Tunable colors and conductivity by electroless growth of Cu/Cu2O particles on sol-gel modified cellulose

Nano Research - Development of colored surfaces by formation of nano-structured aggregates is a widely used strategy in nature to color lightweight structures (e.g. butterflies) without the use of...     

Lignin from Annual Plants as Raw Material Source for Flavors and Basic Chemicals

The enzymatic conversion of lignins, possibly in combination with electrochemical oxidation, makes aromatics such as syringol, guaiacol, vanillin and catechol available in the qualities required by the fragrance industry. The lignins were obtained by soda digestion from wheat straw and Miscanthus, characterized and then converted with laccases. The overall yield amounted up to 9 wt % with a product spectrum confined to four substances. Catechol was the major product, with a fraction of ≈75 %. It can easily be isolated by extraction with acetone.     

Tetrahydroindoles as Multipurpose Screening Compounds and Novel Sirtuin Inhibitors

Indoles are privileged structures in medicinal and bioorganic chemistry that are particularly well suited to serve as platforms for diversity. Among many other therapeutic areas, the indole scaffold has been used to design aromatic compounds useful to interfere with enzymes engaged in the regulation of substrate acylation status, such as sirtuins. However, the planarity of the indole ring is not necessarily optimal for all target enzymes, especially when functionalization with aromatic side chains is required. Replacement of flat scaffolds by nonplanar molecular cores dominated by sp³ hybridization is a common strategy to avoid the disadvantages associated with poor solubility and high promiscuity, while covering less-well-explored areas of chemical space. Thus, we synthesized fragment-like tetrahydroindoles suitable for fragment-based drug discovery as well as a well-characterized small library intended as multipurpose screening compounds. For proof of principle, these compounds were screened against sirtuins 1–3, enzymes known to be addressable by indoles. We found that 2,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-1H-indole-3-carboxamides are potent and selective SIRT2 inhibitors. Compound 16 t displayed an IC₅₀ value of 0.98 μm and could serve as exquisite starting point for hit-to-lead profiling.     

Discovery of Affinity-Based Probes for Btk Occupancy Assays

Bruton's tyrosine kinase (Btk) is an attractive target for the treatment of a wide array of B-cell malignancies and autoimmune diseases. Small-molecule covalent irreversible Btk inhibitors targeting Cys481 have been developed for the treatment of such diseases. In clinical trials, probe molecules are required in occupancy studies to measure the level of engagement of the protein by these covalent irreversible inhibitors. The result of this pharmacodynamic (PD) activity provides guidance for appropriate dosage selection to optimize inhibition of the drug target and correlation of target inhibition with disease treatment efficacy. This information is crucial for successful evaluation of drug candidates in clinical trials. Based on the pyridine carboxamide scaffold of a novel solvent-accessible pocket (SAP) series of covalent irreversible Btk inhibitors, we successfully developed a potent and selective affinity-based biotinylated probe 12 (2-[(4-{4-[5-(1-{5-[(3aS,4S,6aR)-2-oxo-hexahydro-1H-thieno[3,4-d]imidazol-4-yl]pentanamido}-3,6,9,12-tetraoxapentadecan-15-amido)pentanoyl]piperazine-1-carbonyl}phenyl)amino]-6-[1-(prop-2-enoyl)piperidin-4-yl]pyridine-3-carboxamide). Compound 12 has been used in Btk occupancy assays for preclinical studies to determine the therapeutic efficacy of Btk inhibition in two mouse lupus models driven by TLR7 activation and type I interferon.     

Macrophage Immunomodulation Through New Polymers that Recapitulate Functional Effects of Itaconate as a Power House of Innate Immunity

Itaconate (ITA) is an emerging powerhouse of innate immunity with therapeutic potential that is limited in its ability to be administered in a soluble form. A library of polyester materials that incorporate ITA into polymer backbones resulting in materials with inherent immunoregulatory behavior is developed. Harnessing hydrolytic degradation release from polyester backbones, ITA polymers result in the mechanism specific immunoregulatory properties on macrophage polarization in vitro. In a functional assay, the polymer-released ITA inhibits bacterial growth on acetate. Translation to an in vivo model of biomaterial associated inflammation, intraperitoneal injection of ITA polymers demonstrate a rapid resolution of inflammation in comparison to a control polymer silicone, demonstrating the value of sustained biomimetic presentation of ITA.     

