Dynamic analysis of geomaterials using microwave sensing.

Precise characterization of geomaterials improves subsurface energy extraction and storage. Understanding geomaterial property, and the complexities between petrophysics and geomechanics, plays a key role in maintaining energy security and the transition to a net zero global carbon economy. Multiple sectors demand accurate and rapid characterization of geomaterial conditions, requiring the extraction of core plugs in the field for full-field characterization and analysis in the laboratory. We present a novel technique for the non-invasive characterization of geomaterials by using Frequency Modulated Continuous Wave (FMCW) radar in the K-band, representing a new application of microwave radar. We collect data through the delivery of FMCW wave interactions with geomaterials under static and dynamic conditions and show that FMCW can detect fluid presence, differentiate fluid type, indicate the presence of metallic inclusions and detect imminent failure in loaded sandstones by up to 15 s, allowing for greater control in loading up to a failure event. Such precursors have the potential to significantly enhance our understanding of, and ability to model, geomaterial dynamics. This low-cost sensing method is easily deployable, provides quicker and more accessible data than many state-of-the-art systems, and new insights into geomaterial behavior under dynamic conditions.

NeoSLAM: Long-Term SLAM Using Computational Models of the Brain.

Simultaneous Localization and Mapping (SLAM) is a fundamental problem in the field of robotics, enabling autonomous robots to navigate and create maps of unknown environments. Nevertheless, the SLAM methods that use cameras face problems in maintaining accurate localization over extended periods across various challenging conditions and scenarios. Following advances in neuroscience, we propose NeoSLAM, a novel long-term visual SLAM, which uses computational models of the brain to deal with this problem. Inspired by the human neocortex, NeoSLAM is based on a hierarchical temporal memory model that has the potential to identify temporal sequences of spatial patterns using sparse distributed representations. Being known to have a high representational capacity and high tolerance to noise, sparse distributed representations have several properties, enabling the development of a novel neuroscience-based loop-closure detector that allows for real-time performance, especially in resource-constrained robotic systems. The proposed method has been thoroughly evaluated in terms of environmental complexity by using a wheeled robot deployed in the field and demonstrated that the accuracy of loop-closure detection was improved compared with the traditional RatSLAM system.

Anomaly Detection Methods in Autonomous Robotic Missions.

Since 2015, there has been an increase in articles on anomaly detection in robotic systems, reflecting its growing importance in improving the robustness and reliability of the increasingly utilized autonomous robots. This review paper investigates the literature on the detection of anomalies in Autonomous Robotic Missions (ARMs). It reveals different perspectives on anomaly and juxtaposition to fault detection. To reach a consensus, we infer a unified understanding of anomalies that encapsulate their various characteristics observed in ARMs and propose a classification of anomalies in terms of spatial, temporal, and spatiotemporal elements based on their fundamental features. Further, the paper discusses the implications of the proposed unified understanding and classification in ARMs and provides future directions. We envisage a study surrounding the specific use of the term anomaly, and methods for their detection could contribute to and accelerate the research and development of a universal anomaly detection system for ARMs.

Structural connectivity of the multiple demand network in humans and comparison to the macaque brain.

Fluid intelligence encompasses a wide range of abilities such as working memory, problem-solving, and relational reasoning. In the human brain, these abilities are associated with the Multiple Demand Network, traditionally thought to involve combined activity of specific regions predominantly in the prefrontal and parietal cortices. However, the structural basis of the interactions between areas in the Multiple Demand Network, as well as their evolutionary basis among primates, remains largely unexplored. Here, we exploit diffusion MRI to elucidate the major white matter pathways connecting areas of the human core and extended Multiple Demand Network. We then investigate whether similar pathways can be identified in the putative homologous areas of the Multiple Demand Network in the macaque monkey. Finally, we contrast human and monkey networks using a recently proposed approach to compare different species' brains within a common organizational space. Our results indicate that the core Multiple Demand Network relies mostly on dorsal longitudinal connections and, although present in the macaque, these connections are more pronounced in the human brain. The extended Multiple Demand Network relies on distinct pathways and communicates with the core Multiple Demand Network through connections that also appear enhanced in the human compared with the macaque.

Evolution of a cross-feeding interaction following a key innovation in a long-term evolution experiment with Escherichia coli.

