A Discourse Analysis of Cheers

This paper analyzes the pragmatics features of the language in an episode of the sitcom Cheers to find out what second language learners need to know about the language of the sitcom and about the background knowledge informing it for that episode to be understandable to them and for it thus to be an effective as an instruction tool. To answer this question, the researcher transcribed the speech in the episode and used a speech act theory-based approach to identify and categorize deixis, locutionary forms, illocutionary types, and instances of reduction and types of indirect speech. Categories in these areas were compared for their relative prevalence and for the prevalence of correlations between them. The paper concludes that the researcher’s speech act theoretical approach was useful in identifying over a third of the indirect speech in the episode of Cheers in the form of non-standard alignments between locutionary form and illocutionary type

The Effect of Lifespan Extending Mutations on Healthspan in Ames Dwarf Mice

Ames dwarf (df/df) mice, exhibit a significant increase in longevity, and carry a homozygous and spontaneous mutation of the prophet of pituitary factor 1 gene (Prop1df/df), which inhibits the development of the anterior pituitary cells: somatotrophs, lactotrophs and thyrotropes. These mice, are therefore characterized by a growth hormone, prolactin and thyrotropin deficiency. Ames dwarf mice, are widely used as a valuable aging research model because they have a significantly longer (40-60%) and healthier lifespan compared to their normal (N) littermate controls. In addition to this extraordinary longevity, df/df mutants carry significant protection from the majority of age-related diseases including insulin resistance, metabolic syndrome, diabetes, cancer or neurodegeneration. Ames dwarf mice exhibit decreased levels of fasting insulin and glucose as well as an improved glucose clearance measured by glucose tolerance test combined with a high sensitivity to injected insulin. These mutants have also shown to have enhanced insulin signaling in diverse insulin target organs. Importantly, insulin tolerance test (ITT), a measure of insulin sensitivity, showed that there is a positive correlation between insulin sensitivity and longevity. However, the basic ITT does not reveal insulin sensitivity in different insulin-responsive organs including skeletal muscle, adipose tissue as well as glucose regulation in the liver. To investigate this tissue-specific response, for the first time, the hyperinsulinemic-euglycemic clamp study was performed in vivo in long-living df/df mice. These findings showed that in df/df mice the glucose infusion rate needed to be ~2-fold higher than in normal (N) control mice to maintain euglycemia at a rate of approximately 160 mg·dL-1. This study presented that df/df mice had significantly greater uptake of glucose in the gastrocnemius and vastus muscles along with adipose tissue. More importantly, there was a pronounced hepatic response in df/df mice indicated by complete suppression of endogenous glucose production, while in N mice only 60% suppression was achieved during the clamp. In addition to the hyperinsulinemic-euglycemic clamp study, the effects of Ames dwarfism mutation on gut microbiota development in df/df and N mice was also investigated. The gut microbiome was never studied before in these long-living dwarf mice, while there is an overall increasing interest in understanding gut microbiome in diverse diseases including diabetes, cardiovascular diseases, cancer, aging and many others. There is also strong evidence showing that the gut microbiome changes over the lifespan of an individual and might be related to development or protection from diverse age-related diseases. In this study, the changes in the gut microbiome of df/df and N mice were examined through a comparison of parents before mating and littermate mice at three different time points during early life development. Furthermore, as calorie restriction is shown to be an intervention that significantly enhances longevity in animal models, it was studied the effects of a 6-month calorie restricted (CR) diet on the microbiota. These results show that the gut microbiota composition changes significantly with the aging process and it also demonstrates divergences in the abundance of several bacteria when comparing df/df mice with N littermates already during early life development. Overall, the gut microbiota showed significant differences in genotype, time-point and in the animal breeding pair when comparing df/df and N mice. Additionally, it was also demonstrated that CR causes significant changes in the gut microbiome when comparing different GI location (Distal Colon, Ileum and Cecum), genotypes and the diet. Overall, the effect of the genotype was more evident than the one of the diet. In conclusion, the results of the hyperinsulinemic-euglycemic clamp study suggests that improved insulin sensitivity in various insulin responsive organs and enhancement in overall metabolic condition might promote prolonged life-span of Ames dwarf mice. In addition, these findings of the gut microbiota study indicated that the microbiota have significant impact during postnatal development in promoting longevity in df/df mice and that CR could