1. |
- Pleskac, R., et al.
(author)
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The FIRST experiment at GSI
- 2012
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In: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 678, s. 130-138
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Journal article (peer-reviewed)abstract
- The FIRST (Fragmentation of Ions Relevant for Space and Therapy) experiment at the SIS accelerator of GSl laboratory in Darmstadt has been designed for the measurement of ion fragmentation crosssections at different angles and energies between 100 and 1000 MeV/nucleon. Nuclear fragmentation processes are relevant in several fields of basic research and applied physics and are of particular interest for tumor therapy and for space radiation protection applications. The start of the scientific program of the FIRST experiment was on summer 2011 and was focused on the measurement of 400 MeV/nucleon C-12 beam fragmentation on thin (8 mm) graphite target. The detector is partly based on an already existing setup made of a dipole magnet (ALADiN). a time projection chamber (TP-MUSIC IV), a neutron detector (LAND) and a time of flight scintillator system (TOFWALL). This pre-existing setup has been integrated with newly designed detectors in the Interaction Region, around the carbon target placed in a sample changer. The new detectors are a scintillator Start Counter, a Beam Monitor drift chamber, a silicon Vertex Detector and a Proton Tagger scintillator system optimized for the detection of light fragments emitted at large angles. In this paper we review the experimental setup, then we present the simulation software, the data acquisition system and finally the trigger strategy of the experiment.
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2. |
- Lukasik, J., et al.
(author)
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Discriminant analysis and secondary-beam charge recognition
- 2008
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In: Nuclear Instruments and Methods in Physics Research, Section A: Accelerators, Spectrometers, Detectors and Associated Equipment. - : Elsevier BV. - 0168-9002. ; 587:2-3, s. 413-419
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Journal article (peer-reviewed)abstract
- The discriminant-analysis method has been applied to optimize the exotic-beam charge recognition in a projectile fragmentation experiment. The experiment was carried out at the GSI using the fragment separator (FRS) to produce and select the relativistic secondary beams, and the ALADIN setup to measure their fragmentation products following collisions with Sn target nuclei. The beams of neutron poor isotopes around La-124 and Sn-107 were selected to study the isospin dependence of the limiting temperature of heavy nuclei by comparing with results for stable Sn-124 projectiles. A dedicated detector to measure the projectile charge upstream of the reaction target was not used, and alternative methods had to be developed. The presented method, based on the multivariate discriminant analysis, allowed to increase the efficacy of charge recognition up to about 90%, which was about 20% more than achieved with the simple scalar methods.
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4. |
- Santangelo, James S., et al.
(author)
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Global urban environmental change drives adaptation in white clover
- 2022
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 375
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Journal article (peer-reviewed)abstract
- Urbanization transforms environments in ways that alter biological evolution. We examined whether urban environmental change drives parallel evolution by sampling 110,019 white clover plants from 6169 populations in 160 cities globally. Plants were assayed for a Mendelian antiherbivore defense that also affects tolerance to abiotic stressors. Urban-rural gradients were associated with the evolution of clines in defense in 47% of cities throughout the world. Variation in the strength of clines was explained by environmental changes in drought stress and vegetation cover that varied among cities. Sequencing 2074 genomes from 26 cities revealed that the evolution of urban-rural dines was best explained by adaptive evolution, but the degree of parallel adaptation varied among cities. Our results demonstrate that urbanization leads to adaptation at a global scale.
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5. |
- Trautmann, W., et al.
(author)
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Isotopic dependence of the caloric curve
- 2009
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In: Progress in Particle and Nuclear Physics. - : Elsevier BV. - 0146-6410. ; 62:2, s. 407-412
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Journal article (peer-reviewed)abstract
- Isotopic effects in projectile fragmentation at relativistic energies have been studied with the ALADIN forward spectrometer at SIS. Stable and radioactive Sn and La beams with an incident energy of 600 MeV per nucleon have been used in order to explore a wide range of isotopic compositions. Chemical freeze-out temperatures are found to be nearly invariant with respect to the A/Z ratio of the produced spectator sources, consistent with predictions for expanded systems. Consequences for the proposed interpretation of chemical breakup temperatures as representing the limiting temperatures predicted by microscopic models are discussed. (C) 2009 Elsevier B.V. All rights reserved.
