The Advantage of Arriving First: Characteristic Times in Finite Size Populations of Error-Prone Replicators

We study the evolution of a finite size population formed by mutationally isolated lineages of error-prone replicators in a two-peak fitness landscape. Computer simulations are performed to gain a stochastic description of the system dynamics. More specifically, for different population sizes, we compute the probability of each lineage being selected in terms of their mutation rates and the amplification factors of the fittest phenotypes. We interpret the results as the compromise between the characteristic time a lineage takes to reach its fittest phenotype by crossing the neutral valley and the selective value of the sequences that form the lineages. A main conclusion is drawn: for finite population sizes, the survival probability of the lineage that arrives first to the fittest phenotype rises significantly

La influencia del "Home Advantage" en el resultado de los momentos críticos en los partidos de baloncesto

El objeto de estudio del presente trabajo ha sido identificar las variables que determinan ganar o perder en los momentos críticos en los partidos de baloncesto en función de la localización del partido. Se han analizado un total de 41 momentos críticos, correspondientes a 30 partidos de la liga regular de la ACB de la temporada 2007-2008, que cumplen, según la literatura, con la noción de momento crítico y corresponden a los tiempos extras y los últimos 5 minutos de partidos donde la diferencia de puntos es menor o igual a 6. Los resultados muestran mejores valores en los equipos ganadores cuando juegan como local, en los rebotes defensivos y los tiros libres anotados; y cuando juegan como visitante en los lanzamientos de 2 puntos fallados.

Energetic considerations of ciliary beating and the advantage of metachronal coordination

The internal mechanism of cilia is among the most ancient biological motors on an evolutionary scale. It produces beat patterns that consist of two phases: during the effective stroke, the cilium moves approximately as a straight rod, and during the recovery stroke, it rolls close to the surface in a tangential motion. It is commonly agreed that these two phases are designed for efficient functioning: the effective stroke encounters strong viscous resistance and generates thrust, whereas the recovery stroke returns the cilium to starting position while avoiding viscous resistance. Metachronal coordination between cilia, which occurs when many of them beat close to each other, is believed to be an autonomous result of the hydrodynamical interactions in the system. Qualitatively, metachronism is perceived as a way for reducing the energy expenditure required for beating. This paper presents a quantitative study of the energy expenditure of beating cilia, and of the energetic significance of metachronism. We develop a method for computing the work done by model cilia that beat in a viscous fluid. We demonstrate that for a single cilium, beating in water, the mechanical work done during the effective stroke is approximately five times the amount of work done during the recovery stroke. Investigation of multicilia configurations shows that having neighboring cilia beat metachronally is energetically advantageous and perhaps even crucial for multiciliary functioning. Finally, the model is used to approximate the number of dynein arm attachments that are likely to occur during the effective and recovery strokes of a beat cycle, predicting that almost all of the available dynein arms should participate in generating the motion.

Binding of Signal Recognition Particle Gives Ribosome/Nascent Chain Complexes a Competitive Advantage in Endoplasmic Reticulum Membrane Interaction

Most secretory and membrane proteins are sorted by signal sequences to the endoplasmic reticulum (ER) membrane early during their synthesis. Targeting of the ribosome-nascent chain complex (RNC) involves the binding of the signal sequence to the signal recognition particle (SRP), followed by an interaction of ribosome-bound SRP with the SRP receptor. However, ribosomes can also independently bind to the ER translocation channel formed by the Sec61p complex. To explain the specificity of membrane targeting, it has therefore been proposed that nascent polypeptide-associated complex functions as a cytosolic inhibitor of signal sequence- and SRP-independent ribosome binding to the ER membrane. We report here that SRP-independent binding of RNCs to the ER membrane can occur in the presence of all cytosolic factors, including nascent polypeptide-associated complex. Nontranslating ribosomes competitively inhibit SRP-independent membrane binding of RNCs but have no effect when SRP is bound to the RNCs. The protective effect of SRP against ribosome competition depends on a functional signal sequence in the nascent chain and is also observed with reconstituted proteoliposomes containing only the Sec61p complex and the SRP receptor. We conclude that cytosolic factors do not prevent the membrane binding of ribosomes. Instead, specific ribosome targeting to the Sec61p complex is provided by the binding of SRP to RNCs, followed by an interaction with the SRP receptor, which gives RNC–SRP complexes a selective advantage in membrane targeting over nontranslating ribosomes.

