Добірка наукової літератури з теми "Scaffolds 2.5D et 3D"

This study is to investigate the effect of PAM on protein adsorption and osteoblastic cells adhesion to HA bioceramics. PAM was immobilized on the surface of HA bioceramics for bone scaffold by chelating. The outermost layer of the specimens was analyzed by XPS and FT-IR. The protein adsorption test was performed using the 10% bovine calf serum absorbed on the specimens in vitro. The osteoblastic cells were inoculated and cultured on the scaffolds. SEM, MTT test and ALP activity test evaluated the cell attachment, proliferation and activity on the scaffolds. Characteristic peaks in XPS and FT-IR spectra indicated PAM being immobilized on the surface of the bioceramics. PAGE and 2-D DIGE results indicated that HA absorbed more acidic proteins, while PAM-HA absorbed more basic and neutral proteins.The cell culture test indicated that the cells actively proliferated on the scaffolds. There was no significant difference between the ALP activity of the cells cultured for 1d, 3d, 5d and 7d on PAM-HA and that of the controls. PAM had no obvious effect on the cytocompatibility of HA, and PAM-HA bioceramics could be used as bone scaffold with potential ability to improve osteogenesis.

Lithium metal is the most promising candidate for a high-capacity anode in Li-ion batteries due to the highest theoretical specific capacity (3,860 mAh g-1) and the lowest redox potential (-3.04 V vs S.H.E.) [1]. However, the Li metal anode (LMA) is still challenging to be used practically due to mossy-like dendrite formation, dead Li growth, and infinite volume expansion resulting in safety hazards. Various approaches have been proposed to suppress Li dendrite growth, such as constructing an artificial solid electrolyte layer (ASEI) [2], modifying organic electrolyte [3], preparing lithiophilic substrates [4], and using a 3D scaffold [5]. Among them, introducing a 3D scaffold is one effective method to prevent Li dendrite growth due to its high surface area to greatly reduce low local current density, based on Sand’s formula [6]. Furthermore, the 3D scaffold can accommodate Li metals inside a porous structure, reducing the cell volume expansion. In fact, owing to the advantages of a 3D scaffold, a variety of 3D scaffolds based on Cu [5], Ni [7], and carbon [8] have been reported over the past several years. However, the lithium metal is preferentially deposited on the top of the 3D scaffold since the top of the bare 3D scaffolds has low diffusion resistance than the bottom of the scaffold due to the short diffusion length. As one of the solutions, introducing lithiophilic materials to the bottom of the 3D scaffold can be regarded as an effective way to induce Li nucleation inside the porous scaffold [9]. However, since morphological properties like porosity, pore size, and thickness also affect the Li deposition behaviors inside the 3D scaffold [9, 10], both factors should be considered simultaneously. Here, we propose a rational design of a 3D porous scaffold for dendrite-free LMA, adopting lithiophilic silver on a current collector. Specifically, we suggest optimal structural properties of 3D scaffolds, such as porosity, pore size, and thickness to induce the Li nucleation inside the bottom of the current collector, thereby achieving inner space Li deposition. We deposited Ag nanoparticles with 20 nm evaporation thickness by a thermal evaporation method on the commercial copper foils. (thickness ≈ 25 µm). The 3D scaffold was obtained by simple mixing and casting processes. The Cu nanoparticles (Cu NPs), silica particles, and PVdF binder were added to PP bottles at a weight ratio of 1:1:0.1, and the mixture was mixed by a high-energy ball mill. A mixed sample was cast on the copper foil and Ag coated copper foil. Cu NPs were welded by heating at 350 ℃ in a H2/Ar flow (1:1=v:v) for 2h. Afterward, silica particles were etched with 5% hydrofluoric acid (aq). As a result, porous copper scaffold (pCu) and Ag coated porous copper scaffold (AgpCu) were fabricated for Li metal anodes. The SEM images of pCu are shown in Fig. 1a, b, and c from which we can see the uniformly distributed sphere-like pore generated through the etching of silica particles. The average diameter of the formed pore is around 1 µm, which