The individual and society in the GDR under Honecker : orthodoxy, dissidence and internal debate.

The thesis offers a comparative interdisciplinary approach to the examination of the intellectual debates about the relationship between individual and society in the GDR under Honecker. It shows that there was not only a continuum of debate between the academic disciplines, but also from the radical critics of the GDR leadership such as Robert Havemann, Rudolf Bahro and Stefan Heym through the social scientists, literary critics and legal theorists working in the academic institutions to theorists close to the GDR leadership. It also shows that the official line and policy of the ruling party itself on the question of the individual and society was not static over the period, but changed in response to internal and external pressures. Over the period 1971 - 1989 greater emphasis was placed by many intellectuals on the individual, his needs and interests. It was increasingly recognised that conflicts could exist between the individual and society in GDR socialism. Whereas the radical critics argued that these conflicts were due to features of GDR society, such as the hierarchical system of labour functions and bureaucracy, and extrapolated from this a general conflict between the political leadership and population, orthodox critics argued that conflicts existed between a specific individual and society and were largely due to external and historical factors. The internal critics also pointed to the social phenomena which were detrimental to the individual's development in the GDR, but they put forward less radical solutions. With the exception of a few radical young writers, all theorists studied in this thesis gave precedence to social interests over individual interests and so did not advocate a return to `individualistic' positions. The continuity of sometimes quite controversial discussions in the GDR academic journals and the flexibility of the official line and policy suggests that it is inappropriate to refer to GDR society under Honecker simply as totalitarian, although it did have some totalitarian features. What the thesis demonstrates is the existence of `Teiloffentlichkeiten' in which critical discussion is conducted even as the official, orthodox line is given out for public consumption in the high-circulation media.

The effectiveness of lamotrigine in the treatment of photosensitive epilepsy

Photosensitive epilepsy and associated pattern sensitivity are more prevalent in females and are usually treated with sodium valproate. Sodium valproate has an adverse effect profile, which particularly affects females, including teratogenicity, association with the polycystic ovary syndrome and weight gain. It would be useful therefore if an alternative treatment for photosensitive epilepsy could be found. The principle aim of this study was to investigate the effectiveness of lamotrigine in the treatment of photosensitive epilepsy in adults and children. Patients were either drug-naive, commencing lamotrigine therapy or were transferring from other antiepileptic drugs to lamotrigine (primarily sodium valproate) due to lack of response, adverse effects or desired pregnancy. The photoparoxsymal response in the electroencephalograph was used as the primary measure of photo and pattern sensitivity. In addition the effects of lamotrigine on occipital spikes and normal responses in the EEG to visual stimuli were investigated. Secondary measures also included the resting EEG, seizures, body mass index, menstrual function, mood and cognitive function. The results suggest that in adult patients lamotrigine is efficacious in the treatment of photosensitive epilepsy, although it appears inferior to sodium valproate. Lamotrigine does however have a more favourable adverse effect profile than valproate. The results indicate that lamotrigine therapy is suitable for photosensitive epilepsy in women of childbearing age or in patients experiencing unacceptable adverse effects with valproate therapy. Patients are more likely to respond to lamotrigine treatment if they present with sensitivity to a limited number of frequencies. Lamotrigine does not seem to be as efficacious in the treatment of children, although against it may be considered a second line drug if the child does not respond to or will not tolerate sodium valproate.

