Colonizing the Thames

A case in which colonial engineers and administrators, working in concert with engineers and officials based in Britain, sought to employ the "tools of empire" on the metropole

Enlarged cerebrospinal fluid spaces in opiate-dependent male patients: A stereological CT study

Computed tomography was performed in 9 male patients with a diagnosis of opiate dependence and in 9 age-matched psychiatric controls (neurotic depression). Patients with a history or diagnosis of another substance dependence (alcohol, cocaine, cannabis) were excluded from the study. The volumes of internal and external components of cerebrospinal fluid (CSF) were measured with a point-counting stereological method. Analysis of variance with age as a covariate revealed a significant enlargement of external and external CSF spaces in male patients with opiate dependence. There was no significant correlation between the length of opiate dependence and the volumes of internal and external CSF spaces. The present results suggest that opiate dependence is associated with structural brain alterations. However, the relationship between opiate dependence and structural brain changes is complex and still not well understood

Pathological regional blood flow in opiate-dependent patients during withdrawal: A HMPAO-SPECT study

The aims of the present study were to investigate regional cerebral blood flow (rCBF) in heroin-dependent patients during withdrawal and to assess the relation between these changes and duration of heroin consumption and withdrawal data. The rCBF was measured using brain SPECT with Tc-99m-HMPAO in 16 heroin-dependent patients during heroin withdrawal. Thirteen patients received levomethadone at the time of the SPECT scans. The images were analyzed both visually and quantitatively, a total of 21 hypoperfused brain regions were observed in 11 of the 16 patients. The temporal lobes were the most affected area, hypoperfusions of the right and left temporal lobe were observed in 5 and 5 patients, respectively. Three of the patients had a hypoperfusion of the right frontal lobe, 2 patients showed perfusion defects in the left frontal lobe, right parietal lobe and left parietal lobe. The results of the quantitative assessments of the rCBF were consistent with the results of the qualitative findings. The stepwise regression analysis showed a significant positive correlation (r = 0.54) between the dose of levomethadone at the time of the SPECT scan and the rCBF of the right parietal lobe. Other significant correlations between clinical data and rCBF were not found. The present results suggest brain perfusion abnormalities during heroin withdrawal in heroin-dependent patients, which are not due to the conditions of withdrawal

Performance assessment in elite football players: field level test versus spiroergometry

The purpose of this study was to demonstrate that elite football players with the same anaerobic threshold calculated from the lactate performance curve during a field level test may have substantially different values describing endurance performance capacity determined from spiroergometric laboratory tests. A group of 28 male elite football players underwent a field level test and a spiroergometric laboratory test. A subgroup of players with the same anaerobic threshold was selected, and the endurance performance capacity obtained from spiroergometric measurements during treadmill level tests were compared descriptively within this subgroup. Among the three players with the same anaerobic threshold, test duration for the treadmill level test and consequently also the maximal lactate value achieved during the test varied substantially. The tests were aborted after 5 min at 4.4, 4.8 and 4.0 m·s-1 for players 1, 2 and 3, respectively. VO2-values at V4 were 87 %, 75 % and 96 % of their personal VO2-peak, respectively. Maximum lactate concentrations were 8.8, 9.2 and 5.3 mmol·L-1, respectively. Peak relative VO2 values were 55.0, 61.6 and 59.7 ml·min-1·kg-1, respectively. The result of this study clearly show that conventional field level tests yield insufficient information on underlying physiological and metabolic mechanisms of endurance performance capacity. Taking result of spiroergometric tests into account is critical for designing and evaluating player-specific training programs aimed at optimizing each player’s performance

A low power clock generator with adaptive inter-phase charge balancing for variability compensation in 40-nm CMOS

Power dissipation besides chip area is still one main optimization issue in high performance CMOS design. Regarding high throughput building blocks for digital signal processing architectures which are optimized down to the physical level a complementary two-phase clocking scheme (CTPC) is often advantageous concerning ATE-efficiency. The clock system dissipates a significant part of overall power up to more than 50% in some applications. <br><br> One efficient power saving strategy for CTPC signal generation is the charge balancing technique. To achieve high efficiency with this approach a careful optimization of timing relations within the control is inevitable. <br><br> However, as in modern CMOS processes device variations increase, timing relations between sensitive control signals can be affected seriously. In order to compensate for the influence of global and local variations in this work, an adaptive control system for charge balancing in a CTPC generator is presented. An adjustment for the degree of charge recycling is performed in each clock cycle. In the case of insufficient recycling the delay elements which define duration and timing position of the recycling pulse are corrected by switchable timing units. <br><br> In a benchmark with the conventional clock generation system, a power reduction gain of up to 24.7% could be achieved. This means saving in power of more than 12% for a complete number-crunching building block

