Series Of Experiments Research Articles

Abstract PR015: Sepsis-induced inflammation alters natural killer cell-mediated surveillance of liver metastasis

Abstract A majority of pancreatic ductal adenocarcinoma (PDAC) patients who undergo surgery for primary tumor resection will develop lethal metastases, despite having no evidence of metastasis at the time of their initial diagnosis. Liver metastases constitute nearly half of recurrences detected within the first six months following PDAC resection. Several clinical and experimental studies provide evidence that perioperative inflammation, including infectious complications like sepsis, positively correlates with liver metastasis across several malignancies. Despite these observations, it is still unknown whether there is a causal link between perioperative inflammation and PDAC liver metastasis. To gain mechanistic insight into the regulation of PDAC liver metastasis in the context of perioperative inflammation, we established mouse models that combine experimental PDAC liver metastasis with either the cecal ligation and puncture (CLP) model of polymicrobial sepsis or the lipopolysaccharide (LPS) model of acute sterile endotoxemia. Mice challenged with CLP prior to seeding PDAC cells in the liver had increased metastatic burden at endpoint compared to sham laparotomy controls. In contrast, mice challenged with LPS prior to PDAC cell seeding had reduced metastatic burden at endpoint compared to PBS-injected controls. We hypothesized that these opposing pro- and anti-metastatic effects of CLP and LPS, respectively, were due to qualitatively distinct inflammatory responses elicited in the liver. Our profiling of the host response to either CLP or LPS revealed shared systemic changes, including activation of the acute-phase protein response. However, LPS-associated inflammation uniquely upregulated a distinct set of interferon-regulated genes in the liver important for modifying immune cell activity (i.e., Ccl2, Ccl5, Cxcl9, Cxcl10). Accordingly, immunostaining and flow cytometry of the liver revealed that LPS uniquely increased the abundance of activated natural killer (NK) cells and MPO+ myeloid cells. We utilized Tlr4 -/- mice, which lack the primary receptor for LPS, to determine that the anti-metastatic effect of LPS required a host-facilitated response downstream of TLR4-mediated signaling. Through a series of genetic models and short-term depletion experiments, we determined that NK cells restrict PDAC cell seeding and outgrowth in our experimental liver metastasis model, and that this protective effect is further enhanced by activation of type-I interferon signaling in the host. Our findings confirm prior work identifying NK cell-mediated surveillance of disseminated cancer cells as an important mechanism in protecting against liver metastasis and show sterile endotoxemia and its associated inflammation establish a protective ‘anti-metastatic niche’ marked by enhanced NK cell activity. Further insights into the establishment of this niche may reveal potential therapeutic strategies to reduce the incidence of liver metastasis among resected PDAC patients. Citation Format: Nicole Sivetz, Patrick J. Cunniff, Christopher R. Vakoc, Semir Beyaz, Mikala Egeblad. Sepsis-induced inflammation alters natural killer cell-mediated surveillance of liver metastasis [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr PR015.

Abstract B027: ISG15 modulate cancer cell mechanics and metastasis in breast cancer

Abstract Metastasis in breast cancer is a major challenge for prognosis and effective treatment, primarily because cancer cells can create an immune-suppressive microenvironment that supports their progression and spread. The physical properties of cancer cells significantly influence their metastatic potential and their interaction with the environment. Identifying targets that impact both the physical characteristics of cancer cells, and their microenvironment is crucial for tackling metastatic disease. Interferon-stimulated gene 15 (ISG15), a ubiquitin-like protein, is often overexpressed in breast cancer tissues and is associated with poor prognosis, higher tumor grade, and increased invasiveness. Despite these associations, the precise role of ISG15 and its post-translational modification, ISGylation, in cancer cell behavior and interactions with their microenvironment remains unclear. To explore this, we interrogated the biophysical role of ISG15 by using mouse modeling and in vitro loss of function approaches. We utilized whole- body ISG15-deficient mice and conducted a series of experiments to assess the impact of ISG15 on cancer cell properties and their surrounding environment. Our preliminary results indicate that cells lacking ISG15 exhibit altered physical traits, such as increased stiffness and size, which may influence their metastatic behavior. Additionally, targeting ISG15 or disrupting ISGylation enhances the susceptibility of cancer cells to immune cell-mediated destruction. In ISG15- deficient mice, we observed significantly reduced tumor growth and metastasis compared to wild-type controls. These findings suggest that ISG15 modulates critical aspects of cancer cell behavior and their interactions with the microenvironment, contributing to immune evasion and metastatic spread. Our research highlights ISG15 as a promising therapeutic target and provides a foundation for developing new strategies to prevent and treat metastatic cancer Citation Format: Mohamed Haloul, Priya Shah, Vinay Pai, Faruk Hossen, James James Lee, Ekrem Emrah Er. ISG15 modulate cancer cell mechanics and metastasis in breast cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr B027.

