239 research outputs found

    Structure and diffusion in amorphous aluminium silicate: A molecular dynamics computer simulation

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    The amorphous aluminium silicate (Al2O3)2(SiO2) [AS2] is investigated by means of large scale molecular dynamics computer simulations. We consider fully equilibrated melts in the temperature range 6100K >= T >= 2300K as well as glass configurations that were obtained from cooling runs from T=2300K to 300K with a cooling rate of about 10^12K/s. Already at temperatures as high as 4000K, most of the Al and Si atoms are four-fold coordinated by oxygen atoms. Thus, the structure of AS2 is that of a disordered tetrahedral network. The packing of AlO4 tetrahedra is very different from that of SiO4 tetrahedra in that Al is involved with a relatively high probability in small-membered rings and in triclusters in which an O atom is surrounded by four cations. We find as typical configurations two-membered rings with two Al atoms in which the shared O atoms form a tricluster. On larger length scales, the system shows a microphase separation in which the Al-rich network structure percolates through the SiO2 network. The latter structure gives rise to a prepeak in the static structure factor at a wavenumber q=0.5\AA^{-1}. The comparison of experimental X-ray data with the results from the simulation shows a good agreement for the structure function. The diffusion dynamics in AS2 is found to be much faster than in SiO2. We show that the self-diffusion constants for O and Al are very similar and that they are by a factor of 2-3 larger than the one for Si.Comment: 30 pages of Latex, 13 figure

    Normoxic cardiopulmonary bypass reduces oxidative myocardial damage and nitric oxide during cardiac operations in the adult

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    AbstractObjective: Hyperoxic cardiopulmonary bypass is widely used during cardiac operations in the adult. This management may cause oxygenation injury induced by oxygen-derived free radicals and nitric oxide. Oxidative damage may be significantly limited by maintaining a more physiologic oxygen tension strategy (normoxic cardiopulmonary bypass). Methods: During elective coronary artery bypass grafting, 40 consecutive patients underwent either hyperoxic (oxygen tension = 400 mm Hg) or normoxic (oxygen tension = 140 mm Hg) cardiopulmonary bypass. At the beginning and the end of bypass this study assessed polymorphonuclear leukocyte elastase, nitrate, creatine kinase, and lactic dehydrogenase, antioxidant levels, and malondialdehyde in coronary sinus blood. Cardiac index was measured before and after cardiopulmonary bypass. Results: There was no difference between groups with regard to age, sex, severity of disease, ejection fraction, number of grafts, duration of cardiopulmonary bypass, or ischemic time. Hyperoxic bypass resulted in higher levels of polymorphonuclear leukocyte elastase (377 ± 34 vs 171 ± 32 ng/ml, p = 0.0001), creatine kinase 672 ± 130 vs 293 ± 21 U/L, p = 0.002), lactic dehydrogenase (553 ± 48 vs 301 ± 12 U/L, p = 0.003), antioxidants (1.97 ± 0.10 vs 1.41 ± 0.11 mmol/L, p = 0.01), malondialdehyde (1.36 ± 0.1 μmol/L, p = 0.005), and nitrate (19.3 ± 2.9 vs 10.1 ± 2.1 μmol/L, p = 0.002), as well as reduction in lung vital capacity (66% ± 2% vs 81% ± 1%, p = 0.01) and forced 1-second expiratory volume (63% ± 10% vs 93% ± 4%, p = 0.005) compared with normoxic management. Cardiac index after cardiopulmonary bypass at low filling pressure was similar between groups (3.1 ± 0.2 vs 3.3 ± 0.3 L/min per square meter). [Data are mean ± standard error (analysis of variance), with p values compared with an oxygen tension of 400 mm Hg. Conclusions: Hyperoxic cardiopulmonary bypass during cardiac operations in adults results in oxidative myocardial damage related to oxygen-derived free radicals and nitric oxide. These adverse effects can be markedly limited by reduced oxygen tension management. The concept of normoxic cardiopulmonary bypass may be applied to surgical advantage during cardiac operations. (J Thorac Cardiovasc Surg 1998;116:327-34

    Influence of biological sex, age and smoking on Graves’ orbitopathy – a ten-year tertiary referral center analysis

