Trustworthy exams without trusted parties

in Computer and Security (2017), 67

Historically, exam security has mainly focused on threats ascribed to candidate cheating. Such threats have been normally mitigated by invigilation and anti-plagiarism methods. However, as recent exam ... [more ▼]

Historically, exam security has mainly focused on threats ascribed to candidate cheating. Such threats have been normally mitigated by invigilation and anti-plagiarism methods. However, as recent exam scandals confirm, also invigilators and authorities may pose security threats. The introduction of computers into the different phases of an exam, such as candidate registration, brings new security issues that should be addressed with the care normally devoted to security protocols. This paper proposes a protocol that meets a wide set of security requirements and resists threats that may originate from candidates as well as from exam administrators. By relying on a combination of oblivious transfer and visual cryptography schemes, the protocol does not need to rely on any trusted third party. We analyse the protocol formally in ProVerif and prove that it verifies all the stated security requirements. [less ▲]

Tschechen in der deutschen Wehrmacht. Totgeschwiegene Schicksale

in CLIO-online (2021)

TTCA: an R package for the identification of differentially expressed genes in time course microarray data

in BMC Bioinformatics (2017), 18(1), 33

Background: The analysis of microarray time series promises a deeper insight into the dynamics of the cellular response following stimulation. A common observation in this type of data is that some genes ... [more ▼]

Background: The analysis of microarray time series promises a deeper insight into the dynamics of the cellular response following stimulation. A common observation in this type of data is that some genes respond with quick, transient dynamics, while other genes change their expression slowly over time. The existing methods for detecting significant expression dynamics often fail when the expression dynamics show a large heterogeneity. Moreover, these methods often cannot cope with irregular and sparse measurements. Results: The method proposed here is specifically designed for the analysis of perturbation responses. It combines different scores to capture fast and transient dynamics as well as slow expression changes, and performs well in the presence of low replicate numbers and irregular sampling times. The results are given in the form of tables including links to figures showing the expression dynamics of the respective transcript. These allow to quickly recognise the relevance of detection, to identify possible false positives and to discriminate early and late changes in gene expression. An extension of the method allows the analysis of the expression dynamics of functional groups of genes, providing a quick overview of the cellular response. The performance of this package was tested on microarray data derived from lung cancer cells stimulated with epidermal growth factor (EGF). Conclusion: Here we describe a new, efficient method for the analysis of sparse and heterogeneous time course data with high detection sensitivity and transparency. It is implemented as R package TTCA (transcript time course analysis) and can be installed from the Comprehensive R Archive Network, CRAN. The source code is provided with the Additional file 1. [less ▲]

Tug of War over Financial Assistance: Which Way Forward for Eurozone Stability Mechanisms?

in Politics and Governance (2021), 9(2), 173184

Tumor necrosis factor alpha induces gamma-glutamyltransferase expression via nuclear factor-kappaB in cooperation with Sp1

in Biochemical Pharmacology (2009), 77(3), 397-411

Gamma-glutamyltransferase (GGT) cleaves the gamma-glutamyl moiety of glutathione (GSH), an endogenous antioxidant, and is involved in mercapturic acid metabolism and in cancer drug resistance when ... [more ▼]

Gamma-glutamyltransferase (GGT) cleaves the gamma-glutamyl moiety of glutathione (GSH), an endogenous antioxidant, and is involved in mercapturic acid metabolism and in cancer drug resistance when overexpressed. Moreover, GGT converts leukotriene (LT) C4 into LTD4 implicated in various inflammatory pathologies. So far the effect of inflammatory stimuli on regulation of GGT expression and activity remained to be addressed. We found that the proinflammatory cytokine tumor necrosis factor alpha (TNFalpha) induced GGT promoter transactivation, mRNA and protein synthesis, as well as enzymatic activity. Remicade, a clinically used anti-TNFalpha antibody, small interfering RNA (siRNA) against p50 and p65 nuclear factor-kappaB (NF-kappaB) isoforms, curcumin, a well characterized natural NF-kappaB inhibitor, as well as a dominant negative inhibitor of kappaB alpha (IkappaBalpha), prevented GGT activation at various levels, illustrating the involvement of this signaling pathway in TNFalpha-induced stimulation. Over-expression of receptor of TNFalpha-1 (TNFR1), TNFR-associated factor-2 (TRAF2), TNFR-1 associated death domain (TRADD), dominant negative (DN) IkappaBalpha or NF-kappaB p65 further confirmed GGT promoter activation via NF-kappaB. Linker insertion mutagenesis of 536 bp of the proximal GGT promoter revealed NF-kappaB and Sp1 binding sites at -110 and -78 relative to the transcription start site, responsible for basal GGT transcription. Mutation of the NF-kappaB site located at -110 additionally inhibited TNFalpha-induced promoter induction. Chromatin immunoprecipitation (ChIP) assays confirmed mutagenesis results and further demonstrated that TNFalpha treatment induced in vivo binding of both NF-kappaB and Sp1, explaining increased GGT expression, and led to RNA polymerase II recruitment under inflammatory conditions. [less ▲]

