A simple randomized algorithm for consistent sequential prediction of ergodic time series

We present a simple randomized procedure for the prediction of a binary sequence. The algorithm uses ideas from recent developments of the theory of the prediction of individual sequences. We show that if thesequence is a realization of a stationary and ergodic random process then the average number of mistakes converges, almost surely, to that of the optimum, given by the Bayes predictor.

Functional analysis of human POT1 and RPA : insights into the role of single stranded DNA binding proteins at telomeres

Abstract Telomeres, the natural ends of chromosomes, need to be protected from chromosome end fusions, aberrant homologous recombination and degradation. In humans, chromosome ends are specified through arrays of tandemly repeated 5'-TTAGGG-3' hexamers, ending in a 3' overhang. A complex formed by the six proteins TRF1, TRF2, hRap1, TIN2, TPP1 and POT1 specifically assocìates with and protects telomeres. Telomeres are maintained by semiconservative DNA replication and by a specialized reverse transcriptase, telomerase, that carries an RNA subunit which templates new telomeric repeat synthesis. The telomeric single stranded (ss) DNA binding protein POT1 protects the telomeric 3' overhang and modulates telomerase-mediated telomere elongation. It is possible that POT1 also influences DNA synthesis during semiconservative DNA replication, which is initiated by the DNA polymerase alpha-primase complex. The heterotrimeric ss DNA-binding protein RPA plays essential roles during DNA replication. RPA binds to ss DNA with high affinity in order to stabilize ss DNA and facilitate nascent strand synthesis at the replication fork. Here we investigate how the two proteins RPA and POT1 contribute to telomere maintenance by regulating semi-conservative DNA replication and telomerase. Using chromatin immunoprecipitation experiments, we show that RPA associates with telomeres during S-phase. Analysis of telomere structure in cells shRNA-depleted for RPA and POT1 reveals that loss of RPA and POT1 causes exposure of single-stranded DNA at telomeres, suggestive of incomplete DNA replication. Biochemical experiments using purified recombinant POT1 and RPA show that saturating telomeric oligonucleotides with POT1 or RPA reduces the primase activity of the DNA polymerase alpha-primase complex and the overall activity of telomerase. POT1 and RPA also increase the primer extension by DNA polymerase alpha-primase complex and the processivity of telomerase under certain conditions, although POT1 increases the activities to a greater extent than RPA. We propose that POT1 is required for proper replication of the lagging strand of telomeres and that some phenotypes observed in POT1-depleted cells may stern from incomplete DNA replication rather than de-protection of the single-stranded overhang. Résumé Les télomères, les extrémités normales des chromosomes linéaires, doivent être protégés des fusions chromosomiques, d'événements de recombinaison homologue aberrants et de phénomènes de dégradation. Chez l'Homme, les extrémités des chromosomes sont constitués d'ADN double brin répétitif de séquence 5'-TTAGGG-3', d'une extension simple brin 3' sortante et d'un complexe protéique formé des six facteurs TRF1, TRF2, hRap1, TIN2, TPP1 et POT1 qui, s'associant à cette séquence, protègent l'ADN télomèrique. Les télomères sont maintenus par la télomérase, une transcriptase inverse capable d'allonger l'extension 3' sortante télomérique. POT1 lie l'ADN simple brin télomérique et module l'élongation des télomères par la télomérase. POT1 pourrait en théorie également influencer la réplication semi-conservative de l'ADN. L'ADN-polymérase Pal alpha-primase amorce et initie la synthèse d'ADN. Pendant la réplication, l'ADN simple brin est stabilisé par RPA, un complexe hétérotrimèrique qui lie l'ADN simple brin. RPA facilite la synthèse du brin naissant à la fourche de réplication. Ici nous avons étudié comment ces deux protéines qui lient l'ADN simple brin, RPA et POT1, régulent la réplication des télomères par la télomérase et la machinerie classique de réplication de l'ADN. Par immunoprécipitation de chromatine (ChIP), nous montrons que RPA est localisé aux télomères lors de la phase S du cycle cellulaire. De plus, l'analyse de la structure des télomeres indique que !a perte de RPA ou de POT1 conduit à l'apparition d'ADN simple brin télomérique, suggérant une réplication incomplète de l'ADN télomérique in vivo. Par une approche complémentaire biochimique utilisant les protéines POT1 et RPA recombinantes purifiées, nous montrons également que la liaison de POT1 ou de RPA à des oligonucléotides télomériques bloque l'activité primase du complexe polymérase alpha/primase et réduit l'activité télomérase sur ces substrats. En revanche, leur liaison augmente l'activité ADN-polymérase du complexe polymérase alpha/primase, ainsi que fa processivité de la télomérase dans certaines conditions, POT1 étant le plus efficace des deux facteurs. Nous proposons que POT1 est nécessaire à la réplication du brin retardé au niveau des télomères, ce qui suggère que certains phénotypes des cellules déplétés en POT1 puissent résulter d'une réplication incomplète de l'ADN télémétrique plutôt que d'une déprotection de l'extrémité sortante des télomères.

