In formation: Support for flexibility, mobility, collaboration, and coherence

This paper describes support for flexibility, mobility and collaboration in engaging with, and making sense of, information. Our focus lies on the transitions people make between different, dynamic configurations of digital and physical materials, technologies, people and spaces. The technologies we describe have been developed in partnership with landscape architects over the past two years. We show that appliances and people can come together in a way that creates scope for such transitions, collaboration, and the emergence of new ways of working.     

Hyperinsulinemic Hypoglycemia Associated with a CaV1.2 Variant with Mixed Gain- and Loss-of-Function Effects

The voltage-dependent L-type calcium channel isoform Ca_V1.2 is critically involved in many physiological processes, e.g., in cardiac action potential formation, electromechanical coupling and regulation of insulin secretion by beta cells. Gain-of-function mutations in the calcium voltage-gated channel subunit alpha 1 C (CACNA1C) gene, encoding the Ca_V1.2 α₁-subunit, cause Timothy syndrome (TS), a multisystemic disorder that includes autism spectrum disorders and long QT (LQT) syndrome. Strikingly, TS patients frequently suffer from hypoglycemia of yet unproven origin. Using next-generation sequencing, we identified a novel heterozygous CACNA1C mutation in a patient with congenital hyperinsulinism (CHI) and associated hypoglycemic episodes. We characterized the electrophysiological phenotype of the mutated channel using voltage-clamp recordings and in silico action potential modeling experiments. The identified Ca_V1.2^L566P mutation causes a mixed electrophysiological phenotype of gain- and loss-of-function effects. In silico action potential modeling supports that this mixed electrophysiological phenotype leads to a tissue-specific impact on beta cells compared to cardiomyocytes. Thus, CACNA1C variants may be associated with non-syndromic hyperinsulinemic hypoglycemia without long-QT syndrome, explained by very specific electrophysiological properties of the mutated channel. We discuss different biochemical characteristics and clinical impacts of hypoglycemia in the context of CACNA1C variants and show that these may be associated with significant morbidity for Timothy Syndrome patients. Our findings underline that the potential of hypoglycemia warrants careful attention in patients with CACNA1C variants, and such variants should be included in the differential diagnosis of non-syndromic congenital hyperinsulinism.     

Effect of thermal treatment on glucosinolates and antioxidant-related parameters in red cabbage (Brassica oleracea L. ssp. capitata f. rubra)

The effects of various thermal processing treatments (blanching, boiling and steaming) of red cabbage, Brassica oleracea L. ssp. capitata f. rubra cv. ‘Autoro’, were assessed for the levels of glucosinolates (GLS), total phenols (TP), total monomeric anthocyanins (TMA), l-ascorbic acid (L-AA) and soluble sugars, as well as for the antioxidant potential by the ferric reducing ability power (FRAP) and oxygen radical absorbance capacity (ORAC) assays. Individual native GLS were determined by ion-pair HPLC-MS/DAD. There were significant (p < 0.05) losses in blanched red cabbage: TP, 43%, TMA 59%, FRAP 42%, ORAC 51%, L-AA 48% and soluble sugars 45%. Boiling gave less extensive reductions: TP 16%, TMA 41%, FRAP 17%, ORAC 19%, L-AA 24% and soluble sugars 19%. Steaming caused no losses for TP, ORAC, FRAP or soluble sugars. However, significant reductions were found for TMA and L-AA, with 29% and 11%, respectively. In general losses were accounted for in the processing waters; however, TMA was not fully recovered, indicating degradation. Total GLS were severely affected by processing, with reductions of 64%, 38% and 19% in blanched, boiled and steamed red cabbage, respectively. Total aliphatic and indole GLS were similarly affected. Lost GLS were partially recovered in the processing water.     

Diagenetic transformation of dissolved organic nitrogen compounds under contrasting sedimentary redox conditions in the Black Sea

Remineralization of organic matter in reactive marine sediments releases nutrients and dissolved organic matter (DOM) into the ocean. Here we focused on the molecular-level characterization of DOM by high-resolution Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) in sediment pore waters and bottom waters from contrasting redox regimes in the northern Black Sea with particular emphasis on nitrogen-bearing compounds to derive an improved understanding of the molecular transformations involved in nitrogen release. The number of nitrogen-bearing molecules is generally higher in pore waters than in bottom waters. This suggests intensified degradation of nitrogen-bearing precursor molecules such as proteins in anoxic sediments: No significant difference was observed between sediments deposited under oxic vs anoxic conditions (average O/C ratios of 0.55) suggesting that the different organic matter quality induced by contrasting redox conditions does not impact protein diagenesis in the subseafloor. Compounds in the pore waters were on average larger, less oxygenated, and had a higher number of unsaturations. Applying a mathematical model, we could show that the assemblages of nitrogen-bearing molecular formulas are potential products of proteinaceous material that was transformed by the following reactions: (a) hydrolysis and deamination, both reducing the molecular size and nitrogen content of the products and intermediates; (b) oxidation and hydration of the intermediates; and (c) methylation and dehydration.     

