Miracle-dz/UniFAR-FTUs huggingface dataset:
Haptic communication for mobile robot operations

Teleoperations in hazardous environments are often hampered by the lack of available information regarding the state of the remote robotic device. Typically, ideal camera placements are not possible, and an operator is left with the problem of performing complex manoeuvres in the presence of severe blind‐spots. To address this dilemma, we have been investigating the use of a haptic interface, which not only allows an operator to communicate motion commands to a robot, but also allows the robot to communicate to the operator its motion when performing autonomous collision avoidance. This haptic interface provides total operator control, plus vital information that can be used to decide if and how a robot's autonomous operation should be overridden. This paper details our work in this area and presents the results we have obtained from operator/task performance experimentation with this new haptic communication approach.
Protein biomarkers on tissue as imaged via MALDI mass spectrometry: A systematic approach to study the limits of detection

MALDI mass spectrometry imaging (MSI) is emerging as a tool for protein and peptide imaging across tissue sections. Despite extensive study, there does not yet exist a baseline study evaluating the potential capabilities for this technique to detect diverse proteins in tissue sections. In this study, we developed a systematic approach for characterizing MALDI‐MSI workflows in terms of limits of detection, coefficients of variation, spatial resolution, and the identification of endogenous tissue proteins. Our goal was to quantify these figures of merit for a number of different proteins and peptides, in order to gain more insight in the feasibility of protein biomarker discovery efforts using this technique. Control proteins and peptides were deposited in serial dilutions on thinly sectioned mouse xenograft tissue. Using our experimental setup, coefficients of variation were <30% on tissue sections and spatial resolution was 200 μm (or greater). Limits of detection for proteins and peptides on tissue were in the micromolar to millimolar range. Protein identification was only possible for proteins present in high abundance in the tissue. These results provide a baseline for the application of MALDI‐MSI towards the discovery of new candidate biomarkers and a new benchmarking strategy that can be used for comparing diverse MALDI‐MSI workflows.
Automation in the sky

Purpose – Aims to summarise the programme of UV Europe, a conference on unmanned vehicles that took place in Paris in June 2005.Design/methodology/approach – Selects key conference presentations and summarises their contents, indicating the main themes.Findings – Finds very strong international activity in the field of unmanned aerial vehicles (UAVs). Most progress has been made in the military sector so far. Concern about air space safety is holding back the industry.Originality/value – Presents the topics relating to UAVs that concern the market today, and summarises the main areas of research and development.
Use dependence of peripheral nociceptive conduction in the absence of tetrodotoxin‐resistant sodium channel subtypes

This study examines conduction in peripheral nerves and its use dependence in tetrodotoxin‐resistant (TTXr) sodium channel (Nav1.8, Nav1.9) knockout and wildtype animals. We observed use‐dependent decreases of single fibre and compound action potential amplitude in peripheral mouse C‐fibres (wildtype). This matches the previously published hypothesis that increased Na/K‐pump activity is not the underlying mechanism for use‐dependent changes of neural conduction. Knocking out TTXr sodium channels influences use‐dependent changes of conductive properties (action potential amplitude, latency, conduction safety) in the order Nav1.8 KO > Nav1.9KO > wildtype. This is most likely explained by different subsets of presumably (relatively) Nav1.7‐rich conducting fibres in knockout animals as compared to wildtypes, in combination with reduced per‐pulse sodium influx.
A novel, multiplexed targeted mass spectrometry assay for quantification of complement factor H (CFH) variants and CFH‐related proteins 1–5 in human plasma

