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The present study focused on comparing the gene expression profiles of different mouse models of prostate cancer, focusing on the TRAMP transgenic model and its derived cell lines and extending the comparisons to relevant genetically engineered mouse models and human prostate cancer datasets. Employing RNA sequencing, we examined different levels of prostate cancer aggressiveness from the original TRAMP cells to the TRAMP-C2 (TC2) derived cell line and extending to the aggressive TC2-Ras (TC2R) cells and tumors. TC2R acquire the ability to grow in bone tissue upon implantation, unlike the parental TC2 cells. Analysis identified upregulated genes in cell cycle regulation, immune response, and mitotic processes in TRAMP compared to wild-type tissues. TC2 cells exhibited unique gene profiles enriched in ECM organization and tissue development pathways, while TC2R cells showed increased cytokine signaling and motility genes, with decreased ECM and immune response pathways. In vivo TC2R models demonstrated enhanced ECM organization and receptor tyrosine kinase signaling in tumors, notably enriching immune processes and collagen degradation pathways in intratibial tumors. Comparative analysis among mouse and human datasets showed overlaps, particularly in pathways relating to mitotic cycle regulation, ECM organization, and immune interactions. A gene signature identified in TC2R tumors correlated with aggressive tumor behavior and poor survival in human datasets. Further immune cell landscape analysis of TC2R tumors revealed altered T cell subsets and macrophages, confirmed in single-cell RNA-seq from human samples. TC2R models thus hold significant promise in helping advance preclinical therapeutics, potentially contributing to improved prostate cancer patient outcomes.

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The number of known alien ant species throughout Europe has been steadily increasing during the last few decades and Italy has been no exception, with four new taxa reported in the last five years. Here, we document new data on the Asian needle ant Brachyponerachinensis (Emery, 1895), an invasive alien species whose first establishment in Europe was detected in the southern Italian city of Naples in 2022 and which has now been found near Lake Como in northern Italy, representing the second European record, about 730 km distant from the first. Furthermore, we report for the first time the presence of Nylanderiavividula (Nylander, 1846) in the country, based on specimens collected both in Rome and near Lake Como. This is at least the second Nylanderia species established in the country after N.jaegerskioeldi, first reported in 2018. Unlike B.chinensis, N.vividula is not considered an ecological and health threat in the invaded range and is already known to occur in several other European countries. While only a few introduced ants in Europe are considered serious ecological, economic or health threats, the increasing circulation of several alien species and the poor ability to swiftly track their movements and detect their establishment can render management very difficult.

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Background: Tempol is a redox-cycling nitroxide considered a potent antioxidant. The present study investigated the tempol effects on oxidative stress and mitochondrial markers on prostate cancer (PCa). Methods: PC-3 and LnCaP cells were exposed to tempol. Cell viability test, western blot and Amplex Red analyses were performed. In vivo, five experimental groups evaluated tempol effects in the early (CT12 and TPL12 groups) and late stages (CT20, TPL20-I, and TLP20-II) of PCa development. The TPL groups were treated with 50 or 100 mg/kg tempol doses. Control groups received water as the vehicle. The ventral lobe of the prostate and the blood were collected and submitted to western blotting or enzymatic activity analyses. Results: In vitro, tempol decreased cell viability and differentially altered the H2O2 content for PC-3 and LNCaP. Tempol increased SOD2 levels in both cell lines and did not alter Catalase protein levels. In vivo, tempol increased SOD2 levels in the early stage and did not change Catalase levels in the different PCa stages. Systemically, tempol decreased SOD2 levels in the late-stage and improved redox status in the early and late stages, which was confirmed by reduced LDH in tempol groups. Alterations on energetic metabolism and oxidative phosphorylation were observed in TRAMP model. Conclusion: Tempol can be considered a beneficial therapy for PCa treatment considering its antioxidant and low toxicity properties, however the PCa progression must be evaluated to get successful therapy.

