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1.
  • Tabiri, S, et al. (author)
  • 2021
  • swepub:Mat__t
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2.
  • Bravo, L, et al. (author)
  • 2021
  • swepub:Mat__t
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4.
  • Barucca, G., et al. (author)
  • Study of excited Ξ baryons with the P¯ ANDA detector
  • 2021
  • In: European Physical Journal A. - : Springer Nature. - 1434-6001 .- 1434-601X. ; 57:4
  • Journal article (peer-reviewed)abstract
    • The study of baryon excitation spectra provides insight into the inner structure of baryons. So far, most of the world-wide efforts have been directed towards N∗ and Δ spectroscopy. Nevertheless, the study of the double and triple strange baryon spectrum provides independent information to the N∗ and Δ spectra. The future antiproton experiment P¯ANDA will provide direct access to final states containing a Ξ¯ Ξ pair, for which production cross sections up to μb are expected in p¯p reactions. With a luminosity of L= 10 31 cm- 2 s- 1 in the first phase of the experiment, the expected cross sections correspond to a production rate of ∼106events/day. With a nearly 4 π detector acceptance, P¯ANDA will thus be a hyperon factory. In this study, reactions of the type p¯p → Ξ¯ +Ξ∗ - as well as p¯p → Ξ¯ ∗ +Ξ- with various decay modes are investigated. For the exclusive reconstruction of the signal events a full decay tree fit is used, resulting in reconstruction efficiencies between 3 and 5%. This allows high statistics data to be collected within a few weeks of data taking.
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11.
  • Keskin, M, et al. (author)
  • Oral Cavity Calprotectin and Lactoferrin Levels in Relation to Radiotherapy
  • 2022
  • In: Current issues in molecular biology. - : MDPI AG. - 1467-3045. ; 44:10, s. 4439-4446
  • Journal article (peer-reviewed)abstract
    • Background: Lactoferrin, an iron-binding glycoprotein, and calprotectin, a calcium binding protein, are sensitive markers of inflammation and their fecal levels increase during radiotherapy of prostate cancer patients. With this background, we analyzed mouthrinse calprotectin and lactoferrin levels of head- and neck-cancer patients before, during and after radiotherapy. Methods: Twenty cancer patients (mean age 55.85 ± 15.01, 80% male), who had been planned to undergo radiotherapy to the head and neck area, were included in this study. Mouthrinse samples were collected before radiotherapy, at the 3rd and 6th weeks of radiotherapy and 4 weeks after the radiotherapy. Mouthrinse samples were analyzed for calprotectin and lactoferrin using commercial ELISA kits. Results: Calprotectin levels increased significantly during radiotherapy (p = 0.022). Both markers, lactoferrin (p = 0.011) and calprotectin (p = 0.006), decreased significantly after the treatment. Conclusions: Present study results may suggest that the elevations in calprotectin and lactoferrin levels during radiotherapy reflect the increased and emerging inflammatory environment in the oral cavity, thus may increase the risk of periodontal disease initiation or progression.
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12.
  • Keskin, U., et al. (author)
  • An engineering approach to synchronization based on overrun for compositional real-time systems
  • 2011
  • In: SIES 2011 - 6th IEEE International Symposium on Industrial Embedded Systems, Conference Proceedings. - 9781612848204 ; , s. 274-283
  • Conference paper (peer-reviewed)abstract
    • Hierarchical scheduling frameworks (HSFs) provide means for composing complex real-time systems from well-defined independently developed and analyzed subsystems. To support shared logical resources requiring mutual exclusive access in two-level HSFs, overrun without payback has been proposed as a mechanism to prevent budget depletion during resource access arbitrated by the stack resource policy (SRP). In this paper, we revisit the global schedulability analysis of synchronization protocols based on SRP and overrun without payback for fixed-priority scheduled HSFs. We derive a new global schedulability analysis based on the observation that the overrun budget is merely meant to prevent budget depletion during global resource access. The deadline of a subsystem therefore only needs to hold for its normal budget rather than the sum of the normal and overrun budget. Our novel analysis is considerably simpler than an earlier, initially improved analysis, which improved both the original local and global schedulability analyses. We evaluate the new analysis based on an extensive simulation study and compare the results with the existing analysis. Our simplified analysis does not significantly affect schedulability compared to the initially improved analysis. It is therefore proposed as a preferable engineering approach to synchronization protocols for compositional real-time systems. We accordingly present the implementation of our improvement in an OSEK-compliant real-time operating system to sketch its applicability in today's industrial automotive standards. Both implementation and run-time overheads are discussed providing measured results1. © 2011 IEEE.
