Performance en frottement de composites alumine-métal avec ou sans nanotubes de carbone densifiés par frittage flash : Identification des conditions de grippage et des mécanismes d’usure

Des composites à matrice alumine contenant des nanoparticules métalliques (FeCr ou Fe) avec ou sans nanotubes de carbone (NTC) et densifiés par frittage flash (Spark Plasma Sintering, SPS) ont été étudiés dans des conditions de frottement oscillant de faible amplitude (fretting-usure) et de glissement alternatif. Un dispositif de fretting à débattement non imposé a été utilisé pour permettre aux matériaux en contact de s'adapter librement afin de simuler et d'identifier le phénomène de grippage dans différentes conditions de chargement (constant, progressif, avec ou sans ouverture de contact). Une modélisation paramétrique a permis de définir précisément les coefficients de frottement, les seuils de grippage et les énergies dissipées dans le contact. Les résultats obtenus présentent de grandes similitudes à faibles charges, mais on constate systématiquement une transition de charge brutale conduisant à une forte dégradation des composites avec NTC juste avant un grippage prématuré. Un dispositif d'acquisition d'émission acoustique a été utilisé sur certains essais pour identifier et suivre in situ les différentes phases de dégradation observées au cours du frottement. Des essais complémentaires en glissement alternatif, avec débattements imposés, ont également été réalisés afin de préciser le comportement en usure des composites étudiés. L'ensemble des résultats de fretting et de glissement ont permis de hiérarchiser les performances tribologiques des différents composites et conduit à l'identifier l'évolution des mécanismes d'usure en relation avec la présence d'un tribofilm à l'interface de contact. ABSTRACT : Alumina matrix composites containing metal nanoparticles (Fe or FeCr) with or without carbon nanotubes (CNT) densified by spark plasma sintering (SPS) were studied under low amplitude oscillating friction conditions (fretting-wear) and reciprocating sliding. A free displacement fretting machine was used to enable contact materials to adapt freely to simulate and identify the seizure phenomenon under different loading conditions (constant, progressive, with or without contact aperture). Parametric modeling has helped to define precisely friction coefficients, seizure thresholds and dissipated energy in the contact. The results are very similar at low loads, but there is always a sharp transition at higher loads leading to severe degradation of composites with CNT just before an early seizure. An acquisition instrument of acoustic emission has been used during several tests to identify and monitor in situ different stages of degradation observed during friction. Additional tests under reciprocating sliding with imposed displacements have also been made for further understanding of wear behavior of composites. The overall results of fretting and reciprocating sliding helped to prioritize the tribological performances of different composites and lead to identify changes in wear mechanisms in relation with occurrence of a tribofilm in the contact interface

The Effect of Combustion Chamber Deposits on Heat Transfer and Combustion in a Homogeneous Charge Compression Ignition Engine

Homogenous Charge Compression Ignition (HCCI) engines have the potential to achieve diesel-like fuel efficiency while virtually eliminating NOx and soot emissions. Realizing the full fuel economy potential of the gasoline HCCI engine hinges upon our ability to expand the operating range. Due to the strong dependence of HCCI combustion to in-cylinder thermal conditions, understanding the effects of changes in the thermal boundary of the combustion chamber is essential for addressing combustion stability and HCCI operating limits. Combustion chamber deposits (CCD) are known to increase the propensity of a conventional spark-ignition engine to knock through an increase in local wall temperature, therefore it is expected they would affect the main combustion event in an HCCI engine. The objective of this work is to determine the effect of CCD on HCCI combustion. This requires a thorough understanding of the effects of deposits on heat transfer to the chamber walls. This experimental investigation was performed using a gasoline fueled single cylinder research engine. Combustion analysis is performed based on in-cylinder pressure measurements and combustion chamber wall heat transfer effects are characterized through the use of fast response thermocouples. Using these measurements, it was found that there is a clear relationship between instantaneous peak temperature phasing measured below the CCD layer and the layer thickness. Based on these findings, a methodology for calculating the thermal diffusivity of the deposit layer was developed, specific for HCCI engines. These measurements were also used to develop the Lead-Corrector method, which uses numerical finite-difference based calculation of the deposit layer instantaneous surface temperature to give insight into the direct effects of CCD on chamber heat loss. It was found that the effect of deposit formation was of a much greater magnitude on HCCI combustion than on standard combustion modes. Specifically, it was found that reduced heat loss during intake and compression resulted in earlier ignition timings while higher wall temperature swings during heat release resulted in shorter burn duration of the peripheral regions of the air/fuel charge. The heat storage effects of CCD cause the range of operability of HCCI combustion to shift downward in load value.Ph.D.Mechanical EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/58488/1/oguralp_1.pd

