Semi-orthogonal subspaces for value mediate a tradeoff between binding and generalization

When choosing between options, we must associate their values with the action needed to select them. We hypothesize that the brain solves this binding problem through neural population subspaces. To test this hypothesis, we examined neuronal responses in five reward-sensitive regions in macaques performing a risky choice task with sequential offers. Surprisingly, in all areas, the neural population encoded the values of offers presented on the left and right in distinct subspaces. We show that the encoding we observe is sufficient to bind the values of the offers to their respective positions in space while preserving abstract value information, which may be important for rapid learning and generalization to novel contexts. Moreover, after both offers have been presented, all areas encode the value of the first and second offers in orthogonal subspaces. In this case as well, the orthogonalization provides binding. Our binding-by-subspace hypothesis makes two novel predictions borne out by the data. First, behavioral errors should correlate with putative spatial (but not temporal) misbinding in the neural representation. Second, the specific representational geometry that we observe across animals also indicates that behavioral errors should increase when offers have low or high values, compared to when they have medium values, even when controlling for value difference. Together, these results support the idea that the brain makes use of semi-orthogonal subspaces to bind features together.Comment: arXiv admin note: substantial text overlap with arXiv:2205.0676

Exploring the acute cardiovascular effects of Floatation-REST

The central nervous system (CNS) exerts a strong regulatory influence over the cardiovascular system in response to environmental demands. Floatation-REST (Reduced Environmental Stimulation Therapy) is an intervention that minimizes stimulation from the environment, yet little is known about the autonomic consequences of reducing external sensory input to the CNS. We recently found that Floatation-REST induces a strong anxiolytic effect in anxious patients while paradoxically enhancing their interoceptive awareness for cardiorespiratory sensations. To further investigate the physiologic nature of this anxiolytic effect, the present study measured acute cardiovascular changes during Floatation-REST using wireless and waterproof equipment that allowed for concurrent measurement of heart rate, heart rate variability (HRV), breathing rate, and blood pressure. Using a within-subjects crossover design, 37 clinically anxious participants with high levels of anxiety sensitivity and 20 non-anxious comparison participants were randomly assigned to undergo a 90-min session of either Floatation-REST or an exteroceptive comparison condition that entailed watching a relaxing nature film. Measures of state anxiety and serenity were collected before and after each session, while indices of autonomic activity were measured throughout each session. HRV was calculated using both time-series and frequency domain analyses. Linear mixed-effects modeling revealed a significant main effect of condition such that relative to the film condition, Floatation-REST elicited significant decreases (p < 0.001) in diastolic blood pressure, systolic blood pressure, breathing rate, and certain metrics of HRV including the standard deviation of the interbeat interval (SDNN), low-frequency HRV, and very low-frequency HRV. Heart rate showed a non-significant trend (p = 0.073) toward being lower in the float condition, especially toward the beginning of the session. The only metric that showed a significant increase during Floatation-REST was normalized high-frequency HRV (p < 0.001). The observed physiological changes were consistent across both anxious and non-anxious participants, and there were no significant group by condition interactions. Blood pressure was the only cardiac metric significantly associated with float-related reductions in state anxiety and increases in serenity. These findings suggest that Floatation-REST lowers sympathetic arousal and alters the balance of the autonomic nervous system toward a more parasympathetic state.Clinical trial registration[https://clinicaltrials.gov/show/NCT03051074], identifier [NCT03051074]

Experimental Infection of Cynomolgus Macaques (Macaca fascicularis) with Aerosolized Monkeypox Virus

Monkeypox virus (MPXV) infection in humans results in clinical symptoms very similar to ordinary smallpox. Aerosol is a route of secondary transmission for monkeypox, and a primary route of smallpox transmission in humans. Therefore, an animal model for aerosol exposure to MPXV is needed to test medical countermeasures. To characterize the pathogenesis in cynomolgus macaques (Macaca fascicularis), groups of macaques were exposed to four different doses of aerosolized MPXV. Blood was collected the day before, and every other day after exposure and assessed for complete blood count (CBC), clinical chemistry analysis, and quantitative PCR. Macaques showed mild anorexia, depression, and fever on day 6 post-exposure. Lymphadenopathy, which differentiates monkeypox from smallpox, was observed in exposed macaques around day 6 post-exposure. CBC and clinical chemistries showed abnormalities similar to human monkeypox cases. Whole blood and throat swab viral loads peaked around day 10, and in survivors, gradually decreased until day 28 post-exposure. Survival was not dose dependent. As such, doses of 4×104 PFU, 1×105 PFU, or 1×106 PFU resulted in lethality for 70% of the animals, whereas a dose of 4×105 PFU resulted in 85% lethality. Overall, cynomolgus macaques exposed to aerosolized MPXV develop a clinical disease that resembles that of human monkeypox. These findings provide a strong foundation for the use of aerosolized MPXV exposure of cynomolgus macaques as an animal model to test medical countermeasures against orthopoxviruses

Characterization and Generation of Male Courtship Song in Cotesia congregata (Hymenoptera: Braconidae)