Mutational inactivation of the proapoptotic gene BAX confers selective advantage during tumor clonal evolution

A remarkable instability at simple repeated sequences characterizes gastrointestinal cancer of the microsatellite mutator phenotype (MMP). Mutations in the DNA mismatch repair gene family underlie the MMP, a landmark for hereditary nonpolyposis colorectal cancer. These tumors define a distinctive pathway for carcinogenesis because they display a particular spectrum of mutated cancer genes containing target repeats for mismatch repair deficiency. One such gene is BAX, a proapoptotic member of the Bcl-2 family of proteins, which plays a key role in programmed cell death. More than half of colon and gastric cancers of the MMP contain BAX frameshifts in a (G)8 mononucleotide tract. However, the functional significance of these mutations in tumor progression has not been established. Here we show that inactivation of the wild-type BAX allele by de novo frameshift mutations confers a strong advantage during tumor clonal evolution. Tumor subclones with only mutant alleles frequently appeared after inoculation into nude mice of single-cell clones of colon tumor cell lines with normal alleles. In contrast, no clones of BAX-expressing cells were found after inoculation of homozygous cell clones without wild-type BAX. These results support the interpretation that BAX inactivation contributes to tumor progression by providing a survival advantage. In this context, survival analyses show that BAX mutations are indicators of poor prognosis for both colon and gastric cancer of the MMP.

Homologous genetic recombination as an intrinsic dynamic property of a DNA structure induced by RecA/Rad51-family proteins: A possible advantage of DNA over RNA as genomic material

Heteroduplex joints are general intermediates of homologous genetic recombination in DNA genomes. A heteroduplex joint is formed between a single-stranded region (or tail), derived from a cleaved parental double-stranded DNA, and homologous regions in another parental double-stranded DNA, in a reaction mediated by the RecA/Rad51-family of proteins. In this reaction, a RecA/Rad51-family protein first forms a filamentous complex with the single-stranded DNA, and then interacts with the double-stranded DNA in a search for homology. Studies of the three-dimensional structures of single-stranded DNA bound either to Escherichia coli RecA or Saccharomyces cerevisiae Rad51 have revealed a novel extended DNA structure. This structure contains a hydrophobic interaction between the 2′ methylene moiety of each deoxyribose and the aromatic ring of the following base, which allows bases to rotate horizontally through the interconversion of sugar puckers. This base rotation explains the mechanism of the homology search and base-pair switch between double-stranded and single-stranded DNA during the formation of heteroduplex joints. The pivotal role of the 2′ methylene-base interaction in the heteroduplex joint formation is supported by comparing the recombination of RNA genomes with that of DNA genomes. Some simple organisms with DNA genomes induce homologous recombination when they encounter conditions that are unfavorable for their survival. The extended DNA structure confers a dynamic property on the otherwise chemically and genetically stable double-stranded DNA, enabling gene segment rearrangements without disturbing the coding frame (i.e., protein-segment shuffling). These properties may give an extensive evolutionary advantage to DNA.

Significant competitive advantage conferred by meiosis and syngamy in the yeast Saccharomyces cerevisiae.

