11‐Substituted Benzo[c]phenanthridines: New Structures and Insight into Their Mode of Antiproliferative Action

The synthesis of various new structures of a library of 11‐substituted 6‐amino‐11,12‐dihydrobenzo[c]phenanthridines (BP) and 11‐substituted 6‐aminobenzo[c]phenanthridines (BP‐D) is presented. These structures, further synthetic modifications, and the preparation of follow‐up products which delivered about 40 new derivatives are described. Their potential as antiproliferative drug candidates was investigated by comparison of NCI 60 developmental therapeutics program (DTP) human tumor cell line screening data based on the results of in vitro tumor cell growth inhibition, including about 40 hitherto unpublished compound test results with up to 60 cancer cell lines. NCI‐COMPARE studies helped to suggest the modes of action of the highly active antiproliferative drugs. These findings are supported by in vitro biological investigations showing either inhibition of tubulin polymerization and depolymerization or topoisomerase inhibition. Together with physicochemical parameters of the drug candidates, structure–activity relationships are critically discussed. Tubulin interaction or inhibition of topoisomerase I and IIα/β activity are two rationales that can explain the antiproliferative activity observed in the NCI 60 DTP human tumor cell line screen. However, it can also be reasonably assumed that these compounds address several targets, thus prohibiting the identification of simple structure–activity relationships. The new structures described herein are thought to act as so‐called multitarget drugs, thus being of special interest in the area of multidrug resistance.     

An approach for reverse engineering of design patterns

For the maintenance of software systems, developers have to completely understand the existing system. The usage of design patterns leads to benefits for new and young developers by enabling them to reuse the knowledge of their experienced colleagues. Design patterns can support a faster and better understanding of software systems. There are different approaches for supporting pattern recognition in existing systems by tools. They are evaluated by the Information Retrieval criteria precision and recall. An automated search based on structures has a highly positive influence on the manual validation of the results by developers. This validation of graphical structures is the most intuitive technique. In this paper a new approach for automated pattern search based on minimal key structures is presented. It is able to detect all patterns described by the GOF [15]. This approach is based on positive and negative search criteria for structures and is prototypically implemented using Rational Rose and Together.     

Ab initio study of vibrational dephasing of electronic excitations in semiconducting carbon nanotubes

Phonon-induced dephasing of electronic transitions in semiconducting single-wall carbon nanotubes (CNT) is investigated by ab initio molecular dynamics. Pure-dephasing is shown to be the source of the photoluminescence linewidths observed experimentally in isolated CNTs at low and room temperatures. In ideal tubes, the dephasing is found to occur by coupling to optical phonons. The dephasing proceeds notably faster in the presence of some defects due to stronger coupling to local modes, suggesting that the defects can be identified in CNTs by broadened optical bands.     

Composition,toxic and antinutritional factors of newly developed cultivars of Brazilian soybean (Glycine max)

Five different recently released Brazilian soybean cultivars (Bays, BR-10, Rio Balsas, Serido and Tropical) were compared for their proximate analyses and presence of antinutritional or toxic factors. As expected, the seeds are rich in proteins, varying from 360·7 to 485·4 g kg⁻¹ flour, and they also have a high amount of fat (from 183·0 to 215·3 g kg⁻¹ flour). Crude extracts from seeds of Bays, BR-10, Serido and Tropical were highly toxic to mice within 1–12 h, depending on the administration route (intraperitoneal, intramuscular or subcutaneous) and dose used while Rio Balsas was not. These acute effects were very similar to those produced by the soytoxin, a neurotoxin that has been recently purified from the commercial soybean sold in Brazil. The amount of trypsin inhibited in the presence of crude extracts ranged from 28·5 to 62·5 g kg⁻¹ flour. Urease was also present and the seed lectin agglutinated preferentially rabbit erythrocytes. A heat treatment at 92°C for 1 min destroyed completely the toxic activity while the haemagglutinating and trypsin inhibitor activities were abolished within 5 min. At these conditions urease was still active. Due to its high protein content, lack of soytoxin, and low levels of trypsin inhibitor, lectin, and urease it is suggested that Rio Balsas could be an alternative for breeding programmes aimed to improve the nutritional quality of soybeans. ©1997 SCI     

