The effects of temperature on ATPase activity and force generation in skinned muscle fibers from the Pacific blue marlin (Makaira nigricans)

Summary ATPase activity and force generation have been measured simultaneously in isolated, demembranated muscle fibers of the Pacific blue marlin (Makaira nigricans) between 0 and 30°C. Tension generation is relatively independent of temperature above 15°C and falls with a Q₁₀ of <1.5 on decreasing the temperature to 0°C. In contrast, the Q₁₀ for ATPase activity is 2.2 over the range 0–30°C. The results are interpreted in terms of the cross bridge theory of contraction.     

Quantum decoherence and the approach to equilibrium (II)

In a previous paper [Hemmo, M & Shenker, O (2003). Quantum decoherence and the approach to equilibrium I. Philosophy of Science, 70, 330–358] we discussed a recent proposal by Albert [(2000). Time and chance. Cambridge, MA: Harvard University Press. Chapter 7] to recover thermodynamics on a purely dynamical basis, using the quantum theory of the collapse of the quantum state of [Ghirardi, G, Rimini, A and Weber, T., (1986). Unified dynamics for microscopic and macroscopic systems. Physical Review, D 34, 470–479]. We proposed an alternative way to explain thermodynamics within no collapse interpretations of quantum mechanics. In this paper some difficulties faced by both approaches are discussed and solved: the spin echo experiments, and the problem of extremely light gases. In these contexts, we point out several ways in which the above quantum mechanical approaches as well as some other classical approaches to the foundations of statistical mechanics may be distinguished experimentally.     

Substrate binding and catalytic mechanism of class B β-lactamases: a molecular modelling study

Increased resistance to β-lactam antibiotics is mainly due to β-lactamases whose production by pathogenic bacteria makes their broad activity spectrum especially frightening. X-ray structures of several zinc β-lactamases have revealed the coordination of the two metal ions, but their mode of action remains unclear. Geometry optimisation of stable complexes along the reaction pathway of benzylpenicillin hydrolysis highlighted a proton shuttle occurring from D120 of the Bacillus cereus β-lactamase to the β-lactam nitrogen via Zn2 which is central to the network. First, the Zn1 ion has a structural role maintaining Zn-bound waters, WAT1 and WAT2, either directly or through the Zn1 tetrahedrally coordinated histidine ligands. The Zn2 ion has a more catalytic role, stabilising the tetrahedral intermediate, accepting the β-lactam nitrogen atom as a ligand. The role of Zn2 and the flexibility in the coordination geometry of both Zn ions is of crucial importance for catalysis. Received 14 August 2001; received after revision 19 October 2001; accepted 30 October 2001     

A remark on Fuchs’ Bayesian interpretation of quantum mechanics

Quantum mechanics is a theory whose foundations spark controversy to this day. Although many attempts to explain the underpinnings of the theory have been made, none has been unanimously accepted as satisfactory. Fuchs has recently claimed that the foundational issues can be resolved by interpreting quantum mechanics in the light of quantum information. The view proposed is that quantum mechanics should be interpreted along the lines of the subjective Bayesian approach to probability theory. The quantum state is not the physical state of a microscopic object. It is an epistemic state of an observer; it represents subjective degrees of belief about outcomes of measurements. The interpretation gives an elegant solution to the infamous measurement problem: measurement is nothing but Bayesian belief updating in a analogy to belief updating in a classical setting. In this paper, we analyze an argument that Fuchs gives in support of this latter claim. We suggest that the argument is not convincing since it rests on an ad hoc construction. We close with some remarks on the options left for Fuchs’ quantum Bayesian project.     

Genomic sources of regulatory variation in cis and in trans

Regulatory variation results from genetic changes with both cis and trans acting effects on gene expression. Here I describe the types of genetic variants that alter cis and trans regulation and discuss differences in the potential for cis and trans changes among different classes of genes. I argue that the molecular function of the protein encoded by each gene and how the gene is wired into the genomic regulatory network may influence its propensity for cis and trans regulatory changes.Received 15 February 2005; received after revision 12 April 2005; accepted 26 April 2005     

