SUPRENUM: System essentials and grid applications

The SUPRENUM idea, the project, and the system has generally been described and presented in several papers. There is also a great deal of more detailed technical papers describing SUPRENUM as a whole or certain elements of it.

Here we want to give only a very general and rough survey on the essentials of the SUPRENUM system in order to enable the reader to categorize and understand the more specific SUPRENUM papers in this special issue.

Most of the supercomputer applications today are based on grid or grid-like data structures. Grid applications play also an essential role in the SUPRENUM development: in the top-down design of the architecture, in the programming environment, in the parallelization concept of algorithms, and, of course, in the application software development itself. We therefore place some emphasis on this grid orientation in our presentation.     

Comparison of Different Mass Spectrometry Workflows for the Proteomic Analysis of Tear Fluid

The tear film is a multi-layer fluid that covers the corneal and conjunctival epithelia of the eye and provides lubrication, nutrients, and protection from the outside environment. Tear fluid contains a high concentration of proteins and has thus been recognized as a potential source of biomarkers for ocular disorders due to its proximity to disease sites on the ocular surface and the non-invasive nature of its collection. This is particularly true in the case of dry eye disease, which directly impacts the tear film and its components. Proteomic analysis of tear fluid is challenging mainly due to the wide dynamic range of proteins and the small sample volumes. However, recent advancements in mass spectrometry have revolutionized the field of proteomics enabling unprecedented depth, speed, and accuracy, even with small sample volumes. In this study using the Orbitrap Fusion Tribrid mass spectrometer, we compared four different mass spectrometry workflows for the proteomic analysis of tear fluid collected via Schirmer strips. We were able to establish a method of in-strip protein digestion that identified >3000 proteins in human tear samples from 11 healthy subjects. Our method offers a significant improvement in the number of proteins identified compared to previously reported methods without pooling samples.     

Structural Basis of Cyclic 1,3-Diene Forming Acyl-Coenzyme A Dehydrogenases

The biologically important, FAD-containing acyl-coenzyme A (CoA) dehydrogenases (ACAD) usually catalyze the anti-1,2-elimination of a proton and a hydride of aliphatic CoA thioesters. Here, we report on the structure and function of an ACAD from anaerobic bacteria catalyzing the unprecedented 1,4-elimination at C3 and C6 of cyclohex-1-ene-1-carboxyl-CoA (Ch1CoA) to cyclohex-1,5-diene-1-carboxyl-CoA (Ch1,5CoA) and at C3 and C4 of the latter to benzoyl-CoA. Based on high-resolution Ch1CoA dehydrogenase crystal structures, the unorthodox reactivity is explained by the presence of a catalytic aspartate base (D91) at C3, and by eliminating the catalytic glutamate base at C1. Moreover, C6 of Ch1CoA and C4 of Ch1,5CoA are positioned towards FAD-N5 to favor the biologically relevant C3,C6- over the C3,C4-dehydrogenation activity. The C1,C2-dehydrogenation activity was regained by structure-inspired amino acid exchanges. The results provide the structural rationale for the extended catalytic repertoire of ACADs and offer previously unknown biocatalytic options for the synthesis of cyclic 1,3-diene building blocks.     

Fluorescence Lifetime Imaging Microscopy (FLIM) of Intracellular Transport by Means of Doubly Labelled siRNA Architectures

For monitoring the intracellular pathway of small interfering RNA (siRNA), both strands were labelled at internal positions by two ATTO dyes as an interstrand Förster resonance energy transfer pair. siRNA double strands show red emission and a short donor lifetime as readout, whereas siRNA antisense single strands show green emission and a long donor lifetime. This readout signals if GFP silencing can be expected (green) or not (red). We attached both dyes to three structurally different alkyne anchors by postsynthetic modifications. There is only a slight preference for the ribofuranoside anchors with the dyes at their 2’-positions. For the first time, the delivery and fate of siRNA in live HeLa cells was tracked by fluorescence lifetime imaging microscopy (FLIM), which revealed a clear relationship between intracellular transport using different transfection methods and knockdown of GFP expression, which demonstrates the potential of our siRNA architectures as a tool for future development of effective siRNA.     