Adaptive compensation using long short‐term memory networks for improved control performance in real‐time hybrid simulation

AbstractReal‐time hybrid simulation (RTHS) divides structural systems into numerical and experimental substructures, providing a cost‐effective solution for analyzing structural systems, especially those that are large or complex. However, the actuation systems between these substructures inevitably introduce delays, affecting the stability and accuracy of RTHS. To address this issue, this study proposes an adaptive compensation method based on a conditional adaptive time series (CATS) compensator and a long short‐term memory (LSTM) network, termed CATS‐LSTM. The LSTM model predicts actuator responses for parameter estimation and calculates prediction errors, improving control performance and reducing delays. The effectiveness of the proposed CATS‐LSTM method and the accuracy of the LSTM prediction are validated through a series of simulations and experiments. The results indicate that the proposed CATS‐LSTM method outperforms both the CATS and phase lead (PL) methods. Compared to the CATS method, the proposed method reduces the maximum delay, root mean square error, and peak error by 3 ms, 3.66%, and 4.78%, respectively, while achieving reductions of 12 ms, 8.4%, and 10.05%, compared to the PL method. Furthermore, the CATS‐LSTM method is significantly less sensitive to initial parameter estimates, compared to the CATS method, enhancing robustness and mitigating the effects of inaccurate or varying initial parameter estimates.

Energy distribution in 1D chains of foam disks subjected to low-velocity impact at different temperatures

A series of experiments is conducted to study energy transfer in a chain of foam disks as a function of temperature. These experiments use two different densities of closed-cell Polyvinyl Chloride foams as an array. A puncture testing machine impacts the chain at a velocity of 1 m/s at five different temperatures. Piezoelectric sensors capture the output and input forces of the chain during the impact, while high-speed cameras record the disk deformations. The chain’s energy retention is computed using disk deformations and loading forces. Results indicate that high-density foam chains exhibit significantly higher force and energy retention than low-density counterparts. Notably, the foam’s stiffness decreases with rising temperature, more prominently in higher-density foam. However, the proportion of energy retained by the chains remains relatively consistent across different temperatures. Additionally, both foam types show a pattern of exponential decay in energy retention along the chain. These insights offer implications for designing and optimizing energy-absorbing foam systems, paving the way for enhanced energy mitigation in low-velocity impact applications.

Analysis of the effectiveness of using U-net architecture for classification and segmentation of glioma in MRI images

The purpose of the research is to analyze the efficiency of the U-net neural network architecture in decision support systems for glioma diagnostics and segmentation of brain areas affected by it on MRI images.Methods. To conduct experimental studies, a training dataset was generated and the data was normalized. A software implementation of the U-Net neural network architecture was performed using the Keras framework in the Python programming language. The neural network model was trained.Results. A series of experiments were conducted, during which error and classification matrices were obtained, the efficiency of classification of the trained neural network model for the "Tumor" and "No tumor" classes was assessed using metrics such as Recall, Precision and F1-measure, and the quality of segmentation of glioma-affected areas on the test data set was assessed. The quality of segmentation was assessed using the IoU metric, which reflects the ratio of the areas of the bounding boxes and is used to assess the accuracy of the spatial correspondence of the predicted segmented areas highlighted on the masks. Based on the results of testing the neural network model in solving the problem of segmenting brain areas affected by glioma, the average value of the IoU metric was 0.812, which is an acceptable result.Conclusion. The testing results showed that the neural network model based on the U-net architecture is able to effectively diagnose the presence of glioma with acceptable values of the classification and segmentation quality metrics, which indicates the possibility of using this neural network model in medical decision support systems for glioma diagnostics, as well as its segmentation on MRI images. However, it is advisable to refine this neural network model to reduce the number of false negative classification results, which is critically important in medical diagnostics.

