Study of neutral Fe(III) complexes of pyridoxal-N-substituted thiosemicarbazone with desolvation induced spin-state transformation above room temperature

The preparation and characterization of two new neutral ferric complexes with desolvation-induced discontinuous spin-state transformation above room temperature are reported. The compounds, Fe(Hthpy)(thpy).CH3OH.3H2O (1) and Fe(Hmthpy)(mthpy).2H2O (2), are low-spin (LS) at room temperature and below, whereas their nonsolvated forms are high-spin (HS), exhibiting zero-field splitting. In these complexes, Hthpy, Hmthpy, and thpy, mthpy are the deprotonated forms of pyridoxal thiosemicarbazone and pyridoxal methylthiosemicarbazone, respectively; each is an O,N,S-tridentate ligand. The molecular structures have been determined at 100(1) K using single-crystal X-ray diffraction techniques and resulted in a triclinic system (space group P1) and monoclinic unit cell (space group P21/c) for 1 and 2, respectively. Structures were refined to the final error indices, where RF = 0.0560 for 1 and RF = 0.0522 for 2. The chemical inequivalence of the ligands was clearly established, for the "extra" hydrogen atom on the monodeprotonated ligands (Hthpy, Hmthpy) was found to be bound to the nitrogen of the pyridine ring. The ligands are all of the thiol form; the doubly deprotonated chelates (thpy, mthpy) have C-S bond lengths slightly longer than those of the singly deprotonated forms. There is a three-dimensional network of hydrogen bonds in both compounds. The discontinuous spin-state transformation is accompanied with liberation of solvate molecules. This is evidenced also from DSC analysis. Heat capacity data for the LS and HS phases are tabulated at selected temperatures, the values of the enthalpy and entropy changes connected with the change of spin state were reckoned at DeltaH = 12.5 0.3 kJ mol-1 and DeltaS = 33.3 0.8 J mol-1 K-1, respectively, for 1 and DeltaH = 6.5 0.3 kJ mol-1 and DeltaS = 17.6 0.8 J mol-1 K-1, respectively, for 2

Ranibizumab versus Bevacizumab to treat neovascular age-related macular degeneration:one-year findings from the IVAN Randomized Trial

PURPOSE: To compare the efficacy and safety of ranibizumab and bevacizumab intravitreal injections to treat neovascular age-related macular degeneration (nAMD). DESIGN: Multicenter, noninferiority factorial trial with equal allocation to groups. The noninferiority limit was 3.5 letters. This trial is registered (ISRCTN92166560). PARTICIPANTS: People >50 years of age with untreated nAMD in the study eye who read =25 letters on the Early Treatment Diabetic Retinopathy Study chart. METHODS: We randomized participants to 4 groups: ranibizumab or bevacizumab, given either every month (continuous) or as needed (discontinuous), with monthly review. MAIN OUTCOME MEASURES: The primary outcome is at 2 years; this paper reports a prespecified interim analysis at 1 year. The primary efficacy and safety outcome measures are distance visual acuity and arteriothrombotic events or heart failure. Other outcome measures are health-related quality of life, contrast sensitivity, near visual acuity, reading index, lesion morphology, serum vascular endothelial growth factor (VEGF) levels, and costs. RESULTS: Between March 27, 2008 and October 15, 2010, we randomized and treated 610 participants. One year after randomization, the comparison between bevacizumab and ranibizumab was inconclusive (bevacizumab minus ranibizumab -1.99 letters, 95% confidence interval [CI], -4.04 to 0.06). Discontinuous treatment was equivalent to continuous treatment (discontinuous minus continuous -0.35 letters; 95% CI, -2.40 to 1.70). Foveal total thickness did not differ by drug, but was 9% less with continuous treatment (geometric mean ratio [GMR], 0.91; 95% CI, 0.86 to 0.97; P = 0.005). Fewer participants receiving bevacizumab had an arteriothrombotic event or heart failure (odds ratio [OR], 0.23; 95% CI, 0.05 to 1.07; P = 0.03). There was no difference between drugs in the proportion experiencing a serious systemic adverse event (OR, 1.35; 95% CI, 0.80 to 2.27; P = 0.25). Serum VEGF was lower with bevacizumab (GMR, 0.47; 95% CI, 0.41 to 0.54; P

The verbal transformation effect:an exploration of the perceptual organization of speech

