Determining the feasibility of a real-time geophysical magnetic and electric measurement system for monitoring strain underground

In deep mining environments, rockbursts can occur in areas of high stress. The unpredictable nature, and sometimes fatal consequences of the rockbursts, makes identifying increases in stress that occur prior to failure events, important for mine safety. The piezoelectric, electrokinetic, and seismo-electric/magnetic effects result in rocks that are stressed emitting electric and magnetic fields that can potentially be measured in (or close to) a rock mass. Electric, magnetic and seismic data were collected during a four-day period at Coleman Mine, Sudbury, Ontario, and later analysed. No signals due to strain were evident in the magnetic or electric data, so a more careful three-part experiment was proposed to see if strain related signals could be identified in magnetic data. In the first part of the experiment thirty-two rocks were stressed until failure. Measurable magnetic signals associated with audible cracking sounds were found for most rock samples, as well as consistent signals across all samples prior to failure. The implementation of real-time monitoring of these signals has the potential to significantly improve deep mine safety by mapping the evolution of strain underground and potentially indicating areas susceptible to failure.Master of Science (MSc) in Geolog

Maternal inheritance of twist and analysis of MAPK activation in embryos of the polychaete Annelid Platynereis dumerilii

In this study, we aimed to identify molecular mechanisms involved in the specification of the 4d (mesentoblast) lineage in Platynereis dumerilii. We employ RT-PCR and in situ hybridization against the Platynereis dumerilii twist homolog (Pdu-twist) to reveal mesodermal specification within this lineage. We show that Pdu-twist mRNA is already maternally distributed. After fertilization, ooplasmatic segregation leads to relocation of Pdu-twist transcripts into the somatoblast (2d) lineage and 4d, indicating that the maternal component of Pdu-twist might be an important prerequisite for further mesoderm specification but does not represent a defining characteristic of the mesentoblast. However, after the primordial germ cells have separated from the 4d lineage, zygotic transcription of Pdu-twist is exclusively observed in the myogenic progenitors, suggesting that mesodermal specification occurs after the 4d stage. Previous studies on spiral cleaving embryos revealed a spatio-temporal correlation between the 4d lineage and the activity of an embryonic organizer that is capable to induce the developmental fates of certain micromeres. This has raised the question if specification of the 4d lineage could be connected to the organizer activity. Therefore, we aimed to reveal the existence of such a proposed conserved organizer in Platynereis employing antibody staining against dpERK. In contrast to former observations in other spiralian embryos, activation of MAPK signaling during 2d and 4d formation cannot be detected which questions the existence of a conserved connection between organizer function and specification of the 4d lineage. However, our experiments unveil robust MAPK activation in the prospective nephroblasts as well as in the macromeres and some micromeres at the blastopore in gastrulating embryos. Inhibition of MAPK activation leads to larvae with a shortened body axis, defects in trunk muscle spreading and improper nervous system condensation, indicating a critical function for MAPK signaling for the reorganization of embryonic tissues during the gastrulation process

Molekulare Mechanismen der Mesodermbildung in Platynereis dumerilii (Annelida, Polychaeta)

