A Database of >20 keV Electron Green's Functions of Interplanetary Transport at 1 AU

We use interplanetary transport simulations to compute a database of electron Green's functions, i.e., differential intensities resulting at the spacecraft position from an impulsive injection of energetic (>20 keV) electrons close to the Sun, for a large number of values of two standard interplanetary transport parameters: the scattering mean free path and the solar wind speed. The nominal energy channels of the ACE, STEREO, and Wind spacecraft have been used in the interplanetary transport simulations to conceive a unique tool for the study of near-relativistic electron events observed at 1 AU. In this paper, we quantify the characteristic times of the Green's functions (onset and peak time, rise and decay phase duration) as a function of the interplanetary transport conditions. We use the database to calculate the FWHM of the pitch-angle distributions at different times of the event and under different scattering conditions. This allows us to provide a first quantitative result that can be compared with observations, and to assess the validity of the frequently used term beam-like pitch-angle distribution.

Protein interaction studies point to new functions for Escherichia coli glyceraldehyde-3-phosphate dehydrogenase

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is considered a multifunctional protein with defined functions in numerous mammalian cellular processes. GAPDH functional diversity depends on various factors such as covalent modifications, subcellular localization, oligomeric state and intracellular concentration of substrates or ligands, as well as protein-protein interactions. In bacteria, alternative GAPDH functions have been associated with its extracellular location in pathogens or probiotics. In this study, new intracellular functions of E. coli GAPDH were investigated following a proteomic approach aimed at identifying interacting partners using in vivo formaldehyde cross-linking followed by mass spectrometry. The identified proteins were involved in metabolic processes, protein synthesis and folding or DNA repair. Some interacting proteins were also identified in immunopurification experiments in the absence of cross-linking. Pull-down experiments and overlay immunoblotting were performed to further characterize the interaction with phosphoglycolate phosphatase (Gph). This enzyme is involved in the metabolism of 2-phosphoglycolate formed in the DNA repair of 3"-phosphoglycolate ends generated by bleomycin damage. We show that interaction between Gph and GAPDH increases in cells challenged with bleomycin, suggesting involvement of GAPDH in cellular processes linked to DNA repair mechanisms.

Executive functions profile in extreme eating/weight conditions: from anorexia nervosa to obesity

Extreme weight conditions (EWC) groups along a continuum may share some biological risk factors and intermediate neurocognitive phenotypes. A core cognitive trait in EWC appears to be executive dysfunction, with a focus on decision making, response inhibition and cognitive flexibility. Differences between individuals in these areas are likely to contribute to the differences in vulnerability to EWC. The aim of the study was to investigate whether there is a common pattern of executive dysfunction in EWC while comparing anorexia nervosa patients (AN), obese subjects (OB) and healthy eating/weight controls (HC).

The Human Mesenchymal Stromal Cell-Derived Osteocyte Capacity to Modulate Dendritic Cell Functions Is Strictly Dependent on the Culture System.

In vitro differentiation of mesenchymal stromal cells (MSC) into osteocytes (human differentiated osteogenic cells, hDOC) before implantation has been proposed to optimize bone regeneration. However, a deep characterization of the immunological properties of DOC, including their effect on dendritic cell (DC) function, is not available. DOC can be used either as cellular suspension (detached, Det-DOC) or as adherent cells implanted on scaffolds (adherent, Adh-DOC). By mimicking in vitro these two different routes of administration, we show that both Det-DOC and Adh-DOC can modulate DC functions. Specifically, the weak downregulation of CD80 and CD86 caused by Det-DOC on DC surface results in a weak modulation of DC functions, which indeed retain a high capacity to induce T-cell proliferation and to generate CD4(+)CD25(+)Foxp3(+) T cells. Moreover, Det-DOC enhance the DC capacity to differentiate CD4(+)CD161(+)CD196(+) Th17-cells by upregulating IL-6 secretion. Conversely, Adh-DOC strongly suppress DC functions by a profound downregulation of CD80 and CD86 on DC as well as by the inhibition of TGF-β production. In conclusion, we demonstrate that different types of DOC cell preparation may have a different impact on the modulation of the host immune system. This finding may have relevant implications for the design of cell-based tissue-engineering strategies.

