Modellierung und Optimierung von Energiespeichern in Kraft-Wärme-Kopplungsanlagen

In dieser Arbeit wurde das Zusammenspiel von wärmegeführten Kraft-Wärme-Kopplung-Anlagen (kurz: KWK-Anlagen) für Ein- und Mehrfamilienhäuser mit verschiedenen elektrischen Energiespeichern simuliert und evaluiert. Neben dem Vergleich verschiedener KWK-Systeme und elektrischer Energiespeicher wurde auch die Untersuchungsmethode an sich mittels stochastischer Verfahren, wie der Monte-Carlo-Methode, evaluiert und auf ihre Aussagegenauigkeit hin getestet. Somit können mit dieser Arbeit geeignete Speichertechnologien für wärmegeführte KWK-Anlagen identifiziert und ausgelegt werden.In this work, the interaction of thermal-controlled combined heat and power (CHP) systems for single-family and multi-family houses with different electrical energy storage systems was simulated and evaluated. In addition to the comparison of different CHP systems and electrical energy storage systems, the research method itself was also evaluated using stochastic procedures, such as the Monte Carlo method, and tested for its accuracy. This work can thus be used to identify and design suitable storage technologies for heat-controlled CHP plants

A systematic review of the scientifically demonstrated effects of densification

One of the current dominant strategies proposed for sustainable urban development is densification. UN Habitat prescribes a density of over 150 inhabitants per hectare to realize the UN Sustainable Development Goals. While some authors advocate the very reasonable benefits of density, others emphasize the potential drawbacks. The main goal of this paper is to provide a systematic review of international research on urban density and its potential benefits and drawbacks for sustainable urban development. 1208 articles were selected from Web of Science and after the screening of abstracts, 330 papers were found eligible to be included in the quantitative synthesis. Results show that the effects of densification that dominate literature are transport related studies (41%), followed by studies focusing on economics (14%), social effects (12%) and human health (11%). Least studied effects are resource efficiency (1%), service (3%) and urban environment (4%). Positive correlations with higher density are reported for transport and economics, while ecology, social impact and health show mainly negative correlations with higher density. The findings reported are generic as similar trends are found in North America, Asia and Europe and only minor differences in outcome are found in studies using different measures of density, unit or scale of analysis

Treatment effects of once-weekly dulaglutide versus insulin glargine in patients with different baseline glycemic patterns (based on high/low fasting or high/low postprandial glucose): a post hoc analysis of the AWARD-2 clinical trial

The effects of DU 1.5 mg and Glar were compared in patients with T2D at 52 weeks from the AWARD-2 study with prevalent elevations in fasting glucose (FG), postprandial glucose (PPG), or both FG and PPG at baseline. Changes in glycated hemoglobin (A1c), FG, PPG, body weight, and hypoglycemia were investigated

Systematic review and comparison of densification effects and planning motivations

Do higher urban densities contribute to more sustainable cities and communities? This paper examines the effectiveness of higher density (as a means) for achieving sustainable urban development (the goal) following three lines of enquiry. First, a systematic review of the scientific literature (n = 229 peer-reviewed empirical studies) is presented on the effects of urban density. Second, the motivations for increasing urban density are studied in a systematic review of Swedish planning practices based on the comprehensive urban plans in 59 municipalities. Third, these two studies are compared to find matches and mismatches between evidence and practice. Although positive effects exist for public infrastructure, transport and economics, there are also considerable negative environmental, social and health impacts. This creates a challenging task for urban planners to assess the trade-offs involving densification and accommodate current urbanisation rates. Some topics are found to be over-represented in research (transport effects), seldom discussed in practice (environmental impact), and misaligned when comparing motives and evidence (social impact). Furthermore, for some topics, urban density thresholds are found that are important because they may explain some of the divergences in the results between studies. PRACTICE RELEVANCE The transfer of knowledge from research to planning practice is a serious concern as planning strategies are not aligned with scientific evidence. Planning practice in Sweden is more positive about the contribution of higher density to sustainable urban development than the results of empirical studies warrant. The largest deviation is found in relation to the social impacts of higher density where the planning arguments are not aligned with the evidence. Several reported negative effects of densification (e.g. water management, recreational infrastructure, biodiversity) are not sufficiently accounted for in Sweden’s planning policy and strategy. The narrow planning focus on decarbonising cities and densification needs to be broadened to ensure cities are resilient against the effects of climate change and include mitigation strategies to reduce negative social, environmental and health impacts. The findings can be used to develop evidence-based planning strategies. Other countries can apply this process to assess their planning strategies

An Obesity Risk SNP (rs17782313) near the MC4R Gene Is Associated with Cerebrocortical Insulin Resistance in Humans