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14.
  • Piwowar, A. M., et al. (author)
  • C60-ToF SIMS imaging of frozen hydrated HeLa cells
  • 2013
  • In: Surface and Interface Analysis. - : Wiley. - 0142-2421 .- 1096-9918. ; 45:1, s. 302-304
  • Journal article (peer-reviewed)abstract
    • Sample preparation continues to be a major challenge for SIMS studies of biological materials. Maintaining the native hydrated state of the material is important for preserving both chemical and spatial information. Here, we discuss a method that combines a sample wash and dry protocol followed by plunge-freezing in liquid ethane for a frozen-hydrated analysis of mammalian cells (HeLa). This method allows for the removal of the growth medium and maintains the hydrated state of the cells so that they can be prepared frozen-hydrated without the need for a freeze-fracture device. The cells, which were grown on silicon, were successfully regrown after the cleaning procedure, confirming that a significant portion of the cells remain undamaged during the wash and dry procedure. Results from preliminary SIMS measurements show that is it possible to detect a large variety of biomolecular signals, including intact lipids from the plasma membrane in the mass range of 700–900Da from single cells, with little external water interference at the surface.
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  • Synofzik, M., et al. (author)
  • Mutant superoxide dismutase-1 indistinguishable from wild-type causes ALS
  • 2012
  • In: Human Molecular Genetics. - : Oxford University Press (OUP): Policy B - Oxford Open Option B. - 0964-6906 .- 1460-2083. ; 21:16, s. 3568-3574
  • Journal article (peer-reviewed)abstract
    • A reason for screening amyotrophic lateral sclerosis (ALS) patients for mutations in the superoxide dismutase-1 (SOD1) gene is the opportunity to find novel mutations with properties that can give information on pathogenesis. A novel c.352Cgreater thanG (L117V) SOD1 mutation was found in two Syrian ALS families living in Europe. The disease showed unusually low penetrance and slow progression. In erythrocytes, the total SOD1 activity, as well as specific activity of the mutant protein, was equal in carriers of the mutation and family controls lacking SOD1 mutations. The structural stabilities of the L117V mutant and wild-type SOD1 under denaturing conditions were likewise equal, but considerably lower than that of murine SOD1. As analyzed with an ELISA specific for misfolded SOD1 species, no differences were found in the content of misfolded SOD1 protein between extracts of fibroblasts from wild-type controls and from an L117V patient. In contrast, elevated levels of misfolded SOD1 protein were found in fibroblasts from ALS patients carrying seven other mutations in the SOD1 gene. We conclude that mutations in SOD1 that result in a fully stable protein are associated with low disease penetrance for ALS and may be found in cases of apparently sporadic ALS. Wild-type human SOD1 is moderately stable, and was found here to be within the stability range of ALS-causing SOD1 variants, lending support to the hypothesis that wild-type SOD1 could be more generally involved in ALS pathogenesis.
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17.
  • Baquero Barneto, Carlos, et al. (author)
  • Millimeter-wave Mobile Sensing and Environment Mapping: Models, Algorithms and Validation
  • 2022
  • In: IEEE Transactions on Vehicular Technology. - 0018-9545 .- 1939-9359. ; 71:4, s. 3900-3916
  • Journal article (peer-reviewed)abstract
    • Integrating efficient connectivity, positioning and sensing functionalities into 5G New Radio (NR) and beyond mobile cellular systems is one timely research paradigm, especially at mm-wave and sub-THz bands. In this article, we address the radio-based sensing and environment mapping prospect with specific emphasis on the user equipment (UE) side. We first describe an efficient $\ell_1$-regularized least-squares (LS) approach to obtain sparse range--angle charts at individual measurement or sensing locations. For the subsequent environment mapping, we then introduce a novel state model for mapping diffuse and specular scattering, which allows efficient tracking of individual scatterers over time using interacting multiple model (IMM) extended Kalman filter and smoother. Also the related measurement selection and data association problems are addressed. We provide extensive numerical indoor mapping results at the 28~GHz band deploying OFDM-based 5G NR uplink waveform with 400~MHz channel bandwidth, covering both accurate ray-tracing based as well as actual RF measurement results. The results illustrate the superiority of the dynamic tracking-based solutions, compared to static reference methods, while overall demonstrate the excellent prospects of radio-based mobile environment sensing and mapping in future mm-wave networks.
