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1.
Sensors (Basel) ; 24(13)2024 Jun 25.
Article in English | MEDLINE | ID: mdl-39000897

ABSTRACT

Effective security surveillance is crucial in the railway sector to prevent security incidents, including vandalism, trespassing, and sabotage. This paper discusses the challenges of maintaining seamless surveillance over extensive railway infrastructure, considering both technological advances and the growing risks posed by terrorist attacks. Based on previous research, this paper discusses the limitations of current surveillance methods, particularly in managing information overload and false alarms that result from integrating multiple sensor technologies. To address these issues, we propose a new fusion model that utilises Probabilistic Occupancy Maps (POMs) and Bayesian fusion techniques. The fusion model is evaluated on a comprehensive dataset comprising three use cases with a total of eight real life critical scenarios. We show that, with this model, the detection accuracy can be increased while simultaneously reducing the false alarms in railway security surveillance systems. This way, our approach aims to enhance situational awareness and reduce false alarms, thereby improving the effectiveness of railway security measures.

2.
Sensors (Basel) ; 22(23)2022 Nov 26.
Article in English | MEDLINE | ID: mdl-36501907

ABSTRACT

Rapid and accurate reconnaissance in the event of radiological and nuclear (RN) incidents or attacks is vital to launch an appropriate response. This need is made stronger by the increasing threat of RN attacks on soft targets and critical infrastructure in densely populated areas. In such an event, even small radioactive sources can cause major disruption to the general population. In this work, we present a real-time radiological source localization method based on an optimization problem considering a background and radiation model. Supported by extensive real-world experiments, we show that an airborne system using this method is capable for reliably locating category 3-4 radioactive sources according to IAEA safety standards in real time from altitudes up to 150 m. A sensor bundle including a LiDAR sensor, a Gamma probe as well as a communication module was mounted on a UAV that served as a carrier platform. The method was evaluated on a comprehensive set of test flights, including 28 flight scenarios over 316 min using three different radiation sources. All additional gamma sources were correctly detected, multiple sources were detected if they were sufficiently separated from each other, with the distance between the true source position and the estimated source averaging 17.1 m. We also discuss the limitations of the system in terms of detection limit and source separation.

3.
Sensors (Basel) ; 22(19)2022 Sep 28.
Article in English | MEDLINE | ID: mdl-36236450

ABSTRACT

Wide area surveillance has become of critical importance, particularly for border control between countries where vast forested land border areas are to be monitored. In this paper, we address the problem of the automatic detection of activity in forbidden areas, namely forested land border areas. In order to avoid false detections, often triggered in dense vegetation with single sensors such as radar, we present a multi sensor fusion and tracking system using passive infrared detectors in combination with automatic person detection from thermal and visual video camera images. The approach combines weighted maps with a rule engine that associates data from multiple weighted maps. The proposed approach is tested on real data collected by the EU FOLDOUT project in a location representative of a range of forested EU borders. The results show that the proposed approach can eliminate single sensor false detections and enhance accuracy by up to 50%.


Subject(s)
Radar , Humans , Monitoring, Physiologic
4.
Sensors (Basel) ; 16(11)2016 Oct 29.
Article in English | MEDLINE | ID: mdl-27801874

ABSTRACT

Sensors, and also actuators or external sources such as databases, serve as data sources in order to realise condition monitoring of industrial applications or the acquisition of characteristic parameters like production speed or reject rate. Modern facilities create such a large amount of complex data that a machine operator is unable to comprehend and process the information contained in the data. Thus, information fusion mechanisms gain increasing importance. Besides the management of large amounts of data, further challenges towards the fusion algorithms arise from epistemic uncertainties (incomplete knowledge) in the input signals as well as conflicts between them. These aspects must be considered during information processing to obtain reliable results, which are in accordance with the real world. The analysis of the scientific state of the art shows that current solutions fulfil said requirements at most only partly. This article proposes the multilayered information fusion system MACRO (multilayer attribute-based conflict-reducing observation) employing the µBalTLCS (fuzzified balanced two-layer conflict solving) fusion algorithm to reduce the impact of conflicts on the fusion result. The performance of the contribution is shown by its evaluation in the scope of a machine condition monitoring application under laboratory conditions. Here, the MACRO system yields the best results compared to state-of-the-art fusion mechanisms. The utilised data is published and freely accessible.