Functional response of Telenomus remus Nixon(Hymenoptera, Scelionidae) to Spodoptera frugiperda (J. E. Smith) (Lepidoptera, Noctuidae) eggs: effect of female age

Functional response of Telenomus remus Nixon (Hymenoptera, Scelionidae) to Spodoptera frugiperda (J. E. Smith) (Lepidoptera, Noctuidae) eggs: effect of female age. Functional response of 24-h and 48-h-old Telenomus remus adults was studied on Spodoptera frugiperda eggs. The study was carried out in climatic chamber regulated at 25 ± 1°C, 70 ± 10% RH and 12:12h (L: D). Females of T. remus were honey fed and individualized in glass vials along with 25, 50, 75, 100, 150, 200, 250 or 300 eggs of S. frugiperda for 24 h. Complete randomized design with ten replications was adopted. The parameters evaluated to construct the functional response curve were daily average parasitism, searching rate and oviposition time. It was observed that the higher the egg density, the higher the parasitism for 24-h and 48-h-old females although there was a tendency of parasitism stabilization at 150-egg density. The results showed a type II functional response curve for both 24-h and 48-h-old female.

Precursors of functional MHC class I- or class II-restricted CD8alphaalpha(+) T cells are positively selected in the thymus by agonist self-peptides.

The origin and specificity of alphabeta TCR(+) T cells that express CD8alphaalpha have been controversial issues. Here we provide direct evidence that precursors of functional CD8alphaalpha T cells are positively selected in the thymus in the presence of agonist self-peptides. Like conventional positive selection, this agonist selection process requires functional TCR alpha-CPM, whereas it is independent of CD8beta expression. Furthermore, CD8alphaalpha expression on mature, agonist-selected T cells does not imply selection by MHC class I, and CD8alphaalpha(+) T cells can be either class I or class II restricted. Our data define a distinct agonist-dependent, positive selection process in the thymus, and they suggest a function for CD8alphaalpha distinct from the conventional TCR coreceptor function of CD8alphabeta or CD4.

Electron microscopy of RecA-DNA complexes: Two different states, their functional significance and relation to the solved crystal structure

Seven different electron microscopy techniques habe been employed to study the RecA protein of E. coli. This review provides a summary of the conclusions that have been drawn from these studies, and attempts to relate these observations to models for the role of RecA protein in homologous recombination.

Testing the response of macroinvertebrate functional structure and biodiversity to flooding and confinement

The aim of the present study was to investigate the relative importance of flooding- and confinement-related environmentalfeatures in explaining macroinvertebrate trait structure and diversity in a pool of wetlands located in a Mediterranean riverfloodplain. To test hypothesized trait-environment relationships, we employed a recently implemented statistical procedure, thefourth-corner method. We found that flooding-related variables, mainly pH and turbidity, were related to traits that confer an abilityof the organism to resist flooding (e.g., small body-shape, protection of eggs) or recuperate faster after flooding (e.g., short life-span, asexual reproduction). In contrast, confinement-related variables, mainly temperature and organic matter, enhanced traits that allow organisms to interact and compete with other organisms (e.g., large size, sexual reproduction) and to efficiently use habitat and resources (e.g., diverse locomotion and feeding strategies). These results are in agreement with predictions made under the River Habitat Templet for lotic ecosystems, and demonstrate the ability of the fourth-corner method to test hypothesis that posit traitenvironment relationships. Trait diversity was slightly higher in flooded than in confined sites, whereas trait richness was not significantly different. This suggests that although trait structure may change in response to the main environmental factors, as evidenced by the fourth-corner method, the number of life-history strategies needed to persist in the face of such constraints remains more or less constant; only their relative dominance differs

Functional Sub-Types

The paper argues that a functional reduction of ordinary psychology to neuropsychology is possible by means of constructing fine-grained functional, mental sub-types that are coextensive with neuropsychological types. We establish this claim by means of considering as examples the cases of the disconnection syndrome and schizophrenia. We point out that the result is a conservative reduction, vindicating the scientific quality of the mental types of ordinary psychology by systematically linking them with neuroscience. That procedure of conservative reduction by means of functional sub-types is in principle repeatable down to molecular neuroscience.