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  • Gholami, Mohammad Reza, et al. (author)
  • Cooperative Positioning in Wireless Networks
  • 2016
  • In: Wiley Encyclopedia of Electrical and Electronics Engineering. - : John Wiley & Sons. - 9780471346081 ; , s. 1-19
  • Book chapter (peer-reviewed)abstract
    • In this article, we study cooperative positioning in wireless networks in which target nodes at unknown locations locally collaborate with each other to find their locations. We review different models available for positioning and categorize the model-based algorithms in two groups: centralized and distributed. We then investigate a lower bound on the variance of unbiased estimators, namely the Cramer–Rao lower bound, which is a common benchmark in the positioning literature. We finally discuss some open problems and research topics in the area of positioning that are worth exploring in future studies.
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  • Gonzalez-Prelcic, Nuria, et al. (author)
  • The Integrated Sensing and Communication Revolution for 6G: Vision, Techniques, and Applications
  • 2024
  • In: Proceedings of the IEEE. - 1558-2256 .- 0018-9219. ; In Press
  • Journal article (peer-reviewed)abstract
    • Future wireless networks will integrate sensing, learning, and communication to provide new services beyond communication and to become more resilient. Sensors at the network infrastructure, sensors on the user equipment (UE), and the sensing capability of the communication signal itself provide a new source of data that connects the physical and radio frequency (RF) environments. A wireless network that harnesses all these sensing data can not only enable additional sensing services but also become more resilient to channel-dependent effects such as blockage and better support adaptation in dynamic environments as networks reconfigure. In this article, we provide a vision for integrated sensing and communication (ISAC) networks and an overview of how signal processing, optimization, and machine learning (ML) techniques can be leveraged to make them a reality in the context of 6G. We also include some examples of the performance of several of these strategies when evaluated using a simulation framework based on a combination of ray-tracing measurements and mathematical models that mix the digital and physical worlds.
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  • Keskin, Furkan, 1988, et al. (author)
  • Peak Sidelobe Level Based Waveform Optimization for OFDM Joint Radar-Communications
  • 2021
  • In: EuRAD 2020 - 2020 17th European Radar Conference. ; , s. 1-4
  • Conference paper (peer-reviewed)abstract
    • We propose a novel joint radar communication waveform design method based on OFDM spectrum allocation to trade off radar and communication performance. The proposed approach combines the water filling optimization to maximize the communication rate for slow fading channels with windowing to reduce pulse compression peak sidelobe level (PSL) for the radar. A trade-off between communication and radar performance is demonstrated by modifying the constraints of the optimization problem. The results show that, depending on the channel response, the proposed optimization method can significantly reduce PSL with limited impact on the data rate.
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24.
  • Keskin, Isil, et al. (author)
  • Comprehensive analysis to explain reduced or increased SOD1 enzymatic activity in ALS patients and their relatives
  • 2017
  • In: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration. - : TAYLOR & FRANCIS LTD. - 2167-8421 .- 2167-9223. ; 18:5-6, s. 457-463
  • Journal article (peer-reviewed)abstract
    • Objective: To characterise stabilities in erythrocytes of mutant SOD1 proteins, compare SOD1 enzymatic activities between patients with different genetic causes of ALS and search for underlying causes of deviant SOD1 activities in individuals lacking SOD1 mutations.Methods: Blood samples from 4072 individuals, ALS patients with or without a SOD1 mutation, family members and controls were studied. Erythrocyte SOD1 enzymatic activities normalised to haemoglobin content were determined, and effects of haemoglobin disorders on dismutation assessed. Coding SOD1 sequences were analysed by Sanger sequencing, exon copy number variations by fragment length analysis and by TaqMan Assay.Results: Of the 44 SOD1 mutations found, 75% caused severe destabilisation of the mutant protein but in 25% it was physically stable. Mutations producing structural changes caused halved erythrocyte SOD1 activities. There were no differences in SOD1 activities between patients without a SOD1 mutation and control individuals or carriers of TBK1 mutations and C9orf72(HRE). In the low and high SOD1 activity groups no deviations were found in exon copy numbers and intron gross structures. Thalassemias and iron deficiency were associated with increased SOD1 activity/haemoglobin ratios.Conclusion: Adjunct erythrocyte SOD1 activity analysis reliably signals destabilising SOD1 mutations including intronic mutations that are missed by exon sequencing.
