Deliberately Losing Control of C−H Activation Processes in the Design of Small-Molecule-Fragment Arrays Targeting Peroxisomal Metabolism

Combined photochemical arylation, “nuisance effect” (S_NAr) reaction sequences have been employed in the design of small arrays for immediate deployment in medium-throughput X-ray protein–ligand structure determination. Reactions were deliberately allowed to run “out of control” in terms of selectivity; for example the ortho-arylation of 2-phenylpyridine gave five products resulting from mono- and bisarylations combined with S_NAr processes. As a result, a number of crystallographic hits against NUDT7, a key peroxisomal CoA ester hydrolase, have been identified.     

On the Possibility of Observing Third Sound on 3He

This paper focuses on the hydrodynamics of third sound on a superfluid ³ He film. We solve the hydrodynamical equations in the limit of thick films with weak interaction with the substrate. The surface tension at the free interface is shown to have a large effect on the third sound velocity and on the attenuation for frequencies larger than 1Hz. In the case of a diffusely scattering substrate a ripplon-like dispersion relation is found for this frequency range.     

Knowledge about asthma among Danish primary school teachers. Results of a questionnaire study

An anonymous questionnaire inquiry performed among 324 school teachers in the Randers area with the purpose of elucidating teachers' knowledge about asthma is presented. To a series of statements about asthma, the teachers should answer yes, no or don't know. A limited knowledge about asthma in children was found. The knowledge about medicamental treatment was particularly limited. Only 57 per cent knew that wheezing after physical exertion is a strong indicator of asthma. Only five per cent had received proper instruction. This latter group had a significantly better knowledge of medical treatment (p < 0.0001-0.05). It is recommended that instruction in children's diseases, especially asthma should be reintroduced in teachers' training colleges.     

Experiences with large-scale operational trials of ALTO-enhanced P2P filesharing in an intra-ISP scenario

Application Layer Traffic Optimization (ALTO) has recently gained attention in the research and standardisation community as a way for a network operator to guide the peer selection process of distributed applications by providing network layer topology information. In particular P2P applications are expected to gain from ALTO, due to the many connections peers form among each other, often without taking network layer topology information into account. In this paper, we present results of an extensive intra-ISP trial with an ALTO-enhanced P2P filesharing software. In summary, our results show that—depending on the concrete setting and on the distribution of upload capacity in the network—ALTO enables an ISP to save operational costs significantly while not degrading application layer performance noticeably. In addition, based on our experience we are able to give advice to operators on how to save costs with ALTO while not sacrificing application layer performance at all.     

Mikromethode zur quantitativen Bestimmung von Coffein

Zusammenfassung Zur quantitativen Bestimmung von Coffein in biologischem Material wird ein kombiniertes Verfahren aus Dünnschichtchromatographie und Densitometrie beschrieben. Das Verfahren läßt Bestimmungen im Nanogramm-Bereich zu. Das Probenvolumen liegt unter 100 l.Die Proben — Capillarblut — werden zunächst mit dem gleichen Volumen Chloroform extrahiert. Anschließend wird das Coffein mittels Dünnschichtchromatographie von Begleitstoffen und störenden Substanzen abgetrennt. Es werden Kieselgel-60-Fertigplatten und Chlorofom/Aceton (9 + 1; v/v) als Fließmittel verwendet, dabei beträgt die Laufzeit 30 min.Die quantitative densitometrische Auswertung erfolgt durch Remissionsmessung bei 273 nm. Im Bereich von 10–60 ng Coffein/Fleck verläuft die Eichkurve linear. 1 mg/I Coffein kann noch sicher quantitativ erfaßt werden. Die Nachweisgrenze liegt bei 0,1 mg/1.

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A quantitative micromethod for the caffeine determination

Summary A combined procedure with thin-layer-chromatography and densitometry is described for the quantitative estimation of caffeine in biological material. This method ist applicable in the nanogram range. Test samples of less than 100 l may be used. The samples (capillary-blood) are extracted with the same volume of chloroform. Caffeine is separated from interfering compounds by thin-layer-chromatography. Commercial silica-60-plates with chloroform/acetone (9 + 1; v/v) as solvent are used. The running time is about 30 min. The quantitative densitometric determinations are performed in the remission mode at 273 nm. In the range from 10 to 60 ng/spot the calibration curve is linear. Accurate quantitative data will be obtained even at concentrations of 1 mg/1 caffeine. The detection limit is at about 0.1 mg/1.

     

Platelet-Released Growth Factors Influence Wound Healing-Associated Genes in Human Keratinocytes and Ex Vivo Skin Explants

Platelet-released growth factors (PRGFs) or other thrombocyte concentrate products, e.g., Platelet-Rich Fibrin (PRF), have become efficient tools of regenerative medicine in many medical disciplines. In the context of wound healing, it has been demonstrated that treatment of chronic or complicated wounds with PRGF or PRF improves wound healing in the majority of treated patients. Nevertheless, the underlying cellular and molecular mechanism are still poorly understood. Therefore, we aimed to analyze if PRGF-treatment of human keratinocytes caused the induction of genes encoding paracrine factors associated with successful wound healing. The investigated genes were Semaphorin 7A (SEMA7A), Angiopoietin-like 4 (ANGPLT4), Fibroblast Growth Factor-2 (FGF-2), Interleukin-32 (IL-32), the CC-chemokine-ligand 20 (CCL20), the matrix-metalloproteinase-2 (MMP-2), the chemokine C-X-C motif chemokine ligand 10 (CXCL10) and the subunit B of the Platelet-Derived Growth Factor (PDGFB). We observed a significant gene induction of SEMA7A, ANGPLT4, FGF-2, IL-32, MMP-2 and PDGFB in human keratinocytes after PRGF treatment. The CCL20- and CXCL10 gene expressions were significantly inhibited by PRGF therapy. Signal transduction analyses revealed that the PRGF-mediated gene induction of SEMA7A, ANGPLT4, IL-32 and MMP-2 in human keratinocytes was transduced via the IL-6 receptor pathway. In contrast, EGF receptor signaling was not involved in the PRGF-mediated gene expression of analyzed genes in human keratinocytes. Additionally, treatment of ex vivo skin explants with PRGF confirmed a significant gene induction of SEMA7A, ANGPLT4, MMP-2 and PDGFB. Taken together, these results describe a new mechanism that could be responsible for the beneficial wound healing properties of PRGF or related thrombocytes concentrate products such as PRF.