112 research outputs found
A (G-to-A) mutation in the initiation codon of the proteolipid protein gene causing a relatively mild form of Pelizaeus-Merzbacher disease in a Dutch family
Thyrotrophin and thyroxine support immune homeostasis in humans
The endocrine and the immune systems interact by sharing receptors for hormones and cytokines, cross-control and feedback mechanisms. To date, no comprehensive study has assessed the impact of thyroid hormones on immune homeostasis. By studying immune phenotype (cell populations, antibody concentrations, circulating cytokines, adipokines and acute-phase proteins, monocyte-platelet interactions and cytokine production capacity) in two large independent cohorts of healthy volunteers of Western European descent from the Human Functional Genomics Project (500FG and 300BCG cohorts), we identified a crucial role of the thyroid hormone thyroxin (T4) and thyroid-stimulating hormone (TSH) on the homeostasis of lymphocyte populations. TSH concentrations were strongly associated with multiple populations of both effector and regulatory T cells, whereas B-cell populations were significantly associated with free T4 (fT4). In contrast, fT4 and TSH had little impact on myeloid cell populations and cytokine production capacity. Mendelian randomization further supported the role of fT4 for lymphocyte homeostasis. Subsequently, using a genomics approach, we identified genetic variants that influence both fT4 and TSH concentrations and immune responses, and gene set enrichment pathway analysis showed enrichment of fT4-affected gene expression in B-cell function pathways, including the CD40 pathway, further supporting the importance of fT4 in the regulation of B-cell function. In conclusion, we show that thyroid function controls the homeostasis of the lymphoid cell compartment. These findings improve our understanding of the immune responses and open the door for exploring and understanding the role of thyroid hormones in the lymphocyte function during disease
Nuclear Polarization of Molecular Hydrogen Recombined on a Non-metallic Surface
The nuclear polarization of molecules formed by recombination
of nuclear polarized H atoms on the surface of a storage cell initially coated
with a silicon-based polymer has been measured by using the longitudinal
double-spin asymmetry in deep-inelastic positron-proton scattering. The
molecules are found to have a substantial nuclear polarization, which is
evidence that initially polarized atoms retain their nuclear polarization when
absorbed on this type of surfac
Flavor decomposition of the sea quark helicity distributions in the nucleon from semi-inclusive deep-inelastic scattering
Double-spin asymmetries of semi-inclusive cross sections for the production
of identified pions and kaons have been measured in deep-inelastic scattering
of polarized positrons on a polarized deuterium target. Five helicity
distributions including those for three sea quark flavors were extracted from
these data together with re-analyzed previous data for identified pions from a
hydrogen target. These distributions are consistent with zero for all three sea
flavors. A recently predicted flavor asymmetry in the polarization of the light
quark sea appears to be disfavored by the data.Comment: 5 pages, 3 figure
Molecular subtypes of breast cancer and amplification of topoisomerase IIα: predictive role in dose intensive adjuvant chemotherapy
Benefit from chemotherapy treatment in breast cancer patients is determined by the molecular make-up of the tumour. In a retrospective analysis, we determined the molecular subtypes of breast cancer originally defined by expression microarrays by immunohistochemistry in tumours of patients who took part in a randomised study of adjuvant high-dose chemotherapy in breast cancer. In addition, the topoisomerase IIα (TOP2A) amplification status was determined by fluorescence in situ hybridisation and chromogenic in situ hybridisation. 411 of the 753 tumours (55%) were classified as luminal-like, 137 (18%) as basal-like and 205 (27%) as human epithelial receptor type 2 (HER2) amplified. The basal-like tumours were defined as having no expression of ER and HER2; 98 of them did express epidermal growth factor receptor and/or cytokeratin 5/6. The luminal-like tumours had a significantly better recurrence free and overall survival than the other two groups. From the 194 HER2-positive tumours, 47 (24%) were shown to harbour an amplification of TOP2A. Patients with an HER2-amplified tumour randomised to the high-dose therapy arm did worse than those in the conventional treatment arm, possibly caused by the lower cumulative anthracycline dose in the high-dose arm. The tumours with a TOP2A amplification contributed hardly to this difference, suggesting that TOP2A amplification is not the cause of the steep dose–response curve for anthracyclines in breast cancer. Possibly, the difference of the cumulative dose of only 25% between the treatment arms was insufficient to yield a survival difference
