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Haarmann, Axel, and Mathias Buttmann. "MS-Therapien im Kindesalter: Behandeln wir kleine Erwachsene?" DNP - Der Neurologe & Psychiater 20, no. 3 (2019): 27–28. http://dx.doi.org/10.1007/s15202-019-2200-1.
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Peng, Xiyan, Cuihua Du, Zhenyu Wu, Jun Ma, and Xu Zhou. "The stellar metallicity distribution of the Galaxy from the BATC survey." Proceedings of the International Astronomical Union 9, S298 (2013): 432. http://dx.doi.org/10.1017/s1743921313006984.
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AbstractUsing ~2200 BATC main sequence (MS) stars which include SDSS stellar atmospheric parameters, we develop the polynomial photometric calibration method to evaluate the stellar effective temperature and metallicity for BATC data. This calibration method has been applied to about 160 000 MS stars. The mean stellar metallicity smoothly decreases from −0.65 to −0.78 dex in the interval 0.5 < |Z| ≤ 2 kpc. Metallicity distributions in the halo and the thick disk seem invariant with the distance from the Galactic plane.
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Park, Lee, Byeon, et al. "Pharmacokinetic and Metabolism Studies of Monomethyl Auristatin F via Liquid Chromatography-Quadrupole-Time-of-Flight Mass Spectrometry." Molecules 24, no. 15 (2019): 2754. http://dx.doi.org/10.3390/molecules24152754.
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A simple liquid chromatography–quadrupole-time-of-flight–mass spectrometric assay (LC-TOF-MS/MS) has been developed for the evaluation of metabolism and pharmacokinetic (PK) characteristics of monomethyl auristatin F (MMAF) in rat, which is being used as a payload for antibody-drug conjugates. LC-TOF-MS/MS method was qualified for the quantification of MMAF in rat plasma. The calibration curves were acceptable over the concentration range from 3.02 to 2200 ng/mL using quadratic regression. MMAF was stable in various conditions. There were no significant matrix effects between rat and other preclinical species. The PK studies showed that the bioavailability of MMAF was 0% with high clearance. Additionally, the metabolite profiling studies, in vitro/in vivo, were performed. Seven metabolites for MMAF were tentatively identified in liver microsome. The major metabolic pathway was demethylation, which was one of the metabolic pathways predicted by MedChem Designer. Therefore, these results will be helpful to understand the PK, catabolism, and metabolism behavior of MMAF comprehensively when developing antibody-drug conjugates (ADCs) in the future.
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Das, Anath Bandhu, Iswar Chandra Mohanty, Dawanidhi Mahapatra, Suprava Mohanty, and Ashutosh Ray. "Genetic variation of Indian potato (Solanum tuberosum L.) genotypes using chromosomal and RAPD markers." Crop Breeding and Applied Biotechnology 10, no. 3 (2010): 238–46. http://dx.doi.org/10.1590/s1984-70332010000300009.
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Genetic diversity in thirty Indian potatoes were analyzed employing karyotype, genome size and RAPD markers. Chromosome analysis revealed 2n = 4x = 48 except cv. K. Chandramukhi (2n = 4x + 2 = 50). Total genomic chromosome length and chromosome volume varied from 21.14µm in cv. K. Pukhraj to 31.91µm in cv. MS/89-60 and 14.31µm³ in cv. MS/92-1090 to 33.16µm³ in cv. JW-160 respectively. 4C DNA content was significantly varied from 3.640 pg (~891 Mbp) in cv. MS/92-1090 to 11.12 pg (~2747 Mbp) in cv. K. Chandramukhi. RAPD revealed 131 amplified DNA fragments (300 to 2200 bp) with 79 unique bands (7 to 71% polymorphism) among the genotypes. Similarity coefficients (ranged from 0.29 to 0.93) and cluster analysis reflected the expected trends in relationships of the full and half-sib potato genotypes. Genetic distances obtained from a dendrogram could help breeders to choose the diverse parents for a breeding program aimed at varietal improvement.
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Smeds, Annika I., Patrik C. Eklund, and Stefan M. Willför. "Characterization of high-molar-mass fractions in a Scots pine (Pinus sylvestris L.) knotwood ethanol extract." Holzforschung 72, no. 3 (2018): 201–13. http://dx.doi.org/10.1515/hf-2017-0079.
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AbstractThe identification of compounds in Scots pine (Pinus sylvestrisL.) knotwood (KnW), obtained by extracting with hydrophilic organic solvents, has been performed previously almost exclusively by gas chromatography-mass spectrometry (GS-MS) equipped with long GC columns (≥25 m). That means that the molar mass (MM) of the majority of the identified compounds was below 500–600 Da, and the analytical data accounted for only about half of the dry extract weight. In the present work, high-molar-mass (HMM) fractions in a Scots pine KnW-EtOH extract were isolated and chemically characterized by means of several advanced analytical techniques, such as high performance size-exclusion chromatography-evaporative light scattering detector (HPSEC-ELSD), high performance liquid chromatography (HPLC)-electrospray ionization-ion trap-mass spectrometry [(HPLC)ESI-IT-MS], ESI-quadrupole time of flight-mass spectrometry (QTOF-MS), pyrolysis-gas chromatography-mass spectrometry (Py-GC-MS), thermally assisted hydrolysis and methylation-gas chromatography-mass spectrometry (THM-GC-MS), nuclear magnetic resonance (NMR) and GC-MS. The results indicate that the MM maxima of the HMM fractions ranged from approximately 500 to 2200 Da, and that the compounds consist mainly of oligomers of hydroxylated resin acids (RAs), especially dehydroabietic acid, but also of fatty acids (FAs), stilbenes and sterols. A large number of RA dimers were tentatively identified in the HMM fractions. However, it remains unknown how the monomer units are linked together, as it was not possible to isolate a RA dimer fraction pure enough for NMR characterization. RA dimers in native KnW have not been identified previously.
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Patterson, Jeffrey, Xiaojian Shi, William Bresette, et al. "A Metabolomic Analysis of the Sex-Dependent Hispanic Paradox." Metabolites 11, no. 8 (2021): 552. http://dx.doi.org/10.3390/metabo11080552.
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In Mexican Americans, metabolic conditions, such as obesity and type 2 diabetes (T2DM), are not necessarily associated with an increase in mortality; this is the so-called Hispanic paradox. In this cross-sectional analysis, we used a metabolomic analysis to look at the mechanisms behind the Hispanic paradox. To do this, we examined dietary intake and body mass index (BMI; kg/m2) in men and women and their effects on serum metabolomic fingerprints in 70 Mexican Americans (26 men, 44 women). Although having different BMI values, the participants had many similar anthropometric and biochemical parameters, such as systolic and diastolic blood pressure, total cholesterol, and LDL cholesterol, which supported the paradox in these subjects. Plasma metabolomic phenotypes were measured using liquid chromatography tandem mass spectrometry (LC-MS/MS). A two-way ANOVA assessing sex, BMI, and the metabolome revealed 23 significant metabolites, such as 2-pyrrolidinone (p = 0.007), TMAO (p = 0.014), 2-aminoadipic acid (p = 0.019), and kynurenine (p = 0.032). Pathway and enrichment analyses discovered several significant metabolic pathways between men and women, including lysine degradation, tyrosine metabolism, and branch-chained amino acid (BCAA) degradation and biosynthesis. A log-transformed OPLS-DA model was employed and demonstrated a difference due to BMI in the metabolomes of both sexes. When stratified for caloric intake (<2200 kcal/d vs. >2200 kcal/d), a separate OPLS-DA model showed clear separation in men, while females remained relatively unchanged. After accounting for caloric intake and BMI status, the female metabolome showed substantial resistance to alteration. Therefore, we provide a better understanding of the Mexican-American metabolome, which may help demonstrate how this population—particularly women—possesses a longer life expectancy despite several comorbidities, and reveal the underlying mechanisms of the Hispanic paradox.
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de Luces Fortes*, Gerson Renan, and Ana Carolina Pereira e Silva. "In Vitro Multiplication of Brazilian Ginseng (Pfaffia spp.) for in Vitro Conservation Purposes." HortScience 39, no. 4 (2004): 753D—753. http://dx.doi.org/10.21273/hortsci.39.4.753d.
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Brazilian ginseng (Pfaffia sp.) is largely known as having anabolic, analgesic, anticancerous, anti-inflammatory, antileukemic properties, and more. Embrapa Genetic Resources and Biotechnology is the major Conservation Center in Brazil. This species could only be stored under in vitro conditions. There are more than two hundred native acessions collected from different locations in the country. So far very few works are found in the literature and there is no specific protocol for in vitro conservation. The aim of this study was to test five different acessions from in vitro collection under one specific nutrient medium. The acessions were catalogued as 2205-12; 2202-04; 2209-11; 2209-10 and 2205-21. One-bud microcutting was inoculated on a MS nutrient medium without growth regulators and added with vitamins, myoinositol (100 mg·L-1), sucrose (30 mg·L-1) and agar (6 mg·L-1). The pH was adjusted to 5.7 before the agar addition. Each treatment was replicated 7 (seven) times and each plot consisted of six test tubes with 5-mL solution. The trial was replicated twice. The evaluations were performed once weekly where the shoot growth was taken along with the number of buds and roots formed. The highest shoot growth were obtained for the acessions 2205-12 and 2209-10. Acession 2209-11 had an intermediate shoot growth and number of buds, but had the highest number of roots per shoot (4.27) compared to 2.14 and 3.75 for acessions 2205-21 and 2209-10, respectively. The highest rate of multiplication was achieved for acessions 2205-12 (4.49) and 2202-04 (4.46) as compared to 3.60 for acession 2205-21. It was clearly shown that acession 2205-21 is a recalcitrant one as in vitro multiplication is concerned. All the acessions rooted in this medium.