Age‐related macular degeneration (AMD) is a leading cause of visual loss among older adults. Two variants in the complement factor H (CFH) gene, Y402H and I62V, are strongly associated with risk of AMD. CFH is encoded in regulator of complement activation gene cluster in chromosome 1q32, which includes complement factor related (CFHR) proteins, CFHR1 to CFHR5, with high amino acid sequence homology to CFH. Our goal was to build a SRM assay to measure plasma concentrations of CFH variants Y402, H402, I62, and V62, and CFHR1‐5. The final assay consisted of 24 peptides and 72 interference‐free SRM transition ion pairs. Most peptides showed good linearity over 0.3–200 fmol/μL concentration range. Plasma concentrations of CFH variants and CFHR1‐5 were measured using the SRM assay in 344 adults. Plasma CFH concentrations (mean, SE in μg/mL) by inferred genotype were: YY402, II62 (170.1, 31.4), YY402, VV62 (188.8, 38.5), HH402, VV62 (144.0, 37.0), HY402, VV62 (164.2, 42.3), YY402, IV62 (194.8, 36.8), HY402, IV62 (181.3, 44.7). Mean (SE) plasma concentrations of CFHR1‐5 were 1.63 (0.04), 3.64 (1.20), 0.020 (0.001), 2.42 (0.18), and 5.49 (1.55) μg/mL, respectively. This SRM assay should facilitate the study of the role of systemic complement and risk of AMD.
Relative protein quantification and accessible biology in lung tumor proteomes from four LC‐MS/MS discovery platforms

Discovery proteomics experiments include many options for sample preparation and MS data acquisition, which are capable of creating datasets for quantifying thousands of proteins. To define a strategy that would produce a dataset with sufficient content while optimizing required resources, we compared (1) single‐sample LC‐MS/MS with data‐dependent acquisition to single‐sample LC‐MS/MS with data‐independent acquisition and (2) peptide fractionation with label‐free (LF) quantification to peptide fractionation with relative quantification of chemically labeled peptides (sixplex tandem mass tags (TMT)). These strategies were applied to the same set of four frozen lung squamous cell carcinomas and four adjacent tissues, and the overall outcomes of each experiment were assessed. We identified 6656 unique protein groups with LF, 5535 using TMT, 3409 proteins from single‐sample analysis with data‐independent acquisition, and 2219 proteins from single‐sample analysis with data‐dependent acquisition. Pathway analysis indicated the number of proteins per pathway was proportional to the total protein identifications from each method, suggesting limited biological bias between experiments. The results suggest the use of single‐sample experiments as a rapid tissue assessment tool and digestion quality control or as a technique to maximize output from limited samples and use of TMT or LF quantification as methods for larger amounts of tumor tissue with the selection being driven mainly by instrument time limitations. Data are available via ProteomeXchange with identifiers PXD004682, PXD004683, PXD004684, and PXD005733.
Identification of interacting proteins of the TaFVE protein involved in spike development in bread wheat

WD‐40 repeat‐containing protein MSI4 (FVE)/MSI4 plays important roles in determining flowering time in Arabidopsis. However, its function is unexplored in wheat. In the present study, coimmunoprecipitation and nanoscale liquid chromatography coupled to MS/MS were used to identify FVE in wheat (TaFVE)‐interacting or associated proteins. Altogether 89 differentially expressed proteins showed the same downregulated expression trends as TaFVE in wheat line 5660M. Among them, 62 proteins were further predicted to be involved in the interaction network of TaFVE and 11 proteins have been shown to be potential TaFVE interactors based on curated databases and experimentally determined in other species by the STRING. Both yeast two‐hybrid assay and bimolecular fluorescence complementation assay showed that histone deacetylase 6 and histone deacetylase 15 directly interacted with TaFVE. Multiple chromatin‐remodelling proteins and polycomb group proteins were also identified and predicted to interact with TaFVE. These results showed that TaFVE directly interacted with multiple proteins to form multiple complexes to regulate spike developmental process, e.g. histone deacetylate, chromatin‐remodelling and polycomb repressive complex 2 complexes. In addition, multiple flower development regulation factors (e.g. flowering locus K homology domain, flowering time control protein FPA, FY, flowering time control protein FCA, APETALA 1) involved in floral transition were also identified in the present study. Taken together, these results further elucidate the regulatory functions of TaFVE and help reveal the genetic mechanisms underlying wheat spike differentiation.
Nicotinic receptor activation contrasts pathophysiological bursting and neurodegeneration evoked by glutamate uptake block on rat hypoglossal motoneurons