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  • Keskin, Isil, 1987-, et al. (author)
  • Comprehensive analysis to explain reduced or increased SOD1 enzymatic activity in erythrocytes in ALS patients and their relatives
  • Other publication (other academic/artistic)abstract
    • Our objective was to in blood samples from 3723 individuals including ALS patients without a coding SOD1 mutation and 372 control individuals characterize stabilities of mutant SOD1s, compare SOD1 enzymatic activities between patients with different genetic causes of ALS, and search for underlying causes of deviant SOD1 activities in individuals lacking SOD1 mutations. Erythrocyte SOD1 enzymatic activities normalized to hemoglobin content were determined. Coding SOD1 sequences were analyzed by Sanger sequencing, copy number variations by fragment length analysis and by TaqMan Assay. Hemoglobin disorders were searched for. Of the 46 SOD1 mutations found, ¾ caused severe destabilization of the mutant protein but in ¼ SOD1 was essentially physically stable. Mutations producing structural changes all caused halved SOD activities. There were no differences in SOD1 activities between controls and patients without any detected SOD1 mutations or patients with C9ORF72HRE or TBK1 mutations. In the low and high SOD1 activity groups no deviations were found in exon copy numbers and intron gross structures. Also, no uncommon variants in exon-flanking sequences were detected. Thalassemias and iron deficiency anemia were associated with increased SOD1 activity/hemoglobin ratios. In conclusion, adjunct erythrocyte SOD activity analysis is of value to signal the presence of exon and splice-site-intron mutations that influence the SOD1 structure.
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26.
  • Keskin, Isil, et al. (author)
  • Effects of Cellular Pathway Disturbances on Misfolded Superoxide Dismutase-1 in Fibroblasts Derived from ALS Patients
  • 2016
  • In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:2
  • Journal article (peer-reviewed)abstract
    • Mutations in superoxide dismutase-1 (SOD1) are a common known cause of amyotrophic lateral sclerosis (ALS). The neurotoxicity of mutant SOD1s is most likely caused by misfolded molecular species, but disease pathogenesis is still not understood. Proposed mechanisms include impaired mitochondrial function, induction of endoplasmic reticulum stress, reduction in the activities of the proteasome and autophagy, and the formation of neurotoxic aggregates. Here we examined whether perturbations in these cellular pathways in turn influence levels of misfolded SOD1 species, potentially amplifying neurotoxicity. For the study we used fibroblasts, which express SOD1 at physiological levels under regulation of the native promoter. The cells were derived from ALS patients expressing 9 different SOD1 mutants of widely variable molecular characteristics, as well as from patients carrying the GGGGCC-repeat-expansion in C9orf72 and from non-disease controls. A specific ELISA was used to quantify soluble, misfolded SOD1, and aggregated SOD1 was analysed by western blotting. Misfolded SOD1 was detected in all lines. Levels were found to be much lower in non-disease control and the non-SOD1 C9orf72 ALS lines. This enabled us to validate patient fibroblasts for use in subsequent perturbation studies. Mitochondrial inhibition, endoplasmic reticulum stress or autophagy inhibition did not affect soluble misfolded SOD1 and in most cases, detergent-resistant SOD1 aggregates were not detected. However, proteasome inhibition led to uniformly large increases in misfolded SOD1 levels in all cell lines and an increase in SOD1 aggregation in some. Thus the ubiquitin-proteasome pathway is a principal determinant of misfolded SOD1 levels in cells derived both from patients and controls and a decline in activity with aging could be one of the factors behind the mid-to late-life onset of inherited ALS.
