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| 6. |
- Maharana, S., et al.
(författare)
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Bright-Moon sky as a wide-field linear Polarimetric flat source for calibration
- 2023
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Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 679
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Tidskriftsartikel (refereegranskat)abstract
- Context. Next-generation wide-field optical polarimeters such as Wide-Area Linear Optical Polarimeters (WALOPs) have a field of view (FoV) of tens of arcminutes. Wide-field polarimetric flat sources are essential to the efficient and accurate calibration of these instruments. However, no established wide-field polarimetric standard or flat sources exist at present. Aims. This study tests the feasibility of using the polarized sky patches of the size of around 10 × 10 arcminutes2, at a distance of up to 20 from the Moon, on bright-Moon nights as a wide-field linear polarimetric flat source. Methods. We observed 19 patches of the sky adjacent to the bright-Moon with the RoboPol instrument in the SDSS-r broadband filter. These patches were observed on five nights within two days of the full-Moon across two RoboPol observing seasons. Results. We find that for 18 of the 19 patches, the uniformity in the measured normalized Stokes parameters q and u is within 0.2%, with 12 patches exhibiting uniformity within 0.07% or better for both q and u simultaneously, making them reliable and stable wide-field linear polarization flats. Conclusions. We demonstrate that the sky on bright-Moon nights is an excellent wide-field linear polarization flat source. Various combinations of the normalized Stokes parameters q and u can be obtained by choosing suitable locations of the sky patch with respect to the Moon.
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| 7. |
- Marazioti, Antonia, et al.
(författare)
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KRAS signaling in malignant pleural mesothelioma
- 2022
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Ingår i: EMBO Molecular Medicine. - : EMBO. - 1757-4684 .- 1757-4676. ; 14:2
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Tidskriftsartikel (refereegranskat)abstract
- Malignant pleural mesothelioma (MPM) arises from mesothelial cells lining the pleural cavity of asbestos-exposed individuals and rapidly leads to death. MPM harbors loss-of-function mutations in BAP1, NF2, CDKN2A, and TP53, but isolated deletion of these genes alone in mice does not cause MPM and mouse models of the disease are sparse. Here, we show that a proportion of human MPM harbor point mutations, copy number alterations, and overexpression of KRAS with or without TP53 changes. These are likely pathogenic, since ectopic expression of mutant KRASG12D in the pleural mesothelium of conditional mice causes epithelioid MPM and cooperates with TP53 deletion to drive a more aggressive disease form with biphasic features and pleural effusions. Murine MPM cell lines derived from these tumors carry the initiating KRASG12D lesions, secondary Bap1 alterations, and human MPM-like gene expression profiles. Moreover, they are transplantable and actionable by KRAS inhibition. Our results indicate that KRAS alterations alone or in accomplice with TP53 alterations likely play an important and underestimated role in a proportion of patients with MPM, which warrants further exploration.
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| 8. |
- Pelgrims, V., et al.
(författare)
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The first degree-scale starlight-polarization-based tomography map of the magnetized interstellar medium
- 2024
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Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 684
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Tidskriftsartikel (refereegranskat)abstract
- We present the first degree-scale tomography map of the dusty magnetized interstellar medium (ISM) from stellar polarimetry and distance measurements. We used the RoboPol polarimeter at Skinakas Observatory to conduct a survey of the polarization of starlight in a region of the sky of about four square degrees. We propose a Bayesian method to decompose the stellar-polarization source field along the distance to invert the three-dimensional (3D) volume occupied by the observed stars. We used this method to obtain the first 3D map of the dusty magnetized ISM. Specifically, we produced a tomography map of the orientation of the plane-of-sky component of the magnetic field threading the diffuse, dusty regions responsible for the stellar polarization. For the targeted region centered on Galactic coordinates (l, b) (103.3, 22.3), we identified several ISM clouds. Most of the lines of sight intersect more than one cloud. A very nearby component was detected in the foreground of a dominant component from which most of the polarization signal comes and which we identified as being an intersection of the wall of the Local Bubble and the Cepheus Flare. Farther clouds, with a distance of up to 2 kpc, were similarly detected. Some of them likely correspond to intermediate-velocity clouds seen in H I spectra in this region of the sky. We found that the orientation of the plane-of-sky component of the magnetic field changes along distance for most of the lines of sight. Our study demonstrates that starlight polarization data coupled to distance measures have the power to reveal the great complexity of the dusty magnetized ISM in 3D and, in particular, to provide local measurements of the plane-of-sky component of the magnetic field in dusty regions. This demonstrates that the inversion of large data volumes, as expected from the PASIPHAE survey, will provide the necessary means to move forward in the modeling of the Galactic magnetic field and of the dusty magnetized ISM as a contaminant in observations of the cosmic microwave background polarization.
