Unexpected correlations between gene expression and codon usage bias from microarray data for the whole Escherichia coli K-12 genome

Escherichia coli has long been regarded as a model organism in the study of codon usage bias (CUB). However, most studies in this organism regarding this topic have been computational or, when experimental, restricted to small datasets; particularly poor attention has been given to genes with low CUB. In this work, correspondence analysis on codon usage is used to classify E.coli genes into three groups, and the relationship between them and expression levels from microarray experiments is studied. These groups are: group 1, highly biased genes; group 2, moderately biased genes; and group 3, AT-rich genes with low CUB. It is shown that, surprisingly, there is a negative correlation between codon bias and expression levels for group 3 genes, i.e. genes with extremely low codon adaptation index (CAI) values are highly expressed, while group 2 show the lowest average expression levels and group 1 show the usual expected positive correlation between CAI and expression. This trend is maintained over all functional gene groups, seeming to contradict the E.coli–yeast paradigm on CUB. It is argued that these findings are still compatible with the mutation–selection balance hypothesis of codon usage and that E.coli genes form a dynamic system shaped by these factors

Solving the riddle of codon usage preferences: a test for translational selection

Translational selection is responsible for the unequal usage of synonymous codons in protein coding genes in a wide variety of organisms. It is one of the most subtle and pervasive forces of molecular evolution, yet, establishing the underlying causes for its idiosyncratic behaviour across living kingdoms has proven elusive to researchers over the past 20 years. In this study, a statistical model for measuring translational selection in any given genome is developed, and the test is applied to 126 fully sequenced genomes, ranging from archaea to eukaryotes. It is shown that tRNA gene redundancy and genome size are interacting forces that ultimately determine the action of translational selection, and that an optimal genome size exists for which this kind of selection is maximal. Accordingly, genome size also presents upper and lower boundaries beyond which selection on codon usage is not possible. We propose a model where the coevolution of genome size and tRNA genes explains the observed patterns in translational selection in all living organisms. This model finally unifies our understanding of codon usage across prokaryotes and eukaryotes. Helicobacter pylori, Saccharomyces cerevisiae and Homo sapiens are codon usage paradigms that can be better understood under the proposed model

Comparison of Queueing Data-Structures for Kinetic Monte Carlo Simulations of Heterogeneous Catalysts

On-lattice Kinetic Monte Carlo (KMC) is a computational method used to simulate (among others) physico-chemical processes on catalytic surfaces. The KMC algorithm propagates the system through discrete configurations by selecting (with the use of random numbers) the next elementary process to be simulated, e.g. adsorption, desorption, diffusion or reaction. An implementation of such a selection procedure is the first-reaction method in which all realizable elementary processes are identified and assigned a random occurrence time based on their rate constant. The next event to be executed will then be the one with the minimum inter-arrival time. Thus, a fast and efficient algorithm for selecting the most imminent process and performing all the necessary updates on the list of realizable processes post-execution, is of great importance. In the current work, we implement five data-structures to handle the elementary process queue during a KMC run: an unsorted list, a binary heap, a pairing heap, a 1-way skip list, and finally, a novel 2-way skip list with a mapping array specialized for KMC simulations. We also investigate the effect of compiler optimizations on the performance of these data-structures on three benchmark models, capturing CO-oxidation, a simplified water-gas shift mechanism, and a temperature programmed desorption run. Excluding the least efficient and impractical for large problems unsorted list, we observe a 3× speedup of the binary or pairing heaps (most efficient) compared to the 1-way skip list (least efficient). Compiler optimizations deliver a speedup of up to 1.8×. These benchmarks provide valuable insight on the importance of, often-overlooked, implementation-related aspects of KMC simulations, such as the queueing data-structures. Our results could be particularly useful in guiding the choice of data-structures and algorithms that would minimize the computational cost of large-scale simulations

Economies of scale and scope in hospitals: an empirical study of volume spillovers

