Escape System Research Articles

Programmed Cell Death Ligand 1 (PD-L1) Immunohistochemical Expression in Advanced Urothelial Bladder Carcinoma: An Updated Review with Clinical and Pathological Implications.

The management of advanced bladder carcinoma involves a multidisciplinary approach, but the prognosis remains poor for many patients. The immune system plays a crucial role in this disease, influencing both tumor development and response to treatment, and exploiting the immune system against the tumor can be a valuable strategy to destroy neoplastic cells. This is the biological principle underlying Bacillus Calmette-Guérin (BCG) use and, more recently, immune checkpoint inhibitors (ICIs), like PD-1 (programmed death-1)/PD-L1 (programmed death-ligand 1) inhibitors. In fact, one of the best studied immune checkpoints is represented by the PD-1/PD-L1 axis, which is a well-known immune escape system adopted by neoplastic bladder cells. PD-L1 expression has been associated with a higher pathologic stage and has shown prognostic value in bladder carcinoma. Interestingly, high-grade bladder cancers tend to express higher levels of PD-1 and PD-L1, suggesting a potential role of such an axis in mediating disease progression. Immunotherapy with PD-1 and PD-L1 inhibitors has therefore emerged as a valuable treatment option and has shown efficacy in advanced bladder cancer patients, with high PD-L1 expression levels associated with better treatment responses. Our review aims to provide a comprehensive overview of the role of PD-L1 in advanced bladder cancer, focusing on its implications for treatment decisions and the prediction of treatment response. Overall, our work aims to contribute to the understanding of PD-L1 as a predictive biomarker and highlight its role in shaping therapeutic approaches for advanced bladder cancer.

Automated escape system: identifying prey's kinematic and behavioral features critical for predator evasion.

Identifying the kinematic and behavioral variables of prey that influence the evasion from predator attacks remains challenging. To address this challenge, we have developed an automated escape system that responds quickly to an approaching predator and pulls the prey away from the predator rapidly, as real prey. Reaction distance, response latency, escape speed, and other variables can be adjusted in the system. By repeatedly measuring the response latency and escape speed of the system, we demonstrated the system's ability to exhibit fast and rapid responses while maintaining consistency across successive trials. Using the live predatory fish species, Coreoperca kawamebari, we show that escape speed and reaction distance significantly affect the outcome of predator-prey interactions. These findings indicate that the developed escape system is useful for identifying kinematic and behavioral features of prey that are critical for predator evasion, as well as for measuring the performance of predators.

Programmed Cell Death Ligand 1 Immunohistochemical Expression and Cutaneous Melanoma: A Controversial Relationship.

Cutaneous melanoma (CM) is traditionally considered one of the most "immunogenic" tumors, eliciting a high immune response. However, despite the presence of tumor-infiltrating lymphocytes (TILs), melanoma cells use strategies to suppress antitumor immunity and avoid being eliminated by immune surveillance. The PD-1 (programmed death-1)/PD-L1 (programmed death-ligand 1) axis is a well-known immune escape system adopted by neoplastic cells. Therefore, immunotherapy with PD-1 and PD-L1 inhibitors is quickly becoming the main treatment approach for metastatic melanoma patients. However, the clinical utility of PD-L1 expression assessment in CM is controversial, and the interpretation of PD-L1 scores in clinical practice is still a matter of debate. Nonetheless, the recent literature data show that by adopting specific PD-L1 assessment methods in melanoma samples, a correlation between the expression of such a biomarker and a positive response to PD-1-based immunotherapy can be seen. Our review aims to describe the state-of-the-art knowledge regarding the prognostic and predictive role of PD-L1 expression in CM while also referring to possible biological explanations for the variability in its expressions and related treatment responses.

On the biomorphology of Matteuccia struthiopteris (L.) Tod.

