171 research outputs found
Flow cytometric measurement of STAT5 phosphorylation in cytomegalovirus-stimulated T cells
Cytomegalovirus (CMV)-specific T cells expand with CMV reactivation and are probably prerequisite for control and protection. Given the critical role STAT5A phosphorylation (pSTAT5A) in T cell proliferation, this study presents a simple and sensitive flow cytometric-based pSTAT5A assay to quickly identify CMV-specific T cell proliferation. We determined pSTAT5A in T cells treated with CMV-specific peptide mix (pp65 + IE1 peptides) from 20 healthy adult subjects and three immunodeficient patients with CARMIL-2 mutation. After stimulation, the percentage of pSTAT5A+ T cells in CMV-seropositive (CMV+) subjects significantly increased from 3.0% ± 1.9% (unstimulated) to 11.4% ± 5.9% (stimulated) for 24 h. After 7 days of stimulation, the percentage of expanded T cells amounted to 26% ± 17.2%. Conversely, the percentage of pSTAT5A+ T cells and T cell proliferation from CMV-seronegative (CMV−) subjects hardly changed (from 3.0% ± 1.3% to 3.7% ± 1.8% and from 4.3% ± 2.1% to 5.7% ± 1.7%, respectively). We analyzed the correlation between the percentage of pSTAT5A+ T cells versus (1) CMV-IgG concentrations versus (2) the percentage of expanded T cells and versus (3) the percentage of initial CMV-specific T cells. In immunodeficient patients with CARMIL-2 mutation, CMV-specific pSTAT5A and T cell proliferation were completely deficient. In conclusion, flow cytometric-based pSTAT5A assay represents an appropriate tool to quickly identify CMV-specific T cell proliferation and helps to understand dysfunctions in controlling other pathogens. Flow cytometric-based pSTAT5A assay may be a useful test in clinical practice and merits further validation in large studies
A self-consistent empirical model atmosphere, abundance and stratification analysis of the benchmark roAp star alpha Circini
Chemically peculiar (CP) stars are unique natural laboratories for
investigation of the microscopic diffusion processes of chemical elements. The
element segregation under the influence of gravity and radiation pressure leads
to the appearance of strong abundance gradients in the atmospheres of CP stars.
Consequently, the atmospheric temperature-pressure structure of these objects
could deviate significantly from the atmospheres of normal stars with
homogeneous abundances. In this study we performed a self-consistent, empirical
model atmosphere study of the brightest rapidly oscillating Ap star alpha Cir.
We account for chemical stratification in the model atmosphere calculations and
assess the importance of non-uniformed vertical element distribution on the
model structure, energy distribution and hydrogen line profiles. Based on an
iterative procedure of the chemical abundance analysis of 52 ions of 35
elements, stratification modeling of 4 elements (Si, Ca, Cr and Fe) and
subsequent re-calculations of the atmospheric structure, we derived a new model
atmosphere of alpha Cir, which is consistent with the inferred atmospheric
chemistry of the star. We find Teff=7500 K, logg=4.1, and demonstrate that
chemical stratification has a noticeable impact on the model structure and
modifies the formation of the hydrogen Balmer lines. Our spectroscopically
determined Teff of alpha Cir agrees with the fundamental effective temperature
of this star. This shows that temperatures inferred in detailed spectroscopic
analyses of cool magnetic CP stars are not affected by a large systematic bias.Comment: 14 pages, 11 figures; accepted for publication in Astronomy &
Astrophysic
Immunometabolic Markers in a Small Patient Cohort Undergoing Immunotherapy
Although the discovery of immune checkpoints was hailed as a major breakthrough in can cer therapy, generating a sufficient response to immunotherapy is still limited. Thus, the objective of
this exploratory, hypothesis-generating study was to identify potentially novel peripheral biomarkers
and discuss the possible predictive relevance of combining scarcely investigated metabolic and hor monal markers with immune subsets. Sixteen markers that differed significantly between responders
and non-responders were identified. In a further step, the correlation with progression-free survival
(PFS) and false discovery correction (Benjamini and Hochberg) revealed potential predictive roles
for the immune subset absolute lymphocyte count (rs = 0.51; p = 0.0224 *), absolute basophil count
(rs = 0.43; p = 0.04 *), PD-1+ monocytes (rs = −0.49; p = 0.04 *), hemoglobin (rs = 0.44; p = 0.04 *),
metabolic markers LDL (rs = 0.53; p = 0.0224 *), free androgen index (rs = 0.57; p = 0.0224 *) and CRP
