Automated CPX support system preliminary design phase

The development of the Distributed Command and Control System (DCCS) is discussed. The development of an automated C2 system stimulated the development of an automated command post exercise (CPX) support system to provide a more realistic stimulus to DCCS than could be achieved with the existing manual system. An automated CPX system to support corps-level exercise was designed. The effort comprised four tasks: (1) collecting and documenting user requirements; (2) developing a preliminary system design; (3) defining a program plan; and (4) evaluating the suitability of the TRASANA FOURCE computer model

Magnetoencephalography—theory, instrumentation, and applications to noninvasive studies of the working human brain

Magnetoencephalography (MEG) is a noninvasive technique for investigating neuronal activity in the living human brain. The time resolution of the method is better than 1 ms and the spatial discrimination is, under favorable circumstances, 2-3 mm for sources in the cerebral cortex. In MEG studies, the weak 10 fT-1 pT magnetic fields produced by electric currents flowing in neurons are measured with multichannel SQUID (superconducting quantum interference device) gradiometers. The sites in the cerebral cortex that are activated by a stimulus can be found from the detected magnetic-field distribution, provided that appropriate assumptions about the source render the solution of the inverse problem unique. Many interesting properties of the working human brain can be studied, including spontaneous activity and signal processing following external stimuli. For clinical purposes, determination of the locations of epileptic foci is of interest. The authors begin with a general introduction and a short discussion of the neural basis of MEG. The mathematical theory of the method is then explained in detail, followed by a thorough description of MEG instrumentation, data analysis, and practical construction of multi-SQUID devices. Finally, several MEG experiments performed in the authors' laboratory are described, covering studies of evoked responses and of spontaneous activity in both healthy and diseased brains. Many MEG studies by other groups are discussed briefly as well.Peer reviewe

Laughter as a paradigm of socio-emotional signal processing in dementia

Laughter is a fundamental communicative signal in our relations with other people and is used to convey a diverse repertoire of social and emotional information. It is therefore potentially a useful probe of impaired socio-emotional signal processing in neurodegenerative diseases. Here we investigated the cognitive and affective processing of laughter in forty-seven patients representing all major syndromes of frontotemporal dementia, a disease spectrum characterised by severe socio-emotional dysfunction (twenty-two with behavioural variant frontotemporal dementia, twelve with semantic variant primary progressive aphasia, thirteen with nonfluent-agrammatic variant primary progressive aphasia), in relation to fifteen patients with typical amnestic Alzheimer's disease and twenty healthy age-matched individuals. We assessed cognitive labelling (identification) and valence rating (affective evaluation) of samples of spontaneous (mirthful and hostile) and volitional (posed) laughter versus two auditory control conditions (a synthetic laughter-like stimulus and spoken numbers). Neuroanatomical associations of laughter processing were assessed using voxel-based morphometry of patients' brain MR images. While all dementia syndromes were associated with impaired identification of laughter subtypes relative to healthy controls, this was significantly more severe overall in frontotemporal dementia than in Alzheimer's disease and particularly in the behavioural and semantic variants, which also showed abnormal affective evaluation of laughter. Over the patient cohort, laughter identification accuracy was correlated with measures of daily-life socio-emotional functioning. Certain striking syndromic signatures emerged, including enhanced liking for hostile laughter in behavioural variant frontotemporal dementia, impaired processing of synthetic laughter in the nonfluent-agrammatic variant (consistent with a generic complex auditory perceptual deficit) and enhanced liking for numbers ('numerophilia') in the semantic variant. Across the patient cohort, overall laughter identification accuracy correlated with regional grey matter in a core network encompassing inferior frontal and cingulo-insular cortices; and more specific correlates of laughter identification accuracy were delineated in cortical regions mediating affective disambiguation (identification of hostile and posed laughter in orbitofrontal cortex) and authenticity (social intent) decoding (identification of mirthful and posed laughter in anteromedial prefrontal cortex) (all p < .05 after correction for multiple voxel-wise comparisons over the whole brain). These findings reveal a rich diversity of cognitive and affective laughter phenotypes in canonical dementia syndromes and suggest that laughter is an informative probe of neural mechanisms underpinning socio-emotional dysfunction in neurodegenerative disease

