317 research outputs found
Of autoregressive continuous time model parameters estimation
This article revisits a sequential approach to the estimation of the parameter in a first-order autoregressive model (AR(1)) with continuous time. There is provided a numerical study to get a results of sequential estimations of the parameter in first-order autoregressive model with continuous time and is computed a stopping rule and the optimal time of observations. Also there is provided a comparing analysis of estimation results with using the sequential approach both the optimal time of observations
A genome-wide screen in macrophages identifies new regulators of IFNγ-inducible MHCII that contribute to T cell activation [preprint]
Cytokine-mediated activation of host immunity is central to the control of pathogens. A key cytokine in protective immunity is interferon-gamma (IFNγ), which is a potent activator of antimicrobial and immunomodulatory effectors within the host. A major role of IFNγ is to induce major histocompatibility complex class II molecules (MHCII) on the surface of cells, which is required for CD4+ T cell activation. Despite its central role in host immunity, the complex and dynamic regulation of IFNγ-induced MHCII is not well understood. Here, we integrated functional genomics and transcriptomics to comprehensively define the genetic control of IFNγ-mediated MHCII surface expression in macrophages. Using a genome-wide CRISPR-Cas9 library we identified genes that control MHCII surface expression, many of which have yet to be associated with MHCII. Mechanistic studies uncovered two parallel pathways of IFNγ-mediated MHCII control that require the multifunctional glycogen synthase kinase 3 beta (GSK3β) or the mediator complex subunit MED16. Both pathways are necessary for IFNγ-mediated induction of the MHCII transactivator CIITA, MHCII expression, and CD4+ T cell activation. Using transcriptomic analysis, we defined the regulons controlled by GSK3β and MED16 in the presence and absence of IFNγ and identified unique networks of the IFNγ-mediated transcriptional landscape that are controlled by each gene. Our analysis suggests GSK3β and MED16 control distinct aspects of the IFNγ-response and are critical for macrophages to respond appropriately to IFNγ. Our results define previously unappreciated regulation of MHCII expression that is required to control CD4+ T cell responses by macrophages. These discoveries will aid in our basic understanding of macrophage-mediated immunity and will shed light on mechanisms of failed adaptive responses pervasive in infectious disease, autoimmunity, and cancer
Associations of adherence to the New Nordic Diet with risk of preeclampsia and preterm delivery in the Norwegian Mother and Child Cohort Study (MoBa)
Preeclampsia and preterm delivery are serious complications of pregnancy and leading causes of perinatal mortality and morbidity worldwide. Dietary factors might be associated with these adverse outcomes. We investigated whether adherence to the New Nordic Diet (NND) was associated with preeclampsia and preterm delivery risks in the Norwegian Mother and Child Cohort Study (MoBa). Participants were recruited from all over Norway during the period 1999-2008. A previously constructed diet score assessing meal frequency, and the consumption of Nordic fruits, root vegetables, cabbages, potatoes, oatmeal porridge, whole grains, wild fish, game, berries, milk and water, was used to assess NND adherence. Associations between NND adherence and the outcomes were estimated in adjusted multivariate logistic regression models. Odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated. A total of 72,072 women was included in the study. High versus low NND adherence was associated with lower risk of total preeclampsia (OR 0.86; 95 % CI 0.78-0.95) and early preeclampsia (OR 0.71; 95 % CI 0.52-0.96). High compared with low NND adherence was associated with a lower risk of spontaneous preterm delivery among nulliparous women (OR 0.77; 95 % CI 0.66-0.89), whereas multiparous women with high NND adherence had a marginally significant higher risk of preterm delivery (OR 1.24; 95 % CI 1.00-1.53). High NND adherence was associated with a lower relative risk of preeclampsia and of spontaneous preterm delivery among nulliparous women; however, among multiparous women there was a higher relative risk of preterm delivery
Multidimensional Conservation Laws: Overview, Problems, and Perspective
Some of recent important developments are overviewed, several longstanding
open problems are discussed, and a perspective is presented for the
mathematical theory of multidimensional conservation laws. Some basic features
and phenomena of multidimensional hyperbolic conservation laws are revealed,
and some samples of multidimensional systems/models and related important
problems are presented and analyzed with emphasis on the prototypes that have
been solved or may be expected to be solved rigorously at least for some cases.