The presumed advantages of genetic recombinations are difficult to demonstrate directly. To investigate the effects of recombination and background heterozygosity on competitive ability, we have performed serial-transfer competition experiments between isogenic sexual and asexual strains of the yeast Saccharomyces cerevisiae. The members of these diploid pairs of strains differed only in being heterozygous (sexual) or homozygous (asexual) at the mating type or MAT locus. Competing pairs had either a completely homozygous or a heterozygous genetic background, the latter being heterozygous at many different loci throughout the genome. A round of meiotic recombination (automixis) conferred a large and statistically significant enhancement of competitive ability on sexual strains with a heterozygous genetic background. By contrast, in homozygous background competitions, meiosis decreased the sexual strains' initial relative competitive ability. In all cases, however, the sexual strains outcompeted their isogenic asexual counterparts, whether meiotic recombination had occurred or not. In some genetic backgrounds, this was due in part to an overdominance effect on competitive advantage of heterozygosity at the MAT locus. The advantage of the sexual strains also increased significantly during the course of the homozygous background competitions, particularly when meiosis had occurred. This latter effect either did not occur or was very weak in heterozygous background competitions. Overall, sexual strains with heterozygous genetic backgrounds had a significantly higher initial relative competitive ability than those with homozygous backgrounds. The advantage of mating type heterozygosity in this organism extends far beyond the ability to recombine meiotically.

Intercellular mobility and homing of an archaeal rDNA intron confers a selective advantage over intron- cells of Sulfolobus acidocaldarius.

Some intron-containing rRNA genes of archaea encode homing-type endonucleases, which facilitate intron insertion at homologous sites in intron- alleles. These archaeal rRNA genes, in contrast to their eukaryotic counterparts, are present in single copies per cell, which precludes intron homing within one cell. However, given the highly conserved nature of the sequences flanking the intron, homing may occur in intron- rRNA genes of other archaeal cells. To test whether this occurs, the intron-containing 23S rRNA gene of the archaeal hyperthermophile Desulfurococcus mobilis, carried on nonreplicating bacterial vectors, was electroporated into an intron- culture of Sulfolobus acidocaldarius. PCR experiments demonstrated that the intron underwent homing and spread through the culture. By using a double drug-resistant mutant of S. acidocaldarius, it was shown that spreading resulted partly from a selective advantage of intron+ cells and partly from intercellular mobility of the intron and homing.

Different cellular backgrounds confer a marked advantage to either mutant or wild-type mitochondrial genomes.

After the introduction of mitochondria with a mixture of mutant and wild-type mitochondrial DNA (mtDNA) into a human rho degree cell line (143B.206), Yoneda et al. [Yoneda, M., Chomyn, A., Martinuzzi, A., Hurko, O. & Attardi, G. (1992) Proc. Natl. Acad. Sci. USA 89, 11164-11168] observed a shift in the proportion of the two mitochondrial genotypes in a number of cybrid clones. In every case where a shift was observed, there was an increase in the proportion of mutant mtDNA. By using the same cell line (143B.206 rho degree), we also generated cybrids that were either stable in their mitochondrial genotype or showed an increase in the proportion of mutant mtDNA. However, temporal analysis of the same mutant mtDNA type in another rho degree cell line revealed a quite distinct outcome. Those clones that showed a change shifted toward higher levels of wild-type rather than mutant mtDNA. These results indicate that the nuclear genetic background of the recipient (rho degree) cell can influence the segregation of mutant and wild-type mitochondrial genomes in cell cybrids.

Human Resource's Role in Leveraging Knowledge Management as a Competitive Advantage

The ultra-competitiveness in the twenty-first century's business environment suggests that, to survive, human resource (HR) must prove its value. The knowledge economy presents HR the opportunity to demonstrate its added value through leveraging knowledge management (KM) as a competitive advantage. This capstone reviews the literature on business strategy, knowledge, KM, KM success, and HR to reveal links between these subjects and illustrate three roles HR can undertake to leverage KM as a competitive advantage. The capstone also assesses HR's current contributions to KM through a survey of 42 HR professionals. Survey results suggest that, although HR contributes to the three KM roles, HR is not currently fully capitalizing on the opportunity to become a strategic business partner through KM.

Is the date of birth an advantage/ally to excel in handball?

