Miracle-dz/UniFAR-FTUs huggingface dataset:
Metabolomics analyses to better understand complex phenotypes

In dieser Doktorarbeit werden drei Metabolomics-Studien der KORA Kohorte behandelt. Das Ziel dieser Doktorarbeit war, ein besseres Verstandnis der Rolle des Metabolismus von komplexen Phanotypen anhand von Unterschieden im Blutbild, des Geschlechts und anhand von Veranderungen des Metabolitenprofils bei multifaktoriellen Krankheiten wie Typ 2 Diabetes mellitus zu erhalten. Um Artefakte auszuschliesen wurden strikte Qualitatskontrollen aller gemessenen Metaboliten durchgefuhrt. Durch die Analyse von Blutplasma und -serum von 377 Personen konnten wir zeigen, dass die Konzentrationen der Metaboliten in Blutplasma und -serum stark korrelieren und daruber hinaus eine hohe Reproduktionsrate zeigen, bei der Blutplasma besser abschneidet. Im Gegensatz dazu zeigt das Blutserum hohere Metabolitenkonzentrationen und konnte deswegen besser fur den Nachweis von Konzentrationsunterschieden geeignet sein. Ein weiteres Ergebnis dieser Doktorarbeit war der Nachweis von signifikanten geschlechtsspezifischen Unterschieden der Konzentrationen von 102 der ausgewerteten 131 Metaboliten. Dabei wurden die Daten von mehr als 3300 Personen der KORA Kohorte verwendet und die Analysen einer konservativen Bonferroni-Korrektur unterzogen. Daruber hinaus identifizierten wir potentielle Biomarker fur Pra-Diabetes durch die Analyse von 140 Metaboliten in nuchtern abgegebenen Blutseren von 4297 Personen der KORA Kohorte. Wir konnten zeigen, dass Personen mit gestorter Glukosetoleranz (IGT) signifikant unterschiedliche Konzentrationen von drei Metaboliten (Glycin, lysoPhosphatidylcholine (LPC) 18:2 und acetylcarnitine) im Vergleich zu gesunden Personen aufweisen. Daruber hinaus konnten wir nachweisen, dass geringere Konzentrationen der Metaboliten Glycin und LPC bei Probanden mit Typ 2 Diabetes oder IGT vorhanden sind. Die in dieser Studie identifizierten Metaboliten sind biologisch unabhangig von zuvor entdeckten Diabetes Risikofaktoren. Durch weitere Analysen und die Einbeziehung systembiologischer Ansatze entdeckten wir sieben Diabetesrisiko Susseptibilitatsgene, welche durch Expressionsdaten bestatigt wurden. Metabolomics welches auf der Analyse von Stoffwechselzwischen- und Endprodukten basiert, ist eine wertvolle Methode besonders in der biomedizinischen Forschung, um Krankheitsmechanismen aufzuklaren. Nachdem angemessene Qualitatskontrollen etabliert und der Einfluss von komplexen Storfaktoren (z.B. das Geschlecht) aufgeklart wurden, konnte der Zusammenhang zwischen Krankheit und Metabolismus weiter an Klarheit gewinnen. Die Entdeckungen in unserer T2D Studie zeigen, dass die Analyse von Konzentrationsprofilen helfen kann neue Krankheitsrisikomarker genauso wie neue Wirkungspfade zu identifizieren, die moglicherweise das Ziel zur Heilung einer Krankheit sein konnten.
Wake-up times following sedation with sevoflurane versus propofol after cardiac surgery

