Divergent Annexin A1 expression in periphery and gut is associated with systemic immune activation and impaired gut immune response during SIV infection.

HIV-1 disease progression is paradoxically characterized by systemic chronic immune activation and gut mucosal immune dysfunction, which is not fully defined. Annexin A1 (ANXA1), an inflammation modulator, is a potential link between systemic inflammation and gut immune dysfunction during the simian immunodeficiency virus (SIV) infection. Gene expression of ANXA1 and cytokines were assessed in therapy-naïve rhesus macaques during early and chronic stages of SIV infection and compared with SIV-negative controls. ANXA1 expression was suppressed in the gut but systemically increased during early infection. Conversely, ANXA1 expression increased in both compartments during chronic infection. ANXA1 expression in peripheral blood was positively correlated with HLA-DR+CD4+ and CD8+ T-cell frequencies, and negatively associated with the expression of pro-inflammatory cytokines and CCR5. In contrast, the gut mucosa presented an anergic cytokine profile in relation to ANXA1 expression. In vitro stimulations with ANXA1 peptide resulted in decreased inflammatory response in PBMC but increased activation of gut lymphocytes. Our findings suggest that ANXA1 signaling is dysfunctional in SIV infection, and may contribute to chronic inflammation in periphery and with immune dysfunction in the gut mucosa. Thus, ANXA1 signaling may be a novel therapeutic target for the resolution of immune dysfunction in HIV infection

Identification of Myeloid Derived Suppressor Cells in Dogs with Naturally Occurring Cancer

Dogs with naturally occurring cancer represent an important large animal model for drug development and testing novel immunotherapies. However, poorly defined immunophenotypes of canine leukocytes have limited the study of tumor immunology in dogs. The accumulation of myeloid derived suppressor cells (MDSCs) is known to be a key mechanism of immune suppression in tumor-bearing mice and in human patients. We sought to identify MDSCs in the blood of dogs with cancer. Peripheral blood mononuclear cells (PBMCs) from dogs with advanced or early stage cancer and from age-matched healthy controls were analyzed by flow cytometry and microscopy. Suppressive function was tested in T cell proliferation and cytokine elaboration assays. Semi-quantitative RT-PCR was used to identify potential mechanisms responsible for immunosuppression. PBMCs from dogs with advanced or metastatic cancer exhibited a significantly higher percentage of CD11b+CD14−MHCII− cells compared to dogs diagnosed with early stage non-metastatic tumors and healthy dogs. These CD11b+ CD14−MHCII− cells constitute a subpopulation of activated granulocytes that co-purify with PBMCs, display polymorphonuclear granulocyte morphology, and demonstrate a potent ability to suppress proliferation and IFN-γ production in T cells from normal and tumor-bearing donors. Furthermore, these cells expressed hallmark suppressive factors of human MDSC including ARG1, iNOS2, TGF-β and IL-10. In summary our data demonstrate that MDSCs accumulate in the blood of dogs with advanced cancer and can be measured using this three-marker immunophenotype, thereby enabling prospective studies that can monitor MDSC burden

Phenotypic heterogeneity of peripheral monocytes in healthy dogs

Monocytes are key cells of the innate immune system. Their phenotypic and functional roles have been investigated in humans, mice and other animals, such as the rat, pig and cow. To date, detailed phenotypic analysis of monocytes has not been undertaken in dogs. Two important surface markers in human monocytes are CD14 and MHC class II (MHC II). By flow cytometry, we demonstrated that canine monocytes can be subdivided into three separate populations: CD14posMHC IIneg, CD14posMHC IIpos and CD14negMHC IIpos. Both light and transmission electron microscopy confirmed the monocytic identity of all three populations. The CD14posMHC IIneg population could be distinguished on an ultrastructural level by their smaller size, the presence of more numerous, larger granules, and more pseudopodia than both of the other populations

An energy-preserving description of nonlinear beam vibrations in modal coordinates

AbstractConserved quantities are identified in the equations describing large-amplitude free vibrations of beams projected onto their linear normal modes. This is achieved by writing the geometrically exact equations of motion in their intrinsic, or Hamiltonian, form before the modal transformation. For nonlinear free vibrations about a zero-force equilibrium, it is shown that the finite-dimensional equations of motion in modal coordinates are energy preserving, even though they only approximate the total energy of the infinite-dimensional system. For beams with constant follower forces, energy-like conserved quantities are also obtained in the finite-dimensional equations of motion via Casimir functions. The duality between space and time variables in the intrinsic description is finally carried over to the definition of a conserved quantity in space, which is identified as the local cross-sectional power. Numerical examples are used to illustrate the main results

