| 1. |
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| 2. |
- de Graauw, Th., et al.
(author)
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The Herschel-Heterodyne Instrument for the Far-Infrared (HIFI)
- 2010
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 518, s. L6-
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Journal article (peer-reviewed)abstract
- Aims: This paper describes the Heterodyne Instrument for the Far-Infrared (HIFI) that was launched onboard ESA's Herschel Space Observatory in May 2009. Methods: The instrument is a set of 7 heterodyne receivers that are electronically tuneable, covering 480-1250 GHz with SIS mixers and the 1410-1910 GHz range with hot electron bolometer (HEB) mixers. The local oscillator (LO) subsystem comprises a Ka-band synthesizer followed by 14 chains of frequency multipliers and 2 chains for each frequency band. A pair of auto-correlators and a pair of acousto-optical spectrometers process the two IF signals from the dual-polarization, single-pixel front-ends to provide instantaneous frequency coverage of 2 × 4 GHz, with a set of resolutions (125 kHz to 1 MHz) that are better than 0.1 km s-1. Results: After a successful qualification and a pre-launch TB/TV test program, the flight instrument is now in-orbit and completed successfully the commissioning and performance verification phase. The in-orbit performance of the receivers matches the pre-launch sensitivities. We also report on the in-orbit performance of the receivers and some first results of HIFI's operations. Herschel is an ESA space observatory with science instruments provided by European-led Principal Investigator consortia and with important participation from NASA.
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| 3. |
- Lis, D. C., et al.
(author)
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Herschel/HIFI discovery of interstellar chloronium (H2Cl+)
- 2010
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 521:1
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Journal article (peer-reviewed)abstract
- We report the first detection of chloronium, H_2Cl^+, in the interstellar medium, using the HIFI instrument aboard the Herschel Space Observatory. The 2_12-1_01 lines of ortho-H\_2^35Cl^+ and ortho-H\_2^37Cl^+ are detected in absorption towards NGC 6334I, and the 1_11-0_00 transition of para-H\_2^35Cl^+ is detected in absorption towards NGC 6334I and Sgr B2(S). The H_2Cl^+ column densities are compared to those of the chemically-related species HCl. The derived HCl/H_2Cl^+ column density ratios, ~1-10, are within the range predicted by models of diffuse and dense photon dominated regions (PDRs). However, the observed H_2Cl^+ column densities, in excess of 10^13 cm^-2, are significantly higher than the model predictions. Our observations demonstrate the outstanding spectroscopic capabilities of HIFI for detecting new interstellar molecules and providing key constraints for astrochemical models.
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| 4. |
- Gupta, H., et al.
(author)
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Detection of OH+ and H2O+ towards Orion KL
- 2010
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 521, s. L47-
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Journal article (peer-reviewed)abstract
- We report observations of the reactive molecular ions OH+, H2O+, and H3O+ towards Orion KL with Herschel/HIFI. All three N = 1-0 fine-structure transitions of OH+ at 909, 971, and 1033 GHz and both fine-structure components of the doublet ortho-H2O+ 111-000 transition at 1115 and 1139 GHz were detected; an upper limit was obtained for H3O+. OH+ and H2O+ are observed purely in absorption, showing a narrow component at the source velocity of 9 km s-1, and a broad blueshifted absorption similar to that reported recently for HF and para-H218O, and attributed to the low velocity outflow of Orion KL. We estimate column densities of OH+ and H2O+ for the 9 km s-1 component of 9 ± 3 × 1012 cm-2 and 7 ± 2 × 1012 cm-2, and those in the outflow of 1.9 ± 0.7 × 1013 cm-2 and 1.0 ± 0.3 × 1013 cm-2. Upper limits of 2.4 × 1012 cm-2 and 8.7 × 1012 cm-2 were derived for the column densities of ortho and para-H3O+ from transitions near 985 and 1657 GHz. The column densities of the three ions are up to an order of magnitude lower than those obtained from recent observations of W31C and W49N. The comparatively low column densities may be explained by a higher gas density despite the assumption of a very high ionization rate.