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    PurposeSeverity of Graves’ orbitopathy (GO) shows wide individual differences. For optimal treatment, it is important to be able to predict the natural course of the disease as accurate as possible to counteract with anti-inflammatory and surgical treatment. Therefore, we aimed to further elucidate the impact of sex, age and smoking on GO.MethodsWe collected the clinical and demographic data of all patients of our tertiary referral center from January 2008 till December 2018 and analyzed it with descriptive statistics. Only patients with a complete data set were included in the further analysis. Odds ratio’s for moderate-to-severe and sight-threatening GO in relation to age, sex and smoking were calculated by means of multivariate logistic regression models.ResultsWe evaluated the data of 4260 patient with GO and complete data sets. Most of these were women (83%). There were no significant differences between male and female patients regarding smoking habits and thyroid treatment. Men were significantly older at initial manifestation of TED (51.8 vs. 49.9y, p<0.01) and showed significant more often severe stages (61% vs. 53%, p<0.0001). Therefore, they needed significantly more intense treatment with steroids, irradiation, orbital decompression and muscle surgery. In multivariate logistic regression analyses age (OR 0.97, 95% CI:0.97-0.98, p<0.0001), male sex (OR 1.64, 95% CI:1.38-1.9, p<0.0001), smoking (OR 1.19, 95% CI:1.04-1.36, p=0.01), Grave’s disease (OR 1.55, 95% CI:1.26-1.90, p<0.0001) and history of radioiodine treatment (RAI) (OR 2.44, 95% CI:2.10-2.86, p<0.0001) showed an significant association with severe stages of GO.DiscussionOur retrospective analysis showed once more that women are more often afflicted by GO. In contrast, men seem to be more severely afflicted and in need of anti-inflammatory and surgical treatments. This might be due to a different approach to the health system and resilience to GO specific symptoms, as well as previously described worse thyroid control. Estrogen mediated effects might also play a role as in other autoimmune diseases and should be subject of further trials. Besides the biological sex, smoking could again be confirmed as serious risk factor for severe GO. Of note, RAI was associated with more severe stages of GO, which should be subject to further investigation

    High (but Not Low) Urinary Iodine Excretion Is Predicted by Iodine Excretion Levels from Five Years Ago

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    Background: It has not been investigated whether there are associations between urinary iodine (UI) excretion measurements some years apart, nor whether such an association remains after adjustment for nutritional habits. The aim of the present study was to investigate the relation between iodine-creatinine ratio (ICR) at two measuring points 5 years apart. Methods: Data from 2,659 individuals from the Study of Health in Pomerania were analyzed. Analysis of covariance and Poisson regressions were used to associate baseline with follow-up ICR. Results: Baseline ICR was associated with follow-up ICR. Particularly, baseline ICR >300 mu g/g was related to an ICR >300 mu g/g at follow-up (relative risk, RR: 2.20; p < 0.001). The association was stronger in males (RR: 2.64; p < 0.001) than in females (RR: 1.64; p = 0.007). In contrast, baseline ICR <100 mu g/g was only associated with an ICR <100 mu g/g at follow-up in males when considering unadjusted ICR. Conclusions: We detected only a weak correlation with respect to low ICR. Studies assessing iodine status in a population should take into account that an individual with a low UI excretion in one measurement is not necessarily permanently iodine deficient. On the other hand, current high ICR could have been predicted by high ICR 5 years ago. Copyright (C) 2011 S. Karger AG, Base

    Operation of a high-Tc_{c} SQUID gradiometer with a two-stage Joule-Thomson micro-cooler