General hospitals across the world are becoming larger (i.e. admitting more patients each year) and more complex (i.e. offering a wider range of services to patients with more diverse care needs). Prior work suggests that an increase in patient volume in a hospital service is associated with reduced costs per patient in that service. However, it is unclear how volume changes in one service affect the costs of the other services in the same hospital. This paper investigates such volume-cost spillover effects between elective and emergency admissions and across specialties, using condition-level panel data comprising all acute hospital trusts in England over a period of ten years. We provide evidence that increased elective volume at a hospital is associated with an increase in the cost of emergency care (a negative spillover). Furthermore, for emergency admissions, we find evidence that increased emergency activity in one specialty is associated with lower costs of emergency care in other specialties (a positive spillover). By contrast, we find no evidence of spillover effects across specialties for elective admissions. We discuss the implications of these findings for individual hospital growth strategies and for the regional organization of hospital systems

How do potentially inappropriate medications and polypharmacy affect mortality in frail and non-frail cognitively impaired older adults?:A cohort study

OBJECTIVES: To test whether the use of potentially inappropriate central nervous system acting medications, proton pump inhibitors (PPIs) or polypharmacy are associated with mortality in cognitively impaired older adults and whether frailer people are at greater risk of harm. SETTING: A cohort study nested within the Cognitive Function and Ageing Study II, a population representative cohort study of the older population in Cambridgeshire, Nottingham and Newcastle, UK. PARTICIPANTS: A total of 1154 cognitively impaired participants, aged 65 years or older. EXPOSURES: Any use of antipsychotics, antidepressants, other anticholinergic medication, benzodiazepines or PPIs, polypharmacy (5-9) and hyperpolypharmacy (≥10 reported medications) were ascertained at baseline. Frailty was assessed using the Fried criteria. PRIMARY OUTCOME: Mortality up to 8 years follow-up. HRs associated with potentially inappropriate medication (PIM), frailty and their interaction were estimated adjusting for covariates. RESULTS: Within the sample, 44% were taking one or more PIM. Apart from antipsychotics (adjusted HR=3.24, 95% CI 1.83 to 5.73), use of specific PIM was not associated with greater subsequent mortality. Polypharmacy (HR=1.17, 95% CI 0.95 to 1.45) and hyperpolypharmacy were associated with mortality (HR=1.60, 95% CI 1.16 to 2.22). Being frail (HR=1.90, 95% CI 1.32 to 2.72) or prefrail (HR=1.56, 95% CI 1.10 to 2.20) was associated with increased mortality. There was some evidence that the HR for polypharmacy on mortality was lower among frailer individuals, but the overall polypharmacy by frailty interaction was not statistically significant (p=0.102). CONCLUSIONS: For those with cognitive impairment, greater concern should be afforded to the number of medications than the prescription of specific classes. Frailer individuals may have a lower relative risk of mortality associated with polypharmacy than less frail individuals

О двух древнерусских надписях из Белоруссии и Польши

Two Old Russian graffiti inscriptions are examined in the present paper. The first one, dating back to the late 13th–early 14th centuries, is located on one of the walls of the Savior Transfiguration Church in the St. Euphrosyne convent in Polotsk, Belarus. It reads Marъkova žana dobra ‘Mark’s wife is good.’ The second graffito was inscribed on a knife handle excavated in Drohiczyn, Eastern Poland (Old Russian Dorogyčinъ), and dates to the end of the 11th through the 12th centuries. The inscription reads Ežьkovъ nožь a iže i ukradetь proklętъ  . . . ‘Ezhko’s knife. Whoever steals it, be cursed . . .’ Although both inscriptions have been published, the present study adds more in-depth paleographic and linguistic commentary and suggests corrected readings. The laudatory inscription from Polotsk is particularly interesting because it contains an early example of a spelling reflecting yakanye, a trait of Belarusian phonetics, whereas the interest of the Drohiczyn inscription lies in its unusual paleographic features.В данной заметке рассматриваются два древнерусских граффити: надпись Маръкова жана добра ‘Маркова жена — добрая / хорошая’ конца XIII или начала XIV века со стены Спасо-Преображенской церкви Спасо-Евфросиниевского монастыря в Полоцке и надпись Ежьковъ ножь а иже и ѫкрадеть проклѧтъ . . . ‘Ежков нож. А кто его украдет, проклят . . .’ конца XI – XII века на костяной рукояти ножа, происходящей из раскопок в Дрохичине (древнерусском Дорогычине) на востоке Польши. Обе надписи уже публиковались ранее, однако их прочтение требует нескольких уточнений, а их палеография и язык — более обстоятельного комментария. Как показано в заметке, полоцкая надпись, интересная своей восхваляющей формулой, содержит ранний пример отражения яканья, белорусской фонетической особенности. Дрогичинская же надпись выделяется весьма нестандартной палеографией

