The BGOOD experimental setup at ELSA Alef, S.; Bauer, P.; Bayadilov, D. ...
The European physical journal. A, Hadrons and nuclei,
04/2020, Letnik:
56, Številka:
4
Journal Article
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The BGOOD experiment at the ELSA facility in Bonn has been commissioned within the framework of an international collaboration. The experiment pursues a systematic investigation of non-strange and ...strange meson photoproduction, in particular
t
-channel processes at low momentum transfer. The setup uniquely combines a central almost
4
π
acceptance BGO crystal calorimeter with a large aperture forward magnetic spectrometer providing excellent detection of both neutral and charged particles, complementary to other setups such as Crystal Barrel, Crystal Ball, LEPS and CLAS.
The region of Diwalwal, dominated by Mt. Diwata, is a gold rush area on Mindanao (Philippines) where approximately 15
000 people live. The fertile plain of Monkayo is situated downstream, where ...people grow crops such as rice and bananas; locally caught fish is eaten frequently. The ore is dug in small-scale mines and ground to a powder by ball-mills while still in Diwalwal. The gold is then extracted by adding liquid mercury (Hg), forming gold-amalgam. To separate the gold from the Hg, in most cases the amalgam is simply heated in the open by blow-torches. A high external Hg burden of the local population must be assumed. To evaluate the internal Hg burden of the population and the extent of possible negative health effects, 323 volunteers from Mt. Diwalwal, Monkayo and a control group from Davao were examined by a questionnaire, neurological examination and neuro-psychological testing. Blood, urine and hair samples were taken from each participant and analyzed for total Hg. A statistical evaluation was possible for 102 workers (occupationally Hg burdened ball-millers and amalgam-smelters), 63 other inhabitants from Mt. Diwata (‘only’ exposed from the environment), 100 persons, living downstream in Monkayo, and 42 inhabitants of Davao (serving as controls). The large volume of data was reduced to yes/no decisions. Alcohol as a possible bias factor was excluded (level of alcohol consumption and type, see
Section 4.4). Each factor with a statistically significant difference of at least one exposed group to the control group was included in a medical score (0–21 points). In each of the exposed groups this score was significantly worse than in the control group (median control, 3; downstream, 9; Mt. Diwata, non-occupational exposed, 6; Hg workers, 10). In comparison to the surprisingly high Hg concentration in blood (median, 9.0 μg/l; max, 31.3) and in hair (2.65 μg/g; max, 34.7) of the control group, only the workers show elevated levels: Hg-blood median 11.4, max 107.6; Hg-hair median 3.62, max 37.8. The Hg urine concentrations of the occupational exposed and non-exposed population on Mt. Diwata was significantly higher than in the control group: control median 1.7 μg/l, max 7.6; non-occupational burdened median 4.1, max 76.4; and workers median 11.0, max 294.2. The participants, living downstream on the plain of Monkayo show no statistically significant difference in Hg-blood, Hg-urine or Hg-hair in comparison with the control group. The German Human-Biological-Monitoring value II (HBM II) was exceeded in 19.5% (control), 26.0% (downstream), 19.4% (Mt. Diwata, non-occupational) and 55.4% (workers) of the cases, the German occupational threshold limit in 19.6% of the workers. Only some of the clinical data, characteristic for Hg intoxication (e.g. tremor, loss of memory, bluish discoloration of the gingiva, etc.), correlate with Hg in blood or urine, but not with Hg in hair. The medical score sum correlates only with Hg in urine. The poor correlation between the Hg concentration in the biomonitors to classic clinical signs of chronic Hg intoxication may be explained by several factors: Hg in blood, urine and hair do not adequately monitor the Hg burden of the target tissues, especially the brain. Inter-individual differences in the sensitiveness to Hg are extremely large. In this area a mixed burden of Hg species must be assumed (Hg vapor, inorganic Hg, methyl-Hg). Chronic Hg burden may have established damage months or even years before the actual determination of the Hg concentrations in the bio-monitors under quite different burden was performed (Drasch G. Mercury. In: Seiler HG, Sigel A, Sigel H, editors. Handbook on metals in clinical and analytical chemistry. New York: Marcel Dekker, 1994:479–494). Therefore, a ‘Hg intoxication’, that should be treated, was not diagnosed by the Hg concentration in the bio-monitors alone, but by a balanced combination of these Hg values and the medical score sum. In principle, this means the higher the Hg concentration in the bio-monitors, the lower the number of characteristic adverse effects are required for a positive diagnosis. By this method, 0% of the controls, 38% downstream, 27% from Mt. Diwata, non-occupational exposed and 71.6% of the workers were classified as Hg intoxicated. A reduction of the external Hg burden on Mt. Diwata is urgently recommended. An attempt to treat the intoxicated participants with the chelating agent dimercaptopropanesulfonic acid (DMPS) is planned.
