Spatial gradient of P300 area of the brain visual evoked potential in the brain-computer interface paradigm

In 12 adult healthy subjects we studied Brain-Computer-Interface recognition of different intended letters by the square of P300 wave in the averaged VEP. Horizontal and vertical spatial gradient of this square was studied as well as tuning acuteness of visual attention to a significant letter. High acuteness of this tuning was found (width of the tuning curve at its half height was equal to 1.6 grad) independent of the letter position on the letter matrix. Horizontal and vertical gradient of P300 were found to be very similar, but in the half of cases the first one revealed some kind of the "lateral inhibition": decrease of P300 square for the columns neighboring to the meaningful one. Tuning acuteness was found to be reliable and directly interrelated with P300 square. The data are discussed in relation to selectivity of the local visual attention.     

Model analyses of visual biofeedback training for EEG-based brain-computer interface

The primary goal of this study was to construct a simulation model of a biofeedback brain-computer interface (BCI) system to analyze the effect of biofeedback training on BCI users. A mathematical model of a man-machine visual-biofeedback BCI system was constructed to simulate a subject using a BCI system to control cursor movements. The model consisted of a visual tracking system, a thalamo-cortical model for EEG generation, and a BCI system. The BCI system in the model was realized for real experiments of visual biofeedback training. Ten sessions of visual biofeedback training were performed in eight normal subjects during a 3-week period. The task was to move a cursor horizontally across a screen, or to hold it at the screen’s center. Experimental conditions and EEG data obtained from real experiments were then simulated with the model. Three model parameters, representing the adaptation rate of gain in the visual tracking system and the relative synaptic strength between the thalamic reticular and thalamo-cortical cells in the Rolandic areas, were estimated by optimization techniques so that the performance of the model best fitted the experimental results. The serial changes of these parameters over the ten sessions, reflecting the effects of biofeedback training, were analyzed. The model simulation could reproduce results similar to the experimental data. The group mean success rate and information transfer rate improved significantly after training (56.6 to 81.1% and 0.19 to 0.76 bits/trial, respectively). All three model parameters displayed similar and statistically significant increasing trends with time. Extensive simulation with systematic changes of these parameters also demonstrated that assigning larger values to the parameters improved the BCI performance. We constructed a model of a biofeedback BCI system that could simulate experimental data and the effect of training. The simulation results implied that the improvement was achieved through a quicker adaptation rate in visual tracking gain and a larger synaptic gain from the visual tracking system to the thalamic reticular cells. In addition to the purpose of this study, the constructed biofeedback BCI model can also be used both to investigate the effects of different biofeedback paradigms and to test, estimate, or predict the performances of other newly developed BCI signal processing algorithms.     

Poliovirus translation: a paradigm for a novel initiation mechanism

All eukaryotic cellular mRNAs, and most viral mRNAs, are blocked at their 5' ends with a cap structure (m7GpppX, where X is any nucleotide). Poliovirus, along with a small number of other animal and plant viral mRNAs, does not contain a 5' cap structure. Since the cap structure functions to facilitate ribosome binding to mRNA, translation of polio-virus must proceed by a cap-independent mechanism. Consistent with this, recent studies have shown that ribosomes can bind to an internal region within the long 5' noncoding sequence of poliovirus RNA. Possible mechanisms for cap-independent translation are discussed. Cap-independent translation of poliovirus RNA is of major importance to the mechanism of shut-off of host protein synthesis after infection. Moreover, it is likely to play a role in determining poliovirus neurovirulence and attenuation.     

