Novel Approach to Simulate Sleep Apnea Patients for Evaluating Positive Pressure Therapy Devices

Bench testing is a useful method to characterize the response of different automatic positive airway pressure (APAP) devices under well-controlled conditions. However, previous models did not consider the diversity of obstructive sleep apnea (OSA) patients’ characteristics and phenotypes. The objective of this proof-of-concept study was to design a new bench test for realistically simulating an OSA patient’s night, and to implement a one-night example of a typical female phenotype for comparing responses to several currently-available APAP devices. We developed a novel approach aimed at replicating a typical night of sleep which includes different disturbed breathing events, disease severities, sleep/wake phases, body postures and respiratory artefacts. The simulated female OSA patient example that we implemented included periods of wake, light sleep and deep sleep with positional changes and was connected to ten different APAP devices. Flow and pressure readings were recorded; each device was tested twice. The new approach for simulating female OSA patients effectively combined a wide variety of disturbed breathing patterns to mimic the response of a predefined patient type. There were marked differences in response between devices; only three were able to overcome flow limitation to normalize breathing, and only five devices were associated with a residual apnea-hypopnea index of <5/h. In conclusion, bench tests can be designed to simulate specific patient characteristics, and typical stages of sleep, body position, and wake. Each APAP device behaved differently when exposed to this controlled model of a female OSA patient, and should lead to further understanding of OSA treatment.     

On Comparing Correlated Means in the Presence of Incomplete Data

Two statistics are proposed for testing the hypothesis of equality of the means of a bivariate normal distribution with unknown common variance and correlation coefficient when observations are missing on both variates. One of the statistics reduces to the one proposed by Bhoj (1978, 1984) when the unpaired observations on the variates are equal. The distributions of the statistics are approximated by well known distributions under the null hypothesis. The empirical powers of the tests are computed and compared with those of some known statistics. The comparison supports the use of one of the statistics proposed in this paper.     

Modeling of nitrogen transformations and translocations

Different submodels within complex model packages on N regimes-for plant N-uptake, net N-mineralization, nitrate leaching and microbial N immobilization-are critically reviewed mainly with regard to their prediction ability on the basis of three comparative papers. Only for some of the processes adequate statistical evaluation of the models was possible. Compared to the other statistically evaluable process, nitrate leaching, modeling of plant N-uptake yields the better results. Most models for mineralization use arbitrary approaches rather than empirical ones. Although only approximate estimates of N mineralisation were at hand, the models generally behave expectedly poor. Only one model-DAISY-out of 16 involved in the comparison uses an explicit microbial biomass sub-model including microbial growth, decline and maintenance terms. So DAISY is the only model coupling C and N cycles. But what is true for an individual model describing the C and N transformation of a lab incubation experiment seems to be valid for most of the complex simulation work on the C and N regimes: this model was said to be overparameterized with respect to the available data.     

Plant regeneration via somatic embryogenesis in chickpea (Cicer arietinum L.)

Efficient plant regeneration via somatic embryogenesis has been developed in chickpea cultivar C235. Leaf explants, on MS medium supplemented with 1.25 mg/l 2,4-D and 0.25 mg/l kinetin, yielded somatic embryos with high efficiency during dark incubation. MS medium supplemented with B₅ vitamins, 0.125 mg/l IBA and 2 mg/l BAP was found suitable for embryo maturation. The well formed embryos germinated into plantlets on basal B₅ medium supplemented with 0.25 mg/l BAP. Further development into healthy plantlets was obtained on basal B₅ medium. Hardened plantlets produced normal, fertile plants upon transfer to soil.Abbreviations 2,4-D 2,4-dichlorophenoxyacetic acid - BAP 6-Benzyl-aminopurine - IAA IndoIe-3-acetic acid - IBA Indole-3-butyric acid - NAA 1-Naphthalene acetic acid - Kinetin 6-furfuryl aminopurine - Zeatin 6-(4-hydroxy-3-methylbut-2-enylamino)-purine     

Determination of chemical biodegradation by direct and indirect methods

Summary Degradation of 10 organic chemicals by pre-acclimated microorganisms in BOD dilution water was determined directly by UV spectrophotometry and indirectly by a modified BOD method. Residual chemical concentrations were periodically measured and pseudo-first-order biodegradation rate constants (k ₁) were calculated. Thek ₁ spectrophotometry values ranged from 0.006/h to 0.077/h andk ₁-BOD values from 0.002/h to 0.043/h for 1-methylnaphthalene and indole, respectively. The ratios ofk spectrophotometry to k₁-BOD were between 1.5 for salicylic acid and 3.0 for 1-methylnaphthalene with a mean of 2.7. A significant (=0.001) linear correlation (r ²=0.854,F=46.630) existed between the two sets of rate constants. Results from this study suggest that the modified BOD method may be used to estimate chemical biodegradation rates in synthetic media.     

