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The performance of a novel water vapor broadband differential absorption lidar (BB-DIAL) is evaluated. This compact, eye-safe, diode-laser-based prototype was developed by Vaisala. It was designed to operate unattended in all weather conditions and to provide height-resolved measurements of water vapor mixing ratio in the lower troposphere. Evaluation of the Vaisala prototype was carried out at the U.S. Department of Energy's Atmospheric Radiation Measurement site in north-central Oklahoma (i.e., the Southern Great Plains site) from 15 May to 12 June 2017. BB-DIAL measurements were compared with observations from radiosondes that were launched within 200 m of the BB-DIAL's location. Radiosonde measurements are also compared with observations from a collocated Raman lidar and an Atmospheric Emitted Radiance Interferometer. During the evaluation period, the BB-DIAL operated continuously and did not experience any failures or malfunctions. The data availability was greater than 90% below 900 m but then decreased rapidly with height above this level to less than 10% above 1500 m AGL. From 106 radiosonde profiles, the overall mean difference (averaged temporally and vertically up to 1500 m) between the BB-DIAL and the radiosonde was −0.01 g kg−1, with a standard deviation of 0.65 g kg−1, and a linear correlation coefficient of 0.98. For comparison, the overall mean difference between the Raman lidar and the radiosonde was 0.07 g kg−1, with a standard deviation of 0.74 g kg−1, and a linear correlation coefficient of 0.97. [ABSTRACT FROM AUTHOR]

Service life of nine wind power unit pedestals, which concrete grades between C45 and C55, were studied with four different service life models. The exact service life could be calculated only with two of them with the initial data.

Christina S Saghaug,1,2 Christian Klotz,3 Juha P Kallio,4 Toni Aebischer,3 Nina Langeland,1,2,5 Kurt Hanevik1 1Department of Clinical Science, University of Bergen, Bergen, Norway; 2Norwegian National Advisory Unit on Tropical Infectious Diseases, Department of Medicine, Haukeland University Hospital, Bergen, Norway; 3Department of Infectious Diseases, Unit 16 Mycotic and Parasitic Agents and Mycobacteria, Robert Koch-Institute, Berlin, Germany; 4Department of Biomedicine, University of Bergen, Bergen, Norway; 5Department of Medicine, Haraldsplass Deaconess Hospital, Bergen, NorwayCorrespondence: Christina S SaghaugDepartment of Clinical Science, University of Bergen, 8th Floor, Lab-Building, Bergen N-5021, NorwayTel +47 90 13 24 14Email christina.saghaug@uib.noPurpose: The flavohemoprotein (gFlHb) in Giardia plays an important role in managing nitrosative and oxidative stress, and potentially also in virulence and nitroimidazole drug tolerance. The aim of this study was to analyze the genetic diversity of gFlHb in Giardia assemblages A and B clinical isolates.Methods: gFlHb genes from 20 cultured clinical Giardia isolates were subjected to PCR amplification and cloning, followed by Sanger sequencing. Sequences of all cloned PCR fragments from each isolate were analyzed for single nucleotide variants (SNVs) and compared to genomic Illumina sequence data. Identical clone sequences were sorted into alleles, and diversity was further analyzed. The number of gFlHb gene copies was assessed by mining PacBio de novo assembled genomes in eight isolates. Homology models for assessment of SNV’s potential impact on protein function were created using Phyre2.Results: A variable copy number of the gFlHb gene, between two and six copies, depending on isolate, was found. A total of 37 distinct sequences, representing different alleles of the gFlHb gene, were identified in AII isolates, and 41 were identified in B isolates. In some isolates, up to 12 different alleles were found. The total allelic diversity was high for both assemblages (> 0.9) and was coupled with a nucleotide diversity of < 0.01. The genetic variation (SNVs per CDS length) was 4.8% in sub-assemblage AII and 5.4% in assemblage B. The number of non-synonymous (ns) SNVs was high in gFIHb of both assemblages, 1.6% in A and 3.0% in B, respectively. Some of the identified nsSNV are predicted to alter protein structure and possibly function.Conclusion: In this study, we present evidence that gFlHb, a putative protective enzyme against oxidative and nitrosative stress in Giardia, is a variable copy number gene with high allelic diversity. The genetic variability of gFlHb may contribute metabolic adaptability against metronidazole toxicity.Keywords: Giardia, genetic diversity, copy number variation, flavohemoprotein, oxidative stress, nitrosative stress, allele

