Homology Assessment in Molecular Phylogenetics : Evaluation, Improvement, and Influence of Data Quality on Tree Reconstruction

Considering the final goal of every phylogenetic analysis, the reconstruction of taxon relationships from underlying data, little attention has been paid to the role of alignment accuracy and its impact on tree reconstruction. Alignment masking approaches are methods which detect and remove erroneously aligned sections before tree reconstruction. I describe the effect of two masking methods on alignment quality and tree reconstruction. While masking methods are commonly efficient in detecting ambiguously aligned sequence blocks, all methods more or less lack the ability to detect heterogeneous sequence divergence within sequence alignments. This is a main disadvantage of masking approaches, because undetected heterogeneous sequence divergence can result in a strong bias in tree reconstructions. I give a detailed description of a new developed algorithm and the possibility of tagging branches as an indirect estimation of reliability of a subset of possible splits guided by a topology. The performance of the new algorithm was tested on simulated and empirical data. Considering the tree reconstruction process, the first task is the choice of an appropriate tree reconstruction method. Examining theoretical studies and comparative tests Maximum Likelihood turns out as the first choice for phylogenetic tree reconstructions. I show that the success of Maximum Likelihood depends not only on the degree of alignment quality, but also on the relation of branch length differences of underlying topologies. I tested the robustness of Maximum Likelihood towards different classes of long branch effects in multiple taxon topologies by using simulated fixed data sets under two different 11-taxon trees and a broad range of different branch length conditions with sequence alignments of different length. Some of the most important scripts and pipelines which have been written for the accomplishment of this thesis are also described

Using Activated Charcoal to Reuse Anesthetic Gas

General anesthesia enables surgery, with anesthesia machines being the predominant tool to do so. However, these machines are hard to maintain, costly, and require significant supporting infrastructure. The current design of anesthesia machines demands the disposal of anesthetic gases at a rate equal to fresh oxygen entering the system. This causes several orders of magnitude more anesthetic vaporized than needed, yielding negative economic and environmental impact. To address this, we propose utilizing the porous surface of activated charcoal to absorb and desorb the anesthetic gases to be reused

Parametric and non-parametric masking of randomness in sequence alignments can be improved and leads to better resolved trees

<p>Abstract</p> <p>Background</p> <p>Methods of alignment masking, which refers to the technique of excluding alignment blocks prior to tree reconstructions, have been successful in improving the signal-to-noise ratio in sequence alignments. However, the lack of formally well defined methods to identify randomness in sequence alignments has prevented a routine application of alignment masking. In this study, we compared the effects on tree reconstructions of the most commonly used profiling method (GBLOCKS) which uses a predefined set of rules in combination with alignment masking, with a new profiling approach (ALISCORE) based on Monte Carlo resampling within a sliding window, using different data sets and alignment methods. While the GBLOCKS approach excludes variable sections above a certain threshold which choice is left arbitrary, the ALISCORE algorithm is free of <it>a priori </it>rating of parameter space and therefore more objective.</p> <p>Results</p> <p>ALISCORE was successfully extended to amino acids using a proportional model and empirical substitution matrices to score randomness in multiple sequence alignments. A complex bootstrap resampling leads to an even distribution of scores of randomly similar sequences to assess randomness of the observed sequence similarity. Testing performance on real data, both masking methods, GBLOCKS and ALISCORE, helped to improve tree resolution. The sliding window approach was less sensitive to different alignments of identical data sets and performed equally well on all data sets. Concurrently, ALISCORE is capable of dealing with different substitution patterns and heterogeneous base composition. ALISCORE and the most relaxed GBLOCKS gap parameter setting performed best on all data sets. Correspondingly, Neighbor-Net analyses showed the most decrease in conflict.</p> <p>Conclusions</p> <p>Alignment masking improves signal-to-noise ratio in multiple sequence alignments prior to phylogenetic reconstruction. Given the robust performance of alignment profiling, alignment masking should routinely be used to improve tree reconstructions. Parametric methods of alignment profiling can be easily extended to more complex likelihood based models of sequence evolution which opens the possibility of further improvements.</p

Improved Phylogenetic Analyses Corroborate a Plausible Position of Martialis heureka in the Ant Tree of Life

