Phenotypic Variation among Thick-billed Murres from Colonies in Hudson Strait

Thick-billed Murres (Uria lomvia) breeding in the Canadian Arctic are restricted to a small number of colonies, all comprising more that 10,000 pairs. Five of these colonies are scattered through Hudson Strait. We collected adult breeders at three of the colonies - Digges Island, Hantzsch Island, and Akpatok Island - and compared wing and bill measurements and body weights to look for inter-colony differences. Significant inter-colony differences were present for all measurements and a discriminant function analysis showed that some individuals fall completely outside the range of variation for the other colonies. Because of the presence of the Laurentide ice-sheet over Hudson Strait, the present colony sites could not have been occupied for more than 10,000 years. If the observed differences reflect differences in genotype then their evolution must have occurred over this period.Key words: Thick-billed murre, Uria lomvia, phenotypic variation, Hudson Strait, evolutionMots clés: Marmettes de Brunnïch, Uria lomvia, variation des phénotypes, détroit d'Hudson, évolutio

Similarities and differences of pumping conventional and self-compacting concrete

In Practice, Self-Compacting Concrete (SCC) is Considered as a Simple Extension of Conventional Vibrated Concrete (CVC) When Pumping is Concerned. the Same Equipment, Materials, Pumping Procedures and Guidelines Used for CVC Are Applied When Pumping SCC. on the Other Hand, It Has Been Clearly Shown that the Rheological Properties and the Mix Design of SCC Are Different Than CVC. Can the Same Pumping Principles Employed for CVC Be Applied for SCC? This Paper Compares the Some Published Results of Pumping of CVC with Those for SCC. a First Striking Difference between Pumping of CVC and SCC is the Flow Behaviour in the Pipes. the Flow of CVC is a Plug, Surrounded by a Lubricating Layer, While during the Flow of SCC, Part of the Concrete Volume itself is Sheared Inside the Pipe. as a Result, the Importance of Viscosity Increases in Case of SCC. Due to the Low Yield Stress of SCC, the Behaviour in Bends is Different, But Quite Complex to Study. Due to the Lower Content of Aggregate and Better Stability of SCC, as It is Less Prone to Internal Water Migration, Blocking is Estimated to Occur at Lower Frequency in Case of SCC. © RILEM 2010

The Complexity of Reasoning for Fragments of Default Logic

Default logic was introduced by Reiter in 1980. In 1992, Gottlob classified the complexity of the extension existence problem for propositional default logic as \SigmaPtwo-complete, and the complexity of the credulous and skeptical reasoning problem as SigmaP2-complete, resp. PiP2-complete. Additionally, he investigated restrictions on the default rules, i.e., semi-normal default rules. Selman made in 1992 a similar approach with disjunction-free and unary default rules. In this paper we systematically restrict the set of allowed propositional connectives. We give a complete complexity classification for all sets of Boolean functions in the meaning of Post's lattice for all three common decision problems for propositional default logic. We show that the complexity is a hexachotomy (SigmaP2-, DeltaP2-, NP-, P-, NL-complete, trivial) for the extension existence problem, while for the credulous and skeptical reasoning problem we obtain similar classifications without trivial cases.Comment: Corrected versio

Genes in the postgenomic era

We outline three very different concepts of the gene - 'instrumental', 'nominal', and 'postgenomic'. The instrumental gene has a critical role in the construction and interpretation of experiments in which the relationship between genotype and phenotype is explored via hybridization between organisms or directly between nucleic acid molecules. It also plays an important theoretical role in the foundations of disciplines such as quantitative genetics and population genetics. The nominal gene is a critical practical tool, allowing stable communication between bioscientists in a wide range of fields grounded in well-defined sequences of nucleotides, but this concept does not embody major theoretical insights into genome structure or function. The post-genomic gene embodies the continuing project of understanding how genome structure supports genome function, but with a deflationary picture of the gene as a structural unit. This final concept of the gene poses a significant challenge to conventional assumptions about the relationship between genome structure and function, and between genotype and phenotype

