Academic literature on the topic 'Astronomical sciences not elsewhere classified'

This article offers an approach through administrative and cultural history to the problems associated with gathering and processing data for the Spanish national census of 1920, and by implication for earlier Spanish censuses. It focuses on the Basque province of Guipúzcoa, making use of correspondence between the central statistical office in Madrid, the provincial jefe de estadística and the localities, and of reports on three problematic towns within the province. The issues that emerge regarding ‘undercounting’, the definition of administrative boundaries and the classification of demographic characteristics are set in the wider context of census-taking practices and problems elsewhere in Spain and in other cultures.

Kinematical and photometric studies of nests of interacting galaxies are described. Velocity fields of 22 nests were obtained using the 6-meter telescope of the Special Astronomical Observatory of Sciences Academy of USSR. UBV-photometry carried out with 125-cm telescope of Sternberg Institute has shown that the majority of nests is blue and undergoes intense star formation. Nests are found to be of different types:among them there are single SB and dwarf Irr galaxies with super-giant HII -regions as well as tight pairs and multiple systems of galaxies. Multiple systems classified as nests are shown to be dynamically stable.

Latour’s notion of immutable mobiles relates the circulability of certain objects to, among other features, their immutability, readability and combinability. As such it does not distinguish between, say, hand-drawn maps and machine-generated graphs. How, though, does the medial ‘microstructure’ of immutable mobiles matter to socially shared uses? Would, for example, digital images as bounded grids of nonoverlapping square pixels, each representing a numerical value, shape how distributed scientific work unfolds? In this article, I begin with reviewing attempts to link the microstructure of media to their communicative uses, focusing on Luhmann’s relational account of media as loosely coupled substrates in which more rigid forms can become manifest. Drawing on an ethnography of astronomical research, I then inquire into how the scientists involved reasoned about their uses of media from within their practices. They used digital photographic exposures as ‘workable objects’ whose usefulness was not guaranteed initially. Local work was oriented to potential reuses of images (as processed exposures) by researchers elsewhere, as demonstrated by concerns over the integrity of images, the possibility of describing their work with reasonable efforts, as well as by negotiating acceptable elements in calculations so as to reveal stabilized phenomena. In doing so, scientists insisted on the need to play or experiment, suspending sequential work for explorations oriented toward deciding which action among alternatives to make consequential. This was part of a more extended ‘calculative game’ that points, through its orientation to reasonable agreement and delimitations of legitimate efforts, to the social order of this work. The medium, here conceived as images deemed accountable to reuses elsewhere, is a social achievement. Recognizing this may help to better understand the reusability of scientific data and its challenges.

Retinal vasculitis (RV) refers to an entity in which the retinal vasculature is inflamed, frequently with indications of inflammation elsewhere in the eye. Non-infectious RV can be idiopathic or associated with systemic disease, ocular conditions, and malignancy. It can also be classified based on the vessel affected: artery, vein, or both. Due to the lack of strong evidence-based treatment trials and algorithms for RV, physicians must often rely on their experience, which creates great variability in treating this entity. This article provides an overview of various treatment modalities used in the management of non-infectious RV, with a focus on immunomodulatory therapies. We outline a potential stepwise approach of starting with steroids to control the acute inflammation and subsequently changing to immunomodulatory therapy (IMT) for long-term treatment.

SummaryThe family registration records from a village population in a small island of Japan are used to assess the effect of demographic differentiation within a population on genetic measures. When the couples studied are classified by birth cohorts and origins, wives of the couples where one spouse came from elsewhere were older at marriage and had a shorter duration of marriage or registration than wives where both spouses were natives of the village. The mean number of offspring is statistically smaller in the former except for the latest cohort, due mainly to out-migration during the reproductive ages which also resulted in low rates of marriage among the offspring within the village. This leads to a small effective population size and an increased likelihood of genetic drift in the overall population.

