Alexander II and Gorbachev: The Doomed Reformers of Russia

During Mikhail Gorbachev’s tenure as head of the Soviet Union, Russian and foreign journalists sometimes compared him to Tsar Alexander II for his sweeping, but destabilizing reforms. The purpose and significance of this thesis is to test this concept, moving from journalistic opinion to scholarly investigation. Both Gorbachev and Alexander II attempted to reform their country in order to modernize. The reforms of both leaders had many extreme unintended consequences, ultimately ending in the assassination of Alexander II and the ousting of Gorbachev, as well as the collapse of the Soviet Union

Monitoring the premalignant potential of Barrett's oesophagus'.

The landscape for patients with Barrett's oesophagus (BE) has changed significantly in the last decade. Research and new guidelines have helped gastroenterologists to better identify those patients with BE who are particularly at risk of developing oesophageal adenocarcinoma. In parallel, developments in endoscopic image enhancement technology and optical biopsy techniques have improved our ability to detect high-risk lesions. Once these lesions have been identified, the improvements in minimally invasive endoscopic therapies has meant that these patients can potentially be cured of early cancer and high-risk dysplastic lesions without the need for surgery, which still has a significant morbidity and mortality. The importance of reaching an accurate diagnosis of BE remains of paramount importance. More work is needed, however. The vast majority of those undergoing surveillance for their BE do not progress towards cancer and thus undergo a regular invasive procedure, which may impact on their psychological and physical well-being while incurring significant cost to the health service. New work that explores cheaper endoscopic or non-invasive ways to identify the at-risk individual provides exciting avenues for research. In future, the diagnosis and monitoring of patients with BE could move away from hospitals and into primary care

Entropy concepts and DNA investigations

Topological and metric entropies of the DNA sequences from different organisms were calculated. Obtained results were compared each other and with ones of corresponding artificial sequences. For all envisaged DNA sequences there is a maximum of heterogeneity. It falls in the block length interval [5,7]. Maximum distinction between natural and artificial sequences is shifted on 1-3 position from the maximum of heterogeneity to the right as for metric as for topological entropy. This point on the specificity of real DNA sequences in the interval.Comment: 10 pages 7 figures submitted to PL

Adjacency Matrices of Configuration Graphs

In 1960, Hoffman and Singleton \cite{HS60} solved a celebrated equation for square matrices of order $n$, which can be written as $$(\kappa - 1) I_n + J_n - A A^{\rm T} = A$$ where $I_n$, $J_n$, and $A$ are the identity matrix, the all one matrix, and a $(0,1)$--matrix with all row and column sums equal to $\kappa$, respectively. If $A$ is an incidence matrix of some configuration $\cal C$ of type $n_\kappa$, then the left-hand side $\Theta(A):= (\kappa - 1)I_n + J_n - A A^{\rm T}$ is an adjacency matrix of the non--collinearity graph $\Gamma$ of $\cal C$. In certain situations, $\Theta(A)$ is also an incidence matrix of some $n_\kappa$ configuration, namely the neighbourhood geometry of $\Gamma$ introduced by Lef\`evre-Percsy, Percsy, and Leemans \cite{LPPL}. The matrix operator $\Theta$ can be reiterated and we pose the problem of solving the generalised Hoffman--Singleton equation $\Theta^m(A)=A$. In particular, we classify all $(0,1)$--matrices $M$ with all row and column sums equal to $\kappa$, for $\kappa = 3,4$, which are solutions of this equation. As a by--product, we obtain characterisations for incidence matrices of the configuration $10_3F$ in Kantor's list \cite{Kantor} and the $17_4$ configuration #1971 in Betten and Betten's list \cite{BB99}

Deposit? Yes, please! The effect of different modes of assigning reward- and deposit-based financial incentives on effort

The effectiveness and uptake of financial incentives can differ substantially between reward- and deposit-based incentives. Therefore, it is unclear to whom and how different incentives should be assigned. In this study, the effect of different modes of assigning reward- and deposit-based financial incentives on effort is explored in a two-session experiment. First, students' (n = 228, recruited online) discounting, loss aversion and willingness to pay a deposit were elicited. Second, an incentivized real-effort task was completed (n = 171, 25% drop-out). Two modes of assigning reward- or deposit-based financial incentives were compared: random assignment and 'nudged' assignment - assignment based on respondent characteristics allowing opting out. Our results show that respondents receiving nudged assignment earned more and persisted longer on the real-effort task than respondents randomly assigned to incentives. We find no differences in effectiveness between reward-based or deposit-based incentives. Overall, 39% of respondents in the nudged assignment mode followed-up the advice to take deposit-based incentives. The effect of deposit-based incentives was larger for the respondents who followed-up the advice than for respondents that randomly received deposit-based incentives. Overall, these findings suggest that nudged assignment may increase incentives' effect on effort. Future work should extend this approach to other contexts (e.g., behaviour change).</p

