Deltaretroviruses infect a broad range of mammalian species and have circulated since the Paleogene

The Deltaretrovirus genus of retroviruses (family Retroviridae) includes the human T cell leukemia viruses and bovine leukemia virus (BLV). Relatively little is known about the biology and evolution of these viruses, because only a few species have been identified and the genomic ‘fossil record’ is relatively sparse. Here, we report the discovery of multiple novel endogenous retroviruses (ERVs) derived from ancestral deltaretroviruses. These sequences—two of which contain complete or near complete internal coding regions—reside in genomes of several distinct mammalian orders, including bats, carnivores, cetaceans, and insectivores. We demonstrate that two of these ERVs contain unambiguous homologs of the tax gene, indicating that complex gene regulation has ancient origins within the Deltaretrovirus genus. ERVs demonstrate that the host range of the deltaretrovirus genus is much more extensive than suggested by the relatively small number of exogenous deltaretroviruses described so far, and allow the evolutionary timeline of deltaretrovirus-mammal interaction to be more accurately calibrated

Characterization of Chicken Tumor Necrosis Factor-alpha, a Long Missed Cytokine in Birds

Tumor necrosis factor-alpha (TNF-alpha) is a pleiotropic cytokine playing critical roles in host defense and acute and chronic inflammation. It has been described in fish, amphibians, and mammals but was considered to be absent in the avian genomes. Here, we report on the identification and functional characterization of the avian ortholog. The chicken TNF-alpha (chTNF-alpha) is encoded by a highly GC-rich gene, whose product shares with its mammalian counterpart 45% homology in the extracellular part displaying the characteristic TNF homology domain. Orthologs of chTNF-alpha were identified in the genomes of 12 additional avian species including Palaeognathae and Neognathae, and the synteny of the closely adjacent loci with mammalian TNF-alpha orthologs was demonstrated in the crow (Corvus cornix) genome. In addition to chTNF-alpha, we obtained full sequences for homologs of TNF-alpha receptors 1 and 2 (TNFR1, TNFR2). chTNF-a mRNA is strongly induced by lipopolysaccharide (LPS) stimulation of monocyte derived, splenic and bone marrow macrophages, and significantly upregulated in splenic tissue in response to i.v. LPS treatment. Activation of T-lymphocytes by TCR crosslinking induces chTNF-alpha expression in CD4(+) but not in CD8(+) cells. To gain insights into its biological activity, we generated recombinant chTNF-alpha in eukaryotic and prokaryotic expression systems. Both, the full-length cytokine and the extracellular domain rapidly induced an NF kappa B-luciferase reporter in stably transfected CEC-32 reporter cells. Collectively, these data provide strong evidence for the existence of a fully functional TNF-alpha/TNF-alpha receptor system in birds thus filling a gap in our understanding of the evolution of cytokine systems

Multi-Factor Optimization and Factor Interactions during Product Innovation

In this paper, we develop core of an expert system for planning of innovation. The practical outcome of the paper is based on rules determination for search of perspective innovation and its distinguish from commercially unperceptive innovation. The second practical outcome of the paper is a research of interactions between factors during optimization of the product. In general, we gain process synergy, which can be a source of competitive advantage during product innovation in the presence of organizational complexity by systematically moving through the process definition, control, and improvement elements. The improvement elements can cause interactions between these elements (or factors/process parameters). First, we have to distinguish between synergistic and antagonistic interactions. For synergistic interaction can be used graphic illustration - lines on the plot do not cross each other. In contrast, for antagonistic interaction, the lines on the plot cross each other. In this case, the change in mean response for factor at low level is noticeable high compared to high level. Searching for positive interactions leading to the creation of synergies in the performances we can do at each stage of management innovations. At first, we realize only part of the possible gain, with unrealized potential remaining. Using process control, over time, we stabilize our process and obtain additional limited gain. Using process improvement, we can realize additional gain (it looks as short vertical line during the time), with some potential gain remaining. When new, feasible options develop, we can redefined our process and continue with our control and improvement efforts. Hence, each process-related issue definition, control, improvement has a distinct role to play. Confusion between roles or the omission of any of the roles creates disharmony and frustration in the production system, which ultimately limits production system effectiveness and efficiency. Sometimes, in the presence of confusion, it is possible that effectiveness and efficiency may decrease. In this situation, we hope to learn from our negative factor interactions (or failures) and subsequently improvement trends in long term with using sophisticated methods and own intuition. This paper objective is to create rules for planning innovation expert system. According to this rules will be possible to distinguish perspective innovation from commercially unperceptive innovation. The second paper objective is to explore interactions between factors during a product optimization. For this purpose will be used the methodology based on minimization of logic functions and design of experiments (analytical tools of DOE)