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Berendt, F., T. Froehlich, M. Boelhauve, T. Guengoer, E. Wolf, and G. J. Arnold. "239 OOCYTE MATURATION IN VITRO: PROTEOME ALTERATIONS ANALYZED BY ULTRA-SENSITIVE FLUOROCHROME LABELING AND NANO-ESI-MS-MS." Reproduction, Fertility and Development 20, no. 1 (2008): 199. http://dx.doi.org/10.1071/rdv20n1ab239.
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In mammals, oocytes are arrested in the diplotene stage of the first prophase until the beginning of the estrous cycle. Directly before ovulation, the oocyte completes the first meiotic division and progresses to metaphase II. This process is mimicked by oocyte maturation in vitro, which is critical in assisted reproduction techniques in humans and animals. A sensitive 2-dimensional (2D) difference gel electrophoresis (DIGE) saturation labeling approach including an internal pooled standard was used for quantitative proteome profiling of immature v. in vitro-matured bovine oocytes. A mixture of 0.25 µg of oocyte sample and 0.25 µg of the internal pooled standard was separated on each analytical 2D gel, corresponding to the protein content of approximately five oocytes. In total, the study comprised 48 2D gel images representing 24 DIGE experiments [6 independent samples � 2 gels per stage (immature/mature) � 2 pH gradients]. DeCyder differential in-gel analysis (DIA; Amersham Biosciences, Piscataway, NJ, USA) detected 2244 spots (SD = 100) in pH 4–7 images, and 1291 spots (SD = 65) in pH 6–9 images. In total, 38 spots with different intensity were detected (abundance ratio ≥2; Student's t-test, P ≤ 0.01). Differently abundant spots were identified by nano-LC-MS/MS analysis of matched spots in a preparative gel of saturation-labeled protein extract from 2200 immature oocytes. Ten spots could be unambiguously identified and comprised, e.g., interesting proteins such as clusterin, 14-3-3 ε, redox enzymes, and new polymorphic forms of glutathione-S-transferases. Clusterin is suggested to interact with components of the complement membrane attack complex, and 14-3-3 ε is a mediator of the activation of the maturation promoting factor, a key enzyme of the meiosis. Our study demonstrates the feasibility of differential oocyte proteomics using saturation labeling. Several of the proteins identified in this study are already known to play an important role in oocyte maturation, which reflects the relevance and reliability of our approach. Furthermore, we found proteins which are so far unknown in the context of oocyte development. A more detailed knowledge of the role of these candidates during oocyte maturation may help to optimize the in vitro-maturation process in order to increase the rate of successful in vitro fertilization and other assisted reproduction techniques in cattle and other mammals. This work was supported by grant Deutsche Forschungsgemeinschaft (FOR 478, GRK 1029).
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Almeida, Edison Xavier de, Gerzy Ernesto Maraschin, Oscar Emilio Ludtke Harthmann, Henrique Mendonça Nunes Ribeiro Filho, and Elena Apesteguia Setelich. "Oferta de forragem de capim-elefante anão 'Mott' e o rendimento animal." Revista Brasileira de Zootecnia 29, no. 5 (2000): 1288–95. http://dx.doi.org/10.1590/s1516-35982000000500005.
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A pesquisa foi realizada durante as estações de crescimento de 1994/95 e 1995/96 (out./abr.), na Estação Experimental de Ituporanga/EPAGRI - SC, objetivando determinar o potencial de produção animal e as respostas em termos de taxa de acúmulo de matéria seca (MS) e qualidade de forragem e estrutura do perfil de uma pastagem de capim-elefante anão `Mott' (CEAM) submetida a quatro níveis de oferta de forragem (OF). Os níveis reais de FO foram 3,8; 7,5; 10,2 e 14,0 kg de MS de lâminas verdes (MSLV)/100 kg de PV/dia, num delineamento em blocos casualizados completos com duas repetições e três novilhos (8 a 10 meses) por potreiro, sob pastejo contínuo e uso da técnica "put-and-take". As OF determinaram resíduos médios de MSLV (RMSLV) de 722; 1537; 2332; e 2542 kg/ha, respectivamente. Ofertas de forragem crescentes condicionaram acréscimos na taxa de acúmulo de MSLV/ha/dia e na densidade da forragem. A OF de 11,3 kg de MSLV/100 kg de PV/dia (RMSLV de 2200 kg/ha) maximiza o desempenho animal com 1,06 kg/dia de ganho médio diário e assegura ganho/ha de 5,6 kg/dia, em condição de sustentabilidade da pastagem de CEAM, em pastejo contínuo.
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Nelson, Robert E., Stefan K. Grebe, Dennis J. O’Kane, and Ravinder J. Singh. "Liquid Chromatography–Tandem Mass Spectrometry Assay for Simultaneous Measurement of Estradiol and Estrone in Human Plasma." Clinical Chemistry 50, no. 2 (2004): 373–84. http://dx.doi.org/10.1373/clinchem.2003.025478.
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Abstract Background: Estradiol (E2) and estrone (E1) measurements form an integral part of the assessment of female reproductive function and have expanding roles in other fields. However, many E1 and E2 immunoassays have limited functional sensitivity, suffer from cross-reactivity, and display poor intermethod agreement. To overcome these problems, we developed a sensitive liquid chromatography–tandem mass spectrometry (LC-MS/MS) assay for the simultaneous measurement of E1 and E2. Methods: After dansyl chloride derivatization, samples were separated by fast gradient chromatography and injected into a tandem mass spectrometer after formation of positive ions with atmospheric pressure chemical ionization. The limits of detection and quantification, recovery, linearity, precision, and reference intervals were determined, and performance was compared with several immunoassays. Results: Total run time per sample was 5 min. The multiple-reaction monitoring ion pairs were m/z 506/171 for 3-dansyl-estradiol and m/z 504/171 for 3-dansyl-estrone. The limits of detection for E1 and E2 were 12.9 pmol/L (3.5 ng/L) and 10.3 pmol/L (2.8 ng/L), respectively. Interassay imprecision (CV) was 4–20% (n = 20). The limits of quantification (functional sensitivities) for E1 and E2 were 44.1 pmol/L (11.9 ng/L) and 23.2 pmol/L (6.3 ng/L), respectively. The assay was linear to &gt;2200 pmol/L (∼600 ng/L) for each analyte. Recoveries were 93–108% for E1 and 100–110% for E2. No cross-reactivity was observed. Method comparison with several immunoassays revealed that the latter were inaccurate and prone to interferences at low E1 and E2 concentrations. Conclusions: LC-MS/MS allows rapid, simultaneous, sensitive, and accurate quantification of E1 and E2 in human serum.
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Craig, GF, DT Bell, and CA Atkins. "Response to Salt and Waterlogging Stress of Ten Taxa of Acacia Selected From Naturally Saline Areas of Western Australia." Australian Journal of Botany 38, no. 6 (1990): 619. http://dx.doi.org/10.1071/bt9900619.
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Ten taxa of Acacia were selected from areas of moderate to high soil salinity (electrical conductivities of saturated soil paste extracts (ECe) between 1000 mS m--1 and 4800 mS m-1 at 50-600 mm depth) and sodicity to test the tolerance of young, symbiotic plants to increasing levels of salinity both with and without waterlogging. Nodulated plants, 3 months old, were grown in glasshouse experiments which consisted of four treatments: non-saline drained control (12 weeks); saline drained (12 weeks); non-saline waterlogged (5 weeks); and saline waterlogged (5 weeks). Acacia cyclops, A. brumalis, A. redolens (Ravensthorpe) and A. aff. lineolata had 100% survival after 12 weeks irrigation with saline solution (final ECw = 9500 mS m-1). Generally, the species tested were sensitive to waterlogging with A. patagiata, A. cyclops and A. brumalis being the most sensitive, having 19-44% mortality with no salt in the solution. The combined treatment of salt and waterlogging greatly increased the mortality of plants, with four species having > 70% dead after 5 weeks treatment (ECw = 3900 mS m-1). A. aff. lineolata and A. mutabilis subsp. ,stipulifera were highly tolerant of salt plus waterlogging, with 100% and 96% survival respectively. In salt plus waterlogged treatments, Na+ concentration in phyllodes of all taxa exceeded (0.37-2.13 mmol g-1 dry wt) that taken up by plants in freely drained salt treatments (0.03-0.42 mmol g-1 dry wt). Taxa with the slowest rates of growth tended to accumulate the highest concentrations of Na+ in the uppermost phyllodes. Provenances of A. redolens and A. patagiata collected from sites of high soil salinity (ECe > 2200 mS m-1) had less than half the Na+ concentration in uppermost phyllodes (0.22 mmol -1 dry wt) at the termination of the salt treatment, compared with provenances of the same species collected from moderately saline areas (ECe = 1100 mS m-1). This indicates that Acacia provenances collected from the most saline sites had greater potential to survive high levels of external salinity in the longer term than those from less saline sites.
