partially defined integer function over multiple arguments

In OLAP (OnLine Analitical Processing) data are analysed in an n-dimensional cube. The cube may be represented as a partially defined function over n arguments. Considering that often the function is not defined everywhere, we ask: is there a known way of representing the function or the points in which it is defined, in a more compact manner than the trivial one