This article introduces a novel micro-optical electromechanical system safety and arming (S&A) device that utilizes both electrothermal and centrifugal actuators to ensure the reliability and ...efficiency of the device. The S&A device comprises a pair of V-shaped latching actuators, a pair of U-shaped latching actuators, a reverse blocking actuator, a centrifugal alignment actuator, and two sets of status monitoring units. The V- and U-shaped latching actuators serve as safety features to prevent accidental triggering, while the centrifugal alignment actuator aligns the optical fibers. The mechanical responses of the device under dual-environment loads are analyzed using a finite element model, while a theoretical model is introduced to predict the centrifugal acceleration required for alignment. The device is fabricated using deep reactive ion etching on silicon-on-insulator wafers. Experimental tests confirm the effectiveness of the safety features and the device's capability to transmit high-power optical energy. The optical efficiency ranges from 71.8% to 76.4% (1.17-1.44 dB insertion loss), and the maximum power transfer is 902 mW from an 1180 mW input.
Tumor-selectively replicating (oncolytic) viruses are promising tools for therapy of solid cancers and have been initially developed to achieve potent tumor lysis with acceptable side effects on ...healthy tissue. However, in recent years, oncolytic viruses have been recognized as therapeutic vehicles exhibiting multipronged anti-tumoral activity. Apart from direct cytolysis, stimulation of both innate and adaptive tumor-directed immune responses have been recognized as important mechanisms of oncolytic virotherapy, which were probably decisive in achieving the long-term tumor remissions that oncolytic viruses have shown in clinical trials in advanced melanoma. In this short review, we will introduce basic mechanisms of viral oncolysis and the current state of clinical development. With a focus on oncolytic adenoviruses, we will describe the efforts to restrict oncolytic virus infection to tumor tissue using conditional replication and targeted delivery. Furthermore, we will discuss ways to optimize virus-mediated immunostimulation and the potential of virotherapy as an integrative part of systemic tumor immunotherapies.
Oncolytic virotherapy has emerged as a promising treatment for human cancers owing to an ability to elicit curative effects via systemic administration. Tumor cells often create an unfavorable ...immunosuppressive microenvironment that degrade viral structures and impede viral replication; however, recent studies have established that viruses altered via genetic modifications can serve as effective oncolytic agents to combat hostile tumor environments. Specifically, oncolytic vaccinia virus (OVV) has gained popularity owing to its safety, potential for systemic delivery, and large gene insertion capacity. This review highlights current research on the use of engineered mutated viruses and gene-armed OVVs to reverse the tumor microenvironment and enhance antitumor activity in vitro and in vivo, and provides an overview of ongoing clinical trials and combination therapies. In addition, we discuss the potential benefits and drawbacks of OVV as a cancer therapy, and explore different perspectives in this field.
•Soybean seed coat peroxidase was displayed on the cell surface of Yarrowia lipolytica to generate a whole-cell biocatalyst.•The recombinant enzyme activity was greatly increased after a series of ...culture optimization.•This biocatalyst exhibited outstanding enzyme activity and stability without obvious negative effect to the host cells.
Whole-cell biocatalysts could be used in wide-ranging applications. In this study, a new kind of whole-cell biocatalyst was successfully constructed by genetically immobilizing soybean seed coat peroxidase (SBP) on the cell surface of Yarrowia lipolytica Po1h, using a new integrative surface display expression vector (pMIZY05). The coding sequence of SBP was optimized and chemically synthesized, then inserted into pMIZY05 to generate expression plasmid pMIZY05-oEp. A DNA fragment corresponding to SBP and selection marker expression cassettes, without bacterial sequences, was released from pMIZY05-oEp by enzyme digestion and used to transform host yeast cells. A transformant (CM11) with a high recombinant SBP activity of 1571.9 U/mL was obtained, and recombinant SBP was proved to be successfully anchored on cell surface by testing the activities of different cellular fractions. After optimization of culture conditions, the recombinant SBP activity of CM11 was increased to 4187.8 U/mL. Afterwards, biochemical properties of the recombinant SBP were determined: optimum catalytic conditions were 37.5℃ at pH 3.5, and recombinant SBP exhibited high stability during thermal or acidic treatment. Recombinant activity of cell-displayed SBP was re-examined at optimum temperature and pH, which promoted an increase up to 4432.5 U/mL. To our knowledge, this represents the highest activity ever reported for heterologous expression of SBP. This study also provides a useful strategy for heterologous expression of proteins which could be toxic to intracellular content of host cells.
