3,404 research outputs found
Классификация моделей комплексной оценки финансового состояния предприятия
There is an urgent need to develop reliable strategies for the rapid assembly of complex oligosaccharides. This paper presents a set of strategically selected orthogonal protecting groups, glycosyl donors modified by a (S)-phenylthiomethylbenzyl ether at C-2, and a glycosyl acceptor containing a fluorous tag, which makes it possible to rapidly prepare complex branched oligosaccharides of biological importance. The C-2 auxiliary controlled the 1,2-cis anomeric selectivity of the various galactosylations. The orthogonal protecting groups, 2-naphthylmethyl ether (Nap) and levulinic ester (Lev), made it possible to generate glycosyl acceptors and allowed the installation of a crowded branching point. After the glycosylations, the chiral auxiliary could be removed using acidic conditions, which was compatible with the presence of the orthogonal protecting groups Lev and Nap, thereby allowing the efficient installation of 1,2-linked glycosides. The light fluorous tag made it possible to purify the compounds by a simple filtration method using silica gel modified by fluorocarbons. The set of building blocks was successfully employed for the preparation of the carbohydrate moiety of the GPI anchor of Trypanosoma brucei, which is a parasite that causes sleeping sickness in humans and similar diseases in domestic animals
Probing the A1 to L10 Transformation in FeCuPt Using the First Order Reversal Curve Method
The A1- L10 phase transformation has been investigated in (001) FeCuPt thin
films prepared by atomic-scale multilayer sputtering and rapid thermal
annealing (RTA). Traditional x-ray diffraction is not always applicable in
generating a true order parameter, due to non-ideal crystallinity of the A1
phase. Using the first-order reversal curve (FORC) method, the A1 and L10
phases are deconvoluted into two distinct features in the FORC distribution,
whose relative intensities change with the RTA temperature. The L10 ordering
takes place via a nucleation-and-growth mode. A magnetization-based phase
fraction is extracted, providing a quantitative measure of the L10 phase
homogeneity.Comment: 17 pages, 5 figures, 4 page supplementary material (4 figures
Four-quark scatterings in QCD II
In [1], we initiated a program for the quantitative investigation of
dynamical chiral symmetry breaking and resonant bound states in QCD with the
functional renormalisation group, concentrating on the full infrared dynamics
of four-quark scatterings. In the present work we extend this study and take
into account a three-momentum channel approximation (-channel) for the
Fierz-complete four-quark vertices. We find that the four-quark vertex in this
approximation is quantitatively reliable. In particular, we have computed the
pion pole mass, pion decay constant, Bethe-Salpeter amplitudes, the quark mass
function and wave function. Our results confirm previous findings that low
energy effective theories only reproduce QCD quantitatively, if initiated with
a relatively low ultraviolet cutoff scale of the order of 500 MeV. The
quantitative description set up here paves the way for reliable quantitative
access to the resonance structure in QCD within the fRG approach to QCD.Comment: 20 pages, 19 figures; v2: minor typos correcte
Four-quark scatterings in QCD I
We investigate dynamical chiral symmetry breaking and the emergence of
mesonic bound states from the infrared dynamics of four-quark scatterings. Both
phenomena originate from the resonant scalar-pseudoscalar channel of the
four-quark scatterings, and we compute the functional renormalisation group
(fRG) flows of the Fierz-complete four-quark interaction of up and down quarks
with its channel momentum dependence. This is done in the isospin symmetric
case, also including the flow of the quark two-point function. This system can
be understood as the fRG analogues of the complete Bethe-Salpeter equations and
quark gap equation. The pole mass of the pion is determined from both direct
calculations of the four-quark flows in the Minkowski regime of momenta and the
analytic continuation based on results in the Euclidean regime, which are
consistent with each other.Comment: 26 pages, 20 figures, 3 tables; v2: minor typos correcte
Comparative global immune-related gene profiling of somatic cells, human pluripotent stem cells and their derivatives: implication for human lymphocyte proliferation.
