47 research outputs found
Impairment of non-muscle myosin IIA in human CD4+ T cells contributes to functional deficits in the elderly.
Physiological aging imposes significant alterations in the repertoire of T cells and all associated functions. Although several studies have reported defects upon antigen-induced activation of T cells during aging, the molecular mechanisms that control T-cell receptor (TCR) downmodulation remain to be fully defined. While previous studies have assessed the role of F-actin in regulating activation-induced TCR internalization, few have delineated the roles of motor proteins, such as non-muscle myosin IIA (NMMIIA). In this study, we describe a series of experiments supporting the hypothesis that effective TCR downmodulation requires not only efficient reorganization of the actin cytoskeleton, but also functional NMMIIA. For the first time, we show that CD4(+) T cells from elderly human donors have dysfunctional NMMIIA that contributes to delaying activation-induced TCR internalization and impairing calcium mobilization. Additionally, our results demonstrate that chemical inhibition of NMMIIA in CD4(+) T cells from young donors also results in complete abrogation of TCR internalization, strongly supporting the fundamental role of NMMIIA in modulating this event. Recent observations that the generation of an efficient T-cell response requires migration prompted us to investigate whether NMMIIA also plays a regulatory role in CD4(+) T-cell migration. We show that chemical inhibition of NMMIIA downmodulates chemotactic migration in CD4(+) T cells from both young and elderly donors. Together, these data demonstrate a significant contribution of dysfunctional NMMIIA to TCR-mediated functional defects during agin
Bound on Lorentz- and CPT-Violating Boost Effects for the Neutron
A search for an annual variation of a daily sidereal modulation of the
frequency difference between co-located Xe and He Zeeman
masers sets a stringent limit on boost-dependent Lorentz and CPT violation
involving the neutron, consistent with no effect at the level of 150 nHz. In
the framework of the general Standard-Model Extension, the present result
provides the first clean test for the fermion sector of the symmetry of
spacetime under boost transformations at a level of GeV.Comment: 4 pages, 1 figur
Rotational and high-resolution infrared spectrum of HCN: global ro-vibrational analysis and improved line catalogue for astrophysical observations
HCN is an ubiquitous molecule in interstellar environments, from external
galaxies, to Galactic interstellar clouds, star forming regions, and planetary
atmospheres. Observations of its rotational and vibrational transitions provide
important information on the physical and chemical structure of the above
environments. We present the most complete global analysis of the spectroscopic
data of HCN. We have recorded the high-resolution infrared spectrum from
450 to 1350 cm, a region dominated by the intense and
fundamental bands, located at 660 and 500 cm, respectively, and their
associated hot bands. Pure rotational transitions in the ground and
vibrationally excited states have been recorded in the millimetre and
sub-millimetre regions in order to extend the frequency range so far considered
in previous investigations. All the transitions from the literature and from
this work involving energy levels lower than 1000 cm have been fitted
together to an effective Hamiltonian. Because of the presence of various
anharmonic resonances, the Hamiltonian includes a number of interaction
constants, in addition to the conventional rotational and vibrational l-type
resonance terms. The data set contains about 3400 ro-vibrational lines of 13
bands and some 1500 pure rotational lines belonging to 12 vibrational states.
More than 120 spectroscopic constants have been determined directly from the
fit, without any assumption deduced from theoretical calculations or
comparisons with similar molecules. An extensive list of highly accurate rest
frequencies has been produced to assist astronomical searches and data
interpretation. These improved data, have enabled a refined analysis of the
ALMA observations towards Sgr B2(N2).Comment: 35 pages, 14 figures, accepted for pubblication in ApJ Supplemen
Myeloid Diagnostic and Prognostic Markers of Immune Suppression in the Blood of Glioma Patients.