Currently, many flowering plants have been studied from the standpoint of the doctrine of plant life forms, their structure, development in ontogenesis, distribution, ecology, biology and evolution. Higher spores, including ferns, remain a poorly studied group. Therefore, the purpose of this work is to clarify the features of the structural organization of Matteuccia struthiopteris in order to study the specifics of the species under the conditions of introduction to the botanical garden of Vyatka State University, located in the Ladoga-Vychegodsky South Taiga biome. In the course of the research, the modular organization of the M. struthiopteris escape system was analyzed. It is represented by elementary, universal and basic modules. There are 8 variants in the structure of elementary modules. They differ in the type of frond and their modifications, as well as the presence of subordinate roots. The universal module of M. struthiopteris is a polycyclic anisotropic upper-rosette shoot. The main module of the plant is a system of monopodially increasing polycyclic upper-rosett shoot with lateral underground stolons. As a result, a short-lived sympodium of polycyclic shoots is formed. In the course of a comparative morphological description of individual structures of the plant’s shoot system, the life form of M. struthiopteris is characterized as: vegetatively mobile, yavnopolycentric, sympodially growing rosette stolon-forming herbaceous perennial with early complete morphological disintegration; hemicryptophyte.

Development of a mixed reality assisted escape system for underground mine- based on the mine water-inrush accident background

The underground mine is an essential infrastructure for national resources and economy, and its safety system is an important issue, especially the miners’ safety. They should not only enhance their preventive awareness of disasters but also enhance their response capability. When miners are in danger with invalid escape lighting, it is difficult for them to overcome panic. Therefore, the automatic assisted escape system has a particular engineering significance in underground space. This study attempts to develop a reference technical framework for emergency evacuation of underground space workers. A human-environment-computer interaction system is developed, which combines the A*-3D Time algorithm with mixed reality (MR) technology. It is constrained by the spatial geometric information of the mine and the escape time. Firstly, the target mine’s geographic information and spatial structure are surveyed on the field, and a 3D digital model is built by the 3DMine; the BIM is used to integrate 3DMine information (data and material) and design the spatial structure. Secondly, based on the A* algorithm in 3D space, the escape time is introduced to evaluate the escape capability and construct the A*-3D Time model. Thirdly, the timeliness of mine water-inrush scenario is simulated by the Comsol; the interaction method and navigation map are developed by the OpenXR and MR Toolkit (MRTK) in Game Engine; the A*-3D Time model is introduced into the C# script and assigned to the digital objects (Mine and Miners). Finally, the performance of this system is analyzed based on the underground metal mine. Based on game thinking to solve safety problems can be used as a reference for underground space engineering.

The ESCAPE system: A combined Raman and time-resolved laser-induced fluorescence instrument to analyze planetary material in a controlled environment

Several sample-return missions such as OSIRIS-REx, Hayabusa2, and Mars 2020 recently have or are currently, collecting the most pristine planetary samples we can analyze on Earth since the Apollo missions. Therefore, it is essential to create instrumentation that will allow preliminary compositional analysis of these materials while preventing oxidation, alteration, or contamination from Earth’s environment. At York University, a small, transportable environmental chamber with temperature, pressure, and atmosphere control has been integrated on an optical table with a combined UV (266 nm) and Green (532 nm) Raman, laser-induced fluorescence, and time-resolved laser-induced fluorescence instrument. This system can collect high-resolution 2D spectroscopic maps, long accumulation point analysis and time-resolved fluorescence ‘fingerprinting’. The sample chamber is capable of pressures <10−4 mbar, temperatures <−20 °C, and different atmospheric compositions such nitrogen, argon, or carbon dioxide via gas hookup. The intended use of the system is to detect and identify minerals and organics within sensitive or fragile planetary samples using minimally destructive laser-based techniques, while maintaining specific environmental conditions to preserve and maintain the pristineness of the material being analyzed, such as samples returned from planetary missions.

