C\bar lr and C\bar ls subcomponents of human complement: Two serine proteinases lacking the ‘histidine-loop’ disulphide bridge

The N-terminal amino acid sequence of human C \(\bar l\) s b chain has been extended to 52 residues. The histidine residue involved in the charge-relay system is located at position 38, whereas the ‘histidine-loop’ disulphide bridge is missing. So far, human complement subcomponents C \(\bar l\) r and C \(\bar l\) s are the only known mammalian serine proteinases lacking this disulphide bridge.     

Sur l'espace topologique lié à une nouvelle théorie de l'apprentissage

There have been two contrasting doctrines concerning learning, more generally about acquisition of knowledge: empiricism and rationalism. The theory of learning in such a field as artificial intelligence seems to fall within the empiricist framework. On the hand, N. Chomsky and his followers have discussed, during the last decade, concerning learning, especially about language learning, from the rationalist point of view (Chomsky, 1965). The main feature in the rationalist approach toward a theory of learning lies in the speculation that in order to acquire knowledge it is indispensable for a learner to be endowed with “innate ideas”, and that “experience” in the external world are merely subsidiary types of information for the learner. If this is acceptable, we can inquire: Under what kind of innate ideas can the learner understand the structure of the external world? In our previous paper (Uesaka, Aizawa, Ebara, and Ozeki, 1973), we formalized this by introducing the mathematical notion of “learnability”, and gave a partial answer to the above inquiry. In this formalization we assumed that the set F of objects to be learned consists of mappings of N to itself, where N is the set of positive integers. Then, constructing a topological space (F, \(\mathcal{O}\) ) by an appropriate family \(\mathcal{O}\) of open sets, we observed that the notion of learnability can be well described in terms of topological properties of the learning space (F, \(\mathcal{O}\) ). Many problems must be solved, however, before we raise the theory to a complete model of the rationalist theory of learning. The topological study of the space (F, \(\mathcal{O}\) ) is, we believe, the first step toward this approach. In this context, we discuss the topological aspects of this space. Now we define \(\mathcal{O}\) as follows: By N ² we mean the direct product of two N's. Let s be a subset of N ². If, for any (x, y), (x′, y′) in s, x=x′ implies y=y′, then we say that s is single-valued. Let f ∈ F, If, for any (x, y) in s, y=f(x), then f is said to be on s, denoted as \(f\underline \supseteq s\) . Let \(\pi \left( s \right) = \left\{ {g;g \in F,g\underline \supseteq s} \right\}\) . A single-valued finite subset of N ² is called datum. Let D denote the family of all data. Let \(\mathcal{O}* = \left\{ \phi \right\} \cup \left\{ {\pi \left( d \right);d \in D} \right\}\) , and \(\mathcal{O}\) denote the family of all subsets of F, each of which is written as \(\mathop \cup \limits_\alpha W_{\alpha }\) , where W _α is in \(\mathcal{O}*\) . Then, it is easily seen that \(\mathcal{O}\) satisfies the axiom of the open system of a topological space. It is shown that the learning space (F, \(\mathcal{O}\) ) has the following properties:

1. It satisfies the first and the second countability axioms.
2. It is separable and is totally disconnected.
3. It is a Hausdorff space and, further, is regular and normal.
4. It is neither compact nor locally compact.
5. It is metrizable, or more precisely there exists a complete but not totally bounded metric space which is homeomorphic to learning space.
6. Any of its subspace can be embedded into its special subspace.

     

Kinetic models of coupling between H+ and Na+-translocation and ATP synthesis/hydrolysis by F0F1-ATPases: Can a cell utilize both\Delta \bar \mu _{H^ + } and\Delta \bar \mu _{Na^ + } for ATP synthesis underin vivo conditions using the same enzyme?

