A biomimetic enzyme-linked immunosorbent assay (BELISA) for the analysis of gonadorelin by using molecularly imprinted polymer-coated microplates

An original biomimetic enzyme-linked immunoassay (BELISA) to target the small peptide hormone gonadorelin is presented. This peptide has been recently listed among the substances banned in sports by the World Antidoping Agency (WADA) since its misuse by male athletes triggers testosterone increase. Hence, in response to this emerging issue in anti-doping controls, we proposed BELISA which involves the growth of a polynorepinephrine (PNE)–based molecularly imprinted polymer (MIP) directly on microwells. PNE, a polydopamine (PDA) analog, has recently displayed impressive performances when it was exploited for MIP preparation, giving even better results than PDA. Gonadorelin quantification was accomplished via a colorimetric indirect competitive bioassay involving the competition between biotinylated gonadorelin linked to the signal reporter and the unlabeled analyte. These compete for the same MIP binding sites resulting in an inverse correlation between gonadorelin concentration and the output color signal (λ = 450 nm). A detection limit of 277 pmol L−1 was achieved with very good reproducibility in standard solutions (avCV% = 4.07%) and in urine samples (avCV% = 5.24%). The selectivity of the assay resulted adequate for biological specimens and non-specific control peptides. In addition, the analytical figures of merit were successfully validated by mass spectrometry, the reference anti-doping benchtop platform for the analyte. BELISA was aimed to open real perspectives for PNE-based MIPs as alternatives to antibodies, especially when the target analyte is a poorly or non-immunogenic small molecule, such as gonadorelin. Graphical abstract

Hybrid mass damper: theoretical and experimental power flow analysis

In this paper, a hybrid mass damper (HMD) and its hyperstability thanks to a power flow approach are studied. The HMD proposed combines an active control system with an optimal passive device. The initial passive system is an electromagnetic Tuned Mass Damper (TMD) and the control law is a modified velocity feedback with a phase compensator. The resulting hybrid controller system is theoretically hyperstable and ensures fail-safe behavior. Experiments are performed to validate the numerical simulation and provide good results in terms of vibration attenuations. Both excitation from the bottom in the frequency domain and shock response in the time domain are tested and analyzed. The different power flows in terms of active and reactive powers are estimated numerically and experimentally on the inertial damper (passive and active) and on the HMD. More over, through a mechanical analogy of the proposed system, it is shown that this hybrid device can be seen as an active realization of an inerter based tuned-mass-damper associated with a sky-hook damper. Observations and analysis provide insight into the hyperstable behavior imposed by the specific control law.

An Ultrasensitive Silicon-Based Electrolyte-Gated Transistor for the Detection of Peanut Allergens

The highly sensitive detection of peanut allergens (PAs) using silicon-based electrolyte-gated transistors (Si-EGTs) was demonstrated. The Si-EGT was made using a top-down technique. The fabricated Si-EGT showed excellent intrinsic electrical characteristics, including a low threshold voltage of 0.7 V, low subthreshold swing of <70 mV/dec, and low gate leakage of <10 pA. Surface functionalization and immobilization of antibodies were performed for the selective detection of PAs. The voltage-related sensitivity (SV) showed a constant behavior from the subthreshold regime to the linear regime. The current-related sensitivity (SI) was high in the subthreshold regime and then significantly decreased as the drain current increased. The limit of detection (LOD) was calculated to be as low as 25 pg/mL based on SI characteristics, which is the lowest value reported to date in the literature for various sensor methodologies. The Si-EGT showed selective detection of PA through a non-specific control test. These results confirm that Si-EGT is a high-sensitivity and low-power biosensor for PA detection.

Adapting a Requirements Engineering Process by Key Factors Estimation

Literature mainly focuses the adaptation of any requirements engineering process on the possible variations of elicitation techniques, mainly due to information sources characteristics. However, these particularities, usually called situational factors, are seldom considered in other activities of the requirements process. Most situational factors, when considered in software projects, have a high influence on the requirements process. Therefore, the different situations that may attempt against or may favor a successful requirements process should be identified at the beginning of the project. Additionally, some of such factors may evolve along software development life cycle; this should motivate a reengineering of the requirements process at some strategic milestones. In this chapter, a process for constructing and dynamically adapting a requirements process is proposed, focusing on the evolving factors. The process follows rules based on different combinations of situational factors at specific control points and manages a repository of process blocks to perform the tailoring.

