Improving GIS-Based Heat Demand Modelling and Mapping for Residential Buildings with Census Data Sets at Regional and Sub-Regional Scales

Heat demand of buildings and related CO2 emissions caused by energy supply contribute to global climate change. Spatial data-based heat planning enables municipalities to reorganize local heating sectors towards efficient use of regional renewable energy resources. Here, annual heat demand of residential buildings is modeled and mapped for a German federal state to provide regional basic data. Using a 3D building stock model and standard values of building-type-specific heat demand from a regional building typology in a Geographic Information Systems (GIS)-based bottom-up approach, a first base reference is modeled. Two spatial data sets with information on the construction period of residential buildings, aggregated on municipality sections and hectare grid cells, are used to show how census-based spatial data sets can enhance the approach. Partial results from all three models are validated against reported regional data on heat demand as well as against gas consumption of a municipality. All three models overestimate reported heat demand on regional levels by 16% to 19%, but underestimate demand by up to 8% on city levels. Using the hectare grid cells data set leads to best prediction accuracy values at municipality section level, showing the benefit of integrating this high detailed spatial data set on building age

Prmt5 is a regulator of muscle stem cell expansion in adult mice.

Skeletal muscle stem cells (MuSC), also called satellite cells, are indispensable for maintenance and regeneration of adult skeletal muscles. Yet, a comprehensive picture of the regulatory events controlling the fate of MuSC is missing. Here, we determine the proteome of MuSC to design a loss-of-function screen, and identify 120 genes important for MuSC function including the arginine methyltransferase Prmt5. MuSC-specific inactivation of Prmt5 in adult mice prevents expansion of MuSC, abolishes long-term MuSC maintenance and abrogates skeletal muscle regeneration. Interestingly, Prmt5 is dispensable for proliferation and differentiation of Pax7(+) myogenic progenitor cells during mouse embryonic development, indicating significant differences between embryonic and adult myogenesis. Mechanistic studies reveal that Prmt5 controls proliferation of adult MuSC by direct epigenetic silencing of the cell cycle inhibitor p21. We reason that Prmt5 generates a poised state that keeps MuSC in a standby mode, thus allowing rapid MuSC amplification under disease conditions

Pazopanib, Cabozantinib, and Vandetanib in the Treatment of Progressive Medullary Thyroid Cancer with a Special Focus on the Adverse Effects on Hypertension

Medullary thyroid cancer (MTC) is a rare malignancy with a poor prognosis. First line therapy is surgery, which is the only curative method of the disease. However, in non-operable cases or with tumor progression and metastases, a systemic treatment is necessary. This form of cancer is often insensitive to conventional chemotherapy, but the use of tyrosine kinase inhibitors (TKIs), such as pazopanib, cabozantinib, and vandetanib, has shown promising results with an increase in progression-free survival and prolonged lifetime. Therefore, we focused on the pharmacological characteristics of TKIs, their mechanism of action, their application as a secondary treatment option for MTC, their efficacy as a cancer drug treatment, and reviewed the ongoing clinical trials. TKIs also act systemically causing various adverse events (AEs). One common AE of this treatment is hypertension, known to be associated with cardiovascular disease and can therefore potentially worsen the well-being of the treated patients. The available treatment strategies of drug-induced hypertension were discussed. The mechanism behind the development of hypertension is still unclear. Therefore, the treatment of this AE remains symptomatic. Thus, future studies are necessary to investigate the link between tumor growth inhibition and hypertension. In addition, optimized, individual treatment strategies should be implemented

Loading and Maintenance Doses of Digoxin in Patients with Normal Renal Function and Those with Severely Impaired Renal Function

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/97205/1/j.1552-4604.1974.tb01408.x.pd

Proteome Mapping of Adult Zebrafish Marrow Neutrophils Reveals Partial Cross Species Conservation to Human Peripheral Neutrophils

Neutrophil granulocytes are pivotal cells within the first line of host defense of the innate immune system. In this study, we have used a gel-based LC-MS/MS approach to explore the proteome of primary marrow neutrophils from adult zebrafish. The identified proteins originated from all major cellular compartments. Gene ontology analysis revealed significant association of proteins with different immune-related network and pathway maps. 75% of proteins identified in neutrophils were identified in neutrophils only when compared to neutrophil-free brain tissue. Moreover, cross-species comparison with human peripheral blood neutrophils showed partial conservation of immune-related proteins between human and zebrafish. This study provides the first zebrafish neutrophil proteome and may serve as a valuable resource for an understanding of neutrophil biology and innate immunity

