Magnetically induced stiffening for soft robotics.

Soft robots are well-suited for human-centric applications, but the compliance that gives soft robots this advantage must also be paired with adequate stiffness modulation such that soft robots can achieve more rigidity when needed. For this reason, variable stiffening mechanisms are often a necessary component of soft robot design. Many techniques have been explored to introduce variable stiffness structures into soft robots, such as pneumatically-controlled jamming and thermally-controlled phase change materials. Despite fast response time, jamming methods often require a bulkier pneumatic pressure line which limits portability; and while portable via electronic control, thermally-induced methods require compatibility with high temperatures and often suffer from slow response time. In this paper, we present a magnetically-controlled stiffening approach that combines jamming-based stiffening principles with magnetorheological fluid to create a hybrid mechanical and materials approach. In doing so, we combine the advantages of fast response time from pneumatically-based jamming with the portability of thermally-induced phase change methods. We explore the influence of magnetic field strength on the stiffening of our magnetorheological jamming beam samples in two ways: by exploiting the increase in yield stress of magnetorheological fluid, and by additionally using the clamping force between permanent magnets to further stiffen the samples via a clutch effect. We introduce an analytical model to predict the stiffness of our samples as a function of the magnetic field. Finally, we demonstrate electronic control of the stiffness using electropermanent magnets. In this way, we present an important step towards a new electronically-driven stiffening mechanism for soft robots that interact safely in close contact with humans, such as in wearable devices.

1,000 ancient genomes uncover 10,000 years of natural selection in Europe.

Ancient DNA has revolutionized our understanding of human population history. However, its potential to examine how rapid cultural evolution to new lifestyles may have driven biological adaptation has not been met, largely due to limited sample sizes. We assembled genome-wide data from 1,291 individuals from Europe over 10,000 years, providing a dataset that is large enough to resolve the timing of selection into the Neolithic, Bronze Age, and Historical periods. We identified 25 genetic loci with rapid changes in frequency during these periods, a majority of which were previously undetected. Signals specific to the Neolithic transition are associated with body weight, diet, and lipid metabolism-related phenotypes. They also include immune phenotypes, most notably a locus that confers immunity to Salmonella infection at a time when ancient Salmonella genomes have been shown to adapt to human hosts, thus providing a possible example of human-pathogen co-evolution. In the Bronze Age, selection signals are enriched near genes involved in pigmentation and immune-related traits, including at a key human protein interactor of SARS-CoV-2. Only in the Historical period do the selection candidates we detect largely mirror previously-reported signals, highlighting how the statistical power of previous studies was limited to the last few millennia. The Historical period also has multiple signals associated with vitamin D binding, providing evidence that lactase persistence may have been part of an oligogenic adaptation for efficient calcium uptake and challenging the theory that its adaptive value lies only in facilitating caloric supplementation during times of scarcity. Finally, we detect selection on complex traits in all three periods, including selection favoring variants that reduce body weight in the Neolithic. In the Historical period, we detect selection favoring variants that increase risk for cardiovascular disease plausibly reflecting selection for a more active inflammatory response that would have been adaptive in the face of increased infectious disease exposure. Our results provide an evolutionary rationale for the high prevalence of these deadly diseases in modern societies today and highlight the unique power of ancient DNA in elucidating biological change that accompanied the profound cultural transformations of recent human history.

Pitfalls in the diagnosis of subdural hemorrhage - Mimics and uncommon causes.

PURPOSE: Subdural hemorrhage (SDH), the accumulation of blood between the dura and arachnoid mater, is one of the most commonly encountered traumatic findings in emergency radiology setting. The purpose of this essay is to review the pitfalls in the diagnosis of SDH including a) mimics on CT imaging and b) etiology other than accidental trauma. We describe several entities that closely mimic SDH on non-contrast CT scans. A knowledge of these mimics is essential in the emergency setting since overdiagnosis of SDH can lead to unnecessary hospital admissions, potentially invasive procedures, or even delay in necessary treatment. The mimics of SDH on non-contrast head CT include: PATHOLOGIC ENTITIES IATROGENIC MIMICS ANATOMIC/PHYSIOLOGIC MIMICS ARTIFACTUAL MIMICSWe also briefly review non-accidental and non-traumatic causes of SDH. Although, the most common cause of SDH is accidental trauma, other routinely encountered causes of SDH include coagulopathy, non-accidental trauma, cranial surgery, vascular malformations etc. CONCLUSION: Clinicians dealing with SDH in the emergency setting should consider SDH mimics and less common etiologies of SDH in order to facilitate appropriate patient management.

Electronic cigarette exposures reported to the British Columbia Drug and Poison Information Centre: an observational case series.

BACKGROUND: Electronic nicotine delivery systems (ENDSs), including electronic cigarettes (e-cigarettes), are rapidly gaining popularity. The aim of this study was to use poison centre data to describe epidemiological trends in ENDS-related exposures. METHODS: We conducted an observational case series study using records containing both coded fields and free-text narratives from the British Columbia Drug and Poison Information Centre for all calls involving exposure to ENDS received from 2012 to 2017. We described trends in exposures and exposed people, as well as clinical effects. RESULTS: A total of 243 calls were recorded for 186 unique exposures to ENDS devices, e-juice, e-cigarette cartridges and other associated paraphernalia over the study period. Calls related to ENDS exposures increased nearly sixfold between 2013 and 2014 and did not decline subsequently. Exposures were most frequently documented in children aged 4 years or less (81 [43.5%]), with 58 (31.0%) in 1- and 2-year-olds. Seventy-two exposures (89%) in children aged 4 years or less were due to accidental ingestion, whereas adults aged 25 years or more called the poison centre following ENDS malfunctions (7 [23%], spills (4 [13%]) and exposure to e-juice mistaken for other substances (4 [13%]). Of the 186 exposed people, 87 (46.8%) reported symptoms. INTERPRETATION: British Columbia experienced a sixfold increase in ENDS-related calls to the provincial poison centre between 2012 and 2017, driven by ingestions in young children. Regulatory approaches aimed at minimizing children's access to ENDS, clear labelling of nicotine concentration, and packaging that reduces the likelihood of spills, product confusion and malfunction should be considered.

