Multivariate analysis reveals that BVDV field isolates do not show a close VN-based antigenic relationship to US vaccine strains

Objective Evaluate bovine viral diarrhea virus (BVDV) antigenicity by using virus neutralization titers (VNT) analyzed using the principal component analysis (PCA) from antisera generated against US-based vaccine strains against both US-origin field isolates and non-US-origin field isolates. Results Data from both independent analyses demonstrated that several US-origin and non-US-origin BVDV field isolates appear to be antigenically divergent from the US-based vaccine strains. Results from the combined analysis provided greater insight into the antigenic diversity observed among BVDV isolates. Data from this study further support genetic assignment into BVDV subgenotypes, as well as strains within subgenotypes is not representative of antigenic relatedness. PCA highlights isolates that are antigenically divergent from members of the same species and subgenotype and conversely isolates that belong to different subgenotypes have similar antigenic characteristics when using antisera from US-based vaccine isolates

In vitro method to evaluate virus competition between BVDV-1 and BVDV-2 strains using the PrimeFlow RNA assay

Bovine viral diarrhea viruses (BVDV), segregated in BVDV-1 and BVDV-2 species, lead to substantial economic losses to the cattle industry worldwide. It has been hypothesized that there could be differences in level of replication, pathogenesis and tissue tropism between BVDV-1 and BVDV-2 strains. Thus, this study developed an in vitro method to evaluate virus competition between BVDV-1 and BVDV-2 strains. To this end the competitive dynamics of BVDV-1a, BVDV-1b, and BVDV-2a strains in cell cultures was evaluated by a PrimeFlow RNA assay. Similar results were observed in this study, as was observed in an earlier in vivo transmission study. Competitive exclusion was observed as the BVDV-2a strains dominated and excluded the BVDV-1a and BVDV-1b strains. The in vitro model developed can be used to identify viral variations that result in differences in frequency of subgenotypes detected in the field, vaccine failure, pathogenesis, and strain dependent variation in immune responses

Use of multivariate analysis to evaluate antigenic relationships between US BVDV vaccine strains and non-US genetically divergent isolates

Bovine viral diarrhea virus (BVDV) comprises two species, BVDV-1 and BVDV-2. But given the genetic diversity among pestiviruses, at least 22 subgenotypes are described for BVDV-1 and 3-4 for BVDV-2. Genetic characterization is generally accomplished through complete or partial sequencing and phylogeny, but it is not a reliable method to define antigenic relationships. The traditional method for evaluating antigenic relationships between pestivirus isolates is the virus neutralization (VN) assay, but interpretation of the data to define antigenic relatedness can be difficult to discern for BVDV isolates within the same BVDV species. Data from this study utilized a multivariate analysis for visualization of VN results to analyze the antigenic relationships between US vaccine strains and field isolates from Switzerland, Italy, Brazil, and the UK. Polyclonal sera were generated against six BVDV strains currently contained in vaccine formulations, and each serum was used in VNs to measure the titers against seven vaccine strains (including the six homologous strains) and 23 BVDV field isolates. Principal component analysis (PCA) was performed using VN titers, and results were interpreted from PCA clustering within the PCA dendrogram and scatter plot. The results demonstrated clustering patterns among various isolates suggesting antigenic relatedness. As expected, the BVDV-1 and BVDV-2 isolates did not cluster together and had the greatest spatial distribution. Notably, a number of clusters representing antigenically related BVDV-1 subgroups contain isolates of different subgenotypes. The multivariate analysis may be a method to better characterize antigenic relationships among BVDV isolates that belong to the same BVDV species and do not have distinct antigenic differences. This might be an invaluable tool to ameliorate the composition of current vaccines, which might well be important for the success of any BVDV control program that includes vaccination in its scheme

Use of multivariate analysis to evaluate antigenic relationships between US BVDV vaccine strains and non-US genetically divergent isolates.

