Convolutional spiking neural networks for intent detection based on anticipatory brain potentials using electroencephalogram.

Spiking neural networks (SNNs) are receiving increased attention because they mimic synaptic connections in biological systems and produce spike trains, which can be approximated by binary values for computational efficiency. Recently, the addition of convolutional layers to combine the feature extraction power of convolutional networks with the computational efficiency of SNNs has been introduced. This paper studies the feasibility of using a convolutional spiking neural network (CSNN) to detect anticipatory slow cortical potentials (SCPs) related to braking intention in human participants using an electroencephalogram (EEG). Data was collected during an experiment wherein participants operated a remote-controlled vehicle on a testbed designed to simulate an urban environment. Participants were alerted to an incoming braking event via an audio countdown to elicit anticipatory potentials that were measured using an EEG. The CSNN's performance was compared to a standard CNN, EEGNet and three graph neural networks via 10-fold cross-validation. The CSNN outperformed all the other neural networks, and had a predictive accuracy of 99.06% with a true positive rate of 98.50%, a true negative rate of 99.20% and an F1-score of 0.98. Performance of the CSNN was comparable to the CNN in an ablation study using a subset of EEG channels that localized SCPs. Classification performance of the CSNN degraded only slightly when the floating-point EEG data were converted into spike trains via delta modulation to mimic synaptic connections.

The nuclear import receptor Kapß2 modifies neurotoxicity mediated by poly(GR) in C9orf72-linked ALS/FTD.

Expanded intronic G4C2 repeats in the C9ORF72 gene cause amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). These intronic repeats are translated through a non-AUG-dependent mechanism into five different dipeptide repeat proteins (DPRs), including poly-glycine-arginine (GR), which is aggregation-prone and neurotoxic. Here, we report that Kapß2 and GR interact, co-aggregating, in cultured neurons in-vitro and CNS tissue in-vivo. Importantly, this interaction significantly decreased the risk of death of cultured GR-expressing neurons. Downregulation of Kapß2 is detrimental to their survival, whereas increased Kapß2 levels mitigated GR-mediated neurotoxicity. As expected, GR-expressing neurons displayed TDP-43 nuclear loss. Raising Kapß2 levels did not restore TDP-43 into the nucleus, nor did alter the dynamic properties of GR aggregates. Overall, our findings support the design of therapeutic strategies aimed at up-regulating Kapß2 expression levels as a potential new avenue for contrasting neurodegeneration in C9orf72-ALS/FTD.

Land suitability analysis for turmeric crop for humid tropical Kerala, India, under current and future climate scenarios using advanced geospatial techniques.

BACKGROUND: Turmeric cultivation primarily thrives in India, followed by Bangladesh, Cambodia, Thailand, China, Malaysia, Indonesia and the Philippines. India leads globally in both area and production of turmeric. Despite this, there is a recognized gap in research regarding the impact of climate change on site suitability of turmeric. The primary objective of the present study was to evaluate both the present and future suitability of turmeric cultivation within the humid tropical region of Kerala, India, by employing advanced geospatial techniques. The research utilized meteorological data from the Indian Meteorological Department for the period of 1986-2020 as historical data and projected future data from the Coupled Model Intercomparison Project Phase 6 (CMIP6). Four climatic scenarios of shared socioeconomic pathway (SSP) from the Intergovernmental Panel on Climate Change AR6 model of MIROC6 for the year 2050 (SSP 1-2.6, SSP 2-4.5, SSP 3-7.0 and SSP 5-8.5) were used. RESULTS: The results showed that suitable area for turmeric cultivation is declining in future scenario and this decline can be primarily attributed to fluctuations in temperature and an anticipated increase in rainfall in the year 2050. Notable changes in the spatial distribution of suitable areas over time were observed through the application of geographic information system (GIS) techniques. Importantly, as per the suitability criteria provided by ICAR-National Bureau of Soil Survey and Land Use Planning (ICAR-NBSS & LUP), all the districts in Kerala exhibited moderately suitable conditions for turmeric cultivation. With the GIS tools, the study identified highly suitable, moderately suitable, marginally suitable and not suitable areas of turmeric cultivation in Kerala. Presently 28% of area falls under highly suitable, 41% of area falls under moderately suitable and 11% falls under not suitable for turmeric cultivation. However, considering the projected scenarios for 2050 under the SSP framework, there will be a significant decrease in highly suitable area by 19% under SSP 5-8.5. This reduction in area will have an impact on the productivity of the crop as a result of changes in temperature and rainfall patterns. CONCLUSION: The outcome of the present research suggests that the state of Kerala needs to implement suitable climate change adaptation and management strategies for sustaining the turmeric cultivation. Additionally, the present study includes a discussion on potential management strategies to address the challenges posed by changing climatic conditions for optimizing turmeric production in the region. © 2024 Society of Chemical Industry.

