79 research outputs found
LSF small molecule inhibitors phenocopy LSF-targeted siRNAs causing mitotic defects and senescence in cancer cells
No full textThe oncogene LSF has been proposed as a novel target with therapeutic potential for multiple cancers. LSF overexpression correlates with poor prognosis for both liver and colorectal cancers, for which there are currently limited therapeutic treatment options. In particular, molecularly targeted therapies for hepatocellular carcinoma targeting cellular receptors and kinases have yielded disappointing clinical results, providing an urgency for targeting distinct mechanisms. LSF small molecule inhibitors, Factor Quinolinone Inhibitors (FQIs), have exhibited robust anti-tumor activity in multiple pre-clinical models of hepatocellular carcinoma, with no observable toxicity. To understand how the inhibitors impact cancer cell proliferation, we characterized the cellular phenotypes that result from loss of LSF activity. Phenotypically, inhibition of LSF activity induced a mitotic delay with condensed, but unaligned, chromosomes. This mitotic disruption resulted in improper cellular division leading to multiple outcomes: multi-nucleation, apoptosis, and cellular senescence. The cellular phenotypes observed upon FQI1 treatment were due specifically to the loss of LSF activity, as siRNA specifically targeting LSF produced nearly identical phenotypes. Taken together, these findings confirm that LSF is a promising therapeutic target for cancer treatment.First author draf
Transcription factor LSF facilitiates lysine methylation of α-tubulin by microtubule-associated SET8
No full textMicrotubules are critical for mitosis, cell motility, and protein and organelle transport, and are a validated target for anticancer drugs. However, tubulin regulation and recruitment in these cellular processes is less understood. Post-translational modifications of tubulin are proposed to regulate microtubule functions and dynamics. Although many such modifications have been investigated, tubulin methylations and enzymes responsible for methylation have only recently begun to be described. Here we report that N-lysine methyl transferase KMT5A (SET8/PR-Set7), which methylates histone H4K20, also methylates α-tubulin. Furthermore, the transcription factor LSF binds both tubulin and SET8, and enhances α-tubulin methylation in vitro, countered by FQI1, a specific small molecule inhibitor of LSF. Thus, the three proteins SET8, LSF, and tubulin, all essential for mitotic progression, interact with each other. Overall, these results point to dual functions for both SET8 and LSF not only in chromatin regulation, but also for cytoskeletal modification.First author draf
Experimental study of load-bearing LSF wall panels made of built-up CFS channel studs at ambient and elevated temperatures
No full textLight gauge steel framed (LSF) walls have been increasingly used for low-rise building structures. New applications of LSF walls, such as load-bearing walls in mid-rise buildings, have required more solutions for improving their compression ca- pacity and fire resistance level (FRL). As a simple solution, built-up cold-formed steel (CFS) sections, including back-to- back channels (BC) and nested/boxed channels (NC), have been more popularly used to replace conventional single chan- nel sections for the studs of LSF walls. To improve the knowledge and understanding of LSF walls made of built-up CFS studs, this study focuses on the structural and fire behaviours of LSF wall panels made of either BC or NC studs screwed- connected to tracks at their ends and lined with gypsum plasterboards on both sides. Here, a series of ambient-temperature compression tests and two full-scaled fire tests on these types of wall panels were conducted. The test results revealed good knowledge and understanding of LSF wall panels made of either BC and NC studs in normal and fire conditions. Based on the test results, a simple and conservative design method for predicting the compression capacity of LSF walls made of either BC or NC studs was proposed. The discussion on the FRL of LSF walls made of either BC or NC studs was also included in this study.The authors wish to thank QUT, Australian Research Coun- cil (Grant Number LP170100951) and National Association of Steel Framed Housing (NASH) for providing financial sup- port, research facilities and test materials, and Banyo Labor- atory Technical staff for their assistance during the tests. They also appreciate the valuable technical guidance and support provided by NASH Executive Director Ken Watson, and NASH Standards Committee members to this research study. The first author appreciates Building 4.0 CRC for providing top-up scholarship, and the helps of Dr. Anthony Deloge Ariyanayagam, PhD researchers Mithum Peiris and Jashnav Pancheti, and undergraduate student Canh Long Nguyen from QUT in relation to full-scaled fire tests
Lisofylline protects β-cells from PIC-induced apoptosis.