The Maximal Denumerant of a Numerical Semigroup

Given a numerical semigroup S = and n in S, we consider the factorization n = c_0 a_0 + c_1 a_1 + ... + c_t a_t where c_i >= 0. Such a factorization is maximal if c_0 + c_1 + ... + c_t is a maximum over all such factorizations of n. We provide an algorithm for computing the maximum number of maximal factorizations possible for an element in S, which is called the maximal denumerant of S. We also consider various cases that have connections to the Cohen-Macualay and Gorenstein properties of associated graded rings for which this algorithm simplifies.Comment: 13 Page

The relationship of protein conservation and sequence length

BACKGROUND: In general, the length of a protein sequence is determined by its function and the wide variance in the lengths of an organism's proteins reflects the diversity of specific functional roles for these proteins. However, additional evolutionary forces that affect the length of a protein may be revealed by studying the length distributions of proteins evolving under weaker functional constraints. RESULTS: We performed sequence comparisons to distinguish highly conserved and poorly conserved proteins from the bacterium Escherichia coli, the archaeon Archaeoglobus fulgidus, and the eukaryotes Saccharomyces cerevisiae, Drosophila melanogaster, and Homo sapiens. For all organisms studied, the conserved and nonconserved proteins have strikingly different length distributions. The conserved proteins are, on average, longer than the poorly conserved ones, and the length distributions for the poorly conserved proteins have a relatively narrow peak, in contrast to the conserved proteins whose lengths spread over a wider range of values. For the two prokaryotes studied, the poorly conserved proteins approximate the minimal length distribution expected for a diverse range of structural folds. CONCLUSIONS: There is a relationship between protein conservation and sequence length. For all the organisms studied, there seems to be a significant evolutionary trend favoring shorter proteins in the absence of other, more specific functional constraints

Long intervals of stasis punctuated by bursts of positive selection in the seasonal evolution of influenza A virus

BACKGROUND: The interpandemic evolution of the influenza A virus hemagglutinin (HA) protein is commonly considered a paragon of rapid evolutionary change under positive selection in which amino acid replacements are fixed by virtue of their effect on antigenicity, enabling the virus to evade immune surveillance. RESULTS: We performed phylogenetic analyses of the recently obtained large and relatively unbiased samples of the HA sequences from 1995–2005 isolates of the H3N2 and H1N1 subtypes of influenza A virus. Unexpectedly, it was found that the evolution of H3N2 HA includes long intervals of generally neutral sequence evolution without apparent substantial antigenic change ("stasis" periods) that are characterized by an excess of synonymous over nonsynonymous substitutions per site, lack of association of amino acid replacements with epitope regions, and slow extinction of coexisting virus lineages. These long periods of stasis are punctuated by shorter intervals of rapid evolution under positive selection during which new dominant lineages quickly displace previously coexisting ones. The preponderance of positive selection during intervals of rapid evolution is supported by the dramatic excess of amino acid replacements in the epitope regions of HA compared to replacements in the rest of the HA molecule. In contrast, the stasis intervals showed a much more uniform distribution of replacements over the HA molecule, with a statistically significant difference in the rate of synonymous over nonsynonymous substitution in the epitope regions between the two modes of evolution. A number of parallel amino acid replacements – the same amino acid substitution occurring independently in different lineages – were also detected in H3N2 HA. These parallel mutations were, largely, associated with periods of rapid fitness change, indicating that there are major limitations on evolutionary pathways during antigenic change. The finding that stasis is the prevailing modality of H3N2 evolution suggests that antigenic changes that lead to an increase in fitness typically result from epistatic interactions between several amino acid substitutions in the HA and, perhaps, other viral proteins. The strains that become dominant due to increased fitness emerge from low frequency strains thanks to the last amino acid replacement that completes the set of replacements required to produce a significant antigenic change; no subset of substitutions results in a biologically significant antigenic change and corresponding fitness increase. In contrast to H3N2, no clear intervals of evolution under positive selection were detected for the H1N1 HA during the same time span. Thus, the ascendancy of H1N1 in some seasons is, most likely, caused by the drop in the relative fitness of the previously prevailing H3N2 lineages as the fraction of susceptible hosts decreases during the stasis intervals. CONCLUSION: We show that the common view of the evolution of influenza virus as a rapid, positive selection-driven process is, at best, incomplete. Rather, the interpandemic evolution of influenza appears to consist of extended intervals of stasis, which are characterized by neutral sequence evolution, punctuated by shorter intervals of rapid fitness increase when evolutionary change is driven by positive selection. These observations have implications for influenza surveillance and vaccine formulation; in particular, the possibility exists that parallel amino acid replacements could serve as a predictor of new dominant strains. REVIEWERS: Ron Fouchier (nominated by Andrey Rzhetsky), David Krakauer, Christopher Le