Sum-of-Squares approach to feedback control of laminar wake flows

A novel nonlinear feedback control design methodology for incompressible fluid flows aiming at the optimisation of long-time averages of flow quantities is presented. It applies to reduced-order finite-dimensional models of fluid flows, expressed as a set of first-order nonlinear ordinary differential equations with the right-hand side being a polynomial function in the state variables and in the controls. The key idea, first discussed in Chernyshenko et al. 2014, Philos. T. Roy. Soc. 372(2020), is that the difficulties of treating and optimising long-time averages of a cost are relaxed by using the upper/lower bounds of such averages as the objective function. In this setting, control design reduces to finding a feedback controller that optimises the bound, subject to a polynomial inequality constraint involving the cost function, the nonlinear system, the controller itself and a tunable polynomial function. A numerically tractable approach to the solution of such optimisation problems, based on Sum-of-Squares techniques and semidefinite programming, is proposed. To showcase the methodology, the mitigation of the fluctuation kinetic energy in the unsteady wake behind a circular cylinder in the laminar regime at Re=100, via controlled angular motions of the surface, is numerically investigated. A compact reduced-order model that resolves the long-term behaviour of the fluid flow and the effects of actuation, is derived using Proper Orthogonal Decomposition and Galerkin projection. In a full-information setting, feedback controllers are then designed to reduce the long-time average of the kinetic energy associated with the limit cycle. These controllers are then implemented in direct numerical simulations of the actuated flow. Control performance, energy efficiency, and physical control mechanisms identified are analysed. Key elements, implications and future work are discussed

A Higher-Order Generalized Singular Value Decomposition for Rank Deficient Matrices

The higher-order generalized singular value decomposition (HO-GSVD) is a matrix factorization technique that extends the GSVD to $N \ge 2$ data matrices, and can be used to identify shared subspaces in multiple large-scale datasets with different row dimensions. The standard HO-GSVD factors $N$ matrices $A_i\in\mathbb{R}^{m_i\times n}$ as $A_i=U_i\Sigma_i V^\text{T}$, but requires that each of the matrices $A_i$ has full column rank. We propose a reformulation of the HO-GSVD that extends its applicability to rank-deficient data matrices $A_i$. If the matrix of stacked $A_i$ has full rank, we show that the properties of the original HO-GSVD extend to our reformulation. The HO-GSVD captures shared right singular vectors of the matrices $A_i$, and we show that our method also identifies directions that are unique to the image of a single matrix. We also extend our results to the higher-order cosine-sine decomposition (HO-CSD), which is closely related to the HO-GSVD. Our extension of the standard HO-GSVD allows its application to datasets with $m_i < n$, such as are encountered in bioinformatics, neuroscience, control theory or classification problems.Comment: 13 pages, 2 figure

Vertical And Horizontal Integration Of Laboratory Curricula And Course Projects Across The Electronic Engineering Technology Program

This paper discusses the details of the curricular development effort with a focus on the vertical and horizontal integration of laboratory curricula and course projects within the Electronic Engineering Technology (EET) program at Texas A&amp;M University. Both software and hardware aspects are addressed. A common set of software tools are introduced to the sophomore students in the EET curriculum; these tools are then used in several junior and senior level courses. Through early and repeated exposure to these tools, students learn to use them more effectively to solve various engineering problems in laboratory and course projects. A DC permanent magnetic motor is identified as one of the common hardware platforms for multiple course projects. By using a common platform for different course projects, the students can spend much less time preparing for the course projects. With each course adding different features to the common platform, the learning experience in several courses becomes seamlessly integrated. Surveys were conducted to show that the curriculum development effort improved the efficiency of student learning and enhanced the students’ educational experience.

Cerebral Melanoma Metastases: A Critical Review on Diagnostic Methods and Therapeutic Options

Malignant melanoma represents the third most common cause for cerebral metastases after breast and lung cancer. Central nervous system (CNS) metastases occur in 10 to 40% of patients with melanoma. Most of the symptoms of CNS melanoma metastases are unspecific and depend on localization of the lesion. All patients with new neurological signs and a previous primary melanoma lesion must be investigated. Although primary diagnosis may rely on computed tomography scan, magnetic resonance images are usually used in order to study more precisely the characteristics of the lesions in and to embase the surgical plan. Other possible complementary exams are: positron emission tomography, iofetamine cintilography, immunohistochemistry of liquor, monoclonal antibody immunocytology, optical coherence tomography, and transcriptase-polymerase chain reaction. Treatment procedures are indicated based on patient clinical status, presence of unique or multiple lesions, and family agreement. Often surgery, radiosurgery, whole brain radiotherapy, and chemotherapy are combined in order to obtain longer remissions and optimal symptom relieve. Corticoids may be also useful in those cases that present with remarkable peritumoral edema and important mass effect. Despite of the advance in therapeutic options, prognosis for patients with melanoma brain metastases remains poor with a median survival time of six months after diagnosis

Multi-Array Electron Beam Stabilization using Block-Circulant Transformation and Generalized Singular Value Decomposition

We introduce a novel structured controller design for the electron beam stabilization problem of the UK's national synchrotron light source. Because changes to the synchrotron will not allow the application of existing control approaches, we develop a novel method to diagonalize the multi-input multi-output (MIMO) system. A generalized singular value decomposition (GSVD) is used to simultaneously diagonalize the actuator response matrices, which is applicable to an arbitrary number of actuator dynamics in a cross-directional setting. The resulting decoupled systems are regulated using mid-ranged control and the controller gains derived as a function of the generalized singular values. In addition, we exploit the inherent block-circulant symmetry of the system. The performance of our controller is demonstrated using simulations that involve machine data