Kinetic models of the F₀F₁-ATPase able to transport H⁺ or/and Na⁺ ions are proposed. It is assumed that (i) H⁺ and Na⁺ compete for the same binding sites, (ii) ion translocation through F₀ is coupled to the rate-limiting step of the F₁-catalyzed reaction. The main characteristics of the dependences of ATP synthesis and hydrolysis rates on Δφ, ΔpH, and ΔpNa are predicted for various versions of the coupling model. The mechanism of the switchover from \(\Delta \bar \mu _{H^ + } \) -dependent synthesis to the \(\Delta \bar \mu _{Na^ + } \) -dependent one is demonstrated. It is shown that even with a drastic drop in \(\Delta \bar \mu _{H^ + } \) , ATP hydrolysis by the proton mode of catalysis can be effectively inhibited by Δφ and ΔpNa. The results obtained strongly support the possibility that the same F₀F₁-ATPase in bacterial cells can utilize both \(\Delta \bar \mu _{H^ + } \) and \(\Delta \bar \mu _{Na^ + } \) for ATP synthesis underin vivo conditions.     

On biomass diversity in ecology

We postulate that the biomass distribution function for an ecological population may be derived from the condition that the biomas diversity functional is maximal subject to an energetic constraint on the total biomass. This leads to a biomass distribution of the form \(p(m) = \bar m^{ - 1} \exp ( - m/\bar m)\) , where \(\bar m\) is the mean biomass per individual. The same condition yields a unique value for the biomass diversity functional. These predictions are tested against fishery data and found to be in good agreement. It is argued that the existence of a unique value for biomass diversity may provide a preliminary theoretical foundation for the observed upper limit to species diversity.     

Synchronization of non-linear biochemical oscillators coupled by diffusion

The behaviour of similar coupled non-linear oscillators of the type \(\dot x\) =f(x, y, µ \(\dot y\) =g(x, y, µ is to be investigated. The oscillators are assumed to be coupled by diffusion gradients. If some conditions on the magnitude of the diffusion coefficients are satisfied, it is proved that: 1) if the oscillators have the same period (identical value of the parameter μ) and different phases before coupling, after coupling they tend to synchronize the phases; 2) if the periods of the oscillators are not too different (in terms of the values of the parameter μ) before coupling, after coupling they tend to oscillate with the same period. It is suggested the possible role of diffusion as a synchronizing mechanism in some biological phenomena.     

Linear and nonlinear stiffness and friction in biological rhythmic movements

Biological rhythmic movements can be viewed as instances of self-sustained oscillators. Auto-oscillatory phenomena must involve a nonlinear friction function, and usually involve a nonlinear elastic function. With respect to rhythmic movements, the question is: What kinds of nonlinear friction and elastic functions are involved? The nonlinear friction functions of the kind identified by Rayleigh (involving terms such as $\dot \theta ^3 $ ) and van der Pol (involving terms such as $\theta ^2 \dot \theta $ ), and the nonlinear elastic functions identified by Duffing (involving terms such as $\theta ^3 $ ), constitute elementary nonlinear components for the assembling of self-sustained oscillators. Recently, additional elementary nonlinear friction and stiffness functions expressed, respectively, through terms such as $\theta ^2 \dot \theta ^3 $ and $\theta \dot \theta ^2 $ , and a methodology for evaluating the contribution of the elementary components to any given cyclic activity have been identified. The methodology uses a quantification of the continuous deviation of oscillatory motion from ideal (harmonic) motion. Multiple regression of this quantity on the elementary linear and nonlinear terms reveals the individual contribution of each term to the oscillator's non-harmonic behavior. In the present article the methodology was applied to the data from three experiments in which human subjects produced pendular rhythmic movements under manipulations of rotational inertia (experiment 1), rotational inertia and frequency (experiment 2), and rotational inertia and amplitude (experiment 3). The analysis revealed that the pendular oscillators assembled in the three experiments were compositionally rich, braiding linear and nonlinear friction and elastic functions in a manner that depended on the nature of the task.     

