The motivation to develop materials for quantum technologies has put exploration of novel quantum states of matter at the focus of several research fields, with particular efforts towards understanding and controlling the behaviour of quantum entangled and other strongly interacting electronic states. Experimental investigation is of primary importance, but requires measurements at ultra-low temperatures where the quantum states of interest have long lifetimes. Under these conditions, low energy interactions, such as hyperfine or nuclear exchange interactions, become relevant, and can modify electronic ground states and their associated excitations in multiple ways that are not well understood or characterised. In this work, we use a recently developed magnetic susceptibility technique, compatible with ultra-low temperatures and high magnetic fields, to probe the influence of nuclear interactions on superconducting and multipole ordered ground states in the strongly correlated electron system PrOs4Sb12. We find that the multipole order develops a novel, entangled nuclear-electronic character at the lowest temperatures, which significantly modifies the phase boundary and leads to a nuclear quantum critical point. In the superconducting phase, we find that hyperfine interactions suppress superconductivity in a manner that provides evidence for superconducting pairing mediated by crystal field excitations. Our results on PrOs4Sb12 experimentally establish a new type of non-magnetic, nuclear quantum critical point, and give revealing insight into a highly unusual superconducting state. They also demonstrate more generally the feasibility of exploiting hyperfine interactions as a tuning parameter for experimental creation and investigation of a variety of quantum states and phenomena in correlated electron materials.

We report a previously unobserved quantum oscillation frequency in YbRh 2 Si 2 . This is the first quantum oscillation that can definitely be assigned to the second of the two major sheets of the Fermi surface predicted by band structure calculations. These calculations have been done for two scenarios: the “large” Fermi surface, which includes the Yb 4 f ‐hole in the Fermi volume, and the “small” Fermi surface, which does not. Previously observed frequencies were interpreted in terms of a “large” Fermi surface that has been so strongly spin‐split that it closely resembles the “small” Fermi surface. The new frequency can also be incorporated into this picture, however there are some indications that the situation is more complicated than was assumed, suggesting a need for more advanced band structure calculations.

Vascular pericytes can differentiate into osteoblast-like cells in vitro, suggesting that these cells may represent a potential source of osteoprogenitor cells in the adult. Pericyte differentiation is associated with a characteristic pattern of nodule formation and mineralisation. Nodules are formed in post-confluent cultures by the retraction of multilayered areas. Crystals of hydroxyapatite are deposited on the extracellular matrix of these nodules which then becomes mineralised. We now demonstrate that thrombospondin-1 (TSP-1) gene expression is modulated during pericyte differentiation in vitro. That is, the relative levels of TSP-1 (protein and mRNA) increased markedly during nodule formation and then decreased when mineralisation of the nodules had taken place. TSP-1 was localised throughout non-mineralised nodules but it was largely excluded from the inner mass of mineralised nodules. The production of a mineralised matrix by vascular pericytes was promoted by the presence of antibodies to TSP-1 in the culture medium and was inhibited by exogenous TSP-1. These effects did not appear to be mediated through the activation of latent TGF-beta, since neither exogenous TGF-beta nor neutralising antibodies to TGF-beta had any effect on the rate or extent of mineralisation seen in the pericyte cultures. Taken together these results suggest that high levels of TSP-1 inhibit pericyte mineralisation, supporting the view that this protein plays a role in pericyte differentiation and bone formation.

Pericytes are defined in vivo by their location: They are embedded within the basement membrane of microvessels. They form an integral part of the microvascular wall and are believed to participate in angiogenesis, although their precise role is not clear. Pericytes derived from the retinal microvasculature have been cultured and identified by a series of phenotypic characteristics that clearly distinguishes them from other stromal cells such as smooth muscle cells. Pericytes in vitro form multicellular nodules rich in extracellular matrix. This matrix becomes mineralized in the presence of growth medium containing serum, without exogenous beta-glycerophosphate. These results indicate that pericytes represent primitive mesenchymal cells able to differentiate into an osteogenic phenotype. Pericyte differentiation also is defined by alterations in their response to transforming growth factor beta 1 and changes in the synthesis and/or deposition of various extracellular matrix proteins such as laminin, Type IV collagen, tenascin, Type X collagen osteonectin, and thrombospondin-1. Angiogenesis is associated commonly with mineralization. These data suggest that pericytes may contribute to mineralization in vivo.

