Influence of Powder Morphology and Chemical Composition on Metallic Foams produced by SlipReactionFoamSintering (SRFS)‐ Process

The SlipReactionFoamSintering (SRFS)‐ process is a metallurgical method to produce open‐cell metallic foams of iron based materials, steels and nickel based materials. In this process several chemical reactions take place. Through the most influential parameter, the morphology of the metallic powder, different properties of the foam can be adjusted, such as the viscosity of the slip, the cell structure and the mechanical properties. Several examples are presented in this paper. Moreover, the thermal conductivity of three foams is measured with the transient‐heat‐source‐technique.     

Partial Reduction in BRCA1 Gene Dose Modulates DNA Replication Stress Level and Thereby Contributes to Sensitivity or Resistance

BRCA1 is a well-known breast cancer risk gene, involved in DNA damage repair via homologous recombination (HR) and replication fork protection. Therapy resistance was linked to loss and amplification of the BRCA1 gene causing inferior survival of breast cancer patients. Most studies have focused on the analysis of complete loss or mutations in functional domains of BRCA1. How mutations in non-functional domains contribute to resistance mechanisms remains elusive and was the focus of this study. Therefore, clones of the breast cancer cell line MCF7 with indels in BRCA1 exon 9 and 14 were generated using CRISPR/Cas9. Clones with successful introduced BRCA1 mutations were evaluated regarding their capacity to perform HR, how they handle DNA replication stress (RS), and the consequences on the sensitivity to MMC, PARP1 inhibition, and ionizing radiation. Unexpectedly, BRCA1 mutations resulted in both increased sensitivity and resistance to exogenous DNA damage, despite a reduction of HR capacity in all clones. Resistance was associated with improved DNA double-strand break repair and reduction in replication stress (RS). Lower RS was accompanied by increased activation and interaction of proteins essential for the S phase-specific DNA damage response consisting of HR proteins, FANCD2, and CHK1.     

Improved Bladder Tumor RNA Isolation from Archived Tissues Using Methylene Blue for Normalization,Multiplex RNA Hybridization,Sequencing and Subtyping

Methylene blue (MB) is a dye used for histology with clinical importance and intercalates into nucleic acids. After MB staining of formalin fixed paraffin embedded (FFPE) muscle invasive bladder cancer (MIBC) and normal urothelium, specific regions could be microdissected. It is not known if MB influences RNA used for gene expression studies. Therefore, we analyzed MIBC using five different RNA isolation methods comparing patient matched FFPE and fresh frozen (FF) tissues pre-stained with or without MB. We demonstrate a positive impact of MB on RNA integrity with FF tissues using real time PCR with no interference of its chemical properties. FFPE tissues showed no improvement of RNA integrity, which we propose is due to formalin induced nucleotide crosslinks. Using direct multiplex RNA hybridization the best genes for normalization of MIBC and control tissues were identified from 34 reference genes. In addition, 5SrRNA and 5.8SrRNA were distinctive reference genes detecting <200 bp fragments important for mRNA analyses. Using these normalized RNAs from MB stained MIBC and applying multiplex RNA hybridization and mRNA sequencing, a minimal gene expression panel precisely identified luminal and basal MIBC tumor subtypes, important for diagnosis, prognosis and chemotherapy response.     

Automatic image annotation using visual content and folksonomies

Automatic image annotation is an important and challenging task, and becomes increasingly necessary when managing large image collections. This paper describes techniques for automatic image annotation that take advantage of collaboratively annotated image databases, so called visual folksonomies. Our approach applies two techniques based on image analysis: First, classification annotates images with a controlled vocabulary and second tag propagation along visually similar images. The latter propagates user generated, folksonomic annotations and is therefore capable of dealing with an unlimited vocabulary. Experiments with a pool of Flickr images demonstrate the high accuracy and efficiency of the proposed methods in the task of automatic image annotation. Both techniques were applied in the prototypical tag recommender “tagr”.     

