Prediction of adverse neonatal outcome at admission for early-onset preeclampsia with severe features

Preeclampsia remains the leading cause of maternal morbidity and mortality. Consequently, research has focused on validating tools to predict maternal outcomes regarding clinical and biochemical features from the maternal compartment. However, preeclampsia also leads to neonatal complications due to placental insufficiency and prematurity, being the early-onset type associated with the poorest outcome. Hence, it is imperative to study whether these existing tools can predict adverse neonatal outcome.To assess the predictive value for adverse neonatal outcome of Doppler ultrasound, angiogenic factors and multi-parametric risk-score models in women with early-onset severe preeclampsia.This is a prospective cohort study of consecutive singleton pregnancies complicated by early-onset (developed before 34 week's gestation) severe preeclampsia.63 women with early-onset severe preeclampsia, 18 (28.6%) presented an adverse neonatal outcome. Placental growth factor (PlGF) showed the best discrimination between neonatal outcomes among angiogenic factors. PREP-L score is a multi-parametric risk-score for the prediction of complications in early-onset preeclampsia which includes maternal characteristics and clinical and analytical data obtained at admission. Good predictive values for the prediction of neonatal complications were found with the combination of PREP-L score with advanced Doppler (AUC ROC 0.9 95% CI 0.82-0.98]) and with PlGF levels (AUC ROC 0.91 [95% CI 0.84-0.98]).The combination of maternal risk scoring (PREP-L score) with angiogenic factors or fetal Doppler ultrasound at the time of diagnosis of early-onset preeclampsia with severe features performs well in predicting adverse neonatal outcome.Copyright © 2023 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved

Time-optimal CNOT between indirectly coupled qubits in a linear Ising chain

We give analytical solutions for the time-optimal synthesis of entangling gates between indirectly coupled qubits 1 and 3 in a linear spin chain of three qubits subject to an Ising Hamiltonian interaction with equal coupling $J$ plus a local magnetic field acting on the intermediate qubit. The energy available is fixed, but we relax the standard assumption of instantaneous unitary operations acting on single qubits. The time required for performing an entangling gate which is equivalent, modulo local unitary operations, to the $\mathrm{CNOT}(1, 3)$ between the indirectly coupled qubits 1 and 3 is $T=\sqrt{3/2} J^{-1}$, i.e. faster than a previous estimate based on a similar Hamiltonian and the assumption of local unitaries with zero time cost. Furthermore, performing a simple Walsh-Hadamard rotation in the Hlibert space of qubit 3 shows that the time-optimal synthesis of the $\mathrm{CNOT}^{\pm}(1, 3)$ (which acts as the identity when the control qubit 1 is in the state $\ket{0}$, while if the control qubit is in the state $\ket{1}$ the target qubit 3 is flipped as $\ket{\pm}\rightarrow \ket{\mp}$) also requires the same time $T$.Comment: 9 pages; minor modification

Immunomodulation induced by synthetic peptides derived from Staphylococcus aureus protein A

Peptides from 10 to 22 amino acids containing sequences encompassed by Staphylococcus aureus protein A were synthesized. Some of these peptides, when present in cultures of lymphomononuclear cells from healthy donors or from cancer patients (melanoma, breast carcinoma, non-Hodgkin lymphoma and renal cell carcinoma) promoted: (i) changes in the phenotype of the lymphomononuclear population, (ii) stimulation of monocytes (release of IL-1 and TNF-alpha), and (iii) an increase in cytotoxicity against K562, Daudi and HT-29 cells. Isolated monocytes responded also to those peptides with a release of IL-1 and TNF alpha and an increase of cytotoxicity against HT-29 cells. It was found that the active peptides had the following structural pattern: a length of at least 15 amino-acid residues with a proline at position 6, valine, leucine, isoleucine, glycine, alanine or lysine at position 2, and glutamic or aspartic acid at position 11. Replacement of Pro at position 6 with any other residue turned the peptide inactive. Replacement of residues at positions 2 and 11 with amino-acid residues other than those required for activity resulted in compounds with a marked decrease in the immunomodulating properties described, or lacking these properties altogether

Characterization of an immunologically conserved epitope from hepatitis C virus E2 glycoprotein recognized by HLA-A2 restricted cytotoxic T lymphocytes

BACKGROUND/AIMS: Identification of epitopes recognized by cytotoxic T lymphocytes (CTL) in hepatitis C virus (HCV) proteins is of importance because they can be used for vaccination, treatment of infection or monitoring of immune responses. Our purpose was to characterize new CTL epitopes in HCV structural proteins. METHODS: Peptides were synthesized and tested in HLA-A2 binding assays. Binder peptides were used to stimulate peripheral blood mononuclear cells from HCV+ patients and controls, and activity measured in chromium release and ELISPOT assays. RESULTS: Twenty binder peptides were found, and stimulation of HCV+ patient cells with nine peptides showing high binding ability led to the growth of CD8+ CTL recognizing peptide E2(614-622) in association with HLA-A2. Peptide E2(614-622) was recognized by 30% of HLA-A2+ patients with chronic HCV infection, but no responses were observed in control groups. Five peptides derived from region E2(614-622) from 26 different viral isolates bound to HLA-A2 molecules, and all of them but one, containing Phe at position 622, were recognized by E2(614-622) specific CTL. CONCLUSIONS: These results show that peptide E2(614-622) belongs to a highly conserved region of HCV E2, and might be a good candidate to induce anti-HCV CTL responses in HLA-A2+ subjects

Enhancement of peptide immunogenicity by insertion of a cathepsin B cleavage site between determinants recognized by B and T cells