5.
Stem Cell Reports ; 1(5): 371-8, 2013.
Article in English | MEDLINE | ID: mdl-24286025

ABSTRACT

Transcription factors control cell-specific gene expression programs by binding regulatory elements and recruiting cofactors and the transcription apparatus to the initiation sites of active genes. One of these cofactors is cohesin, a structural maintenance of chromosomes (SMC) complex that is necessary for proper gene expression. We report that a second SMC complex, condensin II, is also present at transcriptional regulatory elements of active genes during interphase and is necessary for normal gene activity. Both cohesin and condensin II are associated with genes in euchromatin and not heterochromatin. The two SMC complexes and the SMC loading factor NIPBL are particularly enriched at super-enhancers, and the genes associated with these regulatory elements are especially sensitive to reduced levels of these complexes. Thus, in addition to their well-established functions in chromosome maintenance during mitosis, both cohesin and condensin II make important contributions to the functions of the key transcriptional regulatory elements during interphase.


Subject(s)
Adenosine Triphosphatases/metabolism , Cell Cycle Proteins/metabolism , Chromosomal Proteins, Non-Histone/metabolism , DNA-Binding Proteins/metabolism , Enhancer Elements, Genetic , Multiprotein Complexes/metabolism , Transcriptional Activation , Animals , Cell Line, Tumor , Cells, Cultured , Chromatin/metabolism , Embryonic Stem Cells/metabolism , Gene Expression Regulation, Developmental , Humans , Mice , Mice, Inbred C57BL , Protein Binding , Cohesins
6.
Curr Opin Genet Dev ; 23(2): 89-95, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23270812

ABSTRACT

Cell type specific transcriptional regulation must be adhered to in order to maintain cell identity throughout the lifetime of an organism, yet it must be flexible enough to allow for responses to endogenous and exogenous stimuli. This regulation is mediated not only by molecular factors (e.g. cell type specific transcription factors, histone and DNA modifications), but also on the level of chromatin and genome organization. In this review we focus on recent findings that have contributed to our understanding of higher order chromatin structure and genome organization within the nucleus. We highlight new findings on the dynamic positioning of genes relative to each other, as well as to their chromosome territory and the nuclear lamina, and how the position of genes correlates with their transcriptional activity.


Subject(s)
Chromatin/genetics , Gene Expression Regulation , Genome , Transcription, Genetic , Cell Nucleus/metabolism , Histones/genetics , Histones/metabolism , Humans , Nuclear Lamina/genetics , Transcriptional Activation/genetics
7.
Phys Chem Chem Phys ; 14(38): 13249-54, 2012 Oct 14.
Article in English | MEDLINE | ID: mdl-22918269

ABSTRACT

The role of Au additives in SnO(2)-based thick film gas sensors was investigated by a combination of operando investigation techniques, namely spectroscopic high energy resolved fluorescence detected X-ray absorption spectroscopy (HERFD-XAS) and simultaneous DC resistance and work function change measurements. The results have shown that the Au is present in the form of small metallic particles at the surface of the host metal oxide without changing its bulk or surface electronic properties. The sensitization effect of Au can therefore be attributed to the "spill-over effect", meaning that the Au particles enrich the surface of the active metal oxide with oxygen species which consequently react with reducing gases such as CO and H(2). This is in contrast to the effect of Pd and Pt promoters which were found to be distributed at an atomic level on the surface and in the bulk of the supporting sensing material and therefore have a tremendous effect on its bulk and surface electronic properties.