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| 9. |
- Pelgrims, Vincent, et al.
(författare)
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Starlight-polarization-based tomography of the magnetized ISM: PASIPHAE's line-of-sight inversion method
- 2023
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 670
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Tidskriftsartikel (refereegranskat)abstract
- We present the first Bayesian method for tomographic decomposition of the plane-of-sky orientation of the magnetic field with the use of stellar polarimetry and distance. This standalone tomographic inversion method presents an important step forward in reconstructing the magnetized interstellar medium (ISM) in three dimensions within dusty regions. We develop a model in which the polarization signal from the magnetized and dusty ISM is described by thin layers at various distances, a working assumption which should be satisfied in small-angular circular apertures. Our modeling makes it possible to infer the mean polarization (amplitude and orientation) induced by individual dusty clouds and to account for the turbulence-induced scatter in a generic way. We present a likelihood function that explicitly accounts for uncertainties in polarization and parallax. We develop a framework for reconstructing the magnetized ISM through the maximization of the log-likelihood using a nested sampling method. We test our Bayesian inversion method on mock data, representative of the high Galactic latitude sky, taking into account realistic uncertainties from Gaia and as expected for the optical polarization survey PASIPHAE according to the currently planned observing strategy. We demonstrate that our method is effective at recovering the cloud properties as soon as the polarization induced by a cloud to its background stars is higher than ~0.1% for the adopted survey exposure time and level of systematic uncertainty. The larger the induced polarization is, the better the method's performance, and the lower the number of required stars. Our method makes it possible to recover not only the mean polarization properties but also to characterize the intrinsic scatter, thus creating new ways to characterize ISM turbulence and the magnetic field strength. Finally, we apply our method to an existing data set of starlight polarization with known line-of-sight decomposition, demonstrating agreement with previous results and an improved quantification of uncertainties in cloud properties.
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- Xochelli, Aliki, et al.
(författare)
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Clonal B-cell lymphocytosis exhibiting immunophenotypic features consistent with a marginal-zone origin : is this a distinct entity?
- 2014
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 123:8, s. 1199-1206
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Tidskriftsartikel (refereegranskat)abstract
- The biological and clinical significance of a clonal B-cell lymphocytosis with an immunophenotype consistent with marginal-zone origin (CBL-MZ) is poorly understood. We retrospectively evaluated 102 such cases with no clinical evidence to suggest a concurrent MZ lymphoma. Immunophenotyping revealed a clonal B-cell population with Matutes score <= 2 in all cases; 19/102 were weakly CD5 positive and all 35 cases tested expressed CD49d. Bone marrow biopsy exhibited mostly mixed patterns of small B-lymphocytic infiltration. A total of 48/66 (72.7%) cases had an abnormal karyotype. Immunogenetics revealed overusage of the IGHV4-34 gene and somatic hypermutation in 71/79 (89.8%) IGHV-IGHD-IGHJ gene rearrangements. With a median follow-up of 5 years, 85 cases remain stable (group A), whereas 17 cases (group B) progressed, of whom 15 developed splenomegaly. The clonal B-cell count, degree of marrow infiltration, immunophenotypic, or immunogenetic findings at diagnosis did not distinguish between the 2 groups. However, deletions of chromosome 7q were confined to group A and complex karyotypes were more frequent in group B. Although CBL-MZ may antedate SMZL/SLLU, most cases remain stable over time. These cases, not readily classifiable within the World Heath Organization classification, raise the possibility that CBL-MZ should be considered as a new provisional entity within the spectrum of clonal MZ disorders.
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| 13. |
- Makrakis, D, et al.
