Programming Substrate-Independent Kinetic Barriers With Thermodynamic Binding Networks.

Engineering molecular systems that exhibit complex behavior requires the design of kinetic barriers. For example, an effective catalytic pathway must have a large barrier when the catalyst is absent. While programming such energy barriers seems to require knowledge of the specific molecular substrate, we develop a novel substrate-independent approach. We extend the recently-developed model known as thermodynamic binding networks, demonstrating programmable kinetic barriers that arise solely from the thermodynamic driving forces of bond formation and the configurational entropy of forming separate complexes. Our kinetic model makes relatively weak assumptions, which implies that energy barriers predicted by our model would exist in a wide variety of systems and conditions. We demonstrate that our model is robust by showing that several variations in its definition result in equivalent energy barriers. We apply this model to design catalytic systems with an arbitrarily large energy barrier to uncatalyzed reactions. Our results could yield robust amplifiers using DNA strand displacement, a popular technology for engineering synthetic reaction pathways, and suggest design strategies for preventing undesired kinetic behavior in a variety of molecular systems.

Attention bias to infant faces in pregnant women predicts maternal sensitivity.

While research has shown that attention bias to infant faces is linked to parenting, this work is largely cross-sectional and limited to the postpartum period. Because the transition to motherhood from pregnancy to birth constitutes a sensitive period in cortical reorganization linked to the quality of mother-infant interactions, evaluating attention processes in the maternal cortex prior to the experience of mother-infant face-to-face interactions is critical. To assess behavioural attention and neural responses to infant faces in pregnant mothers, behavioral and electrocortical indices were collected using a Go/No Go task, in which infant and adult faces served as distractors. Results showed that heightened processing of infant faces relative to adult faces (behavioral and electrocortical indices) was related to observations of greater maternal sensitivity. These findings show that prenatal maternal attention bias to and the perceived salience of infant faces serves as an individual cognitive hallmark of maternal sensitivity that acts independently of caregiving experience.

The COVID-19 pandemic: local to global implications as perceived by urban ecologists.

The global COVID-19 pandemic is affecting everyone, but in many different ways, stimulating contrasting reactions and responses: opportunities for some, difficulties for many. A simple survey of how individual workers in urban ecology have been coping with COVID-19 constraints found divergent responses to COVID-19 on people's activities, both within countries and between continents. Many academics felt frustrated at being unable to do fieldwork, but several saw opportunities to change ways of working and review their engagement with the natural world. Some engaging with social groups found new ways of sharing ideas and developing aspirations without face-to-face contact. Practitioners creating and managing urban greenspaces had to devise ways to work and travel while maintaining social distancing. Many feared severe funding impacts from changed local government priorities. Around the world, the COVID-19 pandemic has amplified issues, such as environmental injustice, disaster preparation and food security, that have been endemic in most countries across the global south in modern times. However, developing and sustaining the strong community spirit shown in many places will speed economic recovery and make cities more resilient against future geophysical and people-made disasters. Significantly, top-down responses and one-size-fits-all solutions, however good the modelling on which they are based, are unlikely to succeed without the insights that local knowledge and community understanding can bring. We all will have to look at disaster preparation in a more comprehensive, caring and consistent way in future.

Changes in Cortical Sensitivity to Infant Facial Cues From Pregnancy to Motherhood Predict Mother-Infant Bonding.

The transition to motherhood triggers changes in human brain structure that may facilitate mother-infant bonding. Although much research on maternal cortical responses to infant faces has focused on the postpartum period, no previous study has examined whether longitudinal functional changes in the maternal cortex during pregnancy and postpartum are associated with mother-infant bonding. Using electroencephalography, prenatal to postnatal changes in cortical sensitivity (P1, P2, late positive potential, N170 event-related potentials) to infant and adult faces were examined in relation to reported mother-infant bonding in 40 mothers (Mage  = 30.5 years). Prenatal to postnatal increases in P1 and P2 responses to infant faces predicted stronger bonding. Findings suggest that cortical changes in attention allocation rather than in face-specific encoding enhance bonding.

