A two-state recurrent stochastic model with time-dependent transition rates.

The two-state recurrent stochastic model with time-independent transition rates is generalized to a model with time-dependent transition rates. The rates can be any general function of external time, that is, any general function of the calendar time in which the process unfolds. Formulas for the state transition probabilities, the proportion of individuals in a particular state at time t, the distribution function, and the expectation of the number of individuals in a particular state at time t are derived.     

Cholesterol rules: direct observation of the coexistence of two fluid phases in native pulmonary surfactant membranes at physiological temperatures

Pulmonary surfactant, the lipid-protein material that stabilizes the respiratory surface of the lungs, contains approximately equimolar amounts of saturated and unsaturated phospholipid species and significant proportions of cholesterol. Such lipid composition suggests that the membranes taking part in the surfactant structures could be organized heterogeneously in the form of inplane domains, originating from particular distributions of specific proteins and lipids. Here we report novel results concerning the lateral organization of bilayer membranes made of native pulmonary surfactant where the coexistence of two distinct micrometer sized fluid phases (fluid ordered and fluid disordered-like phases) is observed at physiological temperatures by using fluorescence microscopy and atomic force microscopy. Additional experiments using fluorescent-labeled proteins SP-B and SP-C show that at physiological temperatures these hydrophobic proteins are located exclusively in the fluid disordered-like phase. Most interestingly, the microscopic coexistence of fluid phases is maintained up to 37.5 degrees C, where most fluid ordered phases melt. This observation suggests that the particular composition of this material is naturally designed to be at the "edge" of a lateral structure transition under physiological conditions, likely providing particular structural and dynamic properties for its mechanical function. The observed lateral structure in native pulmonary surfactant membranes is dramatically affected by the extraction of cholesterol, an effect not observed upon extraction of the surfactant proteins. Furthermore, the spreading properties of the native surfactant material at the air-liquid interface were also greatly affected by cholesterol extraction, suggesting a connection between the observed lateral structure and a physiologically relevant function of the material. We suggest that the particular lipid composition of surfactant could be finely tuned to provide, under physiological conditions, a structural scaffold for surfactant proteins to act at appropriate local densities and lipid composition.     

The evolution of recombination in permanent translocation heterozygotes

The evolution of a selectively neutral locus that controls the degree to which alleles at a single selected locus are linked with a particular set of chromosomes in a permanent translocation heterozygote is studied. With complete selfing and fitness overdominance a new allele at the modifying locus will increase in frequency if it increases the linkage of all alleles at the selected locus to a particular set of chromosomes. With random mating a new allele at the modifying locus will increase when rare if it increases the linkage of alleles at the selected locus to a particular set of chromosomes. In addition, a parameter analogous to the coefficient of linkage disequilibrium in usual two-locus models with random mating must be nonzero if a new allele at the modifying locus is to increase in frequency at a geometric rate when rare. With mixed selfing and random mating a new allele at the modifying locus will apparently increase when rare only if it increases the linkage of alleles at the selected locus to a particular set of chromosomes.     

The determination of the best interests in relation to childhood immunisation

There are many different ethical arguments that might be advanced for and against childhood vaccinations. In this paper I explore one particular argument that focuses on the idea that such vaccinations are justifiable because they are held to be in the best interests of a particular child. Two issues arise from this idea. The first issue is how best interests are to be determined in this case. The second issue is what follows from this to justify potential interventions within the family in relation to such vaccinations. I argue that best interests must be characterised objectively in such situations and that this means that, in at least some cases, parental decision-making about vaccinating their children may be overridden.     

