Passive Response Research Articles

Uncovering the features of industrial odors-derived environmental complaints and proactive countermeasures by using machine-learning

Industrial odor-derived environmental complaints pose an emerging and far-reaching challenge in cities worldwide with intensive industries. Developing effective odor complaint management strategies is essential for mitigating the public impact of industrial odors. Based on a typical case of persistent tire manufacturing odors affecting local communities, we proposed an environmental complaint risks (ECR) prediction model using machine-learning (ML) approaches, which combined complaints with temporal-resolution manufacturing-meteorology-environment data. Through intensive match-making between ML algorithms and multi-source parameters, Random Forest models can achieve a reliable ECR-prediction model performance with an average ROC-AUC of 0.79at a monthly timescale, indicating the effectiveness of ML-based ECR prediction models. The interpretable ML model quantitively depicted the underlying mechanisms of ECR prediction, driven by process emission behaviors, local wind direction, and historical high-risk period. Furthermore, to mitigate predictable ECR within a future period, we designed a model framework that integrated ECR prediction models with an adaptive optimization genetic algorithm. This enabled the proactive management by precisely and dynamically allocating limited resources of emission regulatory to high-ECR periods in advance. The strategy was proven effective, achieving a significant 24.7% average reduction in the overall ECR forecast during a period with intensive complaints. Overall, this study proposed a data-driven model framework that efficiently helps the multi-stakeholders shift from passive response to proactive ECR management, thereby enhancing the environmental and social sustainability.

Vision at high latitudes: High sensitivity without specific boreal adaptations in photoreception in reindeer (Rangifer tarandus L.)

Abstract The light climate at high latitudes, in particular the extended twilight of winter and the reduced diel variation in light level in midsummer and midwinter, potentially constrains visual function and the synchronisation of temporal organisation in polar species. In this paper, we describe the temporal pattern and variation in the spectral composition and brightness of skylight (daylight, twilight, moonlight, starlight, airglow and aurorae) at high latitudes and review photoreception of reindeer/caribou (Rangifer tarandus; ‘Rangifer’) which is one of the few polar resident species for which data are available. Experimental data indicate that the rods of Rangifer may be stimulated by levels of ambient light lower than those occurring during astronomical twilight (solar angle <−18°). Several features of the eyes of Rangifer contribute to their visual capability under extended twilight. These include transmission of UV through the optical media, which enables the animals to exploit the shorter wavelengths characteristic of twilight, and a shift in the peak spectral reflectance of the tapetum lucidum (TL) from around 640 nm in summer to around 450 nm in winter, which increases retinal illumination at short wavelengths. Enhanced sensitivity to short wavelengths is likely to enhance the contrast of some objects and hence the ability of Rangifer to discriminate forage plants and to detect other animals (conspecifics or predators) against a snowy background under low illuminance. There is, nevertheless, currently no evidence of any specific boreal adaptation in their visual system: (i) The eyes of Rangifer, and by inference the area of the dilated pupil, are no larger than expected based on the allometry of eye size in ruminants. (ii) There is no evidence of a change in the spectral sensitivity of photoreceptors associated with detection of UVa. (iii) Transmission of UV through the anterior eye is not unique to Rangifer. (iv) The blue shift in the reflectance of the winter TL appears to be a passive response to prolonged dilation of the pupil and there is no a priori reason not to predict the same response in other large ungulates exposed to low light levels. (v) There is no conclusive evidence of a seasonal shift in absolute retinal sensitivity in Rangifer. (vi) Weak circadian organisation in Rangifer has tentatively been linked to mutations within the circadian molecular clockwork but it remains unclear to what extent this represents a specific adaptation to high latitude. Read the free Plain Language Summary for this article on the Journal blog.

An Ocean Memory Perspective: Disentangling Atmospheric Control of Decadal Variability in the North Atlantic Ocean

AbstractAn ocean memory framework is proposed to reveal the atmosphere's influence on ocean temperatures. Anomalous atmospheric forcing alters the ocean state through two mechanisms: short‐term, local effects involving airsea heat fluxes and Ekman circulation, and long‐term, far‐field effects involving changes from overturning and gyre circulations. The framework employs the Green function's method to incorporate both effects, enabling the quantification of ocean memory and the contribution of atmospheric forcing to ocean thermal variability. The framework is employed to examine the North Atlantic Oscillation's (NAO) influence on the North Atlantic Ocean variability, including the Atlantic Multidecadal Variability, with its memory estimated to be years. The NAO and variability in the North Atlantic jet speed explain up to 30% of ocean decadal variability, primarily driven by temporal changes in ocean heat transport. Therefore, decadal fluctuations in ocean temperatures cannot be accurately modeled solely as a passive response to stochastic atmospheric forcing.

