Broad ranges of investment configurations for renewable power systems, robust to cost uncertainty and near-optimality.

Achieving ambitious CO2 emission reduction targets requires energy system planning to accommodate societal preferences, such as transmission reinforcements or onshore wind parks, and acknowledge uncertainties in technology cost projections among many other uncertainties. Current models often solely minimize costs using a single set of cost projections. Here, we apply multi-objective optimization techniques in a fully renewable European electricity system to explore trade-offs between system costs and technology deployment for electricity generation, storage, and transport. We identify ranges of cost-efficient capacity expansion plans incorporating future technology cost uncertainties. For example, we find that some grid reinforcement, long-term storage, and large wind capacities are important to keep costs within 8% of least-cost solutions. Near the cost optimum a technologically diverse spectrum of options exist, allowing policymakers to make trade-offs regarding unpopular infrastructure. Our analysis comprises 50,000+ optimization runs, managed efficiently through multi-fidelity surrogate modeling techniques using sparse polynomial chaos expansions and low-discrepancy sampling.

In oxygen-deprived tumor cells ERp57 provides radioprotection and ensures proliferation via c-Myc, PLK1 and the AKT pathway.

The disulfide isomerase ERp57, originally found in the endoplasmic reticulum, is located in multiple cellular compartments, participates in diverse cell functions and interacts with a huge network of binding partners. It was recently suggested as an attractive new target for cancer therapy due to its critical role in tumor cell proliferation. Since a major bottleneck in cancer treatment is the occurrence of hypoxic areas in solid tumors, the role of ERp57 in cell growth was tested under oxygen depletion in the colorectal cancer cell line HCT116. We observed a severe growth inhibition when ERp57 was knocked down in hypoxia (1% O2) as a consequence of downregulated c-Myc, PLK1, PDPK1 (PDK1) and AKT (PKB). Further, irradiation experiments revealed also a radiosensitizing effect of ERp57 depletion under oxygen deprivation. Compared to ERp57, we do not favour PDPK1 as a suitable pharmaceutical target as its efficient knockdown/chemical inhibition did not show an inhibitory effect on proliferation.

Grazing Preference of Dairy Cows and Pasture Productivity for Different Cultivars of Perennial Ryegrass under Contrasting Managements.

The objective of this study was to evaluate the pasture performance of different cultivars of perennial ryegrass, two "high sugar" and two standard cultivars, under two contrasting agronomic managements (aimed at either decreasing or increasing water soluble carbohydrates concentration), and their effects on the grazing preference of dairy cows. Eight treatments arising from the factorial combination of four cultivars and two managements were randomly applied to 31-m2 plots in three blocks. Pasture dry matter production and growth rate were measured for one year. Three grazing assessments were performed to establish the grazing preferences of six dairy cows in spring, summer and autumn. High sugar cultivars produced less dry matter per hectare than the standard cultivars. Cows consumed more grass and harvested a greater proportion of the pasture under the agronomic management aimed at decreasing sugar concentration, i.e., with a greater nitrogen fertilization rate and under a more frequent defoliation regime, which could be explained by the greater crude protein concentration achieved under this management. The results suggest that the genetic selection for greater levels of sugars was at the expense of herbage yield, and that cows preferred to graze herbage with a greater crude protein level instead of a greater sugar concentration.

Does the "high sugar" trait of perennial ryegrass cultivars express under temperate climate conditions?

The objective was to evaluate water-soluble carbohydrate (WSC) and crude protein (CP) concentration of perennial ryegrass (PRG) cultivars with different genetic potential for producing WSC under two contrasting agronomic managements in temperate climate (southern Chile). A 4 × 2 factorial design was randomly allocated to 24 plots (31 m2 each, three blocks): four PRG cultivars (diploid standard cultivar, "2nSt"; tetraploid standard cultivar, "4nSt"; diploid high sugar cultivar developed in New Zealand, "2nHSNZ"; and tetraploid high sugar cultivar developed in Europe, "4nHSEU") and two agronomic managements ("favourable," defoliations at three leaves per tiller and nitrogen (N) fertilization rate of 83.3 kg N ha-1 year-1; "unfavourable," defoliations at two leaves per tiller and N fertilization rate of 250 kg N ha-1 year-1). Herbage samples were collected in early spring, spring, summer and autumn. Concentration of WSC did not differ among cultivars in spring and summer, averaging 194 and 251 g/kg DM, respectively. The cultivar 4nHSEU had the greatest WSC concentration in early spring and autumn (187 and 266 g/kg DM, respectively) and the greatest CP concentration across samplings (average 230 g/kg DM). Favourable management improved WSC concentrations in early spring and summer and decreased CP in spring, summer and autumn. Annual DM yield did not vary with cultivar or management, averaging 8.43 t/ha. Within a 12-month study at one site in a temperate environment in southern Chile, PRG cultivars have not shown a consistent expression of the "high sugar" trait, where a genetic × environment interaction might be operating.

