| 1. |
- Ricci, C., et al.
(författare)
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A Tight Correlation between Millimeter and X-Ray Emission in Accreting Massive Black Holes from
- 2023
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Ingår i: Astrophysical Journal Letters. - 2041-8213 .- 2041-8205. ; 952:2
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Tidskriftsartikel (refereegranskat)abstract
- Recent studies have proposed that the nuclear millimeter continuum emission observed in nearby active galactic nuclei (AGNs) could be created by the same population of electrons that gives rise to the X-ray emission that is ubiquitously observed in accreting black holes. We present the results of a dedicated high-spatial-resolution (∼60-100 mas) Atacama Large Millimeter/submillimeter Array (ALMA) campaign on a volume-limited (<50 Mpc) sample of 26 hard X-ray (>10 keV) selected radio-quiet AGNs. We find an extremely high detection rate (25/26 or 94 − 6 + 3 % ), which shows that nuclear emission at millimeter wavelengths is nearly ubiquitous in accreting SMBHs. Our high-resolution observations show a tight correlation between the nuclear (1-23 pc) 100 GHz and the intrinsic X-ray emission (1σ scatter of 0.22 dex). The ratio between the 100 GHz continuum and the X-ray emission does not show any correlation with column density, black hole mass, Eddington ratio, or star formation rate, which suggests that the 100 GHz emission can be used as a proxy of SMBH accretion over a very broad range of these parameters. The strong correlation between 100 GHz and X-ray emission in radio-quiet AGNs could be used to estimate the column density based on the ratio between the observed 2-10 keV ( F 2 - 10 keV obs ) and 100 GHz (F 100 GHz) fluxes. Specifically, a ratio log ( F 2 - 10 keV obs / F 100 GHz ) ≤ 3.5 strongly suggests that a source is heavily obscured ( log ( N H / cm − 2 ) ≳ 23.8 ). Our work shows the potential of ALMA continuum observations to detect heavily obscured AGNs (up to an optical depth of one at 100 GHz, i.e., N H ≃ 1027 cm−2), and to identify binary SMBHs with separations <100 pc, which cannot be probed by current X-ray facilities.
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| 2. |
- Terpos, Evangelos, et al.
(författare)
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High Serum Sclerostin Correlates with Advanced Stage, Increased Bone Resorption, Reduced Osteoblast Function, and Poor Survival in Newly-Diagnosed Patients with Multiple Myeloma.
- 2009
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 114:22, s. 425-425
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Tidskriftsartikel (refereegranskat)abstract
- Multiple myeloma (MM) is characterized by the presence of lytic bone disease due to increased osteoclast activity which is accompanied by reduced osteoblast function. To-date dickkopf-1 (Dkk-1) is considered as the main osteoblast inhibitor which is overproduced by myeloma cells and inhibits Wnt signaling leading to osteoblast exhaustion. Sclerostin is another canonical Wnt antagonist through its binding to low-density lipoprotein-receptor-related protein 5/6. Sclerostin is specifically expressed by osteocytes and inhibits bone morphogenic protein-induced osteoblast differentiation and ectopic bone formation. Osteonectin (SPARC) is a multi-faceted protein that belongs to a family of matricellular proteins. It is secreted by osteoblasts during bone formation, initiating mineralization and promoting mineral crystal formation. SPARC shows affinity for collagen in addition to bone mineral calcium. The aim of this study contacted by the Greek Myeloma Study Group in collaboration with Biomarker Design Forschungs GmbH (BDF), Vienna, Austria was to evaluate, for the first time in the literature, the serum levels of sclerostin in patients with MM and explore possible correlations with clinical and laboratory data, including SPARC levels, ISS stage and survival. One hundred and fifty-seven patients (87M/70F, median age 68 years) with MM at diagnosis before the administration of any type of therapy, including bisphosphonates, were evaluated. Serum sclerostin and SPARC were measured using an ELISA methodology developed by BDF for Biomedica Medizinprodukte GmbH & Co KG (Vienna, Austria). Both assays are sandwich type ELISA using biotinylated antibodies/HRP-streptavidine for the detection of sclerostin and SPARC in the serum. The detection limit of the sclerostin ELISA was 0.18 ng/ml and the coefficient of variation (CV) 6%. The standard range was set from 0.3-3 ng/ml. For the SPARC ELISA we found a detection limit of 1.95 ng/ml and CVs of 8% using a standard range from 5-130 ng/ml. Serum sclerostin and SPARC were determined in MM patients, 21 patients with MGUS and 21 healthy controls, of similar gender and age. Bone remodeling was also studied by the measurement of a series of serum indices within one week from diagnosis: i) osteoclast regulators [sRANKL and osteoprotegerin (OPG)], ii) Dkk-1, iii) bone resorption markers [C-terminal cross-linking telopeptide of collagen type-I (CTX) and 5b-isoenzyme of tartrate resistant acid phosphatase (TRACP-5b)], and iv) bone formation markers [bone-specific alkaline phosphatase (bALP) and osteocalcin (OC)]. Patients with MM had increased levels of serum sclerostin compared with MGUS patients (mean value±SD: 0.48±0.46 vs. 0.26±0.29 ng/ml; p=0.004) and healthy controls (0.31±0.20 ng/ml, p=0.01). In contrast, both patients with MM and MGUS had reduced levels of serum SPARC (26.3±16.2 and 27.2±18.0 ng/ml, respectively) compared to controls (52.8±50.2 ng/ml; p<0.001). Sclerostin values strongly correlated with beta2-microglobulin (r=0.354, p<0.0001), cystatin-C (r=0.389, p<0.0001), serum creatinine (r=0.380, p<0.0001), and bALP (r=-0.541, p<0.0001). No correlations were observed between sclerostin with sRANKL, OPG, Dkk-1 or SPARC. Patients with advanced bone disease assessed by conventional radiography (>3 lytic lesions and/or a pathological fracture) had a borderline increase of sclerostin compared to all others (median value: 0.51 vs. 0.41 ng/ml, p=0.09). Patients with ISS-3 disease had increased levels of sclerostin compared to patients with ISS-1 and ISS-2 MM (ANOVA p=0.001). Median survival of MM patients was 48 months and median follow-up period was 20 months. Patients who had a serum sclerostin of ≥0.62 ng/ml (upper quartile, n=40 patients) had a median survival of 27 months, while median survival of all other patients was 98 months (p=0.031). In conclusion, our study provided evidence that sclerostin is increased in the serum of patients with MM and correlates with advanced ISS stage, increased bone resorption, reduced osteoblast function and poor survival. SPARC is reduced in MM possibly confirming the reduced osteoblast function observed in these patients. Sclerostin seems to participate in the biology of MM and thus it may be a possible target for the development of novel therapies that can both increase osteoblast function and target myeloma cells.
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