Kinetically differentiating influenza hemagglutinin fusion and hemifusion machines

Membrane fusion mediated by influenza virus hemagglutinin (HA) yields different phenotypes depending on the surface density of activated HAs. A key question is whether different phenotypes arise from different fusion machines or whether different numbers of identical fusion machines yield different probabilistic outcomes. If fusion were simply a less probable event than hemifusion, requiring a larger number of identical fusion machines to occur first, then two predictions can be made. First, fusion should have a shorter average delay time than hemifusion, since there are more machines. Second, fusion should have a longer execution time of lipid mixing after it begins than hemifusion, since the full event cannot be faster than the partial event. Using a new automated video microscopy technique, we simultaneously monitored many HA-expressing cells fusing with erythrocytes and identified individual cell pairs with either full or only partial redistribution of fluorescent lipids. The full lipid mixing phenotype also showed contents mixing, i.e., fusion. Kinetic screening of the digitized fluorescence data showed that the execution of lipid mixing after the onset is faster for fusion than hemifusion. We found no correlation between the delay times before the onset of lipid mixing and the final fusion phenotype. We also found that the execution time for fusion was faster than that for hemifusion. Thus, we provide the first experimental evidence for fusion and hemifusion arising from different machines.     

A Genetic Algorithm Approach to the Scheduling of FMSs with Multiple Routes

Usually, most of the typical job shop scheduling approaches deal with the processing sequence of parts in a fixed routing condition. In this paper, we suggest a genetic algorithm (GA) to solve the job-sequencing problem for a production shop that is characterized by flexible routing and flexible machines. This means that all parts, of all part types, can be processed through alternative routings. Also, there can be several machines for each machine type. To solve these general scheduling problems, a genetic algorithm approach is proposed and the concepts of virtual and real operations are introduced. Chromosome coding and genetic operators of GAs are defined during the problem solving. A minimum weighted tardiness objective function is used to define code fitness, which is used for selecting species and producing a new generation of codes. Finally, several experimental results are given.     

How a neutral evolutionary ratchet can build cellular complexity

Complex cellular machines and processes are commonly believed to be products of selection, and it is typically understood to be the job of evolutionary biologists to show how selective advantage can account for each step in their origin and subsequent growth in complexity. Here, we describe how complex machines might instead evolve in the absence of positive selection through a process of "presuppression," first termed constructive neutral evolution (CNE) more than a decade ago. If an autonomously functioning cellular component acquires mutations that make it dependent for function on another, pre-existing component or process, and if there are multiple ways in which such dependence may arise, then dependence inevitably will arise and reversal to independence is unlikely. Thus, CNE is a unidirectional evolutionary ratchet leading to complexity, if complexity is equated with the number of components or steps necessary to carry out a cellular process. CNE can explain "functions" that seem to make little sense in terms of cellular economy, like RNA editing or splicing, but it may also contribute to the complexity of machines with clear benefit to the cell, like the ribosome, and to organismal complexity overall. We suggest that CNE-based evolutionary scenarios are in these and other cases less forced than the selectionist or adaptationist narratives that are generally told.     

A heuristic approach to minimize expected makespan in open shops subject to stochastic processing times and failures

Many real world situations exist where job scheduling is required. This is the case of some entities, machines, or workers who have to execute certain jobs as soon as possible. Frequently what happens is that several workers or machines are not available to perform their activities during some time periods, due to different circumstances. This paper deals with these situations, and considers stochastic scheduling models to study these problems. When scheduling models are used in practice, they have to take into account that some machines may not be working. That temporal lack of machine availability is known as breakdowns, which happen randomly at any time. The times required to repair those machines are also random variables. The jobs have operations with stochastic processing times, their own release times, and there is no precedence between them. Each job is divided into operations and each operation is performed on the corresponding specialized machine. In addition, in the problems considered, the order in which the operations of each job are done is irrelevant. We develop a heuristic approach to solve these stochastic open-shop scheduling problems where random machine breakdowns can happen. The proposed approach is general and it does not depend on the distribution types of the considered random input data. It provides solutions to minimize the expected makespan. Computational experiences are also reported. The results show that the proposed approach gives a solid performance, finding suitable solutions with short CPU times.     