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6. |
- Pawlowski, P., et al.
(author)
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Neutron recognition in the LAND detector for large neutron multiplicity
- 2012
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In: Nuclear Instruments and Methods in Physics Research, Section A: Accelerators, Spectrometers, Detectors and Associated Equipment. - : Elsevier BV. - 0168-9002. ; 694, s. 47-54
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Journal article (peer-reviewed)abstract
- The performance of the LAND neutron detector is studied. Using an event-mixing technique based on one-neutron data obtained in the S107 experiment at the GSI laboratory, we test the efficiency of various analytic tools used to determine the multiplicity and kinematic properties of detected neutrons. A new algorithm developed recently for recognizing neutron showers from spectator decays in the ALADIN experiment S254 is described in detail. Its performance is assessed in comparison with other methods. The properties of the observed neutron events are used to estimate the detection efficiency of LAND in this experiment. (C) 2012 Elsevier B.V. All rights reserved.
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8. |
- Parrillo, L., et al.
(author)
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The Transcription Factor HOXA5: Novel Insights into Metabolic Diseases and Adipose Tissue Dysfunction
- 2023
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In: Cells. ; 12:16
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Journal article (peer-reviewed)abstract
- The transcription factor HOXA5, from the HOX gene family, has long been studied due to its critical role in physiological activities in normal cells, such as organ development and body patterning, and pathological activities in cancer cells. Nonetheless, recent evidence supports the hypothesis of a role for HOXA5 in metabolic diseases, particularly in obesity and type 2 diabetes (T2D). In line with the current opinion that adipocyte and adipose tissue (AT) dysfunction belong to the group of primary defects in obesity, linking this condition to an increased risk of insulin resistance (IR) and T2D, the HOXA5 gene has been shown to regulate adipocyte function and AT remodeling both in humans and mice. Epigenetics adds complexity to HOXA5 gene regulation in metabolic diseases. Indeed, epigenetic mechanisms, specifically DNA methylation, influence the dynamic HOXA5 expression profile. In human AT, the DNA methylation profile at the HOXA5 gene is associated with hypertrophic obesity and an increased risk of developing T2D. Thus, an inappropriate HOXA5 gene expression may be a mechanism causing or maintaining an impaired AT function in obesity and potentially linking obesity to its associated disorders. In this review, we integrate the current evidence about the involvement of HOXA5 in regulating AT function, as well as its association with the pathogenesis of obesity and T2D. We also summarize the current knowledge on the role of DNA methylation in controlling HOXA5 expression. Moreover, considering the susceptibility of epigenetic changes to reversal through targeted interventions, we discuss the potential therapeutic value of targeting HOXA5 DNA methylation changes in the treatment of metabolic diseases.
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9. |
- Lorente, A. Sanchez, et al.
(author)
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Performance of HPGe detectors in high magnetic fields
- 2007
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In: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 573:3, s. 410-417
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Journal article (peer-reviewed)abstract
- A new generation of high-resolution hypernuclear gamma-spectroscopy experiments with high-purity germanium detectors (HPGe) are presently designed at the FINUDA spectrometer at DA Phi NE, the Frascati phi-factory, and at (P) over bar ANDA, the (p) over barp hadron spectrometer at the future FAIR facility. Both, the FINUDA and (P) over bar ANDA spectrometers are built around the target region covering a large solid angle. To maximise the detection efficiency the HPGe detectors have to be located near the target, and therefore they have to be operated in strong magnetic fields (B approximate to I T). The performance of HPGe detectors in such an environment has not been well investigated so far. In the present work VEGA and EUROBALL Cluster HPGe detectors were tested in the field provided by the ALADiN magnet at GSI. No significant degradation of the energy resolution was found, and a change in the rise time distribution of the pulses from preamplifiers was observed. A correlation between rise time and pulse height was observed and is used to correct the measured energy, recovering the energy resolution almost completely. Moreover, no problems in the electronics due to the magnetic field were observed.
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10. |
- Mirra, P., et al.
