Unconventional Magnetization below 25 K in Nitrogen-doped Diamond provides hints for the existence of Superconductivity and Superparamagnetism

The magnetization of nitrogen-doped single crystalline diamond bulk samples shows unconventional field and temperature hysteresis loops at T ≲ 25 K. The results suggest the existence of superparamagnetic and superconducting regions in samples with nitrogen concentration <200 ppm. Both phases vanish at temperatures above 25 K where the samples show diamagnetic behavior similar to undoped diamond. The observation of superparamagnetism and superconductivity is attributed to the nitrogen doping and to the existence of defective regions. From particle-induced X-ray emission with ppm resolution we rule out that the main observations below 25 K are due to magnetic impurities. We investigated also the magnetic properties of ferromagnetic/high-temperature superconducting oxide bilayers. The magnetization results obtained from those bilayers show remarkable similarities to the ones in nitrogen-doped diamond

A comparison of extreme value theory approaches for determining value at risk

This paper compares a number of different extreme value models for determining the value at risk (VaR) of three LIFFE futures contracts. A semi-nonparametric approach is also proposed, where the tail events are modeled using the generalised Pareto distribution, and normal market conditions are captured by the empirical distribution function. The value at risk estimates from this approach are compared with those of standard nonparametric extreme value tail estimation approaches, with a small sample bias-corrected extreme value approach, and with those calculated from bootstrapping the unconditional density and bootstrapping from a GARCH(1,1) model. The results indicate that, for a holdout sample, the proposed semi-nonparametric extreme value approach yields superior results to other methods, but the small sample tail index technique is also accurate

Human cancers over express genes that are specific to a variety of normal human tissues

We have analyzed gene expression data from 3 different kinds of samples: normal human tissues, human cancer cell lines and leukemic cells from lymphoid and myeloid leukemia pediatric patients. We have searched for genes that are over expressed in human cancer and also show specific patterns of tissue-dependent expression in normal tissues. Using the expression data of the normal tissues we identified 4346 genes with a high variability of expression, and clustered these genes according to their relative expression level. Of 91 stable clusters obtained, 24 clusters included genes preferentially expressed either only in hematopoietic tissues or in hematopoietic and 1-2 other tissues; 28 clusters included genes preferentially expressed in various non-hematopoietic tissues such as neuronal, testis, liver, kidney, muscle, lung, pancreas and placenta. Analysis of the expression levels of these 2 groups of genes in the human cancer cell lines and leukemias, identified genes that were highly expressed in cancer cells but not in their normal counterparts, and were thus over expressed in the cancers. The different cancer cell lines and leukemias varied in the number and identity of these over expressed genes. The results indicate that many genes that are over expressed in human cancer cells are specific to a variety of normal tissues, including normal tissues other than those from which the cancer originated. It is suggested that this general property of cancer cells plays a major role in determining the behavior of the cancers, including their metastatic potential.Comment: To appear in PNA

Structure-guided design and optimization of small molecules targeting the protein-protein interaction between the von hippel-lindau (VHL) E3 ubiquitin ligase and the hypoxia inducible factor (HIF) alpha subunit with in vitro nanomolar affinities

E3 ubiquitin ligases are attractive targets in the ubiquitin-proteasome system, however, the development of small-molecule ligands has been rewarded with limited success. The von Hippel-Lindau protein (pVHL) is the substrate recognition subunit of the VHL E3 ligase that targets HIF-1α for degradation. We recently reported inhibitors of the pVHL:HIF-1α interaction, however they exhibited moderate potency. Herein, we report the design and optimization, guided by X-ray crystal structures, of a ligand series with nanomolar binding affinities

Inhibition of mTOR with sirolimus slows disease progression in Han:SPRD rats with autosomal dominant polycystic kidney disease (ADPKD)