The Impact of Reinforcement Ratio on the Punching Shear of CFRP Grid-Reinforced Concrete Two-Way Slabs

Corrosion of steel reinforcement in concrete slabs undermines structural durability and shortens the lifespan of concrete structures. Carbon Fiber-Reinforced Polymer (CFRP) is a promising material offering benefits such as high strength, corrosion resistance, and light weight. This study aims to investigate the punching shear performance of concrete slabs reinforced with CFRP grids, focusing on the effects of different reinforcement ratios. A series of experiments were conducted on two-way concrete slabs reinforced solely with CFRP grids to assess their punching shear resistance. Experimental results show that the CFRP grid achieves an ultimate tensile strength of 2181 MPa, with the cracking load of CFRP grid-reinforced slabs reaching approximately 20% of the ultimate load, highlighting a strong correlation between the ultimate load and grid reinforcement ratio. The observed punching failure exhibited clear brittle characteristics, characterized by the formation of radial and circumferential cracks on the tensile surface of the slab. The reinforcement ratio significantly influences the failure mode of the slabs; as the reinforcement ratio increases, the ultimate punching loads also increase. Additionally, a mathematical formula is proposed to predict the punching bearing capacity, achieving calculation errors below 20%. These findings contribute valuable insights into using CFRP grids as primary reinforcement, enhancing the design and application of durable concrete slab structures.

Inventing with bacteriology: controversy over anti-cholera therapeutic serum and tensions between transnational science and local practice in Tokyo and Berlin (1890-1902).

The present article examines the material, epistemological, and social dimensions of late nineteenth-century anti-cholera serum controversies that unfolded in Tokyo and Berlin. It seeks to shed light on the conflicting values embedded in the construction of scientific evidence during the transnational exploration of bacteriology as an effective response to controlling epidemics. Driven by Japanese health authorities' initiatives, Japanese bacteriologist Kitasato Shibasaburo participated in the elaboration of bacteriological research oriented toward therapeutic application during his stay in Berlin. This work coincided with the rise of a controversy over anti-cholera serum in relation to the animal experiments conducted by Richard Pfeiffer, a German bacteriologist. After presenting a series of animal experiments and certain clinical cases conducted in Germany, France, and Egypt in the context of the controversies, the article analyzes a therapeutic trial conducted by Kitasato in Japan during an 1895 cholera epidemic. His strategy, bringing new data to the transnational debate through an intensive investment of resources in the trial, provoked criticism from his Japanese and German colleagues. These critics questioned Kitasato's method and pointed out the low social value of this experimental serum therapy, performed in highly equipped conditions. Through this case study, the present article highlights: a) a strong tension between transnational research interactions among bacteriologists and local medical practices during public health campaigns against epidemics at the turn of the twentieth century; b) the importance of analyzing the interconnected effects of local, national and transnational frameworks of medical science when examining the increasingly intertwined relationships between laboratory science and clinical medicine.

Understanding the Impact of Soil Characteristics and Field Management Strategies on the Degradation of a Sprayable, Biodegradable Polymeric Mulch

The use of non-degradable plastic mulch has become an essential agricultural practice for increasing crop yields, but continued use has led to contamination problems and in some cropping areas decreases in agricultural productivity. The subsequent emergence of biodegradable plastic mulches is a technological solution to these issues, so it is important to understand how different soil characteristics and field management strategies will affect the rate at which these new materials degrade in nature. In this work, a series of lab-scale hydrolytic degradation experiments were conducted to determine how different soil characteristics (type, pH, microbial community composition, and particle size) affected the degradation rate of a sprayable polyester–urethane–urea (PEUU) developed as a biodegradable mulch. The laboratory experiments were coupled with long-term, outdoor, soil degradation studies, carried out in Clayton, Victoria, to build a picture of important factors that can control the rate of PEUU degradation. It was found that temperature and acidity were the most important factors, with increasing temperature and decreasing pH leading to faster degradation. Other important factors affecting the rate of degradation were the composition of the soil microbial community, the mass loading of PEUU on soil, and the degree to which the PEUU was in contact with the soil.

