Einfluss der Verarbeitungstechnologie und Werkstoffzusammensetzung auf die Struktur-Eigenschafts-Beziehungen von thermoplastischen Nanoverbundwerkstoffen

Die Einarbeitung von nanoskaligen Füllstoffen zur Steigerung von polymeren Eigenschaftsprofilen ist sehr viel versprechend und stößt daher heutzutage sowohl in der Forschung als auch in der Industrie auf großes Interesse. Bedingt durch ausgeprägte Oberflächen und hohe Anziehungskräfte, liegen Nanopartikel allerdings nicht singulär sondern als Partikelanhäufungen, so genannten Agglomeraten oder Aggregaten, vor. Zur Erzielung der gewünschten Materialverbesserungen gilt es, diese aufzuspalten und homogen in der polymeren Matrix zu verteilen. Bei thermoplastischen Kunststoffen ist die gleichläufige Doppelschneckenextrusion eines der gängigsten Verfahren zur Einarbeitung von Additiven und Füllstoffen. Aus diesem Grund war es Ziel dieser Arbeit, mittels dieses Verfahrens verbesserte Verbundwerkstoffe mit Polyamid 66- und Polyetheretherketon-Matrix, durch Einarbeitung von nanoskaligem Titandioxid (15 und 300 nm), zu generieren. In einem ersten Schritt wurden die verfahrenstechnischen Parameter, wie Drehzahl und Durchsatz, sowie die Prozessführung und damit deren Einfluss auf die Materialeigenschaften beleuchtet. Der spezifische Energieeintrag ist ausschlaggebend zur Deagglomeration der Nanopartikel. Dieser zeigte leichte Abhängigkeiten von der Drehzahl und dem Durchsatz und verursachte bei der Einarbeitung der Partikel keine wesentlichen Unterschiede in der Aufspaltung der Partikel sowie gar keine in den resultierenden mechanischen Eigenschaften. Die Prozessführung wurde unterteilt in Mehrfach- und Einfachextrusion. Die Herstellung eines hochgefüllten Masterbatches, dessen mehrfaches Extrudieren und anschließendes Verdünnen, führte zu einer sehr guten Deagglomeration und stark verbesserten Materialeigenschaften. Mittels Simulation des Extrusionsprozesses konnte festgestellt werden, dass das Vorhandensein von ungeschmolzenem Granulat in der Verfahrenszone zu einer Schmelze/Nanopartikel/ Feststoffreibung führt, die die Ursache für eine sehr gute Aufspaltung der Partikel zu sein scheint. Durch Modifikation des Extrusionsprozesses erreichte die Einfachextrusion annähernd den Grad an Deagglomeration bei Mehrfachextrusion, wobei die Materialien bei letzterem Verfahren die besten Eigenschaftsprofile aufwiesen. In einem zweiten Schritt wurde ein Vergleich der Einflüsse von unterschiedlichen Partikelgrößen und –gehalten auf die polymeren Matrizes vollzogen. Die 15 nm Partikel zeigten signifikant bessere mechanische Ergebnisse auf als die 300 nm Partikel, und die Wirkungsweise des 15 nm Partikels auf Polyetheretherketon war stärker als auf Polyamid 66. Es konnten Steigerungen in Steifigkeit, Festigkeit und Zähigkeit erzielt werden. Rasterelektronenmikroskopische Aufnahmen bestätigten diese Ergebnisse. Eine Berechnung der Plan-Selbstkosten von einem Kilogramm PEEK-Nanoverbundwerkstoff im Vergleich zu einem Kilogramm unverstärktem PEEK verdeutlichte, dass ein Material kreiert wurde, welches deutlich verbesserte Eigenschaften bei gleichem Preis aufweist. Zusammenfassend konnte in dieser Arbeit ein tieferes Verständnis des Extrusionsvorganges zur Herstellung von kostengünstigen und verbesserten Thermoplasten durch das Einbringen von Nanopartikeln gewonnen werden

Histology and CHD5 expression in xenografts derived from NLF and IMR5 cells transfected with either CHD5 sense or CHD5 antisense constructs

