Quantifying signal changes in nano-wire based biosensors

In this work, we present a computational methodology for predicting the change in signal (conductance sensitivity) of a nano-BioFET sensor (a sensor based on a biomolecule binding another biomolecule attached to a nano-wire field effect transistor) upon binding its target molecule. The methodology is a combination of the screening model of surface charge sensors in liquids developed by Brandbyge and co-workers [Sørensen et al., Appl. Phys. Lett., 2007, 91, 102105], with the PROPKA method for predicting the pH-dependent charge of proteins and protein-ligand complexes, developed by Jensen and co-workers [Li et al., Proteins: Struct., Funct., Bioinf., 2005, 61, 704-721, Bas et al., Proteins: Struct., Funct., Bioinf., 2008, 73, 765-783]. The predicted change in conductance sensitivity based on this methodology is compared to previously published data on nano-BioFET sensors obtained by other groups. In addition, the conductance sensitivity dependence from various parameters is explored for a standard wire, representative of a typical experimental setup. In general, the experimental data can be reproduced with sufficient accuracy to help interpret them. The method has the potential for even more quantitative predictions when key experimental parameters (such as the charge carrier density of the nano-wire or receptor density on the device surface) can be determined (and reported) more accurately. © 2011 The Royal Society of Chemistry

Increased protein aggregation in Zucker Diabetic Fatty rat brain:identification of key mechanistic targets and the therapeutic application of hydrogen sulfide

Background: Diabetes and particularly high blood glucose levels are implicated in neurodegeneration. One of the hallmarks of neurodegeneration is protein aggregation. We investigated the presence of protein aggregation in the frontal brain of Zucker diabetic fatty (ZDF) rats, an animal model for diabetes. Further, the effect of NaHS in suppressing protein aggregation in cultured brain slices from ZDF was assessed. Results: The levels of protein synthesis, protein/gene expression, autophagy and anti-oxidant defense were evaluated in ZDF and control (Lean) brains. Compared to Lean, ZDF brains displayed a significant increase in protein aggregates, p-tau, fibronectin expression and protein glycosylation. Increased phosphorylation of mTOR and S6 ribosomal protein in ZDF indicated higher protein synthesis, while the increase in ubiquitinated proteins and LC3-I in ZDF brains accompanied by lower LC3-II expression and LC3-II/LC3-I levels indicated the blockage of proteolytic pathways. CBS (cystathionine beta synthase) protein and mRNA expression and thiol group levels in ZDF brains were lower compared to Lean. ZDF brains show a higher level of reactive oxygen species. In vitro NaHS treatment normalized proteostasis while counteracting oxidative stress. Conclusion: Our data demonstrate increased protein synthesis and aggregation in the diabetic ZDF rat brain, which was reversible by NaHS treatment. This is the first report on the potential use of NaHS as a novel strategy against protein aggregation in diabetic brain

Interfacial growth of HfOxNy gate dielectrics deposited using [(C2H5)2N]4Hf with O2 and NO

The interfacegrowth by oxygen diffusion has been investigated for 5 nm thick HfOxNy gate-quality dielectric films deposited on Si(100) by low-pressure pulsed metalorganic chemical vapor deposition.Analysis by x-ray photoelectron spectroscopy of the films deposited using the precursor tetrakis (diethylamido) hafnium with O2 showed that the films contained 4 at.\u200a% nitrogen. This increased to 11 at.\u200a% N when NO was used as the oxidant. Significant growth of the interface layer was observed for films exposed to air at ambient temperature and lower rates of growth were observed for vacuum annealedfilms and those with the higher N content. For filmsannealed in O2 at temperatures in the range 600\u2013900\u200a\ub0C, the activation energies of the interfacial growth were 0.36 and 0.25 eV for N concentrations of 11 and 4 at.\u200a%, respectively. The results were interpreted in terms of atomic oxygen formation in the bulk and reaction at the interface. The increase in N incorporation from 4 to 11 at.\u200a% increases the crystallization temperature from between 500 and 600\u200a\ub0C to between 600 and 700\u200a\ub0C.NRC publication: Ye

Ultrathin zirconium silicate films deposited on Si(100) using Zr(Oi-Pr)2(thd)2, Si(Ot-Bu)2(thd)2 and nitric oxide