They only hate the term: policy branding and the politics of critical race theory

Abstract How does the public form preferences on racialized policy issues that are both widely discussed and broadly misunderstood? This has been the question centering around the sudden attacks on academic terms like “critical race theory” (CRT). I argue that the politicization of, and opinion polarization around, critical race theory is evidence of what I call policy branding, where political parties or organizations brand an arbitrary concept that has national salience into a policy issue. Using a series of original survey experiments, this study shows that one of the primary sources of opposition to critical race theory is the literal use of the term. I juxtapose this with evidence that the education policy issue at the core, antiracist teaching, maintained strong public, bipartisan support. This study has implications for the consequences of political elite capture of academic concepts and ideas.

Experimental Study on Interlayer Interference Characteristics During Commingled Production in a Multilayer Tight Sandstone Gas Reservoir

In this study, a practical and comprehensive experimental technique has been proposed to investigate the interlayer interference characteristics in multilayer tight sandstone gas reservoirs with multi-pressure systems and different reserves. Firstly, single-layer depletion simulation experiments were conducted to measure the gas flow rate and gas extraction efficiency for each of the six layers. A series of physical simulation experiments were then conducted to monitor gas production and pressure variations in commingled multilayer production scenarios under various conditions. Finally, interlayer interference characteristics and gas extraction efficiencies and the main controlling factors were evaluated, analyzed, and identified. The interlayer pressure differential is found to be the primary factor dictating both interference and gas production, followed by initial gas production rates, and permeability variations in the order of positive significance. A higher interlayer pressure differential, a lower initial gas production rate, and a larger permeability variation result in an increase in interlayer interference and a reduction in gas production during commingled production. Increasing the number of commingled layers leads to an overall increase in gas production losses of 10.95% for two layers to 13.35% for four layers. Layers exhibiting small interlayer pressure difference are positively compatible for commingled production.

Explainable Pre-Trained Language Models for Sentiment Analysis in Low-Resourced Languages

Sentiment analysis is a crucial tool for measuring public opinion and understanding human communication across digital social media platforms. However, due to linguistic complexities and limited data or computational resources, it is under-represented in many African languages. While state-of-the-art Afrocentric pre-trained language models (PLMs) have been developed for various natural language processing (NLP) tasks, their applications in eXplainable Artificial Intelligence (XAI) remain largely unexplored. In this study, we propose a novel approach that combines Afrocentric PLMs with XAI techniques for sentiment analysis. We demonstrate the effectiveness of incorporating attention mechanisms and visualization techniques in improving the transparency, trustworthiness, and decision-making capabilities of transformer-based models when making sentiment predictions. To validate our approach, we employ the SAfriSenti corpus, a multilingual sentiment dataset for South African under-resourced languages, and perform a series of sentiment analysis experiments. These experiments enable comprehensive evaluations, comparing the performance of Afrocentric models against mainstream PLMs. Our results show that the Afro-XLMR model outperforms all other models, achieving an average F1-score of 71.04% across five tested languages, and the lowest error rate among the evaluated models. Additionally, we enhance the interpretability and explainability of the Afro-XLMR model using Local Interpretable Model-Agnostic Explanations (LIME) and Shapley Additive Explanations (SHAP). These XAI techniques ensure that sentiment predictions are not only accurate and interpretable but also understandable, fostering trust and reliability in AI-driven NLP technologies, particularly in the context of African languages.

Human Operator Mental Fatigue Assessment Based on Video: ML-Driven Approach and Its Application to HFAVD Dataset

The detection of the human mental fatigue state holds immense significance due to its direct impact on work efficiency, specifically in system operation control. Numerous approaches have been proposed to address the challenge of fatigue detection, aiming to identify signs of fatigue and alert the individual. This paper introduces an approach to human mental fatigue assessment based on the application of machine learning techniques to the video of a working operator. For validation purposes, the approach was applied to a dataset, “Human Fatigue Assessment Based on Video Data” (HFAVD) integrating video data with features computed by using our computer vision deep learning models. The incorporated features encompass head movements represented by Euler angles (roll, pitch, and yaw), vital signs (blood pressure, heart rate, oxygen saturation, and respiratory rate), and eye and mouth states (blinking and yawning). The integration of these features eliminates the need for the manual calculation or detection of these parameters, and it obviates the requirement for sensors and external devices, which are commonly employed in existing datasets. The main objective of our work is to advance research in fatigue detection, particularly in work and academic settings. For this reason, we conducted a series of experiments by utilizing machine learning techniques to analyze the dataset and assess the fatigue state based on the features predicted by our models. The results reveal that the random forest technique consistently achieved the highest accuracy and F1-score across all experiments, predominantly exceeding 90%. These findings suggest that random forest is a highly promising technique for this task and prove the strong connection and association among the predicted features used to annotate the videos and the state of fatigue.