Land surface phenological response to decadal climate variability across Australia using satellite remote sensing

© 2014 Author(s). Land surface phenological cycles of vegetation greening and browning are influenced by variability in climatic forcing. Quantitative spatial information on phenological cycles and their variability is important for agricultural applications, wildfire fuel accumulation, land management, land surface modeling, and climate change studies. Most phenology studies have focused on temperature-driven Northern Hemisphere systems, where phenology shows annually recurring patterns. However, precipitation-driven non-annual phenology of arid and semi-arid systems (i.e., drylands) received much less attention, despite the fact that they cover more than 30% of the global land surface. Here, we focused on Australia, a continent with one of the most variable rainfall climates in the world and vast areas of dryland systems, where a detailed phenological investigation and a characterization of the relationship between phenology and climate variability are missing. To fill this knowledge gap, we developed an algorithm to characterize phenological cycles, and analyzed geographic and climate-driven variability in phenology from 2000 to 2013, which included extreme drought and wet years. We linked derived phenological metrics to rainfall and the Southern Oscillation Index (SOI). We conducted a continent-wide investigation and a more detailed investigation over the Murray-Darling Basin (MDB), the primary agricultural area and largest river catchment of Australia. Results showed high inter-and intra-annual variability in phenological cycles across Australia. The peak of phenological cycles occurred not only during the austral summer, but also at any time of the year, and their timing varied by more than a month in the interior of the continent. The magnitude of the phenological cycle peak and the integrated greenness were most significantly correlated with monthly SOI within the preceding 12 months. Correlation patterns occurred primarily over northeastern Australia and within the MDB, predominantly over natural land cover and particularly in floodplain and wetland areas. Integrated greenness of the phenological cycles (surrogate of vegetation productivity) showed positive anomalies of more than 2 standard deviations over most of eastern Australia in 2009-2010, which coincided with the transition from the El Niño-induced decadal droughts to flooding caused by La Niña