Although gliomas are confined to the central nervous system, their negative influence over the immune system extends to peripheral circulation. The immune suppression exerted by myeloid cells can affect both response to therapy and disease outcome. We analyzed the expansion of several myeloid parameters in the blood of low- and high-grade gliomas and assessed their relevance as biomarkers of disease and clinical outcome. Methods: Peripheral blood was obtained from 134 low- and high-grade glioma patients. CD14+, CD14+/p-STAT3+, CD14+/PD-L1+, CD15+ cells and four myeloid-derived suppressor cell (MDSC) subsets, were evaluated by flow cytometry. Arginase-1 (ARG1) quantity and activity was determined in the plasma. Multivariable logistic regression model was used to obtain a diagnostic score to discriminate glioma patients from healthy controls and between each glioma grade. A glioblastoma prognostic model was determined by multiple Cox regression using clinical and myeloid parameters. Results: Changes in myeloid parameters associated with immune suppression allowed to define a diagnostic score calculating the risk of being a glioma patient. The same parameters, together with age, permit to calculate the risk score in differentiating each glioma grade. A prognostic model for glioblastoma patients stemmed out from a Cox multiple analysis, highlighting the role of MDSC, p-STAT3, and ARG1 activity together with clinical parameters in predicting patient's outcome. Conclusions: This work emphasizes the role of systemic immune suppression carried out by myeloid cells in gliomas. The identification of biomarkers associated with immune landscape, diagnosis, and outcome of glioblastoma patients lays the ground for their clinical use
Ghost Condensation and a Consistent Infrared Modification of Gravity
We propose a theoretically consistent modification of gravity in the
infrared, which is compatible with all current experimental observations. This
is an analog of Higgs mechanism in general relativity, and can be thought of as
arising from ghost condensation--a background where a scalar field \phi has a
constant velocity, = M^2. The ghost condensate is a new kind of
fluid that can fill the universe, which has the same equation of state, \rho =
-p, as a cosmological constant, and can hence drive de Sitter expansion of the
universe. However, unlike a cosmological constant, it is a physical fluid with
a physical scalar excitation, which can be described by a systematic effective
field theory at low energies. The excitation has an unusual low-energy
dispersion relation \omega^2 \sim k^4 / M^2. If coupled to matter directly, it
gives rise to small Lorentz-violating effects and a new long-range 1/r^2 spin
dependent force. In the ghost condensate, the energy that gravitates is not the
same as the particle physics energy, leading to the possibility of both sources
that can gravitate and antigravitate. The Newtonian potential is modified with
an oscillatory behavior starting at the distance scale M_{Pl}/M^2 and the time
scale M_{Pl}^2/M^3. This theory opens up a number of new avenues for attacking
cosmological problems, including inflation, dark matter and dark energy.Comment: 42 pages, LaTeX 2
Discrimination between uterine serous papillary carcinomas and ovarian serous papillary tumours by gene expression profiling.
High-grade ovarian serous papillary cancer (OSPC) and uterine serous papillary carcinoma (USPC) represent two histologically similar malignancies characterised by markedly different biological behavior and response to chemotherapy. Understanding the molecular basis of these differences may significantly refine differential diagnosis and management, and may lead to the development of novel, more specific and more effective treatment modalities for OSPC and USPC. We used an oligonucleotide microarray with probe sets complementary to >10 000 human genes to determine whether patterns of gene expression may differentiate OSPC from USPC. Hierarchical cluster analysis of gene expression in OSPC and USPC identified 116 genes that exhibited >two-fold differences (P<0.05) and that readily distinguished OSPC from USPC. Plasminogen activator inhibitor (PAI-2) was the most highly overexpressed gene in OSPC when compared to USPC, while c-erbB2 was the most strikingly overexpressed gene in USPC when compared to OSPC. Overexpression of the c-erbB2 gene and its expression product (i.e., HER-2/neu receptor) was validated by quantitative RT-PCR as well as by flow cytometry on primary USPC and OSPC, respectively. Immunohistochemical staining of serous tumour samples from which primary OSPC and USPC cultures were derived as well as from an independent set of 20 clinical tissue samples (i.e., 10 OSPC and 10 USPC) further confirmed HER-2/neu as a novel molecular diagnostic and therapeutic marker for USPC. Gene expression fingerprints have the potential to predict the anatomical site of tumour origin and readily identify the biologically more aggressive USPC from OSPC. A therapeutic strategy targeting HER-2/neu may be beneficial in patients harbouring chemotherapy-resistant USPC
Overview of the SME: Implications and Phenomenology of Lorentz Violation
The Standard Model Extension (SME) provides the most general
observer-independent field theoretical framework for investigations of Lorentz
violation. The SME lagrangian by definition contains all Lorentz-violating
interaction terms that can be written as observer scalars and that involve
particle fields in the Standard Model and gravitational fields in a generalized
theory of gravity. This includes all possible terms that could arise from a
process of spontaneous Lorentz violation in the context of a more fundamental
theory, as well as terms that explicitly break Lorentz symmetry. An overview of