Activation of melanocortin-4 receptor (MC4R) by insulin sensitive neurons is a central mechanism in body weight regulation, and genetic variants in the MC4R gene (e.g., rs17782313) are associated with obesity. By using magnetoencephalography, we addressed whether rs17782313 affects the cerebrocortical insulin response. We measured the cerebrocortical insulin response by using magnetoencephalography in a hyperinsulinemic euglycemic clamp (versus placebo) in 51 nondiabetic humans (26 f/25 m, age 35 ± 3 years, BMI 28 ± 1 kg/m2). The C-allele of rs17782313 was minor allele (frequency 23%), and the genotype distribution (TT 30, TC 19, CC 2) was in Hardy-Weinberg-Equilibrium. Insulin-stimulated cerebrocortical theta activity was decreased in the presence of the C-allele (TT 33 ± 16 fT; TC/CC −27 ± 20 fT; P = .023), and this effect remained significant after adjusting for BMI and peripheral insulin sensitivity (P = .047). Cerebrocortical theta activity was impaired in carriers of the obesity risk allele. Therefore, cerebral insulin resistance may contribute to the obesity effect of rs17782313

Association of obesity risk SNPs in PCSK1 with insulin sensitivity and proinsulin conversion

<p>Abstract</p> <p>Background</p> <p>Prohormone convertase 1 is involved in maturation of peptides. Rare mutations in gene <it>PCSK1</it>, encoding this enzyme, cause childhood obesity and abnormal glucose homeostasis with elevated proinsulin concentrations. Common single nucleotide polymorphisms (SNPs) within this gene, rs6232 and rs6235, are associated with obesity. We studied whether these SNPs influence the prediabetic traits insulin resistance, β-cell dysfunction, or glucose intolerance.</p> <p>Methods</p> <p>We genotyped 1498 German subjects for SNPs rs6232 and rs6235 within <it>PCSK1</it>. The subjects were metabolically characterized by oral glucose tolerance test with glucose, insulin, proinsulin, and C-peptide measurements. A subgroup of 512 subjects underwent a hyperinsulinemic-euglycemic clamp.</p> <p>Results</p> <p>The minor allele frequencies were 25.8% for SNP rs6235 and 6.0% for rs6232. After adjustment for sex and age, we found no association of SNPs rs6235 and rs6232 with BMI or other weight-related traits (all p ≥ 0.07). Both minor alleles, adjusted for sex, age, BMI and insulin sensitivity were associated with elevated AUC_proinsulinand AUC_proinsulin/AUC_insulin(rs6235: p_{additive model}≤ 0.009, effect sizes 8/8%, rs6232: p_{dominant model}≤ 0.01, effect sizes 10/21%). Insulin secretion was not affected by the variants (different secretion parameters, all p ≥ 0.08). The minor allele of SNP rs6232 was additionally associated with 15% higher OGTT-derived and 19% higher clamp-derived insulin sensitivity (p_dom≤ 0.0047), 4.5% lower HOMA_IR(p_dom= 0.02) and 3.5% lower 120-min glucose (p_dom= 0.0003) independently of BMI and proinsulin conversion. SNP rs6235 was not associated with parameters of glucose metabolism.</p> <p>Conclusions</p> <p>Like rare mutations in <it>PCSK1</it>, the more common variants tested determine glucose-stimulated proinsulin conversion, but not insulin secretion. In addition, rs6232, encoding the amino acid exchange N221D, influences insulin sensitivity and glucose homeostasis.</p

The dual glucose-dependent insulinotropic peptide and glucagon-like peptide-1 receptor agonist, tirzepatide, improves lipoprotein biomarkers associated with insulin resistance and cardiovascular risk in patients with type 2 diabetes

Aim To better understand the marked decrease in serum triglycerides observed with tirzepatide in patients with type 2 diabetes, additional lipoprotein-related biomarkers were measured post hoc in available samples from the same study. Materials and Methods Patients were randomized to receive once-weekly subcutaneous tirzepatide (1, 5, 10 or 15 mg), dulaglutide (1.5 mg) or placebo. Serum lipoprotein profile, apolipoprotein (apo) A-I, B and C-III and preheparin lipoprotein lipase (LPL) were measured at baseline and at 4, 12 and 26 weeks. Lipoprotein particle profile by nuclear magnetic resonance was assessed at baseline and 26 weeks. The lipoprotein insulin resistance (LPIR) score was calculated. Results At 26 weeks, tirzepatide dose-dependently decreased apoB and apoC-III levels, and increased serum preheparin LPL compared with placebo. Tirzepatide 10 and 15 mg decreased large triglyceride-rich lipoprotein particles (TRLP), small low-density lipoprotein particles (LDLP) and LPIR score compared with both placebo and dulaglutide. Treatment with dulaglutide also reduced apoB and apoC-III levels but had no effect on either serum LPL or large TRLP, small LDLP and LPIR score. The number of total LDLP was also decreased with tirzepatide 10 and 15 mg compared with placebo. A greater reduction in apoC-III with tirzepatide was observed in patients with high compared with normal baseline triglycerides. At 26 weeks, change in apoC-III, but not body weight, was the best predictor of changes in triglycerides with tirzepatide, explaining up to 22.9% of their variability. Conclusions Tirzepatide treatment dose-dependently decreased levels of apoC-III and apoB and the number of large TRLP and small LDLP, suggesting a net improvement in atherogenic lipoprotein profile.Peer reviewe

