Numerical methods for the analysis of sampled-data systems and for the computation of system zeros

MARSYAS is a computer-aided control system design package for the simulation and analysis of dynamic systems. In the summer of 1991 MARSYAS was updated to allow for the analysis of sampled-data systems in terms of frequency response, stability, etc. This update was continued during the summer of 1992 in order to extend further MARSYAS commands to the study of sampled-data systems. Further work was done to examine the computation of OPENAT transfer functions, root-locii and w-plane frequency response plots

Octave: A MARSYAS post-processor for computer-aideed control system design

MARSYAS is a computer-aided control system analysis package for the simulation and analysis of dynamic systems. In the summer of 1991 MARSYAS was updated to allow for the analysis of sampled-data systems in terms of frequency response, stability, etc. This update was continued during the summer of 1992 in order to extend further MARSYAS commands to the study of sampled data systems. Further work was done to examine the computation of openat transfer functions, root-locii and omega-plane frequency response plots. At the conclusion of the summer of 1992 work, it was proposed that control-system design capability be incorporated into the MARSYAS package. It was decided at that time to develop a separate 'stand-alone' computer-aided control system design (CACSD) package. This report is a brief description of such a package

HIV-1 latent reservoir: size matters.

More than 35 million people remain infected with HIV-1. Upon antiretroviral therapy cessation, HIV-1-positive individuals systematically fail to achieve sustained virological remission, revealing the presence of a reservoir. This reservoir takes into account anatomical sanctuaries where HIV-1 continues to replicate, and latently infected cells also known as the latent reservoir (LR). A better understanding of the nature and features of the LR and its quantification are crucial to evaluate the efficiency of therapeutic strategies aiming at purging HIV-1. Culture- and PCR-based assays have already been implemented to measure the LR, and new assays are continuously being developed. In this review, we will discuss these methods highlighting the difficulties to accurately measure the LR, one main obstacle in curing HIV-1

Stability Metrics for Simulation and Flight-Software Assessment and Monitoring of Adaptive Control Assist Compensators

Due to a need for improved reliability and performance in aerospace systems, there is increased interest in the use of adaptive control or other nonlinear, time-varying control designs in aerospace vehicles. While such techniques are built on Lyapunov stability theory, they lack an accompanying set of metrics for the assessment of stability margins such as the classical gain and phase margins used in linear time-invariant systems. Such metrics must both be physically meaningful and permit the user to draw conclusions in a straightforward fashion. We present in this paper a roadmap to the development of metrics appropriate to nonlinear, time-varying systems. We also present two case studies in which frozen-time gain and phase margins incorrectly predict stability or instability. We then present a multi-resolution analysis approach that permits on-line real-time stability assessment of nonlinear systems

A Singular Perturbation Approach for Time-Domain Assessment of Phase Margin

This paper considers the problem of time-domain assessment of the Phase Margin (PM) of a Single Input Single Output (SISO) Linear Time-Invariant (LTI) system using a singular perturbation approach, where a SISO LTI fast loop system, whose phase lag increases monotonically with frequency, is introduced into the loop as a singular perturbation with a singular perturbation (time-scale separation) parameter Epsilon. First, a bijective relationship between the Singular Perturbation Margin (SPM) max and the PM of the nominal (slow) system is established with an approximation error on the order of Epsilon(exp 2). In proving this result, relationships between the singular perturbation parameter Epsilon, PM of the perturbed system, PM and SPM of the nominal system, and the (monotonically increasing) phase of the fast system are also revealed. These results make it possible to assess the PM of the nominal system in the time-domain for SISO LTI systems using the SPM with a standardized testing system called "PM-gauge," as demonstrated by examples. PM is a widely used stability margin for LTI control system design and certification. Unfortunately, it is not applicable to Linear Time-Varying (LTV) and Nonlinear Time-Varying (NLTV) systems. The approach developed here can be used to establish a theoretical as well as practical metric of stability margin for LTV and NLTV systems using a standardized SPM that is backward compatible with PM

Suppression of planar cell polarity signaling and migration in glioblastoma by Nrdp1-mediated Dvl polyubiquitination.

