Miracle-dz/UniFAR-FTUs huggingface dataset:
Can Nocodazole, an Inhibitor of Microtubule Formation, Be Used to Synchronize Mammalian Cells?

Abstract Nocodazole, a temporary inhibitor of microtubule formation, has been used to partly synchronize Ehrlich ascites tumour cells growing in suspension. the gradual entry of cells into mitosis and into the next cell cycle without division during drug treatment has been studied by flow cytometric determination of mitotic cells, analysing red and green fluorescence after low pH treatment and acridine orange staining. Determination of the mitotic index (MI) by this method has been combined with DNA distribution analysis to measure cell‐cycle phase durations in asynchronous populations growing in the presence of the drug. With synchronized cells, it was shown that in the concentration range 0.4–4.0 μg/l, cells could only be arrested in mitosis for about 7 hr and at 0.04 μg/ml, for about 5 hr. After these time intervals, the DNA content in nocodazole‐blocked cells was found to be increased, and, in parallel, the ratio of red and green fluorescence was found to have changed, showing entry of cells into a next cell cycle without division (polyploidization). It was therefore only possible to partially synchronize an asynchronous population by nocodazole. However, a presynchronized population, e.g. selected G1 cells or metabolically blocked G1/S cells, were readily and without harmful effect resynchronized in M phase by a short treatment (0.4 μg/ml, 3–4 hr) with nocodazole; after removal of the drug, cells divided and progressed in a highly synchronized fashion through the next cell cycle.
GeoPeels: deformation-based technique for exploration of geo-referenced networks

Spatial relations between geographical entities are typically visualized as a node-link diagram that is depicted over a geographical layout. The node-link diagram representation is well-suitable for tasks that require the analysis of the topology and properties of a spatial graph because it is more intuitive with respect to the matrix representation. However, the readability of node-link diagrams is, especially for large sized graphs, one of the issues studied in literature. In this paper we describe an interactive technique for virtual globes, called GeoPeels, which uses spatial deformations to reveal spatial information otherwise hidden behind the geographical layout. The deformed geometries are rendered around the globe, therefore, occupying space that otherwise would be unused. Additionally, our approach facilitates graph-related tasks by reducing the overall number of actions required to visualize and understand the spatial relations. The evaluation of our approach is based on the analysis of the graphical performance and on a comparison between virtual globes and 2D flat maps.
Content Delivery in Vehicular Ad Hoc Networks

Redes Ad hoc Veiculares (VANETs) estao se tornando uma realidade devido, em parte, ao interesse dos fabricantes de veiculos em prover novos tipos de servicos aos seus clientes. Como consequencia, as aplicacoes para esse tipo de rede estao surgindo com o objetivo de tornar o trânsito mais seguro, menos congestionado, mais informativo e prazeroso. Para isso, um dos principais requisitos de tais aplicacoes e a entrega de conteudo aos veiculos. No entanto, algumas caracteristicas especificas das VANETs, como topologia extremamente dinâmica, mudancas frequentes na densidade da rede e sua natureza de larga escala, fazem com que a tarefa de entrega de conteudo seja significativamente complexa. Normalmente, duas abordagens tem sido usadas para a entrega de conteudo em redes tradicionais: Redes de Entrega de Conteudo (CDN) e Redes Par-a-Par (P2P). Porem, as caracteristicas especificas das redes veiculares sugerem que essas abordagens, como originalmente propostas para a Internet, nao sao adequadas para esse tipo de rede, e ate o momento ainda nao esta claro como as redes veiculares podem se beneficiar pela utilizacao dos conceitos de CDN e P2P. Para abordar esse problema, o principal objetivo desta tese e investigar como os conceitos de CDN e P2P podem ser aplicados as VANETs, e propor solucoes adequadas a essas redes. Para alcancar esse objetivo, fizemos um estudo detalhado da literatura para entender como os conceitos de CDN e P2P vem sendo aplicados as VANETs. Em seguida, propusemos um modelo hibrido em que conceitos de CDN e P2P sao herdados e adaptados para VANETs. Para auxiliar os projetistas de aplicacoes, tambem definimos um arcabouco que engloba os principais componentes a serem implementados para o modelo proposto. Para concluir, com base em um estudo de caracterizacao de mobilidade realizado, tambem propusemos e avaliamos duas solucoes com diferentes demandas para demonstrar a eficiencia do modelo proposto para o desempenho das aplicacoes.
European Respiratory Society study on chronic obstructive pulmonary disease (EUROSCOP): hypothesis and design.

