An environment for object-oriented real-time system design

A concise object-oriented method for the development of real-time systems has been composed. Hardware components are modelled by (software) base objects; base objects are controlled by a hierarchy of coordinator objects, expressed in an organizational diagram. The behaviour of objects is specified by state transition diagrams. This approach considerably promotes requirements analysis and communication with the customer. A CASE tool has been constructed with diagram editors for graphical specifications of real-time systems. The tool can generate executable code for PLCs from these graphical specifications; reuse of previous results is supported by the repository function of the tool. Experiences attained in practice with method and tool show that time spent in system testing and installation is reduced considerabl

Identification, distribution and molecular evolution of the pacifastin gene family in Metazoa

<p>Abstract</p> <p>Background</p> <p>Members of the pacifastin family are serine peptidase inhibitors, most of which are produced as multi domain precursor proteins. Structural and biochemical characteristics of insect pacifastin-like peptides have been studied intensively, but only one inhibitor has been functionally characterised. Recent sequencing projects of metazoan genomes have created an unprecedented opportunity to explore the distribution, evolution and functional diversification of pacifastin genes in the animal kingdom.</p> <p>Results</p> <p>A large scale <it>in silico </it>data mining search led to the identification of 83 pacifastin members with 284 inhibitor domains, distributed over 55 species from three metazoan phyla. In contrast to previous assumptions, members of this family were also found in other phyla than Arthropoda, including the sister phylum Onychophora and the 'primitive', non-bilaterian Placozoa. In Arthropoda, pacifastin members were found to be distributed among insect families of nearly all insect orders and for the first time also among crustacean species other than crayfish and the Chinese mitten crab. Contrary to precursors from Crustacea, the majority of insect pacifastin members contain dibasic cleavage sites, indicative for posttranslational processing into numerous inhibitor peptides. Whereas some insect species have lost the pacifastin gene, others were found to have several (often clustered) paralogous genes. Amino acids corresponding to the reactive site or involved in the folding of the inhibitor domain were analysed as a basis for the biochemical properties.</p> <p>Conclusion</p> <p>The absence of the pacifastin gene in some insect genomes and the extensive gene expansion in other insects are indicative for the rapid (adaptive) evolution of this gene family. In addition, differential processing mechanisms and a high variability in the reactive site residues and the inner core interactions contribute to a broad functional diversification of inhibitor peptides, indicating wide ranging roles in different physiological processes. Based on the observation of a pacifastin gene in Placozoa, it can be hypothesized that the ancestral pacifastin gene has occurred before the divergence of bilaterian animals. However, considering differences in gene structure between the placozoan and other pacifastin genes and the existence of a 'pacifastin gene gap' between Placozoa and Onychophora/Arthropoda, it cannot be excluded that the pacifastin signature originated twice by convergent evolution.</p

Adherence to an injury prevention program in male amateur football players is affected by players' age, experience and perceptions

Objectives Adherence to injury prevention programmes in football remains low, which is thought to drastically reduce the effects of injury prevention programmes. Reasons why (medical) staff and players implement injury prevention programmes, have been investigated, but player's characteristics and perceptions about these programmes might influence their adherence. Therefore, this study investigated the relationships between player's characteristics and adherence and between player's perceptions and adherence following an implemented injury prevention programme. Methods Data from 98 of 221 football players from the intervention group of a cluster randomised controlled trial concerning hamstring injury prevention were analysed. Results Adherence was better among older and more experienced football players, and players considered the programme more useful, less intense, more functional and less time-consuming. Previous hamstring injuries, educational level, the programme's difficulty and intention to continue the exercises were not significantly associated with adherence. Conclusion These player's characteristics and perceptions should be considered when implementing injury prevention programmes

Adherence to an injury prevention program in male amateur football players is affected by players’ age, experience and perceptions