The insertion of two lysine residues (cleavage sites of cathepsin B) at the boundary of a peptide recognized by B cells (BD) and a class-II- presentable sequence (TDh) enhanced the anti-BD antibody induction capacity of this type of peptide construct, as well as production of IL2. It is postulated that these lysines generate a neoprocessable site which helps in release of the TDh moiety from the construct, enabling its presentation to class II molecules, an essential step in clonal expansion of the antibody-producing B cell after internalization of the construct via the BD moiety

Specific and general HLA-DR binding motifs: comparison of algorithms

Using panels of peptides well characterized for their ability to bind to HLA DR1, DRB1*1101, or DRB1*0401 molecules, algorithms were deduced to predict binding to these molecules. These algorithms consist of blocks of 8 amino acids containing an amino acid anchor (Tyr, Phe, Trp, Leu, Ile, or Val) at position i and different amino acid combinations at positions i+2 to i+7 depending on the class II molecule. The sensitivity (% of correctly predicted binder peptides) and specificity (% of correctly predicted non-binder peptides) of these algorithms, were tested against different independent panels of peptides and compared to other algorithms reported in the literature. Similarly, using a panel of 232 peptides able to bind to one or more HLA molecules as well as 43 non-binder peptides, we deduced a general motif for the prediction of binding to HLA-DR molecules. The sensitivity and specificity of this general motif was dependent on the threshold score used for the predictions. For a score of 0.1, the sensitivity and specificity were 84.7% and 69.8%, respectively. This motif was validated against several panels of binder and non-binder peptides reported in the literature, as well as against 35, 15-mer peptides from hepatitis C virus core protein, that were synthesized and tested in a binding assay against a panel of 19 HLA-DR molecules. The sensitivities and specificities against these panels of peptides were similar to those attained against the panels used to deduce the algorithm. These results show that comparison of binder and non-binder peptides, as well as correcting for the relative abundance of amino acids in proteins, is a useful approach to deduce performing algorithms to predict binding to HLA molecules

Synthesis and anti-HIV-1 activities of new pyrimido[5,4-b]indoles

A set of new pyrimido[5,4-b]indole derivatives that are structurally related to some non-nucleside HIV-1 reverse transcriptase inhibitors were synthesized and biologically evaluated for their activity as inhibitors of wild and mutant HIV-1 RT types in an 'in vitro' recombinant HIV-1 RT screening assay, as well as anti-infectives in HLT4lacZ-1IIIB cells. Preliminary structure-activity relationships suggest that activity is promoted by simultaneous substitution in positions 2 and 4, especially when chains of alkyldiamine type are present, and by electron-releasing substituents (methoxy) in positions 7 and 8. The inactivity or the very low activity of title derivatives does not suggest interest in AIDS therapy

Identification of an antigenic epitope for helper T lymphocytes from carcinoembryonic antigen

PURPOSE: The product of the carcinoembryonic antigen (CEA) gene is an attractive candidate for T-cell-based immunotherapy because it is frequently expressed in epithelial solid carcinomas. Although many CEA peptide epitopes capable of stimulating CTLs have been identified, no MHC class II-restricted T helper epitope has yet been reported. Experimental Design: The amino acid sequence of CEA was examined for the presence of potential T helper epitopes, and candidate peptides were used to stimulate in vitro T-cell responses. RESULTS: We describe here that using an algorithm to identify promiscuous helper T-cell epitopes, a peptide of CEA occupying residue positions 653 to 667 (CEA(653-667)), was effective in inducing in vitro T helper responses in the context of the HLA-DR4, HLA-DR7, and HLA-DR 9 alleles. Most significantly, some of the peptide-reactive helper T lymphocytes were also capable of recognizing naturally processed antigen in the form of recombinant CEA protein or cell lysates from tumors that express CEA. Interestingly, the newly identified helper T-cell epitope was found to overlap with a previously described HLA-A24-restricted CTL epitope, CEA(652-660), which could facilitate the development of a therapeutic vaccine capable of eliciting both CTL and T helper responses in patients suffering from epithelial carcinomas. CONCLUSION: These results indicate that T helper lymphocytes are capable of recognizing CEA as a tumor antigen and that epitope CEA(653-667) could be used for immunotherapy against tumors expressing CEA

Structural and vibrational study of Bi2Se3 under high pressure

The structural and vibrational properties of bismuth selenide (Bi2Se3) have been studied by means of x-ray diffraction and Raman scattering measurements up to 20 and 30 GPa, respectively. The measurements have been complemented with ab initio total-energy and lattice dynamics calculations. Our experimental results evidence a phase transition from the low-pressure rhombohedral (R-3m) phase (B-Bi2Se3) with sixfold coordination for Bi to a monoclinic C2/m structure (B-Bi2Se3) with sevenfold coordination for Bi above 10 GPa. The equation of state and the pressure dependence of the lattice parameters and volume of a and B phases of Bi2Se3 are reported. Furthermore, the presence of a pressure-induced electronic topological phase transition in B-Bi2Se3 is discussed. Raman measurements evidence that Bi2Se3 undergoes two additional phase transitions around 20 and 28 GPa, likely toward a monoclinic C2/c and a disordered body-centered cubic structure with 8-fold and 9- or 10-fold coordination, respectively. These two high-pressure structures are the same as those recently found at high pressures in Bi2Te3 and Sb2Te3. On pressure release, Bi2Se3 reverts to the original rhombohedral phase after considerable hysteresis. Symmetries, frequencies, and pressure coefficients of the Raman and infrared modes in the different phases are reported and discussed.This work was done under financial support from Spanish Ministry of Science and Innovation under Projects No. MAT2007-66129, No. MAT2010-21270-C04-03/04, and No. CSD-2007-00045 and from the Valencian government under Project No. Prometeo/2011-035. It is also supported by the Ministry of Education, Youth and Sports of the Czech Republic Project No. MSM 0021627501