9.
Mol Cell ; 40(3): 364-76, 2010 Nov 12.
Article in English | MEDLINE | ID: mdl-21035370

ABSTRACT

The histone methyltransferase PR-Set7/Set8 is the sole enzyme that catalyzes monomethylation of histone H4 at K20 (H4K20me1). Previous reports document disparate evidence regarding PR-Set7 expression during the cell cycle, the biological relevance of PR-Set7 interaction with PCNA, and its role in the cell. We find that PR-Set7 is indeed undetectable during S phase and instead is detected during late G2, mitosis, and early G1. PR-Set7 is transiently recruited to laser-induced DNA damage sites through its interaction with PCNA, after which 53BP1 is recruited dependent on PR-Set7 catalytic activity. During the DNA damage response, PR-Set7 interaction with PCNA through a specialized "PIP degron" domain targets it for PCNA-coupled CRL4(Cdt2)-dependent proteolysis. PR-Set7 mutant in its "PIP degron" is now detectable during S phase, during which the mutant protein accumulates. Outside the chromatin context, Skp2 promotes PR-Set7 degradation as well. These findings demonstrate a stringent spatiotemporal control of PR-Set7 that is essential for preserving the genomic integrity of mammalian cells.


Subject(s)
Cullin Proteins/metabolism , DNA Damage , DNA-Binding Proteins/metabolism , Histone-Lysine N-Methyltransferase/metabolism , Histones/metabolism , Nuclear Proteins/metabolism , Proliferating Cell Nuclear Antigen/metabolism , Protein Processing, Post-Translational , Ubiquitin-Protein Ligases/metabolism , Animals , Biocatalysis/radiation effects , Cell Line, Tumor , Enzyme Activation/radiation effects , Enzyme Stability , Histone-Lysine N-Methyltransferase/chemistry , Humans , Intracellular Signaling Peptides and Proteins/metabolism , Mice , Models, Biological , Proteasome Endopeptidase Complex/metabolism , Protein Binding/radiation effects , Protein Processing, Post-Translational/radiation effects , Protein Structure, Tertiary , S Phase/radiation effects , Signal Transduction/radiation effects , Tumor Suppressor p53-Binding Protein 1 , Ubiquitin/metabolism , Ultraviolet Rays
10.
Mol Biol Cell ; 21(23): 4184-96, 2010 Dec.
Article in English | MEDLINE | ID: mdl-20881057

ABSTRACT

Noncoding RNAs play important roles in various aspects of gene regulation. We have identified 7SK RNA to be enriched in nuclear speckles or interchromatin granule clusters (IGCs), a subnuclear domain enriched in pre-mRNA processing factors. 7SK RNA, in association with HEXIM 1 and 2, is involved in the inhibition of transcriptional elongation by RNA polymerase II. Inhibition occurs via sequestration of the active P-TEFb kinase complex (CDK 9 and Cyclin T1/T2a/b or K) that is involved in phosphorylating the C-terminal domain of RNA polymerase II. Our results demonstrate that knock-down of 7SK RNA, by specific antisense oligonucleotides, results in the mislocalization of nuclear speckle constituents in a transcription-dependent manner, and the transcriptional up-regulation of a RNA polymerase II transcribed reporter gene locus. Furthermore, 7SK RNA transiently associates with a stably integrated reporter gene locus upon transcriptional down-regulation and its presence correlates with the efficient displacement of P-TEFb constituents from the locus. Our results suggest that 7SK RNA plays a role in modulating the available level of P-TEFb upon transcriptional down-regulation by sequestering its constituents in nuclear speckles.