Korean has a large number of taste terms and the paradigm is continuously expanding since the lexicalization operates systematically on a few robust principles. Based on the taste terms collected from lexicons, dictionaries, web-postings, and elsewhere, we classified the terms and analyzed the lexicalization patterns. In addition to the widely-known five classes of tastes, i.e., sweet, salty, sour, bitter and umami, Korean has three more classes in the basic category, i.e., pungent, fishy and bland. A large number of tactile sensory words to describe the touch sensations in the mouth at the tasting event and expressions denoting characteristic food texture and mastication also join in creating a rich taste vocabulary. The Korean taste lexicalization system is equipped with the means to signal diverse aspects of gustatory sensation, i.e., intensity, depth, purity and duration. Among such means are vowel polarity, consonantal sound symbolism, reduplication and onomatopoeia. The systematicity of taste lexicalization contributes to the plasticity of the paradigm, making the Korean taste vocabulary one of the most productive and elaborate paradigms.

AbstractU-series chronologies of the emerged coral limestone terraces on Barbados, West Indies, together with those of the terraces from New Guinea, have formed the basis for most late Pleistocene eustatic models. The so-called “Barbados sea level model” has been challenged in recent years, however. A major issue is whether during oxygen isotope stage 5e, when Rendezvous Hill reef complex on Barbados Island formed, the sea rose above the present position for one relatively brief period of <10,000 yr, or for two or more periods spanning approximately from 140,000 to 115,000 yr B.P. Evidence for the latter scenario has not come from initial studies of Barbados but from elsewhere; it is also inconclusive because of the dating uncertainties involved. We have carried out careful redeterminations of U-series ages on a suite of 29 Acropora palmata samples systematically collected from four of the lowest terraces on the island. Diagenetic disturbance may have caused the age spreads at some sampling outcrops. A model for the diagenetic exchange of uranium isotopes in coral samples with those in groundwater explains the anomalous 234U/238U ratios in samples with apparently unaltered mineralogy (aragonite) and trace element (Mg and Sr) chemistry. It shows that age dispersions of 5–10% can be engendered by a U exchange coefficient of the order of 10−6 yr−1. The lower-limit terrace ages, estimated from averaging the multiple measurements, are 81,000 ± 2000 yr (Worthing), 105,000 ± 1000 yr (Ventnor), 120,000 ± 2000 yr (Maxwell), and 117,000 ± 3000 yr (Rendezvous Hill). No evidence was found of previously inferred bipartite sea levels centering around 118,000 and 135,000 yr ago. This study documents the need of dating coral with the high precision/sensitivity mass-spectrometric techniques for future resolution of the temporal relationships among sea level changes, climate oscillations, and astronomical forcing—relationships originally addressed by the Barbados sea level model.

This article presents AgriExp, a remote-based workflow for the rapid mapping and monitoring of archaeological and cultural heritage locations endangered by new agricultural expansion and encroachment. Our approach is powered by the cloud-computing data cataloguing and processing capabilities of Google Earth Engine and it uses all the available scenes from the Sentinel-2 image collection to map index-based multi-aggregate yearly vegetation changes. A user-defined index threshold maps the first per-pixel occurrence of an abrupt vegetation change and returns an updated and classified multi-temporal image aggregate in almost-real-time. The algorithm requires an input vector table such as data gazetteers or heritage inventories, and it performs buffer zonal statistics for each site to return a series of spatial indicators of potential site disturbance. It also returns time series charts for the evaluation and validation of the local to regional vegetation trends and the seasonal phenology. Additionally, we used multi-temporal MODIS, Sentinel-2 and high-resolution Planet imagery for further photo-interpretation of critically endangered sites. AgriExp was first tested in the arid region of the Cholistan Desert in eastern Pakistan. Here, hundreds of archaeological mound surfaces are threatened by the accelerated transformation of barren lands into new irrigated agricultural lands. We have provided the algorithm code with the article to ensure that AgriExp can be exported and implemented with little computational cost by academics and heritage practitioners alike to monitor critically endangered archaeological and cultural landscapes elsewhere.

