Neurophysiological evaluation of convergent afferents innervating the human esophagus and area of referred pain on the anterior chest wall

Noxious stimuli in the esophagus cause pain that is referred to the anterior chest wall because of convergence of visceral and somatic afferents within the spinal cord. We sought to characterize the neurophysiological responses of these convergent spinal pain pathways in humans by studying 12 healthy subjects over three visits (V1, V2, and V3). Esophageal pain thresholds (Eso-PT) were assessed by electrical stimulation and anterior chest wall pain thresholds (ACW-PT) by use of a contact heat thermode. Esophageal evoked potentials (EEP) were recorded from the vertex following 200 electrical stimuli, and anterior chest wall evoked potentials (ACWEP) were recorded following 40 heat pulses. The fear of pain questionnaire (FPQ) was administered on V1. Statistical data are shown as point estimates of difference +/- 95% confidence interval. Pain thresholds increased between V1 and V3 [Eso-PT: V1-V3 = -17.9 mA (-27.9, -7.9) P < 0.001; ACW-PT: V1-V3 = -3.38 degrees C (-5.33, -1.42) P = 0.001]. The morphology of cortical responses from both sites was consistent and equivalent [P1, N1, P2, N2 complex, where P1 and P2 are is the first and second positive (downward) components of the CEP waveform, respectively, and N1 and N2 are the first and second negative (upward) components, respectively], indicating activation of similar cortical networks. For EEP, N1 and P2 latencies decreased between V1 and V3 [N1: V1-V3 = 13.7 (1.8, 25.4) P = 0.02; P2: V1-V3 = 32.5 (11.7, 53.2) P = 0.003], whereas amplitudes did not differ. For ACWEP, P2 latency increased between V1 and V3 [-35.9 (-60, -11.8) P = 0.005] and amplitudes decreased [P1-N1: V1-V3 = 5.4 (2.4, 8.4) P = 0.01; P2-N2: 6.8 (3.4, 10.3) P < 0.001]. The mean P1 latency of EEP over three visits was 126.6 ms and that of ACWEP was 101.6 ms, reflecting afferent transmission via Adelta fibers. There was a significant negative correlation between FPQ scores and Eso-PT on V1 (r = -0.57, P = 0.05). These data provide the first neurophysiological evidence of convergent esophageal and somatic pain pathways in humans.

Novel evaluation procedure for internal and extraction efficiency of high-power blue LEDs

Internal quantum efficiency (IQE) of a high-brightness blue LED has been evaluated from the external quantum efficiency measured as a function of current at room temperature. Processing the data with a novel evaluation procedure based on the ABC-model, we have determined separately IQE of the LED structure and light extraction efficiency (LEE) of UX:3 chip. Full text Nowadays, understanding of LED efficiency behavior at high currents is quite critical to find ways for further improve­ment of III-nitride LED performance [1]. External quantum ef­ficiency ηe (EQE) provides integral information on the recom­bination and photon emission processes in LEDs. Meanwhile EQE is the product of IQE ηi and LEE ηext at negligible car­rier leakage from the active region. Separate determination of IQE and LEE would be much more helpful, providing correla­tion between these parameters and specific epi-structure and chip design. In this paper, we extend the approach of [2,3] to the whole range of the current/optical power variation, provid­ing an express tool for separate evaluation of IQE and LEE. We studied an InGaN-based LED fabricated by Osram OS. LED structure grown by MOCVD on sapphire substrate was processed as UX:3 chip and mounted into the Golden Dragon package without molding. EQE was measured with Labsphere CDS-600 spectrometer. Plotting EQE versus output power P and finding the power Pm corresponding to EQE maximum ηm enables comparing the measurements with the analytical rela­tionships ηi = Q/(Q+p1/2+p-1/2) ,p = P/Pm , and Q = B/(AC) 1/2 where A, Band C are recombination constants [4]. As a result, maximum IQE value equal to QI(Q+2) can be found from the ratio ηm/ηe plotted as a function of p1/2 +p1-1/2 (see Fig.la) and then LEE calculated as ηext = ηm (Q+2)/Q . Experimental EQE as a function of normalized optical power p is shown in Fig. 1 b along with the analytical approximation based on the ABC­model. The approximation fits perfectly the measurements in the range of the optical power (or operating current) variation by eight orders of magnitude. In conclusion, new express method for separate evaluation of IQE and LEE of III-nitride LEDs is suggested and applied to characterization of a high-brightness blue LED. With this method, we obtained LEE from the free chip surface to the air as 69.8% and IQE as 85.7% at the maximum and 65.2% at the operation current 350 rnA. [I] G. Verzellesi, D. Saguatti, M. Meneghini, F. Bertazzi, M. Goano, G. Meneghesso, and E. Zanoni, "Efficiency droop in InGaN/GaN blue light-emitting diodes: Physical mechanisms and remedies," 1. AppL Phys., vol. 114, no. 7, pp. 071101, Aug., 2013. [2] C. van Opdorp and G. W. 't Hooft, "Method for determining effective non radiative lifetime and leakage losses in double-heterostructure las­ers," 1. AppL Phys., vol. 52, no. 6, pp. 3827-3839, Feb., 1981. [3] M. Meneghini, N. Trivellin, G. Meneghesso, E. Zanoni, U. Zehnder, and B. Hahn, "A combined electro-optical method for the determination of the recombination parameters in InGaN-based light-emitting diodes," 1. AppL Phys., vol. 106, no. II, pp. 114508, Dec., 2009. [4] Qi Dai, Qifeng Shan, ling Wang, S. Chhajed, laehee Cho, E. F. Schubert, M. H. Crawford, D. D. Koleske, Min-Ho Kim, and Yongjo Park, "Carrier recombination mechanisms and efficiency droop in GalnN/GaN light-emitting diodes," App/. Phys. Leu., vol. 97, no. 13, pp. 133507, Sept., 2010. © 2014 IEEE.

