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This paper deals with the analysis of TRIP steel HCT690 deformation behaviour. The mechanical properties and deformation characteristics of the tested material are determined using selected material tests and tests that consider the required stress states used to define the yield criterion boundary condition and subsequent deformation behaviour in the region of severe plastic deformation. The measured data are subsequently implemented in the numerical simulation of sheet metal forming, where they are used as input data for the computational process in the form of a selected material model defining the yield criterion boundary and, furthermore, the material hardening law during deformation of the material. The chosen numerical simulation process corresponds to the sheet metal forming process, including the subsequent spring-back of the material, when the force does not affect the material. Furthermore, the influence of the chosen computational model and selected process parameters on the deformation and spring-back process of the material is evaluated. In addition to that, at the end of the paper, the results from the numerical simulation are compared with experimentally produced sheet stamping.
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The nickel-iron-based alloy Inconel 718 is a progressive material with very good mechanical properties at elevated and lower temperatures. It is used both as wrought and cast alloys as well as material for additive manufacturing technologies. This is the reason why it has received so much attention, as supported by numerous publications. However, these are almost exclusively focused on a specific type of production and processing, and thus only report differences in the mechanical properties between samples prepared by different technologies. Therefore, the major aim of this research was to show how the structure and mechanical properties differ between samples produced by conventional production (wrought alloy) and additively manufactured SLM (Selective Laser Melting). It is shown that by applying appropriate heat treatment, similar strength properties at room and elevated temperatures can be achieved for SLM samples as for wrought samples. In addition, the mechanical properties are also tested up to a temperature of 900 °C, in contrast to the results published so far. Furthermore, it is proven that the microstructures of the wrought (here rolled) and SLM alloys differ significantly both in terms of grain shape and the size and distribution of precipitates.
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Gene expression is a fundamental process that enables cells to produce specific proteins in a timely and spatially dependent manner. In eukaryotic cells, the complex organization of the cell body requires precise control of protein synthesis and localization. Certain mRNAs encode proteins with an N-terminal signal sequences that direct the translation apparatus toward a specific organelle. Here, we focus on the mechanisms governing the translation of mRNAs, which encode proteins with an endoplasmic reticulum (ER) signal in human cells. The binding of a signal-recognition particle (SRP) to the translation machinery halts protein synthesis until the mRNA-ribosome complex reaches the ER membrane. The commonly accepted model suggests that mRNA that encodes a protein that contains an ER signal peptide continuously repeats the cycle of SRP binding followed by association and dissociation with the ER. In contrast to the current view, we show that the long mRNAs remain on the ER while being translated. On the other hand, due to low ribosome occupancy, the short mRNAs continue the cycle, always facing a translation pause. Ultimately, this leads to a significant drop in the translation efficiency of small, ER-targeted proteins. The proposed mechanism advances our understanding of selective protein synthesis in eukaryotic cells and provides new avenues to enhance protein production in biotechnological settings.
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Concerning the increasingly widespread utilization of the finite element method (FEM), the concept of the so-called virtual factory is also gaining ground, and not only in the engineering industry. This approach does not use numerical simulations of individual production technologies separately but treats the entire production process as a chain of interrelated technologies. Thus, the output data from one technology is taken as input data for the following technology. The resulting thermal and mechanical effects are then not only dealt with within one technology but always comprehensively within the production process. In the consideration of the loading and subsequent service lives of manufactured components, values of residual stresses are one of the very important characteristics. For these reasons, this paper deals with the effect of residual stresses' magnitude and distribution during the formation and the final springback of the seamed pipe end section with and without respect to the influence of the preceding welding. The resulting residual stress values from numerical simulations are subsequently compared with the actual values of residual stresses experimentally measured using X-ray diffraction.
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The t(8;21)(q22;q22) is one of the most common chromosomal abnormalities in acute myeloid leukemia (AML). Approximately 3-4% of AML cases are associated with additional chromosomal abnormalities. Their impact on the prognosis of the disease remains to be established. Here we report a case of t(8;10;21) AML with mutated c-KIT that shared key morphological features with classical t(8;21) leukemias, including the M2 morphology pattern and CD34, HLA-DR phenotype. The 63-year-old female was treated with two inductioncontaining Daunoribicine and Cytarabine and four cycles of intermediate-dose Cytarabine (1.5 g/m2) and achieved long-lasting remission.
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This article deals with a comprehensive study of the processing and mechanical properties of the ceramic material Al2O3 on Fused Filament Fabrication technology (FFF). It describes the basic input analyses of the material, such as TGA, FTIR, and MVR. These analyses enabled the design and testing of process parameters for the 3D printing of parts. The article also presents the post-processes, including the technological parameters required to finalize parts made from this material, i.e., chemical debinding in acetone at elevated temperatures + thermal debinding and sintering. The microhardness was measured on the processed samples, depending on the density of the inner filling. The resulting hardness had an almost linear relationship between the percentage of filler (20-40-60-80-100%) and the resulting microhardness (1382-2428 HV10). Flexural strength was also measured on the test specimens with different degrees of internal filling (80-90-100%). However, inner filling do not affect the flexural strength (316.12-327.84-331.61 MPa). The relative density of the final parts was measured on a ZEISS METROTOM 1500 CT machine and reached 99.54%.
