Controls on the location of compressional deformation on the NW European margin

The distribution of Cenozoic compressional structures along the NW European margin has been compared with maps of the thickness of the crystalline crust derived from a compilation of seismic refraction interpretations and gravity modelling, and with the distribution of high-velocity lower crust and/or partially serpentinized upper mantle detected by seismic experiments. Only a subset of the mapped compressional structures coincide with areas susceptible to lithospheric weakening as a result of crustal hyperextension and partial serpentinization of the upper mantle. Notably, partially serpentinized upper mantle is well documented beneath the central part of the southern Rockall Basin, but compressional features are sparse in that area. Where compressional structures have formed but the upper mantle is not serpentinized, simple rheological modelling suggests an alternative weakening mechanism involving ductile lower crust and lithospheric decoupling. The presence of pre-existing weak zones (associated with the properties of the gouge and overpressure in fault zones) and local stress magnitude and orientation are important contributing factors

Search for the K(L) --> PI0 PI0 E+ E- Decay in the KTeV Experiment

The recent discovery of a large CP violating asymmetry in K(L) --> PI+ PI- E+ E- mode has prompted us to seach for the associated K(L) --> PI0 PI0 E+ E- decay mode in the KTeV-E799 experiment at Fermilab. In 2.7E+11 K(L) decays, one candidate event has been observed with an expected background of 0.3 event, resulting in an upper limit for the K(L) --> PI0 PI0 E+ E- branching ratio of 6.6E-09 at the 90% confidence level.Comment: To be published in Phys. Rev. Let

The standard model at low energies

The hadronic sector of the standard model at low energies is described by a non--decoupling effective field theory, chiral perturbation theory. An introduction is given to the construction of effective chiral Lagrangians, both in the purely mesonic sector and with inclusion of baryons. The connection between the relativistic formulation and the heavy baryon approach to chiral perturbation theory with baryons is reviewed.Comment: Lectures given at the 6th Indian-Summer School on Intermediate Energy Physics, Prague, Aug. 1993, Latex, 26 pages (with a4.sty), UWThPh-1993-3

Tectono-stratigraphic evolution and crustal architecture of the Orphan Basin during North Atlantic rifting

The Orphan Basin is located in the deep offshore of the Newfoundland margin, and it is bounded by the continental shelf to the west, the Grand Banks to the south, and the continental blocks of Orphan Knoll and Flemish Cap to the east. The Orphan Basin formed in Mesozoic time during the opening of the North Atlantic Ocean between eastern Canada and western Iberia–Europe. This work, based on well data and regional seismic reflection profiles across the basin, indicates that the continental crust was affected by several extensional episodes between the Jurassic and the Early Cretaceous, separated by events of uplift and erosion. The preserved tectono-stratigraphic sequences in the basin reveal that deformation initiated in the eastern part of the Orphan Basin in the Jurassic and spread towards the west in the Early Cretaceous, resulting in numerous rift structures filled with a Jurassic–Lower Cretaceous syn-rift succession and overlain by thick Upper Cretaceous to Cenozoic post-rift sediments. The seismic data show an extremely thinned crust (4–16 km thick) underneath the eastern and western parts of the Orphan Basin, forming two sub-basins separated by a wide structural high with a relatively thick crust (17 km thick). Quantifying the crustal architecture in the basin highlights the large discrepancy between brittle extension localized in the upper crust and the overall crustal thinning. This suggests that continental deformation in the Orphan Basin involved, in addition to the documented Jurassic and Early Cretaceous rifting, an earlier brittle rift phase which is unidentifiable in seismic data and a depth-dependent thinning of the crust driven by localized lower crust ductile flow

Willingness to pay for multifunctional megaprojects: A stated preference analysis among firms in the Amsterdam Zuidas area

http://hdl.handle.net/1871/1621

Basic science of osteoarthritis

Osteoarthritis (OA) is a prevalent, disabling disorder of the joints that affects a large population worldwide and for which there is no definitive cure. This review provides critical insights into the basic knowledge on OA that may lead to innovative end efficient new therapeutic regimens. While degradation of the articular cartilage is the hallmark of OA, with altered interactions between chondrocytes and compounds of the extracellular matrix, the subchondral bone has been also described as a key component of the disease, involving specific pathomechanisms controlling its initiation and progression. The identification of such events (and thus of possible targets for therapy) has been made possible by the availability of a number of animal models that aim at reproducing the human pathology, in particular large models of high tibial osteotomy (HTO). From a therapeutic point of view, mesenchymal stem cells (MSCs) represent a promising option for the treatment of OA and may be used concomitantly with functional substitutes integrating scaffolds and drugs/growth factors in tissue engineering setups. Altogether, these advances in the fundamental and experimental knowledge on OA may allow for the generation of improved, adapted therapeutic regimens to treat human OA.(undefined

A patient-derived xenograft pre-clinical trial reveals treatment responses and a resistance mechanism to karonudib in metastatic melanoma

Karonudib (TH1579) is a novel compound that exerts anti-tumor activities and has recently entered phase I clinical testing. The aim of this study was to conduct a pre-clinical trial in patient-derived xenografts to identify the possible biomarkers of response or resistance that could guide inclusion of patients suffering from metastatic melanoma in phase II clinical trials. Patient-derived xenografts from 31 melanoma patients with metastatic disease were treated with karonudib or a vehicle for 18 days. Treatment responses were followed by measuring tumor sizes, and the models were categorized in the response groups. Tumors were harvested and processed for RNA sequencing and protein analysis. To investigate the effect of karonudib on T-cell-mediated anti-tumor activities, tumor-infiltrating T cells were injected in mice carrying autologous tumors and the mice treated with karonudib. We show that karonudib has heterogeneous anti-tumor effect on metastatic melanoma. Thus, based on the treatment responses, we could divide the 31 patient-derived xenografts in three treatment groups: progression group (32%), suppression group (42%), and regression group (26%). Furthermore, we show that karonudib has anti-tumor effect, irrespective of major melanoma driver mutations. Also, we identify high expression of ABCB1, which codes for p-gp pumps as a resistance biomarker. Finally, we show that karonudib treatment does not hamper T-cell-mediated anti-tumor responses. These findings can be used to guide future use of karonudib in clinical use with a potential approach as precision medicine