Detaillierte Untersuchungen der Oxidationschemie verschiedener konventioneller und alternativer Brennstoffe und Brennstoffgemische

Pieper J. Detaillierte Untersuchungen der Oxidationschemie verschiedener konventioneller und alternativer Brennstoffe und Brennstoffgemische. Bielefeld: Universität Bielefeld; 2018.It is well known that emissions from combustion processes are harmful and dangerous for climate, air quality, environment and health. However, a significant increase of anthropogenic CO2, particulate matter, and soot has been measured over the past years. Since more than 80% of the global primary energy is still covered by fossil energy sources, an immediate substitution by renewable energy is not yet possible and efficient and cleaner alternatives are needed for the transition period in the next 10-20~years. To achieve such cleaner combustion goals, several changes in different fields should be considered, while in engine combustion two main approaches are pursued. These suggested developments include the technical approach of a homogeneous low-temperature combustion, which is supposed to lead to a lower emission of pollutants, as well as the use of alternative fuels (e.g. alcohols, ethers, esters) with a proposed cleaner emission than prototypical fuels. However, due to their different molecular structures including heteroatoms, they often exhibit a very different species distribution in their combustion. The respective chemical composition can lead to the emission of toxic species or pollutants that can have negative influences on human health and the atmosphere by photochemical reactions. Therefore, the combustion behavior of these types of fuels needs to be analyzed in more detail to gain understanding of their complex reaction pathways, especially in the low-temperature regime. Technical studies often analyze global parameters of combustion as e.g. ignition delay times, flame speeds or the concentration of unburnt hydrocarbons at the tailpipe. However, from the chemical point-of-view, the combustion process is highly complex. Therefore, the aim of this work was to achieve detailed knowledge about specific reaction pathways in the combustion process of different fuels and fuel mixtures to help evaluating the potential of possible alternative fuels and fuel additives. For this purpose, laminar premixed low-pressure flames and a laminar flow reactor were used as model experiments on a laboratory scale to cover a broad range of the relevant phase space including temperature, pressure and stoichiometry. The species distributions in different oxidation processes were analyzed by molecular-beam mass spectrometry serving as a universal technique to measure a multitude of species at the same time. A combination of different ionization techniques covering electron impact ionization, photoionization and photoelectron/photoion coincidence spectroscopy has been used to cross-validate the obtained data and to gain complementary information for a detailed structure analysis of species occuring in the oxidation processes. Therefore measurements at Bielefeld University were combined with several measurements at large-scale setups using synchrotron-generated vacuum-ultraviolet radiation from the Advanced Light Source in Berkeley, USA, the National Synchrotron Radiation Laboratory in Hefei, China and the SOLEIL Synchrotron in Gif-sur-Yvette, France. Furthermore, the experimental data has been complemented by specific and internally consistent reference measurements, theoretical calculations and kinetic modeling as a connection between laboratory-scale experiments and technical processes. The main focus of this work was the investigation of alternative fuels and their influences on the combustion process of mixtures, as these are already used on the road (e.g. E10, biodiesel). Adding alternative fuels to prototypical compounds can have a significant impact on the reacitivity and the reaction pathways of the oxidation leading to interaction between species rising from the oxidation process. Currently, only little information is available on these mixing effects. Therefore, several pure fuels as well as mixtures of prototypical and alternative fuel candidates have been analyzed in the low- and high-temperature environment to investigate the influence of fuel additives and interactive effects in mixtures. As a fundamental result of this work it could be confirmed that a combination of several experimental techniques together with theoretical calculations and kinetic modeling is very important and necessary to obtain the complex information needed on the combustion process of fuels. The results revealed that the molecular structure of the fuel molecules as well as the oxidation environment are of significant influence for the reaction pathways and therefore the formation of possible pollutants. For the addition of alcohols and ethers very strong and partially contrary influences on the fuels reactivity and the resulting species distribution could be observed for the low- and high-temperature regime. While in a high-temperature environment only small effects and mainly on the formation of soot precursors were found, the reactivity of the mixtures was dramatically influenced in a low-temperature environment leading to a different species distribution, enabling the possibility to influence the combustion process by changing the oxidation environment and a selective addition of specific components. Furthermore, the experimental results of this work have contributed to the further development and validation of several kinetic models by detecting new species and possible reaction pathways that have not been included in simulations before, but can be used to improve the predictability of such mechanisms in the future

Social anxiety in adolescents and young adults from the general population: an epidemiological characterization of fear and avoidance in different social situations

