Water network dynamics at the critical moment of a peptide's ß-turn formation:a molecular dynamics study

All-atom molecular dynamics simulations for a single molecule of Leu-Enkephalin in aqueous solution have been used to study the role of the water network during the formation of ß-turns. We give a detailed account of the intramolecular hydrogen bonding, the water-peptide hydrogen bonding, and the orientation and residence times of water molecules focusing on the short critical periods of transition to the stable ß-turns. These studies suggest that, when intramolecular hydrogen bonding between the first and fourth residue of the ß-turn is not present, the disruption of the water network and the establishment of water bridges constitute decisive factors in the formation and stability of the ß-turn. Finally, we provide possible explanations and mechanisms for the formations of different kinds of ß-turns.

Failure of steel gusset plates

This thesis examines the parameters associated with the failure of triangular steel gusset plates. Eighty two results are presented investigating the position of the applied load, the gusset plate height to length ratio, size, thickness, internal angle and the removal of the inside corner. The thickness of the loaded plate and its influence on the gusset plates failure is also investigated. Twenty two similar gusset plates were tested to investigate the welds connecting the gusset plate to the adjacent loaded and support edges. The experimental results are compared with existing methods, none of which cover all the variables tested. Some methods do not consider buckling and most of those that do are inadequate. Most of the methods do not accurately take account of the load position. An alternative method based on experimental observations is presented for design purposes. The method covers any combination of the variables tested. To test assumptions made in the theoretical work forty seven strut tests took place to investigate buckling characteristics and fifteen special gusset plates were also tested. The gusset plates were found to fail in an elastic-plastic buckling manner. A gusset plate has a specific moment of resistance capacity about it’s inside corner and the ultimate load that can be applied is dependent upon the position of the load relative to the supported edge. There is an optimum height to length ratio for strength and any increase in the internal angle from 90 degrees produces little change in moment capacity. The removal of small portions of the inside corner of a gusset plate has little effect upon its moment capacity. The loaded plate does not provide any significant moment of resistance to the applied load at failure. The main functions of the loaded and supported edge welds is to prevent the gusset plate from slipping from between the plates.

Design of sway frames

The aim of the work presented in this thesis is to produce a direct method to design structures subject to deflection constraints at the working loads. The work carried out can be divided into four main parts. In the first part, a direct design procedure for plane steel frames subjected to sway limitations is proposed. The stiffness equations are modified so that the sway in each storey is equal to some specified values. The modified equations are then solved by iteration to calculate the cross-sectional properties of the columns as well as the other joint displacements. The beam sections are selected initially and then altered in an effort to reduce the total material cost of the frame. A linear extrapolation technique is used to reduce this cost. In this design, stability functions are used so that the effect of axial loads in the members are taken into consideration. The final reduced cost design is checked for strength requirements and the members are altered accordingly. In the second part, the design method is applied to the design of reinforced concrete frames in which the sway in the columns play an active part in the design criteria. The second moment of area of each column is obtained by solving the modified stiffness equations and then used to calculate the mlnlmum column depth required. Again the frame has to be checked for all the ultimate limit state load cases. In the third part, the method is generalised to design pin-jointed space frames for deflection limitatlions. In these the member areas are calculated so that the deflection at a specified joint is equal to its specified value. In the final part, the Lagrange multiplier technique is employed to obtain an optimum design for plane rigidly jointed steel frames. The iteration technique is used here to solve the modified stiffness equations as well as derivative equations obtained in accordance to the requirements of the optimisation method.

OCT retinal thickness ratios and frequency of follow-up in Wet AMD

Poster Introduction: In neovascular age-related macular degeneration (nAMD), optical coherence tomography (OCT) is an important tool to determine when intravitreal injections of ranibizumab should be administered. Current guidelines recommend that patients should be reviewed four weekly and OCT indications for further treatment include subretinal fluid and intraretinal fluid or cysts. Purpose: We have reviewed the OCT scans of subjects who have successfully responded to ranibizumab to look for factors that might predict which patients will not require injection and could have extended appointments. Method: This was a prospective study in which we observed for 6 consecutive months the OCT images of 28 subjects who had received intravitreal ranibizumab for nAMD and were judged to be clinically inactive at recruitment to the study. Ratios between full retinal thickness (FRT = neurosensory retina + outer reflective band) and outer reflective band (ORB) thickness at the fovea were calculated for each subject at the moment of entering the study and at each successive visit for 6 consecutive months. Results: Patients with lower FRT/ORB ratios were found to be less likely to require an additional injection of ranibizumab and no subject with a ratio of 1.75 or less needed further injections. Conclusion: This small pilot study suggests that on macular OCT, the FRT/ORB ratio, and in particular values of 1.75 or less, may prove to be a useful, practical tool when deciding the follow up period for subjects undergoing treatment with intravitreal ranibizumab for nAMD.