(författare)
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Effect of body tissue composition on the outcome of patients with metastatic non-small cell lung cancer treated with PD-1/PD-L1 inhibitors
- 2023
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 18:2, s. e0277708-
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Tidskriftsartikel (refereegranskat)abstract
- Obesity and sarcopenia have been reported to affect outcomes in patients with non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs). We analyzed prospective data from 52 patients with non-oncogene driven metastatic NSCLC treated with ICIs. Body tissue composition was calculated by measuring the fat and muscle densities at the level of 3rd lumbar vertebra in each patient computed tomography scan before ICI initiation using sliceOmatic tomovision. We converted the densities to indices [Intramuscular Fat Index (IMFI), Visceral Fat Index (VFI), Subcutaneous Fat Index (SFI), Lumbar Skeletal Muscle Index (LSMI)] by dividing them by height in meters squared. Patients were dichotomized based on their baseline IMFI, VFI and SFI according to their gender-specific median value. The cut-offs that were set for LMSI values were 55 cm2/m2 for males and 39 cm2/m2 for females. SFI distribution was significantly higher (p = 0.040) in responders compared to non-responders. None of the other variables affected response rates. Low LSMI HR: 2.90 (95% CI: 1.261–6.667, p = 0.012) and low SFI: 2.20 (95% CI: 1.114–4.333, p = 0.023) values predicted for inferior OS. VFI and IMFI values did not affect survival. Subcutaneous adipose and skeletal muscle tissue composition significantly affected immunotherapy outcomes in our cohort.
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| 14. |
- Monastirioti, A, et al.
(författare)
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Plasma-Based microRNA Expression Analysis in Advanced Stage NSCLC Patients Treated with Nivolumab
- 2022
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 14:19
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Tidskriftsartikel (refereegranskat)abstract
- Since circulating microRNAs (miRNAs) are involved in the modulation of the immune response, they are tested as liquid biopsy-based biomarkers in patients with NSCLC treated with immunotherapy. We analyzed the expression levels and examined the clinical significance of immunoregulatory miRNAs involved in immune checkpoint regulation (miR-34a, miR-200b, miR-200c), T-cell activity (miR-155), and the function of myeloid-derived suppressive cells (MDSCs) (miR-223) or regulatory T lymphocytes (Tregs) (miR-146a), in patients with advanced NSCLC (N = 69) treated with anti-PD-1 (Nivolumab) immunotherapy as 2nd or 3rd line of treatment therapy. Plasma levels of circulating miRNAs were analyzed by RT-qPCR before the initiation of immunotherapy. Expression of miR-34a, miR-146a, mir-200c, and miR-223 was found to be associated with response to immunotherapy. High miR-200c expression emerged as an independent prognostic factor for inferior overall survival in all patients with NSCLC (OS, HR: 2.243, 95% CI: 1.208–4.163; p = 0.010) and in patients with non-Squamous (non-SqCC) subtype (N = 38) (HR: 2.809, 95% CI: 1.116–7.074; p = 0.028). Low miR-34a expression independently predicted for shorter OS (HR: 3.189, 95% CI: 1.193–8.527; p = 0.021) in the non-SqCC subgroup. Our findings suggest that alterations in circulating miR-200c and miR-34a expression levels are associated with the response and outcome in patients with advanced NSCLC treated with anti-PD1 immunotherapy.
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- Vignola, Cristiano, et al.
(författare)
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Mid-late Holocene vegetation history of the Argive Plain (Peloponnese, Greece) as inferred from a pollen record from ancient Lake Lerna
- 2022
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 17:7
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Tidskriftsartikel (refereegranskat)abstract
- This study provides a high-resolution reconstruction of the vegetation of the Argive Plain (Peloponnese, Greece) covering 5000 years from the Early Bronze Age onwards. The well dated pollen record from ancient Lake Lerna has been interpreted in the light of archaeological and historical sources, climatic data from the same core and other regional proxies. Our results demonstrate a significant degree of human impact on the environments of the Argive Plain throughout the study period. During the Early Bronze Age evidence of a thermophilous vegetation is seen in the pollen record, representing the mixed deciduous oak woodland of the Peloponnesian uplands. The plain was mainly used for the cultivation of cereals, whereas local fen conditions prevailed at the coring site. Towards the end of this period an increasing water table is recorded and the fen turns into a lake, despite more arid conditions. In the Late Bronze Age, the presence of important palatial centres modified the landscape resulting in decrease of mixed deciduous oak woodland and increase in open land, partly used for grazing. Possibly, the human management produced a permanent hydrological change at Lake Lerna. From the Archaic period onwards the increasing human pressure in association with local drier conditions caused landscape instability, as attested by a dramatic alluvial event recorded in the Pinus curve at the end of the Hellenistic Age. Wet conditions coincided with Roman times and favoured a forest regeneration pattern in the area, at the same time as we see the most intensive olive cultivation in the pollen record. The establishment of an economic landscape primarily based on pastures is recorded in the Byzantine period and continues until modern times. Overgrazing and fires in combination with arid conditions likely caused degradation of the vegetation into garrigue, as seen in the area of the Argive Plain today.
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- Chigrinova, Ekaterina, et al.
