Probing the mechanism of electron capture and electron transfer dissociation using tags with variable electron affinity

Electron capture dissociation (ECD) and electron transfer dissociation (ETD) of doubly protonated electron affinity (EA)-tuned peptides were studied to further illuminate the mechanism of these processes. The model peptide FQpSEEQQQTEDELQDK, containing a phosphoserine residue, was converted to EA-tuned peptides via β-elimination and Michael addition of various thiol compounds. These include propanyl, benzyl, 4-cyanobenzyl, perfluorobenzyl, 3,5-dicyanobenzyl, 3-nitrobenzyl, and 3,5-dinitrobenzyl structural moieties, having a range of EA from −1.15 to +1.65 eV, excluding the propanyl group. Typical ECD or ETD backbone fragmentations are completely inhibited in peptides with substituent tags having EA over 1.00 eV, which are referred to as electron predators in this work. Nearly identical rates of electron capture by the dications substituted by the benzyl (EA = −1.15 eV) and 3-nitrobenzyl (EA = 1.00 eV) moieties are observed, which indicates the similarity of electron capture cross sections for the two derivatized peptides. This observation leads to the inference that electron capture kinetics are governed by the long-range electron−dication interaction and are not affected by side chain derivatives with positive EA. Once an electron is captured to high-n Rydberg states, however, through-space or through-bond electron transfer to the EA-tuning tags or low-n Rydberg states via potential curve crossing occurs in competition with transfer to the amide π* orbital. The energetics of these processes are evaluated using time-dependent density functional theory with a series of reduced model systems. The intramolecular electron transfer process is modulated by structure-dependent hydrogen bonds and is heavily affected by the presence and type of electron-withdrawing groups in the EA-tuning tag. The anion radicals formed by electron predators have high proton affinities (approximately 1400 kJ/mol for the 3-nitrobenzyl anion radical) in comparison to other basic sites in the model peptide dication, facilitating exothermic proton transfer from one of the two sites of protonation. This interrupts the normal sequence of events in ECD or ETD, leading to backbone fragmentation by forming a stable radical intermediate. The implications which these results have for previously proposed ECD and ETD mechanisms are discussed

SLoMo: automated site localization of modifications from ETD/ECD mass spectra

Recently, software has become available to automate localization of phosphorylation sites from CID data and to assign associated confidence scores. We present an algorithm, SLoMo (Site Localization of Modifications), which extends this capability to ETD/ECD mass spectra. Furthermore, SLoMo caters for both high and low resolution data and allows for site-localization of any UniMod post-translational modification. SLoMo accepts input data from a variety of formats (e.g., Sequest, OMSSA). We validate SLoMo with high and low resolution ETD, ECD, and CID data

Determinants of Successful Implementation of Early Childhood Development Education by County Governments in Kenya; Implementing Partners Perspective

The purpose of this study was to assess the determinants of successful implementation of Early Childhood Development Education (ECDE) by County Governments in Kenya from the implementing partners‟ perspective. This study was guided by the following specific objectives: to determine the influence of the capacities of the County Government staff on the implementation of early childhood development education by County Governments in Kenya, to determine the how management of early childhood development education affects its implementation by County Governments in Kenya, to assess how availability of physical facilities affect the implementation of early childhood development education by County Governments in Kenya and to examine how policies affect the implementation of early childhood development education by County Governments in Kenya. Decentralization theory and organization learning theory were used to explain the relationship between the study variables. Descriptive research design was used in the study. The population for the study was implementing partners working with County Governments in Kenya to support ECDE. Purposive sampling technique was used to select the respondents to participate in the study. A total of 100 respondents were targeted from the 10 organizations studied out of which 70 participated giving a response rate of 70%. Questionnaire was used as instrument for data collection. Both qualitative and quantitative data analysis techniques were used to analyze the data. The study found that the implementation of ECDE by County governments in Kenya was generally successful from the implementing partners‟ perspective and indicated by 56.8%. It is also worth noting that beside the general success, there were myriads of challenges facing the implementation of the program by county governments. Findings from regression analysis showed that the coefficient of determination indicated that 63.5% of the variations on the implementation of ECDE by county governments can be explained by staff capacity, management of ECDE, availability of physical facilities and ECDE policies. The remaining 36.5% can be explained by other variables not included in the study. R square and adjusted R is above average an implication that an above average variation can be explained by the model. The study recommended that county governments should allocate more funds for the renovation and construction of more ECDE centres, allocate adequate funds for the implementation of ECDE and that they should organize consistent in-service training for ECDE teachers and at the same time employ more ECDE staff to cater for the large number of children in ECDE centres.

Influence of metallic artifact filtering on MEG signals for source localization during interictal epileptiform activity

Objective. Medical intractable epilepsy is a common condition that affects 40% of epileptic patients that generally have to undergo resective surgery. Magnetoencephalography (MEG) has been increasingly used to identify the epileptogenic foci through equivalent current dipole (ECD) modeling, one of the most accepted methods to obtain an accurate localization of interictal epileptiform discharges (IEDs). Modeling requires that MEG signals are adequately preprocessed to reduce interferences, a task that has been greatly improved by the use of blind source separation (BSS) methods. MEG recordings are highly sensitive to metallic interferences originated inside the head by implanted intracranial electrodes, dental prosthesis, etc and also coming from external sources such as pacemakers or vagal stimulators. To reduce these artifacts, a BSS-based fully automatic procedure was recently developed and validated, showing an effective reduction of metallic artifacts in simulated and real signals (Migliorelli et al 2015 J. Neural Eng. 12 046001). The main objective of this study was to evaluate its effects in the detection of IEDs and ECD modeling of patients with focal epilepsy and metallic interference. Approach. A comparison between the resulting positions of ECDs was performed: without removing metallic interference; rejecting only channels with large metallic artifacts; and after BSS-based reduction. Measures of dispersion and distance of ECDs were defined to analyze the results. Main results. The relationship between the artifact-to-signal ratio and ECD fitting showed that higher values of metallic interference produced highly scattered dipoles. Results revealed a significant reduction on dispersion using the BSS-based reduction procedure, yielding feasible locations of ECDs in contrast to the other two approaches. Significance. The automatic BSS-based method can be applied to MEG datasets affected by metallic artifacts as a processing step to improve the localization of epileptic foci.Postprint (published version