Tumor suppressor Ras-association domain family 1 isoform A is a novel regulator of cardiac hypertrophy.

in Circulation (2009), 120(7), 607-16

BACKGROUND: Ras signaling regulates a number of important processes in the heart, including cell growth and hypertrophy. Although it is known that defective Ras signaling is associated with Noonan ... [more ▼]

BACKGROUND: Ras signaling regulates a number of important processes in the heart, including cell growth and hypertrophy. Although it is known that defective Ras signaling is associated with Noonan, Costello, and other syndromes that are characterized by tumor formation and cardiac hypertrophy, little is known about factors that may control it. Here we investigate the role of Ras effector Ras-association domain family 1 isoform A (RASSF1A) in regulating myocardial hypertrophy. METHODS AND RESULTS: A significant downregulation of RASSF1A expression was observed in hypertrophic mouse hearts, as well as in failing human hearts. To further investigate the role of RASSF1A in cardiac (patho)physiology, we used RASSF1A knock-out (RASSF1A(-)(/)(-)) mice and neonatal rat cardiomyocytes with adenoviral overexpression of RASSF1A. Ablation of RASSF1A in mice significantly enhanced the hypertrophic response to transverse aortic constriction (64.2% increase in heart weight/body weight ratio in RASSF1A(-)(/)(-) mice compared with 32.4% in wild type). Consistent with the in vivo data, overexpression of RASSF1A in cardiomyocytes markedly reduced the cellular hypertrophic response to phenylephrine stimulation. Analysis of molecular signaling events in isolated cardiomyocytes indicated that RASSF1A inhibited extracellular regulated kinase 1/2 activation, likely by blocking the binding of Raf1 to active Ras. CONCLUSIONS: Our data establish RASSF1A as a novel inhibitor of cardiac hypertrophy by modulating the extracellular regulated kinase 1/2 pathway. [less ▲]

Tumorigenesis and eye abnormalities in transgenic mice expressing MSV-SV40 large T-antigen.

in Oncogene (1990), 5(2), 225-32

Transgenic mice which expressed SV40 large T-antigen under the control of the MSV enhancer and the SV40 promoter were generated. In animals containing an intact MSV enhancer, total lens cataracts and ... [more ▼]

Transgenic mice which expressed SV40 large T-antigen under the control of the MSV enhancer and the SV40 promoter were generated. In animals containing an intact MSV enhancer, total lens cataracts and neuroectodermal brain tumors, originating in the pineal organ were observed. In contrast, 5' deletion of the MSV enhancer to a residual 53 bp resulted in a different spectrum of pathologies. Whilst lens cataracts still occurred, no brain tumors could be detected. Instead, fibrosarcomas and adenocarcinomas of the kidneys were induced. In addition, tumors of the endocrine pancreas were observed with both transgene constructs. We conclude that the MSV enhancer element is sufficient to direct the expression of the viral reporter gene to the lens and the pineal organ in transgenic mice. Deletion of the MSV enhancer correlates with the loss of DNA elements responsible for the pineal cell specific expression of SV40 large T-antigen. [less ▲]

TUMOUR-ASSOCIATED MICROGLIA/MACROPHAGE HETEROGENEITY IN GLIOBLASTOMA

Doctoral thesis (2021)

Glioblastoma (GBM) is the most common and aggressive primary brain tumour in adults, characterized by high degrees of both inter- and intra-tumour heterogeneity. GBM cells secrete numerous factors ... [more ▼]

