Glucocorticoid Receptor Variants Modulate the Sensitivity to Cortisol

Synthetic glucocorticoids are used therapeutically for numerous indications. However, due to their broad physiological effects across many systems, side effects of GC therapy can be extensive and limit the clinical utility of GCs as a drug. One of the main urgent questions at this moment is to develop insights into the cause of the differences in the response between individuals to therapeutically applied GCs. Some patients respond to low doses, with or without side effects, while others do not respond at all. This thesis discusses a number of possible explanations for these differences in GC sensitivity and is focused on genetic, but also on transcriptional and translational aspects of the GR gene. Furthermore, it is also described how glucocorticoid sensitivity disorders can be characterized clinically and biochemically. An important tool in these studies has been a newly developed bioassay, measuring cellular GC sensitivity ex vivo, based on GR action at the transcriptional level by studying GC-regulated mRNA expression (chapter 2). Various polymorphism in the GR gene (N363S, ER22/23EK, and 9beta) are shown to affect GC sensitivity in vivo and in/ex vitro and result in a wide variety of phenotypic signs (chapters 3, 4, and 5). Furthermore, studies described in chapter 4, 5, 6, and 7 have demonstrated that also transcriptional and translational variants of the GR and the use of different promoters could modulate GC sensitivity. These factors modulating inter- individual sensitivity to GCs may have consequences for the use of GCs in a clinical setting. When treating patients with GCs, they need an individually determined optimal dose to obtain a balance between beneficial and adverse effects

On the Automatic Guidance System with Crab-Steering

Among the steering modes of farm tractor, the crab-steering has hardly been taken up in production and also in research. That mode of steering may be unapplicable to manual operating that has made familiar with normal mode of steering for long time, but because the vehicle with that mode can always hold its body in a certine direction, that type has a profitable property for the automatic guidance in field operation, and positional relation of sensor and implement is one-dimensional problem and attaching point of sensor to body is unrestricted. This type vehicle can not turn, but travelling of field operation necessitates no turning in many kinds of operations except at head land. At head land, it may be solved to change steering mode. The authors aspect to the property of crab-steering and aimed to develop the automatic guidance system with this steering mode. In this paper, the stability of relay-control system of automatic guidance was considered with describing-function method, and the results of tracking tests with trial vehicle were discussed and considered by means of time varying Fourier coefficients of tracking pass

Chronic Air Pollution Exposure during Pregnancy and Maternal and Fetal C-Reactive Protein Levels: The Generation R Study

Background: Exposure to air pollution has been associated with higher C-reactive protein (CRP) levels, suggesting an inflammatory response. Not much is known about this association in pregnancy

Mass Spectrometry for Identification, Monitoring, and Minimal Residual Disease Detection of M-Proteins

BACKGROUND: Monoclonal gammopathies (MGs) are plasma cell disorders defined by the clonal expansion of plasma cells, resulting in the characteristic excretion of a monoclonal immunoglobulin (M-protein). M-protein detection and quantification are integral parts of the diagnosi

Klinische chemie voor iedereen: het Wikipedia-project

Public relations (PR) and information to patients are key goals of the Dutch Society of Clinical Chemistry (NVKC). In this paper several initiatives will be discussed that have been undertaken to meet this statement. The Wikipedia project is one of those initiatives in which information concerning clinical chemistry is added or revised to the Dutch version of the online encyclopaedia Wikipedia. Over 100 tests and items of clinical chemistry have been added or revised and are recognized as a separate category within this online encyclopaedia. Statistical analysis showed an increase in the number of visitors to these articles of Wikipedia. Furthermore, by adding and improving the available information, the quality of the information provided online is enhanced. In conclusion: the attribution of health care professionals to this public domain leads to enhanced access of high quality information for the main public to clinical chemistry in general and to specific laboratory blood tests

Observation of charge-dependent azimuthal correlations and possible local strong parity violation in heavy ion collisions

Parity-odd domains, corresponding to non-trivial topological solutions of the QCD vacuum, might be created during relativistic heavy-ion collisions. These domains are predicted to lead to charge separation of quarks along the orbital momentum of the system created in non-central collisions. To study this effect, we investigate a three particle mixed harmonics azimuthal correlator which is a \P-even observable, but directly sensitive to the charge separation effect. We report measurements of this observable using the STAR detector in Au+Au and Cu+Cu collisions at $\sqrt{s_{NN}}$=200 and 62~GeV. The results are presented as a function of collision centrality, particle separation in rapidity, and particle transverse momentum. A signal consistent with several of the theoretical expectations is detected in all four data sets. We compare our results to the predictions of existing event generators, and discuss in detail possible contributions from other effects that are not related to parity violation.Comment: 17 pages, 14 figures, as accepted for publication in Physical Review C

Longitudinal Spin Transfer to Λ\Lambda and Λˉ\bar{\Lambda} Hyperons in Polarized Proton-Proton Collisions at s\sqrt{s} = 200 GeV

The longitudinal spin transfer, $D_{LL}$, from high energy polarized protons to $\Lambda$ and $\bar{\Lambda}$ hyperons has been measured for the first time in proton-proton collisions at $\sqrt{s} = 200 \mathrm{GeV}$ with the STAR detector at RHIC. The measurements cover pseudorapidity, $\eta$, in the range $|\eta| < 1.2$ and transverse momenta, $p_\mathrm{T}$, up to $4 \mathrm{GeV}/c$. The longitudinal spin transfer is found to be $D_{LL}= -0.03\pm 0.13(\mathrm{stat}) \pm 0.04(\mathrm{syst})$ for inclusive $\Lambda$ and $D_{LL} = -0.12 \pm 0.08(\mathrm{stat}) \pm 0.03(\mathrm{syst})$ for inclusive $\bar{\Lambda}$ hyperons with $= 0.5$ and $= 3.7 \mathrm{GeV}/c$. The dependence on $\eta$ and $p_\mathrm{T}$ is presented.Comment: 5 pages, 4 figure

Studying Parton Energy Loss in Heavy-Ion Collisions via Direct-Photon and Charged-Particle Azimuthal Correlations

Charged-particle spectra associated with direct photon ($\gamma_{dir}$) and $\pi^0$ are measured in $p$+$p$ and Au+Au collisions at center-of-mass energy $\sqrt{s_{_{NN}}}=200$ GeV with the STAR detector at RHIC. A hower-shape analysis is used to partially discriminate between $\gamma_{dir}$ and $\pi^0$. Assuming no associated charged particles in the $\gamma_{dir}$ direction (near side) and small contribution from fragmentation photons ($\gamma_{frag}$), the associated charged-particle yields opposite to $\gamma_{dir}$ (away side) are extracted. At mid-rapidity ($|\eta|<0.9$) in central Au+Au collisions, charged-particle yields associated with $\gamma_{dir}$ and $\pi^0$ at high transverse momentum ($8< p_{T}^{trig}<16$ GeV/$c$) are suppressed by a factor of 3-5 compared with $p$ + $p$ collisions. The observed suppression of the associated charged particles, in the kinematic range $|\eta|<1$ and $3< p_{T}^{assoc} < 16$ GeV/$c$, is similar for $\gamma_{dir}$ and $\pi^0$, and independent of the $\gamma_{dir}$ energy within uncertainties. These measurements indicate that the parton energy loss, in the covered kinematic range, is insensitive to the parton path length.Comment: submitted to Phys. Rev. Lett, 6 pages, 4 figure