No full text<p>(A) IL-12 p40 and (B) IL-12 p35 gene expression in PIC-treated βTC-3 cells without or with 20μM Lisofylline (LSF). (C) PIC-induced caspase-3 activation in the absence or presence of 20μM LSF or 50μM c47 in βTC-3 cells. Graph shows pro-caspase-3 cleavage relative fluorescent units (RFU). (D) Apoptosis was measured in PIC-treated βTC-3 cells without or with 20μM LSF or 50μM c47. Cells were examined microscopically following labeling with the viability dye, YO-PRO-1 (green). Representative images are shown for untreated (Ctl), PIC-treated, PIC with 50μM c47, or PIC with 20μM LSF respectively. (E) Graph shows quantified apoptotic index. ** <i>p</i> < 0.01, *** <i>p</i> < 0.001 relative to ctl, ## <i>p</i> < 0.01 relative to PIC and n ≥ 3.</p
Post-Processing of Topology Optimized Results: A method for retrieving smooth and crisp geometries
No full textStructural design optimization is the process of obtaining an optimized structure while satisfying a set of criteria. The process can be divided into three stages: topology optimization (stage one), geometry extraction (stage two) and shape optimization (stage three). The last two stages are regarded to be the post-processor of topology optimized results and this MSc. Thesis proposes a new method for this part. At stage one, topology optimized results show unwanted features, namely jagged boundaries (i.e. poor smoothness) and intermediate densities (i.e. poor crispness). The post-processor should overcome these unwanted properties.During post-processing the geometry is described implicitly by a Level Set Function (LSF). The zero-level contour of the LSF describes the actual geometry. The LSF is constructed by summing a set of Radial Basis Functions (RBFs) each multiplied with a weight, resulting in a smooth summation. At stage two, a geometry is extracted by setting up and solving a set of equations linking the RBFs to the densities obtained at stage one.At stage three, a shape optimization is done to compensate the loss of structural performance, which resulted from translating the densities to an LSF at stage two. The geometry described by the LSF does not match the mesh created for stage one. A fictitious domain method called the Finite Cell Method (FCM) is used to perform a structural analysis on the non-matching mesh. A sensitivity analysis is done to provide gradient information to the gradient-based optimizer, the Method of Moving Asymptotes (MMA). Controlling the slope of the LSF is needed to make sure the sensitivities do not become zero throughout the domain. The maximum possible slope of the LSF can be fixed by setting a bound on the weights of the RBFs. Furthermore, intermediate densities are penalized such that these provide relatively low stiffness compared to its material use.Several case studies are done using the proposed method. The post-processor: (1) improves the smoothness due to the use of the smooth LSF, (2) decreases the amount of intermediate densities by an average factor of 5.5 and (3) achieves an average 10\% improve in performance between stage two and three. The computation time is strongly problem dependent, test cases are either: slower, equally fast or faster than the topology optimization of stage one
Developing a grid computing system for commercial-off-the-shelf simulation packages
No full textToday simulation is becoming an increasingly
pervasive technology across major business
sectors. Advances in COTS Simulation Packages
and Commercial Simulation Software have made
it easier for users to build models, often of large complex processes. These two factors combined are to be welcomed and when used correctly can be of great benefit to organisations that make use of the technology. However, it is also the case
that users hungry for answers do not always have the time, or possibly the patience, to wait for results from multiple replications and multiple experiments as standard simulation practice would demand. There is therefore a need to support this advance in the use of simulation within today’s business with improved computing technology. Grid computing has been put forward as a potential commercial solution to this requirement. To this end, Saker Solutions and the Distributed Systems Research Group at Brunel University have developed a dedicated Grid Computing System (SakerGrid) to support the deployment of simulation models across a desktop grid of PCs. The paper identifies route taken to solve this challenging issue and suggests where the future may lie for this exciting integration of two effective but underused technologies
