Miracle-dz/UniFAR-FTUs huggingface dataset:
Toxicity of preserved and unpreserved antiglaucoma topical drugs in an in vitro model of conjunctival cells

Purpose. To compare the toxicity of a short-time application of timolol with benzalkonium chloride (timolol-BAC+) and unpreserved timolol (timolol-BAC-) in a human conjunctival cell line. Methods. Chang’s conjunctival cell line (ATCC CCL 20.2) was treated for 15min. with 0.1%, 0.25% or 0.4% timolol-BAC(+) or BAC(-) and then examined immediately or 24h later. Cell viability, chromatin condensation and free radicals production were studied by microplate cold light cytometry. Moreover, relative cell number was evaluated by crystal violet colorimetric test. The comparison was done with an oxidative stress model of cells treated with 0.001–0.000001% hydrogen peroxide (H 2 O 2) . In addition, cell size and the expression of an apoptotic marker Apo2.7 were evaluated by flow cytometry. Results. Timolol-BAC(+) induced a rapid decrease in cell viability ranging from 40% immediately after treatment to 85% 24h later. A small initial decrease in cell viability was also observed with all tested concentrations of timolol-BAC(-) but, 24h later, cell viability either tended to remain constant or cells completely recovered. Cell viability fell down after 24h exposure to 0.001% H 2 O 2 whereas it was not modified at lower concentrations. 24h after treatment with 0.25% timolol-BAC(+), the relative cell number was reduced by 55% whereas it did not vary after 0.25% timolol-BAC(-) treatment. Only timolol-BAC(+) induced chromatin condensation and cell size reduction. Moreover, cells treated with timolol-BAC(+) overexpressed the apoptotic marker Apo2.7. Both timolol-BAC(+) and BAC(-) induced reactive oxygen species (ROS) production which was significantly more important when 0.25% or 0.4% timolol-BAC(+) were applied. Only 0.001% and 0.0001% H 2 O 2 generated a significant free radicals production. Conclusion. In our model of conjunctival cells in vitro timolol-BAC(+) induced irreversible cytotoxic damage with some characteristics of apoptosis. The active compound of timolol-BAC(-) could be responsible for reactive oxygen species production and for cell viability variations. The role of oxidative stress in timolol-BAC(+)-induced toxicity seems not to be predominant. In vitro toxic effects of antiglaucoma drugs could, in part, explain some ocular surface disorders in long-term treated patients.
APP Transgenic Mice Tg2576 Accumulate Aβ Peptides That Are Distinct from the Chemically Modified and Insoluble Peptides Deposited in Alzheimer's Disease Senile Plaques†

The amyloid (Abeta) peptides generated in Hsiao's APP Tg2576 transgenic (Tg) mice are physically and chemically distinct from those characteristic of Alzheimer's disease (AD). Transgenic mouse Abeta peptides were purified using sequential size-exclusion and reverse-phase chromatographic systems and subjected to amino acid sequencing and mass spectrometry analyses. The mouse Abeta peptides lacked the extensive N-terminal degradations, posttranslational modifications, and cross-linkages abundant in the stable Abeta peptide deposits observed in AD. Truncated Abeta molecules appear to be generated in vivo by hydrolysis at multiple sites rather than by post-mortem C-terminal degradation. In contrast to AD amyloid cores, the Tg mice peptides were soluble in Tris-SDS-EDTA solutions, revealing both monomeric and SDS-stable oligomeric species of Abeta. In contrast to our report on Novartis Pharma APP23 Tg mice [Kuo et al. (2001) J. Biol. Chem. 276, 12991], which maintain high levels of soluble Abeta early on with later development of extensive vascular amyloid, Tg2576 mice exhibited an age-related elevation of soluble Abeta with relatively limited vascular amyloid deposition. The transgenic mouse levels of carboxy-terminal (CT) APP fragments were nearly 10-fold greater than those of human brains, and this condition may contribute to the unique pathology observed in these animals. Immunization of transgenic mice may act to prevent the pathological effects of betaAPP overproduction by binding CT molecules or halting their processing to toxic forms, in addition to having any effects on Abeta itself. Thus, differences in disease evolution and biochemistry must be considered when using transgenic animals to evaluate drugs or therapeutic interventions intended to reduce the Abeta burden in Alzheimer's disease.
Statistical performance of TV/HDTV traffic over broadband digital networks

