Modeling the hazard of transition into the absorbing state in the illness-death model

The illness-death model is the simplest multistate model where the transition from the initial state 0 to the absorbing state 2 may involve an intermediate state 1 (e.g., disease relapse). The impact of the transition into state 1 on the subsequent transition hazard to state 2 enables insight to be gained into the disease evolution. The standard approach of analysis is modeling the transition hazards from 0 to 2 and from 1 to 2, including time to illness as a time-varying covariate and measuring time from origin even after transition into state 1. The hazard from 1 to 2 can be also modeled separately using only patients in state 1, measuring time from illness and including time to illness as a fixed covariate. A recently proposed approach is a model where time after the transition into state 1 is measured in both scales and time to illness is included as a time-varying covariate. Another possibility is a model where time after transition into state 1 is measured only from illness and time to illness is included as a fixed covariate. Through theoretical reasoning and simulation protocols, we discuss the use of these models and we develop a practical strategy aiming to (a) validate the properties of the illness-death process, (b) estimate the impact of time to illness on the hazard from state 1 to 2, and (c) quantify the impact that the transition into state 1 has on the hazard of the absorbing state. The strategy is also applied to a literature dataset on diabetes.     

An alternative method of estimating the cranial capacity of Olduvai Hominid 7

The cranial capacity of Olduvai Hominid 7 is estimated to be 690 cc, with a standard uncertainty range of 538 to 868 cc. The estimate is derived from a systematic consideration of the relationships between Bregma-Asterion chords and cranial capacities obtained from a large sample of Homo sapiens and Pan troglodytes and from available fossil hominids. The estimation technique is applicable to other characters and specimens.     

腊玛古猿和西瓦古猿的形态特征及其系统关系——颅骨的形态与比较

本文通过具体的形态比较指出,禄丰腊玛古猿和西瓦古猿应为同一类型的雌雄个体,它们与现代猩猩比较相似,而与大猩猩和黑猩猩差别较大,因此,它们可看作是猩猩的祖先。猩猩这一支大约是在一千二百万年前开始从人猿超科的进化主干上分化出来的。     

SYSTEMATICS AND TAXONOMY OF EOCENE TOMISTOMINE CROCODYLIANS FROM BRITAIN AND NORTHERN EUROPE

Abstract:  The holotype of Dollosuchus dixoni (Owen) from the Early–Middle Eocene Bracklesham Beds of England is a set of mandibular fragments that cannot be distinguished from corresponding parts of other longirostrine crocodylians. An isolated humerus from the Bracklesham Beds is consistent with a gavialoid, but it cannot be referred to the holotype of D. dixoni . The name Dollosuchoides densmorei is established for the well-preserved skull and skeleton of a tomistomine from the Middle Eocene of Belgium that had been referred to D. dixoni . It can be clearly distinguished from the basal tomistomine ' Crocodilus ' spenceri Buckland from the Lower Eocene of England, which cannot be referred to Dollosuchoides and is provisionally referred to Kentisuchus Mook. Although basal within Tomistominae, Dollosuchoides is more closely related to Tomistoma than to Kentisuchus .     

An affinity-column procedure for the purification of veratrate O-demethylase from fungi.

An affinity column procedure is reported for purifying veratrate O-demethylase from higher fungi. The procedure is based on the affinity of the fungal demethylases for veratrate, which was coupled to AH-Sepharose 4B. An over 300-fold purification of the enzyme from an Ascomycete (Chaetomium piluliferum), and a lower degree of purification (20-fold) from a Basidiomycete (Xerocomus badius), were obtained. The O-demethylases from higher fungi require NADH and oxygen. The enzyme activity is sensitive to exposure to oxygen. The pH optima are 5 for enzyme from Chaetomium, and 7 for demethylase from Xerocomus, respectively. The enzymes are not specific for veratrate. They also demethylate p- and m-anisate and 3,4-dimethoxycinnamate, but to a lower degree.     

Rhopalotrema (Digenea: Didymozoidae), a new genus from Australian platycephalid fishes

Rhopalotrema n. g. is erected to accommodate two new species of didymozoid collected from platycephalid fishes from South-east Queensland, Australia and is assigned to the subfamily Didymozoinae. Rhopalotrema elusiva n. sp. is described from the fins of Platycephalus fuscus and R. pterygionastes n. sp. is described from the fins of P. indicus. The new genus is similar to Neometadidymozoon, but is distinguished from it by the structure of the testes, which are convoluted and extend from near the anterior end of the hindbody to a point only a short distance into the forebody. The two new species are distinguished from each other by their size and the size and shape of the oral sucker and pharynx.     