Breaking plates: Creation of the East Anatolian fault, the Anatolian plate, and a tectonic escape system

Abstract Lateral movement of lithospheric fragments along strike-slip faults in response to collision (escape tectonics) has characterized convergent settings since the onset of plate tectonics and is a mechanism for the formation of new plates. The Anatolian plate was created by the sequential connection of strike-slip faults following ≥10 m.y. of distributed deformation that ultimately localized into plate-bounding faults. Thermochronology data and seismic images of lithosphere structure near the East Anatolian fault zone (EAFZ) provide insights into the development of the new plate and escape system. Low-temperature thermochronology ages of rocks in and near the EAFZ are significantly younger than in other fault zones in the region, e.g., apatite (U-Th)/He: 11–1 Ma versus 27–13 Ma. Young apatite (U-Th)/He ages and thermal history modeling record thermal resetting along the EAFZ over the past ~5 m.y. and are interpreted to indicate thermal activity triggered by strike-slip faulting in the EAFZ as it formed as a through-going, lithosphere-scale structure. The mechanism for EAFZ formation may be discerned from S-wave velocity images from the Continental Dynamics–Central Anatolian Tectonics (CD-CAT) seismic experiment. These images indicate that thin but strong Arabian lithospheric mantle extends ~50–150 km north beneath Anatolian crust and would have been located near the present surficial location of the Bitlis-Zagros suture zone (co-located with the EAFZ in our study area) at ca. 5 Ma. Underthrusting of strong Arabian lithosphere facilitated localization of the EAFZ and thus was a fundamental control on the formation of the Anatolian plate and escape system.

Application of Perforated Stabilizers for Static Stability at Subsonic Flight Speeds of the Separation Unit of a Spacecraft Emergency Escape System

Application of Perforated Stabilizers for Static Stability at Subsonic Flight Speeds of the Separation Unit of a Spacecraft Emergency Escape System

Hepatitis B Virus (HBV) Upregulates TRAIL-R3 Expression in Hepatocytes Resulting in Escape From Both Cell Apoptosis and Suppression of HBV Replication by TRAIL.

Hepatitis B virus (HBV) evades host immunity by regulating intracellular signals. To clarify this immune tolerance mechanism, we performed gene expression analysis using HBV-infected humanized mouse livers. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor 3 (TRAIL-R3) was significantly upregulated in livers of HBV-infected human hepatocyte transplanted mice by cDNA microarray and next-generation sequencing. We analyzed the significance of TRAIL-R3 upregulation in HBV infection using human hepatocyte transplanted mice and HepG2 cell lines. TRAIL-R3 induction by HBV infection was verified by in vitro and in vivo HBV replication models, and induction was inhibited by antiviral nucleot(s)ide analogue treatment. TRAIL-R3 transcription was regulated by the TRAIL-R3 promoter at -969 to -479 nucleotides upstream from the transcription start site, and by hepatitis B x (HBx) via activation of nuclear factor-κB (NF-κB) signal. TRAIL not only induced cell apoptosis but also inhibited HBV replication. TRAIL-R3 upregulation could inhibit both TRAIL-dependent apoptosis in HBV-infected hepatocytes and TRAIL-mediated suppression of HBV replication. These results suggest a mechanism by which HBV persists by escaping host immunity through upregulation of TRAIL-R3. Development of novel drugs to inhibit this escape system might lead to complete HBV elimination from human hepatocytes.

Transcriptional expression changes during compensatory plasticity in the\xa0terminal ganglion of the adult cricket Gryllus bimaculatus