Cisplatin-induced genes as potential markers for thyroid cancer

Despite the uncontested role of p53 in cycle arrest/cell death after cisplatin treatment, to date the question whether wild-type p53 confers a resistant or sensitive status on the cell is still a matter of debate. Isogenic and isophenotypic human thyroid papillary carcinoma cell line variants for p53 differently expressed cycle genes after cisplatin treatment. Seven genes (CDC6-related protein, CCNC, GAS1, TFDP2, MAPK10/JNK3, WEE1, RPA1) selected after expression on an Atlas human cell cycle array were analyzed by quantitative real-time PCR. While cisplatin treatment increased their expression in p53 wild-type cells it decreased it in cells with inactivated p53 and had no or less effect on cells with mutated p53. These results show that in a well-defined system, different alterations of p53 can lead to a different regulation of genes and hence to either resistance or sensitivity to cisplatin. Moreover for the first time, MAPK10/JNK3 was identified in human thyroid cells and tissue. Four of the genes (CDC6-related protein, CCNC, GAS1 and TFDP2) were decreased in human papillary carcinoma tissues. Relevance of these genes (especially a decrease in GAS1 in thyroid papillary carcinoma) in various malignant pathologies has already been shown. These genes may be explored as new markers in advanced thyroid cancer such as metastatic and anaplastic forms displaying p53 alterations.Received 26 July 2004; received after revision 14 September 2004; accepted 26 October 2004     

Temporal Aggregation in Dynamic Linear Models

One important aspect concerning the analysis and forecasting of time series that is sometimes neglected is the relationship between a model and the sampling interval, in particular, when the observation is cumulative over the sampling period. This paper intends to study the temporal aggregation in Bayesian dynamic linear models (DLM). Suppose that a time series Y_t is observed at time units t and the observations of the process are aggregated over r units of time, defining a new time series Z_k=Σ^r_i=1Y_rk+i. The relevant factors explaining the variation of Z_k can, and in general will, be different, depending on how the sampling interval r is chosen. It is shown that if Y_t follows certain dynamic linear models, then the aggregated series can also be described by possibly different DLM. In the examples, the industrial production of Brazil is analysed under various aggregation periods and the results are compared. © 1997 John Wiley & Sons, Ltd.     

Endocrine-dependent expression of circadian clock genes in insects

Current models state that insect peripheral oscillators are directly responsive to light, while mammalian peripheral clock genes are coordinated by a master clock in the brain via intermediate factors, possibly hormonal. We show that the expression levels of two circadian clock genes, period (per) and Par Domain Protein 1 (Pdp1) in the peripheral tissue of an insect model species, the linden bug Pyrrhocoris apterus, are inversely affected by contrasting photoperiods. The effect of photoperiod on per and Pdp1 mRNA levels was found to be mediated by the corpus allatum, an endocrine gland producing juvenile hormone. Our results provide the first experimental evidence for the effect of an endocrine gland on circadian clock gene expression in insects. Received 31 October 2007; received after revision 7 January 2008; accepted 9 January 2008 D. Dolezel, L. Zdechovanova: These authors contributed equally to this work.     

What leads from <Emphasis Type="Italic">dead-end?</Emphasis>

The 129 mouse strain develops congenital testicular germ cell tumors (TGCTs) at a low frequency. TGCTs in mice resemble the testicular tumors (teratomas) that occur in human infants. The genes that cause these tumors in 129 have not been identified. The defect at the Ter locus increases TGCT incidence such that 94% of 129-Ter/Ter males develop TGCTs. The primary effect of the Ter mutation is progressive loss of primordial germ cells (PGCs) during embryonic development. This results in sterility in adult Ter/Ter mice on all mouse strain backgrounds. However, on the 129 background, Ter causes tumor development in addition to sterility. Therefore, Ter acts as a modifier of 129-derived TGCT susceptibility genes. Ter was identified to be a mutation that inactivates the Dead-end1 (Dnd1) gene. In this perspective, I discuss the possible areas of future investigations to elucidate the mechanism of TGCT development due to Dnd1 inactivation. Received 29 September 2006; received after revision 29 January 2007; accepted 19 February 2007     

Localization and the interface between quantum mechanics, quantum field theory and quantum gravity II: The search of the interface between QFT and QG

The main topics of this second part of a two-part essay are some consequences of the phenomenon of vacuum polarization as the most important physical manifestation of modular localization. Besides philosophically unexpected consequences, it has led to a new constructive “outside-inwards approach” in which the pointlike fields and the compactly localized operator algebras which they generate only appear from intersecting much simpler algebras localized in noncompact wedge regions whose generators have extremely mild almost free field behavior.Another consequence of vacuum polarization presented in this essay is the localization entropy near a causal horizon which follows a logarithmically modified area law in which a dimensionless area (the area divided by the square of dR where dR is the thickness of a light-sheet) appears. There are arguments that this logarithmically modified area law corresponds to the volume law of the standard heat bath thermal behavior. We also explain the symmetry enhancing effect of holographic projections onto the causal horizon of a region and show that the resulting infinite dimensional symmetry groups contain the Bondi–Metzner–Sachs group. This essay is the second part of a partitioned longer paper.     