Regressive models for risk prediction of repeated multinomial outcomes: An illustration using Health and Retirement Study data

Life expectancy is increasing in many countries and this may lead to a higher frequency of adverse health outcomes. Therefore, there is a growing demand for predicting the risk of a sequence of events based on specified factors from repeated outcomes. We proposed regressive models and a framework to predict the joint probabilities of a sequence of events for multinomial outcomes from longitudinal studies. The Markov chain is used to link marginal and sequence of conditional probabilities to predict the joint probability. Marginal and sequence of conditional probabilities are estimated using marginal and regressive models. An application is shown using the Health and Retirement Study data. The bias of parameter estimates for all models from all bootstrap simulation is less than 1% in most of the cases. The estimated mean squared error is also very low. Results from the simulation study show negligible bias and the usefulness of the proposed model. The proposed model and framework would be useful to solve real-life problems from various fields and big data analysis.     

Orientational relaxation time of bottom-heavy squirmers in a semi-dilute suspension

One of the important quantities to characterize unsteady behaviour of a cell suspension is the orientational relaxation time, which is the time scale for a micro-organism to re-orientate to its preferred direction from disorientated conditions. In this paper, a swimming micro-organism is modelled as a squirming sphere with prescribed tangential surface velocity, in which the centre of mass of the sphere is displaced from the geometric centre (bottom-heaviness). The orientational relaxation time of bottom-heavy squirmers in a suspension is investigated both analytically and numerically. The three-dimensional movement of 64 identical squirmers in a fluid otherwise at rest, contained in a cube with periodic boundary conditions, is dynamically computed, for random initial positions and orientations. The effects of volume fraction of squirmers, the bottom-heaviness and the squirming mode on the relaxation time are discussed. The results for a semi-dilute suspension show that both the mean stresslet strength and the orientational relaxation time decrease from those for a dilute suspension. We also observe a stress overshoot in some cases. The mechanism for this is different from that for a visco-elastic fluid, and is explained by the change with time of the orientation of squirmers.     

Archaeoparasitology in North America

The study of prehistoric parasitism through analysis of coprolites, mummies, skeletons, and latrine soils is rapidly growing. Its development in North America is interdisciplinary and is derived from the fields of physical anthropology, parasitology, and archaeology. The various parasite finds from North America are reviewed. The data show that prehistoric peoples in North America suffered from a variety of parasitic diseases. The validity of the findings are then considered. Although most finds of parasites from prehistoric contexts result from human infections, some finds cannot be verified as such. However, in combination with data from South America, it is clear that prehistoric peoples in the Americas were host to a variety of human parasites, some of which were not previously thought to be present before historic times.     

Identity and taxonomic affinity of some members of the Amaranthaceae from the Galápagos Islands

ELIASSON, U. H. 1985. Identity and taxonomic affinity of some members of the Amaranthaceae from the Galápagos Islands. The type species of Pleuropetalum, P. DarwiniI, is endemic to the Galápagos and is morphologically closer to P. pleiogynum than to P. sprucei. Pleuropetalum pleiogynum has a wider distribution than previously assumed, ranging from Costa Rica to Peru. Amaranlhus anderssonii is closely related to A. urceolatus, a species of the Pacific coast of S America, and to A. berlandieri, a species of Texas and NE Mexico. Amaranlhus squamulatus, previously regarded as endemic to the Galápagos, is reported from the Guayas province of Ecuador. The genus Galápagosus, proposed for Amaranlhus sclerantoides, is rejected. Lithophila scirpoides, an overlooked taxon from the Galápagos, is believed to be an aberrant specimen of L. radicala. Lithophila subscaposa from the islands of Santiago and Pinzon differs morphologically from the specimens of Floreana. Iresine edmonstonii, probably erroneously reported from the Galápagos, is conspecific with J. angusti/olia. Blutaparon rigidum is morphologically divergent from other members of the genus, being adapted to arid conditions, and is assumed to be extinct.     

