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Independent Component Analysis is a widely used method in EEG data processing for removing unwanted artefacts from the measured data. The drawback of this method is its high computational cost, resulting in long execution times. A massively parallel GPU implementation of the popular FastICA algorithm is presented in this paper. The implementation uses standard CUDA library functions where possible and custom parallel kernels for the remaining steps. The results show that for typical EEG processing setups our version can be executed within real-time limits, allowing sophisticated automatic artefact removal algorithms to be executed during measurement.

Protein-based vaccines offer a safer alternative to live-attenuated or inactivated vaccines but have limited immunogenicity. The identification of adjuvants that augment immunogenicity, specifically in a manner that is durable and antigen-specific, is therefore critical for advanced development. In this study, we use the filovirus virus-like particle (VLP) as a model protein-based vaccine in order to evaluate the impact of four candidate vaccine adjuvants on enhancing long term protection from Ebola virus challenge. Adjuvants tested include poly-ICLC (Hiltonol), MPLA, CpG 2395, and alhydrogel. We compared and contrasted antibody responses, neutralizing antibody responses, effector T cell responses, and T follicular helper (Tfh) cell frequencies with each adjuvant's impact on durable protection. We demonstrate that in this system, the most effective adjuvant elicits a Th1-skewed antibody response and strong CD4 T cell responses, including an increase in Tfh frequency. Using immune-deficient animals and adoptive transfer of serum and cells from vaccinated animals into naïve animals, we further demonstrate that serum and CD4 T cells play a critical role in conferring protection within effective vaccination regimens. These studies inform on the requirements of long term immune protection, which can potentially be used to guide screening of clinical-grade adjuvants for vaccine clinical development., Highlights • Adjuvants can prolong the protection afforded by protein-based vaccines and impact adaptive immune responses • Enhanced CD4 T cell responses, helper and effector, correlate with duration of protection • Durable protection from ma-EBOV is associated with Tfh frequency, Th1 antibody titers, and effector CD4 T cells Protein-based vaccines are extremely safe, but they sometimes require the addition of adjuvants to enhance immunogenicity. In this study, we compared the impact of multiple adjuvants on immunogenicity, focusing on the duration of vaccine-mediated protection in mice. We then looked at how each adjuvant impacted the immune response in order to identify correlates of that long lasting immunity. The most effective adjuvant/vaccine combinations elicited multifunctional CD4 T cell responses and a Th1-skewed antibody response. By transferring antigen-experienced CD4 T cells and serum into naïve animals, we demonstrated that both CD4 T cells and serum were critical for durable vaccine-mediated protection.

Recent advances in the next-generation sequencing of B-cell receptors (BCRs) enable the characterization of humoral responses at a repertoire-wide scale and provide the capability for identifying unique features of immune repertoires in response to disease, vaccination, or infection. Immunosequencing now readily generates 103–105 sequences per sample; however, statistical analysis of these repertoires is challenging because of the high genetic diversity of BCRs and the elaborate clonal relationships among them. To date, most immunosequencing analyses have focused on reporting qualitative trends in immunoglobulin (Ig) properties, such as usage or somatic hypermutation (SHM) percentage of the Ig heavy chain variable (IGHV) gene segment family, and on reducing complex Ig property distributions to simple summary statistics. However, because Ig properties are typically not normally distributed, any approach that fails to assess the distribution as a whole may be inadequate in (1) properly assessing the statistical significance of repertoire differences, (2) identifying how two repertoires differ, and (3) determining appropriate confidence intervals for assessing the size of the differences and their potential biological relevance. To address these issues, we have developed a technique that uses Wilcox’ robust statistics toolbox to identify statistically significant vaccine-specific differences between Ig repertoire properties. The advantage of this technique is that it can determine not only whether but also where the distributions differ, even when the Ig repertoire properties are non-normally distributed. We used this technique to characterize murine germinal center (GC) B-cell repertoires in response to a complex Ebola virus-like particle (eVLP) vaccine candidate with known protective efficacy. The eVLP-mediated GC B-cell responses were highly diverse, consisting of thousands of clonotypes. Despite this staggering diversity, we identified statistically significant differences between non-immunized, vaccine only, and vaccine-plus-adjuvant groups in terms of Ig properties, including IGHV-family usage, SHM percentage, and characteristics of the BCR complementarity-determining region. Most notably, our analyses identified a robust eVLP-specific feature—enhanced IGHV8-family usage in B-cell repertoires. These findings demonstrate the utility of our technique in identifying statistically significant BCR repertoire differences following vaccination. More generally, our approach is potentially applicable to a wide range of studies in infection, vaccination, auto-immunity, and cancer.