Confucian culture, public education expenditure, and economic growth

Confucian culture has been found to have significant effects on economic outcomes, yet current studies seldom delve into its impact on regional economic growth in China and the role of government behavior as a mechanism. From the perspective of government response to public demands for education, this paper examines whether Confucian culture fosters economic growth by driving up public education expenditure. Using panel data at the prefecture-level over 2003–2018 and taking the historical population density of jinshi in the Ming and Qing Dynasties as the proxy of the Confucian culture, the empirical analysis is done mainly through pooled OLS and IV analysis. Results show that Confucian culture has a significant and positive effect on economic growth, which can be partially explained by its positive influence on public education expenditure. The channel still holds after controlling human capital in regression. Further discussion of the clan culture and local governors’ cultural backgrounds suggests that higher public education expenditure results from the local government’s passive response to public demands for education. Thus, local governments are suggested to widen and improve the channels for expressing public demands and increase public education expenditure while balancing public demands and the need to boost economic growth.

Multi-functional periodically heterogeneous structures for energy harvesting and vibration attenuation-effects of piezoelectricity and shunting circuits

Abstract We explore a kind of metamaterial plate structures intended for simultaneous energy harvesting and vibration control. These structures are designed using a periodically perforated piezoelectric plate (the matrix) with elastic inclusions situated in the holes and serving for the resonators. The design options comprise two- and three-phase configurations related to the mechanical connection between the matrix and inclusions. By introducing a singularity—the focal spot created as a defect in the perfectly periodic structure and using the theory of super-cell, an enhanced piezoelectric energy harvester is obtained. It is observed that such a meta-structure serves as a dual-purpose system: efficiently capturing vibrational energy at a focal spot while maintaining the overall vibration attenuation throughout the structure. The band gap analysis based on the Bloch’s wave decomposition theory shows that by concentrating energy and halting vibration propagation, approximately 10 times energy harvesting enhancement and a remarkable 100 dB reduction in vibrations are achieved simultaneously. Besides the passive response of these meta-structures, we consider its extension by an external electric circuit (EC). Such modified configurations enable to exploit ‘actively’ the piezoelectric plate property to transmit the mechanical response between two, or more distant locations. Due to nonlocal interactions introduced by means the controllable EC, we consider optimization of the EC impedance to reduce the vibrations at a selected location of the whole structure without any external energy supply. The computational study discovers perspectives and benefits of designing such active self-powered meta-structures.

Sex differences in fear expression and persistence in an animal model of Post-Traumatic Stress Disorder

Post-Traumatic Stress Disorder (PTSD) is a complex psychiatric condition arising from traumatic experiences, marked by abnormal fear memories. Despite women are twice as likely as men to develop PTSD, the biological mechanisms underlying this disparity remain inadequately explored, particularly in preclinical studies involving female subjects.Previous research shows that female rats exhibit active fear responses, while males display passive behaviors. Additionally, sex differences in ultrasonic vocalizations (USVs) during fear conditioning have been observed, indicating varying emotional responses.Here, we validated a traumatic stress model consisting of footshock exposure paired with social isolation − originally developed in male rats − on females for the first time, focusing on sex differences in fear memory expression, retention and extinction. Our findings reveal that only during trauma exposure, males predominantly exhibited passive responses, whereas females demonstrated more active responses, despite both sexes emitting similar numbers of alarm USVs. Females also showed lower levels of freezing and USV emissions throughout extinction sessions and displayed a higher extinction rate compared to males. Notably, only males displayed a conditioned fear response when triggered by a single mild stressor.These findings highlight sex differences in trauma responses and fear memory processes. The study emphasizes the importance of incorporating 22-kHz USV evaluations along with other behavioral metrics for a comprehensive understanding of fear memory. This research contributes to the existing literature on traumatic stress models as well as underscores the necessity of including female subjects in preclinical studies to better inform treatment and prevention strategies tailored to both sexes.