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Prostate cancer (PCa) is the second cause of cancer death among men worldwide. Several processes are involved in the development and progression of PCa such as angiogenesis, inflammation and oxidative stress. The present study investigated the effect of short- or long-term Tempol treatment at different stages of prostate adenocarcinoma progression, focusing on angiogenic, proliferative, and stromal remodeling processes in TRAMP mice. The dorsolateral lobe of the prostate of TRAMP mice were evaluated at two different stages of PCa progression; early and late stages. Early stage was again divided into, short- or long-term. 50 mg/kg Tempol dose was administered orally. The results demonstrated that Tempol mitigated the prostate histopathological lesion progressions in the TRAMP mice in all treated groups. However, Tempol increased molecules involved in the angiogenic process such as CD31 and VEGFR2 relative frequencies, particularly in long-term treatment. In addition, Tempol upregulated molecule levels involved in angiogenesis and stromal remodeling process VEGF, TGF-ß1, VE-cadherin and vimentin, particularly, in T8-16 group. Thus, it was concluded that Tempol treatment delayed prostatic lesion progression in the dorsolateral lobe of the TRAMP mice. However, Tempol also led to pro-angiogenic effects and glandular stromal microenvironment imbalance, especially, in the long-term treatment.

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Anthropogenic disturbances and seasonal changes significantly impact diversity and community composition of ants, but their effects are often intertwined. We investigated these drivers on Lang Tengah Island, a location with a pronounced monsoon season and three resorts that close during this period. We surveyed four sites, two disturbed and two undisturbed, before and after the monsoon season, using pitfall traps to sample epigaeic ant communities. Undisturbed habitats had higher species diversity, but both habitats (undisturbed and disturbed sites) have a high proportion of ants with characteristics of being encroached by generalist and invasive/tramp ant species. Post-monsoon sampling yielded an increase in species richness and diversity. Seasonal changes, such as monsoonal rains, can temporarily alter ant interactions and resource distribution, potentially maintaining diversity. Future studies should validate these findings for ant communities under similar pressures, using ant composition and functional roles for conservation and management purposes.

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The little fire ant (LFA), Wasmannia auropunctata, is a serious invasive pest first reported on Hawaii Island in 1999, and has since spread and established itself across the island. LFA is considered one of the worst 100 invasive species and has significant ecological, agricultural, and public health impacts in invaded areas, which include much of the tropical New World. Although localized eradication efforts have proven successful, they are intensive and difficult to implement. Furthermore, LFA's high invasive-ability resists these control efforts in areas where the species is established and can re-infest treated areas. This research set out to determine whether LFA queens have a suppressant effect on new queen production in nests, as a first step in identifying a potential queen pheromone for LFA. A queen pheromone could offer a means to shutdown LFA reproductive capability, potentially by suppressing the production of new queens or inducing the execution of queens or queen-destined larvae. When queenless experimental nests and polygyne experimental nests were compared, six out of eight queenless nests successfully reared both new alate queens (2.25 queens/nest) and drones (3.63 drones/nest) to adulthood, whereas only three of eight polygyne nests reared sexual larvae that failed to develop to adulthood or even the pupal stage. These results suggest that dealate mature LFA queens suppress the production of new alate queens in LFA nests, and is the first evidence that LFA may utilize a queen pheromone.

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Delayed cancer progression in the ventral prostate of the Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) model has been previously reported upon celecoxib and nintedanib co-administration. Herein, we sought to further investigate the effects of these drugs association in some of their direct molecular targets (COX-2, VEGF and VEGFR-2) and in reactive stroma markers (TGF-ß, αSMA, vimentin and pro-collagen 1) in the dorsolateral prostate, looking for lobe-specific responses. Male TRAMP mice were treated with celecoxib (10 mg/Kg, i.o.) and/or nintedanib (15 mg/Kg, i.o.) for 6 weeks and prostate was harvested for morphological and protein expression analyses. Results showed that combined therapy resulted in unique antitumor effects in dorsolateral prostate, especially due to the respective stromal or epithelial antiproliferative actions of these drugs, which altogether led to a complete inversion in high-grade (HGPIN) versus low-grade (LGPIN) premalignant lesion incidences in relation to controls. At the molecular level, this duality in drug action was paralleled by the differential down/upregulation of TGF-ß signaling by celecoxib/nintedanib, thus leading to associated changes in stroma composition towards regression or quiescence, respectively. Additionally, combined therapy was able to promote decreased expression of inflammatory (COX-2) and angiogenesis (VEGF/VEGFR-2) mediators. Overall, celecoxib and nintedanib association provided enhanced antitumor effects in TRAMP dorsolateral as compared to former registers in ventral prostate, thus demonstrating lobe-specific responses of this combined chemoprevention approach. Among these responses, we highlight the ability in promoting TGF-ß signaling and its associated stromal maturation/stabilization, thus yielding a more quiescent stromal milieu and resulting in greater epithelial proliferation impairment.