Untersuchung der Influenza-A-Rezeptor-Aktivierung auf Einzelmolekül-Ebene

Influenza virus infections cost hundreds of thousands of lives worldwide every year and are a burden to the global economy and healthcare systems with costs in the billions. New virus strains with pandemic potential emerge at regular intervals due to mutations and antigenic shift of different influenza subtypes. However, the exact processes of the viral infection are still unclear and the identity of the viral entry receptor is still unknown. Current studies indicate that the epidermal growth factor receptor, EGFR, is significantly involved in the infection process. However, the exact mechanism by which influenza viruses use this receptor for infection is still unknown. In this study, an experimental setup is presented with which the early infection processes in living cells can be visualized by super-resolution microscopy and the interaction between the entry receptor and different influenza virus strains can be observed at the single-molecule level. For this setup, the viruses are fluorescently labelled and immobilized on a glass surface. This experimental setup was used to investigate the interaction between EGFR and two different low-pathogenic influenza A strains. The diffusion coefficients of individual receptors in the cell membrane were determined from the super-resolution microscopy measurements using a novel software presented in this thesis. A specific, statistically significant reduction in diffusivity as well as an increased proportion of immobile receptors in the vicinity of both influenza strains could be shown. Additionally, a novel H18N11 bat-derived influenza virus and its interaction with HLADR was investigated. To demonstrate that the experimental setup allows to visualize the virus-host cell interaction beyond receptor binding, the dynamics of two of the proteins responsible for clathrin-mediated endocytosis, namely clathrin-light-chain and adaptor protein-2, were measured at the virus binding site. The dynamics of both proteins were found to be similar to those described for infections with non-immobilized viruses.Durch das Influenzavirus versursachte Infektionen kosten jedes Jahr weltweit hunderttausende Menschenleben und belasten das Gesundheitssystem durch Kosten in Milliardenhöhe. Dabei kommt es durch Mutationen und Kreuzungen verschiedener Influenzasubtypen regelmäßig zu neuen Virusstämmen mit Pandemiepotential. Die genauen Vorgänge einer Virusinfektion sind jedoch noch unklar und die Identität des viralen Eintrittsrezeptors ungeklärt. Studien deuten darauf hin, dass der epidermale growth factor receptor, EGFR, maßgeblich am Infektionsgeschehen beteiligt ist. Wie genau das Virus den Rezeptor nutzt, um in die Zelle einzudringen ist bisher jedoch nicht vollständig aufgeklärt. In dieser Arbeit wird ein Versuchsaufbau vorgestellt, mit dem man die frühen Infektionsprozesse in lebenden Zellen mikroskopieren kann und die Interaktion zwischen Eintrittsrezeptor und verschiedenen Influenzastämmen auf Einzelmolekülebene betrachten kann. Für diesen Aufbau werden die Viren fluoreszent markiert und auf einer Glasoberfläche immobilisiert. Mittels dieses Versuchsaufbaus wurde die Interaktion zwischen EGFR und zwei niedrigpathogenen Influenzastämmen untersucht. Dabei wurden aus den Messungen, mithilfe einer in dieser Arbeit vorgestellten Software, die Diffusionskoeffizienten einzelner Rezeptoren in der Zellmembran bestimmt. Es konnte eine spezifische, statistisch signifikante Reduktion in der Diffusivität, so wie ein erhöhter Anteil immobiler Rezeptoren in der Nähe immobilisierter Viren beider Stämme gezeigt werden. Darüber hinaus wurde ein neuartiges, von Fledermäusen stammendes H18N11-Influenzavirus und seine Interaktion mit HLADR untersucht. Um zu demonstrieren, dass der Versuchsaufbau es zulässt die virus-wirtszellen Interaktion bis über die Rezeptorbindung hinaus darzustellen, wurde die Dynamik der von den für die Clathrin vermittelte Endozytose verantwortlichen Proteine Clathrin-light-chain und Adaptor protein-2 an der Virusbindestelle gemessen. Dabei konnte für beide Proteine eine ähnliche Dynamik festgestellt werden, wie sie auch für Infektionen mit nicht-immobilisierten Viren beschrieben ist

Experimental investigations of reproduction biology and embryo transfer in the European Roe Deer (Capreolus capreolus)