In particular, multidimensional steady supersonic problems and transonic
problems, shock reflection-diffraction problems, and related effective
nonlinear approaches are analyzed. A theory of divergence-measure vector fields
and related analytical frameworks for the analysis of entropy solutions are
discussed.Comment: 43 pages, 3 figure
Oxidative Stability of Polyunsaturated Edible Oils Mixed With Microcrystalline Cellulose
The oxidative stability of mixtures of edible oils containing polyunsaturated fatty acids (PUFA) and microcrystalline cellulose (MCC) was investigated. The mixtures studied consisted of oils of either camelina (CAM), cod liver (CLO), or salmon (SO) mixed with either colloidal or powdered MCC. A 50:50 (w/w) ratio of oil:MCC resulted in an applicable mixture containing high levels of PUFA edible oil and dietary fiber. The oxidative stability of the formulated mixtures and the pure oils was investigated over a period of 28 days. The peroxide value (PV) was assessed as a parameter for primary oxidation products and dynamic headspace gas chromatography mass spectrometry (GC/MS) was used to analyze secondary volatile organic compounds (VOC). CAM and the respective mixtures were oxidatively stable at both 4 and 22 °C during the storage period. The marine oils and the respective mixtures were stable at 4 °C. At 22 °C, an increase in hydroperoxides was found, but no increase in VOC was detected during the time-frame investigated. At 42 °C, prominent increases in PV and VOC were found for all oils and mixtures. Hexanal, a common marker for the degradation of n-6 fatty acids, propanal and 2,4-heptadienal (E,E), common indicators for the degradation of n-3 fatty acids, were among the volatiles detected in the headspace of oils and mixtures. This study showed that a mixture containing a 50:50 ratio of oil:MCC can be obtained by a low-tech procedure that does not induce oxidation when stored at low temperatures during a period of 1 month
Схиигумен Сергий как маргинальная языковая личность в пространстве религиозно-политической коммуникации
SummaryThaumarchaeota are globally distributed and abundantmicroorganisms occurring in diverse habitats and thusrepresent a major source of archaeal lipids. The scopeof lipids as taxonomic markers in microbial ecologicalstudies is limited by the scarcity of comparative dataon the membrane lipid composition of cultivated representatives,including the phylum Thaumarchaeota.Here, we comprehensively describe the core and intactpolar lipid (IPL) inventory of ten ammonia-oxidisingthaumarchaeal cultures representing all four characterizedphylogenetic clades. IPLs of these thaumarchaealstrains are generally similar and consist of membranespanning,glycerol dibiphytanyl glycerol tetraetherswith monoglycosyl, diglycosyl, phosphohexose andhexose-phosphohexose headgroups. However, the relativeabundances of these IPLs and their core lipidcompositions differ systematically between the phylogeneticsubgroups, indicating high potential forchemotaxonomic distinction of thaumarchaeal clades.Comparative lipidomic analyses of 19 euryarchaeal andcrenarchaeal strains suggested that the lipid methoxyarchaeol is synthesized exclusively by Thaumarchaeotaand may thus represent a diagnostic lipidbiomarker for this phylum. The unprecedented diversityof the thaumarchaeal lipidome with 118 differentlipids suggests that membrane lipid composition andadaptation mechanisms in Thaumarchaeota are morecomplex than previously thought and include uniquelipids with as yet unresolved properties
Effects of Place of Articulation Changes on Auditory Neural Activity: A Magnetoencephalography Study
In casual speech, phonemic segments often assimilate such that they adopt features from adjacent segments, a typical feature being their place of articulation within the vocal tract (e.g., labial, coronal, velar). Place assimilation (e.g., from coronal /n/ to labial /m/: rainbow→*raimbow) alters the surface form of words. Listeners' ability to perceptually compensate for such changes seems to depend on the phonemic context, on whether the adjacent segment (e.g., the /b/ in “rainbow”) invites the particular change. Also, some assimilations occur frequently (e.g., /n/→/m/), others are rare (e.g., /m/→/n/). We investigated the effects of place assimilation, its contextual dependency, and its frequency on the strength of auditory evoked mismatch negativity (MMN) responses, using pseudowords. Results from magnetoencephalography (MEG) revealed that the MMN was modulated both by the frequency and contextual appropriateness of assimilations
High-Efficiency Stem Cell Fusion-Mediated Assay Reveals Sall4 as an Enhancer of Reprogramming
