Using Provenance to support Good Laboratory Practice in Grid Environments

Conducting experiments and documenting results is daily business of scientists. Good and traceable documentation enables other scientists to confirm procedures and results for increased credibility. Documentation and scientific conduct are regulated and termed as "good laboratory practice." Laboratory notebooks are used to record each step in conducting an experiment and processing data. Originally, these notebooks were paper based. Due to computerised research systems, acquired data became more elaborate, thus increasing the need for electronic notebooks with data storage, computational features and reliable electronic documentation. As a new approach to this, a scientific data management system (DataFinder) is enhanced with features for traceable documentation. Provenance recording is used to meet requirements of traceability, and this information can later be queried for further analysis. DataFinder has further important features for scientific documentation: It employs a heterogeneous and distributed data storage concept. This enables access to different types of data storage systems (e. g. Grid data infrastructure, file servers). In this chapter we describe a number of building blocks that are available or close to finished development. These components are intended for assembling an electronic laboratory notebook for use in Grid environments, while retaining maximal flexibility on usage scenarios as well as maximal compatibility overlap towards each other. Through the usage of such a system, provenance can successfully be used to trace the scientific workflow of preparation, execution, evaluation, interpretation and archiving of research data. The reliability of research results increases and the research process remains transparent to remote research partners.Comment: Book Chapter for "Data Provenance and Data Management for eScience," of Studies in Computational Intelligence series, Springer. 25 pages, 8 figure

Continent-wide decoupling of Y-chromosomal genetic variation from language and geography in native South Americans

Numerous studies of human populations in Europe and Asia have revealed a concordance between their extant genetic structure and the prevailing regional pattern of geography and language. For native South Americans, however, such evidence has been lacking so far. Therefore, we examined the relationship between Y-chromosomal genotype on the one hand, and male geographic origin and linguistic affiliation on the other, in the largest study of South American natives to date in terms of sampled individuals and populations. A total of 1,011 individuals, representing 50 tribal populations from 81 settlements, were genotyped for up to 17 short tandem repeat (STR) markers and 16 single nucleotide polymorphisms (Y-SNPs), the latter resolving phylogenetic lineages Q and C. Virtually no structure became apparent for the extant Y-chromosomal genetic variation of South American males that could sensibly be related to their inter-tribal geographic and linguistic relationships. This continent-wide decoupling is consistent with a rapid peopling of the continent followed by long periods of isolation in small groups. Furthermore, for the first time, we identified a distinct geographical cluster of Y-SNP lineages C-M217 (C3*) in South America. Such haplotypes are virtually absent from North and Central America, but occur at high frequency in Asia. Together with the locally confined Y-STR autocorrelation observed in our study as a whole, the available data therefore suggest a late introduction of C3* into South America no more than 6,000 years ago, perhaps via coastal or trans-Pacific routes. Extensive simulations revealed that the observed lack of haplogroup C3* among extant North and Central American natives is only compatible with low levels of migration between the ancestor populations of C3* carriers and non-carriers. In summary, our data highlight the fact that a pronounced correlation between genetic and geographic/cultural structure can only be expected under very specific conditions, most of which are likely not to have been met by the ancestors of native South Americans

Prospective individual patient data meta-analysis of two randomized trials on convalescent plasma for COVID-19 outpatients

Data on convalescent plasma (CP) treatment in COVID-19 outpatients are scarce. We aimed to assess whether CP administered during the first week of symptoms reduced the disease progression or risk of hospitalization of outpatients. Two multicenter, double-blind randomized trials (NCT04621123, NCT04589949) were merged with data pooling starting when = 50 years and symptomatic for <= 7days were included. The intervention consisted of 200-300mL of CP with a predefined minimum level of antibodies. Primary endpoints were a 5-point disease severity scale and a composite of hospitalization or death by 28 days. Amongst the 797 patients included, 390 received CP and 392 placebo; they had a median age of 58 years, 1 comorbidity, 5 days symptoms and 93% had negative IgG antibody-test. Seventy-four patients were hospitalized, 6 required mechanical ventilation and 3 died. The odds ratio (OR) of CP for improved disease severity scale was 0.936 (credible interval (CI) 0.667-1.311); OR for hospitalization or death was 0.919 (CI 0.592-1.416). CP effect on hospital admission or death was largest in patients with <= 5 days of symptoms (OR 0.658, 95%CI 0.394-1.085). CP did not decrease the time to full symptom resolution