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Dual phase steels combine very good corrosion resistance with relatively high values of mechanical properties. In addition, they can maintain good plastic properties and toughness at both room temperature and lower temperatures as well. Despite all the advantages mentioned above, their utility properties can be reduced by technological processing, especially by the application of the temperature cycles. As a result, in the material remain residual stresses with local stress peaks, which are quite problematic especially during cyclic loading. Moreover, determining the level and especially the distribution of such residual stresses is very difficult for duplex steels both due to the structure duality and in light of the very small width of the heat-affected zone (HAZ). This is why the paper presents the possibilities of using physical simulations to study the effect of temperature cycles in residual stresses' magnitude and distribution, where it is possible to study the HAZ in more detail as well as on a much larger sample width due to the utilization of special samples. In the thermal-mechanical simulator Gleeble 3500, temperature-stress cycles were applied to testing samples, generating stress fields with local peaks in the testing samples. In addition, the supplied steel X2CrMnNiN21-5-1 had different phase rations in the individual directions. Therefore, as the residual stresses were measured in several directions and at the same time, it was possible to safely confirm the suitability of the used measurement method. Moreover, the effect of the stress and strain on the change of partial phases' ratios was observed. It has been experimentally confirmed that annealing temperatures of at least 700 °C are required to eliminate local stress peaks after welding. However, an annealing temperature of 550 °C seems to be optimal to maintain sufficient mechanical properties.
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The paper deals with research related to the production of metal cellular aluminium systems, in which production is based on the application of sodium chloride particles. In this paper, the properties of porous aluminium materials that were produced by an unconventional method-by pressing salt particles into the melt of aluminium alloy-are described. The new methodology was developed and verified for the production of these materials. The main feature of this methodology is a hydraulic forming press and a simple-shaped foundry mould. For these purposes, four different groups of sodium chloride particle sizes (1 to 3, 3 to 5, 5 to 7 and 8 to 10 mm) were applied. The preferred aluminium foundry alloy (AlSi12) was used to produce the porous aluminium samples. Based upon this developed methodology, samples of porous aluminium materials were produced and analysed. Their weight and volume were monitored, their density and relative density were calculated, and their porosity was determined. In addition, the porosity of samples and continuity of their air cells were monitored as well. An industrial computed tomograph and a scanning electron microscope were applied for these purposes.
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Cellular immunotherapy is becoming a new pillar in cancer treatment after recent striking results in different clinical trials with chimeric antigen receptor T cells. However, this innovative therapy is not exempt from challenges such as off-tumor toxicity, tumor recurrence in heterogeneous tumors, and affordability. To surpass these limitations, we exploit the unique anti-tumor characteristics of natural killer (NK) cells. In this study, we aimed to obtain a clinically relevant number of allogeneic NK cells derived from peripheral blood (median of 14,050 million cells from a single donor) to target a broad spectrum of solid and liquid tumor types. To boost their anti-tumor activity, we combined allogeneic NK cells with the approved anti-cluster of differentiation 38 (CD-38) monoclonal antibody Daratumumab to obtain a synergistic therapeutic effect against incurable multiple myeloma. The combination therapy was refined with CD16 polymorphism donor selection and uncomplicated novel in vitro pretreatment to avoid undesired fratricide, increasing the in vitro therapeutic effect against the CD-38 positive multiple myeloma cell line by more than 20%. Time-lapse imaging of mice with established human multiple myeloma xenografts revealed that combination therapy of selected and pretreated NK cells with Daratumumab presented tumor volumes 43-fold smaller than control ones. Combination therapy with an allogeneic source of fully functional NK cells could be beneficial in future clinical settings to circumvent monoclonal antibodies' low therapeutic efficiency due to NK cell dysfunctionality in MM patients.