Several methods allow reprogramming of differentiated somatic cells to embryonic stem cell-like cells. However, the process of reprogramming remains inefficient and the underlying molecular mechanisms are poorly understood. Here, we report the optimization of somatic cell fusion with embryonic stem cells in order to provide an efficient, quantitative assay to screen for factors that facilitate reprogramming. Following optimization, we achieved a reprogramming efficiency 15–590 fold higher than previous protocols. This allowed observation of cellular events during the reprogramming process. Moreover, we demonstrate that overexpression of the Spalt transcription factor, Sall4, which was previously identified as a regulator of embryonic stem cell pluripotency and early mouse development, can enhance reprogramming. The reprogramming activity of Sall4 is independent of an N-terminal domain implicated in recruiting the nucleosome remodeling and deacetylase corepressor complex, a global transcriptional repressor. These results indicate that improvements in reprogramming assays, including fusion assays, may allow the systematic identification and molecular characterization of enhancers of somatic cell reprogramming
The Impact of Acute Psychosocial Stress on Magnetoencephalographic Correlates of Emotional Attention and Exogenous Visual Attention
Stress-induced acute activation of the cerebral catecholaminergic systems has often been found in rodents. However, little is known regarding the consequences of this activation on higher cognitive functions in humans. Theoretical inferences would suggest increased distractibility in the sense of increased exogenous attention and emotional attention. The present study investigated the influence of acute stress responses on magnetoencephalographic (MEG) correlates of visual attention. Healthy male subjects were presented emotional and neutral pictures in three subsequent MEG recording sessions after being exposed to a TSST-like social stressor, intended to trigger a HPA-response. The subjects anticipation of another follow-up stressor was designed to sustain the short-lived central catecholaminergic stress reactions throughout the ongoing MEG recordings. The heart rate indicates a stable level of anticipatory stress during this time span, subsequent cortisol concentrations and self-report measures of stress were increased. With regard to the MEG correlates of attentional functions, we found that the N1m amplitude remained constantly elevated during stressor anticipation. The magnetic early posterior negativity (EPNm) was present but, surprisingly, was not at all modulated during stressor anticipation. This suggests that a general increase of the influence of exogenous attention but no specific effect regarding emotional attention in this time interval. Regarding the time course of the effects, an influence of the HPA on these MEG correlates of attention seems less likely. An influence of cerebral catecholaminergic systems is plausible, but not definite
Modulation of Transcriptional and Inflammatory Responses in Murine Macrophages by the Mycobacterium tuberculosis Mammalian Cell Entry (Mce) 1 Complex
The outcome of many infections depends on the initial interactions between agent and host. Aiming at elucidating the effect of the M. tuberculosis Mce1 protein complex on host transcriptional and immunological responses to infection with M. tuberculosis, RNA from murine macrophages at 15, 30, 60 min, 4 and 10 hrs post-infection with M. tuberculosis H37Rv or Δ-mce1 H37Rv was analyzed by whole-genome microarrays and RT-QPCR. Immunological responses were measured using a 23-plex cytokine assay. Compared to uninfected controls, 524 versus 64 genes were up-regulated by 15 min post H37Rv- and Δ-mce1 H37Rv-infection, respectively. By 15 min post-H37Rv infection, a decline of 17 cytokines combined with up-regulation of Ccl24 (26.5-fold), Clec4a2 (23.2-fold) and Pparγ (10.5-fold) indicated an anti-inflammatory response initiated by IL-13. Down-regulation of Il13ra1 combined with up-regulation of Il12b (30.2-fold), suggested switch to a pro-inflammatory response by 4 hrs post H37Rv-infection. Whereas no significant change in cytokine concentration or transcription was observed during the first hour post Δ-mce1 H37Rv-infection, a significant decline of IL-1b, IL-9, IL-13, Eotaxin and GM-CSF combined with increased transcription of Il12b (25.1-fold) and Inb1 (17.9-fold) by 4 hrs, indicated a pro-inflammatory response. The balance between pro-and anti-inflammatory responses during the early stages of infection may have significant bearing on outcome
- …