Hepatic ChREBP orchestrates intrahepatic carbohydrate metabolism to limit hepatic glucose 6-phosphate and glycogen accumulation in a mouse model for acute Glycogen Storage Disease type Ib.

OBJECTIVE: Carbohydrate Response Element Binding Protein (ChREBP) is a glucose 6-phosphate (G6P)-sensitive transcription factor that acts as a metabolic switch to maintain intracellular glucose and phosphate homeostasis. Hepatic ChREBP is well-known for its regulatory role in glycolysis, the pentose phosphate pathway, and de novo lipogenesis. The physiological role of ChREBP in hepatic glycogen metabolism and blood glucose regulation has not been assessed in detail, and ChREBP's contribution to carbohydrate flux adaptations in hepatic Glycogen Storage Disease type 1 (GSD I) requires further investigation. METHODS: The current study aimed to investigate the role of ChREBP as a regulator of glycogen metabolism in response to hepatic G6P accumulation, using a model for acute hepatic GSD type Ib. The immediate biochemical and regulatory responses to hepatic G6P accumulation were evaluated upon G6P transporter inhibition by the chlorogenic acid S4048 in mice that were either treated with a short hairpin RNA (shRNA) directed against ChREBP (shChREBP) or a scrambled shRNA (shSCR). Complementary stable isotope experiments were performed to quantify hepatic carbohydrate fluxes in vivo. RESULTS: ShChREBP treatment normalized the S4048-mediated induction of hepatic ChREBP target genes to levels observed in vehicle- and shSCR-treated controls. In parallel, hepatic shChREBP treatment in S4048-infused mice resulted in a more pronounced accumulation of hepatic glycogen and further reduction of blood glucose levels compared to shSCR treatment. Hepatic ChREBP knockdown modestly increased glucokinase (GCK) flux in S4048-treated mice while it enhanced UDP-glucose turnover as well as glycogen synthase and phosphorylase fluxes. Hepatic GCK mRNA and protein levels were induced by shChREBP treatment in both vehicle- and S4048-treated mice, while glycogen synthase 2 (GYS2) and glycogen phosphorylase (PYGL) mRNA and protein levels were reduced. Finally, knockdown of hepatic ChREBP expression reduced starch domain binding protein 1 (STBD1) mRNA and protein levels while it inhibited acid alpha-glucosidase (GAA) activity, suggesting reduced capacity for lysosomal glycogen breakdown. CONCLUSIONS: Our data show that ChREBP activation controls hepatic glycogen and blood glucose levels in acute hepatic GSD Ib through concomitant regulation of glucose phosphorylation, glycogenesis, and glycogenolysis. ChREBP-mediated control of GCK enzyme levels aligns with corresponding adaptations in GCK flux. In contrast, ChREBP activation in response to acute hepatic GSD Ib exerts opposite effects on GYS2/PYGL enzyme levels and their corresponding fluxes, indicating that GYS2/PYGL expression levels are not limiting to their respective fluxes under these conditions.

C9orf72 poly(PR) mediated neurodegeneration is associated with nucleolar stress.

The ALS/FTD-linked intronic hexanucleotide repeat expansion in the C9orf72 gene is aberrantly translated in the sense and antisense directions into dipeptide repeat proteins, among which poly proline-arginine (PR) displays the most aggressive neurotoxicity in-vitro and in-vivo. PR partitions to the nucleus when heterologously expressed in neurons and other cell types. We show that by lessening the nuclear accumulation of PR, we can drastically reduce its neurotoxicity. PR strongly accumulates in the nucleolus, a nuclear structure critical in regulating the cell stress response. We determined that, in neurons, PR caused nucleolar stress and increased levels of the transcription factor p53. Downregulating p53 levels also prevented PR-mediated neurotoxicity both in in-vitro and in-vivo models. We investigated if PR could induce the senescence phenotype in neurons. However, we did not observe any indications of such an effect. Instead, we found evidence for the induction of programmed cell death via caspase-3 activation.