Comparative use of amino acids by three auxotypes of Neisseria gonorrhoeae

Auxotypes of Neisseria gonorrhoeae are usually distinguishable by their particular requirements for growth; these requirements often include amino acids. It is possible that strains needing particular substrates to grow can be distinguished not merely by their growth requirements but also by their metabolism of these particular substrates. In this work amino acid utilization and oxidation studies were performed enabling prototype, pro- and thia-strains to be distinguished. The metabolism study also underlined the importance of proline as an energy source and pointed to the probability of distinct relationships with the metabolism of the key amino acids, glutamic and aspartic acids, for the three auxotypes.It is proposed that the specific amino acid required by the naturally occurring auxotype serves as an energy source at the site of infection and has important implications with respect to particular auxotypes at various sites.     

The determination of 'best interests' in relation to childhood vaccinations

There are many different ethical arguments that might be advanced for and against childhood vaccinations. In this paper I will explore one particular argument that focuses on the idea that childhood vaccinations are justifiable because they are held to be in the best interests of a particular child. Two issues arise from this idea. The first issue is how best interests are to be determined in the case of childhood vaccinations. The second issue is what follows from this to justify potential interventions within the family in relation to such vaccinations. I argue that best interests must be characterised objectively in such situations and that this means that, in at least some cases, parental decision-making about vaccinating their children may be overridden.     

Vision in Flies: Measuring the Attention Span

A visual stimulus at a particular location of the visual field may elicit a behavior while at the same time equally salient stimuli in other parts do not. This property of visual systems is known as selective visual attention (SVA). The animal is said to have a focus of attention (FoA) which it has shifted to a particular location. Visual attention normally involves an attention span at the location to which the FoA has been shifted. Here the attention span is measured in Drosophila. The fly is tethered and hence has its eyes fixed in space. It can shift its FoA internally. This shift is revealed using two simultaneous test stimuli with characteristic responses at their particular locations. In tethered flight a wild type fly keeps its FoA at a certain location for up to 4s. Flies with a mutation in the radish gene, that has been suggested to be involved in attention-like mechanisms, display a reduced attention span of only 1s.     

The mathematical logic of life

Protein synthesis can be likened to a particular coded information storage, transmission and execution system. Noise, error or mutations are the essential phenomena to which a living organism is subjected. Genetic coding aims at preserving the integrity of a structure under aggression from the surroundings. It can be shown that the different amino acids translated in the proteins, except the particular case of SER, obey a logical code for optimization of resistance to mutation effects. The study of the structure of this code allows a better comprehension of the logic of life.     

一种作物种植的气候适应性模糊综合评价方法的探讨

提出了一种作物种植的气候适应性的模糊综合评价方法．作物种植的气候适应性可定义为一定地理环境下,其自然气候条件能满足作物生长所需适宜气候条件的能力．在相同的地理环境下,作物种植的气候适应性因作物种类不同而表现不一,并可表示为该地理环境提供的自然气候条件对不同作物生长所需适宜气候条件的满足程度．作物种植的气候适应性的模糊综合评价包括以下主要步骤：确定影响作物种植的主要气候因子,确定各因子的权重,建立评价因子集并确定气候因子评价标准、建立评价矩阵和计算作物生长气候适应性等.采用该方法对武夷山北坡不同海拔高度柑桔和茶树种植的气候适应性进行了综合评价．     

Analysis of slow-binding enzyme inhibitors at elevated enzyme concentrations

The improvement in the characterization of slow-binding inhibitors achieved by performing experiments at elevated enzyme concentrations is presented. In particular, the characterization of slow-binding inhibitors conforming to a two-step mode of inhibition with a steady-state dissociation constant that is much lower than the initial dissociation constant with enzyme is discussed. For these systems, inhibition is rapid and low steady-state product concentrations are produced at saturating inhibitor concentrations. By working at elevated enzyme concentrations, improved signal-to-noise ratios are achieved and data may be collected at saturating inhibitor levels. Numerical simulations confirmed that improved parameter estimates are obtained and useful data to discern the mechanism of slow-binding inhibition are produced by working at elevated enzyme concentrations. The saturation kinetics that were unobservable in two previous studies of an enzyme inhibitor system were measured by performing experiments at an elevated enzyme concentration. These results indicate that consideration of the quality of the data acquired using a particular assay is an important factor when selecting the enzyme concentration at which to perform experiments used to characterize the class of enzyme inhibitors examined herein.     

