Toward the prediction of class I and II mouse major histocompatibility complex-peptide-binding affinity:in silico bioinformatic step-by-step guide using quantitative structure-activity relationships

Quantitative structure-activity relationship (QSAR) analysis is a cornerstone of modern informatics. Predictive computational models of peptide-major histocompatibility complex (MHC)-binding affinity based on QSAR technology have now become important components of modern computational immunovaccinology. Historically, such approaches have been built around semiqualitative, classification methods, but these are now giving way to quantitative regression methods. We review three methods--a 2D-QSAR additive-partial least squares (PLS) and a 3D-QSAR comparative molecular similarity index analysis (CoMSIA) method--which can identify the sequence dependence of peptide-binding specificity for various class I MHC alleles from the reported binding affinities (IC50) of peptide sets. The third method is an iterative self-consistent (ISC) PLS-based additive method, which is a recently developed extension to the additive method for the affinity prediction of class II peptides. The QSAR methods presented here have established themselves as immunoinformatic techniques complementary to existing methodology, useful in the quantitative prediction of binding affinity: current methods for the in silico identification of T-cell epitopes (which form the basis of many vaccines, diagnostics, and reagents) rely on the accurate computational prediction of peptide-MHC affinity. We have reviewed various human and mouse class I and class II allele models. Studied alleles comprise HLA-A*0101, HLA-A*0201, HLA-A*0202, HLA-A*0203, HLA-A*0206, HLA-A*0301, HLA-A*1101, HLA-A*3101, HLA-A*6801, HLA-A*6802, HLA-B*3501, H2-K(k), H2-K(b), H2-D(b) HLA-DRB1*0101, HLA-DRB1*0401, HLA-DRB1*0701, I-A(b), I-A(d), I-A(k), I-A(S), I-E(d), and I-E(k). In this chapter we show a step-by-step guide into predicting the reliability and the resulting models to represent an advance on existing methods. The peptides used in this study are available from the AntiJen database (http://www.jenner.ac.uk/AntiJen). The PLS method is available commercially in the SYBYL molecular modeling software package. The resulting models, which can be used for accurate T-cell epitope prediction, will be made are freely available online at the URL http://www.jenner.ac.uk/MHCPred.

Hybrid tilted fiber grating based refractive index and liquid level sensing system

We report a refractive index (RI) and liquid level sensing system based on a hybrid grating structure comprising of a 45° and an 81° tilted fiber gratings (TFGs) that have been inscribed into a single mode fiber in series. In this structure, the 45°-TFG is used as a polarizer to filter out the transverse electric (TE) component and enable the 81°-TFG operating at single polarization for RI and level sensing. The experiment results show a lower temperature cross-sensitivity, only about 7.33 pm/°C, and a higher RI sensitivity, being around 180 nm/RIU at RI=1.345 and 926 nm/RIU at RI=1.412 region, which are significantly improved in comparison with long period fiber gratings. The hybrid grating structure has also been applied as a liquid level sensor, showing 3.06 dB/mm linear peak ratio sensitivity.

Optical sensor based on hybrid LPG/FBG in D-fiber for simultaneous refractive index and temperature measurement

A dual-parameter optical sensor has been realized by UV-writing a long-period and a Bragg grating structure in D-fiber. The hybrid configuration permits the detection of the temperature from the latter and measuring the external refractive index from the former responses, respectively. The employment of the D-fiber allows as effective modification and enhancement of the device sensitivity by cladding etching. The grating sensor has been used to measure the concentrations of aqueous sugar solutions, demonstrating the potential capability to detect concentration changes as small as 0.01%.

Low thermal sensitivity grating devices based on ex-45° tilting structure capable of forward-propagating cladding modes coupling

The authors describe a detailed investigation on tilted fiber Bragg grating (TFBG) structures with tilted angles exceeding 45°. In contrast to the backward mode coupling mechanism of Bragg gratings with normal and small tilting structures, the ex-45° TFBGs facilitate the light coupling to the forward-propagating cladding modes. The authors have also theoretically and experimentally examined the mode coupling transition of TFBGs with small, medium, and large tilt angles. In particular, experiments are conducted to investigate the spectra and far-field distribution, as well as temperature, strain, and refractive-index sensitivities of ex-45° devices. It has been revealed that these ex-45° gratings exhibit ultralow thermal sensitivity. As in-fiber devices, they may be superior to conventional Bragg and long-period gratings when the low thermal cross sensitivity is required. © 2006 IEEE.