Proposals to arm teachers with guns have emerged in reaction to high-profile school shootings in the United States. Though controversial, these proposals have gained the support of various ...policymakers and special-interest groups. Public opinion, however, is largely divided on the issue and split on political lines. This study seeks to unpack the reasons why Americans may support arming teachers, drawing from multiple theoretical perspectives. Findings indicate support for the culture conflict perspective, with conservative respondents being more likely to support arming teachers and Black respondents and those who are more educated and have higher incomes less likely to support arming teachers. While instrumental concerns such as economic pessimism and anger at the country's direction are associated with less support, those with children are more likely to support arming teachers. Findings on the role of feelings toward law enforcement on arming teachers are mixed. Implications for policy and research are discussed.
Oncolytic viruses are smart therapeutics against cancer due to their potential to replicate and produce the needed therapeutic dose in the tumor, and to their ability to self-exhaust upon tumor ...clearance. Oncolytic virotherapy strategies based on the herpes simplex virus are reaching their thirties, and a wide variety of approaches has been envisioned and tested in many different models, and on a range of tumor targets. This huge effort has culminated in the primacy of an oncolytic HSV (oHSV) being the first oncolytic virus to be approved by the FDA and EMA for clinical use, for the treatment of advanced melanoma. The path has just been opened; many more cancer types with poor prognosis await effective and innovative therapies, and oHSVs could provide a promising solution, especially as combination therapies and immunovirotherapies. In this review, we analyze the most recent advances in this field, and try to envision the future ahead of oHSVs.
In this study, we present a multistage robust multiobjective optimization (MRMO) method that takes into consideration uncertainties stemming from fabrication errors. This efficient method has been ...employed to optimize an inertial setback feature (ISF) within the micro-electromechanical system (MEMS) safety and arming device (SAD). Sensitivity analysis and meta-model techniques are utilized to reduce the computational dimension and cost of optimizing the objectives. The accuracy of the approximation between the global meta-model (GMM) in the method and finite element analysis (FEA) results is guaranteed through appropriate calculation samples. Two optimization algorithms, the fuzzy multiobjective particle swarm optimization (f-MOPSO) algorithm and the adaptive accelerated gravitational search algorithm (AAGSA), are performed to global optimization and local search for the fitness values sequentially to enhance the optimization performance. Robust optimal solutions are shortlisted and selected from among candidate solutions exhibiting superior performance. The effectiveness of the method is demonstrated through a comparison of the results obtained from FEA and the GMM with experimental data collected from some fabricated ISF prototypes. This method achieves the objective of reducing the burden of repetitive FEA calculations and better performance enhancement in robustness optimization.
As an essential component of ammunition, pyrotechnics can control ignition with high reliability. However, due to limits of fabrication technology, traditional pyrotechnics are bulky. To achieve both ...functionality and miniaturization, MEMS pyrotechnics integrate initiator, safety-and-arming (S&A) device and lead charge and keep all components within a small size. MEMS S&A devices, as the core component to ensure system safety, are difficult to achieve active and rapid response to control signals with high safety and reliability. In order to overcome the difficulty, we propose the design and characterization of a MEMS pyrotechnic with a double-layer barrier S&A device. The MEMS pyrotechnic is a high-integrated device with an overall size of 13.4 × 8.5 × 5.2 mm3. The initiator is a NiCr bridge foil covered with an Al/CuO energetic film, which can generate flame when ignited by an excitation voltage. To match the flame energy, lead styphnate is chosen in this study as the lead charge. The S&A device contains four semi-circular barriers, which are directly driven by V-shape electro-thermal actuators to gain active control of the pyrotechnics' ignition condition with rapid response. To improve the system's reliability, the four barriers are axisymmetrically placed in two layers, two barriers for each layer, to constitute a double-layer structure with a thickness of 100 μm. The ignition test results show that the S&A device can prevent the initiator from detonating the lead charge in safety condition. In arming condition, the lead charge will be detonated.
The issue of school safety has been interrogated as school shootings have occurred multiple times each year in the United States. This devastating reality has captured the attention of many ...throughout the United States. School leaders have implemented strategies to increase school safety, including the creation of practices to deter shooting incidences in schools. One such practice, the arming of school district employees, is the focus of this study. We sought to answer the following research questions: 1) How do superintendents describe their experiences implementing and leading the practice? and 2) What lessons have superintendents learned related to the practice? The data sources for this study included superintendent interviews, school district policies, and relevant documents. The findings included descriptions of the practice, the process of implementation, legal and policy guidelines, and advice for school leaders.