is the same as the size of silica used in the experiment. Fig. 1c presents a cross-sectional SEM image of a pCu with a thickness of ~80 µm. The deposited Li morphology is investigated by optical and SEM images in Fig. 2. When Li is deposited at 0.5 mA cm-2 for 4 mAh cm-2, shiny Li is observed on the top of the pCu in optical images (Fig. 2a). In contrast with pCu, AgpCu shows a clean brown optical image on the top without Li metals in Fig. 2c. In addition, the SEM images of Fig. 2b and d shows the morphologies of Li deposits Li on the pCu and AgpCu, respectively, indicating that a silver inside layer in AgpCu effectively induces inner deposition of Li. References [1] X.-B. Cheng et al., Chem. Rev, 117, 10403, 2017. [2] N.-W. Li et al., Adv. Mater. 28, 1853–1858, 2015. [3] X. Fan, et al., Nat. Nanotechnol. 13, 715–722, 2018. [4] K.-Y. Cho et al., Appl. Surf. Sci. 554, 149578, 2021. [5] Q. Yun et al., Adv. Mater. 28, 6932–6939, 2016. [6] R. Zhang et al., Adv. Mater. 28, 2155–2162, 2016. [7] S.-S. Chi et al., Adv. Funct. Mater. 27, 1700348, 2017. [8] C. Yang et al., Adv. Mater. 29, 1702714, 2017. [9] Yun et al., Chem. Eng. J. 430, 132897, 2022. [10] H. Song et al., Energy Stor. Mater. 36, 326–332, 2021. Figure 1

Introduction: Next generation sequencing techniques have identified a large number of MDS associated acquired molecular lesions. However, translation of these possible molecular targets into new therapeutic strategies has been lagging behind. This is also due to a lack of functional experimental models of MDS, in which new hypotheses can be evaluated pre-clinically. Xenograft models in NSG mice have emerged as versatile preclinical platforms for investigation of functional pathomechanisms in MDS ([1] Medyouf et al., 2014, [2] Rouault-Pierre et al., 2017). The limiting factor of these models is the low engraftment of patient-derived CD34+ hematopoietic stem cells (HSCs). Efficient humanized 3D scaffolds in immune-compromised mouse models have been established, enabling to increase engraftment rates of normal and malignant hematopoiesis ([3] Reinisch et al., 2016, [4] Abarrategi et al., 2017). Therefore, we evaluated engraftment ability of IPSS low-risk, int-1 and high-risk-patient samples, in four different 3D scaffolds. Methods: Currently we transplanted samples from 10 MDS patients in parallel into NSG mice testing the following conditions: A) Intrafemoral co-injection of CD34+ HSCs and MSCs according to [1]. Subcutaneous implantation of 3D scaffolds. Gelfoam (B) and Bio-OSS (C) [4], Matrigel ossicles (D) [3] and primary human bone isolated after hip replacement, inserted with Gelfoam, preseeded in vitro with MSCs and mononuclear cells (MNCs) and injected in vivo with CD34+ HSCs 8 weeks after implantation (human bone ossicles) (E). Ossicles, bone marrow (BM), peripheral blood and spleens were analyzed 12 weeks after implantation of hematopoietic cells. Results: Gelfoam and human bone ossicles showed significantly higher hCD45+cell numbers compared to intrafemoral injection analyzed by flow cytometry. Engraftment in those two conditions was similarly robust. However, Gelfoam scaffolds showed higher percentual engraftment levels ranging up to 70% as compared to human bone ossicles ranging from 0.2% to 27%. Interestingly, we found systemic engraftment of hCD45+cells outside the injected bone fragment in the BM, peripheral blood and spleen solely in mice, which received human bone ossicles. In all other methods, hCD45+ cells could only be detected within the ossicles themselves. This result could possibly be explained due to transplantation of MNCs in this condition. That hypothesis was supported by another set of experiments using human bone ossicles (n=10), which showed that colonization of the scaffold was similar when transplanting either CD34+ cells + MSCs, MNCs+MSCs or MNCs only but systemic engraftment could only be seen in MNC transplanted mice. Conclusion: Our data show that hCD45+cells and MSCs from MDS BM were able to colonize humanized ossicle scaffolds. Gelfoam and human bone ossicles were the most promising novel methods to improve MDS xenograft models. For systemic engraftment, application of MNCs seems to be necessary. Disclosures Nolte: Novartis: Honoraria, Research Funding; Celgene: Honoraria, Research Funding.