Aspects of signal transduction in the gastrointestinal tract

This study was undertaken to increase knowledge of the mechanisms of inter- and intracellular signalling in the gastrointestinal tract. Specific aims were: to use cell lines to elucidate factors affecting growth of gastric cells, to investigate the distribution and aspects of function of isoforms of protein kinase C in a gastric cell line and in the rat gastrointestinal tract and to determine the presence and regulation of nitric oxide synthase in gastrointestinal tissues from the rat and in cell lines. The gastric cancer cell line HGT-1 was used to investigate control of growth. Increases in cell number were found to be dependent on the seeding density of the cells. In cells plated at low density insulin, epidermal growth factor and gastrin all increased cell number. Gastrin produced a bell-shaped dose response curve with a maximum activity at 5nM. No effect of gastrin was apparent in cells plated at high density. α and β isoforms of protein kinase C were found, by immunoblotting procedures, to be widespread in the gastrointestinal tract of the rat, but protein kinase Cε was confined to the gastric mucosa and gastrointestinal smooth muscle. HGT-1 cells contained protein kinase C α and ε but β or γ were not detected. Preincubation of HGT-1 cells for 24h with 1μM phorbol-12,13-dibutyrate down-regulated protein kinase C α but not ε. The inhibition by the activator of protein kinase C, 12-O-tetradecanoylphorbol 13-acetate (TPA) of the histamine-stimulated increase in cAMP in HGT-1 cells was down regulated by phorbol-12,13-dibutyrate. Inhibition of histamine-stimulation of adenylate cyclase by TPA was Ca2+-dependent and inhibited by the addition of an antibody to protein kinase C α. A role for protein kinase C α in modulating the effect of histamine on adenylate cyclase in HGT-1 cells is suggested. No nitric oxide synthase activity was detected in the gastrointestinal cell lines HGT-l, MKN-45 or CaCo-2. Ca2+-dependent nitric oxide synthase activity was observed in the gastric mucosa and the gastrointestinal smooth muscle from stomach to colon. The gastric: mucosal enzyme was soluble and showed half-maximal activity at 400nM Ca2+. Pretreatment of rats with endotoxin (3mg/kg body weight) induced nitric oxide synthase activity in both jejunal, ileal and colonic mucosa and muscle. A major portion of the induced activity in ileal and colonic mucosa was Ca2+-independent. Nitric oxide synthase activity in a high-density fraction of gastric mucosal cells was inhibited in a dose-dependent fashion by L-nitroarginine, NG-monomethyl-L-arginine, trifluoperazine and L-canavanine (in descending order of potency). Preincubation with okadaic acid and addition of ATPlMg2+ to the homogenisation buffer inhibited enzyme activity, which implies that phosphorylation inhibits gastric mucosal nitric oxide synthase.

Investigations of the site and mechanisms of drug-induced reductions in the reabsorption of divalent cations by the kidney