(författare)
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Two main genetic pathways lead to the transformation of chronic lymphocytic leukemia to Richter syndrome
- 2013
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 122:15, s. 2673-2682
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Tidskriftsartikel (refereegranskat)abstract
- Richter syndrome (RS) occurs in up to 15% of patients with chronic lymphocytic leukemia (CLL). Although RS, usually represented by the histologic transformation to a diffuse large B-cell lymphoma (DLBCL), is associated with a very poor outcome, especially when clonally related to the preexisting CLL, the mechanisms leading to RS have not been clarified. To better understand the pathogenesis of RS, we analyzed a series of cases including 59 RS, 28 CLL phase of RS, 315 CLL, and 127 de novo DLBCL. RS demonstrated a genomic complexity intermediate between CLL and DLBCL. Cell-cycle deregulation via inactivation of TP53 and of CDKN2A was a main mechanism in the histologic transformation from CLL phase, being present in approximately one half of the cases, and affected the outcome of the RS patients. A second major subgroup was characterized by the presence of trisomy 12 and comprised one third of the cases. Although RS shared some of the lesions seen in de novo DLBCL, its genomic profile was clearly separate. The CLL phase preceding RS had not a generalized increase in genomic complexity compared with untransformed CLL, but it presented clear differences in the frequency of specific genetic lesions.
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- Gavriilidis, GI, et al.
(författare)
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Stem cell factor is implicated in microenvironmental interactions and cellular dynamics of chronic lymphocytic leukemia
- 2021
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Ingår i: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 1592-8721 .- 0390-6078. ; 106:3, s. 692-700
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Tidskriftsartikel (refereegranskat)abstract
- The inflammatory cytokine Stem Cell Factor (SCF, ligand of c-kit receptor) has been implicated as a pro-oncogenic driver and an adverse prognosticator in several human cancers. Increased SCF levels have recently been reported in a small series of patients with chronic lymphocytic leukemia (CLL), however its precise role in CLL pathophysiology remains elusive. In this study, CLL cells were found to predominantly express the membrane isoform of SCF that is known to elicit a more robust activation of the c-kit receptor. SCF was significantly overexpressed in CLL cells compared to healthy tonsillar B cells whilst it correlated with adverse-prognostic biomarkers, shorter time-to-first treatment and shorter overall survival. Activation of immune receptors and long-term cell-cell interactions with the mesenchymal stroma led to an elevation of SCF primarily in adverse-prognostic CLL cases. On the contrary, suppression of oxidative stress and the BTK inhibitor Ibrutinib negated SCF levels. Interestingly, SCF significantly correlated with mitochondrial dynamics and HIF-1α which have previously been linked with clinical aggressiveness in CLL. SCF was able to elicit direct biological effects in CLL cells affecting redox homeostasis and cell proliferation. Overall, the aberrantly expressed SCF in CLL cells emerges as a key response regulator to microenvironmental stimuli whilst correlating with poor prognosis. On these grounds, specific targeting of this inflammatory molecule could serve as a novel therapeutic approach in CLL.
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| 29. |
- Maes, Lea, et al.
(författare)
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Pilot evaluation of the HELENA (Healthy Lifestyle in Europe by Nutrition in Adolescence) Food-O-Meter, a computer-tailored nutrition advice for adolescents : a study in six European cities
- 2011
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Ingår i: Public Health Nutrition. - 1368-9800 .- 1475-2727. ; 14:7, s. 1292-1302
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Tidskriftsartikel (refereegranskat)abstract
- Objective: investigating the feasibility and impact of the Food-O-Meter, an internet based computer-tailored nutrition intervention in adolescents.Design: participants in the intervention condition received the computer-tailored advice at baseline and at one month. Participants in the control condition received a generic standard advice. Effects were evaluated at one month (n=621) and at three months (n=558) using multi-level modelling.Setting: secondary schools in 6 European cities.Subjects: adolescents (12-17 year old) out of the 6 centres of the HELENA study, Vienna (Austria), Ghent (Belgium), Heraklion (Crete), Dortmund (Germany), Athens (Greece) and Stockholm (Sweden), were randomised into intervention and control schools.Results: after 1 month students receiving the standardised advice reported an increase in their fat intake while in the intervention condition, fat intake was stable (F=4.82, P<0;05). After 3 months, there was in the total group a trend for an intervention effect of the tailored advice on fat intake (F=2.80, p<0.10). In the overweight group there was a clear positive effect (F=5.76, p<0.05).For sugared soft drinks consumption both the standardised, and the tailored advice, resulted after 3 months in a decrease in the consumption of soft drinks, but the effect was slightly greater for the standardised advice (F=4.52, p<0.05). No effects were found for other foods and nutrients.Conclusions: this pilot study showed that in most study centres the implementation of a web based tailored intervention was feasible and well appreciated by the adolescents. The results were modest but clear for percent energy from fat, specifically in the overweight group.
