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The antiferromagnet and semimetal EuCd2As2 has recently attracted a lot of attention due to a wealth of topological phases arising from the interplay of topology and magnetism. In particular, the presence of a single pair of Weyl points is predicted for a ferromagnetic configuration of Eu spins along the c-axis in EuCd2As2. In the search for such phases, we investigate here the effects of hydrostatic pressure in EuCd2As2. For that, we present specific heat, transport and μSR measurements under hydrostatic pressure up to ∼2.5GPa, combined with {\it ab initio} density functional theory (DFT) calculations. Experimentally, we establish that the ground state of EuCd2As2 changes from in-plane antiferromagnetic (AFMab) to ferromagnetic at a critical pressure of ≈2\,GPa, which is likely characterized by the moments dominantly lying within the ab plane (FMab). The AFMab-FMab transition at such a relatively low pressure is supported by our DFT calculations. Furthermore, our experimental and theoretical results indicate that EuCd2As2 moves closer to the sought-for FMc state (moments ∥ c) with increasing pressure further. We predict that a pressure of ≈\,23\,GPa will stabilize the FMc state, if Eu remains in a 2+ valence state. Thus, our work establishes hydrostatic pressure as a key tuning parameter that (i) allows for a continuous tuning between magnetic ground states in a single sample of EuCd2As2 and (ii) enables the exploration of the interplay between magnetism and topology and thereby motivates a series of future experiments on this magnetic Weyl semimetal.
The antiferromagnet and semimetal EuCd2As2 has recently attracted a lot of attention due to a wealth of topological phases arising from the interplay of topology and magnetism. In particular, the presence of a single pair of Weyl points is predicted for a ferromagnetic configuration of Eu spins along the c-axis in EuCd2As2. In the search for such phases, we investigate here the effects of hydrostatic pressure in EuCd2As2. For that, we present specific heat, transport and μSR measurements under hydrostatic pressure up to ∼2.5GPa, combined with {\it ab initio} density functional theory (DFT) calculations. Experimentally, we establish that the ground state of EuCd2As2 changes from in-plane antiferromagnetic (AFMab) to ferromagnetic at a critical pressure of ≈2\,GPa, which is likely characterized by the moments dominantly lying within the ab plane (FMab). The AFMab-FMab transition at such a relatively low pressure is supported by our DFT calculations. Furthermore, our experimental and theoretical results indicate that EuCd2As2 moves closer to the sought-for FMc state (moments ∥ c) with increasing pressure further. We predict that a pressure of ≈\,23\,GPa will stabilize the FMc state, if Eu remains in a 2+ valence state. Thus, our work establishes hydrostatic pressure as a key tuning parameter that (i) allows for a continuous tuning between magnetic ground states in a single sample of EuCd2As2 and (ii) enables the exploration of the interplay between magnetism and topology and thereby motivates a series of future experiments on this magnetic Weyl semimetal.
We present a study of the influence of disorder on the Mott metal-insulator transition for the organic charge-transfer salt κ -(BEDT-TTF) 2 Cu[N(CN) 2 ]Cl. To this end, disorder was introduced into the system in a controlled way by exposing the single crystals to X-ray irradiation. The crystals were then fine-tuned across the Mott transition by the application of continuously controllable He-gas pressure at low temperatures. Measurements of the thermal expansion and resistance show that the first-order character of the Mott transition prevails for low irradiation doses achieved by irradiation times up to 100 h. For these crystals with a moderate degree of disorder, we find a first-order transition line which ends in a second-order critical endpoint, akin to the pristine crystals. Compared to the latter, however, we observe a significant reduction of both, the critical pressure pc and the critical temperature Tc . This result is consistent with the theoretically-predicted formation of a soft Coulomb gap in the presence of strong correlations and small disorder. Furthermore, we demonstrate, similar to the observation for the pristine sample, that the Mott transition after 50 h of irradiation is accompanied by sizable lattice effects, the critical behavior of which can be well described by mean-field theory. Our results demonstrate that the character of the Mott transition remains essentially unchanged at a low disorder level. However, after an irradiation time of 150 h, no clear signatures of a discontinuous metal-insulator transition could be revealed anymore. These results suggest that, above a certain disorder level, the metal-insulator transition becomes a smeared first-order transition with some residual hysteresis.