Subject(s)
Gene Expression Regulation , Positive Transcriptional Elongation Factor B/metabolism , RNA Polymerase II/metabolism , RNA, Small Nuclear/genetics , RNA, Small Nuclear/metabolism , Cyclin T/metabolism , Cyclin-Dependent Kinase 9/genetics , Cyclin-Dependent Kinase 9/metabolism , Fluorescent Antibody Technique , Gene Knockdown Techniques , Genes, Reporter , HeLa Cells , Humans , Oligonucleotides, Antisense , Positive Transcriptional Elongation Factor B/genetics , RNA Polymerase II/antagonists & inhibitors , RNA Polymerase II/genetics , RNA-Binding Proteins/metabolism , Ribonucleoproteins, Small Nuclear/metabolism , Transcription Factors , Transcription, Genetic/genetics , Transcription, Genetic/physiology , Transcriptional Activation
11.
Annu Rev Biophys ; 39: 471-89, 2010.
Article in English | MEDLINE | ID: mdl-20462379

ABSTRACT

The expression patterns of many protein-coding genes are orchestrated in response to exogenous stimuli, as well as cell-type-specific developmental programs. In recent years, researchers have shown that dynamic chromatin movements and interactions in the nucleus play a crucial role in gene regulation. In this review, we highlight our current understanding of the organization of chromatin in the interphase nucleus and the impact of chromatin dynamics on gene expression. We also discuss the current state of knowledge with regard to the localization of active and inactive genes within the three-dimensional nuclear space. Furthermore, we address recent findings that demonstrate the movements of chromosomal regions and genomic loci in association with changes in transcriptional activity. Finally, we discuss the role of intra- and interchromosomal interactions in the control of coregulated genes.


Subject(s)
Cell Nucleus/metabolism , Chromatin/metabolism , Gene Expression Regulation , Animals , Humans , Interphase
12.
Phys Chem Chem Phys ; 11(38): 8620-5, 2009 Oct 14.
Article in English | MEDLINE | ID: mdl-19774296

ABSTRACT

SnO2 gas sensors with palladium as additive in the range of 0.2 wt% and 3 wt% were studied by in situ X-ray absorption spectroscopy under idealized and real operating conditions. Simultaneously to the structural studies, measurements of the sensing properties were undertaken allowing for the determination of structure-function relationships. For this purpose a new in situ spectroscopic cell was designed which permitted on the one hand sensing on conventional screen printed 50 microm thick sensing layers and on the other hand structural analysis with X-rays provided by an insertion device at a 3rd generation synchrotron facility in fluorescence mode. Pd K-edge XANES and EXAFS results on gas sensors showed that palladium, present in an oxidized state, is finely dispersed if it is added in small quantities (0.2 wt%) while it forms clusters at higher concentrations (3 wt%). This is also reflected by the much easier reduction of palladium in the latter, higher concentrated ones. Under realistic sensing conditions (30-200 ppm H2; 10-50 ppm CO in dry and humid air at 200 and 300 degrees C) for the low additive concentration samples, no change in oxidation state was observed, i.e. palladium remained in its oxidized state. This has important consequences on the understanding and modeling of the gas sensing mechanism.

13.
EMBO J ; 23(18): 3653-66, 2004 Sep 15.
Article in English | MEDLINE | ID: mdl-15343269

ABSTRACT

Unliganded (apo-) estrogen receptor alpha (ERalpha, NR3A1) is classically considered as transcriptionally unproductive. Reassessing this paradigm demonstrated that apo-human ERalpha (ERalpha66) and its N-terminally truncated isoform (ERalpha46) are both predominantly nuclear transcription factors that cycle on the endogenous estrogen-responsive pS2 gene promoter in vivo. Importantly, isoform-specific consequences occur in terms of poising the promoter for transcription, as evaluated by determining (i) the engagement of several cofactors and the resulting nucleosomal organization; and (ii) the CpG methylation state of the pS2 promoter. Although transcriptionally unproductive, cycling of apo-ERalpha66 prepares the promoter to respond to ligand, through sequentially targeting chromatin remodeling complexes and general transcription factors. Additionally, apo-ERalpha46 recruits corepressors, following engagement of cofactors identical to those recruited by apo-ERalpha66. Together, these data describe differential activities of ERalpha isoforms. Furthermore, they depict the maintenance of a promoter in a repressed state as a cyclical process that is intrinsically dependent on initial poising of the promoter.