PDI is an essential redox-sensitive activator of PERK during the unfolded protein response (UPR).

Endoplasmic reticulum (ER) stress leads to activation of the unfolded protein response (UPR) that results in transient suppression of protein translation to allow recovery but leads to cell death when stress cannot be resolved. Central to initiation of the UPR is the activation of the ER transmembrane kinase protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK). Here we report that the thiol oxidoreductase ERp57 and protein disulfide isomerase-A1 (PDI), which belong to the same family of luminal ER oxidoreductases, have strikingly opposing roles in the regulation of PERK function. In HCT116 colon carcinoma cells, lentiviral depletion of ERp57 resulted in oxidation of PDI and activation of PERK, whereas depletion or chemical inhibition of PDI reduced PERK signaling and sensitized the cancer cells to hypoxia and ER stress. We conclude that oxidized PDI acts as a PERK activator, whereas ERp57 keeps PDI in a reduced state in the absence of ER stress. Thus, our study defines a new interface between metabolic redox signaling and PERK-dependent activation of the UPR and has the potential to influence future cancer therapies that target PERK signaling.

Depletion of the thiol oxidoreductase ERp57 in tumor cells inhibits proliferation and increases sensitivity to ionizing radiation and chemotherapeutics.

Rapidly growing tumor cells must synthesize proteins at a high rate and therefore depend on an efficient folding and quality control system for nascent secretory proteins in the endoplasmic reticulum (ER). The ER resident thiol oxidoreductase ERp57 plays an important role in disulfide bond formation. Lentiviral, doxycycline-inducible ERp57 knockdown was combined with irradiation and treatment with chemotherapeutic agents. The knockdown of ERp57 significantly enhanced the apoptotic response to anticancer treatment in HCT116 colon cancer cells via a p53-dependent mechanism. Instead of a direct interaction with p53, depletion of ERp57 induced cell death via a selective activation of the PERK branch of the Unfolded Protein Response (UPR). In contrast, apoptosis was reduced in MDA-MB-231 breast cancer cells harboring mutant p53. Nevertheless, we observed a strong reduction of proliferation in response to ERp57 knockdown in both cell lines regardless of the p53 status. Depletion of ERp57 reduced the phosphorylation activity of the mTOR-complex1 (mTORC1) as demonstrated by reduction of p70S6K phosphorylation. Our data demonstrate that ERp57 is a promising target for anticancer therapy due to synergistic p53-dependent induction of apoptosis and p53-independent inhibition of proliferation.

[Using network planning techniques for work flow analysis in a clinical environment]. / Anwendung der Netzplantechnik für die Arbeitsprozessanalyse im klinischen Bereich.

In the face of increasing financial pressure on our health care system, one way to reduce costs while maintaining or even improving outcome quality is to improve work flow efficiency. Network Planning Technique (NPT) is a tool for mapping and analyzing work flows. Designing a network plan requires four steps. Step 1 is concerned with the determination of the work flow structure. Step 2 deals with data acquisition. Based on the data retrieved a network plan is created in Step 3. Step 4 includes the calculation of the critical path and slack times under optimistic, realistic and pessimistic conditions. Applied to the ultrasound division in our department a total examination time of 34:14 minutes was calculated with 23:09 minutes total slack time for the technician under realistic conditions. Using NPT creates transparency in work flows and allows us to estimate resource demands. A comparison between two different divisions with a similar work flow structure but different resource allocation demonstrates this method's potential for improving work flows. Limitations of the NPT can be noted when considering cycle overlap in repetitive work flows and modeling non-regular activities.

The effect of thermotherapy using magnetic nanoparticles on rat malignant glioma.