The Relative Age Effect (RAE) has been analyzed in a population of Spanish international handball players (n=161) divided into four different levels: Senior, Junior, Juvenile and Promising Talents. The variables registered were quarter, half year and year of birth using the initial information of their date of birth. The data were collected from the Royal Spanish Handball Federation on-line data base. The statistical method used was the χ2 and the minimum level of significance was set at p<0.05. The total results on distribution by quarter show a significant difference (χ2= 21.68; p<0.01) with a greater frequency of players born in the first quarter (40.37%) compared to those born in the second (22.36%), third (16.15%) and fourth quarter (21.12%). The total results on the distribution of birth date by half year show a significant difference (χ2= 10.44; p<0.01) with a greater frequency of players born in the first half of the year (62.73%). With regard to the rate of births registered in an even numbered or odd numbered year there are significant differences when the rates for an even numbered year (64.60%) and an odd numbered year (35.40%) are compared with those of the general population (χ2= 13.72; p<0.001). Based on the data collected and analyzed it can be concluded that there is a RAE in the basic categories of the Spanish national men’s handball teams according to quarter, half year and year of birth (even or odd numbered), but there exists little knowledge about the causes and consequence which may be produced by, or derive from, this effect.

The effects of quality and environmental management on competitive advantage: A mixed methods study in the hotel industry

This paper reports results derived from a mixed methods study where 13 hotel managers were initially interviewed, followed by a quantitative study of 355 additional managers. Data were analysed using partial least squares path modelling. The research question related to the relationship between quality and environmental management and the competitive advantage sought by hotels. The results indicate that quality management and environmental management permit the improvement of competitive advantage in terms of both costs and differentiation. Moreover, hotels implementing quality programmes find fewer obstacles in implementing environmental management.

Organizational design, quality management and competitive advantage in hotels

Purpose – The aim of this study is to examine the relationship between practices of quality management (QM) and the characteristics of organizational design, and QM and competitive advantage. Design/methodology/approach – The study uses a partial least squares approach to test these relationships in 350 hotels in Spain. Findings – The findings show that QM influences specialization, formalization and interdepartmental interactions, and that QM practices influence both cost and differentiation competitive advantage. The results also indicate the importance of QM strategic and operational systems as practices that have a key impact on the characteristics of organizational design. Similarly, the QM operational system is key in the relationship between QM and cost competitive advantage. Finally, the QM operational, information and strategic systems positively influence differentiation competitive advantage. Practical implications – When hotels adopt QM practices, there will be significant changes in a number of organizational variables, including specialization, formalization and interdepartmental interactions. This paper provides empirical evidence that QM practices improve both cost and differentiation competitive advantage in the hotel industry. Originality/value – There has been little research on the effects of QM on organizational design in the hotel industry. The contribution of this paper is that analyze the effects of QM on organizational design and competitive advantage, extending knowledge about these issues in a specific sector.

Short nomenclator or vocabular in English and Hebrew: composed alphabetically for the use and benefit of my pupils in particular and for the advantage of those who are desirous to obtain the knowledge of the Hebrew tongue in general, which may be that great help to understand not only ye sacred oracles in their original, but even any Jewish author (so far as concern owns) as also it may give great insight in ye tongue to those, as to compose it, a work altogether new, [ca. 1735]

Headed on the first page with the words "Nomenclatura hebraica," this handwritten volume is a vocabulary with the Hebrew word in the left column, and the English translation on the right. While the book is arranged in sections by letter, individual entries do not appear in strict alphabetical order. The small vocabulary varies greatly and includes entries like enigma, excommunication, and martyr, as well as cucumber and maggot. There are translations of the astrological signs at the end of the volume. Poem written at the bottom of the last page in different hand: "Women when good the best of saints/ that bright seraphick lovely/ she, who nothing of an angel/ wants but truth & immortality./ Verse 2: Who silken limbs & charming/ face. Keeps nature warm."