Broadband digital networks are considered a promising communication support for the new generation of broadcasting services. In this paper, we examine the TV/HDTV statistical multiplexing gain (SMG) for two different source smoothing levels that are related to the video sampling frequency. The TV/HDTV arrival samples were generated from a modified version of the fractional Brownian motion (fBm) process. The analyzed TV sequences were encoded with the MPEG-2 and CCIR-TV Recommendation 723 coders. Our results have shown a SMG increasing when using the appropriate smoothing level and taking into account the image and delay requirements. These results demonstrate that broadband networks are an interesting transmission support for TV traffic and that video source smoothing usage can improve the network performance.
Neural network structures with constant weights to implement dis-jointly removed non-convex (DJRNC) decision regions: part a - properties, model, and simple case

This is a series of studies to discuss the partitioning capabilities of multi-layer perceptrons on dis-jointly removed non-convex (DJRNC) decision regions. There are two papers proposed in the series of studies including part A and part B. In part A, we propose a network structure to implement DJRNC decision regions using multi-layer perceptrons. In the proposed structure, all weights and the parameters of the activation functions are pre-determined when a DJRNC decision region is established. No constructive algorithm is needed for implementing the DJRNC decision regions and each weight determined by this paper is either 1 or -1. This makes the hardware implementations of the proposed network structures easy. Three cases are discussed in this paper including single, nested, and disconnected decision regions. The first case is shown in part A, and the rest of two are demonstrated in part B. We also provide three multi-layer perceptrons to implement the three decision regions and prove the implementation feasibilities of the proposed model.
Mathematical Programming Method Based on Chaos Anti-Control for the Solution of Forward Displacement of Parallel Robot Mechanisms

The pose of the moving platform in parallel robots is possible thanks to the strong coupling, but it consequently is very difficult to obtain its forward displacement. Different methods establishing forward displacement can obtain different numbers of variables and different solving speeds with nonlinear equations. The nonlinear equations with nine variables for forward displacement in the general 6-6 type parallel mechanism were created using the rotation transformation matrix R, translation vector P and the constraint conditions of the rod length. Given the problems of there being only one solution and sometimes no convergence when solving nonlinear equations with the Newton method and the quasi-Newton method, the Euler equation for free rotation in a rigid body was applied to a chaotic system by using chaos anti-control and chaotic sequences were produced. Combining the characteristics of the chaotic sequence with the mathematical programming method, a new mathematical programming method was put forward, which was based on chaos anti-control with the aim of solving all real solutions of nonlinear equations for forward displacement in the general 6-6 type parallel mechanism. The numerical example shows that the new method has some positive characteristics such as that it runs in the initial value range, it has fast convergence, it can find all the possible real solutions that be found out and it proves the correctness and validity of this method when compared with other methods.
Actualités sur les norovirus

Noroviruses belong to the Caliciviridae family. They are a major cause of sporadic cases and outbreaks of gastroenteritis in all age groups, and are responsible for a considerable disease burden in industrialized countries. Noroviruses are single-stranded RNA viruses, and show great genetic diversity making their detection difficult. Noroviruses can be divided into 5 genogroups, which themselves are subdivided into genotypes. Besides chance mutations that occur during viral replication, the great heterogeneity observed among noroviruses is also due to intra and inter-genotypic recombination events between strains. Some of these new variants or new recombinants are frequently associated with new epidemic waves of gastroenteritis. Finally, it is worth pointing out that the discovery of mechanisms involved in NoV infections through blood antigen-related receptors and cultivation of the first norovirus, a murine norovirus, are milestones in research on this virus. These advances open new promising avenues of research that will help to the understanding of the -pathogenicity of this important pathogen.
Centrosome and microtubule instability in aging Drosophila cells