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De Corte, Frans. "Convergences And Divergences Of 2200 ms-1(η,γ) Cross Section Data Selected From 1981-2001 Editions Of General And k0-NAA Evaluated Data Libraries". Journal of Nuclear Science and Technology 39, sup2 (2002): 904–7. http://dx.doi.org/10.1080/00223131.2002.10875245.
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Svärd, Antonia, Olena Sevastyanova, Galina Dobele, Vilhemina Jurkjane, and Elisabet Brännvall. "COST Action FP1105: effect of raw materials and pulping conditions on the characteristics of dissolved kraft lignins." Holzforschung 70, no. 12 (2016): 1105–14. http://dx.doi.org/10.1515/hf-2016-0057.
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Abstract The composition, molecular weight (MW), and chemical structure of technical lignins as byproducts of pulping influence their application in terms of physical and chemical properties, reactivity, and performance. It is important to know how the analytical data of technical lignins are influenced by the wood species and the parameters of pulping. The present study focuses on kraft pulping and how the wood species (eucalyptus, pine, and spruce) and variable cooking times influence the characteristics of dissolved lignins. The black liquor (BL) was recovered after three different cooking times and the precipitated lignin was characterized by total acid hydrolysis including the determination of the acid insoluble part (Klason lignin, KL) and the sugars in the hydrolysate, elemental analysis, 31P NMR spectroscopy, analytical pyrolysis (Py-GC/MS), gel permeation chromatography (GPC), thermogravimetry (TG), and differential scanning calorimetry (DSC). The results indicate that the phenolic OH content, MW and glass transition temperature increased with longer cooking times for the softwood (SW) lignins. These lignins had also a higher MW (Mw 5500–8000 g mol-1), than the eucalyptus lignin (Mw 2200–2400 g mol-1). Eucalyptus lignin had higher sulfur content compared to SW.
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Timmermans, C. J., G. M. W. Kroesen, P. M. Vallinga, and D. C. Schram. "Plasma Parameters and Weakly Non-Ideal Behaviour of a High Density, Super-Atmospheric 2kA Cascade Arc in Argon." Zeitschrift für Naturforschung A 43, no. 8-9 (1988): 806–18. http://dx.doi.org/10.1515/zna-1988-8-915.
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AbstractExperimental results are reported for simultaneous pressure and current pulses up to 14 bar and 2200 A superimposed on an atmospheric pressure 60 A dc cascade arc. A current density over 108 A/m2, previously 107 A/m2 (power density 1012W m3, previously 1010W/m3) has been obtained. The electron temperature of the thermal plasma was deduced from the end-on measured radiance of argon lines, and the electron density from the absolute continuum emission. The values found for the quantities mentioned during the quasi-stationary phase of the current pulse, lasting ~ 1 ms, were 27000 K and 3 · 1023 m-3, respectively, at a pressure of ~ 1.5 bar (ionization degree 100%), and 18000 K and > 1024 m-3, respectively, for a pressure of 14 bar (ionization degree 60%). These values satisfy the LTE relation. Deviations from the Spitzer conductivity have been observed in this weakly non-ideal plasma.In general, the high ionized thermal plasma studied with its composition of neutral, singly ionized and doubly ionized argon atoms can serve as a useful medium for spectroscopic studies of highly ionized systems and as a valuable source of radiation in the visible a well as in the near and far ultraviolet parts of the spectrum.
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Lu, Y. N., and N. J. Tighe. "Microcracks and Micro-Twins in Partially Stabilized Zirconia Alloys (PSZ)." Proceedings, annual meeting, Electron Microscopy Society of America 43 (August 1985): 220–21. http://dx.doi.org/10.1017/s0424820100118023.
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Three commercial magnesia-doped partially stabilized zirconia ceramics (Nilsen MS and TS and Coors TT), have been examined before and after aging for 100 hours at 1000°C The proposed use of these ceramics for components in diesel engines requires long term reliability at temperatures up to 1000°C. The microscopy is being used to identify the microstructural changes that can result during high temperature tests carried out in this laboratory.Pure zirconia exists in three polymorphs which on cooling transform from cubic to tetragonal (at -2200°C) to monoclinic (at -950°C). With MgO additions and under appropriate conditions of temperature and time, the tetragonal to monoclinic transition can be controlled to produce partially stabilized magnesia zirconia alloys with grains and intergranular phases that are mixtures of monoclinic, tetragonal and cubic phases. The morphology of the grains and intergranular phases is readily distinguished in polished sections; however, the phase distributions can be confirmed only with electron microscopy. For example, the intergranular phase is predominantly monoclinic and grains can have: transgranular monoclinic plates in a cubic matrix; twinned monoclinic plates in a cubic matrix; distributions of tetragonal precipitates in a cubic matrix. The microcracks are found by examining interfacial regions at high magnifications.
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Arnold Bruns, H. "Flag Leaf Photosynthesis and Stomatal Function of Grain Sorghum as Influenced by Changing Photosynthetic Photon Flux Densities." International Journal of Agronomy 2016 (2016): 1–6. http://dx.doi.org/10.1155/2016/1363740.
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Photosynthesis (A) and stomatal function research in grain sorghum (Sorghum bicolor (L.) Moench) is limited compared to other crops. Flag leaves from three plants of two hybrids, grown with added N-fertilizer of 0.0, 112, and 224 kg ha−1 near Elizabeth, MS, were measured for A and stomatal functions at growth stages GS6 and GS7. A Li-Cor LI-6400XT set at 355 µmol [CO2], a flow rate of 500 µmol s−1, and a 6400-02 LED light source were used to collect data. Light levels were initially set at 2200 µmol m−2 s−1 indicated photosynthetic photon flux density (PPFD), A was allowed to stabilize, data was recorded, indicated PPFD level was reduced by 200 µmol m−2 s−1, and the process was repeated to a level of 200 µmol m−2 s−1. At GS6 all data were unaffected by N-fertility, hybrids, or years. Data on Ci at GS6 indicated A declines faster with decreasing PPFD than gs. Intrinsic water use efficiency (IWUE) data supports prior research showing stomata function more to regulate water loss and only marginally limit A. Nitrogen fertility was null on A and stomatal functions and minimal on yield; thus no attempt was made to correlate yield with these data.
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Kolawole, Oluwatobi, Abigail Graham, Caroline Donaldson, et al. "Low Doses of Mycotoxin Mixtures below EU Regulatory Limits Can Negatively Affect the Performance of Broiler Chickens: A Longitudinal Study." Toxins 12, no. 7 (2020): 433. http://dx.doi.org/10.3390/toxins12070433.
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Several studies have reported a wide range of severe health effects as well as clinical signs, when livestock animals are exposed to high concentration of mycotoxins. However, little is known regarding health effects of mycotoxins at low levels. Thus, a long-term feeding trial (between May 2017 and December 2019) was used to evaluate the effect of low doses of mycotoxin mixtures on performance of broiler chickens fed a naturally contaminated diet. In total, 18 successive broiler performance trials were carried out during the study period, with approximately 2200 one-day-old Ross-308 chicks used for each trial. Feed samples given to birds were collected at the beginning of each trial and analysed for multi-mycotoxins using a validated LC-MS/MS method. Furthermore, parameters including feed intake, body weight and feed efficiency were recorded on a weekly basis. In total, 24 mycotoxins were detected in samples analysed with deoxynivalenol (DON), zearalenone (ZEN), fumonisins (FBs), apicidin, enniatins (ENNs), emodin and beauvericin (BEV), the most prevalent mycotoxins. Furthermore, significantly higher levels (however below EU guidance values) of DON, ZEN, FBs, BEV, ENNs and diacetoxyscirpenol (DAS) were detected in 6 of the 18 performance trials. A strong positive relationship was observed between broilers feed efficiency and DON (R2 = 0.85), FBs (R2 = 0.53), DAS (R2 = 0.86), ZEN (R2 = 0.92), ENNs (R2 = 0.60) and BEV (R2 = 0.73). Moreover, a three-way interaction regression model revealed that mixtures of ZEN, DON and FBs (p = 0.01, R2 = 0.84) and ZEN, DON and DAS (p = 0.001, R2 = 0.91) had a statistically significant interaction effect on the birds’ feed efficiency. As farm animals are often exposed to low doses of mycotoxin mixtures (especially fusarium mycotoxins), a cumulative risk assessment in terms of measuring and mitigating against the economic, welfare and health impacts is needed for this group of compounds.
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Shin, Seok-Ho, Min-Ho Park, Jin-Ju Byeon, et al. "Analysis of Vipadenant and Its In Vitro and In Vivo Metabolites via Liquid Chromatography-Quadrupole-Time-of-Flight Mass Spectrometry." Pharmaceutics 10, no. 4 (2018): 260. http://dx.doi.org/10.3390/pharmaceutics10040260.