Alle bilateralsymmetrischen Tiere (Bilateria) sind durch den Besitz dreier Keimblätter (Triploblastie), die während ihrer Embryonalentwicklung entstehen, gekennzeichnet. Die Spezifizierung der Keimblätter und deren Trennung durch den Gastrulationsprozess ist einer der grundlegendsten Schritte während der Embryonalentwicklung der Bilateria. Die Untersuchung der zugrunde liegenden molekularen Mechansimen beschränkte sich bis vor kurzem auf die Vertreter der Deuterostomia und der Ecdysozoa. Über die molekularen Grundlagen der Determination der Keimblätter bei den Lophotrochozoa, war bisher fast nichts bekannt. Einen großen Teil der Lophotrochozoa machen die Spiralia aus und inzwischen sind auch einige der Vertreter der Spiralia für die molekularen Methoden der modernen Entwicklungsbiologie zugänglich. Es sind bis heute aber keine molekularen Faktoren identifiziert worden, die das mesodermale Keimblatt der Spiralier determinieren. Zur weiteren Analyse dieser Fragestellung bot sich der Polychaet Platynereis dumerilii als Modellsystem an. In dieser Arbeit wurden die zu twist und snail homologen Gene von Platynereis als Kandidatengene kloniert und ihre Expression in der Früh- und Larvalentwicklung charakterisiert und lokalisiert. Sowohl Platynereis twist als auch Platynereis snail werden maternal in die Eizelle eingelagert und ihre Expression findet sich während der gesamten Embryonalentwicklung. Eine durch Furchungsarrest mit Cytochalasin B vermittelte Zelllinienuntersuchung ergab, dass Pdu-twist in der 4d Zelllinie, die das komplette Rumpfmesoderm der Larve bildet, exprimiert wird. In der Trochophora werden sowohl Pdu-twist als auch Pdu-snail in den Mesodermanlagen, sowie in einem Teil des viszeralen Mesoderms der Larve exprimiert. In atoken Jungwürmern findet sich Pdu-twist Expression in der Wachstumszone in der neue Segmente durch Sprossung gebildet werden, ebenso wie bei regenerierenden Tieren, im präsumptiven Mesoderm sich bildender Segmente. Durch die Injektion von dsRNA in adulte Tiere wurden parentale RNAi vermittelte, funktionelle Analysen durchgeführt. Diese Analysen ergaben, dass es sich bei Pdu-twist, wahrscheinlich in Kooperation mit Pdu-snail, um einen „Master-Regulator“ für mesodermales Zellschicksal in Platynereis handelt, der sowohl eine maternale, als auch eine zygotische Komponente besitzt und dessen Funktionsverlust sowohl zum Ausbleiben der morphogenetischen Gastrulationsbewegungen, als auch der Determination und Differenzierung des Mesoderms im sich entwickelnden Embryo führt. Um die Ergebnisse dieser Experimente zu verifizieren, wurde Pdu-twist heterolog in E. coli exprimiert, das Protein aufgereinigt und durch Immunisierung von Kaninchen polyklonale Antiseren gegen Pdu-Twist hergestellt. Die aufgereinigten Immunseren wurden durch Western Blot Analysen und Immun-fluoreszenzfärbungen auf ihre Spezifität überprüft. Zur Analyse einer in der Evolution eventuell konservierten Funktion der Twist Transkriptionsfaktoren, wurden UAS-Pdu-twist transgene Drosophila hergestellt und für Rettungsexperimente an twist– und twist-, snail- Drosophila Stämmen benutzt. In den Experimenten fanden sich keine geretteten Phänotypen, was dafür spricht, dass Drosophila twist nicht durch Platynereis twist ersetzt werden kann. Dies ist das erste Mal, dass außerhalb der Insekta ein funktioneller Zusammenhang zwischen der Expression eines Twist Transkriptionsfaktors und der Spezifizierung mesodermalen Zellschicksals sowie der Gastrulation experimentell nachgewiesen wurde. Diese Ergebnisse eröffnen die Möglichkeit die molekularen Grundlagen der Mesodermspezifizierung bei inäqual furchenden Spiraliern näher zu analysieren und die durchgeführten Zellstammbaumanalysen mit molekularen Daten zu kombinieren. Platynereis twist ist die erste Keimblattdeterminante, die in Spiraliern bisher identifiziert wurde. Ebenfalls lassen sich durch vergleichende Analysen Rückschlüsse auf eine ursprüngliche Funktion der Twist-like Transkriptionsfaktoren bei der Aktivierung von Transkriptionskasetten, die für Zellbewegung, Zellform und Zellteilung zuständig sind, ziehen

Towards advanced understanding of scale-up: From computational fluid dynamics to systems biotechnology approaches