Twist-bend nematic drops as colloidal particles: Electric instabilities.

The mesogen 1,''7''-bis(4-cyanobiphenyl-4'-yl)heptane (CB7CB), doped with a small quantity of an amphiphilic compound, is examined in its biphasic state in which twist-bend nematic (N_{TB}) drops are dispersed in the isotropic fluid. Various flexoelectric and electrokinetic responses of small drops in their escaped-radial-like (ER) geometry, and also of larger ones with parabolic focal conic defects, are discussed. A pair of confocal parabolas with their axes along the applied low-frequency electric field undergo periodic dimensional changes so as to contribute flexoelectrically to free-energy reduction. In an ER droplet, the same result is achieved by periodic relocations of the hedgehog core. Sine-wave fields of low frequency and high voltage excite patterned states near zero-voltage crossings and homeotropic alignment at peak voltages. ER drops also exhibit electrohydrodynamic effects; in relatively weak fields, they undergo translatory motion with a velocity that is a quadratic in the field strength; the drift, which occurs over a very wide frequency range, extending from dc to MHz region, is enabled by radial symmetry breaking that their off-centered geometry entails; and the drift direction reverses across a critical frequency. In high fields, vortical flows occurring within an ER N_{TB} drop become discernible. The hydrodynamic effects are discussed based on the Taylor-Melcher leaky dielectric model.

Twist-bend nematic drops as colloidal particles: Structural features.

The mesogen CB7CB [1″,7″-bis(4-cyanobiphenyl-4'-yl)heptane], mixed with a small quantity of a long chain amphiphile, is examined for the structural features of twist-bend nematic (N_{TB}) drops acting as colloidal inclusions in the isotropic and nematic environments. In the isotropic phase, the drops nucleating in the radial (splay) geometry develop toward escaped radial, off-centered structures, involving both splay and bend distortions. With further growth, they transform into low-birefringence (near-homeotropic) objects, within which remarkably well-organized networks of parabolic focal conic defects evolve in time. In electrically reoriented near-homeotropic N_{TB} drops, the pseudolayers develop an undulatory boundary possibly attributable to saddle-splay elasticity. In the matrix of the planar nematic phase, N_{TB} droplets appearing as radial hedgehogs attain stability in the dipolar geometry, through their association with hyperbolic hedgehogs. With growth, on transformation of the hyperbolic defect into its topologically equivalent Saturn ring around the N_{TB} drop, the geometry turns quadrupolar. Significantly, dipoles are stable in smaller drops, while quadrupoles are stable in larger ones. The dipole-quadrupole transformation is reversible, but is hysteretic with respect to drop size. Importantly, this transformation is often mediated by nucleation of two loop disclinations, one appearing at a marginally lower temperature than the other. The existence of a metastable state with partial formation of a Saturn ring and persistence of the hyperbolic hedgehog raises a question relating to the conservation of topological charge. In twisted nematics, this state features in the formation of a giant unknot that binds all N_{TB} drops together.

C9orf72 poly(PR) mediated neurodegeneration is associated with nucleolar stress.

The ALS/FTD-linked intronic hexanucleotide repeat expansion in the C9orf72 gene is translated into dipeptide repeat proteins, among which poly-proline-arginine (PR) displays the most aggressive neurotoxicity in-vitro and in-vivo . PR partitions to the nucleus when expressed in neurons and other cell types. Using drosophila and primary rat cortical neurons as model systems, we show that by lessening the nuclear accumulation of PR, we can drastically reduce its neurotoxicity. PR accumulates in the nucleolus, a site of ribosome biogenesis that regulates the cell stress response. We examined the effect of nucleolar PR accumulation and its impact on nucleolar function and determined that PR caused nucleolar stress and increased levels of the transcription factor p53. Downregulating p53 levels, either genetically or by increasing its degradation, also prevented PR-mediated neurotoxic phenotypes both in in-vitro and in-vivo models. We also investigated whether PR could cause the senescence phenotype in neurons but observed none. Instead, we found induction of apoptosis via caspase-3 activation. In summary, we uncovered the central role of nucleolar dysfunction upon PR expression in the context of C9-ALS/FTD.