also modulate longevity by altering gut microbiota. In summary, it can be said that both studies have shown potential novel longevity markers in Ames dwarf mice.Zusammenfassung Ames dwarf (df/df) Mäuse weisen eine signifikant höhere Lebenserwartung auf und tragen eine homozygote und spontane Mutation des Gens, welches als prophet of pituitary factor 1 gene (Prop1df/df), bezeichnet wird. Aufgrund dessen gibt es keine Entwicklung der vorderen Somatotropin, Lactotropin und Thyreotropin produzierenden Hypophysenzellen. Diese Mäuse sind daher durch einen Mangel an Wachstumshormon, Prolaktin und Thyreotropin gekennzeichnet. Ames dwarf Mäuse werden häufig als wertvolles Forschungsmodell für das Altern verwendet, da sie im Vergleich zu ihren normalen (N) Wurfgeschwister-Kontrollen eine signifikant längere (40-60%) und gesündere Lebensdauer haben. Zusätzlich zu der verlängerten Lebensdauer sind die df/df-Mutanten auch vor den meisten altersbedingten Krankheiten wie Insulinresistenz, Metabolisches Syndrom, Diabetes, Krebs oder neurodegenerativen Erkrankungen geschützt. Ames dwarf Mäuse weisen einen verringerten Nüchterninsulin- und Glukosespiegel sowie eine verbesserte Glukose Freigabe auf. Letztere wurde durch einen Glukosetoleranztest und durch eine hohe Empfindlichkeit gegenüber injiziertem Insulin gemessen. Zusätzlich konnte gezeigt werden, dass diese Mutanten eine verstärkte Insulinsignalisierung in den verschiedenen Insulin-Zielorganen aufweisen. Der Insulintoleranztest (ITT), welcher ein Maß für die Insulinsensitivität ist, zeigte, dass eine positive Korrelation zwischen Insulinsensitivität und Langlebigkeit besteht. Allerdings zeigt der grundlegende ITT keine Insulinsensitivität in den verschiedenen auf Insulin ansprechenden Organen an. Betroffen sind hier der Skelettmuskel, das Fettgewebe sowie die Glukoseregulierung in der Leber. Um diese gewebespezifische Reaktion zu untersuchen, wurde zum ersten Mal die hyperinsulinämisch-euglykämische Clamp-Studie in vivo an langlebigen df/df-Mäusen durchgeführt. Diese Ergebnisse haben gezeigt, dass bei df/df- Mäusen die Glukoseinfusionsrate ~ 2-fach höher sein musste als bei den normalen (N) Kontrollmäusen, um die Euglykämie bei gleicher Insulininfusion bei etwa 160 mg·dL-1 zu halten. Ebenfalls hat diese Studie gezeigt, dass df/df-Mäuse eine signifikant höhere Aufnahme von Glucose im Gastrocnemius- und Vastus-Muskel sowie im Fettgewebe aufwiesen. Noch wichtiger ist, dass bei df/df-Mäusen eine ausgeprägte Leberreaktion auftrat, die durch eine vollständige Unterdrückung der endogenen Glukose Produktion angezeigt wurde, während bei N-Mäusen nur eine Unterdrückung von 60% erreicht wurde. Zusätzlich zur hyperinsulinämisch-euglykämischen Clamp-Studie wurden auch die Auswirkungen der Ames dwarf Mutation auf die Entwicklung der Darmmikrobiota bei df/df- und N-Mäusen erforscht. Das Darmmikrobiom wurde noch nie zuvor bei diesen langlebigen Zwergmäusen untersucht, während das Interesse am Verständnis des Darmmikrobioms bei verschiedenen Krankheiten wie Diabetes, Herz-Kreislauf-Erkrankungen, Krebs, Altern und vielen anderen insgesamt zunimmt. Es gibt auch starke Hinweise darauf, dass sich das Darmmikrobiom im Laufe der Lebensdauer eines Individuums verändert und möglicherweise mit der Entwicklung oder dem Schutz vor verschiedenen altersbedingten Krankheiten zusammenhängt. In dieser Studie wurden die Veränderungen im Darmmikrobiom von df/df- und N-Mäusen durch einen Vergleich der Eltern vor der Paarung und der Wurfgeschwister zu drei verschiedenen Zeitpunkten während der frühen Lebensentwicklung untersucht. Da sich gezeigt hat, dass Kalorienreduzierung eine Intervention ist, die die Langlebigkeit in Tiermodellen signifikant verlängert, wurden die Auswirkungen einer 6-monatigen kalorienreduzierten (CR) Diät auf die Mikrobiota untersucht. Die Ergebnisse haben gezeigt, dass sich die Zusammensetzung der Darmmikrobiota mit dem Alterungsprozess signifikant verändert. Zusätzlich wurden Unterschiede in der Häufigkeit mehrerer Bakterienstämme zwischen df/df- und N-Mäusen bereits während der frühen Lebensentwicklung gezeigt. Insgesamt zeigte das Darmmikrobiom beim Vergleich von df/df- und N-Mäusen signifikante Unterschiede im Genotyp, Zeitpunkt und Brutpaar. Zusätzlich wurde gezeigt, dass CR signifikante Veränderungen im Darmmikrobiom verursacht, wenn die verschiedenen Bereiche innerhalb des Gastrointestinaltrakts (Distal Colon, Ileum und Cecum), die Genotypen und auch die kalorienreduzierte Diät verglichen werden. Insgesamt war die Auswirkung innerhalb des Genotyps jedoch deutlicher zu sehen als die der Diät. Zusammenfassend legen die Ergebnisse der hyperinsulinämisch-euglykämischen Clamp- Studie nahe, dass eine verbesserte Insulinsensitivität in den verschiedenen auf Insulin ansprechenden Organen sowie eine Verbesserung des gesamten Stoffwechsels, die verlängerte Lebensdauer von den Ames dwarf Mäusen fördern könnte. Darüber hinaus haben die Ergebnisse der Darmmikrobiota-Studie gezeigt, dass die Mikrobiota während der postnatalen Entwicklung eine wichtige Rolle bei der Förderung der Langlebigkeit bei df/df- Mäusen spielt und dass CR auch die Lebensdauer durch Veränderung der Darmmikrobiota modulieren könnte. Zusammenfassend kann gesagt werden, dass die beiden untersuchten Studien neue potenzielle Langlebigkeitsmarker bei Ames dwarf Mäusen gezeigt haben

