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Systemic treatment with the active transcription inhibitor lurbinectedin aims at inducing tumor cell death in hyperproliferative neoplasms. Here we show that cell death induced by lurbinectedin reinstates and enhances systemic anticancer immune responses. Lurbinectedin treatment showed traits of immunogenic cell death, including the exposure of calreticulin, the release of ATP, the exodus of high mobility group box 1 (HMGB1) and type 1 interferon responses in vitro. Lurbinectedin treated cells induced antitumor immunity when injected into immunocompetent animals and treatment of transplanted fibrosarcomas reduced tumor growth in immunocompetent yet not in immunodeficient hosts. Anticancer effects resulting from lurbinectedin treatment were boosted in combination with PD-1 and CTLA-4 double immune checkpoint blockade (ICB), and lurbinectedin combined with double ICB exhibited strong antineoplastic effects. Cured animals exhibited long term immune memory effects that rendered them resistant to rechallenge with syngeneic tumors underlining the potency of combination therapy with lurbinectedin. [ABSTRACT FROM AUTHOR]

In this article, the author offers personal reflections of two faculty members and a student at Wilkes Honors College in Florida to the February 14, 2018 shootings at Marjory Stoneman Douglas (MSD) High School in Parkland, Florida. The authors recount how faculty and staff reached out directly to support MSD alumni psychologically, socially, and academically, and where classroom activities shifted to apply disciplinary lenses to topics related to the shooting.

Immunogenic cell death (ICD) has initially been discovered in the context of chemotherapy. High-dose crizotinib also stimulates ICD, as we described for non-small cell lung cancer lacking activating chromo- somal aberrations of ALK or ROS1, the usual targets of crizotinib, indicating that crizotinib may act through off-target effects. However, we found that low-dose of ALK inhibitors, crizotinib and ceritinib, may stimulate ICD in anaplastic large cell lymphoma, in which ALK is activated due to a chromosomal translocation, suggesting on target ICD-promoting effects. [ABSTRACT FROM AUTHOR]

A new locomotion method for unmanned (autonomous) ground vehicles (UGV) is proposed based around six independently driven wheels mounted on three separate modules. Each module is attached to the overall robot via a pivot point and capable of independently controlling its orientation and velocity. This configuration allows the UGV to perform maneuvers conventional vehicles cannot perform, and in particular to control the body orientation separately from the movement direction. The locomotion method is mathematically analyzed to develop appropriate control algorithms and to demonstrate the vehicle performance criteria. A vehicle was constructed according to the proposed configuration and experimentally tested in the UK Ministry Of Defense grand challenge. The performance of the developed locomotion schemes helped the robot make it to the finale of the competition. [ABSTRACT FROM AUTHOR]

Flexible structures with collocated force actuators and position sensors lead to negative imaginary dynamics. However, in some cases, the mathematical models obtained for these systems, for example, using system identification methods may not yield a negative imaginary system. This paper provides two methods for enforcing negative imaginary dynamics on such mathematical models, given that it is known that the underlying dynamics ought to belong to this system class. The first method is based on a study of the spectral properties of Hamiltonian matrices. A test for checking the negativity of the imaginary part of a corresponding transfer function matrix is first developed. If an associated Hamiltonian matrix has pure imaginary axis eigenvalues, the mathematical model loses the negative imaginary property in some frequency bands. In such cases, a first-order perturbation method is proposed for iteratively collapsing the frequency bands whose negative imaginary property is violated and finally displacing the eigenvalues of the Hamiltonian matrix away from the imaginary axis, thus restoring the negative imaginary dynamics. In the second method, direct spectral properties of the imaginary part of a transfer function are used to identify the frequency bands where the negative imaginary properties are violated. A pointwise-in-frequency scheme is then proposed to restore the negative imaginary system properties in the mathematical model. [ABSTRACT FROM AUTHOR]

In this paper, the complete stability domain for both single- and multi-parameter dependent LTI systems is synthesized by extending existing results in the literature. This domain is calculated through a guardian map which involves the determinant of the Kronecker sum of a matrix with itself. The single parameter case is easily computable, whereas the multi-parameter case is more involved. The determinant of the bialternate sum of a matrix with itself is also exploited to reduce the computational complexity of the results presented in this paper. [ABSTRACT FROM AUTHOR]

A novel robust trajectory/force controller is developed on the basis of a combination of sliding-mode and adaptive control techniques. Exact knowledge of robot dynamics and environment stiffness is not required. The controller is constructed so as to track reference trajectories in the unconstrained directions and to regulate force at a desired value in the constrained directions. Changes in constraints are also taken into account in the design of the control law. The synthesis presented assumes a non-redundant rigid manipulator and known location/geometry of the environment. Simulation and experimental results are also presented. [ABSTRACT FROM AUTHOR]

Immunosurveillance is generally conceived as a mechanism through which the immune system detects and eliminates (pre-)malignant cells, thus reducing the risk of developing cancer. A recent paper by Ovadya et al. demonstrates that knockout of the gene coding for perforin-1 causes accelerated accumulation of senescent cells in multiple mouse organs, thereby speeding up the aging process. These results suggest that immunosurveillance plays a much broader role in maintaining organismal health than it had been suspected. [ABSTRACT FROM AUTHOR]