The Internet is a remarkably complex technical system. Its rapid growth has also brought technical issues such as problems to information retrieval. Search engines retrieve requested information ...based on the provided keywords. Consequently, it is difficult to accurately find the required information without understanding the syntax and semantics of the content. Multiple approaches are proposed to resolve this problem by employing the semantic web and linked data techniques. Such approaches serialize the content using the Resource Description Framework (RDF) and execute the queries using SPARQL to resolve the problem. However, an exact match between RDF content and query structure is required. Although, it improves the keyword-based search; however, it does not provide probabilistic reasoning to find the semantic relationship between the queries and their results. From this perspective, in this paper, we propose a deep learning-based approach for searching RDF graphs. The proposed approach treats document requests as a classification problem. First, we preprocess the RDF graphs to convert them into N-Triples format. Second, bag-of-words (BOW) and word2vec feature modeling techniques are combined for a novel deep representation of RDF graphs. The attention mechanism enables the proposed approach to understand the semantic between RDF graphs. Third, we train a convolutional neural network for the accurate retrieval of RDF graphs using the deep representation. We employ 10-fold cross-validation to evaluate the proposed approach. The results show that the proposed approach is accurate and surpasses the state-of-the-art. The average accuracy, precision, recall, and f-measure are up to 97.12%, 98.17%, 95.56%, and 96.85%, respectively.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Manufacturing titanium aluminides (TiAls) parts are challenging due to their low ductility and fracture toughness. However, processing these materials is of significant interest for applications in ...high-temperature environments such as the aerospace and automotive industries. Traditional production methods such as casting and forging have been prominent in TiAl manufacturing. Currently, direct energy deposition (DED), electron beam additive manufacturing (EBAM), and laser powder bed fusion (L-PBF) additive manufacturing processes are being considered promising technologies for manufacturing TiAl parts. Recent results suggest the potential for these AM methods to be used for the industrial processing of TiAls. This article reviews the different processing methods for TiAls, highlighting the advantages and progress in using additive manufacturing (AM) technologies. Process characteristics, processing challenges and their causes, and potential mitigation strategies are discussed for each AM method considered. The process-structure–property (PSP) relationships are reviewed, highlighting the optimum process parameters and related mechanical properties. In addition, L-PBF is emphasized as a prospective solution for manufacturing different TiAl alloys. Prospects and recommendations for future studies are also suggested.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Tumor cells express programmed death ligand 1 (PD-L1) and is a key immune evasion mechanism. PD-L1 expression in multiple breast cancer cell lines was evaluated to identify intrinsic differences that ...affect their potential for immune evasion.
PD-L1 expression was analyzed in six breast cancer cell lines: AU565&MCF7 (luminal), BT20&HCC1143 (basal A), MDA231&HCC38 (basal B). Surface and intracellular PD-L1 expression +/- interferon γ for 48 hours was measured by flow cytometry. PD-L1 gene expression data for all breast cancer cell lines in the Comprehensive Cell Line Encyclopedia (CCLE) was analyzed. Correlation between PD-L1 levels and clinicopathologic parameters was analyzed within Oncomine datasets. A tissue microarray containing 61 invasive breast cancer primary tumor cores was stained for PD-L1 expression and analyzed.
Basal breast cancer cells constitutively express the highest levels of PD-L1. All cell lines increased PD-L1 expression with interferon γ, but basal B cells (MDA-231 and HCC38) demonstrated the largest increases. There were no differences in protein localization between cell lines. In the CCLE data, basal cell lines demonstrated higher mean PD-L1 expression compared to luminal cell lines. High PD-L1 expressing basal cell lines over-express genes involved in invasion, proliferation, and chemoresistance compared to low PD-L1 basal cell lines. High PD-L1 basal cell lines had lower expression of IRF2BP2 and higher STAT1 levels compared to low PD-L1 expressing cell lines. Within Oncomine datasets PDL1 mRNA levels were higher in basal type tumors. The TMA analysis demonstrated that lymph node positive cases had higher levels of PD-L1 protein expression compared to lymph node negative cases.