the SME is presented, including its motivations and construction. Some of the
theoretical issues arising in the case of spontaneous Lorentz violation are
discussed, including the question of what happens to the Nambu-Goldstone modes
when Lorentz symmetry is spontaneously violated and whether a Higgs mechanism
can occur. A minimal version of the SME in flat Minkowski spacetime that
maintains gauge invariance and power-counting renormalizability is used to
search for leading-order signals of Lorentz violation. Recent Lorentz tests in
QED systems are examined, including experiments with photons, particle and
atomic experiments, proposed experiments in space and experiments with a
spin-polarized torsion pendulum.Comment: 40 pages, Talk presented at Special Relativity: Will it Survive the
Next 100 Years? Potsdam, Germany, February, 200
Gravitational physics with antimatter
The production of low-energy antimatter provides unique opportunities to
search for new physics in an unexplored regime. Testing gravitational
interactions with antimatter is one such opportunity. Here a scenario based on
Lorentz and CPT violation in the Standard- Model Extension is considered in
which anomalous gravitational effects in antimatter could arise.Comment: 5 pages, presented at the International Conference on Exotic Atoms
(EXA 2008) and the 9th International Conference on Low Energy Antiproton
Physics (LEAP 2008), Vienna, Austria, September 200
The HITRAN2020 Molecular Spectroscopic Database
The HITRAN database is a compilation of molecular spectroscopic parameters. It was established in the early 1970s and is used by various computer codes to predict and simulate the transmission and emission of light in gaseous media (with an emphasis on terrestrial and planetary atmospheres). The HITRAN compilation is composed of five major components: the line-by-line spectroscopic parameters required for high-resolution radiative-transfer codes, experimental infrared absorption cross-sections (for molecules where it is not yet feasible for representation in a line-by-line form), collision-induced absorption data, aerosol indices of refraction, and general tables (including partition sums) that apply globally to the data. This paper describes the contents of the 2020 quadrennial edition of HITRAN. The HITRAN2020 edition takes advantage of recent experimental and theoretical data that were meticulously validated, in particular, against laboratory and atmospheric spectra. The new edition replaces the previous HITRAN edition of 2016 (including its updates during the intervening years).
All five components of HITRAN have undergone major updates. In particular, the extent of the updates in the HITRAN2020 edition range from updating a few lines of specific molecules to complete replacements of the lists, and also the introduction of additional isotopologues and new (to HITRAN) molecules: SO, CH3F, GeH4, CS2, CH3I and NF3. Many new vibrational bands were added, extending the spectral coverage and completeness of the line lists. Also, the accuracy of the parameters for major atmospheric absorbers has been increased substantially, often featuring sub-percent uncertainties. Broadening parameters associated with the ambient pressure of water vapor were introduced to HITRAN for the first time and are now available for several molecules.
The HITRAN2020 edition continues to take advantage of the relational structure and efficient interface available at www.hitran.org and the HITRAN Application Programming Interface (HAPI). The functionality of both tools has been extended for the new edition
The HITRAN2020 molecular spectroscopic database
The HITRAN database is a compilation of molecular spectroscopic parameters. It was established in the early 1970s and is used by various computer codes to predict and simulate the transmission and emission of light in gaseous media (with an emphasis on terrestrial and planetary atmospheres). The HITRAN compilation is composed of five major components: the line-by-line spectroscopic parameters required for high-resolution radiative-transfer codes, experimental infrared absorption cross-sections (for molecules where it is not yet feasible for representation in a line-by-line form), collision-induced absorption data, aerosol indices of refraction, and general tables (including partition sums) that apply globally to the data. This paper describes the contents of the 2020 quadrennial edition of HITRAN. The HITRAN2020 edition takes advantage of recent experimental and theoretical data that were meticulously validated, in particular, against laboratory and atmospheric spectra. The new edition replaces the previous HITRAN edition of 2016 (including its updates during the intervening years). All five components of HITRAN have undergone major updates. In particular, the extent of the updates in the HITRAN2020 edition range from updating a few lines of specific molecules to complete replacements of the lists, and also the introduction of additional isotopologues and new (to HITRAN) molecules: SO, CH3F, GeH4, CS2, CH3I and NF3. Many new vibrational bands were added, extending the spectral coverage and completeness of the line lists. Also, the accuracy of the parameters for major atmospheric absorbers has been increased substantially, often featuring sub-percent uncertainties. Broadening parameters associated with the ambient pressure of water vapor were introduced to HITRAN for the first time and are now available for several molecules. The HITRAN2020 edition continues to take advantage of the relational structure and efficient interface available at www.hitran.org and the HITRAN Application Programming Interface (HAPI). The functionality of both tools has been extended for the new edition