A simpler, more general method of finding the optimal foraging strategy for Bayesian birds

Oaten's (1977) stochastic model for optimal foraging in patches has been solved for a number of particular cases. A few cases, such as Poisson prey distribution and either systematic or random search, are easy to solve. In other cases, such as binomial prey distribution and random search, the form of the optimal strategy may be found using a theorem of McNamara, although more work is required to find which particular rule of the proper form is actually best. More generally (but not completely generally), optimal strategies may be found using dynamic programming. This requires that the number of prey found up to a particular time is a sufficient statistic for the number of prey remaining in a patch. This requirement cannot be dispensed with, but other simplifying assumptions that were used in the past are not necessary. In particular, it is not necessary, even for the sake of convenience, to assume that prey distribution has a form convenient for Bayesian analysis, such as a beta mixture of binomials or a gamma mixture of Poissons. Any prey distribution may be used if whatever prey are in a patch are located at random, and if search either is systematic for discrete time or for continuous time, or is random for continuous time. In earlier work, some pains had to be taken to find the rate of finding prey achieved by a given candidate strategy, but this is not necessary if expected gains and expected times are calculated routinely for each potential stopping point during dynamic programming. A new, simple method of finding optimal strategies is illustrated for discrete time and systematic search. This paper is based on a talk given at the Fifth Hans Kristiansson Symposium held in Lund, Sweden in August, 2003. The subject of the symposium was Bayesian foraging.     

Moral agency,moral worth and the question of double standards in medical research in developing countries

International regulations governing medical research, healthcare and medical practice, are, obviously, meant to be guidelines and not detailed procedural rules of thumb that can be applied unreflectively without any danger of doing moral wrong. Moreover, such regulations are meant to apply internationally, and no set of straight-jacketed rules of thumb can conceivably apply to all societies and communities of the world, extremely diverse and differently situated as they are. The mark of a good international guideline or regulation, in my view, is that it should provide a clear principle of action that applies equally to all global communities and societies without seeking to foist the particular or momentary moral dilemmas, quandaries, obsessions and preoccupations of some on all. In this paper, I propose to argue that, because moral obligations are obligations only from the point of view of a particular moral agent, we should avoid making the peculiar problems of any particular moral agent(s) the obsessive concern of all moral agents, and that we need, in particular, to make appropriate distinctions between the ethics of developed world research in the developing world, collaborative or cooperative research between the developed and developing worlds, developed world research in the developed world and developing world research in the developing world. A consequence of looking at things this way is that, while it should be clear that there are ethical concerns, imperatives and obligations at all levels, different standards may and, in fact, cannot but be applied in different contexts at different levels, without resorting to the use of double standards, which can never be morally justified. Finally, I venture to propose a formula for a solemn pledge of moral integrity and noble intent, from the perspective of the agent, that is to say, the investigator, sponsor and funder of any research, to complement and balance the widely accepted informed consent requirement, from the perspective of the patient, the subject of any biomedical research.     

Optimization of gut structure and diet for higher vertebrate herbivores.

A generalized herbivore gut is modelled as (i) a well-stirred anterior chamber in which microbial fermentation occurs; (ii) a tubular reactor in which digestion but no fermentation occurs; and (iii) a posterior fermentation chamber. The rate at which the herbivore gains metabolizable energy is calculated for diets that can be eaten at different rates and contain different energy densities of easily digested cell contents, and of cell wall materials that can be fermented but not digested. The optimum gut structure for each diet is determined. Chewing probably speeds digestion and fermentation but reduces eating time. Optimal chewing times are determined for particular diets and guts. Herbivores often have a choice between poorer food that can be eaten fast and richer food that can only be eaten more slowly. Energy costs may be incurred in travelling between patches of the richer food. Optimal diet choices are predicted for herbivores with particular gut structures.     

