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Concurrent multiscale techniques such as Adaptive Resolution Scheme (AdResS) can offer ample computational advantages over conventional atomistic (AT) molecular dynamics simulations. However, they typically rely on aphysical hybrid regions to maintain numerical stability when high-resolution degrees of freedom (DOFs) are randomly re-inserted at the resolution interface. We propose an Energy Minimized AT (DOF) Insertion (EMATI) method that uses an informed rather than random AT DOF insertion to tackle the root cause of the issue, i.e., overlapping AT potentials. EMATI enables us to directly couple AT and coarse-grained resolutions without any modifications of the interaction potentials. We exemplify AdResS-EMATI in a system of liquid butane and show that it yields improved structural and thermodynamic properties at the interface compared to competing AdResS approaches. Furthermore, our approach extends the applicability of the AdResS without a hybrid region to systems for which force capping is inadequate. [ABSTRACT FROM AUTHOR] more...

Health recommendations clearly show that in Austria and other highly developed countries less animal and more plant based food should be consumed. A meat based diet is held responsible for a number of environmental problems. We explore the impacts on nutrient fluxes (nitrogen and phosphorus) and land use as the result of a change from a meat based diet to a healthier balanced diet consisting of less animal based products and more plant based food in Austria. We use a detailed material flow analysis and the nutrient emissions model MONERIS in combination with scenarios. The scenarios address differing farming methods, varying trade options and different use of potentially available agricultural area. Our findings show that overall, a shift to a healthy balanced diet leads to less land being used for agricultural production (−30%), less resource consumption (20% to 25% less phosphorus) and lower transfer of nutrients from agriculture into the environment compared to the reference situation. Total emissions of nitrogen and phosphorus into water decrease (between 15% and 11% for nitrogen and by 5% to 6% for phosphorus) and nitrogen concentrations in groundwater change substantially depending on the intensity of farming assumed by different scenarios. [ABSTRACT FROM AUTHOR] more...

PurposeTo investigate the biocompatibility of the new cyanine dye: 3,3′-Di-(4-sulfobutyl)-1,1,1′,1′-tetramethyl-di-1H-benz[e]indocarbocyanine (DSS) as a vital dye for intraocular application in an in vivo rat model and to evaluate the effects of this dye on retinal structure and function.MethodsDSS at a concentration of 0.5% was applied via intravitreal injections to adult Brown Norway rats with BSS serving as a control. Retinal toxicity was assessed 7 days later by means of retinal ganglion cell (RGC) counts, light microscopy, optical coherence tomography (OCT), and electroretinography (ERG).ResultsNo significant decrease in RGC numbers was observed. No structural changes of the central retina were observed either in vivo (OCT) or under light microscopy. ERGs detected a temporary reduction of retinal function 7 days after injection; this was no longer evident 14 days after injection.ConclusionsDSS showed good biocompatibility in a well-established experimental in vivo setting and may be usable for intraocular surgery as an alternative to other cyanine dyes. In contrast to indocyanine green, it additionally offers fluorescence in the visual spectrum. Further studies with other animal models are needed before translation into clinical application. [ABSTRACT FROM AUTHOR] more...

The Ras association domain family 1 isoform A (RASSF1A) is a tumor suppressor whose inactivation is implicated in the development of many human cancers, including breast carcinomas. Little is known about the tumor-suppressive function of RASSF1A in breast tissue and whether its inactivation is mechanistically involved in the initiation and progression of breast tumors. Here, we show that RASSF1A inhibits breast cancer growth in vivo, and suppresses estrogen receptor (ERα) expression and function. Reconstitution of RASSF1A in MCF7 cells led to decreased ERα levels and reduced sensitivity to estrogen (E2). Concomitantly, we observed decreased expression of Id1 as well as the E2-responsive genes Bcl-2 and c-Myc that cooperatively contribute to the immortalization and transformation of breast epithelial cells. This downregulation was associated with induction of cell-cycle arrest and senescence that constitute early barriers to cancer initiation and progression. Knockdown of ERα showed that downregulation of ERα suffices to increase senescence and inhibit expression of Bcl-2, c-Myc and Id1. However, enforced expression of ERα only partially rescued RASSF1A-mediated growth inhibition and senescence, suggesting that suppression of ERα expression and activity is not the only mechanism by which RASSF1A inhibits growth and survival of breast cancer cells. Ectopic expression of Bcl-2, c-Myc and Id1 had little or no effect on RASSF1A-mediated growth arrest, indicating that RASSF1A acts dominantly over these oncogenes. Mechanistically, RASSF1A was found to suppress ERα expression through Akt1. It also transiently inhibited ERα-induced Ras-MAPK activity after exposure of cells to E2. Together, our data show that RASSF1A acts as a tumor suppressor in ERα+ mammary epithelial cells, in part through inhibiting ERα expression and activity. These findings suggest that RASSF1A has a key role in suppressing the transformation of human breast epithelial cells and ERα+ breast cancer initiation. [ABSTRACT FROM AUTHOR] more...