A Gradient based algorithm for blind inversion of Wiener System using multi-variate score functions

A Wiener system is a linear time-invariant filter, followed by an invertible nonlinear distortion. Assuming that the input signal is an independent and identically distributed (iid) sequence, we propose an algorithm for estimating the input signal only by observing the output of the Wiener system. The algorithm is based on minimizing the mutual information of the output samples, by means of a steepest descent gradient approach.

Sidelobe elimination for generalized synthetic discriminant functions by a two-filter correlation and subsequent postprocessing of the intensity distributions

One of the most important problems in optical pattern recognition by correlation is the appearance of sidelobes in the correlation plane, which causes false alarms. We present a method that eliminate sidelobes of up to a given height if certain conditions are satisfied. The method can be applied to any generalized synthetic discriminant function filter and is capable of rejecting lateral peaks that are even higher than the central correlation. Satisfactory results were obtained in both computer simulations and optical implementation.

Biological interpretation of genome-wide association studies using predicted gene functions.

The main challenge for gaining biological insights from genetic associations is identifying which genes and pathways explain the associations. Here we present DEPICT, an integrative tool that employs predicted gene functions to systematically prioritize the most likely causal genes at associated loci, highlight enriched pathways and identify tissues/cell types where genes from associated loci are highly expressed. DEPICT is not limited to genes with established functions and prioritizes relevant gene sets for many phenotypes.

Implementing Role Based Access Control into the Enterprise Environment to Support Business and IT Functions

The thesis studies role based access control and its suitability in the enterprise environment. The aim is to research how extensively role based access control can be implemented in the case organization and how it support organization’s business and IT functions. This study points out the enterprise’s needs for access control, factors of access control in the enterprise environment and requirements for implementation and the benefits and challenges it brings along. To find the scope how extensively role based access control can be implemented into the case organization, firstly is examined the actual state of access control. Secondly is defined a rudimentary desired state (how things should be) and thirdly completed it by using the results of the implementation of role based access control application. The study results the role model for case organization unit, and the building blocks and the framework for the organization wide implementation. Ultimate value for organization is delivered by facilitating the normal operations of the organization whilst protecting its information assets.

New kernel functions and learning methods for text and data mining

Recent advances in machine learning methods enable increasingly the automatic construction of various types of computer assisted methods that have been difficult or laborious to program by human experts. The tasks for which this kind of tools are needed arise in many areas, here especially in the fields of bioinformatics and natural language processing. The machine learning methods may not work satisfactorily if they are not appropriately tailored to the task in question. However, their learning performance can often be improved by taking advantage of deeper insight of the application domain or the learning problem at hand. This thesis considers developing kernel-based learning algorithms incorporating this kind of prior knowledge of the task in question in an advantageous way. Moreover, computationally efficient algorithms for training the learning machines for specific tasks are presented. In the context of kernel-based learning methods, the incorporation of prior knowledge is often done by designing appropriate kernel functions. Another well-known way is to develop cost functions that fit to the task under consideration. For disambiguation tasks in natural language, we develop kernel functions that take account of the positional information and the mutual similarities of words. It is shown that the use of this information significantly improves the disambiguation performance of the learning machine. Further, we design a new cost function that is better suitable for the task of information retrieval and for more general ranking problems than the cost functions designed for regression and classification. We also consider other applications of the kernel-based learning algorithms such as text categorization, and pattern recognition in differential display. We develop computationally efficient algorithms for training the considered learning machines with the proposed kernel functions. We also design a fast cross-validation algorithm for regularized least-squares type of learning algorithm. Further, an efficient version of the regularized least-squares algorithm that can be used together with the new cost function for preference learning and ranking tasks is proposed. In summary, we demonstrate that the incorporation of prior knowledge is possible and beneficial, and novel advanced kernels and cost functions can be used in algorithms efficiently.

New insights into cellular prion protein (PrPc) functions: the 'ying and yang' of a relevant protein.