Analysis of wear mechanism in TPU-steel contact pair by means of long stroke tribometer tests

A complete wear characterisation of a thermoplastic polyurethane (TPU) sliding against steel is presented. Wear tests were performed using a long stroke tribometer under sliding reciprocating movement and dry conditions. The dependence of some of the most significant parameters was studied. Before and after wear tests, complementary observations, analyses and measurements were also performed on both contacting materials. These various characterisations involved weight loss of TPU, physico-chemical and thermo- mechanical analyses of TPU, included topographical measurements and morphological observations of worn surfaces of contacting pairs and calculations of the temperature rise generated by friction

Mechanisms of T-Cell Exhaustion in Pancreatic Cancer.

T-cell exhaustion is a phenomenon that represents the dysfunctional state of T cells in chronic infections and cancer and is closely associated with poor prognosis in many cancers. The endogenous T-cell immunity and genetically edited cell therapies (CAR-T) failed to prevent tumor immune evasion. The effector T-cell activity is perturbed by an imbalance between inhibitory and stimulatory signals causing a reprogramming in metabolism and the high levels of multiple inhibitory receptors like programmed cell death protein-1 (PD-1), cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3), and Lymphocyte-activation gene 3 (Lag-3). Despite the efforts to neutralize inhibitory receptors by a single agent or combinatorial immune checkpoint inhibitors to boost effector function, PDAC remains unresponsive to these therapies, suggesting that multiple molecular mechanisms play a role in stimulating the exhaustion state of tumor-infiltrating T cells. Recent studies utilizing transcriptomics, mass cytometry, and epigenomics revealed a critical role of Thymocyte selection-associated high mobility group box protein (TOX) genes and TOX-associated pathways, driving T-cell exhaustion in chronic infection and cancer. Here, we will review recently defined molecular, genetic, and cellular factors that drive T-cell exhaustion in PDAC. We will also discuss the effects of available immune checkpoint inhibitors and the latest clinical trials targeting various molecular factors mediating T-cell exhaustion in PDAC

βIII-tubulin: a novel mediator of chemoresistance and metastases in pancreatic cancer

Pancreatic cancer is a leading cause of cancer-related deaths in Western societies. This poor prognosis is due to chemotherapeutic drug resistance and metastatic spread. Evidence suggests that microtubule proteins namely, β-tubulins are dysregulated in tumor cells and are involved in regulating chemosensitivity. However, the role of β-tubulins in pancreatic cancer are unknown. We measured the expression of different β-tubulin isotypes in pancreatic adenocarcinoma tissue and pancreatic cancer cells. Next, we used RNAi to silence βIII-tubulin expression in pancreatic cancer cells, and measured cell growth in the absence and presence of chemotherapeutic drugs. Finally, we assessed the role of βIII-tubulin in regulating tumor growth and metastases using an orthotopic pancreatic cancer mouse model. We found that βIII-tubulin is highly expressed in pancreatic adenocarcinoma tissue and pancreatic cancer cells. Further, we demonstrated that silencing βIII-tubulin expression reduced pancreatic cancer cell growth and tumorigenic potential in the absence and presence of chemotherapeutic drugs. Finally, we demonstrated that suppression of βIII-tubulin reduced tumor growth and metastases in vivo. Our novel data demonstrate that βIII-tubulin is a key player in promoting pancreatic cancer growth and survival, and silencing its expression may be a potential therapeutic strategy to increase the long-term survival of pancreatic cancer patients

