Dealing with missing data under stratified sampling designs where strata are study domains.

A quick count seeks to estimate the voting trends of an election and communicate them to the population on the evening of the same day of the election. In quick counts, the sampling is based on a stratified design of polling stations. Voting information is gathered gradually, often with no guarantee of obtaining the complete sample or even information in all the strata. However, accurate interval estimates with partial information must be obtained. Furthermore, this becomes more challenging if the strata are additionally study domains. To produce partial estimates, two strategies are proposed: (1) a Bayesian model using a dynamic post-stratification strategy and a single imputation process defined after a thorough analysis of historic voting information; additionally, a credibility level correction is included to solve the underestimation of the variance and (2) a frequentist alternative that combines standard multiple imputation ideas with classic sampling techniques to obtain estimates under a missing information framework. Both solutions are illustrated and compared using information from the 2021 quick count. The aim was to estimate the composition of the Chamber of Deputies in Mexico.

Advancing Multicomponent Strategies to Macrobicyclic Peptides.

Macrocyclization of peptides is typically used to fix specific bioactive conformations and improve their pharmacological properties. Recently, macrobicyclic peptides have received special attention owing to their capacity to mimic protein structures or be key components of peptide-drug conjugates. Here, we describe the development of novel synthetic strategies for two distinctive types of peptide macrobicycles. A multicomponent macrocyclo-dimerization approach is introduced for the production of interconnected ß-turns, allowing two macrocyclic rings to be formed and dimerized in one pot. Also, an on-resin double stapling strategy is described for the assembly of lactam-bridged macrobicycles with stable tertiary folds.

Insights into the secondary structures of lactam N-substituted stapled peptides.

Stapled peptides derived from the Ugi macrocyclization comprise a special class of cyclopeptides with an N-substituted lactam bridge cross-linking two amino acid side chains. Herein we report a comprehensive analysis of the structural factors influencing the secondary structure of these cyclic peptides in solution. Novel insights into the s-cis/s-trans isomerism and the effect of N-functionalization on the conformation are revealed.

Improved Stability and Tunable Functionalization of Parallel ß-Sheets via Multicomponent N-Alkylation of the Turn Moiety.

In contrast to the myriad of methods available to produce α-helices and antiparallel ß-sheets in synthetic peptides, just a few are known for the construction of stable, non-cyclic parallel ß-sheets. Herein, we report an efficient on-resin approach for the assembly of parallel ß-sheet peptides in which the N-alkylated turn moiety enhances the stability and gives access to a variety of functionalizations without modifying the parallel strands. The key synthetic step of this strategy is the multicomponent construction of an N-alkylated turn using the Ugi reaction on varied isocyano-resins. This four-component process assembles the orthogonally protected turn fragment and incorporates handles serving for labeling/conjugation purposes or for reducing peptide aggregation. NMR and circular dichroism analyses confirm the better-structured and more stable parallel ß-sheets in the N-alkylated peptides compared to the non-functionalized variants.

Realización de un seminario práctico de toma de decisiones obstétricas con formato de concurso por equipos. Experiencia piloto con estudiantes de medicina / Practical seminar on obstetric decision-making with a team contest format. Pilot experience with medical students

Objetivo: Se presenta la experiencia piloto de un seminario de toma de decisiones obstétricas, cuyos objetivos son fomentar el trabajo en equipo, entrenar la toma de decisiones en obstetricia e incrementar el interés de los alumnos y su aprendizaje. El fin del estudio es evaluar la satisfacción del alumno sobre el seminario. Sujetos y métodos: El seminario se diseñó con un formato de concurso por equipos y se realizó con estudiantes de sexto curso de medicina de la Universidad Europea (Madrid, España). Los participantes en el seminario cumplimentaron una encuesta de satisfacción. Los alumnos fueron distribuidos en dos grupos: participantes y no participantes en el seminario. Se analizó la diferencia en la nota media del examen final entre ambos grupos. Resultados: Nueve de 23 estudiantes participaron en el seminario. Los alumnos participantes tuvieron un alto grado de satisfacción y se sintieron más motivados y preparados tanto para el estudio de la asignatura como para afrontar su examen final. Se objetivó un mayor rendimiento estadísticamente significativo en el examen final de la asignatura por parte de los participantes en el seminario, de manera que obtuvieron una media 1,03 puntos (sobre 10) superior que los alumnos que no asistieron al seminario, aunque tanto por el número de participantes como por un más que probable sesgo de selección no pueden extraerse conclusiones válidas al respecto. Conclusión: El seminario aumentó la motivación de los alumnos y fue satisfactorio para ellos

