1,375 research outputs found
Association of Intrauterine and Early-Life Exposures with Diagnosis of Uterine Leiomyomata by 35 Years of Age in the Sister Study
Importance of highly selective LC–MS/MS analysis for the accurate quantification of tamoxifen and its metabolites: focus on endoxifen and 4-hydroxytamoxifen
The antiestrogenic effect of tamoxifen is mainly attributable to the active metabolites endoxifen and 4-hydroxytamoxifen. This effect is assumed to be concentration-dependent and therefore quantitative analysis of tamoxifen and metabolites for clinical studies and therapeutic drug monitoring is increasing. We investigated the large discrepancies in reported mean endoxifen and 4-hydroxytamoxifen concentrations. Two published LC–MS/MS methods are used to analyse a set of 75 serum samples from patients treated with tamoxifen. The method from Teunissen et al. (J Chrom B, 879:1677–1685, 2011) separates endoxifen and 4-hydroxytamoxifen from other tamoxifen metabolites with similar masses and fragmentation patterns. The second method, published by Gjerde et al. (J Chrom A, 1082:6–14, 2005) however lacks selectivity, resulting in a factor 2–3 overestimation of the endoxifen and 4-hydroxytamoxifen levels, respectively. We emphasize the use of highly selective LC–MS/MS methods for the quantification of tamoxifen and its metabolites in biological samples
A new concept for the combination of optical interferometers and high-resolution spectrographs
The combination of high spatial and spectral resolution in optical astronomy
enables new observational approaches to many open problems in stellar and
circumstellar astrophysics. However, constructing a high-resolution
spectrograph for an interferometer is a costly and time-intensive undertaking.
Our aim is to show that, by coupling existing high-resolution spectrographs to
existing interferometers, one could observe in the domain of high spectral and
spatial resolution, and avoid the construction of a new complex and expensive
instrument. We investigate in this article the different challenges which arise
from combining an interferometer with a high-resolution spectrograph. The
requirements for the different sub-systems are determined, with special
attention given to the problems of fringe tracking and dispersion. A concept
study for the combination of the VLTI (Very Large Telescope Interferometer)
with UVES (UV-Visual Echelle Spectrograph) is carried out, and several other
specific instrument pairings are discussed. We show that the proposed
combination of an interferometer with a high-resolution spectrograph is indeed
feasible with current technology, for a fraction of the cost of building a
whole new spectrograph. The impact on the existing instruments and their
ongoing programs would be minimal.Comment: 27 pages, 9 figures, Experimental Astronomy; v2: accepted versio
A mathematical and computational review of Hartree-Fock SCF methods in Quantum Chemistry
We present here a review of the fundamental topics of Hartree-Fock theory in
Quantum Chemistry. From the molecular Hamiltonian, using and discussing the
Born-Oppenheimer approximation, we arrive to the Hartree and Hartree-Fock
equations for the electronic problem. Special emphasis is placed in the most
relevant mathematical aspects of the theoretical derivation of the final
equations, as well as in the results regarding the existence and uniqueness of
their solutions. All Hartree-Fock versions with different spin restrictions are
systematically extracted from the general case, thus providing a unifying
framework. Then, the discretization of the one-electron orbitals space is
reviewed and the Roothaan-Hall formalism introduced. This leads to a exposition
of the basic underlying concepts related to the construction and selection of
Gaussian basis sets, focusing in algorithmic efficiency issues. Finally, we
close the review with a section in which the most relevant modern developments
(specially those related to the design of linear-scaling methods) are commented
and linked to the issues discussed. The whole work is intentionally
introductory and rather self-contained, so that it may be useful for non
experts that aim to use quantum chemical methods in interdisciplinary
applications. Moreover, much material that is found scattered in the literature
has been put together here to facilitate comprehension and to serve as a handy
reference.Comment: 64 pages, 3 figures, tMPH2e.cls style file, doublesp, mathbbol and
subeqn package
Phenomenology and Cosmology of an Electroweak Pseudo-Dilaton and Electroweak Baryons
In many strongly-interacting models of electroweak symmetry breaking the
lowest-lying observable particle is a pseudo-Goldstone boson of approximate
scale symmetry, the pseudo-dilaton. Its interactions with Standard Model
particles can be described using a low-energy effective nonlinear chiral
Lagrangian supplemented by terms that restore approximate scale symmetry,
yielding couplings of the pseudo-dilaton that differ from those of a Standard
Model Higgs boson by fixed factors. We review the experimental constraints on
such a pseudo-dilaton in light of new data from the LHC and elsewhere. The
effective nonlinear chiral Lagrangian has Skyrmion solutions that may be
identified with the `electroweak baryons' of the underlying
strongly-interacting theory, whose nature may be revealed by the properties of
the Skyrmions. We discuss the finite-temperature electroweak phase transition
in the low-energy effective theory, finding that the possibility of a
first-order electroweak phase transition is resurrected. We discuss the
evolution of the Universe during this transition and derive an
order-of-magnitude lower limit on the abundance of electroweak baryons in the
absence of a cosmological asymmetry, which suggests that such an asymmetry
would be necessary if the electroweak baryons are to provide the cosmological
density of dark matter. We revisit estimates of the corresponding