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A simple and sensitive liquid chromatography–quadrupole-time-of-flight–mass spectrometric (LC-QTOF-MS) assay has been developed for the evaluation of drug metabolism and pharmacokinetics (PK) properties of vipadenant in rat, a selective A2a receptor antagonist as one of the novel immune checkpoint inhibitors. A simple protein precipitation method using acetonitrile was used for the sample preparation and the pre-treated samples were separated by a reverse-phase C18 column. The calibration curve was evaluated in the range of 3.02 ~ 2200 ng/mL and the quadratic regression (weighted 1/concentration) was used for the best fit of the curve with a correlation coefficient ≥0.997. The in vivo PK studies in rats showed that vipadenant bioavailability was 30.4 ± 8.9% with a low to moderate drug clearance. In addition, in vitro/in vivo metabolite profiles in rat were also explored. Five different metabolites were observed in our experimental conditions and the major metabolites were different between in vitro and in vivo conditions. As far as we know, there has been no report on the development of quantitative methods for its PK samples nor the identification of its metabolites since vipadenant was developed. Therefore, this paper would be very useful to better understand the pharmacokinetic and drug metabolism properties of vipadenant in rat as well as other species.
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Zaki, Osama, Matthew Dunnigan, Valentin Robu, and David Flynn. "Reliability and Safety of Autonomous Systems Based on Semantic Modelling for Self-Certification." Robotics 10, no. 1 (2021): 10. http://dx.doi.org/10.3390/robotics10010010.
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A novel modelling paradigm for online diagnostics and prognostics for autonomous systems is presented. A model for the autonomous system being diagnosed is designed using a logic-based formalism. The model supports the run-time ability to verify that the autonomous system is safe and reliable for operation within a dynamic environment. The paradigm is based on the philosophy that there are different types of semantic relationships between the states of different parts of the system. A finite state automaton is devised for each sensed component and some of the non-sensed components. To capture the interdependencies of components within such a complex robotic platform, automatons were related to each other by semantic relationships. Modality was utilised by the formalism to abstract the relationships and to add measures for the possibility and uncertainty of the relationships. The complexity of the model was analysed to evaluate its scalability and applicability to other systems. The results demonstrate that the complexity is not linear and a computational time of 10 ms was required to achieve run-time diagnostics for 2200 KB of knowledge for complex system interdependences. The ability to detect and mitigate hardware related failures was demonstrated within a confined space autonomous operation. Our findings provide evidence of the applicability of our approach for the significant challenge of run-time safety compliance and reliability in autonomous systems.
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Terneus Jácome, Esteban. "Vegetación acuática y estado trófico de las lagunas andinas de San Pablo y Yahuarcocha, provincia de Imbabura, Ecuador." Revista Ecuatoriana de Medicina y Ciencias Biológicas 35, no. 1-2 (2017): 121–31. http://dx.doi.org/10.26807/remcb.v35i1-2.255.
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San Pablo y Yahuarcocha son dos de las cuatro lagunas que se encuentran entre 2200 y 2800 m de altitud en Ecuador. Al estar localizadas en este rango altitudinal, son más productivas que las de la zona de páramo, por la elevada concentración de nutrientes en sus aguas, producto de la influencia humana en sus áreas circundantes. El presente estudio analiza el estado trófico de las lagunas de San Pablo y Yahuarcocha y su repercusión en la estratificación de la vegetación acuática y en su composición florística.
 Se registraron veintiún especies de plantas acuáticas en San Pablo y nueve en Yahuarcocha; cinco especies se encuentran en ambas lagunas incluyendo la “Totora” (Scirpus californicus (C.A. Mey.) Steud), utilizada en la elaboración de esteras. En San Pablo, una de las especies más importantes es Ceratophyllum demersum Hutch.& Dalziel, 1930 única especie registrada para el Ecuador en lagunas andinas y que crece hasta los siete metros de profundidad. Esta especie sirve como alimento para el Bass (Morone saxatilis Walbaum, 1792), el principal recurso en la pesca artesanal de los indígenas de la zona y que también se encuentra presente únicamente en esta laguna. En Yahuarcocha, Potamogeton pusillus L., crece hasta los 3.10 m de profundidad y también constituye una fuente de recursos alimentarios para peces como la Tilapia (Tilapia Mozambique (Peters, 1852) y los Guppis (Poecilia reticulata W. K. H. Peters, 1859).
 Yahuarcocha se puede catalogar como una laguna eutrófica, debido a que su alcalinidad fue de 956 mg/l, y su conductividad fue superior a 620 ms; la transparencia del agua fue menor a dos metros de profundidad y estuvo dominada por una sola especie (Potamogeton pusillus). En cambio, San Pablo es un lago mesotrófico, con una conductividad menor a 320 ms y una alcalinidad de 226 mg/l, transparencia de agua sobre los 3 m de profundidad y presencia de al menos veinte especies de plantas acuáticas que originan hábitats heterogéneos, óptimos para el establecimiento de comunidades mixtas de plantas alrededor de toda la laguna.
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Carreiro, Luiz Renato Rodrigues, Rafael Angulo Condoretti Barros Novaes, Mayara Miyahara Moraes Silva, and Vera Rocha Reis Lellis. "TEMPORAL SUSTENANCE OF ATTENTION IN CHILDREN DURING INFANCY USING REACTION TIME MEASURES." International Journal for Innovation Education and Research 6, no. 12 (2018): 120–28. http://dx.doi.org/10.31686/ijier.vol6.iss12.1255.
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Sustained attention corresponds to the ability to maintain attentional focus on an activity for a longer period with the same consistency pattern. Knowledge about the development of mental abilities is essential for the understanding of how cognitive processes establishes throughout development and their relation to brain organization. This study aims to analyze the ability to sustain attentional focus in time in children of different age groups. The study included 78 children aged 6 to 11 years old (44 girls and 34 boys), enrolled from the 1st year to the 5th year of private school in São Paulo, Brazil. Each participant was instructed to fixate the gaze at the fixation point (FP), prepare to respond after it changed color to blue and respond as quickly as possible to the occurrence of the target (0.3-degree square superimposed to the central point) pressing the space bar, measuring the reaction time (RT). The target would come after one of 12 equal possible time intervals (100; 400; 700; 1000; 1300; 1600; 1900; 2200; 2500; 2800; 3100 and 3400 ms) in milliseconds. Multifactor ANOVA with repeated measures results demonstrated a significant effect (F (4, 73) = 13.001, p <0.001) for Schooling. It was also verified a systematic decrease of the RT as a function of cue-target time interval increase (F (11, 803) = 26,708, p <0.001). In this manner, we observed a systematic decrease in the RT due to the increase in schooling and in function of increase cue-target time interval.
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Chen, X. L., L. Yu, M. M. Wang, C. X. Lin, C. G. Liu, and J. Y. Li. "Brief Communication: Landslides triggered by the <i>M</i><sub>s</sub> = 7.0 Lushan earthquake, China." Natural Hazards and Earth System Sciences 14, no. 5 (2014): 1257–67. http://dx.doi.org/10.5194/nhess-14-1257-2014.
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Abstract. Earthquake-triggered landslides have drawn much attention around the world because of the severe hazards they pose. The 20 April 2013 Ms = 7.0 Lushan Earthquake, which occurred in the Longmen Shan region in Sichuan province, China, triggered more than 1000 landslides throughout an area of about 2200 km2, and completely blocked many roads and exacerbated overall transportation problems in the mountainous terrain. Preliminary landslide inventory is complied immediately following the earthquake, mainly based on the high-resolution remote sensing images. At the same time, the distribution of these landslides is statistically investigated to determine how the occurrence of landslides correlates with distance from the earthquake epicenter, slope steepness, seismic intensity and rock type. Statistic analysis is conducted using landslide point density (LPD), which is defined as the number of landslides per square kilometer. It is found that LPD has a strong positive correlation with slope gradients and a negative-exponential decline with the distance from the epicenter. The higher LPD values occur in younger strata systems like Quaternary and Tertiary sediments in the study area. Spatially, the triggered landslides are controlled by the causative faults and mainly concentrated around the epicenter. All the landslides are located within the area with seismic intensity ≥ VII and in line with seismic intensity. Generally, LPD value decreases with increasing distance from the epicenter, and sometimes landslides are densely distributed along the roads in the mountainous region. Also, this study reveals that the empirical relationship between distance and seismic magnitude is more suitable for estimating the landslide concentration area during the Lushan earthquake compared to other methods.
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Szypuła, Wojciech J., Beata Wileńska, Aleksandra Misicka, and Agnieszka Pietrosiuk. "Huperzine A and Huperzine B Production by Prothallus Cultures of Huperzia selago (L.) Bernh. ex Schrank et Mart." Molecules 25, no. 14 (2020): 3262. http://dx.doi.org/10.3390/molecules25143262.