Abstract Background Retention in care is critical for treatment and prevention of HIV. Many HIV care clinics measure retention rate, but data are often incomplete for patients who are classified as lost to follow-up but may be actually in care elsewhere, moved, or died. The Data to Care (D2C) initiative supports data sharing between health departments and HIV providers to confirm patient care status and facilitate reengagement efforts for out of care HIV patients. Methods The University of Chicago Medicine (UCM) provided an electronic list to the Chicago Department of Public Health (CDPH) of adult HIV-positive patients whose retention status was not certain. Retention in care was defined as at least 2 visits &gt;90 days apart within the prior 12 months. CDPH matched this list of patients with data from the Chicago electronic HIV surveillance database. Matches were based on patient name, including alternative spellings and phonetics, and birth date. CDPH also cross-checked patient names with the CDC’s national enhanced HIV-AIDS Reporting System (eHARS) database. CDPH provided UCM with patient current care status, i.e., patient was in care elsewhere (as verified by lab data), moved out of state, or deceased. Results 780 HIV-positive patients received care in the UCM adult HIV clinic from January 1, 2013 to March 31, 2017. Of these, 360 were retained in care as of March 2017. We shared data with CDPH for 492 patients. Of these, 294 (59.8%) were matched, and 168 (34.1%) had a date of last medical care provided. See Table 1 for patient dispositions, before and after data sharing. 24 (13.4%) of patients believed to be lost to follow up according to UCM records were confirmed either transferred care or deceased according to health department data. Conclusion Data sharing between the health department and HIV providers can improve data accuracy regarding retention in care among people living with HIV. Disclosures J. P. Ridgway, Gilead FOCUS: Grant Investigator, Grant recipient; D. Pitrak, Gilead Sciences FOCUS: Grant Investigator, Grant recipient

Although well over 1000 journal articles, conference papers, books, technical notes and theses have been written on the subject of information technology (IT) evaluation, only a relatively small subset of this literature has been concerned with the core issues of what precisely is meant by the term ‘value’ and with the process of making (specifically) IT investment decisions. All too often, the problem and highly complex issue of value is either simplified, ignored or assumed away. Instead the focus of much of the research to date has been on evaluation methodologies and, within this literature, there are different strands of thought which can be classified as partisan, composite and meta approaches to evaluation. Research shows that a small number of partisan techniques are used by most decision makers with a minority using a single technique and a majority using a mixture of such techniques of whom a substantial minority use a formal composite approach. It is argued that, in mapping the set of evaluation methodologies on to what is termed the investment opportunity space, that there is a limit to what can be achieved by formal rational evaluation methods. This limit becomes evident when decision makers fall back on ‘gut feel’ and other non-formal/rigorous ways of making decisions. It is suggested that an understanding of these more complex processes and decision making, in IT as elsewhere, needs tools drawn from philosophy and psychology.

When an astronomical observer discovers a transient event in the sky, how can the information be immediately shared and delivered to others? Not too long time ago, people shared the information about what they discovered in the sky by books, telegraphs, and telephones. The new generation of transferring the event data is the way by the Internet. The information of astronomical events is able to be packed and put online as an Internet feed. For receiving these packed data, an Internet feed listener software would be required in a terminal computer. In other applications, the listener would connect to an intelligent robotic telescope network and automatically drive a telescope to capture the instant Astrophysical phenomena. However, because the technologies of transferring the astronomical event data are in the initial steps, the only resource available is the Perl-based Internet feed listener developed by the team of eSTAR. In this research, a Java-based Internet feed listener was developed. The application supports more features than the Perl-based application. After applying the rich Java benefits, the application is able to receive, parse and manage the Internet feed data in an efficient way with the friendly user interface. Keywords: Java, socket programming, VOEvent, real-time astronomy