Abstract Objectives. Intravenous sedation in the intensive care unit (ICU) may contribute to altered consciousness and prolonged mechanical ventilation. We tested the hypothesis that replacing intravenous propofol with inhaled sevoflurane for sedation after cardiac surgery would lead to shorter wake-up times, quicker patient cooperation, and less delusional memories. Design. Following coronary artery bypass surgery with cardiopulmonary bypass, 100 patients were randomized to sedation with sevoflurane via the anesthetic conserving device or propofol. Study drugs were administered for a minimum of 2 hours until criteria for extubation were met. Primary endpoints were time from drug stop to extubation and to adequate verbal response. Secondary endpoints were adverse recovery events, memories reported in the ICU Memory Tool test, and ICU/hospital stay. Results. Median time from drug stop to extubation (interquartile range/total range) was shorter after sevoflurane compared to propofol sedation; 10 (10/100) minutes versus 25 (21/240) minutes (p <0.001). Time from extubation to adequate verbal response was shorter (p =0.036). No differences were found in secondary endpoints. Conclusions. Sevoflurane sedation after cardiac surgery leads to shorter wake-up times and quicker cooperation compared to propofol. No differences were seen in ICU-stay, adverse memories or recovery events in our short-term sedation.
Cloning of the Human Thiamine Transporter, a Member of the Folate Transporter Family*

We have isolated a cDNA from human placenta, which, when expressed heterologously in mammalian cells, mediates the transport of the water-soluble vitamin thiamine. The cDNA codes for a protein of 497 amino acids containing 12 putative transmembrane domains. Northern blot analysis indicates that this transporter is widely expressed in human tissues. When expressed in HeLa cells, the cDNA induces the transport of thiamine (Kt = 2.5 ± 0.6 μm) in a Na+-independent manner. The cDNA-mediated transport of thiamine is stimulated by an outwardly directed H+ gradient. Substrate specificity assays indicate that the transporter is specific to thiamine. Even though thiamine is an organic cation, the cDNA-induced thiamine transport is not inhibited by other organic cations. Similarly, thiamine is not a substrate for the known members of mammalian organic cation transporter family. The thiamine transporter gene, located on human chromosome 1q24, consists of 6 exons and is most likely the gene defective in the metabolic disorder, thiamine-responsive megaloblastic anemia. At the level of amino acid sequence, the thiamine transporter is most closely related to the reduced-folate transporter and thus represents the second member of the folate transporter family.
The Camps at Ardoch, Stracathro and Ythan Wells: Recent Excavations

North of the Antonine Wall, four series of temporary camps have recently been distinguished. They are described as the ‘Stracathro-type’, from the distinctive gateway-plan first clearly demonstrated at Stracathro, and the 30-acre, 63-acre and 120-acre camps, after the average size of the different series. Much knowledge is to be gained if these camps can be related to the various Roman campaigns beyond the Antonine Wall, but temporary camps are notably difficult to date. Consideration of the distribution of the four series, and of the relative ages of the few camps that actually overlap, as demonstrated by excavation, has gone far towards solving the problem. Excavations at three key sites are here reported: since the crucial evidence is provided by ditch-sections, these are described minutely with the aid of detailed drawings (FIGS. 3–4, 5 and 9), specially prepared by Mr. D. R. Wilson. The excavations at Stracathro took place in September 1967, those at Ythan Wells in September 1968, and those at Ardoch in September 1969.
The kiss of the spiderbot

Some people call it "designing for our future selves," in order to get the message across that one day we will all benefit from a Web that has been designed by people who think of more than the visible. But in fact, some of us could even benefit today from an accessible Web—for instance driving in a car while having the route read aloud to you from a browser on the Web. The current Web is a terrible mess for accessibility. Try turning off images in your browser next time you use it in order to appreciate what blind people have to deal with. If you build Web sites, do it once a week to keep yourself alert. There is no reason for building inaccessible Web sites; it is not difficult to do it right. But even well-meaning Web site builders ask: How can I justify the extra cost for such a small percentage of the public? The answer is: Google. Looking at my Web site logs, it is clear that at least half of the visitors find the sites via Google. And what Google sees is exactly what a blind person sees. Google is a blind user—a billionaire blind user, with millions of friends who listen to its every word. If a blind user can't see your site, neither can Google, and your site will suffer. Here are some examples of things to avoid if you want Google to like you (although not all of these improve accessibility, they almost all improve the Web):
Age, Growth, and Mortality of Introduced Flathead Catfish in Atlantic Rivers and a Review of Other Populations