Dynamical systems under constant organization I. Topological analysis of a family of non-linear differential equations —A model for catalytic hypercycles

The paper presents a qualitative analysis of the following systems ofn differential equations: \(\dot x_i = x_i x_j - x_i \sum\nolimits_r^n { = 1} x_r x_s {\mathbf{ }}(j = i - 1 + n\delta _{i1} {\mathbf{ }}and{\mathbf{ }}s = r - 1 + n\delta _{r1} )\) , which show cyclic symmetry. These dynamical systems are of particular interest in the theory of selforganization and biological evolution as well as for application to other fields.     

Reconstructing a Phylogenetic Level-1 Network from Quartets

We describe a method that will reconstruct an unrooted binary phylogenetic level-1 network on \(n\) taxa from the set of all quartets containing a certain fixed taxon, in \(O(n^3)\) time. We also present a more general method which can handle more diverse quartet data, but which takes \(O(n^6)\) time. Both methods proceed by solving a certain system of linear equations over the two-element field \(\mathrm{GF}(2)\) . For a general dense quartet set, i.e. a set containing at least one quartet on every four taxa, our \(O(n^6)\) algorithm constructs a phylogenetic level-1 network consistent with the quartet set if such a network exists and returns an \(O(n^2)\) -sized certificate of inconsistency otherwise. This answers a question raised by Gambette, Berry and Paul regarding the complexity of reconstructing a level-1 network from a dense quartet set, and more particularly regarding the complexity of constructing a cyclic ordering of taxa consistent with a dense quartet set.     

Isolation,assay, biosynthesis,metabolism, uptake and translocation,and function of proline in plant cells and tissues

The amino acid L-proline has been the subject of intensive research during the past ten to fifteen years. This stems from the observations that it incorporates into peptide linkage thereby serving as a precursor to peptidyl-bound L-hydroxyproline, a constituent of “extensin,” and that it accumulates when some plants are exposed to diverse biological and environmental stresses. The contents of selected papers which have been published during the last quarter of a century regarding the isolation, assay, biosynthesis, metabolism, transport and function of L-proline within various plant tissues and their cells are both interpreted and summarized in this review. Occasionally, relevant information from animal and bacterial systems concerning these topics is included. Hydroxyproline-containing proteins are not considered. L-proline was reported to be a constituent of leaves as early as the 1950’s. Since then, it and its analogues have been extracted from the organs of a variety of plants. The analogues include: methyl-hydroxylproline; 4-methylene-DL-proline; L-azetidine-2-carboxylic acid; 2,3,cis-3,4-trans-dihydroxy-L-proline; L-pipecolic acid and 4-trans-hydroxypro-line. L-proline can be both detected and quantified by colorimetric, combined fluorometric-amino acid analyzer and gas Chromatographic procedures. L-proline may be synthesized from L-glutamic acid via the following biosynthetic pathway: L-glutamic acid \(\underrightarrow {\gamma - glutamic acid kinase}\) γ-glutamyl phosphate \(\underrightarrow {\gamma - glutamyl phosphate reductase}\) γ-glutamyl semialdehyde \(\underrightarrow {spontaneous cyclization}\) Δ′-pyrroline-5-Carboxylate (P5C) \(\underrightarrow {P5C reductase}\) L-proline. Proline can also originate from L-arginine and L-ornithine. Biosynthesis from the latter compound proceeds either through the γ-glutamyl semialdehyde and pyrroline-5-carboxylate pathway or alternatively a α-keto-δ-aminovaleric and pyrroline-2-carboxylate pathway. The metabolism of L-proline most likely involves the reverse of the biosynthetic pathway with an initial prolyl dehydrogenaseor prolyl oxidasemediated conversion of L-proline to Δ′-pyrroline-5-carboxylate. The metabolism of L-proline has been demonstrated to occur in excised tissues and cell free extracts, cell suspension cultures and reproductive structures. Little is known about the mechanism by which L-proline is taken up by cultured plant cells and excised tissues. Once within the plant Lproline can be translocated through the phloem at velocities similar to those for carbon dioxide assimilates. In addition to serving as a substrate for peptidyl-bound hydroxyproline, L-proline may function as an adaptation to diverse biological and environmental stresses, a cryoprotectant, a nitrogen pool, a precursor for chlorophyll synthesis upon relief of stress, a regulator together with L-histidine of fertility and sterility and/or a substrate for respiration.     

