Empirical prediction of peptide octanol-water partition coefficients

Peptides are of great therapeutic potential as vaccines and drugs. Knowledge of physicochemical descriptors, including the partition coefficient P (commonly expressed in logarithm form: logP), is useful for screening out unsuitable molecules and also for the development of predictive Quantitative Structure-Activity Relationships (QSARs). In this paper we develop a new approach to the prediction of LogP values for peptides based on an empirical relationship between global molecular properties and measured physical properties. Our method was successful in terms of peptide prediction (total r2 = 0.641). The final model consisted of 5 physicochemical descriptors (molecular weight, number of single bonds, 2D-VDW volume, 2D-VSA hydrophobic and 2D-VSA polar). The approach is peptide specific and its predictive accuracy was high. Overall, 67% of the peptides were able to be predicted within +/-0.5 log units from the experimental values. Our method thus represents a novel prediction method with proven predictive ability.

Objective accommodative amplitude and dynamics with the 1CU accommodative intraocular lens

PURPOSE. To compare the objective accommodative amplitude and dynamics of eyes implanted with the one-compartment-unit (1CU; HumanOptics AG, Erlangen, Germany) accommodative intraocular lenses (IOLs) with that measured subjectively. METHODS. Twenty eyes with a 1CU accommodative IOL implanted were refracted and distance and near acuity measured with a logMAR (logarithm of the minimum angle of resolution) chart. The objective accommodative stimulus-response curve for static targets between 0.17 and 4.00 D accommodative demand was measured with the SRW-5000 (Shin-Nippon Commerce Inc., Tokyo, Japan) and PowerRefractor (PlusOptiX, Nürnberg, Germany) autorefractors. Continuous objective recording of dynamic accommodation was measured with the SRW-5000, with the subject viewing a target moving from 0 to 2.50 D at 0.3 Hz through a Badal lens system. Wavefront aberrometry measures (Zywave; Bausch & Lomb, Rochester, NY) were made through undilated pupils. Subjective amplitude of accommodation was measured with the RAF (Royal Air Force accommodation and vergence measurement) rule. RESULTS. Four months after implantation best-corrected acuity was -0.01 ± 0.16 logMAR at distance and 0.60 ± 0.09 logMAR at near. Objectively, the static amplitude of accommodation was 0.72 ± 0.38 D. The average dynamic amplitude of accommodation was 0.71 ± 0.47 D, with a lag behind the target of 0.50 ± 0.48 seconds. Aberrometry showed a decrease in power of the lens-eye combination from the center to the periphery in all subjects (on average, -0.38 ± 0.28 D/mm). Subjective amplitude of accommodation was 2.24 ± 0.42 D. Two years after 1CU implantation, refractive error and distance visual acuity remained relatively stable, but near visual acuity, and the subjective and objective amplitudes of accommodation decreased. CONCLUSIONS. The objective accommodating effects of the 1CU lens appear to be limited, although patients are able to track a moving target. Subjective and objective accommodation was reduced at the 2-year follow-up. The greater subjective amplitude of accommodation is likely to result from the eye's depth of focus of and the aspheric nature of the IOL. Copyright © Association for Research in Vision and Ophthalmology.

Cell exclusion in couette flow:evaluation through flow visualisation and mechanical forces

Cell exclusion is the phenomenon whereby the hematocrit and viscosity of blood decrease in areas of high stress. While this is well known in naturally occurring Poiseuille flow in the human body, it has never previously been shown in Couette flow, which occurs in implantable devices including blood pumps. The high-shear stresses that occur in the gap between the boundaries in Couette flow are known to cause hemolysis in erythrocytes. We propose to mitigate this damage by initiating cell exclusion through the use of a spiral-groove bearing (SGB) that will provide escape routes by which the cells may separate themselves from the plasma and the high stresses in the gap. The force between two bearings (one being the SGB) in Couette flow was measured. Stained erythrocytes, along with silver spheres of similar diameter to erythrocytes, were visualized across a transparent SGB at various gap heights. A reduction in the force across the bearing for human blood, compared with fluids of comparable viscosity, was found. This indicates a reduction in the viscosity of the fluid across the bearing due to a lowered hematocrit because of cell exclusion. The corresponding images clearly show both cells and spheres being excluded from the gap by entering the grooves. This is the first time the phenomenon of cell exclusion has been shown in Couette flow. It not only furthers our understanding of how blood responds to different flows but could also lead to improvements in the future design of medical devices.