Genomic predictions to leverage phenotypic data across genebanks

Genome-wide prediction is a powerful tool in breeding. Initial results suggest that genome-wide approaches are also promising for enhancing the use of the genebank material: predicting the performance of plant genetic resources can unlock their hidden potential and fill the information gap in genebanks across the world and, hence, underpin prebreeding programs. As a proof of concept, we evaluated the power of across-genebank prediction for extensive germplasm collections relying on historical data on flowering/heading date, plant height, and thousand kernel weight of 9,344 barley (Hordeum vulgare L.) plant genetic resources from the German Federal Ex situ Genebank for Agricultural and Horticultural Crops (IPK) and of 1,089 accessions from the International Center for Agriculture Research in the Dry Areas (ICARDA) genebank. Based on prediction abilities for each trait, three scenarios for predictive characterization were compared: 1) a benchmark scenario, where test and training sets only contain ICARDA accessions, 2) across-genebank predictions using IPK as training and ICARDA as test set, and 3) integrated genebank predictions that include IPK with 30% of ICARDA accessions as a training set to predict the rest of ICARDA accessions. Within the population of ICARDA accessions, prediction abilities were low to moderate, which was presumably caused by a limited number of accessions used to train the model. Interestingly, ICARDA prediction abilities were boosted up to ninefold by using training sets composed of IPK plus 30% of ICARDA accessions. Pervasive genotype × environment interactions (GEIs) can become a potential obstacle to train robust genome-wide prediction models across genebanks. This suggests that the potential adverse effect of GEI on prediction ability was counterbalanced by the augmented training set with certain connectivity to the test set. Therefore, across-genebank predictions hold the promise to improve the curation of the world’s genebank collections and contribute significantly to the long-term development of traditional genebanks toward biodigital resource centers

The shared frameshift mutation landscape of microsatellite-unstable cancers suggests immunoediting during tumor evolution

The immune system can recognize and attack cancer cells, especially those with a high load of mutation-induced neoantigens. Such neoantigens are abundant in DNA mismatch repair (MMR)-deficient, microsatellite-unstable (MSI) cancers. MMR deficiency leads to insertion/deletion (indel) mutations at coding microsatellites (cMS) and to neoantigen-inducing translational frameshifts. Here, we develop a tool to quantify frameshift mutations in MSI colorectal and endometrial cancer. Our results show that frameshift mutation frequency is negatively correlated to the predicted immunogenicity of the resulting peptides, suggesting counterselection of cell clones with highly immunogenic frameshift peptides. This correlation is absent in tumors with Beta-2-microglobulin mutations, and HLA-A*02:01 status is related to cMS mutation patterns. Importantly, certain outlier mutations are common in MSI cancers despite being related to frameshift peptides with functionally confirmed immunogenicity, suggesting a possible driver role during MSI tumor evolution. Neoantigens resulting from shared mutations represent promising vaccine candidates for prevention of MSI cancers. DNA mismatch repair (MMR)-deficient cancers with microsatellite-instability are characterized by a high load of frameshift mutation-derived neoantigens. Here, by mapping the frameshift mutation landscape and predicting the immunogenicity of the resulting peptides, the authors show evidence of immunoediting in MMR-deficient colorectal and endometrial cancers.Peer reviewe

Hsp90 inhibition differentially destabilises MAP kinase and TGF-beta signalling components in cancer cells revealed by kinase-targeted chemoproteomics

<p>Abstract</p> <p>Background</p> <p>The heat shock protein 90 (Hsp90) is required for the stability of many signalling kinases. As a target for cancer therapy it allows the simultaneous inhibition of several signalling pathways. However, its inhibition in healthy cells could also lead to severe side effects. This is the first comprehensive analysis of the response to Hsp90 inhibition at the kinome level.</p> <p>Methods</p> <p>We quantitatively profiled the effects of Hsp90 inhibition by geldanamycin on the kinome of one primary (Hs68) and three tumour cell lines (SW480, U2OS, A549) by affinity proteomics based on immobilized broad spectrum kinase inhibitors ("kinobeads"). To identify affected pathways we used the KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway classification. We combined Hsp90 and proteasome inhibition to identify Hsp90 substrates in Hs68 and SW480 cells. The mutational status of kinases from the used cell lines was determined using next-generation sequencing. A mutation of Hsp90 candidate client RIPK2 was mapped onto its structure.</p> <p>Results</p> <p>We measured relative abundances of > 140 protein kinases from the four cell lines in response to geldanamycin treatment and identified many new potential Hsp90 substrates. These kinases represent diverse families and cellular functions, with a strong representation of pathways involved in tumour progression like the BMP, MAPK and TGF-beta signalling cascades. Co-treatment with the proteasome inhibitor MG132 enabled us to classify 64 kinases as true Hsp90 clients. Finally, mutations in 7 kinases correlate with an altered response to Hsp90 inhibition. Structural modelling of the candidate client RIPK2 suggests an impact of the mutation on a proposed Hsp90 binding domain.</p> <p>Conclusions</p> <p>We propose a high confidence list of Hsp90 kinase clients, which provides new opportunities for targeted and combinatorial cancer treatment and diagnostic applications.</p