•Miniature mechanical safety and arming device is proposed for actual munition firing.•Reliable arming delay performance was achieved by runaway escapement mechanism.•Compact design of the device was ...available by stainless steel wet etching process.•The device showed successful safety and arming performance under actual field tests.•The device found to be appropriate under variety of environmental conditions.
In this research, a miniature mechanical SAD (Safety and Arming Device) with arming delay was developed for actual munitions application. Reliable arming delay performance was achieved by applying a runaway escapement system that operates by a rack-and-pinion motion. The miniature mechanical SAD was fabricated using a stainless steel wet etching process that provided not only miniaturization but also a high processing yield. The miniature mechanical SAD performed successfully under the desired safety and arming conditions in lab tests and showed fine agreement with the finite element method simulation results. Field tests were performed with a grenade launcher to validate its performance under the actual firing conditions. One hundred samples that were shot 23.6 m (safety distance) and 200 m (arming distance), and every specific test criterion was met successfully. The new SAD was also found to be appropriate for safe use in artillery fuzes by conducting environmental tests under a variety of temperature, vibration, and impact conditions.
Concepts in Oncolytic Adenovirus Therapy Mantwill, Klaus; Klein, Florian Gerhard; Wang, Dongbiao ...
International journal of molecular sciences,
10/2021, Letnik:
22, Številka:
19
Journal Article
Recenzirano
Odprti dostop
Oncolytic adenovirus therapy is gaining importance as a novel treatment option for the management of various cancers. Different concepts of modification within the adenovirus vector have been ...identified that define the mode of action against and the interaction with the tumour. Adenoviral vectors allow for genetic manipulations that restrict tumour specificity and also the expression of specific transgenes in order to support the anti-tumour effect. Additionally, replication of the virus and reinfection of neighbouring tumour cells amplify the therapeutic effect. Another important aspect in oncolytic adenovirus therapy is the virus induced cell death which is a process that activates the immune system against the tumour. This review describes which elements in adenovirus vectors have been identified for modification not only to utilize oncolytic adenovirus vectors into conditionally replicating adenoviruses (CRAds) that allow replication specifically in tumour cells but also to confer specific characteristics to these viruses. These advances in development resulted in clinical trials that are summarized based on the conceptual design.
We analyze a dynamic, two-country model that highlights the various trade-offs each country faces between current consumption and competing investments in its future productive and military ...capacities as it prepares for a possible conflict in the future. Our focus is on the circumstances under which the effects of current trade between the two countries on the future balance of power render trade unappealing to one of them. We find that a positive probability of future conflict induces the country with less resource wealth to “prey” on the relatively more “prudent” behavior of its larger rival, and more so as conflict becomes more likely. While a shift from autarky to trade always raises the current incomes of both countries, the smaller country realizes the relatively larger income gain from trade and also devotes a relatively larger share of its income gain towards arming. Our analysis shows that the larger country rationally chooses not to trade today when the difference in initial resource wealth is sufficiently large and is more likely to prefer autarky when the probability of future conflict is higher.
The yeast surface display system is a valuable platform for constructing cells with novel functions for various applications and high-throughput screening of protein or peptide libraries containing ...random mutations. Among the host microorganisms used for surface display, yeast is the most suitable microorganism for surface engineering owing to its eukaryotic features. In yeast, proper folding and glycosylation of expressed eukaryotic proteins can be performed. Furthermore, in this system, multiple kinds of proteins can be simultaneously displayed on the cell surface. This allows for a synergistic effect between the displayed enzymes, leading to an efficient multistep reaction. Alternatively, the ratio of the enzymes to be displayed can be controlled by the co-culture of surface-engineered yeasts displaying a single kind of enzyme. Therefore, yeast surface display systems have been applied to the construction of various whole-cell biocatalysts. Here, we describe methods for the simultaneous display of multiple kinds of proteins on the yeast cell surface.
To improve the load identification capability and high overloading-resistibility of the silicon-based micro electromechanical system (MEMS) setback safety device, a MEMS setback safety device with ...curved zig-zag tracks as the primary load identification mechanism is designed in this paper. The dynamic response of the device under launch and drop load is obtained by the finite Element Method (FEM) simulation. The result shows that the setback safety device can effectively identify the launch load and distinguish the service load. Moreover, the strength model of the curved zig-zag tracks in the collision is established by the quasi-static method. The strength model is verified by FEM simulation, and the result is highly consistent with the FEM simulation result. The influence of structure parameters on the strength of zig-zag tracks was analyzed. Moreover, the methods to improve the overloading-resistibility of structure with surfaces collision are given. The impact experiment platform was established by Marchant Hammer and two types of experiments were conducted: (a) Multiple impact with increasing load amplitude on a single device. (b) Single high amplitude impact on the device. The result shows that the device has sufficient strength while being able to effectively differentiate between drop loads.