Chronic obstructive pulmonary disease (COPD) is a common disease in industrialised countries and responsible for a considerable morbidity and mortality. Cigarette smoking is the most important aetiological factor. The EUROSCOP trial aims at investigating the hypothesis that airway inflammation plays an important pathogenic role in the development of chronic obstructive airway disease in smokers. In cigarette smokers with poorly reversible airflow obstruction, the effect over 3 yrs of an inhaled glucocorticosteroid, budesonide 400 micrograms b.i. d. , on the decline of lung function, measured as postbronchodilator forced expiratory volume in one second (FEV1), will be compared with that of placebo. The trial has been designed to detect a difference in yearly decline of at least 30 ml.year-1. The study is a parallel group, randomised, double-blind, multicentre study. Patients will be recruited from 47 centres in 12 countries in Europe. It will start with a run-in consisting of two 3 month periods. During the first 3 months, the patients will be offered a smoking cessation programme. All patients who have not stopped smoking during this period will enter the second half of the run-in where compliance with the dosage regimen will be tested. After these two periods, patients will be randomised to receive either inhaled budesonide, 400 micrograms b.i. d. , or placebo for a period of 3 yrs.
Ultrastructural Analysis of Differentiation in Legionella pneumophila

ABSTRACT Legionella pneumophila is an adaptive pathogen that replicates in the intracellular environment of fundamentally divergent hosts (freshwater protozoa and mammalian cells) and is capable of surviving long periods of starvation in water when between hosts. Physiological adaptation to these quite diverse environments seems to be accompanied by morphological changes (Garduño et al., p. 82-85, in Marre et al., ed., Legionella, 2001) and conceivably involves developmental differentiation. In following the fine-structural pathway of L. pneumophila through both in vitro and in vivo growth cycles, we have now discovered that this bacterium displays an unprecedented number of morphological forms, as revealed in ultrathin sections and freeze-fracture replicas for transmission electron microscopy. Many of the forms were identified by the obvious ultrastructural properties of their cell envelope, which included changes in the relative opaqueness of membrane leaflets, vesiculation, and/or profuse invagination of the inner membrane. These changes were best documented with image analysis software to obtain intensity tracings of the envelope in cross sections. Also prominent were changes in the distribution of intramembranous particles (clearly revealed in replicas of freeze-fractured specimens) and the formation of cytoplasmic inclusions. Our results confirm that L. pneumophila is a highly pleomorphic bacterium and clarify some early observations suggesting sporogenic differentiation in L. pneumophila. Since morphological changes occurred in a conserved sequence within the growth cycle, our results also provide strong evidence for the existence of a developmental cycle in L. pneumophila that is likely accompanied by profound physiological alterations and stage-specific patterns of gene expression.
Soluble Conformers of Aβ and Tau Alter Selective Proteins Governing Axonal Transport