Definitions of state variables and state space for brain-computer interface

Neocortical state variables are defined and evaluated at three levels: microscopic using multiple spike activity (MSA), mesoscopic using local field potentials (LFP) and electrocorticograms (ECoG), and macroscopic using electroencephalograms (EEG) and brain imaging. Transactions between levels occur in all areas of cortex, upwardly by integration (abstraction, generalization) and downwardly by differentiation (speciation). The levels are joined by circular causality: microscopic activity upwardly creates mesoscopic order parameters, which downwardly constrain the microscopic activity that creates them. Integration dominates in sensory cortices. Microscopic activity evoked by receptor input in sensation induces emergence of mesoscopic activity in perception, followed by integration of perceptual activity into macroscopic activity in concept formation. The reverse process dominates in motor cortices, where the macroscopic activity embodying the concepts supports predictions of future states as goals. These macroscopic states are conceived to order mesoscopic activity in patterns that constitute plans for actions to achieve the goals. These planning patterns are conceived to provide frames in which the microscopic activity evolves in trajectories that adapted to the immediate environmental conditions detected by new stimuli. This circular sequence forms the action-perception cycle. Its upward limb is understood through correlation of sensory cortical activity with behavior. Now brain-machine interfaces (BMI) offer a means to understand the downward sequence through correlation of behavior with motor cortical activity, beginning with macroscopic goal states and concluding with recording of microscopic MSA trajectories that operate neuroprostheses. Part 1 develops a hypothesis that describes qualitatively the neurodynamics that supports the action-perception cycle and derivative reflex arc. Part 2 describes episodic, “cinematographic” spatial pattern formation and predicts some properties of the macroscopic and mesoscopic frames by which the embedded trajectories of the microscopic activity of cortical sensorimotor neurons might be organized and controlled. URL: http://sulcus.berkeley.edu     

Bayesian classifier for brain-computer interface based on mental representation of movements

This paper proposes Bayesian approach to classification of EEG patterns on the basis of imaginary movements of extremities based on analysis ofcovariance matrices of native EEG recordings. An efficacy of a Brain-Computer Interface (BCI) based on the proposed classifier is evaluated. Bayesian classifier is shown to be competitive with the MCSP (Multiclass Common Spatial Patterns) classifier known from the literature as one of the efficient variant for BCI implementation. The influence of eye movement and blinking artifacts on the BCI performance is investigated. It is shown that the presence of such artifacts does not affect the classification accuracy.     

The P300 based brain-computer interface: effect of stimulus position in a stimulus train

The P300 brain-computer interface (BCI) is currently the most efficient BCI. This interface is based on detection of the P300 wave of the brain potentials evoked when a symbol related to the intended input is highlighted. To increase operation speed of the P300 BCI, reduction of the number of stimuli repetitions is needed. This reduction leads to increase of the relative contribution to the input symbol detection from the reaction to the first target stimulus. It is known that the event-related potentials (ERP) to the first stimulus presentations can be different from the ERP to stimuli presented latter. In particular, the amplitude of responses to the first stimulus presentations is often increased, which is beneficial for their recognition by the BCI. However, this effect was not studied within the BCI framework. The current study examined the ERP obtained from healthy participants (n = 14) in the standard P300 BCI paradigm using 10 trials, as well as in the modified P300 BCI with stimuli presented on moving objects in triple-trial (n = 6) and single-trial (n = 6) stimulation modes. Increased ERP amplitude was observed in response to the first target stimuli in both conditions, as well as in the single-trial mode comparing to triple-trial. We discuss the prospects of using the specific features of the ERP to first stimuli and the single-trial ERP for optimizing the high-speed modes in the P300 BCIs.     

Continuous three-dimensional control of a virtual helicopter using a motor imagery based brain-computer interface