A bridge for two views: Checkland’s soft systems methodology and Maturana’s ontology of the observer

© 2019, © Operational Research Society 2019. Checkland and Maturana’s work aim to understand and to improve problematic situations in organisations and in our everyday life. Maturana’s phenomenological onto-epistemology (we are immersed in the praxis of living in an ontological multi-universe) seems to resonate with Soft Systems Methodology (SSM) interpretivist epistemology. We argue that this concurrence makes it possible to reflect and explore some of Maturana’s ideas (structural determinism/structural coupling/organisational closure) when they are grafted into the phases of the Checkland’s SSM seven-step process. This article aims to complement SSM by proposing a framework in which some key concepts from Maturana’s Ontology of the Observer (OoO) might enhance and expand the understanding of the SSM application process. An enriched and enhanced SSM process could have significant consequences in the Management Science/Operational Research (MS/OR) and Systems community practice. The framework proposed can have major social repercussions since it will incorporate the well-known influential OoO ideas into MS/OR practice

Circular sensor array and nonlinear analysis of homopolar magnetic bearings

Magnetic bearings use variable attractive forces generated by electromagnetic control coils to support rotating shafts with low friction and no material wear while providing variable stiffness and damping. Rotor deflections are stabilized by position feedback control along two axes using non-contacting displacement sensors. These sensor signals contain sensor runout error which can be represented by a Fourier series composed of harmonics of the spin frequency. While many methods have been proposed to compensate for these runout harmonics, most are computationally intensive and can destabilize the feedback loop. One attractive alternative is to increase the number of displacement sensors and map individual probe voltages to the two independent control signals. This approach is implemented using a circular sensor array and single weighting gain matrix in the present work. Analysis and simulations show that this method eliminates runout harmonics from 2 to n-2 when all sensors in an ideal n-sensor array are operational. Sensor failures result in reduced synchronous amplitude and increased harmonic amplitudes after failure. These amplitudes are predicted using derived expressions and synchronous measurement error can be corrected using an adjustment factor for single failures. A prototype 8-sensor array shows substantial runout reduction and bandwidth and sensitivity comparable to commercial systems. Nonlinear behavior in homopolar magnetic bearings is caused primarily by the quadratic relationship between coil currents and magnetic support forces. Governing equations for a permanent magnet biased homopolar magnetic bearing are derived using magnetic circuit equations and linearized using voltage and position stiffness terms. Nonlinear hardening and softening spring behavior is achieved by varying proportional control gain and frequency response is determined for one case using numerical integration and a shooting algorithm. Maximum amplitudes and phase reversal for this nonlinear system occur at lower frequencies than the linearized system. Rotor oscillations exhibit amplitude jumps by cyclic fold bifurcations, creating a region of hysteresis where multiple stable equilibrium states exist. One of these equilibrium states contains subharmonic frequency components resulting in quasiperiodic rotor motion. This nonlinear analysis shows how nonlinear rotor oscillations can be avoided for a wide range of operation by careful selection of design parameters and operating conditions

Occurrence of the Tamarix Leafhopper, Opsius stactogalus Fieber (Hemiptera: Cicadellidae), in Argentina