Basal type breast cancer (especially basal B) express greater levels of PD-L1 constitutively and with IFN γ. High PD-L1 basal cells over-express genes involved in invasion, motility, and chemoresistance. Targeting PD-L1 may enhance eradication of aggressive breast cancer cells by the immune system.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The blend of digital and physical worlds changed the Internet significantly. Accordingly, trends to collect, access, and deliver information have changed over the Web. Such changes raised the ...problems of information retrieval. Search engines retrieve requested information based on the provided keywords which is not an efficient way for rich information retrieval. Consequently, the fetching of the required information is difficult without understanding the syntax and semantics of the content. The multiple existing approaches to resolve this problem by exploiting linked data and semantic Web techniques. Such approaches serialize the content leveraging the Resource Description Framework (RDF) and process the queries using SPARQL to resolve the problem. However, an exact match between RDF content and query structure is required. Although it improves the keyword-based search, it does not provide probabilistic reasoning to find the relationship accuracy between the query and results. In this perspective, this paper proposes a machine learning (random forest) based approach to predict the fetching status of RDF by treating RDFs' requests as a classification problem. First, we preprocess the RDF to convert them into N-Triples format. Then, a feature vector is constructed for each RDF using the preprocessed RDF. After that, a random forest classifier is trained for the prediction of the fetching status of RDFs. The proposed approach is evaluated on an open-source DBpedia dataset. The 10-fold cross-validation results indicate that the performance of the proposed approach is accurate and surpasses the state-of-the-art.
Tumors recognized by the host immune system are associated with better survival. However, the immune system is often suppressed in patients with established tumor burden. Stimulating the immune ...system to detect and kill tumor cells has been a challenge in cancer therapy for some time. Recently, novel cancer immunotherapies, such as immune checkpoint inhibitors, monoclonal antibodies, and vaccine therapies, have emerged as promising therapeutic approaches for many solid tumors. However, for some tumors, immunotherapy alone has not provided significant benefits, and some may even be fully resistant to immunotherapy. It has been suggested that the immune system may require "priming" before an immunotherapy can elicit an immune response. Although chemotherapies are believed to be immunosuppressive, when given at the right dose and sequence these agents may provide this "priming" effect for the immune system. In addition to direct cytotoxic killing of tumor cells, standard chemotherapeutic agents can elicit immunogenicity through various mechanisms. This review highlights the general immunomodulatory properties of chemotherapy agents. It also provides a rationale for combined therapy with
-paclitaxel and immune checkpoint inhibitors. Recent clinical trial data with these combination regimens in solid tumors are presented, along with a summary of ongoing trials.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
CD4 is a nonpolymorphic transmembrane glycoprotein molecule that is expressed on the surface of T-helper cells and plays an essential role in the immune response. It functions as a coreceptor with ...the T-cell receptor by binding to major histocompatibility complex class II on the surface of dendritic cells that present antigens. CD4
T cells hold a key position in coordinating the immune system through production of several cytokines after activation and differentiation. The CD4
T helper subtypes (T-helper 1, T-helper 2, T-helper 17, T-helper 9, and regulatory-T cells) perform different immune functions subsequent to their differentiation from the naive T cells. Different types of CD4
T cells require different cytokines such as drivers and effectors, as well as master transcription factors for their activation. Fish cells that express CD4-related genes are activated in the presence of a pathogen and release cytokines against the pathogen. This review highlights the types of CD4
T cells in fish and describes their direct role in cell-mediated and humoral immunity for protection against the intracellular bacterial as well as viral infections in fish.
Postprocessing is essential for improving titanium aluminide (TiAl) microstructure and part quality after using the laser powder bed fusion (L-PBF) method. It has been reported that Ti-48Al-2Cr-2Nb ...(%at) processed by L-PBF has internal defects and low fracture toughness. Microstructure control by heat treatment (HT) showed a significant improvement in the ductility of the material. Alternatively, hot isostatic pressing (HIPing) could be applied to reduce the residual stresses and internal defects formed during the L-PBF. Combining the benefits of these two subsequent processes into a single predetermined process is appealing for Ti-48Al-2Cr-2Nb (%at) to minimize cost. This work presents a novel strategy to postprocess L-PBF TiAl by applying combined heat treatment and hot isostatic pressing in one process, namely HT-HIP. The process includes three cycles with different conditions (i.e., temperature, time, and pressure). These conditions were determined to achieve improved part quality and microstructure. The results show that the tensile residual stresses decreased from a peak of 249 MPa in the as-built sample to compressive stresses that peaked at -90 MPa after the HT-HIP process. The number and size of internal defects could be greatly reduced. The defects were transformed into a regular spherical shape, which is good in terms of fatigue strength. Additionally, a duplex microstructure with lamellar α
/γ colonies could be introduced for better ductility. Different levels of duplex microstructure could be achieved along with the process cycles. The grain structure using EBSD analysis showed refined equiaxed grains, which demonstrate better strength after the HT-HIP process. Twinning boundaries were also observed in the HT-HIP sample. The grain orientation tendency to the build direction significantly reduced after the HT-HIP process. The nanoindentation test was applied to evaluate the nanohardness of the as-built and HT-HIP samples. It could be demonstrated that the nanohardness is dependent on the formed phases and lamellar density inside the grains. The mean hardness value was 8.19 GPa for the as-built sample, while it was 5.48 GPa for the HT-HIP sample.
