Modified moving average analysis of T-wave alternans to predict ventricular fibrillation with high accuracy.

T-wave alternans is a marker of cardiac electrical instability with the potential for arrhythmia risk stratification. The modified moving average method was developed to measure alternans in settings with artifacts, noise, and nonstationary data. Algorithms were developed and performance characteristics were validated with simulated electrocardiograms (ECGs). Experimental laboratory ECGs with dynamically changing alternans values were analyzed. Alternans values estimated by modified moving average analysis correlated strongly with input alternans values (r(2) = 0.9999). Rapidly changing alternans levels and phase reversals did not perturb the measurement. When heart rate was increased from 60 to 180 beats/min, with T-wave alternans apex moving from 237 to 103 ms after the R wave, the measured alternans peak varied <5% from input value. Simulated 50- to 1,000-microV motion artifact spikes typical of treadmill ECGs produced inaccuracies <2%. Alternans values in experimental laboratory study using standard electrodes tracked vulnerability to myocardial ischemia-induced ventricular fibrillation with 100% sensitivity and specificity at a cut point of 0.75 mV. Modified moving average analysis is a robust method that precisely measures T-wave alternans in settings with artifacts, noise, and nonstationary data typical of clinical ECGs and yields an accurate estimate of risk for ventricular fibrillation.     

How reliable are dung counts for estimating elephant numbers?

Dung counts are the most commonly used techniques for estimating elephant numbers in forests, yet there is considerable scepticism concerning their accuracy. Published accounts of dung counts show that they give estimates similar to those from other methods for vertebrates ranging in size from lizards to elephants. For ungulates, macropods and elephants there are strong correlations between estimates from dung counts and other methods. Thus, dung counts are as accurate or inaccurate as other methods for estimating vertebrate numbers, including elephants. Dung counts for elephants give estimates that are as precise as, and sometimes more precise than, those from aerial surveys of elephants. This is because the variance in dung density is usually low and results in a lower than expected variance for the final elephant estimate when combined with the variances of defecation and decay rates. Dung counts may be more appropriate than aerial surveys for monitoring small or declining elephant populations.     

Micropropagation of Dendrocalamus asper {Schult. & Schult. F.} Backer ex k. Heyne): an exotic edible bamboo

Effect of season, media type, carbon source, growth regulators and transplanting media on micropropagation of Dendrocalamus asper, an important bamboo species, was examined. The season of explant collection played an important role in axillary bud sprouting and spring (February?CApril) was found to be the best period for explant collection. Among the different media MS was found to be the best for micropropagation. Maximum numbers (4.83/explant) of shoots were initiated in MS?+?15???M BAP. For shoot multiplication, MS medium supplemented with 10???M BAP and 75???M Adenine sulfate was used. BAP was superior to KIN for both explant establishment, as well as, shoot multiplication. Optimal rooting was achieved in shoots cultured on ? strength MS medium supplemented with 5???M each of IBA and NAA. Regenerated plantlets were acclimatized and hardened in green house using dune sand and vermi-compost (3:1) with 92.34% success and transferred to the field with 100% survival rate. In the field, plants supplied with FYM along with urea showed better growth and development. Macroproliferation, plant multiplication by separating the rooted tillers of well established in vitro raised plantlets after 5 to 6?months of growth in the green house could double the multiplication rate. More than 25000 in vitro raised plants were successfully transferred to the field and no morphological variations in growth were observed, thus proving the potential of tissue culture for raising large scale plantations of D. asper.     

Signaling pathways involved in thyroid hyperfunction and growth in Graves' disease.

The elucidation of the multiple signaling cascades coupled to the TSH receptor has offered new approaches in the understanding of the pathogenesis of Graves' disease. Here we review findings showing that immunoglobulins from Graves' patients are heterogeneous, bind to different epitopes and, similarly to TSH, activate different signaling pathways, including adenylyl cyclase, phospholipase C and phospholipase A2. Evidence that the multiplicity of signals correlates with the different manifestations of the disease is also summarized. We believe that the dissection of the molecular mechanisms involved in the pathogenesis of Graves' disease offers the basis for developing novel therapeutical approaches to this disease.     

Alterations in catalytic activity and virus maturation produced by mutation of the conserved histidine residues of herpes simplex virus type 1 protease.

Mutant herpes simplex virus type 1 (HSV-1) viruses were constructed to characterize the roles of the conserved histidine residues (H61 and H148) of HSV-1 protease in the regulation of catalytic activity and virus maturation. Viruses containing mutations at H61 (H61V-V711, H61Y-V715, and H61A-V730) were unable to grow on Vero cells. These mutant viruses could process neither Pra to N0 nor ICP-35cd to ICP-35ef. Transmission electron microscopy studies of H61A-V730-infected Vero cells indicated that capsid maturation is arrested at a state characterized by the predominance of large symmetrical arrays of B capsids within the nucleus. Two mutations at H148 (in viruses H148A-V712 and H148E-V728) gave rise to mutant viruses that grew with a small-plaque phenotype; one of the viruses, H148E-V728, was particularly attenuated when grown at a low multiplicity of infection. The rate of processing of Pra to N0 in infected Vero cells increased in the order H148A-V712 < H148E-V728 < parental strain HSV-1-V731. The observation that H148A-V712 processes Pra to N0 and ICP-35cd to ICP-35ef, whereas H61A does not, establishes H61 as the catalytically essential conserved His assuming that HSV-1 protease, like other serine proteases, utilizes an active-site histidine residue in catalysis. Two of the mutations at H148 (viruses H148K-V729 and H148Y-V716) produced nonviable viruses. H148K-V729 processed neither Pra to N0 nor ICP-35cd to ICP-35ef, whereas H148Y-V716 processed Pra to N0 but did not process ICP-35cd to ICP-35ef. The range of phenotypes observed with the H148 mutant viruses suggests that residue 148 of the HSV-1 protease is a determinant of virus growth rate and viability because of its effects on the activity of the protease and/or the role of the protease domain in capsid assembly and DNA packaging.     

Contrast-FEL—A Test for Differences in Selective Pressures at Individual Sites among Clades and Sets of Branches

A number of evolutionary hypotheses can be tested by comparing selective pressures among sets of branches in a phylogenetic tree. When the question of interest is to identify specific sites within genes that may be evolving differently, a common approach is to perform separate analyses on subsets of sequences and compare parameter estimates in a post hoc fashion. This approach is statistically suboptimal and not always applicable. Here, we develop a simple extension of a popular fixed effects likelihood method in the context of codon-based evolutionary phylogenetic maximum likelihood testing, Contrast-FEL. It is suitable for identifying individual alignment sites where any among the K≥2 sets of branches in a phylogenetic tree have detectably different ω ratios, indicative of different selective regimes. Using extensive simulations, we show that Contrast-FEL delivers good power, exceeding 90% for sufficiently large differences, while maintaining tight control over false positive rates, when the model is correctly specified. We conclude by applying Contrast-FEL to data from five previously published studies spanning a diverse range of organisms and focusing on different evolutionary questions.