PhAST : pharmacophore alignment search tool

We developed the Pharmacophore Alignment Search Tool (PhAST), a text-based technique for rapid hit and lead structure searching in large compound databases. For each molecule, a two-dimensional graph of potential pharmacophoric points (PPPs) is created, which has an identical topology as the original molecule with implicit hydrogen atoms. Each vertex is coloured by a symbol representing the corresponding PPP. The vertices of the graph are canonically labelled. The symbols associated with the vertices are combined to a so-called PhAST-Sequence beginning with the vertex with the lowest canonical label. Due to the canonical labelling the created PhAST-Sequence is characteristic for each molecule. For similarity assessment, PhAST-Sequences are compared using the sequence identity in their global pairwise alignment. The alignment score lies between 0 (no similarity) and 1 (identical PhAST-Sequences). In order to use global pairwise sequence alignment, a score matrix for pharmacophoric symbols was developed and gap penalties were optimized. PhAST performed comparably and sometimes superior to other similarity search tools (CATS2D, MOE pharmacophore quadruples) in retrospective virtual screenings using the COBRA collection of drugs and lead structures. Most importantly, the PhAST alignment technique allows for the computation of significance estimates that help prioritize a virtual hit list

ADJUSTING A TOOL FOR COLLABORATIVE PLANNING TO REQUIREMENTS IN PRACTICE -REALISATION OF A CLIENT-SERVER ARCHITECTURE

ABSTRACT: The planning of projects in building engineering is a complex process which is characterized by a dy

Electric pulse characteristics can enable species recognition in African weakly electric fish species

Nagel R, Kirschbaum F, Hofmann V, Engelmann J, Tiedemann R. Electric pulse characteristics can enable species recognition in African weakly electric fish species. SCIENTIFIC REPORTS. 2018;8(1): 10799.Communication is key to a wide variety of animal behaviours and multiple modalities are often involved in this exchange of information from sender to receiver. The communication of African weakly electric fish, however, is thought to be predominantly unimodal and is mediated by their electric sense, in which species-specific electric organ discharges (EODs) are generated in a context-dependent and thus variable sequence of pulse intervals (SPI). While the primary function of the electric sense is considered to be electrolocation, both of its components likely carry information regarding identity of the sender. However, a clear understanding of their contribution to species recognition is incomplete. We therefore analysed these two electrocommunication components (EOD waveform and SPI statistics) in two sympatric mormyrid Campylomormyrus species. In a set of five playback conditions, we further investigated which components may drive interspecific recognition and discrimination. While we found that both electrocommunication components are species-specific, the cues necessary for species recognition differ between the two species studied. While the EOD waveform and SPI were both necessary and sufficient for species recognition in C. compressirostris males, C. tamandua males apparently utilize other, non-electric modalities. Mapped onto a recent phylogeny, our results suggest that discrimination by electric cues alone may be an apomorphic trait evolved during a recent radiation in this taxon

Population Coding and Correlated Variability in Electrosensory Pathways

The fact that perception and behavior depend on the simultaneous and coordinated activity of neural populations is well established. Understanding encoding through neuronal population activity is however complicated by the statistical dependencies between the activities of neurons, which can be present in terms of both their mean (signal correlations) and their response variability (noise correlations). Here, we review the state of knowledge regarding population coding and the influence of correlated variability in the electrosensory pathways of the weakly electric fish Apteronotus leptorhynchus. We summarize known population coding strategies at the peripheral level, which are largely unaffected by noise correlations. We then move on to the hindbrain, where existing data from the electrosensory lateral line lobe (ELL) shows the presence of noise correlations. We summarize the current knowledge regarding the mechanistic origins of noise correlations and known mechanisms of stimulus dependent correlation shaping in ELL. We finish by considering future directions for understanding population coding in the electrosensory pathways of weakly electric fish, highlighting the benefits of this model system for understanding the origins and impact of noise correlations on population coding

The Possibly Hypogene Karstic Iron Ore Deposit of Warda Near Ajloun (Northern Jordan), its Mineralogy, Geochemistry and Historic Mine