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This is the first report of an efficient and effective procedure to optimize the biosynthesis of huperzine A (HupA) and huperzine B (HupB) in vitro from Huperzia selago gametophytes. Axenic tissue cultures were established using spores collected from the sporophytes growing in the wild. The prothalia were obtained after 7–18 months. Approximately 90 up to 100% of the gametophytes were viable and grew rapidly after each transfer on to a fresh medium every 3 months. The best biomass growth index for prothallus calculated on a fresh (FW) and dry weight (DW) basis, at 24 weeks of culture, was 2500% (FW) and 2200% (DW), respectively. The huperzine A content in the gametophytes was very high and ranged from 0.74 mg/g to 4.73 mg/g DW. The highest yield HupA biosynthesis at >4 mg/g DW was observed on W/S medium without growth regulators at 8 to 24 weeks of culture. The highest HupB content ranged from 0.10 mg/g to 0.52 mg/g DW and was obtained on the same medium. The results demonstrate the superiority of H. selago gametophyte cultures, with the level of HupA biosynthesis approximately 42% higher compared to sporophyte cultures and 35-fold higher than when the alkaloid was isolated from H. serrata, its current source for the pharmaceutical industry. Moreover, the biosynthesis of HupB was several-fold more efficient than in H. selago sporophytes growing in the wild. HPLC-HR-MS analyses of the extracts identified eight new alkaloids previously unreported in H. selago: deacetylfawcettine, fawcettimine, 16-hydroxyhuperzine B, deacetyllycoclavine, annopodine, lycopecurine, des-N-methylfastigiatine and flabelline.
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Nishiyama, Jun, Takuya Yonemochi, Kazuma Yokota, et al. "NI-08 TRIAL AND PROBLEM OF USING ASL IN INTRAOPERATIVE MRI." Neuro-Oncology Advances 1, Supplement_2 (2019): ii27. http://dx.doi.org/10.1093/noajnl/vdz039.121.
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Abstract INTRODUCTION Magnetic resonance perfusion imaging is considered to be available as grading of brain tumor and follow-up of brain treatment. One of the methods, arterial spin labeling (ASL), is a test that is useful for patients with renal impairment and contrast agent allergy and has low invasiveness because it does not use a contrast agent. However, there have been no reports of ASL in intraoperative MRI (iMRI). PURPOSE In this hospital iMRI (1.5T), it was examined whether ASL could be used to evaluate residual tumor in patients under general anesthesia. CASE STUDY A 75-year-old woman with right temporal lobe Glioblastoma. 43-year-old man, left temporal lobe Diffuse astrocytoma. All performed ASL at the time of MRI imaging for navigation before induction of anesthesia just before surgery and iMRI. In all cases, the blood pressure at iMRI was maintained, and Post Label Delay (PLD) calculated the optimal PLD from the carotid artery velocity measured by iMRI, and defined it as 1800–2200 ms, and performed ASL. RESULTS Actually, imaging by iMRI was almost difficult to visualize, and reflux was not recognized not only in the tumor but also in the gray matter. DISCUSSION The blood flow velocity measurement in the internal carotid artery is performed by the phase contrast method by intraoperative MRI, and the CBF decreases because propofol used during the operation decreases the CBF and also the brain metabolism. However, it has been suggested that it is one of the factors that make evaluation with ASL difficult. Although the iMRI of our hospital is 1.5 T, which is also a subject of investigation, it is thought that there is a limit to ASL imaging in the case of general anesthesia with propofol even from the calculated PLD. CONCLUSION ASL in iMRI at our hospital was not useful.
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Shah, Payal, Kadden Heinrich Kothmann, Cassandra Suzanne Skenandore, et al. "Dietary Coconut Oil Mitigates Hyperandrogenemia in Obese Female Pigs Due to Suppression of Androgen Steroidogenesis in the Adrenal Cortex and Theca Externa." Journal of the Endocrine Society 5, Supplement_1 (2021): A764—A765. http://dx.doi.org/10.1210/jendso/bvab048.1555.
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Abstract Western-style diets (WSD) cause cardiometabolic disease and hyperandrogenemia in reproductive-age women. A promising alternative for improved fertility in obese women may derive from the nutraceutical, coconut oil. We hypothesized that dietary coconut oil included in a high fat diet would mitigate hyperandrogenemia due to obesity through depression of androgen steroidogenesis in theca externa and adrenal cortex. Seventeen sexually mature female Ossabaw pigs were divided into 3 diet groups: control (n=6; C; 2200 kcal/pig/day), WSD (n=5; WSD; 5000 kcal/pig/day), or high fat coconut oil diet (n=6; COC; 5000 kcal/pig/day). Ingredients in WSD and COC diets were the same except 9% of calories in WSD were from lard and 9% of calories in COC were from coconut oil. Pigs were fed for 9 cycles (~ 8 mos) and fasting blood was collected at cycle 0 (baseline), 7, and 9. After cycle 7, ovarian steroidogenesis was suppressed by oral progestogen for 18 days. On day 18 while ovarian steroidogenesis was still suppressed, an ACTH stimulation was performed. On day 19, progestogen was withdrawn and 7.5 µg/kg IM dexamethasone was given every 12 hours to suppress adrenal steroidogenesis. On day 20, 3000 IU/m2 human chorionic gonadotropin (hCG) was given IV. Pigs underwent a washout cycle post-stimulations and were euthanized when they had dominant ovarian follicles in cycle 9 for collection of follicular fluid (FF), theca externa, and adrenal cortex. FF was assessed for steroid hormones by LC-MS/MS. Adrenal cortex and theca cells were cultured as follows for 48 hours after which cells and media were collected: 1) theca: control, insulin (I; 100 ng/ml), LH (10 ng/ml), or LH+I (10 ng/ml + 100 ng/ml); 2) adrenal: control or 1 µM ACTH. WSD pigs had a protracted estrous cycle length and increased FF testosterone, dehydroepiandrosterone sulfate, androstenedione (A4), androstenediol, and allo-pregnanolone (Allo-Preg) compared to C pigs. Both serum and cell culture media A4 concentrations were higher in response to ACTH in WSD pigs. By 72 hours post-hCG, COC pigs had higher serum A4 than C or WSD pigs, but in vitro LH yielded decreased cell culture media A4 in both WSD and COC pigs. COC pigs had increased FF dihydrotestosterone and Allo-Preg compared to C pigs. These results suggest that dietary coconut oil administration in obese females may depress excessive androgen steroidogenesis by adrenal cortex but may only partially mitigate excessive androgen production by theca externa.
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Searle, M. P., J. M. Cottle, M. J. Streule, and D. J. Waters. "Crustal melt granites and migmatites along the Himalaya: melt source, segregation, transport and granite emplacement mechanisms." Earth and Environmental Science Transactions of the Royal Society of Edinburgh 100, no. 1-2 (2009): 219–33. http://dx.doi.org/10.1017/s175569100901617x.
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ABSTRACTIndia–Asia collision resulted in crustal thickening and shortening, metamorphism and partial melting along the 2200 km-long Himalayan range. In the core of the Greater Himalaya, widespread in situ partial melting in sillimanite+K-feldspar gneisses resulted in formation of migmatites and Ms+Bt+Grt+Tur±Crd±Sil leucogranites, mainly by muscovite dehydration melting. Melting occurred at shallow depths (4–6 kbar; 15–20 km depth) in the middle crust, but not in the lower crust. 87Sr/86Sr ratios of leucogranites are very high (0·74–0·79) and heterogeneous, indicating a 100 crustal protolith. Melts were sourced from fertile muscovite-bearing pelites and quartzo-feldspathic gneisses of the Neo-Proterozoic Haimanta–Cheka Formations. Melting was induced through a combination of thermal relaxation due to crustal thickening and from high internal heat production rates within the Proterozoic source rocks in the middle crust. Himalayan granites have highly radiogenic Pb isotopes and extremely high uranium concentrations. Little or no heat was derived either from the mantle or from shear heating along thrust faults. Mid-crustal melting triggered southward ductile extrusion (channel flow) of a mid-crustal layer bounded by a crustal-scale thrust fault and shear zone (Main Central Thrust; MCT) along the base, and a low-angle ductile shear zone and normal fault (South Tibetan Detachment; STD) along the top. Multi-system thermochronology (U–Pb, Sm–Nd, 40Ar–39Ar and fission track dating) show that partial melting spanned ̃24–15 Ma and triggered mid-crustal flow between the simultaneously active shear zones of the MCT and STD. Granite melting was restricted in both time (Early Miocene) and space (middle crust) along the entire length of the Himalaya. Melts were channelled up via hydraulic fracturing into sheeted sill complexes from the underthrust Indian plate source beneath southern Tibet, and intruded for up to 100 km parallel to the foliation in the host sillimanite gneisses. Crystallisation of the leucogranites was immediately followed by rapid exhumation, cooling and enhanced erosion during the Early–Middle Miocene.
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Engeland, Kolbjørn, Anna Aano, Ida Steffensen, Eivind Støren, and Øyvind Paasche. "New flood frequency estimates for the largest river in Norway based on the combination of short and long time series." Hydrology and Earth System Sciences 24, no. 11 (2020): 5595–619. http://dx.doi.org/10.5194/hess-24-5595-2020.