Progress in muscular dystrophy research with special emphasis on gene therapy

Duchenne muscular dystrophy (DMD) is an X-linked, progressive muscle-wasting disease caused by mutations in the DMD gene. Since the disease was described by physicians in the 19th century, information about the subject has been accumulated. One author (Sugita) was one of the coworkers who first reported that the serum creatine kinase (CK) level is elevated in progressive muscular dystrophy patients. Even 50 years after that first report, an elevated serum CK level is still the most useful marker in the diagnosis of DMD, a sensitive index of the state of skeletal muscle, and useful to evaluate therapeutic effects. In the latter half of this article, we describe recent progress in the therapy of DMD, with an emphasis on gene therapies, particularly exon skipping

Lte1 contributes to Bfa1 localization rather than stimulating nucleotide exchange by Tem1

Reevaluation of Lte1’s involvement in the mitotic exit network reveals that it is involved in localizing Bfa1 to the spindle pole body but does not function as a GEF for Tem1

Representing Fitness Landscapes by Valued Constraints to Understand the Complexity of Local Search

Local search is widely used to solve combinatorial optimisation problems and to model biological evolution, but the performance of local search algorithms on different kinds of fitness landscapes is poorly understood. Here we introduce a natural approach to modelling fitness landscapes using valued constraints. This allows us to investigate minimal representations (normal forms) and to consider the effects of the structure of the constraint graph on the tractability of local search. First, we show that for fitness landscapes representable by binary Boolean valued constraints there is a minimal necessary constraint graph that can be easily computed. Second, we consider landscapes as equivalent if they allow the same (improving) local search moves; we show that a minimal normal form still exists, but is NP-hard to compute. Next we consider the complexity of local search on fitness landscapes modelled by valued constraints with restricted forms of constraint graph. In the binary Boolean case, we prove that a tree-structured constraint graph gives a tight quadratic bound on the number of improving moves made by any local search; hence, any landscape that can be represented by such a model will be tractable for local search. We build two families of examples to show that both the conditions in our tractability result are essential. With domain size three, even just a path of binary constraints can model a landscape with an exponentially long sequence of improving moves. With a treewidth two constraint graph, even with a maximum degree of three, binary Boolean constraints can model a landscape with an exponentially long sequence of improving moves

Advances in gene therapy for muscular dystrophies

Duchenne muscular dystrophy (DMD) is a recessive lethal inherited muscular dystrophy caused by mutations in the gene encoding dystrophin, a protein required for muscle fibre integrity. So far, many approaches have been tested from the traditional gene addition to newer advanced approaches based on manipulation of the cellular machinery either at the gene transcription, mRNA processing or translation levels. Unfortunately, despite all these efforts, no efficient treatments for DMD are currently available. In this review, we highlight the most advanced therapeutic strategies under investigation as potential DMD treatments

Evolutionary History of Tissue Kallikreins

The gene family of human kallikrein-related peptidases (KLKs) encodes proteins with diverse and pleiotropic functions in normal physiology as well as in disease states. Currently, the most widely known KLK is KLK3 or prostate-specific antigen (PSA) that has applications in clinical diagnosis and monitoring of prostate cancer. The KLK gene family encompasses the largest contiguous cluster of serine proteases in humans which is not interrupted by non-KLK genes. This exceptional and unique characteristic of KLKs makes them ideal for evolutionary studies aiming to infer the direction and timing of gene duplication events. Previous studies on the evolution of KLKs were restricted to mammals and the emergence of KLKs was suggested about 150 million years ago (mya). In order to elucidate the evolutionary history of KLKs, we performed comprehensive phylogenetic analyses of KLK homologous proteins in multiple genomes including those that have been completed recently. Interestingly, we were able to identify novel reptilian, avian and amphibian KLK members which allowed us to trace the emergence of KLKs 330 mya. We suggest that a series of duplication and mutation events gave rise to the KLK gene family. The prominent feature of the KLK family is that it consists of tandemly and uninterruptedly arrayed genes in all species under investigation. The chromosomal co-localization in a single cluster distinguishes KLKs from trypsin and other trypsin-like proteases which are spread in different genetic loci. All the defining features of the KLKs were further found to be conserved in the novel KLK protein sequences. The study of this unique family will further assist in selecting new model organisms for functional studies of proteolytic pathways involving KLKs