Subject(s)
Apoproteins/genetics , Estrogen Receptor alpha/genetics , Membrane Proteins/genetics , Promoter Regions, Genetic/genetics , Transcription, Genetic , Apoproteins/metabolism , Biological Clocks , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Chromatin/metabolism , Chromatin Immunoprecipitation , CpG Islands , DNA Methylation , Epigenesis, Genetic/genetics , Estrogen Receptor alpha/metabolism , Estrogens/metabolism , Gene Expression Regulation, Neoplastic , Growth Substances/metabolism , Humans , Ligands , Membrane Proteins/metabolism , Nucleosomes/metabolism , Presenilin-2 , Protein Isoforms , Transcription Factors/metabolism , Transcriptional Activation
14.
Cell ; 115(6): 751-63, 2003 Dec 12.
Article in English | MEDLINE | ID: mdl-14675539

ABSTRACT

Transcriptional activation of a gene involves an orchestrated recruitment of components of the basal transcription machinery and intermediate factors, concomitant with an alteration in local chromatin structure generated by posttranslational modifications of histone tails and nucleosome remodeling. We provide here a comprehensive picture of events resulting in transcriptional activation of a gene, through evaluating the estrogen receptor-alpha (NR3A1) target pS2 gene promoter in MCF-7 cells. This description integrates chromatin remodeling with a kinetic evaluation of cyclical networks of association of 46 transcription factors with the promoter, as determined by chromatin immunoprecipitation assays. We define the concept of a "transcriptional clock" that directs and achieves the sequential and combinatorial assembly of a transcriptionally productive complex on a promoter. Furthermore, the unanticipated findings of key roles for histone deacetylases and nucleosome-remodeling complexes in limiting transcription implies that transcriptional activation is a cyclical process that requires both activating and repressive epigenetic processes.


Subject(s)
Promoter Regions, Genetic/genetics , Proteins/metabolism , Receptors, Estrogen/metabolism , Transcriptional Activation/genetics , Biological Clocks/genetics , Cell Line, Tumor , Epigenesis, Genetic/genetics , Estrogen Receptor alpha , Estrogens/metabolism , Histone Deacetylases/genetics , Humans , Nucleosomes/genetics , Proteins/genetics , Receptors, Estrogen/genetics , Trefoil Factor-1 , Tumor Suppressor Proteins
15.
Mol Cell ; 11(3): 695-707, 2003 Mar.
Article in English | MEDLINE | ID: mdl-12667452

ABSTRACT

We present an integrated model of hERalpha-mediated transcription where both unliganded and liganded receptors cycle on estrogen-responsive promoters. Using ChIP, FRAP, and biochemical analysis we evaluate hERalpha at several points in these cycles, establishing the ubiquitination status and subnuclear distribution of hERalpha, its mobility, the kinetics of transcriptional activation, and the cyclic recruitment of E3 ligases and the 19S regulatory component of the proteasome. These experiments, together with an evaluation of the inhibition of transcription and proteasome action, demonstrate that proteasome-mediated degradation and hERalpha-mediated transactivation are inherently linked and act to continuously turn over hERalpha on responsive promoters. Cyclic turnover of hERalpha permits continuous responses to changes in the concentration of estradiol.