Effect of linkers on immobilization of scFvs with biotin-streptavidin interaction.

Single-chain variable fragment antibodies (scFvs) are attractive for use in applications that require high specificity and binding to a target, such as biosensors. Previously, we demonstrated that a variety of scFvs can be immobilized onto a streptavidin surface through in vivo biotinylation of the biotin carboxyl carrier protein (BCCP) or smaller AviTag fused to the scFvs. However, the BCCP constructs showed better immobilization than the AviTag constructs. In this work, we investigated whether the discrepancy between the biotinylation tags could be alleviated by incorporating a flexible (G4 S)n linker of varying lengths or a rigid (EA3 K)3 linker between the biotinylation tags and the scFvs scFv13R4 and scFv5. Fusion of the (G4 S)5 linker or the (G4 S)3 linker to the AviTag construct of scFv13R4 or scFv5, respectively, and fusion of the (EA3 K)3 linkers to the AviTag constructs of both scFvs enhanced immobilization. Meanwhile, the robust immobilization of the BCCP construct of the scFv constructs remained unaffected. The positive to neutral effects of the linkers, with no adverse effects, make them beneficial tools to incorporate into fusion proteins that show poor immobilization without a linker.

Neuroanatomical characterization of the cellular and axonal architecture of subcortical band heterotopia in the BXD29-Tlr4lps-2J/J mouse cortex.

Subcortical band heterotopia (SBH) are malformations of the human cerebral cortex typically associated with epilepsy and cognitive delay/disability. Rodent models of SBH have demonstrated strong face validity as they are accompanied by both cognitive deficits and spontaneous seizures or reduced seizure threshold. BXD29-Tlr4lps-2J/J recombinant inbred mice display striking bilateral SBH, partial callosal agenesis, morphological changes in subcortical structures of the auditory pathway, and display sensory deficits in behavioral tests (Rosen et al., 2013; Truong et al., 2013, 2015). Surprisingly, these mice show no cognitive deficits and have a higher seizure threshold to chemi-convulsive treatment (Gabel et al., 2013) making them different than other rodent SBH models described previously. In the present report, we perform a detailed characterization of the cellular and axonal constituents of SBH in BXD29-Tlr4lps-2J/J mice and demonstrate that various types of interneurons and glia as well as cortical and subcortical projections are found in SBH. In addition, the length of neuronal cilia was reduced in SBH compared to neurons in the overlying and adjacent normotopic cortex. Finally, we describe additional and novel malformations of the hippocampus and neocortex present in BXD29-Tlr4lps-2J/J mice. Together, our findings in BXD29-Tlr4lps-2J/J mice are discussed in the context of the known neuroanatomy and phenotype of other SBH rodent models.

Neonatal seizures induced by pentylenetetrazol or kainic acid disrupt primary cilia growth on developing mouse cortical neurons.

Neonatal or early-life seizures (ELS) are often associated with life-long neurophysiological, cognitive and behavioral deficits, but the underlying mechanisms contributing to these deficits remain poorly understood. Newborn, post-migratory cortical neurons sprout ciliary buds (procilia) that mature into primary cilia. Disruption of the growth or signaling capabilities of these cilia has been linked to atypical neurite outgrowth from neurons and abnormalities in neuronal circuitry. Here, we tested the hypothesis that generalized seizures induced by pentylenetetrazol (PTZ) or kainic acid (KA) during early postnatal development impair neuronal and/or glial ciliogenesis. Mice received PTZ (50 or 100mg/kg), KA (2mg/kg), or saline either once at birth (P0), or once daily from P0 to P4. Using immunohistochemistry and electron microscopy, the cilia of neurons and glia were examined at P7, P14, and P42. A total of 83 regions were analyzed, representing 13 unique neocortical and hippocampal regions. Neuronal cilia were identified by co-expression of NeuN and type 3 adenylyl cyclase (ACIII) or somatostatin receptor 3 (SSTR3), while glial cilia were identified by co-expression of GFAP, Arl13b, and gamma-tubulin. We found that PTZ exposure at either P0 or from P0 to P4 induced convulsive behavior, followed by acute and lasting effects on neuronal cilia lengths that varied depending on the cortical region, PTZ dose, injection frequency, and time post-PTZ. Both increases and decreases in neuronal cilia length were observed. No changes in the length of glial cilia were observed under any of the test conditions. Lastly, we found that a single KA seizure at P0 led to similar abnormalities in neuronal cilia lengths. Our results suggest that seizure(s) occurring during early stages of cortical development induce persistent and widespread changes in neuronal cilia length. Given the impact neuronal cilia have on neuronal differentiation, ELS-induced changes in ciliogenesis may contribute to long-term pathology and abnormal cortical function.