Logical Probability and Risk Assessment

A risk assessment is intended to provide a statement of current knowledge which is intended to inform a decision-maker of the current state of knowledge in response to a particular concern. Because answering the concerns of decision-makers often requires inferences to be drawn, doubt often arises over how the inference is to be drawn. In quantitative risk assessment, where a mathematical equation or model is used to draw the inference, this uncertainty is referred to as model uncertainty. A two-step process, which is referred to as logical probability, is proposed as a technique for representing model uncertainty in a risk assessment. The first step involves assigning model weights in which the degree of evidential support for each of the alternative models is considered. The second step involves assigning a unique interval in the range of 0 to 1 for each model which reflects the models' weight, to form a probability distribution. While the second step is straightforward, the first step is not. Assigning model weights requires consideration of any line of evidence that may reasonably impact the validity of the assertion of a model. While the development of a procedure for doing so may be expected to be a process which reflects the subjective preferences of whomever is involved in creating it, there are some historical precedents on which to build. Foremost among these are (1) the use of a correlation coefficient or other goodness-of-fit criteria to measure the degree of correspondence between a given model and a set of observations which are used as evidence to support it, and (2) preference given to models which are simpler, which may be ascertained as the number of adjustable parameters the model contains. Additional principles, which have little or no tradition to stand on, must be used to reflect the impact of other empirically supported beliefs on model preference. The procedure proposed is comparable to the procedure known as decision analysis, in which probabilities are assigned to alternative models based on expert or subjective input. The principal difference in the present case is that it is suggested that principles which transcend the decision at hand should be sought and articulated in order to generate a consistent measure of uncertainty arising from interpretation.     

Length control of extended protein structures in bacteria and bacteriophages

The length of the tail of bacteriophages is controlled by a protein which acts as a molecular ruler. The needle of the injectisome, which is assembled by the polymerization of subunits that are exported through the nascent injectisome, is functionally related to the tail of bacteriophages. Interestingly, its length is controlled by a protein, which is itself exported and acts as a molecular ruler that is coupled to a substrate specificity switch. The bacterial flagellum is evolutionarily related to the injectisome. The length of the hook is also controlled by a secreted protein. This protein acts as a substrate specificity switch and, possibly, also as a ruler.     

Brain death and brain life: rethinking the connection

The connection between brain life and brain death is neither as simple nor as defensible as it might at first appear. The problem rests with the two dominant competing definitions of death:...the loss of that which is necessary for the organism to continue to function as a whole;....the loss of that which is essentially significant to the nature of the organism... If death is understood as the loss of that which is necessary for the continued functioning of the organism as whole, then the apparent symmetry breaks down. If...death could be understood as the loss of that which is essentially significant to the nature of the organism....consciousness, then the symmetry would hold. However, that definition of death is indefensible. Therefore...statements about the status of anencephalic infants and early human embryos based upon a connection between brain death and brain life are unfounded.     

Development of the protonema and bud formation in mosses

In the course of their development the protonemata of Funaria hygrometrica produce two different substances which diffuse into the substrate. In the chloronema a thermo-labile growth-promoting substance is formed. In the caulonema, after about 10 days, a substance is produced which is thermostable and soluble in amyl alcohol, which can be dialysed, and which functions as a growth inhibitor. Both substances also influence bud formation. This is at an optimum only when there is a certain balance between these two substances.
This promotion is fundamentally different from that brought about by treatment with kinetin, because kinetin can function only as an additional factor in promoting bud formation. Very probably it acts as an agent which creates centres of attraction toward which morphogenetic substances are drawn. This assumption is supported by the fact that kinetin cannot be transported and therefore has no 'after-effect'. It probably functions only in the caulonema cell it penetrates. It converts every caulonema cell into a 'reaction cell'.     

Cloning and characterization of senC, a gene involved in both aerobic respiration and photosynthesis gene expression in Rhodobacter capsulatus.