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| 5. |
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| 6. |
- Vastel, C., et al.
(author)
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Ortho-to-para ratio of interstellar heavy water
- 2010
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 521:1, s. Article Number: L31 -
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Journal article (peer-reviewed)abstract
- Context. Despite the low elemental deuterium abundance in the Galaxy, enhanced molecular D/H ratios have been found in the environments of low-mass star-forming regions, and in particular the Class 0 protostar IRAS 16293-2422. Aims. The CHESS (Chemical HErschel Surveys of Star forming regions) key program aims to study the molecular complexity of the interstellar medium. The high sensitivity and spectral resolution of the Herschel/HIFI instrument provide a unique opportunity to observe the fundamental 1(1,1)-0(0,0) transition of the ortho-D2O molecule, which is inaccessible from the ground, and determine the ortho-to-para D2O ratio. Methods. We detected the fundamental transition of the ortho-D2O molecule at 607.35 GHz towards IRAS 16293-2422. The line is seen in absorption with a line opacity of 0.62 +/- 0.11 (1 sigma). From the previous ground-based observations of the fundamental 1(1,0)-1(0,1) transition of para-D2O seen in absorption at 316.80 GHz, we estimate a line opacity of 0.26 +/- 0.05 (1 sigma). Results. We show that the observed absorption is caused by the cold gas in the envelope of the protostar. Using these new observations, we estimate for the first time the ortho-to-para D2O ratio to be lower than 2.6 at a 3 sigma level of uncertainty, which should be compared with the thermal equilibrium value of 2:1.
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| 7. |
- Kanis, J A, et al.
(author)
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The use of clinical risk factors enhances the performance of BMD in the prediction of hip and osteoporotic fractures in men and women.
- 2007
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In: Osteoporosis international. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 18:8, s. 1033-46
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Journal article (peer-reviewed)abstract
- SUMMARY: BMD and clinical risk factors predict hip and other osteoporotic fractures. The combination of clinical risk factors and BMD provide higher specificity and sensitivity than either alone. INTRODUCTION AND HYPOTHESES: To develop a risk assessment tool based on clinical risk factors (CRFs) with and without BMD. METHODS: Nine population-based studies were studied in which BMD and CRFs were documented at baseline. Poisson regression models were developed for hip fracture and other osteoporotic fractures, with and without hip BMD. Fracture risk was expressed as gradient of risk (GR, risk ratio/SD change in risk score). RESULTS: CRFs alone predicted hip fracture with a GR of 2.1/SD at the age of 50 years and decreased with age. The use of BMD alone provided a higher GR (3.7/SD), and was improved further with the combined use of CRFs and BMD (4.2/SD). For other osteoporotic fractures, the GRs were lower than for hip fracture. The GR with CRFs alone was 1.4/SD at the age of 50 years, similar to that provided by BMD (GR = 1.4/SD) and was not markedly increased by the combination (GR = 1.4/SD). The performance characteristics of clinical risk factors with and without BMD were validated in eleven independent population-based cohorts. CONCLUSIONS: The models developed provide the basis for the integrated use of validated clinical risk factors in men and women to aid in fracture risk prediction.
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| 8. |
- Wiedner, M.C., et al.
(author)
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Heterodyn receiver for the Origins Space Telescope concept 2
- 2018
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In: Proceedings of SPIE - The International Society for Optical Engineering. - : SPIE. - 0277-786X .- 1996-756X. ; 10698
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Conference paper (peer-reviewed)abstract
- The Origins Space Telescope (OST) is a NASA study for a large satellite mission to be submitted to the 2020 Decadal Review. The proposed satellite has a fleet of instruments including the HEterodyne Receivers for OST (HERO). HERO is designed around the quest to follow the trail of water from the ISM to disks around protostars and planets. HERO will perform high-spectral resolution measurements with 2x9 pixel focal plane arrays at any frequency between 468GHz to 2,700GHz (617 to 111 μm). HERO builds on the successful Herschel/HIFI heritage, as well as recent technological innovations, allowing it to surpass any prior heterodyne instrument in terms of sensitivity and spectral coverage.
