Retrieving the hemodynamic response function in resting state fMRI: methodology and application

In this paper we present a procedure to retrieve the hemodynamic response function (HRF) from resting state functional magnetic resonance imaging (fMRI) data. The fundamentals of the procedures are further validated by considering simultaneous electroencephalographic (EEG) recordings. The typical HRF shape at rest for a group of healthy subject is presented. Then we present the modifications to the shape of the HRF at rest following two physiological modulations: eyes open versus eyes closed and propofol-induced modulations of consciousness

β2-adrenergic agonists modulate TNF-α induced astrocytic inflammatory gene expression and brain inflammatory cell populations

Background: The NF-kappa B signaling pathway orchestrates many of the intricate aspects of neuroinflammation. Astrocytic beta(2)-adrenergic receptors have emerged as potential regulators in central nervous system inflammation and are potential targets for pharmacological modulation. The aim of this study was to elucidate the crosstalk between astrocytic beta(2)-adrenergic receptors and the TNF-alpha induced inflammatory gene program. Methods: Proinflammatory conditions were generated by the administration of TNF-alpha. Genes that are susceptible to astrocytic crosstalk between beta(2)-adrenergic receptors (stimulated by clenbuterol) and TNF-alpha were identified by qPCR-macroarray-based gene expression analysis in a human 1321 N1 astrocytoma cell line. Transcriptional patterns of the identified genes in vitro were validated by RT-PCR on the 1321 N1 cell line as well as on primary rat astrocytes. In vivo expression patterns were examined by intracerebroventricular administration of clenbuterol and/or TNF-alpha in rats. To examine the impact on the inflammatory cell content of the brain we performed extensive FACS analysis of rat brain immune cells after intracerebroventricular clenbuterol and/or TNF-alpha administration. Results: Parallel transcriptional patterns in vivo and in vitro confirmed the relevance of astrocytic beta(2)-adrenergic receptors as modulators of brain inflammatory responses. Importantly, we observed pronounced effects of beta(2)-adrenergic receptor agonists and TNF-alpha on IL-6, CXCL2, CXCL3, VCAM1, and ICAM1 expression, suggesting a role in inflammatory brain cell homeostasis. Extensive FACS-analysis of inflammatory cell content in the brain demonstrated that clenbuterol/TNF-alpha co-administration skewed the T cell population towards a double negative phenotype and induced a shift in the myeloid brain cell population towards a neutrophilic predominance. Conclusions: Our results show that astrocytic beta(2)-adrenergic receptors are potent regulators of astrocytic TNF-alpha-activated genes in vitro and in vivo, and ultimately modulate the molecular network involved in the homeostasis of inflammatory cells in the central nervous system. Astrocytic beta(2)-adrenergic receptors and their downstream signaling pathway may serve as potential targets to modulate neuroinflammatory responses

Neurological manifestations and neuro-invasive mechanisms of the severe acute respiratory syndrome coronavirus type 2

Background and purpose Infections with coronaviruses are not always confined to the respiratory tract and various neurological manifestations have been reported. The aim of this study was to perform a review to describe neurological manifestations in patients with COVID-19 and possible neuro-invasive mechanisms of Sars-CoV-2. Methods PubMed, Web of Science and COVID-dedicated databases were searched for the combination of COVID-19 terminology and neurology terminology up to 10 May 2020. Social media channels were followed up between 15 March and 10 May 2020 for postings with the same scope. Neurological manifestations were extracted from the identified papers and combined to provide a useful summary for the neurologist in clinical practice. Results Neurological manifestations potentially related to COVID-19 have been reported in large studies, case series and case reports and include acute cerebrovascular diseases, impaired consciousness, cranial nerve manifestations and autoimmune disorders such as the Guillain-Barre syndrome often present in patients with more severe COVID-19. Cranial nerve symptoms such as olfactory and gustatory dysfunctions are highly prevalent in patients with mild to moderate COVID-19 even without associated nasal symptoms and often present in an early stage of the disease. Conclusion Physicians should be aware of the neurological manifestations in patients with COVID-19, especially when rapid clinical deterioration occurs. The neurological symptoms in COVID-19 patients may be due to direct viral neurological injury or indirect neuroinflammatory and autoimmune mechanisms. No antiviral treatments against the virus or vaccines for its prevention are available and the long-term consequences of the infection on human health remain uncertain especially with regard to the neurological system

Understanding the interaction between a steel microstructure and hydrogen

The present work provides an overview of the work on the interaction between hydrogen (H) and the steel’s microstructure. Different techniques are used to evaluate the H-induced damage phenomena. The impact of H charging on multiphase high-strength steels, i.e., high-strength low-alloy (HSLA), transformation-induced plasticity (TRIP) and dual phase (DP) is first studied. The highest hydrogen embrittlement resistance is obtained for HSLA steel due to the presence of Ti- and Nb-based precipitates. Generic Fe-C lab-cast alloys consisting of a single phase, i.e., ferrite, bainite, pearlite or martensite, and with carbon contents of approximately 0, 0.2 and 0.4 wt %, are further considered to simplify the microstructure. Finally, the addition of carbides is investigated in lab-cast Fe-C-X alloys by adding a ternary carbide forming element to the Fe-C alloys. To understand the H/material interaction, a comparison of the available H trapping sites, the H pick-up level and the H diffusivity with the H-induced mechanical degradation or H-induced cracking is correlated with a thorough microstructural analysis

The cost of human capital depreciation during unemployment

Skill erosion during unemployment was of particular concern as unemployment duration increased in the Great Recession. I argue that it generates an externality in job creation: firms ignore how their hiring decisions affect the unemployment pool’s skill composition, and hence the expected output produced by new hires. As a consequence, job creation is too low from a social point of view. But the extent to which it is too low varies over the cycle. This is because the externality’s magnitude, which depends on the impact of job creation on the pool’s skill composition, reduces when the share of unemployed workers who already have eroded skills increases

Initiation of hydrogen induced cracks at secondary phase particles

The goal of this work is to propose a general mechanism for hydrogen induced crack initiation in steels based on a microstructural study of multiple steel grades. Four types of steels with strongly varying microstructures are studied for this purpose, i.e. ultra low carbon (ULC) steel, TRIP (transformation induced plasticity) steel, Fe-C-Ti generic alloy, and pressure vessel steel. A strong dependency of the initiation of hydrogen induced cracks on the microstructural features in the materials is observed. By use of SEM-EBSD characterization, initiation is found to always occur at the hard secondary phase particles in the materials