Advancing NMR-based metabolomics using complete reduction to amplitude frequency table: Cultivar differentiation of black ripe table olives as a case study.

In NMR-based untargeted analysis, Fourier transformation is applied to the time-domain data to extract observables such as frequency and intensity. Despite its wide application, this approach has several limitations that can prevent NMR from reaching its highest potential. Here, we utilized Bayesian analysis through CRAFT as an alternative method, using California-style table olives as a model system. Our hypothesis was that the time-domain analysis through CRAFT will be as successful as the traditional approach. The results showed that CRAFT generated efficient unsupervised and supervised models in a robust, and rapid/automated manner. The duration of CRAFT analysis can be further reduced by using the first 14 k complex data points of the initial part of the FID, without affecting the performance of the untargeted analysis. For unsupervised analysis, CRAFT was generally more efficient, while for supervised analysis both approaches were effective. CRAFT can be also used for identifying marker compounds driving classifications.

Structure, stability, and electro-optic features of nematic drops in 1

Binary mixtures of the mesogen [1″,7″-bis(4-cyanobiphenyl-4'-yl)heptane] and a long chain amphiphile (e.g., 2-octadecoxypropanol) are examined for the structure, stability, and electro-optical behavior of nematic drops dispersed in the isotropic phase, in planar cells. Subjected to tangential boundary conditions, the drops adopt, besides the escaped concentric and untwisted bipolar geometries, the less common bound vortex geometry with a pair of half-strength disclination lines. The concentric drop, as it grows, switches its axis from an in-layer to the layer-normal direction corresponding to the stablest of all geometries. Bipolar drops in equilibrium have their axes parallel to the easy axis of the cell. Obliquely oriented bipolar drops rotate to attain the equilibrium disposition by the shorter of the clockwise and anticlockwise routes, the extent of rotation decreasing exponentially with time. The bipolar structure is marginally less stable than the concentric, and transforms to the latter geometry occasionally. In bound vortex drops, the separation between the lines varies as the drop diameter, the bipolar and concentric geometries appearing as the limiting cases. The complex course of Fréedericksz transition in all the different types of drops terminates in the division of the original large drop into many smaller drops, each with a surface charge 2, in conformity with the Poincaré-Hopf theorem. In low frequency electric fields, concentric drops exhibit flexoelectro-optic rotation in evidence of their escaped character.

Multimodal Ensemble Deep Learning to Predict Disruptive Behavior Disorders in Children.

Oppositional defiant disorder and conduct disorder, collectively referred to as disruptive behavior disorders (DBDs), are prevalent psychiatric disorders in children. Early diagnosis of DBDs is crucial because they can increase the risks of other mental health and substance use disorders without appropriate psychosocial interventions and treatment. However, diagnosing DBDs is challenging as they are often comorbid with other disorders, such as attention-deficit/hyperactivity disorder, anxiety, and depression. In this study, a multimodal ensemble three-dimensional convolutional neural network (3D CNN) deep learning model was used to classify children with DBDs and typically developing children. The study participants included 419 females and 681 males, aged 108-131 months who were enrolled in the Adolescent Brain Cognitive Development Study. Children were grouped based on the presence of DBDs (n = 550) and typically developing (n = 550); assessments were based on the scores from the Child Behavior Checklist and on the Schedule for Affective Disorders and Schizophrenia for School-age Children-Present and Lifetime version for DSM-5. The diffusion, structural, and resting-state functional magnetic resonance imaging (rs-fMRI) data were used as input data to the 3D CNN. The model achieved 72% accuracy in classifying children with DBDs with 70% sensitivity, 72% specificity, and an F1-score of 70. In addition, the discriminative power of the classifier was investigated by identifying the cortical and subcortical regions primarily involved in the prediction of DBDs using a gradient-weighted class activation mapping method. The classification results were compared with those obtained using the three neuroimaging modalities individually, and a connectome-based graph CNN and a multi-scale recurrent neural network using only the rs-fMRI data.

The importance of vaccine stockpiling to respond to epidemics and remediate global supply shortages affecting immunization: strategic challenges and risks identified by manufacturers.