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  • Keskin, Isil, 1987-, et al. (author)
  • Peripheral administration of SOD1 aggregates does not transmit pathogenic aggregation to the CNS of SOD1 transgenic mice
  • 2021
  • In: Acta neuropathologica communications. - : BioMed Central. - 2051-5960. ; 9:1
  • Journal article (peer-reviewed)abstract
    • The deposition of aggregated proteins is a common neuropathological denominator for neurodegenerative disorders. Experimental evidence suggests that disease propagation involves prion-like mechanisms that cause the spreading of template-directed aggregation of specific disease-associated proteins. In transgenic (Tg) mouse models of superoxide dismutase-1 (SOD1)-linked amyotrophic lateral sclerosis (ALS), inoculation of minute amounts of human SOD1 (hSOD1) aggregates into the spinal cord or peripheral nerves induces premature ALS-like disease and template-directed hSOD1 aggregation that spreads along the neuroaxis. This infectious nature of spreading pathogenic aggregates might have implications for the safety of laboratory and medical staff, recipients of donated blood or tissue, or possibly close relatives and caregivers. Here we investigate whether transmission of ALS-like disease is unique to the spinal cord and peripheral nerve inoculations or if hSOD1 aggregation might spread from the periphery into the central nervous system (CNS). We inoculated hSOD1 aggregate seeds into the peritoneal cavity, hindlimb skeletal muscle or spinal cord of adult Tg mice expressing mutant hSOD1. Although we used up to 8000 times higher dose—compared to the lowest dose transmitting disease in spinal cord inoculations—the peripheral inoculations did not transmit seeded aggregation to the CNS or premature ALS-like disease in hSOD1 Tg mice. Nor was any hSOD1 aggregation detected in the liver, kidney, skeletal muscle or sciatic nerve. To explore potential reasons for the lack of disease transmission, we examined the stability of hSOD1 aggregates and found them to be highly vulnerable to both proteases and detergent. Our findings suggest that exposed individuals and personnel handling samples from ALS patients are at low risk of any potential transmission of seeded hSOD1 aggregation.
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  • Keskin, Isil, 1987- (author)
  • SOD, ORF and ALS: On the role of SOD1 and C9ORF72 in the pathogenesis of ALS
  • 2016
  • Doctoral thesis (other academic/artistic)abstract
    • Amyotrophic lateral sclerosis (ALS) is characterized by adult-onset degeneration of upper and lower motor neurons. Symptoms begin focally in one muscle and then spread contiguously, resulting in progressive paralysis and death from respiratory failure. Hexanucleotide repeat expansion in C9ORF72 is the most common genetic cause, however, mutations in SOD1 were the first identified and are found in 1-9% of patients. Misfolded SOD1 aggregates in the CNS are hallmarks of ALS associated with SOD1 mutations. However, accumulation of misfolded or aggregated SOD1 protein has also been reported in sporadic and familial ALS without SOD1 mutations, suggesting that wild-type SOD1 could play a role in ALS pathology in general.The aims of this thesis are: 1) To describe the resulting disease phenotype and specific characteristics of the SOD1 protein carrying the stable disease- associated mutation L117V. 2) To set up cell-based in vitro models to study the mechanisms of SOD1 misfolding and aggregation under physiologically relevant expression levels. 3) To compare SOD1 activity in patient-derived samples and screen for underlying causes of deviant SOD1 activities in individuals lacking SOD1 mutations.1) We identified a novel L117V SOD1 mutant in two families of Syrian origin that co-segregated with the disease. This mutation was associated with slow disease progression, reduced penetrance and a uniform phenotype. The L117V mutant protein was indistinguishable from wild-type SOD1 in terms of stability, dismutation activity and misfolding in patient-derived cell lines.2) We established patient-derived fibroblast and iPSC-MN lines expressing mutant SOD1 at physiological levels as in vitro models to study misfolding and aggregation of SOD1. We investigated the effects of several cellular pathway disturbances on SOD1 misfolding. Misfolded SOD1 was increased by inhibition of the ubiquitin-proteasome pathway in fibroblasts derived from both patients and controls. An age-related decline in proteasome activity could contribute to the late onset of ALS.Next, we studied the effects of low oxygen tension on misfolding and aggregation of SOD1 in patient-derived cells. Low O2 tensions were found to markedly increase C57-C146 disulphide reduction, misfolding and aggregation of SOD1. Importantly, the largest effects were detected in iPSC-MNs. This suggests that motor neurons are specifically vulnerable to misfolding and aggregation of SOD1 under low O2 tension.3) We compared the enzymatic activity of SOD1 in blood samples from a large number of ALS patients and controls. We screened for potential underlying causes of deviant SOD1 activities in individuals lacking SOD1 mutations. No aberrations in copy number, other large structural changes in introns and exons or intronic mutations in the 30-50 bp flanking the exons were found in the 142 outliers, with either very low or very high SOD1 dismutation activities. However, hemoglobinopathies, including thalassemias and iron deficiency anemia, were associated with high SOD1/mg Hb ratios. Erythrocytes from patients with destabilizing SOD1 mutations showed half the normal activity. There were no significant differences in SOD1 activity between control individuals and ALS patients without a coding SOD1 mutation, or carriers of TBK1 mutations or the hexanucleotide repeat expansion in C9ORF72. Our result suggests that SOD1 enzymatic activity is not associated with the disease in non-SOD1 mutation ALS.