Dilatometric studies on single crystalline barlowite – a structurally perfect spin-1/2 Kagome system
(2015)
We present results of high-resolution thermal expansion measurements on single crystalline barlowite – a structurally perfect spin-1/2 kagome system. The data reveal strongly pronounced and anisotropic second-order phase transition anomalies at the Néel transition at TN = 16K. From these data, together with literature results on the specific heat, the uniaxial-pressure dependences of TN are derived. We find a rather large positive pressure coefficient for uniaxial pressure along the hexagonal c axis of ∂TN/∂pc = (2.3 ± 0.2) K/GPa and smaller negative in-plane pressure coefficient of ∂TN/∂pin-plane = -(0.6 ± 0.03) K/GPa. These effects result in a small positive pressure coefficient under hydrostatic-pressure conditions of ∂TN/∂phydr = (1.1 ± 0.2) K/GPa. Bond-lengths considerations indicate that inter-layer Cu-O bonds, being larger than those typically found in stable Cu-O complexes, are responsible for this behavior.
Platelets comprise a highly interactive immune cell subset of the circulatory system traditionally known for their unique haemostatic properties. Although platelets are considered as a vault of growth factors, cytokines and chemokines with pivotal role in vascular regeneration and angiogenesis, the exact mechanisms by which they influence vascular endothelial cells (ECs) function remain underappreciated. In the present study, we examined the role of human IL-17A/IL-17RA axis in platelet-mediated pro-angiogenic responses. We reveal that IL-17A receptor (IL-17RA) mRNA is present in platelets transcriptome and a profound increase is documented on the surface of activated platelets. By quantifying the protein levels of several factors, involved in angiogenesis, we identified that IL-17A/IL17RA axis selectively induces the release of vascular endothelial growth factor, interleukin -2 and -4, as well as monocyte chemoattractant protein -1 from treated platelets. However, IL-17A exerted no effect on the release of IL-10, an anti-inflammatory factor with potentially anti-angiogenic properties, from platelets. Treatment of human endothelial cell two-dimensional tubule networks or three-dimensional spheroid and mouse aortic ring structures with IL-17A-induced platelet releasate evoked pro-angiogenic responses of ECs. Our findings suggest that IL-17A may critically affect platelet release of pro-angiogenic factors driving ECs towards a pro-angiogenic state.
Rhabdomyosarcomas are the most common pediatric soft tissue sarcoma and are a major cause of death from cancer in young patients requiring new treatment options to improve outcomes. High-risk patients include those with metastatic or relapsed disease and tumors with PAX3-FOXO1 fusion genes that encode a potent transcription factor that drives tumourigenesis through transcriptional reprogramming. Polo-Like Kinase-1 (PLK1) is a serine/threonine kinase that phosphorylates a wide range of target substrates and alters their activity. PLK1 functions as a pleiotropic master regulator of mitosis and regulates DNA replication after stress. Taken together with high levels of expression that correlate with poor outcomes in many cancers, including rhabdomyosarcomas, it is an attractive therapeutic target. This is supported in rhabdomyosarcoma models by characterization of molecular and phenotypic effects of reducing and inhibiting PLK1, including changes to the PAX3-FOXO1 fusion protein. However, as tumor re-growth has been observed, combination strategies are required. Here we review preclinical evidence and consider biological rationale for PLK1 inhibition in combination with drugs that promote apoptosis, interfere with activity of PAX3-FOXO1 and are synergistic with microtubule-destabilizing drugs such as vincristine. The preclinical effects of low doses of the PLK1 inhibitor volasertib in combination with vincristine, which is widely used in rhabdomyosarcoma treatment, show particular promise in light of recent clinical data in the pediatric setting that support achievable volasertib doses predicted to be effective. Further development of novel therapeutic strategies including PLK1 inhibition may ultimately benefit young patients with rhabdomyosarcoma and other cancers.
Motor function after hemispheric lesions has been associated with the structural integrity of either the pyramidal tract (PT) or alternate motor fibers (aMF). In this study, we aimed to differentially characterize the roles of PT and aMF in motor compensation by relating diffusion-tensor-imaging-derived parameters of white matter microstructure to measures of proximal and distal motor function in patients after hemispherotomy. Twenty-five patients (13 women; mean age: 21.1 years) after hemispherotomy (at mean age: 12.4 years) underwent Diffusion Tensor Imaging and evaluation of motor function using the Fugl-Meyer Assessment and the index finger tapping test. Regression analyses revealed that fractional anisotropy of the PT explained (p = 0.050) distal motor function including finger tapping rate (p = 0.027), whereas fractional anisotropy of aMF originating in the contralesional cortex and crossing to the ipsilesional hemisphere in the pons explained proximal motor function (p = 0.001). Age at surgery was found to be the only clinical variable to explain motor function (p < 0.001). Our results are indicative of complementary roles of the PT and of aMF in motor compensation of hemispherotomy mediating distal and proximal motor compensation of the upper limb, respectively.
