A new method for inferring hidden markov models from noisy time sequences

We present a new method for inferring hidden Markov models from noisy time sequences without the necessity of assuming a model architecture, thus allowing for the detection of degenerate states. This is based on the statistical prediction techniques developed by Crutchfield et al. and generates so called causal state models, equivalent in structure to hidden Markov models. The new method is applicable to any continuous data which clusters around discrete values and exhibits multiple transitions between these values such as tethered particle motion data or Fluorescence Resonance Energy Transfer (FRET) spectra. The algorithms developed have been shown to perform well on simulated data, demonstrating the ability to recover the model used to generate the data under high noise, sparse data conditions and the ability to infer the existence of degenerate states. They have also been applied to new experimental FRET data of Holliday Junction dynamics, extracting the expected two state model and providing values for the transition rates in good agreement with previous results and with results obtained using existing maximum likelihood based methods. The method differs markedly from previous Markov-model reconstructions in being able to uncover truly hidden states.     

Pulmonary fibrosis in L-NAME-treated mice is dependent on an activated endothelin system

Activation of the endothelin (ET) system promotes vasoconstriction, inflammation, and fibrosis in various tissues, including the lung. Therefore, ET-1 transgenic mice overexpressing ET-1 develop pulmonary fibrosis in a slow, age-dependent manner. In vivo, NO is the most important counterregulatory mediator of the ET system and decreases ET-1 promoter activity. The aim of our study was to elucidate the impact on pulmonary inflammation and fibrosis of the interaction between NO and the ET system in young ET-1 transgenic mice before the onset of pulmonary fibrosis. Male ET-1 transgenic mice and wild-type littermates at the age of 8 weeks were randomly allocated to the following 6 groups: WT (n = 11), wild-type animals without treatment; WT + l-NAME (n = 14), wild-type animals receiving l-NAME, an inhibitor of NO synthase; WT + l-NAME + LU (n = 13), wild-type animals receiving l-NAME and LU 302872, a dual ETA/ETB-receptor antagonist; ET1tg (n = 10), ET-1 transgenic mice; ET1tg + l-NAME (n = 13); and ET1tg + l-NAME + LU (n = 13). After 6 weeks, animals were euthanized, and hearts and lungs were harvested for histology and immunohistochemistry. No differences in pulmonary inflammation, as indicated by macrophage infiltration, or in interstitial fibrosis were observed between WT and ET1tg mice at baseline; however, inflammation and interstitial fibrosis were significantly enhanced in ET1tg mice, but not in WT groups, after l-NAME treatment. The combined ETA/ETB-receptor antagonist LU 302872 abolished inflammation and interstitial fibrosis in l-NAME-treated ET1tg mice. Perivascular fibrosis and media/lumen ratio of pulmonary bronchi and arteries did not differ between all study groups. In our study l-NAME induced pulmonary fibrosis and inflammation only in young ET1tg mice. Additional treatment with LU 302872 abolished these effects. We thus conclude that an imbalance between an activated ET system and a suppressed NO system contributes to pulmonary inflammation and fibrosis.     

An improved enzyme-linked immunoassay for the detection and quantification of the entomocidal parasporal crystal proteins of Bacillus thuringiensis subsp. kurstaki and israelensis

An improved and simplified enzyme-linked immunosorbent assay (ELISA) was developed for the detection and quantification of parasporal crystalline toxins from Bacillus thuringiensis subsp. kurstaki. The improved procedure involved pretreatment of the polystyrene cuvettes with glutaraldehyde before antibody coating. A direct comparison of treated and untreated cuvettes is provided. ELISAs were then used for the analysis of the entomocidal crystalline proteins in commercial and experimental formulations of B. thuringiensis subspp. kurstaki and israelensis.     

Chromosomal investigations in children with pyknolepsy on dipropylacetate monotherapy

Summary We analyzed chromosome preparations obtained from leukocytes of ten children with pyknolepsy and treated with dipropylacetate (DPA) as monotherapy. Structural or numerical aberrations were not found more frequently in our patients than in five normal children (control group).     

Physical and biological properties of an epsilon-heavy chain mRNA and a kappa-light chain mRNA coding for rat immunoglobulin E

The mRNA coding for epsilon-heavy chain and kappa-light chain have been highly enriched from a rat IgE-producing myeloma, IR-162. Based on denaturing gel analyses, the 20 S epsilon-heavy chain mRNA has an estimated molecular weight of 850,000, equivalent to about 2500 nucleotides. The 14S rat kappa-light chain mRNA has an estimated molecular weight of 410,000, equivalent to about 1200 nucleotides. Only about two-thirds of the length of these mature cytoplasmic rat mRNA code for protein. The 20 S mRNA stimulates the in vitro synthesis of a single major serologically related protein which is large enough to be epsilon-heavy chain. It is unglycosylated and has an apparent molecular weight of about 62,000. The in vivo unglycosylated epsilon-heavy chain, obtained in the presence of tunicamycin, has an apparent molecular weight of about 59,000, compared with about 76,000 for the glycosylated heavy chain of the secreted rat IgE. Therefore, the in vitro synthesized epsilon-heavy chain protein is about Mr = 3000 larger than the in vivo unglycosylated epsilon-heavy chain, equivalent to about 25 extra amino acids. This is consistent with the synthesis of an epsilon-heavy chain putative precursor. Likewise, the 14 S mRNA stimulates the in vitro synthesis of a single putative precursor protein, which is serologically related to kappa chain, is unglycosylated, and is about an extra 20 amino acids. This is the first report on the physical and biological properties of an epsilon-heavy chain mRNA, as well as any rat immunoglobulin mRNA.     

Spatiotemporal Effects of Supplementary Feeding of Wild Boar (Sus scrofa) on Artificial Ground Nest Depredation

Supplementary feeding of ungulates, being widely used in game management, may have unwanted consequences. Its role in agricultural damage is well-studied, but few studies have considered the potential for the practice to attract ground nest predators. Our goal was to identify the factors influencing ground nest predation in the vicinity of year-round supplementary feeding sites for wild boar and to characterise their spatiotemporal scope. We conducted two separate artificial ground nest experiments in five different hunting districts in south-eastern Estonia. The quantity of food provided and distance of a nest from the feeding site were the most important factors determining predation risk. Larger quantities of food resulted in higher predation risk, while predation risk responded in a non-linear fashion to distance from the feeding site. Although predation risk eventually decreases if supplementary feeding is ceased for at least four years, recently abandoned feeding sites still pose a high predation risk.