Disturbances in electrolyte homeostasis are a frequent adverse side-effect of the administration of aminoglycoside antibiotics such as gentamicin, and the antineoplastic agent cis-platinum. The aims of this work were to further elucidate the site(s) and mechanism(s) by which these drugs may produce disturbances in the renal reabsorption of calcium and magnesium. These investigations were undertaken using a range of in vivo and in vitro techniques and models. Initially, a series of in vivo studies was conducted to delineate aspects of the acute and chronic effects of both drugs on renal electrolyte handling and to select and evaluate an appropriate animal model: subsequent investigations were focused on gentamicin. In a study of the acute and chronic effects of cis-platinum administration, there were pronounced acute changes in a variety of indices of nephrotoxic injury, including electrolyte excretion. Most effects resolved but there were chronic increases in the urinary excretion of calcium and magnesium. The renal response of three strains of rat (Fischer 344, Sprague-Dawley (SD), and Wistar) to a ranges of doses of gentamicin was also investigated. Drug administration produced substantially different responses between strains, in particular marked differences in calcium and magnesium excretion. The results suggested that the SD rat was an appropriately sensitive strain for use in further investigations. Acute infusion of gentamicin in the anaesthetised SD rat produced rapid, substantial increases in the fractional excretion of calcium and magnesium, while sodium and potassium output were unaffected, confirming previous results of similar experiments using F344 rats. Studies using lithium clearance measurements in the anaesthetised SD rat were undertaken to investigate the effects of gentamicin on proximal tubular calcium reabsorption. Lithium clearance was unaffected by acute gentamicin infusion, suggesting that the site of acute gentamicin-induced hypercalciuria may not be located in the proximal tubule. Inhibition of Ca2+ ATPase activity was investigated as a potential mechanism by which calcium reabsorption could be affected after aminoglycoside administration. In vitro, both Ca2+ ATPase and Na+/K+ ATPase activity could be similarly inhibited by the presence of aminoglycosides, in a dose-related manner. Whilst inhibition of Na+/K+ ATPase could be demonstrated biochemically after in vivo administration of gentamicin, there were no concurrent effects on Ca2+ ATPase activity, suggesting that inhibition of Ca2+ ATPase activity is unlikely to be a primary mechanism of aminoglycoside-induced reductions of calcium reabsorption. Histochemical studies could not discern inhibition of either Na+/K+ ATPase or Ca2+ ATPase activity after in vivo administration of gentamicin. Selection of renal cell lines for further investigative in vitro studies on the mechanisms of altered cation reabsorption was considered using MTT (3-(4,5,-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and Neutral Red cytotoxicity assays. The ability of LLC-PK1 and LLC-RK1 cell lines to correctly rank a series of nephrotoxic compounds with their known nephrotoxic potency in vivo was studied. Using these cell lines grown on semi-permeable inserts, alterations in the paracellular transport of 45Ca was investigated as a possible mechanism by which gentamicin could alter calcium reabsorption in vivo. Short term exposure (I h) of LLC-RK1 cells to gentamicin, via both cell surfaces, resulted in a reduction in paracellular permeability to both transepithelial 3H-mannitol and 45Ca fluxes. When LLC-RK1 cells were exposed via the apical surface only, similar dose-related reductions were seen to those observed when cells were exposed to the drug from both sides. Short-term basal exposure to gentamicin appeared to contribute less to the observed reductions in 3H-mannitol and 45Ca fluxes. Experiments investigating transepithelial movement of 45Ca and 3H-mannitol on LLC-PK1 cells after acute gentamicin exposure were inconclusive. Longer exposure (48 h) to gentamicin caused an increase in the permeability of the monolayer and a consequent increase in transepithelial 45Ca flux in the LLC-RK1 cell line; increases in permeability of LLC-PK1 cells to 45Ca and 3H-mannitol were not apparent under the same conditions. The site and mechanism at which gentamicin, in particular, alters calcium reabsorption cannot be definitively described from these studies. However, indirect evidence from lithium clearance studies suggests that the site of the lesion is unlikely to be located in the proximal tubule. The mechanism by which gentamicin exposure alters calcium reabsorption may be by reducing paracellular permeability to calcium rather than by altering active calcium transport processes.

Application of long-period-grating sensors to respiratory plethysmography

A series of in-line curvature sensors on a garment are used to monitor the thoracic and abdominal movements of a human during respiration. These results are used to obtain volumetric tidal changes of the human torso in agreement with a spirometer used simultaneously at the mouth. The curvature sensors are based on long-period gratings (LPGs) written in a progressive three-layered fiber to render the LPGs insensitive to the refractive index external to the fiber. A curvature sensor consists of the fiber long-period grating laid on a carbon fiber ribbon, which is then encapsulated in a low-temperature curing silicone rubber. The sensors have a spectral sensitivity to curvature, d lambda/dR from similar to 7-nm m to similar to 9-nm m. The interrogation technique is borrowed from derivative spectroscopy and monitors the changes in the transmission spectral profile of the LPG's attenuation band due to curvature. The multiplexing of the sensors is achieved by spectrally matching a series of distributed feedback (DFB) lasers to the LPGs. The versatility of this sensing garment is confirmed by it being used on six other human subjects covering a wide range of body mass indices. Just six fully functional sensors are required to obtain a volumetric error of around 6%. (C) 2007 Society of Photo-Optical Instrumentation Engineers.

