Miracle-dz/UniFAR-FTUs huggingface dataset:
Dominant transformation by mutated human ras genes in vitro requires more than 100 times higher expression than is observed in cancers.

The gene-mutation-cancer hypothesis holds that mutated cellular protooncogenes, such as point-mutated proto-ras, "play a dominant part in cancer," because they are sufficient to transform transfected mouse cell lines in vitro [Alberts, B. , Bray, D. , Lewis, J., Raff, M. , Roberts, K. & Watson, J. D. (1994) Molecular Biology of the Cell (Garland, New York)]. However, in cells transformed in vitro mutated human ras genes are expressed more than 100-fold than in the cancers from which they are isolated. In view of the discrepancy between the very low levels of ras transcription in cancers and the very high levels in cells transformed in vitro, we have investigated the minimal level of human ras expression for transformation in vitro. Using point-mutated human ras genes recombined with different promoters from either human metallothionein-IIA or human fibronectin or from retroviruses we found dominant in vitro transformation of the mouse C3H cell line only with ras genes linked to viral promoters. These ras genes were expressed more than 120-fold higher than are native ras genes of C3H cells. The copy number of transfected ras genes ranged from 2-6 in our system. In addition, nondominant transformation was observed in a small percentage (2-7%) of C3H cells transfected with ras genes that are expressed less than 20 times higher than native C3H ras genes. Because over 90% of cells expressing ras at this moderately enhanced level were untransformed, transformation must follow either a nondominant ras mechanism or a non-ras mechanism. We conclude that the mutated, but normally expressed, ras genes found in human and animal cancers are not likely to "play a dominant part in cancer. " The conclusion that mutated ras genes are not sufficient or dominant for cancer is directly supported by recent discoveries of mutated ras in normal animals, and in benign human tissue, "which has little potential to progress" [Jen, J., Powell, S. M. , Papadopoulos, N. , Smith, K. J., Hamilton, S. R. , Vogelstein, B. & Kinzler, K. W. (1994) Cancer Res. 54, 5523-5526]. Even the view that mutated ras is necessary for cancer is hard to reconcile with (i) otherwise indistinguishable cancers with and without ras mutations, (ii) metastases of the same human cancers with and without ras mutations, (iii) retroviral ras genes that are oncogenic without point mutations, and (iv) human tumor cells having spontaneously lost ras mutation but not tumorigencity.
A Model Driven Method for Multilevel Security Systems Design

The article presents the application of methods of simulation of UML models for analysis and designing specialized computer systems, processing data with multilevel security. The integration of security models with models of system described in UML enables their simulation, which allows identifying security problems at the stage of modeling. By using UML extensions and ALF language it is possible to build a topological model and perform efficient simulations of topological models. The authors used an IBM simulator for simulation.
The data grid: Towards an architecture for the distributed management and analysis of large scientific datasets

In an increasing number of scientific disciplines, large data collections are emerging as important community resources. In this paper, we introduce design principles for a data management architecture called the data grid. We describe two basic services that we believe are fundamental to the design of a data grid, namely, storage systems and metadata management. Next, we explain how these services can be used to develop higher-level services for replica management and replica selection. We conclude by describing our initial implementation of data grid functionality.
Obesity, intentional weight loss and physical disability in older adults

We examine obesity, intentional weight loss and physical disability in older adults. Based on prospective epidemiological studies, body mass index exhibits a curvilinear relationship with physical disability; there appears to be some protective effect associated with older adults being overweight. Whereas the greatest risk for physical disability occurs in older adults who are ≥class II obesity, the effects of obesity on physical disability appears to be moderated by both sex and race. Obesity at age 30 years constitutes a greater risk for disability later in life than when obesity develops at age 50 years or later; however, physical activity may buffer the adverse effects obesity has on late life physical disability. Data from a limited number of randomized clinical trials reinforce the important role that physical activity plays in weight loss programmes for older adults. Furthermore, short‐term studies have found that resistance training may be particularly beneficial in these programmes as this mode of exercise attenuates the loss of fat‐free mass during caloric restriction. Multi‐year randomized clinical trials are needed to examine whether weight loss can alter the course of physical disablement in aging and to determine the long‐term feasibility and effects of combining resistance exercise with weight loss in older adults.
Can maturity indicators be used to estimate chronological age in children?