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Abstract. The Glomma River is the largest in Norway, with a catchment area of 154 450 km2. People living near the shores of this river are frequently exposed to destructive floods that impair local cities and communities. Unfortunately, design flood predictions are hampered by uncertainty since the standard flood records are much shorter than the requested return period and the climate is also expected to change in the coming decades. Here we combine systematic historical and paleo information in an effort to improve flood frequency analysis and better understand potential linkages to both climate and non-climatic forcing. Specifically, we (i) compile historical flood data from the existing literature, (ii) produce high-resolution X-ray fluorescence (XRF), magnetic susceptibility (MS), and computed tomography (CT) scanning data from a sediment core covering the last 10 300 years, and (iii) integrate these data sets in order to better estimate design floods and assess non-stationarities. Based on observations from Lake Flyginnsjøen, receiving sediments from Glomma only when it reaches a certain threshold, we can estimate flood frequency in a moving window of 50 years across millennia revealing that past flood frequency is non-stationary on different timescales. We observe that periods with increased flood activity (4000–2000 years ago and <1000 years ago) correspond broadly to intervals with lower than average summer temperatures and glacier growth, whereas intervals with higher than average summer temperatures and receding glaciers overlap with periods of reduced numbers of floods (10 000 to 4000 years ago and 2200 to 1000 years ago). The flood frequency shows significant non-stationarities within periods with increased flood activity, as was the case for the 18th century, including the 1789 CE (“Stor-Ofsen”) flood, the largest on record for the last 10 300 years at this site. Using the identified non-stationarities in the paleoflood record allowed us to estimate non-stationary design floods. In particular, we found that the design flood was 23 % higher during the 18th century than today and that long-term trends in flood variability are intrinsically linked to the availability of snow in late spring linking climate change to adjustments in flood frequency.
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Latour, Lawrence L., and Steven Warach. "Conventional Diffusion Weighted Imaging In Acute Stroke Overestimates Apparent Diffusion Coefficient (ADC): Improved Accuracy of ADC Measurements of Brain Using Fluid-Inversion Prepared Diffusion (FLIPD) Imaging." Stroke 32, suppl_1 (2001): 318. http://dx.doi.org/10.1161/str.32.suppl_1.318-a.
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13 Background: The measurement of ADC of water in brains of stroke patients is used in developing tissue models of reversible from irreversible injury. Cerebrospinal fluid (CSF) has a higher ADC and T2 value than parenchyma and measurement of lesion ADC by conventional EPI methods may be overestimated by the presence of CSF in sulci and perivascular spaces. We investigated whether the suppression of signal from CSF using an inversion recovery MRI method would give different ADC values than with the conventional DWI technique. Methods: Thirteen consecutive patients with stroke onset of less than 6 hours and an acute lesion on conventional DWI were studied. Conventional isotropic DWI was a T2-weighted single shot EPI technique with a b value of 1000 s/mm2. CSF suppression was achieved by the addition of an inversion pulse (TI = 2200 ms) at the beginning of the DWI sequence. The method is termed Fluid-Inversion Prepared Diffusion (FLIPD), and it is a combination of FLAIR and DWI in a single sequence. The region of the acute lesion was identified on the conventional DWI and the ADC of that region was measured in both the conventional and FLIPD ADC images. Results: In all 13 patients, FLIPD ADC was lower than conventional ADC. The mean (SD) of the 13 patients’ lesion ADC was 0.587 (0.075) x 10 -3 mm/s with FLIPD and 0.696 (0.078) x 10 -3 mm/s with conventional DWI (p < 0.0001). The distribution of ADC values in all voxels pooled across all subjects indicated a narrower distribution of for FLIPD ADC (SD = 0.128 vs. 0.220 x 10 -3 mm/s for lesions and (SD = 0.151 vs. 0.514 x 10 -3 mm/s for normal brain). The reduced variance in FLIPD ADC improved the diagnostic conspicuity of FLIPD ADC lesions. Conclusions: Suppression of CSF leads to lesion ADC values more homogeneous and greater than 15% lower than with conventional EPI DWI techniques. We suggest that FLIPD ADC measurements are more accurate and give more diagnostically useful images than conventional ADC maps. Because FLIPD measures water diffusion within parenchyma only, it should be more sensitive to ischemic changes.
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Trabelsi, Hajer, Justin Renaud, Wahid Herchi, Mohamed L. Khouja, Sadok Boukhchina, and Paul Mayer. "LC–ESI–QTOF–MS, MS/MS Analysis of Glycerophospholipid Species in Three Tunisian Pistacia lentiscus Fruit Populations." Journal of the American Oil Chemists' Society 90, no. 5 (2013): 611–18. http://dx.doi.org/10.1007/s11746-013-2203-6.
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Freye, Reimund. "MS: Kontinuierliche Behinderungsprogression adressieren." DNP - Der Neurologe & Psychiater 20, no. 3 (2019): 63. http://dx.doi.org/10.1007/s15202-019-2206-8.
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Seo, Hee Won, Min-Geun Kim, Hanmin Lee, and Jeong Sam Han. "Automation Tool for VDI 2230 Based Structural Analysis and Evaluation of Bolted Joints Using ANSYS and MS Excel." Transactions of the Korean Society of Mechanical Engineers - A 44, no. 2 (2020): 149–58. http://dx.doi.org/10.3795/ksme-a.2020.44.2.149.
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Diao, Xingxing, Ariane Wohlfarth, Shaokun Pang, Karl B. Scheidweiler, and Marilyn A. Huestis. "High-Resolution Mass Spectrometry for Characterizing the Metabolism of Synthetic Cannabinoid THJ-018 and Its 5-Fluoro Analog THJ-2201 after Incubation in Human Hepatocytes." Clinical Chemistry 62, no. 1 (2016): 157–69. http://dx.doi.org/10.1373/clinchem.2015.243535.
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Abstract BACKGROUND Despite increasing prevalence of novel psychoactive substances, no human metabolism data are currently available, complicating laboratory documentation of intake in urine samples and assessment of the drugs' pharmacodynamic, pharmacokinetic, and toxicological properties. In 2014, THJ-018 and THJ-2201, synthetic cannabinoid indazole analogs of JWH-018 and AM-2201, were identified, with the National Forensic Laboratory Information System containing 220 THJ-2201 reports. Because of numerous adverse events, the Drug Enforcement Administration listed THJ-2201 as Schedule I in January 2015. METHODS We used high-resolution mass spectrometry (HR-MS) (TripleTOF 5600+) to identify optimal metabolite markers after incubating 10 μmol/L THJ-018 and THJ-2201 in human hepatocytes for 3 h. Data were acquired via full scan and information-dependent acquisition triggered product ion scans with mass defect filter. In silico metabolite predictions were performed with MetaSite and compared with metabolites identified in human hepatocytes. RESULTS Thirteen THJ-018 metabolites were detected, with the major metabolic pathways being hydroxylation on the N-pentyl chain and further oxidation or glucuronidation. For THJ-2201, 27 metabolites were observed, predominantly oxidative defluorination plus subsequent carboxylation or glucuronidation, and glucuronidation of hydroxylated metabolites. Dihydrodiol formation on the naphthalene moiety was observed for both compounds. MetaSite prediction matched well with THJ-018 hepatocyte metabolites but underestimated THJ-2201 oxidative defluorination. CONCLUSIONS With HR-MS for data acquisition and processing, we characterized THJ-018 and THJ-2201 metabolism in human hepatocytes and suggest appropriate markers for laboratories to identify THJ-018 and THJ-2201 intake and link observed adverse events to these new synthetic cannabinoids.
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Mitrokhina, N. M., and I. N. Polunin. "The effect of isoptin on sinus arrhythmias arising from hypoxia." Kazan medical journal 67, no. 4 (1986): 296–97. http://dx.doi.org/10.17816/kazmj70548.
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It was found that exposure to isoptin reduced the amplitude of action potentials by 15.8 mV (41.19%), the pre-potential value by 11.5 mV (68.6%); prolongs the phase of slow diastolic depolarization by 176.5 ms (54.5%), the phase of systolic depolarization by 20.12 ms (29.1%); shortens repolarization by 34.5 ms (17.5%) and slows the frequency of spontaneous activity by 22.0 per 1 min (18.4%).
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Minakata, Kayoko, Itaru Yamagishi, Koutaro Hasegawa, et al. "In vitro and in vivo human metabolism of a synthetic cannabinoid EAM-2201 detected by LC–quadrupole-ion trap-MS/MS and high-resolution LC–Orbitrap-MS/MS." Forensic Toxicology 37, no. 2 (2019): 432–42. http://dx.doi.org/10.1007/s11419-019-00484-z.
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Manley, Paul W., Jürgen Mestan, Jennifer Sheng, Phi Tran, and Mark Kagan. "Clinical and Preclinical Characterisation Of The Metabolites Of The BCR-ABL Tyrosine Kinase Inhibitor Nilotinib." Blood 122, no. 21 (2013): 4011. http://dx.doi.org/10.1182/blood.v122.21.4011.4011.
