Proton beam writing and electroplating for the fabrication of high aspect ratio Au microstructures

We present an approach to fabricate tall high aspect ratio Au microstructures by means of proton beam direct writing. Combining proton beam direct writing and electroplating, we successfully produced gold structures with sub-micrometer lateral dimensions, structure heights in excess of 11 μm, and aspect ratios over 28. Sidewall quality of the Au structures was improved by lowering the process temperature to 20 °C when developing PMMA patterns with GG developer. The application of such structures as X-ray masks for deep X-ray lithography with synchrotron radiation was demonstrated.     

Pyryliumverbindungen. 38. Zur Ringtransformation von 2,4,6-Triaryl-thiopyryliumsalzen mit Essigsäureanhydrid zu Arylbenzenen und Thiobenzophenonen

Pyrylium Compounds. 38. About the Ring Transformation of 2,4,6-Triarylthiopyrylium Salts by Acetic Acid Anhydride to Arylbenzenes and Thiobenzophenones 2,4,6-Triarylthiopyrylium salts 5 react in the presence of an appropriate condensing agent (sodium acetate, carbonate, methoxide, tert-butoxide or potassium acetate) with acetic acid anhydride to yield arylbenzenes 3 and thiobenzophenones 6 . This ring transformation represents the first example of the conversion of the moiety into the thiocarbonyl group Under the same conditions 3,5-dimethyl-2,4,6-triphenylthiopyrylium perchlorate ( 13 ) forms via [1,5]-sigmatropic rearrangement the thiobenzophenone 15 . The structure of the new compounds 6 was proved by spectroscopic methods as well as by degradation reactions. Thus, hydrogen peroxide converts 6a to the known benzophenone 4 . Alkaline saponification gives the 2-hydroxy-benzophenone 8 , whereas heating with hydrochloric acid causes a selective cleavage of the acetoxy group to the 2-hydroxy-thiobenzophenone 7 .     

Pyryliumverbindungen. XVIII, 2-Alkoxy-2H-pyrane aus tetra- und pentasubstituierten Pyryliumsalzen

Pyrylium Compounds. XVIII. 2-Alkoxy-2H-pyrans from Tetra- and Pentasubstituted Pyrylium Salts Alkali alkoxides add regioselectively to 2,3,4,6-tetrasubstituted pyrylium salts 7 (R' H), affording high yields of colourless crystalline 2-alkoxy-2H-pyrans 9 . The latte are also formed simply on refluxing 7 in the corresponding alcohol with triethylamine as proton acceptor. 3,5-Dialkylsubstituted 2,4,6-triarylpyrylium salts react analogously. The 2H-pyran structure of the adducts obtained follows from their n.m.r., i.r., u.v. and mass spectra as well as from their reaction with tetracyanoethylene to cycloadducts of type 10 . Acids regenerate from 9 the original pyrylium cations, whereas reaction of 9 with nitromethane or ethyl cyanoacetate provides benzene derivatives. -- The novel starting pyrylium salts 7b--o are characterized by u.v./vis data and by transformation into the corresponding pyridine derivatives     

Pre-Transplant Serum Leptin Levels and Relapse of Acute Myeloid Leukemia after Allogeneic Transplantation

Weight loss and metabolic activity influence outcome after allogeneic stem cell transplantation (alloSCT). This study evaluates pre-conditioning Leptin, a peptide hormone involved in metabolism and immune homeostasis, as a prognostic factor for survival, relapse and non-relapse mortality (NRM) following alloSCT. Leptin serum levels prior to conditioning were determined in a cohort of patients transplanted for various hematologic malignancies (n = 524) and correlated retrospectively with clinical outcome. Findings related to patients with acute leukemia (AL) from this sample were validated in an independent cohort. Low pre-conditioning serum Leptin was an independent prognostic marker for increased risk of relapse (but not of NRM and overall mortality) following alloSCT for AL of intermediate and advanced stage (beyond first complete remission). Multivariate analysis revealed a hazard ratio (HR) for relapse of 0.75 per log2 increase (0.59–0.96, p = 0.020). This effect was similar in an independent validation cohort. Pre-conditioning serum Leptin was validated as a prognostic marker for early relapse by fitting the multivariate Cox model to the validation data. Pre-conditioning serum Leptin levels may serve as an independent prognostic marker for relapse following alloSCT in intermediate and advanced stage AL patients. Prospective studies are required to prove whether serum Leptin could be used for guiding nutritional intervention in patients with AL undergoing alloSCT.     

Pyryliumverbindungen. 37. Arylbenzene aus 2,4,6-Triaryl-pyryliumsalzen und Carbonsäureanhydriden

Pyrylium Compounds. 37. Arylbenzenes from 2,4,6-Triarylpyrylium Salts and Carboxylic Acid Anhydrides Refluxing 2,4,6-triarylpyrylium salts 1 with excess carboxylic acid anhydrides (RCH₂CO)₂O ( 2a : R = H, 2b : R = Me) in the presence of condensing agents like sodium or potassium acetate, sodium carbonate or methoxide, triethylamine or pyridine results in 1,3,5-triarylbenzenes 3 (R = H, Me). Under similar conditions, phenylacetic acid anhydride ( 2c ), generated in situ from sodium phenylacetate and excess 2a or 2b , yields 1,2,3,5-tetraarylbenzenes 3 (R = Ph). Thus, the reaction 1 + 2 → 3 represents a new and simple method for replacing the pyrylium heteroatom =O^⊕– by the =CR– moiety (R = H, Me, Ph). The structure of the arylbenzenes 3 was proved by spectroscopic methods, by comparison with literature data or by independent synthesis. As by-products 2-acyloxy-benzophenones 10 are formed. Reaction of 3,5-dimethyl-2,4,6-triphenyl-pyrylium perchlorate ( 11 ) with acetic acid anhydride/sodium acetate (or sodium phenylacetate) takes another course leading to 2-acetoxy-3,5-dimethyl-4,6-diphenyl-benzophenone ( 15 ), whereas treatment of 11 with propionic acid anhydride/sodium acetate follows the reaction scheme 1 + 2 → 3 giving 1,3,5-trimethyl-2,4,6-triphenylbenzene ( 16 ). The mechanisms of the different pyrylium ring transformations are discussed.     