Despite the demonstration that amyloid-β (Aβ) can trigger increased tau phosphorylation and neurofibrillary tangle (NFT) formation in vivo, the molecular link associating Aβ and tau pathologies remains ill defined. Here, we observed that exposure of cultured primary neurons to Aβ trimers isolated from brain tissue of subjects with Alzheimer's disease led to a specific conformational change of tau detected by the antibody Alz50. A similar association was supported by postmortem human brain analyses. To study the role of Aβ trimers in vivo, we created a novel bigenic Tg-Aβ+Tau mouse line by crossing Tg2576 (Tg-Aβ) and rTg4510 (Tg-Tau) mice. Before neurodegeneration and amyloidosis, apparent Aβ trimers were increased by ∼2-fold in 3-month-old Tg-Aβ and Tg-Aβ+Tau mice compared with younger mice, whereas soluble monomeric Aβ levels were unchanged. Under these conditions, the expression of soluble Alz50-tau conformers rose by ∼2.2-fold in the forebrains of Tg-Aβ+Tau mice compared with nontransgenic littermates. In parallel, APP accumulated intracellularly, suggestive of a putative dysfunction of anterograde axonal transport. We found that the protein abundance of the kinesin-1 light chain (KLC1) was reduced selectively in vivo and in vitro when soluble Aβ trimers/Alz50-tau were present. Importantly, the reduction in KLC1 was prevented by the intraneuronal delivery of Alz50 antibodies. Collectively, our findings reveal that specific soluble conformers of Aβ and tau cooperatively disrupt axonal transport independently from plaques and tangles. Finally, these results suggest that not all endogenous Aβ oligomers trigger the same deleterious changes and that the role of each assembly should be considered separately. SIGNIFICANCE STATEMENT The mechanistic link between amyloid-β (Aβ) and tau, the two major proteins composing the neuropathological lesions detected in brain tissue of Alzheimer's disease subjects, remains unclear. Here, we report that the trimeric Aβ species induce a pathological modification of tau in cultured neurons and in bigenic mice expressing Aβ and human tau. This linkage was also observed in postmortem brain tissue from subjects with mild cognitive impairment, when Aβ trimers are abundant. Further, this modification of tau was associated with the intracellular accumulation of the precursor protein of Aβ, APP, as a result of the selective decrease in kinesin light chain 1 expression. Our findings suggest that Aβ trimers might cause axonal transport deficits in AD.
Pathogenesis of Type 1 and Type 2 Diabetes Mellitus in Sub-Saharan Africa: Implications for Transitional Populations

The increasing prevalence and incidence of diabetes and its long-term complications in sub-Saharan Africa (SSA) could have devastating human and economic toll if the trends remain unabated in the future. Approximately 90% or majority of patients with diabetes belongs to the adult onset, type 2 diabetes category while 10% have type 1 diabetes in SSA. However, because of the paucity of metabolic and clinical data, a clear understanding of the natural history of both diseases and the classification of diabetes subtypes has been hampered. Nevertheless, we have attempted to provide a concise review of the pathophysiology of both type 1 and type 2 diabetes as well as phenotypic and clinical variations in patients residing in SSA. The limited metabolic data, (albeit increasing), from high-risk and diabetic individuals in the SSA, have contributed significantly to the understanding of the pathogenetic mechanisms of diabetes and the variations in the presentation of the disease. Sub-Saharan African patients with type 1 diabetes have essentially absolute insulin deficiency. In addition, patients with type 2 diabetes in SSA region also manifest severe insulin deficiency with varying degrees of insulin resistance. Although the exact genetic markers of both diseases are unknown, we believe studies in patients of SSA origin who reside in diverse geographic environments (African diaspora) could potentially contribute to our understanding of the genetic and environmental mediators of both diseases. However, many intrinsic, individual and societal obstacles such as poor education and illiteracy, low socio-economic status and lack of access to health care make uncertain the translation of diabetes research in SSA. In this regard, effective management and/or prevention of diabetes in SSA individuals should adopt multidisciplinary approaches. Finally, innovative health care delivery and educational models will be needed to manage diabetes and its long-term complications in SSA.
Elastic password: A new mechanism for strengthening passwords using time delays between keystrokes

Text passwords were and still an easy, common, practical and reliable authentication method. To ensure the desired goal of access protection, passwords should be implemented carefully. This study proposes a new mechanism to strengthen passwords through introducing time gaps (delays) between some password characters during the sign-up process. During sign-in, users should not only enter their correct passwords, but also they must leave time delays in the correct position(s) as it was designated during the sign-up process. Any attempt to login using a real password without adding time delays in the correct position(s) will be rejected. Laboratory experiments were conducted to test the proposed mechanism. These experiments are based on known password but hidden delay position(s). The obtained results show that the False Acceptance Rate (FAR) was 11.33% and the False Rejection Rate (FRR) was 17.3%. These ratios could be improved when users became more familiar with the system.
A CK19CreERT knockin mouse line allows for conditional DNA recombination in epithelial cells in multiple endodermal organs