The evolution of a novel trait can profoundly change an organism's effects on its environment, which can in turn affect the further evolution of that organism and any coexisting organisms. We examine these effects and feedbacks following the evolution of a novel function in the Long-Term Evolution Experiment (LTEE) with Escherichia coli. A characteristic feature of E. coli is its inability to grow aerobically on citrate (Cit-). Nonetheless, a Cit+ variant with this capacity evolved in one LTEE population after 31 000 generations. The Cit+ clade then coexisted stably with another clade that retained the ancestral Cit- phenotype. This coexistence was shaped by the evolution of a cross-feeding relationship based on C4-dicarboxylic acids, particularly succinate, fumarate, and malate, that the Cit+ variants release into the medium. Both the Cit- and Cit+ cells evolved to grow on these excreted resources. The evolution of aerobic growth on citrate thus led to a transition from an ecosystem based on a single limiting resource, glucose, to one with at least five resources that were either shared or partitioned between the two coexisting clades. Our findings show that evolutionary novelties can change environmental conditions in ways that facilitate diversity by altering ecosystem structure and the evolutionary trajectories of coexisting lineages.

Erratum: "Causal Contributions of the Domain-General (Multiple Demand) and the Language-Selective Brain Networks to Perceptual and Semantic Challenges in Speech Comprehension".

[This corrects the article DOI: 10.1162/nol_a_00081.].

Iatrogenic Rhinolith: A Case Report and Review of Literature.

INTRODUCTION: Unilateral nasal obstruction is a common complaint with a broad differential diagnosis that includes anatomic asymmetry, unilateral infective or inflammatory conditions, and benign and malignant sinonasal masses. A rhinolith is an uncommon foreign body in the nose, which serves as a nidus for calcium salt deposition. The foreign body can be endogenous or exogenous in origin and may remain asymptomatic for many years before incidental discovery. When left untreated, stones may cause unilateral nasal obstruction, rhinorrhea, nasal discharge, epistaxis or, in rare cases, progressive destruction leading to septal/palatal perforation or oro-antral fistula. Surgical removal is an effective intervention with limited complications reported. CASE REPORT: This article describes a 34-year-old male who presented to the emergency department (ED) with unilateral obstructing nasal mass and epistaxis, which was found to be an iatrogenic rhinolith. Successful surgical removal was performed. CONCLUSION: Epistaxis and nasal obstruction are common presentations to the ED. Rhinolith is an uncommon clinical etiology that if left undiagnosed may lead to progressive destructive disease; it should be included in the differential for any unilateral nasal symptoms of unclear origin. Appropriate work-up for any suspected rhinolith includes computed tomography, as biopsy is risky given the broad differential of unilateral nasal mass. When identified, surgical removal has a high success rate with limited complications reported.

Parental Scaffolding during Book-Sharing Predicts Child General Intelligence.

While much variance in general intelligence or g is genetic, a substantial environmental component suggests a possible role for parent-child interaction. In particular, previous evidence suggests the importance of parental scaffolding, or provision of cognitive structure to shape child behaviour. A role for scaffolding is consistent with the proposal that, in adult cognition, a critical aspect of g is decomposition of complex problems into a structure of simpler parts. Building on previous work, we recruited 162 parents attending Children's Centres with a child aged 2-4 years, and examined parental scaffolding during a book-sharing activity. Scaffolding was measured as the first principal component of a variety of parental behaviours, including sensitivity, focusing attention, extending comprehension, and promoting child participation. Child g was measured as the first principal component of a broad cognitive battery, including language, attention, working memory, and executive function. Importantly, we assessed contributions of the parent's own intelligence, education, and family income. Though these variables were all associated with both child g and parental scaffolding, scaffolding remained predictive of child g even once the influence of these variables was removed. In contrast to the correlation with cognitive proficiency, scaffolding did not predict child pro-social behaviour. We suggest that parental scaffolding supports the child's development of a broad skill of attentional structuring, promoting the across-the-board cognitive proficiency that is reflected in g.

Lifespan differences in visual short-term memory load-modulated functional connectivity.

