Robust 3D Bloch-Siegert based B 1 + mapping using multi-echo general linear modeling

PURPOSE: Quantitative MRI applications, such as mapping the T1 time of tissue, puts high demands on the accuracy and precision of transmit field ( B 1 + ) estimation. A candidate approach to satisfy these requirements exploits the difference in phase induced by the Bloch-Siegert frequency shift (BSS) of 2 acquisitions with opposite off-resonance frequency radiofrequency pulses. Interleaving these radiofrequency pulses ensures robustness to motion and scanner drifts; however, here we demonstrate that doing so also introduces a bias in the B 1 + estimates. THEORY AND METHODS: It is shown here by means of simulation and experiments that the amplitude of the error depends on MR pulse sequence parameters, such as repetition time and radiofrequency spoiling increment, but more problematically, on the intrinsic properties, T1 and T2 , of the investigated tissue. To solve these problems, a new approach to BSS-based B 1 + estimation that uses a multi-echo acquisition and a general linear model to estimate the correct BSS-induced phase is presented. RESULTS: In line with simulations, phantom and in vivo experiments confirmed that the general linear model-based method removed the dependency on tissue properties and pulse sequence settings. CONCLUSION: The general linear model-based method is recommended as a more accurate approach to BSS-based B 1 + mapping

T helper cell subsets specific for pseudomonas aeruginosa in healthy individuals and patients with cystic fibrosis

Background: We set out to determine the magnitude of antigen-specific memory T helper cell responses to Pseudomonas aeruginosa in healthy humans and patients with cystic fibrosis. Methods: Peripheral blood human memory CD4+ T cells were co-cultured with dendritic cells that had been infected with different strains of Pseudomonas aeruginosa. The T helper response was determined by measuring proliferation, immunoassay of cytokine output, and immunostaining of intracellular cytokines. Results: Healthy individuals and patients with cystic fibrosis had robust antigen-specific memory CD4+ T cell responses to Pseudomonas aeruginosa that not only contained a Th1 and Th17 component but also Th22 cells. In contrast to previous descriptions of human Th22 cells, these Pseudomonal-specific Th22 cells lacked the skin homing markers CCR4 or CCR10, although were CCR6+. Healthy individuals and patients with cystic fibrosis had similar levels of Th22 cells, but the patient group had significantly fewer Th17 cells in peripheral blood. Conclusions: Th22 cells specific to Pseudomonas aeruginosa are induced in both healthy individuals and patients with cystic fibrosis. Along with Th17 cells, they may play an important role in the pulmonary response to this microbe in patients with cystic fibrosis and other conditions

Second order QCD corrections to inclusive semileptonic b \to Xc l \bar \nu_l decays with massless and massive lepton

We extend previous computations of the second order QCD corrections to semileptonic b \to c inclusive transitions, to the case where the charged lepton in the final state is massive. This allows accurate description of b \to c \tau \bar \nu_\tau decays. We review techniques used in the computation of O(\alpha_s^2) corrections to inclusive semileptonic b \to c transitions and present extensive numerical studies of O(\alpha_s^2) QCD corrections to b \to c l \bar \nu_l decays, for l =e, \tau.Comment: 30 pages, 4 figures, 5 table

The Absence of MIST1 Leads to Increased Ethanol Sensitivity and Decreased Activity of the Unfolded Protein Response in Mouse Pancreatic Acinar Cells

Background: Alcohol abuse is a leading cause of pancreatitis in humans. However, rodent models suggest that alcohol only sensitizes the pancreas to subsequent insult, indicating that additional factors play a role in alcohol-induced pancreatic injury. The goal of this study was to determine if an absence of MIST1, a transcription factor required for complete differentiation of pancreatic acinar cells in mice, increased the sensitivity to alcohol. Methods: Two to four month-old mice lacking MIST1 (Mist1 2/2) or congenic C57 Bl6 mice were placed on a Lieber-DeCarli diet (36 % of total kcal from ethanol and fat), a control liquid diet (36 % kcal from fat) or a regular breeding chow diet (22% kcal from fat). After six weeks, pancreatic morphology was assessed. Biochemical and immunofluorescent analysis was used to assess mediators of the unfolded protein response (UPR). Results: Ethanol-fed Mist1 2/2 mice developed periductal accumulations of inflammatory cells that did not appear in wild type or control-fed Mist1 2/2 mice. Wild type mice fed diets high in ethanol or fat showed enhancement of the UPR based on increased accumulation of peIF2a and spliced XBP1. These increases were not observed in Mist1 2/2 pancreatic tissue, which had elevated levels of UPR activity prior to diet exposure. Indeed, exposure to ethanol resulted in a reduction of UPR activity in Mist1 2/2 mice. Conclusions: Our findings suggest that an absence of MIST1 increases the sensitivity to ethanol that correlated wit

Extragalactic Results from the Infrared Space Observatory

More than a decade ago the IRAS satellite opened the realm of external galaxies for studies in the 10 to 100 micron band and discovered emission from tens of thousands of normal and active galaxies. With the 1995-1998 mission of the Infrared Space Observatory the next major steps in extragalactic infrared astronomy became possible: detailed imaging, spectroscopy and spectro-photometry of many galaxies detected by IRAS, as well as deep surveys in the mid- and far- IR. The spectroscopic data reveal a wealth of detail about the nature of the energy source(s) and about the physical conditions in galaxies. ISO's surveys for the first time explore the infrared emission of distant, high-redshift galaxies. ISO's main theme in extragalactic astronomy is the role of star formation in the activity and evolution of galaxies.Comment: 106 pages, including 17 figures. Ann.Rev.Astron.Astrophys. (in press), a gzip'd pdf file (667kB) is also available at http://www.mpe.mpg.de/www_ir/preprint/annrev2000.pdf.g