Cre/LoxP‐mediated DNA recombination allows for gene function and cell lineage analyses during embryonic development and tissue regeneration. Here, we describe the derivation of a K19CreERT mouse line in which the tamoxifen‐activable CreERT was knocked into the endogenous cytokeratin 19 locus. In the absence of tamoxifen, leaky Cre activity could be detected only in less than 1% of stomach and intestinal epithelial cells, but not in pancreatic or hepatic epithelial tissues. Tamoxifen administration in postnatal animals induced widespread DNA recombination in epithelial cells of pancreatic ducts, hepatic ducts, stomach, and intestine in a dose‐dependent manner. Significantly, we found that Cre activity could be induced in the putative gut stem/progenitor cells that sustained long‐term gut epithelial expression of a Cre reporter. This mouse line should therefore provide a valuable reagent for manipulating gene activity and for cell lineage marking in multiorgans during normal tissue homeostasis and regeneration. genesis 46:318–323, 2008. © 2008 Wiley‐Liss, Inc.
Severe hypoglycemia rates are not associated with HbA1c: a cross‐sectional analysis of 3 contemporary pediatric diabetes registry databases

To examine the association between glycated hemoglobin (HbA1c) and severe hypoglycemia rates in patients with type 1 diabetes receiving usual care, by analysing data from the US Type 1 Diabetes Exchange (T1DX), German/Austrian Diabetes Patienten Verlaufsdokumenation (DPV), and Western Australian Children Diabetes Database (WACDD) diabetes registries.
Serious games education for working life needs - a pilot study

Serious games possess huge market opportunities and offer possible solutions for various real-life challenges in different fields of businesses. Although the potential of serious games is well recognized, the educational and training possibilities in the field are scarce. Through cooperation and multiform learning solutions, the lack of education particularly around serious games could be filled in to answer the requirements of the future job descriptions. This paper presents results of student feedback (n=27) around a pilot study of a serious games course that bases on the survey of actual working life needs (company interviews) and was designed to bring closer the substance experts and the game development experts.
The neuroscience of recovery and rehabilitation: what have we learned from animal research?

OBJECTIVES To encourage rehabilitation specialists to develop a critical approach to the animal research literature that is relevant to human neurorehabilitation and to encourage clinicians to lend their perspectives to basic research. ATA SOURCES: Scientific publications cited in MEDLINE, PubMed, and PsychInfo, and professional presentations of leading neuroscience researchers. The focus was on current publications to 2001, with historical works included when appropriate. STUDY SELECTION Studies were selected based on their relevance to the objectives. DATA EXTRACTION Reviewed study methodology and findings and extracted key principles relevant to rehabilitation. DATA SYNTHESIS Many themes emerging from neuroscience research are relevant to human rehabilitation, including issues related to timing of intervention and recovery, and characteristics of nervous system plasticity. CONCLUSIONS Although animal research has many limitations, it provides a unique window on nervous system recovery and has generated important directions for future human research. Clinician involvement in basic animal research will improve the extent to which results are relevant to human rehabilitation and recovery.
Server Resource Dimensioning and Routing of Service Function Chain in NFV Network Architectures

The Network Function Virtualization NFV technology aims at virtualizing the network service with the execution of the single service components in Virtual Machines activated on Commercial-off-the-shelf COTS servers. Any service is represented by the Service Function Chain SFC that is a set of VNFs to be executed according to a given order. The running of VNFs needs the instantiation of VNF instances VNFI that in general are software components executed on Virtual Machines. In this paper we cope with the routing and resource dimensioning problem in NFV architectures. We formulate the optimization problem and due to its NP-hard complexity, heuristics are proposed for both cases of offline and online traffic demand. We show how the heuristics works correctly by guaranteeing a uniform occupancy of the server processing capacity and the network link bandwidth. A consolidation algorithm for the power consumption minimization is also proposed. The application of the consolidation algorithm allows for a high power consumption saving that however is to be paid with an increase in SFC blocking probability.
A low-overhead structure maintenance approach for building robust structured P2P systems

