Generation of a catalytic module on a self-folding RNA

It is theoretically possible to obtain a catalytic site of an artificial ribozyme from a random sequence consisting of a limited numbers of nucleotides. However, this strategy has been inadequately explored. Here, we report an in vitro selection technique that exploits modular construction of a structurally constrained RNA to acquire a catalytic site for RNA ligation from a short random sequence. To practice the selection, a sequence of 30 nucleotides was located close to the putative reaction site in a derivative of a naturally occurring self-folding RNA whose crystal structure is known. RNAs whose activity depended on the starting three-dimensional structure were selected with 3'-5' ligation specificity, indicating that the strategy can be used to acquire a variety of catalytic sites and other functional RNA modules.     

Voltammetry of a "protein on a rope"

A periplasmic electron-transfer protein, cytochrome c(555)(m) from Aquifex aeolicus contains a 62-residue N-terminal extension by which it is anchored to the membrane--most probably via a thioester bond to its N-terminal cysteine. This linker can act as a "rope" to tether the protein close to its reaction partners. Mimicking this principle, a recombinant cytochrome c(555)(m), expressed in Escherichia coli, has been attached covalently to a gold electrode modified with 6-mercaptohexan-1-ol. The "tethered" cytochrome c(555)(m) displays remarkably fast electron-transfer kinetics, with an electrochemical exchange rate constant k(0) of 1.4 x 10(4) s(-1). The results show that fast electron transfer is associated with weak interactions: importantly, the tethered cytochrome can explore many different orientations without escaping into solution.     

一个污染环境中的单种群模型的动力学性质

以脉冲微分方程为基础建立了一个污染环境中在固定时刻对污染净化处理的单种群模型,详细研究了此模型的动力学性质,给出了种群灭绝和持续生存的充分条件.结果表明,当脉冲作用的周期小于某个阈值时,种群将持续生存;否则,种群将趋于灭绝.     

Darwinian evolution on a chip

Computer control of Darwinian evolution has been demonstrated by propagating a population of RNA enzymes in a microfluidic device. The RNA population was challenged to catalyze the ligation of an oligonucleotide substrate under conditions of progressively lower substrate concentrations. A microchip-based serial dilution circuit automated an exponential growth phase followed by a 10-fold dilution, which was repeated for 500 log-growth iterations. Evolution was observed in real time as the population adapted and achieved progressively faster growth rates over time. The final evolved enzyme contained a set of 11 mutations that conferred a 90-fold improvement in substrate utilization, coinciding with the applied selective pressure. This system reduces evolution to a microfluidic algorithm, allowing the experimenter to observe and manipulate adaptation.     

Bathymetry on a Carboniferous reef

Broadhurst, F. M. & Simpson, I. M.: Bathymetry on a Carboniferous reef.
In the Lower Carboniferous deposits of Castleton, Derbyshire, well bedded shelf limestones, apparently of shallow water origin, pass northwards into a marginal tract of poorly bedded apron-reef limestones which dip at about 30° downwards and away from the 'shelf'. Geopetal infillings of shell cavities in the apron-reef indicate only minor movement since deposition, and the observed dip must be due to deposition on a sloping sea floor. At certain times this sea floor was colonised by stromatolitic algae and corals such as Lithostrotion at the apron-reef crest where there was minimum water depth, followed to progressively increasing depths by (1) a fauna dominated by the coral Michelinia , (2) a fauna of small brachiopods, bryozoa, molluscs, trilobites, and other organisms and (3) a fauna dominated by Pseudamussium . At other times crinoidal debris was the dominant component of the apron-reef, when an alignment of crinoid stems parallel to the dip of the slope occurred at low levels, but a random orientation at the apronreef crest. Other sediments on the apron-reef are apparently devoid of macrofossils. Volcanic activity occurred during the development of the apron-reef, and it is suggested that uplift of the shelf area preceded the subaerial flow of a lava tongue which reached and plunged down the apron-reef slope and into the sea.     

