Use of inert gas jets to measure the forces required for mechanical gene transfection

Background

Abnormal blood glucose (BG) concentrations have been associated with increased morbidity and mortality in both critically ill adults and infants. Furthermore, hypoglycaemia and glycaemic variability have both been independently linked to mortality in these patients. Continuous Glucose Monitoring (CGM) devices have the potential to improve detection and diagnosis of these glycaemic abnormalities. However, sensor noise is a trade-off of the high measurement rate and must be managed effectively if CGMs are going to be used to monitor, diagnose and potentially help treat glycaemic abnormalities.

Aim

To develop a tool that will aid clinicians in identifying unusual CGM behaviour and highlight CGM data that potentially need to be interpreted with care.

Methods

CGM data and BG measurements from 50 infants at risk of hypoglycaemia were used. Unusual CGM measurements were classified using a stochastic model based on the kernel density method and historical CGM measurements from the cohort. CGM traces were colour coded with very unusual measurements coloured red, highlighting areas to be interpreted with care. A 5-fold validation of the model was Monte Carlo simulated 25 times to ensure an adequate model fit.

Results

The stochastic model was generated using ~67,000 CGM measurements, spread across the glycaemic range ~2-10?mmol/L. A 5-fold validation showed a good model fit: the model 80% confidence interval (CI) captured 83% of clinical CGM data, the model 90% CI captured 91% of clinical CGM data, and the model 99% CI captured 99% of clinical CGM data. Three patient examples show the stochastic classification method in use with 1) A stable, low variability patient which shows no unusual CGM measurements, 2) A patient with a very sudden, short hypoglycaemic event (classified as unusual), and, 3) A patient with very high, potentially un-physiological, glycaemic variability after day 3 of monitoring (classified as very unusual).

Conclusions

This study has produced a stochastic model and classification method capable of highlighting unusual CGM behaviour. This method has the potential to classify important glycaemic events (e.g. hypoglycaemia) as true clinical events or sensor noise, and to help identify possible sensor degradation. Colour coded CGM traces convey the information quickly and efficiently, while remaining computationally light enough to be used retrospectively or in real-time.     

Flora Europaea Notulae Systematicae ad Floram Europaeam spectantes No. 20 Corrigenda et Addenda

Following the publication of the last of the series of Flora Europaea Notulae, No. 20 in the Botanical Journal of the Linnean Society , 76: 297–384 (1978), a number of additions or alterations have been drawn to our attention. These are published in continuation.     

Asymmetry of the amplitude-temporal properties of visually-guided saccades in monkeys depending on the complexity of the spatial scheme of the visual stimulation

The properties of visually-guided saccades were studied in three monkeys (Macaca rhesus). Traditional single-step GAP-OVERLAP temporal paradigms were used. Target stimuli were presented in accordance with two spatial stimulation schemes: (i) along the horizontal meridian (one-dimensional scheme) and (ii) within rectangle part of the visual field (two-dimensional scheme). We revealed asymmetric focuses of short- and long-latency saccades in the two-dimensional scheme of stimulation. The MANOVA revealed that the factor of dimensionality influenced saccadic latency to a greater extent than the factor of lateralization of stimuli (presenting in the right or left visual hemifields). Accuracy of saccades decreased with increasing in their eccentricity in both spatial schemes of stimulation.     

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.

     

A method for the chronic electromagnetic recording of eye and head movements in monkeys

A search-coil method for two-dimensional chronic registration of eye and head movements is described. The method is based on the analysis of the electromotive force induced by a magnetic field in a search coil. The output parameters of the original dual system were measured using both the standard search coil and that implanted into monkey's eye. The precision of eye movement recording was evaluated in real time. Standard deviation of spontaneous noise level for both channels was equal to 0.16 degrees (deg). The same parameters representing eye movement error during gaze fixation in the horizontal (in the range of -20/+20 deg) and vertical (in the range of -13/+13 deg) directions were equal to 0.27-0.38 and 0.23-0.31 deg, respectively. The obtained errors were comparable with the angular size of the peripheral target stimuli (0.20 deg), which had to be traced by an animal with saccadic movements.     

Groups of passive and active control state in longitudinal experiments: an electrophysiological study

Long-term electrophysiological experiments were carried out with rats with chronically implanted electrodes into dopaminergic brain structures. Within 4 weeks after surgery, the relative spectral power of electrical activity in the delta1 and delta2 frequency bands decreased, while the relative spectral power in the alpha, beta1 and beta2 bands increased. A delayed (to the 4-5th week after surgery) increase in the total amount of sleep and REM sleep percent was observed in the sleep architecture of these animals. Multiple (during 2 weeks daily) intraperitoneal saline injections altered the dynamic of electrophysiological indices on the 2nd-3rd postsurgery weeks. The total sleep amount being not increased, the total and mean REM sleep durations increased, and the dynamic of the relative spectral power of electrical activity in the dopaminergic brain structures in the delta1, alpha and beta2 bands was found to be changed.     

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.     

Activation of morphogenesis and proliferation by low specificity chemical effectors

Activation of highly specific biochemical processes by simple chemical agents is demonstrated for morphogenesis (anlage and development of female gametophyte in cereal) and mitosis (in cell cultures and animal and plant tissues). The effects of these agents are tissue-specific. Structure--activity relationship is analyzed in this group of compounds. Thus, the phenomenon reveals the exact pathways of the influence of allelopathic and anthropogenic chemical agents on evolution of plant biocenoses.