In today’s world, antimicrobial resistance is one of the biggest global health issues that mankind is facing. This most effective way to ensure a wound does not become infected is through cleanliness and continued disinfection of the wound site. There is a lack of new antimicrobial drugs coming to the market due to economical and clinical reasons, this is evident in Lord O’Neill’s 2016 report and is addressed by Professor Dame Sally Davies in Parliament, (“We have reached a critical point and must act now on a global scale to slow down antimicrobial resistance”2). Prescription drugs have led to this epidemic that was highlighted by O’Neill. The latest report (2016) by O’Neill states, it is critical to improve sanitation and hygiene, refrain from overusing antibiotics in agriculture and the environment as well as introducing rapid diagnostics and vaccines3. This is leading to the need for photodynamic antimicrobial chemotherapy (PACT) that involves the use of a reactive oxygen species (ROS), photosensitiser, and light to cause microbial death. PACT is a treatment for resistant and non-resistant pathogens that is included in the treatment of multidrug resistant infections. The approach is to use novel antimicrobial drugs topically, avoiding systemic photo-toxicity, thus leading itself towards topical infection control. Herein, we report the development of a range of novel photosensitisers based on the second generation photodynamic therapeutic dyes (PDT) that are based on the tricyclic isoalloxazine structure of riboflavin, vitamin B2. Photosensitisers were synthesised using similar strategies to the isoalloxazine for a number of reasons: e.g. photoactivity and capability of degradation. In order to investigate which photosensitisers gave the highest reactive oxygen yield, functional group changes were made on the N-phenyl ring by substituting a range of electron withdrawing/donating substituents at different positions (ortho, meta, para). The free amide moiety was used to attach the photosensitiser to a solid support that would act as proof of principal of a photosensitiser attached to a bandage. These dyes show a phototherapeutic response via a Type I and II mechanism upon illumination by light of a selected wavelength. The mechanisms produce highly toxic oxygen-species, such as radical production via Type I pathway and singlet oxygen generation by Type II, thus causing terminal damage to microbes in a short time period. The synthesised photosensitisers are illuminated using blue light (440 - 490 nm) and white light in order to monitor and compare the singlet oxygen and radical yields generated as they absorb approximately at 440 nm, thus blue light being ideal for irradiation. The outstanding singlet oxygen result generated by compound 12c of 172% and a radical production by 11c of 227% show promising generators of cytotoxic species, resulting in microbial death. The synthesised photosensitisers have been tested against two opportunistic microbes (Gram positive and Gram negative bacteria; Staphylococcus aureus (S. aureus), and Escherichia coli (E.coli). They have proven to be problematic from its presence within the healthcare system especially when found on surgical site infections. From the statistics generated for the National Health Service (NHS) in the UK we can see that 52.4 % of S. aureus, and 43.1 % E.coli originates within the hospital environment. Antimicrobial activity was observed for several compounds under different light regimes on and off the solid support. As a result, the best observed MIC value of 0.25 mM/mL was achieved for S. aureus in darkness and in blue light without the polymer support. Additionally, when these compounds were linked to a polymer support (mimicking a bandage), antimicrobial activity was retained when irradiated using blue light at 1.0 mM/mL. These results show potential towards the next generation of antimicrobial disinfection agents. In time, these compounds could be integrated into the healthcare system for use as a new generation of self- cleaning bandages towards post-operative wound disinfection rather than employing front line antimicrobials. This is a moot subject under review in parliament and former UK prime minister has highlighted the concern. In a statement recently released, he states “If we fail to act, we are looking at an almost unthinkable scenario where antibiotics no longer work and we are cast back into the dark ages of medicine" – David Cameron, UK Prime Minister2.

Stroke is the third leading cause of death in the western world, and the primary cause of adult disability. There is a great need for methods to identify patients at risk of stroke and decide appropriate treatment. The main criterion for identifying patients at risk of stroke is the percentage of the narrowing in the carotid arteries, which lead blood from the heart to the brain, which currently is quantified manually. This project is in collaboration with Blackpool Victoria Hospital and Christies Hospital in Manchester. The aim of this project is to develop software methods to improve computer-assisted carotid artery stenosis measurement based on Magnetic Resonance Images. A methodology is therefore presented, based on 3D geometry extracted from Contract-Enhanced MR Angiograms, to identify and segment the internal carotid arteries for stenosis quantification. The MRA data volume is initially automatically reduced, by locating the carotid arteries and creating two volumes of interest, each including a single set of carotids (either left or right). The artery of interest (Internal Carotid Artery - ICA) is identified in each sub-volume automatically, by tracking the carotid bifurcation and selecting the artery branch with no further arterial branches. The central axis of the ICA is consequently determined by calculating and connecting together the centres of gravity (centroids) of the 2D contours of the carotid in the axial plane. Segmentation of the ICA is carried out, perpendicular to the central axis, by applying adaptive thresholds along the ICA central axis based on local image characteristics. Hence, the cross-sectional area of the segmented ICA is then measured at different points along the vessel. The most stenotic area is identified, and a reference region is manually selected. The degree of stenosis is then quantified based on the reference and stenosed area measurements, according to the NASCET criterion. This provides a fully automated methodology to locate, identify, and measure the internal carotid stenosis. It is the first time that such complete methodology that covers the processing of the MRI data until the stenosis measurement is taken is developed and is fully automatic. The segmentation results are thoroughly evaluated against the manual delineations of two clinical experts (each performed the delineations twice), and against two popular segmentation techniques. The results were found successful and perform better than manual measurements and other current techniques. They present smaller variability than manual measurements and are able to deal with irregularities in the arterial structure, where other computerised techniques fail. The suggested methodologies seem promising and able to improve considerably both current clinical practice and other existing methodologies.