The artist Carl Abrahams and the cosmopolitan work of centring and peripheralizing the self⋆

The article looks at the work and life of Jamaican artist and ‘citizen of the world’ Carl Abrahams. Responding to Gell's argument that art should be thought of as a ‘technology of enchantment’, and to a wider approach that seeks to explain art by reference to cultural context, the article takes Abrahams's own Weltkenntnis, or world‐knowledge, as its focus. The Weltkenntnis of an artist, or indeed any person, is often at odds both with their surrounding cultural situation and the technical means they have to express themselves. It is never entirely possible to reduce a particular form of self‐expression either to the wider worldview or to a particular set of technical effects. The article explores the conceptual tensions involved in Abrahams's claims to be a cosmopolitan artist and his work of centring and peripheralizing himself in colonial and postcolonial Jamaica.     

A symmetrical six-base-pair target site sequence determines Tn10 insertion specificity

Transposon Tn10 inserts at many sites in the bacterial chromosome, but preferentially inserts at particular hotspots. We believe we have identified the target DNA signal responsible for this specificity. We have determined the DNA sequences of 11 Tn10 insertion sites and identified a particular 6 base pair (bp) symmetrical consensus sequence (GCTNAGC) common to those sites. The sequences at some sites differ from the consensus sequence but only in limited and well defined ways. The sequences at some sites differ from the consensus sequence than do sequences at other sites, and the consensus sequence and closely related sequences are generally absent from potential target regions where Tn10 is known not to insert. Other aspects of the target DNA can significantly influence the efficiency with which a particular target site sequence is used. The 6 bp consensus sequence is symmetrically located within the 9 bp target DNA sequence that is cleaved and duplicated during Tn10 insertion. This juxtaposition of recognition and cleavage sites plus the symmetry of the perfect consensus sequence suggest that the target DNA may be both recognized and cleaved by the symmetrically disposed subunits of a single protein, as suggested for type II restriction endonucleases. There is plausible homology between the consensus sequence and the very ends of Tn10, compatible with recognition of transposon ends and target DNA by the same protein. The sequences of actual insertion sites deviate from the perfect consensus sequence in a way which suggests that the 6 bp specificity determinant may be recognized through protein-DNA contacts along the major groove of the DNA double helix.     

Orphan genes: Function,evolution, and composition

The origin and function of orphan genes (OGs) is a mysterious problem in modern molecular biology. The recently developed PHOG database helped to shed light on some aspects in the evolution of these genes. Presumably, a rapid evolution is the main factor that influences the origin of OGs. The evolutionary rate of particular genes reflects the degree of their conservation, although exceptions from this rule contribute to the dynamic process of genome evolution during speciation. It is demonstrated that a great number of OGs detected is an artifact of insufficient sequencing. If DNAs of all organisms living on Earth were sequenced, then the OG number would be greatly reduced, giving the way to genes specific of particular taxonomic groups.     

A new method for estimating the effort required to control an infectious disease

We propose a new threshold quantity for the analysis of the epidemiology of infectious diseases. The quantity is similar in concept to the familiar basic reproduction ratio, R0, but it singles out particular host types instead of providing a criterion that is uniform for all host types. Using this methodology we are able to identify the long-term effects of disease-control strategies for particular subgroups of the population, to estimate the level of control necessary when targeting control effort at a subset of host types, and to identify host types that constitute a reservoir of infection. These insights cannot be obtained by using R0 alone.     

An approximation method for estimating cell loss from a growing tumor

A simple self-consistent calculational scheme is developed for estimating cell loss for a growing tumor (or other population) when the growth fraction can be estimated at regular intervals. This is applied to published data for a particular much-studied Ehrlich ascites tumor. The loss rate is found to be substantially higher than that estimated by previous, less precise means.