Understanding the two-component sensing System of virulent bacteria

Report for the scientific sojourn carried out at the l’ Institute for Computational Molecular Science of the Temple University, United States, from 2010 to 2012. Two-component systems (TCS) are used by pathogenic bacteria to sense the environment within a host and activate mechanisms related to virulence and antimicrobial resistance. A prototypical example is the PhoQ/PhoP system, which is the major regulator of virulence in Salmonella. Hence, PhoQ is an attractive target for the design of new antibiotics against foodborne diseases. Inhibition of the PhoQ-mediated bacterial virulence does not result in growth inhibition, presenting less selective pressure for the generation of antibiotic resistance. Moreover, PhoQ is a histidine kinase (HK) and it is absent in animals. Nevertheless, the design of satisfactory HK inhibitors has been proven to be a challenge. To compete with the intracellular ATP concentrations, the affinity of a HK inhibidor must be in the micromolar-nanomolar range, whereas the current lead compounds have at best millimolar affinities. Moreover, the drug selectivity depends on the conformation of a highly variable loop, referred to as the “ATP-lid, which is difficult to study by X-Ray crystallography due to its flexibility. I have investigated the binding of different HK inhibitors to PhoQ. In particular, all-atom molecular dynamics simulations have been combined with enhanced sampling techniques in order to provide structural and dynamic information of the conformation of the ATP-lid. Transient interactions between these drugs and the ATP-lid have been identified and the free energy of the different binding modes has been estimated. The results obtained pinpoint the importance of protein flexibility in the HK-inhibitor binding, and constitute a first step in developing more potent and selective drugs. The computational resources of the hosting institution as well as the experience of the members of the group in drug binding and free energy methods have been crucial to carry out this work.

A genomic analysis identifies a novel component in the genetic structure of sub-Saharan African populations

Studies of large sets of SNP data have proven to be a powerful tool in the analysis of the genetic structure of human populations. In this work, we analyze genotyping data for 2,841 SNPs in 12 Sub-Saharan African populations, including a previously unsampled region of south-eastern Africa (Mozambique). We show that robust results in a world-wide perspective can be obtained when analyzing only 1,000 SNPs. Our main results both confirm the results of previous studies, and show new and interesting features in Sub-Saharan African genetic complexity. There is a strong differentiation of Nilo-Saharans, much beyond what would be expected by geography. Hunter-gatherer populations (Khoisan and Pygmies) show a clear distinctiveness with very intrinsic Pygmy (and not only Khoisan) genetic features. Populations of the West Africa present an unexpected similarity among them, possibly the result of a population expansion. Finally, we find a strong differentiation of the south-eastern Bantu population from Mozambique, which suggests an assimilation of a pre-Bantu substrate by Bantu speakers in the region.

Impedance boundary conditions for pseudo-spectral time-domain methods in room acoustics

The pseudo-spectral time-domain (PSTD) method is an alternative time-marching method to classicalleapfrog finite difference schemes in the simulation of wave-like propagating phenomena. It is basedon the fundamentals of the Fourier transform to compute the spatial derivatives of hyperbolic differential equations. Therefore, it results in an isotropic operator that can be implemented in an efficient way for room acoustics simulations. However, one of the first issues to be solved consists on modeling wallabsorption. Unfortunately, there are no references in the technical literature concerning to that problem. In this paper, assuming real and constant locally reacting impedances, several proposals to overcome this problem are presented, validated and compared to analytical solutions in different scenarios.

Impedance boundary conditions for pseudo-spectral time-domain methods in room acoustics

The Pseudo-Spectral Time Domain (PSTD) method is an alternative time-marching method to classical leapfrog finite difference schemes inthe simulation of wave-like propagating phenomena. It is based on the fundamentals of the Fourier transform to compute the spatial derivativesof hyperbolic differential equations. Therefore, it results in an isotropic operator that can be implemented in an efficient way for room acousticssimulations. However, one of the first issues to be solved consists on modeling wall absorption. Unfortunately, there are no references in thetechnical literature concerning to that problem. In this paper, assuming real and constant locally reacting impedances, several proposals toovercome this problem are presented, validated and compared to analytical solutions in different scenarios.

