Toward Estimating Noise–Power–Distance Curves for Propeller-Powered Zero-Emission Hydrogen Aircraft

As part of the UK Research and Innovation project New Aviation, Propulsion, Knowledge and Innovation Network (NAPKIN), a high-level framework was developed for the assessment of the noise impact of the proposed regional-sized hydrogen-powered aircraft. This study consists of the methodology used to generate the industry-standard noise–power–distance (NPD) curves from individual component noise analysis, specifically propeller tonal noise. The model is based on an asymptotic analysis of a frequency domain propeller tonal noise model combined with a linear approximation, taking advantage of the logarithmic nature of noise. An error analysis on the linear approximation assumption proves that the relative error between predicted and actual values of the noise remains below 10% for appropriately chosen baseline points. Verification of the framework was achieved through a bench-marking procedure that compared predictions of departure NPD curves for current technology regional aircraft against published ones over a range of operational power settings. Finally, departure and approach NPD predictions for three of the NAPKIN hydrogen concept aircraft are presented. Concepts featuring a larger, slower-rotating propeller with an increased number of blades relative to the reference aircraft showed benefits over the reference aircraft, despite, in some cases, increases in maximum takeoff weight

The Adaptability of Full Cast Crown in Preclinical Practice

A study was made to evaluate the adaptability of full cast crowns in preclinical practice of the fifth year students at Matsumoto Dental College in 1984. Gap space between the inner surface of the full cast crown and the surface of the abutment tooth was investigated with silicon material. The results were as follows: 1) The adaptability of crowns was better at the mesial surface than at the distal surface, and better at the lingual surface than at the buccal surface. 2) The adaptability of crowns was better at the axial walls, especialy in the middle, than in the cervical margin. 3) At the occulusal surface, the adaptability of crowns was worst

Factors regulating Hb F synthesis in thalassemic diseases

BACKGROUND: The thalassemic syndromes originate from mutations of the globin genes that cause, besides the characteristic clinical picture, also an increased Hb F amount. It is not yet clear if there are more factors, besides the beta globin genotype, determining the Hb F production. We have tried to find out if there are relations between total Hb and Hb F, between erythropoietin (Epo) and Hb F, between Hb F and point mutations of the gamma gene promoters. MATERIALS AND METHODS: Hematologic parameters, iron status, alpha/non-alpha globin ratio, Epo level, and thalassemic defects of the alpha-, beta-, and gamma-globin genes were explored using standard methods in patients affected by thalassemic diseases. Ninety-five non thalassemic individuals have been examined as controls. RESULTS: Two clinical variants of beta-thalassemia intermedia referred to as beta-thal int sub-silent and evident are associated with distinct sets of mutations of the beta-globin gene. Silent beta thal mutations are invariably associated with sub-silent beta thal int; beta° or severe beta(+) thal mutations are associated with evident beta thal int (88%) and almost invariably (98%) with thalassemia major. A positive correlation was observed between the severity of the disease and the Hb F level, but no correlation was found between the Hb F and erythropoietin (Epo) level. The mutation Ggamma -158 C→T was detected in 26.9% of patients affected by beta-thal int sub-silent and evident, respectively, but only in 2% of patients with thalassemia major. CONCLUSIONS: The severity of beta-thal int and the increased Hb F level are strictly dependent from the type of beta-globin gene mutations. No relation is found between Hb F synthesis and Epo secretion. The mutation Ggamma -158 C→T, common among patients affected by beta-thal int and very rare in thal major patients, does not seem, in this study, to influence the Hb F content in beta thal int patients

α-thalassaemia

Alpha-thalassaemia is inherited as an autosomal recessive disorder characterised by a microcytic hypochromic anaemia, and a clinical phenotype varying from almost asymptomatic to a lethal haemolytic anaemia

Adapting the ACMG/AMP variant classification framework: a perspective from the ClinGen Hemoglobinopathy Variant Curation Expert Panel

Accurate and consistent interpretation of sequence variants is integral to the delivery of safe and reliable diagnostic genetic services. To standardize the interpretation process, in 2015, the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) published a joint guideline based on a set of shared standards for the classification of variants in Mendelian diseases. The generality of these standards and their subjective interpretation between laboratories has prompted efforts to reduce discordance of variant classifications, with a focus on the expert specification of the ACMG/AMP guidelines for individual genes or diseases. Herein, we describe our experience as a ClinGen Variant Curation Expert Panel to adapt the ACMG/AMP criteria for the classification of variants in three globin genes (HBB, HBA2, and HBA1) related to recessively inherited hemoglobinopathies, including five evidence categories, as use cases demonstrating the process of specification and the underlying rationale.Genetics of disease, diagnosis and treatmen

Phenylketonuria in Portugal: Genotype-Phenotype Correlations Using Molecular, Biochemical, and Haplotypic Analyses

The impairment of the hepatic enzyme phenylalanine hydroxylase (PAH) causes elevation of phenylalanine levels in blood and other body fluids resulting in the most common inborn error of amino acid metabolism (phenylketonuria). Persistently high levels of phenylalanine lead to irreversible damage to the nervous system. Therefore, early diagnosis of the affected individuals is important, as it can prevent clinical manifestations of the disease.info:eu-repo/semantics/publishedVersio

