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Dual inhibition of sirtuins 1 and 2:reprogramming metabolic energy dynamics in chronicmyeloid leukemia as an immunogenic anticancer strategy

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Cancer Communications 2024年第8期44卷 921-925页

作者： Michael Schnekenburger Anne Lorant Sruthi Reddy Gajulapalli Ridhika Rajora Jin-Young Lee Aloran Mazumder Haeun Yang Christo Christov Hyoung Jin Kang Bernard Pirotte Marc Diederich Laboratoire de Biologie Moleculaire et Cellulaire du Cancer LuxembourgLuxembourg Research Institute of Pharmaceutical Sciences&Natural Products Research Institute College of PharmacySeoul National UniversitySeoulRepublic of Korea Faculte de Medecine Universite de LorraineVandoeuvre-les-NancyFrance Department of Pediatrics Seoul National University College of MedicineSeoul National University Cancer Research InstituteSeoul National University Children’s HospitalSeoulRepublic of Korea Laboratory of Medicinal Chemistry Center for Interdisciplinary Research on Medicines(CIRM)University of LiegeLiegeBelgium

Chronicmyeloid leukemia(CML)is a lethal hematopoietic malignancy with a global incidence primarily attributed to the breakpoint cluster region-Abelson(BCR-ABL1)fusion oncogene in over 95%of *** introduction of tyrosine kinase inhibitors(TKIs)has revolutionized CML management;however,a subset of patients encounters challenges such as resistance and relapse,hindering the achievement of complete *** these challenges in CML also requires addressing persistent leukemia stem cells(LSCs)with inherent resistance *** regulators of LSC metabolism,proliferation,and survival,as well as genetic and epigenetic alterations,provide potential targets[1].

关键词： metabolism myeloid alterations

XDEM multi-physics and multi-scale simulation technology: Review of DEM-CFD coupling, methodology and engineering applications

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Particuology 2019年第3期17卷 176-193页

作者： Bernhard Peters Maryam Baniasadi Mehdi Baniasadi Xavier Besseron Alvaro Estupinan Donoso Mohammad Mohseni Gabriele Pozzetti Universite du luxembourg 6. rue Coudenhove-Kalergi L-1359 Luxembourg

The extended discrete element method (XDEM) multi-physics and multi-scale simulation platform is being developed at the Institute of Computational Engineering, the University of luxembourg. The platform is an advanced multi-physics simulation technology that combines flexibility and versatility to establish the next generation of multi-physics and multi-scale simulation tools. For this purpose, the simulation framework relies on coupling various predictive tools based on an Eulerian and Lagrangian approach. The Euleria n approach represents the wide field of con tinuum models;the Lagra ngian approach is perfect for characterising discrete phases. Continuum models thus include classical simulation tools, such as computational fluid dynamics simulation and finite element analysis, while an extended configuration of the classical discrete element method addresses the discrete (e.g., particulate) phase. Apart from predicting the trajectories of in dividual particles, XDEM-suite extends the application of the XDEM to estimating the thermodynamic state of each particle using advanced and optimised algorithms. The thermodynamic state may include temperature and species distributions due to chemical reaction and external heat sources. Hence, coupling these extended features with either computational fluid dynamics simulation or finite element analysis opens a wide range of applications as diverse as pharmaceuticals, agriculture, food processing, mining, construction and agricultural machinery, metals manufacturing, energy production and systems biology.

关键词： Multi-phase modelling Coupled computational fluid dynamics-discrete element method

Is serine racemase(SRR) a second hit target for LRRK2-G2019S induced Parkinson's disease?

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Neural Regeneration Research 2021年第3期16卷 498-499页

作者： Sarah Louise Nickels Jens Christian Schwamborn luxembourg Centre for Systems Biomedicine(LCSB) University of LuxembourgBelvauxLuxembourg Riken Institute for Medical Sciences(IMS) KanagawaJapan

To date,at least 7 million people are suffering from Parkinson's disease(PD)worldwide,which is the second most prevalent,age-associated,and progressive neurodegenerative disorder(Tysnes and Storstein,2017).Given the accelerated global pace of aging,it becomes of fundamental importance that we start understanding the origins of neurodegeneration in order to develop effective disease modifying *** PD patients suffer from a combination of motor and nonmotor disabilities.

