| 1. |
- Licciardello, Marco P., et al.
(författare)
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A combinatorial screen of the CLOUD uncovers a synergy targeting the androgen receptor
- 2017
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Ingår i: Nature Chemical Biology. - : Nature Publishing Group. - 1552-4450 .- 1552-4469. ; 13:7, s. 771-778
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Tidskriftsartikel (refereegranskat)abstract
- Approved drugs are invaluable tools to study biochemical pathways, and further characterization of these compounds may lead to repurposing of single drugs or combinations. Here we describe a collection of 308 small molecules representing the diversity of structures and molecular targets of all FDA-approved chemical entities. The CeMM Library of Unique Drugs (CLOUD) covers prodrugs and active forms at pharmacologically relevant concentrations and is ideally suited for combinatorial studies. We screened pairwise combinations of CLOUD drugs for impairment of cancer cell viability and discovered a synergistic interaction between flutamide and phenprocoumon (PPC). The combination of these drugs modulates the stability of the androgen receptor (AR) and resensitizes AR-mutant prostate cancer cells to flutamide. Mechanistically, we show that the AR is a substrate for gamma-carboxylation, a post-translational modification inhibited by PPC. Collectively, our data suggest that PPC could be repurposed to tackle resistance to antiandrogens in prostate cancer patients.
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| 2. |
- Moros, Matthias, et al.
(författare)
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Towards an event stratigraphy for Baltic Sea sediments deposited since AD 1900 : approaches and challenges
- 2017
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Ingår i: Boreas. - : Wiley. - 0300-9483 .- 1502-3885. ; 46:1, s. 129-142
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Tidskriftsartikel (refereegranskat)abstract
- Reconstructions of environmental changes at sub-decadal to decadal resolution based on central Baltic Sea sediments rely on accurate and precise high-resolution sediment depth/age relationships. A model chronology for Baltic Sea sediments is presented here based on established historical records of anthropogenic radionuclides (Cs-137/Am-241/bomb(14)C), polychlorinated biphenyls (PCBs), lead (Pb) and stable lead isotope (Pb-206/207 ratios), and radionuclide Pb-210 and C-14 decay dating methods. Marker horizons consisting of chemical precipitates formed by documented Major Baltic Inflow (MBIs) events and an extended diatom bloom period were also integrated into the model. The main time markers in Baltic Sea sediments that formed during the last 120years were the following: (i) the deepest observation of Pb-210(unsupp.) (marking the Pb-210 dating horizon) and departure of Hg from natural background levels at c.AD 1900; (ii) first detectable presence of PCBs at AD 1935; (iii) radionuclide production (i.e. Am-241) due to nuclear weapons testing between AD 1954 and AD 1975, with a peak in AD 1963; (iv) maximum heavy metal and PCB concentrations in the AD 1960s/1970s; (v) the Chernobyl nuclear accident in AD 1986 as a sharp Cs-137 increase; (vi) exceptionally strong diatom blooms with a massive diatom layer found in the Eastern Gotland Basin in AD 1988-1990; and (vii) characteristic manganese-carbonate layers in the deeper central basins formed by MBIs in AD 1993 and AD 2003. A precise and accurate sediment depth/age relationship can only be achieved in restricted areas of the Baltic Sea where continuous sedimentation has prevailed and there has been limited postdepositional disturbance. We demonstrate that parallel Hg and Cs-137 measurements can be used to assess the quality of sediment sequences for high-resolution environmental reconstructions. We show examples of sediment profiles that conform to the historical record, and examples from Western Baltic Sea areas where it appears to be impossible to establish accurate geochronologies.
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| 3. |
- Uhlmann, Eckart, et al.