Christina S Saghaug,1,2 Christian Klotz,3 Juha P Kallio,4 Hans-Richard Brattbakk,1,5 Tomasz Stokowy,1,5 Toni Aebischer,3 Inari Kursula,4,6 Nina Langeland,1–2,7 Kurt Hanevik1,21Department of Clinical Science, University of Bergen, Bergen, Hordaland, Norway; 2Norwegian National Advisory Unit on Tropical Infectious Diseases, Department of Medicine, Haukeland University Hospital, Bergen, Hordaland, Norway; 3Department of Infectious Diseases, Unit 16 Mycotic and Parasitic Agents and Mycobacteria, Robert Koch-Institute, Berlin, Germany; 4Department of Biomedicine, University of Bergen, Bergen, Hordaland, Norway; 5Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Hordaland, Norway; 6Biocenter Oulu and Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland; 7Department of Medicine, Haraldsplass Deaconess Hospital, Bergen, Hordaland, NorwayPurpose: Treatment-refractory Giardia cases have increased rapidly within the last decade. No markers of resistance nor a standardized susceptibility test have been established yet, but several enzymes and their pathways have been associated with metronidazole (MTZ) resistant Giardia. Very limited data are available regarding genetic variation in these pathways. We aimed to investigate genetic variation in metabolic pathway genes proposed to be involved in MTZ resistance in recently acquired, cultured clinical isolates.Methods: Whole genome sequencing of 12 assemblage A2 and 8 assemblage B isolates was done, to decipher genomic variation in Giardia. Twenty-nine genes were identified in a literature search and investigated for their single nucleotide variants (SNVs) in the coding/non-coding regions of the genes, either as amino acid changing (non-synonymous SNVs) or non-changing SNVs (synonymous).Results: In Giardia assemblage B, several genes involved in MTZ activation or oxidative stress management were found to have higher numbers of non-synonymous SNVs (thioredoxin peroxidase, nitroreductase 1, ferredoxin 2, NADH oxidase, nitroreductase 2, alcohol dehydrogenase, ferredoxin 4 and ferredoxin 1) than the average variation. For Giardia assemblage A2, the highest genetic variability was found in the ferredoxin 2, ferredoxin 6 and in nicotinamide adenine dinucleotide phosphate (NADPH) oxidoreductase putative genes. SNVs found in the ferredoxins and nitroreductases were analyzed further by alignment and homology modeling. SNVs close to the iron-sulfur cluster binding sites in nitroreductase-1 and 2 and ferredoxin 2 and 4 could potentially affect protein function. Flavohemoprotein seems to be a variable-copy gene, due to higher, but variable coverage compared to other genes investigated.Conclusion: In clinical Giardia isolates, genetic variability is common in important genes in the MTZ metabolizing pathway and in the management of oxidative and nitrosative stress and includes high numbers of non-synonymous SNVs. Some of the identified amino acid changes could potentially affect the respective proteins important in the MTZ metabolism.Keywords: drug metabolism, resistance, genetic analysis, metronidazole genes, ferredoxin, genetic diversity

Saghaug CS, Klotz C, Kallio JP, et al. Infect Drug Resist. 2019;12:1221–1235. The authors have advised NR-1 was used throughout the paper to denote the gene named in GiardiaDB as “Nitroreductase family protein fused to ferredoxin domain Fd-NR1” (DHA2_153380/GSB_153178), while in recent literature this is often denoted NR2/GlNR2. Likewise, NR-2 was used to denote the gene named in GiardiaDB as “Nitroreductase Fd-NR-2” (DHA2_22677/GSB_22677), while in recent literature this is often denoted NR1/GlNR1. The authors acknowledge that using the NR gene names as annotated in GiardiaDB may cause confusion and therefore, bring this to the attention of readers that more correctly what is named “NR-1” in the paper should be read as “NR-2”, and “NR-1” should be read as “NR-2”. The authors apologize for not having considered this issue in the original manuscript. Read the original article

Reports on pilot-scale tests to enhance phosphorus removal with ferrous sulphate in a biological phosphorus and nitrogen removal process for treating municipal wastewater. Competition of iron with the BioP organisms and inhibition of the biological phosphorus removal process; Development of a centrifugation method to evaluate the dewatering properties of sludge.

Transforming growth factor-β (TGF-β) superfamily related growth factors signal by binding to transmembrane type I and type II receptor serine/threonine kinases (RSTK), which phosphorylate intracellular Smad transcription factors in response to ligand binding. Here we describe the cloning of the human type I RSTK activin receptor-like kinase 7 (ALK7), an orthologue of the previously identified rat ALK7. Nodal, a TGF-β member expressed during embryonic development and implicated in developmental events like mesoderm formation and left-right axis specification, was recently shown to signal through ALK7. We found ALK7 mRNA to be most abundantly expressed in human brain, pancreas and colon. A cDNA encoding the open reading frame of ALK7 was obtained from a human brain cDNA library. Furthermore, a P1 artificial chromosome (PAC) clone containing the human ALK7 gene was isolated and fluorescent in situ hybridization (FISH) on metaphase chromosomes identified the gene locus as chromosome 2q24.1→q3. To test the functionality of the ALK7 signaling, we generated recombinant adenoviruses containing a constitutively active form of ALK7 (Ad-caALK7), which is capable of activating downstream targets in a ligand independent manner. Infection with Ad-caALK7 of MIN6 insulinoma cells, in which ALK7 has previously been shown to be endogenously expressed, led to a marked increase in the phosphorylation of Smad2, a signaling molecule also used by TGF-βs and activins. Copyright © 2002 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The in vivo inhibitory effect of five beta-adrenoceptor antagonists and levomepromazine on debrisoquine metabolism was assessed in 37 subjects. The debrisoquine phenotyping test was performed before and after 7 days' treatment with oxprenolol (40 mg three times daily), propranolol (20 mg three times daily), timolol (10 mg twice daily), pindolol (5 mg twice daily), metoprolol (50 mg twice daily) or levomepromazine (10 mg daily), each of which was given to six-seven subjects. No clear change in the urinary metabolic ratio of debrisoquine/4-OH-debrisoquine (MR) was seen with any of the single beta-adrenoceptor antagonist treatments, but the MR value increased significantly when all beta- adrenoceptor blocker treatments were considered together. Debrisoquine metabolism was clearly impaired after levomepromazine 10 mg daily for 7 days; the mean MR increased from 1.24 +/− 1.6 to 4.70 +/− 5.23 (P = 0.018) and the excretion of 4-hydroxydebrisoquine decreased from 0.92 +/− 0.46 mg to 0.31 +/− 0.19 mg (P = 0.043). Thus, levomepromazine changes MRs towards those characteristic of phenotypically poor metabolizers, but beta-adrenoceptor antagonists at the doses examined have only a marginal effect. [ABSTRACT FROM AUTHOR]

