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| 12. |
- Abdo, A. A., et al.
(författare)
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The on-orbit calibration of the Fermi Large Area Telescope
- 2009
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Ingår i: Astroparticle physics. - : Elsevier BV. - 0927-6505 .- 1873-2852. ; 32:3-4, s. 193-219
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Tidskriftsartikel (refereegranskat)abstract
- The Large Area Telescope (LAT) on-board the Fermi Gamma-ray Space Telescope began its on-orbit operations on June 23, 2008. Calibrations, defined in a generic sense, correspond to synchronization of trigger signals, optimization of delays for latching data, determination of detector thresholds, gains and responses, evaluation of the perimeter of the South Atlantic Anomaly (SAA), measurements of live time, of absolute time, and internal and spacecraft boresight alignments. Here we describe on-orbit calibration results obtained using known astrophysical sources, galactic cosmic rays, and charge injection into the front-end electronics of each detector. Instrument response functions will be described in a separate publication. This paper demonstrates the stability of calibrations and describes minor changes observed since launch. These results have been used to calibrate the LAT datasets to be publicly released in August 2009.
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| 13. |
- Aalbers, Jelle, et al.
(författare)
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Solar neutrino detection sensitivity in DARWIN via electron scattering
- 2020
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Ingår i: European Physical Journal C. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 80:12
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Tidskriftsartikel (refereegranskat)abstract
- We detail the sensitivity of the proposed liquid xenon DARWIN observatory to solar neutrinos via elastic electron scattering. We find that DARWIN will have the potential to measure the fluxes of five solar neutrino components: pp, 7Be, 13N, 15O and pep. The precision of the 13N, 15O and pep components is hindered by the double-beta decay of 136Xe and, thus, would benefit from a depleted target. A high-statistics observation of pp neutrinos would allow us to infer the values of the electroweak mixing angle, sin2 theta w, and the electron-type neutrino survival probability, Pee, in the electron recoil energy region from a few keV up to 200 keV for the first time, with relative precision of 5% and 4%, respectively, with 10 live years of data and a 30 tonne fiducial volume. An observation of pp and 7Be neutrinos would constrain the neutrino-inferred solar luminosity down to 0.2%. A combination of all flux measurements would distinguish between the high- (GS98) and low-metallicity (AGS09) solar models with 2.1-2.5 sigma significance, independent of external measurements from other experiments or a measurement of 8B neutrinos through coherent elastic neutrino-nucleus scattering in DARWIN. Finally, we demonstrate that with a depleted target DARWIN may be sensitive to the neutrino capture process of 131Xe.
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| 14. |
- Caceres, L., et al.
(författare)
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Nuclear structure studies of F-24
- 2015
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Ingår i: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 92:1
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Tidskriftsartikel (refereegranskat)abstract
- The structure of the F-24 nucleus has been studied at GANIL using the beta decay of O-24 and the in-beam.-ray spectroscopy from the fragmentation of Na-27,Na-28, Ne-25,Ne-26, and Mg-29,Mg-30 nuclei. Combining these complementary experimental techniques, the level scheme of F-24 has been constructed up to 3.6 MeV by means of particle-gamma and particle-gamma gamma coincidence relations. Experimental results are compared to shell-model calculations using the standard USDA and USDB interactions as well as ab initio valence-space Hamiltonians calculated from the in-medium similarity renormalization group based on chiral two- and three-nucleon forces. Both methods reproduce the measured level spacings well, and this close agreement allows unidentified spins and parities to be consistently assigned.
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| 15. |
- Vajta, Zs., et al.
(författare)
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Excited states in the neutron-rich nucleus F-25
- 2014
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Ingår i: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 89:5, s. 054323-
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Tidskriftsartikel (refereegranskat)abstract
- The structure of the nucleus F-25(9) was investigated through in-beam. gamma-ray spectroscopy of the fragmentation of Ne-26 and Na-27,Na-28 ion beams. Based on the particle-gamma and particle-gamma gamma coincidence data, a level scheme was constructed and compared with shell model and coupled-cluster calculations. Some of the observed states were interpreted as quasi-single-particle states built on top of the closed-shell nucleus O-24, while the others were described as states arising from coupling of a single proton to the 2(broken vertical bar) core excitation of O-24.
