The role of language and languages in doctoral education: A transversal perspective

in Byram, Mike; Stoicheva, Maria (Eds.) The Doctorate as Experience in Europe and Beyond (2020)

The role of LEGO in numeracy development: A case study

in Xu, Shuang Shuang; Marsico, Giuseppina (Eds.) Where culture grows: Social ecology of a Chinese kindergarten (2021)

Role of long cycles in excitable dynamics on graphs.

in Physical Review. E ,Statistical, Nonlinear, and Soft Matter Physics (2014), 90(5-1), 052805

Topological cycles in excitable networks can play an important role in maintaining the network activity. When properly activated, cycles act as dynamic pacemakers, sustaining the activity of the whole ... [more ▼]

Topological cycles in excitable networks can play an important role in maintaining the network activity. When properly activated, cycles act as dynamic pacemakers, sustaining the activity of the whole network. Most previous research has focused on the contributions of short cycles to network dynamics. Here, we identify the specific cycles that are used during different runs of activation in sparse random graphs, as a basis of characterizing the contribution of cycles of any length. Both simulation and a refined mean-field approach evidence a decrease in the cycle usage when the cycle length increases, reflecting a trade-off between long time for recovery after excitation and low vulnerability to out-of-phase external excitations. In spite of this statistical observation, we find that the successful usage of long cycles, though rare, has important functional consequences for sustaining network activity: The average cycle length is the main feature of the cycle length distribution that affects the average lifetime of activity in the network. Particularly, use of long, rather than short, cycles correlates with higher lifetime, and cutting shortcuts in long cycles tends to increase the average lifetime of the activity. Our findings, thus, emphasize the essential, previously underrated role of long cycles in sustaining network activity. On a more general level, the findings underline the importance of network topology, particularly cycle structure, for self-sustained network dynamics. [less ▲]

The role of metabolites and metabolomics in clinically applicable biomarkers of disease.

in Archives of toxicology (2011), 85(1), 5-17

Metabolomics allows the simultaneous and relative quantification of thousands of different metabolites within a given sample using sensitive and specific methodologies such as gas or liquid chromatography ... [more ▼]

Metabolomics allows the simultaneous and relative quantification of thousands of different metabolites within a given sample using sensitive and specific methodologies such as gas or liquid chromatography coupled to mass spectrometry, typically in discovery phases of studies. Biomarkers are biological characteristics that are objectively measured and evaluated as indicators of normal biological processes, pathological processes or pharmacologic responses to a therapeutic intervention. Biomarkers are widely used in clinical practice for the diagnosis, assessment of severity and response to therapy in a number of clinical disease states. In human studies, metabolomics has been applied to define biomarkers related to prognosis or diagnosis of a disease or drug toxicity/efficacy and in doing so hopes to provide greater pathophysiological understanding of disease or therapeutic toxicity/efficacy. This review discusses the application of metabolomics in the discovery and subsequent application of biomarkers in the diagnosis and management of inborn errors of metabolism, cardiovascular disease and cancer. We critically appraise how novel biomarkers discovered through metabolomic analysis may be utilized in future clinical practice by addressing the following three fundamental questions: (1) Can the clinician measure them? (2) Do they add new information? (3) Do they help the clinician to manage patients? Although a number of novel biomarkers have been discovered through metabolomic studies of human diseases in the last decade, none have currently made the transition to routine use in clinical practice. Metabolites identified from these early studies will need to form the basis of larger, prospective, externally validated studies in clinical cohorts for their future use as biomarkers. At this stage, the absolute quantification of these biomarkers will need to be assessed epidemiologically, as will the ultimate deployment in the clinic via routine biochemistry, dip stick or similar rapid at- or near-patient care technologies. [less ▲]

Role of methyl-induced polarization in ion binding

in Proceedings of the National Academy of Sciences of the United States of America (2013), 110(32), 12978-12983

The chemical property of methyl groups that renders them indispensable to biomolecules is their hydrophobicity. Quantum mechanical studies undertaken here to understand the effect of point substitutions ... [more ▼]

The chemical property of methyl groups that renders them indispensable to biomolecules is their hydrophobicity. Quantum mechanical studies undertaken here to understand the effect of point substitutions on potassium (K-) channels illustrate quantitatively how methyl-induced polarization also contributes to biomolecular function. K- channels regulate transmembrane salt concentration gradients by transporting K+ ions selectively. One of the K+ binding sites in the channel's selectivity filter, the S4 site, also binds Ba2+ ions, which blocks K+ transport. This inhibitory property of Ba2+ ions has been vital in understanding K-channel mechanism. In most K-channels, the S4 site is composed of four threonine amino acids. The K channels that carry serine instead of threonine are significantly less susceptible to Ba2+ block and have reduced stabilities. We find that these differences can be explained by the lower polarizability of serine compared with threonine because serine carries one less branched methyl group than threonine. A T -> S substitution in the S4 site reduces its polarizability, which, in turn, reduces ion binding by several kilocalories per mole. Although the loss in binding affinity is high for Ba2+, the loss in K+ binding affinity is also significant thermodynamically, which reduces channel stability. These results highlight, in general, how biomolecular function can rely on the polarization induced by methyl groups especially those that are proximal to charged moieties, including ions titratable amino acids, sulfates, phosphates, and nucleotides. [less ▲]

The Role of Motivation and Self-regulation in Dropping Out of School

in Procedia Social and Behavioral Sciences (2013), 89

Dropping out of secondary education is a major problem in modern economies. Several explanations have been put forward, but not all have been systematically tested due to methodological and ethical ... [more ▼]