Working memory is critical to higher-order executive processes and declines throughout the adult lifespan. However, our understanding of the neural mechanisms underlying this decline is limited. Recent work suggests that functional connectivity between frontal control and posterior visual regions may be critical, but examinations of age differences therein have been limited to a small set of brain regions and extreme group designs (i.e., comparing young and older adults). In this study, we build on previous research by using a lifespan cohort and a whole-brain approach to investigate working memory load-modulated functional connectivity in relation to age and performance. The article reports on analysis of the Cambridge center for Ageing and Neuroscience (Cam-CAN) data. Participants from a population-based lifespan cohort (N = 101, age 23-86) performed a visual short-term memory task during functional magnetic resonance imaging. Visual short-term memory was measured with a delayed recall task for visual motion with three different loads. Whole-brain load-modulated functional connectivity was estimated using psychophysiological interactions in a hundred regions of interest, sorted into seven networks (Schaefer et al., 2018, Yeo et al., 2011). Results showed that load-modulated functional connectivity was strongest within the dorsal attention and visual networks during encoding and maintenance. With increasing age, load-modulated functional connectivity strength decreased throughout the cortex. Whole-brain analyses for the relation between connectivity and behavior were non-significant. Our results give additional support to the sensory recruitment model of working memory. We also demonstrate the widespread negative impact of age on the modulation of functional connectivity by working memory load. Older adults might already be close to ceiling in terms of their neural resources at the lowest load and therefore less able to further increase connectivity with increasing task demands.

Tinker, tailor, soldier, cell: the role of C-type lectins in the defense and promotion of disease.

C-type lectins (CTLs) represent a large family of soluble and membrane-bound proteins which bind calcium dependently via carbohydrate recognition domains (CRDs) to glycan residues presented on the surface of a variety of pathogens. The deconvolution of a cell's glycan code by CTLs underpins several important physiological processes in mammals such as pathogen neutralization and opsonization, leukocyte trafficking, and the inflammatory response. However, as our knowledge of CTLs has developed it has become apparent that the role of this innate immune family of proteins can be double-edged, where some pathogens have developed approaches to subvert and exploit CTL interactions to promote infection and sustain the pathological state. Equally, CTL interactions with host glycoproteins can contribute to inflammatory diseases such as arthritis and cancer whereby, in certain contexts, they exacerbate inflammation and drive malignant progression. This review discusses the 'dual agent' roles of some of the major mammalian CTLs in both resolving and promoting infection, inflammation and inflammatory disease and highlights opportunities and emerging approaches for their therapeutic modulation.

Neural Contributions to Reduced Fluid Intelligence across the Adult Lifespan.

Fluid intelligence, the ability to solve novel, complex problems, declines steeply during healthy human aging. Using fMRI, fluid intelligence has been repeatedly associated with activation of a frontoparietal brain network, and impairment following focal damage to these regions suggests that fluid intelligence depends on their integrity. It is therefore possible that age-related functional differences in frontoparietal activity contribute to the reduction in fluid intelligence. This paper reports on analysis of the Cambridge Center for Ageing and Neuroscience data, a large, population-based cohort of healthy males and females across the adult lifespan. The data support a model in which age-related differences in fluid intelligence are partially mediated by the responsiveness of frontoparietal regions to novel problem-solving. We first replicate a prior finding of such mediation using an independent sample. We then precisely localize the mediating brain regions, and show that mediation is specifically associated with voxels most activated by cognitive demand, but not with voxels suppressed by cognitive demand. We quantify the robustness of this result to potential unmodeled confounders, and estimate the causal direction of the effects. Finally, exploratory analyses suggest that neural mediation of age-related differences in fluid intelligence is moderated by the variety of regular physical activities, more reliably than by their frequency or duration. An additional moderating role of the variety of nonphysical activities emerged when controlling for head motion. A better understanding of the mechanisms that link healthy aging with lower fluid intelligence may suggest strategies for mitigating such decline.SIGNIFICANCE STATEMENT Global populations are living longer, driving urgency to understand age-related cognitive declines. Fluid intelligence is of prime importance because it reflects performance across many domains, and declines especially steeply during healthy aging. Despite consensus that fluid intelligence is associated with particular frontoparietal brain regions, little research has investigated suggestions that under-responsiveness of these regions mediates age-related decline. We replicate a recent demonstration of such mediation, showing specific association with brain regions most activated by cognitive demand, and robustness to moderate confounding by unmodeled variables. By showing that this mediation model is moderated by the variety of regular physical activities, more reliably than by their frequency or duration, we identify a potential modifiable lifestyle factor that may help promote successful aging.