Prediction of subcutaneous fatty acid composition from ham of CLA fed boars and gilts using a NIRS fiber optic probe

The aim of this work was the use of NIR technology by direct application of a fiber optic probe on back fat to analyze the fatty acid composition of CLA fed boars and gilts. 265 animals were fed 3 different diets and the fatty acid profile of back fat from Gluteus medius was analyzed using gas chromatography and FT-NIR. Spectra were acquired using a Bruker Optics Matrix-F duplex spectrometer equipped with a fiber optic probe (IN-268-2). Oleic and stearic fatty acids were predicted accurately; myristic, vaccenic and linoleic fatty acids were predicted with lower accuracy, while palmitic and α-linolenic fatty acids were poorly predicted. The relative percentage of fatty acids and NIR spectra showed differences in fatty acid composition of back fat from pigs fed CLA which increased the relative percentage of SFA and PUFA while MUFA decreased. Results suggest that a NIR fiber optic probe can be used to predict total saturated and unsaturated fatty acid composition, as well as the percentage of stearic and oleic. NIR showed potential as a rapid and easily implemented method to discriminate carcasses from animals fed different diets.

Ruling out coronary heart disease in primary care patients with chest pain: a clinical prediction score.

ABSTRACT: BACKGROUND: Chest pain raises concern for the possibility of coronary heart disease. Scoring methods have been developed to identify coronary heart disease in emergency settings, but not in primary care. METHODS: Data were collected from a multicenter Swiss clinical cohort study including 672 consecutive patients with chest pain, who had visited one of 59 family practitioners' offices. Using delayed diagnosis we derived a prediction rule to rule out coronary heart disease by means of a logistic regression model. Known cardiovascular risk factors, pain characteristics, and physical signs associated with coronary heart disease were explored to develop a clinical score. Patients diagnosed with angina or acute myocardial infarction within the year following their initial visit comprised the coronary heart disease group. RESULTS: The coronary heart disease score was derived from eight variables: age, gender, duration of chest pain from 1 to 60 minutes, substernal chest pain location, pain increases with exertion, absence of tenderness point at palpation, cardiovascular risks factors, and personal history of cardiovascular disease. Area under the receiver operating characteristics curve was of 0.95 with a 95% confidence interval of 0.92; 0.97. From this score, 413 patients were considered as low risk for values of percentile 5 of the coronary heart disease patients. Internal validity was confirmed by bootstrapping. External validation using data from a German cohort (Marburg, n = 774) revealed a receiver operating characteristics curve of 0.75 (95% confidence interval, 0.72; 0.81) with a sensitivity of 85.6% and a specificity of 47.2%. CONCLUSIONS: This score, based only on history and physical examination, is a complementary tool for ruling out coronary heart disease in primary care patients complaining of chest pain.

Identification of optimal structural connectivity using functional connectivity and neural modeling.

The complex network dynamics that arise from the interaction of the brain's structural and functional architectures give rise to mental function. Theoretical models demonstrate that the structure-function relation is maximal when the global network dynamics operate at a critical point of state transition. In the present work, we used a dynamic mean-field neural model to fit empirical structural connectivity (SC) and functional connectivity (FC) data acquired in humans and macaques and developed a new iterative-fitting algorithm to optimize the SC matrix based on the FC matrix. A dramatic improvement of the fitting of the matrices was obtained with the addition of a small number of anatomical links, particularly cross-hemispheric connections, and reweighting of existing connections. We suggest that the notion of a critical working point, where the structure-function interplay is maximal, may provide a new way to link behavior and cognition, and a new perspective to understand recovery of function in clinical conditions.

Mutation spectrum of MLL2 in a cohort of Kabuki syndrome patients.