A thermomechanical framework for reconciling the effects of ultraviolet radiation exposure time and wavelength on connective tissue elasticity

Augmentation of the mechanical properties of connective tissue using ultraviolet (UV) radiation—by targeting collagen cross-linking in the tissue at predetermined UV exposure time \((t)\) and wavelength \((\lambda )\) —has been proposed as a therapeutic method for supporting the treatment for structural-related injuries and pathologies. However, the effects of \(\lambda \) and \(t\) on the tissue elasticity, namely elastic modulus \((E)\) and modulus of resilience \((u_\mathrm{Y})\) , are not entirely clear. We present a thermomechanical framework to reconcile the \(t\) - and \(\lambda \) -related effects on \(E\) and \(u_\mathrm{Y}\) . The framework addresses (1) an energy transfer model to describe the dependence of the absorbed UV photon energy, \(\xi \) , per unit mass of the tissue on \(t\) and \(\lambda \) , (2) an intervening thermodynamic shear-related parameter, \(G\) , to quantify the extent of UV-induced cross-linking in the tissue, (3) a threshold model for the \(G\) versus \(\xi \) relationship, characterized by   \(t_\mathrm{C}\) —the critical \(t\) underpinning the association of \(\xi \) with \(G\) —and (4) the role of \(G\) in the tissue elasticity. We hypothesized that \(G\) regulates \(E\) (UV-stiffening hypothesis) and \(u_\mathrm{Y}\) (UV-resilience hypothesis). The framework was evaluated with the support from data derived from tensile testing on isolated ligament fascicles, treated with two levels of \(\lambda \) (365 and 254 nm) and three levels of \(t\) (15, 30 and 60 min). Predictions from the energy transfer model corroborated the findings from a two-factor analysis of variance of the effects of \(t\) and \(\lambda \) treatments. Student’s t test revealed positive change in \(E\) and \(u_\mathrm{Y}\) with increases in \(G\) —the findings lend support to the hypotheses, implicating the implicit dependence of UV-induced cross-links on \(t\) and \(\lambda \) for directing tissue stiffness and resilience. From a practical perspective, the study is a step in the direction to establish a UV irradiation treatment protocol for effective control of exogenous cross-linking in connective tissues.     

Modulation of the cAMP Response by G\alpha _i and G\beta \gamma : A Computational Study of G Protein Signaling in Immune Cells

Cyclic AMP is important for the resolution of inflammation, as it promotes anti-inflammatory signaling in several immune cell lines. In this paper, we present an immune cell specific model of the cAMP signaling cascade, paying close attention to the specific isoforms of adenylyl cyclase (AC) and phosphodiesterase that control cAMP production and degradation, respectively, in these cells. The model describes the role that G protein subunits, including G \(\alpha _s\) , G \(\alpha _i\) , and G \(\beta \gamma \) , have in regulating cAMP production. Previously, G \(\alpha _i\) activation has been shown to increase the level of cAMP in certain immune cell types. This increase in cAMP is thought to be mediated by \(\beta \gamma \) subunits which are released upon G \(\alpha \) activation and can directly stimulate specific isoforms of AC. We conduct numerical experiments in order to explore the mechanisms through which G \(\alpha _i\) activation can increase cAMP production. An important conclusion of our analysis is that the relative abundance of different G protein subunits is an essential determinant of the cAMP profile in immune cells. In particular, our model predicts that limited availability of \(\beta \gamma \) subunits may both \((i)\) enable immune cells to link inflammatory G \(\alpha _i\) signaling to anti-inflammatory cAMP production thereby creating a balanced immune response to stimulation with low concentrations of PGE2, and \((ii)\) prohibit robust anti-inflammatory cAMP signaling in response to stimulation with high concentrations of PGE2.     