In defence of the high energy phosphate bond

The concept of the “high energy phosphate bond” has recently been strongly criticised by Banks &; Vernon. The criticisms were: (i) energy cannot be stored in molecules; let alone in bonds; (ii) a muscle is an open system, so that the free energy of hydrolysis of ATP is irrelevant; (iii) biological reactions cannot be at equilibrium, therefore they must be inefficient. It is argued that all of these criticisms arise because the timescale appropriate to molecular events has been left out; in particular “stored energy” needs to be defined relative to the machine which uses that energy. The criticisms may be answered using a conceptual framework which overcomes this deficiency and which was developed previously to extend classical thermodynamics to the molecular level. Criticism (i) is refuted by discussing in detail the chemiluminescent reaction of rubrene oxide, which can only be described as liberating internal energy stored in a single molecule; while it is true that entropy cannot be retained in a single molecule for long enough to do useful work with it, there is nothing which forbids internal energy from being so stored. Criticism (ii) would be true if, and only if, a muscle uses the same kind of mechanism as do the ordinary chemical machines with which we are familiar (batteries, etc). But this assumption is shown to be false; a muscle cannot use this type of mechanism. Criticism (iii) is answered by finding the conditions under which a biological machine could in fact approach 100% efficiency. These conditions are: (i) in metabolism ΔF = 0; the steps are in thermal equilibrium; (ii) in the molecular machines themselves ΔS = 0, so that ΔF = ΔH; the machines are mechanical. It is also shown that not only are these conditions perfectly conceivable, but also that there is good evidence that, over the course of evolution, they have actually been attained.     

Production Capacity Modeling of Alternative, Nonidentical, Flexible Machines

Analyzing the production capacity of a flexible manufacturing system consisting of a number of alternative, nonidentical, flexible machines, where each machine is capable of producing several different part types simultaneously (by flexibly allocating its production capacity among these part types), is not a trivial task. The production capacity set of such a system is naturally expressed in terms of the machine-specific production rates of all part types. In this paper we also express it in terms of the total production rates of all part types over all machines. More specifically, we express the capacity set as the convex hull of a set of points corresponding to all possible assignments of machines to part types, where in each assignment each machine allocates all its capacity to only one part type. First, we show that within each subset of assignments having a given number of machines assigned to each part type, there is a unique assignment that corresponds to an extreme point of the capacity set. Then, we propose a procedure for generating all the extreme points and facets of the capacity set. Numerical experience shows that when the number of part types is less than four, the size of the capacity set (measured in terms of the number of variables times the number of constraints) is smaller, if the capacity set is expressed in terms of the total production rates of all part types over all machines than if it is expressed in terms of the machine-specific production rates of all part types. When the number of part types is four or more, however, the opposite is true.     

Abstract biological systems as sequential machines II: Strong connectedness and reversibility

It was previously shown that the abstract biological systems called. (ℳ, ℛ)-systems could be regarded formally as sequential machines, and that when this was done, the reversibility of environmentally induced structural changes in these systems was closely related to the strong connectedness of the corresponding machines. In the present work it is shown that the sequential machines arising in this way are characterized by the property that the size of the input alphabet is very small compared with the size of the set of states of the machine. It is further shown that machines with this property almost always fail to be strongly connected. Therefore, it follows that one of the following alternatives holds: either most environmentally induced structural alterations are not environmentally reversible, or else many mappings in the category from which the (ℳ, ℛ)-systems are formed must not be physically realizable.     

Structural and organisational conditions for being a machine

Although the analogy between macroscopic machines and biological molecular devices plays an important role in the conceptual framework of both neo-mechanistic accounts and nanotechnology, it has recently been claimed that certain complex molecular devices (consisting of biological or synthetic macromolecular aggregates) cannot be considered machines since they are subject to physicochemical forces that are different from those of macroscopic machines. However, the structural and physicochemical conditions that allow both macroscopic machines and microscopic devices to work and perform new functions, through a combination of elemental functional parts, have not yet been examined. In order to fill this void, this paper has a threefold aim: first, to clarify the structural and organisational conditions of macroscopic machines and microscopic devices; second, to determine whether the machine-like analogy fits nanoscale devices; and third, to assess whether the machine-like analogy is appropriate for describing the behaviour of some biological macromolecules. Finally, the paper gives an account of ‘machine’ which, while acknowledging the physicochemical and organisational differences between man-made machines and biological microscopic devices, nevertheless identifies a common conceptual core that allows us to consider the latter ‘machines’.     