The effect of Plasmodium falciparum exposure and maternal anti-circumsporozoite protein antibodies on responses to RTS,S/AS01E vaccination in infants and children: an ancillary observational immunological study to a phase 3, randomised clinical trial

The RTS,S/AS01E malaria vaccine showed lower antibody response and protective efficacy in infants aged 6-12 weeks compared with children aged 5-17 months (for whom this vaccine is recommended). We aimed to study the effect of previous Plasmodium falciparum exposure on the antibody responses to RTS,S/AS01E vaccination in infants and children, and the mediating effect of baseline (including maternal) anti-circumsporozoite protein (CSP) antibodies. In this observational study, we included children and infants from six African countries (Burkina Faso, Gabon, Ghana, Kenya, Mozambique, and Tanzania) enrolled in the MAL067 immunology ancillary study of the RTS,S/AS01E phase 3 clinical trial from March 27, 2009, to Jan 21, 2011. We used comparator-vaccinated infants and children to identify antibody-based signatures of previous P falciparum exposure, which were later applied to RTS,S/AS01E-vaccinated infants and children. In these participants, we explored the relationship between vaccine antibody immunoglobulin G (IgG) responses measured by ELISA and pre-vaccination serological markers of malaria exposure by assessing the IgG levels against 1000 P falciparum antigens using partial proteome microarrays. We included 718 comparator-vaccinated infants (348 [48%]) and children (370 [52%]) and 606 RTS,S/AS01E-vaccinated infants (329 [54%]) and children (277 [46%]). Anti-CSP IgG responses to primary vaccination did not correlate with a baseline signature of previous exposure in children, suggesting that prior P falciparum exposure does not significantly affect antibody immunogenicity in children (Pearson's r=-0·02 [95% CI -0·13 to 0·10]). By contrast, high P falciparum exposure signature levels at the time of vaccination in infants, presumably driven by maternally transferred antibodies and declining within the initial 6-12 months of life, correlated with reduced RTS,S/AS01E responses (r=-0·17 [-0·27 to -0·06]). This negative correlation was stronger for anti-CSP IgG than for the exposure signature or any other more immunogenic blood stage P falciparum antigens (r=-0·42 [-0·50 to -0·33]), persisted after adjustment by baseline levels of the exposure signature (semi-partial correlation r=-0·44 [-0·55 to -0·33]), and involved antibodies to the central NANP region (r=-0·39 [-0·49 to -0·28]) but not the C-terminal region (r=0·02 [-0·10 to 0·15]) of CSP. The negative effect of maternal anti-CSP IgG in infants did not appear to be confounded by other malaria transmission-dependent variables. Interference between passive immunity and vaccine response is clinically significant and might affect the implementation of next-generation CSP-based vaccines for young infants and mothers as well as passive immunisation with human monoclonal antibodies. US National Institutes of Health, National Institute of Allergy and Infectious Diseases; PATH-Malaria Vaccine Initiative; Spanish Ministerio de Economía y Competitividad (Instituto de Salud Carlos III), European Regional Development Fund and European Social Fund; Fundación Ramón Areces; Spanish Ministry of Science and Innovation; and Generalitat de Catalunya (CERCA Program).

Boolean Logic Gate Operation in Bacteriorhodopsin of Purple Membrane Based on a Molten Globule-like State.

Bacteriorhodopsin (bR) of purple membrane (PM) has increasing technical interests, particularly in photonic devices and bioelectronics. The present work has concerned with monitoring the temperature dependence of passive electric responses in-plane and out-of-plane of the membranes. Based on thermal properties observed orthogonally here for PM, a high-temperature intermediate of bR has been suggested to populate at around 60 °C, which may be ascribed to a molten globule-like state. This intermediate has been found to be enclosed between two reversible thermal transitions for PM. Large-scale turnover in the energy of activation, for these two thermal transitions, occurs steeply at such state at 60 °C, above which does bR reverse the sign of dielectric anisotropy (i.e. crossover) provided the operating frequency should be above the crossover frequency, at which the reversal occurs. No such crossover was found to occur below the crossover frequency, even above the crossover temperature (i.e. 60 °C). Likewise, no such crossover was found to occur below the crossover temperature, even above the crossover frequency. Relying on this reasoning, a logic gate operation may be declared implicating bR for bioelectronics and sense technological relevance. In addition, the results specify "dual frequency" as well as "dual temperature" characteristics to bacteriorhodopsin.

