It is in the best interests of sportsmen and sportswomen to try to avoid muscle stiffness and soreness. Apart from the discomfort experienced, muscle stiffness and soreness can cause unnecessary interruptions to training, may lead to injury and will reduce performance. Changes in muscle tone were quantified in terms of the Resonant Frequency (squared) (RF2) and the Amplitude of Movement (AM) in response to an applied torque. Muscle soreness was measured at twelve sites on the arm. Study One investigated the effects of a single bout of eccentric exercise on muscle stiffness and muscle soreness. RF2 increased and AM decreased following exercise and reached a maximum and minimum, respectively, 24-48 hours post exercise (p < 0.01). Muscle soreness also reached a peak 24-48 hours post-exercise (p < 0.01). Greatest soreness was in the biceps brachii and in the proximal ends of the brachioradialis and the flexor carpi radialis (p < 0.01). Voluntary extension was more painful than voluntary flexion following eccentric exercise. Study Two investigated the effect of performing two subsequent exercise bouts (EX1 and EX2), each separated by six days and an adaptation was observed. Each of the variables measured (RF2, AM, Soreness, Creatine Kinase, Limb Girth) showed a reduced response following EX2 when compared to the results of EX1 (p < 0.01). The resting angle of elbow flexion appeared to decrease following exercise. Study Three investigated the effect of muscle soreness on motor performance. The ability to perform a simple perception test was not affected while suffering from muscle soreness. The eccentric exercise is thought to cause damage to the connective tissue and muscle cell membrane leading to a build-up of fluid around the joint. This increased edema may explain the increase in muscle stiffness observed. Further research is required to determine whether changes in muscle tone are also observed following isometric and concentric exercise.

The preparation and attempted preparation of diaminomethylene-sulphuranes (thiouronium ylides) by various routes is described. The principal route chosen was by proton abstraction from the conjugate acid (thiouronium salt) using a suitable non-hydroxylic base, usually phenyl lithium or triethylamine. In the range of compounds examined where the carbanionic substituents contained electron withdrawing groups such as carbonyl, sulphonyl, nitrile and nitro groups, considerable difficulty was encountered in the preparation of the precursor salts. Of the few salts in this category that were obtainable, only one (disulphonyl substituted) gave rise to a stable ylide. On the other hand, many salts containing the cyclopentadiene ring gave rise to ylides. Some of these, notably the fluorenylides, could be isolated and characterised, while the properties of others could only be observed in solution and they decomposed or rearranged on attempted isolation. A second preparative route was briefly investigated, namely the thermal decomposition of 9-diazofluorene in the presence of arylthioureas, but in several cases this led to unexpected products. Comparative studies of the reactivities of the fluorenylides towards carbonyl compounds and hydrolysis have been made, and some other reactions of these ylides are also described. The 2,3,4-triphenylcyclopentadienylides have been found to undergo novel cyclisation reactions with aldehydes and nitrosobenzene. A product from the former reaction was dehydrogenated to give a stable heterocycle with a 14Π electron periphery. An attempt to prepare a selenium analogue of one of the thiouronium fluorenylides is described. The attempted preparation of guanidinium fluorenylides by various methods is described, principally the 'salt' and 'diazo' methods. The former method was more suitable for alkyl substituted guanidines, whereas the latter method was of benefit with aryl substituents. Proton abstraction from ono of the alkylguanidinium salts gave rise to a product which showed some evidence for ylide character. On the other hand, the aryl substituted products appeared to show no ylide-like properties, A further point of interest arose in the diazo reaction, whore the fluorene nucleus was shown to have substituted on the more sterically hindered position, which was verified later by synthesis.