The purple nonsulfur photosynthetic eubacterium Rhodobacter capsulatus is a versatile organism that can obtain cellular energy by several means, including the capture of light energy for photosynthesis as well as the use of light-independent respiration, in which molecular oxygen serves as a terminal electron acceptor. In this study, we have identified and characterized a novel gene, senC, mutations in which affect respiration as well as the induction of photosynthesis gene expression. The protein coded by senC exhibits 33% sequence identity to the yeast nucleus-encoded protein SCO1, which is thought to be a mitochondrion-associated cytochrome c oxidase assembly factor. Like yeast SCO1, SenC is required for optimal cytochrome c oxidase activity in aerobically grown R. capsulatus cells. We further show that senC is required for maximal induction from the puf and puh operons, which encode the structural polypeptides of the light-harvesting and reaction center complexes.     

Micronuclei and the cytoplasm of growing Tetrahymena contain a histone acetylase activity which is highly specific for free histone H4

Salt extracts prepared from purified micronuclei and the cytoplasm of growing Tetrahymena contain a histone acetylase (also referred to as histone acetyltransferase) activity which is highly specific for H4 when tested as a free histone. With both extracts, H4 is acetylated first at position 4 (monoacetylated) or positions 4 and 11 (diacetylated), sites diagnostic of deposition-related acetylation of newly synthesized H4 in vivo. As the concentration of cytosolic extract is decreased in the in vitro reactions, acetylation of H3 is also observed. Neither activity acetylates histone in a chromatin form. These activities are distinct from a macronuclear acetylase which acetylates H3 and H4 (macro- or micronuclear) equally well as free histones and which acetylates all four core histones when mononucleosomes are used as substrate. As well, the micronuclear and cytoplasmic activities give similar thermal-inactivation profiles which are different from that of the macronuclear activity. In situ enzyme assays demonstrate a macronuclear-specific activity which acetylates endogenous macronuclear chromatin and an independent micronuclear-cytosolic activity which is able to act upon exogenously added free H4. These results argue strongly that an identical acetylase is responsible for the micronuclear and cytoplasmic activity which is either modified or altogether distinct from that in macronuclei.     

共生概念发展的历史,现状及展望

本文从回顾历史出发,勾划出国际上极为热门的共生学说发展轨迹,指出共生是一切群体中密切联合的能力,不但是诸多生命分支科学的理论网络,涉及到许多应用问题,而且是一种生物哲学,自然界和人文科学莫不如此。     

Assuring the safety of genetically modified (GM) foods: the importance of an holistic,integrative approach

Genes change continuously by natural mutation and recombination enabling man to select and breed crops having the most desirable traits such as yield or flavour. Genetic modification (GM) is a recent development which allows specific genes to be identified, isolated, copied and inserted into other plants with a high level of specificity. The food safety considerations for GM crops are basically the same as those arising from conventionally bred crops, very few of which have been subject to any testing yet are generally regarded as being safe to eat. In contrast a rigorous safety testing paradigm has been developed for GM crops, which utilises a systematic, stepwise and holistic approach. The resultant science based process, focuses on a classical evaluation of the toxic potential of the introduced novel trait and the wholesomeness of the transformed crop. In addition, detailed consideration is given to the history and safe use of the parent crop as well as that of the gene donor. The overall safety evaluation is conducted under the concept known as substantial equivalence which is enshrined in all international crop biotechnology guidelines. This provides the framework for a comparative approach to identify the similarities and differences between the GM product and its comparator which has a known history of safe use. By building a detailed profile on each step in the transformation process, from parent to new crop, and by thoroughly evaluating the significance from a safety perspective, of any differences that may be detected, a very comprehensive matrix of information is constructed which enables the conclusion as to whether the GM crop, derived food or feed is as safe as its traditional counterpart. Using this approach in the evaluation of more than 50 GM crops which have been approved worldwide, the conclusion has been that foods and feeds derived from genetically modified crops are as safe and nutritious as those derived from traditional crops. The lack of any adverse effects resulting from the production and consumption of GM crops grown on more than 300 million cumulative acres over the last 5 years supports these safety conclusions.     