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Evaluating the aggressiveness of prostate cancer (PCa) is crucial for PCa diagnosis and prognosis. Previously, studies have shown that photoacoustic spectral analysis (PASA) can assess prostate tissue microarchitecture for evaluating the aggressiveness of PCa. In this study, in a transgenic mouse (TRAMP) model of PCa, we utilized methylene blue polyacrylamide nanoparticles (MB PAA NPs) to label the cancer cells in prostate in vivo. MB PAA NPs can specifically target proliferating cancer cells as a contrast agent, allowing photoacoustic (PA) imaging to better detect PCa tumors, and also assessing prostate glandular architecture. With the PA signals from the prostates measured simultaneously by a needle hydrophone and a PA and ultrasound (US) dual-imaging system, we conducted PASA and correlated the quantified spectral parameter slopes with the cancer grading from histopathology. The PASA results from 18 mice showed significant differences between normal and cancer, and also between low-score cancer and high-score cancer. This study in the clinically relevant TRAMP model of PCa demonstrated that PA imaging and PASA, powered by MB PAA NPs that can label the PCa microarchitectures in vivo after systemic administration, can detect PCa and, more importantly, evaluate cancer aggressiveness.

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The longlegged ant Anoplolepis gracilipes (Smith) is a highly invasive tramp ant species known for its deleterious effects on native ecosystems. While tramp ants are associated with human activity, information on how different intensities of human activity affect their distribution is limited. This study investigated how anthropogenic activities affected the distribution of A. gracilipes in Penang, a tropical island in northern peninsular Malaysia. Three study sites (Youth Park, Sungai Ara, and Bukit Jambul/Relau) were selected, containing four sub-locations corresponding to different levels of human activity (low, moderate, high, and very high), determined by the average number of passersby observed over 30 min. Baited index cards were placed at each sub-location to evaluate ant abundance and distribution. The results demonstrated that A. gracilipes worker abundance was highest in areas of moderate human activity, as opposed to areas with low and higher human activity. The low abundance of A. gracilipes in comparatively undisturbed localities may be attributed to unsuitable microclimate, lack of propagule pressure, and diminished honeydew availability. In contrast, its exclusion from more urbanized localities could be explained by high interspecific competition with other tramp species and the absence of preferred nesting sites.

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BACKGROUND: Prostate cancer (PCa) is one of the most common cancers worldwide and oxidative stress is involved in its occurrence, development and progression. In fact, in transgenic adenocarcinoma of mouse prostate (TRAMP) mice, prostate cancer onset is associated with the methylation of the first five CpG in the nuclear factor erythroid 2-related factor 2 (NRF2) promoter, a key regulator of oxidative stress response, leading to its downregulation and accumulation of reactive oxygen species (ROS). It has been demonstrated that both natural and synthetic compounds can reactivate NRF2 expression inhibiting the methylation status of its promoter by downregulation of DNA methyltransferases (DNMTs) and histone deacetylases (HDACs). Interestingly, NRF2 re-expression significantly reduced prostate cancer onset in TRAMP mice highlighting an important role of NRF2 in prostate tumorigenesis. METHODS AND RESULTS: We analysed the current literature regarding the role of natural and synthetic compounds in modulating NRF2 pathway in TRAMP mice, an in vivo model of prostate cancer, to give an overview on prostate carcinogenesis and its possible prevention. CONCLUSION: We can conclude that specific natural and synthetic compounds can downregulate DNMTs and/or HDACs inhibiting the methylation status of NRF2 promoter, then reactivating the expression of NRF2 protecting normal prostatic cells from ROS damage and tumorigenesis.