Impaired uptake of glutamate builds up the extracellular level of this excitatory transmitter to trigger rhythmic neuronal bursting and delayed cell death in the brainstem motor nucleus hypoglossus. This process is the expression of the excitotoxicity that underlies motoneuron degeneration in diseases such as amyotrophic lateral sclerosis affecting bulbar motoneurons. In a model of motoneuron excitotoxicity produced by pharmacological block of glutamate uptake in vitro, rhythmic bursting is suppressed by activation of neuronal nicotinic receptors with their conventional agonist nicotine. Emergence of bursting is facilitated by nicotinic receptor antagonists. Following excitotoxicity, nicotinic receptor activity decreases mitochondrial energy dysfunction, endoplasmic reticulum stress and production of toxic radicals. Globally, these phenomena synergize to provide motoneuron protection. Nicotinic receptors may represent a novel target to contrast pathological overactivity of brainstem motoneurons and therefore to prevent their metabolic distress and death.
Inhibition linearizes firing rate responses in human motor units: implications for the role of persistent inward currents

Motor neurons are the output neurons of the central nervous system and are responsible for controlling muscle contraction. When initially activated during voluntary contraction, firing rates of motor neurons increase steeply but then level out at modest rates. Activation of an intrinsic source of excitatory current at recruitment onset may underlie the initial steep increase in firing rate in motor neurons. We attempted to disable this intrinsic excitatory current by artificially activating an inhibitory reflex. When motor neuron activity was recorded while the inhibitory reflex was engaged, firing rates no longer increased steeply, suggesting that the intrinsic excitatory current was probably responsible for the initial sharp rise in motor neuron firing rate.
Proximity Labeling of Interacting Proteins: Application of BioID as a Discovery Tool

Proteins perform biochemical functions by forming complexes, or protein–protein interactions (PPIs). Many different approaches such as phage display, yeast hybridization, etc. were developed to illustrate the PPIs, and disclose the composition and organization of protein complexes. However, none of these approaches are based on the real‐time and in vivo PPI analysis. Proximity‐dependent labeling (PDL) of interacting proteins has recently been proposed by taking advantage of several enzymes, which are capable of attaching the known reactive groups to the nearby proteins covalently. Among the PDL methods, BioID is the earliest and the most widely used one and has been upgraded from its prototype, making it an extremely convenient research tool. In this review, we describe the BioID technology development, its potential applications according to the nature of the target protein, and some recent efforts to circumvent the technical limitations. Moreover, some comparable PDL methods are introduced, including selective proteomic proximity labeling assay using tyramide, enzyme‐mediated activation of radical sources, Proximity Labeling with Ascorbate Peroxidase, in vivo proximal labeling, etc., and we propose that systematic comparison of the working radius of these methods may be helpful to develop a tool box, from which the right method can be selected for a given target protein for PPI research.
Dynamics of Ionic Shifts in Cortical Spreading Depression

Cortical spreading depression is a slowly propagating wave of near-complete depolarization of brain cells followed by temporary suppression of neuronal activity. Accumulating evidence indicates that cortical spreading depression underlies the migraine aura and that similar waves promote tissue damage in stroke, trauma, and hemorrhage. Cortical spreading depression is characterized by neuronal swelling, profound elevation of extracellular potassium and glutamate, multiphasic blood flow changes, and drop in tissue oxygen tension. The slow speed of the cortical spreading depression wave implies that it is mediated by diffusion of a chemical substance, yet the identity of this substance and the pathway it follows are unknown. Intercellular spread between gap junction-coupled neurons or glial cells and interstitial diffusion of K+ or glutamate have been proposed. Here we use extracellular direct current potential recordings, K+-sensitive microelectrodes, and 2-photon imaging with ultrasensitive Ca2+ and glutamate fluorescent probes to elucidate the spatiotemporal dynamics of ionic shifts associated with the propagation of cortical spreading depression in the visual cortex of adult living mice. Our data argue against intercellular spread of Ca2+ carrying the cortical spreading depression wavefront and are in favor of interstitial K+ diffusion, rather than glutamate diffusion, as the leading event in cortical spreading depression.
In vitro models of the cardiac microenvironment to study myocyte and non‐myocyte crosstalk: bioinspired approaches beyond the polystyrene dish