Schéma de la communication et LSF (enregistrement 2)
No full textConférence -débats avec Rachild Benelhocine dans la cadre de la commémoration du Bicentenaie de la création de l'INJS de Paris. Fin de la conférence donnée par Rachild Benelhocine sur une relecture structurale et historique de la communication en LSF chez les sourds en regard du schéma de la communication de Roman Jakobson suivi du débat.00:00:00 - 00:01:08 fin de la conférence de Rachild Benelhocine (voix Corinne Gache) 00:01:13 - 00:03:22 Remarques de Jean Rouvière (voix Corinne Gache) 00:03:32 - 00:05:12 Remarques de Françoise Masson (voix Corinne Gache) 00:05:26 - 00:06:44 Questions du Stéphane Faustinelli (Corinne Gache) 00:06:45 - 00:06:48 Réponse de Rachild Benelhocine (voix Corinne Gache) 00:06:50 - 00:09:54 Questions de Saliha Heouaine (voix Corinne Gache) 00:09:54 - 00:13:20 Réponses de Rachild Benelhocine (voix Corinne Gache) 00:13:25 - 00:16:03 Remarques de Jean Winckel (voix Corinne Gache) 00:16:08 - 00:23:08 Remarques de Guy Bouchauveau (voix Corinne Gache) 00:23:13 - 00:25:30 Remarques de Jean Bergeron (voix Corinne Gache) 00:25:31 - 00:32:07 Questions de Jean l'Henaff et réponses de Rachild Benelhocine (voix Corinne Gache) 00:32:10 - 00:33:30 Question de Michel Leman (voix Corinne Gache) 00:33:31 - 00:35:36 Remarques conclusives d'Alexis Karacostas (Corinne Gache) 00:35:36 - 00:36:49 Informations de Bruno Moncelle (voix Corinne Gache
Calcite dissolution behaviour during low salinity water flooding in carbonate rock
No full textLow salinity water flooding (LSF) has been proved to be a promising enhanced oil recovery method for sandstone reservoirs. The efficiency of LSF in carbonate reservoirs has not been proven completely yet, because there are still uncertainties about the LSF recovery mechanism in carbonate. From experimental studies, it was shown that wettability alteration, due to salinity reduction, is able to mobilize the remaining oil. Some studies attributed the wettability alteration by LSF to Calcite dissolution. Furthermore, Calcite dissolution can influence the salinity and pH of injected brines, and hence the oil recovery. However, there is a lack of experimental data on the Calcite dissolution effect of LSF in carbonate rock. The objective of this experimental study was to get a better understanding of the Calcite dissolution behaviour and how it might affect the oil recovery. Bulk and coreflood experiments have been performed; the experimental data was history matched with the use of PHREEQC. Calcite dissolution decreased with decreasing PCO2 and increased with decreasing pH and increasing NaCl salinity from 500-2000PPM. Increasing the injection rate reduced the interaction time and therefore Calcite dissolution did not reach equilibrium in coreflood at high rates. Calcite dissolution from chalk matched with the Calcite dissolution from pure Calcite, while Calcium concentration in effluent from limestone was higher. The two-phase coreflood experiment confirmed that Calcite dissolution occurs as well if oil is present in the porous media, but showed lower values than in single-phase coreflood experiment. pH increased from 5-6 to 9.5 due to Calcite dissolution, which might have an effect on the rock and oil surface charges, and hence oil recovery improvement. The effluent of the two-phase coreflood showed that an emulsion was formed, which suggested formation of in-situ surfactants. From CT scans, micro-CT scans and material mass balance calculations an increase in porosity around 1 % was observed. The increase in the total dissolved species due to Calcite dissolution was not significant, which will not harm LSF effect.Petroleum EngineeringGeoscience & EngineeringCivil Engineering and Geoscience
Unified First-Principles Study of Gilbert Damping, Spin-Flip Diffusion, and Resistivity in Transition Metal Alloys
No full textUsing a formulation of first-principles scattering theory that includes disorder and spin-orbit coupling on an equal footing, we calculate the resistivity ?, spin-flip diffusion length lsf, and Gilbert damping parameter ? for Ni1-xFex substitutional alloys as a function of x. For the technologically important Ni80Fe20 alloy, Permalloy, we calculate values of ?=3.5±0.15?????cm, lsf=5.5±0.3??nm, and ?=0.0046±0.0001 compared to experimental low-temperature values in the range 4.2–4.8?????cm for ?, 5.0–6.0 nm for lsf, and 0.004–0.013 for ?, indicating that the theoretical formalism captures the most important contributions to these parameters.QN/Quantum NanoscienceApplied Science