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New treatment options to battle hormone-refractory prostate carcinoma (PC) are a pressing medical need. Chronic inflammation has been implicated in PC etiology. The pro-inflammatory cytokines IL-6, IL-23 and IL-17 are key mediators to promote growth of PC. Here, we evaluate the potential of immunoproteasome inhibition for anti-inflammatory and direct anti-tumorigenic therapy of PC. The anti-tumor effect of immunoproteasome inhibitor ONX 0914 was tested in mouse and human PC cells and the in vivo therapeutic efficacy of immunoproteasome inhibition was analyzed in transgenic adenocarcinoma of the mouse prostate (TRAMP) mice in preventive and therapeutic settings and in castration-resistant (CR)PC after castration. Inhibition of the immunoproteasome subunit LMP7 induced apoptotic cell death in PC cell lines. In TRAMP mice, ONX 0914-treatment resulted in significant inhibition of PC growth with a decreased frequency of malignant prostatic lesions and inhibition of metastasis formation. The number of immunosuppressive myeloid cells in PC was greatly reduced in response to ONX 0914. Thus, immunoproteasome inhibition shows remarkable efficacy against PC progression in vivo and impedes tumor recurrence in CRPC-TRAMP mice by blocking the immunosuppressive inflammatory response in the tumor microenvironment. In conclusion, we show that the immunoproteasome is a promising drug target for the treatment of PC.

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BACKGROUND: Tempol is a redox-cycling nitroxide that acts directly on inflammation. However, few studies have reported the use of tempol in prostate cancer (PCa). The present study investigated the effects of tempol on inflammation related to NF-κB signaling, using hormone-dependent or hormone-independent cell lines and the transgenic adenocarcinoma of the mouse prostate PCa animal model in the early and late stages of cancer progression. METHODS: PC-3 and LnCaP cells were exposed to different tempol doses in vitro, and cell viability assays were performed. The optimal treatment dose was chosen for subsequent analysis using western blotting. Five experimental groups were evaluated in vivo to test for tempol effects in the early (CT12 and TPL12 groups) and late stages (CT20, TPL20-I, and TLP20-II) of PCa development. The TPL groups were treated with 50 or 100 mg/kg tempol. All control groups received water as the vehicle. The ventral lobe of the prostate was collected and subjected to immunohistochemical and western blot analysis. RESULTS: Tempol treatment reduced cellular proliferation in vitro and improved prostatic morphology in vivo, thereby decreasing tumor progression. Tempol reduced inflammation in preclinical models, and downregulated the initial inflammatory signaling through toll-like receptors, not always mediated by the MyD88 pathway. In addition, it upregulated iκB-α and iκB -ß levels, leading to a decrease in NF-κB, TNF-α, and other inflammatory markers. Tempol also influenced cell survival markers. CONCLUSIONS: Tempol can be considered a beneficial therapy for PCa treatment owing to its anti-inflammatory and antiproliferative effects. Nevertheless, the action of tempol was different depending on the degree of the prostatic lesion in vivo and hormone reliance in vitro. This indicates that tempol plays a multifaceted role in the prostatic tissue environment.

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Prostate cancer is a major public health concern and one of the most prevalent forms of cancer worldwide. The definition of altered signaling pathways implicated in this complex disease is thus essential. In this context, abnormal expression of the receptor of Macrophage Colony-Stimulating Factor-1 (M-CSF or CSF-1) has been described in prostate cancer cells. Yet, outcomes of this expression remain unknown. Using mouse and human prostate cancer cell lines, this study has investigated the functionality of the wild-type CSF-1 receptor in prostate tumor cells and identified molecular mechanisms underlying its ligand-induced activation. Here, we showed that upon CSF-1 binding, the receptor autophosphorylates and activates multiple signaling pathways in prostate tumor cells. Biological experiments demonstrated that the CSF-1R/CSF-1 axis conferred significant advantages in cell growth and cell invasion in vitro. Mouse xenograft experiments showed that CSF-1R expression promoted the aggressiveness of prostate tumor cells. In particular, we demonstrated that the ligand-activated CSF-1R increased the expression of spp1 transcript encoding for osteopontin, a key player in cancer development and metastasis. Therefore, this study highlights that the CSF-1 receptor is fully functional in a prostate cancer cell and may be a potential therapeutic target for the treatment of prostate cancer.