Social Anxiety Disorder (SAD) and, more generally, social fears are common in young people. Although avoidance behaviors are known to be an important maintaining factor of social anxiety, little is known about the severity and occurrence of avoidance behaviors in young people from the general population, hampering approaches for early identification and intervention. Symptoms, syndromes, and diagnoses of DSM-5 mental disorders including SAD were assessed in a random population-based sample of 14-21-year-olds (n = 1,180) from Dresden, Germany, in 2015/2016 using a standardized diagnostic interview (DIA-X-5/D-CIDI). An adapted version of the Liebowitz Social Anxiety Scale was used to ascertain the extent of social fears and avoidance. Diagnostic criteria for lifetime SAD were met by n = 82 participants, resulting in a weighted lifetime prevalence of 6.6%. Social anxiety was predominantly reported for test situations and when speaking or performing in front of others. Avoidance was most prevalent in the latter situations. On average, anxiety and avoidance first occurred at ages 11 and 12, respectively, with avoidance occurring in most cases either at about the same age as anxiety or slightly later. In the total sample, lifetime prevalence for most DSM-5 disorders increased with the severity of social anxiety and avoidance. Results underline the need for preventive or early intervention efforts especially regarding test anxiety and fear and avoidance of speaking in front of others. These situations are particularly relevant in youth. Avoidance behaviors may also be discussed as diagnostic marker for early case identification

Process data of allogeneic ex vivo-expanded ABCB5+ mesenchymal stromal cells for human use: Off-the-shelf GMP-manufactured donor-independent ATMP

© 2020, The Author(s). Background: Human dermal mesenchymal stromal cells (MSCs) expressing the ATP-binding cassette (ABC) efflux transporter ABCB5 represent an easily accessible MSC population that, based on preclinical and first-in-human data, holds significant promise to treat a broad spectrum of conditions associated not only with skin-related but also systemic inflammatory and/or degenerative processes. Methods: We have developed a validated Good Manufacturing Practice-compliant expansion and manufacturing process by which ABCB5+ MSCs derived from surgical discard skin tissues are processed to an advanced-therapy medicinal product (ATMP) for clinical use. Enrichment for ABCB5+ MSCs is achieved in a three-step process involving plastic adherence selection, expansion in a highly efficient MSC-selecting medium, and immunomagnetic isolation of the ABCB5+ cells from the mixed culture. Results: Product Quality Review data covering 324 cell expansions, 728 ABCB5+ MSC isolations, 66 ABCB5+ MSC batches, and 85 final drug products reveal high process robustness and reproducible, reliable quality of the manufactured cell therapy product. Conclusion: We have successfully established an expansion and manufacturing process that enables the generation of homogenous ABCB5+ MSC populations of proven biological activity manufactured as a standardized, donor-independent, highly pure, and highly functional off-the-shelf available ATMP, which is currently tested in multiple clinical trials

The prevalence of pain at pressure areas and pressure ulcers in hospitalised patients.

Background: Patients with pressure ulcers (PUs) report that pain is their most distressing symptom, but there are few PU pain prevalence studies. We sought to estimate the prevalence of unattributed pressure area related pain (UPAR pain) which was defined as pain, soreness or discomfort reported by patients, on an " at risk" or PU skin site, reported at a patient level.Methods: We undertook pain prevalence surveys in 2 large UK teaching hospital NHS Trusts (6 hospitals) and a district general hospital NHS Trust (3 hospitals) during their routine annual PU prevalence audits. The hospitals provide secondary and tertiary care beds in acute and elective surgery, trauma and orthopaedics, burns, medicine, elderly medicine, oncology and rehabilitation. Anonymised individual patient data were recorded by the ward nurse and PU prevalence team. The analysis of this prevalence survey included data summaries; no inferential statistical testing was planned or undertaken. Percentages were calculated using the total number of patients from the relevant population as the denominator (i.e. including all patients with missing data for that variable).Results: A total of 3,397 patients in 9 acute hospitals were included in routine PU prevalence audits and, of these, 2010 (59.2%) patients participated in the pain prevalence study. UPAR pain prevalence was 16.3% (327/2010). 1769 patients had no PUs and of these 223 patients reported UPAR pain, a prevalence of 12.6%. Of the 241 people with pressure ulcers, 104 patients reported pain, a UPAR pain prevalence of 43.2% (104/241).Conclusion: One in six people in acute hospitals experience UPAR pain on 'at risk' or PU skin sites; one in every 8 people without PUs and, more than 2 out of every five people with PUs. The results provide a clear indication that all patients should be asked if they have pain at pressure areas even when they do not have a PU

Mapping genetic variations to three- dimensional protein structures to enhance variant interpretation: a proposed framework

