Damage index for reinforced concrete columns

Jaki seizmički pomaci tla mogu uzrokovati različite razine oštećenja armiranobetonskih građevina. Indeks oštećenja (DI) jedan je od pouzdanih načina za kvantitativno mjerenje razine oštećenja koju građevine mogu izdržati u takvim okolnostima. U ovom se radu prikazuju postojeći koncepti te se predlaže novi koncept u kojem se u obzir uzima duktilnost s obzirom na pomak uzoraka opterećenih pri malim kutovima zaokreta ili u pokusu niskocikličnog zamora. Predloženi DI uspješno je primijenjen za predviđanje razine oštećenja u okviru nekoliko slučajeva.Severe earthquake ground motions can cause various levels of damage to reinforced concrete structures. Among others, damage index (DI) is a reliable means to quantitatively measure the extent of damage that can be endured by a structure in such circumstances. This paper outlines available concepts with a view to propose a new concept taking into account the displacement ductility of specimens loaded under low rotation angles or subjected to low fatigue test. The proposed DI has been successfully applied to predict damage levels in several case studies

Scalar and vector-valued fragility analysis of typical Algerian RC bridge piers

Ovaj rad predstavlja i analizira pristup za izvođenje skalarne i vektorske ocjene ranjivosti tipskih AB stupova mostova u Alžiru. Putem inkrementalne dinamičke analize, seizmički je odziv izračunan uzimajući u obzir 60 seizmičkih gibanja tla i 10 mjera intenziteta (IM). Optimalni IM za skalarnu analizu procijenjen je i odabran pomoću regresijske analize. Provjeren je na temelju nekoliko metrika uključujući korelaciju, učinkovitost, praktičnost i sposobnost. Vektorska analiza ranjivosti, uz primjenu dva para IM-ova izračunana je i uspoređena s krivuljama ranjivosti dobivenim skalarnom analizom. Usporedba je pokazala da se u analizi ranjivosti vjerojatnost štete može podcijeniti ili precijeniti.This paper presents and discusses an approach for performing scalar and vector vulnerability assessments of typical Algerian RC bridge piers. Across incremental dynamic analysis, the seismic response was calculated while considering 60 seismic ground motions and 10 intensity measures (IMs). An optimal scalar-valued IM was assessed and selected through regression analyses. It was validated based on several metrics including the correlation, efficiency, practicality, and proficiency. The fragility of vector-valued functions that use two pairs of IMs were calculated and compared with fragility curves based on scalars. The comparison indicated that the damage probability can be underestimated or overestimated in vulnerability analysis

High-speed analysis of large sample sets – how can this key aspect of the omics be achieved?

High-speed analysis of large (prote)omics sample sets at the rate of thousands or millions of samples per day on a single platform has been a challenge since the beginning of proteomics. For many years, electrospray ionisation (ESI)-based mass spectrometry (MS) methods have dominated proteomics due to their high sensitivity and great depth in analysing complex proteomes. However, despite improvements in speed, ESI-based MS methods are fundamentally limited by their sample introduction, which excludes off-line sample preparation/fractionation due to the time required to switch between individual samples/sample fractions, and therefore being dependent on the speed of on-line sample preparation methods such as liquid chromatography. Laser-based ionisation methods have the advantage of moving from one sample to the next without these limitations, being mainly restricted by the speed of modern sample stages, i.e. 10 ms or less between samples. This speed matches the data acquisition speed of modern high-performing mass spectrometers while the pulse repetition rate of the lasers (>1 kHz) provides a sufficient number of desorption/ionisation events for successful ion signal detection from each sample at the above speed of the sample stages. Other advantages of laser-based ionisation methods include the generally higher tolerance to sample additives and contamination compared to ESI MS, and the contact-less and pulsed nature of the laser used for desorption, reducing the risk of cross-contamination. Furthermore, new developments in matrix-assisted laser desorption/ionisation (MALDI) have expanded its analytical capabilities, now being able to fully exploit high-performing hybrid mass analysers and their strengths in sensitivity and MS/MS analysis by generating an ESI-like stable yield of multiply charged analyte ions. Thus, these new developments and the intrinsically high speed of laser-based methods now provide a good basis for tackling extreme sample analysis speed in the omics