Children's autonomic nervous system activity while transgressing: Relations to guilt feelings and aggression.

Despite the well-established protective functions of guilt across childhood, its underlying physiological mechanisms have received little attention. We used latent difference scores (LDS) to model changes in children's (N = 267; 4- and 8-year-olds, 51% girls) skin conductance (SC) and respiratory sinus arrhythmia (RSA) while they imagined themselves committing antisocial acts. We then tested if their later reports of guilt, caregiver-reported aggressive behavior, and age were associated with these physiological changes. For 8-year-olds, changes in RSA leading up to and during transgressions were uniquely associated with the intensity of guilt feelings after transgressions. Eight-year-olds with higher guilt were rated lower in aggression, although children's physiology and aggression were not directly related. We discuss how fluctuations in physiology while transgressing may prepare children to mount adaptive guilt responses afterward and-more broadly-implications for understanding the mechanisms behind guilt and related behavior in early and middle childhood. (PsycINFO Database Record

The special status of sad infant faces: age and valence differences in adults' cortical face processing.

Understanding the relative and joint prioritization of age- and valence-related face characteristics in adults' cortical face processing remains elusive because these two characteristics have not been manipulated in a single study of neural face processing. We used electroencephalography to investigate adults' P1, N170, P2 and LPP responses to infant and adult faces with happy and sad facial expressions. Viewing infant vs adult faces was associated with significantly larger P1, N170, P2 and LPP responses, with hemisphere and/or participant gender moderating this effect in select cases. Sad faces were associated with significantly larger N170 responses than happy faces. Sad infant faces were associated with significantly larger N170 responses in the right hemisphere than all other combinations of face age and face valence characteristics. We discuss the relative and joint neural prioritization of infant face characteristics and negative facial affect, and their biological value as distinct caregiving and social cues.

Infant Cries Rattle Adult Cognition.

The attention-grabbing quality of the infant cry is well recognized, but how the emotional valence of infant vocal signals affects adult cognition and cortical activity has heretofore been unknown. We examined the effects of two contrasting infant vocalizations (cries vs. laughs) on adult performance on a Stroop task using a cross-modal distraction paradigm in which infant distractors were vocal and targets were visual. Infant vocalizations were presented before (Experiment 1) or during each Stroop trial (Experiment 2). To evaluate the influence of infant vocalizations on cognitive control, neural responses to the Stroop task were obtained by measuring electroencephalography (EEG) and event-related potentials (ERPs) in Experiment 1. Based on the previously demonstrated existence of negative arousal bias, we hypothesized that cry vocalizations would be more distracting and invoke greater conflict processing than laugh vocalizations. Similarly, we expected participants to have greater difficulty shifting attention from the vocal distractors to the target task after hearing cries vs. after hearing laughs. Behavioral results from both experiments showed a cry interference effect, in which task performance was slower with cry than with laugh distractors. Electrophysiology data further revealed that cries more than laughs reduced attention to the task (smaller P200) and increased conflict processing (larger N450), albeit differently for incongruent and congruent trials. Results from a correlation analysis showed that the amplitudes of P200 and N450 were inversely related, suggesting a reciprocal relationship between attention and conflict processing. The findings suggest that cognitive control processes contribute to an attention bias to infant signals, which is modulated in part by the valence of the infant vocalization and the demands of the cognitive task. The findings thus support the notion that infant cries elicit a negative arousal bias that is distracting; they also identify, for the first time, the neural dynamics underlying the unique influence that infant cries and laughs have on cognitive control.

Energy-efficient adaptive modulation in wireless communication for implanted medical devices.