Effect of structure on the glass transition temperatures of linear and crosslinked poly(isobornylacrylate-co-isobutylacrylate)

A series of linear acrylic copolymers based on Isobornyl acrylate (IBOA) and isobutyl acrylate (IsoBA) were elaborated by radical photopolymerization. In addition, several photochemically crosslinked poly(IBOA-co-IsoBA) were prepared by introducing small amounts of 1,6-hexanedioldiacrylate as crosslinking agent. The evolution of the glass transition temperature was determined experimentally by differential scanning calorimetry as a function of composition for both linear and crosslinked poly(IBOA-co-IsoBA), yielding T_g values ranging from (~249) to (~315 K). Theoretical modeling was performed applying Fox, Gordon-Taylor and Couchman-Karasz models by simple calculations using experimental data, leading to only fair agreement between theoretical and experimental values, or by applying fitting procedures involving one or two adjustable parameters. Likewise, the Kwei model, known to take into account hydrogen bonding interactions between monomers, could not describe well the evolution of T_g, indicating the existence of other factors influencing T_g. Finally, a thermodynamic approach based on entropy considerations allowed to attribute an explanation of the evolution of T_g.     

Low-Cost Membranen für die Vanadium-Redox-Flow-Batterie

Reinforced proton exchange membranes (gPEM) are fabricated by coating a polymer suspension onto a polymer mesh. The polymer suspension contains solved poly(ether sulfone) (PES) and dispersed poly(styrene). The poly(styrene) is cross linked, sulfonylated and sulfonated. By using a poly(ether ether ketone) (PEEK) mesh with a thickness of 128 µm higher proton conductivities were measured compared to Selemion CMVN and Nafion N115 at 25 °C. An energy efficiency of 68.6 % was measured with Nafion N115, an energy efficiency of 53.1 % with CMVN and an energy efficiency of 69.4 % with a fabricated reinforced membrane at a current density of 100 mA cm⁻² in a vanadium redox flow cell.     

Exploring the impact of organisational,technological and relational contingencies on innovation speed in the light of open innovation

ABSTRACT

Striving for competitive advantage pushes firms to innovate at a high speed along innovation contingencies and resource limitations they face. Yet, little is known about how management of contingencies such as absorptive capacity or technology radicalness can impact the innovation speed of firms. In this explorative study, we provide new empirical evidence to the innovation speed literature. We examine to what extent innovation speed is affected by organisational, technological, and relational contingencies that preoccupy firms with open innovation practices. Taking the firm perspective, we track innovation timeline and emphasise the complex trade-offs that firms encounter while innovating. Our results show that many of the contingencies, emphasised by the literature promoting innovation, could slow down its speed. Thus, strengthening competitiveness by accommodating contingencies can hinder time-critical adaptations. Furthermore, we find that innovation assets and capabilities can become liabilities for technologically innovative firms.     

A Drug Screening Pipeline Using 2D and 3D Patient-Derived In Vitro Models for Pre-Clinical Analysis of Therapy Response in Glioblastoma

Glioblastoma is one of the most common and lethal types of primary brain tumor. Despite aggressive treatment with chemotherapy and radiotherapy, tumor recurrence within 6–9 months is common. To overcome this, more effective therapies targeting cancer cell stemness, invasion, metabolism, cell death resistance and the interactions of tumor cells with their surrounding microenvironment are required. In this study, we performed a systematic review of the molecular mechanisms that drive glioblastoma progression, which led to the identification of 65 drugs/inhibitors that we screened for their efficacy to kill patient-derived glioma stem cells in two dimensional (2D) cultures and patient-derived three dimensional (3D) glioblastoma explant organoids (GBOs). From the screening, we found a group of drugs that presented different selectivity on different patient-derived in vitro models. Moreover, we found that Costunolide, a TERT inhibitor, was effective in reducing the cell viability in vitro of both primary tumor models as well as tumor models pre-treated with chemotherapy and radiotherapy. These results present a novel workflow for screening a relatively large groups of drugs, whose results could lead to the identification of more personalized and effective treatment for recurrent glioblastoma.     

Durchgangswiderstand von partikulären Systemen

The electrical properties of particles especially the volume resistance of bulk particles have decisive implication on a multitude of processes in the process engineering such as, product qualification or fire and explosion protection. Since the charge transport in a disperse system and a homogeneously solid is different, the product properties of the particles and the fluid are crucial for the volume resistance. In this work the dependence of the volume resistance on the internal structure of the bed, the relative humidity, the conditioning time at different climates and the average particle size was investigated. All measurements were carried out in a concentric measuring cell.     

Hohlfaser-Membrankontaktoren zur Stickstoffrückgewinnung aus Prozesswasser einer kommunalen Kläranlage

Process water deriving from digested sludge dewatering at municipal wastewater treatment plants (WWTP) represents an additional load for the plant in terms of nitrogen. Münster WWTP is the first German plant to operate an innovative full-scale membrane contactor facility for nitrogen removal and recovery from process water. Within the scope of this study, aspects influencing the membrane performance and operation as well as utilization of the produced fertilizer are investigated. First results reveal nitrogen removal efficiencies around 85 % and a regional usability of the produced fertilizer.