A unified treatment of optimum pilot overhead in multipath fading channels

The optimization of the pilot overhead in single-user wireless fading channels is investigated, and the dependence of this overhead on various system parameters of interest (e.g., fading rate, signal-to-noise ratio) is quantified. The achievable pilot-based spectral efficiency is expanded with respect to the fading rate about the no-fading point, which leads to an accurate order expansion for the pilot overhead. This expansion identifies that the pilot overhead, as well as the spectral efficiency penalty with respect to a reference system with genie-aided CSI (channel state information) at the receiver, depend on the square root of the normalized Doppler frequency. It is also shown that the widely-used block fading model is a special case of more accurate continuous fading models in terms of the achievable pilot-based spectral efficiency. Furthermore, it is established that the overhead optimization for multiantenna systems is effectively the same as for single-antenna systems with the normalized Doppler frequency multiplied by the number of transmit antennas.

Applying recommendations to aligncompetences, methodology and assessment in Telematics, Computing and Electronic Engineering courses

The alignment between competences, teaching-learning methodologies and assessment is a key element of the European Higher Education Area. This paper presents the efforts carried out by six Telematics, Computer Science and Electronic Engineering Education teachers towards achieving this alignment in their subjects. In a joint work with pedagogues, a set of recommended actions were identified. A selection of these actions were applied and evaluated in the six subjects. The cross-analysis of the results indicate that the actions allow students to better understand the methodologies and assessment planned for the subjects, facilitate (self-) regulation and increase students’ involvement in the subjects.

Mutual information of IID complex Gaussian signals on block Rayleigh-faded channels

We present a method to compute, quickly and efficiently, the mutual information achieved by an IID (independent identically distributed) complex Gaussian signal on a block Rayleigh-faded channel without side information at the receiver. The method accommodates both scalar and MIMO (multiple-input multiple-output) settings. Operationally, this mutual information represents the highest spectral efficiency that can be attained using Gaussiancodebooks. Examples are provided that illustrate the loss in spectral efficiency caused by fast fading and how that loss is amplified when multiple transmit antennas are used. These examples are further enriched by comparisons with the channel capacity under perfect channel-state information at the receiver, and with the spectral efficiency attained by pilot-based transmission.

Per-antenna rate and power control for MIMO layered architectures in the low- and high-power regimes

In a MIMO layered architecture, several codewordsare transmitted from a multiplicity of antennas. Although thespectral efficiency is maximized if the rates of these codewordsare separately controlled, the feedback rate within the linkadaptation loop is reduced if they are constrained to be identical.This poses a direct tradeoff between performance andfeedback overhead. This paper provides analytical expressionsthat quantify the difference in spectral efficiency between bothapproaches for arbitrary numbers of antennas. Specifically, thecharacterization takes place in the realm of the low- and highpowerregimes via expansions that are shown to have a widerange of validity.In addition, the possibility of adjusting the transmit powerof each codeword individually is considered as an alternative tothe separate control of their rates. Power allocation, however,turns out to be inferior to rate control within the context of thisproblem.

Mutual Information of IID complex Gaussian signals on block Rayleigh-faded channels

We present a method to compute, quickly and efficiently, the mutual information achieved by an IID (independent identically distributed) complex Gaussian signal on a block Rayleigh-faded channel without side information at the receiver. The method accommodates both scalar and MIMO (multiple-input multiple-output) settings. Operationally, this mutual information represents the highest spectral efficiency that can be attained using Gaussiancodebooks. Examples are provided that illustrate the loss in spectral efficiency caused by fast fading and how that loss is amplified when multiple transmit antennas are used. These examples are further enriched by comparisons with the channel capacity under perfect channel-state information at the receiver, and with the spectral efficiency attained by pilot-based transmission.

Marco metodológico para la definición de un perfil profesional en educación superior = Methodological framework for the definition of a professional profile in higher education

En el marco del Espacio Europeo de Educación Superior 1 se inscriben innumerables acciones que están desarrollando todas las universidades europeas con la intención de llegar al 2010 con un bagaje lo suficientemente importante como para afrontar este cambio con entereza y sobretodo conservando (o incrementando) la calidad de los procesos de enseñanza- aprendizaje que hasta el momento han predominado. Dentro de este amplio proceso de transformación se encuentra el diseño de los nuevos Grados que brinda la oportunidad de replantear los planes de estudios, por tanto, la organización de las asignaturas, estructura de los contenidos, metodologías y sistemas de evaluación. Toda esta reflexión debe girar, a nuestro entender, alrededor de tres núcleos que se encuentran en estado deinterdependencia: los escenarios profesionales, los perfiles profesionales y las competencias que en ellos se inscriben.Para poder plantear los nuevos Grados en coherencia con la era del EEES debe hacerse un análisis minucioso de los perfil profesionales demandados por el mercado de trabajo que, al fin y al cabo será el destino de los profesionales que se forman en nuestras universidades, es por ello, que la tarea de definir el perfil profesional a priori del diseño de los nuevos Grados resulta una máxima para garantizar la calidad de estos. En este trabajo se presenta un ejemplo de metodología a seguir para la definición de un perfil profesional en Educación Superior, concretamente, el del Ingeniero TIC mediante el Análisis Funcional.