The translation of personal genomics to precision medicine depends on the accurate interpretation of the multitude of genetic variants observed for each individual. However, even when genetic variants are predicted to modify a protein, their functional implications may be unclear. Many diseases are caused by genetic variants affecting important protein features, such as enzyme active sites or interaction interfaces. The scientific community has catalogued millions of genetic variants in genomic databases and thousands of protein structures in the Protein Data Bank. Mapping mutations onto three-dimensional (3D) structures enables atomic-level analyses of protein positions that may be important for the stability or formation of interactions; these may explain the effect of mutations and in some cases even open a path for targeted drug development. To accelerate progress in the integration of these data types, we held a two-day Gene Variation to 3D (GVto3D) workshop to report on the latest advances and to discuss unmet needs. The overarching goal of the workshop was to address the question: what can be done together as a community to advance the integration of genetic variants and 3D protein structures that could not be done by a single investigator or laboratory? Here we describe the workshop outcomes, review the state of the field, and propose the development of a framework with which to promote progress in this arena. The framework will include a set of standard formats, common ontologies, a common application programming interface to enable interoperation of the resources, and a Tool Registry to make it easy to find and apply the tools to specific analysis problems. Interoperability will enable integration of diverse data sources and tools and collaborative development of variant effect prediction methods

Milvexian vs Apixaban for Stroke Prevention in Atrial Fibrillation: The LIBREXIA Atrial Fibrillation Trial Rationale and Design

BACKGROUND: Direct oral anticoagulants are the standard of care for stroke prevention in eligible patients with atrial fibrillation and atrial flutter; however, bleeding remains a significant concern, limiting their use. Milvexian is an oral Factor XIa inhibitor that may offer similar anticoagulant efficacy with less bleeding risk. METHODS: LIBREXIA AF (NCT05757869) is a global phase III, randomized, double-blind, parallel-group, event-driven trial to compare milvexian with apixaban in participants with atrial fibrillation or atrial flutter. Participants are randomly assigned to milvexian 100 mg or apixaban (5 mg or 2.5 mg per label indication) twice daily. The primary efficacy objective is to evaluate if milvexian is noninferior to apixaban for the prevention of stroke and systemic embolism. The principal safety objective is to evaluate if milvexian is superior to apixaban in reducing the endpoint of International Society of Thrombosis and Hemostasis (ISTH) major bleeding events and the composite endpoint of ISTH major and clinically relevant nonmajor (CRNM) bleeding events. In total, 15,500 participants from approximately 1,000 sites in over 30 countries are planned to be enrolled. They will be followed until both 430 primary efficacy outcome events and 530 principal safety events are observed, which is estimated to take approximately 4 years. CONCLUSION: The LIBREXIA AF study will determine the efficacy and safety of the oral Factor XIa inhibitor milvexian compared with apixaban in participants with either atrial fibrillation or atrial flutter. TRIAL REGISTRATION: ClinicalTrials.gov NCT05757869

In-situ estimation of ice crystal properties at the South Pole using LED calibration data from the IceCube Neutrino Observatory

The IceCube Neutrino Observatory instruments about 1 km3 of deep, glacial ice at the geographic South Pole using 5160 photomultipliers to detect Cherenkov light emitted by charged relativistic particles. A unexpected light propagation effect observed by the experiment is an anisotropic attenuation, which is aligned with the local flow direction of the ice. Birefringent light propagation has been examined as a possible explanation for this effect. The predictions of a first-principles birefringence model developed for this purpose, in particular curved light trajectories resulting from asymmetric diffusion, provide a qualitatively good match to the main features of the data. This in turn allows us to deduce ice crystal properties. Since the wavelength of the detected light is short compared to the crystal size, these crystal properties do not only include the crystal orientation fabric, but also the average crystal size and shape, as a function of depth. By adding small empirical corrections to this first-principles model, a quantitatively accurate description of the optical properties of the IceCube glacial ice is obtained. In this paper, we present the experimental signature of ice optical anisotropy observed in IceCube LED calibration data, the theory and parametrization of the birefringence effect, the fitting procedures of these parameterizations to experimental data as well as the inferred crystal properties.</p

In situ estimation of ice crystal properties at the South Pole using LED calibration data from the IceCube Neutrino Observatory

The IceCube Neutrino Observatory instruments about 1 km3 of deep, glacial ice at the geographic South Pole. It uses 5160 photomultipliers to detect Cherenkov light emitted by charged relativistic particles. An unexpected light propagation effect observed by the experiment is an anisotropic attenuation, which is aligned with the local flow direction of the ice. We examine birefringent light propagation through the polycrystalline ice microstructure as a possible explanation for this effect. The predictions of a first-principles model developed for this purpose, in particular curved light trajectories resulting from asymmetric diffusion, provide a qualitatively good match to the main features of the data. This in turn allows us to deduce ice crystal properties. Since the wavelength of the detected light is short compared to the crystal size, these crystal properties include not only the crystal orientation fabric, but also the average crystal size and shape, as a function of depth. By adding small empirical corrections to this first-principles model, a quantitatively accurate description of the optical properties of the IceCube glacial ice is obtained. In this paper, we present the experimental signature of ice optical anisotropy observed in IceCube light-emitting diode (LED) calibration data, the theory and parameterization of the birefringence effect, the fitting procedures of these parameterizations to experimental data, and the inferred crystal properties.Peer Reviewe