Scheduling algorithms for a two-machine flexible manufacturing system

The flexible manufacturing system (FMS) considered in this paper is composed of two CNC machines working in series—a punching machine and a bending machine connected through rollers acting as a buffer system of finite capacity. The main difference between the present problem and the standard two-machine flow shop problem with finite intermediate capacity is precisely the buffer system, which in our problem consists of two stacks of parts supported by rollers: the first stack contains the output of the punching machine, while the second stack contains the input for the bending machine. When the second stack is empty, the first stack may be moved over. Furthermore, the capacity of each stack depends on the particular part type being processed. The FMS can manufacture a wide range of parts of different types. Processing times on the two machines are usually different so that an unbalance results in their total workload. Furthermore, whenever there is a change of the part type in production, the machines must be properly reset—that is, some tools need to be changed or repositioned. A second important difference between the present problem and the usual two-machine flow shop problem is the objective. Given a list ofp part types to be produced in known quantities, the problem considered here is how to sequence or alternate the production of the required part types so as to achieve various hierarchical targets: minimize the makespan (the total time needed to complete production) and, for instance, compress the idle periods of the machine with less workload into a few long enough intervals that could be utilized for maintenance or other reasons. Although Johnson's rule is optimal in some particular cases, the problem addressed in the paper isNP-hard in general: heuristic procedures are therefore provided.     

Sieving experiment: the controlled recovery of charred plant remains from modern and archaeological samples

Results of experimental retrieval of plant remains (both charred modern and fossil) from three sediment types (clay, gravel and sandy loam) carried out by environmental archaeologists from the Ancient Monuments Laboratory and the Central Archaeology Service, English Heritage, are reported. For each sediment type, six different treatments were carried out using three flotation machines of the Siraf type, two other machines in use in two archaeological units and one experimental machine. The results show that there is invariably considerable discrepancy between the amount of plant material present and that recovered, that the Serif-type machine is among the best currently available and that pretreatment of particular mineral soils may improve recovery of plant macrofossil material.     

Biophysics; fifty years after Schrödinger

E. Schrödinger described his mechanistic view on life in his book “What is Life?” published in 1944. H. Yukawa stated that life is like a building of bricks. Is life understandable in this manner?In 1950–1960 the generation of structure and function in living cells was shown to be analyzable, step by step, within the theoretical framework of physics. In the 1970's the concept of a molecular machine or unit machine in living cells was clearly presented and the effort to experimentally define unit machines was promoted. Recently, new techniques to directly observe their behaviors have been developed. The machines are not always rigid. In sliding machines, the influx-efflux coupling has been found to be loose. For loose coupling, intramachine flexibility seems to be useful.Living cells can be regarded as an organized system composed of many unit machines, some of which exhibit deterministic behaviors while others exhibit probabilistic behaviors. The cells do not always show a definite response to a given input. We need new statistical mechanics for the study of unit machines and their systems which have complex spatial and temporal structures. They may have a mechanism beyond a simple building of bricks.     

Coagulase-negative staphylococci and coliform bacteria associated with mechanical defeathering of poultry carcasses

Coagulase-negative staphylococci and coliform bacteria were isolated from defeathering machines and carcasses at a commercial poultry processing plant Initially, the predominant staphylococci on carcasses were Staphylococcus xylosus and Staph simulans but during defeathering, these organisms were replaced by Staph. sciuri. Since Staph sciuri predominated in the defeathering machines, the machinery appeared to be responsible for contaminating carcasses.
Among the coliform bacteria, Escherichia coli was the principal organism isolated from both carcasses and defeathering machines However use of a biotyping scheme revealed no clear change in the pattern of carcass contamination during defeathering and it was concluded that E. coli is unlikely to colonize the machines.     