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  • Keskin, Isil, 1987-, et al. (author)
  • The molecular pathogenesis of superoxide dismutase 1-linked ALS is promoted by low oxygen tension
  • 2019
  • In: Acta Neuropathologica. - New York : Springer. - 0001-6322 .- 1432-0533. ; 138:1, s. 85-101
  • Journal article (peer-reviewed)abstract
    • Mutations in superoxide dismutase 1 (SOD1) cause amyotrophic lateral sclerosis (ALS). Disease pathogenesis is linked to destabilization, disorder and aggregation of the SOD1 protein. However, the non-genetic factors that promote disorder and the subsequent aggregation of SOD1 have not been studied. Mainly located to the reducing cytosol, mature SOD1 contains an oxidized disulfide bond that is important for its stability. Since O2 is required for formation of the bond, we reasoned that low O2 tension might be a risk factor for the pathological changes associated with ALS development. By combining biochemical approaches in an extensive range of genetically distinct patient-derived cell lines, we show that the disulfide bond is an Achilles heel of the SOD1 protein. Culture of patient-derived fibroblasts, astrocytes, and induced pluripotent stem cell-derived mixed motor neuron and astrocyte cultures (MNACs) under low oxygen tensions caused reductive bond cleavage and increases in disordered SOD1. The effects were greatest in cells derived from patients carrying ALS-linked mutations in SOD1. However, significant increases also occurred in wild-type SOD1 in cultures derived from non-disease controls, and patients carrying mutations in other common ALS-linked genes. Compared to fibroblasts, MNACs showed far greater increases in SOD1 disorder and even aggregation of mutant SOD1s, in line with the vulnerability of the motor system to SOD1-mediated neurotoxicity. Our results show for the first time that O2 tension is a principal determinant of SOD1 stability in human patient-derived cells. Furthermore, we provide a mechanism by which non-genetic risk factors for ALS, such as aging and other conditions causing reduced vascular perfusion, could promote disease initiation and progression.
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  • Keskin, M, et al. (author)
  • A Comparative Analysis of Treatment-Related Changes in the Diagnostic Biomarker Active Metalloproteinase-8 Levels in Patients with Periodontitis
  • 2023
  • In: Diagnostics (Basel, Switzerland). - : MDPI AG. - 2075-4418. ; 13:5
  • Journal article (peer-reviewed)abstract
    • Background: Previous studies have revealed the potential diagnostic utility of aMMP-8, an active form of MMP-8, in periodontal and peri-implant diseases. While non-invasive point-of-care (PoC) chairside aMMP-8 tests have shown promise in this regard, there is a dearth of literature on the evaluation of treatment response using these tests. The present study aimed to investigate treatment-related changes in aMMP-8 levels in individuals with Stage III/IV—Grade C periodontitis compared to a healthy control group, using a quantitative chairside PoC aMMP-8 test, and to determine its correlation with clinical parameters. Methods: The study included 27 adult patients (13 smoker, 14 non-smoker) with stage III/IV-grade C periodontitis and 25 healthy adult subjects. Clinical periodontal measurements, real-time PoC aMMP-8, IFMA aMMP-8, and Western immunoblot analyses were performed before and 1 month after anti-infective scaling and root planing periodontal treatment. Time 0 measurements were taken from the healthy control group to test the consistency of the diagnostic test. Results: Both PoC aMMP-8 and IFMA aMMP-8 tests showed a statistically significant decrease in aMMP-8 levels and improvement in periodontal clinical parameters following treatment (p < 0.05). The PoC aMMP-8 test had high diagnostic sensitivity (85.2%) and specificity (100.0%) for periodontitis and was not affected by smoking (p > 0.05). Treatment also reduced MMP-8 immunoreactivity and activation as demonstrated by Western immunoblot analysis. Conclusion: The PoC aMMP-8 test shows promise as a useful tool for the real-time diagnosis and monitoring of periodontal therapy.