(author)
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Adipocyte precursor cells from first degree relatives of type 2 diabetic patients feature changes in hsa-mir-23a-5p, -193a-5p, and -193b-5p and insulin-like growth factor 2 expression
- 2021
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In: FASEB Journal. - 0892-6638. ; 35:4
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Journal article (peer-reviewed)abstract
- First-degree relatives (FDRs) of type 2 diabetics (T2D) feature dysfunction of subcutaneous adipose tissue (SAT) long before T2D onset. miRNAs have a role in adipocyte precursor cells (APC) differentiation and in adipocyte identity. Thus, impaired miRNA expression may contribute to SAT dysfunction in FDRs. In the present work, we have explored changes in miRNA expression associated with T2D family history which may affect gene expression in SAT APCs from FDRs. Small RNA-seq was performed in APCs from healthy FDRs and matched controls and omics data were validated by qPCR. Integrative analyses of APC miRNome and transcriptome from FDRs revealed down-regulated hsa-miR-23a-5p, -193a-5p and -193b-5p accompanied by up-regulated Insulin-like Growth Factor 2 (IGF2) gene which proved to be their direct target. The expression changes in these marks were associated with SAT adipocyte hypertrophy in FDRs. APCs from FDRs further demonstrated reduced capability to differentiate into adipocytes. Treatment with IGF2 protein decreased APC adipogenesis, while over-expression of hsa-miR-23a-5p, -193a-5p and -193b-5p enhanced adipogenesis by IGF2 targeting. Indeed, IGF2 increased the Wnt Family Member 10B gene expression in APCs. Down-regulation of the three miRNAs and IGF2 up-regulation was also observed in Peripheral Blood Leukocytes (PBLs) from FDRs. In conclusion, APCs from FDRs feature a specific miRNA/gene profile, which associates with SAT adipocyte hypertrophy and appears to contribute to impaired adipogenesis. PBL detection of this profile may help in identifying adipocyte hypertrophy in individuals at high risk of T2D.
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11. |
- Parrillo, L., et al.
(author)
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Altered PTPRD DNA methylation associates with restricted adipogenesis in healthy first-degree relatives of Type 2 diabetes subjects
- 2020
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In: Epigenomics. - : Future Medicine Ltd. - 1750-1911 .- 1750-192X. ; 12:10, s. 873-888
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Journal article (peer-reviewed)abstract
- Aim: First-degree relatives (FDR) of individuals with Type 2 diabetes (T2D) feature restricted adipogenesis, which render them more vulnerable to T2D. Epigenetics may contribute to these abnormalities. Methods: FDR pre-adipocyte Methylome and Transcriptome were investigated by MeDIP- and RNA-Seq, respectively. Results:Methylome analysis revealed 2841 differentially methylated regions (DMR) in FDR. Most DMR localized into gene-body and were hypomethylated. The strongest hypomethylation signal was identified in an intronic-DMR at the PTPRD gene. PTPRD hypomethylation in FDR was confirmed by bisulphite sequencing and was responsible for its upregulation. Interestingly, Ptprd-overexpression in 3T3-L1 pre-adipocytes inhibited adipogenesis. Notably, the validated PTPRD-associated DMR was significantly hypomethylated in peripheral blood leukocytes from the same FDR individuals. Finally, PTPRD methylation pattern was also replicated in obese individuals. Conclusion: Our findings indicated a previously unrecognized role of PTPRD in restraining adipogenesis. This abnormality may contribute to increase FDR proclivity toward T2D.
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12. |
- Parrillo, L., et al.
