Cortical potential imaging using L-curve and GCV method to choose the regularisation parameter

Background

The electroencephalography (EEG) is an attractive and a simple technique to measure the brain activity. It is attractive due its excellent temporal resolution and simple due to its non-invasiveness and sensor design. However, the spatial resolution of EEG is reduced due to the low conducting skull. In this paper, we compute the potential distribution over the closed surface covering the brain (cortex) from the EEG scalp potential. We compare two methods – L-curve and generalised cross validation (GCV) used to obtain the regularisation parameter and also investigate the feasibility in applying such techniques to N170 component of the visually evoked potential (VEP) data.

Methods

Using the image data set of the visible human man (VHM), a finite difference method (FDM) model of the head was constructed. The EEG dataset (256-channel) used was the N170 component of the VEP. A forward transfer matrix relating the cortical potential to the scalp potential was obtained. Using Tikhonov regularisation, the potential distribution over the cortex was obtained.

Results

The cortical potential distribution for three subjects was solved using both L-curve and GCV method. A total of 18 cortical potential distributions were obtained (3 subjects with three stimuli each – fearful face, neutral face, control objects).

Conclusions

The GCV method is a more robust method compared to L-curve to find the optimal regularisation parameter. Cortical potential imaging is a reliable method to obtain the potential distribution over cortex for VEP data.

     

Proving of a Mathematical Model of Cell Calculation Based on Apparent Diffusion Coefficient

OBJECTIVES: Recently, Atuegwu et al. proposed a mathematical model based on ADC_mean and ADC_min to calculation of cellularity. Our purpose was to compare the calculated cellularity according to the formula with the estimated cell count by histopathology in different tumors. METHODS: For this study, we re-analyzed our previous data regarding associations between ADC parameters and histopathological findings. Overall, 134 patients with different tumors were acquired for the analysis. For all tumors, the number of tumor cells was calculated according to Atuegwu et al. 2013. We performed a correlation analysis between the calculated and estimated cellularity. Thereby, Pearson's correlation coefficient was used and P < .05 was taken to indicate statistical significance in all instances. RESULTS: The estimated and calculated cellularity correlated well together in HNSCC (r = 0.701, P = .016) and lymphomas (r = 0.661, P = .001), and moderately in rectal cancer (r = 0.510, P = .036). There were no statistically significant correlations between the estimated and calculated cellularity in uterine cervical cancer, meningiomas, and in thyroid cancer. CONCLUSION: The proposed formula for cellularity calculation does not apply for all tumors. It may be used for HNSCC, cerebral lymphomas and rectal cancer, but not for uterine cervical cancer, meningioma, and thyroid cancer. Furthermore, its usefulness should be proved for other tumors.     

Microsatellite loci variation and investigation of gene flow between two karyoforms of <Emphasis Type="Italic">Cricetulus barabensis</Emphasis> sensu lato (Rodentia,Cricetidae)

We examine the diversity of six microsatellite loci and partial RAG1 exon of “barabensis” and “pseudogriseus” karyoforms in Cricetulus barabensis sensu lato species complex. A total of 435 specimens from 68 localities ranging from Altai to the Far East are investigated. The results of the population structure analysis (factor analysis and NJ tree based on Nei genetic distances) support subdivision into two well-differentiated clusters corresponding to the two karyoforms. These karyoforms are also well differentiated by the level of microsatellite variability. In several “barabensis” specimens, we found microsatellite alleles that are common in “pseudogriseus” populations but are otherwise absent in “barabensis.” Most of these specimens originate from a single population in one of the zones of potential contact between karyoforms, Kharkhorin in Central Mongolia. These molecular results are consistent with previously published karyological data in suggesting that rare hybridization events between the two chromosomal races occur in nature.     

New Infestin-4 Mutants with Increased Selectivity against Factor XIIa

Factor XIIa (fXIIa) is a serine protease that triggers the coagulation contact pathway and plays a role in thrombosis. Because it interferes with coagulation testing, the need to inhibit fXIIa exists in many cases. Infestin-4 (Inf4) is a Kazal-type inhibitor of fXIIa. Its specificity for fXIIa can be enhanced by point mutations in the protease-binding loop. We attempted to adapt Inf4 for the selective repression of the contact pathway under various in vitro conditions, e.g., during blood collection and in ‘global’ assays of tissue factor (TF)-dependent coagulation. First, we designed a set of new Inf4 mutants that, in contrast to wt-Inf4, had stabilized canonical conformations during molecular dynamics simulation. Off-target activities against factor Xa (fXa), plasmin, and other coagulation proteases were either reduced or eliminated in these recombinant mutants, as demonstrated by chromogenic assays. Interactions with fXIIa and fXa were also analyzed using protein-protein docking. Next, Mutant B, one of the most potent mutants (its K _i for fXIIa is 0.7 nM) was tested in plasma. At concentrations 5–20 μM, this mutant delayed the contact-activated generation of thrombin, as well as clotting in thromboelastography and thrombodynamics assays. In these assays, Mutant B did not affect coagulation initiated by TF, thus demonstrating sufficient selectivity and its potential practical significance as a reagent for coagulation diagnostics.     