The Ciliogenic Transcription Factor RFX3 Regulates Early Midline Distribution of Guidepost Neurons Required for Corpus Callosum Development

The corpus callosum (CC) is the major commissure that bridges the cerebral hemispheres. Agenesis of the CC is associated with human ciliopathies, but the origin of this default is unclear. Regulatory Factor X3 (RFX3) is a transcription factor involved in the control of ciliogenesis, and Rfx3–deficient mice show several hallmarks of ciliopathies including left–right asymmetry defects and hydrocephalus. Here we show that Rfx3–deficient mice suffer from CC agenesis associated with a marked disorganisation of guidepost neurons required for axon pathfinding across the midline. Using transplantation assays, we demonstrate that abnormalities of the mutant midline region are primarily responsible for the CC malformation. Conditional genetic inactivation shows that RFX3 is not required in guidepost cells for proper CC formation, but is required before E12.5 for proper patterning of the cortical septal boundary and hence accurate distribution of guidepost neurons at later stages. We observe focused but consistent ectopic expression of Fibroblast growth factor 8 (Fgf8) at the rostro commissural plate associated with a reduced ratio of GLIoma-associated oncogene family zinc finger 3 (GLI3) repressor to activator forms. We demonstrate on brain explant cultures that ectopic FGF8 reproduces the guidepost neuronal defects observed in Rfx3 mutants. This study unravels a crucial role of RFX3 during early brain development by indirectly regulating GLI3 activity, which leads to FGF8 upregulation and ultimately to disturbed distribution of guidepost neurons required for CC morphogenesis. Hence, the RFX3 mutant mouse model brings novel understandings of the mechanisms that underlie CC agenesis in ciliopathies

Duljina kritičnog područja AB stupova pri različitim razinama uzdužnog opterećenja

U radu se procjenjuje seizmičko ponašanje AB stupova pri različitim razinama uzdužnog opterećenja. Na temelju rezultata ispitivanja provedenih na ukupno 16 uzoraka AB stupova izloženih različitim razinama uzdužnog opterećenja, predložena je jednadžba koja povezuje duljinu kritičnog područja s primijenjenim uzdužnim opterećenjem, te je uspoređena s alžirskim normama za potres RPA99/V2003. Rezultati su pokazali da je prema navedenim normama duljina kritičnog područja podcijenjena pri visokoj razini uzdužne sile

Confined length of reinforced concrete columns at various axial load levels

The seismic performance of reinforced concrete columns subjected to various levels of axial load is assessed in the paper. An equation relating the confined region to the applied axial load is proposed and compared to the Algerian seismic code RPA99/V2003 specifications, based on the concrete spalling length measured on 16 specimens under different axial load ratios, obtained from the experiments. Results indicate that the length of the confined region of a column subjected to high axial load is underestimated in the above mentioned specifications

Confined length of reinforced concrete columns at various axial load levels

The seismic performance of reinforced concrete columns subjected to various levels of axial load is assessed in the paper. An equation relating the confined region to the applied axial load is proposed and compared to the Algerian seismic code RPA99/V2003 specifications, based on the concrete spalling length measured on 16 specimens under different axial load ratios, obtained from the experiments. Results indicate that the length of the confined region of a column subjected to high axial load is underestimated in the above mentioned specifications

Glioblastoma characterization and monitoring of its chemotherapies by MALDI imaging coupled to top down analysis