There are currently several evaluation methods suited to children within the Child-Computer Interaction (CCI) community. However, these methods are user based leaving a gap in inspection method suited to children, that is, where children will act as the inspection method evaluators. This research focused on how to design an effective and easy to use inspection method where children will perform the evaluation based on their values. To ensure that the above is met, a user centred approach and a mixed methodology was explored and finally resulted in the creation of the Inspection Method for Children (IMCH) with an accompanying guideline. This six stages method could be used by CCI researchers as a guide to develop similar methods for children, by industries to perform inspection method evaluation with children on technologies designed for children and could be used by designers to gather design criteria for children’s technology. The process undertaken within this research to develop the new method is also novel and could be adapted by new and old researchers when adapting method to suit children. Future work will focus on carrying out evaluation with wider age range of children in the method to ensure suitability of the method for more children. Comparative studies of the method with other usability method to determine the effectiveness of the method and as a refinement process to produce a validated and refined IMCH method.

The use of lipid profiles from the immobilised alga Selenastrum capricornuizim was investigated as a potential indicator of heavy metal pollution in freshwater environments. The toxicity of Cu", Zn 2 and Cd2t on algal growth was determined and the effective concentration inhibiting specific growth rate by 50 % (EC5 0) for each metal was found to be 124 pM Cu, 20 pM Zn and 5.7 pM Cd respectively. The Cu 24 EC50 value for immobilised cells was also shown to be 124 j.tM, suggesting that Cu exhibits similar toxic effects on growth in both free and immobilised cells. Studies of the effects of temperature and heavy metal exposure (Cu21, Zn 2 and Cd2 +) on S. caprzcornutum demonstrated that these factors altered the fatty acid and free sterol composition of free algal cells in batch culture. A shift in temperature from 25°C to 10°C led to an increase in the relative proportion of oleate and decrease in linoleate and parinate (18:4), together with a significant increase in the composition of ergostenol. Exposure to heavy metal ions led to an increase in oleate (with all three metals) and altered relative proportions of linoleate and parinate (changes being metal specific). Metal ion treatment also increased a22 desaturation of chondrillasterol. This characteristic lipid signature when S. capricornutum was exposed to heavy metal ions was significantly different from changes associated with other environmental factors. These changes in lipid composition upon heavy metal treatment were also observed during exposure of S. capricornuiwn to lower metal concentrations typically found in polluted environments. Studies of cells immobilised within alginate beads showed that gel confinement significantly affected the biochemistry and physiology of algal cells, with a reduction in growth rate and final cells numbers. Scanning electron microscopy demonstrated that growth was mainly limited to the bead periphery. Immobilisation altered the lipid of composition of cells as a consequence of alterations in membrane fluidity and membrane disruption. The Cu uptake from solution was greater in immobilised cells than free cells, thus gel confinement did not confer any protection to cells. The characteristic and significant changes within the lipid composition of free cells with Cu treatment were similarly observed in immobilised cells but were only apparent at 124 pM Cu. Thus lipid profiles, especially sterol composition of immobilised algal cells, may potentially be utilised as sensitive and novel indicators of heavy metal pollution in freshwater environments.

