Thresholds of bifurcation of the degree of circular polarization of the bremsstrahlung-generated pump field harmonics in plasma

It is established that, for a Maxwellian plasma in a monochromatic pump field, the phenomenon of bifurcation of the degree of circular polarization of the field harmonics is of a universal nature. A general equation determining the thresholds for this phenomenon for arbitrary harmonics is derived, and a set of its solutions is presented for illustrative purposes.     

Mass Ligand Binding Screening for Receptor Antagonists: Prototype New Drugs and Blind Alleys

Abstract

The ligand binding assay is a powerful tool in the search for antagonists for novel receptors, and for identification of novel classes of antagonists for well-known receptors. Ligand binding mass screening can be adapted for very high throughput. In order for mass screening to be useful, it is necessary to strictly define the binding characteristics for a compound to be considered a putative receptor antagonist. In practice, we have found that synthetic pursuit of a compound with a K_i of ± 1 uM is likely to lead down a blind alley unless very good evidence for specificity is available. Even potent competitors for binding should be thoroughly evaluated in assays of biological activity before a synthetic program is initiated in earnest.     

Open access

Scientific communication is a misnomer. The process of scientific publication is much less a forum where information is exchanged for information than a market where information is exchanged for attention. Nevertheless, the exchange of information for attention is a somewhat peculiar market, since it seems much more natural to sell the information one has produced laboriously for money. Why publish a discovery, why share it with other researchers when knowledge is power?     

On the influence of polyvalent ligands on membrane curvature

The suggestion is made that a polyvalent ligand attached to a membrane will induce a curvature in that membrane which is concave toward the side to which that ligand is bound. This article presents a semiquantitative thermodynamic analysis predicting this effect for a simple system. The criterion for equilibrium of the ligand membrane complex is stated and for the simple system this is calculated for an arbitrary set of parameters. The influence of changes in these parameters is discussed. The energies calculated for this effect are of the order of 0·1 kcal/mol suggesting that for observable effects on curvature an array of such ligands will be needed. Some real systems in which this effect may be playing a role are discussed.     

On evaluation of infection probabilities for different age groups

It is well known that evaluation of parameters for any mathematical model is always very important and often a very difficult problem. This is especially true for agents-based models because as a rule the evaluation of an agent's parameters can be made only based on available information from the higher levels of a complex system. Such problems can be ill-posed or even have a non-unique solution. That is why there is no general algorithm for solving these problems and a researcher has to search for it for every specific model type.     

On statistical inference for the random set generated Cox process with set-marking

Cox point process is a process class for hierarchical modelling of systems of non-interacting points in Rd under environmental heterogeneity which is modelled through a random intensity function. In this work a class of Cox processes is suggested where the random intensity is generated by a random closed set. Such heterogeneity appears for example in forestry where silvicultural treatments like harvesting and site-preparation create geometrical patterns for tree density variation in two different phases. In this paper the second order property, important both in data analysis and in the context of spatial sampling, is derived. The usefulness of the random set generated Cox process is highly increased, if for each point it is observed whether it is included in the random set or not. This additional information is easy and economical to obtain in many cases and is hence of practical value; it leads to marks for the points. The resulting random set marked Cox process is a marked point process where the marks are intensity-dependent. The problem with set-marking is that the marks are not a representative sample from the random set. This paper derives the second order property of the random set marked Cox process and suggests a practical estimation method for area fraction and covariance of the random set and for the point densities within and outside the random set. A simulated example and a forestry example are given.     

Mathematical modeling for functional divergence after gene duplication.

In this paper, I present a statistical framework for modeling the functional divergence after gene duplication. A rate-component model to describe the rate covariation among homologous genes of a gene family is implemented when a phylogenetic tree is known. The Markov chain model is rigorous but may require a huge amount of computational time when the number of sequences is large. On the other hand, the Poisson-based model is mathematically analytical so that computation is very fast even for a large dataset. Moreover, under the posterior framework, we have developed a site-specific profile for predicting important amino acid residues responsible for these functional differences between member genes of a gene family. Our study may have great potential for functional genomics because it is cost-effective, and these predictions can be further tested by biological experimentation.     

Genome analysis technologies: towards species identification by genotype.

