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This volume of the series Springer Briefs in Space Life Sciences explains the physics and biology of radiation in space, defines various forms of cosmic radiation and their dosimetry, and presents a range of exposure scenarios. It also discusses the effects of radiation on human health and describes the molecular mechanisms of heavy charged particles’ deleterious effects in the body. Lastly, it discusses countermeasures and addresses the vital question: Are we ready for launch?
Written for researchers in the space life sciences and space biomedicine, and for master’s students in biology, physics, and medicine, the book will also benefit all non-experts endeavoring to understand and enter space.
The present thesis elucidates the development of (i) a series of small molecule inhibitors reacting in a covalent-irreversible manner with the targeted proteases and (ii) a fluorescently labeled activity-based probe as a pharmacological tool compound for investigation of specific functions of the mentioned enzymes in vitro. Herein, the rational design, organic synthesis and quantitative structure-activity-relationships are described extensively.
Multiwalled carbon nanotubes (MWCNTs) were easily and efficiently functionalised with highly cross-linked polyamines. The radical polymerisation of two bis-vinylimidazolium salts in the presence of pristine MWCNTs and azobisisobutyronitrile (AIBN) as a radical initiator led to the formation of materials with a high functionalisation degree. The subsequent treatment with sodium borohydride gave rise to the reduction of imidazolium moieties with the concomitant formation of secondary and tertiary amino groups. The obtained materials were characterised by thermogravimetric analysis (TGA), elemental analysis, solid state 13C-NMR, Fourier-transform infrared spectroscopy (FT-IR), transmission electron microscopy (TEM), potentiometric titration, and temperature programmed desorption of carbon dioxide (CO2-TPD). One of the prepared materials was tested as a heterogeneous base catalyst in C–C bond forming reactions such as the Knoevenagel condensation and Henry reaction. Furthermore, two examples concerning a sequential one-pot approach involving two consecutive reactions, namely Knoevenagel and Michael reactions, were reported.
The development of metals tailored to the metallurgical conditions of laser-based additive manufacturing is crucial to advance the maturity of these materials for their use in structural applications. While efforts in this regard are being carried out around the globe, the use of high strength eutectic alloys have, so far, received minor attention, although previous works showed that rapid solidification techniques can result in ultrafine microstructures with excellent mechanical performance, albeit for small sample sizes. In the present work, a eutectic Ti-32.5Fe alloy has been produced by laser powder bed fusion aiming at exploiting rapid solidification and the capability to produce bulk ultrafine microstructures provided by this processing technique.
Process energy densities between 160 J/mm³ and 180 J/mm³ resulted in a dense and crack-free material with an oxygen content of ~ 0.45 wt.% in which a hierarchical microstructure is formed by µm-sized η-Ti4Fe2Ox dendrites embedded in an ultrafine eutectic β-Ti/TiFe matrix. The microstructure was studied three-dimensionally using near-field synchrotron ptychographic X-ray computed tomography with an actual spatial resolution down to 39 nm to analyse the morphology of the eutectic and dendritic structures as well as to quantify their mass density, size and distribution. Inter-lamellar spacings down to ~ 30–50 nm were achieved, revealing the potential of laser-based additive manufacturing to generate microstructures smaller than those obtained by classical rapid solidification techniques for bulk materials. The alloy was deformed at 600 °C under compressive loading up to a strain of ~ 30% without damage formation, resulting in a compressive yield stress of ~ 800 MPa.
This study provides a first demonstration of the feasibility to produce eutectic Ti-Fe alloys with ultrafine microstructures by laser powder bed fusion that are suitable for structural applications at elevated temperature.
This work presents the development of a measuring system for the quality control of ultrapure water. The new systems combines ozonation and UV radiation for the oxidation of organic substances. The change in conductivity caused by the oxidation is furthermore correlated with the TOC of the solution.
Background: 3-hydroxy-3-methylglutaryl-coenzyme A lyase deficiency (HMGCLD) is an autosomal recessive disorder of ketogenesis and leucine degradation due to mutations in HMGCL.