Brain-computer interfaces (BCIs) allow a user to interact with a computer system using thought. However, only recently have devices capable of providing sophisticated multi-dimensional control been achieved non-invasively. A major goal for non-invasive BCI systems has been to provide continuous, intuitive, and accurate control, while retaining a high level of user autonomy. By employing electroencephalography (EEG) to record and decode sensorimotor rhythms (SMRs) induced from motor imaginations, a consistent, user-specific control signal may be characterized. Utilizing a novel method of interactive and continuous control, we trained three normal subjects to modulate their SMRs to achieve three-dimensional movement of a virtual helicopter that is fast, accurate, and continuous. In this system, the virtual helicopter's forward-backward translation and elevation controls were actuated through the modulation of sensorimotor rhythms that were converted to forces applied to the virtual helicopter at every simulation time step, and the helicopter's angle of left or right rotation was linearly mapped, with higher resolution, from sensorimotor rhythms associated with other motor imaginations. These different resolutions of control allow for interplay between general intent actuation and fine control as is seen in the gross and fine movements of the arm and hand. Subjects controlled the helicopter with the goal of flying through rings (targets) randomly positioned and oriented in a three-dimensional space. The subjects flew through rings continuously, acquiring as many as 11 consecutive rings within a five-minute period. In total, the study group successfully acquired over 85% of presented targets. These results affirm the effective, three-dimensional control of our motor imagery based BCI system, and suggest its potential applications in biological navigation, neuroprosthetics, and other applications.     

Targeting the glycans of glycoproteins: a novel paradigm for antiviral therapy

Several chronic viral infections (such as HIV and hepatitis C virus) are highly prevalent and are a serious health risk. The adaptation of animal viruses to the human host, as recently exemplified by influenza viruses and the severe acute respiratory syndrome coronavirus, is also a continuous threat. There is a high demand, therefore, for new antiviral lead compounds and novel therapeutic concepts. In this Review, an original therapeutic concept for suppressing enveloped viruses is presented that is based on a specific interaction of carbohydrate-binding agents (CBAs) with the glycans present on viral-envelope glycoproteins. This approach may also be extended to other pathogens, including parasites, bacteria and fungi.     

Towards a unified paradigm for sequence‐based identification of fungi

The nuclear ribosomal internal transcribed spacer (ITS) region is the formal fungal barcode and in most cases the marker of choice for the exploration of fungal diversity in environmental samples. Two problems are particularly acute in the pursuit of satisfactory taxonomic assignment of newly generated ITS sequences: (i) the lack of an inclusive, reliable public reference data set and (ii) the lack of means to refer to fungal species, for which no Latin name is available in a standardized stable way. Here, we report on progress in these regards through further development of the UNITE database ( http://unite.ut.ee ) for molecular identification of fungi. All fungal species represented by at least two ITS sequences in the international nucleotide sequence databases are now given a unique, stable name of the accession number type (e.g. Hymenoscyphus pseudoalbidus|GU586904|SH133781.05FU), and their taxonomic and ecological annotations were corrected as far as possible through a distributed, third‐party annotation effort. We introduce the term ‘species hypothesis’ (SH) for the taxa discovered in clustering on different similarity thresholds (97–99%). An automatically or manually designated sequence is chosen to represent each such SH. These reference sequences are released ( http://unite.ut.ee/repository.php ) for use by the scientific community in, for example, local sequence similarity searches and in the QIIME pipeline. The system and the data will be updated automatically as the number of public fungal ITS sequences grows. We invite everybody in the position to improve the annotation or metadata associated with their particular fungal lineages of expertise to do so through the new Web‐based sequence management system in UNITE.     

Evolution of brain-computer interface: action potentials, local field potentials and electrocorticograms

Brain computer interfaces (BCIs) were originally developed to give severely motor impaired patients a method to communicate and interact with their environment. Initially most BCI systems were based on non-invasive electroencephalographic recordings from the surface of the scalp. To increase control speed, accuracy and complexity, researchers began utilizing invasive recording modalities. BCIs using multi-single unit action potentials have provided elegant multi-dimensional control of both computer cursors and robotic limbs in the last few years. However, long-term stability issues with single-unit arrays has lead researchers to investigate other invasive recording modalities such as high-frequency local field potentials and electrocorticography (ECoG). Although ECoG originally evolved as a replacement for single-unit BCIs, it has come full circle to become an effective tool for studying cortical neurophysiology.     