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| 9. |
- Wiedner, M.C., et al.
(author)
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Heterodyne Receiver for Origins
- 2021
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In: Journal of Astronomical Telescopes, Instruments, and Systems. - 2329-4221 .- 2329-4124. ; 7:1
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Journal article (peer-reviewed)abstract
- The Heterodyne Receiver for Origins (HERO) is the first detailed study of a heterodyne focal plane array receiver for space applications. HERO gives the Origins Space Telescope the capability to observe at very high spectral resolution (R = 107) over an unprecedentedly large far-infrared (FIR) wavelengths range (111 to 617 μm) with high sensitivity, with simultaneous dual polarization and dual-frequency band operation. The design is based on prior successful heterodyne receivers, such as Heterodyne Instrument for the Far-Infrared/Herschel, but surpasses it by one to two orders of magnitude by exploiting the latest technological developments. Innovative components are used to keep the required satellite resources low and thus allowing for the first time a convincing design of a large format heterodyne array receiver for space. HERO on Origins is a unique tool to explore the FIR universe and extends the enormous potential of submillimeter astronomical spectroscopy into new areas of astronomical research.
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| 10. |
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| 11. |
- Johansson, Helena, 1981, et al.
(author)
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A meta-analysis of the association of fracture risk and body mass index in women.
- 2014
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In: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. - : Wiley. - 1523-4681. ; 29:1, s. 223-33
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Journal article (peer-reviewed)abstract
- Several recent studies suggest that obesity may be a risk factor for fracture. The aim of this study was to investigate the association between body mass index (BMI) and future fracture risk at different skeletal sites. In prospective cohorts from more than 25 countries, baseline data on BMI were available in 398,610 women with an average age of 63 (range, 20-105) years and follow up of 2.2 million person-years during which 30,280 osteoporotic fractures (6457 hip fractures) occurred. Femoral neck BMD was measured in 108,267 of these women. Obesity (BMI ≥ 30kg/m(2) ) was present in 22%. A majority of osteoporotic fractures (81%) and hip fractures (87%) arose in non-obese women. Compared to a BMI of 25kg/m(2) , the hazard ratio (HR) for osteoporotic fracture at a BMI of 35kg/m(2) was 0.87 (95% confidence interval [CI], 0.85-0.90). When adjusted for bone mineral density (BMD), however, the same comparison showed that the HR for osteoporotic fracture was increased (HR, 1.16; 95% CI, 1.09-1.23). Low BMI is a risk factor for hip and all osteoporotic fracture, but is a protective factor for lower leg fracture, whereas high BMI is a risk factor for upper arm (humerus and elbow) fracture. When adjusted for BMD, low BMI remained a risk factor for hip fracture but was protective for osteoporotic fracture, tibia and fibula fracture, distal forearm fracture, and upper arm fracture. When adjusted for BMD, high BMI remained a risk factor for upper arm fracture but was also a risk factor for all osteoporotic fractures. The association between BMI and fracture risk is complex, differs across skeletal sites, and is modified by the interaction between BMI and BMD. At a population level, high BMI remains a protective factor for most sites of fragility fracture. The contribution of increasing population rates of obesity to apparent decreases in fracture rates should be explored. © 2014 American Society for Bone and Mineral Research.
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| 12. |
- Mottahedin, Amin, et al.