Despite improved knowledge and advanced treatments of high-grade gliomas, the overall survival rate of glioma patients remains low due to the recurrences and locations of the tumour. Evidence shows that the existence of a subpopulation of cells - cancer stem cells (CSCs) may be the major obstacle in treating gliomas. CD133 and nestin have been suggested as the markers of CSCs and natural stem cells. The primary focus of this study was to identify CD133+/nestin+ stem-like cells and discover their association with multidrug resistance (MDR) related genes, i.e. multiple drug resistance I (mdrl) gene and anti-apoptotic gene (bcl-2) in human glioma compared to normal brain tissues and cell lines. Glioma and normal astrocyte cell lines have been employed for CD133 isolating purposes to characterise the association with MDR related genotype and phenotype. The chemosensitivity of the isolated CD 133 population was investigated using chemosensitivity assay. Meanwhile, a serum deprivation method was established in this study to enrich and select CD 133+ CSCs in a glioma (GOS-3) cell line. As a secondary focus of this project, the possibility of immortalisation enzyme hTERT being a discriminative masker between normal and cancer brain stem cells and the transcriptional correlation between cd133 and bmi-lIc-myc oncogenes were investigated. For the first time, findings of the current study demonstrated that 1) there was an evident increase of CD133 gene expression in glioma compared to normal brain tissues where the latter expressed low levels of CD133, P-gp and Bcl-2 than glioma tissues, with an exception of nestin expression, 2) serum deprivation enriched CD133 expression and demonstrated a direct coexpression between CD133 and drug resistance in GOS-3 cells, 3) hTERT may not be a discriminative marker for normal and cancer brain stem cells, 4) although there was a strong transcriptional association between bmil and cmyc, there was an inverse transcriptional association between these genes and cd133 in serum deprived glioma cells, suggesting that bmil may not be essential for the maintenance of glioma stem cells, and 5) CD133+ glioma and normal brain cells showed a significantly high resistance towards chemotherapeutic drugs compared to the autologous CD133- cells. In conclusion, an improved understanding of molecules contributing to the maintenance of CSCs may lead to a combined treatment, targeting both CSCs and their protective MDR phenotypes leading eventually to attractive strategies for the treatment of gliomas.