Le glioblastome est la forme la plus agressive des tumeurs du système nerveux central. Le traitement de référence consiste en l'exérèse chirurgicale, suivie d'une radiothérapie associée à une chimiothérapie concomitante et adjuvante par le témozolomide. Son bénéfice est démontré par une médiane de survie entre 12 et 14 mois. Le glioblastome est caractérisé par une population cellulaire hétérogène hautement infiltrante, angiogénique et résistante à la chimiothérapie. Dans le but d'optimiser l'effet des molécules thérapeutiques, un suivi de leur pharmacocinétique ainsi qu'une bonne caractérisation tumorale sont nécessaires. L'imagerie par désorption laser assistée par matrice en spectrométrie de masse (IMS MALDI) a été utilisée pour l'identification de marqueurs diagnostiques, pronostiques et prédictifs de réponse aux traitements. Elle a aussi permis de suivre la pharmacocinétique in situ des chimiothérapies.L'identification de protéines directement sur tissu par fragmentation en source a permis la mise en évidence de différents isotypes de tubuline, une des cibles majeures en thérapie anticancéreuse. Le couplage de cette stratégie d'identification à l'imagerie MALDI a permis d'identifier et de localiser dans des zones tumorales, des protéines impliquées dans la tumorigenèse. La distribution intra-tissulaire du bévacizumab et du témozolomide a été étudiée pour la première fois.Des marqueurs de réponse aux traitements ont ensuite été identifiés par comparaison des profils d'expression protéique de tumeurs avec et sans traitement. Ces résultats montrent l'intérêt de l'imagerie MALDI pour l'étude des chimiothérapies et permettent d'envisager son utilisation clinique future.Glioblastoma is the most aggressive of the gliomas, a collection of tumors arising from glia or their precursors within the central nervous system. The current standard of care, comprised of surgical resection followed by radiation and the chemotherapeutic agent temozolomide, only provides patients with a 12-14 months survival period post-diagnosis. The glioblastoma is characterized by a heterogeneous population of cells that are highly infiltrative, angiogenic and resistant to chemotherapy. In order to optimize the therapy effect, a pharmacokinetic monitoring and a better understanding and characterization of tumor biology are needed. For this purpose, matrix assisted laser desorption/ionization imaging mass spectrometry imaging mass spectrometry (MALDI IMS) technology was applied to identify diagnostic, prognostic and predictive markers of therapy response; and to understand/follow the pharmacokinetic of chemotherapies. The top-down in-source decay strategy was used for protein identification directly on tissue. This strategy allowed tubulin protein isoforms distinction and identification, which is one of the main targets in cancer therapy. MALDI imaging coupled to ISD identified tumorigenesis proteins within tumor structures. Bevacizumab and temozolmide distribution was followed within brain tissue sections. For the first time a monoclonal antibody was deciphered on tissue. Finally, markers that predict therapy response were demonstrated by a comparison between protein expression profiles from tumors with and without chemotherapy treatment. These results highlight the interest of MALDI imaging for chemotherapy improvement and open the way for its use in the clinics

New flow cytometry procedures to democratize the diagnosis of infectious diseases

La lutte contre les maladies infectieuses repose sur trois piliers : la prévention (hygiène, gestes barrières, vaccination), la surveillance par des outils diagnostiques, et le traitement. Cette stratégie est mise à mal par la constante évolution des pathogènes et de leur environnement conduisant à l’antibiorésistance des bactéries et à l’émergence de nouveaux virus. Actuellement, le diagnostic des infections n’est pas optimal (délai, coût, performance, accessibilité, inefficacité face aux nouveaux pathogènes). Selon l’OMS, il faudrait pouvoir diagnostiquer toute infection, partout, en quelques minutes, de manière non-invasive et pour un coût modique.Un début de solution serait un test de triage rapide distinguant la catégorie de pathogène, par exemple virus ou bactérie, afin de restreindre le nombre de tests spécifiques à réaliser et d’orienter la prise en charge comme l’administration d’antibiotiques en cas d’infection bactérienne, ou l’isolation précoce des cas viraux supposés contagieux. La réponse de l’hôte étant différente selon la nature du pathogène, nous avons étudié des biomarqueurs leucocytaires dont l’expression reflète la présence d’une infection bactérienne ou virale. Nous avons aussi identifié certains biomarqueurs associés à la sévérité de l’infection. En parallèle, nous avons optimisé des procédures de cytométrie en flux permettant une analyse au chevet du patient (« Point of care »), ou alors une analyse délocalisée grâce à la préservation du sang par congélation ou séchage à température ambiante. Ces technologies ont ensuite été évaluées dans plusieurs contextes infectieux dont la COVID-19 et pourraient démocratiser le diagnostic d’autres pathologies.The fight against infectious diseases is based on three pillars: prevention (hygiene, barrier measures, vaccination), surveillance using diagnostic tools, and treatment. This strategy is challenged by the constant evolution of pathogens and their environment leading to antibiotic resistance of bacteria and the emergence of new viruses. Currently, the diagnosis of infections is not optimal (time, cost, performance, accessibility, inefficiency towards new pathogens). According to the WHO, it is necessary to be able to diagnose any infection, anywhere, in a few minutes, in a non-invasive way and for a modest cost.One solution would be a rapid triage test distinguishing the category of pathogen, e.g. virus or bacteria, in order to limit the number of specific tests to be performed and to guide management such as the administration of antibiotics in the case of bacterial infection, or the early isolation of viral cases assumed to be contagious. As the host response is different according to the nature of the pathogen, we studied leukocyte biomarkers whose expression reflects the presence of a bacterial or viral infection. We also identified some biomarkers associated with the severity of the infection. In parallel, we have optimized flow cytometry procedures allowing for point-of-care (POC) analysis or delocalized analysis by freezing or drying blood at room temperature. These technologies were then evaluated in several infectious contexts including COVID-19 and could democratize the diagnosis of other pathologies