The heart is a complex pluricellular organ composed of cardiomyocytes and non‐myocytes including fibroblasts, endothelial cells and immune cells. Myocytes are responsible for electrical conduction and contractile force generation, while the other cell types are responsible for matrix deposition, vascularization, and injury response. Myocytes and non‐myocytes are known to communicate and exert mutual regulatory effects. In concert, they determine the structural, electrical and mechanical characteristics in the healthy and remodelled myocardium. Dynamic crosstalk between myocytes and non‐myocytes plays a crucial role in stress/injury‐induced hypertrophy and fibrosis development that can ultimately lead to heart failure and arrhythmias. Investigations of heterocellular communication in the myocardium are hampered by the intricate interspersion of the different cell types and the complexity of the tissue architecture. In vitro models have facilitated investigations of cardiac cells in a direct and controllable manner and have provided important functional and mechanistic insights. However, these cultures often lack regulatory input from the other cell types as well as additional topographical, electrical, mechanical and biochemical cues from the cardiac microenvironment that all contribute to modulating cell differentiation, maturation, alignment, function and survival. Advancements in the development of more complex pluricellular physiological platforms that incorporate diverse cues from the myocardial microenvironment are expected to lead to more physiologically relevant cardiac tissue‐like in vitro models for mechanistic biological research, disease modelling, therapeutic target identification, drug testing and regeneration.
Oscillatory dynamics and functional connectivity during gating of primary somatosensory responses

Sensory gating is important for preventing excessive environmental stimulation from overloading neural resources. Gating in the human somatosensory cortices is a critically understudied topic, particularly in the lower extremities. We utilize the unique capabilities of magnetoencephalographic neuroimaging to quantify the normative neural population responses and dynamic functional connectivity of somatosensory gating in the lower extremities of healthy human participants. We show that somatosensory processing is subserved by a robust gating effect in the oscillatory domain, as well as a dynamic effect on interhemispheric functional connectivity between primary sensory cortices. These results provide novel insight into the dynamic neural mechanisms that underlie the processing of somatosensory information in the human brain, and will be vital in better understanding the neural responses that are aberrant in gait‐related neurological disorders (e.g. cerebral palsy).
Primary Prevention of Child Mental Health Problems using Primary Health Care Professionals: Cost Comparisons

The importance of an economic dimension in the planning, delivery and evaluation of care and support for children and families is widely recognised.We report a cost analysis of a primary prevention programme using primary health care professionals trained to promote the psychosocial adaptation of children from birth. The programme was established in five European centres. We estimated the cost of the intervention in training and supervision for each country, and measured the impact of the intervention on service use and cost two years after the birth of the index child. Total costs incurred by families at comparison sites where no such training was provided were also calculated, and were compared with total costs at intervention sites. Cost differences between countries were also explored. Differences in total costs between the Intervention and Comparison treatment groups were small and did not reach statistical significance. However, total costs varied substantially between countries. Training primary health care professionals in the primary prevention of child mental health problems is found to be inexpensive, and does not appear to affect total costs in the years immediately following the intervention. Given the outcome findings from the study (see other chapters in this special issue), the cost evaluation provides encouragement for the wider establishment and examination of this preventative intervention.
The effects of streamlined operations on the perceived quality success criteria at Lockheed Martin Aeronautics - Fort Worth