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Abstract Background There is a growing tendency for drugs to be grouped according to their perceived ‘class effects’, regardless of the different pharmacological profiles of the parent drugs and of their metabolites. Imatinib, dasatinib, nilotinib, bosutinib and, most recently ponatinib, are approved tyrosine kinase inhibitor (TKI) therapies for chronic myeloid leukemia (CML), which are clinically efficacious as a result of ABL1/ BCR-ABL inhibition. Following their oral administration at standard therapeutic doses, the parent drugs are the major circulating species by area under the curve (AUC). However in the case of imatinib, dasatinib, bosutinib and ponatinib, the exposure of patients to major metabolites can be substantial compared to that of parent drug, with CGP74588 (which is much less active than imatinib against both BCR-ABL and KIT; Bioorg Med Chem 2013;21:3231) representing 10% of imatinib by AUC (Clin Pharmacokinet 2005;44:879); M20 and M24 representing 45 and 25% of dasatinib (Drug Met Disp 2008;36:1341), M2 and M5 representing 19 and 25% of bosutinib (Clinical Pharmacology Biopharmaceutics Review, http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm) and AP24600 representing 58% of ponatinib (Clinical Pharmacology Biopharmaceutics Review, http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm). Such major metabolites might make significant contributions to the on- and off-target effects of the parent drugs in vivoand may be responsible for some of the side-effects observed in patients. Here we report on the metabolism of the potent and selective BCR-ABL inhibitor, nilotinib and the preclinical profile of its major metabolites. Methods The metabolism of nilotinib was characterised in healthy subjects after oral administration of two capsules containing 200 mg [14C]-labelled nilotinib (50 μCi), and blood plasma, feces and urine samples were assayed in an appropriate scintillant either by counting an aliquot directly or after homogenisation, air-drying and solubilisation. Metabolites were characterised and quantified by HPLC with radioactivity detection and identified by mass spectrometry (LC-MS/MS) and, when possible, co-elution with non-radiolabeled authentic samples. Synthesised samples of the metabolites were evaluated in a large panel of assays for potential effects on kinase and non-kinase enzymes, G-protein coupled receptors, cell transporters, ion channels and nuclear receptors. Results The oral absorption of nilotinib was determined to be ≥30% and excretion was mainly into the feces (93.5% of administered radioactivity), with neither nilotinib nor the identified metabolites being detected in the urine. Unchanged nilotinib was the major circulating component in human plasma, accounting for 87.5±9.2% of the total drug-related AUC. The main circulating metabolites were P41.6 (4.7% AUC), P36.5 (6.1% AUC), formed from oxidation of the methyl group in the methyl-imidazole moiety to a hydroxyl or carboxylic acid group, and P42.1 (1.3% AUC) resulting from oxidation of the phenyl-methyl group. Other, more minor metabolites included the pyridine N-oxide P36 and P50, resulting from degradation of the imidazole. All of the metabolites identified in humans were also observed in one or more of the animal species, employed for preclinical safety studies, with the exception of the minor fecal metabolites P38 (pyridine- + pyrimidine-N-oxide) and P40 (pyridine-N-oxide). In comparison to the parent nilotinib, which inhibits the BCR-ABL and KIT tyrosine kinases with mean cellular IC50 values of 20 and 217 nM, only P41.6 (19 and 284 nM), P42.1 (256 and 714 nM) and P50 (39 and 67 nM) exhibited kinase inhibition at concentrations < 2200 nM. In addition, none of the metabolites showed substantial activity at concentrations < 3000 nM against non-kinase targets. Conclusion Following oral administration of nilotinib to humans the predominant circulating species was the parent drug, with >15 minor and trace metabolites being identified. Given their in vitro potencies and target profiles, none of the metabolites are expected to contribute to the in vivo pharmacology of the parent nilotinib. This data further distinguishes the profile of nilotinib from other TKIs used for the treatment of CML. Disclosures: Manley: Novartis Pharmaceuticals: Employment. Sheng:Novartis Pharmaceuticals: Employment. Tran:Novartis Pharmaceuticals: Employment. Kagan:Novartis Pharmaceuticals: Employment.
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Arreaza, Javier, Ga Hee Kim, Andrew J. Kim, Jeewendra Dulal, and Peter Anthony Goulden. "Calciphylaxis in Association With Hungry Bone Syndrome. A Possible Risk Factor?" Journal of the Endocrine Society 5, Supplement_1 (2021): A186. http://dx.doi.org/10.1210/jendso/bvab048.376.
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Abstract Background: Calciphylaxis (calcific uremic arteriolopathy) is a rare complication seen in, although not limited to, patients with end-stage renal disease (ESRD). The abnormal regulation of calcium (Ca) and phosphorus (P) homeostasis in this patient group results in intravascular Ca deposition. These patients often develop secondary/tertiary hyperparathyroidism, presenting unique treatment challenges. When patients do not respond to medical therapy, parathyroidectomy is an option that may be complicated by hungry bone syndrome (HBS). We present a case of a patient with calciphylaxis with HBS post-parathyroidectomy. Case Report: The patient is a 41 y.o. male with ESRD on hemodialysis who presented with lower extremity ulcers complicated by calciphylaxis. On admission, the PTH was elevated at 2200 U with a normal corrected Ca 8.7 and P 8.5. He was found to have a non-displaced pathologic fracture of the right femoral neck. CT scan of the neck revealed nodular parathyroid hyperplasia affecting all four glands. His hyperparathyroidism was managed medically with cinacalcet, phosphate binder, and sodium thiosulfate to optimize his condition before surgery. He underwent a subtotal parathyroidectomy, with post-op course complicated by HBS. Repeat labs showed PTH 444, P 6.1, corrected Ca 7.4, and ionized Ca &lt;4. Despite frequent repletion with IV Ca and addition of calcitriol, he remained persistently hypocalcemic with symptoms (paresthesia, perioral numbness) and prolonged QTc (560 ms) on 12-lead EKG. After weighing the more imminent risk of unstable arrhythmia versus exacerbation of HBS by targeting too high of a Ca level post-op, ICU admission was decided where Ca levels could be more closely monitored and titrated. The patient eventually demonstrated an improvement in his Ca level and symptoms. Discussion: This patient with ESRD complicated by hyperparathyroidism presented with ulcers and calciphylaxis refractory to medical therapy, requiring parathyroidectomy. HBS was a concern in this particular patient given his risk factors. Hypocalcemia is an expected electrolyte imbalance that usually resolves within 2–4 days after parathyroidectomy. Severe and persistent hypocalcemia on day 4 after the procedure should raise concern for HBS. It has been shown that the risk is higher in patients who have secondary hyperparathyroidism, prolonged duration of elevated PTH, age &gt;60, and radiologic evidence of bone disease. ConclusionCalciphylaxis is an uncommon but potentially fatal illness seen in ESRD patients associated with Ca and P abnormalities. Whether this may increase the risk of HBS status-post parathyroidectomy is unknown; however, HBS requiring ICU management to treat refractory hypocalcemia has been reported in this group1. It is arguable that calciphylaxis may serve to identify such patients. (1) Hassanein M, et al. BMJ Case Rep 2018;11:e226696. doi:10.1136/bcr-2018–226696
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Magi, Emanuele, Marina Di Carro, Carlo Scapolla, and Kieu T. N. Nguyen. "Stir Bar Sorptive Extraction and LC–MS/MS for Trace Analysis of UV Filters in Different Water Matrices." Chromatographia 75, no. 17 (2012): 973–82. http://dx.doi.org/10.1007/s10337-012-2202-z.
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Holm, Niels Bjerre, Rebeca Sequera Pineda, David Wederkinck Andersen, et al. "Screening of Danish traffic cases for synthetic cannabinoids in whole blood by LC-MS/MS." Scandinavian Journal of Forensic Science 19, no. 2 (2013): 45–51. http://dx.doi.org/10.2478/sjfs-2013-0008.
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ABSTRACT A target screening method for the detection of 13 synthetic cannabinoids in whole blood was developed and validated. Samples underwent automated solid-phase extraction, and sample extracts were analyzed by liquid chromatography-positive electrospray ionization-tandem mass spectrometry using two transitions in multiple reaction monitoring mode. The limit of detection was between 0.1-2.5 ng/mL for the compounds except HU-210, and extraction recovery ranged from 59 to 78%. The method was used to screen 393 Danish traffic cases from 2012, where the driver was suspected of driving under the influence of drugs. No synthetic cannabinoids were identified in these samples. Additionally, the method was applied to a clinical intoxication case, and the synthetic cannabinoid AM- 2201 was identified in serum. We conclude that the prevalence of driving under the influence of synthetic cannabinoids in Denmark is likely to be low, and that synthetic cannabinoids are most likely to be encountered in the clinical setting.
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Haarmann, Axel, and Mathias Buttmann. "Gibt es die wirksamste MS-Therapie beim Hämatoonkologen?" DNP - Der Neurologe & Psychiater 20, no. 3 (2019): 28–29. http://dx.doi.org/10.1007/s15202-019-2201-0.
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Claeson, Anna-Sara, Anders �stin, and Anna-Lena Sunesson. "Development of a LC-MS/MS method for the analysis of volatile primary and secondary amines as NIT (naphthylisothiocyanate) derivatives." Analytical and Bioanalytical Chemistry 378, no. 4 (2004): 932–39. http://dx.doi.org/10.1007/s00216-003-2205-6.
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Sirisha, Nagala, and TamanamRaghava Rao. "LIPID PROFILES OF FIVE VARIETIES ARTOCARPUS SEED OILS BY GC-MS- A COMPARATIVE STUDY." International Journal of Advanced Research 4, no. 11 (2016): 1251–57. http://dx.doi.org/10.21474/ijar01/2208.
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Li, Li, Bo Gao, Wen-xue Zhang, et al. "Development of Panax quinquefolius Yaoqu and Panax quinquefolius Sake and determination of ginsenosides Rg1, Rb1, and Re in both samples by HPLC–MS/MS." European Food Research and Technology 239, no. 1 (2014): 137–47. http://dx.doi.org/10.1007/s00217-014-2202-3.
