Heat loss prediction of a confined premixed jet flame using a conjugate heat transfer approach

The presented work addresses the investigation of the heat loss of a confined turbulent jet flame in a lab-scale combustor using a conjugate-heat transfer approach and large-eddy simulation. The analysis includes the assessment of the principal mechanisms of heat transfer in this combustion chamber: radiation, convection and conduction of heat over walls. A staggered approach is used to couple the reactive flow field to the heat conduction through the solid and both domains are solved using two implementations of the same code. Numerical results are compared against experimental data and an assessment of thermal boundary conditions to improve the prediction of the reactive flow field is given.The research leading to these results has received funding through the People Programme (Marie Curie Actions) of the European Union’s Seventh Framework Programme (FP7, 2007–2013) under the Grant agreement No. FP7-290042 for the project COPA-GT as well as the European Union’s Horizon 2020 Programme (2014–2020) and from Brazilian Ministry of Science, Technology and Innovation through Rede Nacional de Pesquisa (RNP) under the HPC4E Project, Grant agreement No. 689772. The authors thankfully acknowledge the computer resources, technical expertise and assistance provided by the Red Española de Supercomputación (RES). Finally, the authors would like to thank O. Lammel for the useful discussions and kindly providing the data for the comparison.Peer ReviewedPostprint (published version

Study of the Wall Thermal Condition Effect in a Lean-Premixed Downscaled Can Combustor Using Large-Eddy Simulation

The primary purpose of this study is to evaluate the ability of LES, with a turbulent combustion model based on steady flamelets, to predict the flame stabilization mechanisms in an industrial can combustor at full load conditions. The test case corresponds to the downscaled Siemens can combustor tested in the high pressure rig at the DLR. The effects of the wall temperature on the prediction capabilities of the codes is investigated by imposing several heat transfer conditions at the pilot and chamber walls. The codes used for this work are Alya and OpenFOAM, which are well established CFD codes in the fluid mechanics community. Prior to the simulation, results for 1-D laminar flames at the operating conditions of the combustor are compared with the detailed solutions. Subsequently, results from both codes at the mid-plane are compared against the experimental data available. Acceptable results are obtained for the axial velocity, while discrepancies are more evident for the mixture fraction and the temperature, particularly with Alya. However, both codes showed that the heat losses influence the size and length of the pilot and main flame.The research leading to these results has received funding through the People Programme (Marie Curie Actions) of the European Union’s Seventh Framework Programme (FP7, 2007-2013) under the grant agreement No. FP7-290042 for the project COPA-GT and the European Union’s Horizon 2020 Programme (2014-2020) and from Brazilian Ministry of Science, Technology and Innovation through Rede Nacional de Pesquisa (RNP) under the HPC4E Project, grant agreement No. 689772. The authors thankfully acknowledge the computer resources, technical expertise and assistance provided by the Red Española de Supercomputación (RES).Peer ReviewedPostprint (author's final draft