L’application de la Loi sur les services en français (LSF) de l’Ontario aux services de santé : la problématique des Réseaux locaux d’intégration des soins de santé (RLISS)
No full textDepuis quelques années, le Commissaire aux services en français attire l’attention du public sur le fait que le gouvernement provincial semble être d’avis que la Loi sur les services en français (LSF) de l’Ontario ne s’applique pas à la grande majorité des services de soins de santé financés par l’État, au motif qu’ils sont principalement offerts par des entités non gouvernementales. Plus précisément, le gouvernement a apparemment conclu que la LSF ne s’applique pas aux prestataires de soins médicaux financés par les Réseaux locaux d’intégration des soins de santé (RLISS). Puisque ces derniers ne prodiguent pas eux-mêmes de tels services, les entités qu’ils financent n’opèrent donc pas « pour leur compte », au sens de cette Loi. Or, puisque la majorité du financement du système de santé public est octroyé par l’entremise des RLISS, il s’agirait là d’une lacune très importante dans l’armature des droits linguistiques du public ontarien. Et, bien que la province ait déclenché un important processus de réforme en 2019 qui cherche à modifier, voire même éliminer les RLISS, on doit donc s’attendre à ce que le gouvernement adopte la même position en ce qui concerne l’application de la LSF qu’auparavant. Le présent article a pour but d’étudier le bien-fondé de cette hypothèse. Au final, l’auteur conclut qu’elle doit être rejetée. La LSF, à titre de loi quasi constitutionnelle ayant pour objet de protéger des droits fondamentaux, s’applique à toute entité non gouvernementale qui prodigue un service public dans le cadre d’un programme ou d’une politique gouvernementale déterminée, ce qui inclut les fournisseurs de soins de santé financés par les RLISS ou par la nouvelle entité qui les remplacera. L’analyse de cette question que propose l’auteur est pertinente non seulement quant à la LSF, mais également à toute loi relative aux droits linguistiques, dont la Loi sur les langues officielles du Canada. Elle intéressera aussi les chercheurs en droits de la personne et en droit administratif.Over the last few years, the French Language Services Commissioner of Ontario has been drawing attention to the fact that the provincial government appears to take the view that the French Language Services Act (FLSA) does not apply to the vast majority of health care services funded by the State, on the grounds that they are primarily offered by non-governmental entities. More specifically, the government has apparently concluded that the FLSA does not apply to health care providers funded by Local Health Integration Networks (LHINs) because the latter do not themselves provide any services, meaning that the entities they fund are not operating “on their behalf” within the meaning of the Act. Given that the majority of funding for the public health care system is funnelled through LHINs, this would constitute a very significant gap in the province’s framework of language rights. And, even though the province has set in motion a major set of reforms aiming to alter or even eliminate LHINs, we can expect the government to maintain its position with respect to the application of the FLSA. This article therefore aims to test the validity of the Province’s legal theory. In the final analysis, the author concludes that the Province is mistaken. The FLSA, as a quasi-constitutional law whose purpose is to protect fundamental rights, applies to non-governmental entities that provide public services in the context of a determined governmental policy or program, which includes health care providers funded by LHINs or by the new entity that will replace them. The analysis offered here is relevant not only to the FLSA, but also to any language rights legislation, including the federal Official Languages Act. It will also be of interest to those working in the areas of human rights and administrative law
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