Reflection on family consent: based on a pregnant death in a beijing hospital

The ‘family consent’ process has been placed at the centre of Chinese clinical practice. Although there has been critical analysis of how the process functions in relation to the autonomy and rights of patients, there has been little examination of the perceptions and attitude of patients and their families and the medical professionals, in relation to moral dilemmas that arise in real cases in the bioethical discourse. When faced with a consent form in an emergency situation, the family member's capacity to act is reduced, as he/she becomes enmeshed in the hospital structure of tacit, socially‐imposed rules. In a questionnaires based on a real death case in 2008, 70.9% of the surveyed medical professionals (n = 3,665) disagreed with performing surgery without the consent of the family even if the patient's life was in danger, while 36.6% of the surveyed patients (n = 1,198) hold the same position. This work demonstrates the weakness of the family consent process as a safeguard of patient's autonomy. Finally, I argue that saving the patient's life should be the overriding obligation rather than the respect for the surrogate's autonomous choice at such a decisive moment.     

Membrane on a chip: a functional tethered lipid bilayer membrane on silicon oxide surfaces

Tethered membranes have been proven during recent years to be a powerful and flexible biomimetic platform. We reported in a previous article on the design of a new architecture based on the self-assembly of a thiolipid on ultrasmooth gold substrates, which shows extremely good electrical sealing properties as well as functionality of a bilayer membrane. Here, we describe the synthesis of lipids for a more modular design and the adaptation of the linker part to silane chemistry. We were able to form a functional tethered bilayer lipid membrane with good electrical sealing properties covering a silicon oxide surface. We demonstrate the functional incorporation of the ion carrier valinomycin and of the ion channel gramicidin.     

The effect of a corona discharge on a lightning attachment

The interaction between the lightning leader and the space charge accumulated near the top of a ground object in the atmospheric electric field is considered using analytical and numerical models developed earlier to describe spark discharges in long laboratory gaps. The specific features of a nonstationary corona discharge that develops in the electric field of a thundercloud and a downward lightning leader are analyzed. Conditions for the development of an upward lightning discharge from a ground object and for the propagation of an upward-connecting leader from the object toward a downward lightning leader (the process determining the point of strike to the ground) are investigated. Possible mechanisms for the interaction of the corona space charge with an upward leader and prospects of using it to control downward lightning discharges are analyzed.     

The effect of a competitor on a model adaptive radiation

The ecological forces shaping adaptive radiations are of great interest to evolutionary ecologists. Here, we experimentally test the hypothesis that the diversification of a lineage should be limited in the presence of competition from another taxon. We do this by studying a model microbial adaptive radiation (the generation of phenotypic diversity in asexual lineages of the bacterium Pseudomonas fluorescens) in the presence or absence of a competitor (Pseudomonas putida). In a spatially heterogeneous environment, the competitor P. putida reduced P. fluorescens population size only slightly and had no effect on diversification. In a spatially homogeneous environment, the competitor reduced P. fuoresecens population size to a much greater extent. Again the final extent of diversification in P. fluorescens was not affected by the competitor, but early diversification was accelerated. In this environment, P. putida suppressed the growth of a common variant of P. fluorescens and directly or indirectly facilitated the growth of a rare morph. Our results suggest that competition experienced by diversifying lineages may have complex effects on adaptive radiations not fully captured by current theory.     

Effect of Adjuvants on the Antibody Response to a Hapten on a Thymus-independent Carrier

IT has been demonstrated in mice that levan (polyfructose), an antigen which interacts only with B lymphocytes¹, can function as a carrier and produce a thymus-independent response to dinitrophenol (DNP)². Using this conjugate, antibody-production against the hapten is totally unaffected in thymectomized animals and is abolished in mice tolerant to levan. The DNP-levan conjugate produces only 19S antibody against DNP.     