Abstract Context: There is widespread concern over the use of maturity indicators to estimate chronological age in children. Objective: To review the definition of maturity indicators, the criteria governing their identification and use and the problems of their interpretation. Methods: The development of maturity indicators, the criteria for their selection and the relationship of maturity to chronological age is critically reviewed. Results and Conclusions: Maturity indicators are not related to the passage of chronological time, but to the progression of the individual from an immature to a mature state. They are discrete events in a continuous process or a series of processes (e.g. skeletal, sexual, dental, etc.) that highlight uneven maturation within the individual, the independence of maturational processes, sexual dimorphism and the relationship of maturity to size. The use of a timescale of development causes considerable problems in translating biological maturity into a developmental scale. One “year” of maturational time does not equate to 1 year of chronological time and, thus, the passage of time determined by developmental rather than temporal landmarks is both variable and inconsistent. Chronological age determination was not the aim of maturational assessment and, thus, its widespread use as an age determinant poses considerable interpretive challenges.
Climate change in Europe. 1. Impact on terrestrial ecosystems and biodiversity. A review

Ecosystems have an essential role in providing services to humankind such as nutrient cycling, pest control, pollination, quality of life, and hydrological, atmospheric and climatic regulation. About 60% of the world’s known ecosystems are currently used unsustainably. In Europe, the richness and abundance of biodiversity is undergoing significant decline, partly due to climate change. This article outlines the impacts of climate change on biodiversity by showing both observed and projected changes in the distribution and phenology of plants and animals (phenology refers to changes in the timing of seasonal events). The four major findings are the following. (1) Concerning the distribution of plant species, climate change is responsible for the observed northward and uphill distribution shifts of many European plant species. By the late 21st century, distributions of European plant species are projected to have shifted several hundred kilometres to the north, forests are likely to have contracted in the south and expanded in the north, and 60% of mountain plant species may face extinction. The rate of change will exceed the ability of many species to adapt. (2) Concerning plant phenology, the timing of seasonal events in plants is changing across Europe due to changes in climate conditions. For instance, 78% of leaf unfolding and flowering records show advancing trends. Between 1971 and 2000, the average advance of spring and summer was 2.5 days per decade. The pollen season starts on average 10 days earlier and is longer than 50 years ago. Trends in seasonal events will continue to advance as climate warming increases in the years and decades to come. (3) Concerning the distribution of animal species, Europe’s birds, insects, and mammals are moving northwards and uphill in response to observed climate change. Rate of climate change, habitat fragmentation and other obstacles will impede the movement of many animal species. Distribution changes are projected to continue. Suitable climatic conditions for Europe’s breeding birds are projected to shift nearly 550 km northeast by the end of the century. Projections for 120 native European mammals suggest that up to 9% face extinction during the 21st century. (4) Concerning animal phenology, climatic warming has caused advancement in the life cycles of many animal groups, including frogs spawning, birds nesting and the arrival of migrant birds and butterflies. Seasonal advancement is particularly strong and rapid in the Arctic. Breeding seasons are lengthening, allowing extra generations of temperature-sensitive insects such as butterflies, dragonflies and pest species to be produced during the year. These trends are projected to continue as climate warming increases in the decades to come. Populations may explode if the young are not exposed to normal predation pressures. Conversely, populations may crash if the emergence of vulnerable young is not in synchrony with their main food source or if shorter hibernation times lead to declines in body condition.
An Alternative View of Schizophrenic Cognition

An alternative view to the traditionally held view that schizophrenia is characterised by severely disordered cognition is presented. It is possible that apparently self-contradictory expressions of schizophrenics are well-formed communicative expressions of highly ordered cognitive systems. Building on the premise that behavior is in general communicative, and using Godels Incompleteness Theorem from logic as a model, it is shown that the most characteristic symptoms of schizophrenia (namely apparently self-contradictory thought, delusions and hallucinations) may indicate truths that cannot be derived within highly ordered cognitive systems.
Mobile Sensor Databases

The main objective of this advanced seminar is to provide a comprehensive and clear overview of the concepts and core research challenges in mobile sensor databases at this point in time. To this end, this seminar starts by introducing emerging applications and projects that produce and manage MSD. We then discuss about the state-of-the-art techniques and their limitations for the key research areas in MSD: data models, querying and indexing, data mining, and uncertainty management.
Dental surgery for patients on anticoagulant therapy with warfarin: a systematic review and meta-analysis.

PURPOSE To evaluate the effect of continuing warfarin therapy on the bleeding risk of patients undergoing elective dental surgical procedures. METHODS Data sources were the MEDLINE and EMBASE databases, the Cochrane Central Register of Controlled Trials, a manual citation review of the relevant literature, content experts and relevant abstracts from the proceedings of the International Association for Dental Research. Study selection was carried out independently by two reviewers, as was quality assessment. Data extraction was done by three reviewers. Differences were resolved by consensus. Eligible studies were randomized controlled trials that compared the effects of continuing the regular dose of warfarin therapy with the effects of discontinuing or modifying the dose on the incidence of bleeding in patients undergoing dental procedures. RESULTS Five trials (a total of 553 patients) met the inclusion criteria. Compared with interrupting warfarin therapy (either partial or complete), perioperative continuation of warfarin with patients' usual dose was not associated with an increased risk for clinically significant nonmajor bleeding (relative risk [RR], 0.71; 95 percent confidence interval [CI]: 0.39-1.28; p = 0.65; 12 = 0%) or an increased risk for minor bleeding (RR, 1.19; 95% CI: 0.90-1.58; p = 0.22; 12 = 0%). CONCLUSIONS Continuing the regular dose of warfarin therapy does not seem to confer an increased risk of bleeding compared with discontinuing or modifying the warfarin dose for patients undergoing minor dental procedures.
Using a knowledge base in developing modification for MS Dynamics AX