(rs = −0.46; p = 0.0352 *). The absolute lymphocyte count, LDL and free androgen index were the
most significant individual markers, and combining the immune subsets with the metabolic markers
into a biomarker ratio enhanced correlation with PFS (rs = −0.74; p ≤ 0.0001 ****). In summary, in
addition to well-established markers, we identified PD-1+ monocytes and the free androgen index as
potentially novel peripheral markers in the context of immunotherapy. Furthermore, the combination
of immune subsets with metabolic and hormonal markers may have the potential to enhance the
power of future predictive scores and should, therefore, be investigated further in larger trials
Chemical stratification in the atmosphere of Ap star HD 133792. Regularized solution of the vertical inversion problem
High spectral resolution studies of cool Ap stars reveal conspicuous
anomalies of the shape and strength of many absorption lines. This is a
signature of large atmospheric chemical gradients produced by the selective
radiative levitation and gravitational settling of chemical species. Here we
present a new approach to mapping the vertical chemical structures in stellar
atmospheres. We have developed a regularized chemical inversion procedure that
uses all information available in high-resolution stellar spectra. The new
technique for the first time allowed us to recover chemical profiles without
making a priori assumptions about the shape of chemical distributions. We have
derived average abundances and applied the vertical inversion procedure to the
high-resolution VLT UVES spectra of the weakly magnetic, cool Ap star HD
133792. Our analysis yielded improved estimates of the atmospheric parameters
of HD 133792. We show that this star has negligible vsini and the mean magnetic
field modulus =1.1+/-0.1 kG. We have derived average abundances for 43 ions
and obtained vertical distributions of Ca, Si, Mg, Fe, Cr, and Sr. All these
elements except Mg show high overabundance in the deep layers and solar or
sub-solar composition in the upper atmosphere of HD 133792. In contrast, the Mg
abundance increases with height. We find that transition from the
metal-enhanced to metal-depleted zones typically occurs in a rather narrow
range of depths in the atmosphere of HD 133792. Based on the derived
photospheric abundances, we conclude that HD 133792 belongs to the rare group
of evolved cool Ap stars, which possesses very large Fe-peak enhancement, but
lacks a prominent overabundance of the rare-earth elements.Comment: Accepted by A&A; 12 pages, 9 figure
The brain's response to pleasant touch: an EEG investigation of tactile caressing
Somatosensation as a proximal sense can have a strong impact on our attitude toward physical objects and other human beings. However, relatively little is known about how hedonic valence of touch is processed at the cortical level. Here we investigated the electrophysiological correlates of affective tactile sensation during caressing of the right forearm with pleasant and unpleasant textile fabrics. We show dissociation between more physically driven differential brain responses to the different fabrics in early somatosensory cortex - the well-known mu-suppression (10-20 Hz) - and a beta-band response (25-30 Hz) in presumably higher-order somatosensory areas in the right hemisphere that correlated well with the subjective valence of tactile caressing. Importantly, when using single trial classification techniques, beta-power significantly distinguished between pleasant and unpleasant stimulation on a single trial basis with high accuracy. Our results therefore suggest a dissociation of the sensory and affective aspects of touch in the somatosensory system and may provide features that may be used for single trial decoding of affective mental states from simple electroencephalographic measurements
Salvage HLA-haploidentical hematopoietic stem cell transplantation with post-transplant cyclophosphamide for graft failure in non-malignant disorders
Graft failure requires urgent salvage HSCT, but there is no universally accepted approach for this situation. We investigated T-cell replete haploidentical HSCT with post-transplantation cyclophosphamide following serotherapy-based, radiation-free, reduced intensity conditioning in children with non-malignant disorders who had rejected their primary graft. Twelve patients with primary or secondary graft failure received T-cell replete bone marrow grafts from haploidentical donors and post-transplantation cyclophosphamide. The recommended conditioning regimen comprised rituximab 375 mg/m2, alemtuzumab 0.4 mg/kg, fludarabine 150 mg/m2, treosulfan 20–24 g/m2 and cyclophosphamide 29 mg/kg. After a median follow-up of 26 months (7–95), eleven of twelve patients (92%) are alive and well with complete donor chimerism in ten. Neutrophil and platelet engraftment were observed in all patients after a median of 18 days (15–61) and 39 days (15–191), respectively. Acute GVHD grade I was observed in 1/12 patients (8%) and mild chronic GVHD in 1/12 patients (8%). Viral reactivations and disease were frequent complications at 75% and 42%, respectively, but no death from infectious causes occurred. In summary, this retrospective analysis demonstrates that a post-transplantation cyclophosphamide-based HLA-haploidentical salvage HSCT after irradiation-free conditioning results in excellent engraftment and overall survival in children with non-malignant diseases
The chemical abundance analysis of normal early A- and late B-type stars
Modern spectroscopy of early-type stars often aims at studying complex
physical phenomena. Comparatively less attention is paid to identifying and
studying the "normal" A- and B-type stars and testing how the basic atomic
parameters and standard spectral analysis allow one to fit the observations. We
wish to stablish whether the chemical composition of the solar photosphere can
be regarded as a reference for early A- and late B-type stars. We have obtained
optical high-resolution, high signal-to-noise ratio spectra of three slowly
rotating early-type stars (HD 145788, 21 Peg and pi Cet) that show no obvious
sign of chemical peculiarity, and performed a very accurate LTE abundance
analysis of up to 38 ions of 26 elements (for 21 Peg), using a vast amount of
spectral lines visible in the spectral region covered by our spectra. We
provide an exhaustive description of the abundance characteristics of the three
analysed stars with a critical review of the line parameters used to derive the
abundances. We compiled a table of atomic data for more than 1100 measured
lines that may be used in the future as a reference. The abundances we obtained
for He, C, Al, S, V, Cr, Mn, Fe, Ni, Sr, Y, and Zr are compatible with the
solar ones derived with recent 3D radiative-hydrodynamical simulations of the
solar photosphere. The abundances of the remaining studied elements show some
degree of discrepancy compared to the solar photosphere. Those of N, Na, Mg,
Si, Ca, Ti, and Nd may well be ascribed to non-LTE effects; for P, Cl, Sc and
Co, non-LTE effects are totally unknown; O, Ne, Ar, and Ba show discrepancies
that cannot be ascribed to non-LTE effects. The discrepancies obtained for O
(in two stars) and Ne agree with very recent non-LTE abundance analysis of
early B-type stars in the solar neighbourhood.Comment: Accepted for publication on Astronomy and Astrophysic
Prospective Newborn Screening for SCID in Germany: A First Analysis by the Pediatric Immunology Working Group (API)
Background: T-cell receptor excision circle (TREC)-based newborn screening (NBS) for severe combined immunodeficiencies (SCID) was introduced in Germany in August 2019. / Methods: Children with abnormal TREC-NBS were referred to a newly established network of Combined Immunodeficiency (CID) Clinics and Centers. The Working Group for Pediatric Immunology (API) and German Society for Newborn Screening (DGNS) performed 6-monthly surveys to assess the TREC-NBS process after 2.5Â years. / Results: Among 1.9 million screened newborns, 88 patients with congenital T-cell lymphocytopenia were identified (25 SCID, 17 leaky SCID/Omenn syndrome (OS)/idiopathic T-cell lymphocytopenia, and 46 syndromic disorders). A genetic diagnosis was established in 88%. Twenty-six patients underwent hematopoietic stem cell transplantation (HSCT), 23/26 within 4Â months of life. Of these, 25/26 (96%) were alive at last follow-up. Two patients presented with in utero onset OS and died after birth. Five patients with syndromic disorders underwent thymus transplantation. Eight syndromic patients deceased, all from non-immunological complications. TREC-NBS missed one patient, who later presented clinically, and one tracking failure occurred after an inconclusive screening result. / Conclusion: The German TREC-NBS represents the largest European SCID screening at this point. The incidence of SCID/leaky SCID/OS in Germany is approximately 1:54,000, very similar to previous observations from North American and European regions and countries where TREC-NBS was implemented. The newly founded API-CID network facilitates tracking and treatment of identified patients. Short-term HSCT outcome was excellent, but NBS and transplant registries will remain essential to evaluate the long-term outcome and to compare results across the rising numbers of TREC-NBS programs across Europe
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