(författare)
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Sustainable Solutions for Machine Tool
- 2017
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Ingår i: Sustainable Manufacturing. - Cham : Springer. - 9783319485133 - 9783319485140 ; , s. 47-69
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Bokkapitel (refereegranskat)abstract
- Environmental, economic and social changes of any significant proportions cannot take place without a major shift in the manufacturing sector. In today’s manufacturing processes, economic efficiency is realised through high volumes with the use of specialised machine tools. Change in society, such as in the form of mobility and digitisation, requires a complete overhaul in terms of thinking in the manufacturing industry. Moreover, the manufacturing industry contributes over 19 % to the world’s greenhouse gas emissions. As a consequence of these issues, a demand for sustainable solutions in the production industry is increasing. In particular, the concept of “cost” in manufacturing processes and thus the “system boundaries” within the production of the future has to be changed. That is, a great number of aspects to the machine tool and production technology industries can be improved upon in order to achieve a more sustainable production environment. Within this chapter, the focus lies on microsystem technology enhanced modular machine tool frames, adaptive mechatronic components, as well as on internallycooled cutting tools. An innovative machine tool concept has been developed recently, featuring a modular machine tool frame using microsystem technology for communication within the frame, which allows for a high level of flexibility. Furthermore, add-on upgrading systems for outdated machine tools—which are particularly relevant for developing and emerging countries—are poised to gain in importance in the upcoming years. The system described here enables the accuracy of outdated machine tools to be increased, thus making these machine tools comparable to modern machine tool systems. Finally, the cutting process requires solutions for dry machining, as the use of cooling lubricants is environmentally damaging and a significant cost contributor in machining processes. One such solution is the use of internally cooled cutting tools.
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| 4. |
- Wagner, Margareta, et al.
(författare)
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Resolving the Structure of a Well-Ordered Hydroxyl Overlayer on In2O3(111) : Nanomanipulation and Theory
- 2017
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Ingår i: ACS Nano. - : American Chemical Society (ACS). - 1936-0851 .- 1936-086X. ; 11:11, s. 11531-11541
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Tidskriftsartikel (refereegranskat)abstract
- Changes in chemical and physical properties resulting from water adsorption play an important role in the characterization and performance of device-relevant materials. Studies of model oxides with well-characterized surfaces can provide detailed information that is vital for a general understanding of water-oxide interactions. In this work, we study single crystals of indium oxide, the prototypical transparent contact material that is heavily used in a wide range of applications and most prominently in optoelectronic technologies. Water adsorbs dissociatively already at temperatures as low as 100 K, as confirmed by scanning tunneling microscopy (STM), photoelectron spectroscopy, and density functional theory. This dissociation takes place on lattice sites of the defect-free surface. While the In2O3(111)-(1 × 1) surface offers four types of surface oxygen atoms (12 atoms per unit cell in total), water dissociation happens exclusively at one of them together with a neighboring pair of 5-fold coordinated In atoms. These O-In groups are symmetrically arranged around the 6-fold coordinated In atoms at the surface. At room temperature, the In2O3(111) surface thus saturates at three dissociated water molecules per unit cell, leading to a well-ordered hydroxylated surface with (1 × 1) symmetry, where the three water OWH groups plus the surface OSH groups are imaged together as one bright triangle in STM. Manipulations with the STM tip by means of voltage pulses preferentially remove the H atom of one surface OSH group per triangle. The change in contrast due to strong local band bending provides insights into the internal structure of these bright triangles. The experimental results are further confirmed by quantitative simulations of the STM image corrugation.
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| 5. |
- Wagner, Margareta, et al.
(författare)
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Well-ordered in adatoms at the In2 O3 (111) surface created by Fe deposition
- 2016
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Ingår i: Physical Review Letters. - 0031-9007. ; 117:20
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Tidskriftsartikel (refereegranskat)abstract
- Metal deposition on oxide surfaces usually results in adatoms, clusters, or islands of the deposited material, where defects in the surface often act as nucleation centers. Here an alternate configuration is reported. After the vapor deposition of Fe on the In2O3(111) surface at room temperature, ordered adatoms are observed with scanning tunneling microscopy. These are identical to the In adatoms that form when the sample is reduced by heating in ultrahigh vacuum. Density functional theory calculations confirm that Fe interchanges with In in the topmost layer, pushing the excess In atoms to the surface where they arrange as a well-ordered adatom array.
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