1. DNA fibre autoradiography has been used to study the replication of chromosomal DNA from chick somatic cells in tissue culture at 37&deg;C, with or without FUdR pre-treatment, and from FUdR-treated chick blastoderm cells. 2. Replication proceeds as first described by Huberman and Riggs (1968). Tandemly arranged units replicate bidirectionally from fork-like growing points, sister strands replicating concurrently. Evidence against the existence of defined termini is presented. 3. The rate of replication in these chicken cells is some 25 to 30mum/hr one-way. The mean interval between adjacent initiation sites for replication is similar in all three cell types but is most accurately determined from FUdR-treated chick somatic cells, being 63 mum. 4. This mean value is either within the range or as much as twice as long as estimates obtained by other authors for various mammals. C-values in the chicken and mammalian species are 1.45 and about 3 pg respectively. Clearly in this comparison the mean initiation interval is not related to C-value. 5. The S-Phase is estimated to be 7.5 hr in chick somatic cells and 5 hr in the blastoderm. The replication pattern is much the same in both and is therefore related to S-phase duration, not cell type. From values of replication rate, mean initiation interval and S-phase, it is clear that only about one-seventh of the DNA is replicated at any one during S in somatic cells. 6. It has been claimed that FUdR does not completely block DNA synthesis, and that it promotes unnatural initiation points from which repair synthesis proceeds. However, FUdR as used in the experiments described in this thesis has neither of these effects. 7. Although initiation intervals and the times of initiations vary, neighbouring intervals tend to be similar in length and neighbouring units tend to initiate together. Clusters of concurrently replicating, neighbouring units are bordered by long stretches of DNA which are replicated at different times. 8. Autoradiographs from unsynchronised somatic cells show "sprays" of closely arranged tandes labelled tracks, in which the track lengths are remarkably uniform. It is suggested that these sprays represent the replication of satellite DNA.

Spectroscopic and photometric observations of six late-type contact and near-contact binaries are presented, and the results of the analyses discussed. Absolute dimensions have been deduced for three systems: YY Ceti. CX Aquarii and RV Corvi. YY Ceti, which has an orbital period of 0.79 days, is found to be composed of a normal main-sequence star of spectral type A8 and an evolved G-type star which completely fills its Roche lobe. We argue that the system will evolve into contact within approximately 10 9 years, either by the nuclear evolution of the primary component, or by the loss of angular momentum via magnetic braking. We also propose that this may represent a route to the A-type contact binaries which does not involve a passage through the W-type phase. The binary CX Aquarii, which has an orbital period of 0.56 days is found to have a similar configuration to YY Ceti, except that its primary component is a main-sequence star of spectral type F5 with an evolved companion of spectral type G9. We argue that the system should achieve contact by loss of angular momentum via magnetic braking within approximately 108 years if the atmosphere of the primary component is convective, or within approximately 5 x 108 years if the primary possesses a radiative atmosphere. RV Corvi is found to consist of an unevolved F2 primary component with a K-type companion which has a much larger radius and luminosity than expected for its mass. The system has an orbital period of 0.75 days. Although the binary may be semi-detached, with the primary component completely filling its Roche lobe, it is most probably in a state of marginal contact. In order to obtain a solution to the photometric data it was necessary to treat the secondary component albedo as a free parameter, yielding a value greater than unity. This result implies that there is an abnormal distribution of luminosity on the surface of the binary, which may be interpreted either as an excess of light on the facing hemisphere of one or both of the components, or as a deficit of light on the averted hemisphere of the secondary. The three remaining binaries, EZ Hydrae, AD Phoenicis and RS Columbae, were all identified as contact systems: EZ Hydrae as a W-type system of orbital period 0.45 days, AD Phoenicis as an A-type system of period 0.38 days, and RS Columbae as an A-type system with a period of 0 .67 days. Although a value for the mass ratio of EZ Hydrae had been obtained from spectroscopic observations, no photometric solution could found because of severe 'disturbances' in its light curve. From our sample of six systems, AD llioenicis and RS Columbae were the only two for which there were no spectroscopic observations. Although photometric solutions were obtained for both systems, these were very insensitive to the value of mass ratio, which tended toward the physically unrealistic value of unity. The results for YY Ceti, CX Aquarii and RV Corvi are combined with the published masses, radii and luminosities of 21 other contact and near-contact binaries. It is shown that the primary components of all contact and near-contact systems are normal main-sequence stars with radii and luminosities appropriate to their masses. The secondary components of the B-type systems and the W-type systems are all overluminous for their masses, due mostly to the radii being increased by a factor of ~1.7. However, these secondary components are segregated on the H-R diagram, where the W-type secondaries appear to the left of the main sequence band due to luminosity transfer from the primary components. The secondary components of the A-type contact systems all have radii and luminosities substantially larger than expected for their masses.