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  • Keskin, M, et al. (author)
  • Oral Cavity Beta-Defensin Levels Are Regulated Differently during Radiotherapy in Head and Neck Cancer Patients
  • 2023
  • In: APPLIED SCIENCES-BASEL. - : MDPI AG. - 2076-3417. ; 13:4
  • Journal article (other academic/artistic)abstract
    • Background: Human beta-defensins (hBDs) are small cationic peptides of the epithelium with broad antimicrobial and immune response-regulatory activities. hBDs are also related to oncogenesis, and their secretion profiles are affected by radiotherapy treatment. The present study aimed to investigate the oral cavity hBD 1-3 levels in head and neck cancer patients and its relation to radiotherapy treatment. Methods: Sixteen head and neck cancer patients (all with a history of smoking) were included in this study. Periodontal parameters were measured before radiotherapy, and medical information was collected from registries. Oral rinses of the patients were collected before radiotherapy; on the 1st, 3rd, and 6th weeks of radiotherapy; and the 1st month following the end of radiotherapy. hBD 1–3 levels were measured using ELISA. Results: Oral hBD-1 levels increased during radiotherapy at week 6 (p = 0.019). hBD-1 levels returned to pretreatment levels after the end of radiotherapy. No significant change was detected for hBD-2 or hBD-3 levels during or after radiotherapy. Conclusions: The constant expression of hBD-1, which is distinct from the infection and inflammation-dependent expression profiles of hBD-2 and hBD-3, may explain why this peptide is the only one affected by radiotherapy.
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35.
  • Park, Julien H., et al. (author)
  • The motor system is exceptionally vulnerable to absence of the ubiquitously expressed superoxide dismutase-1
  • 2023
  • In: Brain Communications. - : Oxford University Press. - 2632-1297. ; 5:1
  • Journal article (peer-reviewed)abstract
    • Superoxide dismutase-1 is a ubiquitously expressed antioxidant enzyme. Mutations in SOD1 can cause amyotrophic lateral sclerosis, probably via a toxic gain-of-function involving protein aggregation and prion-like mechanisms. Recently, homozygosity for loss-of-function mutations in SOD1 has been reported in patients presenting with infantile-onset motor neuron disease. We explored the bodily effects of superoxide dismutase-1 enzymatic deficiency in eight children homozygous for the p.C112Wfs∗11 truncating mutation. In addition to physical and imaging examinations, we collected blood, urine and skin fibroblast samples. We used a comprehensive panel of clinically established analyses to assess organ function and analysed oxidative stress markers, antioxidant compounds, and the characteristics of the mutant Superoxide dismutase-1. From around 8 months of age, all patients exhibited progressive signs of both upper and lower motor neuron dysfunction, cerebellar, brain stem, and frontal lobe atrophy and elevated plasma neurofilament concentration indicating ongoing axonal damage. The disease progression seemed to slow down over the following years. The p.C112Wfs∗11 gene product is unstable, rapidly degraded and no aggregates were found in fibroblast. Most laboratory tests indicated normal organ integrity and only a few modest deviations were found. The patients displayed anaemia with shortened survival of erythrocytes containing decreased levels of reduced glutathione. A variety of other antioxidants and oxidant damage markers were within normal range. In conclusion, non-neuronal organs in humans show a remarkable tolerance to absence of Superoxide dismutase-1 enzymatic activity. The study highlights the enigmatic specific vulnerability of the motor system to both gain-of-function mutations in SOD1 and loss of the enzyme as in the here depicted infantile superoxide dismutase-1 deficiency syndrome.
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36.