Cross-Sectional Shape of Collapsible Tubes

In order to quantify the collapse phenomenon in veins, this paper presents a mathematical analysis of the cross-sectional shape of a flexible tube as its internal pressure varies. Quantitative results are presented in terms of the physical parameters of the tube, such as wall thickness and Young's modulus. It is assumed that the tube is thin walled, that no stretching occurs, that the cross-sectional shape is elliptical when the transmural pressure is zero, and that the longitudinal prestress is zero. The equations were solved on a digital computer which displayed the cross-sectional shapes on an oscilloscope, which were then photographed. A selection of these photographs is presented. Curves are shown which give the cross-sectional area and compliance as functions of transmural pressure. Other curves are shown which are useful for interpolation, and for use in the experimental determination of the physical parameters which may otherwise be difficult or impossible to measure accurately.     

A one-dimensional continuum elastic model for membrane-embedded gramicidin dimer dissociation

Membrane elastic properties, which are subject to alteration by compounds such as cholesterol, lipid metabolites and other amphiphiles, as well as pharmaceuticals, can have important effects on membrane proteins. A useful tool for measuring some of these effects is the gramicidin A channels, which are formed by transmembrane dimerization of non-conducting subunits that reside in each bilayer leaflet. The length of the conducting channels is less than the bilayer thickness, meaning that channel formation is associated with a local bilayer deformation. Electrophysiological studies have shown that the dimer becomes increasingly destabilized as the hydrophobic mismatch between the channel and the host bilayer increases. That is, the bilayer imposes a disjoining force on the channel, which grows larger with increasing hydrophobic mismatch. The energetic analysis of the channel-bilayer coupling is usually pursued assuming that each subunit, as well as the subunit-subunit interface, is rigid. Here we relax the latter assumption and explore how the bilayer junction responds to changes in this disjoining force using a simple one-dimensional energetic model, which reproduces key features of the bilayer regulation of gramicidin channel lifetimes.     

Irradiating the environment: Radiological impacts in life cycle assessment

One of the main shortcomings of Life Cycle Assessment (LCA) when applied to the Nuclear Fuel Cycle, is that there is currently no recognised procedure to deal with radionuclide emissions in the Impact Assessment stage. A framework which considers both human and environmental impacts is required and a methodology which is compatible with the other impact assessment approaches in LCA must be developed. It is important that the discussion is not only restricted to concepts, but that a working methodology is developed which can be readily applied by LCA practitioners. A provisional method is available for assessing radiological impacts on human health, but no consideration has been given to potential effects on the environment. A methodology is proposed in this paper which assesses irradiation of the environment using Environmental Increments (EI) as the quality standard. This approach is based on the same principles as for the Ecotoxicity classification group, and it represents a working methodology which can be continuously improved as knowledge in the area increases.     

The Fungi of Texas

Abstract  T he communication of which the following is an abstract contained an enumeration of a small collection of Fungi made by Mr. H. W. Ravenal in a trip to Texas some few years since. In addition to this, all previously recorded species for that State were collated, and the result was the determination of a total of 149 species as all which, up to the present, have been recorded. This number is exceedingly small, and only serves to prove how very little is known of the mycologic flora of a state which probably is as rich in fungi as South Carolina.     

The DNA scanning mechanism of T4 endonuclease V. Effect of NaCl concentration on processive nicking activity

T4 endonuclease V is a pyrimidine dimer-specific endonuclease which generates incisions in DNA at the sites of pyrimidine dimers by a processive reaction mechanism. A model is presented in which the degree of processivity is directly related to the efficacy of the one-dimensional diffusion of endonuclease V on DNA by which the enzyme locates pyrimidine dimers. The modulation of the processive nicking activity of T4 endonuclease V on superhelical covalently closed circular DNA (form I) which contains pyrimidine dimers has been investigated as a function of the ionic strength of the reaction. Agarose gel electrophoresis was used to separate the three topological forms of the DNA which were generated in time course reactions of endonuclease V with dimer-containing form I DNA in the absence of NaCl, and in 25, 50, and 100 mM NaCl. The degree of processivity was evaluated in terms of the mass fraction of form III (linear) DNA which was produced as a function of the fraction of form I DNA remaining. Processivity is maximal in the absence of NaCl and decreases as the NaCl concentration is increased. At 100 mM NaCl, processivity is abolished and endonuclease V generates incisions in DNA at the site of dimers by a distributive reaction mechanism. The change from the distributive to a processive reaction mechanism occurs at NaCl concentrations slightly below 50 mM. The high degree of processivity which is observed in the absence of NaCl is reversible to the distributive mechanism, as demonstrated by experiments in which the NaCl concentration was increased during the time course reaction. In addition, unirradiated DNA inhibited the incision of irradiated DNA only at NaCl concentrations at which processivity was observed.     