Sarilumab in patients admitted to hospital with severe or critical COVID-19: a randomised, double-blind, placebo-controlled, phase 3 trial

Background: Elevated proinflammatory cytokines are associated with greater COVID-19 severity. We aimed to assess safety and efficacy of sarilumab, an interleukin-6 receptor inhibitor, in patients with severe (requiring supplemental oxygen by nasal cannula or face mask) or critical (requiring greater supplemental oxygen, mechanical ventilation, or extracorporeal support) COVID-19. Methods: We did a 60-day, randomised, double-blind, placebo-controlled, multinational phase 3 trial at 45 hospitals in Argentina, Brazil, Canada, Chile, France, Germany, Israel, Italy, Japan, Russia, and Spain. We included adults (≥18 years) admitted to hospital with laboratory-confirmed SARS-CoV-2 infection and pneumonia, who required oxygen supplementation or intensive care. Patients were randomly assigned (2:2:1 with permuted blocks of five) to receive intravenous sarilumab 400 mg, sarilumab 200 mg, or placebo. Patients, care providers, outcome assessors, and investigators remained masked to assigned intervention throughout the course of the study. The primary endpoint was time to clinical improvement of two or more points (seven point scale ranging from 1 [death] to 7 [discharged from hospital]) in the modified intention-to-treat population. The key secondary endpoint was proportion of patients alive at day 29. Safety outcomes included adverse events and laboratory assessments. This study is registered with ClinicalTrials.gov, NCT04327388; EudraCT, 2020-001162-12; and WHO, U1111-1249-6021. Findings: Between March 28 and July 3, 2020, of 431 patients who were screened, 420 patients were randomly assigned and 416 received placebo (n=84 [20%]), sarilumab 200 mg (n=159 [38%]), or sarilumab 400 mg (n=173 [42%]). At day 29, no significant differences were seen in median time to an improvement of two or more points between placebo (12·0 days [95% CI 9·0 to 15·0]) and sarilumab 200 mg (10·0 days [9·0 to 12·0]; hazard ratio [HR] 1·03 [95% CI 0·75 to 1·40]; log-rank p=0·96) or sarilumab 400 mg (10·0 days [9·0 to 13·0]; HR 1·14 [95% CI 0·84 to 1·54]; log-rank p=0·34), or in proportions of patients alive (77 [92%] of 84 patients in the placebo group; 143 [90%] of 159 patients in the sarilumab 200 mg group; difference −1·7 [−9·3 to 5·8]; p=0·63 vs placebo; and 159 [92%] of 173 patients in the sarilumab 400 mg group; difference 0·2 [−6·9 to 7·4]; p=0·85 vs placebo). At day 29, there were numerical, non-significant survival differences between sarilumab 400 mg (88%) and placebo (79%; difference +8·9% [95% CI −7·7 to 25·5]; p=0·25) for patients who had critical disease. No unexpected safety signals were seen. The rates of treatment-emergent adverse events were 65% (55 of 84) in the placebo group, 65% (103 of 159) in the sarilumab 200 mg group, and 70% (121 of 173) in the sarilumab 400 mg group, and of those leading to death 11% (nine of 84) were in the placebo group, 11% (17 of 159) were in the sarilumab 200 mg group, and 10% (18 of 173) were in the sarilumab 400 mg group. Interpretation: This trial did not show efficacy of sarilumab in patients admitted to hospital with COVID-19 and receiving supplemental oxygen. Adequately powered trials of targeted immunomodulatory therapies assessing survival as a primary endpoint are suggested in patients with critical COVID-19. Funding: Sanofi and Regeneron Pharmaceuticals