1. Single oral doses (100, 200 and 300 mg) of moclobemide, a reversible inhibitor of monoamine oxidase (MAO) with predominant effects on the A- type of the enzyme, were administered to eight young, healthy male volunteers in a double-blind, random-order, placebo-controlled study. The investigation was thereafter continued in an open fashion by administering a single 10 mg dose of the MAO-B inhibitor deprenyl to the same subjects. 2. Deamination of catecholamines was powerfully and dose-dependently inhibited by moclobemide, as evidenced by up to 40% decreases in the urinary excretion of deaminated catecholamine metabolites, corresponding increases in the excretion of non- deaminated, methylated metabolites, and up to 79% average decreases in the plasma concentration of 3,4-dihydroxyphenylglycol (DHPG), a deaminated metabolite of noradrenaline (NA), and up to 75% average decreases in the plasma concentrations of 3,4-dihydroxyphenylacetic acid (DOPAC), a deaminated metabolite of dopamine. The urinary excretion of 5-hydroxyindoleacetic acid (5-HIAA) was only slightly reduced. In contrast, deprenyl, in a dose which almost totally inhibited MAO-B activity in blood platelets, did not appreciably affect the plasma concentrations of DHPG or DOPAC. 3. Due to the rapid, reversible, dose-dependent and MAO-A specific effect of moclobemide on plasma concentrations of DHPG, it is suggested that DHPG in plasma may be a useful indicator of the magnitude and duration of MAO-A inhibition in man. 4. Sympatho-adrenal function at rest was not significantly altered by moclobemide, as judged by unchanged plasma catecholamine concentrations and stable blood pressure and heart rate recordings. 5. Monoamine oxidase type B activity in blood platelets was slightly (less than 30%) and transiently inhibited after moclobemide. 6. The secretion of prolactin was dose-dependently stimulated by moclobemide, whereas the plasma concentrations of growth hormone (hGH) and cortisol remained unchanged. [ABSTRACT FROM AUTHOR]

1. The debrisoquine hydroxylation phenotype was assessed in 211 healthy subjects of Finnish Caucasian origin. 2. A bimodal distribution was observed in the urinary debrisoquine/4-hydroxydebrisoquin ratio. Eleven subjects (about 5%) were poor metabolizers of debrisoquine, when a ratio of 12.6 was used as the cut-off point. 3. The mean metabolic ratio of 35 extensive metabolizers taking oral contraceptives was slightly lower than that of extensive metabolizers not taking contraceptives. This indicates that oral contraceptives may change the phenotyping near the metabolic ratio of 12.6. 4. The metabolic ratios were determined in eight subjects using both 4 h and 6 h urine collection times. The metabolic ratios corresponded well with each other indicating the usefulness of the shorter 4 h collection time. [ABSTRACT FROM AUTHOR]

Abstract Background The purpose of the Finnish Cardiovascular Study (FINCAVAS) is to construct a risk profile – using genetic, haemodynamic and electrocardiographic (ECG) markers – of individuals at high risk of cardiovascular diseases, events and deaths. Methods and design All patients scheduled for an exercise stress test at Tampere University Hospital and willing to participate have been and will be recruited between October 2001 and December 2007. The final number of participants is estimated to reach 5,000. Technically successful data on exercise tests using a bicycle ergometer have been collected of 2,212 patients (1,400 men and 812 women) by the end of 2004. In addition to repeated measurement of heart rate and blood pressure, digital high-resolution ECG at 500 Hz is recorded continuously during the entire exercise test, including the resting and recovery phases. About 20% of the patients are examined with coronary angiography. Genetic variations known or suspected to alter cardiovascular function or pathophysiology are analysed to elucidate the effects and interactions of these candidate genes, exercise and commonly used cardiovascular medications. Discussion FINCAVAS compiles an extensive set of data on patient history, genetic variation, cardiovascular parameters, ECG markers as well as follow-up data on clinical events, hospitalisations and deaths. The data enables the development of new diagnostic and prognostic tools as well as assessments of the importance of existing markers.