关键词： second patients suffering

On Locating Malicious Code in Piggybacked Android Apps

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Journal of Computer Science & Technology 2017年第6期32卷 1108-1124页

作者： Li Li Daoyuan Li Tegawende F. Bissyande Jacques Klein Haipeng Cai David Lo Yves Le Traon Interdisciplinary Centre for Security Reliability and Trust University of Luxembourg Luxembourg 2721 Luxembourg School of Electrical Engineering and Computer Science Washington State University Washington WA 99163 U.S.A. School of Information Systems Singapore Management University Singapore 178902 Singapore

To devise efficient approaches and tools for detecting malicious packages in the Android ecosystem, researchers are increasingly required to have a deep understanding of malware. There is thus a need to provide a framework for dissecting malware and locating malicious program fragments within app code in order to build a comprehensive dataset of malicious samples. Towards addressing this need, we propose in this work a tool-based approach called HookRanker, which provides ranked lists of potentially malicious packages based on the way malware behaviour code is triggered. With experiments on a ground truth of piggybacked apps, we are able to automatically locate the malicious packages from piggybacked Android apps with an accuracy@5 of 83.6% for such packages that are triggered through method invocations and an accuracy@5 of 82.2% for such packages that are triggered independently.

关键词： Android piggybacked app malicious code HookRanker

IGS polar motion measurement accuracy

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Geodesy and Geodynamics 2017年第6期8卷 413-420页

作者： Jim Ray Paul Rebischung Jake Griffiths National Geodetic Survey Silver Spring MD USA IGN LAREG University Paris Diderot Sorbonne Paris Cite France Naval Research Laboratory Washington DC USA

We elaborate an error budget for the long-term accuracy of IGS（International Global Navigation Satellite System Service） polar motion estimates, concluding that it is probably about 25-30 μas（1-sigma）overall, although it is not possible to quantify possible contributions（mainly annual） that might transfer directly from aliases of subdaily rotational tide errors. The leading sources are biases arising from the need to align daily, observed terrestrial frames, within which the pole coordinates are expressed and which are continuously deforming, to the secular, linear international reference frame. Such biases are largest over spans longer than about a year. Thanks to the very large number of IGS tracking stations, the formal covariance errors are much smaller,around 5 to 10 μas. Large networks also permit the systematic frame-related errors to be more effectively minimized but not eliminated. A number of periodic errors probably also influence polar motion results, mainly at annual, GPS（Global Positioning System） draconitic, and fortnightly periods, but their impact on the overall error budget is unlikely to be significant except possibly for annual tidal aliases. Nevertheless, caution should be exercised in interpreting geophysical excitations near any of the suspect periods.

关键词： PM(Polar motion) GPS(Global Positioning System) EOPs(Earth orientation parameters) Accuracy IGS(International GNSS Service)

A LIM Domain Protein from Tobacco Involved in Actin-Bundling and Histone Gene Transcription

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Molecular Plant 2013年第2期6卷 483-502页

作者： Danièle Moes Sabrina Gatti CEline Hoffmann Monika Dieterle Flora Moreau Katrin Neumann Marc Schumacher Marc Diederich Erwin Grill Wen-Hui Shen André Steinmetz Cldment Thomas Centre de Recherche Public-SantE 84 Val Fleuri L-1526 Luxembourg Luxembourg Laboratoire de Biologie Moleculaire et Cellulaire du Cancer HSpital Kirchberg 9 rue Edward Steichen L-2540 Luxembourg Luxembourg Lehrstuhl for Botanik Technische Universitat Munchen EmiI-Ramann-StraBe 4 D-85354 Freising Germany Jnstitut de Biologie Moleculaire des Plantes du CNRS 12 rue du Général Zimmer F-67084 Strasbourg Ceédex France

The two LIM domain-containing proteins from plants （LIMs） typically exhibit a dual cytoplasmic-nuclear dis-tribution, suggesting that, in addition to their previously described roles in actin cytoskeleton organization, they partici-pate in nuclear processes. Using a south-western blot-based screen aimed at identifying factors that bind to plant histone gene promoters, we isolated a positive clone containing the tobacco LIM protein WLIM2 （NtWLIM2） cDNA. Using both green fluorescent protein （GFP） fusion-and immunology-based strategies, we provide clear evidence that NtWLIM2 local-izes to the actin cytoskeleton, the nucleus, and the nucleolus. Interestingly, the disruption of the actin cytoskeleton by latrunculin B significantly increases NtWLIM2 nuclear fraction, pinpointing a possible novel cytoskeletal-nuclear crosstalk. Biochemical and electron microscopy experiments reveal the ability of NtWLIM2 to directly bind to actin filaments and to crosslink the latter into thick actin bundles. Electrophoretic mobility shift assays show that NtWLIM2 specifically binds to the conserved octameric cis-elements （Oct） of the Arabidopsis histone H4A748 gene promoter and that this binding largely relies on both LIM domains. Importantly, reporter-based experiments conducted in Arabidopsis and tobacco proto-plasts confirm the ability of NtWLIM2 to bind to and activate the H4A748 gene promoter in live cells. Expression studies indicate the constitutive presence of NtWLIM2 mRNA and NtWLIM2 protein during tobacco BY-2 cell proliferation and cell cycle progression, suggesting a role of NtWLIM2 in the activation of basal histone gene expression. Interestingly, both live cell and in vitro data support NtWLIM2 di/oligomerization. We propose that NtWLIM2 functions as an actin-stabilizing protein, which, upon cytoskeleton remodeling, shuttles to the nucleus in order to modify gene expression.