In contrast to conventional wireless communication which takes place over the air, Radio Frequency (RF) communication through the human body poses unique challenges. Studies on RF propagation through human body indicate that the heterogeneous body tissues with different dielectric properties constitute a complicated and lossy environment for signal propagation. This environment also varies with different implant positions, individuals, body shapes and postures. As a result, there is a large variation in the path loss value of the in-body communication channel. In this paper, we first examine the energy efficiency of different digital modulation schemes in a basic wireless implant system. We point out that using a fixed type of modulation does not help to achieve the best energy efficiency in the implant system that has varying channel conditions. We then propose an adaptive communication system model which is suitable for wireless medical implant. Simulations results show that adopting adaptive modulation can provide a considerable amount of energy saving.

Investigating social cognition in infants and adults using dense array electroencephalography ((d)EEG).

Dense array electroencephalography ((d)EEG), which provides a non-invasive window for measuring brain activity and a temporal resolution unsurpassed by any other current brain imaging technology¹, ² is being used increasingly in the study of social cognitive functioning in infants and adults. While (d)EEG is enabling researchers to examine brain activity patterns with unprecedented levels of sensitivity, conventional EEG recording systems continue to face certain limitations, including 1) poor spatial resolution and source localization³,42) the physical discomfort for test subjects of enduring the individual application of numerous electrodes to the surface of the scalp, and 3) the complexity for researchers of learning to use multiple software packages to collect and process data. Here we present an overview of an established methodology that represents a significant improvement on conventional methodologies for studying EEG in infants and adults. Although several analytical software techniques can be used to establish indirect indices of source localization to improve the spatial resolution of (d)EEG, the HydroCel Geodesic Sensor Net (HCGSN) by Electrical Geodesics, Inc. (EGI), a dense sensory array that maintains equal distances among adjacent recording electrodes on all surfaces of the scalp, further enhances spatial resolution4,5(,)6 compared to standard (d)EEG systems. The sponge-based HCGSN can be applied rapidly and without scalp abrasion, making it ideal for use with adults7,8 children9,¹°, ¹¹,¹² and infants¹², in both research and clinical 4,5,6,¹³,¹4,¹5settings. This feature allows for considerable cost and time savings by decreasing the average net application time compared to other (d)EEG systems. Moreover, the HCGSN includes unified, seamless software applications for all phases of data, greatly simplifying the collection, processing, and analysis of (d)EEG data. The HCGSN features a low-profile electrode pedestal, which, when filled with electrolyte solution, creates a sealed microenvironment and an electrode-scalp interface. In all Geodesic (d;)EEG systems, EEG sensors detect changes in voltage originating from the participant's scalp, along with a small amount of electrical noise originating from the room environment. Electrical signals from all sensors of the Geodesic sensor net are received simultaneously by the amplifier, where they are automatically processed, packaged, and sent to the data-acquisition computer (DAC). Once received by the DAC, scalp electrical activity can be isolated from artifacts for analysis using the filtering and artifact detection tools included in the EGI software. Typically, the HCGSN can be used continuously for only up to two hours because the electrolyte solution dries out over time, gradually decreasing the quality of the scalp-electrode interface. In the Parent-Infant Research Lab at the University of Toronto, we are using (d)EEG to study social cognitive processes including memory, emotion, goals, intentionality, anticipation, and executive functioning in both adult and infant participants.

Relationship disruption stress in human infants: a validation study with experimental and control groups.

The current study examined whether the psychological stress of the still-face (SF) task (i.e. stress resulting from a parent's unresponsiveness) is a valid laboratory stress paradigm for evaluating infant cortisol reactivity. Given that factors external to the experimental paradigm, such as arriving at a new place, may cause an elevation in cortisol secretion; we tested the hypothesis that infants would show a cortisol response to the SF task but not to a normal FF task (control). Saliva was collected for cortisol measurement from 6-month-old infants (n = 31) randomly assigned to either a repeated SF task or to a continuous FF task. Parent-infant dyads were videotaped. Salivary cortisol concentration was measured at baseline, 20, and 30 min after the start of the procedure. Infant salivary cortisol concentrations showed a significant increase over time for the SF task but not for the FF task. The results provide new evidence that the repeated SF task provides a psychological challenge that is due to the SF condition rather than to some non-task related factor; these results provide internal validity for the paradigm. The study offers new insight into the role of parent-infant interactions in the activation of the infant stress response system.