No description available.

No description available.

Lors de certains scénarios accidentels, percement de cuve de réacteur avec entrée d’air, dénoyage de piscinesde manutention, de stockage ou d’entreposage de combustibles usés, ou encore certains accidents de transport,les assemblages combustibles des Réacteurs à Eau Pressurisée (REP), peuvent se retrouver privés de leurrefroidissement et exposés à l’air. Dans ces conditions, la température des assemblages s’élève et les gaines descrayons combustibles, en alliage à base de zirconium, s’oxydent. Par rapport à une oxydation sous vapeur, lavitesse de dégradation des gaines est beaucoup plus élevée, d’une part à cause de l’enthalpie élevée de laréaction zirconium-oxygène, comparée à la réaction zirconium-vapeur d’eau, et d’autre part parce que l’azotecontribue à la dégradation. Des phénomènes d’emballement sont attendus qui peuvent rapidement conduire à laperte de la fonction de confinement assurée par les gaines.L’objectif de cette thèse a été d’affiner la compréhension des mécanismes d’oxydation sous air à hautetempérature des deux alliages de zirconium les plus utilisés dans les REP français, le Zircaloy-4 et le M5®, et depréciser le rôle de l’azote.Des tronçons de gaines vierges de Zircaloy-4 et M5® ont été oxydés dans une thermobalance sous air enconditions isothermes à des températures comprises entre 800°C et 1000°C. Plusieurs techniquesexpérimentales (spectroscopie micro-Raman, EPMA, DRX, microscopies optique et électronique à balayage…)ont été mises en oeuvre pour caractériser les couches d’oxyde. La formation et l’évolution des différentes phasesqui composent ces couches (zircone monoclinique, quadratique et cubique, oxynitrure de zirconium et ZrN) ontainsi pu être mises en évidence et analysées en fonction de l’avancement de l’oxydation. Des mécanismesd’oxydation ont été proposés, et la résistance à l’oxydation plus importante de l’alliage M5® par rapport auZircaloy-4 a été expliquée.Les informations recueillies permettront d’alimenter des modèles visant à prédire le comportement des gaineslors de l’oxydation en situation accidentelle avec entrée d’air (transitoire de température, composition évolutive dela phase gazeuse…). / In nuclear plants, some accidental situations can result in air exposure of Pressurized Water Reactor (PWR) fuelassemblies: air ingress following a breach in the reactor vessel, deflooding during handling, spent fuel storagepool deflooding. Deprived of cooling source, the assemblies temperature raises and the fuel cladding, made out ofzirconium based alloys, oxidize. Compared to a steam oxidation, the degradation kinetic of the cladding is higher,on the one hand because of the high enthalpy of the zirconium-oxygen reaction (compared to zirconium-steamreaction), on the other hand because of the nitrogen contribution to the degradation. Temperature escalation andreaction runaway are expected and can rapidly lead to the loss of integrity of the cladding tubes.The objective of this PhD thesis was to affine the understanding of the high temperature air oxidation mechanismsof the two mostly used zirconium alloys in French PWR, Zircaloy-4 and M5®. Special attention has been paid toclarify the role of nitrogen.As-received Zircaloy-4 and M5® claddings segments have been oxidized in a thermobalance in air in isothermalconditions at temperatures between 800°C and 1000°C. Several characterization techniques (micro-Ramanspectroscopy, EPMA, XRD, optical and scanning electron microcopies...) have been used to analyze the oxidelayers. Identification and evolution of the different phases (monoclinic, tetragonal and cubic zirconia, zirconiumoxynitride and ZrN) has been evidenced and analyzed at several step of the oxidation process. Oxidationmechanisms have been proposed and the better oxidation resistance of the M5® alloy, compared to Zircaloy-4alloy, has been explained.The collected information will allow improvement of modeling aiming to predict the behavior of the claddings invarious accidental situations with air ingress (temperature transients, evolution of the gas phase composition…).