Ultrathin Zr silicate films were deposited using Zr(Oi\uadPr)2(tetramethylheptanedione,thd)2, Si(Ot\uadBu)2(thd)2 and nitric oxide in a pulse-mode metallorganic chemical-vapor deposition apparatus with a liquid injection source. High resolution transmission electron microscopy, atomic force microscopy, X-ray photoelectron spectroscopy (XPS), and medium energy ion scattering were employed to investigate the structure, surface roughness, chemical state, and composition of the films. The nitric oxide used as oxidizing gas, instead of O2, not only reduced the thickness of the interfacial layer but also removed the carbon contamination effectively from the bulk of the films. The as-deposited Zr silicate films with a Si:Zr ratio of 1.3:1 were amorphous, with an amorphous interfacial layer 0.3-0.6 nm thick. After a spike anneal in oxygen and a 60 s nitrogen anneal at 850\ub0C, these films remained amorphous throughout without phase separation, but the interfacial layer increased in thickness. No evidence of Zr\uadC and Zr\uadSi bonds were found in the films by XPS and carbon concentrations <0.1\u2009atom%, the detection limit, were obtained. The hysteresis, fixed charge density, and leakage current determined from capacitance-voltage analysis improved significantly after postdeposition anneals at 850\ub0C and the films exhibited promising characteristics for deep submicrometer metal-oxide-semiconductor devices.NRC publication: Ye

Crystallographic reconstruction study of the effects of finish rolling temperature on the variant selection during bainite transformation in C-Mn high-strength steels

The effect of finish rolling temperature (FRT) on the austenite- () to-bainite () phase transformation is quantitatively investigated in high-strength C-Mn steels. In particular, the present study aims to clarify the respective contributions of the conditioning during the hot rolling and the variant selection (VS) during the phase transformation to the inherited texture. To this end, an alternative crystallographic reconstruction procedure, which can be directly applied to experimental electron backscatter diffraction (EBSD) mappings, is developed by combining the best features of the existing models: the orientation relationship (OR) refinement, the local pixel-by-pixel analysis and the nuclei identification and spreading strategy. The applicability of this method is demonstrated on both quenching and partitioning (Q&P) and as-quenched lath-martensite steels. The results obtained on the C-Mn steels confirm that the sample finish rolled at the lowest temperature (829{\deg}C) exhibits the sharpest transformation texture. It is shown that this sharp texture is exclusively due to a strong VS from parent brass {110}, S {213} and Goss {110} grains, whereas the VS from the copper {112} grains is insensitive to the FRT. In addition, a statistical VS analysis proves that the habit planes of the selected variants do not systematically correspond to the predicted active slip planes using the Taylor model. In contrast, a correlation between the Bain group to which the selected variants belong and the FRT is clearly revealed, regardless of the parent orientation. These results are discussed in terms of polygranular accommodation mechanisms, especially in view of the observed development in the hot-rolled samples of high-angle grain boundaries with misorientation axes between and

Across‐vendor standardization of semi‐LASER for single‐voxel MRS at 3T

The semi‐adiabatic localization by adiabatic selective refocusing (sLASER) sequence provides single‐shot full intensity signal with clean localization and minimal chemical shift displacement error and was recommended by the international MRS Consensus Group as the preferred localization sequence at high‐ and ultra‐high fields. Across‐vendor standardization of the sLASER sequence at 3 tesla has been challenging due to the B1 requirements of the adiabatic inversion pulses and maximum B1 limitations on some platforms. The aims of this study were to design a short‐echo sLASER sequence that can be executed within a B1 limit of 15 μT by taking advantage of gradient‐modulated RF pulses, to implement it on three major platforms and to evaluate the between‐vendor reproducibility of its perfomance with phantoms and in vivo. In addition, voxel‐based first and second order B0 shimming and voxel‐based B1 adjustments of RF pulses were implemented on all platforms. Amongst the gradient‐modulated pulses considered (GOIA, FOCI and BASSI), GOIA‐WURST was identified as the optimal refocusing pulse that provides good voxel selection within a maximum B1 of 15 μT based on localization efficiency, contamination error and ripple artifacts of the inversion profile. An sLASER sequence (30 ms echo time) that incorporates VAPOR water suppression and 3D outer volume suppression was implemented with identical parameters (RF pulse type and duration, spoiler gradients and inter‐pulse delays) on GE, Philips and Siemens and generated identical spectra on the GE ‘Braino’ phantom between vendors. High‐quality spectra were consistently obtained in multiple regions (cerebellar white matter, hippocampus, pons, posterior cingulate cortex and putamen) in the human brain across vendors (5 subjects scanned per vendor per region; mean signal‐to‐noise ratio [less than] 33; mean water linewidth between 6.5 Hz to 11.4 Hz). The harmonized sLASER protocol is expected to produce high reproducibility of MRS across sites thereby allowing large multi‐site studies with clinical cohorts