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| 16. |
- Aalbers, J., et al.
(författare)
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A next-generation liquid xenon observatory for dark matter and neutrino physics
- 2023
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Ingår i: Journal of Physics G: Nuclear and Particle Physics. - : IOP Publishing. - 0954-3899 .- 1361-6471. ; 50:1
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Forskningsöversikt (refereegranskat)abstract
- The nature of dark matter and properties of neutrinos are among the most pressing issues in contemporary particle physics. The dual-phase xenon time-projection chamber is the leading technology to cover the available parameter space for weakly interacting massive particles, while featuring extensive sensitivity to many alternative dark matter candidates. These detectors can also study neutrinos through neutrinoless double-beta decay and through a variety of astrophysical sources. A next-generation xenon-based detector will therefore be a true multi-purpose observatory to significantly advance particle physics, nuclear physics, astrophysics, solar physics, and cosmology. This review article presents the science cases for such a detector.
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| 17. |
- Cassetta, L, et al.
(författare)
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Differential expansion of circulating human MDSC subsets in patients with cancer, infection and inflammation
- 2020
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Ingår i: Journal for immunotherapy of cancer. - : BMJ. - 2051-1426. ; 8:2
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Tidskriftsartikel (refereegranskat)abstract
- Myeloid-derived suppressor cells (MDSC) are a functional myeloid cell subset that includes myeloid cells with immune suppressive properties. The presence of MDSC has been reported in the peripheral blood of patients with several malignant and non-malignant diseases. So far, direct comparison of MDSC across different diseases and Centers is hindered by technical pitfalls and a lack of standardized methodology. To overcome this issue, we formed a network through the COST Action Mye-EUNITER (www.mye-euniter.eu) with the goal to standardize and facilitate the comparative analysis of human circulating MDSC in cancer, inflammation and infection. In this manuscript, we present the results of the multicenter study Mye-EUNITER MDSC Monitoring Initiative, that involved 13 laboratories and compared circulating MDSC subsets across multiple diseases, using a common protocol for the isolation, identification and characterization of these cells.MethodsWe developed, tested, executed and optimized a standard operating procedure for the isolation and immunophenotyping of MDSC using blood from healthy donors. We applied this procedure to the blood of almost 400 patients and controls with different solid tumors and non-malignant diseases. The latter included viral infections such as HIV and hepatitis B virus, but also psoriasis and cardiovascular disorders.ResultsWe observed that the frequency of MDSC in healthy donors varied substantially between centers and was influenced by technical aspects such as the anticoagulant and separation method used. Expansion of polymorphonuclear (PMN)-MDSC exceeded the expansion of monocytic MDSC (M-MDSC) in five out of six solid tumors. PMN-MDSC expansion was more pronounced in cancer compared with infection and inflammation. Programmed death-ligand 1 was primarily expressed in M-MDSC and e-MDSC and was not upregulated as a consequence of disease. LOX-1 expression was confined to PMN-MDSC.ConclusionsThis study provides improved technical protocols and workflows for the multi-center analysis of circulating human MDSC subsets. Application of these workflows revealed a predominant expansion of PMN-MDSC in solid tumors that exceeds expansion in chronic infection and inflammation.
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| 18. |
- Dahl-Jensen, D., et al.