OBJECTIVES : Adherence to injury prevention programmes in football remains low, which is thought to drastically reduce the effects of injury prevention programmes. Reasons why (medical) staff and players implement injury prevention programmes, have been investigated, but player’s characteristics and perceptions about these programmes might influence their adherence. Therefore, this study investigated the relationships between player’s characteristics and adherence and between player’s perceptions and adherence following an implemented injury prevention programme. METHODS : Data from 98 of 221 football players from the intervention group of a cluster randomised controlled trial concerning hamstring injury prevention were analysed. RESULTS : Adherence was better among older and more experienced football players, and players considered the programme more useful, less intense, more functional and less time-consuming. Previous hamstring injuries, educational level, the programme’s difficulty and intention to continue the exercises were not significantly associated with adherence. CONCLUSION : These player’s characteristics and perceptions should be considered when implementing injury prevention programmes.https://bmjopensem.bmj.comhj2022Sports Medicin

The integrated stress response is tumorigenic and constitutes a therapeutic liability in KRAS-driven lung cancer.

The integrated stress response (ISR) is an essential stress-support pathway increasingly recognized as a determinant of tumorigenesis. Here we demonstrate that ISR is pivotal in lung adenocarcinoma (LUAD) development, the most common histological type of lung cancer and a leading cause of cancer death worldwide. Increased phosphorylation of the translation initiation factor eIF2 (p-eIF2α), the focal point of ISR, is related to invasiveness, increased growth, and poor outcome in 928 LUAD patients. Dissection of ISR mechanisms in KRAS-driven lung tumorigenesis in mice demonstrated that p-eIF2α causes the translational repression of dual specificity phosphatase 6 (DUSP6), resulting in increased phosphorylation of the extracellular signal-regulated kinase (p-ERK). Treatments with ISR inhibitors, including a memory-enhancing drug with limited toxicity, provides a suitable therapeutic option for KRAS-driven lung cancer insofar as they substantially reduce tumor growth and prolong mouse survival. Our data provide a rationale for the implementation of ISR-based regimens in LUAD treatment

Competition and site weakly explain tree growth variability in undisturbed Central African moist forests

peer reviewedIdentifying and quantifying factors that influence tree growth are crucial issues to ensure sustainable forest management, particularly in moist tropical forests. Tree growth depends on several factors comprising ontogenic stage, competition by neighbours and environmental conditions. Several studies have focused on one or two of them, but very few have considered all three, especially in Central Africa. We investigated the effects of diameter and competition on tree growth, in four Central African sites characterized by their soil physicochemical properties, at both tree community and population levels. We calibrated growth models using diameter data collected on 29,741 trees between 2015 and 2018, on twelve 4 or 9-ha plots spread over the four sites. These models included diameter, wood density, competition indices and site effect as explainable variables at the community level and excluded wood density at the population level. At the community level, the best models explained 11% of growth variability with a decreasing effect of species wood density, diameter, site and competition. Our results show that even if low, site effect can result from different soil nutrients depending on both tree size and species wood density. We observed higher tree growth on sites with (i) high exchangeable K, organic C, total N and total P for low wood density species; (ii) high available P and C:N for small trees, high exchangeable Ca and Mg for medium to large trees, all belonging to medium and hard wood density species. At the population level, the best models explained between 0 to 43% of growth variability, with significant competition effect (resp. site effect) for 21 (resp. 9) of the 43 species studied. Site ranking varied greatly between the 9 species concerned, probably reflecting different sensitivities to the scarcity of particular soil nutrients. Synthesis. Our study provides original results on the factors influencing tree growth in Central Africa, showing that the potential effect of soil nutrients depends on tree size and species wood density. Remaining highly unpredictable at the population level, this effect makes it essential to increase the number of dynamics monitoring systems in logging concessions

Tumour microvessel density as predictor of chemotherapy response in breast cancer patients

The aim of this study was to evaluate the predictive value of intratumoural microvessel density in breast cancer. We studied immunohistochemically primary tumours of 104 patients with metastasised breast cancer who took part in a randomised multicentre trial comparing docetaxel to sequential methotrexate and 5-fluorouracil. Vessels were highlighted with factor VIII staining and counted microscopically. Microvessel density was compared with clinical response to chemotherapy and patient survival. The microvessel density of the primary tumour was not significantly associated with patient's response to chemotherapy, time to progression or overall survival in the whole patient population or in the docetaxel or methotrexate and 5-fluorouracil groups. However, disease-free survival was longer in patients with low microvessel density (P=0.01). These findings suggest that microvessel density of the primary tumour cannot be used as a predictive marker for chemotherapy response in advanced breast cancer

