Robust estimation of stationary continuous-time ARMA models via indirect inference

In this paper we present a robust estimator for the parameters of a continuous-time ARMA(p,q) (CARMA(p,q)) process sampled equidistantly which is not necessarily Gaussian. Therefore, an indirect estimation procedure is used. It is an indirect estimation because we first estimate the parameters of the auxiliary AR(r) representation ($r\geq 2p-1$) of the sampled CARMA process using a generalized M- (GM-)estimator. Since the map which maps the parameters of the auxiliary AR(r) representation to the parameters of the CARMA process is not given explicitly, a separate simulation part is necessary where the parameters of the AR(r) representation are estimated from simulated CARMA processes. Then, the parameter which takes the minimum distance between the estimated AR parameters and the simulated AR parameters gives an estimator for the CARMA parameters. First, we show that under some standard assumptions the GM-estimator for the AR(r) parameters is consistent and asymptotically normally distributed. Next, we prove that the indirect estimator is consistent and asymptotically normally distributed as well using in the simulation part the asymptotically normally distributed LS-estimator. The indirect estimator satisfies several important robustness properties such as weak resistance, $\pi_{d_n}$-robustness and it has a bounded influence functional. The practical applicability of our method is demonstrated through a simulation study with replacement outliers and compared to the non-robust quasi-maximum-likelihood estimation method

The Bologna agreement is not suitable for medical education : a German view

Central elements of the Bologna declaration have been implemented in a huge variety of curricula in humanities, social sciences, natural sciences and engineering sciences at German universities. Overall the results have been nothing less than disastrous. Surprisingly, this seems to be the perfect time for German universities to talk about introducing a curriculum that is fully compatible with the Bologna declaration for medical education as well. However, German medical education does not have problems the Bologna declaration is intended to solve, such as quality, mobility, internationalization and employability. It is already in the Post-Bologna age

Community building and virtual teamwork in an online learning environment

In the world of OTIS, an online Internet School for occupational therapists, students from four European countries were encouraged to work collaboratively through problem based learning by interacting with each other in a virtual semi-immersive environment. This paper aims to explore the issues that there was little interaction between students from different tutorial groups and virtual teamwork developed in each of the cross cultural tutorial groups. Synchronous data from European students was captured during tutorial sessions and peer booked meetings and evidence suggests that communities of interest were established. It is possible to conclude that collaborative systems can be designed, which encourage students to build trust and teamwork in a cross cultural online learning environment. </p

On the origin of the cumulative semantic inhibition effect

We report an extension of the cumulative semantic inhibition effect found by Howard, Nickels, Coltheart, and Cole-Virtue (2006). Using more sensitive statistical analyses, we found a significant variation in the magnitude of the effect across categories. This variation cannot be explained by the naming speed of each category. In addition, using a sub-sample of the data, a second cumulative effect arouse for newly-defined supra-categories, over and above the effect of the original ones. We discuss these findings in terms of the representations that drive lexical access, and interpret them as supporting featural or distributed hypotheses

Fuzzy virtual ligands for virtual screening

A new method to bridge the gap between ligand and receptor-based methods in virtual screening (VS) is presented. We introduce a structure-derived virtual ligand (VL) model as an extension to a previously published pseudo-ligand technique [1]: LIQUID [2] fuzzy pharmacophore virtual screening is combined with grid-based protein binding site predictions of PocketPicker [3]. This approach might help reduce bias introduced by manual selection of binding site residues and introduces pocket shape information to the VL. It allows for a combination of several protein structure models into a single "fuzzy" VL representation, which can be used to scan screening compound collections for ligand structures with a similar potential pharmacophore. PocketPicker employs an elaborate grid-based scanning procedure to determine buried cavities and depressions on the protein's surface. Potential binding sites are represented by clusters of grid probes characterizing the shape and accessibility of a cavity. A rule-based system is then applied to project reverse pharmacophore types onto the grid probes of a selected pocket. The pocket pharmacophore types are assigned depending on the properties and geometry of the protein residues surrounding the pocket with regard to their relative position towards the grid probes. LIQUID is used to cluster representative pocket probes by their pharmacophore types describing a fuzzy VL model. The VL is encoded in a correlation vector, which can then be compared to a database of pre-calculated ligand models. A retrospective screening using the fuzzy VL and several protein structures was evaluated by ten fold cross-validation with ROC-AUC and BEDROC metrics, obtaining a significant enrichment of actives. Future work will be devoted to prospective screening using a novel protein target of Helicobacter pylori and compounds from commercial providers

The thermodynamics of human reaction times

I present a new approach for the interpretation of reaction time (RT) data from behavioral experiments. From a physical perspective, the entropy of the RT distribution provides a model-free estimate of the amount of processing performed by the cognitive system. In this way, the focus is shifted from the conventional interpretation of individual RTs being either long or short, into their distribution being\ud more or less complex in terms of entropy. The new approach enables the estimation of the cognitive processing load without reference to the informational content of the stimuli themselves, thus providing a more appropriate estimate of the cognitive impact of dierent sources of information that are carried by experimental stimuli or tasks. The paper introduces the formulation of the theory, followed by an empirical validation using a database of human RTs in lexical tasks (visual lexical decision and word\ud naming). The results show that this new interpretation of RTs is more powerful than the traditional one. The method provides theoretical estimates of the processing loads elicited by individual stimuli. These loads sharply distinguish the responses from different tasks. In addition, it provides upper-bound estimates for the speed at which the system processes information. Finally, I argue that the theoretical proposal, and the associated empirical evidence, provide strong arguments for an adaptive system that systematically adjusts its operational processing speed to the particular demands of each stimulus. This\ud finding is in contradiction with Hick's law, which posits a relatively constant processing speed within an experimental context

Influence of a fluorobenzene nucleobase analogue on the conformational flexibility of RNA studied by molecular dynamics simulations

Chemically modified bases are frequently used to stabilize nucleic acids, to study the driving forces for nucleic acid structure formation and to tune DNA and RNA hybridization conditions. In particular, fluorobenzene and fluorobenzimidazole base analogues can act as universal bases able to pair with any natural base and to stabilize RNA duplex formation. Although these base analogues are compatible with an A-form RNA geometry, little is known about the influence on the fine structure and conformational dynamics of RNA. In the present study, nano-second molecular dynamics (MD) simulations have been performed to characterize the dynamics of RNA duplexes containing a central 1'-deoxy-1'-(2,4-difluorophenyl)-ß-D-ribofuranose base pair or opposite to an adenine base. For comparison, RNA with a central uridine:adenine pair and a 1'-deoxy-1'-(phenyl)-ß-D-ribofuranose opposite to an adenine was also investigated. The MD simulations indicate a stable overall A-form geometry for the RNAs with base analogues. However, the presence of the base analogues caused a locally enhanced mobility of the central bases inducing mainly base pair shear and opening motions. No stable ‘base-paired’ geometry was found for the base analogue pair or the base analogue:adenine pairs, which explains in part the universal base character of these analogues. Instead, the conformational fluctuations of the base analogues lead to an enhanced accessibility of the bases in the major and minor grooves of the helix compared with a regular base pair

Antibiotic Sensitivity of Staph. aureus

Undergraduate Experimental Basi