183 research outputs found

    Mimesis : human-centered digital profiling visual identity

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    Digital profiling is the process of gathering and analyzing information that exists online about an individual. Platforms who provide services always have control of this powerful tool. As a result, I used Twitter API as the principle medium to conduct \u27digital profiling\u27 as a third party. The visual identity of the new digital profile is not an ads interest list anymore, but a graph that stores personal information that could be used as an avatar. On top of the new visual identity, I speculated several possible applications of the new visual outcome. The idea put forward in this thesis is that shifting the purpose of digital profiling toward being human-centered rather than advertising-driven may draw worthwhile arguments about the practicality and policy issues. This thesis is a speculative design project, an avatar design project, a UX design project, a generative design project, and an information design project. My point is multiple mediums to demonstrate my future vision or wish for this technology and propose a mutually beneficial strategy for tech companies

    Criticality in failure under compression: acoustic emission study of coal and charcoal with different microstructures

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    A systematic study of acoustic emission avalanches in coal and charcoal samples under slow uniaxial compression is presented. The samples exhibit a range of organic composition in terms of chemical elements as well as different degrees of heterogeneity in the microstructure. The experimental analysis focuses on the energies E of the individual acoustic emission events as well as on the time correlations between successive events. The studied samples can be classified into three groups. The more homogeneous samples (group I) with pores in the micro and nanoscales, with signatures of hardening effects in the stress-strain curves, exhibit the cleanest critical power-law behavior for the energy distributions g(E)dE∼E-ϵdE with a critical exponent ϵ=1.4. The more heterogeneous samples with voids, macropores, and granular microstructures (group III), show signatures of weakening effects and a larger effective exponent close to the value ϵ=1.66, but in some cases truncated by exponential damping factors. The rest of the samples (group II) exhibit a mixed crossover behavior still compatible with an effective exponent ϵ=1.4 but clearly truncated by exponential factors. These results suggest the existence of two possible universality classes in the failure of porous materials under compression: one for homogeneous samples and another for highly heterogeneous samples. Concerning time correlations between avalanches, all samples exhibit very similar waiting time distributions although some differences for the Omori aftershock distributions cannot be discarded

    The Emerging Epigenetic Role of CD8+T Cells in Autoimmune Diseases: A Systematic Review

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    Autoimmune diseases are usually complex and multifactorial, characterized by aberrant production of autoreactive immune cells and/or autoantibodies against healthy cells and tissues. However, the pathogenesis of autoimmune diseases has not been clearly elucidated. The activation, differentiation, and development of CD8+ T cells can be affected by numerous inflammatory cytokines, transcription factors, and chemokines. In recent years, epigenetic modifications have been shown to play an important role in the fate of CD8+ T cells. The discovery of these modifications that contribute to the activation or suppression of CD8+ cells has been concurrent with the increasing evidence that CD8+ T cells play a role in autoimmunity. These relationships have been studied in various autoimmune diseases, including multiple sclerosis (MS), systemic sclerosis (SSc), type 1 diabetes (T1D), Grave's disease (GD), systemic lupus erythematosus (SLE), aplastic anemia (AA), and vitiligo. In each of these diseases, genes that play a role in the proliferation or activation of CD8+ T cells have been found to be affected by epigenetic modifications. Various cytokines, transcription factors, and other regulatory molecules have been found to be differentially methylated in CD8+ T cells in autoimmune diseases. These genes are involved in T cell regulation, including interferons, interleukin (IL),tumor necrosis factor (TNF), as well as linker for activation of T cells (LAT), cytotoxic T-lymphocyte–associated antigen 4 (CTLA4), and adapter proteins. MiRNAs also play a role in the pathogenesis of these diseases and several known miRNAs that are involved in these diseases have also been shown to play a role in CD8+ regulation

    The Preparation, Antioxidant Activity Evaluation, and Iron-Deficient Anemic Improvement of Oat (Avena sativa L.) Peptides–Ferrous Chelate

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    Iron-chelating peptides have been widely considered as one of the best iron supplements to alleviate the iron deficiency. In this study, a novel oat peptides–ferrous (OP-Fe2+) chelate was prepared from antioxidant oat peptides obtained in the laboratory of the authors. The optimal preparation condition was obtained through the single-factor and response surface methodology, and the chelating rate could reach up to 62.6%. After chelation, the OP-Fe2+ chelate exhibited a significantly higher 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity than oat peptides. It was discovered that the hemoglobin concentration and the number of red blood cell levels in OP-Fe2+-treated iron-deficient anemic (IDA) rats were significantly higher than untreated IDA rats. The OP-Fe2+ chelate could also improve the hypertrophy of the spleen, serum iron (SI), total iron and binding capacity, and serum ferritin levels in the IDA rats. In addition, the OP-Fe2+ treatment significantly increased the antioxidant activities of super oxidase and glutathione in the liver homogenate of the IDA rats. Therefore, the OP-Fe2+ chelate is an effective type of iron supplement for IDA rats, which could be a promising source with anti-anemia and antioxidant activity