Scale-up of mammalian cell culture processes from development scale to commercial manufacturing scale is routinely performed in biopharmaceutical process development. For this purpose, well established biochemical engineering principles, empirical formula and scale-up criteria were developed. Considering well characterized equipment as well as company specific process and platform knowledge, scale-up typically is successfully achieved. Yet, improved understanding of scale-up phenomena is desirable for various reasons. Since miniaturized systems are increasingly used in biopharmaceutical process development and, at the same time, efforts with respect to resources and timelines to achieve final manufacturing scale are to be minimized, scale-up steps need to cope with larger bioreactor volume changes in the future. From a process science perspective, an integrated analysis of scale-up phenomena considering both the biochemical engineering aspects (e.g. power input, kLa) as well as cell-level data is needed. In order to gain more profound understanding of scale-up, comprehensive characterization of our cultivation systems using computational fluid dynamics (CFD) was achieved (Figure 1). To further improve and integrate the understanding of an antibody producing CHO cell in a bioreactor environment across scales, we performed thorough analysis of metabolic rates and fluxes in different cultivation scales. In addition, gene expression data using NGS were obtained (Figure 2). We designed a new method for preparation of liquid marbles by using hydrophilic particles [1] (Fig.1). Salt-hydrogel marbles were prepared by atomising droplets of hydrogel solution in a cold air column followed by rolling of the collected hydrogel microbeads in a bed of micrometre size salt particles. Evaporation of the water from the resulting salt marbles with a hydrogel core yielded hollow-shell salt microcapsules. The method is not limited to hydrophilic particles and could potentially be also applied to other materials, such as graphite, carbon, silica and others. The structure and morphology of the salt-hydrogel marbles were analysed with SEM and their particle size distributions were measured. We also tested the dissolution times of the dried salt marbles compared them to these for table salt samples at the same conditions. The high accessible surface area of the shell of salt microcrystals allows a faster initial release of salt from the hollow-shell salt capsules upon their dissolution in water than from the same amount of table salt. The results suggest that such hollow-shell particles could find applications as a table salt substitute in dry food products and salt seasoning formulations with reduced salt content without the loss of saltiness. Please click Additional Files below to see the full abstract

An algorithm to classify homologous series within compound datasets

Homologous series are groups of related compounds that share the same core structure attached to a motif that repeats to different degrees. Compounds forming homologous series are of interest in multiple domains, including natural products, environmental chemistry, and drug design. However, many homologous compounds remain unannotated as such in compound datasets, which poses obstacles to understanding chemical diversity and their analytical identification via database matching. To overcome these challenges, an algorithm to detect homologous series within compound datasets was developed and implemented using the RDKit. The algorithm takes a list of molecules as SMILES strings and a monomer (i.e., repeating unit) encoded as SMARTS as its main inputs. In an iterative process, substructure matching of repeating units, molecule fragmentation, and core detection lead to homologous series classification through grouping of identical cores. Three open compound datasets from environmental chemistry (NORMAN Suspect List Exchange, NORMAN-SLE), exposomics (PubChemLite for Exposomics), and natural products (the COlleCtion of Open NatUral producTs, COCONUT) were subject to homologous series classification using the algorithm. Over 2000, 12,000, and 5000 series with CH2 repeating units were classified in the NORMAN-SLE, PubChemLite, and COCONUT respectively. Validation of classified series was performed using published homologous series and structure categories, including a comparison with a similar existing method for categorising PFAS compounds. The OngLai algorithm and its implementation for classifying homologues are openly available at: https://github.com/adelenelai/onglai-classify-homologues

No Talking, Just Writing! Efficacy of an Internet-Based Cognitive Behavioral Therapy with Exposure and Response Prevention in Obsessive Compulsive Disorder

Background: Many patients with obsessive-compulsive disorder (OCD) do not receive first-line treatment according to the current guidelines (cognitive behavioral therapy with exposure and response prevention, CBT with ERP) due to barriers to treatment. Internet-based therapy is designed to overcome these barriers. The present study evaluates the efficacy of an Internet-based writing therapy with therapeutic interaction based on the concept of CBT with ERP for patients with OCD. Methods: Thirty-four volunteers with OCD according to DSM-IV-criteria were included in the trial and randomized according to a waiting-list control design with follow-up measures at 8 weeks and 6 months. The intervention consisted of 14 sessions, either starting directly after randomization or with an 8-week delay. Main outcome measure was the change in the severity of OCD symptoms (Yale-Brown Obsessive Compulsive Scale Self- Rating, Y-BOCS SR, and Obsessive-Compulsive Inventory-Revised, OCI-R). Results: Obsessive-compulsive symptoms were significantly improved in the treatment group compared to the waiting-list control group with large effect sizes of Cohen's d = 0.82 (Y-BOCS SR) and d = 0.87 (OCI-R), using an intention-to-treat analysis. This effect remained stable at 6-month follow-up. Only 4 participants (12%) dropped out prematurely from the study. Of the 30 completers, 90% rated their condition as improved and would recommend the program to their friends. Conclusions: Internet-based writing therapy led to a significant improvement of obsessive-compulsive symptoms. Even though replications with larger sample sizes are needed, the results support the notion that Internet-based approaches have the potential for improving the treatment situation for patients with OCD