Abstract Knowledge of individual growth and mortality rates of an introduced fish population is required to determine the success and degree of establishment as well as to predict the fish's impact on native fauna. The age and growth of flathead catfish Pylodictis olivaris have been studied extensively in the species' native and introduced ranges, and estimates have varied widely. We quantified individual growth rates and age structure of three introduced flathead catfish populations in North Carolina's Atlantic slope rivers using sagittal otoliths, determined trends in growth rates over time, compared these estimates among rivers in native and introduced ranges, and determined total mortality rates for each population. Growth was significantly faster in the Northeast Cape Fear River (NECFR) than in the Lumber and Neuse rivers. Fish in the NECFR grew to a total length of 700 mm by age 7, whereas fish in the Neuse and Lumber river populations reached this length by 8 and 10 years, respectively. The growth .
Autofluorescence properties of murine embryonic stem cells during spontaneous differentiation phases

The autofluorescence (AF) analysis allows in vivo, real‐time assessment of cell functional activities, depending on the presence of biomolecules strictly involved in metabolic reactions and acting as endogenous fluorophores. Pluripotent stem cells during differentiation are known to undergo changes in their morphofunctional properties, with particular reference to bioenergetic metabolic signatures involving endogenous fluorophores such as NAD(P)H, flavins, lipofuscin‐like lipopigments. Since the development of regenerative therapies based on pluripotent cells requires a careful monitoring of the successful maturation into the desired phenotype, aim of our work is to evaluate the AF potential to assess the differentiation phases in a murine stem cell model.
Does Cone Beam Computed Tomography–Derived Bone Density Give Predictable Data About Stability Changes of Immediately Loaded Implants?: A 1-Year Resonance Frequency Follow-up Study

AbstractThe aim of this clinical study was to evaluate whether preoperative bone density value derived from cone-beam computed tomography (CBCT) gives predictable data about primary and secondary stability characteristics of immediately loaded dental implants under different clinical variables. A total of 77 immediately loaded implants placed in 23 patients were included the study. Bone density values of the implant recipient sites were recorded using CBCT. The maximum insertion torque values (ITVs) of the implants were recorded using a digital torque meter during surgery. Resonance frequency measurements were taken using the Osstell Mentor at 4 time points; immediately after surgery (implant stability quotient [ISQ]0) and after 1 (ISQ1), 3 months (ISQ3), and 12 months (ISQ12) of loading. Data were analyzed statistically. The mean bone density and ITVs of all implants were 565 ± 81 and 36.8 ± 3.8 N · cm, respectively. The mean ISQ values were 73.6 ± 5.8 at baseline, 71.1 ± 6.5 after 1 month, 74.8 ± 5.6 after 3 months, and 76.6 ± 5.1 after 12 months of loading. Statistically significant differences were observed between ISQ0 and ISQ1 (P < 0.001), and ISQ0 and ISQ12 (P < 0.001), but not between ISQ0 and ISQ3 (P > 0.05). In regard to stability changes over time, statistically significant correlations were found between bone density values from CBCT and ISQ follow-up measurements, and between ITV and ISQ follow-up measurements in all examination periods. Thus, it is possible to predict primary and secondary stability characteristics of immediately loaded implants by using preoperative CBCT scan and perioperative ITV.
Gender differences in antipsychotic prescribing

Objective: Optimum outcome for those with psychosis will necessarily involve treatment with antipsychotic medication. Unfortunately this medication is associated with a high rate of adverse effects and as a consequence non-adherence. Maximizing symptomatic relief whilst minimizing side effects is the aim of treatment. In order to do this adequately prescribers need to be aware of the significant differences between men and women in response to antipsychotic treatment. These differences are not simply biologically mediated; both physiological and sociocultural factors contribute. Method: Findings from a variety of sources were used to summarize gender differences in antipsychotic treatment. Results: Pharmacokinetic and pharmacodynamic factors, the impact of reproductive phases in women and gender differences in antipsychotic prescription across the lifespan (from children and adolescents to the elderly) are discussed. Important ethnic and racial differences are also mentioned. Conclusion: Women require less antipsychotic medication than men to achieve a better symptom response, but this is at the expense of a higher side effect burden, in particular hormonal and metabolic side effects. Children, adolescents and the elderly are at especially high risk of adverse reactions with antipsychotics. In order to optimize outcome in people with psychosis, prescribers should ensure that gender differences are taken into account.
Inside Taiwan's Sunflower Movement: Twenty-Four Days in a Student-Occupied Parliament, and the Future of the Region