Unravelling the theories of pre-eclampsia:Are the protective pathways the new paradigm?

Pre-eclampsia is a vascular disorder of pregnancy where anti-angiogenic factors, systemic inflammation and oxidative stress predominate, but none can claim to cause pre-eclampsia. This review provides an alternative to the 'two-stage model' of pre-eclampsia in which abnormal spiral arteries modification leads to placental hypoxia, oxidative stress and aberrant maternal systemic inflammation. Very high maternal soluble fms-like tyrosine kinase-1 (sFlt-1 also known as sVEGFR) and very low placenta growth factor (PlGF) are unique to pre-eclampsia; however, abnormal spiral arteries and excessive inflammation are also prevalent in other placental disorders. Metaphorically speaking, pregnancy can be viewed as a car with an accelerator and brakes, where inflammation, oxidative stress and an imbalance in the angiogenic milieu act as the 'accelerator'. The 'braking system' includes the protective pathways of haem oxygenase 1 (also referred as Hmox1 or HO-1) and cystathionine-γ-lyase (also known as CSE or Cth), which generate carbon monoxide (CO) and hydrogen sulphide (H2S) respectively. The failure in these pathways (brakes) results in the pregnancy going out of control and the system crashing. Put simply, pre-eclampsia is an accelerator-brake defect disorder. CO and H2S hold great promise because of their unique ability to suppress the anti-angiogenic factors sFlt-1 and soluble endoglin as well as to promote PlGF and endothelial NOS activity. The key to finding a cure lies in the identification of cheap, safe and effective drugs that induce the braking system to keep the pregnancy vehicle on track past the finishing line.

Travelling waves in a complex Ginzburg-Landau equation with time-delay feedback

One of the simplest ways to create nonlinear oscillations is the Hopf bifurcation. The spatiotemporal dynamics observed in an extended medium with diffusion (e.g., a chemical reaction) undergoing this bifurcation is governed by the complex Ginzburg-Landau equation, one of the best-studied generic models for pattern formation, where besides uniform oscillations, spiral waves, coherent structures and turbulence are found. The presence of time delay terms in this equation changes the pattern formation scenario, and different kind of travelling waves have been reported. In particular, we study the complex Ginzburg-Landau equation that contains local and global time-delay feedback terms. We focus our attention on plane wave solutions in this model. The first novel result is the derivation of the plane wave solution in the presence of time-delay feedback with global and local contributions. The second and more important result of this study consists of a linear stability analysis of plane waves in that model. Evaluation of the eigenvalue equation does not show stabilisation of plane waves for the parameters studied. We discuss these results and compare to results of other models.

New negative temperature coefficient thermistor ceramics in Mn-doped CaCu3-xMnxTi4O12 (0≤x≤1) system

New negative temperature coefficient (NTC) ceramics based on CaCu 3-xMnxTi4O12 (0≤x≤1) compositions have been investigated. The grain size of the CaCu 3-xMnxTi4O12 samples decreases at first and then increases with increasing Mn content. The X-ray photoelectron spectroscopy analysis corroborates the presence of Mn3+ and Mn 4+ in Mn-doped samples, which results in a decrease in the activation energy. All the NTC thermistors prepared show a linear relationship between the natural logarithm of the resistivity and the reciprocal temperature, indicative of NTC characteristics. The Mn-doped CaCu3-xMnxTi 4O12 NTC thermistors provide various electrical properties, depending on Mn content. The values of ρ25, B constant and activation energy of the NTC thermistors are in the range of 2.22×106-3.22×108 Ω cm, 5488-8031 K, and 0.473-0.692 eV, respectively. © 2014 Elsevier Ltd and Techna Group S.r.l. All rights reserved.