In Vitro Angiogenesis Inhibition and Endothelial Cell Growth and Morphology

A co-culture assay with human umbilical vein endothelial cells (HUVECs) and normal human dermal fibroblasts (NHDFs) was used to study whether selected angiogenesis inhibitors were able to inhibit differentiation and network formation of HUVECs in vitro. The effect of the inhibitors was determined by the morphology and the calculated percentage area covered by HUVECs. Neutralizing VEGF with avastin and polyclonal goat anti-VEGF antibody and inhibiting VEGFR2 with sorafenib and vatalanib resulted in the formation of HUVEC clusters of variable sizes as a result of inhibited EC differentiation. Furthermore, numerous inhibitors of the VEGF signaling pathways were tested for their effect on the growth and differentiation of HUVECs. The effects of these inhibitors did not reveal a cluster morphology, either individually or when combined to block VEGFR2 downstream pathways. Only the addition of N-methyl-p-bromolevamisole revealed a similar morphology as when targeting VEGF and VEGFR2, meaning it may have an inhibitory influence directly on VEGFR signaling. Additionally, several nuclear receptor ligands and miscellaneous compounds that might affect EC growth and differentiation were tested, but only dexamethasone gave rise to cluster formation similarly to VEGF-neutralizing compounds. These results point to a link between angiogenesis, HUVEC differentiation and glucocorticoid receptor activation.     

Production and Characterization of Peptide Antibodies to the C-Terminal of Frameshifted Calreticulin Associated with Myeloproliferative Diseases

Myeloproliferative Neoplasms (MPNs) constitute a group of rare blood cancers that are characterized by mutations in bone marrow stem cells leading to the overproduction of erythrocytes, leukocytes, and thrombocytes. Mutations in calreticulin (CRT) genes may initiate MPNs, causing a novel variable polybasic stretch terminating in a common C-terminal sequence in the frameshifted CRT (CRTfs) proteins. Peptide antibodies to the mutated C-terminal are important reagents for research in the molecular mechanisms of MPNs and for the development of new diagnostic assays and therapies. In this study, eight peptide antibodies targeting the C-terminal of CRTfs were produced and characterised by modified enzyme-linked immunosorbent assays using resin-bound peptides. The antibodies reacted to two epitopes: CREACLQGWTE for SSI-HYB 385-01, 385-02, 385-03, 385-04, 385-07, 385-08, and 385-09 and CLQGWT for SSI-HYB 385-06. For the majority of antibodies, the residues Cys¹, Trp⁹, and Glu¹¹ were essential for reactivity. SSI-HYB 385-06, with the highest affinity, recognised recombinant CRTfs produced in yeast and the MARIMO cell line expressing CRTfs when examined in Western immunoblotting. Moreover, SSI-HYB 385-06 occasionally reacted to CRTfs from MPN patients when analysed by flow cytometry. The characterized antibodies may be used to understand the role of CRTfs in the pathogenesis of MPNs and to design and develop new diagnostic assays and therapeutic targets.     

Research Validation: Challenges and Opportunities in the Construction Domain

Validation of the research methodology and its results is a fundamental element of the process of scholarly endeavor. Approaches used for construction engineering and management research have included experiments, surveys and observational studies, modeling and simulation, theory building, case studies, and various subtypes thereof. Some studies use more than one approach. A particular contribution of this paper is that it reviews different types of validation using examples of studies, analyzes the specific challenges that were found to be significant, and presents how they were successfully overcome in each case. Another contribution is that it describes new opportunities for research validation that are emerging at the horizon as well as ongoing collaborative efforts to enhance the access of construction researchers to validation tools. This paper increases the awareness of the paramount role that validation techniques play in scholarly work by providing readers with recommendations to properly validate their own research efforts.     

Schlüsselverteilung für Mobilgeräte

Digitale Zertifikate werden bereits in großem Umfang zur Verschlüsselung mit Desktop Clients wie Outlook eingesetzt. Damit ein Benutzer auch an all seinen Mobilgeräten verschlüsselte E-Mails lesen und an beliebige Empfänger verschlüsseln kann, müssen sein privater Schlüssel sowie die Zertifikate der Partner dort verfügbar sein.