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| 30. |
- Mansouri, Larry, et al.
(författare)
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Frequent NFKBIE deletions are associated with poor outcome in primary mediastinal B-cell lymphoma
- 2016
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 128:23, s. 2666-2670
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Tidskriftsartikel (refereegranskat)abstract
- We recently reported a truncating deletion in the NFKBIE gene, which encodes IκBϵ, a negative feedback regulator of NF-κB, in clinically aggressive chronic lymphocytic leukemia (CLL). Preliminary data indicate enrichment of NFKBIE aberrations in other lymphoid malignancies, hence we screened a large patient cohort (n=1460) diagnosed with different lymphoid neoplasms. While NFKBIE deletions were infrequent in follicular lymphoma, splenic marginal-zone lymphoma, and T-cell acute lymphoblastic leukemia (<2%), slightly higher frequencies were seen in diffuse large B-cell lymphoma, mantle cell lymphoma, and primary CNS lymphoma (3-4%). In contrast, a remarkably high frequency of NFKBIE aberrations (46/203 cases, 22.7%) was observed in primary mediastinal B-cell lymphoma (PMBL) and Hodgkin lymphoma (3/11 cases, 27.3%). NFKBIE-deleted PMBL patients were more often therapy-refractory (P=.022) and displayed inferior outcome compared to wildtype patients (5-year survival: 59% vs. 78%; P=.034); however they appeared to benefit from radiotherapy (P=.022) and rituximab-containing regimens (P=.074). NFKBIEaberrations remained an independent factor in multivariate analysis (P=.003), also when restricting to immunochemotherapy-treated patients (P=.008). Whole-exome sequencing and gene expression-profiling verified the importance of NF-κB deregulation in PMBL. In summary, we identify NFKBIE aberrations as a common genetic event across B-cell malignancies and highlight NFKBIE deletions as a novel poor-prognostic marker in PMBL.
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| 31. |
- Mastrodemou, Semeli, et al.
(författare)
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Cytotoxic T cells in chronic idiopathic neutropenia express restricted antigen receptors
- 2017
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Ingår i: Leukemia and Lymphoma. - : TAYLOR & FRANCIS LTD. - 1042-8194 .- 1029-2403. ; 58:12, s. 2926-2933
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Tidskriftsartikel (refereegranskat)abstract
- Chronic idiopathic neutropenia (CIN) is an acquired disorder of granulopoiesis characterized by female predominance and mostly uncomplicated course. Crucial to CIN pathophysiology is the presence of activated T lymphocytes with myelosuppressive properties in both peripheral blood (PB) and bone marrow (BM). We systematically profiled the T cell receptor beta chain (TRB) gene repertoire in CD8(+) cells of 34 CIN patients through subcloning/Sanger sequencing analysis of TRBV-TRBD-TRBJ gene rearrangements. Remarkable repertoire skewing and oligoclonality were observed, along with shared clonotypes between different patients, alluding to antigen selection. Cross-comparison of our sequence dataset with public TRB sequence databases revealed that CIN may rarely share common immunogenetic features with other entities, however, the CIN TRB repertoire is largely disease-biased. Overall, these findings suggest that CIN may be driven by long-term exposure to a restricted set of specific CIN-associated antigens.
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| 33. |
- Salvati, E., et al.
(författare)
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Nanoscale structural damage due to focused ion beam milling of silicon with Ga-ions
- 2018
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Ingår i: Materials letters (General ed.). - : Elsevier. - 0167-577X .- 1873-4979. ; 213, s. 346-349
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Tidskriftsartikel (refereegranskat)abstract
- The exposure of sample to Focused Ion Beam leads to Ga-ion implantation, damage, material amorphisation, and the introduction of sources of residual stress; namely eigenstrain. In this study we employ synchrotron X-ray Reflectivity technique to characterise the amorphous layer generated in a single crystal Silicon sample by exposure to Ga-ion beam. The thickness, density and interface roughness of the amorphous layer were extracted from the analysis of the reflectivity curve. The outcome is compared with the eigenstrain profile evaluated from residual stress analysis by Molecular Dynamics and TEM imaging reported in the literature. (c) 2017 Elsevier B.V. All rights reserved.
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