The Effect of the Chemical Nature of a Decolorizer on Its Functioning. II. the Apparent Isoelectric Point

The isoelectric point of a bacterial system is the hydrogen-ion concentration at which there is equal retention of anion and cation. Defining this point as that at which there is equal retention of acidic and basic stain when acetone is used as a decolorizer, it is shown that acidic decolorizers shift the experimentally determined point to a higher pH-value while basic decolorizers shift it to a lower value. Thus basic decolorizers show abnormally high decolorizing power toward smears stained with acid dyes, and acid decolorizers show the same abnormal behavior toward smears stained with basic dye. By basic decolorizer is meant, not one of high pH-value, but one which will form a salt with acids, as for example pyridin or anilin. This indicates an ionic chemical equilibrium as a factor in the mechanism of staining.     

A system for electromagnetic blood flow measurement with extracorporeal sinusodial field magnet

This paper describes the construction details and circuitry of a system for electromagnetic determination of blood flow by means of intravascular flow sensors passed through angiographic catheters introuced by percutaneous technique. The extracorporeal magnet coil is fed by a sinusodial current and the sinusodial induced flow signal is detected by a phase-sensitive amplifier. The main novel feature of this amplifier is a combination of phase-sensitive detection with a boxcar integrator which results in an exceptionally high signal-to-noise ratio. A two channel system is also described which permits simultaneous monitoring of a signal in phase quadrature with respect to the magnetic field and, hence, to the flow signal. This system makes it also possible to monitor variations in artery diameter which is measured through a transformer e.m.f. induced in a loop of the sensor whose area is modified by the artery diameter in a fashion securing approximate linear relationship between the artery diameter and the loop output. The loop output voltage is also used to ascertain the instrument calibration in case of an arbitrary orientation and distance from the magnet coil of the intravascular sensor.The intravascular sensor is a loop of insulated fine elastic wire which forms an oval frame which collapses as it is introduced through an intravascular catheter and expands maximally as it emerges into an artery which harbors the catheter end portion. Two diametrically opposed electrodes placed across the loop, pick up the flow signal induced in the blood stream by an extracorporeal air-core magnet coil whose magnetic axis is as nearly as possible perpendicular to the area of the sensor and to the artery axis.The paper reviews artifacts and the capabilities as well as the limitations of the method in its present form and suggests a solution for the main weakness--the inability to provide a reliable zero-based line without recourse to arrest of blood flow.     

Decreased sensitivity of spontaneously hypertensive rat aortic smooth muscle to vasorelaxation by atriopeptin III

The effects of a synthetic form of Atrial Natriuretic Factor (ANF) on spontaneously hypertensive rat aortic smooth muscle were investigated using either an alpha-adrenoceptive agonist (phenylephrine) or an agent which partially depolarized the plasma membrane (20mM KCl) as a contractile agent. The relaxant response was studied under conditions resembling normal physiological calcium ion levels (1.5mM) as well as over a range of calcium ion concentrations (0.1-2.5mM). The results demonstrate a hyporesponsiveness of hypertensive aorta to vasorelaxation induced by synthetic ANF, which is more apparent when the tissue is contracted with KCl. The results also suggest that ANF, which has been shown previously to inhibit intracellular and receptor operated calcium channel mobilization only, may additionally work through a mechanism which is related to the voltage induced calcium flux across the membrane, which also is inhibited less in hypertensive smooth muscle.     

An explantion for the determination of "self" versus "non-self" proteins

Deamidation of proteins, which has been linked to turnover, results in the production of a different protein—different in sequence and shape. It is proposed that this is the protein which is normally encountered by the immune system and is therefore viewed as “self”. If the protein in the form in which it exists in situ is released through disease, or introduced by artificial means, it would then be recognized as “non-self.” This is offered as a hypothesis to explain autoimmune response to the basic protein of myelin.