Method: We performed a systematic literature search to identify all published cases. Two hundred eleven patients of whom relevant clinical data were available were included in this analysis. Clinical course, biochemical findings and mutation data are highlighted and discussed. An overview on all published HMGCL variants is provided.
Results: More than 95% of patients presented with acute metabolic decompensation. Most patients manifested within the first year of life, 42.4% already neonatally. Very few individuals remained asymptomatic. The neurologic long-term outcome was favorable with 62.6% of patients showing normal development.
Conclusion: This comprehensive data analysis provides a systematic overview on all published cases with HMGCLD including a list of all known HMGCL mutations.
2-methylacetoacetyl-coenzyme A thiolase (beta-ketothiolase) deficiency: one disease - two pathways
(2020)
Background: 2-methylacetoacetyl-coenzyme A thiolase deficiency (MATD; deficiency of mitochondrial acetoacetyl-coenzyme A thiolase T2/ “beta-ketothiolase”) is an autosomal recessive disorder of ketone body utilization and isoleucine degradation due to mutations in ACAT1.
Methods: We performed a systematic literature search for all available clinical descriptions of patients with MATD. Two hundred forty-four patients were identified and included in this analysis. Clinical course and biochemical data are presented and discussed.
Results: For 89.6% of patients at least one acute metabolic decompensation was reported. Age at first symptoms ranged from 2 days to 8 years (median 12 months). More than 82% of patients presented in the first 2 years of life, while manifestation in the neonatal period was the exception (3.4%). 77.0% (157 of 204 patients) of patients showed normal psychomotor development without neurologic abnormalities. Conclusion: This comprehensive data analysis provides a systematic overview on all cases with MATD identified in the literature. It demonstrates that MATD is a rather benign disorder with often favourable outcome, when compared with many other organic acidurias.
The motor protein myosin drives a wide range of cellular and muscular functions by generating directed movement and force, fueled through adenosine triphosphate (ATP) hydrolysis. Release of the hydrolysis product adenosine diphosphate (ADP) is a fundamental and regulatory process during force production. However, details about the molecular mechanism accompanying ADP release are scarce due to the lack of representative structures. Here we solved a novel blebbistatin-bound myosin conformation with critical structural elements in positions between the myosin pre-power stroke and rigor states. ADP in this structure is repositioned towards the surface by the phosphate-sensing P-loop, and stabilized in a partially unbound conformation via a salt-bridge between Arg131 and Glu187. A 5 Å rotation separates the mechanical converter in this conformation from the rigor position. The crystallized myosin structure thus resembles a conformation towards the end of the two-step power stroke, associated with ADP release. Computationally reconstructing ADP release from myosin by means of molecular dynamics simulations further supported the existence of an equivalent conformation along the power stroke that shows the same major characteristics in the myosin motor domain as the resolved blebbistatin-bound myosin-II·ADP crystal structure, and identified a communication hub centered on Arg232 that mediates chemomechanical energy transduction.
Toshiyuki Fukao
(2020)
Coumarin as a structural component of substrates and probes for serine and cysteine proteases
(2020)
Surface-enhanced Raman spectroscopy (SERS) with subsequent chemometric evaluation was performed for the rapid and non-destructive differentiation of seven important meat-associated microorganisms, namely Brochothrix thermosphacta DSM 20171, Pseudomonas fluorescens DSM 4358, Salmonella enterica subsp. enterica sv. Enteritidis DSM 14221, Listeria monocytogenes DSM 19094, Micrococcus luteus DSM 20030, Escherichia coli HB101 and Bacillus thuringiensis sv. israelensis DSM 5724. A simple method for collecting spectra from commercial paper-based SERS substrates without any laborious pre-treatments was used. In order to prepare the spectroscopic data for classification at genera level with a subsequent chemometric evaluation consisting of principal component analysis and discriminant analysis, a pre-processing method with spike correction and sum normalisation was performed. Because of the spike correction rather than exclusion, and therefore the use of a balanced data set, the multivariate analysis of the data is significantly resilient and meaningful. The analysis showed that the differentiation of meat-associated microorganisms and thereby the detection of important meat-related pathogenic bacteria was successful on genera level and a cross-validation as well as a classification of ungrouped data showed promising results, with 99.5 % and 97.5 %, respectively.