Aim: The present study shows the pilot experience of a seminar on obstetric decision making, whose objectives are to promote teamwork, train decision making in Obstetrics and increase the interest of the students and their learning. The purpose of the study is to evaluate the student's satisfaction with the seminar. Subjects and methods: The seminar was designed with a team contest format and was carried out with students of the sixth course of Medicine of the European University (Madrid, Spain). Participants in the seminar filled out a satisfaction survey. The students were divided into two groups: participants and non-participants in the seminar. The difference in the average qualification of the final exam between the two groups was analyzed. Results: Nine students of 23 participated in the seminar. The participating students had a high degree of satisfaction and felt more motivated and prepared both for the study of the subject and to face the final exam. Higher statistically significant performance was observed in the final exam by the participants in the seminar, so that they obtained 1.03 points on average (over 10) more than the students who did not attend the seminar, although for the number of participants and a probable selection bias, no valid conclusions can be drawn at this level. Conclusion: The seminar increased the motivation of the students and was very satisfactory for them

Macrocyclization of Peptide Side Chains by the Ugi Reaction: Achieving Peptide Folding and Exocyclic N-Functionalization in One Shot.

The cyclization of peptide side chains has been traditionally used to either induce or stabilize secondary structures (ß-strands, helices, reverse turns) in short peptide sequences. So far, classic peptide coupling, nucleophilic substitution, olefin metathesis, and click reactions have been the methods of choice to fold synthetic peptides by means of macrocyclization. This article describes the utilization of the Ugi reaction for the side chain-to-side chain and side chain-to-termini macrocyclization of peptides, thus enabling not only access to stable folded structures but also the incorporation of exocyclic functionalities as N-substituents. Analysis of the NMR-derived structures revealed the formation of helical turns, ß-bulges, and α-turns in cyclic peptides cross-linked at i, i + 3 and i, i + 4 positions, proving the folding effect of the multicomponent Ugi macrocyclization. Molecular dynamics simulation provided further insights on the stability and molecular motion of the side chain cross-linked peptides.

A multicomponent conjugation strategy to unique N-steroidal peptides: first evidence of the steroidal nucleus as a ß-turn inducer in acyclic peptides.

Constraining small peptides into specific secondary structures has been a major challenge in peptide ligand design. So far, the major solution for decreasing the conformational flexibility in small peptides has been cyclization. An alternative is the use of topological templates, which are able to induce and/or stabilize peptide secondary structures by means of covalent attachment to the peptide. Herein a multicomponent strategy and structural analysis of a new type of peptidosteroid architecture having the steroid as N-substituent of an internal amide bond is reported. The approach comprises the one-pot conjugation of two peptide chains (or amino acid derivatives) to aminosteroids by means of the Ugi reaction to give a unique family of N-steroidal peptides. The conjugation efficiency of a variety of peptide sequences and steroidal amines, as well as their consecutive head-to-tail cyclization to produce chimeric cyclopeptide-steroid conjugates, that is, macrocyclic lipopeptides, was assessed. Determination of the three-dimensional structure of an acyclic N-steroidal peptide in solution proved that the bulky, rigid steroidal template is capable of both increasing significantly the conformational rigidity, even in a peptide sequence as short as five amino acid residues, and inducing a ß-turn secondary structure even in the all-s-trans isomer. This report provides the first evidence of the steroid skeleton as ß-turn inducer in linear peptide sequences.