(författare)
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Eemian interglacial reconstructed from a Greenland folded ice core
- 2013
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 493:7433, s. 489-494
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Tidskriftsartikel (refereegranskat)abstract
- Efforts to extract a Greenland ice core with a complete record of the Eemian interglacial (130,000 to 115,000 years ago) have until now been unsuccessful. The response of the Greenland ice sheet to the warmer-than-present climate of the Eemian has thus remained unclear. Here we present the new North Greenland Eemian Ice Drilling ('NEEM') ice core and show only a modest ice-sheet response to the strong warming in the early Eemian. We reconstructed the Eemian record from folded ice using globally homogeneous parameters known from dated Greenland and Antarctic ice-core records. On the basis of water stable isotopes, NEEM surface temperatures after the onset of the Eemian (126,000 years ago) peaked at 8 +/- 4 degrees Celsius above the mean of the past millennium, followed by a gradual cooling that was probably driven by the decreasing summer insolation. Between 128,000 and 122,000 years ago, the thickness of the northwest Greenland ice sheet decreased by 400 +/- 250 metres, reaching surface elevations 122,000 years ago of 130 +/- 300 metres lower than the present. Extensive surface melt occurred at the NEEM site during the Eemian, a phenomenon witnessed when melt layers formed again at NEEM during the exceptional heat of July 2012. With additional warming, surface melt might become more common in the future.
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| 19. |
- Maitrallain, A., et al.
(författare)
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Parametric study of high-energy ring-shaped electron beams from a laser wakefield accelerator
- 2022
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Ingår i: New Journal of Physics. - : IOP Publishing. - 1367-2630. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- Laser wakefield accelerators commonly produce on-axis, low-divergence, high-energy electron beams. However, a high charge, annular shaped beam can be trapped outside the bubble and accelerated to high energies. Here we present a parametric study on the production of low-energy-spread, ultra-relativistic electron ring beams in a two-stage gas cell. Ring-shaped beams with energies higher than 750 MeV are observed simultaneously with on axis, continuously injected electrons. Often multiple ring shaped beams with different energies are produced and parametric studies to control the generation and properties of these structures were conducted. Particle tracking and particle-in-cell simulations are used to determine properties of these beams and investigate how they are formed and trapped outside the bubble by the wake produced by on-axis injected electrons. These unusual femtosecond duration, high-charge, high-energy, ring electron beams may find use in beam driven plasma wakefield accelerators and radiation sources.
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| 20. |
- Spesyvtsev, R., et al.
(författare)
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Generation of electron high energy beams with a ring-like structure by a dual stage laser wakefield accelerator
- 2019
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Ingår i: Relativistic Plasma Waves and Particle Beams as Coherent and Incoherent Radiation Sources III. - : SPIE. - 9781510627383 ; 11036
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Konferensbidrag (refereegranskat)abstract
- The laser wake-field accelerator (LWFA) traditionally produces high brightness, quasi-monoenergetic electron beams with Gaussian-like spatial and angular distributions. In the present work we investigate the generation of ultra-relativistic beams with ring-like structures in the blowout regime of the LWFA using a dual stage accelerator. A density down-ramp triggers injection after the first stage and is used to produce ring-like electron spectra in the 300 - 600 MeV energy range. These well defined, annular beams are observed simultaneously with the on-axis, high energy electron beams, with a divergence of a few milliradians. The rings have quasi-monoenergetic energy spectra with an RMS spread estimated to be less than 5%. Particle-in-cell simulations confirm that off-axis injection provides the electrons with the initial transverse momentum necessary to undertake distinct betatron oscillations within the plasma bubble during their acceleration process.
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| 21. |
- Stanoiu, M., et al.
(författare)
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Spectroscopy of (26)F
- 2012
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Ingår i: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 85:1, s. 017303-
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Tidskriftsartikel (refereegranskat)abstract
- The structure of the weakly bound (26)(9)F(17) odd-odd nucleus, produced from (27,28)Na nuclei, has been investigated at GANIL by means of the in-beam gamma-ray spectroscopy technique. A single gamma-line is observed at 657(7) keV in (26)(9)F which has been ascribed to the decay of the excited J = 2(+) state to the J = 1(+) ground state. The possible presence of intruder negative parity states in (26)F is also discussed.
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| 22. |
- Bhattacharya, S, et al.
(författare)
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Public health. The cholera crisis in Africa.
- 2009
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Ingår i: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 324:5929
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Forskningsöversikt (refereegranskat)abstract
- Long-lasting cholera outbreaks in Africa suggest limitations in the current strategy of disease control.
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| 23. |
- Hussein, A. E., et al.