Several cytoskeletal changes are associated with aging which includes alterations in muscle structure leading to muscular atrophy, and weakening of the microtubule network which affects cellular secretion and maintenance of cell shape. Weakening of the microtubule network during meiosis in aging oocytes can result in aneuploidy or trisomic zygotes with increasing maternal age. Imbalances of cytoskeletal organization can lead to disease such as Alzheimer's, muscular disorders, and cancer. Because many cytoskeletal diseases are related to age we investigated the effects of aging on microtubule organization in cell cultures of the Drosophila cell model system (Schneider S‐1 and Kc23 cell lines). This cell model is increasingly being used as an alternative system to mammalian cell cultures. Drosophila cells are amenable to genetic manipulations and can be used to identify and manipulate genes which are involved in the aging processes. Immunofluorescence, scanning, and transmission electron microscopy were employed for the analysis of microtubule organizing centers (centrosomes) and microtubules at various times after subculturing cells in fresh medium. Our results reveal that centrosomes and the microtubule network becomes significantly affected in aging cells after 5 days of subculture. At 5–14 days of subculture, 1% abnormal out of 3% mitoses were noted which were clearly distinguishable from freshly subcultured control cells in which 3% of cells undergo normal mitosis with bipolar configurations. Microtubules are also affected in the midbody during cell division. The midbody in aging cells becomes up to 10 times longer when compared with midbodies in freshly subcultured cells. During interphase, microtubules are often disrupted and disorganized, which may indicate improper function related to transport of cell organelles along microtubules. These results are likely to help explain some cytoskeletal disorders and diseases related to aging. J. Cell. Biochem. 74:229–241, 1999. © 1999 Wiley‐Liss, Inc.
PERFORMANCE EVALUATION OF REGION-GROWING BASED SEGMENTATION ALGORITHMS FOR SEGMENTING THE AORTA

Region-growing based image segmentation techniques, available for medical images, are reviewed in this paper. In digital image processing, segmentation of humans' organs from medical images is a very challenging task. A number of medical image segmentation techniques have been proposed, but there is no standard automatic algorithm that can generally be used to segment a real 3D image obtained in daily routine by the clinicians. Our criteria for the evaluation of different region-growing based segmentation algorithms are: ease of use, noise vulnerability, effectiveness, need of manual initialization, efficiency, computational complexity, need of training, information used, and noise vulnerability. We test the common region-growing algorithms on a set of abdominal MRI scans for the aorta segmentation. The evaluation results of the segmentation algorithms show that region-growing techniques can be a better choice for segmenting an object of interest from medical images .
Interferon Induces NF-κB-inducing Kinase/Tumor Necrosis Factor Receptor-associated Factor-dependent NF-κB Activation to Promote Cell Survival*

Type I interferons (IFNs) play critical roles in the host defense by modulating the expression of various genes via the IFN-dependent activation of signal transducers and activators of transcription and NF-κB (nuclear factor kappa B) transcription factors. Previous studies established that IFNα/β activates NF-κB to promote cell survival through a phosphatidylinositol 3-kinase (PI3K)/Akt pathway, which involves serine phosphorylation and degradation of IκBα. We now describe a second pathway by which IFNs activate NF-κB that is independent of IκB degradation. This pathway involves NF-κB-inducing kinase (NIK) and the tumor necrosis factor receptor-associated factor-2 (TRAF2) and results in IFNα/β-induced processing of the p100/NF-κB2 precursor into p52. IFNα/β stimulates NF-κB DNA binding and NF-κB-dependent transcription. Whereas expression of NIK and TRAF2 constructs causes NF-κB activation, expression of dominant negative NIK and TRAF2 constructs blocks IFN-promoted NF-κB activation and IFN-stimulated κB-dependent transcription and IFNα/β-induced processing of the p100/NF-κB2 precursor into p52. In contrast, PI3K does not mediate IFNα/β-induced p100 processing, although PI3K is involved in the pathway resulting in IκBα degradation. Moreover, whereas IFN promotes cell survival in lymphoblastoid cells, expression of dominant negative NIK and TRAF2 constructs enhances IFN-induced apoptosis. Our results for the first time place NIK and TRAF2, previously shown to function in TNF signaling, within the IFN signal transduction pathway. Thus, IFN induces NF-κB activation to mediate IFN-dependent cell survival signals through a “canonical” pathway of IκBα proteolysis mediated by PI3K/Akt and a “noncanonical” pathway of p100 processing mediated by NIK/TRAF.
Electromagnetics for High-Speed Analog and Digital Communication Circuits: Acknowledgments