The need for clean energy solutions in order to significantly lower our carbon footprint is placing increasing attention on renewable energy, such as wind and solar. However, these technologies suffer from intermittency issues, thus making efficient energy storage and conversion a major requirement. One of the solutions to this problem is electrochemical CO2 reduction (CO2RR), using renewable energy to produce green fuels and chemicals. However, the reduction of CO2 is thermodynamically and kinetically unfavorable. To overcome this, the development of highly efficient and selective electrocatalysts is a key goal of CO2RR research. Carbon has been attracting interest as a promising candidate due to its high specific surface area, good conductivity, and low-cost. However, its catalytic performance is limited by the electroneutrality of the carbon atoms in the primarily graphitic lattice. In order to activate the CO2 molecules and enhance the adsorption of intermediates, a range of novel carbon catalysts has been developed, with nitrogen doping being the most common approach. The N atom has a similar size as C and thus the lattice mismatch after doping is minimal [1]. At the same time, the N atom also has a higher electronegativity than C which will break the electroneutrality of the carbon lattice and enhance the conductivity of the material [2-3]. Furthermore, N doping results in a range of N-based surface species, thus potentially allowing the tuning of the CO2RR products [4]. In this work, a novel, self-supported, nanoporous carbon scaffold (NCS) was used as the carbon substrate. The NCS is a templated, binder-free mesoporous carbon material with tunable pore sizes, a high surface area, good conductivity, and scalability [5]. Here, N doping of the NCS was achieved by heat treatment in NH3. An in house flow cell that can be switched between flow-through and flow-by modes was developed, allowing the NCS to be used as a model material to understand the impact of fluid flow on mass transfer limitations in the CO2RR and on any local pH effects that may be present. The CO2RR performance was tested in the flow cell using a CO2-saturated KHCO3 solution. The bare NCS was confirmed to generated only H2, while the N-doped NCS gives roughly a 50:50 ratio of H2:CO at all potentials, with the onset potential being ca. -0.55 V vs RHE. The effect of the NCS pore size was also investigated, showing that an NCS membrane with a nominal 85 nm pore diameter produced roughly 45% CO, while the NCS-12 (12 nm pore size) material gave somewhat more CO (ca. 55-60%). At the same time, the NCS-12 gave lower current densities, despite its higher surface area, likely due to poorer pore accessibility. Furthermore, running the cell in the flow-through mode gave higher currents at all of the NCS-based catalysts, most likely due to removal of trapped gases. Current work is focused on determining the effect of the N content and the type of N-based functionalities attached to the NCS surface on the CO2RR performance. References [1] Ji, Yan, et al. “Plasma-regulated N-doped carbon nanotube arrays for efficient electrosynthesis of syngas with a wide CO/H2 ratio.” Science China Materials 63.11 (2020): 2351-2357. [2] Liu, Weiqi, et al. “Utilizing spatial confinement effect of N atoms in micropores of coal-based metal-free material for efficiently electrochemical reduction of carbon dioxide.” Applied Catalysis B: Environmental 272 (2020): 118974. [3] Gao, Kun, et al. "Efficient metal‐free electrocatalysts from N‐doped carbon nanomaterials: mono‐doping and co‐doping." Advanced Materials 31.13 (2019): 1805121. [4] Duan, Xiaochuan, et al. "Metal‐free carbon materials for CO2 electrochemical reduction." Advanced Materials 29.41 (2017): 1701784. [5] Atwa, Marwa, et al. "Scalable nanoporous carbon films allow line-of-sight 3D atomic layer deposition of Pt: towards a new generation catalyst layer for PEM fuel cells." Materials Horizons 8.9 (2021): 2451-2462.

