Reprogramming of metabolic pathways contributes to human disease, especially cancer, but the regulators of this process are unknown. Here, we have generated a mouse knockout for the mitochondrial chaperone TRAP-1, a regulator of bioenergetics in tumors. TRAP-1(-/-) mice are viable and showed reduced incidence of age-associated pathologies, including obesity, inflammatory tissue degeneration, dyspl

PURPOSE: Inhibition of DNA repair is emerging as a new therapeutic strategy for cancer treatment. One promising target is DNA-PK, a pivotal kinase in double-strand break repair. The purpose of this study was to further characterise the activity of the DNA-PK inhibitor NU7441, giving some new insights into the biology of DNA-PK.METHODS: We used NU7441, a potent DNA-PK inhibitor, to evaluate potenti

The retinoid-related molecules (RRMs) ST1926 [(E)-3-(4'-hydroxy-3'-adamantylbiphenyl-4-yl)acrylic acid] and CD437 (6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthalene carboxylic acid) are promising anticancer agents. We compared the retinoic acid receptor (RAR) trans-activating properties of the two RRMs and all-trans-retinoic acid (ATRA). ST1926 and CD437 are better RARgamma agonists than ATRA. We

The income velocity of money declined sharply in Sweden between the 1870's and the outbreak of World War I. This decline is explained by a monetization process. An account of this process is given focusing on (a) the growth of commercial banking, (b) changes in wage contracts and in labor markets, and (c) changes in exchange arrangements in the markets for goods. A number of proxy measures of the

We consider a class of structured covariance completion problems which aim to complete partially known sample statistics in a way that is consistent with the underlying linear dynamics. The statistics of stochastic inputs are unknown and sought to explain the given correlations. Such inverse problems admit many solutions for the forcing correlations, but can be interpreted as an optimal low-rank a

Variants in HNF1A encoding hepatocyte nuclear factor 1a (HNF-1A) are associated with maturity-onset diabetes of the young form 3 (MODY 3) and type 2 diabetes. We investigated whether functional classification of HNF1A rare coding variants can inform models of diabetes risk prediction in the general population by analyzing the effect of 27 HNF1A variants identified in well-phenotyped populations (n

Aims/hypothesis To develop a prediction model that can predict HbA1c levels after six years in the non-diabetic general population, including previously used readily available predictors. Methods Data from 5,762 initially non-diabetic subjects from three population-based cohorts (Hoorn Study, Inter99, KORA S4/F4) were combined to predict HbA1c levels at six year follow-up. Using backward selection

HAMLET (Human Alpha-lactalbumin Made LEthal to Tumor cells) is a tumoricidal protein-lipid complex with broad effects against cancer cells of different origin. The therapeutic potential is emphasized by a high degree of specificity for tumor tissue. Here we review early studies of HAMLET, in collaboration with the Orrenius laboratory, and some key features of the subsequent development of the HAML

Semiconductor nanowires are versatile building blocks for optoelectronic devices, in part because nanowires offer an increased freedom in material design due to relaxed constraints on lattice matching during the epitaxial growth. This enables the growth of ternary alloy nanowires in which the bandgap is tunable over a large energy range, desirable for optoelectronic devices. However, little is kno

This paper examines the conduct and the effects of Swedish monetary policy in the 1930's. Three major conclusions emerge from the study: (1) The conduct of monetary policy specifically the devaluation of the Swedish currency in 1931 and the subsequent program of price stabilization, had a major effect on the aggregative behavior of the Swedish economy in the 1930's. (2) The impact of the new fisca

The purpose of this paper is to study the determination of annual changes in the money wage rate and in the price level in Sweden during the period 1922–1971. We have chosen to examine such a long span of years in order to make comparisons between various time periods and to investigate to what extent a given set of explanatory variables can account for the movements in wages and prices during the

In this article four new ternary phases of RE7Co2Ge4 (RE = La-Nd) are reported. They were synthesized by a solid-state reaction of the elements at high temperature, and their crystal structures were investigated by single crystal X-ray diffraction data. The isostructural phases crystallize in a new monoclinic structure type, space group P21/c, Z = 4, Pearson code mP52, and Wyckoff sequence e13. Th

We discuss whether the enhancement in the diphoton final state at Mgg = 750 GeV, observed recently by the ATLAS and CMS Collaborations could be a neutral pseudoscalar technipion π∼0. We considered two distinct minimal models for the dynamical electroweak symmetry breaking. Here we concentrate only on two-flavor vector-like technicolor model and we assume that the two-photon fusion is a dominant pr

This paper estimates the influence that rural-to-urban commuting has on rural employment growth, and whether the strength and spatial reach of this effect depend on commuters' levels of education. A main finding is that rural-to-urban commuting has a robust positive impact on rural employment growth in services and retail. There is no significant difference in how far these effects reach into rura

The cubic perovskite SrVO3 is generally considered to be a prototype strongly correlated metal with a characteristic three-peak structure of the d-electron spectral function, featuring a renormalized quasiparticle band in between pronounced Hubbard sidebands. Here we show that this interpretation, which has been supported by numerous "ab initio" simulations, has to be reconsidered. Using a fully s

Healthcare inequality is ubiquitous globally, but the effects are most striking in low-resource settings. In these settings, current methods for the design of medical devices are failing to address specific needs. The associated publications rarely describe how the context was studied at the front-end of design. There is a latent need for a holistic contextual framework for guiding the design deci

Water loss is a crucial factor for vegetation in the semi-arid Sahel region of Africa. Global satellite-driven estimates of plant CO2 uptake (gross primary productivity, GPP) have been found to not accurately account for Sahelian conditions, particularly the impact of canopy water stress. Here, we identify the main biophysical limitations that induce canopy water stress in Sahelian vegetation and