ABSTRACT: BACKGROUND: Kabuki syndrome (Niikawa-Kuroki syndrome) is a rare, multiple congenital anomalies/mental retardation syndrome characterized by a peculiar face, short stature, skeletal, visceral and dermatoglyphic abnormalities, cardiac anomalies, and immunological defects. Recently mutations in the histone methyl transferase MLL2 gene have been identified as its underlying cause. METHODS: Genomic DNAs were extracted from 62 index patients clinically diagnosed as affected by Kabuki syndrome. Sanger sequencing was performed to analyze the whole coding region of the MLL2 gene including intron-exon junctions. The putative causal and possible functional effect of each nucleotide variant identified was estimated by in silico prediction tools. RESULTS: We identified 45 patients with MLL2 nucleotide variants. 38 out of the 42 variants were never described before. Consistently with previous reports, the majority are nonsense or frameshift mutations predicted to generate a truncated polypeptide. We also identified 3 indel, 7 missense and 3 splice site. CONCLUSIONS: This study emphasizes the relevance of mutational screening of the MLL2 gene among patients diagnosed with Kabuki syndrome. The identification of a large spectrum of MLL2 mutations possibly offers the opportunity to improve the actual knowledge on the clinical basis of this multiple congenital anomalies/mental retardation syndrome, design functional studies to understand the molecular mechanisms underlying this disease, establish genotype-phenotype correlations and improve clinical management.

Runoff measurement and prediction for a watershed under natural vegetation in central Brazil

This work aimed to measure and analyze total rainfall (P), rainfall intensity and five-day antecedent rainfall effects on runoff (R); to compare measured and simulated R values using the Soil Conservation Service Curve Number method (CN) for each rainfall event; and to establish average R/P ratios for observed R values. A one-year (07/01/96 to 06/30/97) rainfall-runoff data study was carried out in the Capetinga watershed (962.4 ha), located at the Federal District of Brazil, 47° 52' longitude West and 15° 52' latitude South. Soils of the watershed were predominantly covered by natural vegetation. Total rainfall and runoff for the period were 1,744 and 52.5 mm, respectively, providing R/P of 3% and suggesting that watershed physical characteristics favored water infiltration into the soil. A multivariate regression analysis for 31 main rainfall-runoff events totaling 781.9 and 51.0 mm, respectively, indicated that the amount of runoff was only dependent upon rainfall volume. Simulated values of total runoff were underestimated about 15% when using CN method and an area-weighted average of the CN based on published values. On the other hand, when average values of CN were calculated for the watershed, total runoff was overestimated about 39%, suggesting that CN method shoud be used with care in areas under natural vegetation.

Early multimodal outcome prediction after cardiac arrest in patients treated with hypothermia.

OBJECTIVES: Therapeutic hypothermia and pharmacological sedation may influence outcome prediction after cardiac arrest. The use of a multimodal approach, including clinical examination, electroencephalography, somatosensory-evoked potentials, and serum neuron-specific enolase, is recommended; however, no study examined the comparative performance of these predictors or addressed their optimal combination. DESIGN: Prospective cohort study. SETTING: Adult ICU of an academic hospital. PATIENTS: One hundred thirty-four consecutive adults treated with therapeutic hypothermia after cardiac arrest. MEASUREMENTS AND MAIN RESULTS: Variables related to the cardiac arrest (cardiac rhythm, time to return of spontaneous circulation), clinical examination (brainstem reflexes and myoclonus), electroencephalography reactivity during therapeutic hypothermia, somatosensory-evoked potentials, and serum neuron-specific enolase. Models to predict clinical outcome at 3 months (assessed using the Cerebral Performance Categories: 5 = death; 3-5 = poor recovery) were evaluated using ordinal logistic regressions and receiving operator characteristic curves. Seventy-two patients (54%) had a poor outcome (of whom, 62 died), and 62 had a good outcome. Multivariable ordinal logistic regression identified absence of electroencephalography reactivity (p < 0.001), incomplete recovery of brainstem reflexes in normothermia (p = 0.013), and neuron-specific enolase higher than 33 μg/L (p = 0.029), but not somatosensory-evoked potentials, as independent predictors of poor outcome. The combination of clinical examination, electroencephalography reactivity, and neuron-specific enolase yielded the best predictive performance (receiving operator characteristic areas: 0.89 for mortality and 0.88 for poor outcome), with 100% positive predictive value. Addition of somatosensory-evoked potentials to this model did not improve prognostic accuracy. CONCLUSIONS: Combination of clinical examination, electroencephalography reactivity, and serum neuron-specific enolase offers the best outcome predictive performance for prognostication of early postanoxic coma, whereas somatosensory-evoked potentials do not add any complementary information. Although prognostication of poor outcome seems excellent, future studies are needed to further improve prediction of good prognosis, which still remains inaccurate.