While stockpiling vaccines adds another layer of complexity to vaccine manufacturing, it constitutes a crucial component of comprehensive disease preparedness and control strategies in public health management. Stockpiling provides the ability to immediately respond to epidemics, disease outbreaks, vaccine shortages or stock-outs at local, regional or global levels. Some stockpiles are static, not shipped until an emergency occurs; other stockpiles are rotating with vaccines used in on-going routine immunization programmes. Programmatic use indicates which vaccines to stockpile, the nature of the stockpile and the amount of vaccine to be held at any time. For immediate shipment, fully released product must be stockpiled with the challenge of monitoring remaining shelf-life requirements and the potential risk of expiry. Existing stockpiles are managed and financed globally under the purview of international organizations in the global immunization community, except for buffer stocks held by manufacturers for short periods. The added challenges to manufacturers of stockpiling vaccines, including storage, human resources and other related costs including vaccine destruction when no longer useable, needs to be recognized. This is all the more so with the likelihood of vaccine stockpiling becoming more prominent with changing disease patterns due to climate change and population movements, as well as the significant investment in the research and development of new epidemic prevention vaccines. While vaccine stockpiles managed and financed globally provide rapid response to country requests, more attention is needed in the future to ways that vaccine stockpiling can be brought under the direct purview of individual countries or regional groupings.

Symptoms of piper yellow mottle virus in black pepper as influenced by temperature and relative humidity.

Masking of symptoms in winter and their re-appearance in black pepper (Piper nigrum L.) infected with piper yellow mottle virus (PYMoV) in summer is common, especially on new flushes that appear after pre-monsoon showers. Plants of nineteen cultivars of black pepper infected with PYMoV but without any visible symptoms were grown in a polyhouse under natural conditions and in a greenhouse under controlled conditions from January 2019 to January 2020. The number of plants expressing symptoms in the polyhouse increased gradually from 1% during the 3rd standard meteorological week (SMW) (16 January) to 41% during the 21st SMW (22 May), when the afternoon temperature was 30-40 °C and relative humidity (RH) was 75-93%, but began declining thereafter until the 53rd SMW (1 January), when the afternoon temperature was 30-36 °C and RH was 65-86%. The proportion of plants expressing symptoms varied with the cultivar. However, in the greenhouse, in which temperature and RH were maintained at approximately 26 °C and 80%, respectively, not more than 2% of the plants expressed symptoms. The number of symptomatic plants was positively correlated to maximum temperature (T Max) and maximum relative humidity (RH Max) in the afternoon. Based on this observation, a model for predicting the percentage of symptomatic plants was developed using stepwise regression analysis. Plants at the two sites did not differ significantly in the concentration of virus (virus titre) but differed significantly in the content of total carbohydrates, lipid peroxidase, and phenols. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13337-021-00686-3.

Electric response of topological dipoles in nematic colloids with twist-bend nematic droplets as the dispersed phase.

Colloidal systems comprising solid or fluid particles dispersed in nematic monodomains are known to be a convenient means to study topological defects. Recent experiments have shown that twist-bend nematic (N_{TB}) droplets in a nematic matrix act as colloidal particles that lead to the formation of elastic dipoles, quadrupoles, and their ordered clusters. In this study, we examine the effect of low-frequency (f∼mHz) electric fields on such defect configurations. We find that (i) the hyperbolic hedgehogs of elastic dipoles shift toward the negative electrode in static fields and perform oscillatory motion in AC fields, indicating the presence of nonvanishing flexoelectric polarization in the field-free state; (ii) the elastic dipoles, propelled by forces of backflow due to coupled flexoelectric and dielectric distortions, drift uniformly along their axes with the N_{TB} drops in lead; (iii) the translational velocity v_{d} increases linearly with both f and the diameter of N_{TB} drops; and (iv) with increasing applied voltage U, v_{d}(U) exhibits a monotonic, slightly nonlinear variation at f≤200mHz, tending toward linearity at higher frequencies.

Topological defects due to twist-bend nematic drops mimicking colloidal particles in a nematic medium.