Rapid Identification of Viable Bacterial Spores Using a Fluorescence Method

A method has been devised to differentiate viable and nonviable bacterial spores. “Germination-like” changes are initiated in spores with performic acid and lysozyme. The germinated spores are stained with aqueous acridine orange, a fluorescent dye. Nonviable spores fluoresce lemon-green and viable spores orange-red. It is proposed that with the use of a membrane filter resistant to performic acid and lysozyme, the method may be used for spore enumeration in foods in about 4 hr compared to conventional plating methods, which usually require up to 72 hr.     

Xanthone and flavonol constituents of Swertia hookeri

The whole plant of Swertia hookeri, collected at flowering has been shown to contain two tri- and nine tetraoxygenated free, glucosyloxy, and stearyl ester xanthones and one flavonol stearyl ester. Among these, three are previously unreported in nature and one was known previously only as a synthetic compound. The xanthones are based on 1,3,5,-, 1,3,5,8- and 1,3,7,8-oxygenated systems with the middle oxygenation pattern predominating. The two ester compounds appeared only at the flowering stage. Plants collected at the pre-flowering stage gave the corresponding free compounds. The biochemical and biological significance of these findings are appraised.     

Potent growth suppressive activity of curcumin in human breast cancer cells: Modulation of Wnt/β-catenin signaling

Abnormal activation of the Wnt/β-catenin signaling pathway and subsequent upregulation of β-catenin driven downstream targets—c-Myc and cyclin D1 is associated with development of breast cancer. The objective of our study was to determine if curcumin could modulate the key elements of Wnt pathway in breast cancer cells; an effect that might underscore its usefulness for chemoprevention/treatment of this malignancy. Curcumin showed a cytotoxic effect on MCF-7 cells with 50% inhibitory concentration (IC₅₀) of 35 μM; while IC₅₀ for MDA-MB-231 cells was 30 μM. Treatment with low cytostatic dose of 20 μM curcumin showed G₂/M arrest in both breast cancer cells. The effect of curcumin (20 μM) treatment on expression of Wnt/β-catenin pathway components in breast cancer cells (MCF-7 and MDA-MB-231) was analyzed by immunofluorescence and Western blotting. Curcumin was found to effectively inhibit the expression of several Wnt/β-catenin pathway components—disheveled, β-catenin, cyclin D1 and slug in both MCF-7 and MDA-MB-231. Immunofluorescence analysis showed that curcumin markedly reduced the nuclear expression of disheveled and β-catenin proteins. Further, the protein levels of the positively regulated β-catenin targets—cyclin D1 and slug, were downregulated by curcumin treatment. The expression levels of two integral proteins of Wnt signaling, GSK3β and E-cadherin were also altered by curcumin treatment. In conclusion, our data demonstrated that the efficacy of curcumin in inhibition of cell proliferation and induction of apoptosis might occur through modulation of β-catenin pathway in human breast cancer cells.     

An interrupted beta-propeller and protein disorder: structural bioinformatics insights into the N-terminus of alsin

Defects in the human ALS2 gene, which encodes the 1,657-amino-acid residue protein alsin, are linked to several related motor neuron diseases. We created a structural model for the N-terminal 690-residue region of alsin through comparative modelling based on regulator of chromosome condensation 1 (RCC1). We propose that this alsin region contains seven RCC1-like repeats in a seven-bladed beta-propeller structure. The propeller is formed by a double clasp arrangement containing two segments (residues 1–218 and residues 525–690). The 306-residue insert region, predicted to lie within blade 5 and to be largely disordered, is poorly conserved across species. Surface patches of evolutionary conservation probably indicate locations of binding sites. Both disease-causing missense mutations—Cys157Tyr and Gly540Glu—are buried in the propeller and likely to be structurally disruptive. This study aids design of experimental studies by highlighting the importance of construct length, will enhance interpretation of protein–protein interactions, and enable rational site-directed mutagenesis. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

New furofurano lignans from Justicia simplex

A new 3,7-dioxabicyclo[3,3,O]octane lignan, named justisolin, and a new lignan O-glucoside, named simplexoside, were isolated from the whole plant of Justicia simplex D. Don. (Acanthaceae), collected at fruiting. The structure of the free lignan was established as 2e-(3,4-methylenedioxy-6-hydroxy)-phenyl-6e- Piperonyl-3,7-dioxabicyclo[3,3,0]octane (1) and that of the glucoside as 2e-(3-methoxy-4-O-β-d- glucopyranosyl)-phenyl-6e-piperonyl-3,7-dioxabicyclo[3,3,0]octane (2) on the basis of chemical transformation and spectral evidence. The biological functions of these and related lignans are appraised.