Hospital postnatal discharge and sepsis advice: Perspectives of women and midwifery students

Background: Women are discharged home from hospital increasingly early, but there is little evidence examining the postnatal hospital discharge process and how this may impact on the health of women and babies. In particular, there is little on sepsis prevention advice, despite it being the biggest direct cause of maternal mortality. Aim: To explore the perceptions of women and senior student midwives related to the postnatal hospital discharge process and maternal sepsis prevention advice. Methods: Three focus group interviews were undertaken, involving 9 senior student midwives and 14 women attending paid or specialist classes for vulnerable migrant women. Findings: All participants believed that the postnatal hospital discharge process was inadequate, rushed and inconsistent. Sepsis advice was patchy and the condition underplayed. Conclusions: Cost effective, time-efficient and innovative ways to impart vital information are required to support the postnatal hospital discharge process

Establishing a generalized polyepigenetic biomarker for tobacco smoking

Large-scale epigenome-wide association meta-analyses have identified multiple 'signatures'' of smoking. Drawing on these findings, we describe the construction of a polyepigenetic DNA methylation score that indexes smoking behavior and that can be utilized for multiple purposes in population health research. To validate the score, we use data from two birth cohort studies: The Dunedin Longitudinal Study, followed to age-38 years, and the Environmental Risk Study, followed to age-18 years. Longitudinal data show that changes in DNA methylation accumulate with increased exposure to tobacco smoking and attenuate with quitting. Data from twins discordant for smoking behavior show that smoking influences DNA methylation independently of genetic and environmental risk factors. Physiological data show that changes in DNA methylation track smoking-related changes in lung function and gum health over time. Moreover, DNA methylation changes predict corresponding changes in gene expression in pathways related to inflammation, immune response, and cellular trafficking. Finally, we present prospective data about the link between adverse childhood experiences (ACEs) and epigenetic modifications; these findings document the importance of controlling for smoking-related DNA methylation changes when studying biological embedding of stress in life-course research. We introduce the polyepigenetic DNA methylation score as a tool both for discovery and theory-guided research in epigenetic epidemiology.This article is freely available via Open Access. Click on the Publisher URL to access it via the publisher's site.The Dunedin Longitudinal Study is funded by the New Zealand Health Research Council, the New Zealand Ministry of Business, Innovation, and Employment, the National Institute on Aging (AG032282), and the Medical Research Council (MR/P005918/1). The E-Risk Study is funded by the Medical Research Council (G1002190) and the National Institute of Child Health and Human Development (HD077482). Additional support was provided by a Distinguished Investigator Award from the American Asthma Foundation to Dr. Mill, and by the Jacobs Foundation and the Avielle Foundation. Dr. Arseneault is the Mental Health Leadership Fellow for the U.K. Economic and Social Research Council. Dr. Belsky is a Jacobs Foundation Fellow. This work used a high-performance computing facility partially supported by grant 2016-IDG-1013 (“HARDAC + : Reproducible HPC for Next-generation Genomics”) from the North Carolina Biotechnology Center. Illumina DNA methylation data are accessible from the Gene Expression Omnibus (accession code: GSE105018).pre-print, post-print, publisher's PD

High spatial and temporal resolution wide-field imaging of neuron activity using quantum NV-diamond

A quantitative understanding of the dynamics of biological neural networks is fundamental to gaining insight into information processing in the brain. While techniques exist to measure spatial or temporal properties of these networks, it remains a significant challenge to resolve the neural dynamics with subcellular spatial resolution. In this work we consider a fundamentally new form of wide-field imaging for neuronal networks based on the nanoscale magnetic field sensing properties of optically active spins in a diamond substrate. We analyse the sensitivity of the system to the magnetic field generated by an axon transmembrane potential and confirm these predictions experimentally using electronically-generated neuron signals. By numerical simulation of the time dependent transmembrane potential of a morphologically reconstructed hippocampal CA1 pyramidal neuron, we show that the imaging system is capable of imaging planar neuron activity non-invasively at millisecond temporal resolution and micron spatial resolution over wide-fields

Stress-Induced C/EBP Homology Protein (CHOP) Represses MyoD Transcription to Delay Myoblast Differentiation

When mouse myoblasts or satellite cells differentiate in culture, the expression of myogenic regulatory factor, MyoD, is downregulated in a subset of cells that do not differentiate. The mechanism involved in the repression of MyoD expression remains largely unknown. Here we report that a stress-response pathway repressing MyoD transcription is transiently activated in mouse-derived C2C12 myoblasts growing under differentiation-promoting conditions. We show that phosphorylation of the α subunit of the translation initiation factor 2 (eIF2α) is followed by expression of C/EBP homology protein (CHOP) in some myoblasts. ShRNA-driven knockdown of CHOP expression caused earlier and more robust differentiation, whereas its constitutive expression delayed differentiation relative to wild type myoblasts. Cells expressing CHOP did not express the myogenic regulatory factors MyoD and myogenin. These results indicated that CHOP directly repressed the transcription of the MyoD gene. In support of this view, CHOP associated with upstream regulatory region of the MyoD gene and its activity reduced histone acetylation at the enhancer region of MyoD. CHOP interacted with histone deacetylase 1 (HDAC1) in cells. This protein complex may reduce histone acetylation when bound to MyoD regulatory regions. Overall, our results suggest that the activation of a stress pathway in myoblasts transiently downregulate the myogenic program