(författare)
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Laser-wakefield accelerators for high-resolution X-ray imaging of complex microstructures
- 2019
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Laser-wakefield accelerators (LWFAs) are high acceleration-gradient plasma-based particle accelerators capable of producing ultra-relativistic electron beams. Within the strong focusing fields of the wakefield, accelerated electrons undergo betatron oscillations, emitting a bright pulse of X-rays with a micrometer-scale source size that may be used for imaging applications. Non-destructive X-ray phase contrast imaging and tomography of heterogeneous materials can provide insight into their processing, structure, and performance. To demonstrate the imaging capability of X-rays from an LWFA we have examined an irregular eutectic in the aluminum-silicon (Al-Si) system. The lamellar spacing of the Al-Si eutectic microstructure is on the order of a few micrometers, thus requiring high spatial resolution. We present comparisons between the sharpness and spatial resolution in phase contrast images of this eutectic alloy obtained via X-ray phase contrast imaging at the Swiss Light Source (SLS) synchrotron and X-ray projection microscopy via an LWFA source. An upper bound on the resolving power of 2.7 ± 0.3 μm of the LWFA source in this experiment was measured. These results indicate that betatron X-rays from laser wakefield acceleration can provide an alternative to conventional synchrotron sources for high resolution imaging of eutectics and, more broadly, complex microstructures.
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| 24. |
- Mercati, O, et al.
(författare)
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CNTN6 mutations are risk factors for abnormal auditory sensory perception in autism spectrum disorders.
- 2017
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Ingår i: Molecular psychiatry. - : Springer Science and Business Media LLC. - 1476-5578 .- 1359-4184. ; 22, s. 625-633
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Tidskriftsartikel (refereegranskat)abstract
- Contactin genes CNTN5 and CNTN6 code for neuronal cell adhesion molecules that promote neurite outgrowth in sensory-motor neuronal pathways. Mutations of CNTN5 and CNTN6 have previously been reported in individuals with autism spectrum disorders (ASDs), but very little is known on their prevalence and clinical impact. In this study, we identified CNTN5 and CNTN6 deleterious variants in individuals with ASD. Among the carriers, a girl with ASD and attention-deficit/hyperactivity disorder was carrying five copies of CNTN5. For CNTN6, both deletions (6/1534 ASD vs 1/8936 controls; P=0.00006) and private coding sequence variants (18/501 ASD vs 535/33480 controls; P=0.0005) were enriched in individuals with ASD. Among the rare CNTN6 variants, two deletions were transmitted by fathers diagnosed with ASD, one stop mutation CNTN6(W923X) was transmitted by a mother to her two sons with ASD and one variant CNTN6(P770L) was found de novo in a boy with ASD. Clinical investigations of the patients carrying CNTN5 or CNTN6 variants showed that they were hypersensitive to sounds (a condition called hyperacusis) and displayed changes in wave latency within the auditory pathway. These results reinforce the hypothesis of abnormal neuronal connectivity in the pathophysiology of ASD and shed new light on the genes that increase risk for abnormal sensory perception in ASD.Molecular Psychiatry advance online publication, 10 May 2016; doi:10.1038/mp.2016.61.
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| 25. |
- Pougeoise, E., et al.
(författare)
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Experimental characteristics and analysis of transverse modes in 1.3 μm strained InGaAs quantum well VCSELs
- 2006
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Ingår i: Proc SPIE Int Soc Opt Eng. - : SPIE. - 0819462411 - 9780819462411
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Konferensbidrag (refereegranskat)abstract
- In the context of optical interconnection applications, we report on results obtained on strained InGaAs quantum well Vertical Cavity Surface Emitting Lasers (VCSELs). Our devices are top p-type DBR oxide-confined VCSEL, grown by metalorganic vapour-phase epitaxy (MOVPE). These lasers exhibit low threshold currents and deliver up to 1.77 mW in continuous wave operation at room temperature. Fundamental mode continuous-wave lasing at wavelengths beyond 1300 nm at room temperature is reached for a 4 μm oxide diameter VCSEL. The particular design of the active layer based on a large detuning between the gain maximum and the cavity resonance gives our devices a very specific thermal and modal behaviour. Therefore, we study the spectral and spatial distributions of the transverse modes by near field scanning optical microscopy using a micropolymer tip at the end of an optical fibre.