We have investigated how different approaches for water footprint (WF) calculations lead to different results, taking sugar beet production and sugar refining as examples. To a large extent, results obtained from any WF calculation are reflective of the method used and the assumptions made. Real irrigation data for 59 European sugar beet growing areas showed inadequate estimation of irrigation water when a widely used simple approach was used. The method resulted in an overestimation of blue water and an underestimation of green water usage. Dependent on the chosen (available) water quality standard, the final grey WF can differ up to a factor of 10 and more. We conclude that further development and standardisation of the WF is needed to reach comparable and reliable results. A special focus should be on standardisation of the grey WF methodology based on receiving water quality standards. [ABSTRACT FROM AUTHOR] more...

Background/Aims: To evaluate the retinal toxicity of Brilliant Blue G (BBG) following intravitreal injection in rat eyes and examine the biocompatibility and the staining properties in humans. Methods: BBG was injected into the 11 rat eyes to evaluate toxic effects with balanced salt solution (BSS) serving as control. Retinal toxicity was assessed by retinal ganglion cell (RGC) counts and by light microscopy 7 days later. In addition, BBG was applied during vitrectomy for macular hole (MH) (n = 15) or epiretinal membranes (ERM) {n = 3) in a prospective, non-comparative consecutive series of patients. Before and after surgery, all patients underwent a complete clinical examination including measurement of best corrected visual acuity (VA) and intraocular pressure, perimetry, fundus photography and optical coherence tomography. Patients were seen 1 day before surgery and then in approximately four weeks intervals. Results: No significant reduction in RGC numbers and no morphological alterations were noted. A sufficient staining of the internal limiting membrane (ILM) was seen in patients with MH, while the staining pattern in ERM cases was patchy, indicating that parts of the ILM were peeled off along with the ERM in a variable extent. All MHs could be closed successfully. VA improved in 10 eyes (56%; 8/ 15 MH patients, 2/3 ERM patients), was unchanged in four eyes (22%; all MH patients) and was reduced in four eyes (22%; 3/15 MH, 1/3 ERM). No toxic effects attributable to the dye were noted during patient follow-up. The ultrastructure of tissue harvested during surgery was unremarkable. Conclusion: Brilliant Blue provides a sufficient and selective staining of the ILM. No retinal toxicity or adverse effects related to the dye were observed in animal and human studies. The long-term safety of this novel dye will have to be evaluated in larger patient series and a longer follow-up. [ABSTRACT FROM AUTHOR] more...

Continuous long-term simulations of an ensemble of nine crop models covering the 1961–2080 period was employed to assess the expected impacts of climate change on the crop yield and water use for distinct crop rotations (CRs) in Europe. In this study, the likelihood of changes in two differently managed CRs (conventional and alternative) involving four important field crops (winter wheat, spring barley, silage maize, and winter oilseed rape) was assessed. The conventional agricultural practice (CR1) included only mineral fertilization with the removal of crop residues after harvest. The alternative agricultural practice (CR2) included cover crops and the application of mineral and organic fertilizers, with crop residues retained in the field. The simulations covered six sites in five European countries (Mühldorf and Müncheberg in Germany, Ukkel in Belgium, Ødum in Denmark, Milhostov in Slovakia and Lednice in Czechia) based on two distinct soil profiles (universal soil and site-specific soils). The universal soil was the same across all the sites, while the site-specific soils were typical of each region. Eight transient climate change scenarios (4 general circulation models (GCMs) under representative concentration pathways (RCPs) 2.6 and 8.5) were used to capture the possible evolution of future climatic conditions. Compared with those during the 1962–1990 period, the ensemble projections for the 2051–2080 period indicated average increases in the annual yields of all crops of 0.7 t/ha (RCP 2.6) and 0.8 t/ha (PCP 8.5) under both CRs and soil types. Under most climate change scenarios, the crop model ensemble projections of the winter wheat and winter oilseed rape yield increases agreed for CR2 but not for CR1. For spring barley, the simulated increase was more sporadic, with no significant difference between CR1 and CR2. In regard to silage maize, the changes in the simulated yields depended on site-specific climatic conditions. If the same varieties were planted in the future, yield reductions would be expected, except at the Ødum site, where the silage maize growth conditions would remain satisfactory, regardless of the CR and soil type. The results indicated greater cover crop biomass production, which could affect the long-term soil water balance and groundwater replenishment. The crop model ensemble further indicated a greater spatial variability in the yield can be expected, which is likely caused by the expected increase in the air temperature and not by the expected increase, or even decrease, in the total precipitation and increases in the actual evapotranspiration under climate change at all sites. This trend was greater under CR2 and could affect the long-term soil water balance and soil regime in the case of rainfed agriculture. [Display omitted] • 9 models were applied for 2 rotations, 4 crops, 2 soils, 8 scenarios, 6 sites a continuous run over 120 years. • In the projected future, an increase in the annual yields of all crops included in the study can be expected. • The potential for yield increase in the projected future is higher within alternative agricultural practice. • A higher gradient in yield responses across Central Europe caused by the increase in air temperature can be expected. [ABSTRACT FROM AUTHOR] more...