In this study the iron ore deposit of the historic Warda mine (District of Ajloun, Northern Jordan) and its speleological im­portance is discussed. The number of known dissolutional caves in Jordan is very low, in spite of the fact, that large sections of the country are underlain by Cretaceous limestone. The only large cave yet discovered is Al-Daher Cave, a hypogene maze cave (Kempe et al. 2006). The Warda Iron Deposit was mined during the time of the crusades by one of Saladin’s officers to build and stock the castle of Ajloun. The survey shows that the mine consists of two larger rooms, together about 1000 m2 in area. Much of the mine’s floor is now covered with recent flood sediments (680 m2), up to over 2 m deep. The mine cuts natural cavities, fissures with speleothems and a collapse hall in lime­stone, that may or may not have been created by a collapsed mine ceiling. Calculating the mine volume conservatively, a to­tal of about 1100 t of elemental iron may have been extracted. Mineralogical investigation (XRD) shows, that the iron ore is goethitic/limonitic with noticeable hematite contents. Geo­chemical (XRF) analysis shows that the goethite is very pure; impurities of main elements sum up to 1% only. Among the trace-elements W (248 ppm), As (168 ppm) and Co (124 ppm) show the highest concentrations, with all others < 37 (Ba) ppm. Former prospecting results show that the deposit has a spatial extent of 300 x 200 m with a maximal thickness of about 10 m. Textural, mineralogical and geochemical criteria suggest that the ore body could be of speleogene origin, i.e. deposited in a hypogene, deep phreathic setting, possibly before regional up­lift or even prior to the maximal burial depth. A possibly simi­lar ore-body is for example described from the gigantic Lower Cretaceous and sand-filled cave of Wülfrath (North Rhine-Westphalia, Germany) (Drozdzewski et al. 1998)

A reproducible extrusion printing process with highly viscous nanoparticle inks

Printing of functional materials such as nanoparticle inks is a class of additive fabrication techniques complementary to standard subtractive electronics fabrication techniques such as pcb technology on pcb level or silicon based microelectronics on integrated circuit level. To date the majority of digital printing processes for (micro)electronics is inkjet based. Moreover aerosol jet based printing also establishes itself for printing on non-planar substrates and for materials with higher viscosities. A material deposition technique available since decades and mainly used for dispensing of adhesives and sealing materials is fluid-filament printing. It allows to cover a wide range of materials and viscosities and thus, also holds potential for additive manufacturing of electronics. In this paper we systematically study the influences on fluid filament printing both theoretically taking into account ink and equipment tolerances and experimentally using mainly standard dispensing equipment and two commercial screen printing inks. At the end of the paper we derive recommendations for reproducible printing of conductive lines and pads and give an outlook to printing 2.5D structures

Domain level ontology design: DISO and MDMC-NEP Provenance

How can a computer understand the relations of data or objects from the real world? Ontologies are semantic artifacts that capture knowledge about their domain of interest in a machine-understandable form. The main goal of developing ontologies is to formalize concepts and their relations through which humans express meaning and to use them as a communication interface to machines. Thus, ontology development is an important step towards generating linked and FAIR data. Within HMC we support and co-develop domain and application-level ontologies. Here we present two developments: Dislocation Ontology (DISO) and Model and Data-Driven Materials Characterization Provenance (MDMC-PROV). DISO: An important class of materials is crystalline materials, e.g., metals and semiconductors, which nearly always contain defects, the “dislocations”. This type of defect determines many important material properties, e.g., strength and ductility. Over the past years, significant effort has been put into understanding dislocation behavior across different length scales via experimental characterization techniques and simulations. However, there is still a lack of common standards to formally describe and represent disclocations. Thus, in this work we develop the dislocation ontology (DISO), which is a domain ontology that defines the concepts and relationships related to linear defects in crystalline materials. DISO is published [1] through a persistent URL following W3C best practices for publishing Linked data. MDMC-Prov: The rapid development of science and technology in everyday large data generation does not match the data understanding. These days, understanding how experiments are performed and results are derived become more complex due to a lack of provenance documentation. Therefore, the provenance must be tracked, described, and managed over the research process. Thus, in this work, we report an application ontology that can capture provenance information in materials science experiments. The ontology is based on the MDMC glossary [2], which defines the common terms in the materials science experiments. From each term, we map to PROV-O [3]. These ensure the validity, reproducibility, and reusability of the data. [1] https://purls.helmholtz-metadaten.de/diso [2] https://jl-mdmc-helmholtz.de [3] https://www.w3.org/TR/2013/NOTE-prov-primer-20130430/ DISO:  An important class of materials is crystalline materials, e.g., metals and semiconductors, which nearly always contain defects, the “dislocations”. This type of defect determines many important material properties, e.g., strength and ductility. Over the past years, significant effort has been put into understanding dislocation behavior across different length scales via experimental characterization techniques and simulations. However, there is still a lack of common standards to formally describe and represent disclocations. Thus, in this work we develop the dislocation ontology (DISO), which is a domain ontology that defines the concepts and relationships related to linear defects in crystalline materials. DISO is published1 through a persistent URL following W3C best practices for publishing Linked data. MDMC-Prov: The rapid development of science and technology in everyday large data generation does not match the data understanding. These days, understanding how experiments are performed and results are derived become more complex due to a lack of provenance documentation. Therefore, the provenance must be tracked, described, and managed over the research process. Thus, in this work, we report an application ontology that can capture provenance information in materials science experiments. The ontology is based on the MDMC glossary, which defines the common terms in the materials science experiments. From each term, we map to PROV-O3. These ensure the validity, reproducibility, and reusability of the data