Abstract An in vitro model of intestine epithelium with an immune compartment was bioengineered to mimic immunologic responses seen in inflammatory bowel disease [1]. While aspects of intestinal immunity can be modeled in transwells and 2D culture systems, 3D tissue models improve physiological relevance by providing a 3D substrate which enable migration of macrophages towards the epithelium. An intestinal epithelium comprised of non-transformed human colon organoid cells and a subepithelial layer laden with monocyte-derived macrophages was bioengineered to mimic native intestinal mucosa cell organization using spongy silk scaffolds. Confluent epithelial monolayers with microvilli, a mucus layer, and infiltration of macrophages to the basal side of the epithelium were observed. Inflammation, induced by E. coli O111:B4 lipopolysaccharide and interferon γ resulted in morphology changes to the epithelium, resulting in ball-like structures, decreased epithelial coverage, and migration of macrophages to the epithelium. Analysis of cytokines present in the inflamed tissue model demonstrated significantly upregulated secretion of pro-inflammatory cytokines associated with active inflammatory bowel disease, including CXCL10, IL-1β, IL-6, MCP-2, and MIP-1β. The macrophage layer enhanced epithelial and biochemical responses to inflammatory stimuli, and this new tissue system may be useful to study and develop potential therapies for inflammatory bowel disease. References: 6 Roh, T.T., et al., 3D bioengineered tissue model of the large intestine to study inflammatory bowel disease. Biomaterials, 2019: p. 119517. 7 In, J., et al., Enterohemorrhagic Escherichia coli reduce mucus and intermicrovillar bridges in human stem cell-derived colonoids. Cellular and molecular gastroenterology and hepatology, 2015. 2(1): p. 48–62.e3. 8 Chen, Y., et al., In vitro enteroid-derived three-dimensional tissue model of human small intestinal epithelium with innate immune responses. PLoS ONE, 2017. 12(11): p. e0187880. Colonoid and macrophage cultivation scheme in the 3D bilayer system. (A) Human monocytes were isolated from whole blood and human colonoids from large intestine biopsies were cultured according to established protocols [2]. (B) Cell suspensions of colonoids were seeded on the film surface on the inner silk scaffold and monocyte-derived macrophages were seeded throughout the porous outer silk scaffold using established protocols [3]. (C) The model is cultured for 3 weeks total with 2 weeks in High WNT media and 1 week in differentiation media based on established protocol. Colonoids are present in the model throughout the 3 week culture time. 2 sets of macrophages are added with the first set added after the first week of culture and the second set replacing the first set after the second week.

Semi-artificial photosynthesis interfaces biological catalysts with synthetic materials such as electrodes or light absorbers to overcome limitations in natural and artificial photosynthesis. The benefit of using biocatalysts in electrocatalytic CO2 reduction is their electrochemical reversibility that enables their operation at very low overpotentials with high selectivity. This presentation will summarise my research group’s progress in integrating the CO2 reducing enzyme formate dehydrogenase into bespoke hierarchical 3D electrode scaffolds and the exploitation in solar-powered catalysis. I will present the electrochemical features and characterisation of the biocatalyst-material interface and provide my team's understanding of the electrochemical properties of the immobilised formate dehydrogenase. This insight allows the wiring of the biocatalyst into electrocatalytic schemes, photoelectrochemical devices and photocatalytic systems for unique CO2 utilisation reactions. The fundamental insights gained by integrating isolated formate dehydrogenase in electrodes will be presented and the case be made that this enzyme allows opening a solar-to-chemical conversion space that is currently not accessible with purly synthetic or biological catalysts (see uploaded Image as example). Recent publications: (1) Lam et al., Angew. Chem. Int. Ed., 2023, in print. (2) Bhattacharjee et al., Nat. Synth., 2023, 2, 182-92. (3) Badiani et al., J. Am. Chem. Soc., 2022, 144, 14207-16. (4) Cobb et al., Nat. Chem., 2022, 14, 417-24. (5) Edwardes Moore et al., Proc. Natl. Acad. Sci. USA, 2022, 119, e2114097199. (6) Anton Garcia et al., Nat. Synth. 2022, 1, 77-86. Reviews: (1) Fang et al., Chem. Soc. Rev., 2020, 49, 4926–52. (2) Zhang & Reisner, Nature Rev. Chem., 2020, 4, 6–21. (3) Kornienko et al., Acc. Chem. Res., 2019, 52, 1439–44. (4) Kornienko et al., Nature Nanotech., 2018, 13, 890–99

