Cellular adaptations to hypoxia and acidosis during somatic evolution of breast cancer

Conceptual models of carcinogenesis typically consist of an evolutionary sequence of heritable changes in genes controlling proliferation, apoptosis, and senescence. We propose that these steps are necessary but not sufficient to produce invasive breast cancer because intraductal tumour growth is also constrained by hypoxia and acidosis that develop as cells proliferate into the lumen and away from the underlying vessels. This requires evolution of glycolytic and acid-resistant phenotypes that, we hypothesise, is critical for emergence of invasive cancer. Mathematical models demonstrate severe hypoxia and acidosis in regions of intraductal tumours more than 100 m from the basement membrane. Subsequent evolution of glycolytic and acid-resistant phenotypes leads to invasive proliferation. Multicellular spheroids recapitulating ductal carcinoma in situ (DCIS) microenvironmental conditions demonstrate upregulated glucose transporter 1 (GLUT1) as adaptation to hypoxia followed by growth into normoxic regions in qualitative agreement with model predictions. Clinical specimens of DCIS exhibit periluminal distribution of GLUT-1 and Na+/H+ exchanger (NHE) indicating transcriptional activation by hypoxia and clusters of the same phenotype in the peripheral, presumably normoxic regions similar to the pattern predicted by the models and observed in spheroids. Upregulated GLUT-1 and NHE-1 were observed in microinvasive foci and adjacent intraductal cells. Adaptation to hypoxia and acidosis may represent key events in transition from in situ to invasive cancer

High-pressure phases of uranium monophosphide studied by synchrotron x-ray diffraction

X-ray diffraction studies have been performed on UP powder for pressures up to 51 GPa using synchrotron radiation and a diamond-anvil cell. At ambient pressure UP has the rocksalt structure. The bulk modulus has been determined to B$_0$=102(4) GPa and its pressure derivative to B'$_0$ =4.0(8). The cubic phase has been found to transform to a new phase, UP II, at about 10 GPa. UP II can be characterized by a rhombohedral Bravais lattice. UP II transforms to an orthorhombic phase, UP III, at 28 GPa. No volume change has been observed at the two transitions. The influence of the 5f electrons on the transformations is discussed

Associations between job demands, perceptions of noise at work and the psychological contract

Despite the widespread interest in the effects of workload on behaviour, there has been little research on the effects of it on attitudes and values in the workplace and life generally. The aim of the present research was to examine associations between noise exposure (which increases workload) and components of the psychological contract (fairness; trust; organisational commitment; work satisfaction; motivation; organisational citizenship; and intention to stay/quit). 166 workers completed a survey measuring components of the psychological contract, perceptions of noise exposure and other job characteristics. Univariate analyses showed that higher noise exposure was associated with a more negative psychological contract. However, adjustment for other job characteristics, both negative (e.g. job demands) and positive (e.g. control and support), removed the significant effects of noise. These results confirm previous research suggesting that psychosocial stressors have greater behavioural effects than components of the physical working environment such as noise

In Vivo Assessment of Cold Adaptation in Insect Larvae by Magnetic Resonance Imaging and Magnetic Resonance Spectroscopy

Background Temperatures below the freezing point of water and the ensuing ice crystal formation pose serious challenges to cell structure and function. Consequently, species living in seasonally cold environments have evolved a multitude of strategies to reorganize their cellular architecture and metabolism, and the underlying mechanisms are crucial to our understanding of life. In multicellular organisms, and poikilotherm animals in particular, our knowledge about these processes is almost exclusively due to invasive studies, thereby limiting the range of conclusions that can be drawn about intact living systems. Methodology Given that non-destructive techniques like 1H Magnetic Resonance (MR) imaging and spectroscopy have proven useful for in vivo investigations of a wide range of biological systems, we aimed at evaluating their potential to observe cold adaptations in living insect larvae. Specifically, we chose two cold-hardy insect species that frequently serve as cryobiological model systems–the freeze-avoiding gall moth Epiblema scudderiana and the freeze-tolerant gall fly Eurosta solidaginis. Results In vivo MR images were acquired from autumn-collected larvae at temperatures between 0°C and about -70°C and at spatial resolutions down to 27 µm. These images revealed three-dimensional (3D) larval anatomy at a level of detail currently not in reach of other in vivo techniques. Furthermore, they allowed visualization of the 3D distribution of the remaining liquid water and of the endogenous cryoprotectants at subzero temperatures, and temperature-weighted images of these distributions could be derived. Finally, individual fat body cells and their nuclei could be identified in intact frozen Eurosta larvae. Conclusions These findings suggest that high resolution MR techniques provide for interesting methodological options in comparative cryobiological investigations, especially in vivo

Pentacene: PTCDI-C13H27 molecular blends efficiently harvest light for solar cell applications

Solar cells exhibiting efficient photon harvesting are built from molecular blends of pentacene: PTCDI-C13H27. Absorption of the composition spans the whole visible spectrum with an onset at 730 nm. External quantum efficiency approaches unity at the peak absorption of pentacene. A 2.0% power conversion efficiency is obtained under 80 mW cm-2 AM 1.5 illumination, with 8.6 mA cm-2 short-circuit current. The comparison with bilayer devices suggests directions of improvement in conversion efficiency such as controlled growth of the blend layers

The natural history of parallel transjugular intrahepatic portosystemic stent shunts using uncovered stent: the role of host-related factors

Objectives: Parallel shunts (PS) are used in the management of transjugular intrahepatic portosystemic stent‐shunt (TIPS) insufficiency, a major limitation of the technique. This study describes the natural history of PS, and uses them as a model to assess the role of host factors in the development of primary shunt insufficiency. Methods: Out of 338 patients with TIPS, 40 (11.8%) patients required insertion of a PS. Baseline and follow‐up data of these patients were collected. Regular shunt surveillance involved biannual clinic visits and transjugular portography. Results: The non‐PS group (group 1; n=298) and the PS group (group 2; n=40) had similar baseline demographic and disease characteristics. Index shunts of both groups and the PS produced a significant portal pressure gradient drop (P<0.001), which was less in the index shunts of Group 2 (P<0.02 for both). PS had similar cumulative shunt patency rates to those of the index shunts of Group 1, and both were greater than those of index shunts in Group 2 (P<0.001 for both). The intervention rate (number of interventions/number of check portograms × 100) was similar for PS and the index shunts of Group 1 (38.7% and 43% respectively), but was significantly higher in the index shunts of Group 2 (85.6%; P<0.01 for both). In Group 1 and Group 2, 144 patients (48.3%) and 21 patients (52.5%) died during follow‐up after a median period of 23.4 and 8.9 months respectively. Conclusions: These findings do not support the hypothesis that shunt insufficiency is related to host factors