Forecasting Austrian IPOs: An application of linear and neural network error-correction models

In this paper we apply cointegration and Granger-causality analyses to construct linear and neural network error-correction models for an Austrian Initial Public Offerings IndeX (IPOX_ATX). We use the significant relationship between the IPOX_ATX and the Austrian Stock Market Index ATX to forecast the IPOX_ATX. For prediction purposes we apply augmented feedforward neural networks whose architecture is determined by Sequential Network Construction with the Schwartz Information Criterion as an estimator for the prediction risk. Trading based on the forecasts yields results superior to Buy and Hold or Moving Average trading strategies in terms of mean-variance considerations.     

Bromocriptine/SKF38393 ameliorates islet dysfunction in the diabetic (db/db) mouse

Dysfunction of pancreatic islets plays a crucial role in the etiology of type II diabetes. Chronic hyperglycaemia or hyperlipidaemia may impair islet function. Previous studies by our laboratory have demonstrated that dopaminergic agonists ameliorated hyperglycaemia and hyperlipidaemia in obese and diabetic rodents. In the present study, we investigated the effect of a treatment with the dopamine D₂ /D₁ receptor agonists (bromocriptine/SKF38393, BC/SKF) on islet dysfunction in db/db mice. Our results show that a 2-week BC/SKF treatment markedly reduced hyperglycaemia and hyperlipidaemia, and significantly improved islet dysfunction demonstrated by an increase of secretagogue-stimulated insulin release from islets of db/db mice to levels observed in islets from lean mice. There was also a fourfold increase of insulin content in the pancreas of BC/SKF-treated db/db mice compared with that in untreated controls. The effect of BC/SKF on islet function cannot be mimicked in pair-fed animals. BC/SKF had no direct stimulatory effect on islet insulin secretion, suggesting BC/SKF treatment improved islet function via an indirect mechanism. This treatment markedly improved the abnormally elevated daily levels of corticosterone, blood glucose and plasma lipids, supporting the view that BC/SKF may affect the neuroendocrine system that in turn regulates peripheral metabolism and thereby improves islet function. Received 3 April 1998; accepted 27 April 1998     

Forecasting for the generation of trading signals in financial markets

In this paper we show that optimal trading results can be achieved if we can forecast a key summary statistic of future prices. Consider the following optimization problem. Let the return r_i (over time i=1, 2, ..., n) for the ith day be given and the investor has to make investment decision d_i on the ith day with d_i=1 representing a ‘long' position and d_i=0 a ‘neutral' position. The investment return is given by r=Σⁿ_i=1r_id_i−cΣⁿ⁺¹_i=1∣d_i−d_i−1∣, where c is the transaction cost. The mathematical programming problem of choosing d₁, ..., d_n to maximize r under a given transaction cost c is shown to have an analytic solution, which is a function of a key summary statistic called the largest change before reversal. The largest change before reversal is recommended to be used as an output in a neural network for the generation of trading signals. When neural network forecasting is applied to a dataset of Hang Seng Index Futures Contract traded in Hong Kong, it is shown that forecasting the largest change before reversal outperforms the k‐step‐ahead forecast in achieving higher trading profits. Copyright © 2000 John Wiley & Sons, Ltd.     

DNG1, a Dictyostelium homologue of tumor suppressor ING1 regulates differentiation of Dictyostelium cells

dng1 is a Dictyostelium homologue of the mammalian tumor suppressor ING gene. DNG1 protein localizes in the nucleus, and has a highly conserved PHD finger domain found in chromatin-remodeling proteins. Both dng1 disruption and overexpression impaired cell proliferation. In dng1-null cells, the progression of differentiation was delayed in a cell-density-dependent manner, and many tiny aggregates were formed. Exogenously applied cAMP pulses reversed the inhibitory effect caused by dng1 disruption on the aggregation during early development, but formation of tiny aggregates was not restored. dng1-overexpressing cells acquired the ability to undergo chemotaxis to cAMP earlier and exhibited enhanced differentiation. These phenotypes were found to be coupled with altered expressions of early genes such as cAMP receptor 1 (car1) and contact site A (csA). Furthermore, disordered histone modifications were demonstrated in dng1-null cells. These results suggest a regulatory role of dng1 in the transition of cells from growth to differentiation.Received 29 December 2004; received after revision 24 May 2005; accepted 26 May 2005     

Spektrale Phototaxis von Planktonrotatorien

Summary The spectral sensitivity of 3 species of planktonic Rotatoria (Asplanchna priodonta, Polyarthra remata, Filinia longiseta) were measured by means of the positive phototactic reaction.Asplanchna andPolyarthra both have a broad maximum sensitivity range around 540 nm and a near maximum at 440 nm. In the UV direction (to 360 nm) the spectral sensitivity increases. In contrast,Filinia has only a maximum of 460 nm in the visible spectrum, but behaves similarly to the other species in the UV region. The ecological significance of these results is discussed, as well as their bearing on a possible dermal light sense.     