A bio-inspired looming detection for stable landing in unmanned aerial vehicles**This research was funded by the National Natural Science Foundation ofchina, grant number 62206065, and the Bagui Scholar Program of Guangxi.

Flying insects, such as flies and bees, have evolved the capability to rely solely on visual cues for smooth and secure landings on various surfaces. In the process of carrying out tasks, micro unmanned aerial vehicles (UAVs) may encounter various emergencies, and it is necessary to land safely in complex and unpredictable ground environments, especially when altitude information is not accurately obtained, which undoubtedly poses a significant challenge. Our study draws on the remarkable response mechanism of the Lobula Giant Movement Detector to looming scenarios to develop a novel UAV landing strategy. The proposed strategy does not require distance estimation, making it particularly suitable for payload-constrained micro aerial vehicles. Through a series of experiments, this strategy has proven to effectively achieve stable and high-performance landings in unknown and complex environments using only a monocular camera. Furthermore, a novel mechanism to trigger the final landing phase has been introduced, further ensuring the safe and stable touchdown of the drone.

Italian Ryegrass Control Using a Capsule Suspension Formulation of S-metolachlor in Fenclorim-treated Wheat

Abstract Italian ryegrass control is one of the most significant limitations in wheat production in the U.S. today. Resistance to Herbicide Resistance Action Committee (HRAC)/Weed Science Society of America (WSSA) Groups 1, 2, and 9 in Arkansas have further complicated postemergence control, while residual herbicides still show effective weed control. One problem is the potential of HRAC/WSSA Group 15 herbicides to injure wheat when applied preemergence, indicating the need for a herbicide safener. A series of experiments were conducted in Fayetteville, AR, to evaluate crop tolerance and Italian ryegrass control using a capsule suspension formulation of S-metolachlor in conjunction with fenclorim-treated wheat. Experiments were conducted as a two-factor factorial with S-metolachlor applied at three rates (0.37, 0.74, and 1.12 kg ai ha-1) and a microencapsulated formulation of acetochlor at 1.05 kg ai ha-1, and three rates of a fenclorim seed treatment at 0, 0.5, and 2.0 g ai kg-1 of seed. Separate experiments utilized either a preemergence (PRE) or a delayed-preemergence (DPRE) application timing. In both experiments, S-metolachlor at 0.74 and 1.12 kg ai ha-1 provided 77 to 96% control of Italian ryegrass by preharvest, whereas acetochlor only provided 49 to 72% control. Visible wheat injury from PRE applications ranged from 7 to 49% for all treatments 21 d after treatment (DAT), with a reduction in injury when fenclorim-treated wheat was used for both the 0.74 and 1.12 kg ai ha-1 rate of S-metolachlor. In the DPRE experiments, wheat injury ranged from 5 to 16% 21 DAT with no noticeable safening from the presence of fenclorim at any herbicide rate. The results of these experiments indicate that a DPRE application using a CS formulation of S-metolachlor would be more favorable for producers to mitigate the potential for injury to wheat while providing Italian ryegrass control. Additionally, at the DPRE application timing, fenclorim is unnecessary for S-metolachlor to be safely applied at the rates evaluated.

Shock-Induced Fan Cowl Separation During Aeroengine Windmilling at Diversion from Cruise

When a civil aircraft engine is operated at windmill during the cruise flight phase, there is supersonic flow acceleration around the leading edge of the fan cowl toward the external surface. The terminating normal shock wave can separate the turbulent boundary layer developing on this external surface. A series of experiments at a flight-relevant Reynolds number (1.2 million based on lip thickness) are performed in a quasi-two-dimensional wind tunnel rig to investigate the underlying flow physics. At a nominal inflow Mach number of 0.65 and a nacelle incidence angle of 4.5 deg, as the equivalent engine mass-flow rate is reduced, an increase in shock strength results in flow separation when the shock exceeds Mach 1.4. Over a 10% range in the notional engine mass-flow rate, the boundary layer developing on the external fan cowl thickens by a factor of three on the onset of separation. A reduction in the incoming Mach number from 0.65 to 0.60 weakens the shock wave and thus delays separation. An increase in surface roughness has no significant effect in situations where the boundary layer remains attached. However, for separated cases, an increased local roughness height causes a greater separation extent and a thicker boundary layer downstream of the shock wave.