The paper presents a practical approach of using an ontology in modification developing task for the MS Dynamics AX system. Existing development tools do not consider the context of MS Dynamics AX application objects. The proposed ontology of modifications binds MS Dynamics AX application objects and business processes. The paper proposes the structure of the ontology and the conceptual model of the modification support system.
Actors’ Competencies or Methods? A Case Study of Successful Information Systems Development

Research on information systems development methods has by and large acknowledged a significant difference between a method and its use and that the use depends on the situation and the developers, as well as other contingencies. We extend this research and focus in particular on the relationship between actors’ competencies and their deployment of methods, arguing that this relationship is described over-simplistically and needs a better explanation. Through a case study of a successful information systems development project we identify some central situations where a variety of competencies and methods are exercised. Emphasising the intertwining of competencies and methods, we discuss the character of the intertwining process, how different actors relate to different methods, and how methods may be part of the problem rather than part of the solution to challenges in information systems development. The paper suggests elements for a new model for explaining actors’ competencies and their use of methods.
Apoptosis of human gastric adenocarcinoma cells induced by beta-ionone.

AIM To investigate the effect of beta-ionone on the growth and apoptosis of gastric adenocarcinoma cell line SGC-7901. METHODS Using MTT, fluorescence dye (Hoechst-33258), transmission electron microscopy and the TUNEL assay, we examined growth and apoptosis of SGC-7901 cells treated with beta-ionone at various concentrations (i.e. 25, 50, 100 and 200 micromol/L) for 24 h, 48 h. RESULTS The growth of SGC-7901 cells was inhibited by beta-ionone. Seven days after treatment with beta-ionone at four concentrations, the inhibition rates were 12.04%, 30.59%, 78.25% and 94.15%, respectively. The IC(50) value of beta-ionone for SGC-7901 cells was estimated to be 89 micromol/L. The apoptotic morphology was demonstrated in SGC-7901 cells treated with beta-ionone by Hoechst-33258 staining and electron microscopy. Apoptosis was also shown in beta-ionone-treated SGC-7901 cells by the TUNEL assay. CONCLUSION beta-ionone can inhibit cell proliferation and induce apoptosis of SGC-7901 cells. However, the mechanism needs to be further investigated.
The Cornerstones of Medical Informatics

The changes in the health care system over the next decade are goint to make the last 20 years seem like good old days of relative stability. We will continue to see new drugs, new devices, and new techniques; however, the true megachanges of the next decade will center on gathering, managing, and using clinical information. This prediction will prove true for all the health care areas—administrative, clinical, teaching, and research. In health care today, we see pressures for improved access, demands for greater …
The Protestant ethic strikes back: Open source developers and the ethic of capitalism

Free/Open Source software development has initiated new models and theories of social organization and immaterial labor in terms of a “hacker” culture. However, our survey of four developer communities shows that there is a continuum of communities from voluntary communities, corresponding to the “hacker” image, to more business-oriented communities deviating from the image. It is particularly noteworthy that old and familiar modes of organization based on waged labor are increasingly a part of developer communities. This may create new dynamics and tensions both inside communities and between the various partners taking part in Free/Open Source software development projects.
Increasing CNN Robustness to Occlusions by Reducing Filter Support

Convolutional neural networks (CNNs) provide the current state of the art in visual object classification, but they are far less accurate when classifying partially occluded objects. A straightforward way to improve classification under occlusion conditions is to train the classifier using partially occluded object examples. However, training the network on many combinations of object instances and occlusions may be computationally expensive. This work proposes an alternative approach to increasing the robustness of CNNs to occlusion. ,, We start by studying the effect of partial occlusions on the trained CNN and show, empirically, that training on partially occluded examples reduces the spatial support of the filters. Building upon this finding, we argue that smaller filter support is beneficial for occlusion robustness. We propose a training process that uses a special regularization term that acts to shrink the spatial support of the filters. We consider three possible regularization terms that are based on second central moments, group sparsity, and mutually reweighted L1, respectively. When trained on normal (unoccluded) examples, the resulting classifier is highly robust to occlusions. For large training sets and limited training time, the proposed classifier is even more accurate than standard classifiers trained on occluded object examples.
Uma proposta para classificação baseada em contexto para técnicas de visualização