Structured peer-to-peer (P2P) systems have been recognized as an efficient approach to solve the resource discovery problem in large-scale dynamic distributed systems. The efficiency of structured P2P resource discovery approaches is attributed to their structured property. However, system dynamism caused by changes in the system membership, i.e., nodes that join or leave the system or simply fail, perturbs the structure of the system and endangers the expected correctness and efficiency of the resource discovery mechanism. In this paper we propose an event-oriented low-overhead approach to the maintenance of the structure of such systems in the face of node perturbations, by updating only those parts of the system state that are affected by perturbations, upon detection of a node membership change. This way, system robustness is improved too because system structure is kept up-to-date upon each perturbation. The proposed approach is general and can be applied to any structured P2P system. However, we suffice to show how it can be applied to the Chord system to demonstrate its applicability. We show experimentally that our proposed approach has less communication overhead than Chord and that it keeps the system up-to-date and consistent in its lifetime rather than in some periods as in Chord.
Possible therapeutic uses of Salvia triloba and Piper nigrum in Alzheimer's disease-induced rats.

This study aimed to investigate the role of Salvia triloba L. and Piper nigrum extracts in ameliorating neuroinflammatory insults characteristic of Alzheimer's disease (AD) in an experimentally induced rat model. Adult male Sprague-Dawley rats were classified into Group 1 (n=10): normal healthy animals serving as the negative control group; Group 2 (n=60): the AD-induced group. After AD induction, animals in the AD-induced group were divided randomly and equally into 6 subgroups. The first subgroup served as AD control; the second one, which served as positive control, was treated orally with the conventional therapy for AD (rivastigmine) at a dose of 0.3 mg/kg body weight (b.w.) daily for 3 months. The third and fourth subgroups were, respectively, treated orally with the S. triloba extract at a dose of 750 and 375 mg/kg b.w. daily for 3 months. The fifth and sixth subgroups were, respectively, treated orally with the P. nigrum extract at a dose of 187.5 and 93.75 mg/kg b.w. daily for 3 months. Levels of brain acetylcholine (Ach), serum and brain acetylcholinesterase (AchE) activity, C-reactive protein (CRP), total nuclear factor kappa-B (NF-κB), and monocyte chemoattractant protein-1 (MCP-1) were estimated. The results showed that administration of AlCl3 resulted in a significant elevation in the levels of AchE activity, CRP, NF-κB, and MCP-1 accompanied with a significant depletion in the Ach level. Treatment of AD rats with each of the selected medicinal plant extracts caused marked improvement in the measured biochemical parameters. In conclusion, S. triloba and P. nigrum methanolic extracts have potent anti-inflammatory effects against neuroinflammation characterizing AD.
Plasma Membrane Appearance of Phosphatidylethanolamine in Stimulated Macrophages

Mouse peritoneal macrophages were labeled with [1‐3H]ethanolamine, and the presence of radioactive [3H]phosphatidylethanolamine (PE) at the plasma membrane was monitored by reacting the cells with trinitrobenzene sulfonic acid (TNBS) under nonpenetrating conditions. Macrophages stimulated with either the calcium ionophore A23187 or zymosan demonstrated a larger proportion of radiolabeled PE in the plasma membrane than control, nonstimulated cells. In experiments in which macrophages were labeled with ethanolamine for increasing times, appearance of membrane 3[H]PE was stimulated as early as after 2 hr of labeling. Macrophages labeled for 24 hr, then stimulated and returned to fresh medium still reflected a higher amount of membrane 3[H]PE at 2 hr after the stimulation, suggesting stimulation results in long‐term alterations in plasma membrane lipids. Protease‐peptone‐elicited macrophages, which are not stimulated by zymosan or ionophore, did not exhibit an increase in membrane 3[H]PE upon stimulation. The size of the TNBS‐accessible radiolabeled PE pool increased proportionately with a second stimulation; however, a subsequent labeling of the cells with TNBS after brief warming increased the TNBS‐accessible pool in control cells only. As shown in previous studies, macrophage stimulation resulted in an increased incorporation of lipid precursors into phospholipid. The mass of plasma membrane Tnp‐PE relative to mass of PE was not increased in ionophore‐treated macrophages in contrast to a small (~22%) increase in zymosan‐treated cells. These results are suggestive of alterations in lipid synthesis in stimulated macrophages and possible long‐term changes in the structure and function of the plasma membrane of macrophages following stimulation.