Affine arithmetic-based methodology for energy hub operation-scheduling in the presence of data uncertainty

In this study, the role of self-validated computing for solving the energy hub-scheduling problem in the presence of multiple and heterogeneous sources of data uncertainties is explored and a new solution paradigm based on affine arithmetic is conceptualised. The benefits deriving from the application of this methodology are analysed in details, and several numerical results are presented and discussed

Gravity-driven instability in a spherical Hele-Shaw cell

A pair of concentric spheres separated by a small gap form a spherical Hele-Shaw cell. In this cell an interfacial instability arises when two immiscible fluids flow. We derive the equation of motion for the interface perturbation amplitudes, including both pressure and gravity drivings, using a mode coupling approach. Linear stability analysis shows that mode growth rates depend upon interface perimeter and gravitational force. Mode coupling analysis reveals the formation of fingering structures presenting a tendency toward finger tip-sharpening.Comment: 13 pages, 4 ps figures, RevTex, to appear in Physical Review

Analytical approach to viscous fingering in a cylindrical Hele-Shaw cell

We report analytical results for the development of the viscous fingering instability in a cylindrical Hele-Shaw cell of radius a and thickness b. We derive a generalized version of Darcy's law in such cylindrical background, and find it recovers the usual Darcy's law for flow in flat, rectangular cells, with corrections of higher order in b/a. We focus our interest on the influence of cell's radius of curvature on the instability characteristics. Linear and slightly nonlinear flow regimes are studied through a mode-coupling analysis. Our analytical results reveal that linear growth rates and finger competition are inhibited for increasingly larger radius of curvature. The absence of tip-splitting events in cylindrical cells is also discussed.Comment: 14 pages, 3 ps figures, Revte

The quantum state vector in phase space and Gabor's windowed Fourier transform

Representations of quantum state vectors by complex phase space amplitudes, complementing the description of the density operator by the Wigner function, have been defined by applying the Weyl-Wigner transform to dyadic operators, linear in the state vector and anti-linear in a fixed `window state vector'. Here aspects of this construction are explored, with emphasis on the connection with Gabor's `windowed Fourier transform'. The amplitudes that arise for simple quantum states from various choices of window are presented as illustrations. Generalized Bargmann representations of the state vector appear as special cases, associated with Gaussian windows. For every choice of window, amplitudes lie in a corresponding linear subspace of square-integrable functions on phase space. A generalized Born interpretation of amplitudes is described, with both the Wigner function and a generalized Husimi function appearing as quantities linear in an amplitude and anti-linear in its complex conjugate. Schr\"odinger's time-dependent and time-independent equations are represented on phase space amplitudes, and their solutions described in simple cases.Comment: 36 pages, 6 figures. Revised in light of referees' comments, and further references adde

Esbl/ampc-producing escherichia coli in wild boar: Epidemiology and risk factors

The complex health problem of antimicrobial resistance (AMR) involves many host species, numerous bacteria and several routes of transmission. Extended-spectrum β-lactamase and AmpC (ESBL/AmpC)-producing Escherichia coli are among the most important strains. Moreover, wildlife hosts are of interest as they are likely antibiotics free and are assumed as environmental indicators of AMR contamination. Particularly, wild boar (Sus scrofa) deserves attention because of its increased population densities, with consequent health risks at the wildlife–domestic–human interface, and the limited data available on AMR. Here, 1504 wild boar fecal samples were microbiologically and molecularly analyzed to investigate ESBL/AmpC-producing E. coli and, through generalized linear models, the effects of host-related factors and of human population density on their spread. A prevalence of 15.96% of ESBL/AmpC-producing E. coli, supported by blaCTX-M (12.3%), blaTEM (6.98%), blaCMY (0.86%) and blaSHV (0.47%) gene detection, emerged. Young animals were more colonized by ESBL/AmpC strains than older subjects, as observed in domestic animals. Increased human population density leads to increased blaTEM prevalence in wild boar, suggesting that spatial overlap may favor this transmission. Our results show a high level of AMR contamination in the study area that should be further investigated. However, a role of wild boar as a maintenance host of AMR strains emerged

The Saffman-Taylor problem on a sphere

The Saffman-Taylor problem addresses the morphological instability of an interface separating two immiscible, viscous fluids when they move in a narrow gap between two flat parallel plates (Hele-Shaw cell). In this work, we extend the classic Saffman-Taylor situation, by considering the flow between two curved, closely spaced, concentric spheres (spherical Hele-Shaw cell). We derive the mode-coupling differential equation for the interface perturbation amplitudes and study both linear and nonlinear flow regimes. The effect of the spherical cell (positive) spatial curvature on the shape of the interfacial patterns is investigated. We show that stability properties of the fluid-fluid interface are sensitive to the curvature of the surface. In particular, it is found that positive spatial curvature inhibits finger tip-splitting. Hele-Shaw flow on weakly negative, curved surfaces is briefly discussed.Comment: 26 pages, 4 figures, RevTex, accepted for publication in Phys. Rev.