Ring1b-dependent epigenetic remodelling is an essential prerequisite for pancreatic carcinogenesis

BACKGROUND AND AIMS Besides well-defined genetic alterations, the dedifferentiation of mature acinar cells is an important prerequisite for pancreatic carcinogenesis. Acinar-specific genes controlling cell homeostasis are extensively downregulated during cancer development; however, the underlying mechanisms are poorly understood. Now, we devised a novel in vitro strategy to determine genome-wide dynamics in the epigenetic landscape in pancreatic carcinogenesis. DESIGN With our in vitro carcinogenic sequence, we performed global gene expression analysis and ChIP sequencing for the histone modifications H3K4me3, H3K27me3 and H2AK119ub. Followed by a comprehensive bioinformatic approach, we captured gene clusters with extensive epigenetic and transcriptional remodelling. Relevance of Ring1b-catalysed H2AK119ub in acinar cell reprogramming was studied in an inducible Ring1b knockout mouse model. CRISPR/Cas9-mediated Ring1b ablation as well as drug-induced Ring1b inhibition were functionally characterised in pancreatic cancer cells. RESULTS The epigenome is vigorously modified during pancreatic carcinogenesis, defining cellular identity. Particularly, regulatory acinar cell transcription factors are epigenetically silenced by the Ring1b-catalysed histone modification H2AK119ub in acinar-to-ductal metaplasia and pancreatic cancer cells. Ring1b knockout mice showed greatly impaired acinar cell dedifferentiation and pancreatic tumour formation due to a retained expression of acinar differentiation genes. Depletion or drug-induced inhibition of Ring1b promoted tumour cell reprogramming towards a less aggressive phenotype. CONCLUSIONS Our data provide substantial evidence that the epigenetic silencing of acinar cell fate genes is a mandatory event in the development and progression of pancreatic cancer. Targeting the epigenetic repressor Ring1b could offer new therapeutic options

Surrogate broodstock to enhance biotechnology research and applications in aquaculture

Aquaculture is playing an increasingly important role in meeting global demands for seafood, particularly in low and middle income countries. Genetic improvement of aquaculture species has major untapped potential to help achieve this, with selective breeding and genome editing offering exciting avenues to expedite this process. However, limitations to these breeding and editing approaches include long generation intervals of many fish species, alongside both technical and regulatory barriers to the application of genome editing in commercial production. Surrogate broodstock technology facilitates the production of donor-derived gametes in surrogate parents, and comprises transplantation of germ cells of donors into sterilised recipients. There are many successful examples of intra- and inter-species germ cell transfer and production of viable offspring in finfish, and this leads to new opportunities to address the aforementioned limitations. Firstly, surrogate broodstock technology raises the opportunity to improve genome editing via the use of cultured germ cells, to reduce mosaicism and potentially enable in vivo CRISPR screens in the progeny of surrogate parents. Secondly, the technology has pertinent applications in preservation of aquatic genetic resources, and in facilitating breeding of high-value species which are otherwise difficult to rear in captivity. Thirdly, it holds potential to drastically reduce the effective generation interval in aquaculture breeding programmes, expediting the rate of genetic gain. Finally, it provides new opportunities for dissemination of tailored, potentially genome edited, production animals of high genetic merit for farming. This review focuses on the state-of-the-art of surrogate broodstock technology, and discusses the next steps for its applications in research and production. The integration and synergy of genomics, genome editing, and reproductive technologies have exceptional potential to expedite genetic gain in aquaculture species in the coming decades