BackgroundDamage to the adult central nervous system often leads to long-term disruptions in function due to the limited capacity for neurological recovery. The central nervous system of the Mediterranean field cricket, Gryllus bimaculatus, shows an unusual capacity for compensatory plasticity, most obviously in the auditory system and the cercal escape system. In both systems, unilateral sensory disruption leads the central circuitry to compensate by forming and/or strengthening connections with the contralateral sensory organ. While this compensatory plasticity in the auditory system relies on robust dendritic sprouting and novel synapse formation, the compensatory plasticity in the cercal escape circuitry shows little obvious dendritic sprouting and instead may rely on shifts in excitatory and inhibitory synaptic strength.ResultsIn order to better understand what types of molecular pathways might underlie this compensatory shift in the cercal system, we used a multiple k-mer approach to assemble a terminal ganglion transcriptome that included ganglia collected one, three, and 7 days after unilateral cercal ablation in adult, male animals. We performed differential expression analysis using EdgeR and DESeq2 and examined Gene Ontologies to identify candidates potentially involved in this plasticity. Enriched GO terms included those related to the ubiquitin-proteosome protein degradation system, chromatin-mediated transcriptional pathways, and the GTPase-related signaling system.ConclusionFurther exploration of these GO terms will provide a clearer picture of the processes involved in compensatory recovery of the cercal escape system in the cricket and can be compared and contrasted with the distinct pathways that have been identified upon deafferentation of the auditory system in this same animal.

Research on emergency escape system of underground mine based on mixed reality technology

With the continuous development of the mining industry and the continuous advancement of science and technology, increasing new technical methods have been applied in the field of mine safety. In order to solve the problems of backwardness and inefficiency in the traditional disaster avoidance methods of mines, a three-dimensional modeling technique was used to establish a mixed reality model of disaster avoidance in Yanqianshan mine. Subsequently, based on the Floyd algorithm, the overall disaster avoidance line of the underground mine was dynamically optimized, and the man-machine interaction mode and holographic display in mixed reality technology were realized. Finally, in cooperation with HoloLens wearable MR equipment, an underground mine emergency escape system was successfully established. The research results show that the system provides a new solution to the safety of underground mines and can assist underground mine workers well in emergency escape process.

KEY ENGINEERING SOLUTIONS IMPLEMENTED IN ROCKET AND SPACE SYSTEM VOSTOK TO ASSURE CREW SAFETY DURING ASCENT (towards 60th anniversary of the first man in space)

The paper analyzes engineering and operational solutions implemented in rocket and space system Vostok to assure crew safety during ascent in view of the need to complete the work on an extremely short notice. It reviews the results of flight tests of launch vehicles belonging to the R7 family and the status of work to develop a crew escape system by the time when the first manned mission of Vostok spacecraft took place. It provides an analysis of emergencies and measures to assure safety during prelaunch processing and ascent phase. The paper draws comparisons between our country’s project Vostok and US project Mercury. Key words: rocket and space system, spacecraft, descent vehicle, crew safety.

KEY ENGINEERING SOLUTIONS IMPLEMENTED IN ROCKET AND SPACE SYSTEM VOSTOK TO ASSURE CREW SAFETY DURING ASCENT (towards 60th anniversary of the first man in space)

The paper analyzes engineering and operational solutions implemented in rocket and space system Vostok to assure crew safety during ascent in view of the need to complete the work on an extremely short notice. It reviews the results of flight tests of launch vehicles belonging to the R7 family and the status of during prelaunch processing and ascent phase. The paper draws comparisons between work to develop a crew escape system by the time when the first manned mission of Vostok spacecraft took place. It provides an analysis of emergencies and measures to assure safety our country’s project Vostok and US project Mercury. Key words: rocket and space system, spacecraft, descent vehicle, crew safety.

Electromagnetic field and TGF-\u03b2 enhance the compensatory plasticity after sensory nerve injury in cockroach Periplaneta americana

Recovery of function after sensory nerves injury involves compensatory plasticity, which can be observed in invertebrates. The aim of the study was the evaluation of compensatory plasticity in the cockroach (Periplaneta americana) nervous system after the sensory nerve injury and assessment of the effect of electromagnetic field exposure (EMF, 50 Hz, 7 mT) and TGF-β on this process. The bioelectrical activities of nerves (pre-and post-synaptic parts of the sensory path) were recorded under wind stimulation of the cerci before and after right cercus ablation and in insects exposed to EMF and treated with TGF-β. Ablation of the right cercus caused an increase of activity of the left presynaptic part of the sensory path. Exposure to EMF and TGF-β induced an increase of activity in both parts of the sensory path. This suggests strengthening effects of EMF and TGF-β on the insect ability to recognize stimuli after one cercus ablation. Data from locomotor tests proved electrophysiological results. The takeover of the function of one cercus by the second one proves the existence of compensatory plasticity in the cockroach escape system, which makes it a good model for studying compensatory plasticity. We recommend further research on EMF as a useful factor in neurorehabilitation.