Purpose: The purpose was to assess the influence of donor and storage factors on the suitability of organ-cultured corneas for transplantation. Methods: Data from 1340 donor corneas stored between 2009 and 2015 were analyzed retrospectively. Logistic regression analysis was used to assess the influence of different factors on the suitability of grafts for transplantation. Results: Forty-one percent (553/1340) of corneas were discarded. The leading causes were medical contraindication (20.2 %) and poor endothelial quality (19.3 %). Donor age influenced suitability for transplantation significantly. Corneas from donors aged 80 years and older were more likely to be discarded because of endothelial insufficiency ( P < 0.0001). The cause of donor death including infection and multiple organ dsyfunction syndrom (MODS) increased the risk of bacterial or fungal contamination during organ culture ( P = 0.007 and P = 0.014, respectively). Prolonged time between death and enucleation was associated with an increased risk of unsuitability for transplantation ( P < 0.0001). The amount of time between death and corneoscleral disc excision and duration of storage influenced the suitability for transplantation ( P = 0.0007 and P < 0.0001, respectively). Conclusion: Donor age, cause of death, storage time, death to enucleation and death to disc excision times influenced transplantation suitability. The percentage of discarded corneas may be reduced by shortening storage time, death to enucleation, and death to corneoscleral disc excision times. Setting a maximum donor age could reduce the percentage of discarded corneas. However, as long as there is a lack of donor corneas, we do not recommend any donor age limit. [ABSTRACT FROM AUTHOR] more...

Aim: To assess whether low concentrations of a fluorescent dye such as Rhodamine 6G would help the unaided human eye visualise the vitreous and the internal limiting membrane (ILM) under standard halogen illumination. Material/methods: The UV/Vis absorption (E) and fluorescence (I) spectra of Rhodamine 6G in water were measured and compared with Indocyanine Green (ICG). Surgery was performed in two rhesus monkeys and consisted of standard pars plana vitrectomy with halogen light source used for illumination. Rhodamine 60 was diluted in balanced salt solution (BSS). A few drops of the dye in a concentration of 0.1% (307 mOsm) were applied over the posterior pole in the air-filled globe and washed out by irrigation after 1 mm. Immediately after surgery, the globes were enucleated, fixated and prepared for histological evaluation. Results: In contrast to ICG, both the maximum of the absorption and emission of Rhodamin 60 are very much within the spectral sensitivity of the human eye. The Rhodamine 6G-BSS itself appears red in colour. Using a dye concentration of 0.1%, there was no visible red- staining of the ILM as such. As the dye was irrigated out with BSS, a marked green fluorescence of the fluid within the vitreous cavity was noted. With halogen illumination through a standard 20-gauge light pipe, the dye provided a sufficient green fluorescence to identify and safely remove the ILM and to clearly differentiate areas of peeled from non-peeled ILM. During light microscopy, eyes revealed a peeled ILM demarcation with no signs of acute retinal toxicity. Conclusion: The findings indicate that a fluorescent dye can be used for ILM peeling. Assuming that the fluorophore provides a high enough fluorescence quantum yield after adsorption to the ILM, much lower dye concentrations could be used compared with absorbent dyes, thereby minimising toxic effects. [ABSTRACT FROM AUTHOR] more...

Deregulation of apoptosis signalling is commonly found in cancer and results in resistance to cytotoxic therapies. Immunotherapy is a promising strategy to eliminate resistant cancer cells. The transfer of T-lymphocytes during allogeneic stem cell transplantation is clinically explored to induce a‘graft-versus-tumor’effect (GvT). Cytotoxic T-lymphocytes (CTL), which are major effectors of GvT, eliminate cancer cells by inducing apoptosis via multiple parallel pathways. Here, we study in vitro and in vivo the susceptibility of murine cancer cells engineered to express single antiapoptotic genes to CTL-mediated cytotoxicity. Interestingly, we find that single inhibitors of caspase activation, such as BCL-XL or dominant-negative mutants of FADD and caspase-9, protect cancer cells against antigen-specific CTL in vitro. Moreover, expression of BCL-XL impairs the growth suppression by adoptively transplanted CTL of established tumours in vivo. Hence, apoptosis defects that provide protection to cytotoxic cancer therapies can confer crossresistance to immunotherapy by tumour-reactive CTL.Cell Death and Differentiation (2005) 12, 317-325. doi:10.1038/sj.cdd.4401563 Published online 28 January 2005 [ABSTRACT FROM AUTHOR] more...