Fecal Microbiota Transplantation (FMT) as an Adjunctive Therapy for Depression-Case Report

Depression is a debilitating disorder, and at least one third of patients do not respond to therapy. Associations between gut microbiota and depression have been observed in recent years, opening novel treatment avenues. Here, we present the first two patients with major depressive disorder ever treated with fecal microbiota transplantation as add-on therapy. Both improved their depressive symptoms 4 weeks after the transplantation. Effects lasted up to 8 weeks in one patient. Gastrointestinal symptoms, constipation in particular, were reflected in microbiome changes and improved in one patient. This report suggests further FMT studies in depression could be worth pursuing and adds to awareness as well as safety assurance, both crucial in determining the potential of FMT in depression treatment

Into the unknown: expression profiling without genome sequence information in CHO by next generation sequencing

The arrival of next-generation sequencing (NGS) technologies has led to novel opportunities for expression profiling and genome analysis by utilizing vast amounts of short read sequence data. Here, we demonstrate that expression profiling in organisms lacking any genome or transcriptome sequence information is feasible by combining Illumina’s mRNA-seq technology with a novel bioinformatics pipeline that integrates assembled and annotated Chinese hamster ovary (CHO) sequences with information derived from related organisms. We applied this pipeline to the analysis of CHO cells which were chosen as a model system owing to its relevance in the production of therapeutic proteins. Specifically, we analysed CHO cells undergoing butyrate treatment which is known to affect cell cycle regulation and to increase the specific productivity of recombinant proteins. By this means, we identified sequences for >13 000 CHO genes which added sequence information of ∼5000 novel genes to the CHO model. More than 6000 transcript sequences are predicted to be complete, as they covered >95% of the corresponding mouse orthologs. Detailed analysis of selected biological functions such as DNA replication and cell cycle control, demonstrated the potential of NGS expression profiling in organisms without extended genome sequence to improve both data quantity and quality

Randomised controlled comparison of the Health Survey Short Form (SF-12) and the Graded Chronic Pain Scale (GCPS) in telephone interviews versus self-administered questionnaires. Are the results equivalent?

<p>Abstract</p> <p>Background</p> <p>The most commonly used survey methods are self-administered questionnaires, telephone interviews, and a mixture of both. But until now evidence out of randomised controlled trials as to whether patient responses differ depending on the survey mode is lacking. Therefore this study assessed whether patient responses to surveys depend on the mode of survey administration. The comparison was between mailed, self-administered questionnaires and telephone interviews.</p> <p>Methods</p> <p>A four-armed, randomised controlled two-period change-over design. Each patient responded to the same survey twice, once in written form and once by telephone interview, separated by at least a fortnight. The study was conducted in 2003/2004 in Germany. 1087 patients taking part in the German Acupuncture Trials (GERAC cohort study), who agreed to participate in a survey after completing acupuncture treatment from an acupuncture-certified family physician for headache, were randomised. Of these, 823 (664 women) from the ages of 18 to 83 (mean 51.7) completed both parts of the study. The main outcome measure was the comparison of the scores on the 12-Item Short-Form Health Survey (SF-12) and the Graded Chronic Pain Scale (GCPS) questionnaire for the two survey modes.</p> <p>Results</p> <p>Computer-aided telephone interviews (CATI) resulted in significantly fewer missing data (0.5%) than did mailed questionnaires (2.8%; p < 0.001). The analysis of equivalence revealed a difference between the survey modes only for the SF-12 mental scales. On average, reported mental status score was 3.5 score points (2.9 to 4.0) lower on the self-administered questionnaire compared to the telephone interview. The order of administration affected results. Patients who responded to the telephone interview first reported better mental health in the subsequent paper questionnaire (mean difference 2.8 score points) compared to those who responded to the paper questionnaire first (mean difference 4.1 score points).</p> <p>Conclusion</p> <p>Despite the comparatively high cost of telephone interviews, they offer clear advantages over mailed self-administered questionnaires as regards completeness of data. Only items concerning mental status were dependent on the survey mode and sequence of administration. Items on physical status were not affected. Normative data for standardized telephone questionnaires could contribute to a better comparability with the results of the corresponding standardized paper questionnaires.</p