  • Rastorgueva-Foi, Elizaveta, et al. (author)
  • Millimeter-wave Radio SLAM: End-to-End Processing Methods and Experimental Validation
  • 2024
  • In: IEEE Journal on Selected Areas in Communications. - 0733-8716 .- 1558-0008. ; 42:9, s. 2550-2567
  • Journal article (peer-reviewed)abstract
    • In this article, we address the timely topic of cellular bistatic simultaneous localization and mapping (SLAM) with specific focus on end-to-end processing solutions, from raw I/Q samples, via channel parameter estimation to user equipment (UE) and landmark location information in millimeter-wave (mmWave) networks, with minimal prior knowledge. Firstly, we propose a new multipath channel parameter estimation solution that operates directly with beam reference signal received power (BRSRP) measurements, alleviating the need to know the true antenna beam-patterns or the underlying beamforming weights. Additionally, the method has built-in robustness against unavoidable antenna sidelobes. Secondly, we propose new snapshot SLAM algorithms that have increased robustness and identifiability compared to prior art, in practical built environments with complex clutter and multi-bounce propagation scenarios, and do not rely on any a priori motion model. The performance of the proposed methods is assessed at the 60GHz mmWave band, via both realistic ray-tracing evaluations as well as true experimental measurements, in an indoor environment. A wide set of offered results demonstrate the improved performance, compared to the relevant prior art, in terms of the channel parameter estimation as well as the end-to-end SLAM performance. Finally, the article provides the measured 60GHz data openly available for the research community, facilitating results reproducibility as well as further algorithm development.
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37.
  • Sorsa, T, et al. (author)
  • aMMP-8 Oral Fluid PoC Test in Relation to Oral and Systemic Diseases
  • 2022
  • In: Frontiers in oral health. - : Frontiers Media SA. - 2673-4842. ; 3, s. 897115-
  • Journal article (peer-reviewed)abstract
    • The manuscript uses the previously published literature and highlights the benefits of active-matrix metalloproteinase (aMMP)-8 chairside/point-of-care (PoC) diagnostic tools as adjunctive measures in oral and systemic diseases. Previous studies suggest that as a biomarker, aMMP-8 is more precise than total MMP-8, MMP-9, MMP-2, MMP-3, MMP-13, MMP-7, MMP-1, calprotectin, myeloperoxidase (MPO), human neutrophil elastase (HNE), tissue inhibitor of matrix metalloproteinase (TIMP)-1, and bleeding of probing (BOP). Therefore, aMMP-8 could be implemented as the needed key biomarker for the new disease classification for both periodontitis and peri-implantitis. With a sensitivity to the tune of 75–85% and specificity in the range of 80–90%, lateral flow aMMP-8 PoC testing is comparable to catalytic protease activity assays for aMMP-8. The test can be further applied to estimate the glycemic status of an individual, to ascertain whether a person is at risk for COVID-19, in managing the oral side effects of radiotherapy carried in head and neck cancers, and in selected cases pertaining to reproductive health. In the future, aMMP-8 could find application as a potential systemic biomarker in diseases affecting the cardiovascular system, cancers, bacteremia, sepsis, diabetes, obesity, meningitis, as well as pancreatitis. The aMMP-8 PoCT is the first practical test in the emerging new dental clinical field, that is, oral clinical chemistry representing oral medicine, clinical chemistry, peri-implantology, and periodontology.
  •  
38.
  • Talvitie, Jukka, et al. (author)
  • Indoor Mapping with a Mobile Radar Using an EK-PHD Filter
  • 2021
  • In: IEEE International Symposium on Personal, Indoor and Mobile Radio Communications, PIMRC. ; 2021-September
  • Conference paper (peer-reviewed)abstract
    • Integrated communications, localization and sensing is one of the most addressed technologies considered for future mobile communications systems. In this context, a user equipment (UE)-centric mobile radar has been proposed to introduce improved situational awareness, and consequently potential improvement in network performance. In this paper, we derive an extended Kalman probability hypothesis density (EK-PHD) filter with a novel feature model, for a mobile radar based environment mapping, where range-angle detections are used to track map objects over time for dynamic map construction. In order to evaluate the performance of the proposed filtering approach, we employ a realistic ray-tracing-based simulation setup, which models the full transmission chain from the transmitted IQ-samples to mapping results. Besides this, a simplified measurement model considering solely single-bounce specular reflections is exploited for providing further insight into the filter performance. The obtained results show that the proposed EK-PHD filter is able to provide high-quality mapping results, reaching around 10 cm landmark estimation accuracy in the considered millimeter wave simulation setup.
  •  
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