Investigation of different techniques to upgrade legacy WDM communication systems

This thesis presents experimental investigation of different effects/techniques that can be used to upgrade legacy WDM communication systems. The main issue in upgrading legacy systems is that the fundamental setup, including components settings such as EDFA gains, does not need to be altered thus the improvement must be carried out at the network terminal. A general introduction to optical fibre communications is given at the beginning, including optical communication components and system impairments. Experimental techniques for performing laboratory optical transmission experiments are presented before the experimental work of this thesis. These techniques include optical transmitter and receiver designs as well as the design and operation of the recirculating loop. The main experimental work includes three different studies. The first study involves a development of line monitoring equipment that can be reliably used to monitor the performance of optically amplified long-haul undersea systems. This equipment can provide instant finding of the fault locations along the legacy communication link which in tum enables rapid repair execution to be performed hence upgrading the legacy system. The second study investigates the effect of changing the number of transmitted 1s and Os on the performance of WDM system. This effect can, in reality, be seen in some coding systems, e.g. forward-error correction (FEC) technique, where the proportion of the 1s and Os are changed at the transmitter by adding extra bits to the original bit sequence. The final study presents transmission results after all-optical format conversion from NRZ to CSRZ and from RZ to CSRZ using semiconductor optical amplifier in nonlinear optical loop mirror (SOA-NOLM). This study is mainly based on the fact that the use of all-optical processing, including format conversion, has become attractive for the future data networks that are proposed to be all-optical. The feasibility of the SOA-NOLM device for converting single and WDM signals is described. The optical conversion bandwidth and its limitations for WDM conversion are also investigated. All studies of this thesis employ 10Gbit/s single or WDM signals being transmitted over dispersion managed fibre span in the recirculating loop. The fibre span is composed of single-mode fibres (SMF) whose losses and dispersion are compensated using erbium-doped fibre amplifiers (EDFAs) and dispersion compensating fibres (DCFs), respectively. Different configurations of the fibre span are presented in different parts.

A novel extracellular role for tissue transglutaminase in matrix-bound VEGF-mediated angiogenesis

The importance of tissue transglutaminase (TG2) in angiogenesis is unclear and contradictory. Here we show that inhibition of extracellular TG2 protein crosslinking or downregulation of TG2 expression leads to inhibition of angiogenesis in cell culture, the aorta ring assay and in vivo models. In a human umbilical vein endothelial cell (HUVEC) co-culture model, inhibition of extracellular TG2 activity can halt the progression of angiogenesis, even when introduced after tubule formation has commenced and after addition of excess vascular endothelial growth factor (VEGF). In both cases, this leads to a significant reduction in tubule branching. Knockdown of TG2 by short hairpin (shRNA) results in inhibition of HUVEC migration and tubule formation, which can be restored by add back of wt TG2, but not by the transamidation-defective but GTP-binding mutant W241A. TG2 inhibition results in inhibition of fibronectin deposition in HUVEC monocultures with a parallel reduction in matrix-bound VEGFA, leading to a reduction in phosphorylated VEGF receptor 2 (VEGFR2) at Tyr1214 and its downstream effectors Akt and ERK1/2, and importantly its association with b1 integrin. We propose a mechanism for the involvement of matrix-bound VEGFA in angiogenesis that is dependent on extracellular TG2-related activity. © 2013 Macmillan Publishers Limited. All rights reserved.