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The simian malaria parasite Plasmodium knowlesi causes a high number of zoonotic infections in Malaysia. The thrombospondin-related apical merozoite protein (TRAMP) is an essential ligand for binding to the erythrocyte cell surface, whereby it facilitates the invasion. This study is the first attempt to determine the genetic diversity, phylogeography, natural selection and population structure from 97 full-length PkTRAMP gene sequences originating from Malaysia. We found low levels of nucleotide diversity (π~0.0065) for the full-length gene despite samples originating from geographically separated regions (i.e., Peninsular Malaysia and Malaysian Borneo). The rate of synonymous substitutions was significantly higher than that of non-synonymous substitutions, indicating a purifying selection for the full-length gene within the clinical samples. The population genetic analysis revealed that the parasite population is undergoing a significant population expansion. The analysis of the amino acid sequence alignment of 97 PkTRAMP sequences identified 15 haplotypes, of which a major shared haplotype was noted Hap 1 (n = 68, Sarawak; n = 34, Sabah; n = 12, Peninsular Malaysia; n = 22). The phylogenetic analysis using DNA sequences identified two clusters that separated due to geographical distance and three mixed clusters with samples from both Peninsular Malaysia and Malaysian Borneo. Population structure analyses indicated two distinct sub-populations (K = 2). Our findings point to the potential for independent parasite evolution, which could make zoonotic malaria control and elimination even more challenging.

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The effect of tramp elements, mainly Bi and Ca, on the thermal characteristics of Sr-modified Al-Si-Cu and Al-Si-Cu-Mg alloys has been investigated using thermal analysis, X-ray radiography, and field emission scanning electron microscopy (FESEM) techniques. The high affinity of Bi to interact with Sr results in an increase in the Al-Si eutectic temperature, and hence an increase in the size of eutectic silicon particles. In contrast, the Ca-Sr interaction seems to have no significant effect on the alloy thermal behavior. The effect of these interactions on porosity formation has been discussed. Hot zones may be formed in thin cavities, in particular, near the bottom of the mold, leading to formation of unexpected coarse porosity, mostly shrinkage type. The study also highlights the significance of other parameters on porosity formation, such as no melt degassing, SrO, Al2O3 (strings or bifilms), as well as the presence of iron-based intermetallics.

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Herein, we assessed the stage-specific efficacy of inositol hexaphosphate (IP6, phytic acid), a bioactive food component, on prostate cancer (PCa) growth and progression in a transgenic mouse model of prostate cancer (TRAMP). Starting at 4, 12, 20, and 30 weeks of age, male TRAMP mice were fed either regular drinking water or 2% IP6 in water for ~8-15 weeks. Pathological assessments at study endpoint indicated that tumor grade is arrested at earlier stages by IP6 treatment; IP6 also prevented progression to more advanced forms of the disease (~55-70% decrease in moderately and poorly differentiated adenocarcinoma incidence was observed in advanced stage TRAMP cohorts). Next, we determined whether the protective effects of IP6 are mediated via its effect on the expansion of the cancer stem cells (CSCs) pool; results indicated that the anti-PCa effects of IP6 are associated with its potential to eradicate the PCa CSC pool in TRAMP prostate tumors. Furthermore, in vitro assays corroborated the above findings as IP6 decreased the % of floating PC-3 prostaspheres (self-renewal of CSCs) by ~90%. Together, these findings suggest the multifaceted chemopreventive-translational potential of IP6 intervention in suppressing the growth and progression of PCa and controlling this malignancy at an early stage.

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The Ski2-like RNA helicase, Mtr4, plays a central role in nuclear RNA surveillance pathways by delivering targeted substrates to the RNA exosome for processing or degradation. RNA target selection is accomplished by a variety of Mtr4-mediated protein complexes. In S. cerevisiae, the Trf4/5-Air1/2-Mtr4 polyadenylation (TRAMP) complex prepares substrates for exosomal decay through the combined action of polyadenylation and helicase activities. Biophysical and structural studies of Mtr4 and TRAMP require highly purified protein components. Here, we describe robust protocols for obtaining large quantities of pure, active Mtr4 and Trf4-Air2 from S. cerevisiae. The proteins are recombinantly expressed in E. coli and purified using affinity, ion exchange, hydrophobic exchange and size exclusion chromatography. Care is taken to remove nuclease contamination during the prep. Assembly of TRAMP is achieved by combining individually purified Mtr4 and Trf4-Air2. We further describe a strand displacement assay to characterize Mtr4 helicase unwinding activity.