Titelblatt, Inhaltsverzeichnis, Abkuerzungsverzeichnis, Danksagung, Lebenslauf, Selbständigkeitserklaerung 1\. Einleitung 2\. Literaturübersicht 3\. Zielsetzung eigener Untersuchungen 4\. Material und Methoden 5\. Ergebnisse 6\. Diskussion 7.1 Zusammenfassung 7.2 Summary 8\. Verzeichnis der Abbildungen 9\. Liste eigener Veröffentlichungen LiteraturverzeicEs war Ziel der vorliegenden Arbeit, durch Einsatz einer modernen Methode der assistierten Reproduktion, des Embryotransfers, die embryonale Diapause des Europäischen Rehs zu untersuchen und zu charakterisieren. Für den Nutztierbereich etablierte Regime zur hormonellen Zyklussynchronisation und Superovulation von Embryonendonoren und ?rezipienten, Techniken zur Gewinnung und zum Transfer von Embryonen sowie Techniken zum genetischen Abstammungsnachweis der Tiere kamen hierfür erstmals beim Reh zum Einsatz. Die Ergebnisse von Superovulation, Synchronisation, Embryonengewinnung und des Embryotransfers mit ihrer Bedeutung für die Diapause des Rehs werden wie folgt zusammengefaßt: (A) Die Applikation von intravaginalen Gestagen-Schwämmchen resultierte in einer Brunstsynchronisation der Embryonendonoren. Nach Entfernen der Schwämmchen setzte bei allen Tieren der Östrus mit nachfolgenden Deckakten durch den Bock ein. (B)Im Schutze der Gestagen-Schwämmchen als künstliche Lutealphase war es möglich, durch die Applikation von PMSG und dessen späterer Antagonisiering eine Superovulation der Rehe zu induzieren. Durch den Einsatz der Transrektalen Adaptersonographie war es möglich, auf sonografischem Wege die Ovardynamik zu verfolgen und die Zahl der sprungreifen Follikel bzw. der tatsächlich ausgebildeten Corpora lutea zu quantifizieren. Signifikant höhere Zahlen an Gelbkörpern bzw. aufgefundenen Embryonen in Kombination mit höheren Progesteronwerten bei superovulierten Tieren im Vergleich zu nicht-superovulierten Tieren sowie zufriedenstellende Ovulationsraten von durchschnittlich 70 % lassen PMSG/Anti-PMSG als Hormonregime zur Superovulation von Rehen geeignet erscheinen. (C) Aufgrund der anatomischen Gegebenheiten des weiblichen Genitaltraktes beim Reh war es trotz des erfolgreichen Einbringens eines Katheters in das Uteruslumen nicht möglich, Embryonen auf nicht-chirurgischem Wege aus den Uterushörnern zu gewinnen. Die chirurgische Spülung der einzelnen Uterushörner der Tiere erbrachte mit Auffindungsraten von durchschnittlich 41 % (Verhältnis der Anzahl an Embryonen zur Zahl gezählter Gelbkörper) zufriedenstellende und mit den Werten anderer Cervidae vergleichbare Ergebnisse. Im Vergleich zu domestizierten Tierarten wie Ziege und Schaf schnitt die Embryonengewinnung auf chirurgischem Wege beim Reh deutlich schlechter ab. (D) Die terminorientiere Embryonenspülung der Spendertiere an Tag 7 bzw. 9 des berechneten Zyklus erbrachte eine Vielzahl ausschließlich früher embryonaler Entwicklungsstadien. Alle dieser Embryonalstadien wurden in den Uterushörnern und nicht anderen Tierarten entsprechend in den Eileitern aufgefunden. Es wurde geschlossen, daß bereits die frühe Embryonalentwicklung der Rehembryonen eine Verzögerung erfährt und nicht erst nach dem Erreichen des Stadiums der Blastozyste. (E)Die Applikation von PGF2a zur Zyklussynchronisation bei sechs von acht Empfängertieren während der Diapause resultierte innerhalb weniger Tage in einem messbaren Progesteronabfall mit anschließendem Anstieg zurück auf den Anfangswert. Parallel zum Verlauf der Progesteronkurve nach Luteolyse konnte sonographisch und makroskopisch die Rückbildung alter und die Entstehung neuer, sich am Tage des Embryotransfers in Blüte befindlicher Gelbkörper nachgewiesen werden. (F) Nach dem Embryotransfer im Herbst kam es bei drei von insgesamt acht Tieren zu Trächtigkeiten, darunter eine Zwillingsträchtigkeit. Zwei der Trächtigkeiten konnten bereits im Januar kurz nach der Implantation durch transrektale ultrasonographische Untersuchung detektiert werden. Alle der tragenden Tiere waren in ihrem Zyklus mit dem Alter der zu transferierenden Embryonen synchronisiert worden, es entwickelte sich keine Trächtigkeit bei nicht neu synchronisierten Tieren. Obwohl die Geburt der vier Kitze zur physiologischen Setzzeit der Rehe in den Monaten Mai und Juni stattfand, konnte die Hypothese, daß es durch Kryokonservierung der Embryonen und Embryotransfer zu einer künstlichen Verkürzung der Diapause gekommen war, nicht verifiziert werden. Der Blutuntersuchung der drei Rehfamilien uum Zwecke eines genetischen Abstammungsnachweises ergab eindeutig, daß es sich in allen 3 Fällen bei Putativ-Eltern und biologischen Eltern um ein und dieselben Tiere handelt. Alle Kitze sind demnach nicht das Ergebnis des Embryotransfers im Herbst, sondern das des natürlichen Brunstgeschehens im Sommer mit physiologischer Dauer von Trächtigkeit und Diapause. Eine Aussage über die Beeinflussbarkeit der embryonalen Diapause oder über ihre Abhängigkeit von externen oder internen Faktoren kann demnach nicht getroffen werden. Es bleibt weiterhin unklar, wer das Signal zur Wiederaufnahme des embryonalen Wachstums gibt, Mutter