Comparison of model order reduction methods for optimal sensor placement for thermo-elastic models*

In this article an optimal sensor placement problem for a thermo-elastic solid body model is considered. Temperature sensors are placed in a near-optimal way so that their measurements allow an accurate prediction of the thermally induced displacement of a point of interest (POI). Low-dimensional approximations of the transient thermal field are used which allows for efficient calculations. Four model order reduction (MOR) methods are applied and subsequently compared with respect to the accuracy of the estimated POI displacement and the location of the sensors obtained.     

Exosomal Aβ-Binding Proteins Identified by “In Silico” Analysis Represent Putative Blood-Derived Biomarker Candidates for Alzheimer´s Disease

The potential of exosomes as biomarker resources for diagnostics and even for therapeutics has intensified research in the field, including in the context of Alzheimer´s disease (AD). The search for disease biomarkers in peripheral biofluids is advancing mainly due to the easy access it offers. In the study presented here, emphasis was given to the bioinformatic identification of putative exosomal candidates for AD. The exosomal proteomes of cerebrospinal fluid (CSF), serum and plasma, were obtained from three databases (ExoCarta, EVpedia and Vesiclepedia), and complemented with additional exosomal proteins already associated with AD but not found in the databases. The final biofluids’ proteomes were submitted to gene ontology (GO) enrichment analysis and the exosomal Aβ-binding proteins that can constitute putative candidates were identified. Among these candidates, gelsolin, a protein known to be involved in inhibiting Abeta fibril formation, was identified, and it was tested in human samples. The levels of this Aβ-binding protein, with anti-amyloidogenic properties, were assessed in serum-derived exosomes isolated from controls and individuals with dementia, including AD cases, and revealed altered expression patterns. Identification of potential peripheral biomarker candidates for AD may be useful, not only for early disease diagnosis but also in drug trials and to monitor disease progression, allowing for a timely therapeutic intervention, which will positively impact the patient’s quality of life.     

Effect of Surface Coating on the Photocatalytic Function of Hybrid CdS–Au Nanorods

Hybrid semiconductor–metal nanoparticles are interesting materials for use as photocatalysts due to their tunable properties and chemical processibility. Their function in the evolution of hydrogen in photocatalytic water splitting is the subject of intense current investigation. Here, the effects of the surface coatings on the photocatalytic function are studied, with Au‐tipped CdS nanorods as a model hybrid nanoparticle system. Kinetic measurements of the hydrogen evolution rate following photocatalytic water reduction are performed on similar nanoparticles but with different surface coatings, including various types of thiolated alkyl ligands and different polymer coatings. The apparent hydrogen evolution quantum yields are found to strongly depend on the surface coating. The lowest yields are observed for thiolated alkyl ligands. Intermediate values are obtained with L‐glutathione and poly(styrene‐co‐maleic anhydride) polymer coatings. The highest efficiency is obtained for polyethylenimine (PEI) polymer coating. These pronounced differences in the photocatalytic efficiencies are correlated with ultrafast transient absorption spectroscopy measurements, which show a faster bleach recovery for the PEI‐coated hybrid nanoparticles, consistent with faster and more efficient charge separation. These differences are primarily attributed to the effects of surface passivation by the different coatings affecting the surface trapping of charge carriers that compete with effective charge separation required for the photocatalysis. Further support of this assignment is provided from steady‐state emission and time‐resolved spectral measurements, performed on related strongly fluorescing CdSe/CdS nanorods. The control and understanding of the effect of the surface coating of the hybrid nanosystems on the photocatalytic processes is of importance for the potential application of hybrid nanoparticles as photocatalysts.