The hierarchy-of-hypotheses approach: A synthesis method for enhancing theory development in ecology and evolution

13 páginas.- 4 figuras.- referencias.- Supplemental material is available at BIOSCI online. https://doi.org/10.1093/biosci/biaa130In the current era of Big Data, existing synthesis tools such as formal meta-analyses are critical means to handle the deluge of information. However, there is a need for complementary tools that help to (a) organize evidence, (b) organize theory, and (c) closely connect evidence to theory. We present the hierarchy-of-hypotheses (HoH) approach to address these issues. In an HoH, hypotheses are conceptually and visually structured in a hierarchically nested way where the lower branches can be directly connected to empirical results. Used for organizing evidence, this tool allows researchers to conceptually connect empirical results derived through diverse approaches and to reveal under which circumstances hypotheses are applicable. Used for organizing theory, it allows researchers to uncover mechanistic components of hypotheses and previously neglected conceptual connections. In the present article, we offer guidance on how to build an HoH, provide examples from population and evolutionary biology and propose terminological clarifications.The workshops were funded by Volkswagen Foundation (Az 92,807 and 94,246). TH, CAA, ME, PG, ADS, and JMJ received funding from German Federal Ministry of Education and Research within the Collaborative Project “Bridging in Biodiversity Science” (grant no. 01LC1501A). ME additionally received funding from the Foundation of German Business, JMJ from the Deutsche Forschungsgemeinschaft (grants no. JE 288/9–1 and JE 288/9–2), and IB from German Federal Ministry of Education and Research (grant no. FKZ 01GP1710). CJL was supported by a grant from The Natural Sciences and Engineering Research Council of Canada and in-kind synthesis support from the US National Center for Ecological Analysis and Synthesis. LGA was supported by the Spanish Ministry of Science, Innovation, and Universities through project no. CGL2014–56,739-R, and RRB received funding from the Brazilian National Council for Scientific and Technological Development (process no. 152,289/2018–6)Peer reviewe

Systematic documentation and analysis of human genetic variation in hemoglobinopathies using the microattribution approach

We developed a series of interrelated locus-specific databases to store all published and unpublished genetic variation related to hemoglobinopathies and thalassemia and implemented microattribution to encourage submission of unpublished observations of genetic variation to these public repositories. A total of 1,941 unique genetic variants in 37 genes, encoding globins and other erythroid proteins, are currently documented in these databases, with reciprocal attribution of microcitations to data contributors. Our project provides the first example of implementing microattribution to incentivise submission of all known genetic variation in a defined system. It has demonstrably increased the reporting of human variants, leading to a comprehensive online resource for systematically describing human genetic variation in the globin genes and other genes contributing to hemoglobinopathies and thalassemias. The principles established here will serve as a model for other systems and for the analysis of other common and/or complex human genetic diseases

Recent developments in genetics and medically assisted reproduction : from research to clinical applications

Two leading European professional societies, the European Society of Human Genetics and the European Society for Human Reproduction and Embryology, have worked together since 2004 to evaluate the impact of fast research advances at the interface of assisted reproduction and genetics, including their application into clinical practice. In September 2016, the expert panel met for the third time. The topics discussed highlighted important issues covering the impacts of expanded carrier screening, direct-to-consumer genetic testing, voiding of the presumed anonymity of gamete donors by advanced genetic testing, advances in the research of genetic causes underlying male and female infertility, utilisation of massively parallel sequencing in preimplantation genetic testing and non-invasive prenatal screening, mitochondrial replacement in human oocytes, and additionally, issues related to cross-generational epigenetic inheritance following IVF and germline genome editing. The resulting paper represents a consensus of both professional societies involved.Peer reviewe

Sensitive Monogenic Noninvasive Prenatal Diagnosis by Targeted Haplotyping

During pregnancy, cell-free DNA (cfDNA) in maternal blood encompasses a small percentage of cell-free fetal DNA (cffDNA), an easily accessible source for determination of fetal disease status in risk families through non-invasive procedures. In case of monogenic heritable disease, background maternal cfDNA prohibits direct observation of the maternally inherited allele. Non-invasive prenatal diagnostics (NIPD) of monogenic diseases therefore relies on parental haplotyping and statistical assessment of inherited alleles from cffDNA, techniques currently unavailable for routine clinical practice. Here, we present monogenic NIPD (MG-NIPD), which requires a blood sample from both parents, for targeted locus amplification (TLA)-based phasing of heterozygous variants selectively at a gene of interest. Capture probes-based targeted sequencing of cfDNA from the pregnant mother and a tailored statistical analysis enables predicting fetal gene inheritance. MG-NIPD was validated for 18 pregnancies, focusing on CFTR, CYP21A2, and HBB. In all cases we could predict the inherited alleles with >98% confidence, even at relatively early stages (8 weeks) of pregnancy. This prediction and the accuracy of parental haplotyping was confirmed by sequencing of fetal material obtained by parallel invasive procedures. MG-NIPD is a robust method that requires standard instrumentation and can be implemented in any clinic to provide families carrying a severe monogenic disease with a prenatal diagnostic test based on a simple blood draw