The anarchist's guide to ecological theory. Or, we don't need no stinkin' laws

Several ecologists have recently suggested that ecology has several laws. This conclusion contrasts with the views of some philosophers of science, who have suggested that biology cannot have laws. I argue that the debate has been confused because two very different types of law can be recognised: correlative and causal laws. Once we recognise that there is a difference, the argument against causal laws becomes stronger, and instead I suggest that ecologists should recognise that they can and do produce generalisations that are used to build models – nomological machines – that describe the ecological systems they are studying.     

Human and machine factors in algae monitoring performance

We all take our visual systems for granted, and often assume we are always ‘near perfect’ observers. This is not the case; expert visual recognition is complex and can be error prone. Starting with examples that define the problem I will explore some of the issues of recognition where expert judgements are required.

In addition to ‘expert’ effects, there are a number of cognitive factors that can severely affect performance, including fatigue, boredom, recency effects, positivity bias and short-term memory effects. Experimental evidence of the impact of these on performance are presented and discussed.

The specimen identifications generated by experts are useful not only to ecology, but to researchers developing systems for automatic labelling of marine plankton. Comparisons of performance are presented, where human experts have been pitted against machines to label plankton. Consensus of opinion is important in reducing errors, yet it is the norm for experts to operate alone. The shortcomings of man and machines engaged in plankton recognition are reviewed and the future of automation is assessed.     

Theory of molecular machines. I. Channel capacity of molecular machines

Like macroscopic machines, molecular-sized machines are limited by their material components, their design, and their use of power. One of these limits is the maximum number of states that a machine can choose from. The logarithm to the base 2 of the number of states is defined to be the number of bits of information that the machine could "gain" during its operation. The maximum possible information gain is a function of the energy that a molecular machine dissipates into the surrounding medium (Py), the thermal noise energy which disturbs the machine (Ny) and the number of independently moving parts involved in the operation (dspace): Cy = dspace log2 [( Py + Ny)/Ny] bits per operation. This "machine capacity" is closely related to Shannon's channel capacity for communications systems. An important theorem that Shannon proved for communication channels also applies to molecular machines. With regard to molecular machines, the theorem states that if the amount of information which a machine gains is less than or equal to Cy, then the error rate (frequency of failure) can be made arbitrarily small by using a sufficiently complex coding of the molecular machine's operation. Thus, the capacity of a molecular machine is sharply limited by the dissipation and the thermal noise, but the machine failure rate can be reduced to whatever low level may be required for the organism to survive.     

Adaptive properties of living beings: proposal for a generic mechanism. (Self-programming machines III)

Living systems are capable to have appropriate responses to unpredictable environment. This kind of self-organization seems to operate as a self-programming machine, i.e. an organization able to modify itself. Until now the models of self-organization of living beings proposed are functions solutions of differential systems or transition functions of automata. These functions are fixed and these models are therefore unable to modify their organization. On the other hand, computer science propose a lot of models having the properties of adaptive systems of living beings, but all these models depend on the comparison between a goal and the results and ingenious choices of parameters by programmers, whereas there are no programmer's intention nor choice in the living systems. From two best known examples of adaptive systems of living beings, nervous system and immune system that have in common that the external signals modify the rewriting of their organization and therefore work as self-organizing machines, we devised machines with a finite set of inputs, based upon a recurrence, are able to rewrite their organization (Self-programming machines or m(sp)) whenever external conditions vary and have striking properties of adaptation. M(sp) have similar properties whatever the operation defining the recurrence maybe. These results bring us to make the following statement: adaptive properties of living systems can be explained by their ability to rewrite their organization whenever external conditions vary under the only assumption that the rewriting mechanism be a deterministic constant recurrence in a finite state set.     

A camel passes through the eye of a needle: protein unfolding activity of Clp ATPases

Clp ATPases are protein machines involved in protein degradation and disaggregation. The common structural feature of Clp ATPases is the formation of ring-shaped oligomers. Recent work has shown that the function of all Clp ATPases is based on an energy-dependent threading of substrates through the narrow pore at the centre of the ring. This review gives an outline of known mechanistic principles of threading machines that unfold protein substrates either before their degradation (ClpA, ClpX, HslU) or during their reactivation from aggregates (ClpB). The place of Clp ATPases within a broad AAA+ superfamily of ATPases associated with various cellular activities suggests that similar mechanisms can be used by other protein machines to induce conformational rearrangements in a wide variety of substrates.