Bovine viral diarrhea virus (BVDV) comprises two species, BVDV-1 and BVDV-2. But given the genetic diversity among pestiviruses, at least 22 subgenotypes are described for BVDV-1 and 3-4 for BVDV-2. Genetic characterization is generally accomplished through complete or partial sequencing and phylogeny, but it is not a reliable method to define antigenic relationships. The traditional method for evaluating antigenic relationships between pestivirus isolates is the virus neutralization (VN) assay, but interpretation of the data to define antigenic relatedness can be difficult to discern for BVDV isolates within the same BVDV species. Data from this study utilized a multivariate analysis for visualization of VN results to analyze the antigenic relationships between US vaccine strains and field isolates from Switzerland, Italy, Brazil, and the UK. Polyclonal sera were generated against six BVDV strains currently contained in vaccine formulations, and each serum was used in VNs to measure the titers against seven vaccine strains (including the six homologous strains) and 23 BVDV field isolates. Principal component analysis (PCA) was performed using VN titers, and results were interpreted from PCA clustering within the PCA dendrogram and scatter plot. The results demonstrated clustering patterns among various isolates suggesting antigenic relatedness. As expected, the BVDV-1 and BVDV-2 isolates did not cluster together and had the greatest spatial distribution. Notably, a number of clusters representing antigenically related BVDV-1 subgroups contain isolates of different subgenotypes. The multivariate analysis may be a method to better characterize antigenic relationships among BVDV isolates that belong to the same BVDV species and do not have distinct antigenic differences. This might be an invaluable tool to ameliorate the composition of current vaccines, which might well be important for the success of any BVDV control program that includes vaccination in its scheme

Crystal structures and freezing of dipolar fluids

We investigate the crystal structure of classical systems of spherical particles with an embedded point dipole at T=0. The ferroelectric ground state energy is calculated using generalizations of the Ewald summation technique. Due to the reduced symmetry compared to the nonpolar case the crystals are never strictly cubic. For the Stockmayer (i.e., Lennard-Jones plus dipolar) interaction three phases are found upon increasing the dipole moment: hexagonal, body-centered orthorhombic, and body-centered tetragonal. An even richer phase diagram arises for dipolar soft spheres with a purely repulsive inverse power law potential $\sim r^{-n}$. A crossover between qualitatively different sequences of phases occurs near the exponent $n=12$. The results are applicable to electro- and magnetorheological fluids. In addition to the exact ground state analysis we study freezing of the Stockmayer fluid by density-functional theory.Comment: submitted to Phys. Rev.

Abnormal expression of p27kip1 protein in levator ani muscle of aging women with pelvic floor disorders – a relationship to the cellular differentiation and degeneration

BACKGROUND: Pelvic floor disorders affect almost 50% of aging women. An important role in the pelvic floor support belongs to the levator ani muscle. The p27/kip1 (p27) protein, multifunctional cyclin-dependent kinase inhibitor, shows changing expression in differentiating skeletal muscle cells during development, and relatively high levels of p27 RNA were detected in the normal human skeletal muscles. METHODS: Biopsy samples of levator ani muscle were obtained from 22 symptomatic patients with stress urinary incontinence, pelvic organ prolapse, and overlaps (age range 38–74), and nine asymptomatic women (age 31–49). Cryostat sections were investigated for p27 protein expression and type I (slow twitch) and type II (fast twitch) fibers. RESULTS: All fibers exhibited strong plasma membrane (and nuclear) p27 protein expression. cytoplasmic p27 expression was virtually absent in asymptomatic women. In perimenopausal symptomatic patients (ages 38–55), muscle fibers showed hypertrophy and moderate cytoplasmic p27 staining accompanied by diminution of type II fibers. Older symptomatic patients (ages 57–74) showed cytoplasmic p27 overexpression accompanied by shrinking, cytoplasmic vacuolization and fragmentation of muscle cells. The plasma membrane and cytoplasmic p27 expression was not unique to the muscle cells. Under certain circumstances, it was also detected in other cell types (epithelium of ectocervix and luteal cells). CONCLUSIONS: This is the first report on the unusual (plasma membrane and cytoplasmic) expression of p27 protein in normal and abnormal human striated muscle cells in vivo. Our data indicate that pelvic floor disorders are in perimenopausal patients associated with an appearance of moderate cytoplasmic p27 expression, accompanying hypertrophy and transition of type II into type I fibers. The patients in advanced postmenopause show shrinking and fragmentation of muscle fibers associated with strong cytoplasmic p27 expression

Effects of Deliberate Ingestion of Organophosphate or Paraquat on Brain Stem Auditory-Evoked Potentials