Temperature Adaptation in the Postembryonic Development of Acanthocephalus tenuirostris (Palaeacanthocephala: Echinorhynchidae)

Under experimental conditions, the larval development of a fish parasite, Acanthocephalus tenuirostris was studied. This species is common in the eastern regions of Russia from Primorye Territory to the upper reaches of the Kolyma River. The material for the experiments was collected in different areas of the Magadan region which is located mainly in the subarctic climate zone. In several series of experiments, the infection and maintenance of intermediate hosts, the isopod Asellus hilgendorfii, took place at a constant temperature 15°C. In all cases, no more than 45 days were required for the formation of the final cystacanth stage. At the same time, in the hemocoel of isopods a large number of other larval stages were present simultaneously with cystacants. An additional experiment was conducted for the first 45 days at 15°C and the next 207 days at 4–6°C, showed the possibility of further development of larvae at low temperatures. Based on the comparison with the data available in the literature on the development times of European Acanthocephalus species living in temperate climates, it is concluded that the A. tenuirostris has anadaptation to a cold climate, whichprovides a twofold acceleration of the rate ofits development relative to larval A. lucii in Europe.

Increased survival of aquarium fish under acute hypoxia induced by prior intragastric administration of hydrogen peroxide

BACKGROUND: A solution of 3% hydrogen peroxide is an over-the-counter oxygen-releasing antiseptic, which forms oxygen foam when interacting locally with the wound surface. Therefore, this drug is widely used for mechanical cleansing of the surface of chronic wounds from purulent masses. The release of oxygen during catalase cleavage of hydrogen peroxide indicates the possibility of achieving anti-ischemic and anti-hypoxic action. AIM: A study of the effect of intragastric hydrogen peroxide on the resistance of aquarium fish to acute hypoxia. MATERIALS AND METHODS: Experiments were conducted on 80 adult aquarium fish of the guppy, blue neon, tri-linear parsings, swordtail fish and zebrafish (Danio rerio) breeds. To create acute hypoxia, each fish was placed in a transparent plastic container containing 5, 10 or 20 ml of fresh water at a temperature of +25 - +26 °C together with the fish, after which the container was hermetically sealed. Then, the motor activity of the fish's body, the respiratory movements of the gill arches, the opening of the oral cavity, the fluctuations of the fins and the dynamics of their coloration were monitored until the complete final immobilization of the fish and their death. Immediately before the experiment, 0.05 or 0.1 ml of fresh water in the control series and 0.05 ml or 0.1 ml of 0.05% hydrogen peroxide solution in the experimental series were injected into the stomach of the fish. The liquid was injected into the fish's stomach using a gastric mini-probe connected to an insulin syringe. RESULTS: It is shown that aquarium fish retain their viability in a small volume of fresh water inside a hermetically sealed container for a limited period of time, since fish continuously consume oxygen dissolved in water, thereby deepening hypoxia. At the same time, after sealing the container, the fish very quickly assume a stationary state, in which they remain for a certain period of time until their death. However, just before death, the immobility of the fish is disturbed. At the same time, the fish suddenly appear convulsive body movements, active movements of pectoral fins, mouths and gill arches, pectoral fins change their color, after which the fish defecate into the water. The results showed that the preliminary injection of 0.05 or 0.1 ml of 0.05% hydrogen peroxide solution into the stomach of fish prolongs the period of immobility of fish in hypoxia by an average of 20%. In all likelihood, the immobile state of fish is part of the complex of their adaptive adjustment to the cessation of oxygen supply to the water and reflects the availability of reserves of adaptation to hypoxia. The fact is that the absence of muscle contractions stops the muscles from using oxygen, which they use to generate energy. It is assumed that inside the stomach, hydrogen peroxide is absorbed into the blood, where, under the action of the enzyme catalase, it is split into water and gaseous oxygen, which replaces oxygen in the gills in the absence of oxygen in the surrounding water. CONCLUSIONS: Under model conditions, it was shown that pre-administration of 0.05 or 0.1 ml of 0.05% hydrogen peroxide solution into the stomach of fish increases their survival in conditions of acute hypoxia. Therefore, hydrogen peroxide can be considered as a potential antihypoxant for prolonging life in various types of suffocation, including the final stage of COVID-19.