In the mammal, anaesthetics are known to act via two distinct mechanisms, either increasing inhibition via GABAA receptors (eg. Na-thiopentone) or decreasing excitation via NIvIDA receptors (eg. ketamine). The aim of this thesis is to investigate the effects of both increased inhibition and decreased excitation at the synaptic level within an invertebrate model system, something which cannot readily be done in vertebrate systems. This was achieved by carrying out experiments using both the above mentioned anaesthetics on the whole animal, isolated brain and cultured neurons. In invertebrates it has been shown that GABA and Glutamate can be both excitatory and inhibitory, and injection of GABA into Lymnaea has been shown to result in behavioural changes in feeding, locomotion, escape reactions, male mating and respiration. Injection of Na-thiopentone into the whole animal was carried out in this investigation, in order to establish the anaesthetic response of the animal model to this barbiturate. The presence of gamma-aminobutyric acid (GABA) receptors has been demonstrated in a respiratory interneuron (RPeD1) both electrophysiologically and via molecular techniques, however inmiunostaining has proved negative in RPeD1 and follower cells VD2/3 (unidirectional excitatory synapse) and VD4 (mutual inhibitory synapse). This suggests that these neurons are not themselves GABAergic, although this investigation shows the responses of these neurons to bath and direct application of GABA. Na-thiopentone did not reliably anaesthetise Lymnaea upon injection into the sole of the foot, suggesting that Na-thiopentone binds to proteins within the snail, andlor has a low affininty for the GABAA receptor in Lymnaea. Other anaesthetic studies using propofol and ketaniine have also demonstrated a lack of anaesthetic response. RPeD1 hyperpolarised and became quiescent in response to the application of high concentrations of GABA (10 3-104M), however at lower doses (1O 8-1O 5M), no effect was observed (p < 0.05). Under these conditions simultaneous recordings from VD4 showed hyperpolarisation in response to the application of GABA, whereas VD2 and VD3 exhibited excitatory responses. Presynaptic picoinjection of GABA also resulted in hyperpolarisation and quiescence in RJeD1, but the simultaneous response in VD3 was not observed. Postsynaptic application of GABA directly to 'VD2, and VD4 however, resulted in responses similar to those seen in the whole brain. VD2 and 3 also receive input 2, which hyperpolarises RPeD1 and elicits an excitatory EPSP in VD2 and 3 as this is similar to the response observed in this experiment it is possible that the effects of input 2 on RPeD1 and VD2 & 3 are mediated by GABA. As RPeDI does not stain positively for GABA and hyperpolarises in response to the drug, it seems unlikely that the postsynaptie effects are due to presynaptic release of GABA. RPeD1 has been shown to form reciprocal synapses with VD4 both in vivo and in vitro. When perfused with GABA (lmJ'i4), both cells hyperpolarised reversibly. The postsynaptic response could be due to the action of GABA presynaptically inhibiting RPeDI, or directly on postsynaptic GABA receptors. However VD4 forms connections with other cells in the brain such as input 3 which may also have resulted in this inhibitory response. RPeD1 would however have received a simultaneous excitatory input from this interneuron. Attempts were made to establish the nature of the RPeD1JVD4 synapse in these experiments, but no synapses were evident. These experiments therefore confirm the presence of GABA receptors in RPeD1 and suggest theft presence in VD2, and VD4. This investigation confirms the findings of previous studies, that injection and bath perfusion of barbiturates does not lead to responses in Lymnaea comparable to that of the mammal. In addition to it's main target site, ketamine (a frequently used intravenous anaesthetic) has also been shown to act at cholinergic receptors. The effects of ketamine on learning and memory and apoptosis in the mammalian CNS are well recognised. Within the Lymnaea CNS, VD4 and LPeD1 form a unidirectional excitatory cholinergic synapse, and this was chosen to investigate the effects of ketamine on excitatory synaptic transmission, short term potentiation and synapse formation in the invertebrate animal model. Ketamine decreased synaptic transmission between VD4 and LPeD1 in a concentration dependent manner, but did not significantly affect short term synaptic plasticity (pc0.05). While neurite outgrowth remained extensive, actual sprouting was diminished by all doses of ketamine. Cells exhibited extensive veiling, which was not present in control cells. Percentage chemical synapse formation was reduced by all doses of ketamine, and in some cases inappropriate inhibitory chemical synapses were formed. Furthermore acute, clinically relevant levels of ketamine reduce excitatory cholinergic transmission between VD4 and LPeD1, but short term plasticity is unaffected. Nerve regeneration was seriously compromised, and formation of appropriate chemical synapses greatly reduced. This data has serious implications for the clinical - use of ketamine, particularly in pregnant women, children or critical care patients where nerve regeneration and synapse formation are of great importance and long term exposure common practice. In conclusion, this work supports that of other studies which have showed that invertebrates appear to be relatively insensitive to barbiturates, whereas ketamine appears to effect excitation in a manner similar to that in the mammal.

Antiulcer agents, notably inhibitors of gastric acid secretion, have been the most successful category of drugs to be discovered in recent years; and moreover, there are currently four such agents in the world list of top 25 best selling drugs. Histamine H2 antagonists have been the number one selling pharmaceutical product for more than a decade and inhibitors of the parietal cell HIC-ATPase, so called "proton pump inhibitors" (PPI), look set to continue this success. The proposed study was designed to establish the relative efficacy and mechanisms of action of three novel agents using both in vitro and in vivo models. The three compounds namely AG-1749 (Lansoprazole), PD-136450 and transforming growth factor alpha (TGF(x) were studied to evaluate their antisecretory and antiulccr activities. Lansoprazole, the second PPI to be developed for clinical use, is a non-competitive inhibitor of the H1C-ATPase and has recently been launched in a number of countries. PD-136450 is a competitive antagonist of central and peripheral cholecystokinin-B (CCK-B) receptors (gastrin receptor) and it under clinical development as an anxiolytic but which has actions on the stomach and pancreas. Anxiolytic drug is otherwise known as anti-anxiety drugs, which are used to treat anxiety disorders, like depression, panic disorders, phobias and many personality disorders. TOFu is a polypeptide growth factor, which acts at the EGF receptor and displays potent mitogenic and antisecretory activity. The initial study deals with the comparison of the three compounds with omeprazole and ranitidine in terms of their ability to inhibit acid secretion and their activity in a range of experimental ulcer models. Potency, duration of action and activity against a range of stimulants of acid secretion (histamine, pentagastrin and basal) was determined in anaesthetized rat models by establishing dose-response relationships. The compounds represent a spectrum of activities in as much as lansoprazole is a potent, long acting inhibitor, PD-136450 is an orally active but selective inhibitor, while TOFu has a very short duration and is only active after parenteral administration. In a view to find out the mechanism of action of these drugs on gastric acid secretion, isolated gastric glands from rabbits were employed as an in vitro technique using radiolabeled 14C-aminopyrine as a marker. The results show that lansoprazole was the most potent antisecretory agent compared to other two drugs. The second phase of the study deals with the activity of the three compounds against gastric ulcers induced by acid hypersecretion, indomethacin and stress. This study enabled us to assess the extent to which antisecretory activity per se compared with other actions such as wound healing (TGFa) or anxiolytic activity (PD-136450) contribute to ulcer healing. As other workers already established that prostaglandins and nitric oxide are involved in the cytoprotective activity, the present study investigated the influence of prostaglandin and nitric oxide by using indomethacin and L-NAME pretreatment on the cytoprotective activity of lansoprazole, PD-136450 and TGFcz. Moreover, the three drugs were tested for their activities on the mucus and bicarbonate production in the stomach. It was found that lansoprazole and TGFc increased the gastric mucus secretion while PD-136450 did not show any change. Moreover it was evidenced from this study that the protective activity of PD-136450 is associated with the influence of bicarbonate secretion from the pancreas. In conclusion, the results of this study have indicated that lansoprazole, PD- 136450 and TGFct are potent antisecretory and antiulcer agents which have great therapeutic importance.