Neurosimilator for Undergraduate Biophysics and Neurophysiology Courses.

Stringent animal welfare principles are forcing undergraduate instructors to avoid the use of animals. Therefore, many hands-on lab sessions using laboratory animals are progressively replaced by computer simulations. These versatile software simulations permit the observation of the behavior of biological systems under a great variety of experimental conditions. While this versatility is important, computer simulations often work even when a student makes wrong assumptions, a situation that poses its own pedagogical problem. Hands-on learning provides pupils with the opportunity to safely make mistakes and learn organically through trial and error and should therefore still be promoted. We propose an electronic model of an excitable cell composed of different modules representing different parts of a neuron - dendrites, soma, axon and node of Ranvier. We describe a series of experiments that allow students to better understand differences between passive and active cell responses and differences between myelinated and demyelinated axons. These circuits can also be used to demonstrate temporal and spatial summation of signals coming to the neuron via dendrites, as well as the neuron coding by firing frequency. Finally, they permit experimental determination along with theoretical calculations of important biophysical properties of excitable cells, such as rheobase, chronaxie and space constant. This open-source model has been successfully integrated into an undergraduate course of the physiology of excitable cells and student feedback assessment reveals that it helped students to understand important notions of the course. Thus, this neuromorphic circuit could be a valuable tool for biophysics and neuroscience courses in other universities.

A comprehensive experimental analysis of the local passive response across the healthy porcine left ventricle

This work provides a comprehensive characterization of porcine myocardial tissue, combining true biaxial (TBx), simple triaxial shear (STS) and confined compression (CC) tests to analyze its elastic behavior under cyclic loads. We expanded this study to different zones of the ventricular free wall, providing insights into the local behavior along the longitudinal and radial coordinates. The aging impact was also assessed by comparing two age groups (4 and 8 months). Resulting data showed that the myocardium exhibits a highly nonlinear hyperelastic and incompressible behavior. We observed an anisotropy ratio of 2-2.4 between averaged peak stresses in TBx tests and 1-0.59-0.40 orthotropy ratios for normalised fiber-sheet-normal peak stresses in STS tests. We obtained a highly incompressible response, reaching volumetric pressures of 2-7 MPa for perfused tissue in CC tests, with notable differences when fluid drainage was allowed, suggesting a high permeability. Regional analysis showed reduced stiffness and anisotropy (20-25%) at the apical region compared to the medial, which we attributed to differences in the fiber field dispersion. Compressibility also increased towards the epicardium and apical regions. Regarding age-related variations, 8-month animals showed stiffer response (at least 25% increase), particularly in directions where the mechanical stress is absorbed by collagenous fibers (more than 90%), as supported by a histological analysis. Although compressibility of perfused tissue remained unchanged, permeability significantly reduced in 8-month-old animals. Our findings offer new insights into myocardial properties, emphasizing on local variations, which can help to get a more realistic understanding of cardiac mechanics in this common animal model. Statement of significanceIn this work, we conducted a comprehensive analysis of the passive mechanical behavior of porcine myocardial tissue through biaxial, triaxial shear, and confined compression tests. Unlike previous research, we investigated the variation in mechanical response across the left ventricular free wall, conventionally assumed homogeneous, revealing differences in terms of stiffness and compressibility. Additionally, we evaluated age-related effects on mechanical properties by comparing two age groups, observing significant variations in stiffness and permeability. To date, there has been no such in-depth exploration of myocardial elastic response and compressibility considering regional variations along the wall and may contribute to a better understanding of the cardiac tissue’s passive mechanical response.