New capillaries arise from the pre-existing vasculature (arterioles, venules and capillaries) through a series of steps that involve the endothelium and the surrounding extracellular matrix (ECM). The principal morphological events involved in angiogenesis were described in the 1940s. Electron microscopic studies performed over 20 years later have confirmed these initial observations and added further detailed information [1–3].

Pericytes are defined by their characteristic morphology and location in vivo, i.e. stellate cells, embedded within the basement membrane of arterioles, venules and capillaries. Depending on the vessel and the age of the animal, pericytes have been reported to cover from 26 to 100% of the surface of the microvessels [1–5].

Alpha-smooth muscle actin is considered a reliable marker for distinguishing between arterial smooth muscle and endothelial cells. Several authors have reported heterogeneity in the expression of this actin isoform in atherosclerotic lesions. Such heterogeneity appears to result from the presence of different smooth muscle cell phenotypes (contractile and synthetic) in these lesions. In the present study, we show that bovine aortic endothelial cells, which are characterised by the presence of Factor VIII-related antigen (FVIII) and by the absence of alpha-smooth muscle actin (alpha-SM actin) may be induced to express the latter when exposed to TGF-beta 1. FVIII was detected by immunofluorescence, alpha-SM actin was detected by immunofluorescence and immunoblotting. The number of cells expressing alpha-SM actin increased with time of incubation with TGF-beta 1, and this increase occurred concomitantly with a decrease in the expression of FVIII. Double immunofluorescence demonstrated the presence of cells that expressed both FVIII and alpha-SM actin after 5 days of incubation with TGF-beta 1. With longer incubation times (10-20 days) the loss of FVIII expression was complete and over 90% of the cells expressed alpha-SM actin. Ultrastructurally, cells in control cultures showed the typical features of endothelial cells. In the TGF-beta 1-treated cultures, cells which appeared indistinguishable from contractile and synthetic smooth muscle cells were observed. Withdrawal of TGF-beta 1 after 10 days incubation resulted in the re-appearance of polygonal cells which were FVIII-positive and alpha-SM actin-negative.(ABSTRACT TRUNCATED AT 250 WORDS)

Endothelial cells plated on two-dimensional (2-D) substrata proliferate until they form a tightly apposed confluent monolayer of quiescent cells that display a typical 'cobblestone' morphology. When added to proliferating cultures TGF-beta-1 (transforming growth factor-beta-1) inhibited cell growth and caused marked morphological changes, with the cells becoming enlarged and ragged. These effects were dose-dependent and reversible. TGF-beta-1 also reduced the cloning efficiency and colony size of these cells, indicating that TGF-beta-1 is cytotoxic and cytostatic for endothelial cells. By contrast, TGF-beta-1 added to quiescent cobblestone cultures did not affect cell morphology or cell numbers. In the presence of 20% serum, the level of total protein synthesis per cell was significantly increased by TGF-beta-1 in a dose-dependent manner when the cells were cultured on a 2-D substratum, regardless of whether the cells were proliferating or cobblestone quiescent. The level of plasminogen activator inhibitor type 1 was specifically increased in these cultures, as demonstrated by reverse fibrin zymography and immunoprecipitation. Endothelial cells embedded within a 3-D collagen gel display an elongated 'sprouting' morphology. Such cells self-associate to form three-dimensional cellular networks within the gel, but do not proliferate. The addition of TGF-beta-1 to these quiescent sprouting cells initially induced rounding-up without altering protein synthesis, and cell death occurred later. The effects of TGF-beta-1 on sprouting endothelial cells were also examined using two culture systems where both the cobblestone and the sprouting phenotypes were present. TGF-beta-1 reduced the number of cells present and the extent of migration of sprouting cells embedded within a type I collagen gel, but had no effect upon sprouting cells embedded within a complex endothelial-produced extracellular matrix. Large vessel (aortic) and microvessel (retinal) endothelial cells responded in a similar way to TGF-beta-1; the only difference being that an increased synthesis of PAI-1 was not observed with sub-confluent BREC cultures. Our results suggest that the effects of TGF-beta-1 upon endothelial cells depend on the shape (cobblestone or sprouting), on the proliferative state of the cells, and on the nature of the matrix surrounding the cells. The response of these cells to TGF-beta-1 in vivo may be similarly modulated during angiogenesis by changes in the cell phenotype and the composition of the surrounding matrix.