关键词： actin BY-2 cytoskeleton DNA-binding histone genes LIM Nicotiana tabacum promoter regulation trans-acting factors.

On Identifying and Explaining Similarities in Android Apps

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Journal of Computer Science & Technology 2019年第2期34卷 437-455页

作者： Li Li Tegawende F.Bissyande Hao-Yu Wang Jacques Klein Faculty of Information Technology Monash University Melbourne 3168 Australia Interdisciplinary Centre for Security Reliability and Trust University of Luxembourg Luxembourg 2721 Luxembourg School of Computer Science Beijing University of Posts and Telecommunications Beijing 100876 China

App updates and repackaging are recurrent in the Android ecosystem,filling markets with similar apps that must be *** the existence of several approaches to improving the scalability of detecting repackaged/cloned apps,researchers and practitioners are eventually faced with the need for a comprehensive pairwise comparison(or simultaneously multiple app comparisons)to understand and validate the similarities among *** this work,we present the design and implementation of our research-based prototype tool called SimiDroid for multi-level similarity comparison of Android *** is built with the aim to support the comprehension of similarities/changes among app versions and among repackaged *** particular,we demonstrate the need and usefulness of such a framework based on different case studies implementing different dissection scenarios for revealing various insights on how repackaged apps are *** further show that the similarity comparison plugins implemented in SimiDroid yield more accurate results than the state of the art.

关键词： Android similarity analysis app clone

Non-coding RNAs and stem cells:the dream team for neural regeneration in Parkinson’s disease?

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Neural Regeneration Research 2021年第10期16卷 2017-2018页

作者： Shubhra Acharya Andrew I.Lumley Yvan Devaux Cardiovascular Research Unit Department of Population HealthLuxembourg Institute of HealthL-1445 StrassenLuxembourg Faculty of Science Technology and MedicineUniversity of LuxembourgL-4365 Esch-sur-AlzetteLuxembourg

Parkinson’s disease(PD)is a widely spread neurodegenerative movement disorder,affecting approximately 10 million people *** is primarily caused by the loss of dopaminergic neurons in the substantia nigra,which causes decreased secretion of dopamine leading to tremors,bradykinesia and rigid muscle *** development of PD is complex and needs to be better *** treatment strategies primarily involve targeting disease symptoms,however,since there is a continuous loss of dopaminergic neurons in the brain,PD appears to be ***,treatment strategies often carry severe side effects related to dopamine production,where too little or too much can cause debilitating issues such as *** pool of neural stem/progenitor cells(NSCs)located in sub-ventricular zone and hippocampal dentate gyrus,proliferate and are responsible to give rise to neurons and glia in response to any cellular *** this activation of NSCs is highly regulated,it is insufficient to overcome the loss of dopaminergic neurons in *** this line,non-coding RNAs(ncRNAs)are involved in the underlying mechanisms of PD and are known to have important functional roles in neural regeneration(Acharya et al.,2020).Thus,the study of ncRNAs in NSC activation and adult neurogenesis post PD development is an extremely attractive area of research with significant clinical application potential.

关键词： neural primarily overcome

Algorithms for tractable compliance problems

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Frontiers of Computer Science 2015年第1期9卷 55-74页

作者： Silvano COLOMBO TOSATTO Pierre KELSEN Qin MA Marwane el KHARBILI Guido GOVERNATORI Leendert van der TORRE Computer Science and Communication Unit University of Luxembourg Luxembourg L- 1359 Luxembourg NICTA Brisbane QLD 4001 Australia Dipartment di Informatica Universith di Torino Torino 10149 Italy

In general the problem of verifying whether a structured business process is compliant with a given set of regulations is NP-hard. The present paper focuses on identifying a tractable subset of this problem, namely verifying whether a structured business process is compliant with a single global obligation. Global obligations are those whose validity spans for the entire execution of a business process. We identify two types of obligations： achievement and maintenance.In the present paper we firstly define an abstract framework capable to model the problem and secondly we define procedures and algorithms to deal with the compliance problem of checking the compliance of a structured business process with respect to a single global obligation. We show that the algorithms proposed in the paper run in polynomial time.

关键词： compliance business process models algorithms computational complexity