The paleartic tamarix leafhopper, Opsius stactogalus Fieber (Hemiptera: Cicadellidae), can reduce the growth of tamarisk due to the aggregate feeding imposed by their populations. The species was mentioned for Argentina in Metcalf's catalogue (1967) without locality or region reference, and the contributions on Cicadellidae published by many authors after Metcalf omitted this distributional data. Populations of O. stactogalus on Tamarix sp. were found in 12 sites between 28° 48′ to 39° 17′ S and 64° 06′ to 70° 04′ W, located in both the Neotropical and Andean biogeographic regions

The effect of calorie restriction on insulin signaling in skeletal muscle and adipose tissue of Ames dwarf mice

Long-living Ames dwarf (df/df) mice are homozygous for a mutation of the Prop1(df) gene. As a result, mice are deficient in growth hormone (GH), prolactin (PRL) and thyrotropin (TSH). In spite of the hormonal deficiencies, df/df mice live significantly longer and healthier lives compared to their wild type siblings. We studied the effects of calorie restriction (CR) on the expression of insulin signaling genes in skeletal muscle and adipose tissue of normal and df/df mice. The analysis of genes expression showed that CR differentially affects the insulin signaling pathway in these insulin target organs. Moreover, results obtained in both normal and Ames dwarf mice indicate more direct effects of CR on insulin signaling genes in adipose tissue than in skeletal muscle. Interestingly, CR reduced the protein levels of adiponectin in the epididymal adipose tissue of normal and Ames dwarf mice, while elevating adiponectin levels in skeletal muscle and plasma of normal mice only. In conclusion, our findings suggest that both skeletal muscle and adipose tissue are important mediators of insulin effects on longevity. Additionally, the results revealed divergent effects of CR on expression of genes in the insulin signaling pathway of normal and Ames dwarf mice

A novel class of CoA-transferase involved in short-chain fatty acid metabolism in butyrate-producing human colonic bacteria

Peer reviewedPublisher PD

A proteomic and transcriptional view of acidogenic and solventogenic steady-state cells of Clostridium acetobutylicum in a chemostat culture

The complex changes in the life cycle of Clostridium acetobutylicum, a promising biofuel producer, are not well understood. During exponential growth, sugars are fermented to acetate and butyrate, and in the transition phase, the metabolism switches to the production of the solvents acetone and butanol accompanied by the initiation of endospore formation. Using phosphate-limited chemostat cultures at pH 5.7, C. acetobutylicum was kept at a steady state of acidogenic metabolism, whereas at pH 4.5, the cells showed stable solvent production without sporulation. Novel proteome reference maps of cytosolic proteins from both acidogenesis and solventogenesis with a high degree of reproducibility were generated. Yielding a 21% coverage, 15 protein spots were specifically assigned to the acidogenic phase, and 29 protein spots exhibited a significantly higher abundance in the solventogenic phase. Besides well-known metabolic proteins, unexpected proteins were also identified. Among these, the two proteins CAP0036 and CAP0037 of unknown function were found as major striking indicator proteins in acidogenic cells. Proteome data were confirmed by genome-wide DNA microarray analyses of the identical cultures. Thus, a first systematic study of acidogenic and solventogenic chemostat cultures is presented, and similarities as well as differences to previous studies of batch cultures are discussed

Coenzyme A-transferase-independent butyrate re-assimilation in Clostridium acetobutylicum - evidence from a mathematical model

The hetero-dimeric CoA-transferase CtfA/B is believed to be crucial for the metabolic transition from acidogenesis to solventogenesis in Clostridium acetobutylicum as part of the industrial-relevant acetone-butanol-ethanol (ABE) fermentation. Here, the enzyme is assumed to mediate re-assimilation of acetate and butyrate during a pH-induced metabolic shift and to faciliate the first step of acetone formation from acetoacetyl-CoA. However, recent investigations using phosphate-limited continuous cultures have questioned this common dogma. To address the emerging experimental discrepancies, we investigated the mutant strain Cac-ctfA398s::CT using chemostat cultures. As a consequence of this mutation, the cells are unable to express functional ctfA and are thus lacking CoA-transferase activity. A mathematical model of the pH-induced metabolic shift, which was recently developed for the wild type, is used to analyse the observed behaviour of the mutant strain with a focus on re-assimilation activities for the two produced acids. Our theoretical analysis reveals that the ctfA mutant still re-assimilates butyrate, but not acetate. Based upon this finding, we conclude that C. acetobutylicum possesses a CoA-tranferase-independent butyrate uptake mechanism that is activated by decreasing pH levels. Furthermore, we observe that butanol formation is not inhibited under our experimental conditions, as suggested by previous batch culture experiments. In concordance with recent batch experiments, acetone formation is abolished in chemostat cultures using the ctfa mutant