Минеи двух Домок: Еще раз о писцах служебных миней из новгородского Лазарева монастыря

The article deals with the history of several manuscripts related to the Novgorod convent of St. Lazarus.The study focuses on two sets of ancient Menaia: the Menaia of the 1090s for the first three months of the liturgical year, which were jointly written by Jacob Domka and Michael, and five Menaia for other months, written by Matthew and Lawrence. The handwriting of the first scribe of the January Menaion, previously anonymous, is attributed to St. Lazarus’ priest Domka, the first scribe of the Milyatino Gospel and the second scribe of the St. Lazarus (or Skovorodka) Prophetologion, the oldest known Slavic Prophetologion.Analysis of the colophons of Jacob Domka, Domka the priest and Matthew suggests that the Menaia for September, October and November were written for the Zverin convent of the Mother of God, whereas the Milyatino Gospel and the Menaia for January, February, April, July and August—for St. Lazarus convent. Circumstantial evidence suggests that the Menaia for January—August were created in the nearby Holy Spirit Friary.Also, the paper discusses the history of manuscripts received at the Moscow Printing House in 1679 from the Novgorod convent of St. Lazarus and the monastery of Archangel Michael on Skovorodka and includes revised texts of all scribal notes found in the two abovementioned sets of Menaia. DOI: 10.31168/2305-6754.2019.8.2.1Статья посвящена истории рукописей, связанных с новгородским женским монастырем Св. Лазаря.В центре исследования находятся два комплекта древних миней: минеи 1090-х гг. за три первых месяца богослужебного года, которые объединяет между собой участие в их написании Якова Домки и Михаила, и минеи за другие пять месяцев, вышедшие из-под пера Матфея и Лаврентия. Почерк не известного прежде по имени первого писца январской минеи атрибутирован лазаревскому попу Домке, первому писцу Милятина евангелия и второму писцу древнейшего славянского паремейника — Лазаревского (или Сковородского) паремейника.Анализ сведений выходных записей Якова Домки, попа Домки и Матфея позволяет сделать вывод, что минеи за сентябрь, октябрь и ноябрь предназначались для женского монастыря Богородицы в Зверинце, а Милятино евангелие и минеи за январь, февраль, апрель, июль и август — для Лазарева монастыря. Косвенные признаки указывают на то, что минеи за январь–август были созданы в соседнем мужском Духовом монастыре.Попутно в работе рассматривается история рукописей, поступивших на московский Печатный двор в 1679 г. из новгородских монастырей Св. Лазаря и Арх. Михаила на Сковородке, а также опубликованы выверенные тексты всех записей писцов двух минейных комплектов.DOI: 10.31168/2305-6754.2019.8.2.

The Menaia of Two Domkas. Once More on the Scribes of the Menaia from the Novgorod Convent of St. Lazarus

The article deals with the history of several manuscripts related to the Novgorod convent of St. Lazarus. The study focuses on two sets of ancient Menaia: the Menaia of the 1090s for the first three months of the liturgical year, which were jointly written by Jacob Domka and Michael, and five Menaia for other months, written by Matthew and Lawrence. The handwriting of the first scribe of the January Menaion, previously anonymous, is attributed to St. Lazarus’ priest Domka, the first scribe of the Milyatino Gospel and the second scribe of the St. Lazarus (or Skovorodka) Prophetologion, the oldest known Slavic Prophetologion. Analysis of the colophons of Jacob Domka, Domka the priest and Matthew suggests that the Menaia for September, October and November were written for the Zverin convent of the Mother of God, whereas the Milyatino Gospel and the Menaia for January, February, April, July and August—for St. Lazarus convent. Circumstantial evidence suggests that the Menaia for January—August were created in the nearby Holy Spirit Friary. Also, the paper discusses the history of manuscripts received at the Moscow Printing House in 1679 from the Novgorod convent of St. Lazarus and the monastery of Archangel Michael on Skovorodka and includes revised texts of all scribal notes found in the two abovementioned sets of Menaia