A novelty-based multi-objective evolutionary algorithm for identifying functional dependencies in complex technical infrastructures from alarm data

In this work, a Multi-Objective Evolutionary Algorithm (MOEA) is developed to identify Functional Dependencies (FDEPs) in Complex Technical Infrastructures (CTIs) from alarm data. The objectives of the search are the maximization of a measure of novelty, which drives the exploration of the solution space avoiding to get trapped in local optima, and of a measure of dependency among alarms, which drives the uncovering of functional dependencies. The main contribution of the work is the direct identification of patterns of dependent alarms; this avoids going through the preliminary step of mining association rules, as typically done by state-of-the-art methods which, however, fail to identify rare functional dependencies due to the need of setting a balanced minimum occurrence threshold. The proposed framework for FDEPs identification is applied to a synthetic alarm database generated by a simulated CTI model and to a real large-scale database of alarms collected at the CTI of CERN (European Organization for Nuclear Research). The obtained results show that the framework enables the thorough exploration of the solution space and captures also rare functional dependencies.

Generation of a NES-mScarlet Red Fluorescent Reporter Human iPSC Line for Live Cell Imaging and Flow Cytometric Analysis and Sorting Using CRISPR-Cas9-Mediated Gene Editing

Advances in the regenerative stem cell field have propelled the generation of tissue-specific cells in the culture dish for subsequent transplantation, drug screening purposes, or the elucidation of disease mechanisms. One major obstacle is the heterogeneity of these cultures, in which the tissue-specific cells of interest usually represent only a fraction of all generated cells. Direct identification of the cells of interest and the ability to specifically isolate these cells in vitro is, thus, highly desirable for these applications. The type VI intermediate filament protein NESTIN is widely used as a marker for neural stem/progenitor cells (NSCs/NPCs) in the developing and adult central and peripheral nervous systems. Applying CRISPR-Cas9 technology, we have introduced a red fluorescent reporter (mScarlet) into the NESTIN (NES) locus of a human induced pluripotent stem cell (hiPSC) line. We describe the generation and characterization of NES-mScarlet reporter hiPSCs and demonstrate that this line is an accurate reporter of NSCs/NPCs during their directed differentiation into human midbrain dopaminergic (mDA) neurons. Furthermore, NES-mScarlet hiPSCs can be used for direct identification during live cell imaging and for flow cytometric analysis and sorting of red fluorescent NSCs/NPCs in this paradigm.

Intracellular bound chlorophyll residues identify 1 Gyr-old fossils as eukaryotic algae

The acquisition of photosynthesis is a fundamental step in the evolution of eukaryotes. However, few phototrophic organisms are unambiguously recognized in the Precambrian record. The in situ detection of metabolic byproducts in individual microfossils is the key for the direct identification of their metabolisms. Here, we report a new integrative methodology using synchrotron-based X-ray fluorescence and absorption. We evidence bound nickel-geoporphyrins moieties in low-grade metamorphic rocks, preserved in situ within cells of a ~1 Gyr-old multicellular eukaryote, Arctacellularia tetragonala. We identify these moieties as chlorophyll derivatives, indicating that A. tetragonala was a phototrophic eukaryote, one of the first unambiguous algae. This new approach, applicable to overmature rocks, creates a strong new proxy to understand the evolution of phototrophy and diversification of early ecosystems.

The direct identification of quantum cutting in Tm3+ ion and energy transfer in Tm3+/Yb3+ system based on Ba2Gd2Si4O13 oxide host

Quantum cutting (QC) is an important physical process, the occurrence of which still needs further verifying in different luminescent ions. In this work, a series of Tm3+/Yb3+ doped Ba2Gd2Si4O13 (BGS)...

Performance and Impact on Initial Antibiotic Choice of Direct Identification of Pathogens from Pediatric Blood Culture Bottles Using an In-House MALDI-TOF MS Protocol

We demonstrate the performance and early impact on the antimicrobial management of bloodstream infections of an inexpensive, in-house preparation method for direct identification of bloodstream pathogens in pediatric blood culture bottles by matrix-assisted laser desorption/ionization–time-of-flight mass spectrometry.

Mapping of the autophagosomal degradome identifies IL-7Rα as key cargo in proliferating CD4+ T-cells

CD4+ T cells orchestrate both humoral and cytotoxic immune responses. While it is known that CD4+ T cell proliferation relies on autophagy, direct identification of the autophagosomal cargo involved is still missing. Here, we created a transgenic mouse model, which, for the first time, enables us to directly map the proteinaceous content of autophagosomes in any primary cell by LC3 proximity labelling. IL-7Rα, a cytokine receptor mostly found in naive and memory T cells, was reproducibly detected in autophagosomes of activated CD4+ T cells. Consistently, CD4+ T cells lacking autophagy showed increased IL-7Rα surface expression, while no defect in internalisation was observed. Mechanistically, excessive surface IL-7Rα sequestrates the common gamma chain, impairing the IL-2R assembly and downstream signalling crucial for T cell proliferation. This study provides proof-of-principle that key autophagy substrates can be reliably identified with this model to help mechanistically unravel autophagy's contribution to healthy physiology and disease.

Spatiotemporal Analysis of Waves in Compressively Driven Magnetohydrodynamics Turbulence

Using direct numerical simulations (DNSs), the interaction between linear waves and turbulence under the compressible magnetohydrodynamic (CMHD) approach was studied. A set of DNSs in three dimensions for a spatial resolution of 1283 and 2563 were performed. A parametric study was carried out varying the sonic Mach number, the mean-magnetic field, and the compressibility amplitude of the forcing. Spatiotemporal spectra of the magnetic energy were built and analyzed, allowing for direct identification of all wave modes in a CMHD turbulent system and quantification of the amount of energy in each mode as a function of the wavenumber. Thus, linear waves were detected, that is Alfvén waves and fast and slow magnetosonic waves. Furthermore, different responses of the plasma were found according to whether the Mach number or the mean-magnetic field was varied. On the other hand, making use of spatiotemporal spectra and two different integration methods, we accurately quantified the amount of energy present in each of the normal modes. Finally, although the presence of linear waves was observed, in all the cases studied the system was mainly dominated by the nonlinear dynamics of the plasma.

Fukaya A∞-structures associated to Lefschetz fibrations. V

We (re)consider how the Fukaya category of a Lefschetz fibration is related to that of the fiber. The distinguishing feature of the approach here is a more direct identification of the bimodule homomorphism involved.

Ultra-fast direct method for identifying microorganisms from BACTEC lytic/10 anaerobic/F flasks

Background: Fast diagnosis of bloodstream infections remains the most important challenge for clinical microbiologists. The introduction of the mass-spectrometry represents a breakthrough, although several methods are already commonly used for the direct identification from positive blood cultures we present a faster method (ultra fast) for Lytic anaerobic flasks. Methods: We compare the ultra-fast (UF) method with the extensively employed differential centrifugation method (DC) and both to routine identification after 18–24 h of incubation. UF and DC method correlation rates to the gold standard were calculated, and statistical significance was proved with the Z test. Results: UF performed better overall than DC, with this difference being statistically significant. This tendency was observed in every subanalysis.