Infant anticipatory stress.

In humans, anticipatory stress involves activation of the limbic-hypothalamic-pituitary-adrenal axis, which releases stress hormones such as cortisol in response to an impending stressor. Conditioning of the stress response to anticipate and prepare for future challenges is a hallmark of adaptation. It is unknown whether human infants in the first year of life have developed the neural circuitry to support the anticipation of stressful events in an attachment context. Here, we show that human infants at six months of age produce an anticipatory stress response, as indicated by the release of stress hormones, when re-exposed after 24 h to a context in which they demonstrated a stress response to a disruption in the parent-infant relationship. Although infant stress response (cortisol elevation) was greater to the stressful event (parent unresponsiveness) than to the second exposure to the stress context (room, chair, presence of parent and experimenter, etc.), it was greater in the stress group than in the control group on both days. Results suggest that human infants have the capacity to produce an anticipatory stress response that is based on expectations about how their parents will treat them in a specific context.

Physiological correlates of memory recall in infancy: vagal tone, cortisol, and imitation in preterm and full-term infants at 6 months.

We examined the role of physiological regulation (heart rate, vagal tone, and salivary cortisol) in short-term memory in preterm and full-term 6-month-old infants. Using a deferred imitation task to evaluate social learning and memory recall, an experimenter modeled three novel behaviors (removing, shaking, and replacing a glove) on a puppet. Infants were tested immediately after being shown the behaviors as well as following a 10-min delay. We found that greater suppression of vagal tone was related to better memory recall in full-term infants tested immediately after the demonstration as well as in preterm infants tested later after a 10-min delay. We also found that preterm infants showed greater coordination of physiology (i.e., tighter coupling of vagal tone, heart rate, and cortisol) at rest and during retrieval than full-term infants. These findings provide new evidence of the important links between changes in autonomic activity and memory recall in infancy. They also raise the intriguing possibility that social learning, imitation behavior, and the formation of new memories are modulated by autonomic activity that is coordinated differently in preterm and full-term infants.

Contingency Learning and Reactivity in Preterm and Full-Term Infants at 3 Months.

Learning difficulties in preterm infants are thought to reflect impairment in arousal regulation. We examined relationships among gestational age, learning speed, and behavioral and physiological reactivity in 55 preterm and 49 full-term infants during baseline, contingency, and nonreinforcement phases of a conjugate mobile paradigm at 3 months corrected age. For all infants, negative affect, looking duration, and heart rate levels increased during contingency and nonreinforcement phases, whereas respiratory sinus arrhythmia (RSA, an index of parasympathetic activity) decreased and cortisol did not change. Learners showed greater RSA suppression and less negative affect than nonlearners. This pattern was particularly evident in the preterm group. Overall, preterm infants showed less learning, spent less time looking at the mobile, and had lower cortisol levels than full-term infants. Preterm infants also showed greater heart rate responses to contingency and dampened heart rate responses to nonreinforcement compared to full-term infants. Findings underscore differences in basal and reactivity measures in preterm compared to full-term infants and suggest that the capacity to regulate parasympathetic activity during a challenge enhances learning in preterm infants.

Maternal stress and behavior modulate relationships between neonatal stress, attention, and basal cortisol at 8 months in preterm infants.

There is evidence that the developmental trajectory of cortisol secretion in preterm infants is altered, with elevated basal cortisol levels observed postnatally through at least 18 months corrected age (CA). This alteration is possibly due to neonatal pain-related stress. High cortisol levels might contribute to greater risk of impaired neurodevelopment. Since maternal factors are important for the regulation of infant stress responses, we investigated relationships between infant (neonatal pain-related stress, attention, cortisol) and maternal (stress, interactive behaviors) factors at age 8 months CA. We found that interactive maternal behaviors buffered the relationship between high neonatal pain-related stress exposure and poorer focused attention in mothers who self-reported low concurrent stress. Furthermore, in preterm infants exposed to high concurrent maternal stress and overwhelming interactive maternal behaviors, higher basal cortisol levels were associated with poor focused attention. Overall, these findings suggest that maternal factors can influence the cognitive resilience at 8 months of preterm infants exposed to early life stress.