Background Male parasitic wasps attract females with a courtship song produced by rapid wing fanning. Songs have been described for several parasitic wasp species; however, beyond association with wing fanning, the mechanism of sound generation has not been examined. We characterized the male courtship song of Cotesia congregata (Hymenoptera: Braconidae) and investigated the biomechanics of sound production. Methods and Principal Findings Courtship songs were recorded using high-speed videography (2,000 fps) and audio recordings. The song consists of a long duration amplitude-modulated “buzz” followed by a series of pulsatile higher amplitude “boings,” each decaying into a terminal buzz followed by a short inter-boing pause while wings are stationary. Boings have higher amplitude and lower frequency than buzz components. The lower frequency of the boing sound is due to greater wing displacement. The power spectrum is a harmonic series dominated by wing repetition rate ~220 Hz, but the sound waveform indicates a higher frequency resonance ~5 kHz. Sound is not generated by the wings contacting each other, the substrate, or the abdomen. The abdomen is elevated during the first several wing cycles of the boing, but its position is unrelated to sound amplitude. Unlike most sounds generated by volume velocity, the boing is generated at the termination of the wing down stroke when displacement is maximal and wing velocity is zero. Calculation indicates a low Reynolds number of ~1000. Conclusions and Significance Acoustic pressure is proportional to velocity for typical sound sources. Our finding that the boing sound was generated at maximal wing displacement coincident with cessation of wing motion indicates that it is caused by acceleration of the wing tips, consistent with a dipole source. The low Reynolds number requires a high wing flap rate for flight and predisposes wings of small insects for sound production

Effects of infection-induced migration delays on the epidemiology of avian influenza in wild mallard populations

Wild waterfowl populations form a natural reservoir of Avian Influenza (AI) virus, and fears exist that these birds may contribute to an AI pandemic by spreading the virus along their migratory flyways. Observational studies suggest that individuals infected with AI virus may delay departure from migratory staging sites. Here, we explore the epidemiological dynamics of avian influenza virus in a migrating mallard (Anas platyrhynchos) population with a specific view to understanding the role of infection-induced migration delays on the spread of virus strains of differing transmissibility. We develop a host-pathogen model that combines the transmission dynamics of influenza with the migration, reproduction and mortality of the host bird species. Our modeling predicts that delayed migration of individuals influences both the timing and size of outbreaks of AI virus. We find that (1) delayed migration leads to a lower total number of cases of infection each year than in the absence of migration delay, (2) when the transmission rate of a strain is high, the outbreak starts at the staging sites at which birds arrive in the early part of the fall migration, (3) when the transmission rate is low, infection predominantly occurs later in the season, which is further delayed when there is a migration delay. As such, the rise of more virulent AI strains in waterfowl could lead to a higher prevalence of infection later in the year, which could change the exposure risk for farmed poultry. A sensitivity analysis shows the importance of generation time and loss of immunity for the effect of migration delays. Thus, we demonstrate, in contrast to many current transmission risk models solely using empirical information on bird movements to assess the potential for transmission, that a consideration of infection-induced delays is critical to understanding the dynamics of AI infection along the entire flyway.<br /

Single-cell meta-analysis of SARS-CoV-2 entry genes across tissues and demographics

Angiotensin-converting enzyme 2 (ACE2) and accessory proteases (TMPRSS2 and CTSL) are needed for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cellular entry, and their expression may shed light on viral tropism and impact across the body. We assessed the cell-type-specific expression of ACE2, TMPRSS2 and CTSL across 107 single-cell RNA-sequencing studies from different tissues. ACE2, TMPRSS2 and CTSL are coexpressed in specific subsets of respiratory epithelial cells in the nasal passages, airways and alveoli, and in cells from other organs associated with coronavirus disease 2019 (COVID-19) transmission or pathology. We performed a meta-analysis of 31 lung single-cell RNA-sequencing studies with 1,320,896 cells from 377 nasal, airway and lung parenchyma samples from 228 individuals. This revealed cell-type-specific associations of age, sex and smoking with expression levels of ACE2, TMPRSS2 and CTSL. Expression of entry factors increased with age and in males, including in airway secretory cells and alveolar type 2 cells. Expression programs shared by ACE2+TMPRSS2+ cells in nasal, lung and gut tissues included genes that may mediate viral entry, key immune functions and epithelial-macrophage cross-talk, such as genes involved in the interleukin-6, interleukin-1, tumor necrosis factor and complement pathways. Cell-type-specific expression patterns may contribute to the pathogenesis of COVID-19, and our work highlights putative molecular pathways for therapeutic intervention

AN5D: Automated Stencil Framework for High-Degree Temporal Blocking on GPUs

Stencil computation is one of the most widely-used compute patterns in high performance computing applications. Spatial and temporal blocking have been proposed to overcome the memory-bound nature of this type of computation by moving memory pressure from external memory to on-chip memory on GPUs. However, correctly implementing those optimizations while considering the complexity of the architecture and memory hierarchy of GPUs to achieve high performance is difficult. We propose AN5D, an automated stencil framework which is capable of automatically transforming and optimizing stencil patterns in a given C source code, and generating corresponding CUDA code. Parameter tuning in our framework is guided by our performance model. Our novel optimization strategy reduces shared memory and register pressure in comparison to existing implementations, allowing performance scaling up to a temporal blocking degree of 10. We achieve the highest performance reported so far for all evaluated stencil benchmarks on the state-of-the-art Tesla V100 GPU