Refractive index sensor based on a pair of hybrid 45° and 81° tilted fiber gratings

A hybrid structure comprising of a 45° and an 81° TFG based RI sensor has been demonstrated. The experiment results show a higher RI sensitivity, being around 180nm/RIU at RI=1.345 and 926nm/RIU at RI=1.412 region. © 2014 OSA.

Refractive index and temperature sensitivity characteristics of a micro-slot fiber Bragg grating

Fabrication and characterization of a UVinscribed fiber Bragg grating (FBG) with a micro-slot liquid core is presented. Femtosecond (fs) laser patterning/chemical etching technique was employed to engrave a micro-slot with dimensions of 5.74 μm(h) × 125 μm(w) × 1388.72 μm(l) across the whole grating. The device has been evaluated for refractive index (RI) and temperature sensitivities and exhibited distinctive thermal response and RI sensitivity beyond the detection limit of reported fiber gratings. This structure has not just been RI sensitive, but also maintained the robustness comparing with the bare core FBGs and long-period gratings with the partial cladding etched off. © 2012 Optical Society of America.

Differences between younger and older adults in the structure of suicidal intent and its correlates

OBJECTIVE: To analyze differences in the variables associated with severity of suicidal intent and in the main factors associated with intent when comparing younger and older adults. DESIGN: Observational, descriptive cross-sectional study. SETTING: Four general hospitals in Madrid, Spain. PARTICIPANTS: Eight hundred seventy suicide attempts by 793 subjects split into two groups: 18-54 year olds and subjects older than 55 years. MEASUREMENTS: The authors tested the factorial latent structure of suicidal intent through multigroup confirmatory factor analysis for categorical outcomes and performed statistical tests of invariance across age groups using the DIFFTEST procedure. Then, they tested a multiple indicators-multiple causes (MIMIC) model including different covariates regressed on the latent factor "intent" and performed two separate MIMIC models for younger and older adults to test for differential patterns. RESULTS: Older adults had higher suicidal intent than younger adults (z = 2.63, p = 0.009). The final model for the whole sample showed a relationship of intent with previous attempts, support, mood disorder, personality disorder, substance-related disorder, and schizophrenia and other psychotic disorders. The model showed an adequate fit (chi²[12] = 22.23, p = 0.035; comparative fit index = 0.986; Tucker-Lewis index = 0.980; root mean square error of approximation = 0.031; weighted root mean square residual = 0.727). All covariates had significant weights in the younger group, but in the older group, only previous attempts and mood disorders were significantly related to intent severity. CONCLUSIONS: The pattern of variables associated with suicidal intent varies with age. Recognition, and treatment of geriatric depression may be the most effective measure to prevent suicidal behavior in older adults.

High-sensitivity refractive index sensor based on large-angle tilted fiber grating with carbon nanotube deposition

This paper presents a highly sensitive ambient refractive index (RI) sensor based on 81° tilted fiber grating (81°-TFG) structure UV-inscribed in standard telecom fiber (62.5μm cladding radius) with carbon nanotube (CNT) overlay deposition. The sensing mechanism is based on the ability of CNT to induce change in transmitted optical power and the high sensitivity of 81°-TFG to ambient refractive index. The thin CNT film with high refractive index enhances the cladding modes of the TFG, resulting in the significant interaction between the propagating light and the surrounding medium. Consequently, the surrounding RI change will induce not only the resonant wavelength shift but also the power intensity change of the attenuation band in the transmission spectrum. Result shows that the change in transmitted optical power produces a corresponding linear reduction in intensity with increment in RI values. The sample shows high sensitivities of ∼207.38nm/RIU, ∼241.79nm/RIU at RI range 1.344-1.374 and ∼113.09nm/RIU, ∼144.40nm/RIU at RI range 1.374-1.392 (for X-pol and Y-pol respectively). It also shows power intensity sensitivity of ∼ 65.728dBm/RIU and ∼ 45.898 (for X-pol and Y-pol respectively). The low thermal sensitivity property of the 81°-TFG offers reduction in thermal cross-sensitivity and enhances specificity of the sensor.