Dynamic stability of a human standing on a balance board

The neuromuscular system used to stabilize upright posture in humans is a nonlinear dynamical system with time delays. The analysis of this system is important for improving balance and for early diagnosis of neuromuscular disease. In this work, we study the dynamic coupling between the neuromuscular system and a balance board—an unstable platform often used to improve balance in young athletes, and older or neurologically impaired patients. Using a simple inverted pendulum model of human posture on a balance board, we describe a surprisingly broad range of divergent and oscillatory CoP/CoM responses associated with instabilities of the upright equilibrium. The analysis predicts that a variety of sudden changes in the stability of upright postural equilibrium occurs with slow continuous deterioration in balance board stiffness, neuromuscular gain, and time delay associated with the changes in proprioceptive/vestibular/visual-neuromuscular feedback. The analysis also provides deeper insight into changes in the control of posture that enable stable upright posture on otherwise unstable platforms.     

Misunderstanding death on a respirator

As Tom Tomlinson's study indicates, there is considerable misunderstanding and confusion among physicians and nurses working in the area. Brain death is often not well-understood by healthcare professionals and hence inadequately explained to relatives, leaving them confused as to whether their loved-one is alive or dead. Whilst these healthcare professionals are using whole-brain death as the criterion of death, they have no clear understanding of the definition of death which underpins the brain-death criterion. Lack of this philosophical rationale makes the use of the brain-death criterion a mere technicality, rather than the expression of a well-grounded conceptual and ethical understanding. The other difficulty is that a brain-dead respirator patient just does not look dead. This appearance of life, Tomlinson suggests, can trigger deep emotions in caregivers and family members which will compound the intellectual perplexity already felt by them.     

Effects of a disease affecting a predator on the dynamics of a predator-prey system

We study the effects of a disease affecting a predator on the dynamics of a predator-prey system. We couple an SIRS model applied to the predator population, to a Lotka-Volterra model. The SIRS model describes the spread of the disease in a predator population subdivided into susceptible, infected and removed individuals. The Lotka-Volterra model describes the predator-prey interactions. We consider two time scales, a fast one for the disease and a comparatively slow one for predator-prey interactions and for predator mortality. We use the classical “aggregation method” in order to obtain a reduced equivalent model. We show that there are two possible asymptotic behaviors: either the predator population dies out and the prey tends to its carrying capacity, or the predator and prey coexist. In this latter case, the predator population tends either to a “disease-free” or to a “disease-endemic” state. Moreover, the total predator density in the disease-endemic state is greater than the predator density in the “disease-free” equilibrium (DFE).     

Comments on a skeleton design paradigm for a demosponge

The ball-shaped marine sponge Cinachyrellalevantinensis is 3-5 cm in diameter. It filters large quantities of seawater for feeding. Sponges contain numerous, hydrated, brittle amorphous SiO? spicules of several types that form 70-80% by weight of the sponge. We performed mechanical tests to determine the functionality of the sponge skeleton. The potential effect of habitat on skeleton properties was investigated by comparing sponges from 0.5 m and 30 m depth. We determined how spicules contribute to maintaining the strength and macroscopic structural integrity of a sponge, and studied their deformation mechanisms under external loading, and their microscopic design parameters. Compression tests of cylindrical samples cut from sponges revealed their macroscopic deformation mechanisms. Experiments solely with the organic material (following spicules dissolution) revealed the contribution of the spicules to the load carrying capacity and structural integrity of the sponge. Cantilever bending tests of anchored spicules determined the strength of individual spicules, the sponge's main skeletal elements. As the strength of brittle spicules is statistical in nature, we used Weibull Statistics to define their strength and evaluate their Young's modulus. Shallow and deep-water sponges did not differ significantly neither in response to compression, nor in spicule strength under bending and tension. Spicule weight fraction within a sponge was significantly higher in shallow-water individuals. We conclude that the structural integrity and strength of this sponge's skeleton is derived from its low-strength, small spicules, produced by a cost-effective process. The operating deformation of the spicules (bending) and their design parameters make them highly efficient.     