(author)
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Targeting succinate metabolism to decrease brain injury upon mechanical thrombectomy treatment of ischemic stroke
- 2023
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In: Redox Biology. - : Elsevier BV. - 2213-2317. ; 59
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Journal article (peer-reviewed)abstract
- Current treatments for acute ischemic stroke aim to reinstate a normal perfusion in the ischemic territory but can also cause significant ischemia-reperfusion (IR) injury. Previous data in experimental models of stroke show that ischemia leads to the accumulation of succinate, and, upon reperfusion, the accumulated succinate is rapidly oxidized by succinate dehydrogenase (SDH) to drive superoxide production at mitochondrial complex I. Despite this process initiating IR injury and causing further tissue damage, the potential of targeting succinate metabolism to minimize IR injury remains unexplored. Using both quantitative and untargeted high -resolution metabolomics, we show a time-dependent accumulation of succinate in both human and mouse brain exposed to ischemia ex vivo. In a mouse model of ischemic stroke/mechanical thrombectomy mass spectrometry imaging (MSI) shows that succinate accumulation is confined to the ischemic region, and that the accumulated succinate is rapidly oxidized upon reperfusion. Targeting succinate oxidation by systemic infusion of the SDH inhibitor malonate upon reperfusion leads to a dose-dependent decrease in acute brain injury. Together these findings support targeting succinate metabolism upon reperfusion to decrease IR injury as a valuable adjunct to mechanical thrombectomy in ischemic stroke.
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| 13. |
- Rankin, Erinn B, et al.
(author)
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Direct regulation of GAS6/AXL signaling by HIF promotes renal metastasis through SRC and MET.
- 2014
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In: Proceedings of the National Academy of Sciences. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 111:37, s. 13373-13378
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Journal article (peer-reviewed)abstract
- Dysregulation of the von Hippel-Lindau/hypoxia-inducible transcription factor (HIF) signaling pathway promotes clear cell renal cell carcinoma (ccRCC) progression and metastasis. The protein kinase GAS6/AXL signaling pathway has recently been implicated as an essential mediator of metastasis and receptor tyrosine kinase crosstalk in cancer. Here we establish a molecular link between HIF stabilization and induction of AXL receptor expression in metastatic ccRCC. We found that HIF-1 and HIF-2 directly activate the expression of AXL by binding to the hypoxia-response element in the AXL proximal promoter. Importantly, genetic and therapeutic inactivation of AXL signaling in metastatic ccRCC cells reversed the invasive and metastatic phenotype in vivo. Furthermore, we define a pathway by which GAS6/AXL signaling uses lateral activation of the met proto-oncogene (MET) through SRC proto-oncogene nonreceptor tyrosine kinase to maximize cellular invasion. Clinically, AXL expression in primary tumors of ccRCC patients correlates with aggressive tumor behavior and patient lethality. These findings provide an alternative model for SRC and MET activation by growth arrest-specific 6 in ccRCC and identify AXL as a therapeutic target driving the aggressive phenotype in renal clear cell carcinoma.
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| 14. |
- Zanello, Marc, et al.
(author)
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Predictors of Epileptic Seizures and Ability to Work in Supratentorial Cavernous Angioma Located Within Eloquent Brain Areas
- 2019
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In: Neurosurgery. - : Ovid Technologies (Wolters Kluwer Health). - 0148-396X .- 1524-4040. ; 85:4, s. E702-E713
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Journal article (peer-reviewed)abstract
- BACKGROUND: The postoperative outcomes and the predictors of seizure control are poorly studied for supratentorial cavernous angiomas (CA) within or close to the eloquent brain area.OBJECTIVE: To assess the predictors of preoperative seizure control, postoperative seizure control, and postoperative ability to work, and the safety of the surgery.METHODS: Multicenter international retrospective cohort analysis of adult patients benefitting from a functional-based surgical resection with intraoperative functional brain mapping for a supratentorial CA within or close to eloquent brain areas.RESULTS: A total of 109 patients (66.1% women; mean age 38.4 ± 12.5 yr), were studied. Age >38 yr (odds ratio [OR], 7.33; 95% confidence interval [CI], 1.53-35.19; P = .013) and time to surgery > 12 mo (OR, 18.21; 95% CI, 1.11-296.55; P = .042) are independent predictors of uncontrolled seizures at the time of surgery. Focal deficit (OR, 10.25; 95% CI, 3.16-33.28; P < .001) is an independent predictor of inability to work at the time of surgery. History of epileptic seizures at the time of surgery (OR, 7.61; 95% CI, 1.67-85.42; P = .003) and partial resection of the CA and/or of the hemosiderin rim (OR, 12.02; 95% CI, 3.01-48.13; P < .001) are independent predictors of uncontrolled seizures postoperatively. Inability to work at the time of surgery (OR, 19.54; 95% CI, 1.90-425.48; P = .050), Karnofsky Performance Status ≤ 70 (OR, 51.20; 95% CI, 1.20-2175.37; P = .039), uncontrolled seizures postoperatively (OR, 105.33; 95% CI, 4.32-2566.27; P = .004), and worsening of cognitive functions postoperatively (OR, 13.71; 95% CI, 1.06-176.66; P = .045) are independent predictors of inability to work postoperatively.CONCLUSION: The functional-based resection using intraoperative functional brain mapping allows safe resection of CA and the peripheral hemosiderin rim located within or close to eloquent brain areas.