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| 26. |
- Stanoiu, M., et al.
(författare)
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Disappearance of the N=14 shell gap in the carbon isotopic chain
- 2008
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Ingår i: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 78:3
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Tidskriftsartikel (refereegranskat)abstract
- The structure of C-17-20(6) nuclei was investigated by means of the in-beam gamma-ray spectroscopy technique using fragmentation reactions of radioactive beams. Based on particle-gamma and particle-gamma gamma coincidence data, level schemes are constructed for the neutron-rich C17-20 nuclei. The systematics of the first excited 2(+) states in the carbon isotopes is extended for the first time to A = 20 showing that in contrast to the case of the oxygen isotopes, the N = 14 subshell closure disappears. Experimental results are compared with shell-model calculations. Agreement between them is found only if a reduced neutron-neutron effective interaction is used. Implications of this reduced interaction in some properties of weakly bound neutron-rich Carbon are discussed.
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| 27. |
- Stanoiu, M., et al.
(författare)
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Study of drip line nuclei through two-step fragmentation
- 2004
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Ingår i: European Physical Journal A. - : Springer Science and Business Media LLC. - 1434-6001 .- 1434-601X. ; 20:1, s. 95-96
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Tidskriftsartikel (refereegranskat)abstract
- We have studied the structure of light neutron-rich nuclei around N = 16 by employing the in-beam gamma-ray spectroscopy technique using the fragmentation of secondary beams of Ne-25,Ne-26, Na-27,Na-28 and Mg-29,Mg-30 isotopes. This secondary-beam cocktail was obtained by the fragmentation of a 36 S beam at 77.5 MeV.A by the SISSI/GANIL facility. By a second-step fragmentation, we have measured gamma-ray-residue coincidences in C17-20 and O-23,O-24 and described the obtained levels in the framework of the shell model.
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| 28. |
- Stanoiu, M., et al.
(författare)
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Study of neutron rich carbon and oxygen nuclei up to drip line
- 2004
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Ingår i: Nuclear Physics A. - : Elsevier BV. - 0375-9474 .- 1873-1554. ; 746, s. 135C-139C
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Tidskriftsartikel (refereegranskat)abstract
- In-beam gamma-spectroscopy using fragmentation reactions of radioactive beams have been performed in order to study the structure of excited states in neutron rich oxygen and carbon isotopes. For the produced fragments, gamma-ray energies, intensities and gamma-gamma coincidences have been measured. The experiment was performed at GANIL. New gamma-lines have been identified and placed in level schemes for C17-20. The non observation of any gamma-ray in O-23,O-24 suggests that their first excited states lie above the neutron threshold. These results are discussed in the framework of shell model calculations.
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| 29. |
- Streeter, M. J.V., et al.
(författare)
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Characterization of laser wakefield acceleration efficiency with octave spanning near-IR spectrum measurements
- 2022
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Ingår i: Physical Review Accelerators and Beams. - 2469-9888. ; 25:10
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Tidskriftsartikel (refereegranskat)abstract
- We report on experimental measurements of energy transfer efficiencies in a GeV-class laser wakefield accelerator. Both the transfer of energy from the laser to the plasma wakefield and from the plasma to the accelerated electron beam was diagnosed by simultaneous measurement of the deceleration of laser photons and the acceleration of electrons as a function of plasma length. The extraction efficiency, which we define as the ratio of the energy gained by the electron beam to the energy lost by the self-guided laser mode, was maximized at 19±3% by tuning the plasma density and length. The additional information provided by the octave-spanning laser spectrum measurement allows for independent optimization of the plasma efficiency terms, which is required for the key goal of improving the overall efficiency of laser wakefield accelerators.
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| 30. |
- Fisher, D. A., et al.