    Induction of RIPK3/MLKL-mediated necroptosis by Erigeron breviscapus injection exhibits potent antitumor effect

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    Colorectal cancer (CRC) is the second leading cause of tumor-related deaths worldwide. Resistance of tumor cells to drug-induced apoptosis highlights the need for safe and effective antitumor alternatives. Erigeron breviscapus (Dengzhanxixin in China) injection (EBI), extracted from the natural herb Erigeron breviscapus (Vant.) Hand.-Mazz (EHM), has been widely used in clinical practice for cardiovascular diseases. Recent studies have suggested that EBI’s main active ingredients exhibit potential antitumor effects. This study aims to explore the anti-CRC effect of EBI and elucidate the underlying mechanism. The anti-CRC effect of EBI was evaluated in vitro using CCK-8, flow cytometry, and transwell analysis, and in vivo through a xenograft mice model. RNA sequencing was utilized to compare the differentially expressed genes, and the proposed mechanism was verified through in vitro and in vivo experiments. Our study demonstrates that EBI significantly inhibits the proliferation of three human CRC cell lines and effectively suppresses the migration and invasion of SW620 cells. Moreover, in the SW620 xenograft mice model, EBI markedly retards tumor growth and lung metastasis. RNA-seq analysis revealed that EBI might exert antitumor effects by inducing necroptosis of tumor cells. Additionally, EBI activates the RIPK3/MLKL signaling pathway, a classical pathway of necroptosis and greatly promotes the generation of intracellular ROS. Furthermore, the antitumor effect of EBI on SW620 is significantly alleviated after the pretreatment of GW806742X, the MLKL inhibitor. Our findings suggest that EBI is a safe and effective inducer of necroptosis for CRC treatment. Notably, necroptosis is a non-apoptotic programmed cell death pathway that can effectively circumvent resistance to apoptosis, which provides a novel approach for overcoming tumor drug resistance

    Assessing real-world safety concerns of Sacituzumab govitecan: a disproportionality analysis using spontaneous reports in the FDA adverse event reporting system

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    AimThe aim of this study was to identify potential safety concerns associated with Sacituzumab Govitecan (SG), an antibody-drug conjugate targeting trophoblastic cell-surface antigen-2, by analyzing real-world safety data from the largest publicly available worldwide pharmacovigilance database.MethodsAll data obtained from the FDA Adverse Event Reporting System (FAERS) database from the second quarter of 2020 to the fourth quarter of 2022 underwent disproportionality analysis and Bayesian analysis to detect and assess the adverse event signals of SG, considering statistical significance when the lower limit of the 95% CI >1, based on at least 3 reports.ResultsTotal of 1072 cases were included. The main safety signals were blood and lymphatic system disorders [ROR(95CI)=7.23 (6.43-8.14)], gastrointestinal disorders [ROR(95CI)=2.01 (1.81-2.22)], and relative infection adverse events, such as neutropenic sepsis [ROR(95CI)=46.02 (27.15-77.99)] and neutropenic colitis [ROR(95CI)=188.02 (120.09-294.37)]. We also noted unexpected serious safety signals, including large intestine perforation [ROR(95CI)=10.77 (3.47-33.45)] and hepatic failure [ROR(95CI)=3.87 (1.45-10.31)], as well as a high signal for pneumonitis [ROR(95CI)=9.93 (5.75-17.12)]. Additionally, age sub-group analysis revealed that geriatric patients (>65 years old) were at an increased risk of neutropenic colitis [ROR(95CI)=282.05 (116.36-683.66)], neutropenic sepsis [ROR(95CI)=101.11 (41.83-244.43)], acute kidney injury [ROR(95CI)=3.29 (1.36-7.94)], and atrial fibrillation [ROR(95CI)=6.91 (2.86-16.69)].ConclusionThis study provides crucial real-world safety data on SG, complementing existing clinical trial information. Practitioners should identify contributing factors, employ monitoring and intervention strategies, and focus on adverse events like neutropenic sepsis, large intestine perforation, and hepatic failure. Further prospective studies are needed to address these safety concerns for a comprehensive understanding and effective management of associated risks

    Large expert-curated database for benchmarking document similarity detection in biomedical literature search

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    Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

    31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

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    Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival
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