Thermotherapy using magnetic nanoparticles is a new technique for interstitial hyperthermia and thermoablation based on magnetic field-induced excitation of biocompatible superparamagnetic nanoparticles. To evaluate the potential of this technique for minimally invasive treatment, we carried out a systematic analysis of its effects on experimental glioblastoma multiforme in a rat tumor model. Tumors were induced by implantation of RG-2-cells into the brains of 120 male Fisher rats. Animals were randomly allocated to 10 groups of 12 rats each, including controls. Animals received two thermotherapy treatments following a single intratumoral injection of two different magnetic fluids (dextran- or aminosilane-coated iron-oxide nanoparticles). Treatment was carried out on days four and six after tumor induction using an alternating magnetic field applicator system operating at a frequency of 100 kHz and variable field strength of 0-18 kA/m. The effectiveness of treatment was determined by the survival time of the animals and histopathological examinations of the brain and the tumor.Thermotherapy with aminosilane-coated nanoparticles led up to 4.5-fold prolongation of survival over controls, while the dextran-coated particles did not indicate any advantage. Intratumoral deposition of the aminosilane-coated particles was found to be stable, allowing for serial thermotherapy treatments without repeated injection. Histological and immunohistochemical examinations after treatment revealed large necrotic areas close to particle deposits, a decreased proliferation rate and a reactive astrogliosis adjacent to the tumor.Thus, localized interstitial thermotherapy with magnetic nanoparticles has an antitumoral effect on malignant brain tumors. This method is suitable for clinical use and may be a novel strategy for treating malignant glioma, which cannot be treated successfully today. The optimal treatment schedules and potential combinations with other therapies need to be defined in further studies.

Efficacy of contrast medium use for neuroimaging at 3.0 T: utility of IR-FSE compared to other T1-weighted pulse sequences.

As inversion-recovery (IR) technique improves T1 contrast at high field strength, signal enhancement by T1-shortening contrast media may be affected. To clarify the different enhancement properties at 3.0 T, the authors compared T1-weighted sequences. Twelve contrast-enhancing lesions were investigated by spin-echo (SE), inversion recovery fast spin-echo (IR-FSE), two-dimensional gradient-echo (2D GE), and magnetization-prepared three-dimensional gradient-echo (3D GE) sequences and evaluated by comparing signal-intensity enhancements within the lesions. In addition, signal-to-noise-ratios (SNR) and contrast-to-noise-ratios (CNR) were measured. On average, signal enhancement of the lesions amounted to 60% for SE, 57% for IR-FSE, 32% for 2D GE, and 35% for 3D GE images. CNR of gray matter versus white matter was significantly higher for IR SE and GE imaging than for genuine SE and 2D GE acquisitions (Wilcoxon test), while 2D GE imaging alone had an excellent SNR. As IR-FSE images provide an excellent CNR for gray and white matter in the brain and contrast enhancement performs almost similarly well compared with SE imaging, this technique appears to be well suited for T1-weighted neuroimaging without and with contrast enhancement at 3.0 T. However, the inherent blurring of the IR-FSE can lead to poor performance for very small lesions.

Imaging of single human carcinoma cells in vitro using a clinical whole-body magnetic resonance scanner at 3.0 T.

The purpose of the present study was to examine whether single human carcinoma cells labeled with iron oxide nanoparticles could be detected by magnetic resonance (MR) imaging on a clinical 3-T scanner using a surface coil only. WiDr human colon carcinoma cells were loaded with two kinds of iron oxide nanoparticles differing by coating and size: aminosilan-coated (MagForce) and carboxy-dextran-coated particles (Resovist). The latter were preferred by the colon carcinoma cell line used here and taken up much faster (12 h) than the smaller carboxydextran-coated Resovist (48 h). Labeled single carcinoma cells, distributed in an agarose gel in a monodisperse layer as controlled by light microscopy, became detectable as punctuate signal extinctions when using a small circularly polarized surface coil in conjunction with a T(2)*-weighted GE sequence at 3 T. The threshold for the detectability of labeled colon carcinoma cells ranged at a load of 4-5 mug iron/10(6) cells. Obviating the need for special hardware additions, this study opens a new lane for single-cell tracking on clinical 3-T MR scanners amenable to patient studies.