Colloids formed of solid/fluid particle dispersions in oriented nematic liquid crystals are known to be an ideal means of realizing fundamentally significant topological defect geometries. We find, experimentally, that twist-bend nematic (NTB) droplets formed in the N-NTB biphasic regime, either of pure compounds or mesogenic mixtures, completely mimic colloidal particles in their ability to generate a rich variety of defects. In the biphasic regime, the topological features of both liquid crystal colloids and chiral nematic droplets are revealed by (i) topological dipoles, quadrupoles and their patterned clusters formed in planar nematic liquid crystals orientationally perturbed by coexisting NTB drops, (ii) the transformation of hyperbolic hedgehogs into knotted Saturn rings encircling the NTB drops dispersed in a 90°-twisted nematic matrix and (iii) the Frank-Pryce defect texture evident in smaller (relative to sample thickness) NTB drops. In larger drops with fingerlike outgrowths, additional line defects appear; most of these are deemed to be pairs of disclinations to which are attached pairs of screw dislocations intervening in the growth process of the NTB droplets.

Saddle-splay-induced periodic edge undulations in smectic-A disks immersed in a nematic medium.

We report experimental studies on the phase behavior of binary mixtures of 1″,7″-bis(4-cyanobiphenyl-4'-yl)heptane (CB7CB) and 4,4-diheptyloxyazoxybenzene, which exhibit, apart from the nematic (N) and twist-bend nematic (N_{TB}) phases, the induced smectic-A (Sm-A) phase for weight fraction of CB7CB between 0.05 and 0.70. In planar nematic layers, the N_{TB} phase separates as droplets of tactoidlike planform; the chirality of droplets manifests in the optical dissimilarity between their opposite angular ends. Our main result is that, in the appropriate two phase region, Sm-A nuclei with positive dielectric anisotropy change over to disks immersed in the nematic above some electric field, their edges decorated by periodic bright spots, a result which was earlier reported in another binary system exhibiting the induced Sm-A phase [R. Pratibha and N. V. Madhusudana, Physica A 224, 9 (1996)10.1016/0378-4371(95)00311-8]. We develop a simple theory for the threshold of this distortion, which is a periodic undulation of the edge of the disk, demonstrating that it arises from saddle-splay elasticity of Sm-A, the low Sm-A-N interfacial tension unable to suppress the distortion. The observed increases in the number of bright spots with field, and with the radius of the disk at a given field, in both the experimental systems are also accounted for by the model. The distortion, which results in the most direct visualization of saddle splay in Sm-A, is also exhibited by disks nucleating on surfaces treated for homeotropic anchoring.

Variation in timing of decisions to withdraw life-sustaining treatment in adult ICU patients from three centres in different geographies: Do clinical factors explain the difference?

Background: Decisions to withdraw life-sustaining treatment (WLST) are common in intensive care units (ICUs). Clinical and non-clinical factors are important, although the extent to which each plays a part is uncertain. Objectives: To determine whether the timing of decisions to WLST varies between ICUs in a single centre in three countries and whether differences in timing are explained by differences in clinical decision-making. Methods: The study involved a convenience sample of three adult ICUs - one in each of the UK, USA and South Africa (SA). Data were prospectively collected on patients whose life-sustaining treatment was withdrawn over three months. The timing of decisions was collected, as were patients' premorbid functional status and illness severity 24 hours prior to decision to WLST. Multivariate analysis was used to identify factors associated with decisions to WLST. Clinicians participated in interviews involving hypothetical case studies devoid of non-clinical factors. Results: Deaths following WLST accounted for 23% of all deaths during the study period at the USA site v. 37% (UK site) and 70% (SA site) (p<0.0010 across the three sites). Length of stay (LOS) prior to WLST decision varied between sites. Controlling for performance status, age, and illness severity, study site predicted LOS prior to decision (p<0.0010). In the hypothetical cases, LOS prior to WLST was higher for USA clinicians (p<0.017). Conclusion: There is variation in the proportion of ICU patients in whom WLST occurs and the timing of these decisions between sites; differences in clinical decision-making may explain the variation observed, although clinical and non-clinical factors are inextricably linked. Contributions of the study: This study has identified variation in the timing of decisions to withdraw life-sustaining treatment in adult ICUs in three centres in three different healthcare systems. Although differences in clinical decision-making likely explain some of the variation, non-clinical factors (relating to the society in which the clinicians live and work) may also play a part.