Theory of Brain Function, Quantum Mechanics and Superstrings

Recent developments/efforts to understand aspects of the brain function at the {\em sub-neural} level are discussed. MicroTubules (MTs) participate in a wide variety of dynamical processes in the cell, especially in bioinformation processes such as learning and memory, by possessing a well-known binary error-correcting code with 64 words. In fact, MTs and DNA/RNA are unique cell structures that possess a code system. It seems that the MTs' code system is strongly related to a kind of ``Mental Code" in the following sense. The MTs' periodic paracrystalline structure make them able to support a superposition of coherent quantum states, as it has been recently conjectured by Hameroff and Penrose, representing an external or mental order, for sufficient time needed for efficient quantum computing. Then the quantum superposition collapses spontaneously/dynamically through a new, string-derived mechanism for collapse proposed recently by Ellis, Mavromatos, and myself. At the moment of collapse, organized quantum exocytosis occurs, and this is how a ``{\em mental order}" may be translated into a ``{\em physiological action}". Our equation for quantum collapse, tailored to the MT system, predicts that it takes 10,000 neurons ${\cal O}(1\,{\rm sec})$ to dynamically collapse (process and imprint information). Different observations/experiments and various schools of thought are in agreement with the above numbers concerning ``{\em conscious events}". If indeed MTs, may be considered as the {\em microsites of consciousness}, then several unexplained properties of consciousness/awareness, get easily explained, including ``{\em backward masking}", ``{\em referal backwards in time}". The {\em non-locality} in the cerebral cortex of neurons related to particular missions, and the related {\em unitary sense of self} as well asComment: 72 pages, 1 figure (uuencoded

Boron and other trace elements in human tissues and fluids.

The multielemental technique of inductively coupled plasma source mass spectrometry (ICP-MS) was used to measure the elemental concentration of boron and 28 other elements within blood and its fractions, saliva, urine, hair, nails, synovial fluid, brain and bone samples. A number of biological standard reference materials were also analysed: IAEA A13 animal blood and H4 animal muscle, NIST 1577A bovine liver and SRM909 human serum, and SINR 0920 Chinese hair. Boron levels were found to be in the order of 30-40ng/mL in saliva and synovial fluid, 150ng/mL in blood, 1mug/mL in urine, 2-4mug/g in hair, bone and brain, and 10mug/g in nails. Other elements ranged in concentration from sub-nanogram/gram (or mL) to percentage (%w/w) levels. Associations of boron with other trace elements, such as boron and calcium in blood, were also investigated in the various tissues and fluids, as were variations due to age and sex. Frequency distribution curves were plotted for trace elements and micronutrients in all tissues and fluids. Since most elements demonstrated a symmetrical distribution in blood, this was thought to be indicative of the amount of homeostatic regulation, rather than the essentiality of the element. The distribution of elements among the various sample matrices, and occurrences of elemental or matrix interdependence, were investigated. Rubidium and caesium, also calcium and strontium, for example, were consistently found to behave in similar ways among the clinical specimens. In addition, alterations in elemental levels due to factors such as age and sex were assessed in the range of tissues and fluids. Full descriptions of the elemental content of brain, bone and synovial fluid samples were obtained. Comparisons were made between rheumatoid arthritic (RA) and control subjects for brain and bone, and between RA and osteoarthritic (OA) patients for the synovial fluid. Boron was shown to be "very highly significantly" depleted in RA bone (at the 0.1% level). Other elements showing variations in bone and brain were lithium and iron. Iron was also at lower levels in RA synovial fluid compared to OA, in contrast to phosphorus, copper and zinc, where increases were seen. Elemental levels were linked with other clinical parameters in synovial fluid, such as crystal content and white blood cell count (a measure of the extent of inflammation), to assess any possible variations. Fluid containing crystals displayed elevated levels of scandium, strontium and caesium. Several elements showed a positive correlation with white blood cell count; these were caesium, magnesium, phosphorus, copper, zinc and rubidium

Mathematical model of the cerebral circulation and distribution of cerebrospinal fluid

Shifts in cerebral fluid are known to be important in a number of diseases, and in conditions of microgravity such as space travel. In this work we develop a fluid mechanical model from firstprinciples incorporating key features of the flow of both blood and cerebrospinal fluid (CSF) in the intracranial and spinal spaces. For the cerebral blood vessels, we model the arteries and veins as symmetric bifurcating trees with constant geometrical scaling factors between generations, assume one-dimensional flow in each vessel and account for elastic effects via a pressure-area relationship, and we assume the capillaries have a constant resistance. We treat the vessel walls as porous media to find the transmural flux of plasma. We assume flow between the other compartments to be proportional to the pressure difference; additionally, the flow to the outer-dural space is assumed to be one-way. The set of ordinary differential equations for the evolution of the fluid pressures and volumes of each compartment can be solved numerically. Additional features include autoregulation, which we model by ensuring constant pressure at the microcirculation, meaning the resulting model must be solved iteratively. Also, we can model the effect of postural changes by including hydrostatic effects in the spinal column. The results are in accordance with physiological measurements and indicate that the pressure in the vasculature is highly sensitive to changes in vessel geometry, which also affects the transmural flux, whilst ventricular and spinal subarachnoid spaces are sensitive to compliances. We investigate transitions from supine to standing and upside down positions and also the effect of the external pressure surrounding the outer-dural spinal compartment. The model is computationally inexpensive and can be used as a platform for further analysis of cerebrovascular behaviour.Open Acces