“Say goodbye to Taiwan,” wrote political scientist John Mearsheimer in a widely read article in the March-April 2014 issue of The National Interest. Threatened by China's rising economic might and abandoned by a weakening United States, one of Asia's most vibrant democracies was facing, in his “realist” analysis, an almost inevitable annexation via economic if not military force. “Time,” he wrote, “is running out for the little island coveted by its gigantic, growing neighbor. ” But only days after publication, on March 18, activists and armchair analysts alike said hello to a new reality.
Three‐dimensional lattice Boltzmann interface capturing method for incompressible flows

This paper presents a new three‐dimensional lattice Boltzmann interface capturing method for incompressible flows following the work of Zheng et al. (Phys. Rev. E 2005; 72:056705). As shown in the paper, the fourth rank isotropic property of the lattice tensor is not needed for interface capturing. As a result, a new D3Q7 (D3 means three dimensional, Q7 means seven velocity bits) lattice velocity model and its associated equilibrium distribution functions are proposed in the paper. The proposed model is validated by comparing its numerical results with those of an existing lattice Boltzmann interface capturing model (J. Comput. Phys. 2004; 198:628–644) and three‐dimensional direction split flux‐corrected transport method (Int. J. Numer. Meth. Fluids 1997; 24:671–691). Numerical results showed that the present model performs better than the existing methods in capturing the interface. It greatly improves the computational efficiency and saves at least half of the memory as compared to other lattice Boltzmann interface capturing models. Copyright © 2007 John Wiley & Sons, Ltd.
Interferon alfa down‐regulates CD81 in patients with chronic hepatitis C

CD81 protein has been shown to bind hepatitis C virus (HCV) envelope 2 (E2) glycoprotein in vitro and may act as a (co)receptor for HCV. Regulation of CD81 expression by interferon alfa (IFN‐α) and ribavirin could thereby affect the response to antiviral therapy. In the present study, the effects of IFN‐α and ribavirin on CD81 protein and CD81 mRNA were assessed in peripheral blood lymphocytes (PBL) and isolated human hepatocytes by fluorescence‐activated cell sorter (FACS) analysis and real‐time polymerase chain reaction (PCR), respectively. In addition, regulation of CD81 in PBL was investigated in 10 patients treated with combination therapy. Incubation with IFN‐α (50 U/mL) down‐regulated total CD81 in PBL (81.7 ± 11.6% of control; P = .003) and in isolated human hepatocytes (91.6 ± 8.1% of control; P = .034). Incubation with IFN‐α with and without ribavirin (2.2 μg/mL) significantly reduced cell surface–associated CD81 protein (83.9 ± 10.3% of control; P = .003). PBL of untreated patients chronically infected with HCV had significantly higher levels of total CD81 protein compared with PBL obtained from healthy donors (631.1 ± 93.3 vs. 538.9 ± 95.2 relative fluorescence units [RFU]; P = .030). Pretreatment cell surface–associated CD81 protein was lower in patients infected with genotype HCV‐3 than those infected with HCV‐1 (111.8 ± 15.0 vs. 162.0 ± 41.3 RFU; P = .019). Furthermore, cell surface–associated CD81 protein was lower 4 weeks after initiation of therapy in patients with an initial virologic response compared with initial virologic nonresponders (110.5 ± 8.5 vs. 139.8 ± 27.5 RFU; P = .057). In conclusion, IFN‐α and ribavirin regulate CD81 expression in vitro and in vivo. CD81 expression correlates with HCV genotype and initial virologic response in patients with chronic hepatitis C.
Mitochondrial DNA sequence diversity in bipolar affective disorder.