Item does not contain fulltext RATIONALE: Administration of tuberculosis (TB) vaccines in participants with previous or current pulmonary TB may have the potential for causing harmful postvaccination immunologic (Koch-type) reactions. OBJECTIVES: To assess the safety and immunogenicity of three dose levels of the AERAS-402 live, replication-deficient adenovirus 35-vectored TB candidate vaccine, containing three mycobacterial antigens, in individuals with current or previous pulmonary TB. METHODS: We performed a phase II randomized, placebo-controlled, double-blinded dose-escalation study in an HIV-negative adult South African cohort (n = 72) with active pulmonary TB (on treatment for 1-4 mo) or pulmonary TB treated at least 12 months before study entry and considered cured. Safety endpoints included clinical assessment, flow volume curves, diffusing capacity of the lung for carbon monoxide, pulse oximetry, chest radiograph, and high-resolution thoracic computerized tomography scans. Cytokine expression by CD4 and CD8 T cells, after stimulation with Ag85A, Ag85B, and TB10.4 peptide pools, was examined by intracellular cytokine staining. MEASUREMENTS AND MAIN RESULTS: No apparent temporal or dose-related changes in clinical status (specifically acute, Koch phenomenon-like reactions), lung function, or radiology attributable to vaccine were observed. Injection site reactions were mild or moderate. Hematuria (by dipstick only) occurred in 25 (41%) of 61 AERAS-402 recipients and 3 (27%) of 11 placebo recipients, although no gross hematuria was reported. AERAS-402 induced robust CD8+ and moderate CD4+ T-cell responses, mainly to Ag85B in both vaccine groups. CONCLUSIONS: Administration of the AERAS-402 candidate TB vaccine to participants with current or previous pulmonary TB induced a robust immune response and is not associated with clinically significant pulmonary complications. Clinical trial registered with www.clinicaltrials.gov (NCT 02414828) and in the South African National Clinical Trials Register ( www.sanctr.gov.za DOH 27-0808-2060).

Background Efforts to reduce risk of tuberculosis disease in children include development of effective vaccines. Our aim was to test safety and immunogenicity of the new adenovirus 35-vectored tuberculosis vaccine candidate AERAS-402 in infants, administered as a boost following a prime with the Bacille Calmette-Guerin vaccine. Methods In a phase 1 randomised, double-blind, placebo-controlled, dose-escalation trial, BCG-vaccinated infants aged 6–9 months were sequentially assigned to four study groups, then randomized to receive an increasing dose-strength of AERAS-402, or placebo. The highest dose group received a second dose of vaccine or placebo 56 days after the first. The primary study outcome was safety. Whole blood intracellular cytokine staining assessed immunogenicity. Results Forty-two infants received AERAS-402 and 15 infants received placebo. During follow-up of 182 days, an acceptable safety profile was shown with no serious adverse events or discontinuations related to the vaccine. AERAS-402 induced a specific T cell response. A single dose of AERAS-402 induced CD4T cells predominantly expressing single IFN-γ whereas two doses induced CD4T cells predominantly expressing IFN-γ, TNF-α and IL-2 together. CD8T cells were induced and were more likely to be present after 2 doses of AERAS-402. Conclusions AERAS-402 was safe and immunogenic in healthy infants previously vaccinated with BCG at birth. Administration of the highest dose twice may be the most optimal vaccination strategy, based on the induced immunity. Multiple differences in T cell responses when infants are compared with adults vaccinated with AERAS-402, in the same setting and using the same whole blood intracellular cytokine assay, suggest specific strategies may be important for vaccination for each population.