High performance liquid level monitoring system based on polymer fiber Bragg gratings embedded in silicone rubber diaphragm

Liquid-level sensing technologies have attracted great prominence, because such measurements are essential to industrial applications, such as fuel storage, flood warning and in the biochemical industry. Traditional liquid level sensors are based on electromechanical techniques; however they suffer from intrinsic safety concerns in explosive environments. In recent years, given that optical fiber sensors have lots of well-established advantages such as high accuracy, costeffectiveness, compact size, and ease of multiplexing, several optical fiber liquid level sensors have been investigated which are based on different operating principles such as side-polishing the cladding and a portion of core, using a spiral side-emitting optical fiber or using silica fiber gratings. The present work proposes a novel and highly sensitive liquid level sensor making use of polymer optical fiber Bragg gratings (POFBGs). The key elements of the system are a set of POFBGs embedded in silicone rubber diaphragms. This is a new development building on the idea of determining liquid level by measuring the pressure at the bottom of a liquid container, however it has a number of critical advantages. The system features several FBG-based pressure sensors as described above placed at different depths. Any sensor above the surface of the liquid will read the same ambient pressure. Sensors below the surface of the liquid will read pressures that increase linearly with depth. The position of the liquid surface can therefore be approximately identified as lying between the first sensor to read an above-ambient pressure and the next higher sensor. This level of precision would not in general be sufficient for most liquid level monitoring applications; however a much more precise determination of liquid level can be made by linear regression to the pressure readings from the sub-surface sensors. There are numerous advantages to this multi-sensor approach. First, the use of linear regression using multiple sensors is inherently more accurate than using a single pressure reading to estimate depth. Second, common mode temperature induced wavelength shifts in the individual sensors are automatically compensated. Thirdly, temperature induced changes in the sensor pressure sensitivity are also compensated. Fourthly, the approach provides the possibility to detect and compensate for malfunctioning sensors. Finally, the system is immune to changes in the density of the monitored fluid and even to changes in the effective force of gravity, as might be obtained in an aerospace application. The performance of an individual sensor was characterized and displays a sensitivity (54 pm/cm), enhanced by more than a factor of 2 when compared to a sensor head configuration based on a silica FBG published in the literature, resulting from the much lower elastic modulus of POF. Furthermore, the temperature/humidity behavior and measurement resolution were also studied in detail. The proposed configuration also displays a highly linear response, high resolution and good repeatability. The results suggest the new configuration can be a useful tool in many different applications, such as aircraft fuel monitoring, and biochemical and environmental sensing, where accuracy and stability are fundamental. © (2015) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE). Downloading of the abstract is permitted for personal use only.

Effect of initial retinal thickness on outcome of intravitreal bevacizumab therapy for diabetic macular edema

Purpose: To investigate whether eyes with diabetic macular edema (DME) and central retinal thickness (CRT) >400 μm had better visual and anatomical outcomes compared to eyes with a CRT <400 μm when treated with intravitreal bevacizumab in a real-world setting. Patients and methods: Patients undergoing intravitreal bevacizumab therapy for DME were identified from the departmental database of a tertiary referral unit. Following the initial injection, a retreatment was performed for any persistent macular edema, unless there had been no previous response to repeated doses. Recorded parameters included visual acuity, CRT on optical coherence tomography (spectral domain optical coherence tomography [SD-OCT]), and SD-OCT characteristics. Comparisons were made between data at baseline and 12 months after the first injection, and differences were tested for statistical significance using the Student's t-test. Results: In all, 175 eyes of 142 patients were analyzed. Patients in group 2 (CRT >400 μm) had significantly more injections than group 1 (CRT <400 μm) (4.0 versus 3.3; P=0.003). Both groups had similar numbers of eyes with preexisting epiretinal membrane and/or vitreomacular traction at baseline. The reduction in CRT was significantly greater in group 2 when compared to group 1 (P<0.0001). In terms of visual gain between baseline and month 12, each gained significantly by a mean of 0.12 logarithm of the minimum angle of resolution units (P=0.0001), but there was no difference between groups 1 and 2 (P=0.99). Conclusion: These results do not support a 400 μm baseline CRT cut-off for treating DME with bevacizumab, in contrast to published data on ranibizumab. Our results also indicate that patients with a thicker CRT require more bevacizumab injections, making treatment less cost-effective for these patients. Our results could be used by practitioners to support the use of bevacizumab in DME without applying a CRT cut-off. © 2014 Mushtaq et al.