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Blockade of the inhibitory receptor TIM-3 shows efficacy in cancer immunotherapy clinical trials. TIM-3 inhibits production of the chemokine CXCL9 by XCR1+ classical dendritic cells (cDC1), thereby ...limiting antitumor immunity in mammary carcinomas. We found that increased CXCL9 expression by splenic cDC1s upon TIM-3 blockade required type I interferons and extracellular DNA. Chemokine expression as well as combinatorial efficacy of TIM-3 blockade and paclitaxel chemotherapy were impaired by deletion of Cgas and Sting. TIM-3 blockade increased uptake of extracellular DNA by cDC1 through an endocytic process that resulted in cytoplasmic localization. DNA uptake and efficacy of TIM-3 blockade required DNA binding by HMGB1, while galectin-9-induced cell surface clustering of TIM-3 was necessary for its suppressive function. Human peripheral blood cDC1s also took up extracellular DNA upon TIM-3 blockade. Thus, TIM-3 regulates endocytosis of extracellular DNA and activation of the cytoplasmic DNA sensing cGAS-STING pathway in cDC1s, with implications for understanding the mechanisms underlying TIM-3 immunotherapy.
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•TIM-3 blockade promotes endocytosis of extracellular DNA by dendritic cells•DNA uptake and CXCL9 expression by dendritic cells is HMGB1 dependent•Galectin-9 regulates TIM-3 cell surface clustering and inhibitory function•Antitumor efficacy of TIM-3 mAb and paclitaxel is dependent upon cGAS and STING
Blockade of the inhibitory receptor TIM-3 shows efficacy in cancer immunotherapy clinical trials. de Mingo Pulido et al. provide insight into the underlying mechanisms by revealing that TIM-3 suppresses HMGB1-dependent endocytosis of extracellular DNA and the subsequent activation of the cGAS-STING pathway in intra-tumoral dendritic cells.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
A unique 12-chemokine gene expression score (CS) accurately predicted the presence of tumor-localized, ectopic lymph node-like structures (TL-ELNs) and improved overall survival (OS) in primary ...colorectal cancer and metastatic melanoma. We analyzed the correlation between CS, clinicopathological variables, molecular data, and 366 survival in Moffitt Cancer Center's Total Cancer Care (TCC) patients with non-metastatic breast cancer.
Affymetrix gene expression profiles were used to interrogate the CS by the principal component method. Breast tumors were classified as high or low score based on median split, and correlations between clinicopathologic variables, PAM50 molecular subtype, and ELN formation were analyzed using the TCC dataset. Differences in overall survival (OS) and recurrence-free survival (RFS) in the larger KM Plot breast cancer public datasets were compared using Kaplan-Meier curves.
We divided the Total Cancer Care (TCC) breast cancer patients into two groups of high or low CS. Mean CS was 0.24 (range, 2.2-2.1). Patients with higher CS were more likely to be white (172 vs. 159; p = 0.03), had poorly differentiated tumors (112 vs. 59; p <0.0001), ER/PR negative (41 vs. 26) and HER2 positive (36 vs. 19; p = 0.001), and contain TL-ELNs. Higher CS scores were also seen in the basal and HER2+ molecular subtypes. In the KM Plot breast cancer datasets higher CS patients demonstrated superior OS (HR = 0.73, p = 0.008) and RFS (HR 0.76, p = <0.0001), especially in basal and HER2+ patients.
High CS breast tumors tend to be higher grade, basal or HER2+, and present more frequently in Caucasians. However, this group of patients also shows the presence of TL-ELNs within the tumor microenvironment and has better survival outcomes. The CS is a novel tool that can identify breast cancer patients with tumors of a unique intratumoral immune composition and better prognosis. Whether or not the CS is a predictive response marker in breast cancer patients undergoing immunotherapy remains to be determined.
Immunotherapy has resulted in unprecedented gains in long-term outcomes for many cancer types and has revolutionized the treatment landscape of solid tumor oncology. Checkpoint inhibition in ...combination with chemotherapy has proven to be effective for the treatment of a subset of advanced triple-negative breast cancer in the first-line setting. This initial success is likely just the tip of the iceberg as there is much that remains unknown about how to best harness the immune system as a therapeutic strategy in all breast cancer subtypes. Therefore, numerous ongoing studies are currently underway to evaluate the safety and efficacy of immunotherapy in breast cancer. In this review, we will discuss emerging immunotherapeutic strategies for breast cancer treatment including the following: (1) Intratumoral therapies, (2) Anti-tumor vaccines, (3) B-specific T-cell engagers, and (4) Chimeric antigen receptor T-cell therapy, and (5) Emerging systemic immunotherapy strategies. For each topic, we will review the existing preclinical and clinical literature, discuss ongoing clinical trials, and highlight future directions in the field.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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