Head impact accelerations for brain strain-related responses in contact sports: a model-based investigation

Both linear \((\mathbf{a}_{\mathrm{lin}})\) and rotational \((\mathbf{a}_{\mathrm{rot}} )\) accelerations contribute to head impacts on the field in contact sports; however, they are often isolated in injury studies. It is critical to evaluate the feasibility of estimating brain responses using isolated instead of full degrees-of-freedom (DOFs) accelerations. In this study, we investigated the sensitivities of regional brain strain-related responses to resultant \(\mathbf{a}_{\mathrm{lin}}\) and \(\mathbf{a}_{\mathrm{rot}}\) as well as the relative contributions of these acceleration components to the responses via random sampling and linear regression using parameterized, triangulated head impacts with kinematic variable values based on on-field measurements. Two independently established and validated finite element models of the human head were employed to evaluate model-consistency and dependency in results: the Dartmouth Head Injury Model and Simulated Injury Monitor. For the majority of the brain, volume-weighted regional peak strain, strain rate, and von Mises stress accumulated from the simulation significantly correlated with the product of the magnitude and duration of \(\mathbf{a}_{\mathrm{rot}}\) , or effectively, the rotational velocity, but not to \(\mathbf{a}_{\mathrm{lin}}\) . Responses from \(\mathbf{a}_{\mathrm{rot}}\) -only were comparable to the full-DOF counterparts especially when normalized by injury-causing thresholds (e.g., volume fractions of large differences virtually diminished (i.e., \(<\) 1 %) at typical difference percentage levels of 1–4 % on average). These model-consistent results support the inclusion of both rotational acceleration magnitude and duration into kinematics-based injury metrics and demonstrate the feasibility of estimating strain-related responses from isolated \(\mathbf{a}_{\mathrm{rot}}\) for analyses of strain-induced injury relevant to contact sports without significant loss of accuracy, especially for the cerebrum.     

Investigation of the possibility of exceeding the Greenwald density limit during ECRH in T-10

In T-10 experiments, attempts were made to significantly exceed the Greenwald limit $\bar n_{Gr} $ during high-power (P _ab=750 kW) electron-cyclotron resonance heating (ECRH) and gas puffing. Formally, the density limit $(\bar n_e )_{\lim } $ exceeding the Greenwald limit $({{(\bar n_e )_{\lim } } \mathord{\left/ {\vphantom {{(\bar n_e )_{\lim } } {\bar n_{Gr} }}} \right. \kern-0em} {\bar n_{Gr} }} = 1.8)$ was achieved for q _L=8.2. However, as q _L decreased, the ratio ${{(\bar n_e )_{\lim } } \mathord{\left/ {\vphantom {{(\bar n_e )_{\lim } } {\bar n_{Gr} }}} \right. \kern-0em} {\bar n_{Gr} }}$ also decreased, approaching unity at q _L≈3. It was suggested that the “current radius” (i.e., the radius of the magnetic surface enclosing the bulk of the plasma current I _p), rather than the limiter radius, was the parameter governing the value of $(\bar n_e )_{\lim } $ . In the ECRH experiments, no substantial degradation of plasma confinement was observed up to $\bar n_e \sim 0.9(\bar n_e )_{\lim } $ regardless of the ratio ${{(\bar n_e )_{\lim } } \mathord{\left/ {\vphantom {{(\bar n_e )_{\lim } } {\bar n_{Gr} }}} \right. \kern-0em} {\bar n_{Gr} }}$ . In different scenarios of the density growth up to $(\bar n_e )_{\lim } $ , two types of disruptions related to the density limit were observed.     

Oxygen removal from water versus arterial oxygen delivery: calibrating the Fick equation in Pacific salmon