Frequency drift in MR spectroscopy at 3T

Purpose: Heating of gradient coils and passive shim components is a common cause of instability in the B-0 field, especially when gradient intensive sequences are used. The aim of the study was to set a benchmark for typical drift encountered during MR spectroscopy (MRS) to assess the need for real-time field-frequency locking on MRI scanners by comparing field drift data from a large number of sites.Method: A standardized protocol was developed for 80 participating sites using 99 3T MR scanners from 3 major vendors. Phantom water signals were acquired before and after an EPI sequence. The protocol consisted of: minimal preparatory imaging; a short pre-fMRI PRESS; a ten-minute fMRI acquisition; and a long post-fMRI PRESS acquisition. Both pre- and post-fMRI PRESS were non-water suppressed. Real-time frequency stabilization/adjustment was switched off when appropriate. Sixty scanners repeated the protocol for a second dataset. In addition, a three-hour post-fMRI MRS acquisition was performed at one site to observe change of gradient temperature and drift rate. Spectral analysis was performed using MATLAB. Frequency drift in pre-fMRI PRESS data were compared with the first 5:20 minutes and the full 30:00 minutes of data after fMRI. Median (interquartile range) drifts were measured and showed in violin plot. Paired t-tests were performed to compare frequency drift pre- and post-fMRI. A simulated in vivo spectrum was generated using FID-A to visualize the effect of the observed frequency drifts. The simulated spectrum was convolved with the frequency trace for the most extreme cases. Impacts of frequency drifts on NAA and GABA were also simulated as a function of linear drift. Data from the repeated protocol were compared with the corresponding first dataset using Pearson's and intraclass correlation coefficients (ICC).Results: Of the data collected from 99 scanners, 4 were excluded due to various reasons. Thus, data from 95 scanners were ultimately analyzed. For the first 5:20 min (64 transients), median (interquartile range) drift was 0.44 (1.29) Hz before fMRI and 0.83 (1.29) Hz after. This increased to 3.15 (4.02) Hz for the full 30 min (360 transients) run. Average drift rates were 0.29 Hz/min before fMRI and 0.43 Hz/min after. Paired t-tests indicated that drift increased after fMRI, as expected (p &lt; 0.05). Simulated spectra convolved with the frequency drift showed that the intensity of the NAA singlet was reduced by up to 26%, 44 % and 18% for GE, Philips and Siemens scanners after fMRI, respectively. ICCs indicated good agreement between datasets acquired on separate days. The single site long acquisition showed drift rate was reduced to 0.03 Hz/min approximately three hours after fMRI.Discussion: This study analyzed frequency drift data from 95 3T MRI scanners. Median levels of drift were relatively low (5-min average under 1 Hz), but the most extreme cases suffered from higher levels of drift. The extent of drift varied across scanners which both linear and nonlinear drifts were observed.</p

Nucleation of ferrite in austenite: The role of crystallography

The nucleation mechanisms during solid-state phase transformations in polycrystalline materials are still not completely understood. The nucleation stage has a strong influence on the overall evolution of phase transformations, which determines the final microstructure and thereby the properties of the material. The understanding of grain nucleation is important for controlling the production process, the design of new steel grades with optimal mechanical properties, and the production of tailor-made steel. The scope of this fundamental research is to study the influence of crystallography on nucleation of the ferrite phase in the austenite phase during the transformation of austenite to ferrite in an iron-chromium-nickel alloy and a cobalt-iron alloy.Materials Science & EngineeringMechanical, Maritime and Materials Engineerin

The Role of Austenite Grain Misorientation on on Ferrite Nucleation in an Fe-Cr-Ni Alloy

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The role of alpha/gamma orientation relationships during ferrite nucleation in an Fe-Cr-Ni alloy

The role of the alpha/gamma orientation relationships during ferrite nucleation is investigated. EBSD measurements were performed on an especially developed high purity ternary iron-based alloy with 20 wt.% Cr and 12 wt.% Ni with both austenite and ferrite present at room temperature to measure the orientation relationship between the austenite and ferrite crystallites. The experimental results are compared to the nucleation models of Clemm and Fisher and Aaronson and co-workers