Altered basal cortisol levels at 3, 6, 8 and 18 months in infants born at extremely low gestational age.

OBJECTIVE: Little is known about the developmental trajectory of cortisol levels in preterm infants after hospital discharge. STUDY DESIGN: In a cohort of 225 infants (gestational age at birth <33 weeks) basal salivary cortisol levels were compared in infants born at extremely low gestational age (ELGA, 23-28 weeks), very low gestational age (29-32 weeks), and term (37-42 weeks) at 3, 6, 8, and 18 months corrected age (CA). Infants with major neurosensory or motor impairment were excluded. RESULTS: At 3 months CA, salivary cortisol levels were lower in both preterm groups compared with the term infants (P = .003). Conversely, at 8 and 18 months CA, the ELGA infants had significantly higher basal cortisol levels than the very low gestational age and term infants (P = .016 and P = .006, respectively). CONCLUSIONS: In ELGA infants, the shift from low basal cortisol levels at 3 months to significantly high levels at 8 and 18 months CA suggests long-term "resetting" of endocrine stress systems. Multiple factors may contribute to these higher cortisol levels in the ELGA infants, including physiological immaturity at birth, cumulative stress related to multiple procedures, and mechanical ventilation during lengthy hospitalization. Prolonged elevation of the cortisol "set-point" may have negative implications for neurodevelopment and later health.

Infant stress reactivity and prenatal alcohol exposure.

BACKGROUND: Animal studies have shown that prenatal alcohol exposure (PAE) is linked to alterations in the stress response systems. To date, little is known about the impact of PAE on stress systems in human infants. The current study examined PAE effects on the stress response, as evidenced by the activation of the limbic-hypothalamic-pituitary-adrenal (L-HPA) axis and autonomic system and changes in negative affect during a social-emotional challenge in human infants. We also examined whether the effects of PAE on infant responsiveness differed in boys and girls. METHODS: Measures of cortisol, heart rate, and negative affect were obtained during a modified version of Tronick's still-face procedure, a standardized developmental paradigm used to study emotion and stress regulation. Our sample included fifty-five 5- to 7-month-old infants whose mothers were enrolled in an alcohol intervention study. Measures of maternal alcohol consumption during pregnancy and after delivery were obtained using Timeline Followback interviewing methods. Relationships between prenatal alcohol consumption and infant outcomes were examined. In addition, mothers were divided into high and low-frequency drinkers, based on the mean percent of prenatal drinking days (PDD) to facilitate between-group comparisons of infant stress measures. RESULTS: Mothers enrolled in our study reported significant reductions in alcohol consumption after learning of their pregnancies. Nevertheless, PDD from conception to pregnancy recognition was related to increases in cortisol reactivity, elevated heart rate, and negative affect in their infants. The effects of PAE on infant responsiveness were significant after controlling for the effects of maternal depression and annual income. In addition, the effects of PAE on cortisol reactivity differed for boys and girls. CONCLUSIONS: Greater PAE was related to greater activation of stress response systems. Our findings suggest that PAE affects the development of infant stress systems and that these effects differ in boys and girls. This work supports the possibility that PAE is related to alterations in infant stress systems, which could underlie problems in cognitive and social-emotional functioning that are common among persons exposed prenatally to alcohol.

Cortisol, contingency learning, and memory in preterm and full-term infants.