What is the value of joint processing of pilots and data in block-fading channels?

The spectral efficiency achievable with joint processing of pilot and data symbol observations is compared with that achievable through the conventional (separate) approach of first estimating the channel on the basis of the pilot symbols alone, and subsequently detecting the datasymbols. Studied on the basis of a mutual information lower bound, joint processing is found to provide a non-negligible advantage relative to separate processing, particularly for fast fading. It is shown that, regardless of the fading rate, only a very small number of pilot symbols (at most one per transmit antenna and per channel coherence interval) shouldbe transmitted if joint processing is allowed.

Optimum pilot overhead in wireless communication: a unified treatment of continuous and block-fading channels

The optimization of the pilot overhead in wireless fading channels is investigated, and the dependence of this overhead on various system parameters of interest (e.g., fading rate, signal-to-noise ratio) is quantified. The achievable pilot-based spectral efficiency is expanded with respect to the fading rate about the no-fading point, which leads to an accurate order expansion for the pilot overhead. This expansion identifies that the pilot overhead, as well as the spectral efficiency penalty with respect to a reference system with genie-aided CSI (channel state information) at the receiver, depend on the square root of the normalized Doppler frequency. It is also shown that the widely-usedblock fading model is a special case of more accurate continuous fading models in terms of the achievable pilot-based spectral efficiency. Furthermore, it is established that the overhead optimization for multiantenna systems is effectively the same as for single-antenna systems with thenormalized Doppler frequency multiplied by the number of transmit antennas.

The impact of labour market status on second and higher-order births. A comparative study of Denmark, Italy, Spain and United Kingdom

This paper investigates the effects of women‘s labour force participation on fertility, as well as the effects of the combined labour force participation of both members of a couple. It specifically focuses on such dimensions as unemployment, earnings, temporary contracts and part-time jobs, and it shows that their effects differ in accordance with national institutions and labour market regulations. Event-history methods and a longitudinal sample of the European Community Household Panel are used in the analyses, concerning the years 1993-2000. The results show that labour market insecurity of one or both members of a couple has a particularly strong impact in reducing birth rates in the Southern European countries studied. The more conventional model of men’s employment combined with housewifery has a positive impact on second or higher order births in United Kingdom, Spain and Italy, while in Denmark the effect is the opposite. These differences are consistent with different national models of combining parental responsibilities and participation by gender across the life course.

Overeducation among European university graduates : a comparative analysis ot its incidence and the importance of higher education differentiation

The incidence of over-education is here assessed by applying some standard subjective and objective indicators and a new skill-based indicator of over-education to the national samples of eight European countries in the REFLEX survey. With the exception of Spain, the results reveal that over-education is a minor risk amongst European tertiary graduates. Yet, the contrast between the standard indicators and the skill-based indicator reveals the existence of an over-education of a moderate kind in countries with high tertiary attainment rates (Norway, Finland and Netherlands). Such a type of over-education does not come to the surface when applying the standard indicators. Our results also reveal the importance of higher education differentiation (i.e. field of study and branch of higher education) for understanding the risk of over-education. Graduates from humanistic fields, bachelor courses and vocational colleges are more exposed to over-education, though their disadvantage varies across-nationally to a significant extent.

Power transformations in correspondence analysis

Power transformations of positive data tables, prior to applying the correspondence analysis algorithm, are shown to open up a family of methods with direct connections to the analysis of log-ratios. Two variations of this idea are illustrated. The first approach is simply to power the original data and perform a correspondence analysis this method is shown to converge to unweighted log-ratio analysis as the power parameter tends to zero. The second approach is to apply the power transformation to thecontingency ratios, that is the values in the table relative to expected values based on the marginals this method converges to weighted log-ratio analysis, or the spectral map. Two applications are described: first, a matrix of population genetic data which is inherently two-dimensional, and second, a larger cross-tabulation with higher dimensionality, from a linguistic analysis of several books.