ELECTRON MICROSCOPE STUDY OF A DIPLOGRAPTUS SPECIES

Specimens of Diplograptus sp. from the late Middle Ordovician Lebanon Limestone in central Tennessee have been isolated from the matrix and examined with transmission electron microscopes at 60 and 650 kv. The fine structure of the fusellar layer in the metasicula and in the thecae is a mesh formed from fibers. The cortical layer has two sublayers, one of which is a mesh that is closely similar to the mesh of the fusellar layer and the other is formed from two sets of long fibers that are oriented at moderate to high angles to each other. The prosicula outer wall is a loosely-woven, open mesh formed of fibers that are 0.080–0.165 microns in diameter. The spiral thread appears to be a band that is also formed of interwoven fibers. The longitudinal rod is a bundle of long fibers. Prosicula microstructures of this Diplograptus are significantly different from those in an Orthograptus of the O. quadrimucronatus (Hall) group.     

Potential for assessing quality of protein structure based on contact number prediction

We developed a novel knowledge-based residue environment potential for assessing the quality of protein structures in protein structure prediction. The potential uses the contact number of residues in a protein structure and the absolute contact number of residues predicted from its amino acid sequence using a new prediction method based on a support vector regression (SVR). The contact number of an amino acid residue in a protein structure is defined by the number of residues around a given residue. First, the contact number of each residue is predicted using SVR from an amino acid sequence of a target protein. Then, the potential of the protein structure is calculated from the probability distribution of the native contact numbers corresponding to the predicted ones. The performance of this potential is compared with other score functions using decoy structures to identify both native structure from other structures and near-native structures from nonnative structures. This potential improves not only the ability to identify native structures from other structures but also the ability to discriminate near-native structures from nonnative structures.     

Pugnose eels, Simenchelys parasiticus (Synaphobranchidae) from the heart of a shortfin mako, Isurus oxyrinchus (Lamnidae)

The body depth of crucian carp, Carassius carassius, increases in the presence of predator fish, thereby decreasing the vulnerability of crucian carp to predation. This phenotypic change is mediated by chemical signals, and is believed to result from a piscivorous diet of predators. We have shown that exposure to a piscivorous predator is insufficient to induce growth changes in crucian carp, since water from northern pike, Esox lucius, fed Arctic charr, Salvelinus alpinus, does not induce a change in crucian carp morphology, while water from pike fed crucian carp does. The determining factor is a chemical signal from the skin of crucian carp, as demonstrated by exposure to skin extracts from conspecifics. We suggest that alarm substances from conspecifics, expressing primer pheromone effects, are the most likely candidates for induction of the phenotypical changes.     

Metlegoglobin reductase from lupine nodules. Purification and properties]

The purification procedure and properties of metlegoglobin reductase from the soluble fraction of lupine (Lupinus luteus L.) nodules and from the proteins secreted by bacteroids Rhizobium lupini in vitro are described. The properties of both forms of enzyme were found to be similar. A metlegoglobin reductase preparation purified 125-fold with a yield of 21% was obtained. The enzyme is strictly specific to the cofactor (NADH). No substrate specificity was revealed. The enzyme reduces oxidized cytochrome c, Mb+, Lb+, Hb+ and exygen. The pH optimum for the enzyme is 7,4. The enzyme is inhibited by p-chloromercurybenzoate. In some properties the enzyme from lupine nodules is close to methemoglobin reductase from the erythrocytes. It was shown that apart from metlegoglobin reductase, bacteroids secrete some other proteins, which is indicative of a close interrelationship between the bacteroids and the plant in a symbiotic nitrogen-fixing system.     

A new species and first record of the genus Triacanthella Schäffer, 1897 (Collembola, Poduromorpha, Hypogastruridae) for Africa

The first species of the genus Triacanthella to be recorded from Africa is described. Triacanthella madibasp. n. belongs to the Southern Hemisphere group of the genus. It is morphologically closely related to Triacanthella vogeli Weiner & Najt, 1997 from Chile, and appears to be a gondwanian relict. The new species is also the first Triacanthella recorded from a guano habitat.     

Transition state of the glycolytic pathway under FDP saturating conditions: experimental studies and a theoretical model

1. The transition state of the glycolytic pathway, under FDP saturating conditions, from no ADP to ADP-saturating levels, is studied in a metabolic model in vitro obtained from rat skeletal muscle. 2. When ADP is absent from the reaction mixture a steady state for NADH concentration is observed. After ADP addition, a new steady state is reached. The transition state from the first steady state to the second one shows a pulse of NADH. Both the profile and the size of this pulse depend on the enzyme concentration. 3. A kinetic model of the lower part of glycolysis (after PFK reaction) is proposed, and this is described by a set of first order coupled nonlinear differential equations. The results obtained through stability analysis and numerical integration of these equations agree with the experimental ones. 4. The possible role of the above mentioned transition state on the transmitter mechanism of glycolytic oscillations from PFK to the lower part of the glycolysis is discussed.     