Assessment of Enterobacter, Clostridium, Lactobacillus, and Bifidobacterium Population in a Mouse Model of Alzheimer's Disease

Background: Today, according to various studies, the gut microbiome is closely linked to various diseases such as cardiovascular disease, metabolic disorders, and neurological disorders like Alzheimer's disease (AD). Objectives: The primary purpose of this investigation was to evaluate the quality and quantity of the gut microbiota in a mouse model of AD. Methods: The mice were randomly divided into either an AD group injected with streptozotocin (STZ, 3 mg/kg) or a control group. After 16 - 17 days, the mice were evaluated for their memory capacity and learning, using the Morris water maze (MWM) and passive avoidance response tests. Specific primers were designed to target the 16S rRNA genes of Enterobacter, Clostridium, Lactobacillus, and Bifidobacterium species in the fecal samples of mice by real‐time PCR assay. Results: The MWM and passive avoidance tests confirmed that STZ caused AD in the mouse model. According to the results of real-time PCR assays, unlike Lactobacillus, Clostridium, and Enterobacter, the population of Bifidobacterium decreased significantly in mice after AD in day 28 (P < 0.05). In other words, mean difference of Bifidobacterium CFU between AD group in day 28 and control group was -5.680 (95% CI: -11.3826 to -0.0174). Conclusions: Restructuring the gut microbiota using personalized dietary approaches or targeted interventions aimed at beneficial microbiota can potentially modify the composition of microbial communities and their metabolic byproducts, offering novel therapeutic possibilities for AD.

Effects of continuous negative pressure suction combined with autologous platelet-rich gel on the levels of CRP, IL-6, wound healing and length of stay in clients with diabetic foot

ObjectiveContinuous passive pressure suction and APG gel therapy effect diabetic foot IL-6, CRP, wound healing, and hospitalization. MethodsClinicopathological data from 102 diabetic foot ulcer patients treated at our institution between March 2018 and May 2022 was examined. Tables generated 51 joint and controlling teams randomly. The observation team received passive pressure suction and APG gel whereas the controlled team received conventional treatment. Teams monitored therapy outcomes, adverse responses, wound healing, hospital stay, and costs. Both teams compared blood uric acid, cystatin C, homocysteine, and serum IL-6, IL-10, and CRP before and after medication. ResultsThe joint team had higher hospitalization costs, shorter stays, and faster wound healing than the controlled team. Diaparity was significant (P < 0.05). The united team worked 100 %, unlike the controlling team. This difference was significant (P < 0.05). Both teams showed significant decreases in CRP, IL-6, and IL-10 levels after therapy (P < 0.05). After therapy, both the combined and controlled teams had substantial differences in blood CRP, IL-6, and IL-10 levels (P < 0.05). Both teams had significantly decreased uric acid, cystatin C, and homocysteine after treatment. The combined team showed significantly decreased uric acid, cystatin C, homocysteine levels following therapy compared to the control team (P < 0.05). ConclusionThe joint team experienced considerably fewer adverse events (3.92 % vs. 17.65 %) than the controls team (P < 0.05). Permanent passive pressure suction and APG gel therapy lower inflammatory response, blood uric acid, cystatin C, and homocysteine, speeding wound healing, reducing side effects.

Exploring Influential Factors Shaping Passive Resistance Responses to Address Workplace Incivility

Exploring Influential Factors Shaping Passive Resistance Responses to Address Workplace Incivility

Multimodal soft valve enables physical responsiveness for preemptive resilience of soft robots.

Resilience is crucial for the self-preservation of biological systems: Humans recover from wounds thanks to an immune system that autonomously enacts a multistage response to promote healing. Similar passive mechanisms can enable pneumatic soft robots to overcome common faults such as bursts originating from punctures or overpressurization. Recent technological advancements, ranging from fault-tolerant controllers for robot reconfigurability to self-healing materials, have paved the way for robot resilience. However, these techniques require powerful processors and large datasets or external hardware. How to extend the operational life span of damaged soft robots with minimal computational and physical resources remains unclear. In this study, we demonstrated a multimodal pneumatic soft valve capable of passive resilient reactions, triggered by faults, to prevent or isolate damage in soft robots. In its forward operation mode, the valve, requiring a single supply pressure, isolated punctured soft inflatable elements from the rest of the soft robot in as fast as 21 milliseconds. In its reverse operation mode, the valve can passively protect robots against overpressurization caused by external disturbances, avoiding plastic deformations and bursts. Furthermore, the two modes combined enabled the creation of an endogenously controlled valve capable of autonomous burst isolation. We demonstrated the passive and quick response and the possibility of monolithic integration of the soft valve in grippers and crawling robots. The approach proposed in this study provides a distributed small-footprint alternative to controller-based resilience and is expected to help soft robots achieve uninterrupted long-lasting operation.