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| 15. |
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| 16. |
- Burger, N., et al.
(author)
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ND3 Cys39 in complex I is exposed mitochondrial
- 2022
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In: Cell Chemical Biology. - : Elsevier BV. - 2451-9448 .- 2451-9456. ; 29:4
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Journal article (peer-reviewed)abstract
- Mammalian complex I can adopt catalytically active (A-) or deactive (D-) states. A defining feature of the reversible transition between these two defined states is thought to be exposure of the ND3 subunit Cys39 residue in the D-state and its occlusion in the A-state. As the catalytic A/D transition is important in health and disease, we set out to quantify it by measuring Cys39 exposure using isotopic labeling and mass spectrometry, in parallel with complex I NADH/CoQ oxidoreductase activity. To our surprise, we found significant Cys39 exposure during NADH/CoQ oxidoreductase activity. Furthermore, this activity was unaffected if Cys39 alkylation occurred during complex I-linked respiration. In contrast, alkylation of catalytically inactive complex I irreversibly blocked the reactivation of NADH/CoQ oxidoreductase activity by NADH. Thus, Cys39 of ND3 is exposed in complex I during mitochondrial respiration, with significant implications for our understanding of the A/D transition and the mechanism of complex I.
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| 17. |
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| 18. |
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| 19. |
- Freyschlag, Christian F, et al.
(author)
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Imaging practice in low-grade gliomas among European specialized centers and proposal for a minimum core of imaging.
- 2018
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In: Journal of Neuro-Oncology. - : Springer Science and Business Media LLC. - 0167-594X .- 1573-7373. ; 139:3, s. 699-711
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Journal article (peer-reviewed)abstract
- OBJECTIVE: Imaging studies in diffuse low-grade gliomas (DLGG) vary across centers. In order to establish a minimal core of imaging necessary for further investigations and clinical trials in the field of DLGG, we aimed to establish the status quo within specialized European centers.METHODS: An online survey composed of 46 items was sent out to members of the European Low-Grade Glioma Network, the European Association of Neurosurgical Societies, the German Society of Neurosurgery and the Austrian Society of Neurosurgery.RESULTS: A total of 128 fully completed surveys were received and analyzed. Most centers (n = 96, 75%) were academic and half of the centers (n = 64, 50%) adhered to a dedicated treatment program for DLGG. There were national differences regarding the sequences enclosed in MRI imaging and use of PET, however most included T1 (without and with contrast, 100%), T2 (100%) and TIRM or FLAIR (20, 98%). DWI is performed by 80% of centers and 61% of centers regularly performed PWI.CONCLUSION: A minimal core of imaging composed of T1 (w/wo contrast), T2, TIRM/FLAIR, PWI and DWI could be identified. All morphologic images should be obtained in a slice thickness of ≤ 3 mm. No common standard could be obtained regarding advanced MRI protocols and PET.IMPORTANCE OF THE STUDY: We believe that our study makes a significant contribution to the literature because we were able to determine similarities in numerous aspects of LGG imaging. Using the proposed "minimal core of imaging" in clinical routine will facilitate future cooperative studies.