) Histology of NLF and IMR5 xenograft tumors (see ) after 5 weeks of growth. NLF--AS tumors were composed of undifferentiated cells with scant cytoplasm (top left), whereas NLF- tumors showed areas of necrosis () and differentiation (; top right). Cells in the IMR5--AS tumors were undifferentiated (bottom left), whereas cells in the IMR5- tumors had a more elongated appearance (bottom right). Bar = 20 μm. ) Relative expression of CHD5, normalized to glyceraldehyde-3-phosphate dehydrogenase (GAPDH), was determined by real-time reverse transcription–polymerase chain reaction in parental NLF and IMR5 cell lines, as well as the CHD5 sense and CHD5 antisense transfected lines used for the xenograft experiments. The normalized values indicated by each bar graph represent the mean of three measurements. Replicate measurements were within 10% of the mean for each bar shown. ) Expression of CHD5 protein, as detected by immunoblotting, is shown for the NLF and IMR5 parental lines and the corresponding sense- and antisense-transfected cells used in these experiments.<p><b>Copyright information:</b></p><p>Taken from ", a Tumor Suppressor Gene Deleted From 1p36.31 in Neuroblastomas"</p><p></p><p>JNCI Journal of the National Cancer Institute 2008;100(13):940-949.</p><p>Published online 2 Jul 2008</p><p>PMCID:PMC2483574.</p><p></p

Effect of altered CHD5 expression on clonogenicity in neuroblastoma cell lines

Plasmids containing CHD5 or antisense CHD5 (CHD5-AS) were stably transfected into NLF and IMR5 neuroblastoma cell lines, both of which have hemizygous 1p deletion and amplification, and into SK-N-SH and SK-N-FI neuroblastoma cell lines, which have neither. Transfected cells were plated on soft agar, and colonies were counted 3 weeks later. ) NLF cells. CHD5 vs CHD5-AS, < .001. ) IMR5 cells. CHD5 vs CHD5-AS, = .001. ) SK-N-SH cells. CHD5 vs CHD5-AS, = .16. ) SK-N-FI cells. CHD5 vs CHD5-AS, = .10. Means and 95% confidence intervals () are shown. values (two-sided) were calculated using the Student test. Data are representative of three independent experiments performed in quadruplicate.<p><b>Copyright information:</b></p><p>Taken from ", a Tumor Suppressor Gene Deleted From 1p36.31 in Neuroblastomas"</p><p></p><p>JNCI Journal of the National Cancer Institute 2008;100(13):940-949.</p><p>Published online 2 Jul 2008</p><p>PMCID:PMC2483574.</p><p></p

Methylation of the CHD5 promoter and 5′ coding region in four neuroblastoma cell lines

–) CHD5 promoter methylation in NLF () and IMR5 () cells, both of which have hemizygous 1p deletions and virtually no CHD5 expression. –) CHD5 promoter methylation in SK-N-SH () and SK-N-FI cells (), which lack 1p deletion and have low expression of CHD5. Methylation at a given GC dinucleotide, as determined by methylation-specific sequencing, is shown as a percentage of sequences analyzed (10 per site). Methylation was determined as the number of clones with methylation of the given region divided by 10 and is expressed as a percentage.<p><b>Copyright information:</b></p><p>Taken from ", a Tumor Suppressor Gene Deleted From 1p36.31 in Neuroblastomas"</p><p></p><p>JNCI Journal of the National Cancer Institute 2008;100(13):940-949.</p><p>Published online 2 Jul 2008</p><p>PMCID:PMC2483574.</p><p></p

Association of CHD5 expression with risk factors and outcome in primary neuroblastomas

) Normalized CHD5 expression in 101 primary neuroblastomas stratified based on the presence (n = 26) or absence (n = 75) of 1p deletion (two-sample test, < .001). ) Association of normalized CHD5 expression with the risk group (low, intermediate, high, and ultrahigh) as defined above and in (). Briefly, for this study, low-risk patients were defined as infants (<p><b>Copyright information:</b></p><p>Taken from ", a Tumor Suppressor Gene Deleted From 1p36.31 in Neuroblastomas"</p><p></p><p>JNCI Journal of the National Cancer Institute 2008;100(13):940-949.</p><p>Published online 2 Jul 2008</p><p>PMCID:PMC2483574.</p><p></p