ABSTRACT
We present a general method to compute the non-linear matter power spectrum for dark energy (DE) and modified gravity scenarios with per cent-level accuracy. By adopting the halo model and ...non-linear perturbation theory, we predict the reaction of a lambda cold dark matter (ΛCDM) matter power spectrum to the physics of an extended cosmological parameter space. By comparing our predictions to N-body simulations we demonstrate that with no-free parameters we can recover the non-linear matter power spectrum for a wide range of different w0–wa DE models to better than 1 per cent accuracy out to k ≈ 1 $h \,{\rm Mpc}^{-1}$. We obtain a similar performance for both DGP and f(R) gravity, with the non-linear matter power spectrum predicted to better than 3 per cent accuracy over the same range of scales. When including direct measurements of the halo mass function from the simulations, this accuracy improves to 1 per cent. With a single suite of standard ΛCDM N-body simulations, our methodology provides a direct route to constrain a wide range of non-standard extensions to the concordance cosmology in the high signal-to-noise non-linear regime.
Steroid hormones are essential for carbohydrate metabolism, stress management, and reproduction and are synthesized from cholesterol in mitochondria of adrenal glands and gonads/ovaries. In acute ...stress or hormonal stimulation, steroidogenic acute regulatory protein (StAR) transports substrate cholesterol into the mitochondria for steroidogenesis by an unknown mechanism. Here, we report for the first time that StAR interacts with voltage-dependent anion channel 2 (VDAC2) at the mitochondria-associated endoplasmic reticulum membrane (MAM) prior to its translocation to the mitochondrial matrix. In the MAM, StAR interacts with mitochondrial proteins Tom22 and VDAC2. However, Tom22 knockdown by siRNA had no effect on pregnenolone synthesis. In the absence of VDAC2, StAR was expressed but not processed into the mitochondria as a mature 30-kDa protein. VDAC2 interacted with StAR via its C-terminal 20 amino acids and N-terminal amino acids 221–229, regulating the mitochondrial processing of StAR into the mature protein. In the absence of VDAC2, StAR could not enter the mitochondria or interact with MAM-associated proteins, and therefore steroidogenesis was inhibited. Furthermore, the N terminus was not essential for StAR activity, and the N-terminal deletion mutant continued to interact with VDAC2. The endoplasmic reticulum-targeting prolactin signal sequence did not affect StAR association with the MAM and thus its mitochondrial targeting. Therefore, VDAC2 controls StAR processing and activity, and MAM is thus a central location for initiating mitochondrial steroidogenesis.
Background: Steroidogenic acute regulatory protein (StAR) fosters cholesterol into the adrenal and gonadal mitochondria to initiate steroidogenesis.
Results: Voltage-dependent anion channel 2 (VDAC2) knockdown ablated pregnenolone synthesis and StAR processing into the mitochondria.
Conclusion: Interaction between StAR and VDAC2 is critical for steroidogenesis.
Significance: VDAC2 is a crucial regulator for initiating steroidogenesis.
ABSTRACT
We present observations of ASASSN-19dj, a nearby tidal disruption event (TDE) discovered in the post-starburst galaxy KUG 0810+227 by the All-Sky Automated Survey for Supernovae (ASAS-SN) at ...a distance of d ≃ 98 Mpc. We observed ASASSN-19dj from −21 to 392 d relative to peak ultraviolet (UV)/optical emission using high-cadence, multiwavelength spectroscopy and photometry. From the ASAS-SN g-band data, we determine that the TDE began to brighten on 2019 February 6.8 and for the first 16 d the rise was consistent with a flux ∝t2 power law. ASASSN-19dj peaked in the UV/optical on 2019 March 6.5 (MJD = 58548.5) at a bolometric luminosity of L = (6.2 ± 0.2) × 1044 erg s−1. Initially remaining roughly constant in X-rays and slowly fading in the UV/optical, the X-ray flux increased by over an order of magnitude ∼225 d after peak, resulting from the expansion of the X-ray emitting region. The late-time X-ray emission is well fitted by a blackbody with an effective radius of ∼1 × 1012 cm and a temperature of ∼6 × 105 K. The X-ray hardness ratio becomes softer after brightening and then returns to a harder state as the X-rays fade. Analysis of Catalina Real-Time Transient Survey images reveals a nuclear outburst roughly 14.5 yr earlier with a smooth decline and a luminosity of LV ≥ 1.4 × 1043 erg s−1, although the nature of the flare is unknown. ASASSN-19dj occurred in the most extreme post-starburst galaxy yet to host a TDE, with Lick HδA = 7.67 ± 0.17 Å.
Based on genomic analysis, 50% of high-grade serous ovarian cancers (HGSC) are predicted to have DNA repair defects. Whether this substantial subset of HGSCs actually have functional repair defects ...remains unknown. Here, we devise a platform for functional profiling of DNA repair in short-term patient-derived HGSC organoids. We tested 33 organoid cultures derived from 22 patients with HGSC for defects in homologous recombination (HR) and replication fork protection. Regardless of DNA repair gene mutational status, a functional defect in HR in the organoids correlated with PARP inhibitor sensitivity. A functional defect in replication fork protection correlated with carboplatin and CHK1 and ATR inhibitor sensitivity. Our results indicate that a combination of genomic analysis and functional testing of organoids allows for the identification of targetable DNA damage repair defects. Larger numbers of patient-derived organoids must be analyzed to determine whether these assays can reproducibly predict patient response in the clinic.
Patient-derived ovarian tumor organoids grow rapidly and match the tumors from which they are derived, both genetically and functionally. These organoids can be used for DNA repair profiling and therapeutic sensitivity testing and provide a rapid means of assessing targetable defects in the parent tumor, offering more suitable treatment options.
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