(författare)
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The effects of flowline length evolution on chemistry - δ18O profiles from Penny Ice Cap, Baffin Island, Canada
- 2002
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Ingår i: Annals of Glaciology. - : International Glaciological Society. - 0260-3055 .- 1727-5644. ; 35:1, s. 150-156
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Tidskriftsartikel (refereegranskat)abstract
- The isotopic and chemical signatures for ice-age and Holocene ice from Summit, Greenland, and Penny Ice Cap, Baffin Island, Canada, are compared. The usual pattern of low δ180, high Ca2+ and high Cl- is presented in the Summit records, but Penny Ice Cap has lower than present Cl- in its ice-age ice. A simple extension of the Hansson model (Hansson, 1994) is developed and used to simulate these signatures. The low ice age Cl- from Penny Ice Cap is explained by having the ice-age ice originating many thousands of km inland near the centre of the Laurentide ice sheet and much further from the marine sources. Summit's flowlines all start close to the present site. The Penny Ice Cap early-Holocene δ180's had to be corrected to offset the Laurentide meltwater distortion.The analysis suggests that presently the Summit and Penny Ice Cap marine impurity ori ginates about 500 km away, and that presently Penny Ice Cap receives a significant amountoflocal continental impurity.
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| 31. |
- Kettle, B., et al.
(författare)
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Single-Shot Multi-keV X-Ray Absorption Spectroscopy Using an Ultrashort Laser-Wakefield Accelerator Source
- 2019
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Ingår i: Physical Review Letters. - 0031-9007. ; 123:25
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Tidskriftsartikel (refereegranskat)abstract
- Single-shot absorption measurements have been performed using the multi-keV x rays generated by a laser-wakefield accelerator. A 200 TW laser was used to drive a laser-wakefield accelerator in a mode which produced broadband electron beams with a maximum energy above 1 GeV and a broad divergence of ≈15 mrad FWHM. Betatron oscillations of these electrons generated 1.2±0.2×106 photons/eV in the 5 keV region, with a signal-to-noise ratio of approximately 300 1. This was sufficient to allow high-resolution x-ray absorption near-edge structure measurements at the K edge of a titanium sample in a single shot. We demonstrate that this source is capable of single-shot, simultaneous measurements of both the electron and ion distributions in matter heated to eV temperatures by comparison with density functional theory simulations. The unique combination of a high-flux, large bandwidth, few femtosecond duration x-ray pulse synchronized to a high-power laser will enable key advances in the study of ultrafast energetic processes such as electron-ion equilibration.
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| 32. |
- Lee, C.K., et al.
(författare)
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Prognostic nomogram to predict progression-free survival in patients with platinum-sensitive recurrent ovarian cancer
- 2011
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Ingår i: British Journal of Cancer. - : Cancer Research UK. - 0007-0920 .- 1532-1827. ; 105:8, s. 1144-1150
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Patients with platinum-sensitive recurrent ovarian cancer are a heterogeneous group, and it is not possible to accurately predict the progression-free survival (PFS) in these patients. We developed and validated a nomogram to help improve prediction of PFS in patients treated with platinum-based chemotherapy. METHODS: The nomogram was developed in a training cohort (n = 955) from the CALYPSO trial and validated in the AGO-OVAR 2.5 Study (n = 340). The proportional-hazards model (nomogram) was based on pre-treatment characteristics. RESULTS: The nomogram had a concordance index (C-index) of 0.645. Significant predictors were tumour size platinum-chemotherapy-free interval, CA-125, number of organ metastatic sites and white blood count. When the nomogram was applied without CA-125 (CA-125 was not available in validation cohort), the C-indices were 0.624 (training) and 0.594 (validation). When classification was based only on the platinum-chemotherapy-free interval, the indices were 0.571 (training) and 0.560 (validation). The calibration plot in the validation cohort based on four predictors (without CA-125) suggested good agreement between actual and nomogram-predicted 12-month PFS probabilities. CONCLUSION: This nomogram, using five pre-treatment characteristics, improves prediction of PFS in patients with platinum-sensitive ovarian cancer having platinum-based chemotherapy. It will be useful for the design and stratification of patients in clinical trials and also for counselling patients.