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Surfactant protein D (SP-D), a pattern recognition molecule, is emerging as a potent anti-tumoural innate immune defense molecule in a range of cancers. Previously, SP-D expression was found to be significantly downregulated at the malignant sites of human prostate adenocarcinoma and associated with an increasing Gleason score and severity. We recently reported selective induction of intrinsic apoptosis by a recombinant fragment of human SP-D (rfhSP-D) in the human Prostate cancer (PCa) biopsy explants and cells with glucose regulated protein of 78 (GRP78) as one of the key interacting partners. The present study evaluated the expression of SP-D in early and advanced stages of PCa using transgenic adenocarcinoma of mouse prostate (TRAMP) model. Both early and late stages of PCa showed significantly decreased SP-D mRNA expression and increased proteolytic degradation of SP-D protein. Systemic and tumoural immunophenotyping of TRAMP model revealed increased serine proteases producing granulocytes and polymorphonuclear myeloid-derived suppressor cells (PMN MDSCs) in the late stage; the serine proteases secreted by these cells could be involved in the degradation of SP-D. Susceptibility of rfhSP-D to elastase-mediated proteolysis provided the rationale to use an elastase-inhibitor to sustain intact rfhSP-D in the tumour microenvironment. The study revealed an immunomodulatory potential of rfhSP-D and elastase inhibitor, sivelestat, to induce macrophage polarization towards M1 with downregulation of PMN MDSCs in ex-vivo cultured TRAMP tumours. Furthermore, rfhSP-D induced immunogenic cell death in murine PCa cells and in TRAMP explants. The findings highlight that SP-D plays an anti-tumourigenic role in PCa by inducing immunogenic cell death and immunomodulation while the prostate tumour milieu adversely impacts SP-D by inhibiting its transcription, and enhancing its proteolytic degradation. Transformation of an immunologically "cold tumour" into a "hot tumour" implicates therapeutic potential of rfhSP-D in PCa.

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Evaporation kinetics of tramp elements (M = As and Sn) in liquid iron were investigated by high-temperature gas-liquid reaction experiments and a phenomenological kinetic model. Residual content of As or Sn in the liquid iron ([pct M]) during the evaporation was measured in the temperature range of 1680 °C to 1760 °C. [pct As] and [pct Sn] decreased faster as the reaction temperature and [pct C]0 increased. Assuming first-order reaction kinetics, the apparent rate constants (kM) were obtained at each reaction temperature and [pct C]0. [pct M] in a liquid iron during the top-blown oxygen steelmaking process was simulated, with an emphasis on enlarging the reaction surface area by forming a large number of liquid iron droplets. The surface area and the droplet generation rate were obtained based on the oxygen-blowing condition. The whole surface area increased up to ∼163 times the initial liquid iron (bath) surface area, due to the generation of the droplets. Using the kM obtained in the present study, the evaporation of M during the top-blown oxygen steelmaking process for 200 tonnes of liquid iron was simulated. For a condition of [pct M]0 = 0.005 (M = As and Sn), As and Sn could be removed from the liquid iron, which was seen to be much improved by the consideration of the droplet generation. However, additional actions are required to improve the evaporation rate, as the evaporation rate in the BOF process was not fast enough to be practically considered.

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T cell therapy has become a new therapeutic opportunity against solid cancers. Predicting T cell behaviour and efficacy would help therapy optimization and clinical implementation. In this work, we model responsiveness of mouse prostate adenocarcinoma to T cell-based therapies. The mathematical model is based on a Cahn-Hilliard diffuse interface description of the tumour, coupled with Keller-Segel type equations describing immune components dynamics. The model is fed by pre-clinical magnetic resonance imaging data describing anatomical features of prostate adenocarcinoma developed in the context of the Transgenic Adenocarcinoma of the Mouse Prostate model. We perform computational simulations based on the finite element method to describe tumor growth dynamics in relation to local T cells concentrations. We report that when we include in the model the possibility to activate tumor-associated vessels and by that increase the number of T cells within the tumor mass, the model predicts higher therapeutic effects (tumor regression) shortly after therapy administration. The simulated results are found in agreement with reported experimental data. Thus, this diffuse-interface mathematical model well predicts T cell behavior in vivo and represents a proof-of-concept for the role such predictive strategies may play in optimization of immunotherapy against cancer.

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