Modeling the Air Temperature Profiles in the Cavity of a Double-skin Façade

The paper addresses a modeling approach to reduce energy use for conditioning a double-skin façade cavity of an existing large pharmaceutical production facility featuring 10 structural levels. Upon an examination of the limits of available building energy software a decision was made towards developing a new computation program, which offers dynamic resolution of the building physics involved while also taking into account the intended control strategy of the fan-supported cavity ventilation. To obtain the full picture of the façade performance during the operation time (24 * 7), simulations were carried out for 10 main representative cases. On the basis of the overall analysis of the simulation results, a façade performance control strategy was found which allows for extensive energy savings during most parts of the year, although, as requested by building operator, the proposed measures do not involve any significant retrofitting of the production facility

Supramolecular Assembly of Aminoethylene‐Lipopeptide PMO Conjugates into RNA Splice‐Switching Nanomicelles

Phosphorodiamidate morpholino oligomers (PMOs) are oligonucleotide analogs that can be used for therapeutic modulation of pre‐mRNA splicing. Similar to other classes of nucleic acid‐based therapeutics, PMOs require delivery systems for efficient transport to the intracellular target sites. Here, artificial peptides based on the oligo(ethylenamino) acid succinyl‐tetraethylenpentamine (Stp), hydrophobic modifications, and an azide group are presented, which are used for strain‐promoted azide‐alkyne cycloaddition conjugation with splice‐switching PMOs. By systematically varying the lead structure and formulation, it is determined that the type of contained fatty acid and supramolecular assembly have a critical impact on the delivery efficacy. A compound containing linolenic acid with three cis double bonds exhibits the highest splice‐switching activity and significantly increases functional protein expression in pLuc/705 reporter cells in vitro and after local administration in vivo. Structural and mechanistic studies reveal that the lipopeptide PMO conjugates form nanoparticles, which accelerate cellular uptake and that the content of unsaturated fatty acids enhances endosomal escape. In an in vitro Duchenne muscular dystrophy exon skipping model using H2K‐mdx52 dystrophic skeletal myotubes, the highly potent PMO conjugates mediate significant splice‐switching at very low nanomolar concentrations. The presented aminoethylene‐lipopeptides are thus a promising platform for the generation of PMO‐therapeutics with a favorable activity/toxicity profile

Targeting RNS/caveolin-1/MMP signaling cascades to protect against cerebral ischemia-reperfusion injuries: potential application for drug discovery

Reactive nitrogen species (RNS) play important roles in mediating cerebral ischemia-reperfusion injury. RNS activate multiple signaling pathways and participate in different cellular events in cerebral ischemia-reperfusion injury. Recent studies have indicated that caveolin-1 and matrix metalloproteinase (MMP) are important signaling molecules in the pathological process of ischemic brain injury. During cerebral ischemia-reperfusion, the production of nitric oxide (NO) and peroxynitrite (ONOO-), two representative RNS, down-regulates the expression of caveolin-1 (Cav-1) and, in turn, further activates nitric oxide synthase (NOS) to promote RNS generation. The increased RNS further induce MMP activation and mediate disruption of the blood-brain barrier (BBB), aggravating the brain damage in cerebral ischemia-reperfusion injury. Therefore, the feedback interaction among RNS/Cav-1/MMPs provides an amplified mechanism for aggravating ischemic brain damage during cerebral ischemia-reperfusion injury. Targeting the RNS/Cav-1/MMP pathway could be a promising therapeutic strategy for protecting against cerebral ischemia-reperfusion injury. In this mini-review article, we highlight the important role of the RNS/Cav-1/MMP signaling cascades in ischemic stroke injury and review the current progress of studies seeking therapeutic compounds targeting the RNS/Cav-1/MMP signaling cascades to attenuate cerebral ischemia-reperfusion injury. Several representative natural compounds, including calycosin-7-O-β-D-glucoside, baicalin, Momordica charantia polysaccharide (MCP), chlorogenic acid, lutein and lycopene, have shown potential for targeting the RNS/Cav-1/MMP signaling pathway to protect the brain in ischemic stroke. Therefore, the RNS/Cav-1/MMP pathway is an important therapeutic target in ischemic stroke treatment.published_or_final_versio

BOSMI: A framework for non-intrusive monitoring and testing of embedded multithreaded software on the logical level

Traditional software testing methods are inefficient in cases where data inputs alone do not determine the outcome of a program's execution. In order to verify such software, testing is often complemented by analysis of the execution trace. For monitoring the execution trace, most approaches today insert additional instructions at the binary level, making the monitoring intrusive. Binary instrumentation operate on a low level, making it difficult to properly modify a program's states and to quantify its code coverage. In this paper, we present a framework for testing complex embedded multithreaded software on the logical level. Testing software on this level avoids dependency on concrete compilers and relates the execution to the source code, thus enabling coverage. Our non-intrusive execution monitoring and control is implemented using the LLVM interpreter compiler infrastructure. Instead of forcing thread interleaving, we suggest simulating interleaving effects through non-intrusive changes of shared variables. This makes it possible to test a single thread without executing the full software stack, which is especially useful in situations where the full software stack is not available (e.g., pre-integration testing). We complement existing approaches with new features such as dynamic configuration of monitoring and execution rollback to the checkpoints. Our approach introduces acceptable overhead without any complex setup

Central retinal artery occlusion and traumatic optic neuropathy following blunt ocular trauma

Letter to the edito

A Framework for Non-intrusive Trace-driven Simulation of Manycore Architectures with Dynamic Tracing Configuration

Traditional software testing methods are inefficient for multithreaded software. In order to verify such software, testing is often complemented by analysis of the execution trace. To monitor the execution trace, most approaches today use binary instrumentation or rigid frameworks based on system simulators. Most existing approaches are intrusive, as they tend to change the monitored software. Furthermore, their monitoring configuration is static, resulting in huge, often non-relevant, traces. In this paper, we present a light, non-intrusive execution monitoring and control approach, implemented using the gem5 system simulator. We complement existing approaches with dynamic configuration of the monitoring, making it possible to dynamically change the monitoring focus to the parts of the software that are of interest. This configuration results in reduced execution trace size. Our approach does not change the software under test, but rather the virtual platform that executes the software