Pyryliumverbindungen. 31 [1]. Reaktion 3-alkylsubstituierter 2,4,6-Triaryl-pyryliumsalze mit 1,3-Diketonaten: Ein Weg zur Darstellung 3-acylsubstituierter Benzophenone

Pyrylium Compounds. 31. Reaction of 3-Alkyl-2,4,6-triarylpyrylium Salts with 1,3-Diketonates: A Method for the Preparation of 3-Acylsubstituted Benzophenones Reaction of 3-alkyl-2,4,6-triarylpyrylium salts with 1,3-diketones in the presence of one equivalent of triethylamine or potassium tert-butoxide does not lead — as originally suspected — to the primary adducts of 2H-pyran structure 6 , but to the open-chain valence isomers 7 . Treatment of the latter with one equivalent of tert-butoxide in tert-butyl alcohol gives the same 3-alkyl-2,4,6-triarylacetophenones 9 which are obtained directly from 5 , 1,3-diketones and two equivalents of potassium tert-butoxide. However, on treating 7 with aqueous ethanolic sodium hydroxide 3-acylsubstituted benzophenones 10 are formed in good yields. The reaction sequence 5→7→10 can also be performed through a one-pot-procedure. — The i.r., u.v., n.m.r. and mass spectroscopic data of the novel products 7, 9 , and 10 are reported.     

Anti-Inflammatory Characteristics of Local Anesthetics: Inhibition of TNF-α Secretion of Lipopolysaccharide-Stimulated Leucocytes in Human Blood Samples

Background. Local anesthetics (LAs) have potent anti-inflammatory properties. Inflammatory down-regulation is crucial in diseases with overactive immune reactions, such as acute respiratory distress syndrome (ARDS) and chronic inflammation. We investigated the influence of four LAs, procaine, lidocaine, mepivacaine, and bupivacaine, on the reduction of tumor necrosis factor-alpha (TNF-α) secretion in lipopolysaccharide (LPS)-activated human leucocytes. Methods. Blood samples of 28 individuals were stimulated with LPS. The reduction of TNF-α production by each of the four LAs added (0.5 mg/mL) was measured and correlated with biometric variables. A response was defined as reduction to <85% of initial levels. Results. All four LAs down-regulated the TNF-α secretion in 44–61%: Bupivacaine (44.4%), lidocaine (61.5%), mepivacaine (44.4%), and procaine (50% of the individuals, “responders”). The TNF-α secretion was reduced to 67.4, 68.0, 63.6, and 67.1% of the initial values in responders. The effects in both patients and healthy persons were the same. Interindividual responses to LAs were not correlated with the duration or type of complaints, basal TNF-α serum level, sex, BMI, or age of responders. Conclusions. Four clinically relevant LAs (amid-LA and ester-LA) attenuate the inflammatory response provoked by LPS. They are potential candidates for drug repositioning in treating overactive immune reactions and chronic inflammation.     

Differential Metabotypes in Synovial Fibroblasts and Synovial Fluid in Hip Osteoarthritis Patients Support Inflammatory Responses

Changes in cellular metabolism have been implicated in mediating the activated fibroblast phenotype in a number of chronic inflammatory disorders, including pulmonary fibrosis, renal disease and rheumatoid arthritis. The aim of this study was therefore to characterise the metabolic profile of synovial joint fluid and synovial fibroblasts under both basal and inflammatory conditions in a cohort of obese and normal-weight hip OA patients. Furthermore, we sought to ascertain whether modulation of a metabolic pathway in OA synovial fibroblasts could alter their inflammatory activity. Synovium and synovial fluid was obtained from hip OA patients, who were either of normal-weight or obese and were undergoing elective joint replacement surgery. The synovial fluid metabolome was determined by 1H NMR spectroscopy. The metabolic profile of isolated synovial fibroblasts in vitro was characterised by lactate secretion, oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) using the Seahorse XF Analyser. The effects of a small molecule pharmacological inhibitor and siRNA targeted at glutaminase-1 (GLS1) were assessed to probe the role of glutamine metabolism in OA synovial fibroblast function. Obese OA patient synovial fluid (n = 5) exhibited a different metabotype, compared to normal-weight patient fluid (n = 6), with significantly increased levels of 1, 3-dimethylurate, N-Nitrosodimethylamine, succinate, tyrosine, pyruvate, glucose, glycine and lactate, and enrichment of the glutamine–glutamate metabolic pathway, which correlated with increasing adiposity. In vitro, isolated obese OA fibroblasts exhibited greater basal lactate secretion and aerobic glycolysis, and increased mitochondrial respiration when stimulated with pro-inflammatory cytokine TNFα, compared to fibroblasts from normal-weight patients. Inhibition of GLS1 attenuated the TNFα-induced expression and secretion of IL-6 in OA synovial fibroblasts. These findings suggest that altered cellular metabolism underpins the inflammatory phenotype of OA fibroblasts, and that targeted inhibition of glutamine–glutamate metabolism may provide a route to reducing the pathological effects of joint inflammation in OA patients who are obese.