A field experiment was laid out in RBD having three replications to investigate the morphological performance, yield and shelf life of five different tomato (Solanum lycopersicum L.) varieties under ...organic and inorganic ambient. The different tomato varieties behaved significantly different from each other for various growth parameters. The organic ambient grown tomato var. Angoorlata gave the highest plant height, number of branches, leaves and flowers; the variety Pusa Sheetal recorded highest fruit length, fruit diameter, fruit shelf life and fruit yield. The var. Pusa Sheetal also grown inorganic ambient gave highest performance for number of fruits, fruit diameter, fruit weight, shelf life at room temperature and yield production. The potential of the variety Pusa Sheetal for accumulation of higher concentration of soluble solids such as sugars, Vitamin C, polyphenols and best performance for yield contributing attributes as well as highest shelf life at refrigerated condition in organic ambience reflects that it is an eco-health friendly genotype for organic tomato and longer shelf life. This novel finding reported for the first time for the variety Pusa Sheetal opens a new avenue for its larger scientific and practical utility for breeding of new genotypes suitable for organic farming with enhanced shelf life to meet out the increasing fondness and requirement of future consumers.
To solve the structural strength problem of a MEMS arming device for a fuze, a kind of arming device applied to a certain type of 40 mm grenade is designed. This paper introduces the working ...principle of the arming device; simulates the shear pin, rotary pin and locking mechanism in the device; designs a variety of different test tools for test verification; and further increases the explosion reliability and arming safety tests. The results show that the arming device improves the structural strength and can meet the action requirements of a certain type of 40 mm grenade for safety release, as well as the application requirements of explosion reliability and arming safety.
Antibodies and other recognition molecules direct cancer cell death by multiple types of immune cells. Therapy directed at only one target typically results in tumor regrowth because of tumor ...heterogeneity. Our goal is to direct therapy to multiple targets simultaneously. Our previous studies showed that multiple antibodies targeting mutated tumor proteins inhibited tumor growth when injected subcutaneously near the time of cancer cell implantation.
A cocktail of rabbit antibodies against B16-F10 cell surface related mutated proteins were generated. Implanted B16-F10 cells were allowed to grow to palpable size before treatment. Antibodies were administered using different routes of exposure. Free antibody was compared to antibody armed on mouse splenic white blood cells (WBCs). Binding of the antibody cocktail was determined for mouse and human WBCs.
The antibody cocktail inhibited tumor growth and prolonged survival when administered as free antibody or armed on WBCs. The antibody cocktail armed on WBCs achieved similar tumor inhibition as free antibody but at a dose 1000-fold less. Armed WBCs achieved tumor inhibition by intravenous and subcutaneous administration. The antibody cocktail bound well to human WBCs and saturation dose was defined. Binding was stable under simulated in vivo condition in human plasma at 37 °C.
Antibodies targeting multiple tumor mutated proteins inhibited tumor growth and prolonged survival. Effective antibody dose was reduced 1000-fold by arming WBCs. Rabbit antibodies saturated human WBCs using <1 mg per billion cells. A phase I trial in cancer patients using this strategy has been approved by the FDA.
•Multiple antibodies targeting multiple cell membrane mutated proteins inhibit tumor.•Administration of antibodies armed on WBCs inhibits tumor growth.•Dose of antibody reduced 1000-fold by arming WBCs instead of free antibody.•Rabbit antibodies bind well to human WBCs.
The micro-electromechanical system (MEMS) safety-and-arming (S&A) device has the features of integration and miniaturization, which is one of the important directions of weapon development. Confined ...by the fabrication process, the silicon-based devices are too fragile, and the metal-based devices are low precision. In order to solve the contradiction between high precision and high structure strength, a metal/silicon composite structure is proposed in this paper, and a hybrid fabrication process is introduced. This new method mainly consists of metal sputtering, electroplating, and (inductively−coupled-plasma) ICP etching. As the resolution of the thick dry film is limited, the process of a femtosecond laser is applied to refine the structure, and the Ni plate (a block of 1 mm × 3 mm × 0.3 mm with a cavity of ϕ 0.85 mm × 0.3 mm in the center) is fabricated on the silicon-on-insulator (SOI) wafer successfully. After the double sides are etched by ICP, the SOI wafer is immersed in a buffered-oxide-etch (BOE) etchant to remove the buried layer. The cover plate acts as the encapsulation and is bonded with the SOI wafer by the epoxy glue. Then, the temporary support beam of the device is broken by the probe, and the suspended composite structure can be fully released. The hybrid process is the integration of the silicon-based process and the metal-based process, which can combine the advantages of both high precision and a high structure strength. The process proposed here is suitable for the application of weapon miniaturization.
We analyze how trade openness matters for interstate conflict over productive resources. Our analysis features a terms-of-trade channel that makes security policies trade-regime dependent. ...Specifically, trade between two adversaries reduces each one's incentive to arm given the opponent's arming. If these countries have a sufficiently similar mix of initial resource endowments, greater trade openness brings with it a reduction in resources diverted to conflict and thus wasted, as well as the familiar gains from trade. Although a move to trade can otherwise induce greater arming by one country and thus need not be welfare improving for both, aggregate arming falls. By contrast, when the two adversaries do not trade with each other but instead trade with a third (friendly) country, a move from autarky to trade intensifies conflict between the two adversaries, inducing greater arming. With data from the years surrounding the end of the Cold War, we exploit the contrasting implications of trade costs between enemies versus trade costs between friends to provide some suggestive evidence in support of the theory.