Quantum dot-based terahertz photoconductive antennas

We present novel Terahertz (THz) emitting optically pumped Quantum Dot (QD) photoconductive (PC) materials and antenna structures on their basis both for pulsed and CW pumping regimes. Full text Quantum dot and microantenna design - Presented here are design considerations for the semiconductor materials in our novel QD-based photoconductive antenna (PCA) structures, metallic microantenna designs, and their implementation as part of a complete THz source or transceiver system. Layers of implanted QDs can be used for the photocarrier lifetime shortening mechanism[1,2]. In our research we use InAs:GaAs QD structures of varying dot layer number and distributed Bragg reflector(DBR)reflectivity range. According to the observed dependence of carrier lifetimes on QD layer periodicity [3], it is reasonable to assume that electron lifetimes can be potentially reduced down to 0.45ps in such structures. Both of these features; long excitation wavelength and short carriers lifetime predict possible feasibility of QD antennas for THz generation and detection. In general, relatively simple antenna configurations were used here, including: coplanar stripline (CPS); Hertzian-type dipoles; bow-ties for broadband and log-spiral(LS)or log-periodic(LP)‘toothed’ geometriesfor a CW operation regime. Experimental results - Several lasers are used for antenna pumping: Ti:Sapphire femtosecond laser, as well as single-[4], double-[5] wavelength, and pulsed [6] QD lasers. For detection of the THz signal different schemes and devices were used, e.g. helium-cooled bolometer, Golay cell and a second PCA for coherent THz detection in a traditional time-domain measurement scheme.Fig.1shows the typical THz output power trend from a 5 um-gap LPQD PCA pumped using a tunable QD LD with optical pump spectrum shown in (b). Summary - QD-based THz systems have been demonstrated as a feasible and highly versatile solution. The implementation of QD LDs as pump sources could be a major step towards ultra-compact, electrically controllable transceiver system that would increase the scope of data analysis due to the high pulse repetition rates of such LDs [3], allowing real-time THz TDS and data acquisition. Future steps in development of such systems now lie in the further investigation of QD-based THz PCA structures and devices, particularly with regards to their compatibilitywith QD LDs as pump sources. [1]E. U. Rafailov et al., “Fast quantum-dot saturable absorber for passive mode-locking of solid-State lasers,”Photon.Tech.Lett., IEEE, vol. 16 pp. 2439-2441(2004) [2]E. Estacio, “Strong enhancement of terahertz emission from GaAs in InAs/GaAs quantum dot structures. Appl.Phys.Lett., vol. 94 pp. 232104 (2009) [3]C. Kadow et al., “Self-assembled ErAs islands in GaAs: Growth and subpicosecond carrier dynamics,” Appl. Phys. Lett., vol. 75 pp. 3548-3550 (1999) [4]T. Kruczek, R. Leyman, D. Carnegie, N. Bazieva, G. Erbert, S. Schulz, C. Reardon, and E. U. Rafailov, “Continuous wave terahertz radiation from an InAs/GaAs quantum-dot photomixer device,” Appl. Phys. Lett., vol. 101(2012) [5]R. Leyman, D. I. Nikitichev, N. Bazieva, and E. U. Rafailov, “Multimodal spectral control of a quantum-dot diode laser for THz difference frequency generation,” Appl. Phys. Lett., vol. 99 (2011) [6]K.G. Wilcox, M. Butkus, I. Farrer, D.A. Ritchie, A. Tropper, E.U. Rafailov, “Subpicosecond quantum dot saturable absorber mode-locked semiconductor disk laser, ” Appl. Phys. Lett. Vol 94, 2511 © 2014 IEEE.