Eine funktionale Charakterisierung der Transplantat-Akzeptanz-Induzierende Zelle

Clinical organ transplantation became the therapy of choice for endstage organ diseases. This development was closed related to the history of potent immunosuppressive drugs. Although major progress in the improvement of immunosuppressive therapy regimes was made, long-term graft survival is still limited and recipients are affected due to several adverse effects. For this reason numerous attempts were undertaken to induce operational tolerance. This thesis engaged in an attempt in which a subset of monocytes, named Transplant Acceptance Inducing Cells (TAIC), is given to patients in order to substitute conventional immunosuppressive therapy. The focus of the thesis was the detection of potential immunosuppressive effects to allogeneic lymphocytes induced by TAIC cells in in-vitro co-cultures. Further a case study was performed to demonstrate an interesting outcome of a renal transplant patient who received TAIC cells and to show the clinical feasibility of this treatment. First experiments indicated that TAIC cells are able to suppress the proliferation of allogeneic CD8+ T cells under co-culture conditions, provided that the T cells are existent in a mitogen activated state. Without the addition of mitogen to co-cultures, TAIC cells promoted the survival of allogeneic lymphocytes. Under changed conditions, which were closer related to previous undertaken clinical TAIC trials, TAIC cells suppressed both CD4+ and CD8+ mitogen stimulated allogeneic lymphocytes. In absence of mitogen stimulation TAIC cells were not able to rescue allogeneic lymphocytes from death by neglect. Although these results apparently demonstrate immunosuppressive properties of TAIC cells adverse activated allogeneic lymphocytes, it is obligatory to identify the exact mode of function of these cells in order to distinguish them clearly from other macrophage subsets with immunoregulatory features. The described renal transplant patient in the case study received TAIC cells afterwards the transplantation as an adjunct immunosuppressive therapy within an alternative healing attempt. The infusion of TAIC cells proceeded without any complications and the subsequent reduction of immunosuppressants up to a low grade tacrolimus monotherapy was well tolerated by the patient for the almost last five years. A biopsy, which was taken in the 17th week after transplantation, showed an unusual pattern of focal lymphocytic infiltration how it was already seen in spontaneously tolerant kidney transplant patients. Both the undertaken experiments and the described case study in this thesis demonstrate that TAIC cells have immunosuppressive characteristics which might have the potential to become a feasible immunosuppressive therapy approach in the clinic. But therefore it is necessary that further studies depict the specific mode of function of those cells and that meaningful clinical trials definitely prove the beneficial effect of TAIC cells in transplant patient. Furthermore it is needed that long-term experiments exclude potential adverse effects.Die Transplantation von Organen hat sich zur Therapie der Wahl von zahlreichen Organerkrankungen im Endstadium entwickelt. Insbesondere die Zunahme potenter immunsuppressiver Medikamente hat einen entscheidenden Beitrag zu dieser Entwicklung geleistet. Dennoch ist das langfristige Transplantatüberleben begrenzt und die Patienten müssen beträchtliche Nebenwirkung der immunsuppressiven Therapie in Kauf nehmen. Aus diesem Grund ist einer der zentralen Forschungsansätze der Transplantationsmedizin die Induktion peripherer Toleranz im Organempfänger. Diese Arbeit beschäftigt sich mit einer speziellen Form regulatorischer Makrophagen, so genannter Transplantat Akzeptanz-Induzierender Zellen (TAIZ), die Patienten verabreicht werden mit dem Ziel die konventionelle immunsuppressive Therapie zu ersetzen. Der Schwerpunkt dieser Arbeit liegt auf der Untersuchung möglicher immunsuppressiver Effekte humaner TAIZ Zellen gegenüber allogenen Lymphozyten in in-vitro Kokulturen. Weiterhin wurde ein Case Report erstellt, um das interessante klinische Ergebnis eines nierentransplantierten Patienten vorzustellen, der mit TAIZ Zellen behandelt wurde. Ziel dieses Berichtes ist es aufzuzeigen, dass die Therapie mit TAIZ Zellen ein potentiell klinisch anwendbares Verfahren darstellt. In den ersten Experimenten wird dargelegt, dass TAIZ Zellen in der Lage sind unter Kokultur-Bedingungen die Proliferation allogener CD8+ T-Zellen zu unterdrücken; vorausgesetzt, dass sich T-Zellen in einem Mitogen-aktivierten Zustand befinden. Ohne die Zugabe eines Mitogens zu den Kokulturen verlängerten TAIZ Zellen das Überleben allogener Lymphozyten. Unter ähnlichen Bedingungen wie in zuvor durchgeführten klinischen Studien mit TAIZ Zellen, unterdrückten TAIZ Zellen sowohl CD4+, als auch CD8+ Mitogen-stimulierte allogene Lymphozyten. Ohne die Zugabe eines Mitogens waren TAIZ Zellen nicht in der Lage allogene Lymphozyten vor dem "death by neglect" zu retten. Obwohl diese Resultate deutlich immunsuppressive Eigenschaften von TAIZ Zellen gegenüber aktivierten allogen Lymphozyten demonstrieren, ist es notwendig die exakte Funtkionsweise dieser Zellen zu identifizieren, um sie klar von anderen Makrophagen mit immunregulatorischen Eigenschaften zu unterscheiden. Der in dem Fallbericht beschriebene Patient hat TAIZ Zellen nach einer Nierentransplantation als eine ergänzende immunsuppressive Therapie im Rahmen eines alternativen Heilansatzes erhalten. Die Infusion der TAIZ Zellen verlief komplikationslos und die anschließende Reduktion der Immunsuppression bis hin zu einer geringgradigen Tacrolimus Monotherapie wurde von dem Patienten über einen Zeitraum von fünf Jahren gut vertragen. Eine Biopsie, die in der siebzehnten Woche nach der Transplantation durchgeführt wurde, zeigte ein ungewöhnliches Bild fokaler Lymphozyteninfiltrate wie es bereits in spontan toleranten nierentransplantierten Patienten gesehen wurde. Sowohl die durchgeführten Experimente, als auch der beschriebene Fallbericht in dieser Arbeit zeigen, dass TAIZ Zellen immunsuppressive Eigenschaften besitzen, die durchaus das Potential für eine klinisch praktikable immunsuppressive Therapie haben. Dafür ist es zunächst jedoch noch notwendig, dass die genaue Funktionsweise dieser Zellen dargestellt wird und dass aussagekräftige Studien die Wirksamkeit von TAIZ Zellen belegen. Weiterhin müssen langfristige Nebenwirkungen ausgeschlossen werden