Organophosphate (OP) and paraquat (PQ) ingestion is a serious health problem. A common pathology behind OP or PQ poisoning is the generation of reactive oxygen species (ROS) which is known to cause ototoxicity. The aim of the study was to identify the effects of deliberate ingestion of OP or PQ on brain stem auditory-evoked potentials (BAEPs). Consecutive patients with deliberate self-poisoning with OP or PQ who were admitted to a secondary and a tertiary care hospital in the Southern province of Sri Lanka and matched controls were recruited. BAEPs were performed at 1 week (first assessment) and 6 weeks (second assessment) after the exposure. Interpeak latencies of I–III, III–V, and I–V were measured. There were 70 and 28 patients in the OP and PQ arms with the mean age of 32 ± 12 and 29 ± 12 years, respectively. There were 70 controls and their mean age was 33 ± 12 years. In OP and PQ poisoning, 53/70 and 18/28 came for the second assessment, respectively. The interpeak latency was not statistically different in the controls vs the first assessment, controls vs the second assessment, and the first vs the second assessment. There were no significant lesions in the auditory pathway in OP or PQ poisoned patients. The generation of ROS within the perilymphatic space following the ingestion of OP or PQ may not be sufficient to cause lesions in the auditory pathway. Further studies with the assessment of auditory threshold are needed

Evaluating privacy-preserving record linkage using cryptographic long-term keys and multibit trees on large medical datasets.

Background: Integrating medical data using databases from different sources by record linkage is a powerful technique increasingly used in medical research. Under many jurisdictions, unique personal identifiers needed for linking the records are unavailable. Since sensitive attributes, such as names, have to be used instead, privacy regulations usually demand encrypting these identifiers. The corresponding set of techniques for privacy-preserving record linkage (PPRL) has received widespread attention. One recent method is based on Bloom filters. Due to superior resilience against cryptographic attacks, composite Bloom filters (cryptographic long-term keys, CLKs) are considered best practice for privacy in PPRL. Real-world performance of these techniques using large-scale data is unknown up to now. Methods: Using a large subset of Australian hospital admission data, we tested the performance of an innovative PPRL technique (CLKs using multibit trees) against a gold-standard derived from clear-text probabilistic record linkage. Linkage time and linkage quality (recall, precision and F-measure) were evaluated. Results: Clear text probabilistic linkage resulted in marginally higher precision and recall than CLKs. PPRL required more computing time but 5 million records could still be de-duplicated within one day. However, the PPRL approach required fine tuning of parameters. Conclusions: We argue that increased privacy of PPRL comes with the price of small losses in precision and recall and a large increase in computational burden and setup time. These costs seem to be acceptable in most applied settings, but they have to be considered in the decision to apply PPRL. Further research on the optimal automatic choice of parameters is needed

A Non-Human Primate Model for Gluten Sensitivity

Gluten sensitivity is widespread among humans. For example, in celiac disease patients, an inflammatory response to dietary gluten leads to enteropathy, malabsorption, circulating antibodies against gluten and transglutaminase 2, and clinical symptoms such as diarrhea. There is a growing need in fundamental and translational research for animal models that exhibit aspects of human gluten sensitivity.Using ELISA-based antibody assays, we screened a population of captive rhesus macaques with chronic diarrhea of non-infectious origin to estimate the incidence of gluten sensitivity. A selected animal with elevated anti-gliadin antibodies and a matched control were extensively studied through alternating periods of gluten-free diet and gluten challenge. Blinded clinical and histological evaluations were conducted to seek evidence for gluten sensitivity.When fed with a gluten-containing diet, gluten-sensitive macaques showed signs and symptoms of celiac disease including chronic diarrhea, malabsorptive steatorrhea, intestinal lesions and anti-gliadin antibodies. A gluten-free diet reversed these clinical, histological and serological features, while reintroduction of dietary gluten caused rapid relapse.Gluten-sensitive rhesus macaques may be an attractive resource for investigating both the pathogenesis and the treatment of celiac disease

Dynamic polarizability of rotating particles in electrorheological fluids

A rotating particle in electrorheological (ER) fluid leads to a displacement of its polarization charges on the surface which relax towards the external applied field ${\bf E}_0$, resulting in a steady-state polarization at an angle with respect to ${\bf E}_0$. This dynamic effect has shown to affect the ER fluids properties dramatically. In this paper, we develop a dynamic effective medium theory (EMT) for a system containing rotating particles of finite volume fraction. This is a generalization of established EMT to account for the interactions between many rotating particles. While the theory is valid for three dimensions, the results in a special two dimensional configuration show that the system exhibits an off-diagonal polarization response, in addition to a diagonal polarization response, which resembles the classic Hall effect. The diagonal response monotonically decreases with an increasing rotational speed, whereas the off-diagonal response exhibits a maximum at a reduced rotational angular velocity $\omega_0$ comparing to the case of isolated rotating particles. This implies a way of measurement on the interacting relaxation time. The dependencies of the diagonal and off-diagonal responses on various factors, such as $\omega_0$, the volume fraction, and the dielectric contrast, are discussed.Comment: 6 pages, 4 figures, accepted to J. Phys. Chem.