Digital Health and Wireless Solutions

This two-volume set constitutes the refereed proceedings of the First Nordic Conference on , Digital Health and Wireless Solutions, NCDHWS 2024, held in Oulu, Finland, during May 7–8, 2024. The 51 full papers included in this book together with 7 short papers were carefully reviewed and selected from 100 submissions. They were organized in topical sections as follows: Part I: Remote Care and Health Connectivity Architectures in 6G Era.- User Experience and Citizen Data.- Digitalization in Health Education.- Digital Health Innovations.- Digital Care Pathways. Part II: Clinical Decision Support and Medical AI.- Digital Care Pathways.- Novel Sensors and Bioinformatics.- Health Technology Assessment and Impact Evaluation.- Wireless Technologies and Medical Devices. This book is open access

Mechanisms of glucocorticoid-mediated inhibition of angiogenesis

Angiogenesis, the formation of new blood vessels from pre-existing vascular beds, is a requirement of embryonic development but only occurs in a limited number of discrete processes in the healthy adult. In contrast, abnormal angiogenesis is central to many pathological processes including: tumour growth, diabetic retinopathy and arthritis. Consequently, pharmacological manipulation of angiogenesis has great clinical potential.Angiogenesis is inhibited by glucocorticoids and this is exploited clinically for the treatment of proliferating capillary haemangiomas in children. Despite this, the exact mechanism(s) through which glucocorticoids inhibit angiogenesis is (are) unknown. Whilst glucocorticoids can act directly on the vessel wall their effects on individual cell types and on molecular signalling remain unclear. The work in this thesis explores the hypothesis that glucocorticoid-mediated inhibition of angiogenesis is the result of direct modulation of growth factor signalling within the vascular endothelial cells.A well-characterised 2-dimensional in vitro model of human endothelial tube formation was introduced. Glucocorticoids were shown to inhibit tube formation in this model via stimulation of glucocorticoid receptors and this process was not influenced by intra-cellular glucocorticoid metabolism by ll(3-hydroxysteroid dehydrogenases. This demonstration that glucocorticoids inhibit angiogenesis by acting directly on the endothelium is consistent with, and extends, observations of glucocorticoid-mediated angiostasis in rodent aortic rings and during cutaneous wound healing. Molecular and biochemical assays suggested that glucocorticoids inhibit tube formation by altering the balance of pro- and anti-angiogenic factor activity. Time-lapse imaging of tube formation, combined with assays of endothelial cell migration and proliferation, indicated that glucocorticoids reduce tube formation, rather than accelerating degradation of existing tubes, by preventing morphological changes in the cells but do not inhibit cell division or migration.In conclusion, these studies demonstrate that glucocorticoids can inhibit angiogenesis by directly inhibiting morphological changes required for tube formation by endothelial cells but without altering migration or proliferation

Mitochondrial lipidome and genome alterations in mouse brain and experimental brain tumors

Thesis advisor: Thomas N. SeyfriedMitochondria are the key regulators of the bioenergetic state of the cell. Damage to mitochondrial protein, DNA, or membrane lipids can result as the cause or affect of disease pathology. Regardless, this damage can impair mitochondrial function resulting in a decreased ability to produce ATP to support cellular viability. This thesis research examined the mitochondrial lipidome by shotgun lipidomics in different populations of C57BL/6J (B6) brain mitochondria (non-synaptic and synaptic) and correlated lipid changes to differences in electron transport chain (ETC) activities. Furthermore, a comparison was made for non-synaptic mitochondria between the B6 and the VM mouse strain. The VM strain has a 1.5% incidence of spontaneous brain tumors, which is 210 fold greater than the B6 strain. I determined that differences in the brain mitochondrial lipidome existed in the VM strain compared to the B6 strain, likely corresponding to an increased rate of spontaneous brain tumor formation. Analysis of the mitochondrial genome in the CT-2A, EPEN, VM-NM1, and VM-M3 brain tumors compared to their syngeneic controls mouse strains, C57BL/6J (B6) and VM mice, was examined to determine if mutations existed in experimental brain cancer models. No pathogenic mtDNA mutations were discovered that would likely cause a decrease in the mitochondrial functionality. A novel hypothesis was devised to examine the tumor mitochondrial lipidome to determine if quantitative or molecular species differences existed that could potentially alter the functionality of the ETC. Brain tumor mitochondria were examined from tumors grown in vivo as well as in vitro. Numerous lipid differences were found in the mitochondria of brain tumors, of which the most interesting involved the unique molecular speciation of cardiolipin. ETC activities were significantly decreased in the primary ETC complexes which contribute protons to the gradient as well as the linked complexes of brain tumor mitochondria compared to controls. Taken together, it is likely that differences in the mitochondrial lipidome of brain tumors results in severe impairment of the mitochondria’s ability to produce ATP through the ETC. This research has provided a new understanding of the role of mitochondrial lipids in brain as well as brain cancer and offers an alternative explanation for metabolic dysfunction in cancer.Thesis (PhD) — Boston College, 2008.Submitted to: Boston College. Graduate School of Arts and Sciences.Discipline: Biology