Antibody-related movement disorders - a comprehensive review of phenotype-autoantibody correlations and a guide to testing

Background: Over the past decade increasing scientific progress in the field of autoantibody–mediated neurological diseases was achieved. Movement disorders are a frequent and often prominent feature in such diseases which are potentially treatable. Main body: Antibody-mediated movement disorders encompass a large clinical spectrum of diverse neurologic disorders occurring either in isolation or accompanying more complex autoimmune encephalopathic diseases. Since autoimmune movement disorders can easily be misdiagnosed as neurodegenerative or metabolic conditions, appropriate immunotherapy can be delayed or even missed. Recognition of typical clinical patterns is important to reach the correct diagnosis. Conclusion: There is a growing number of newly discovered antibodies which can cause movement disorders. Several antibodies can cause distinctive phenotypes of movement disorders which are important to be aware of. Early diagnosis is important because immunotherapy can result in major improvement. In this review article we summarize the current knowledge of autoimmune movement disorders from a point of view focused on clinical syndromes. We discuss associated clinical phenomenology and antineuronal antibodies together with alternative etiologies with the aim of providing a diagnostic framework for clinicians considering underlying autoimmunity in patients with movement disorders

Temporal discrimination is altered in patients with isolated asymmetric and jerky upper limb tremor

Background: Unilateral or very asymmetric upper limb tremors with a jerky appearance are poorly investigated. Their clinical classification is an unsolved problem because their classification as essential tremor versus dystonic tremor is uncertain. To avoid misclassification as essential tremor or premature classification as dystonic tremor, the term indeterminate tremor was suggested. Objectives: The aim of this study was to characterize this tremor subgroup electrophysiologically and evaluate whether diagnostically meaningful electrophysiological differences exist compared to patients with essential tremor and dystonic tremor. Methods: We enrolled 29 healthy subjects and 64 patients with tremor: 26 with dystonic tremor, 23 with essential tremor, and 15 patients with upper limb tremor resembling essential tremor but was unusually asymmetric and jerky (indeterminate tremor). We investigated the somatosensory temporal discrimination threshold, the short-interval intracortical inhibition, and the cortical plasticity by paired associative stimulation. Results: Somatosensory temporal discrimination threshold was significantly increased in patients with dystonic tremor and indeterminate tremor, but it was normal in the essential tremor patients and healthy controls. Significant differences in short-interval intracortical inhibition and paired associative stimulation were not found among the three patient groups and controls. Conclusion: These results indicate that indeterminate tremor, as defined in this study, shares electrophysiological similarities with dystonic tremor rather than essential tremor. Therefore, we propose that indeterminate tremor should be considered as a separate clinical entity from essential tremor and that it might be dystonic in nature. Somatosensory temporal discrimination appears to be a useful tool in tremor classification

The spectrum of involuntary vocalizations in humans: A video atlas

In clinical practice, involuntary vocalizing behaviors are typically associated with Tourette syndrome and other tic disorders. However, they may also be encountered throughout the entire tenor of neuropsychiatry, movement disorders, and neurodevelopmental syndromes. Importantly, involuntary vocalizing behaviors may often constitute a predominant clinical sign, and, therefore, their early recognition and appropriate classification are necessary to guide diagnosis and treatment. Clinical literature and video‐documented cases on the topic are surprisingly scarce. Here, we pooled data from 5 expert centers of movement disorders, with instructive video material to cover the entire range of involuntary vocalizations in humans. Medical literature was also reviewed to document the range of possible etiologies associated with the different types of vocalizing behaviors and to explore treatment options. We propose a phenomenological classification of involuntary vocalizations within different categorical domains, including (1) tics and tic‐like vocalizations, (2) vocalizations as part of stereotypies, (3) vocalizations as part of dystonia or chorea, (4) continuous vocalizing behaviors such as groaning or grunting, (5) pathological laughter and crying, (6) vocalizations resembling physiological reflexes, and (7) other vocalizations, for example, those associated with exaggerated startle responses, as part of epilepsy and sleep‐related phenomena. We provide comprehensive lists of their associated etiologies, including neurodevelopmental, neurodegenerative, neuroimmunological, and structural causes and clinical clues. We then expand on the pathophysiology of the different vocalizing behaviors and comment on available treatment options. Finally, we present an algorithmic approach that covers the wide range of involuntary vocalizations in humans, with the ultimate goal of improving diagnostic accuracy and guiding appropriate treatment