Note on geometric algebras and control problems with SO(3)-symmetries

We study the role of symmetries in control systems by means of geometric algebra approach. We discuss two specific control problems on Carnot group of step 2 invariant with respect to the action of$SO(3). We understand geodesics as curves in suitable geometric algebras which allows us to asses an efficient algorithm for local control.

Input-specific control of interneuron numbers in nascent striatal networks

The assembly of functional neuronal circuits requires appropriate numbers of distinct classes of neurons, but the mechanisms through which their relative proportions are established remain poorly defined. Investigating the mouse striatum, here we found that the two most prominent subtypes of striatal interneurons, parvalbumin-expressing (PV+) GABAergic and cholinergic (ChAT+) interneurons, undergo extensive programmed cell death between the first and second postnatal weeks. Remarkably, the survival of PV+ and ChAT+ interneurons is regulated by distinct mechanisms mediated by their specific afferent connectivity. While long-range cortical inputs control PV+ interneuron survival, ChAT+ interneuron survival is regulated by local input from the medium spiny neurons. Our results identify input-specific circuit mechanisms that operate during the period of programmed cell death to establish the final number of interneurons in nascent striatal networks.

Stage-specific control of oligodendrocyte survival and morphogenesis by TDP-43

Generation of oligodendrocytes in the adult brain enables both adaptive changes in neural circuits and regeneration of myelin sheaths destroyed by injury, disease, and normal aging. This transformation of oligodendrocyte precursor cells (OPCs) into myelinating oligodendrocytes requires processing of distinct mRNAs at different stages of cell maturation. Although mislocalization and aggregation of the RNA binding protein TDP-43 occur in both neurons and glia in neurodegenerative diseases, the consequences of TDP-43 loss within different stages of the oligodendrocyte lineage are not well understood. By performing stage-specific genetic inactivation of Tardbpin vivo, we show that oligodendrocyte lineage cells are differentially sensitive to loss of TDP-43. While OPCs depend on TDP-43 for survival, with conditional deletion resulting in cascading cell loss followed by rapid regeneration to restore their density, oligodendrocytes become less sensitive to TDP-43 depletion as they mature. Deletion of TDP-43 early in the maturation process led to eventual oligodendrocyte degeneration, seizures and premature lethality, while oligodendrocytes that experienced late deletion survived and mice exhibited a normal lifespan. At both stages, TDP-43 deficient oligodendrocytes formed fewer and thinner myelin sheaths and extended new processes that inappropriately wrapped neuronal somata and blood vessels. Transcriptional analysis revealed that in the absence of TDP-43, key proteins involved in oligodendrocyte maturation and myelination were misspliced leading to aberrant incorporation of cryptic exons. Inducible deletion of TDP-43 from oligodendrocytes in the adult CNS induced the same progressive morphological changes and mice acquired profound hindlimb weakness, suggesting that loss of TDP-43 function in oligodendrocytes may contribute to neuronal dysfunction in neurodegenerative disease.

A six-metabolite panel as potential blood-based biomarkers for Parkinson’s disease

Characterisation and diagnosis of idiopathic Parkinson’s disease (iPD) is a current challenge that hampers both clinical assessment and clinical trial development with the potential inclusion of non-PD cases. Here, we used a targeted mass spectrometry approach to quantify 38 metabolites extracted from the serum of 231 individuals. This cohort is currently one of the largest metabolomic studies including iPD patients, drug-naïve iPD, healthy controls and patients with Alzheimer’s disease as a disease-specific control group. We identified six metabolites (3-hydroxykynurenine, aspartate, beta-alanine, homoserine, ornithine (Orn) and tyrosine) that are significantly altered between iPD patients and control participants. A multivariate model to predict iPD from controls had an area under the curve (AUC) of 0.905, with an accuracy of 86.2%. This panel of metabolites may serve as a potential prognostic or diagnostic assay for clinical trial prescreening, or for aiding in diagnosing pathological disease in the clinic.