Six experiments investigated the influence of several grouping cues within the framework of the Verbal Transformation Effect (VTE, Experiments 1 to 4) and Phonemic Transformation Effect (PTE, Experiments 5 and 6), where listening to a repeated word (VTE) or sequence of vowels (PTE) produces verbal transformations (VTs). In Experiment 1, the influence of F0 frequency and lateralization cues (ITDs) was investigated in terms of the pattern of VTs. As the lateralization difference increased between two repeating sequences, the number of forms was significantly reduced with the fewest forms reported in the dichotic condition. Experiment 2 explored whether or not propensity to report more VTs on high pitch was due to the task demands of monitoring two sequences at once. The number of VTs reported was higher when listeners were asked to attend to one sequence only, suggesting smaller attentional constraints on the task requirements. In Experiment 3, consonant-vowel transitions were edited out from two sets of six stimuli words with ‘strong’ and ‘weak’ formant transitions, respectively. Listeners reported more forms in the spliced-out than in the unedited case for the strong-transition words, but not for those with weak transitions. A similar trend was observed for the F0 contour manipulation used in Experiment 4 where listeners reported more VTs and forms for words following a discontinuous F0 contour. In Experiments 5 and 6, the role of F0 frequency and ITD cues was investigated further using a related phenomenon – the PTE. Although these manipulations had relatively little effect on the number of VTs and forms reported, they did influence the particular forms heard. In summary, the current experiments confirmed that it is possible to successfully investigate auditory grouping cues within the VTE framework and that, in agreement with recent studies, the results can be attributed to the perceptual re-grouping of speech sounds.

Learning in ultrametric committee machines

The problem of learning by examples in ultrametric committee machines (UCMs) is studied within the framework of statistical mechanics. Using the replica formalism we calculate the average generalization error in UCMs with L hidden layers and for a large enough number of units. In most of the regimes studied we find that the generalization error, as a function of the number of examples presented, develops a discontinuous drop at a critical value of the load parameter. We also find that when L>1 a number of teacher networks with the same number of hidden layers and different overlaps induce learning processes with the same critical points.

Racing for radical innovation

How motorsport companies harness network diversity for discontinuous innovation.

Managers' perceptual errors revisited:the role of knowledge calibration

Insights from the stream of research on knowledge calibration, which refers to the correspondence between accuracy and confidence in knowledge, enable a better understanding of consequences of inaccurate perceptions of managers. This paper examines the consequences of inaccurate managerial knowledge through the lens of knowledge calibration. Specifically, the paper examines the antecedent role of miscalibration of knowledge in strategy formation. It is postulated that miscalibrated managers who overestimate external factors and display a high level of confidence in their estimates are likely to enact strategies that are relatively more evolutionary and incremental in nature, whereas miscalibrated managers who overestimate internal factors and display a high level of confidence in their estimates are likely to enact strategies that are relatively more discontinuous and disruptive in nature. Perspectives from social cognitive theory provide support for the underlying processes. The paper, in part, explains the paradox of the prevalence of inaccurate managerial perceptions and efficacious performance. It also advances the literature on strategy formation through the application of the construct of knowledge calibration.

Flow across microvessel walls through the endothelial surface glycocalyx and the interendothelial cleft

A mathematical model is presented for steady fluid flow across microvessel walls through a serial pathway consisting of the endothelial surface glycocalyx and the intercellular cleft between adjacent endothelial cells, with junction strands and their discontinuous gaps. The three-dimensional flow through the pathway from the vessel lumen to the tissue space has been computed numerically based on a Brinkman equation with appropriate values of the Darcy permeability. The predicted values of the hydraulic conductivity Lp, defined as the ratio of the flow rate per unit surface area of the vessel wall to the pressure drop across it, are close to experimental measurements for rat mesentery microvessels. If the values of the Darcy permeability for the surface glycocalyx are determined based on the regular arrangements of fibres with 6nm radius and 8nm spacing proposed recently from the detailed structural measurements, then the present study suggests that the surface glycocalyx could be much less resistant to flow compared to previous estimates by the one-dimensional flow analyses, and the intercellular cleft could be a major determinant of the hydraulic conductivity of the microvessel wall.

Pattern competition in volumetricaly heated fluids

Finite element simulations have been performed along side Galerkin-type calculations that examined the development of volumetrically heated flow patterns in a horizontal layer controlled by the Prandtl number, Pr, and the Grashof number, Gr. The fluid was bounded by an isothermal plane above an adiabatic plane. In the simulations performed here, a number of convective polygonal planforms occurred, as Gr increased above the critical Grashof number, Grc at Pr = 7, while roll structures were observed for Pr < 1 at 2Grc.

A procedure for the reconstruction of a stochastic stationary temperature field

An iterative procedure is proposed for the reconstruction of a temperature field from a linear stationary heat equation with stochastic coefficients, and stochastic Cauchy data given on a part of the boundary of a bounded domain. In each step, a series of mixed well-posed boundary-value problems are solved for the stochastic heat operator and its adjoint. Well-posedness of these problems is shown to hold and convergence in the mean of the procedure is proved. A discretized version of this procedure, based on a Monte Carlo Galerkin finite-element method, suitable for numerical implementation is discussed. It is demonstrated that the solution to the discretized problem converges to the continuous as the mesh size tends to zero.