Martialinae are pale, eyeless and probably hypogaeic predatory ants. Morphological character sets suggest a close relationship to the ant subfamily Leptanillinae. Recent analyses based on molecular sequence data suggest that Martialinae are the sister group to all extant ants. However, by comparing molecular studies and different reconstruction methods, the position of Martialinae remains ambiguous. While this sister group relationship was well supported by Bayesian partitioned analyses, Maximum Likelihood approaches could not unequivocally resolve the position of Martialinae. By re-analysing a previous published molecular data set, we show that the Maximum Likelihood approach is highly appropriate to resolve deep ant relationships, especially between Leptanillinae, Martialinae and the remaining ant subfamilies. Based on improved alignments, alignment masking, and tree reconstructions with a sufficient number of bootstrap replicates, our results strongly reject a placement of Martialinae at the first split within the ant tree of life. Instead, we suggest that Leptanillinae are a sister group to all other extant ant subfamilies, whereas Martialinae branch off as a second lineage. This assumption is backed by approximately unbiased (AU) tests, additional Bayesian analyses and split networks. Our results demonstrate clear effects of improved alignment approaches, alignment masking and data partitioning. We hope that our study illustrates the importance of thorough, comprehensible phylogenetic analyses using the example of ant relationships

Improving Technologies in Anesthesia

General anesthesia is well known to offer physicians access to a broad variety of invasive procedures otherwise deemed too risky. Anesthesia machines provides the means for anesthetizing patients safely in the hospital operating room. However, these devices are increasingly unable to meet the demands and needs outside of the hospital. Developing countries struggle to purchase and maintain these costly devices, leading to a 40-fold increase in anesthesia-related deaths compared to developed countries. Small-office practices in the United States experience significantly poorer anesthesia outcomes and increased legal claims versus their larger hospital counterparts, resulting in 60% more anesthesia-related deaths. Environmental impacts and global health concerns from the emitted anesthetic gases have brought into serious question the prevailing notion that unchecked emissions were sustainable. These factors can all be attributed to anesthesia machine design and technology having the primary intended use in the traditional operating room. The long-term goal of this work is to develop technologies in anesthesia that expand its safe use, decrease underlying costs, and reduce the total emissions. The immediate objective of this work is to create a feedback-controlled anesthetic gas vaporizer-scavenger system and evaluate its performance. The central hypothesis is that the combined use of mesoporous materials and feedback control provide the opportunity for repeatable capture and release of expired anesthetic gases during anesthesia delivery. Our rationale is that such a device will help reduce the amount of anesthetic needed while simultaneously offering improved control over the delivery of anesthetic gases

A New Era of Anesthetic Equipment

Long duration space missions are becoming highly probable, and with them arise new challenges. Maintaining the long term health of astronauts and developing the appropriate equipment for advanced medical interventions suitable for space becomes incredibly important. Surgical interventions especially are a problematic scene given the complexity and size of the required equipment for general anesthesia. As a result, creating advanced inhalational anesthetic devices that are small and light weight is needed for these long duration space missions. The past decade has brought a host of advances that would allow the development of smarter, smaller, lighter, and more efficient machines. These include pharmacokinetic and pharmaco-dynamic models to create feedback delivery systems, better sensing technologies to meter precise gas delivery, and closed breathing circuits that conserve anesthetic agents. However, despite these advances, anesthetic machines and devices still remain incredibly heavy and bulky, and ill-suited for space travel. A brief summary of technological advances will be discussed as well as preliminary results in measuring the concentration of volatile anesthetics using convective heat transfer principles

Molecular phylogenetics: In spite of impressive advances, there remains a need for research on biological and methodical questions:

Die Erforschung der Stammesgeschichte der Organismen hat mit der Entwicklung der Molekulargenetik große Fortschritte gemacht. Wesentlich waren die Entwicklung der Sequenziertechniken für genomische DNA und effiziente heuristische Verfahren für die Datenanalyse. Die traditionelle Klassifikation der Tiere konnte mehrfach revidiert werden, es bleiben jedoch ungeklärte Fragen. Ergebnisse widersprechen sich oft, besonders wenn Ereignisse aus der Frühzeit der Evolution der Vielzeller rekonstruiert werden. In anderen Fällen lassen sich aus DNA-Daten errechnete Stammbäume nicht mit anatomischen Daten in Einklang bringen. Systematische Fehler der Algorithmen sowie die Verfügbarkeit von einem phylogenetischen Signal in den Daten müssen weiter erforscht werden.With the recent development of molecular genetics, research on the phylogeny of organisms has made great progress. In particular, the development of new DNA sequencing techniques and efficient heuristic methods for data analysis have been important. Repeatedly, the traditional classification of animals could be revised; however, there remain unanswered questions. The results are often contradictory, especially when events from the early days of the evolution of multicellular organisms are reconstructed. In other cases, phylogenetic trees obtained from DNA data do not match the anatomical data. Systematic errors of algorithms as well as the availability of a phylogenetic signal in the data need further investigation