Background. Autosomal dominant polycystic kidney disease (ADPKD) is characterized by dysregulated tubular epithelial cell growth, resulting in the formation of multiple renal cysts and progressive renal failure. To date, there is no effective treatment for ADPKD. The mammalian target of rapamycin (mTOR) is an atypical protein kinase and a central controller of cell growth and proliferation. We examined the effect of the mTOR inhibitor sirolimus (rapamycin) on renal functional loss and cyst progression in the Han:SPRD rat model of ADPKD. Methods. Five-week-old male heterozygous cystic (Cy/+) and wild-type normal (+/+) rats were administered sirolimus (2 mg/kg/day) orally through the drinking water for 3 months. The renal function was monitored throughout the treatment phase, and rats were sacrificed thereafter. Kidneys were analysed histomorphometrically, and for the expression and phosphorylation of S6K, a well-characterized target of mTOR in the regulation of cell growth. Results. The steady increase in BUN and creatinine in Cy/+ rats was reduced by 39 and 34%, respectively with sirolimus after 3 months treatment. Kidney weight and 2-kidney/total body weight (2K/TBW) ratios were reduced by 34 and 26% in sirolimus-treated Cy/+ rats. Cyst volume density was also reduced by 18%. Of importance, Cy/+ rats displayed enhanced levels of total and phosphorylated S6K. Sirolimus effectively reduced total and phosphorylated levels of S6K. Conclusion. We conclude that oral sirolimus markedly delays the loss of renal function and retards cyst development in Han:SPRD rats with ADPKD. Our data also suggest that activation of the S6K signalling pathway plays an important role in the pathogenesis of PKD. Sirolimus could be a useful drug to retard progressive renal failure in patients with ADPK

Novel near-infrared emission from crystal defects in MoS2 multilayer flakes

The structural defects in two-dimensional transition metal dichalcogenides, including point defects, dislocations and grain boundaries, are scarcely considered regarding their potential to manipulate the electrical and optical properties of this class of materials, notwithstanding the significant advances already made. Indeed, impurities and vacancies may influence the exciton population, create disorder-induced localization, as well as modify the electrical behaviour of the material. Here we report on the experimental evidence, confirmed by ab initio calculations, that sulfur vacancies give rise to a novel near-infrared emission peak around 0.75 eV in exfoliated MoS2 flakes. In addition, we demonstrate an excess of sulfur vacancies at the flake's edges by means of cathodoluminescence mapping, aberration-corrected transmission electron microscopy imaging and electron energy loss analyses. Moreover, we show that ripplocations, extended line defects peculiar to this material, broaden and redshift the MoS2 indirect bandgap emission

The influence of Ga+^+-irradiation on the transport properties of mesoscopic conducting thin films

We studied the influence of 30keV Ga$^+$-ions -- commonly used in focused ion beam (FIB) devices -- on the transport properties of thin crystalline graphite flake, La$_{0.7}$Ca$_{0.3}$MnO$_3$ and Co thin films. The changes of the electrical resistance were measured in-situ during irradiation and also the temperature and magnetic field dependence before and after irradiation. Our results show that the transport properties of these materials strongly change at Ga$^+$ fluences much below those used for patterning and ion beam induced deposition (IBID), limiting seriously the use of FIB when the intrinsic properties of the materials of interest are of importance. We present a method that can be used to protect the sample as well as to produce selectively irradiation-induced changes.Comment: 14 pages, 11 figures, will be published in Nanotechnology 201

Climate change adaptation, flood risks and policy coherence in integrated water resources management in England

Integrated water resources management (IWRM) assumes coherence between cognate aspects of water governance at the river basin scale, for example water quality, energy production and agriculture objectives. But critics argue that IWRM is often less ‘integrated’ in practice, raising concerns over inter-sectoral coherence between implementing institutions. One increasingly significant aspect of IWRM is adaptation to climate change-related risks, including threats from flooding, which are particularly salient in England. Although multiple institutional mechanisms exist for flood risk management (FRM), their coherence remains a critical question for national adaptation. This paper therefore (1) maps the multi-level institutional frameworks determining both IWRM and FRM in England; (2) examines their interaction via various inter-institutional coordinating mechanisms; and (3) assesses the degree of coherence. The analysis suggests that cognate EU strategic objectives for flood risk assessment demonstrate relatively high vertical and horizontal coherence with river basin planning. However, there is less coherence with flood risk requirements for land-use planning and national flood protection objectives. Overall, this complex governance arrangement actually demonstrates de-coherence over time due to ongoing institutional fragmentation. Recommendations for increasing IWRM coherence in England or re-coherence based on greater spatial planning and coordination of water-use and land-use strategies are proposed