Acute intermittent hypoxia elicits sympathetic neuroplasticity independent of peripheral chemoreflex activation and spinal cord tissue hypoxia in a rodent model of high-thoracic spinal cord injury.

The loss of medullary control of spinal circuits controlling the heart and blood vessels is a unifying mechanism linking both hemodynamic instability and the risk for cardiovascular diseases (CVD) following spinal cord injury (SCI). As such, new avenues to regulate sympathetic activity are essential to mitigate CVD in this population. Acute intermittent hypoxia (AIH) induces a type of neuroplasticity known as long-term facilitation (LTF), a persistent increase in nerve activity post-AIH in spinal motor circuits. Whether LTF occurs within the sympathetic circuit following SCI is largely unknown. We aimed to test whether AIH elicits sympathetic LTF (i.e., sLTF) and attenuates hypoactivity in sub-lesional splanchnic sympathetic circuits in a male rat model of SCI. In 3 experimental series, we tested whether 1) high-thoracic contusion SCI induces hypoactivity in splanchnic sympathetic nerve activity, 2) AIH elicits sLTF following SCI, and 3) sLTF requires carotid chemoreflex or spinal cord tissue hypoxia. Our results indicate that a single-session of AIH therapy (10 × 1 min of FiO2 = 0.1, interspersed with 2 min of FiO2 = 1.0) delivered at 2 weeks following SCI attenuates SCI-induced sympathetic hypoactivity by eliciting sLTF 90 min post-treatment that is independent of peripheral chemoreflex activation and/or spinal cord hypoxia. These findings advance our mechanistic understanding of AIH in the field and yield new insights into factors underpinning AIH-induced sLTF following SCI in a rat model. Our findings also set the stage for the chronic application of AIH to alleviate secondary complications resulting from sympathetic hypoactivity following SCI.

Dynamic-Max-Value ReLU Functions for Adversarially Robust Machine Learning Models

The proliferation of deep learning has transformed artificial intelligence, demonstrating prowess in domains such as image recognition, natural language processing, and robotics. Nonetheless, deep learning models are susceptible to adversarial examples, well-crafted inputs that can induce erroneous predictions, particularly in safety-critical contexts. Researchers actively pursue countermeasures such as adversarial training and robust optimization to fortify model resilience. This vulnerability is notably accentuated by the ubiquitous utilization of ReLU functions in deep learning models. A previous study proposed an innovative solution to mitigate this vulnerability, presenting a capped ReLU function tailored to bolster neural network robustness against adversarial examples. However, the approach had a scalability problem. To address this limitation, a series of comprehensive experiments are undertaken across diverse datasets, and we introduce the dynamic-max-value ReLU function to address the scalability problem.

Arkypallidal neurons in the external globus pallidus can mediate inhibitory control by altering competition in the striatum

Reactive inhibitory control is crucial for survival. Traditionally, this control in mammals was attributed solely to the hyperdirect pathway, with cortical control signals flowing unidirectionally from the subthalamic nucleus (STN) to basal ganglia output regions. Yet recent findings have put this model into question, suggesting that the STN is assisted in stopping actions through ascending control signals to the striatum mediated by the external globus pallidus (GPe). Here, we investigate this suggestion by harnessing a biologically constrained spiking model of the cortico-basal ganglia-thalamic (CBGT) circuit that includes pallidostriatal pathways originating from arkypallidal neurons. Through a series of experiments probing the interaction between three critical inhibitory nodes (the STN, arkypallidal cells, and indirect pathway spiny projection neurons), we find that the GPe acts as a critical mediator of both ascending and descending inhibitory signals in the CBGT circuit. In particular, pallidostriatal pathways regulate this process by weakening the direct pathway dominance of the evidence accumulation process driving decisions, which increases the relative suppressive influence of the indirect pathway on basal ganglia output. These findings delineate how pallidostriatal pathways can facilitate action cancellation by managing the bidirectional flow of information within CBGT circuits.