Human pluripotent stem cells (hPSCs), including embryonic stem cells (ESCs) and induced PSCs (iPSCs), represent potentially unlimited cell sources for clinical applications. Previous studies have suggested that hPSCs may benefit from immune privilege and limited immunogenicity, as reflected by the reduced expression of major histocompatibility complex class-related molecules. Here we investigated the global immune-related gene expression profiles of human ESCs, hiPSCs and somatic cells and identified candidate immune-related genes that may alter their immunogenicity. The expression levels of global immune-related genes were determined by comparing undifferentiated and differentiated stem cells and three types of human somatic cells: dermal papilla cells, ovarian granulosa cells and foreskin fibroblast cells. We identified the differentially expressed genes CD24, GATA3, PROM1, THBS2, LY96, IFIT3, CXCR4, IL1R1, FGFR3, IDO1 and KDR, which overlapped with selected immune-related gene lists. In further analyses, mammalian target of rapamycin complex (mTOR) signaling was investigated in the differentiated stem cells following treatment with rapamycin and lentiviral transduction with specific short-hairpin RNAs. We found that the inhibition of mTOR signal pathways significantly downregulated the immunogenicity of differentiated stem cells. We also tested the immune responses induced in differentiated stem cells by mixed lymphocyte reactions. We found that CD24- and GATA3-deficient differentiated stem cells including neural lineage cells had limited abilities to activate human lymphocytes. By analyzing the transcriptome signature of immune-related genes, we observed a tendency of the hPSCs to differentiate toward an immune cell phenotype. Taken together, these data identify candidate immune-related genes that might constitute valuable targets for clinical applications
Biomarkers to assess right heart pressures in recipients of a heart transplant: a proof-of-concept study
Background: This proof-of-concept study investigated the feasibility of using biomarkers to monitor right heart pressures (RHP) in heart transplanted (HTx) patients.
Methods: In 298 patients, we measured 7.6 years post-HTx mean pressures in the right atrium (mRAP) and pulmonary artery (mPAP) and capillaries (mPCWP) along with plasma high-sensitivity troponin T (hsTnT), a marker of cardiomyocyte injury, and the multidimensional urinary classifiers HF1 and HF2, mainly consisting of dysregulated collagen fragments.
Results: In multivariable models, mRAP and mPAP increased with hsTnT (per 1-SD, +0.91 and +1.26 mm Hg; P < 0.0001) and with HF2 (+0.42 and +0.62 mm Hg; P ≤ 0.035), but not with HF1. mPCWP increased with hsTnT (+1.16 mm Hg; P < 0.0001), but not with HF1 or HF2. The adjusted odds ratios for having elevated RHP (mRAP, mPAP or mPCWP ≥10, ≥24, ≥17 mm Hg, respectively) were 1.99 for hsTnT and 1.56 for HF2 (P ≤ 0.005). In detecting elevated RHPs, areas under the curve were similar for hsTnT and HF2 (0.63 vs 0.65; P = 0.66). Adding hsTnT continuous or per threshold or HF2 continuous to a basic model including all covariables did not increase diagnostic accuracy (P ≥ 0.11), whereas adding HF2 per optimized threshold increased both the integrated discrimination (+1.92%; P = 0.023) and net reclassification (+30.3%; P = 0.010) improvement.
Conclusions: Correlating RHPs with noninvasive biomarkers in HTx patients is feasible. However, further refinement and validation of such biomarkers is required before their clinical application can be considered
Design of Diarylheptanoid Derivatives as Dual Inhibitors Against Class IIa Histone Deacetylase and β-amyloid Aggregation
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder with multiple etiologies. Beta-amyloid (Aβ) self-aggregation and overexpression of class IIa histone deacetylases (HDACs) are strongly implicated with AD pathogenesis. In this study, a series of novel diarylheptanoid derivatives were designed, synthesized and evaluated for use as dual Aβ self-aggregation and class IIa HDAC inhibitors. Among these compounds, 4j, 5c, and 5e displayed effective inhibitions for Aβ self-aggregation, HDAC5 activity and HDAC7 activity with IC50 values of <10 μM. The compounds contain three common features: (1) a catechol or pyrogallol moiety, (2) a carbonyl linker and (3) an aromatic ring that can function as an HDAC cap and create hydrophobic interactions with Aβ1-42. Furthermore, compounds 4j, 5c, and 5e showed no significant cytotoxicity to human neuroblastoma SH-SY5Y cells and also exhibited neuroprotective effect against H2O2-induced toxicity. Overall, these promising in vitro data highlighted compounds 4j, 5c, and 5e as lead compounds that are worthy for further investigation
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