OBJECTIVE Point mutations in mitochondrial DNA (mtDNA) are one mechanism that could explain the apparent excess maternal transmission of bipolar affective disorder observed in some families. The authors sequenced the mtDNA from probands with bipolar disorder and tested nucleotide variants for association with the disorder. METHOD The entire 16.5 kilobase mitochondrial genome was sequenced in nine unrelated probands selected from large pedigrees with exclusively maternal transmission of bipolar affective disorder. Compared to a reference sequence, variants were detected at 107 nucleotide positions. Fifteen variants of possible pathogenic significance were selected for further study. These variants were assayed in 93 unrelated probands with bipolar I, bipolar II, or schizoaffective-manic disorder and 63 comparison subjects, all of whom were classified into the major groups comprising the European mtDNA haplotype structure (haplogroups). RESULTS The major European haplogroups were represented at the expected frequencies among both probands and comparison subjects. There was no significant difference between probands and comparison subjects in the frequency of any variant, although odds ratios >2 or <0.5 were observed for four variants. Frequencies of these four variants were similar in probands and haplogroup-matched comparison subjects. The results of all comparisons were essentially unchanged when probands from families with an apparently paternal transmission pattern were excluded. CONCLUSIONS The results demonstrate that bipolar affective disorder occurs across all of the major European mtDNA haplogroups but do not reveal any point mutations that explain excess maternal transmission of the disorder.
COMPARATIVE METHODS AT THE SPECIES LEVEL: GEOGRAPHIC VARIATION IN MORPHOLOGY AND GROUP SIZE IN GREY‐CROWNED BABBLERS (POMATOSTOMUS TEMPORALIS)

We show that a new comparative method that sheds light on evolutionary trends among species may also illuminate trends within species. This finding comes from a phylogenetic autocorrelation analysis of morphological traits among individuals sampled from ten populations of a cooperatively breeding songbird, the Grey‐crowned Babbler (Pomatostomus temporalis). Highly variable mitochondrial DNA (mtDNA) sequences from both the eastern (Pomatostomus temporalis temporalis) and western (Pomatostomus temporalis rubeculus) lineages were used to define genetic distances among 120 individuals and to estimate correlations among individuals in wing length, tarsus length, and body weight via an intraspecific weighting matrix. The autoregressive model effectively removed intraspecific correlations for all three morphological variables, and the proportion of the total phenotypic variance due to genealogical relationships varied from 0.68 (weight) to 0.23 (tarsus). The analysis revealed correlations among the specific components of traits, in which none were previously detected (type‐I error) and diminished correlations that appeared strong when phylogeny was ignored. Group size was the only trait for which the autoregressive model failed to remove intraspecific correlations, a result likely due to the plasticity, convergence, and clinal variation in this trait in both the eastern and western lineages. The autocorrelation analysis weakened significant negative correlations between group size and total values for wing length and body weight, but the interpretation of this result depends on the adaptive significance ascribed to the “phylogenetic component” of trait values removed by the analysis. Comparative methods employing distance matrices are one useful way of summarizing the pattern of nonhierarchical relationships among conspecific individuals (“tokogenetic” relationships, sensu Hennig).
Unilateral fusion of primary molars with the presence of a succedaneous supernumerary tooth: case report.

Fusion of either primary or permanent molars is rare. Fusion can be either partial or complete, depending on the developmental stage of the teeth when the fusion began. This paper reports a case of unilateral fusion of maxillary primary molars associated with an adjacent succedaneous supernumerary permanent tooth. Three studies have reported primary double molars associated with syndromes. Two of these studies reported "globodontia" in the primary posterior dentition of otodental syndrome,whereas the other was reported in a child with Russell-Silver syndrome. In these studies the authors suggest that the enlarged molars were the result of a partial duplication of growth centers, fusion of the molars with supernumerary elements,4 and/or associated with developmental changes in the dental lamina. Only two cases of fused primary molars have been reported in normal, healthy patients. The first one was reported by Yuen, et al., in a retrospective radiographic study of 376 patients; however, neither radiographs nor photographs of the fused molars were published. More recently Acs, et al., have reported the first documented case of "bilateral double teeth" involving maxillary primary molars in a 5-year-old African-American with an unremarkable medical history. They described two separate pulp chambers and several roots. Two reports have described fused lower permanent molars associated with enlarged pulp chambers and supernumerary roots. ' These were normal healthy patients.