Dropping out of secondary education is a major problem in modern economies. Several explanations have been put forward, but not all have been systematically tested due to methodological and ethical problems. We compared two groups of pupils from the same secondary school classes. The groups were selected by teachers on the basis of their anticipated school outcomes (continuing school, n=585, versus dropping out, n=196). Motivational variables were intrinsic motivation, introjected regulation, identified regulation, external regulation, amotivation, academic self-efficacy and consistency of interest. Self-regulation variables were perseverance of effort, learning strategies and resistance to peer influence. All these dimensions were measured through shortened versions of validated scales. Statistical analyses showed that most, but not all of the tested dimensions were significantly different for both groups. Significant motivational variables were intrinsic motivation, introjected regulation, amotivation, and academic self-efficacy. Self-regulation variables that differentiated the two groups were perseverance of effort, and some learning strategies (elaboration, organisation, rehearsal, but not monitoring, planning and regulating) as well as resistance to peer influence. The factors which have been found are often cited, but in our study they are measured through a systematic design. While motivational factors are difficult to affect, self-regulatory skills could be taught and their systematic integration into school curricula could contribute to reducing dropout rates for students at risk. [less ▲]

The role of national courts for the protection of consumers: a European Union law perspective

Presentation (2014, March 03)

This paper presents the case-law of the Court of Justice on the powers of national courts to raise ex officio protective provisions of consumer contract law. It demonstrates the implications of this ... [more ▼]

This paper presents the case-law of the Court of Justice on the powers of national courts to raise ex officio protective provisions of consumer contract law. It demonstrates the implications of this jurisprudence for national procedural laws. [less ▲]

The role of neuromelanin in dopaminergic neuron demise and inflammation in idiopathic Parkinson's disease

Doctoral thesis (2022)

For a very long time, the main focus in Parkinson’s disease (PD) research was the loss of neuromelanin-containing dopaminergic neurons from the substantia nigra (SN) of the midbrain - the key pathological ... [more ▼]

For a very long time, the main focus in Parkinson’s disease (PD) research was the loss of neuromelanin-containing dopaminergic neurons from the substantia nigra (SN) of the midbrain - the key pathological feature of the disease. However, the association of neuronal vulnerability and neuromelanin presence has not been a common study subject. Recently, cells other than neurons also gained attention as mediators of PD pathogenesis. There are indications that glial cells undergo disease-related changes, however, the exact mechanisms remain unknown. In this thesis, I aimed to explore the contribution of every cell type of the midbrain to PD using single-nuclei RNA sequencing. Additionally, the goal was to explore their association to PD risk gene variants. As we identified microgliosis as a major mechanism in PD, we further extended our research to microglia. We sought to investigate the relation of microglia and neuromelanin. Thus, we aimed to, by means of immunohistochemical staining, imaging and laser-capture microdissection-based transcriptomics, elucidate this association on a single-cell level. This work resulted in the first midbrain single-cell atlas from idiopathic PD subjects and age- and sex-matched controls. We revealed SN-specific microgliosis with GPNMB upregulation, which also seemed to be specific to the idiopathic form of the disease. We further observed an accumulation of (extraneuronal) neuromelanin particles in Parkinson’s midbrain parenchyma, indicative of incomplete degradation. Moreover, we showed that GPNMB can be alleviated in microglia in contact with neuromelanin. Taken together, we provide evidence of a GPNMB-related microglial state as a disease mechanism specific to idiopathic PD, and highlight neuromelanin as an important player in microglia disease pathology. Further investigations are needed to understand whether the modulation of neuromelanin levels could be relevant in the context of PD therapy. [less ▲]

The Role of occupational activities and Work environment in occupational injury and interplay of personal factors in various age groups among Indian and French coalminers.

in International Journal of Occupational Medicine and Environmental Health (2013), 26(6), 910-929

The role of occupational hazards in occupational injury may be mediated by individual factors across various age groups. This study assessed the role of occupational hazards as well as contribution of ... [more ▼]

The role of occupational hazards in occupational injury may be mediated by individual factors across various age groups. This study assessed the role of occupational hazards as well as contribution of individual factors to injuries among Indian and French coalminers. Material and Methods. We conducted a case-control study on 245 injured workers and on 330 controls without any injuries from Indian coal mines using face-to-face interviews, and a retrospective study on 516 French coalminers using a self-administered questionnaire including potential occupational and personal factors. Data were analyzed using logistic models. Results. The annual rate of injuries was 5.5% for Indian coalminers and 14.9% for the French ones. Logistic model including all occupational factors showed that major injury causes were: hand-tools, material handling, machines, and environment/work-geological/strata conditions among Indian miners (adjusted odds-ratios 2.01 to 3.30) and biomechanical exposure score among French miners (adjusted odds-ratio 3.01 for score the 1–4, 3.47 for the score 5–7, and 7.26 for score ≥ 8, vs. score 0). Personal factors among Indian and French coalminers reduced/exacerbated the roles of various occupational hazards to a different extent depending on workers’ age. Conclusion. We conclude that injury roles of occupational hazards were reduced or exacerbated by personal factors depending on workers’ age in both populations. This knowledge is useful when designing prevention which should definitely consider workers’ age. [less ▲]

The role of on- and off-balance-sheet leverage of banks in the late 2000s crisis.

Scientific Conference (2014)