Autophosphorylation at serine 166 regulates RIP kinase 1-mediated cell death and inflammation

Receptor interacting protein kinase 1 (RIPK1) regulates cell death and inflammatory responses downstream of TNFR1 and other receptors, and has been implicated in the pathogenesis of inflammatory and degenerative diseases. RIPK1 kinase activity induces apoptosis and necroptosis, however the mechanisms and phosphorylation events regulating RIPK1-dependent cell death signaling remain poorly understood. Here we show that RIPK1 autophosphorylation at serine 166 plays a critical role for the activation of RIPK1 kinase-dependent apoptosis and necroptosis. Moreover, we show that S166 phosphorylation is required for RIPK1 kinase-dependent pathogenesis of inflammatory pathologies in vivo in four relevant mouse models. Mechanistically, we provide evidence that trans autophosphorylation at S166 modulates RIPK1 kinase activation but is not by itself sufficient to induce cell death. These results show that S166 autophosphorylation licenses RIPK1 kinase activity to induce downstream cell death signaling and inflammation, suggesting that S166 phosphorylation can serve as a reliable biomarker for RIPK1 kinase-dependent pathologies

Changes of Gene Expression in Euglena gracilis Obtained During the 29th DLR Parabolic Flight Campaign

Parabolic flight maneuvers of Novespace’s Airbus A310 ZERO-G produce subsequent phases of hypergravity (about 20 s), microgravity (about 22 s) and another 20 s hypergravity on experiments located in the experiment area of the aircraft. The 29th DLR parabolic flight campaign consisted of four consecutive flight days with thirty-one parabolas each day. Euglena gracilis cells were fixed with TRIzol during different acceleration conditions at the first and the last parabola of each flight. Samples were collected and analyzed with microarrays for one-color gene expression analysis. The data indicate significant changes in gene expression in E. gracilis within short time. Hierarchical clustering shows that changes induced by the different accelerations yield reproducible effects at independent flight days. Transcription differed between the first and last parabolas indicating adaptation effects in the course of the flight. Different gene groups were found to be affected in different phases of the parabolic flight, among others, genes involved in signal transduction, calcium signaling, transport mechanisms, metabolic pathways, and stress-response as well as membrane and cytoskeletal proteins. In addition, transcripts of other areas, e.g., DNA and protein modification, were altered. The study contributes to the understanding of short-term effects of microgravity and different accelerations on cells at a molecular level

Improving Security for Time-Triggered Real-Time Systems against Timing Inference Based Attacks by Schedule Obfuscation

Covert timing channels in real-time systems allow adversaries to not only exfiltrate application secrets but also to mount timing inference based attacks. Much effort has been put into improving real-time system predictability with the additional benefit of reducing the former class of confidentiality attacks. However, the more predictable the system behaves, the easier timing inference based attacks become. Time-triggered scheduling is particularly vulnerable to these types of attacks due to offline constructed tables that are scheduled with clock synchronization and OS-timer predictability. In this paper, we obfuscate timetriggered scheduling to complicate timing inference based attacks while maintaining strong protection against exfiltration attacks

Vulnerability Analysis and Mitigation of Directed Timing Inference Based Attacks on Time-Triggered Systems

Much effort has been put into improving the predictability of real-time systems, especially in safety-critical environments, which provides designers with a rich set of methods and tools to attest safety in situations with no or a limited number of accidental faults. However, with increasing connectivity of real-time systems and a wide availability of increasingly sophisticated exploits, security and, in particular, the consequences of predictability on security become concerns of equal importance. Time-triggered scheduling with offline constructed tables provides determinism and simplifies timing inference, however, at the same time, time-triggered scheduling creates vulnerabilities by allowing attackers to target their attacks to specific, deterministically scheduled and possibly safety-critical tasks. In this paper, we analyze the severity of these vulnerabilities by assuming successful compromise of a subset of the tasks running in a real-time system and by investigating the attack potential that attackers gain from them. Moreover, we discuss two ways to mitigate direct attacks: slot-level online randomization of schedules, and offline schedule-diversification. We evaluate these mitigation strategies with a real-world case study to show their practicability for mitigating not only accidentally malicious behavior, but also malicious behavior triggered by attackers on purpose