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Erstellung einer Software zur Automatisierung des Versuchsbetriebs und der Messdatenerfassung am Gemischbildungskanal

In der vorliegenden Bachelorarbeit, die im Deutschen Zentrum für Luft- und Raumfahrt e.V. am Institut für Aerodynamik und Strömungstechnik in der Abt. Über- und Hyperschalltechnologie angefertigt wurde, wird die Entwicklung einer Software zur Messdatenerfassung beschrieben. Der Gemischbildungskanal, einer der Windkanäle der Abteilung, wurde in den letzten Jahren schrittweise modernisiert, indem eine neue Steuerung eingesetzt und die Messhardware erneuert und erweitert wurde. Diese neue Messhardware benötigte ein angepasstes neues Softwaresystem. Die Messsoftware sollte den Ingenieur bei der Messung und Aufnahme verschiedener Größen wie Druck, Temperatur und Spannung unterstützen und dabei einfach zu verstehen und anpassbar sein. Aufbauend auf einer Anforderungsanalyse wurde mit LabVIEW, dem grafischen Programmiersystem von National Instruments, eine modulare Basisversion der Messwerterfassungssoftware erstellt, die je nach Bedürfnis des Benutzers weiterentwickelt werden kann. Die Basisversion wird als voll funktionsfähiges Programm zur Messung von Werten am Gemischbildungskanal eingesetzt und umfasst Kanalsteuerungs- und Echtzeitvisualisierungsmodule

Enabling a Data Management System to Support the "Good Laboratory Practice"

Conducting experiments and documenting results is daily business of scientists. Documentation enables other scientists to confirm results, reassure interpretations and therefore increase the experiment's credibility. These every day action are regulated and shortly described as: "good laboratory practice". Due to computerized research systems experimental data get more elaborated, this increases the need for electronic notebooks with data storage and computational features. The aim of this thesis is to develop a new approach to substitute paper based notebooks. The new approach shall simplify the scientist's work. With the constraint, that it has to stay as evidential and credible as before. Some of the analysed requirements for laboratory notebooks are traceability of a data item, credibility of an object and preservation mechanisms. The approach of this thesis is to enable an open source data management system with necessary features for a laboratory notebook. As technologies provenance, digital signatures and secure web services are integrated into the data management system. This enriched data management system supports the scientist in his daily work which helps him to concentrate on research

The Provenance Store prOOst for the Open Provenance Model

This paper presents the provenance storing system prOOst which uses a semi-structured approach to store the provenance data based on the Open Provenance Model (OPM). It uses the graph database “Neo4j” for storage and the graph traversal language “Gremlin” for querying. Furthermore, it provides a REST interface to record data into the store, and a web front end to query the database. The prOOst provenance system was published as Open Source software and is available on SourceForge

Cell Cycle Kinetics and Sister Chromatid Exchange in Mosaic Turner Syndrome

Turner syndrome (TS) is caused by a complete or partial absence of an X or Y chromosome, including chromosomal mosaicism, affecting 1 in 2500 female live births. Sister chromatid exchange (SCE) is used as a sensitive indicator of spontaneous chromosome instability. Cells from mosaic patients constitute useful material for SCE evaluations as they grow under the influence of the same genetic background and endogenous and exogenous factors. We evaluated the proliferation dynamics and SCE frequencies of 45,X and 46,XN cells of 17 mosaic TS patients. In two participants, the 45,X cells exhibited a proliferative disadvantage in relation to 46,XN cells after 72 h of cultivation. The analysis of the mean proliferation index (PI) showed a trend for a significant difference between the 45,X and 46,X+der(X)/der(Y) cell lineages; however, there were no intra-individual differences. On the other hand, mean SCE frequencies showed that 46,X+der(X) had the highest mean value and 46,XX the lowest, with 45,X occupying an intermediate position among the lineages found in at least three participants; moreover, there were intra-individual differences in five patients. Although 46,X+der(X)/der(Y) cell lineages, found in more than 70% of participants, were the most unstable, they had a slightly higher mean PI than the 45,X cell lineages in younger (≤17 years) mosaic TS participants. This suggests that cells with a karyotype distinct from 45,X may increase with time in mosaic TS children and adolescents