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Anticuerpos Monoclonales/farmacología , Antineoplásicos Inmunológicos/farmacología , Tratamiento Basado en Trasplante de Células y Tejidos/métodos , Inmunoterapia/métodos , Células Asesinas Naturales/inmunología , Mieloma Múltiple/tratamiento farmacológico , Animales , Estudios de Casos y Controles , Línea Celular Tumoral , Femenino , Humanos , Ratones , Ratones SCIDRESUMEN
To identify cytogenetic features of large cell transformation in mycosis fungoides (T-MF), we selected in 11 patients, 16 samples either from skin tumors (13), lymph node (1), or peripheral blood cells (2) collected at the time of the transformation. Comparative genomic hybridization (CGH), G-banding, fluorescence in situ hybridisation (FISH), multicolour FISH (mFISH), and DNA content analysis were used. Fifteen samples displayed unbalanced CGH profiles, with gains more frequently observed than losses. Recurrent chromosomal alterations were observed for chromosomes 1, 2, 7, 9, 17, and 19. The most common imbalances were gain of chromosome regions 1p36, 7, 9q34, 17q24-qter, 19, and loss of 2q36-qter, 9p21, and 17p. In six samples 1p36-pter gain was associated with 9q34-qter gain and whole chromosome 19 gain. In five of these samples whole or partial gain of chromosome 17 was also observed. No specific pattern was seen with regard to the expression of the CD30 antigen by tumor cells. Cytogenetics and/or DNA content analysis of skin tumor cells revealed an abnormal chromosome number in all tested cases (n = 7) with DNA ploidy ranging from hyperdiploid (2.78) to hypotetraploid (3.69) (mean 3.14+/-0.38). Thus, T-MF displayed frequent chromosomal imbalances associated with hypotetraploidy.
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Transformación Celular Neoplásica , Aberraciones Cromosómicas , Cromosomas Humanos , Micosis Fungoide/genética , Neoplasias Cutáneas/genética , Adulto , Anciano , Anciano de 80 o más Años , Células Sanguíneas/metabolismo , Células Cultivadas , Femenino , Humanos , Hibridación Fluorescente in Situ/métodos , Ganglios Linfáticos/metabolismo , Ganglios Linfáticos/patología , Masculino , Persona de Mediana Edad , Micosis Fungoide/patología , Hibridación de Ácido Nucleico/métodos , Poliploidía , Neoplasias Cutáneas/patologíaRESUMEN
Little is known about the molecular or cytogenetic alterations of mycosis fungoides (MF) large cell transformation. We report our findings on chromosomal rearrangement, based on peripheral blood and skin examination before and after cutaneous MF large cell transformation, using both conventional and molecular cytogenetic techniques. Blood cells exhibited a similar hypodiploid karyotype before and after MF transformation. A near-tetraploid karyotype with complex structural rearrangements was established from a skin tumor after MF large cell transformation. Both recurrent chromosome abnormalities and an identical T-cell receptor gamma-chain rearrangement were shared by blood and skin cells, suggesting that MF large cell transformation derived from a common monoclonal ancestor detected at MF stage. A complex hypotetraploid karyotype was established only from the skin tumor, however. MF large cell transformation may be associated with chromosome duplication followed by chromosome losses and interchromosomal rearrangements. Accordingly, additional parallel blood and skin tumor cytogenetic studies are required to further identify the recurrent cytogenetic changes associated with the aggressiveness of the disease after large cell transformation.
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Transformación Celular Neoplásica , Micosis Fungoide/genética , Poliploidía , Neoplasias Cutáneas/genética , Anciano , Carcinoma de Células Grandes/genética , Carcinoma de Células Grandes/patología , Bandeo Cromosómico , Femenino , Humanos , Hibridación Fluorescente in Situ , Micosis Fungoide/patología , Hibridación de Ácido Nucleico , Piel/patología , Neoplasias Cutáneas/patologíaRESUMEN
Primary cutaneous CD30+ large T-cell lymphoma (CD30+ CTCL) is a subset of non-epidermotropic primary cutaneous T-cell lymphoma. Although frequent spontaneous regression may be observed, skin relapses occur frequently. Cytogenetic abnormalities that could play a role in CD30+ CTCL tumour pathogenesis and relapses remain unknown. The identification of recurrent cytogenetic abnormalities is hampered by difficulty in culturing tumours and the lack of CD30+ CTCL serial studies comparing genetic changes both at diagnosis and at relapse. The purpose of this study was to investigate the cytogenetic abnormalities present in a series of 13 CD30+ CTCL samples obtained from nine patients fulfilling both EORTC and WHO diagnostic criteria, by the use of comparative genomic hybridization (CGH). CGH analysis revealed a non-random distribution of genetic imbalances between relapsing and non-relapsing disease. In relapsing disease, chromosomal abnormalities were detected both in the primary tumour and in relapses. The mean number of changes in non-relapsing disease was 0.33 (range 0-1), compared with 6.29 (range 1-16) in relapsing disease. The recurrent chromosomes involved in relapsing disease were chromosomes 6 (86%), 9 (86%), and 18 (43%). While chromosome 9 was mostly affected by gain, chromosomes 6 and 18 mainly contained regions of loss, exclusively on 6q and 18p. The common regions of deletion were 6q21 and 18p11.3. In one patient, we successfully cultured tumour cells from a skin biopsy from a second relapse. The G-banded karyotype was concordant with both CGH and fluorescence in situ hybridization (FISH) results. Although further studies are required to strengthen these data, this CGH analysis demonstrates chromosomal imbalances that may be involved in the pathogenesis of relapsing CD30+ CTCL.