Functional heterogeneity of immunoregulatory subpopulations implicated in the progression of chronic lymphocytic leukemia

La leucémie lymphoïde chronique est une expansion clonale de lymphocytes B matures. Son évolution clinique hétérogène dépend de sous-populations leucémiques échappant à la surveillance antitumorale. Ces cellules dotées de propriétés régulatrices ont fait l'objet de travaux antérieurs du laboratoire mettant en évidence l'existence de sous-populations lymphocytaires produisant de l'IL-10, du TGFb1 et Foxp3. Mon projet de thèse a consisté à poursuivre cette caractérisation et attribuer un rôle fonctionnel à ces sous-populations. Par une approche de blocage des cytokines, les résultats indiquent le rôle critique du TGFb1 dans le développement et la maintenance des populations Tregs sans affecter le compartiment des lymphocytes Th1 effecteurs dont le rôle est attribué à l'IL-10. Outre ces facteurs régulateurs, mon second objectif a été de caractériser dans les lymphocytes B une enzyme immunorégulatrice "IDO'' exprimée de façon constitutive ou inductible par un mécanisme inflammatoire dépendant de l'IFNg . Cette enzyme métaboliquement active est capable de métaboliser le tryptophane en kynurénine en présence de l'IFNg mais son induction est inhibée par le TGFb1 ce qui suggère des mécanismes régulateurs compétitifs. L'ensemble de ces données souligne l'importance des sous populations régulatrices dans la progression de la LLC et apporte de nouveaux éléments sur les mécanismes d'action des facteurs régulateurs.Chronic lymphocytic leukemia is a clonal expansion of mature B lymphocytes. Its heterogeneous clinical coursedepends on leukemia subpopulations escaping antitumor survey. These cells endowed with regulatoryproperties have been the subject of previous laboratory work highlighting the existence of lymphocytesubpopulations producing IL-10, TGFb1 and Foxp3. My thesis project consisted in pursuing this characterizationand assigning a functional role to these subpopulations. Using a cytokine blockade approach, the results indicatethe critical role of TGFb1 in the development and maintenance of Treg populations without affecting the effectorTh1 cell compartment whose role is attributed to IL-10. In addition to these regulatory factors, my secondobjective was to characterize in B lymphocytes an immunoregulatory enzyme ?IDO? expressed constitutively andinducibly by an IFNg-dependent inflammatory mechanism. This metabolically active enzyme was able tometabolize tryptophan to kynurenine in the presence of IFNg but its induction was inhibited by TGFb1 suggestingunderlying regulatory mechanisms. All of these data highlight the importance of regulatory subpopulations inthe progression of CLL and provide new insights on the mechanisms of action of regulatory factors