Towards a new paradigm of non-captive research on cetacean cognition

Contemporary knowledge of impressive neurophysiology and behavior in cetaceans, combined with increasing opportunities for studying free-ranging cetaceans who initiate sociable interaction with humans, are converging to highlight serious ethical considerations and emerging opportunities for a new era of progressive and less-invasive cetacean research. Most research on cetacean cognition has taken place in controlled captive settings, e.g., research labs, marine parks. While these environments afford a certain amount of experimental rigor and logistical control they are fraught with limitations in external validity, impose tremendous stress on the part of the captive animals, and place burdens on populations from which they are often captured. Alternatively, over the past three decades, some researchers have sought to focus their attention on the presence of free-ranging cetacean individuals and groups who have initiated, or chosen to participate in, sociable interactions with humans in the wild. This new approach, defined as Interspecies Collaborative Research between cetacean and human, involves developing novel ways to address research questions under natural conditions and respecting the individual cetacean's autonomy. It also offers a range of potential direct benefits to the cetaceans studied, as well as allowing for unprecedented cognitive and psychological research on sociable mysticetes. Yet stringent precautions are warranted so as to not increase their vulnerability to human activities or pathogens. When conducted in its best and most responsible form, collaborative research with free-ranging cetaceans can deliver methodological innovation and invaluable new insights while not necessitating the ethical and scientific compromises that characterize research in captivity. Further, it is representative of a new epoch in science in which research is designed so that the participating cetaceans are the direct recipients of the benefits.     

Cattle owners' awareness of bovine tuberculosis in high and low prevalence settings of the wildlife-livestock interface areas in Zambia

Background  

Awareness of bovine tuberculosis (BTB) by cattle owners is of extreme importance to policy makers when considering mitigation. However, to our knowledge, little is known on cattle owners' awareness of BTB in Zambia. Similarly, such knowledge is uncommon within and outside Africa. The current study investigates the epidemiological characteristics of BTB in Zambian cattle in relation to awareness by cattle owners in high and low cattle BTB prevalence settings. A cross sectional study was designed and data was gathered based on 106 cattle owners and cattle herds; subjected to an interviewer-administered questionnaire and comparative intradermal tuberculin test using a cut-off for positivity of 4 mm, respectively.     

Inhibiting TNF-mediated signaling: a novel therapeutic paradigm for androgen independent prostate cancer

The tumor necrosis factor (TNF) receptor super family comprises of members that induce two distinct signaling cascades, leading to either cell survival or apoptosis. However, in prostate cancer (PCa), TNF-mediated prosurvival signaling is the predominant pathway that leads to cell survival and resistance to therapy. Although inhibition of TNF signaling by pharmacological agents or monoclonal antibodies has gained importance in the field of cancer therapy, toxicity to normal cells has impaired their extensive use for cancer treatment. We previously identified a natural, nontoxic compound psoralidin that inhibited viability and induced apoptosis in androgen independent prostate cancer (AIPC) cells. Thus, the goal of our study is to investigate whether psoralidin inhibits TNF-mediated prosurvival signaling in AIPC cells. Our results suggest that psoralidin inhibits constitutive and TNF-induced expression of TNF-α and its downstream prosurvival signaling molecules such as NF-κB and Bcl-2 in AIPC cells. On the other hand, psoralidin simultaneously induces the death receptor (DR)-mediated apoptotic signaling eventually causing the activation of caspase cascade and resultant induction of apoptosis. Oral administration of psoralidin inhibits expression of TNF-α and NF-κB/p65 in tumor sections, resulting in tumor regression in PC-3 xenografts. Our results suggest that psoralidin inhibits TNF-mediated survival signaling in AIPC and thus is a potent therapeutic agent for prostate cancer.     