20007 Background: Allo SCT may benefit patients with R/R HD by providing a graft vs lymphoma effect. Peggs et al (Lancet 2005) demonstrated durable engraftment and reduced non relapse mortality (NRM) in HD pts post RI Allo SCT. Carella et al (JCO2000) and Gutman et al (BMT2005) demonstrated the success of MA Auto SCT followed by RI AlloSCT in adults with refractory lymphoma. We investigated the feasibility of MA Auto SCT followed by RI Allo SCT in children with R/R HD. Methods: MA conditioning prior to AutoSCT was CTX 1,500 mg/m2 x 4 d, BCNU 100 mg/m2 x 3d, VP-16 800 mg/m2 x 3d. AlloSCT conditioning was fludarabine 30 mg/m2 x 5d, busulfan 3.2 mg/kg x 2d, and R ATG 2 mg/kg x 4d (unrel. donor). CD20+ patients received rituximab (375 mg/m2/wk x4) and all pts received involved field radiotherapy (IFRT). Results: Ten pts have enrolled, 2 pts did not proceed (parental withdrawal) to RI AlloSCT (Donors: 1 MRD, 2 MUD, 5 UCB). Median time to RI AlloSCT after MA Auto SCT was 142 d (97–219). The median cell dose was 3.43 x 107 TNC/kg for UCB grafts (n=5). Engraftment was achieved at a median of 20.5 d for PMN and 46.5 d for PLT. Donor chimerism reached ≥ 95% in all pts by day 100 with a median follow up of 703d (128–2025). Toxicities were grade (3) hematuria (n=1), (3–4) infection (n=7), (4) pulmonary fibrosis (n=1), (4) hearing loss (n=1), (4) neurotoxicity (n=1). GVHD: grade II-III aGVHD (3/8), cGVHD (3/8). Six patients are alive and NED post allo SCT. There has been one NRM (cGVHD) and one relapse mortality. The OS at one year is 66.7%. Conclusions: MA AutoSCT followed by RI AlloSCT is feasible and well tolerated in pediatric pts with R/R HD. A larger study with longer follow up is required to determine if this approach will reduce relapse, long term toxicity and/or improve survival. No significant financial relationships to disclose.

BIM diketahui memiliki banyak manfaat yang dapat mempermudah pekerjaan perencanaan maupun evaluasi dari suatu proyek konstruksi. Manfaat ini dapat memberikan pandangan yang menyeluruh untuk membantu klien maupun pemilik proyek sebelum melakukan tahapan pelaksanaan untuk mengurangi risiko yang akan terjadi. Penggunaan BIM dapat membuat pekerjaan lebih efisien. Salah satu upaya pemerintah untuk mensosialisasikan penggunaan BIM yaitu dengan menerapkan BIM sebagai kompetensi keahlian di tingkat SMK. Hal ini untuk meningkatkan jumlah tenaga kerja yang telah paham mengenai konsep BIM. Zhabrinna, et, al (2018) menyatakan jumlah tenaga ahli di Indonesia yang berkompeten dalam menerapkan BIM masih terbilang rendah. Tujuan makalah ini adalah mengkaji pembelajaran BIM di Perguruan Tinggi. Penelitian ini mengambil pembelajaran BIM di tingkat Program Studi Teknik Sipil Universitas Kristen Maranatha sebagai studi kasus. Pembelajaran BIM (3D) di Teknik Sipil Universitas Kristen Maranatha dilakukan pada 2 matakuliah CE214-Komputer Grafis&Struktur Bangunan 1 dan 2. Pembelajaran BIM (4D) dilakukan pada matakuliah CE600- Manajemen Proyek. Pembelajaran BIM (5D) dilakukan pada 2 matakuliah CE600- Manajemen Proyek dan CE832-Introduction Buliding Information Modelling. Pembelajaran BIM di tingkat perguruan tinggi di Indonesia sangatlah dibutuhkan untuk memenuhi permintaan dunia konstruksi di era industri 4.0. Teknik Sipil Universitas Kristen Maranatha sudah memulai untuk mengintegrasikan proses pembelajaran BIM ke dalam beberapa mata kuliah dapat dinilai baik karena dibuktikan dengan angka keberhasilan yang cukup tinggi pada saat mahasiswa mengambil ujian sertifikasi.