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Colepicolo-Neto, Pio, Hosana Maria Debonsi, Gustavo Souza dos Santos, et al. "GC-MS Analysis, Bioactivity-based Molecular Networking and Antiparasitic Potential of the Antarctic Alga Desmarestia antarctica." Planta Medica International Open 07, no. 03 (2020): e122-e132. http://dx.doi.org/10.1055/a-1219-2207.
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AbstractLeishmaniasis, malaria, and neosporosis are parasitic diseases that affect humans and animals, causing public health problems and billions in economic losses. Despite the advances in the development of new drugs, the severe side effects of available leishmaniasis treatments, the Plasmodium spp. resistance to antimalarial drugs, and the lack of a specific treatment against neosporosis lead us to the search for new anti-protozoan molecules from underexplored sources such as the Antarctic marine environment. Herein, we describe for the first time the chemical profile of Desmarestia antarctica crude extract and fractions using GC-MS and LC-MS/MS (molecular networking) approaches, and evaluate their antiparasitic activity against Leishmania amazonensis, Neospora caninum, and multi-drug-resistant Plasmodium falciparum. Furthermore, the cytotoxicity in 3T3 BALB/c fibroblasts and Vero cells was evaluated. D. antarctica fraction E ( IC50 of 53.8±4.4 μg mL− 1 and selectivity index of 3.3) exhibited anti-promastigote activity and was fourfold more selective to L. amazonensis rather than to the host cells. D. antarctica fraction D (IC50 of 1.6±1.3 μg mL− 1 and selectivity index of 27.8), D. antarctica fraction F (IC50 of 3.1±2.1 μg mL− 1 and selectivity index of 23.1), and D. antarctica fraction H (IC50 of 3.1±2.0 μg mL− 1 and selectivity index of 12.9) presented the highest antiparasitic effects against N. caninum with no cytotoxic effects. Also, D. antarctica fraction D presented a significant antiplasmodial inhibitory effect (IC50 of 19.1±3.9 μg mL− 1 and selectivity index of 6.0). GC-MS analysis indicated palmitic acid, myristic acid, fucosterol, phthalic acid, di(2-methylbutyl) ester, loliolide, and neophytadiene as the main components in the active fractions. In addition, this is the first report of a biological screening of macroalgae secondary metabolites against N. caninum parasites.
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Bobey, Antonio, Meri Pinto, Eduardo Cilli, Norberto Lopes, and Vanderlan Bolzani. "A Cyclotide Isolated from Noisettia orchidiflora (Violaceae)." Planta Medica 84, no. 12/13 (2018): 947–52. http://dx.doi.org/10.1055/a-0632-2204.
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AbstractBiologically active cyclotides have been found on some flowering plants species and are involved in the role of the plant protection. As part of studies focusing on peptides from Brazilian plant species, we are reporting the detection by LC-MS of several cyclotides from leaves and stems of Noisettia orchidiflora (Violaceae). From stems it was possible to isolate and characterize a cyclotide named Nor A. Its primary structure (amino acid sequence) was established by MALDI-TOF-MS, based on the y- and b-type ion series, after reduction and alkylation reactions, as well as enzymatic digestion using the enzymes endoproteinase glutamic acid (endoGlu-C), trypsin, and chymotrypsin. Furthermore, the amino acid analysis was also described.
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Silvotti, R., R. Janulis, S. L. Schuh, et al. "The temporal spectrum of the sdB pulsating star HS 2201+2610 at 2 ms resolution." Astronomy & Astrophysics 389, no. 1 (2002): 180–90. http://dx.doi.org/10.1051/0004-6361:20020584.
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Bu, Tian-tian, Jie Shen, Qing Chao, et al. "Dynamic N-glycoproteome analysis of maize seedling leaves during de-etiolation using Concanavalin A lectin affinity chromatography and a nano-LC–MS/MS-based iTRAQ approach." Plant Cell Reports 36, no. 12 (2017): 1943–58. http://dx.doi.org/10.1007/s00299-017-2209-x.
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Cogill, Jan L., Paul J. Taylor, Ian S. Westley, Raymond G. Morris, Stephen V. Lynch, and Anthony G. Johnson. "Evaluation of the tacrolimus II microparticle enzyme immunoassay (MEIA II) in liver and renal transplant recipients." Clinical Chemistry 44, no. 9 (1998): 1942–46. http://dx.doi.org/10.1093/clinchem/44.9.1942.
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Abstract We evaluated the MEIA II with blood samples with added tacrolimus (3.0, 5.0, 11.0, and 22.0 μg/L). The assay had acceptable recoveries (99–103%) and intraday imprecision (&lt;16.0%) across the range of concentrations studied, except for the recoveries at 3.0 μg/L (86.3%) and 5.0 μg/L (80.7%). Comparison of liver (n = 116) and renal (n = 113) patient samples measured by MEIA II against HPLC-tandem mass spectrometry (HPLC-MS/MS) found a mean overestimation of 15.6%. From these comparison data it can be calculated that at values of 5 and 20 μg/L in liver or renal transplant patient samples, measured by HPLC-MS/MS, MEIA II will have the corresponding range estimates of 3.6–7.9 μg/L and 20.9–25.4 μg/L, respectively. No clinically significant difference in results, in terms of overestimation or correlation, was observed between the two transplant groups studied. The MEIA II is an improvement on the previous MEIA I and is suitable for the therapeutic drug monitoring of tacrolimus where HPLC-MS/MS is unavailable.
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Mishra, Rakesh V., and Shashikant N. Dhole. "Enhanced Pharmacological Efficacy of Berberine Hydrochloride Loaded Lipid Based Pellets for the Treatment of Metabolic Diseases." Biomedical and Pharmacology Journal 14, no. 02 (2021): 993–1005. http://dx.doi.org/10.13005/bpj/2201.
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Numerous researchers in past have reported the diversified therapeutic effects of Berberine hydrochloride (BERH) for the management of metabolic diseases, however due to poor systemic bioavailability these effects are dose dependant and desired effects were reported at high dose levels. The objective of present investigation is to evaluate and establish the enhancement in pharmacological efficacy of the designed BERH formulation at low oral dose level for the treatment of metabolic diseases constituting metabolic syndrome (MS). In the present investigation, BERH formulation in the dose level of (25 and 50mg/kg/day) was evaluated in cafeteria diet (CD) induced MS model in male Wistar rats for 42 days and compared with available marketed preparation in similar dose level using orlistat as reference drug. Among the studied dose level of BERH formulation the 25 mg/kg/day dose was adequate to produce significant reduction in calorie intake (P < 0.01), body weight, BMI, (P<0.001), organ weight viz. (stomach; P<0.05, liver; P<0.001, heart; P<0.01) and serum biochemical parameters (P<0.001). A significant improvement in lipid peroxidation (P<0.001), catalase (CAT), reduced glutathione (GSH) and superoxide dismutase (SOD) contents (P<0.001) was observed. The histopathological examinations indicated amelioration of liver, heart and pancreas tissues. The current study indicated significant glucose-lowering, hypophagic, anti-obesity, anti-hyperlipidemic and cardio protective activity of the BERH formulation even in much low oral dose level compared to previously reported studies. The observed behavior is attributed due to the enhanced bioavailability of BERH formulation which could be effectively used for metabolic diseases treatment.
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Ramsaransing, Geeta, Natasha Maurits, Cornelis Zwanikken, and Jacques De Keyser. "Early prediction of a benign course of multiple sclerosis on clinical grounds: a systematic review." Multiple Sclerosis Journal 7, no. 5 (2001): 345–47. http://dx.doi.org/10.1177/135245850100700512.
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Background: There is growing consensus that neurologists should consider disease-modifying therapies early in multiple sclerosis (MS). However, there is a subgroup with a natural benign course, in which treatment could be postponed. We sought to determine the frequency of benign MS and early clinical factors that may predict a benign course. Methods: We performed a systematic review of the existing literature on benign MS, which was defined as minimal or no disability equivalent to a score on the Expanded Disability Status Scale (EDSS) 43.0 at least 10 years after disease onset. Results: Only a small number of studies of adequate quality was available. In total there were nine published studies representing 2204 patients. The estimated frequency of benign MS was 26.7%. Onset with optic neuritis, onset before the age of 40 years, absence of pyramidal signs at presentation, duration of first remission more than 1 year, and only one exacerbation in the first 5 years after onset of MS, were associated with a benign course. Conclusions: From the existing literature a set of unrelated clinical characteristics emerged that was associated with a benign course of MS. However, there is a need for prospective studies to define more precisely clinical and paraclinical predictors of benign MS.
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Kelsey, Rick G., Ovid McCuistion, and Joe Karchesy. "Bark and Leaf Essential Oil of Umbellularia californica, California Bay Laurel, from Oregon." Natural Product Communications 2, no. 7 (2007): 1934578X0700200. http://dx.doi.org/10.1177/1934578x0700200715.
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The bark and leaf essential oil of Umbellularia californica (Hook. & Arn.) Nutt. from west central Oregon, USA, was isolated by steam distillation and the chemical composition analyzed by GC-FID and GC-MS. The three major components in bark oil were 1,8-cineole (36.0%), α-santalene (9.3), and α-terpineol (6.9%), while those in leaf oil were umbellulone (41.0%), 1,8-cineole (22.0%) and sabinene (10.2%).