1. Introduction 2. Capacitance 3. Resistance 4. Ampere, Faraday and Maxwell 5. Inductance 6. Passive deivce design and layout 7. Resonance and impedance matching 8. Small-signal high-speed amplifiers 9. Transmission lines 10. Transformers 11. Distributed circuits 12. High-speed switching circuits 13. Magnetic and electrical coupling and isolation 14. Electromagnetic propagation and radiation 15. Microwave circuits.
COLLABORATIVE LEARNING IN A MOOC ENVIRONMENT

In recent years, Massive Open Online Courses (MOOCs) have become a phenomenon presenting the prospect of free high class education to anyone by offering the possibility to teach Thousands of participants simultaneously. The word of a disruptive technology–rendering universities obsolete– rumbled through the media. By now, as the dust has settled, a more conservative pattern is emerging: MOOCs are a highly effective and valuable tool in the context of lifelong learning. The format is facing a couple of challenges, however. Next to high drop out rates, the pedagogical concept is often criticized for its behaviorist background and frontal teaching styles. The MOOC format itself, originates in the connectivist teaching paradigm, which propagates a very different style of teaching and learning. In this tradition, learning is experienced as the collaborative act of creating a network of learners and digital artefacts, each focussing on certain aspects of a topic. The main problem here is that this approach is limited in its scalability; particularly in its outreach to an audience that is less committed and passionate or just limited in its access to resources, such as time and personal energy. The paper at hand examines the current situation in terms of collaboration features on various MOOC platforms and explores options to foster collaboration amongst participants in this context.
Antiproliferative Activity, Antioxidant Capacity and Tannin Content in Plants of Semi-Arid Northeastern Brazil

The objective of this study was to evaluate antiproliferative activity, antioxidant capacity and tannin content in plants from semi-arid northeastern Brazil (Caatinga). For this study, we selected 14 species and we assayed the methanol extracts for antiproliferative activity against the HEp-2 (laryngeal cancer) and NCI-H292 (lung cancer) cell lines using the (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazole) (MTT) method. In addition, the antioxidant activity was evaluated with the DPPH (2,2-diphenyl-2-picrylhydrazyl) assay, and the tannin content was determined by the radial diffusion method. Plants with better antioxidant activity (expressed in a dose able to decrease the initial DPPH concentration by 50%, or IC50) and with higher levels of tannins were: Poincianella pyramidalis (42.95 ± 1.77 µg/mL IC50 and 8.17 ± 0.64 tannin content), Jatropha mollissima (54.09 ± 4.36µg/mL IC50 and 2.35 ± 0.08 tannin content) and Anadenanthera colubrina (73.24 ± 1.47 µg/mL IC50 and 4.41 ± 0.47 tannin content). Plants with enhanced antiproliferative activity (% living cells) were Annona muricata (24.94 ± 0.74 in NCI-H292), Lantana camara (25.8 ± 0.19 in NCI-H292), Handroanthus impetiginosus (41.8 ± 0.47 in NCI-H292) and Mentzelia aspera (45.61 ± 1.94 in HEp-2). For species with better antioxidant and antiproliferative activities, we suggest future in vitro and in vivo comparative studies with other pharmacological models, and to start a process of purification and identification of the possible molecule(s) responsible for the observed pharmacological activity. We believe that the flora of Brazilian semi-arid areas can be a valuable source of plants rich in tannins, cytotoxic compounds and antioxidant agents.
Traitements des accidents vasculaires cérébraux en phase aiguë et prévention secondaire

Les accidents vasculaires cerebraux (AVC) posent un probleme majeur de sante publique par leur frequence, leur mortalite, les handicaps physiques et cognitifs residuels, le risque de recidive ischemique cerebrale ou myocardique et leur cout. Les traitements en phase aigue ont pour objectif de reduire le risque de deces ou de dependance lorsque l’AVC est installe, alors que la prevention secondaire a pour objectif de reduire le risque d’un nouvel evenement vasculaire (cerebral ou myocardique). Dans cette revue, nous ne traiterons pas des hemorragies meningees sous arachnoidiennes.
Sexual size dimorphism in parasitic oxyurid nematodes