(author)
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Epigenetic Dysregulation of the Homeobox A5 (HOXA5) Gene Associates with Subcutaneous Adipocyte Hypertrophy in Human Obesity
- 2022
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In: Cells. - : MDPI AG. - 2073-4409. ; 11:4
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Journal article (peer-reviewed)abstract
- Along with insulin resistance and increased risk of type 2 diabetes (T2D), lean first-degree relatives of T2D subjects (FDR) feature impaired adipogenesis in subcutaneous adipose tissue (SAT) and subcutaneous adipocyte hypertrophy well before diabetes onset. The molecular mechanisms linking these events have only partially been clarified. In the present report, we show that silencing of the transcription factor Homeobox A5 (HOXA5) in human preadipocytes impaired differentiation in mature adipose cells in vitro. The reduced adipogenesis was accompanied by inappropriate WNT-signaling activation. Importantly, in preadipocytes from FDR individuals, HOXA5 expression was attenuated, with hypermethylation of the HOXA5 promoter region found responsible for its downregulation, as revealed by luciferase assay. Both HOXA5 gene expression and DNA methylation were significantly correlated with SAT adipose cell hypertrophy in FDR, whose increased adipocyte size marks impaired adipogenesis. In preadipocytes from FDR, the low HOXA5 expression negatively correlated with enhanced transcription of the WNT signaling downstream genes NFATC1 and WNT2B. In silico evidence indicated that NFATC1 and WNT2B were directly controlled by HOXA5. The HOXA5 promoter region also was hypermethylated in peripheral blood leukocytes from these same FDR individuals, which was further revealed in peripheral blood leukocytes from an independent group of obese subjects. Thus, HOXA5 controlled adipogenesis in humans by suppressing WNT signaling. Altered DNA methylation of the HOXA5 promoter contributed to restricted adipogenesis in the SAT of lean subjects who were FDR of type 2 diabetics and in obese individuals. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.
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14. |
- Spinelli, R., et al.
(author)
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ZMAT3 hypomethylation contributes to early senescence of preadipocytes from healthy first-degree relatives of type 2 diabetics
- 2022
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In: Aging Cell. - : Wiley. - 1474-9718 .- 1474-9726. ; 21:3
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Journal article (peer-reviewed)abstract
- Senescence of adipose precursor cells (APC) impairs adipogenesis, contributes to the age-related subcutaneous adipose tissue (SAT) dysfunction, and increases risk of type 2 diabetes (T2D). First-degree relatives of T2D individuals (FDR) feature restricted adipogenesis, reflecting the detrimental effects of APC senescence earlier in life and rendering FDR more vulnerable to T2D. Epigenetics may contribute to these abnormalities but the underlying mechanisms remain unclear. In previous methylome comparison in APC from FDR and individuals with no diabetes familiarity (CTRL), ZMAT3 emerged as one of the top-ranked senescence-related genes featuring hypomethylation in FDR and associated with T2D risk. Here, we investigated whether and how DNA methylation changes at ZMAT3 promote early APC senescence. APC from FDR individuals revealed increases in multiple senescence markers compared to CTRL. Senescence in these cells was accompanied by ZMAT3 hypomethylation, which caused ZMAT3 upregulation. Demethylation at this gene in CTRL APC led to increased ZMAT3 expression and premature senescence, which were reverted by ZMAT3 siRNA. Furthermore, ZMAT3 overexpression in APC determined senescence and activation of the p53/p21 pathway, as observed in FDR APC. Adipogenesis was also inhibited in ZMAT3-overexpressing APC. In FDR APC, rescue of ZMAT3 methylation through senolytic exposure simultaneously downregulated ZMAT3 expression and improved adipogenesis. Interestingly, in human SAT, aging and T2D were associated with significantly increased expression of both ZMAT3 and the P53 senescence marker. Thus, DNA hypomethylation causes ZMAT3 upregulation in FDR APC accompanied by acquisition of the senescence phenotype and impaired adipogenesis, which may contribute to FDR predisposition for T2D.
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15. |
- Szymanska, K., et al.
(author)
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Resolution, efficiency and stability of HPGe detector operating in a magnetic field at various gamma-ray energies
- 2008
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In: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 592:3, s. 486-492
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Journal article (peer-reviewed)abstract
- The use of High Purity Germanium detectors (HPGe) has been planned in some future experiments of hadronic physics. The crystals will be located close to large spectrometers where the magnetic fringing field will not be negligible and their performances might change. Moreover high precision is required in these experiments. The contribution of magnetic field presence and long term measurements is unique. In this paper the results of systematic measurements of the resolution, stability and efficiency of a crystal operating inside a magnetic field of 0.8 T, using radioactive sources in the energy range from 0.08 to 1.33 MeV, are reported. The measurements have been repeated during several months in order to test if any permanent damage occurred. The resolution at 1.117 and 1.332 MeV gamma-rays from a Co-60 source has been measured at different magnetic fields in the range of 0-0.8 T and the results are compared with the previous data.
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