A study on a vibratory model of a human body

This paper is concerned with the modeling of the human body as a spring mass system. Based on certain assumptions, an analysis for evaluating the mass and stiffness values of the model is developed. As an illustration of the modeling procedure, a 15-degree-of-freedom model of a male body is considered. The computed natural frequencies of the model are found to be within the range of available experimental values.     

Oligonucleotide synthesis on a cellulose acetate functionalized with a spacer

4-(2-Hydroxyethylsulfonyl)dihydrocinnamate derivative of cellulose acetate (D.S. 1.77) was used for polymer support synthesis of oligonucleotides bearing a phosphodiester function at the 3'-terminal position, taking into consideration that the cellulose derivative is readily soluble in pyridine, but slightly soluble in a solvent such as ethanol.     

Egg laying by a butterfly on a fragmented host plant: a multi-level approach

Egg placement by herbivorous insects is an important step in their interaction with their host plants, and is the result of processes operating at different spatial and temporal scales. Although several studies have examined egg-placement patterns at different scales, this has rarely been achieved simultaneously using a multi-scale hierarchical approach. We studied egg placement in a rare European butterfly, Iolana iolas , whose larvae specifically feed on seeds of plants of the genus Colutea, using a hierarchical approach and Generalised Linear Mixed Modelling. The study was carried out in 2002 and 2003 in a ca 60 km² area in southern Madrid province, Spain, where the host plant, Colutea hispanica , has a highly fragmented distribution. We monitored in detail 132 plants in 24 patches and estimated the abundance of butterflies over the whole reproductive period of C. hispanica . We measured phenological, morphological and landscape variables potentially affecting egg-placement at three hierarchical levels: fruit, plant and host plant patch. Using egg presence–absence on mature fruits as the response variable, we found that eggs were more likely to be laid on fruits aged 1–2 weeks at the middle of the flowering period (fruit level), on large plants with a small number of shoots at the base (plant level), and in well connected host plant patches (patch level). Our results suggest that egg-placement is a process determined by factors operating at different levels: fruit, plant and host plant patch. Because egg-placement studies are often made with spatially correlated data, neglecting their intrinsic hierarchical nature could lead to equivocal conclusions.     

Cost-Minimization Model of a Multidisciplinary Antibiotic Stewardship Team Based on a Successful Implementation on a Urology Ward of an Academic Hospital

BackgroundIn order to stimulate appropriate antimicrobial use and thereby lower the chances of resistance development, an Antibiotic Stewardship Team (A-Team) has been implemented at the University Medical Center Groningen, the Netherlands. Focus of the A-Team was a pro-active day 2 case-audit, which was financially evaluated here to calculate the return on investment from a hospital perspective.MethodsEffects were evaluated by comparing audited patients with a historic cohort with the same diagnosis-related groups. Based upon this evaluation a cost-minimization model was created that can be used to predict the financial effects of a day 2 case-audit. Sensitivity analyses were performed to deal with uncertainties. Finally, the model was used to financially evaluate the A-Team.ResultsOne whole year including 114 patients was evaluated. Implementation costs were calculated to be €17,732, which represent total costs spent to implement this A-Team. For this specific patient group admitted to a urology ward and consulted on day 2 by the A-Team, the model estimated total savings of €60,306 after one year for this single department, leading to a return on investment of 5.9.ConclusionsThe implemented multi-disciplinary A-Team performing a day 2 case-audit in the hospital had a positive return on investment caused by a reduced length of stay due to a more appropriate antibiotic therapy. Based on the extensive data analysis, a model of this intervention could be constructed. This model could be used by other institutions, using their own data to estimate the effects of a day 2 case-audit in their hospital.     

An analysis of a reordering operator on a GA-hard problem

This paper analyzes the performance of a genetic algorithm that combines reproduction, crossover, and a reordering operator. Reordering operators have often been suggested as one way to avoid thecoding traps — the combinations of loose linkage and deception among important, lower order schemata — of fixed codings. The analysis confirms this role and suggests directions for further research.