Subject(s)
Receptors, Estrogen/genetics , Receptors, Estrogen/metabolism , Signal Transduction , Blotting, Western , Cell Nucleus/metabolism , Chromatin/metabolism , Cysteine Endopeptidases/metabolism , Dose-Response Relationship, Drug , Estradiol/metabolism , Estrogen Receptor alpha , Estrogens/metabolism , Humans , Kinetics , Ligands , Models, Biological , Multienzyme Complexes/metabolism , Oligonucleotides/pharmacology , Plasmids/metabolism , Precipitin Tests , Promoter Regions, Genetic , Proteasome Endopeptidase Complex , Protein Binding , Time Factors , Transcription, Genetic , Transcriptional Activation , Transfection , Tumor Cells, Cultured
16.
Mol Cell ; 10(5): 1019-32, 2002 Nov.
Article in English | MEDLINE | ID: mdl-12453411

ABSTRACT

The functional interplay between different domains of estrogen receptor-alpha (ERalpha, NR3A1) is responsible for the overall properties of the full-length protein. We previously identified an interaction between the N-terminal A and C-terminal domains, which we demonstrate here to repress ligand-independent transactivation and transrepression abilities of ERalpha. Using targeted mutations based on ERalpha structural models, we determine the basis for this interaction that defines a regulatory interplay between ERalpha A domain, corepressors, and ERalpha Helix 12 for binding to the same C-terminal surface. We propose a dynamic model where binding of different ligands influences the A/D-F domain interaction and results in specific functional outcomes. This model gives insights into the dynamic properties of full-length ERalpha and into the structure of unliganded ERalpha.


Subject(s)
Receptors, Estrogen/metabolism , Amino Acid Sequence , Estrogen Receptor alpha , Gene Silencing , Genes, Reporter , Glutathione Transferase/metabolism , HeLa Cells , Humans , Ligands , Models, Genetic , Models, Molecular , Molecular Sequence Data , Mutagenesis, Site-Directed , Peptides/chemistry , Plasmids/metabolism , Precipitin Tests , Protein Binding , Protein Biosynthesis , Protein Conformation , Protein Isoforms , Protein Structure, Secondary , Protein Structure, Tertiary , Receptors, Estrogen/chemistry , Recombinant Fusion Proteins/metabolism , Sequence Homology, Amino Acid , Software , Transcription, Genetic , Transcriptional Activation , Tumor Cells, Cultured , beta-Galactosidase/metabolism
17.
EMBO J ; 21(13): 3443-53, 2002 Jul 01.
Article in English | MEDLINE | ID: mdl-12093745

ABSTRACT

The enhancement of the human estrogen receptor alpha (hER alpha, NR3A1) activity by the orphan nuclear receptor COUP-TFI is found to depend on the establishment of a tight hER alpha-COUP-TFI complex. Formation of this complex seems to involve dynamic mechanisms different from those allowing hER alpha homodimerization. Although the hER alpha-COUP-TFI complex is present in all cells tested, the transcriptional cooperation between the two nuclear receptors is restricted to cell lines permissive to hER alpha activation function 1 (AF-1). In these cells, the physical interaction between COUP-TFI and hER alpha increases the affinity of hER alpha for ERK2/p42(MAPK), resulting in an enhanced phosphorylation state of the hER alpha Ser118. hER alpha thus acquires a strengthened AF-1 activity due to its hyperphosphorylation. These data indicate an alternative interaction process between nuclear receptors and demonstrate a novel protein intercommunication pathway that modulates hER alpha AF-1.


Subject(s)
DNA-Binding Proteins/metabolism , Mitogen-Activated Protein Kinase 1/metabolism , Protein Processing, Post-Translational , Receptors, Estrogen/metabolism , Transcription Factors/metabolism , Adenocarcinoma/pathology , Breast Neoplasms/pathology , COUP Transcription Factor I , DNA/metabolism , Enzyme Inhibitors/pharmacology , Estrogen Receptor alpha , Female , Flavonoids/pharmacology , Humans , Macromolecular Substances , Mitogen-Activated Protein Kinase 1/antagonists & inhibitors , Neoplasm Proteins/metabolism , Phosphorylation , Phosphoserine/metabolism , Protein Binding , Protein Interaction Mapping , Protein Structure, Tertiary , Signal Transduction , Transcription, Genetic , Tumor Cells, Cultured
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