Prostate cancer-specific hallmarks of amino acids metabolism: Towards a paradigm of precision medicine

So far multiple differences in prostate cancer-specific amino acids metabolism have been discovered. Moreover, attempts to utilize these alterations for prostate cancer diagnosis and treatment have been made. The prostate cancer metabolism and biosynthesis of amino acids are particularly focused on anaplerosis more than on energy production. Other crucial requirements on amino acids pool come from the serine, one?carbon cycle, glycine synthesis pathway and folate metabolism forming major sources of interproducts for synthesis of nucleobases necessary for rapidly proliferating cells. Considering the lack of some amino acids biosynthetic pathways and/or their extraordinary importance for prostate cancer cells, there is a widespread potential for targeted therapeutic applications with no effect on non-malignant cells. This review summarizes the up-to-date knowledge of the importance of amino acids for prostate cancer pathogenesis with a special emphasis on potential applications of metabolic variabilities in the new oncologic paradigm of precision medicine.     

The mechanism of membrane insertion for a cholesterol-dependent cytolysin: a novel paradigm for pore-forming toxins.

Perfringolysin O (PFO), a water-soluble monomeric cytolysin secreted by pathogenic Clostridium perfringens, oligomerizes and forms large pores upon encountering cholesterol-containing membranes. Whereas all pore-forming bacterial toxins examined previously have been shown to penetrate the membrane using a single amphipathic beta hairpin per polypeptide, cysteine-scanning mutagenesis and multiple independent fluorescence techniques here reveal that each PFO monomer contains a second domain involved in pore formation, and that each of the two amphipathic beta hairpins completely spans the membrane. In the soluble monomer, these transmembrane segments are folded into six alpha helices. The insertion of two transmembrane hairpins per toxin monomer and the major change in secondary structure are striking and define a novel paradigm for the mechanism of membrane insertion by a cytolytic toxin.     

Multicenter evaluation of a novel surveillance paradigm for complications of mechanical ventilation

Background

Ventilator-associated pneumonia (VAP) surveillance is time consuming, subjective, inaccurate, and inconsistently predicts outcomes. Shifting surveillance from pneumonia in particular to complications in general might circumvent the VAP definition''s subjectivity and inaccuracy, facilitate electronic assessment, make interfacility comparisons more meaningful, and encourage broader prevention strategies. We therefore evaluated a novel surveillance paradigm for ventilator-associated complications (VAC) defined by sustained increases in patients'' ventilator settings after a period of stable or decreasing support.

Methods

We assessed 600 mechanically ventilated medical and surgical patients from three hospitals. Each hospital contributed 100 randomly selected patients ventilated 2–7 days and 100 patients ventilated >7 days. All patients were independently assessed for VAP and for VAC. We compared incidence-density, duration of mechanical ventilation, intensive care and hospital lengths of stay, hospital mortality, and time required for surveillance for VAP and for VAC. A subset of patients with VAP and VAC were independently reviewed by a physician to determine possible etiology.

Results

Of 597 evaluable patients, 9.3% had VAP (8.8 per 1,000 ventilator days) and 23% had VAC (21.2 per 1,000 ventilator days). Compared to matched controls, both VAP and VAC prolonged days to extubation (5.8, 95% CI 4.2–8.0 and 6.0, 95% CI 5.1–7.1 respectively), days to intensive care discharge (5.7, 95% CI 4.2–7.7 and 5.0, 95% CI 4.1–5.9), and days to hospital discharge (4.7, 95% CI 2.6–7.5 and 3.0, 95% CI 2.1–4.0). VAC was associated with increased mortality (OR 2.0, 95% CI 1.3–3.2) but VAP was not (OR 1.1, 95% CI 0.5–2.4). VAC assessment was faster (mean 1.8 versus 39 minutes per patient). Both VAP and VAC events were predominantly attributable to pneumonia, pulmonary edema, ARDS, and atelectasis.

Conclusions

Screening ventilator settings for VAC captures a similar set of complications to traditional VAP surveillance but is faster, more objective, and a superior predictor of outcomes.