Intra-tumoural microvessel density in human solid tumours

Over the last decade assessment of angiogenesis has emerged as a potentially useful biological prognostic and predictive factor in human solid tumours. With the development of highly specific endothelial markers that can be assessed in histological archival specimens, several quantitative studies have been performed in various solid tumours. The majority of published studies have shown a positive correlation between intra-tumoural microvessel density, a measure of tumour angiogenesis, and prognosis in solid tumours. A minority of studies have not demonstrated an association and this may be attributed to significant differences in the methodologies employed for sample selection, immunostaining techniques, vessel counting and statistical analysis, although a number of biological differences may account for the discrepancy. In this review we evaluate the quantification of angiogenesis by immunohistochemistry, the relationship between tumour vascularity and metastasis, and the clinicopathological studies correlating intra-tumoral microvessel density with prognosis and response to anti-cancer therapy. In view of the extensive nature of this retrospective body of data, comparative studies are needed to identify the optimum technique and endothelial antigens (activated or pan-endothelial antigens) but subsequently prospective studies that allocate treatment on the basis of microvessel density are required

Distribution and functional characterization of PSTI-like protease inhibitors in Insecta.

In mammalian pancreatic cells, the pancreatic secretory trypsin inhibitor (PSTI) prevents the premature activation of digestive enzymes and thus plays an important role in a protective mechanism against tissue destruction by these enzymes, a process which may ultimately cause diseases such as pancreatitis and pancreatic cancer. Insects, however, lack a pancreas and so far no PSTI-like peptides have been functionally characterized.In several insect species protease inhibitors that structurally resemble the mammalian PSTI were predicted in silico. Putative PSTI-like proteins were cloned and sequenced in the African migratory locust, Locusta migratoria (LmPSTI), and in the red flour beetle, Tribolium castaneum (TcPSTI-A1, -A2 and B). The expression of LmPSTI was shown to be restricted to the digestive enzyme producing organs (midgut and caeca) and further antibody-based experiments showed that LmPSTI is also secreted. Real-time RT-PCR analysis revealed that TcPSTI-A1 is the most abundant form in the beetle s gut. Subsequently, LmPSTI and TcPSTI-A1 were produced via a bacterial expression system and were found to be potent inhibitors of bovine trypsin (and chymotrypsin, although to a lesser extent), as well as of endogenous (mid)gut serine protease activity. A kinetic analysis of LmPSTI showed that this inhibitor operates via a competitive mechanism and has an inhibitory potency comparable to vertebrate PSTI-homologs. In the caeca of locusts, the RNAi-mediated knockdown of LmPSTI resulted in a significantly upregulated expression (2-fold) of locust ATG8-transcripts (ATG8 is an ubiquitin-like protein crucial for autophagosome formation). These findings were confirmed by an ultrastructural study of the caeca, revealing the presence of autophagy-related structures in RNAi-treated animals, similar to these found in starved animals (positive control for autophagy).In addition, the suitability of LmPSTI as an eco-friendly pest control agent was investigated. The addition of LmPSTI to the diet of fifth larval stage L. migratoria resulted in a significant weight loss. A qRT-PCR analysis of (one type of) trypsin transcript levels did not reveal any significant up regulation of the expression of this digestive enzyme at the mRNA level. The results of this study lead us to believe that PSTI-like inhibitors plays an important role in controlling the proteolytic activity in the digestive system of insects and established for the first time in an insect its functional role in a protective mechanism against damage resulting from prematurely activated digestive enzymes, remarkably similar to its role in vertebrates. These findings provide new evidence for the existence of an ancient protective mechanism in metazoan digestive systems and open new perspectives for the study of autophagy-related processes and diseases in the digestive tract.nrpages: 156status: publishe