Diversification of accommodation offers depending on critical economies of scale for travel business

The world's oldest travel company Thomas Cook, the British tour operator with 19 million yearly clients, after 178 years of service, has officially announced that it would be liquidating its assets and filed for bankruptcy, despite attempts to rescue the brand. The low-cost travel firms and their cut-throat prices have certainly been a boon to customers, but legacy travel companies, who have been forced to decrease their prices, still not align themselves, especially if they have too diversified their activities and lost the scale advantage. In the field of today's travel business, it is not possible only to rely on case studies and best practices. But it is necessary to come up with new approaches that can deal with changes in conditions such as when confronting the tourism business risk diversification and economies of scale. This article aims to create a general identification of the tourism business management system in terms of stable (and thus, sustainable) accommodation (and accompanying services) diversification, depending on the changes in the critical quantity of economies of scale. An analytical mathematical model is used for determining the diversification and economies of scale, and the parameters are determined using a full factorial design. The results of the study verify the functionality, reliability and consistency of the designed solution using a selected enterprise case study. From a practical point of view, the solution represents re-settings of diversification of accommodation offers in terms of changing the value of the critical scale of economies and other contextual factors for business

Reducing production variability using factorial optimisation: A case study from the food-packaging industry

In industry, many phenomena and events that arise that cannot be predicted because they represent changes in production. Such random effects and events can significantly influence all aspects of the manufacturing process. The optimal design of any production system can be generated based on a complete, correct set of input information. However, such a requirement is unrealistic, as manufacturing systems are affected by several random factors. Current practice is based on determining the worst possible conditions in which a production system could run (the longest possible duration of outages in the supply chain, extreme weather conditions in agriculture, etc.). This article aimed to identify factors influencing the variability of the manufacturing process in the field of CNC (Computer Numerical Control) machining for food production. A secondary aim was to minimise the variability of the manufacturing process using a factorial design. The variability reduction was verified using statistical F-tests. The study on reducing variability in production was performed at the Czech Yuncheng Plate Making Co., Ltd., a professional rotogravure cylinder–making company. The cylinders are used for the food industry

Identification of GC-rich LAT genes in birds

Linker for activation of T cells (LAT) plays a key role in T-cell antigenic signaling in mammals. Accordingly, LAT orthologues were identified in the majority of vertebrates. However, LAT orthologues were not identified in most birds. In this study, we show that LAT gene is present in genomes of multiple extant birds. It was not properly assembled previously because of its GC-rich content. LAT expression is enriched in lymphoid organs in chicken. The analysis of the coding sequences revealed a strong conservation of key signaling motifs in LAT between chicken and human. Overall, our data indicate that mammalian and avian LAT genes are functional homologues with a common role in T-cell signaling

Identification of GC-rich LAT genes in birds.

Linker for activation of T cells (LAT) plays a key role in T-cell antigenic signaling in mammals. Accordingly, LAT orthologues were identified in the majority of vertebrates. However, LAT orthologues were not identified in most birds. In this study, we show that LAT gene is present in genomes of multiple extant birds. It was not properly assembled previously because of its GC-rich content. LAT expression is enriched in lymphoid organs in chicken. The analysis of the coding sequences revealed a strong conservation of key signaling motifs in LAT between chicken and human. Overall, our data indicate that mammalian and avian LAT genes are functional homologues with a common role in T-cell signaling

Characterization of Two Historic Smallpox Specimens from a Czech Museum

Although smallpox has been known for centuries, the oldest available variola virus strains were isolated in the early 1940s. At that time, large regions of the world were already smallpox-free. Therefore, genetic information of these strains can represent only the very last fraction of a long evolutionary process. Based on the genomes of 48 strains, two clades are differentiated: Clade 1 includes variants of variola major, and clade 2 includes West African and variola minor (Alastrim) strains. Recently, the genome of an almost 400-year-old Lithuanian mummy was determined, which fell basal to all currently sequenced strains of variola virus on phylogenetic trees. Here, we determined two complete variola virus genomes from human tissues kept in a museum in Prague dating back 60 and 160 years, respectively. Moreover, mass spectrometry-based proteomic, chemical, and microscopic examinations were performed. The 60-year-old specimen was most likely an importation from India, a country with endemic smallpox at that time. The genome of the 160-year-old specimen is related to clade 2 West African and variola minor strains. This sequence likely represents a new endemic European variant of variola virus circulating in the midst of the 19th century in Europe