Cognitive segmentation and fluid reasoning in childhood.

The ability to solve novel complex problems predicts success in a wide range of areas. Recent research suggests that the ability to cognitively segment complex problems into smaller parts constrains nonverbal reasoning in adults. This study aimed to test whether cognitively segmenting problems improves nonverbal reasoning performance for children as it does for adults. A total of 115 children aged 6-10 years completed two versions of a modified traditional matrix reasoning task in which demands on working memory, integration, and processing speed were minimised, such that the only significant requirement was to break each problem into its constituent parts. In one version of the task, participants were presented with a traditional 2×2 Matrix and asked to draw the missing matrix item into a response box below. In a second version, the problem was broken down into its component features across three separate cells, reducing the need for participants to segment the problem. As with adults, performance was better in the condition in which the problems were separated into component parts. Children with lower fluid intelligence did not benefit more in the separated condition than children with higher fluid intelligence, and there was no evidence that segmenting problems was more beneficial for younger than older children. This study demonstrates that cognitive segmentation is a critical component of complex problem-solving for children, as it is for adults. By forcing children to focus their attention on separate parts of a complex visual problem, their performance can be dramatically improved.

Frontal and temporal coding dynamics in successive steps of complex behavior.

Ventrolateral prefrontal cortex (vlPFC), dorsolateral prefrontal cortex (dlPFC), and temporal cortex (TE) all contribute to visual decision-making. Accumulating evidence suggests that vlPFC may play a central role in multiple cognitive operations, perhaps resembling domain-general regions of the human frontal lobe. We trained monkeys in a task calling for learning, retrieval, and spatial selection of rewarded target objects. Recordings of neural activity covered large areas of vlPFC, dlPFC, and TE. Results suggested a central role for vlPFC in each cognitive operation with strong coding of each task feature, while only location was strongly coded in dlPFC and current object identity in TE. During target selection, target location was communicated first from vlPFC to dlPFC, followed by extensive mutual support. In vlPFC, stimulus identities were independently coded in different task operations. The results suggest a central role for the inferior frontal convexity in controlling successive operations of a complex, multi-step task.

Working at the interface of physics and biology: An early career researcher perspective.

We are a network of Early Career Researchers (ECRs) and a Project Manager who are working on UKRI's "Physics of Life" grants which aim to merge ideas and techniques predominantly used in physics and apply them to biological questions. We have been collaborating since early 2021 to share research, experiences, and provide peer to peer support. Interdisciplinary projects are known for presenting challenges, bringing together disparate subjects and people with not only different knowledge bases, methods, and equipment but also varying ways of working and common languages. This has been the subject of commentary by researchers and funders from a management perspective, and we wanted to add to this discourse, using our experience to share the lessons and challenges we have encountered, from an ECR perspective.

Inactivation of the Complement Lectin Pathway by Candida tropicalis Secreted Aspartyl Protease-1.

Candida tropicalisis an opportunistic fungal pathogen and is one of the most frequently isolated non-albicans species. It can cause localised as well as invasive systemic infections particularly in immunocompromised patients. Increased resistance to common anti-fungal drugs is an emerging problem. In order to establish disseminated infections, Candida has evolved several strategies to escape the host immune system. A detailed understanding of how C. tropicalis escapes the host immune attack is needed as it can help develop novel anti-fungal therapies. Secreted aspartyl proteinases (Saps) of C. albicans have been shown to be determinants of virulence and immune evasion. However, the immune evasion properties of C. tropicalis Saps have been poorly characterised. This study investigated the immune evasion properties of C. tropicalis secreted aspartic protease 1 (Sapt1).Sapt1 was recombinantly produced using a Kluyveromyces lactis yeast expression system. A range of complement proteins and immunogloublins were screened to test if Sapt1 had any proteolytic activity. Sapt1 efficiently cleaved human mannose-binding lectin (MBL) and collectin-11, which are the initiating molecules of the lectin pathway of the complement system, but not l-ficolin. In addition, Sapt1 cleaved DC-SIGN, the receptor on antigen presenting dendritic cells. Proteolysis was prominent in acidic condition (pH 5.2), a characteristic of aspartyl protease. No proteolytic activity was detected against complement proteins C1q, C3, C3b, IgG and IgA. In view of the ability of Sapt1 to cleave MBL and collectin-11, we found that Sapt1 could prevent activation of the complement lectin pathway. RT-qPCR analysis using three different C. tropicalis clinical isolates (oral, blood and peritoneal dialysis fluid) revealed relatively higher levels of mRNA expression of Sapt1 gene when compared to a reference strain; Sapt1 protein was found to be secreted by all the tested strains. Lectin pathway and its initiating components are crucial to provide front line defence against Candida infections. For the first time, we have shown that a Candida protease can proteolytically degrade the key initiating components of lectin pathway and inhibit complement activation. Findings from this study highlight the importance of exploring Sapt1 as a potential therapeutic target. We conclude that C. tropicalis secretes Sapt1 to target the complement lectin pathway, a key pattern recognition and clearance mechanism, for its survival and pathogenesis.