The reduction in the US defense budget has resulted in reduced employment at Lockheed Martin Aeronautics – Fort Worth site by more 20,000 employees within the last decade. The company pursued a strategy to increase productivity and quality with the reduced work force while maintaining not only the public trust, but also the trust of its employees. Maintaining employee trust is directly linked to employees’ belief in the security of their employment. While the recently won Joint Strike Fighter contract will cause the need to expand, today’s competitive aerospace environment implies the need to maintain those strategies that resulted in that contract. Due to the requirement for high employee involvement, the company embraced a strategy to develop an environment that fostered a committed and highly motivated workforce. The University of North Texas, Center for Quality and Productivity assisted by completing a quality success factors survey to assess the employees’ perceptions of quality. As the questionnaire was analyzed, it was discovered that the cohesive work force was homogeneous in its strong identification with the quality goals of the company.
Maternal chronic hypoxia increases expression of genes regulating lung liquid movement and surfactant maturation in male fetuses in late gestation

Chronic fetal hypoxaemia is a common pregnancy complication associated with intrauterine growth restriction that may influence respiratory outcome at birth. We investigated the effect of maternal chronic hypoxia for a month in late gestation on signalling pathways regulating fetal lung maturation and the transition to air‐breathing at birth using isobaric hypoxic chambers without alterations to maternal food intake. Maternal chronic hypoxia in late gestation increases fetal lung expression of genes regulating hypoxia signalling, lung liquid reabsorption and surfactant maturation, which may be an adaptive response in preparation for the successful transition to air‐breathing at birth. In contrast to other models of chronic fetal hypoxaemia, late gestation onset fetal hypoxaemia promotes molecular regulation of fetal lung maturation. This suggests a differential effect of timing and duration of fetal chronic hypoxaemia on fetal lung maturation, which supports the heterogeneity observed in respiratory outcomes in newborns following exposure to chronic hypoxaemia in utero.
KCTD12 Auxiliary Proteins Modulate Kinetics of GABAB Receptor‐Mediated Inhibition in Cholecystokinin‐Containing Interneurons

Abstract Cholecystokinin‐expressing interneurons (CCK‐INs) mediate behavior state‐dependent inhibition in cortical circuits and themselves receive strong GABAergic input. However, it remains unclear to what extent GABAB receptors (GABABRs) contribute to their inhibitory control. Using immunoelectron microscopy, we found that CCK‐INs in the rat hippocampus possessed high levels of dendritic GABABRs and KCTD12 auxiliary proteins, whereas postsynaptic effector Kir3 channels were present at lower levels. Consistently, whole‐cell recordings revealed slow GABABR‐mediated inhibitory postsynaptic currents (IPSCs) in most CCK‐INs. In spite of the higher surface density of GABABRs in CCK‐INs than in CA1 principal cells, the amplitudes of IPSCs were comparable, suggesting that the expression of Kir3 channels is the limiting factor for the GABABR currents in these INs. Morphological analysis showed that CCK‐INs were diverse, comprising perisomatic‐targeting basket cells (BCs), as well as dendrite‐targeting (DT) interneurons, including a previously undescribed DT type. GABABR‐mediated IPSCs in CCK‐INs were large in BCs, but small in DT subtypes. In response to prolonged activation, GABABR‐mediated currents displayed strong desensitization, which was absent in KCTD12‐deficient mice. This study highlights that GABABRs differentially control CCK‐IN subtypes, and the kinetics and desensitization of GABABR‐mediated currents are modulated by KCTD12 proteins.
Geniculohypothalamic GABAergic projections gate suprachiasmatic nucleus responses to retinal input

Visual input to the suprachiasmatic nucleus circadian clock is critical for animals to adapt their physiology and behaviour in line with the solar day. In addition to direct retinal projections, the clock receives input from the visual thalamus, although the role of this geniculohypothalamic pathway in circadian photoreception is poorly understood. In the present study, we develop a novel brain slice preparation that preserves the geniculohypothalamic pathway to show that GABAergic thalamic neurons inhibit retinally‐driven activity in the central clock in a circadian time‐dependent manner. We also show that in vivo manipulation of thalamic signalling adjusts specific features of the hypothalamic light response, indicating that the geniculohypothalamic pathway is primarily activated by crossed retinal inputs. Our data provide a mechanism by which geniculohypothalamic signals can adjust the magnitude of circadian and more acute hypothalamic light responses according to time‐of‐day and establish an important new model for future investigations of the circadian visual system.