Cerebral lesions may cause degeneration and neuroplastic reorganization in both the ipsi- and the contralesional hemisphere, presumably creating an imbalance of primarily inhibitory interhemispheric influences produced via transcallosal pathways. The two hemispheres are thought to mutually hamper neuroplastic reorganization of the other hemisphere. The results of preceding degeneration and neuroplastic reorganization of white matter may be reflected by Diffusion Tensor Imaging-derived diffusivity parameters such as fractional anisotropy (FA). In this study, we applied Diffusion Tensor Imaging (DTI) to contrast the white matter status of the contralesional hemisphere of young lesioned brains with and without contralateral influences by comparing patients after hemispherotomy to those who had not undergone neurosurgery. DTI was applied to 43 healthy controls (26 females, mean age ± SD: 25.07 ± 11.33 years) and two groups of in total 51 epilepsy patients with comparable juvenile brain lesions (32 females, mean age ± SD: 25.69 ± 12.77 years) either after hemispherotomy (30 of 51 patients) or without neurosurgery (21 of 51 patients), respectively. FA values were compared between these groups using the unbiased tract-based spatial statistics approach. A voxel-wise ANCOVA controlling for age at scan yielded significant group differences in FA. A post hoc t-test between hemispherotomy patients and healthy controls revealed widespread supra-threshold voxels in the contralesional hemisphere of hemispherotomy patients indicating comparatively higher FA values (p < 0.05, FWE-corrected). The non-surgery group, in contrast, showed extensive supra-threshold voxels indicating lower FA values in the contralesional hemisphere as compared to healthy controls (p < 0.05, FWE-corrected). Whereas lower FA values are suggestive of pronounced contralesional degeneration in the non-surgery group, higher FA values in the hemispherotomy group may be interpreted as a result of preceding plastic remodeling. We conclude that, whether juvenile brain lesions are associated with contralesional degeneration or reorganization partly depends on the ipsilesional hemisphere. Contralesional reorganization as observed in hemispherotomy patients was most likely enabled by the complete neurosurgical deafferentation of the ipsilesional hemisphere and, thereby, the disinhibition of the neuroplastic potential of the contralesional hemisphere. The main argument of this study is that hemispherotomy may be seen as a major plastic stimulus and as a prerequisite for contralesional neuroplastic remodeling in patients with juvenile brain lesions.
Expression of kidney injury molecule-1 (Kim-1) is rapidly upregulated following tubular injury, constituting a biomarker for acute kidney damage. We examined the renal localization of Kim-1 expression in PKD/Mhm (polycystic kidney disease, Mannheim) (cy/+) rats (cy: mutated allel, +: wild type allel), an established model for autosomal dominant polycystic kidney disease, with chronic, mainly proximal tubulointerstitial alterations. For immunohistochemistry or Western blot analysis, kidneys of male adult heterozygously-affected (cy/+) and unaffected (+/+) littermates were perfusion-fixed or directly removed. Kim-1 expression was determined using peroxidase- or fluorescence-linked immunohistochemistry (alone or in combination with markers for tubule segments or differentiation). Compared to (+/+), only in (cy/+) kidneys, a chronic expression of Kim-1 could be detected by Western blot analysis, which was histologically confined to an apical cellular localization in areas of cystically-transformed proximal tubules with varying size and morphology, but not in distal tubular segments. Kim-1 was expressed by cystic epithelia exhibiting varying extents of dedifferentiation, as shown by double labeling with aquaporin-1, vimentin or osteopontin, yielding partial cellular coexpression. In this model, in contrast to other known molecules indicating renal injury and/or repair mechanisms, the chronic renal expression of Kim-1 is strictly confined to proximal cysts. Its exact role in interfering with tubulo-interstitial alterations in polycystic kidney disease warrants future investigations.
In this paper we consider the dynamics of spot and futures prices in the presence of arbitrage. We propose a partially linear error correction model where the adjustment coefficient is allowed to depend non-linearly on the lagged price difference. We estimate our model using data on the DAX index and the DAX futures contract. We find that the adjustment is indeed nonlinear. The linear alternative is rejected. The speed of price adjustment is increasing almost monotonically with the magnitude of the price difference.