spin-independent dark matter scattering cross section, with a view to direct
detection experiments.Comment: 34 pages, 4 figures, additional references adde
Polymorphism rs4919510:C>G in Mature Sequence of Human MicroRNA-608 Contributes to the Risk of HER2-Positive Breast Cancer but Not Other Subtypes
BACKGROUND: A few polymorphisms are located in the mature microRNA sequences. Such polymorphisms could directly affect the binding of microRNA to hundreds of target mRNAs. It remains unknown whether rs4919510:C>G located in the mature miR-608 alters breast cancer susceptibility. METHODS: The association of rs4919510:C>G with risk and pathologic features of breast cancer were investigated in two independent case-control studies, the first set including 1,138 sporadic breast cancer patients (including 927 invasive ductal carcinoma patients, 777 of them with known subtypes: 496 luminal-like, 133 HER2-positive, and 148 triple-negative) and 1,434 community-based controls, and the second set including 294 familial/early-onset breast cancer patients and 500 hospital-based cancer-free controls. Odds ratios (ORs) were estimated by logistic regression. Predicted targets of miR-608 and complementary sequences containing rs4919510:C>G were surveyed to reveal potential pathological mechanism. RESULTS: In the first set, although rs4919510:C>G was unrelated to breast cancer in general patients, variant genotypes (CG/GG) were specifically associated with increased risk of HER2-positive subtype (Adjusted OR = 1.97, 95% CI, 1.34-2.90 in the recessive model). Variant G-allele was the risk allele with OR of 1.62 (95% CI, 1.23-2.15). Patients carrying GG-genotype also had larger HER2-positive tumors (P for Kruskal-Wallis test = 0.006). The relationship between rs4919510:C>G and risk of HER2-positive subgroup was validated in the second set (Bonferroni corrected P = 0.06). The adjusted combined OR (total 164 HER2-positive cases) in the recessive model was 1.97 (95% CI, 1.43-2.72) for GG genotype (corrected P = 1.1 × 10(-4)). Bioinformatic analysis indicated that, HSF1, which is required for HER2-induced tumorigenesis, might be a target of miR-608. The minimum free-energy of ancestral-miR-608 (C-allele) binding to HSF1 is -35.9 kcal/mol, while that of variant-form (G-allele) is -31.5 kcal/mol, indicating a lower affinity of variant-miR-608 to HSF1 mRNA. CONCLUSION: rs4919510:C>G in mature miR-608 may influence HER2-positive breast cancer risk and tumor proliferation
A Genome-Wide Linkage Scan for Distinct Subsets of Schizophrenia Characterized by Age at Onset and Neurocognitive Deficits
As schizophrenia is genetically and phenotypically heterogeneous, targeting genetically informative phenotypes may help identify greater linkage signals. The aim of the study is to evaluate the genetic linkage evidence for schizophrenia in subsets of families with earlier age at onset or greater neurocognitive deficits.Patients with schizophrenia (n = 1,207) and their first-degree relatives (n = 1,035) from 557 families with schizophrenia were recruited from six data collection field research centers throughout Taiwan. Subjects completed a face-to-face semi-structured interview, the Continuous Performance Test (CPT), the Wisconsin Card Sorting Test, and were genotyped with 386 microsatellite markers across the genome.A maximum nonparametric logarithm of odds (LOD) score of 4.17 at 2q22.1 was found in 295 families ranked by increasing age at onset, which had significant increases in the maximum LOD score compared with those obtained in initial linkage analyses using all available families. Based on this subset, a further subsetting by false alarm rate on the undegraded and degraded CPT obtained further increase in the nested subset-based LOD on 2q22.1, with a score of 7.36 in 228 families and 7.71 in 243 families, respectively.We found possible evidence of linkage on chromosome 2q22.1 in families of schizophrenia patients with more CPT false alarm rates nested within the families with younger age at onset. These results highlight the importance of incorporating genetically informative phenotypes in unraveling the complex genetics of schizophrenia
Asteroseismology and Interferometry
Asteroseismology provides us with a unique opportunity to improve our
understanding of stellar structure and evolution. Recent developments,
including the first systematic studies of solar-like pulsators, have boosted
the impact of this field of research within Astrophysics and have led to a
significant increase in the size of the research community. In the present
paper we start by reviewing the basic observational and theoretical properties
of classical and solar-like pulsators and present results from some of the most
recent and outstanding studies of these stars. We centre our review on those
classes of pulsators for which interferometric studies are expected to provide
a significant input. We discuss current limitations to asteroseismic studies,
including difficulties in mode identification and in the accurate determination
of global parameters of pulsating stars, and, after a brief review of those
aspects of interferometry that are most relevant in this context, anticipate
how interferometric observations may contribute to overcome these limitations.
Moreover, we present results of recent pilot studies of pulsating stars
involving both asteroseismic and interferometric constraints and look into the
future, summarizing ongoing efforts concerning the development of future
instruments and satellite missions which are expected to have an impact in this
field of research.Comment: Version as published in The Astronomy and Astrophysics Review, Volume
14, Issue 3-4, pp. 217-36
Prospective evaluation of stapled haemorrhoidopexy versus transanal haemorrhoidal dearterialisation for stage II and III haemorrhoids: three-year outcomes
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