Metabolic model guided CRISPRi identifies a central role for phosphoglycerate mutase in Chlamydia trachomatis persistence.

This study uses a metabolic model to investigate factors that contribute to the persistence of Chlamydia trachomatis serovar L2 (CTL) under tryptophan and iron starvation conditions. As CTL lacks many canonical transcriptional regulators, the model was used to assess two prevailing hypotheses on persistence-that the chlamydial response to nutrient starvation represents a passive response due to the lack of regulators or that it is an active response by the bacterium. K-means clustering of stress-induced transcriptomics data revealed striking evidence in favor of the lack of adaptive (i.e., a passive) response. To find the metabolic signature of this, metabolic modeling pin-pointed pgm as a potential regulator of persistence. Thermodynamic driving force, enzyme cost, and CRISPRi knockdown of pgm supported this finding. Overall, this work introduces thermodynamic driving force and enzyme cost as a tool to understand chlamydial persistence, demonstrating how systems biology-guided CRISPRi can unravel complex bacterial phenomena.

High-performance color and fluorescence switching of cotton fabrics via light-induced proton transfer strategy of spiropyran sulfonate molecule

Light-responsive color-switching materials have garnered persistent interest recently due to their passive response to external stimuli and manifestation of notable visual color variations. Nonetheless, their development into high-end products has been hindered by unsatisfactory overall performance, characterized by challenges such as the inability to combine color contrast and retention time, poor repeatability, and reliance on a single coloring mode. Herein, we present a negative photochromic cotton fabric (NPCF) capable of real-time dual output of optical signals (color change or fluorescence emission), featuring high color contrast and resolution, excellent reversibility, and facile multicolor printing. These attributes stem from the utilization of a unique photoinduced proton transfer (PPT) strategy exhibited by the designed and synthesized spiropyran sulfonate molecule (MC-NO2). Guided by this strategy, NPCF demonstrates significant color changes and fluorescence switching in a real-time and highly reversible manner, leveraging the remote non-contact and non-destructive nature of visible light. Moreover, direct blending of MC-NO2 with commercially available water-soluble non-stimuli-responsive dyes enables customization of various photosensitive color systems for straightforward multi-color printing, aligning well with the environmental principles of green printing. This study serves as a valuable reference for the advancement and design of diverse high-performance, switchable materials suitable for the production of high-end products.

Reducing FKBP51 Expression in the Ventral Hippocampus Decreases Auditory Fear Conditioning in Male Rats.

Fear conditioning evokes a physiologic release of glucocorticoids that assists learning. As a cochaperone in the glucocorticoid receptor complex, FKBP51 modulates stress-induced glucocorticoid signaling and may influence conditioned fear responses. This study combines molecular and behavioral approaches to examine whether locally reducing FKBP51 expression in the ventral hippocampus is sufficient to affect fear-related behaviors. We hypothesized that reducing FKBP51 expression in the VH would increase glucocorticoid signaling to alter auditory fear conditioning. Adult male rats were injected with an adeno-associated virus (AAV) vector expressing short hairpin - RNAs (shRNA) targeting FKBP5 into the ventral hippocampus to reduce FKBP5 levels or a control AAV. Infusion of FKBP5-shRNA into the ventral hippocampus decreased auditory fear acquisition and recall. Although animals injected with FKBP5-shRNA showed less freezing during extinction recall, the difference was due to a reduced fear recall rather than improved extinction. Reducing ventral hippocampus FKBP51 did not affect exploratory behavior in either the open field test or the elevated zero maze test but did increase passive behavior in the forced swim test, suggesting that the reduction in auditory fear recall was not due to more active responses to acute stress. Furthermore, lower ventral hippocampus FKBP51 levels did not alter corticosterone release in response to restraint stress, suggesting that the reduced fear recall was not due to lower corticosterone release. Our findings suggest FKBP51 in the ventral hippocampus plays a selective role in modulating fear-learning processes and passive behavioral responses to acute stress rather than hypothalamic-pituitary-adrenal axis reactivity or exploratory responses.

