Highly Emissive Eu(III) Probes for Biological Assays

Luminescent lanthanide complexes are important tools for molecular sensing and cellular staining due to their unique photophysical properties, including their long luminescence lifetimes that permit the use of time-gated measurements. However, a common drawback of such complexes is the non-specific binding associated with their low solubility in biological media. A new class of bright, highly water soluble, and negatively charged sulfonate or carboxylate derivatives of substituted aryl–alkynyl triazacyclononane complexes has been synthesised and their photophysical properties analysed. In addition, new synthetic methodologies have been explored for the introduction of solubilising moieties into the ligand system and for the incorporation of a linkage point for conjugation with biomolecules. Each complex exhibits extremely high quantum yields (up to 38 % in H2O), large extinction coefficients (60,000 M-1 cm-1) and long luminescence lifetimes (1.1 ms). Introduction of the charged solubilising moieties suppresses cellular uptake or adsorption to living cells, making them applicable for labelling and performing assays on membrane receptors. These Eu(III) complexes have been applied to monitor fluorescent ligand binding on cell-surface proteins (G-protein coupled receptors) with time-resolved fluorescence resonance energy transfer (TR-FRET) assays and TR-FRET microscopy. In addition, the introduction of a linkage point for conjugation on the macrocyclic ring provided complete control of the stereochemistry of the final complex. Direct and selective formation of chiral complexes was observed with > 95 % optical purity resulting in an intense circularly polarised luminescence signal

Qué es (y qué no es) la estadística, usos y abusos de una disciplina clave en la vida de los países y las personas

Qué es (y qué no es) la estadística, usos y abusos de una disciplina clave en la vida de los países y las persona

Concurrent Data Structures Linked in Time

Arguments about correctness of a concurrent data structure are typically carried out by using the notion of linearizability and specifying the linearization points of the data structure's procedures. Such arguments are often cumbersome as the linearization points' position in time can be dynamic (depend on the interference, run-time values and events from the past, or even future), non-local (appear in procedures other than the one considered), and whose position in the execution trace may only be determined after the considered procedure has already terminated. In this paper we propose a new method, based on a separation-style logic, for reasoning about concurrent objects with such linearization points. We embrace the dynamic nature of linearization points, and encode it as part of the data structure's auxiliary state, so that it can be dynamically modified in place by auxiliary code, as needed when some appropriate run-time event occurs. We name the idea linking-in-time, because it reduces temporal reasoning to spatial reasoning. For example, modifying a temporal position of a linearization point can be modeled similarly to a pointer update in separation logic. Furthermore, the auxiliary state provides a convenient way to concisely express the properties essential for reasoning about clients of such concurrent objects. We illustrate the method by verifying (mechanically in Coq) an intricate optimal snapshot algorithm due to Jayanti, as well as some clients

Hoare-style Specifications as Correctness Conditions for Non-linearizable Concurrent Objects

Designing scalable concurrent objects, which can be efficiently used on multicore processors, often requires one to abandon standard specification techniques, such as linearizability, in favor of more relaxed consistency requirements. However, the variety of alternative correctness conditions makes it difficult to choose which one to employ in a particular case, and to compose them when using objects whose behaviors are specified via different criteria. The lack of syntactic verification methods for most of these criteria poses challenges in their systematic adoption and application. In this paper, we argue for using Hoare-style program logics as an alternative and uniform approach for specification and compositional formal verification of safety properties for concurrent objects and their client programs. Through a series of case studies, we demonstrate how an existing program logic for concurrency can be employed off-the-shelf to capture important state and history invariants, allowing one to explicitly quantify over interference of environment threads and provide intuitive and expressive Hoare-style specifications for several non-linearizable concurrent objects that were previously specified only via dedicated correctness criteria. We illustrate the adequacy of our specifications by verifying a number of concurrent client scenarios, that make use of the previously specified concurrent objects, capturing the essence of such correctness conditions as concurrency-aware linearizability, quiescent, and quantitative quiescent consistency. All examples described in this paper are verified mechanically in Coq.Comment: 18 page

Automated glycan assembly of arabinomannan oligosaccharides from Mycobacterium tuberculosis

Arabinomannan (AM) polysaccharides are clinical biomarkers for Mycobacterium tuberculosis (MTB) infections due to their roles in the interaction with host cells and interference with macrophage activation. Collections of defined AM oligosaccharides can help to improve the understanding of these polysaccharides and the development of novel therapeutical and diagnostic agents. Automated glycan assembly (AGA) was employed to prepare the core structure of AM from MTB, containing α-(1,6)-Man, α-(1,5)-Ara, and α-(1,2)-Man linkages. The introduction of a capping step after each glycosylation and further optimized reaction conditions allowed for the synthesis of a series of oligosaccharides, ranging from hexa- to branched dodecasaccharides

Highlights from the 55th Bürgenstock conference on stereochemistry 2022

In May 2022, the 55th Bürgenstock Conference on Stereochemistry happened in person once again. This summary provides insight into the scientific themes discussed during the most recent meeting of this historic and multi-disciplinary conference. [Image: see text

Individualized Conformal

The problem of individualized prediction can be addressed using variants of conformal prediction, obtaining the intervals to which the actual values of the variables of interest belong. Here we present a method based on detecting the observations that may be relevant for a given question and then using simulated controls to yield the intervals for the predicted values. This method is shown to be adaptive and able to detect the presence of latent relevant variables.Comment: 17 pages, 7 tables, 7 figure

Exports, Terms of Trade and Economic Growth: Evidence from Countries with Different Level of Openness

This paper explores the effects of the ratio exports/GDP and the terms of trade on growth among countries with different level of development and openness. These effects vary among subgroups of countries with different openness and per development level. Nonetheless, in general the evidence seems to support the hypothesis stated in this research. In less developed or better endowed for export countries one or both of the explanatory variables mentioned above encourage for economic growth. Specifically, in advanced economies only the ratio exports/GDP is growth promoting when these are open, and have high per capita but small global GDP and/or relative advantages to be growth export-led. In turn, exports or and the terms of trade trends to promote growth in lower middle income countries. Unfortunately, the surprising results came from the poorest countries. They do not are benefited from a more favourable foreign environment. On the contrary, exports are not significant while an improvement in the terms of trade diminishes their growth

Volatility of the capital flows and structural breaks in Latin American and the Caribbean

En este trabajo, se estudia la presencia de quiebres estructurales en los flujos de capitales de 16 economías de Latinoamérica usando el test de raíz unitaria de Zivot y Andrews (1992). Para complementar el análisis, se utiliza el test de quiebres estructurales de Bai Perron (1998). Luego, se procede a analizar la posibilidad de contemporaneidad entre los quiebres encontrados y las crisis que tales países sufrieron en los últimos 40 años. Dichas crisis pueden ser de moneda, bancarias, domésticas o de deuda externa. Se encontraron muchos casos de contemporaneidad, especialmente con las crisis que ocurrieron al final de los 90.This paper studies the presence of structural breaks in the capital flows of sixteen economies of Latin America using the unit root test by Zivot and Andrews (1992). It is complemented by the structural break test by Bai Perron (1998). Afterwards, an analysis of the likelihood of contemporaneity between the breaks found and the crises the countries had suffered in the last forty years is presented. These crises were either of currency, banking, domestic and external debt type. Many cases of contemporaneity were found, especially with the crises that occurred at the end of the 90s.Instituto de Investigaciones Económica