Respiratory function monitoring using a real-time three-dimensional fiber-optic shaping sensing scheme based upon fiber Bragg gratings

An array of in-line curvature sensors on a garment is used to monitor the thoracic and abdominal movements of a human during respiration. The results are used to obtain volumetric changes of the human torso in agreement with a spirometer used simultaneously at the mouth. The array of 40 in-line fiber Bragg gratings is used to produce 20 curvature sensors at different locations, each sensor consisting of two fiber Bragg gratings. The 20 curvature sensors and adjoining fiber are encapsulated into a low-temperature-cured synthetic silicone. The sensors are wavelength interrogated by a commercially available system from Moog Insensys, and the wavelength changes are calibrated to recover curvature. A three-dimensional algorithm is used to generate shape changes during respiration that allow the measurement of absolute volume changes at various sections of the torso. It is shown that the sensing scheme yields a volumetric error of 6%. Comparing the volume data obtained from the spirometer with the volume estimated with the synchronous data from the shape-sensing array yielded a correlation value 0.86 with a Pearson's correlation coefficient p <0.01.

Evolution of optical pulses in fiber lines with lumped nonlinear devices as a mapping problem

We analyze the steady-state propagation of optical pulses in fiber transmission systems with lumped nonlinear optical devices (NODs) placed periodically in the line. For the first time to our knowledge, a theoretical model is developed to describe the transmission regime with a quasilinear pulse evolution along the transmission line and the point action of NODs. We formulate the mapping problem for pulse propagation in a unit cell of the line and show that in the particular application to nonlinear optical loop mirrors, the steady-state pulse characteristics predicted by the theory accurately reproduce the results of direct numerical simulations.

Evolution of optical pulses in fiber lines with lumped nonlinear devices as a mapping problem

We analyze the steady-state propagation of optical pulses in fiber transmission systems with lumped nonlinear optical devices (NODs) placed periodically in the line. For the first time to our knowledge, a theoretical model is developed to describe the transmission regime with a quasilinear pulse evolution along the transmission line and the point action of NODs. We formulate the mapping problem for pulse propagation in a unit cell of the line and show that in the particular application to nonlinear optical loop mirrors, the steady-state pulse characteristics predicted by the theory accurately reproduce the results of direct numerical simulations. © 2005 Springer Science+Business Media, Inc.

Digital fiber nonlinearity compensation:toward 1-Tb/s transport

The world is connected by a core network of long-haul optical communication systems that link countries and continents, enabling long-distance phone calls, data-center communications, and the Internet. The demands on information rates have been constantly driven up by applications such as online gaming, high-definition video, and cloud computing. All over the world, end-user connection speeds are being increased by replacing conventional digital subscriber line (DSL) and asymmetric DSL (ADSL) with fiber to the home. Clearly, the capacity of the core network must also increase proportionally. © 1991-2012 IEEE.

E-HR and international HRM:a critical perspective on the discursive framing of e-HR

In the current global economic climate, international HRM is facing unprecedented pressure to become more innovative, effective and efficient. New discourses are emerging around the application of information technology, with 'e-HR' (electronic-enablement of Human Resources), self-service portals and promises of improved services couched as various HR 'value propositions'. This study explores these issues through our engagement with the emergent stream of 'critical' HRM, the broader study of organizational discourse and ethical management theories. We have found that while there is growing research into the take-up of e-HR applications, there is a dearth of investigation into the impact of e-HR on the people involved; in particular, the (re)structuring of social relations between HR functions and line managers in the move away from face-to-face HR support services, to more technology-mediated 'self-service' relationships. We undertake a close reading of personal narratives from a multinational organization, deploying a critical discourse lens to examine different dimensions of e-HR and raise questions about the strong technocratic framing of the international language of people management, shaping line manager enactment of e-HR duties. We argue for a more reflexive stance in the conceptualization e-HR, and conclude with a discussion about the theoretical and practical implications of our study, limitations and suggestions for future research. © 2014 © 2014 Taylor & Francis.