Pattern of S100-release in benign and malignant diseases beside malignant melanoma/Freisetzung von S100 bei benignen und malignen Erkrankungen jenseits des malignen Melanoms

Background: The usefulness of S100 as a prognostic marker and aid in follow-up care in patients with malignant melanoma as well as in individuals with various neurological pathologies is well known. The aim of this study was to investigate its release and clinical relevance in benign and malignant disorders beyond these indications to elucidate tumor and organ specificity of S100. Methods: S100 levels were studied in serum samples of 1856 untreated patients, among them 59 healthy individuals, 358 patients with benign disorders, and 1439 patients with malignant tumors. Results: Healthy individuals had low S100 levels reaching a median of 0.041 ng/mL and 95th and 100th percentiles of 0.096 ng/mL and 0.144 ng/mL, respectively. The medians of patient groups with benign diseases ranged from 0.030 to 0.057 ng/mL, patients with malignant diseases from 0.020 to 0.059 ng/mL, and thus were comparable to healthy individuals. Only 2% of patients with benign diseases, mainly suffering from infectious, autoimmune, or benign gastrointestinal diseases and 1% of patients with malignant diseases showed slightly higher values than healthy individuals, in most cases up to 0.5 ng/mL. Conclusions: In contrast to many other oncological biomarkers, S100 is only rarely released in elevated levels from most benign and malignant diseases apart from malignant melanoma and neurological diseases, resulting in superior organ and tumor specificity. As potentially influencing factors, severe infectious diseases have to be considered.Hintergrund: S100 ist als nützlicher Biomarker für die Prognoseaschätzung und die Verlaufsbeobachtung bei Patienten mit malignem Melanom und in Patienten mit verschiedenen neurologischen Erkrankungen anerkannt. Das Ziel dieser Studie war, die Freisetzung und klinische Relevanz von S100 bei anderen benignen and malignen Erkrankungen jenseits dieser Indikationen zu untersuchen, um die Tumor- und Organspezifität von S100 zu bewerten. Methoden: S100-Konzentrationen wurden in Serumproben von 1856 unbehandelten Patienten ermittelt, darunter 59 gesunde Personen, 358 Patienten mit benignen Erkrankungen und 1439 Patienten mit malignen Tumoren. Ergebnisse: Gesunde Personen hatten niedrige S100 Serumwerte, die einen Median von 0.041 ng/mL, eine 95. Perzentile von 0.096 ng/mL und ein Maximum von 0.144 ng/mL erreichten. Die Mediane der Patientengruppen lagen bei benignen Erkrankungen zwischen 0.030 und 0.057 ng/mL, bei Patienten mit malignen Tumoren zwischen 0.020 und 0.059 ng/mL – und waren somit vergleichbar zu gesunden Kontrollpersonen. Lediglich 2% der Patienten mit benignen Erkrankungen, v.a. infektiösen, autoimmunen oder benignen gastrointestinalen Erkrankungen, sowie 1% der Patienten mit malignen Tumoren wiesen im Vergleich zu gesunden Personen leicht erhöhte Werte auf – in den meisten Fällen bis 0.5 ng/mL. Schlussfolgerung: Im Gegensatz zu vielen anderen onkologischen Biomarkern wird S100 nur selten in höheren Konzentrationen von den meisten benignen und malignen Erkrankungen – mit Ausnahme des malignen Melanoms und neurologischer Erkrankungen – freigesetzt, was sich in einer sehr hohen Organ- und Tumorspezifität widerspiegelt. Als möglicher Einflussfaktor sind schwere infektiöse Erkrankungen zu berücksichtigen