慕尼黑理工大学建筑博物馆

收藏慕尼黑理工大学建筑博物馆于1868年随着该大学一同建成。以前收集的大量建筑收藏品最初是作为教学资料,并可以在陈列室里供人查阅。第二次世界大战以后,不断地收购使这里成为了德国最大的建筑档案馆, 如今,这里有500位重要建筑师的近40万张图纸、近 10万幅摄影作品和800个模型。最早的图纸来自16世纪,最早的模型则出自1659年,藏品中的大部分是19 世纪和20世纪的德国建筑资料,是建筑摄影以及建筑发展文档编制的开端时期的资料。     

Affordance-based robot object retrieval

Autonomous Robots - Natural language object retrieval is a highly useful yet challenging task for robots in human-centric environments. Previous work has primarily focused on commands specifying...     

Lipidomic Approaches to Study HDL Metabolism in Patients with Central Obesity Diagnosed with Metabolic Syndrome

The metabolic syndrome (MetS) is a cluster of cardiovascular risk factors characterised by central obesity, atherogenic dyslipidaemia, and changes in the circulating lipidome; the underlying mechanisms that lead to this lipid remodelling have only been partially elucidated. This study used an integrated “omics” approach (untargeted whole serum lipidomics, targeted proteomics, and lipoprotein lipidomics) to study lipoprotein remodelling and HDL composition in subjects with central obesity diagnosed with MetS (vs. controls). Compared with healthy subjects, MetS patients showed higher free fatty acids, diglycerides, phosphatidylcholines, and triglycerides, particularly those enriched in products of de novo lipogenesis. On the other hand, the “lysophosphatidylcholines to phosphatidylcholines” and “cholesteryl ester to free cholesterol” ratios were reduced, pointing to a lower activity of lecithin cholesterol acyltransferase (LCAT) in MetS; LCAT activity (directly measured and predicted by lipidomic ratios) was positively correlated with high-density lipoprotein cholesterol (HDL-C) and negatively correlated with body mass index (BMI) and insulin resistance. Moreover, many phosphatidylcholines and sphingomyelins were significantly lower in the HDL of MetS patients and strongly correlated with BMI and clinical metabolic parameters. These results suggest that MetS is associated with an impairment of phospholipid metabolism in HDL, partially led by LCAT, and associated with obesity and underlying insulin resistance. This study proposes a candidate strategy to use integrated “omics” approaches to gain mechanistic insights into lipoprotein remodelling, thus deepening the knowledge regarding the molecular basis of the association between MetS and atherosclerosis.     

Predicting and tuning physicochemical properties in lead optimization: amine basicities

This review describes simple and useful concepts for predicting and tuning the pK(a) values of basic amine centers, a crucial step in the optimization of physical and ADME properties of many lead structures in drug-discovery research. The article starts with a case study of tricyclic thrombin inhibitors featuring a tertiary amine center with pK(a) values that can be tuned over a wide range, from the usual value of around 10 to below 2 by (remote) neighboring functionalities commonly encountered in medicinal chemistry. Next, the changes in pK(a) of acyclic and cyclic amines upon substitution by fluorine, oxygen, nitrogen, and sulfur functionalities, as well as carbonyl and carboxyl derivatives are systematically analyzed, leading to the derivation of simple rules for pK(a) prediction. Electronic and stereoelectronic effects in cyclic amines are discussed, and the emerging computational methods for pK(a) predictions are briefly surveyed. The rules for tuning amine basicities should not only be of interest in drug-discovery research, but also to the development of new crop-protection agents, new amine ligands for organometallic complexes, and in particular, to the growing field of amine-based organocatalysis.     

Synthesis and structure of a dimeric scandium bis(μ-methoxy) complex

Reaction of hydrated scandium nitrate with 1,10-phenanthroline (phen) in methanol leads to formation of the unusual dimeric complex [(phen)(NO₃)₂Sc(μ-OMe)₂Sc(NO₃)₂(phen)], in which the scandium centres are eight co-ordinate. The complex features two bridging methoxy ligands, as well as bidentate nitrates and chelating 1,10-phenanthroline ligands.