Peptide binding to HLA-DP proteins at pH 5.0 and pH 7.0:a quantitative molecular docking study

Background: HLA-DPs are class II MHC proteins mediating immune responses to many diseases. Peptides bind MHC class II proteins in the acidic environment within endosomes. Acidic pH markedly elevates association rate constants but dissociation rates are almost unchanged in the pH range 5.0 - 7.0. This pH-driven effect can be explained by the protonation/deprotonation states of Histidine, whose imidazole has a pKa of 6.0. At pH 5.0, imidazole ring is protonated, making Histidine positively charged and very hydrophilic, while at pH 7.0 imidazole is unprotonated, making Histidine less hydrophilic. We develop here a method to predict peptide binding to the four most frequent HLA-DP proteins: DP1, DP41, DP42 and DP5, using a molecular docking protocol. Dockings to virtual combinatorial peptide libraries were performed at pH 5.0 and pH 7.0. Results: The X-ray structure of the peptide - HLA-DP2 protein complex was used as a starting template to model by homology the structure of the four DP proteins. The resulting models were used to produce virtual combinatorial peptide libraries constructed using the single amino acid substitution (SAAS) principle. Peptides were docked into the DP binding site using AutoDock at pH 5.0 and pH 7.0. The resulting scores were normalized and used to generate Docking Score-based Quantitative Matrices (DS-QMs). The predictive ability of these QMs was tested using an external test set of 484 known DP binders. They were also compared to existing servers for DP binding prediction. The models derived at pH 5.0 predict better than those derived at pH 7.0 and showed significantly improved predictions for three of the four DP proteins, when compared to the existing servers. They are able to recognize 50% of the known binders in the top 5% of predicted peptides. Conclusions: The higher predictive ability of DS-QMs derived at pH 5.0 may be rationalised by the additional hydrogen bond formed between the backbone carbonyl oxygen belonging to the peptide position before p1 (p-1) and the protonated ε-nitrogen of His 79β. Additionally, protonated His residues are well accepted at most of the peptide binding core positions which is in a good agreement with the overall negatively charged peptide binding site of most MHC proteins. © 2012 Patronov et al.; licensee BioMed Central Ltd.

The effect of nutritional supplementation on the multifocal electroretinogram in healthy eyes

BACKGROUND: Previous studies have demonstrated an increase in macular pigment optical density (MPOD) with lutein (L)-based supplementation in healthy eyes. However, not all studies have assessed whether this increase in MPOD is associated with changes to other measures of retinal function such as the multifocal ERG (mfERG). Some studies also fail to report dietary levels of L and zeaxanthin (Z). Because of the associations between increased levels of L and Z, and reduced risk of AMD, this study was designed to assess the effects of L-based supplementation on mfERG amplitudes and latencies in healthy eyes. METHODS: Multifocal ERG amplitudes, visual acuity, contrast sensitivity, MPOD and dietary levels of L and Z were assessed in this longitudinal, randomized clinical trial. Fifty-two healthy eyes from 52 participants were randomly allocated to receive a L-based supplement (treated group), or no supplement (non-treated group). RESULTS: There were 25 subjects aged 18-77 (mean age ± SD; 48 ± 17) in the treated group and 27 subjects aged 21-69 (mean age ± SD; 43 ± 16) in the non-treated group. All participants attended for three visits: visit one at baseline, visit two at 20 weeks and visit three at 40 weeks. A statistically significant increase in MPOD (F = 17.0, p ≤ 0.001) and shortening of mfERG ring 2 P1 latency (F = 3.69, p = 0.04) was seen in the treated group. CONCLUSIONS: Although the results were not clinically significant, the reported trend for improvement in MPOD and mfERG outcomes warrants further investigation.

Engaging future engineers:pedagogy, policy & practice

Despite being frequently misrepresented as outdated or old fashioned (IMechE, 2009, p1), engineering is increasingly called upon to deal with some of societies biggest challenges including those associated with climate, infrastructure and security. In order to meet such challenges there needs to be a supply of engineering talent able to turn its collective mind to what is required. Yet at a time when demands for engineers able to provide innovative solutions to contemporary problems is possibly at its highest, the profession is plagued by shortages and an inability to attract young people (DIUS, 2008; RAE 2008; NSF, 2009). Although the current situation appears critical, potential future shortages of engineers means that unless action is taken urgently, matters will get worse during the next 20 to 30 years. For higher education, the challenge is how to change young peoples perceptions of engineering in such a manner that it is seen as a worthwhile and rewarding career. This paper considers this challenge, looking in detail at why young people fail to view engineering positively. A theoretical framework outlining the various real-life barriers and drivers is proposed. A critical analysis of current policy and practice suggests that in order to promote engineering as a profession that young people want to enter, both pedagogic and policy grounded solutions need to be found. By bringing together pedagogy and policy within an engineering framework the paper adds to current debates in engineering education whilst providing a distinctive look at what seems to be a recurring problem. © 2009 Authors.