40 research outputs found
Disordered Electrons in a Strong Magnetic Field: Transfer Matrix Approaches to the Statistics of the Local Density of States
We present two novel approaches to establish the local density of states as
an order parameter field for the Anderson transition problem. We first
demonstrate for 2D quantum Hall systems the validity of conformal scaling
relations which are characteristic of order parameter fields. Second we show
the equivalence between the critical statistics of eigenvectors of the
Hamiltonian and of the transfer matrix, respectively. Based on this equivalence
we obtain the order parameter exponent for 3D quantum
Hall systems.Comment: 4 pages, 3 Postscript figures, corrected scale in Fig.
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DNA methylation-based classification of central nervous system tumours.
Accurate pathological diagnosis is crucial for optimal management of patients with cancer. For the approximately 100 known tumour types of the central nervous system, standardization of the diagnostic process has been shown to be particularly challenging-with substantial inter-observer variability in the histopathological diagnosis of many tumour types. Here we present a comprehensive approach for the DNA methylation-based classification of central nervous system tumours across all entities and age groups, and demonstrate its application in a routine diagnostic setting. We show that the availability of this method may have a substantial impact on diagnostic precision compared to standard methods, resulting in a change of diagnosis in up to 12% of prospective cases. For broader accessibility, we have designed a free online classifier tool, the use of which does not require any additional onsite data processing. Our results provide a blueprint for the generation of machine-learning-based tumour classifiers across other cancer entities, with the potential to fundamentally transform tumour pathology
The Polycomb Repressive Complex 2 Is a Potential Target of SUMO Modifications
The Polycomb Repressive Complex 2 (PRC2) functions as a transcriptional repressor through a mechanism that involves methylation of Histone H3 at lysine 27. The PRC2 complex activity is essential for cellular proliferation, development, and cell fate decisions. PRC2 target genes include important regulators of development and proliferation as well as tumor suppressor genes. Consistent with this, the activity of several Polycomb group (PcG) proteins is deregulated in human cancer suggesting an important role for PcGs in tumor development. Whereas the downstream functions of PcGs are well characterized, the mechanisms of their recruitment to target genes and the regulation of their activity are not fully understood.Here we show that the two PRC2 components SUZ12 and EZH2 are sumoylated in vitro and in vivo. Among several putative sumoylation sites we have mapped the major site of SUZ12 sumoylation. Furthermore, we show that SUZ12 interacts with the E2-conjugating enzyme UBC9 both in vitro and in vivo and that mutation of the SUZ12 sumoylation site does not abolish this binding. Finally, we provide evidence that the E3-ligase PIASXbeta interacts and enhances the sumoylation of SUZ12 in vivo suggesting that PIASXbeta could function as an E3-ligase for SUZ12.Taken together, our data identify sumoylation as a novel post-translational modification of components of the PRC2 complex, which could suggest a potential new mechanism to modulate PRC2 repressive activity. Further work aimed to identify the physiological conditions for these modifications will be required to understand the role of SUZ12 and EZH2 sumoylation in PcG-mediated epigenetic regulation of transcription
Six years of clinical follow-up with endothelial cell–seeded small-diameter vascular grafts during coronary bypass surgery
This clinical study was performed to investigate the patency rate of endothelial cell–seeded small-diameter expanded polytetrafluoroethylene grafts during coronary artery bypass surgery. Between September 1995 and December 1998, 14 patients (median age: 71 years, range: 61–79 years) received 21 endothelial cell–seeded small-diameter grafts. In all, 43% of the performed implantations were reoperations. Endothelial cells were harvested from a forearm vein, cultured and characterized in the laboratory until a sufficient number was available. After in vitro seeding, the grafts were allowed to mature for another 10 days, prior to implantation. Graft patency was investigated with angiography, angioscopy, and intravascular ultrasonography during follow-up. Cumulative data represented 58 patients’ years and was 100% complete. The seeded autologous vascular endothelial cell density was 1.05 × 10 5 ± 0.12 × 10 5 cells/cm 2 with a cell viability of 95.5 ± 1.5%. Operative mortality was 7.1% (one patient). Patency rate at discharge was 95.2%, and at a mean follow-up of 27 months was 90.5%. The proven patency rate at up to 72 months was at least 50.0%, as five patients refused angiographic evaluation. None of these five patients suffered from angina pectoris and so the best scenario would have shown a patency rate of 85.7%. Angioscopy and intravascular ultrasonography showed absence of atheroma or stenosis in the investigated patent grafts. Autologous vascular endothelial cell seeding improves patency rate of small-caliber expanded polytetrafluoroethylene grafts in patients without suitable autologous graft material