While it is well known that O₂ is directly removed from the water by skin and gill tissues of fish, the mismatch between O₂ removal from water (O₂ uptake; \(\dot{V}{\text{O}}_{ 2}\) ) and the O₂ delivered to tissues by the primary circulation (O₂ consumption; \(\dot{V}{\text{aO}}_{ 2}\) ) has never been measured directly. Using data from four recent studies that simultaneously measured \(\dot{V}{\text{O}}_{ 2}\) and \(\dot{V}{\text{aO}}_{ 2}\) in 2–5 kg Pacific salmon, our analysis revealed that sockeye salmon can remove an additional 12–48 % more O₂ from the water than the primary circulation delivers to the systemic tissues. This percentage did not change significantly during swimming activity, a result that contradicts an earlier prediction that the difference should decrease when \(\dot{V}{\text{O}}_{ 2}\) increases during exercise. In resting Chinook salmon, a similar percentage difference in simultaneously measured \(\dot{V}{\text{O}}_{ 2}\) and \(\dot{V}{\text{O}}_{ 2}\) was observed, yet the difference tended to disappear during acute heat stress to a near lethal temperature. These results emphasize that caution should be exercised when using the Fick equation to estimate cardiac output because the overestimate of cardiac output that results from using the Fick equation in Pacific salmon is not small, may not be fixed and may exist in other teleosts.     

Control of mitochondrial and cellular respiration by oxygen

Control and regulation of mitochondrial and cellular respiration by oxygen is discussed with three aims: (1) A review of intracellular oxygen levels and gradients, particularly in heart, emphasizes the dominance of extracellular oxygen gradients. Intracellular oxygen pressure, $p_{O_2 } $ , is low, typically one to two orders of magnitude below incubation conditions used routinely for the study of respiratory control in isolated mitochondria. The $p_{O_2 } $ range of respiratory control by oxygen overlaps with cellular oxygen profiles, indicating the significance of $p_{O_2 } $ in actual metabolic regulation. (2) A methodologically detailed discussion of high-resolution respirometry is necessary for the controversial topic of respiratory control by oxygen, since the risk of methodological artefact is closely connected with far-reaching theoretical implications. Instrumental and analytical errors may mask effects of energetic state and partially explain the divergent views on the regulatory role of intracellular $p_{O_2 } $ . Oxygen pressure for half-maximum respiration,p ₅₀, in isolated mitochondria at state 4 was 0.025 kPa (0.2 Torr; 0.3 ΜM O₂), whereasp ₅₀ in endothelial cells was 0.06–0.08 kPa (0.5 Torr). (3) A model derived from the thermodynamics of irreversible processes was developed which quantitatively accounts for near-hyperbolic flux/ $p_{O_2 } $ relations in isolated mitochondria. The apparentp ₅₀ is a function of redox potential and protonmotive force. The protonmotive force collapses after uncoupling and consequently causes a decrease inp ₅₀. Whereas it is becoming accepted that flux control is shared by several enzymes, insufficient attention is paid to the notion of complementary kinetic and thermodynamic flux control mechanisms.     

A locally convergent rotationally invariant particle swarm optimization algorithm

Several well-studied issues in the particle swarm optimization algorithm are outlined and some earlier methods that address these issues are investigated from the theoretical and experimental points of view. These issues are the: stagnation of particles in some points in the search space, inability to change the value of one or more decision variables, poor performance when the swarm size is small, lack of guarantee to converge even to a local optimum (local optimizer), poor performance when the number of dimensions grows, and sensitivity of the algorithm to the rotation of the search space. The significance of each of these issues is discussed and it is argued that none of the particle swarm optimizers we are aware of can address all of these issues at the same time. To address all of these issues at the same time, a new general form of velocity update rule for the particle swarm optimization algorithm that contains a user-definable function \(f\) is proposed. It is proven that the proposed velocity update rule guarantees to address all of these issues if the function \(f\) satisfies the following two conditions: (i) the function \(f\) is designed in such a way that for any input vector \(\vec {y}\) in the search space, there exists a region \(A\) which contains \(\vec {y}\) and \( f\!\left( {\vec {y}} \right) \) can be located anywhere in \(A\) , and (ii) \(f\) is invariant under any affine transformation. An example of function \(f\) is provided that satisfies these conditions and its performance is examined through some experiments. The experiments confirm that the proposed algorithm (with an appropriate function \(f)\) can effectively address all of these issues at the same time. Also, comparisons with earlier methods show that the overall ability of the proposed method for solving benchmark functions is significantly better.