Currently, user has access to large volumes of data and also to a variety of information visualization techniques that are used to facilitate understanding of this excess data. Taxonomies and recommendation systems are alternatives used to assist user in selecting the most appropriate visualization technique. The goal of this paper is to present the initial phase of a research that aims to develop a context-based recommendation system. The initial phase was to investigate which elements of context are relevant to the recommendation and set up a classification that would consider contextual information and characteristics of the data.
Electron counting based high-radix multiplication in single electron tunneling technology

This paper investigates the implementation of high-radix multiplication based on the electron counting (EC) paradigm in single electron tunneling (SET) technology. First we propose a multiplication scheme which conceptually speaking follows the structure of traditional full-tree multipliers. The high-radix EC multiplication scheme comprises three steps and of each an implementation is presented. Second, an 8-bit radix 4 EC multiplier is designed and verified by means of simulation. The high-radix multiplication scheme is evaluated in terms of area and delay for different operand sizes and compared with corresponding binary multiplication schemes in SET technology. Both type of implementations prove to have similar delay times, but the EC based scheme requires up to five times less area
Effects of synchronous music on psychological responses, performance indices and physiological functioning among elite triathletes and runners

To date, most studies looking at the effects of music in sport have focused on non-elite populations. The use of synchronous music has demonstrated ergogenic, psychological, and physiological benefits when used as an accompaniment to physical activity. The aim of the present research programme was to extend previous investigations of synchronous music to elite athletes. Study 1 assessed the benefits of synchronous music during submaximal and exhaustive treadmill running among elite triathletes. Time-to-exhaustion, mood responses, feeling states, ratings of perceived exertion (RPE), blood lactate concentration, oxygen consumption, and running economy were measured during three treadmill runs. Participants (n = 11) ran to motivational music using self-selected tracks, a neutral music condition, and a no-music condition. Time-to-exhaustion in the motivational and neutral music conditions increased by 18.1% and 19.7%, respectively, compared to the no-music condition. Other measures that indicated a benefit of music over no music included RPE (lowest in neutral music condition), blood lactate (lowest in motivational music) and oxygen consumption (lower by 1.0%-2.7%). In Study 2, the software necessary to conduct similar testing outdoors using Apple iPhones was developed. Six iPhones were programmed to gather GPS, cadence, RPE, Feeling Scale and BRUMS data, and were evaluated by two experienced runners. Study 3 investigated the benefits of music on training effectiveness. Participants were elite triathletes (n = 2) and elite runners (n = 6) who used iPhones while running to a synchronous music condition, a music-led condition, and a no-music condition. Both music conditions were associated with greater distances covered, lower RPE, and more positive feelings and mood responses. Results suggest that the judicious use of music can potentially provide significant benefits to elite athletes during training activities.
Plumbagin (5-Hydroxy-2-methyl-1,4-naphthoquinone) Induces Apoptosis and Cell Cycle Arrest in A549 Cells through p53 Accumulation via c-Jun NH2-Terminal Kinase-Mediated Phosphorylation at Serine 15 in Vitro and in Vivo

This study first investigates the anticancer effect of plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone) in human nonsmall cell lung cancer cells, A549. Plumbagin has exhibited effective cell growth inhibition by inducing cancer cells to undergo G2/M phase arrest and apoptosis. Blockade of cell cycle was associated with increased levels of p21 and reduced amounts of cyclinB1, Cdc2, and Cdc25C. Plumbagin treatment also enhanced the levels of inactivated phosphorylated Cdc2 and Cdc25C. Blockade of p53 activity by dominant-negative p53 transfection partially decreased plumbagin-induced apoptosis and G2/M arrest, suggesting it might be operated by p53-dependent and independent pathway. Plumbagin treatment triggered the mitochondrial apoptotic pathway indicated by a change in Bax/Bcl-2 ratios, resulting in mitochondrial membrane potential loss, cytochrome c release, and caspase-9 activation. We also found that c-Jun NH2-terminal kinase (JNK) is a critical mediator in plumbagin-induced cell growth inhibition. Activation of JNK by plumbagin phosphorylated p53 at serine 15, resulting in increased stability of p53 by decreasing p53 and MDM2 interaction. SP600125 (anthra [1,9-cd]pyrazol-6(2H)-one-1,9-pyrazoloanthrone), a specific inhibitor of JNK, significantly decreased apoptosis by inhibiting the phosphorylation of p53 (serine 15) and subsequently increased the interaction of p53 and MDM2. SP6000125 also inhibited the phosphorylation of Bcl-2 (Ser70) induced by plumbagin. Further investigation revealed that plumbagin's inhibition of cell growth effect was also evident in a nude mice model. Taken together, these results suggest a critical role for JNK and p53 in plumbagin-induced G2/M arrest and apoptosis of human nonsmall cell lung cancer cells.