oder Embryo. Aus der Tatsache, daß es bei allen tragenden Rezipienten trotz vorangegangener neuer Zyklusinduktion mit Luteolyse, Neuanbildung von Gelbkörpern und zeitweisem Abfall der Progesteron-Werte nicht zur Beendigung der Trächtigkeiten und Resorption vorhandener Embryonen kam, wird gefolgert, daß bei Rehembryonen während des Zeitraumes der Diapause (anders als bei anderen Tierarten) eine weitgehende Unabhängigkeit vom Vorhandensein des eine Trächtigkeit aufrechterhaltenden Hormons Progesteron besteht. Darin wird eine weitere reproduktionsbiologische Besonderheit des Europäischen Rehs gesehen.The aim of this study was to characterise embryonic diapause (eD) in the roe deer using modern techniques of assisted reproduction, especially embryo transfer. Techniques established in domestic cattle such as synchronisation and superovulation of embryo donors and recipients, recovery and transfer of embryos and techniques for the genetic allocation of parentage were applied to this wildlife species for the very first time. The results of synchronisation, superovulation, recovery and transfer of embryos and their meaning for the embryonic diapause in roe deer are summarised as follows: (A) Application of intravaginal gestagene sponges resulted in the synchronisation of all embryo donors. After removal of the sponges, all animals came into oestrus and mated. (B) Under protection of the artificial luteal phase created by the vaginal sponges, it was possible to superovulate the females by injection of ECG followed by subsequent antagonisation with anti-ECG. Transrectal adaptersonography made it possible to monitor ovarian dynamics and to quantify the number of dominant follicles, respectively the number of corpora lutea. Significantly higher numbers of corpora lutea and significantly higher numbers of recovered embryos in combination with higher values of progesterone in the superovulated animals compared to the non-superovulated animals as well as satisfying rates of ovulation of 70 % on average lead to the conclusion that hormone regimes with ECG/anti-ECG are suitable for the superovulation of roe deer. (C) Due to the anatomy of the reproductive tract of female roe deer, embryos could not be recovered non-surgically although insertion of the catheter into the uterine lumen was possible. The results of the surgical flushing of each uterine horn resulted in recovery rates of 41 % on average (relation of the number of embryos to the number of corpora lutea), which is satisfying and comparable to the results reported from other Cervidae. Compared to the recovery rate of embryos reported for domestic species like goat and sheep the surgical flushing of embryos in roe deer was less successful. (D) Flushing of embryos on estimated days 7 and 9 of cycle brought up embryos in a wide variety of developmental stages. All of those early developmental stages were found in the uterine horns and not in the oviducts. It was concluded that embryonic development in roe deer is delayed immediately after conception. (E) Application of PGF2a to synchronise cycles in six of eight recipients during diapause resulted in a measurable decrease of progesterone in the faeces followed by a return back to the starting point. Parallel to these findings it was possible to monitor the regression and the development of new corpora lutea, being at their prime on the day of embryo transfer. (F) After embryo transfer in autumn, three of eight females became pregnant (one of them carrying twins). Two pregnancies could be diagnosed in January shortly after implantation using transrectal ultrasonography. All of the pregnant females had been synchronised with the age of the embryo transferred, there was no pregnancy in the non-synchronised females. Although fawns were born at the pysiological time for roe deer births the hypothesis of an artificially shortened diapause could not be verified. Blood samples taken from all members of the three roe deer families for the genetic allocation of parentage proofed that in all three cases putative parents and biological parents were identical. In conclusion, all fawns were the result of the natural matings in summer with the physiological duration of pregnancy and not the result of the embryo transfer program in autumn. No statement can be made about the possibility to influence embryonic diapause or about the dependence of eD on external or internal factors. It is still not clear who gives the signal for the resumption of embryonic development, mother or embryo. In spite of induction of a new cycle via luteolysis going along with development of new corpora lutea and temporary decrease of progesterone concentrations, none of the pregnancies was terminated and embryos were not resorbed. All females carried their fawns to term, which leads to the conclusion that in contrast to other animal species in roe deer, during the diapause, maintenance of pregnancy must be largely independent from the presence of progesterone. This finding is considered to be another reproductive particularity of European roe deer