Viruses modulate a number of host biological responses including the cell cycle to favor their replication. In this study, we developed a high-content imaging (HCI) assay to measure DNA content and identify different phases of the cell cycle. We then investigated the potential effects of cell cycle arrest on Ebola virus (EBOV) infection. Cells arrested in G1 phase by serum starvation or G1/S phase using aphidicolin or G2/M phase using nocodazole showed much reduced EBOV infection compared to the untreated control. Release of cells from serum starvation or aphidicolin block resulted in a time-dependent increase in the percentage of EBOV infected cells. The effect of EBOV infection on cell cycle progression was found to be cell-type dependent. Infection of asynchronous MCF-10A cells with EBOV resulted in a reduced number of cells in G2/M phase with concomitant increase of cells in G1 phase. However, these effects were not observed in HeLa or A549 cells. Together, our studies suggest that EBOV requires actively proliferating cells for efficient replication. Furthermore, multiplexing of HCI based assays to detect viral infection, cell cycle status and other phenotypic changes in a single cell population will provide useful information during screening campaigns using siRNA and small molecule therapeutics.

The rhesus macaque serves as an animal model for Ebola virus (EBOV) infection. A thorough understanding of EBOV infection in this species would aid in further development of filovirus therapeutics and vaccines. In this study, pathological and immunological data from EBOV-infected rhesus macaques are presented. Changes in blood chemistries, hematology, coagulation, and immune parameters during infection, which were consistently observed in the animals, are presented. In an animal that survived challenge, a delay was observed in the detection of viral RNA and inflammatory cytokines and chemokines which may have contributed to survival. Collectively, these data add to the body of knowledge regarding EBOV pathogenesis in rhesus macaques and emphasize the reproducibility of the rhesus macaque challenge model.

Analysis of the experimental data of joint Russian-Hungarian (FIAN and KFKI) research was carried out at Tien Shan station for the search of sources of primary cosmic rays (PCR) at energies ( E 0 = 10 14 – 10 15 eV ). Maps of extensive air shower (EAS) arrival directions are presented where the standard deviation of mean event numbers in equatorial coordinates exceeded a definite value. The excess of EAS number was observed from some directions. It was observed from an extended galactic object – the SN remnant. The young pulsar PSR 0656+14 is located near the centre of this object.

The level of delayed skin hypersensitivity (DSH) to DNFB and of the primary immune reaction was evaluated in the calves immunized with an inactivated oil IBR vaccine (V group) and in the calves premedicated with glucan (seven days before vaccine administration) and subsequently immunized with the mentioned vaccine (GV group). The DSH test did not reveal an alteration of cellular immunological reactivity in the calves immunized with an inactivated oil IBR vaccine; after the vaccine administration there was no significant difference in the DSH level from the value before vaccine administration nor in comparison with the value of control calves (K group), Tab. I. But in the immunized calves which were glucan-premedicated (from Pleurotus ostreatus; 10 mg/kg l.w.) a significantly higher DSH level was determined not only in comparison with the initial value (P0.05) before glucan administration but also with the value of control calves (P0.05), Tab. I. The categorization of calves according to the DSH level also points to the immunomodulating effect of glucan in this sense (Fig. 1); while the value of skin test ranged from 3.6 to 6.5 mm in the highest percentage of the calves of V and K groups on the dates before and after administration of the mentioned preparations, a marked increase (on the date after administration) in the number of calves (from 22 to 67%) with the value of skin test higher than 6.5 mm was observed in the calves of GV group. The vaccine administration in itself (V group) did not induce the production of measurable amounts of serum IBR antibodies till day 14 after immunization.(ABSTRACT TRUNCATED AT 250 WORDS)

The method of dot-blot hybridization on nitrocellulose filters by various types of DNA probes (ds recombinant plasmids, ss recombinant M13 phages and a 42bp synthetic oligonucleotide) was used for BHV-1 detection. The highest sensitivity was achieved with the 32P-pUR1 probe (1.8 kb random EcoRI-HindIII fragment inserted into pUC9) which detected the BHV-1 genome in 5 x 10(3) infected MDBK cells. Using the pUR1 probe, no cross hybridization was observed with other herpesviruses: BHV-2, 3, 4, and Aujeszky's disease virus. The 32P-pUR1 probe detected BHV-1 in nasal swabs of calves as early as on day 1 after experimental infection. The maximum intensity of BHV-1 detection occurred on day 1-3. The 32P-pUR1 probe also detected BHV-1 in field samples of nasal swabs from cows and calves.