Energy transfer between Chlorophyll C and Chlorophyll A

Spectral properties of solutions containing mixtures of chlorophyll a and chlorophyll c are investigated. The yield of excitation energy migration from chlorophyll c to chlorophyll a is obtained ranging from 23 to 48% dependent on the used dye concentrations. The back transfer from chlorophyll a to chlorophyll c is negligible. The shape of the polarization excitation spectrum of chlorophyll c in the Soret band region is less composed than that of chlorophyll a. Depolarization of chlorophyll a fluorescence by chlorophyll c is in agreement with the conclusion drawn from fluorescence quenching that excitation energy migrates from chlorophyll c to chlorophyll a.     

Characterization of GDP-mannose dehydrogenase from the brown alga Ectocarpus siliculosus providing the precursor for the alginate polymer

Alginate is a major cell wall polymer of brown algae. The precursor for the polymer is GDP-mannuronic acid, which is believed to be derived from a four-electron oxidation of GDP-mannose through the enzyme GDP-mannose dehydrogenase (GMD). So far no eukaryotic GMD has been biochemically characterized. We have identified a candidate gene in the Ectocarpus siliculosus genome and expressed it as a recombinant protein in Escherichia coli. The GMD from Ectocarpus differs strongly from related enzymes in bacteria and is as distant to the bacterial proteins as it is to the group of UDP-glucose dehydrogenases. It lacks the C-terminal ～120 amino acid domain present in bacterial GMDs, which is believed to be involved in catalysis. The GMD from brown algae is highly active at alkaline pH and contains a catalytic Cys residue, sensitive to heavy metals. The product GDP-mannuronic acid was analyzed by HPLC and mass spectroscopy. The K(m) for GDP-mannose was 95 μM, and 86 μM for NAD(+). No substrate other than GDP-mannose was oxidized by the enzyme. In gel filtration experiments the enzyme behaved as a dimer. The Ectocarpus GMD is stimulated by salts even at low molar concentrations as a possible adaptation to marine life. It is rapidly inactivated at temperatures above 30 °C.     

Signalling: basics and evolution

Signalling concerns the transfer of information from one body, a source, to another, a receiver in order to stimulate activity. The problem arises with the word information. It is defined as what is transferred in a sequence of things, say between people, e.g. words or signs. The idea of signalling between people is then obvious but it is not clear in cell biology. Information transfer, signalling, is required for the organisation of all cellular activity but we must ask what is transferred and how is it transmitted and received? Sometimes it is assumed that all information, i.e. organisation in a cell, is represented in the DNA sequence. This is incorrect. We shall show that the environment is a second source of information concerning material and energy. The receiving party from both DNA and the environment is general metabolism. The metabolism then signals back and sends information to both DNA and uptake from the environment. Even then energy is needed with machinery to send out all signals. This paper examines the way signalling evolved from prokaryotes through to man. In this process the environmental information received increased to the extent that finally the brain is a phenotypic as much as a genotypic organ within a whole organism. By phenotypic we mean it is organised by and interactive with information from the environment.     

The structure of an alcohol dehydrogenase from the hyperthermophilic archaeon Aeropyrum pernix

The structure of the recombinant medium chain alcohol dehydrogenase (ADH) from the hyperthermophilic archaeon Aeropyrum pernix has been solved by the multiple anomalous dispersion technique using the signal from the naturally occurring zinc ions. The enzyme is a tetramer with 222 point group symmetry. The ADH monomer is formed from a catalytic and a cofactor-binding domain, with the overall fold similar to previously solved ADH structures. The 1.62 A resolution A.pernix ADH structure is that of the holo form, with the cofactor NADH bound into the cleft between the two domains. The electron density found in the active site has been interpreted to be octanoic acid, which has been shown to be an inhibitor of the enzyme. This inhibitor is positioned with its carbonyl oxygen atom forming the fourth ligand of the catalytic zinc ion. The structural zinc ion of each monomer is present at only partial occupancy and in its absence a disulfide bond is formed. The enhanced thermal stability of the A.pernix ADH is thought to arise primarily from increased ionic and hydrophobic interactions on the subunit interfaces.