11521 Background: Cancer testis antigen NY-ESO-1 is expressed in multiple tumor types, including 80‒90% of MRCLS [1,2]. Overall response rates (ORRs) to MRCLS treatment are low (1L, <20%; 2L, <10%) [2]. Lete-cel, an autologous T-cell therapy, targets NY-ESO-1/LAGE-1a+ tumors using a genetically modified, high-affinity T-cell receptor. High-dose lymphodepletion (LD) was linked with better responses in synovial sarcoma [3]; the current study tested this hypothesis in MRCLS. Methods: This open label, pilot study evaluates lete-cel efficacy and safety in advanced MRCLS following low-dose (Cohort 1 [C1]; 30 mg/m2 fludarabine [flu] x 3d + 600 mg/m2 cyclophosphamide [cy] x 3d) or high-dose (Cohort 2 [C2]; 30 mg/m2 flu x 4d + 900 mg/m2 cy x 3d; initiated based on C1 data) LD. Key eligibility: age ≥18 y; HLA-A*02:01; A*02:05, or A*02:06; advanced high-grade NY-ESO-1+ MRCLS (≥30% of cells 2+/3+ by IHC); prior anthracycline; measurable disease; specified washouts; and active/chronic/intercurrent illness restrictions. Stages include screening, leukapheresis, lete-cel manufacture, LD, lete-cel infusion (1– 8 × 109 transduced T cells), follow-up. Response is assessed at wk 4, 8, 12, and 24, then every 3 mo to disease progression/death/withdrawal. The primary efficacy endpoint is investigator-assessed ORR by RECIST v1.1. In C1 (n=10 patients [pts]), lete-cel was well tolerated and linked with 2 confirmed partial responses (PR; ORR, 20%) and stable disease (SD) in 8 pts. Planned interim analysis for C2, shown here, was done once all 10 treated pts had ≥3 post-baseline disease assessments or progressed/died/withdrew. Efficacy data will be correlated with transduced cell kinetics and pharmacodynamics marker profiles. Results: Durable (1.0–7.8 mo) PR (4/10 pts [ORR, 40%]; 2 ongoing) and prolonged (2.7–10.6 mo) SD (5/10 pts; 3 ongoing) with tumor regression were observed. Treatment-emergent cytopenias occurred in all pts. All experienced T-cell related cytokine release syndrome (5 serious adverse events; 30% Grade 3), with onset ≤5d of infusion and median duration 7.5d. Graft-vs-host disease, immune effector cell–associated neurotoxicity syndrome, pancytopenia, or aplastic anemia were not reported. Conclusions: A single lete-cel infusion after high LD showed antitumor activity in advanced MRCLS and a manageable safety profile consistent with other lete-cel studies. The trial is active but no longer recruiting (NCT02992743). MRCLS is included in a separate, ongoing lete-cel study (NCT03967223). References: 1. D’Angelo SP, et al. J Clin Oncol 2018;36:15_suppl, 3005. 2. Pollack SM, et al. Cancer Med 2020;9(13):4593–602. 3. D’Angelo SP, et al. J Immunother Cancer 2020;8:P298. Funding: GSK (208469; NCT02992743). Editorial support was provided by Eithne Maguire, PhD, of Fishawack Indicia, part of Fishawack Health, and funded by GSK. Clinical trial information: NCT02992743.

INTRODUCTION. Primary chronic lymphocytic leukemia (CLL) cells, despite originating from a proliferative disease, rapidly undergo apoptosis in vitro in absence of microenvironmental survival signals1. Although co-culture with stromal cells or the addition of soluble factors can increase and extend CLL survival, no system permits the long-term expansion of CLL cells in vitro2. The difficulties of mimicking a physiologic microenvironment supporting CLL cells hinder in vitro studies of proliferation, drug screens and prevent propagation of rare subclones. For other cancers, various types of 3D cultures have been introduced utilizing scaffolds, gels, spheroid cultures and fluidic systems, representing a more accurate representation of the in vivo microenvironment3. Unlike solid tumors, secondary lymphoid tissues where CLL cells proliferate in vivo, do not derive from a single stem cell progenitor. Developing an appropriate 3D in vitro culture system for CLL is of obvious importance and may contribute pathophysiological relevance to study long-term CLL proliferation and more accurate drug screening4,5. Within the field of CLL, attempts have focused on bone marrow stroma, but it may be biologically and clinically more relevant to investigate the lymph node niche as this is the critical site of CLL proliferation6. METHODS. Primary CLL cells were cultured in various 3D systems including hydrogels, hanging drop cultures and ultra-low attachment plates (ULA) plates in parallel to an optimal 2D system, consisting of the culture of primary CLL cells on a monolayer of CD40L-presenting fibroblasts (3T40) or 3T3 negative control fibroblasts. CLL cells were either cultured as PBMCs alone, with or without T cells, or co-cultured with 3T40 or primary lymph node fibroblasts. CLL cells were either stimulated directly with IL-2, IL-15, IL-21 and CpG and/or indirectly via a T cell stimulation of anti-CD3/CD28. RESULTS. After testing and comparing multiple systems for the in vitro culture of CLL cells, we optimized a novel CLL culture system utilizing ULA plates creating spheroids of PBMCs isolated from peripheral blood. Without the addition of soluble factors or stroma, primary CLL cells in the ULA 3D model could be maintained in culture for 6 weeks as opposed to 1 week in the 2D system. Aside from significantly promoting CLL survival, cultures could be expanded approximately 3-4-fold over a course of 6 weeks using the ULA 3D model. 