Human surfactant protein D facilitates SARS-CoV-2 pseudotype binding and entry in DC-SIGN expressing cells, and downregulates spike protein induced inflammation.

Lung surfactant protein D (SP-D) and Dendritic cell-specific intercellular adhesion molecules-3 grabbing non-integrin (DC-SIGN) are pathogen recognising C-type lectin receptors. SP-D has a crucial immune function in detecting and clearing pulmonary pathogens; DC-SIGN is involved in facilitating dendritic cell interaction with naïve T cells to mount an anti-viral immune response. SP-D and DC-SIGN have been shown to interact with various viruses, including SARS-CoV-2, an enveloped RNA virus that causes COVID-19. A recombinant fragment of human SP-D (rfhSP-D) comprising of α-helical neck region, carbohydrate recognition domain, and eight N-terminal Gly-X-Y repeats has been shown to bind SARS-CoV-2 Spike protein and inhibit SARS-CoV-2 replication by preventing viral entry in Vero cells and HEK293T cells expressing ACE2. DC-SIGN has also been shown to act as a cell surface receptor for SARS-CoV-2 independent of ACE2. Since rfhSP-D is known to interact with SARS-CoV-2 Spike protein and DC-SIGN, this study was aimed at investigating the potential of rfhSP-D in modulating SARS-CoV-2 infection. Coincubation of rfhSP-D with Spike protein improved the Spike Protein: DC-SIGN interaction. Molecular dynamic studies revealed that rfhSP-D stabilised the interaction between DC-SIGN and Spike protein. Cell binding analysis with DC-SIGN expressing HEK 293T and THP- 1 cells and rfhSP-D treated SARS-CoV-2 Spike pseudotypes confirmed the increased binding. Furthermore, infection assays using the pseudotypes revealed their increased uptake by DC-SIGN expressing cells. The immunomodulatory effect of rfhSP-D on the DC-SIGN: Spike protein interaction on DC-SIGN expressing epithelial and macrophage-like cell lines was also assessed by measuring the mRNA expression of cytokines and chemokines. RT-qPCR analysis showed that rfhSP-D treatment downregulated the mRNA expression levels of pro-inflammatory cytokines and chemokines such as TNF-α, IFN-α, IL-1ß, IL- 6, IL-8, and RANTES (as well as NF-κB) in DC-SIGN expressing cells challenged by Spike protein. Furthermore, rfhSP-D treatment was found to downregulate the mRNA levels of MHC class II in DC expressing THP-1 when compared to the untreated controls. We conclude that rfhSP-D helps stabilise the interaction between SARS- CoV-2 Spike protein and DC-SIGN and increases viral uptake by macrophages via DC-SIGN, suggesting an additional role for rfhSP-D in SARS-CoV-2 infection.

Subchronic feeding, allergenicity, and genotoxicity safety evaluations of single strain bacterial protein.

Microbial proteins are potentially important alternatives to animal protein. A safety assessment was conducted on a Clostridium protein which can serve as a high-quality protein source in human food. A battery of toxicity studies was conducted comprising a 14-day dose-range finding dietary study in rats, 90-day dietary study in rats and in vitro genotoxicity studies. The allergenic potential was investigated by bioinformatics analysis. In the 90-day feeding study, rats were fed diets containing 0, 5.0, 7.5, and 10% Clostridium protein. The Clostridium protein-containing diets were well-tolerated and no adverse effects on the health or growth were observed. Significant reductions in neutrophil counts were observed in all female rats compared to controls, which were slightly outside of reference ranges. These effects were not deemed to be adverse due to the absence of comparable findings in male rats and high physiological variability of measured values within groups. A No-Observed-Adverse-Effect-Level (NOAEL) of at least 10% Clostridium protein, the highest dose tested and corresponding to 5,558 and 6,671 mg/kg body weight/day for male and female rats, respectively, was established. No evidence of genotoxicity was observed and the allergenic potential was low. These results support the use of Clostridium protein as a food ingredient.