Monitoring holograms for therapeutic ultrasound using passive cavitation beamforming

Acoustic holograms can generate cavitation patterns of complex spatial distribution by shaping and steering the focal spot of therapeutic ultrasound systems. However, when monitoring these systems by passive cavitation detection, off-axis therapeutical targets and the receiver directivity may not be aligned. In this paper, we present passive cavitation beamforming to monitor a therapeutical ultrasound system using holograms targeted to arbitrary locations, in which both therapeutic and passive cavitation monitoring systems use 3D-printed acoustic lenses. The therapeutic system uses an acoustic hologram to focus the ultrasound beam on the target, which is off-axis. Then, a second lens is designed to beamform the cavitation signals which emerge from the therapeutic target, steering the directivity of the passive cavitation detector in the direction of the therapeutic focus and, in addition, compensating for skull aberrations. The system is experimentally tested with an ex-vivo macaque skull and a blood vessel phantom with microbubbles. In addition, results are compared with a standard confocal configuration and an off-axis configuration in the absence of the monitor lens. A parametric study is performed by varying the amplitude of the emitted signal and the impact on the behaviour of the microbubbles is analysed based on the cavitation index values. Results show that monitoring holograms align the passive cavitation detector response with the focal spot of the targeted therapeutic transducer. These holograms encode a fixed beamformer for cavitation signals in reception, increasing the sensitivity of cavitation emission at the target. In this way, cavitation doses can be used to locally monitor the cavitation activity of microbubbles, thus opening a new path to low-cost monitoring of therapeutic ultrasound systems.

Oral Administration of Efavirenz Dysregulates the Tph2 Gene in Brain Serotonergic Areas and Alters Weight and Mood in Mice.

Most HIV-antiretroviral drugs have adverse effects. Efavirenz (EFV) is an example of a drug with neuropsychiatric effects, such as anxiety, depression, and suicidal thoughts, in people living with HIV (PLWH). The mechanisms by which EFV causes neuropsychiatric alterations in PLWH are complex, multifactorial, and not fully understood, although several studies in animals have reported changes in brain energy metabolism, alterations in monoamine turnover, GABA, and glutamate levels, and changes in 5-HT receptors. In this report, we studied the effects of EFV on the serotonergic system in healthy mice, specifically, whether EFV results in alterations in the levels of the tryptophan hydroxylase 2 (Tph2) gene in the brain. EFV (10 mg/kg) and distilled water (1.5 µL/kg) (control group) were orally administered to the mice for 36 days. At the end of the treatment, Tph2 expression levels in mouse brains were measured, and mood was evaluated by three trials: the forced swim test, elevated plus maze, and open field test. Our results revealed dysregulation of Tph2 expression in the brainstem, amygdala, and hypothalamus in the EFV group, and 5-HT levels increased in the amygdala in the EFV group. In the behavioral tests, mice given EFV exhibited a passive avoidance response in the forced swim test and anxiety-like behavior in the elevated plus maze, and they lost weight. Herein, for the first time, we showed that EFV triggered dysregulation of the Tph2 gene in the three serotonergic areas studied; and 5-HT levels increased in the amygdala using the ELISA method. However, further studies will be necessary to clarify the increase of 5-HT in the amygdala as well as understand the paradoxical decrease in body weight with the simultaneous increase in food consumption. It will also be necessary to measure 5-HT by other techniques different from ELISA, such as HPLC.

Identification of hypothermia-inducing neurons in the preoptic area and activation of them by isoflurane anesthesia and central injection of adenosine

Hibernation and torpor are not passive responses caused by external temperature drops and fasting but are active brain functions that lower body temperature. A population of neurons in the preoptic area was recently identified as such active torpor-regulating neurons. We hypothesized that the other hypothermia-inducing maneuvers would also activate these neurons. To test our hypothesis, we first refined the previous observations, examined the brain regions explicitly activated during the falling phase of body temperature using c-Fos expression, and confirmed the preoptic area. Next, we observed long-lasting hypothermia by reactivating torpor-tagged Gq-expressing neurons using the activity tagging and DREADD systems. Finally, we found that about 40–60% of torpor-tagged neurons were activated by succeeding isoflurane anesthesia and by icv administration of an adenosine A1 agonist. Isoflurane-induced and central adenosine-induced hypothermia is, at least in part, an active process mediated by the torpor-regulating neurons in the preoptic area.Graphical abstract