Simultaneous continuous recording of accommodation and pupil size using the modified Shin-Nippon SRW-5000 autorefractor

The internal optics of the recent models of the Shin-Nippon SRW-5000 autorefractor (also marketed as the Grand Seiko WV-500) have been modified by the manufacturer so that the infrared measurement ring has been replaced by pairs of horizontal and vertical infrared bars, on either side of fixation. The binocular, open field-of-view, allowing the accommodative state to be objectively monitored while a natural environment is viewed, has made the SRW-5000 a valuable tool in further understanding the nature of the oculomotor response. It is shown that the root-mean-square of model eye measures was least (0.017 ± 0.002D) when the separation of the horizontal measurement bars were averaged twice. The separation of the horizontal bars changes by 3.59 pixels/dioptre (r2 = 0.99), allowing continuous on-line analysis of the refractive state at up to 60 Hz temporal resolution to an accuracy of <0.001D, with pupils >3 mm. The pupil edge is not obscured in the diagonal axis by the measurement bars, unlike the ring of the original optics, so in the newer model pupil size can be measured simultaneously at the same rate with a resolution of <0.001 mm. The measurements of accommodation and pupil size are relatively unaffected by eccentricity of viewing up to ±10° from the visual axis and instrument focusing inaccuracies over a range of 10 mm towards the eye and 5 mm away from the eye. The resolution and temporal properties of the analysis are therefore ideal for the simultaneous measurement of dynamic accommodation and pupil responses. © 2004 The College of Optometrists.

Oxidised LDL-lipids increase beta amyloid production by SH-SY5Y cells through glutathione depletion and lipid raft formation

Elevated total cholesterol in midlife has been associated with increased risk of dementia in later life. We have previously shown that low-density lipoprotein (LDL) is more oxidized in the plasma of dementia patients, although total cholesterol levels are not different from those of age-matched controls. β-Amyloid (Aβ) peptide, which accumulates in Alzheimer disease (AD), arises from the initial cleavage of amyloid precursor protein by β-secretase-1 (BACE1). BACE1 activity is regulated by membrane lipids and raft formation. Given the evidence for altered lipid metabolism in AD, we have investigated a mechanism for enhanced Aβ production by SH-SY5Y neuronal-like cells exposed to oxidized LDL (oxLDL). The viability of SH-SY5Y cells exposed to 4 μg oxLDL and 25 μM 27-hydroxycholesterol (27OH-C) was decreased significantly. Lipids, but not proteins, extracted from oxLDL were more cytotoxic than oxLDL. In parallel, the ratio of reduced glutathione (GSH) to oxidized glutathione was decreased at sublethal concentrations of lipids extracted from native and oxLDL. GSH loss was associated with an increase in acid sphingomyelinase (ASMase) activity and lipid raft formation, which could be inhibited by the ASMase inhibitor desipramine. 27OH-C and total lipids from LDL and oxLDL independently increased Aβ production by SH-SY5Y cells, and Aβ accumulation could be inhibited by desipramine and by N-acetylcysteine. These data suggest a mechanism whereby oxLDL lipids and 27OH-C can drive Aβ production by GSH depletion, ASMase-driven membrane remodeling, and BACE1 activation in neuronal cells. © 2014 The Authors.

Respiratory function monitoring using a real-time three-dimensional fiber-optic shaping sensing scheme based upon fiber Bragg gratings

An array of in-line curvature sensors on a garment is used to monitor the thoracic and abdominal movements of a human during respiration. The results are used to obtain volumetric changes of the human torso in agreement with a spirometer used simultaneously at the mouth. The array of 40 in-line fiber Bragg gratings is used to produce 20 curvature sensors at different locations, each sensor consisting of two fiber Bragg gratings. The 20 curvature sensors and adjoining fiber are encapsulated into a low-temperature-cured synthetic silicone. The sensors are wavelength interrogated by a commercially available system from Moog Insensys, and the wavelength changes are calibrated to recover curvature. A three-dimensional algorithm is used to generate shape changes during respiration that allow the measurement of absolute volume changes at various sections of the torso. It is shown that the sensing scheme yields a volumetric error of 6%. Comparing the volume data obtained from the spirometer with the volume estimated with the synchronous data from the shape-sensing array yielded a correlation value 0.86 with a Pearson's correlation coefficient p <0.01.