Development of parkinsonism after long-standing cervical dystonia – A cohort

INTRODUCTION: Dystonia occurring in the context of parkinsonism is well-known, e.g. as foot dystonia in young-onset Parkinson's disease (PD), anterocollis in multisystem atrophy (MSA) or blepharospasm (levator inhibition) in progressive supranuclear palsy. We have, however, encountered a series of patients whose phenotype differed from the above described entities. METHODS: We describe a cohort of patients in whom typical idiopathic isolated (primary) late-onset focal or segmental (predominantly cervical) dystonia preceded the development of parkinsonism by several years, sometimes decades. RESULTS: In a cohort of 450 patients followed in our botulinum toxin injections clinic, we identified 11 (2.4%; 7 women) who developed parkinsonism at a median of 14 years after the onset of dystonia. Median age at onset of parkinsonism was 70 years (range 59-87), usually manifesting with a new tremor or a change of tremor pattern, complaints of 'slowing down' or new walking difficulties. Parkinsonism resembled PD in 5 (one pathologically confirmed); the remainder had atypical parkinsonism of MSA (n = 3) or indeterminate phenotype (n = 3). CONCLUSION: The relatively frequent occurrence of parkinsonism after long-standing dystonia would suggest a link between the two, in line with evidence from other clinical reports, imaging studies, animal models and genetics. It appears that in some cases of dystonia this could be an antecedent manifestation of a syndrome with parkinsonism developing later, or be a risk factor for parkinsonism. In practice, it is important for clinicians to be alert to new symptoms/signs in patients with long-standing dystonia. From a research point of view, longitudinal case-control studies would be required to further investigate the link between long-standing dystonia and subsequent parkinsonism

The spectrum of involuntary vocalizations in humans: A video atlas

In clinical practice, involuntary vocalizing behaviors are typically associated with Tourette syndrome and other tic disorders. However, they may also be encountered throughout the entire tenor of neuropsychiatry, movement disorders, and neurodevelopmental syndromes. Importantly, involuntary vocalizing behaviors may often constitute a predominant clinical sign, and, therefore, their early recognition and appropriate classification are necessary to guide diagnosis and treatment. Clinical literature and video-documented cases on the topic are surprisingly scarce. Here, we pooled data from 5 expert centers of movement disorders, with instructive video material to cover the entire range of involuntary vocalizations in humans. Medical literature was also reviewed to document the range of possible etiologies associated with the different types of vocalizing behaviors and to explore treatment options. We propose a phenomenological classification of involuntary vocalizations within different categorical domains, including (1) tics and tic-like vocalizations, (2) vocalizations as part of stereotypies, (3) vocalizations as part of dystonia or chorea, (4) continuous vocalizing behaviors such as groaning or grunting, (5) pathological laughter and crying, (6) vocalizations resembling physiological reflexes, and (7) other vocalizations, for example, those associated with exaggerated startle responses, as part of epilepsy and sleep-related phenomena. We provide comprehensive lists of their associated etiologies, including neurodevelopmental, neurodegenerative, neuroimmunological, and structural causes and clinical clues. We then expand on the pathophysiology of the different vocalizing behaviors and comment on available treatment options. Finally, we present an algorithmic approach that covers the wide range of involuntary vocalizations in humans, with the ultimate goal of improving diagnostic accuracy and guiding appropriate treatment

EnzyMiner: automatic identification of protein level mutations and their impact on target enzymes from PubMed abstracts

BACKGROUND: A better understanding of the mechanisms of an enzyme's functionality and stability, as well as knowledge and impact of mutations is crucial for researchers working with enzymes. Though, several of the enzymes' databases are currently available, scientific literature still remains at large for up-to-date source of learning the effects of a mutation on an enzyme. However, going through vast amounts of scientific documents to extract the information on desired mutation has always been a time consuming process. In this paper, therefore, we describe an unique method, termed as EnzyMiner, which automatically identifies the PubMed abstracts that contain information on the impact of a protein level mutation on the stability and/or the activity of a given enzyme. RESULTS: We present an automated system which identifies the abstracts that contain an amino-acid-level mutation and then classifies them according to the mutation's effect on the enzyme. In the case of mutation identification, MuGeX, an automated mutation-gene extraction system has an accuracy of 93.1% with a 91.5 F-measure. For impact analysis, document classification is performed to identify the abstracts that contain a change in enzyme's stability or activity resulting from the mutation. The system was trained on lipases and tested on amylases with an accuracy of 85%. CONCLUSION: EnzyMiner identifies the abstracts that contain a protein mutation for a given enzyme and checks whether the abstract is related to a disease with the help of information extraction and machine learning techniques. For disease related abstracts, the mutation list and direct links to the abstracts are retrieved from the system and displayed on the Web. For those abstracts that are related to non-diseases, in addition to having the mutation list, the abstracts are also categorized into two groups. These two groups determine whether the mutation has an effect on the enzyme's stability or functionality followed by displaying these on the web