Effect of cooling rate on intercritically reheated microstructure and toughness in high strength low alloy steel

High strength low alloy steels have been shown to be adversely affected by the existence of regions of poor impact toughness within the heat affected zone (HAZ) produced during multipass welding. One of these regions is the intercritically reheated coarse grained HAZ or intercritical zone. Since this region is generally narrow and discontinuous, of the order of 0.5 mm in width, weld simulators are often employed to produce a larger volume of uniform microstructure suitable for toughness assessment. The steel usedfor this study was a commercial quenched and tempered steel of 450 MN m -2 yield strength. Specimen blanks were subjected to a simulated welding cycle to produce a coarse grained structure of upper bainite during the first thermal cycle, followed by a second thermal cycle where the peak temperature T p2 was controlled. Charpy tests carried out for T p2 values in the range 650-850°C showed low toughness for T p2 values between 760 and 790°C, in the intercritical regime. Microstructural investigation of the development of grain boundary martensite-retained austenite (MA) phase has been coupled with image analysis to measure the volume fraction of MAformed. Most of the MA constituent appears at the prior austenite grain boundaries during intercritical heating, resulting in a 'necklace' appearance. For values of T p2 greater than 790°C the necklace appearance is lost and the second phase areas are observed throughout the structure. Concurrent with this is the development of the fine grained, predominantly ferritic structure that is associated with the improvement in toughness. At this stage the microstructure is transforming from the intercritical regime structure to the supercritically reheated coarse grained HAZ structure. The toughness improvement occurs even though the MA phase is still present, suggesting that the embrittlement is associated with the presence of a connected grain boundary network of the MA phase. The nature of the second phase particles can be controlled by the cooling rate during the second cycle and variesfrom MA phase at high cooling rates to a pearlitic structure at low cooling rates. The lowest toughness of the intercritical zone is observed only when MA phase is present. The reason suggested for this is that only the MA particles debond readily, a number of debonded particles in close proximity providing sufficient stress concentration to initiate local cleavage. © 1993 The Institute of Materials.

The verbal transformation effect and the perceptual organization of speech:influence of formant transitions and F0-contour continuity

This study explored the role of formant transitions and F0-contour continuity in binding together speech sounds into a coherent stream. Listening to a repeating recorded word produces verbal transformations to different forms; stream segregation contributes to this effect and so it can be used to measure changes in perceptual coherence. In experiment 1, monosyllables with strong formant transitions between the initial consonant and following vowel were monotonized; each monosyllable was paired with a weak-transitions counterpart. Further stimuli were derived by replacing the consonant-vowel transitions with samples from adjacent steady portions. Each stimulus was concatenated into a 3-min-long sequence. Listeners only reported more forms in the transitions-removed condition for strong-transitions words, for which formant-frequency discontinuities were substantial. In experiment 2, the F0 contour of all-voiced monosyllables was shaped to follow a rising or falling pattern, spanning one octave. Consecutive tokens either had the same contour, giving an abrupt F0 change between each token, or alternated, giving a continuous contour. Discontinuous sequences caused more transformations and forms, and shorter times to the first transformation. Overall, these findings support the notion that continuity cues provided by formant transitions and the F0 contour play an important role in maintaining the perceptual coherence of speech.

Fractional Derivatives in Spaces of Generalized Functions

MSC 2010: 26A33, 46Fxx, 58C05 Dedicated to 80-th birthday of Prof. Rudolf Gorenflo

On Generalized Models and Singular Products of Distributions in Colombeau Algebra G(R)

MSC 2010: 46F30, 46F10

Low Volatility Options and Numerical Diffusion of Finite Difference Schemes

2000 Mathematics Subject Classification: 65M06, 65M12.

Changes in intraocular pressure in study and fellow eyes in the IVAN trial

PURPOSE: To describe changes in intraocular pressure (IOP) in the 'alternative treatments to Inhibit VEGF in Age-related choroidal Neovascularisation (IVAN)' trial (registered as ISRCTN92166560). DESIGN: Randomised controlled clinical trial with factorial design. PARTICIPANTS: Patients (n=610) with treatment naïve neovascular age-related macular degeneration were enrolled and randomly assigned to receive either ranibizumab or bevacizumab and to two regimens, namely monthly (continuous) or as needed (discontinuous) treatment. METHODS: At monthly visits, IOP was measured preinjection in both eyes, and postinjection in the study eye. OUTCOME MEASURES: The effects of 10 prespecified covariates on preinjection IOP, change in IOP (postinjection minus preinjection) and the difference in preinjection IOP between the two eyes were examined. RESULTS: For every month in trial, there was a statistically significant rise in both the preinjection IOP and the change in IOP postinjection during the time in the trial (estimate 0.02 mm Hg, 95% CI 0.01 to 0.03, p<0.001 and 0.03 mm Hg, 95% CI 0.01 to 0.04, p=0.002, respectively). There was also a small but significant increase during the time in trial in the difference in IOP between the two eyes (estimate 0.01 mm Hg, 95% CI 0.005 to 0.02, p<0.001). There were no differences between bevacizumab and ranibizumab for any of the three outcomes (p=0.93, p=0.22 and p=0.87, respectively). CONCLUSIONS: Anti-vascular endothelial growth factor agents induce increases in IOP of small and uncertain clinical significance.