Fluid intelligence and naturalistic task impairments after focal brain lesions.

Classical executive tasks, such as Wisconsin card-sorting and verbal fluency, are widely used as tests of frontal lobe control functions. Since the pioneering work of Shallice and Burgess (1991), it has been known that complex, naturalistic tasks can capture deficits that are missed in these classical tests. Matching this finding, deficits in several classical tasks are predicted by loss of fluid intelligence, linked to damage in a specific cortical "multiple-demand" (MD) network, while deficits in a more naturalistic task are not. To expand on these previous results, we examined the effect of focal brain lesions on three new tests-a modification of the previously-used Hotel task, a new test of task switching after extended delays, and a test of decision-making in imagined real-life scenarios. As potential predictors of impairment we measured volume of damage to a priori MD and default mode (DMN) networks, as well as cortical damage outside these networks. Deficits in the three new tasks were substantial, but were not explained by loss of fluid intelligence, or by volume of damage to either MD or DMN networks. Instead, deficits were associated with diverse lesions, and not strongly correlated with one another. The results confirm that naturalistic tasks capture cognitive deficits beyond those measured by fluid intelligence. We suggest, however, that these deficits may not arise from specific control operations required by complex behaviour. Instead, like everyday activities, complex tasks combine a rich variety of interacting cognitive components, bringing many opportunities for processing to be disturbed.

Causal Contributions of the Domain-General (Multiple Demand) and the Language-Selective Brain Networks to Perceptual and Semantic Challenges in Speech Comprehension.

Listening to spoken language engages domain-general multiple demand (MD; frontoparietal) regions of the human brain, in addition to domain-selective (frontotemporal) language regions, particularly when comprehension is challenging. However, there is limited evidence that the MD network makes a functional contribution to core aspects of understanding language. In a behavioural study of volunteers (n = 19) with chronic brain lesions, but without aphasia, we assessed the causal role of these networks in perceiving, comprehending, and adapting to spoken sentences made more challenging by acoustic-degradation or lexico-semantic ambiguity. We measured perception of and adaptation to acoustically degraded (noise-vocoded) sentences with a word report task before and after training. Participants with greater damage to MD but not language regions required more vocoder channels to achieve 50% word report, indicating impaired perception. Perception improved following training, reflecting adaptation to acoustic degradation, but adaptation was unrelated to lesion location or extent. Comprehension of spoken sentences with semantically ambiguous words was measured with a sentence coherence judgement task. Accuracy was high and unaffected by lesion location or extent. Adaptation to semantic ambiguity was measured in a subsequent word association task, which showed that availability of lower-frequency meanings of ambiguous words increased following their comprehension (word-meaning priming). Word-meaning priming was reduced for participants with greater damage to language but not MD regions. Language and MD networks make dissociable contributions to challenging speech comprehension: Using recent experience to update word meaning preferences depends on language-selective regions, whereas the domain-general MD network plays a causal role in reporting words from degraded speech.

Therapeutic Targeting of Exportin-1 in Childhood Cancer.

Overexpression of Exportin-1 (XPO1), a key regulator of nuclear-to-cytoplasmic transport, is associated with inferior patient outcomes across a range of adult malignancies. Targeting XPO1 with selinexor has demonstrated promising results in clinical trials, leading to FDA approval of its use for multiple relapsed/refractory cancers. However, XPO1 biology and selinexor sensitivity in childhood cancer is only recently being explored. In this review, we will focus on the differential biology of childhood and adult cancers as it relates to XPO1 and key cargo proteins. We will further explore the current state of pre-clinical and clinical development of XPO1 inhibitors in childhood cancers. Finally, we will outline potentially promising future therapeutic strategies for, as well as potential challenges to, integrating XPO1 inhibition to improve outcomes for children with cancer.