Sexual behavior mutants revisited: molecular and cellular basis of Drosophila mating

The study of Drosophila melanogaster by a combination of forward genetics with specific mutants, and reverse genetics, in which a given gene is expressed in an appropriate brain area to test its effect on behavior, provides a unique opportunity to explore the causal relationship between a particular gene, its function in the cell and the behavioral outcome at the organismic level. Enhanced male-to-male courtship has been shown to occur as a result of mutations in several different genes. For example, the Voila mutant exhibits intense GAL4 reporter expression in the tarsal gustatory sensilla, suggesting the importance of tapping by a male on the female abdomen with his forelegs. Feminization of parts of the antennal lobe and mushroom body by targeted expression of a female-determining gene transformer ⁺ (tra ⁺) drives the male to court other males. Mutations in the tra target gene fruitless (fru), which is expressed in the antennal lobe as well as the suboesophageal ganglion (the gustatory inputs are processed here), also induce homosexual courtship in males. These results suggest that sensory inputs mediated and/or processed by the tarsal receptors, suboesophageal ganglion, antennal lobe and mushroom body contribute to the regulation of male–female courtship. Mosaic analysis localized the neural center for male courtship behavior to the posterior dorsal brain, in which the sensory information processed by the aforementioned neural structures may be integrated. Another mosaic study mapped the neural center for female sexual behavior, as measured by her receptiveness to copulation, to the anterior dorsal brain. The issue as to how the mutations that reduce female sexual receptiveness, e.g. dissatisfaction (dsf), spinster (spin) and chaste (cht), affect the structure and/or function of this neural center deserves to be addressed urgently. Received 27 April 1999; received after revision 21 June 1999; accepted 8 July 1999     

Kinetik der hepatischen Farbstoffaufnahme von Indocyaningrün. Einfluss von Bilirubin und Natriumglykocholat

Summary Kinetics of hepatic uptake of indocyanine green, a dye which is used for evaluation of liver function, were studied in the rat. The results indicate that the relationship between ICG-dose and initial hepatic dye uptake obeys Michaelis-Menten kinetics suggesting an interaction of the dye with a carrier or fixed site in the liver cell. Thus it was possible to calculate maximum ICG-uptake (v _max ) and the Michaelis constant (K _m ) of this transport system from several submaximal values.v _max was 7.65 (6-06-9.65)²² mg per 100 g liver/min and K _m 0.56 (0.31–0.81)²². Under the influence of substances which inhibit the elimination of dyes by the liver the parametersv _max and K _m showed changes which allowed characterization of the type of inhibition. While sodium glycocholate had no influence on maximum hepatic ICG-uptake and the Michaelis constant bilirubin caused a significant increase of K _m to 1.29 (0.68–1.90)²² without significantly changingv _max . These data suggest that bilirubin interferes with hepatic uptake of indocyanine green by competitive inhibition and that uptake of bile acids is dependent on a different mechanism.     

Über den Einfluss von Desoxycorticosteron auf Kontraktur und Kaliumfreisetzung durch Acetylcholin an der innervierten und denervierten Skelettmuskulatur

Summary The release of potassium ions from striated muscle, and the changes in mechanical tension developed by the gastrocnemius muscle on intraarterial injection of ACh, were investigated by isolated perfusion of the hind limbs in cats. The reaction of the normal innervated and chronically denervated muscle in the same animal were compared before and during perfusion with 2·10^–4 M/l desoxycorticosterone glucoside (DCG). The following results were obtained: after perfusion with DCG no change in the spontaneous release of potassium ions occurred neither on the innervated nor on the denervated muscle. The potassium release following intra-arterial injections of various doses of ACh was significantly reduced on innervated and denervated muscle. On the denervated muscle there was also a considerable reduction of the height of contractures caused by ACh administration. The results make it probable that DCG acts by an inhibition of depolarisation in the same way asd-tubocurarine.