Single-spin asymmetries in semi-inclusive deep-inelastic scattering on a transversely polarized hydrogen target
Single-spin asymmetries for semi-inclusive electroproduction of charged pions
in deep-inelastic scattering of positrons are measured for the first time with
transverse target polarization. The asymmetry depends on the azimuthal angles
of both the pion () and the target spin axis () about the virtual
photon direction and relative to the lepton scattering plane. The extracted
Fourier component \cmpi is a signal of the previously unmeasured quark
transversity distribution, in conjunction with the so-called Collins
fragmentation function, also unknown. The Fourier component \smpi of the
asymmetry arises from a correlation between the transverse polarization of the
target nucleon and the intrinsic transverse momentum of quarks, as represented
by the previously unmeasured Sivers distribution function. Evidence for both
signals is observed, but the Sivers asymmetry may be affected by exclusive
vector meson productio
Quark helicity distributions in the nucleon for up, down, and strange quarks from semi--inclusive deep--inelastic scattering
Polarized deep--inelastic scattering data on longitudinally polarized
hydrogen and deuterium targets have been used to determine double spin
asymmetries of cross sections. Inclusive and semi--inclusive asymmetries for
the production of positive and negative pions from hydrogen were obtained in a
re--analysis of previously published data. Inclusive and semi--inclusive
asymmetries for the production of negative and positive pions and kaons were
measured on a polarized deuterium target. The separate helicity densities for
the up and down quarks and the anti--up, anti--down, and strange sea quarks
were computed from these asymmetries in a ``leading order'' QCD analysis. The
polarization of the up--quark is positive and that of the down--quark is
negative. All extracted sea quark polarizations are consistent with zero, and
the light quark sea helicity densities are flavor symmetric within the
experimental uncertainties. First and second moments of the extracted quark
helicity densities in the measured range are consistent with fits of inclusive
data
Evidence for a narrow |S|=1 baryon state at a mass of 1528 MeV in quasi-real photoproduction
Evidence for a narrow baryon state is found in quasi-real photoproduction on
a deuterium target through the decay channel p K^0_S --> p pi^+ pi^-. A peak is
observed in the p K^0_S invariant mass spectrum at 1528 +/- 2.6 (stat) +/-2.1
(syst) MeV. Depending on the background model,the naive statistical
significance of the peak is 4--6 standard deviations and its width may be
somewhat larger than the experimental resolution of sigma=4.3 -- 6.2 MeV. This
state may be interpreted as the predicted S=+1 exotic Theta^{+}(uuddbar(s))
pentaquark baryon. No signal for an hypothetical Theta^{++} baryon was observed
in the pK^+ invariant mass distribution. The absence of such a signal indicates
that an isotensor Theta is excluded and an isovector Theta is unlikely.Comment: 8 pages, 4 figure
The HERMES Polarized Hydrogen and Deuterium Gas Target in the HERA Electron Storage Ring
The HERMES hydrogen and deuterium nuclear-polarized gas targets have been in
use since 1996 with the polarized electron beam of HERA at DESY to study the
spin structure of the nucleon. Polarized atoms from a Stern-Gerlach Atomic Beam
Source are injected into a storage cell internal to the HERA electron ring.
Atoms diffusing from the center of the storage cell into a side tube are
analyzed to determine the atomic fraction and the atomic polarizations. The
atoms have a nuclear polarization, the axis of which is defined by an external
magnetic holding field. The holding field was longitudinal during 1996-2000,
and was changed to transverse in 2001. The design of the target is described,
the method for analyzing the target polarization is outlined, and the
performance of the target in the various running periods is presented
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