Effects of syllable structure in aphasic errors:implications for a new model of speech production

Current models of word production assume that words are stored as linear sequences of phonemes which are structured into syllables only at the moment of production. This is because syllable structure is always recoverable from the sequence of phonemes. In contrast, we present theoretical and empirical evidence that syllable structure is lexically represented. Storing syllable structure would have the advantage of making representations more stable and resistant to damage. On the other hand, re-syllabifications affect only a minimal part of phonological representations and occur only in some languages and depending on speech register. Evidence for these claims comes from analyses of aphasic errors which not only respect phonotactic constraints, but also avoid transformations which move the syllabic structure of the word further away from the original structure, even when equating for segmental complexity. This is true across tasks, types of errors, and, crucially, types of patients. The same syllabic effects are shown by apraxic patients and by phonological patients who have more central difficulties in retrieving phonological representations. If syllable structure was only computed after phoneme retrieval, it would have no way to influence the errors of phonological patients. Our results have implications for psycholinguistic and computational models of language as well as for clinical and educational practices.

Dynamic complexity of chaotic transitions in high-dimensional classical dynamics:Leu-Enkephalin folding

Leu-Enkephalin in explicit water is simulated using classical molecular dynamics. A ß-turn transition is investigated by calculating the topological complexity (in the "computational mechanics" framework [J. P. Crutchfield and K. Young, Phys. Rev. Lett., 63, 105 (1989)]) of the dynamics of both the peptide and the neighbouring water molecules. The complexity of the atomic trajectories of the (relatively short) simulations used in this study reflect the degree of phase space mixing in the system. It is demonstrated that the dynamic complexity of the hydrogen atoms of the peptide and almost all of the hydrogens of the neighbouring waters exhibit a minimum precisely at the moment of the ß-turn transition. This indicates the appearance of simplified periodic patterns in the atomic motion, which could correspond to high-dimensional tori in the phase space. It is hypothesized that this behaviour is the manifestation of the effect described in the approach to molecular transitions by Komatsuzaki and Berry [T. Komatsuzaki and R.S. Berry, Adv. Chem. Phys., 123, 79 (2002)], where a "quasi-regular" dynamics at the transition is suggested. Therefore, for the first time, the less chaotic character of the folding transition in a realistic molecular system is demonstrated. © Springer-Verlag Berlin Heidelberg 2006.

One- and two-step spin-crossover behavior of [Fe(II)(isoxazole)6]2+ and the structure and magnetic properties of triangular [Fe(III)3O(OAc)6(isoxazole)3][ClO4)]

The structure and spin-crossover magnetic behavior of [FeII16][BF4]2 (1 = isoxazole) and [FeII16][ClO4]2 have been studied. [FeII16][BF4]2 undergoes two reversible spin-crossover transitions at 91 and 192 K, and is the first two-step spin transition to undergo a simultaneous crystallographic phase transition, but does not exhibit thermal hysteresis. The single-crystal structure determinations at 260 [space group P3̄, a = 17.4387(4) Å, c = 7.6847(2) Å] and at 130 K [space group P1̄, a = 17.0901(2) Å, b = 16.7481(2) Å, c = 7.5413(1) Å, α = 90.5309(6)°, β = 91.5231(6)°, γ = 117.8195(8)°] reveal two different iron sites, Fe1 and Fe2, in a 1:2 ratio. The room-temperature magnetic moment of 5.0 μB is consistent with high-spin Fe(II). A plateau in μ(T) having a moment of 3.3 μB centered at 130 K suggests a mixed spin system of some high-spin and some low-spin Fe(II) molecules. On the basis of the Fe−N bond distances at the two temperatures, and the molar fraction of high-spin molecules at the transition plateau, Fe1 and Fe2 can be assigned to the 91 and 192 K transitions, respectively. [FeII16][ClO4]2 [space group P3̄, a = 17.5829(3) Å, c = 7.8043(2) Å, β = 109.820 (3)°, T = 295 K] also possesses Fe1:Fe2 in a 1:2 ratio, and magnetic measurements show a single spin transition at 213 K, indicating that both Fe1 and Fe2 undergo a simultaneous spin transition. [FeII16][ClO4]2 slowly decomposes in solutions containing acetic anhydride to form [FeIII3O(OAc)613][ClO4] [space group I2, a = 10.1547(7) Å, b = 16.5497(11) Å, c = 10.3205(9) Å, β = 109.820 (3)°, T = 200 K]. The isosceles Fe3 unit contains two Fe···Fe distances of 3.2844(1) Å and a third Fe···Fe distance of 3.2857(1) Å. The magnetic data can be fit to a trinuclear model with ℋ = −2J(S1·S2 + S2·S3) − 2J13(S1·S3), where J = −27.1 and J13 = −32.5 cm-1.