Mission Design, Preflight and Flight Performance and Observations for Pad Abort Test

Abort system is initiated to take the Crew Module (CM) away from the launch vehicle in case of an emergency at lift-off or at any point of time after launch for a mission with crew onboard. Crew Escape System (CES)-based abort is carried out from launch pad and during the atmospheric phase of ascent flight. The design and operation of CES play a crucial role in providing abort capability for escape from launch vehicle and return of the crew back to Earth during critical phase of ascent flight. CES motors are used to pull CM away from the launch vehicle during this mode of abort. Mission simulation and analysis is necessary for the design of CES-based abort mission and for its configuration. This article discusses the mission design, challenges faced during the design and strategies formulated towards the successful execution of Pad Abort Test.

Quality Assurance Challenges for Development of Crew Escape System Motors

Quality Assurance Challenges for Development of Crew Escape System Motors

Structural Design, Development and Qualification Tests of Grid Fin

Crew Escape System (CES) is one of the most critical subsystems in a human-rated launch vehicle. It is an emergency escape module to rescue the Crew Module (CM) with the crew to a safe distance from the launch vehicle in an exigency at the launch pad or during atmospheric phase. Pad Abort Test (PAT) is a technology demonstration on the capability of CES to evacuate the crew in case of any exigency at the launch pad, the first in a series of tests to qualify a CES, which is a crucial technology relevant for human spaceflight. There is a wide range of altitude–Mach number regime over which CES is expected to operate and deliver the required performance. Most important among them is the requirement of aerodynamic stability for the entire Mach number regime. The configuration of CES called for an additional lift producing surfaces at its bottom to get the required stability conditions. Accordingly, four grid fins are located at the aft end of CES to move the centre of pressure down for better stability. Grid fin is a lattice structure of several aerodynamic surfaces supported by rectangular outer frames. It is designed for a variable pressure load acting on the fin elements and outer frames. Grid fins are designed and developed with composite material because of its high specific stiffness and specific strength. Composite grid fins are designed, developed, qualified and successfully flown in PAT flight. This article presents the design methodology, development, validation through structural acceptance and deployment tests of composite grid fins meant for the PAT of CES.

Evolution of Crew Escape System Configuration

The Crew Escape System (CES) is used for safe return of crew in case of any malfunctioning of a launch vehicle during ascent, specially in the atmospheric phase of flight. In the present case, as no active control is employed, the aerodynamic stability of CES is essential for safe return of crew in case of any emergency during ascent phase. While finalizing the shape of CES, besides stability, other aerodynamic parameters like acoustic, thermal, structural load, etc. need to be analysed. Based on detailed studies using CFD, a conical-shaped CES has been finalized. This article discusses the challenges involved in aerodynamic shaping of CES and different parameters studied while finalizing the configuration.

Aerothermal Design of Crew Escape System

Aerothermal Design of Crew Escape System

Onset Separation Aerodynamics of Crew Module from Crew Escape System

Aerodynamic characteristics of Crew Module (CM) during its separation from the Crew Escape System (CES) are essential to carry out separation dynamics analysis for confirming collision-free separation. As CM is at the base of CES, it has to clear the complex wake flow that prevails in the aft region. A 1 : 10-scale wind tunnel model is tested at 45 m/s freestream velocity in Indian Institute of Science, Bengaluru lowspeed tunnel. The interaction of CM with the base flows is studied for different attitude conditions in terms angle of attack, longitudinal and lateral movements. Results indicate that CM is recovered from forebody influence beyond X/D = 2, and it experiences reverse flow till it moves to X/D = 1.4D. Stability characteristics of CM are also analysed.