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    Practical applications of high-Tc_{c} SQUIDs require cheap, simple in operation, and cryogen-free cooling. Mechanical cryo-coolers are generally not suitable for operation with SQUIDs due to their inherent magnetic and vibrational noise. In this work, we utilized a Joule-Thomson microfluidic cooling system to operate our high-Tc_{c} SQUIDs [1]. The micro-cooler system is based on a commercial desktop CryoLab unit from DEMCON kryoz [2]. It contains a two-stage MEMS micro-cooler with a base temperature of 75 K, gross cooling power of 75 mW@80 K, and temperature stability ± 50 mK. Our high-TC dc SQUID gradiometers were fabricated from YBa2_{2}Cu3_{3}O7x_{7-x} thin films grown by pulsed laser deposition on 10 mm × 10 mm SrTiO3_{3} bicrystal substrates with 24° misorientation angle. The SQUID chip was glued onto a 0.3 mm thick silicon wafer chip carrier that was attached to the second stage of the cold head. The vacuum housing of the cold stage was made from non-magnetic material (polyethylene terephthalate, PET) and evacuated to a base pressure below 2x103^{-3} mbar. The vacuum chamber features a 0.3 mm thick sapphire window that is placed above the sensor/cold stage. We demonstrated that the equivalent magnetic flux noise of the high-Tc_{c} SQUID gradiometer is largely unaffected by the micro-cooler setup. The cut-off frequency of the 1/f noise in our SQUID measured on the micro-cooler was around 10 Hz. This indicates that the micro-cooler does not introduce significant magnetic fields in the vicinity of the cold stage. We thus demonstrate that such a microfluidic cooling system is a promising technology for cooling of high-Tc_{c} SQUIDs in practical applications. We also used the micro-cooler system to build a prototype a magnetic ac susceptibility (ACS) system for detection of specific binding reactions between DNA target molecules and functionalized magnetic nanoparticles (fMNP) in liquid solution. The detection principle relies on changes in Brownian rotation dynamics of fMNPs. We present the results of experiments with various concentrations of magnetic nanoparticles and discuss further development of the portable magnetic bioassay system for detection of influenza virus using oligonucleotide-tagged magnetic nanoparticles with sub-picomolar sensitivity. [1] A. Kalabukhov et al., Supercond. Sci. Technol. 29 095014 (2016). [2] http://kryoz.nl/portfolio-item/cryolab-msg

    Comparative and functional genomics provide insights into the pathogenicity of dermatophytic fungi

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    ABSTRACT: BACKGROUND: Millions of humans and animals suffer from superficial infections caused by a group of highly specialized filamentous fungi, the dermatophytes, which exclusively infect keratinized host structures. To provide broad insights into the molecular basis of the pathogenicity-associated traits, we report the first genome sequences of two closely phylogenetically related dermatophytes, Arthroderma benhamiae and Trichophyton verrucosum, both of which induce highly inflammatory infections in humans. RESULTS: 97% of the 22.5 megabase genome sequences of A. benhamiae and T. verrucosum are unambiguously alignable and collinear. To unravel dermatophyte-specific virulence-associated traits, we compared sets of potentially pathogenicity-associated proteins, such as secreted proteases and enzymes involved in secondary metabolite production, with those of closely related onygenales (Coccidioides species) and the mould Aspergillus fumigatus. The comparisons revealed expansion of several gene families in dermatophytes and disclosed the peculiarities of the dermatophyte secondary metabolite gene sets. Secretion of proteases and other hydrolytic enzymes by A. benhamiae was proven experimentally by a global secretome analysis during keratin degradation. Molecular insights into the interaction of A. benhamiae with human keratinocytes were obtained for the first time by global transcriptome profiling. Given that A. benhamiae is able to undergo mating, a detailed comparison of the genomes further unraveled the genetic basis of sexual reproduction in this species. CONCLUSIONS: Our results enlighten the genetic basis of fundamental and putatively virulence-related traits of dermatophytes, advancing future research on these medically important pathogens

    Hundreds of variants clustered in genomic loci and biological pathways affect human height

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    Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.

    X-chromosome and kidney function:evidence from a multi-trait genetic analysis of 908,697 individuals reveals sex-specific and sex-differential findings in genes regulated by androgen response elements

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    X-chromosomal genetic variants are understudied but can yield valuable insights into sexually dimorphic human traits and diseases. We performed a sex-stratified cross-ancestry X-chromosome-wide association meta-analysis of seven kidney-related traits (n = 908,697), identifying 23 loci genome-wide significantly associated with two of the traits: 7 for uric acid and 16 for estimated glomerular filtration rate (eGFR), including four novel eGFR loci containing the functionally plausible prioritized genes ACSL4, CLDN2, TSPAN6 and the female-specific DRP2. Further, we identified five novel sex-interactions, comprising male-specific effects at FAM9B and AR/EDA2R, and three sex-differential findings with larger genetic effect sizes in males at DCAF12L1 and MST4 and larger effect sizes in females at HPRT1. All prioritized genes in loci showing significant sex-interactions were located next to androgen response elements (ARE). Five ARE genes showed sex-differential expressions. This study contributes new insights into sex-dimorphisms of kidney traits along with new prioritized gene targets for further molecular research.</p
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