The conversion of cellular prion protein (PrPc), a GPI-anchored protein, into a protease-K-resistant and infective form (generally termed PrPsc) is mainly responsible for Transmissible Spongiform Encephalopathies (TSEs), characterized by neuronal degeneration and progressive loss of basic brain functions. Although PrPc is expressed by a wide range of tissues throughout the body, the complete repertoire of its functions has not been fully determined. Recent studies have confirmed its participation in basic physiological processes such as cell proliferation and the regulation of cellular homeostasis. Other studies indicate that PrPc interacts with several molecules to activate signaling cascades with a high number of cellular effects. To determine PrPc functions, transgenic mouse models have been generated in the last decade. In particular, mice lacking specific domains of the PrPc protein have revealed the contribution of these domains to neurodegenerative processes. A dual role of PrPc has been shown, since most authors report protective roles for this protein while others describe pro-apoptotic functions. In this review, we summarize new findings on PrPc functions, especially those related to neural degeneration and cell signaling.

Two-year follow-op of cognitive functions in Schizophrenia spectrum disorders of adolescent patients treated with electroconvulsive therapy

Objective: The aim of the current study was to investigate the long-term cognitive effects of electroconvulsive therapy (ECT) in a sample of adolescent patients in whom schizophrenia spectrum disorders were diagnosed. Methods: The sample was composed of nine adolescent subjects in whom schizophrenia or schizoaffective disorder was diagnosed according to DSM-IV-TR criteria on whom ECT was conducted (ECT group) and nine adolescent subjects matched by age, socioeconomic status, and diagnostic and Positive and Negative Syndrome Scale (PANSS) total score at baseline on whom ECT was not conducted (NECT group). Clinical and neuropsychological assessments were carried out at baseline before ECT treatment and at 2-year follow-up. Results: Significant differences were found between groups in the number of unsuccessful medication trials. No statistically significant differences were found between the ECT group and theNECT group in either severity as assessed by the PANSS, or in any cognitive variables at baseline.At follow-up, both groups showed significant improvement in clinical variables (subscales of positive, general, and total scores of PANSS and Clinical Global Impressions-Improvement). In the cognitive assessment at follow-up, significant improvement was found in both groups in the semantic category of verbal fluency task and digits forward. However, no significant differences were found between groups in any clinical or cognitive variable at follow-up. Repeated measures analysis found no significant interaction of time · group in any clinical or neuropsychological measures. Conclusions: The current study showed no significant differences in change over time in clinical or neuropsychological variables between the ECT group and the NECT group at 2-year follow-up. Thus, ECT did not show any negative influence on long-term neuropsychological variables in our sample.

Investigating the functions of subregions within anterior hippocampus.

Previous functional MRI (fMRI) studies have associated anterior hippocampus with imagining and recalling scenes, imagining the future, recalling autobiographical memories and visual scene perception. We have observed that this typically involves the medial rather than the lateral portion of the anterior hippocampus. Here, we investigated which specific structures of the hippocampus underpin this observation. We had participants imagine novel scenes during fMRI scanning, as well as recall previously learned scenes from two different time periods (one week and 30 min prior to scanning), with analogous single object conditions as baselines. Using an extended segmentation protocol focussing on anterior hippocampus, we first investigated which substructures of the hippocampus respond to scenes, and found both imagination and recall of scenes to be associated with activity in presubiculum/parasubiculum, a region associated with spatial representation in rodents. Next, we compared imagining novel scenes to recall from one week or 30 min before scanning. We expected a strong response to imagining novel scenes and 1-week recall, as both involve constructing scene representations from elements stored across cortex. By contrast, we expected a weaker response to 30-min recall, as representations of these scenes had already been constructed but not yet consolidated. Both imagination and 1-week recall of scenes engaged anterior hippocampal structures (anterior subiculum and uncus respectively), indicating possible roles in scene construction. By contrast, 30-min recall of scenes elicited significantly less activation of anterior hippocampus but did engage posterior CA3. Together, these results elucidate the functions of different parts of the anterior hippocampus, a key brain area about which little is definitely known.