Mature skeletal muscle fibres can be classified as type I, type IIa, type IIx or type IIb fibres according to the myosin heavy chain (MHC) isoform that they express. More broadly, type I fibres are classified as slow fibres and type IIa, IIx and IIb fibres as fast fibres. However, the phenotype of an adult skeletal muscle fibre is not fixed: it displays plasticity being capable of adapting to changing activity and loading levels by either transition towards a slower phenotype or transition towards a faster phenotype. Overall, the aims of these studies were to further investigate and define the signal transduction pathways implicated in the control of skeletal muscle fibre phenotype. The ability of a fast muscle to undergo a transition towards a slower phenotype in response to chronic low-frequency stimulation (CLFS) was assessed, via metabolic enzyme activity assays and NADH-TR staining, following blockade of the calcineurin signalling pathway. Metabolic enzyme assays and northern blots were employed to assess the changes in enzyme activities and MEC isoform expression levels following blockade of the calcineurin and ERK1/2 signalling pathways in primary cultures of rat myotubes. Differences in the levels of various signal transduction proteins/transcription factors between slow and fast muscle were investigated using western blotting. The nuclear translocation kinetics of NFAT and NF-κB in response to treatment with the calcium ionophore A23187 were investigated in L6 myotubes using immunocytochernistry. Calcineurin blockade using cyclosporin A failed to prevent a decrease in lactate dehydrogenase activity and an increase in NADH-TR staining intensity, both characteristics of a transition towards a slower phenotype, following CLFS of the fast rat tibialis anterior muscle. Blockade of the ERK1/2 pathway in primary cultures of rat myotubes using U0126 significantly decreased MHC Iβ mRNA levels and significantly increased MIHC IIx, MEC IIb and perinatal MHC mRNA levels. Calcineurin blockade significantly decreased MHC Iβ and embryonal mRNA levels and significantly increased MHC IIx mRNA levels. Calcineurin blockade also significantly increased the activities of lactate dehydrogenase and creatine kinase while ERK1/2 blockade significantly increased the activities of lactate dehydrogenase, creatine kinase, hexokinase, malate dehydrogenase and β-hydroxyacyl-CoA deydrogenase. ERK1/2 and NF-κB levels were found to be higher in slow muscle compared to fast muscle while calcineurin and p38α,β levels were higher in fast muscle compared to slow muscle. No nuclear translocation of NF-κB and only limited evidence for NFAT nuclear translocation was seen in L6 myotubes following treatment with A23187. Overall these studies further characterize the roles of the ERK1/2 and calcineurin pathways in the regulation of muscle phenotype suggesting that each pathway controls some, but not all, of the genes that are differentially expressed between slow and fast muscle fibres. Western blotting suggests further signal transduction protein/transcription factor targets, the functions of which may be explored in the future.