Traditional identification of species has been based on phenotypic traits, although it is clear that, theoretically, genotype-based classification is more accurate. This is especially the case for microorganisms which possess less identifiable traits and are more easily influenced by environment. Therefore, technology that allows identification of species based on genotype is highly desirable. Whole genome sequencing can provide a sufficient amount of information and can be determinative for this purpose but is very impractical for routine use. Thus, a competent technology is needed that allows a reproducible reduction in the amount of information required about a whole genome, while still providing sufficiently accurate identification. It is almost imperative for such a technology to be of a high cost-performance and of easy handling. Universality and portability are also strongly desired. Based on these criteria, the current state of genome analysis technologies are reviewed. Among various methodologies discussed here, amplified fragment length polymorphism (AFLP), genome profiling (GP) and microarrays are the subject of particular attention. As species identification is a base for most fields of biology including microbiology, ecology, epidemiology and for various biotechnologies, it is of paramount importance to establish a more efficient, easily handled and more objective methodology, in parallel with conventional phenotype-based methodologies. GP is currently considered to have the most optimal nature for identification of species since it can reproducibly reduce a huge amount of genome information to a manageable size by way of random polymerase chain reaction and can extract a sufficient amount of information for species identification from the DNA fragments thus profiled by temperature gradient gel electrophoresis. The potential ability of DNA microarrays for this purpose is also discussed and promises much for the future.     

Arabidopsis MAP-Kinase 3 Phosphorylates UDP-Glucose Dehydrogenase: a Key Enzyme Providing UDP-Sugar for Cell Wall Biosynthesis

The enzyme UDP-glucose dehydrogenase (UGD) competes with sucrose-phosphate synthase for the common photosynthesis product UDP-glucose. Sucrose-phosphate synthase is part of a pathway for the export of sucrose from source leaves to neighboring cells or the phloem. UGD is a central enzyme in a pathway for many nucleotide sugars used in local cell wall biosynthesis. Here, we identify a highly conserved phosphorylation site in UGD which is readily phosphorylated by MAP-kinase 3 in Arabidopsis. Phosphorylation occurs at a surface-exposed extra loop in all plant UGDs that is absent in UGDs from bacteria or animals. Phosphorylated sucrose-phosphate synthase is shifted to an inactive form which we did not measure for phosphorylated UGD. Plant UGDs have an extra loop which is phosphorylated by AtMPK3. Phosphorylation is not causing a reduction of UGD activity as found for the competitor enzymes and thus sets a preference for maintaining UDP-sugars at a constant level to prioritize cell wall biosynthesis.

     

Deadlock Avoidance for Sequential Resource Allocation Systems: Hard and Easy Cases

Deadlock is a major problem for systems that allocate resources in real time. The key issue in deadlock avoidance is whether or not a given resource allocation state is safe: that is, whether or not there exists a sequence of resource allocations that completes all processes. Although safety is established as NP-complete for certain broad resource allocation classes, newly emerging resource allocation scenarios often exhibit unique features not considered in previous work. In these cases, establishing the underlying complexity of the safety problem is essential for developing the best deadlock avoidance approach. This work investigates the complexity of safe resource allocation for a class of systems relevant in automated manufacturing. For this class, the resource needs of each process are expressed as a well-defined sequence. Each request is for a single unit of a single resource and is accompanied by a promise to release the previously allocated resource. Manufacturing researchers have generally accepted that safety is computationally hard, and numerous suboptimal deadlock avoidance solutions have been proposed for this class. Recent results, however, indicate that safety is often computationally easy. The objective of this article is to settle this question by formally establishing the NP-completeness of safety for this class and investigating the boundary between the hard and easy cases. We discuss several special structures that lead to computationally tractable safety characteristics.     