The lethality of the aggressive brain tumor glioblastoma multiforme (GBM) results in part from its strong propensity to invade surrounding normal brain tissue. Although oncogenic drivers such as epidermal growth factor receptor activation and Phosphatase and Tensin homolog inactivation are thought to promote the motility and invasiveness of GBM cells via phosphatidylinostitol 3-kinase activation, other unexplored mechanisms may also contribute to malignancy. Here we demonstrate that several components of the planar cell polarity (PCP) arm of non-canonical Wnt signaling including VANGL1, VANGL2 and FZD7 are transcriptionally upregulated in glioma and correlate with poorer patient outcome. Knockdown of the core PCP pathway component VANGL1 suppresses the motility of GBM cell lines, pointing to an important mechanistic role for this pathway in glioblastoma malignancy. We further observe that restoration of Nrdp1, a RING finger type E3 ubiquitin ligase whose suppression in GBM also correlates with poor prognosis, reduces GBM cell migration and invasiveness by suppressing PCP signaling. Our observations indicate that Nrdp1 physically interacts with the Vangl1 and Vangl2 proteins to mediate the K63-linked polyubiquitination of the Dishevelled, Egl-10 and Pleckstrin (DEP) domain of the Wnt pathway protein Dishevelled (Dvl). Ubiquitination hinders Dvl binding to phosphatidic acid, an interaction necessary for efficient Dvl recruitment to the plasma membrane upon Wnt stimulation of Fzd receptor and for the propagation of downstream signals. We conclude that the PCP pathway contributes significantly to the motility and hence the invasiveness of GBM cells, and that Nrdp1 acts as a negative regulator of PCP signaling by inhibiting Dvl through a novel polyubiquitination mechanism. We propose that the upregulation of core PCP components, together with the loss of the key negative regulator Nrdp1, act coordinately to promote GBM invasiveness and malignancy

Articular degeneration after subchondral cementation for giant cell tumors at the knee

PURPOSE To quantify joint degeneration and the clinical outcome after curettage and cementation in subchondral giant cell tumors of the bone (GCTB) at the knee. METHODS We conducted a retrospective analysis of 14 consecutive patients (seven female, seven male) with a mean age of 34 years (range 19-51) who underwent curettage and subchondral cementation for a biopsy-confirmed GCTB at the distal femur or the proximal tibia between August 2001 and August 2017, with a mean follow-up period of 54.6 months (range 16.1-156 months). The Whole-Organ Magnetic Resonance Imaging Score (WORMS), Kellgren-Lawrence (KL) classification, and Musculo-Skeletal Tumor Society (MSTS) score were assessed. RESULTS Radiological degeneration progressed from preoperative to the latest follow-up, with a median WORMS from 2.0 to 4.0 (p = 0.006); meanwhile, the median KL score remained at 0 (p = 0.102). Progressive degeneration (WORMS) tended to be associated with the proximity of the tumor to the articular cartilage (mean 1.57 mm; range 0-12 mm) (p = 0.085). The most common degenerative findings were cartilage lesions (n = 11), synovitis (n = 5), and osteophytes (n = 4). Mean MSTS score increased from 23.1 (preoperatively) to 28.3 at the latest follow-up (p < 0.01). Seven patients (50%) were treated for a local recurrence, with six revision surgeries performed. Removal of the cement spacer and filling of the cavity with a cancellous autograft was performed in seven patients. Conversion to a total knee arthroplasty was performed in one patient for local tumor control. CONCLUSIONS Cementation following the curettage of GCTB around the knee is associated with slight degeneration at medium-term follow-up and leads to a significant reduction in pain. Removal of the cement and reconstruction with an autograft may be beneficial in the long term