Abstract As in many invertebrates, female oxyurids are larger than male. Sexual size dimorphism (SSD) of oxyurid nematodes (the hosts of which are both invertebrate and vertebrate), is investigated regarding body size of both host and parasite. SSD of parasites appeared to be weakly, but not significantly, correlated with invertebrate and vertebrate host body size. However, this study reveals a different pattern for SSD with respect to either type of host. SSD does not increase in tandem with body size in vertebrate parasites either at the level of species or genus. SSD is much more pronounced in Syphaciidae than in Heteroxynematidae, two families of vertebrate parasites exhibiting different modes of transmission (members of the Syphaciidae are transmitted through perianal contamination). SSD is investigated in one monophyletic group of parasites of primates, for which a phylogeny is known. Independent comparisons method is used and we find that the body size of female parasite is strongly correlated with that of the male. The hypoallometry (slope
Reactivation of p53 mutants by p53 reactivation and induction of massive apoptosis in thyroid cancer cells

Most undifferentiated thyroid carcinomas express p53 mutants and thereafter, are very resistant to chemotherapy. p53 reactivation and induction of massive apoptosis (Prima‐1) is a compound restoring the tumor‐suppressor activity of p53 mutants. We tested the effect of Prima‐1 in thyroid cancer cells harboring p53 mutations. Increasing doses of Prima‐1 reduced viability of thyroid cancer cells at a variable extent (range 20–80%). Prima‐1 up‐regulated p53 target genes (p21WAF1, BCL2‐associated X protein (Bax), and murine double minute 2 (MDM2)), in BC‐PAP and Hth‐74 cells (expressing D259Y/K286E and K286E p53 mutants) but had no effect in SW1736 (p53 null) and TPC‐1 (expressing wild‐type p53) thyroid cancer cells. Prima‐1 also increased the cytotoxic effects of either doxorubicin or cisplatin in thyroid cancer cells, including the chemo‐resistant 8305C, Hth‐74 and BC‐PAP cells. Moreover, real‐time PCR and Western blot indicated that Prima‐1 increases the mRNA of thyroid‐specific differentiation markers in thyroid cancer cells. Fluorescence‐activated cell sorting analysis revealed that Prima‐1 effect on thyroid cancer cells occurs via the enhancement of both cell cycle arrest and apoptosis. Small interfering RNA experiments indicated that Prima‐1 effect is mediated by p53 mutants but not by the p53 paralog p73. Moreover, in C‐643 thyroid cancer cells, forced to ectopically express wild‐type p53, Prima‐1 prevented the dominant negative effect of double K248Q/K286E p53 mutant. Finally, co‐IP experiments indicated that in Hth‐74 cells Prima‐1 prevents the ability of p53 mutants to sequestrate the p53 paralog TAp73. These in vitro studies imply that p53 mutant reactivation by small compounds may become a novel anticancer therapy in undifferentiated thyroid carcinomas.
The Pertussis Toxin S1 Subunit Is a Thermally Unstable Protein Susceptible to Degradation by the 20S Proteasome

Pertussis toxin (PT) is an AB-type protein toxin that consists of a catalytic A subunit (PT S1) and an oligomeric, cell-binding B subunit. It belongs to a subset of AB toxins that move from the cell surface to the endoplasmic reticulum (ER) before A chain passage into the cytosol. Toxin translocation is thought to involve A chain unfolding in the ER and the quality control mechanism of ER-associated degradation (ERAD). The absence of lysine residues in PT S1 may allow the translocated toxin to avoid ubiquitin-dependent degradation by the 26S proteasome, which is the usual fate of exported ERAD substrates. As the conformation of PT S1 appears to play an important role in toxin translocation, we used biophysical and biochemical methods to examine the structural properties of PT S1. Our in vitro studies found that the isolated PT S1 subunit is a thermally unstable protein that can be degraded in a ubiquitin-independent fashion by the core 20S proteasome. The thermal denaturation of PT S1 was inhibited by its interaction with NAD, a donor molecule used by PT S1 for the ADP-ribosylation of target G proteins. These observations support a model of intoxication in which toxin translocation, degradation, and activity are all influenced by the heat-labile nature of the isolated toxin A chain.