Conformational and NMR study of some furan derivatives by DFT methods.

4'-substituted neutral/protonated furfurylidenanilines and trans-styrylfurans are able to exist in two different conformations related to the rotation around the furan ring-bridge double bond. In this work, the equilibrium geometry and the corresponding rotational barrier of the benzene ring for each furan derivative conformation were calculated by DFT methods. The trend and shape of the rotational barrier are rationalized within natural bond orbitals as well as atoms-in-molecules approach. For the corresponding equilibrium geometries, (1)H and (13)C substituent induced shifts (SIS) were calculated and compared with experimental values. Calculated shielding constants are shown to be sensitive to the substituent effect through a linear fit with substituent's Hammett constants. An alternative approach was followed for assessing the effect of substituents over SIS through comparing the differences in isotropic shielding constants with NBO charges as well as with (1)H and (13)C experimental chemical shifts.

Combined nuclear magnetic resonance spectroscopy and molecular dynamics study of growth hormone releasing hexapeptide GHRP-6 and a cyclic analogue.

The Growth Hormone Releasing Hexapeptide, GHRP-6 was the first of a family of synthetic peptides that enhance the release of the Growth Hormone by the pituitary gland in a dose-dependent manner. Since its discovery, it has been used as a benchmark and starting point in numerous researches aiming to obtain new drugs. Complete resonance assignment of GHRP-6 NMR spectra in both open and cyclic forms are reported, showing some differences to random coil chemical shifts. Connectivities observed in the ROESY spectra indicate spatial proximity between the aromatic residues side-chains in both molecules, as well as between residues DPhe5 and Lys6 sidechains. An ensemble of 10 structures was generated for each one of the molecules, showing RMSD values indicative of nonrandom structures. Molecular Dynamics simulations, both with and without explicit solvent, were carried out for GHRP-6 and its cyclic analogue. Conformational analysis performed on the trajectories showed a nonrandom structure with a well preserved backbone. The presence of geometrical patterns resembling those typical of π-π interactions in both peptides, suggest that this kind of interactions may be relevant for the biological activity of GHRP-6. Same conclusion can be drawn from the spatial proximity of residues DPhe5 and Lys6 sidechains.

Variation in protein C(alpha)-related one-bond J couplings.

Four types of polypeptide (1)J(C alpha X) couplings are examined, involving the main-chain carbon C(alpha) and either of four possible substituents. A total 3105 values of (1)J(C alpha H alpha), (1)J(C alpha C beta), (1)J(C alpha C'), and (1)J(C alpha N') were collected from six proteins, averaging 143.4 +/- 3.3, 34.9 +/- 2.5, 52.6 +/- 0.9, and 10.7 +/- 1.2 Hz, respectively. Analysis of variances (ANOVA) reveals a variety of factors impacting on (1)J and ranks their relative statistical significance and importance to biomolecular NMR structure refinement. Accordingly, the spread in the (1)J values is attributed, in equal proportions, to amino-acid specific substituent patterns and to polypeptide-chain geometry, specifically torsions phi, psi, and chi(1) circumjacent to C(alpha). The (1)J coupling constants correlate with protein secondary structure. For alpha-helical phi, psi combinations, (1)J(C alpha H alpha) is elevated by more than one standard deviation (147.8 Hz), while both (1)J(C alpha N') and (1)J(C alpha C beta) fall short of their grand means (9.5 and 33.7 Hz). Rare positive phi torsion angles in proteins exhibit concomitant small (1)J(C alpha H alpha) and (1)J(C alpha N') (138.4 and 9.6 Hz) and large (1)J(C alpha C beta) (39.9 Hz) values. The (1)J(C alpha N') coupling varies monotonously over the phi torsion range typical of beta-sheet secondary structure and is largest (13.3 Hz) for phi around -160 degrees. All four coupling types depend on psi and thus help determine a torsion that is notoriously difficult to assess by traditional approaches using (3)J. Influences on (1)J stemming from protein secondary structure and other factors, such as amino-acid composition, are largely independent.