Pattern of S100-release in benign and malignant diseases beside malignant melanoma/Freisetzung von S100 bei benignen und malignen Erkrankungen jenseits des malignen Melanoms

Background: The usefulness of S100 as a prognostic marker and aid in follow-up care in patients with malignant melanoma as well as in individuals with various neurological pathologies is well known. The aim of this study was to investigate its release and clinical relevance in benign and malignant disorders beyond these indications to elucidate tumor and organ specificity of S100. Methods: S100 levels were studied in serum samples of 1856 untreated patients, among them 59 healthy individuals, 358 patients with benign disorders, and 1439 patients with malignant tumors. Results: Healthy individuals had low S100 levels reaching a median of 0.041 ng/mL and 95th and 100th percentiles of 0.096 ng/mL and 0.144 ng/mL, respectively. The medians of patient groups with benign diseases ranged from 0.030 to 0.057 ng/mL, patients with malignant diseases from 0.020 to 0.059 ng/mL, and thus were comparable to healthy individuals. Only 2% of patients with benign diseases, mainly suffering from infectious, autoimmune, or benign gastrointestinal diseases and 1% of patients with malignant diseases showed slightly higher values than healthy individuals, in most cases up to 0.5 ng/mL. Conclusions: In contrast to many other oncological biomarkers, S100 is only rarely released in elevated levels from most benign and malignant diseases apart from malignant melanoma and neurological diseases, resulting in superior organ and tumor specificity. As potentially influencing factors, severe infectious diseases have to be considered.Hintergrund: S100 ist als nützlicher Biomarker für die Prognoseaschätzung und die Verlaufsbeobachtung bei Patienten mit malignem Melanom und in Patienten mit verschiedenen neurologischen Erkrankungen anerkannt. Das Ziel dieser Studie war, die Freisetzung und klinische Relevanz von S100 bei anderen benignen and malignen Erkrankungen jenseits dieser Indikationen zu untersuchen, um die Tumor- und Organspezifität von S100 zu bewerten. Methoden: S100-Konzentrationen wurden in Serumproben von 1856 unbehandelten Patienten ermittelt, darunter 59 gesunde Personen, 358 Patienten mit benignen Erkrankungen und 1439 Patienten mit malignen Tumoren. Ergebnisse: Gesunde Personen hatten niedrige S100 Serumwerte, die einen Median von 0.041 ng/mL, eine 95. Perzentile von 0.096 ng/mL und ein Maximum von 0.144 ng/mL erreichten. Die Mediane der Patientengruppen lagen bei benignen Erkrankungen zwischen 0.030 und 0.057 ng/mL, bei Patienten mit malignen Tumoren zwischen 0.020 und 0.059 ng/mL – und waren somit vergleichbar zu gesunden Kontrollpersonen. Lediglich 2% der Patienten mit benignen Erkrankungen, v.a. infektiösen, autoimmunen oder benignen gastrointestinalen Erkrankungen, sowie 1% der Patienten mit malignen Tumoren wiesen im Vergleich zu gesunden Personen leicht erhöhte Werte auf – in den meisten Fällen bis 0.5 ng/mL. Schlussfolgerung: Im Gegensatz zu vielen anderen onkologischen Biomarkern wird S100 nur selten in höheren Konzentrationen von den meisten benignen und malignen Erkrankungen – mit Ausnahme des malignen Melanoms und neurologischer Erkrankungen – freigesetzt, was sich in einer sehr hohen Organ- und Tumorspezifität widerspiegelt. Als möglicher Einflussfaktor sind schwere infektiöse Erkrankungen zu berücksichtigen