Technology-transfer analysis of the materials research program “Matfo”

The commercial success of the German Federal Ministry's materials research program “Mafto” (1985–1994) was recently evaluated to determine the effectiveness of the direct-funding model in supporting innovative industrial research. Based on the results of a questionnaire, where a 97% return rate was achieved, it was found that the results obtained in 27% of the projects have already been commercialized to some degree, for 26% of the projects a commercialization of the results is planned but has not yet taken place, and for 54% of the projects no commercialization is planned. This study included only projects where at least four years had elapsed since project completion. The reasons why scientifically and technically successfully projects were not commercialized were also surveyed.     

Detection of failure sites by focused ion beam and nano-probing in the interconnect of three-dimensional stacked circuit structures

Focused ion beam (FIB) and nano-probing were applied for failure analysis of three-dimensional stacked circuits with copper through-silicon-vias between the stacked chips. The failure analysis was done after high temperature storage and thermal cycling tests. Passive voltage contrast in FIB allowed to pinpoint the open sites. FIB cross-sections showed the presence of opens at the bottom of the copper vias. The failure cause was suspected to be an interlayer particle, which was confirmed by optical profilometry. Nano-probing was used on another sample to pinpoint the failure location through the measurement of the local resistance within the daisy chains. The failure was traced out to be related with surface contamination.     

Decision support for AIDS control programmes in Eastern Africa

The Acquired Immune Deficiency Syndrome (AIDS) constitutes the worst hazard to health care systems in Eastern Africa. Misallocation of scarce resources of AIDS Control Programmes will unavoidably lead to additional infections and casualties. The following paper discusses a system dynamics model which allows to assess the impact of different interventions on a pattern population in Eastern Africa. It becomes obvious that short- and long-term consequences of these programmes differ significantly. The optimal allocation of resources, therefore, is highly complex and calls for decision support systems to sustain AIDS control programmes.     

Associated ulcerative colitis, sclerosing cholangitis, and insulin-dependent diabetes mellitus

We report two young men with clinical and laboratory evidence of macroscopic ulcerative colitis, sclerosing cholangitis, and insulin-dependent diabetes mellitus. The first patient presented at age 15 with vomiting, abdominal pain, weight loss, and abnormal liver function test results. Liver biopsy and endoscopic retrograde cholangiopancreatography (ERCP) demonstrated sclerosing cholangitis. Colonoscopy with biopsy revealed ulcerative colitis which responded to sulfasalazine. Diabetes occurred at age 18 and insulin therapy was begun. The second patient was 19 at presentation with diarrhea, hematochezia, and weight loss. Proctosigmoidoscopy revealed ulcerative colitis, and sulfasalazine led to clinical remission. Three months later he developed diabetes requiring insulin therapy. At age 28, he developed elevated alkaline phosphatase, and ERCP revealed sclerosing cholangitis. At age 37 he expired from adenocarcinoma that metastasized to the liver. Literature review revealed only one possible case report of this association with microscopic asymptomatic ulcerative colitis in that patient. Statistical analysis suggests that this association is real rather than a chance occurrence. An autoimmune process may be involved and a specific histocompatibility locus antigen (HLA) type may exert a regulatory influence.     

Lightweight coarse-grained coordination: a scalable system-level approach

In this paper, our solution to the problem of modelling functionally complex communication systems at the application level, based on lightweight coordination, is extended to seamlessly capture system-level testing as well. This extension could be realized simply by self-application: the bulk of the work for integrating system-level testing into our development environment, the ABC, concerned domain modelling, which can be done using the ABC. Therefore, the extension of the ABC to cover system-level testing was merely an application development on the basis of the ABC, illustrated here in the domain of Computer Telephony Integration. Here the adoption of a coarse-grained approach to test design, which is central to the scalability of the overall testing environment, is the enabling aspect for system-level test automation. Together with our lightweight coordination approach this induces an understandable modelling paradigm of system-wide test cases that is adequate for the needs and requirements of industrial test engineers. In particular, it enables test engineers to graphically design complex test cases that, in addition, can even be automatically checked for their intended purposes via model checking.