Gene Genealogies within Mutant Allelic Classes

A coalescent theory of the gene genealogy within an allelic class that arises by a unique mutational event is developed and analyzed. To interpret this theory it was necessary to expand on existing theory for populations of varying size. Two features of the gene genealogy--the average pairwise distance and the total tree length--within the mutant class and within the nonmutant class are found. An index, I, is proposed that describes the extent to which a genealogy is similar to one from a population of constant size (for which I = 0) or to a star genealogy (for which I = 1). The value of I is positive in growing populations and is generally positive for the gene genealogy for the mutant class. The value of I is negative for a population decreasing in size and for the nonmutant class, if the mutant arose recently. The results are discussed in the context of the infinite sites model of mutation, which is appropriate for nucleotide sequence data, and the generalized stepwise mutation model, which is appropriate for microsatellite loci. The same genealogical methods are used to find the probability of at least one recombination event between a nucleotide that defines an allelic class and a marker at a nearby linked site.     

Stereoscopic and contrast-defined motion in human vision.

There is considerable evidence for the existence of a specialized mechanism in human vision for detecting moving contrast modulations and some evidence for a mechanism for detecting moving stereoscopic depth modulations. It is unclear whether a single second-order motion mechanism detects both types of stimulus or whether they are detected separately. We show that sensitivity to stereo-defined motion resembles that to contrast-defined motion in two important ways. First, when a missing-fundamental disparity waveform is moved in steps of 0.25 cycles, its perceived direction tends to reverse. This is a property of both luminance-defined and contrast-defined motion and is consistent with independent detection of motion at different spatial scales. Second, thresholds for detecting the direction of a smoothly drifting sinusoidal disparity modulation are much higher than those for detecting its orientation. This is a property of contrast-modulated gratings but not luminance-modulated gratings, for which the two thresholds are normally identical. The results suggest that stereo-defined and contrast-defined motion stimuli are detected either by a common mechanism or by separate mechanisms sharing a common principle of operation.     

Visualising and assessing the probable error from downscaling ecological time series data

Collecting natural data at regular, fine scales is an onerous and often costly procedure. However, there is a basic need for fine scale data when applying inductive methods such as neural networks or genetic algorithms for the development of ecological models. This paper will address the issues involved in interpolating data for use in machine learning methods by considering how to determine if a downscaling of the data is valid. The approach is based on a multi-scale estimate of errors. The resulting function has similar properties to a time series variogram; however, the comparison at different scales is based on the variance introduced by rescaling from the original sequence. This approach has a number of properties, including the ability to detect frequencies in the data below the current sampling rate, an estimate of the probable average error introduced when a sampled variable is downscaled and a method for visualising the sequences of a time series that are most susceptible to error due to sampling. The described approach is ideal for supporting the ongoing sampling of ecological data and as a tool for assessing the impact of using interpolated data for building inductive models of ecological response.     

A Novel Method for Single Sample Multi-Axial Nanoindentation of Hydrated Heterogeneous Tissues Based on Testing Great White Shark Jaws

Nanomechanical testing methods that are suitable for a range of hydrated tissues are crucial for understanding biological systems. Nanoindentation of tissues can provide valuable insights into biology, tissue engineering and biomimetic design. However, testing hydrated biological samples still remains a significant challenge. Shark jaw cartilage is an ideal substrate for developing a method to test hydrated tissues because it is a unique heterogeneous composite of both mineralized (hard) and non-mineralized (soft) layers and possesses a jaw geometry that is challenging to test mechanically. The aim of this study is to develop a novel method for obtaining multidirectional nanomechanical properties for both layers of jaw cartilage from a single sample, taken from the great white shark (Carcharodon carcharias). A method for obtaining multidirectional data from a single sample is necessary for examining tissue mechanics in this shark because it is a protected species and hence samples may be difficult to obtain. Results show that this method maintains hydration of samples that would otherwise rapidly dehydrate. Our study is the first analysis of nanomechanical properties of great white shark jaw cartilage. Variation in nanomechanical properties were detected in different orthogonal directions for both layers of jaw cartilage in this species. The data further suggest that the mineralized layer of shark jaw cartilage is less stiff than previously posited. Our method allows multidirectional nanomechanical properties to be obtained from a single, small, hydrated heterogeneous sample. Our technique is therefore suitable for use when specimens are rare, valuable or limited in quantity, such as samples obtained from endangered species or pathological tissues. We also outline a method for tip-to-optic calibration that facilitates nanoindentation of soft biological tissues. Our technique may help address the critical need for a nanomechanical testing method that is applicable to a variety of hydrated biological materials whether soft or hard.     