One current approach in the treatment of cancer is the inhibition of cyclin dependent kinase (CDK) enzymes with small molecules. Here the discovery and development of 2-anilino-4-(thiazol-5-yl)pyrimidine CDK inhibitors is described, including details of the design and successful synthesis of novel ring-constrained thiazolylpyrimidines. The structure-activity relationship (SAR) trends exhibited by this constrained thiazolylpyrimidine family of CDK inhibitors are presented and compared with those from an unconstrained series of analogues. One significant finding from this aspect of the project was that ring-constrained thiazolylpyrimidines in general inhibit CDK2-cyclin E with greater potency than the corresponding unconstrained forms. Furthermore, an X-ray crystal structure of 2-methyl-N-[3-nitrophenyl]-4,5-dihydrothiazolo[4,5-h]quinazolin-8-amine, a representative from the constrained thiazolylpyrimidine series, in complex with CDK2-cyclin A is reported; confirming the binding mode within the CDK2 ATP binding pocket. A further assessment of SARs through the synthesis of control compounds and an extended study into the synthesis of N-substituted derivatives is described. The identification of CDK inhibitors that possess a strong selectivity profile across the CDK family is important. For example, the identification of highly CDK4-selective inhibitors should enable researchers to study the biological role of this important enzyme and to enable a block of cell division in the G1 phase. Here synthetic attempts to prepare a potentially CDK4 selective inhibitor compound, namely 5-methyl-N8-[4-(piperazin-1-yl)phenyl]thiazolo[4,5-h]quinazoline-2,8-diamine, are described. This approach was inspired by SAR data published on a structurally related inhibitor, 8-cyclopentyl-5-methyl-2-[4-(piperazin-1-yl)phenylamino]pyrido[2,3-d]pyrimidin-7(8H)-one.

Knockdown of the M5 acetylcholine muscarinic receptor in the ventral tegmental area (VTA) reduces brain-stimulation reward sensitivity in rats. Knockout (KO) of the M5 receptor in mice reduces morphine-induced dopamine efflux, locomotion, conditionedplace- preference, and mating-induced 30-110 kHz ultrasonic vocalizations (USVs). The GFP-labeled M5 receptor gene was transfected using a Herpes simplex virus either into the VTA or 0.2-0.7 mm posterior in the medial tegmentum (MT) of male M5 KO mice. HSV-M5-GFP transfection in VTA fully restored mating-induced USVs and augmented morphine-induced locomotion and stereotypy consistent with activation of DA neurons by M5 receptors. HSV-M5-GFP transfection sites in the MT inhibited USVs and morphine-induced locomotion presumably through inhibition of DA neurons. Putative transfection of M5 in GABA neurons of the rostromedial tegmental nucleus (RMTg) or 5HT neurons of the median raphe (mR) may explain this inhibition. Therefore, HSV-M5- GFP transfection in the VTA enhances DA-mediated behaviours while MT transfections inhibits these behaviours.

Knockdown of the M5 acetylcholine muscarinic receptor in the ventral tegmental area (VTA) reduces brain-stimulation reward sensitivity in rats. Knockout (KO) of the M5 receptor in mice reduces morphine-induced dopamine efflux, locomotion, conditionedplace- preference, and mating-induced 30-110 kHz ultrasonic vocalizations (USVs). The GFP-labeled M5 receptor gene was transfected using a Herpes simplex virus either into the VTA or 0.2-0.7 mm posterior in the medial tegmentum (MT) of male M5 KO mice. HSV-M5-GFP transfection in VTA fully restored mating-induced USVs and augmented morphine-induced locomotion and stereotypy consistent with activation of DA neurons by M5 receptors. HSV-M5-GFP transfection sites in the MT inhibited USVs and morphine-induced locomotion presumably through inhibition of DA neurons. Putative transfection of M5 in GABA neurons of the rostromedial tegmental nucleus (RMTg) or 5HT neurons of the median raphe (mR) may explain this inhibition. Therefore, HSV-M5- GFP transfection in the VTA enhances DA-mediated behaviours while MT transfections inhibits these behaviours.