3D cultures showed a more consistent and significantly increased CLL proliferation compared to 2D cultures, independent of IGHV mutation status, increasing the average proliferation index of 2.87 to 3.90 (n=10). Additionally, co-culture with LN-derived stromal cells further increased CLL proliferation, reaching a maximum of 8 generations (n=6) (Figure 1). Lastly, when PBMCs were stimulated with IL-2, IL-15, IL-21 and CpG, spheroids developed proliferation center-like structures after 4 weeks of culture. CONCLUSIONS. We established a lymph node-based 3D in vitro culture system for CLL leading to increased CLL proliferation and survival compared to 2D systems. The set-up allows long-term expansion of CLL cells in vitro, as well as formation of proliferation center-like structures. We are currently optimizing drug resistance studies, expansion of specific CLL subclones and performing competition experiments. References: 1. Hamilton et al., Mimicking the tumour microenvironment: three different co-culture systems induce a similar phenotype but distinct proliferative signals in primary chronic lymphocytic leukaemia cells, 2012. 2. Asslaber et al., Mimicking the microenvironment in chronic lymphocytic leukaemia - where does the journey go?, 2013. 3. Gurski et al., 3D Matrices for Anti-Cancer Drug Testing and Development, 2010. 4. Nunes et al., 3D tumor spheroids as in vitro models to mimic in vivo human solid tumors resistance to therapeutic drugs, 2019. 5. Aljitwai et al., A novel three-dimensional stromal-based model for in vitro chemotherapy sensitivity testing of leukemia cells, 2014. 6. Van Gent et al., In vivo dynamics of stable chronic lymphocytic leukemia inversely correlates with somatic hypermutation levels and suggest no major leukemic turnover in bone marrow, 2008. Disclosures Kater: Genentech: Research Funding; Abbvie: Research Funding; Roche: Research Funding; Janssen: Research Funding; Celgene: Research Funding. Eldering:Celgene: Research Funding; Janssen: Research Funding; Genentech: Research Funding.

Afin de beneficier de la continuite laterale des evenements sismiques dans les collections de traces avant sommation une technique de pointe avant sommation des reflexions est elaboree. La construction des collections de traces en eventail d'azimuts et en intervalle d'offsets permet de pointer une reflexion a travers les lignes d'enregistrement d'un tir. Le pointe est propage d'un tir a l'autre utilisant les geophones communs. La projection en position de point milieu des pointes et l'application des corrections dynamiques conduisent au pointe a offset nul de la reflexion 3d choisie et a la selection des traces ou cette reflexion est observee. L'observation des reflexions sur la base de la croute par ce procede aboutit a un pointe avant sommation du moho et a un stack n'utilisant que les enregistrements contenant une information visible relative a la base de la croute. Le volume de stack avec des bins 5050 m obtenu permet de suivre les reflexions sans ambiguite et rend possible l'elaboration et l'application d'une technique d'extraction automatique des reflexions basees sur la detection de leur correlation 3d. Un pointe systematique des reflexions 3d suivi d'une migration 3d du pointe fournissent la construction d'une esquisse structurale dans un volume de 401030 km. Du nord au sud on suit le plan du chevauchement frontal nord pyreneen. La base de la croute se trouve a 30 km de profondeur

Description des phases du titre selon un modele cristallochimique qui utilise la notion de site et d'insertion dans un reseau de metalloides. Cette description fait apparaitre des elements de comparaison entre differentes structures et permet une recherche organisee de nouvelles phases par substitution ou bien construction a partir de motifs predefinis. Parallelement a la mise en evidence des divers avantages de ce modele (prospectives importantes et etudes comparatives des proprietes physiques), on donne des exemples de syntheses de nouveaux produits et on aborde l'etude de leurs proprietes physiques