一类双线性生态系统的无源控制

研究了一类广义双线性系统的无源控制问题,利用广义Lyapunov函数和线性矩阵不等式,给出了广义双线性系统无源且零解渐近稳定的充分条件,并在一定条件下得到存在状态反馈控制器,使得闭环系统无源且零解渐近稳定的充分条件,同时给出相应的控制器构造方法。     

An approximation method for the determination of diffusion and permeability coefficients in nerve trunks

A recently introduced approximation method is applied in order to obtain an expression for the amount of a substance remaining within a nerve at any time, the nerve having been soaked for a long time in a solution containing the substance until the time zero when it is bathed in the same solution but without the substance. The case of a uniform nerve without a sheath leads to substantially the same results as previously obtained by A. V. Hill (1928) for this case. A solution is given for the case of a nerve without sheath but having fibers which are permeable. In this case it is shown how an effective diffusion coefficient for the interstitial fluid can be obtained, as well as the effective inward and outward fiber permeabilities. A solution is given for the case of a nerve with a sheath in which the substance considered does not penetrate the fibers, and it is shown how the effective diffusion coefficients of the sheath and the interstitial fluid can be obtained.     

Homozygosity in a population of variable size and mutation rate

A formula is obtained for the probability that two genes at a single locus, sampled at random from a population at time t, are of particular types. The model assumed is a diffusion approximation to a neutral Wright-Fisher model in which mutation is not necessarily symmetric and the population size is a function of time. It is shown that for symmetric mutation in a population undergoing a step-function type bottleneck, homozygosity increases with decreasing population size. A formula is given for the distribution of the number of segregating sites occurring in two randomly sampled sequences of completely linked sites, with general mutation at a site and identical mutation structure between sites.We give similar results for a population of fixed size but for which the mutation rate is a function of time, and not necessarily symmetric. We confirm the intuitively clear effect that increasing the mutation rate decreases homozygosity.     

Parallel dose-response curves in combination experiments

A possible experimental design for combination experiments is to compare the doseresponse curve of a single agent with the corresponding curve of the same agent using either a fixed amount of a second one or a fixed dose ratio. No interaction is then often defined by a parallel shift of these curves. We have performed a systematic study for various types of doseresponse relations both for the dose-additivity (Loewe additivity) and for the independence (Bliss independence) criteria for defining zero interaction. Parallelism between doseresponse curves of a single agent and those of the same agent in the presence of a fixed amount of another one is found for the Loewe-additivity criterion for linear doseresponse relations. For nonlinear relations, one has to differentiate between effect parallelism (parallel shift on the effect scale) and dose parallelism (parallel shift on the dose scale). In the case of Loewe additivity, zero-interaction dose parallelism is found for power, Weibull, median-effect and logistic doseresponse relations, given that special parameter relationships are fulfilled. The mechanistic model of competitive interaction exhibits dose parallelism but not effect parallelism for Loewe additivity. Bliss independence and Loewe additivity lead to identical results for exponential doseresponse curves. This is the only case for which dose parallelism was found for Bliss independence. Parallelism between single-agent doseresponse relations and Loewe additivity mixture relations is found for examples with a fixed doseratio design. However, this is again not a general property of the design adopted but holds only if special conditions are fulfilled. The comparison of combination doseresponse curves with single-agent relations has to be performed taking into account both potency and shape parameters. The results of this analysis lead to the conclusion that parallelism between zero interaction combination and single-agent doseresponse relations is found only for special cases and cannot be used as a general criterion for defining zero-interaction in combined-action assessment even if the correct potency shift is taken into account.     

Voltage clamp calculations for myelinated and demyelinated axons

Exact cable theory is used to calculate voltage distributions along fully myelinated axons and those with various patterns of demyelination. The model employed uses an R-C circuit for the soma, an equivalent cable for the dendrites, a myelinated axon with n internodes and a cable representing telodendria. For the case of a voltage clamp at the soma, a system of 2n + 1 equations must be solved to obtain the potential distribution and this is done for arbitrary n. An explicit calculation is performed for one internode whereas computer-generated solutions are obtained for several internodes. The relative importance of the position of a single demyelinated internode is determined. An approximate expression is given for the critical internodal length necessary for action potential generation.