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| 33. |
- Portelius, Erik, 1977, et al.
(författare)
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Amyloid-β(1-15/16) as a marker for γ-secretase inhibition in Alzheimer's disease.
- 2012
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Ingår i: Journal of Alzheimer's disease : JAD. - 1875-8908. ; 31:2, s. 335-41
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Tidskriftsartikel (refereegranskat)abstract
- Amyloid-β (Aβ) producing enzymes are key targets for disease-modifying Alzheimer's disease (AD) therapies since Aβ trafficking is at the core of AD pathogenesis. Development of such drugs might benefit from the identification of markers indicating in vivo drug effects in the central nervous system. We have previously shown that Aβ(1-15) is produced by concerted β-and α-secretase cleavage of amyloid-β protein precursor (AβPP). Here, we test the hypothesis that this pathway is more engaged upon γ-secretase inhibition in humans, and cerebrospinal fluid (CSF) levels of Aβ(1-15/16) represent a biomarker for this effect. Twenty healthy men were treated with placebo (n = 5) or the γ-secretase inhibitor semagacestat (100 mg [n = 5], 140 mg [n = 5], or 280 mg [n = 5]). CSF samples were collected hourly over 36 hours and 10 time points were analyzed by immunoassay for Aβ(1-15/16), Aβ(x-38), Aβ(x-40), Aβ(x-42), sAβPPα, and sAβPPβ. The CSF concentration of Aβ(1-15/16) showed a dose-dependent response over 36 hours. In the 280 mg treatment group, a transient increase was seen with a maximum of 180% relative to baseline at 9 hours post administration of semagacestat. The concentrations of Aβ(x-38), Aβ(x-40), and Aβ(x-42) decreased the first 9 hours followed by increased concentrations after 36 hours relative to baseline. No significant changes were detected for CSF sAβPPα and sAβPPβ. Our data shows that CSF levels of Aβ(1-15/16) increase during treatment with semagacestat supporting its feasibility as a pharmacodynamic biomarker for drug candidates aimed at inhibiting γ-secretase-mediated AβPP-processing.
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| 34. |
- Pougeoise, E., et al.
(författare)
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Strained InGaAs quantum well vertical cavity surface emitting lasers emitting at 1.3 mu m
- 2006
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Ingår i: Electronics Letters. - : Institution of Engineering and Technology (IET). - 0013-5194 .- 1350-911X. ; 42:10, s. 584-586
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Tidskriftsartikel (refereegranskat)abstract
- Results on strained InGaAs quantum well vertical cavity surface emitting lasers for optical interconnection applications are reported. Fundamental mode continuous-wave lasing at wavelengths beyond 1300 nm is demonstrated at room temperature. The metal-organic vapour-phase epitaxy grown structure was processed as top p-type distribute Bragg reflector oxide-confined devices.
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| 35. |
- Schüpbach, S., et al.
(författare)
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Greenland records of aerosol source and atmospheric lifetime changes from the Eemian to the Holocene
- 2018
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- The Northern Hemisphere experienced dramatic changes during the last glacial, featuring vast ice sheets and abrupt climate events, while high northern latitudes during the last interglacial (Eemian) were warmer than today. Here we use high-resolution aerosol records from the Greenland NEEM ice core to reconstruct the environmental alterations in aerosol source regions accompanying these changes. Separating source and transport effects, we find strongly reduced terrestrial biogenic emissions during glacial times reflecting net loss of vegetated area in North America. Rapid climate changes during the glacial have little effect on terrestrial biogenic aerosol emissions. A strong increase in terrestrial dust emissions during the coldest intervals indicates higher aridity and dust storm activity in East Asian deserts. Glacial sea salt aerosol emissions in the North Atlantic region increase only moderately (50%), likely due to sea ice expansion. Lower aerosol concentrations in Eemian ice compared to the Holocene are mainly due to shortened atmospheric residence time, while emissions changed little.
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