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| 20. |
- Kohlhauer, M., et al.
(author)
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Protection against cardiac ischemia-reperfusion injury by hypothermia and by inhibition of succinate accumulation and oxidation is additive
- 2019
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In: Basic Research in Cardiology. - : Springer Science and Business Media LLC. - 0300-8428 .- 1435-1803. ; 114:3
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Journal article (peer-reviewed)abstract
- Hypothermia induced at the onset of ischemia is a potent experimental cardioprotective strategy for myocardial infarction. The aim of our study was to determine whether the beneficial effects of hypothermia may be due to decreasing mitochondria-mediated mechanisms of damage that contribute to the pathophysiology of ischemia/reperfusion injury. New Zealand male rabbits were submitted to 30min of myocardial ischemia with hypothermia (32 degrees C) induced by total liquid ventilation (TLV). Hypothermia was applied during ischemia alone (TLV group), during ischemia and reperfusion (TLV-IR group) and normothermia (Control group). In all the cases, ischemia was performed by surgical ligation of the left anterior descending coronary artery and was followed by 3h of reperfusion before assessment of infarct size. In a parallel study, male C57BL6/J mice underwent 30min myocardial ischemia followed by reperfusion under either normothermia (37 degrees C) or conventionally induced hypothermia (32 degrees C). In both the models, the levels of the citric acid cycle intermediate succinate, mitochondrial complex I activity were assessed at various times. The benefit of hypothermia during ischemia on infarct size was compared to inhibition of succinate accumulation and oxidation by the complex II inhibitor malonate, applied as the pro-drug dimethyl malonate under either normothermic or hypothermic conditions. Hypothermia during ischemia was cardioprotective, even when followed by normothermic reperfusion. Hypothermia during ischemia only, or during both, ischemia and reperfusion, significantly reduced infarct size (2.8 +/- 0.6%, 24.2 +/- 3.0% and 49.6 +/- 2.6% of the area at risk, for TLV-IR, TLV and Control groups, respectively). The significant reduction of infarct size by hypothermia was neither associated with a decrease in ischemic myocardial succinate accumulation, nor with a change in its rate of oxidation at reperfusion. Similarly, dimethyl malonate infusion and hypothermia during ischemia additively reduced infarct size (4.8 +/- 2.2% of risk zone) as compared to either strategy alone. Hypothermic cardioprotection is neither dependent on the inhibition of succinate accumulation during ischemia, nor of its rapid oxidation at reperfusion. The additive effect of hypothermia and dimethyl malonate on infarct size shows that they are protective by distinct mechanisms and also suggests that combining these different therapeutic approaches could further protect against ischemia/reperfusion injury during acute myocardial infarction.
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| 21. |
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| 22. |
- Yin, Z., et al.
(author)
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Structural basis for a complex I mutation that blocks pathological ROS production
- 2021
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Journal article (peer-reviewed)abstract
- Mitochondrial complex I is central to the pathological reactive oxygen species (ROS) production that underlies cardiac ischemia–reperfusion (IR) injury. ND6-P25L mice are homoplasmic for a disease-causing mtDNA point mutation encoding the P25L substitution in the ND6 subunit of complex I. The cryo-EM structure of ND6-P25L complex I revealed subtle structural changes that facilitate rapid conversion to the “deactive” state, usually formed only after prolonged inactivity. Despite its tendency to adopt the “deactive” state, the mutant complex is fully active for NADH oxidation, but cannot generate ROS by reverse electron transfer (RET). ND6-P25L mitochondria function normally, except for their lack of RET ROS production, and ND6-P25L mice are protected against cardiac IR injury in vivo. Thus, this single point mutation in complex I, which does not affect oxidative phosphorylation but renders the complex unable to catalyse RET, demonstrates the pathological role of ROS production by RET during IR injury. © 2021, The Author(s).
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