Losartan Treatment Protects Retinal Ganglion Cells and Alters Scleral Remodeling in Experimental Glaucoma

<div><p>Purpose</p><p>To determine if oral losartan treatment decreases the retinal ganglion cell (RGC) death caused by experimental intraocular pressure (IOP) elevation in mice.</p><p>Methods</p><p>We produced IOP increase in CD1 mice and performed unilateral optic nerve crush. Mice received oral losartan, spironolactone, enalapril, or no drug to test effects of inhibiting angiotensin receptors. IOP was monitored by Tonolab, and blood pressure was monitored by tail cuff device. RGC loss was measured in masked axon counts and RGC bodies by β-tubulin labeling. Scleral changes that could modulate RGC injury were measured including axial length, scleral thickness, and retinal layer thicknesses, pressure-strain behavior in inflation testing, and study of angiotensin receptors and pathways by reverse transcription polymerase chain reaction, Western blot, and immunohistochemistry.</p><p>Results</p><p>Losartan treatment prevented significant RGC loss (median loss = 2.5%, p = 0.13), while median loss with water, spironolactone, and enalapril treatments were 26%, 28% and 43%; p < 0.0001). The lower RGC loss with losartan was significantly less than the loss with spironolactone or enalapril (regression model p = 0.001; drug treatment group term p = 0.01). Both losartan and enalapril significantly lowered blood pressure (p< 0.001), but losartan was protective, while enalapril led to worse than water-treated RGC loss. RGC loss after crush injury was unaffected by losartan treatment (difference from control p = 0.9). Survival of RGC in cell culture was not prolonged by sartan treatment. Axonal transport blockade after 3 day IOP elevations was less in losartan-treated than in control glaucoma eyes (p = 0.007). Losartan inhibited effects of glaucoma, including reduction in extracellular signal-related kinase activity and modification of glaucoma-related changes in scleral thickness and creep under controlled IOP.</p><p>Conclusions</p><p>The neuroprotective effect of losartan in mouse glaucoma is associated with adaptive changes in the sclera expressed at the optic nerve head.</p></div

Average IOP after bead injection glaucoma.

<p>All differences among non-glaucoma eye groups and among glaucoma eye groups are statistically insignificant, with lowest p value in t tests = 0.14. Data are mm Hg with mean (standard deviation), including 7 measurements per eye, 40 eyes per group.</p><p>*Both eyes were controls in this treatment group.</p><p>Average IOP after bead injection glaucoma.</p

Immunohistochemical labeling for thrombospondin 1.

<p>Immunostaining for thrombospondin-1 shows mild scleral label (arrowheads) in water-treated fellow eye (A) and dramatically increased label in both sclera and retina of water-glaucoma eye (B). Thrombospondin 1 label was less in sclera and retina of both the losartan fellow eye (C) and losartan-glaucoma eye than the corresponding water controls (D, scale bar = 50μm; DAPI counterstain).</p

Tonolab Calibration.

<p>Calibration of Tonolab tonometer in cannulated eyes from drug-treated and water control eyes after treatment for 1 and 6 weeks. The regression lines for each group closely track with ideal calibration of manometrically-set IOP (error bars are standard error).</p

Fragment-Based Screening of a Natural Product Library against 62 Potential Malaria Drug Targets Employing Native Mass Spectrometry

Natural products are well known for their biological relevance, high degree of three-dimensionality, and access to areas of largely unexplored chemical space. To shape our understanding of the interaction between natural products and protein targets in the postgenomic era, we have used native mass spectrometry to investigate 62 potential protein targets for malaria using a natural-product-based fragment library. We reveal here 96 low-molecular-weight natural products identified as binding partners of 32 of the putative malarial targets. Seventy-nine (79) fragments have direct growth inhibition on <i>Plasmodium falciparum</i> at concentrations that are promising for the development of fragment hits against these protein targets. This adds a fragment library to the published HTS active libraries in the public domain