Glioblastoma (GBM) is the most common and aggressive primary brain tumour in adults, characterized by high degrees of both inter- and intra-tumour heterogeneity. GBM cells secrete numerous factors promoting the recruitment and infiltration of cellular players to the local tumour microenvironment. Tumour-associated microglia/macrophages (TAMs) represent the major cell type of the stromal compartment in GBM playing important roles along tumour development. Along GBM progression, these cells are supposed to be geared towards a tumour-supportive phenotype, therefore TAMs are pursued as key targets for the development of novel strategies aimed at re-educating them towards anti-tumour phenotypes. However, it is yet unclear how these immune suppressive properties are acquired and whether TAM subsets may phenotypically and functionally differently contribute to tumour development. Hence, the main goal of the present PhD project was to elucidate TAM diversity under defined temporal and spatial settings in GBM. Taking advantage of the GBM GL261 syngeneic and patient-derived orthotopic xenograft mouse models, we comprehensively studied the cellular and transcriptional heterogeneity of TAMs by combining single-cell RNA-sequencing, multicolour flow cytometry, immunohistological and functional analyses. We demonstrated that, as observed in patients, the myeloid compartment is the most affected and heterogeneous stromal compartment, with microglia and macrophage-like cells acquiring key transcriptional differences and rapidly adapting along GBM progression. Specifically, we uncovered that TAM transcriptional programmes converge over time, suggesting a context-dependent symbiosis mechanism characterized by decreased antigen-presenting cell signatures at late tumour stages. In the absence of Acod1/Irg1, a key gene involved in the metabolic reprogramming of macrophages towards an anti-inflammatory phenotype, we detected higher TAM diversity in the TME displaying increased immunogenicity and correlating with increased lymphocytic recruitment to the tumour site. Additionally, we uncovered that TAMs exhibit niche-specific functional adaptations in the tumour microenvironment, with microglia in the invasive landscapes displaying higher immune reactive profiles when compared to the corresponding cells in the angiogenic tumour phenotypes. Taken together, our data provide insights into the spatial and molecular heterogeneity of TAMs dynamically adapting along tumour progression or across specific tumour sites and revealing potential reactive anti-tumorigenic cell subsets that may be harnessed for therapeutic intervention in GBM. [less ▲]

Tunable magnetoplasmonics in lattices of Ni/SiO2/Au dimers

in Scientific Reports (2019), 9

We present a systematic study on the optical and magneto-optical properties of Ni/SiO2/Au dimer lattices. By consideringthe excitation of orthogonal dipoles in the Ni and Au nanodisks, we analytically ... [more ▼]

We present a systematic study on the optical and magneto-optical properties of Ni/SiO2/Au dimer lattices. By consideringthe excitation of orthogonal dipoles in the Ni and Au nanodisks, we analytically demonstrate that the magnetoplasmonicresponse of dimer lattices is governed by a complex interplay of near- and far-field interactions. Near-field coupling betweendipoles in Ni and low-loss Au enhances the polarizabilty of single dimers compared to that of isolated Ni nanodisks. Far-fielddiffractive coupling in periodic lattices of these two particle types enlarges the difference in effective polarizability further.This effect is explained by an inverse relationship between the damping of collective surface lattice resonances and theimaginary polarizability of individual scatterers. Optical reflectance measurements, magneto-optical Kerr effect spectra, andfinite-difference time-domain simulations confirm the analytical results. Hybrid dimer arrays supporting intense plasmonexcitations are a promising candidate for active magnetoplasmonic devices. [less ▲]

Tuning halide perovskite energy levels

in Energy and Environmental Science (2020)

Solar energy is playing a significant role in the development of a world powered by clean energy sources. In this context, halide perovskite solar cells (PSCs) are considered one of the most promising ... [more ▼]

Solar energy is playing a significant role in the development of a world powered by clean energy sources. In this context, halide perovskite solar cells (PSCs) are considered one of the most promising research lines thanks to their high efficiencies and flexibility, combined with an easy and cheap fabrication process. The possibility of combining different materials and compositions is an excellent advantage of PSCs. However, still, a big limit is posed by the need for a proper energy level alignment between the layers of materials comprising devices. Therefore, it is of utmost interest to develop methods allowing to tune the energy levels of the different materials. In semiconductors physics, a common technique to achieve this purpose is to functionalize the surface of the materials with dipolar molecules. Nevertheless, this has been rarely applied to perovskites because of the highly rough surface of the films. In this study, we show that it is possible to use this technique in hybrid organic–inorganic perovskite semiconductors systematically and tune the direction and magnitude of the shift by controlling the deposition process. These findings offer a toolbox to simplify the application of halide perovskites in optoelectronic devices. [less ▲]