Nonglutamate pore residues in ion selection and conduction in voltage-gated Ca(2+) channels

High-affinity, intrapore binding of Ca(2+) over competing ions is the essential feature in the ion selectivity mechanism of voltage-gated Ca(2+) channels. At the same time, several million Ca(2+) ions can travel each second through the pore of a single open Ca(2+) channel. How such high Ca(2+) flux is achieved in the face of tight Ca(2+) binding is a current area of inquiry, particularly from a structural point of view. The ion selectivity locus comprises four glutamate residues within the channel's pore. These glutamates make unequal contributions to Ca(2+) binding, underscoring a role for neighboring residues in pore function. By comparing two Ca(2+) channels (the L-type alpha(1C), and the non-L-type alpha(1A)) that differ in their pore properties but only differ at a single amino acid position near the selectivity locus, we have identified the amino-terminal neighbor of the glutamate residue in motif III as a determinant of pore function. This position is more important in the function of alpha(1C) channels than in alpha(1A) channels. For a systematic series of mutations at this pore position in alpha(1C), both unitary Ba(2+) conductance and Cd(2+) block of Ba(2+) current varied with residue volume. Pore mutations designed to make alpha(1C) more like alpha(1A) and vice versa revealed that relative selectivity for Ba(2+) over K(+) depended almost solely on pore sequence and not channel type. Analysis of thermodynamic mutant cycles indicates that the motif III neighbor normally interacts in a cooperative fashion with the locus, molding the functional behavior of the pore.     

Myositis in Lewis rats induced by the superantigen Staphylococcal enterotoxin A

Molecular Biology Reports - The aetiology of inflammatory myopathies is not clearly known. A predominance of activated Cd8+ T lymphocytes in inflammatory infiltrates has already been detected....     

Karyotype reorganisation in the subtilis group of birch mice (Rodentia, Dipodidae, Sicista): unexpected taxonomic diversity within a limited distribution

Conventional cytogenetic studies of Sicista subtilis and S. severtzovi (Dipodidae, Sicistinae), both attributable to the subtilis group of birch mice, revealed extensive karyotype diversity with 2n = 16-26 and NFa values of 26-46 indicating the overwhelming non-Robertsonian nature of chromosomal reorganization in these species. The numerical and structural chromosome variability was principally found in specimens located within a confined region of the East European (Russian) Plain. The approximately 135,000-km(2) area occurs in the vicinity of the Don River bend between 49°13'N/43°46'E and 51°32'N/36°16'E. The detection of cytotypes sharing similar 2n and NF values, but having morphologically distinct chromosomes, suggests that these may result from polymorphisms present both within recognized species and in cryptic taxa not hitherto described. We conducted a comprehensive, comparative chromosome banding analysis of 52 birch mice (21 localities) referable to the subtilis group and report the presence of 5 distinct karyotypes, each characterized by a combination of stable, variable, and partly overlapping 2n/NFa values. These karyotypes differed from each other by 10-29 structural chromosomal rearrangements (18.1 ± 6.3) that comprised Rb fusions/fissions (42.2%), pericentric inversions (31.1%), and tandem translocations (22.2%). The composition, and the high numbers of these chromosomal changes, is likely to provide an effective means of post-mating isolation, suggesting that taxonomic diversity within the subtilis group is larger than currently accepted. Additionally, we report the frequent fixation of tandem translocations in sample populations, one of which was found in a polymorphic state representing, as far as we are aware, the first case of an in statu nascendi tandem fusion in wild populations. Moreover, our data revealed that bi-armed chromosomes were involved in fusions detected in some of the subtilis taxa. In each instance, however, fusions were preceded by pericentric inversions that transform one or both bi-armed chromosomes into acrocentrics resulting in either centromere-telomere or Robertsonian translocations. Finally, a phylogenetic scenario inferred from a cladistic analysis of the chromosomal data suggests that the extensive karyotypic diversification within the subtilis group in the south-east region of the Russian Plain most likely results from fragmentation of a continuously distributed, ancestral population. It is thought that this occurred at the last glacial maximum (18,000-14,000 years B.P.), and that the process of isolation has been exacerbated by increasing human activity in the region in modern times.