VEGF-A/VEGFR-1 signalling and chemotherapy-induced neuropathic pain: therapeutic potential of a novel anti-VEGFR-1 monoclonal antibody

Background Neuropathic pain is a clinically relevant adverse effect of several anticancer drugs that markedly impairs patients' quality of life and frequently leads to dose reduction or therapy discontinuation. The poor knowledge about the mechanisms involved in neuropathy development and pain chronicization, and the lack of effective therapies, make treatment of chemotherapy-induced neuropathic pain an unmet medical need. In this context, the vascular endothelial growth factor A (VEGF-A) has emerged as a candidate neuropathy hallmark and its decrease has been related to pain relief. In the present study, we have investigated the role of VEGF-A and its receptors, VEGFR-1 and VEGFR-2, in pain signalling and in chemotherapy-induced neuropathy establishment as well as the therapeutic potential of receptor blockade in the management of pain. Methods Behavioural and electrophysiological analyses were performed in an in vivo murine model, by using selective receptor agonists, blocking monoclonal antibodies or siRNA-mediated silencing of VEGF-A and VEGFRs. Expression of VEGF-A and VEGFR-1 in astrocytes and neurons was detected by immunofluorescence staining and confocal microscopy analysis. Results In mice, the intrathecal infusion of VEGF-A (VEGF(165) isoforms) induced a dose-dependent noxious hypersensitivity and this effect was mediated by VEGFR-1. Consistently, electrophysiological studies indicated that VEGF-A strongly stimulated the spinal nociceptive neurons activity through VEGFR-1. In the dorsal horn of the spinal cord of animals affected by oxaliplatin-induced neuropathy, VEGF-A expression was increased in astrocytes while VEGFR-1 was mainly detected in neurons, suggesting a VEGF-A/VEGFR-1-mediated astrocyte-neuron cross-talk in neuropathic pain pathophysiology. Accordingly, the selective knockdown of astrocytic VEGF-A by intraspinal injection of shRNAmir blocked the development of oxaliplatin-induced neuropathic hyperalgesia and allodynia. Interestingly, both intrathecal and systemic administration of the novel anti-VEGFR-1 monoclonal antibody D16F7, endowed with anti-angiogenic and antitumor properties, reverted oxaliplatin-induced neuropathic pain. Besides, D16F7 effectively relieved hypersensitivity induced by other neurotoxic chemotherapeutic agents, such as paclitaxel and vincristine. Conclusions These data strongly support the role of the VEGF-A/VEGFR-1 system in mediating chemotherapy-induced neuropathic pain at the central nervous system level. Thus, treatment with the anti-VEGFR-1 mAb D16F7, besides exerting antitumor activity, might result in the additional advantage of attenuating neuropathic pain when combined with neurotoxic anticancer agents

VEGF-A/VEGFR-1 signalling and chemotherapy-induced neuropathic pain: therapeutic potential of a novel anti-VEGFR-1 monoclonal antibody

Abstract Background Neuropathic pain is a clinically relevant adverse effect of several anticancer drugs that markedly impairs patients’ quality of life and frequently leads to dose reduction or therapy discontinuation. The poor knowledge about the mechanisms involved in neuropathy development and pain chronicization, and the lack of effective therapies, make treatment of chemotherapy-induced neuropathic pain an unmet medical need. In this context, the vascular endothelial growth factor A (VEGF-A) has emerged as a candidate neuropathy hallmark and its decrease has been related to pain relief. In the present study, we have investigated the role of VEGF-A and its receptors, VEGFR-1 and VEGFR-2, in pain signalling and in chemotherapy-induced neuropathy establishment as well as the therapeutic potential of receptor blockade in the management of pain. Methods Behavioural and electrophysiological analyses were performed in an in vivo murine model, by using selective receptor agonists, blocking monoclonal antibodies or siRNA-mediated silencing of VEGF-A and VEGFRs. Expression of VEGF-A and VEGFR-1 in astrocytes and neurons was detected by immunofluorescence staining and confocal microscopy analysis. Results In mice, the intrathecal infusion of VEGF-A (VEGF165 isoforms) induced a dose-dependent noxious hypersensitivity and this effect was mediated by VEGFR-1. Consistently, electrophysiological studies indicated that VEGF-A strongly stimulated the spinal nociceptive neurons activity through VEGFR-1. In the dorsal horn of the spinal cord of animals affected by oxaliplatin-induced neuropathy, VEGF-A expression was increased in astrocytes while VEGFR-1 was mainly detected in neurons, suggesting a VEGF-A/VEGFR-1-mediated astrocyte-neuron cross-talk in neuropathic pain pathophysiology. Accordingly, the selective knockdown of astrocytic VEGF-A by intraspinal injection of shRNAmir blocked the development of oxaliplatin-induced neuropathic hyperalgesia and allodynia. Interestingly, both intrathecal and systemic administration of the novel anti-VEGFR-1 monoclonal antibody D16F7, endowed with anti-angiogenic and antitumor properties, reverted oxaliplatin-induced neuropathic pain. Besides, D16F7 effectively relieved hypersensitivity induced by other neurotoxic chemotherapeutic agents, such as paclitaxel and vincristine. Conclusions These data strongly support the role of the VEGF-A/VEGFR-1 system in mediating chemotherapy-induced neuropathic pain at the central nervous system level. Thus, treatment with the anti-VEGFR-1 mAb D16F7, besides exerting antitumor activity, might result in the additional advantage of attenuating neuropathic pain when combined with neurotoxic anticancer agents