In the present study we investigated the dynamics of circulating T and B lymphocytes and serum specific antibodies in calves experimentally infected with IBR virus (I group) and in calves administered glucan (seven days before infection) and the infected (GI group). The percentages of T and B lymphocytes in the peripheral blood were determined from analyses by rosette methods; the titer of serum anti-IBR antibodies was determined by virus-neutralizing test on cell cultures. The dynamics of the percentage of circulating T lymphocytes showed a similar decreasing trend in both groups, with significant values on days 3 to 5 after infection (AI). In comparison with the calves of I group, the outset of T cell reduction was found to be less pronounced (within the first two days after infection), with a statistically significant difference on day 2 AI (P0.05), Fig. 1. A decrease in the percentage of T lymphocytes was related to an increase in the percentage of circulating B lymphocytes, with maximum on days 3 and 4 AI (P0.05), Fig. 1. All the calves before experiment beginning were free of serum anti-BHV 1 antibodies. They started responding to the experimental infection with IBR virus by production of serum antibodies between week 1 and 2 AI. The dynamics of serum anti-IBR antibodies showed an identical course in both experimental groups, with the more pronounced outset (P0.05) of immunological response in the calves of GI group (Fig. 2).(ABSTRACT TRUNCATED AT 250 WORDS)

Two gammaglobulin preparations have been developed: Alga (10% injection solution of serum bovine gamma-globulin and albumin) and Algalev (with addition of levamisole 10 mg/ml, patented under PV 4069/87); their administration to calves in field conditions was evaluated. The Alga preparation at a rate of 1 ml/kg liveweight (two administrations) had good preventive effects in the diarrhoeic syndrome of new-born hypogammaglobulinaemic calves. In comparison with the untreated calves, these parameters were determined: lower incidence of diarrhoea (41% against 75%; Tab. I), its later onset (by 24 hours), shorter duration (by 50 hours; P0.01), lower intensity and easier therapeutical handling (Tab. II). The Algalev preparation (two administrations at a rate of 1 ml/kg liveweight) was suitable for metaphylactic use (combined with antibiotic application) in the respiration syndrome of calves. In comparison with the untreated calves, these parameters were determined: lower incidence of this disorder (42% against 78%), lower intensity of clinical symptoms (intensive symptoms in 20% of the calves against 72%) and importantly higher daily weight gains (0.64 kg against 0.26 kg; Fig. 3). The concentrations of total serum Ig (CS-Ig), serum proteins (SB) and serum albumin (S-Alb) were similar in the compared groups of calves in the whole period of observation (Fig. 1). Certain differences were observed in the dynamics of anti-PI 3 titre of serum antibodies as shown by investigation of specific serum antibodies (Fig. 2); the level of their production was in agreement with morbidity incidence and clinical symptom intensity in both groups of calves.

This paper contrasts present day recruiting practices with the intense aggressive recruiting of a few years ago, illustrates the effect of unethical practices, and acknowledges the graduating engineer’s part in these practices. It emphasizes the need for and the trend toward practices beneficial to the engineering profession and industry as a whole.

The safety and neuroallergic activity of current commercial and experimental rabies vaccine were studied by detecting the patho-histological changes in the central nervous system of laboratory animals (guinea-pigs) according to the method recommended by the World Health Organization (Gispen, 1975). Six rabies vaccines were tested in the experiments. The vaccines are as follows: lyophilized rabies vaccine - human; lyophilized rabies vaccine - veterinary; rabies vaccine U. S. P. duck embryo - human; avianized rabies vaccine - veterinary; inactivated rabies vaccine from strain Vnukov-32 - human; live cell rabies vaccine from strain Vnukovo-32 - veterinary. Patho-histological changes indicating the neuroallergic activity of the vaccines were observed in laboratory animals (varying range and intensity of these activities, to which the following vaccines were applied: lyophilized vaccine - veterinary and lyophilized rabies vaccine - human. The cell rabies vaccines from strain Vnukovo-32 were found to be safe; they can be recommended for their merits (including nonreactogenicity) to be used in veterinary practice in rabies immunoprophylaxis.

The radioprotective effect of alpha-mercaptopropionylglycine and its combinations on animals