One-year outcome of bevacizumab therapy for chronic macular edema in central and branch retinal vein occlusions in real-world clinical practice in the UK

Background: The purpose of this study was to investigate the 12-month outcome of macular edema secondary to both chronic and new central and branch retinal vein occlusions treated with intravitreal bevacizumab in the real-life clinical setting in the UK. Methods: Retrospective case notes analysis of consecutive patients with retinal vein occlusions treated with bevacizumab in 2010 to 2012. Outcome measures were visual acuity (measured with Snellen, converted into logMAR [logarithm of the minimum angle of resolution] for statistical calculation) and central retinal thickness at baseline, 4 weeks post-loading phase, and at 1 year. Results: There were 56 and 100 patients with central and branch retinal vein occlusions, respectively, of whom 62% had chronic edema and received prior therapies and another 32% required additional laser treatments post-baseline bevacizumab. Baseline median visual acuity was 0.78 (interquartile range [IQR] 0.48–1.22) in the central group and 0.6 (IQR 0.3–0.78) in the branch group. In both groups, visual improvement was statistically significant from baseline compared to post-loading (P,0.001 and P=0.03, respectively), but was not significant by month 12 (P=0.058 and P=0.166, respectively); 30% improved by at least three lines and 44% improved by at least one line by month 12. Baseline median central retinal thickness was 449 μm (IQR 388–553) in the central group and 441 µm (IQR 357–501) in the branch group. However, the mean reduction in thickness was statistically significant at post-loading (P,0.001) and at the 12-month time point (P,0.001) for both groups. The average number of injections in 1 year was 4.2 in the central group and 3.3 in the branch group. Conclusion: Our large real-world cohort results indicate that bevacizumab introduced to patients with either new or chronic edema due to retinal vein occlusion can result in resolution of edema and stabilization of vision in the first year.

Crossover evaluation of silicone hydrogel daily disposable contact lenses

PURPOSE: To assess the surface tear breakup time and clinical performance of three daily disposable silicone hydrogel contact lenses over 16 hours of wear. METHODS: Thirty-nine patients (mean [±SD] age, 22.1 [±3.5] years) bilaterally wore (narafilcon A, filcon II-3, and delefilcon A) contact lenses in a prospective, randomized, masked, 1-week crossover clinical trial. Tear film was assessed by the tear meniscus height (TMH), ocular/contact lens surface temperature dynamics, and lens surface noninvasive breakup time at 8, 12, and 16 hours of wear. Clinical performance and ocular physiology were assessed by subjective questionnaire, by high-/low-contrast logMAR (logarithm of the minimum angle of resolution) acuity, and through bulbar and limbal hyperemia grading. Corneal and conjunctival staining were assessed after lens removal. RESULTS: Delefilcon A demonstrated a longer noninvasive breakup time (13.4 [±4.4] seconds) than filcon II-3 (11.6 [±3.7] seconds; p < 0.001) and narafilcon A (12.3 [±3.7] seconds; p < 0.001). A greater TMH (0.35 [±0.11] mm) was shown by delefilcon A than filcon II-3 (0.32 [±0.10] seconds; p = 0.016). Delefilcon A showed less corneal staining after 16 hours of lens wear (0.7 [±0.6] Efron grade) than filcon II-3 (1.1 [±0.7]; p < 0.001) and narafilcon A (0.9 [±0.7]; p = 0.031). Time was not a significant factor for prelens tear film stability (F = 0.594, p = 0.555) or TMH (F = 0.632, p = 0.534). Lens brand did not affect temperature (F = 1.220, p = 0.308), but it decreased toward the end of the day (F = 19.497, p < 0.001). Comfort, quality of vision, visual acuity and contrast acuity, and limbal grading were similar between the lens brands but decreased with time during the day (p < 0.05). CONCLUSIONS: The tear breakup time over the contact lens surface differed between lens types and may have a role in protecting the ocular surface.