Cortisol plays an important role in learning and memory. An inverted-U shaped function has been proposed to account for the positive and negative effects of cortisol on cognitive performance and memory in adults, such that too little or too much impair but moderate amounts facilitate performance. Whether such relationships between cortisol and mental function apply to early infancy, when cortisol secretion, learning, and memory undergo rapid developmental changes, is unknown. We compared relationships between learning/memory and cortisol in preterm and full-term infants and examined whether a greater risk for adrenal insufficiency associated with prematurity produces differential cortisol-memory relationships. Learning in three-month old (corrected for gestational age) preterm and full-term infants was evaluated using a conjugate reinforcement mobile task. Memory was tested by repeating the same task 24h later. Salivary cortisol samples were collected before and 20 min after the presentation of the mobile. We found that preterm infants had lower cortisol levels and smaller cortisol responses than full-term infants. This is consistent with relative adrenal insufficiency reported in the neonatal period. Infants who showed increased cortisol levels from 0 to 20 min on Day 1 had significantly better memory, regardless of prematurity, than infants who showed decreased cortisol levels.

Neonatal procedural pain exposure predicts lower cortisol and behavioral reactivity in preterm infants in the NICU.

Data from animal models indicate that neonatal stress or pain can permanently alter subsequent behavioral and/or physiological reactivity to stressors. However, cumulative effects of pain related to acute procedures in the neonatal intensive care unit (NICU) on later stress and/or pain reactivity has received limited attention. The objective of this study is to examine relationships between prior neonatal pain exposure (number of skin breaking procedures), and subsequent stress and pain reactivity in preterm infants in the NICU. Eighty-seven preterm infants were studied at 32 (+/-1 week) postconceptional age (PCA). Infants who received analgesia or sedation in the 72 h prior to each study, or any postnatal dexamethasone, were excluded. Outcomes were infant responses to two different stressors studied on separate days in a repeated measures randomized crossover design: (1) plasma cortisol to stress of a fixed series of nursing procedures; (2) behavioral (Neonatal Facial Coding System; NFCS) and cardiac reactivity to pain of blood collection. Among infants born

Infant stress and parent responsiveness: regulation of physiology and behavior during still-face and reunion.

This study examined infant response and recovery from a social challenge and parent responses. Behavioral and physiological responses were measured from forty-three 5- and 6-month-olds infants during a modified still-face procedure that used an additional still-face reunion sequence. Results confirm the hypothesis that infants of more responsive parents show more regulation than infants of less responsive parents. Infants of more responsive parents showed greater regulation of heart rate and negative affect during the final episode of the procedure than infants of less responsive parents. In addition, this procedure elicited a cortisol response (from .22 microg/dl to .31 microg/dl). Findings suggest important links between parent behavior and infant stress reactivity and regulation.

Pain measurement with evoked potentials: combination of subjective ratings, randomized intensities, and long interstimulus intervals produces a P300-like confound.

Evoked potentials in response to painful stimuli have been studied as objective measures of pain. Bromm has advocated experimental conditions in which, (1) stimulus intensities are randomized, and (2) subjects rate each stimulus. However, a cognitive, i.e. information processing, 'late positive component' (LPC), e.g. the P300, may be elicited by these same conditions, whether or not the stimuli are painful. The LPC may overlap, and interfere with the measurement of, responses that are only seen with painful stimuli. We compared the LPC in two experimental protocols using ten subjects and electrical stimuli. In the 'Rating Protocol', shocks of different intensity levels were randomly presented and subjects rated the intensity of each stimulus. In the 'Oddball Standards Protocol', the same levels were used, but each was presented in a separate block of a single level. Stimuli were presented more rapidly and subjects had to push a button in response to occasional double shocks (oddball targets), but not to single shocks (oddball standards). The oddball targets served to direct subjects' attention to the stimuli, but only the evoked potential responses to the oddball standards were used for data analysis. To look at the difference between protocols, we computed a difference condition (Rating protocol responses minus Oddball Standards protocol responses) which we called Incremental activity. The Incremental LPC (average amplitudes from 350 to 650 ms) had a more parietal topography (amplitude at electrode Pz greater than at Cz) than the Oddball Standards LPC (Cz > Pz; protocol x electrode interaction P<0.001). This implies that the Rating Protocol LPC included P300-like activity. The parietal Incremental activity began as early as 250-350 ms after the stimulus in the responses to the most painful stimuli and therefore can confound the measurement of pain activity in the evoked potential.