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Application of Analytical Methodologies to the Analysis of Food Flavoring Agents: Part I
Full text linkCl-Amidine and Rapamycin Combination as a Novel Synergistic Co-therapy For Ovarian Cancer
Full text linkPeptidyl arginine deiminases (PADs) are a family of calcium-binding enzymes that catalyze the citrullination of arginine and methylarginine residues as a form of gene regulation. The overexpression of PAD4 in cancer cells contributes to tumorigenesis and metastasis through the accelerated formation of neutrophil extracellular traps (NETs) and the downregulation of the p53 pathway. Significantly elevated PAD4 levels have been observed in various ovarian cancer subtypes, and it has been proposed that this elevation is a significant contributor to the malignancy of these cancers. Thus, the purpose of this research was to explore the effect of Cl-amidine, a small organic compound and irreversible inhibitor of PAD4, on human ovarian adenocarcinoma cell lines. In addition, Cl-amidine has been indicated to have potentially synergistic interactions with rapamycin, an established anticancer drug, against breast cancer cells. Therefore, the potential for Cl-amidine and rapamycin to act synergistically against ovarian cancer was also explored. Cl-amidine alone ultimately resulted in 70% cancer cell death, while Cl-amidine in combination with rapamycin resulted in nearly 90% cancer cell death. Cl-amidine and rapamycin showed significant synergistic activity (FIC50\u3c 0.5) and up to 90% of ovarian cancer cells were in apoptosis following cotreatment. Cl-amidine alone and in combination with rapamycin significantly upregulated the expression of tumor suppressor genes TP53 and CDKN1A. Both compounds were shown to have negligible effects on noncancerous cell lines. Thus, Cl-amidine as a monotherapy and as a co-therapy with rapamycin showed significant antiproliferative, cytotoxic, and pro-apoptotic properties, and may be a promising candidate for the treatment of ovarian cancer
Evaluation of the impact of Urban Stream Syndrome on macroinvertebrate functional feeding diversity and organic matter processing in streams
Full text linkUrbanization causes the degradation of streams described as the Urban Stream Syndrome, resulting in increased contamination, altered stream morphology, and reduced taxonomic richness. Macroinvertebrates vary in their tolerance to the impacts of urbanization, therefore the reduction of taxonomic richness increases the abundance of tolerant species and decreases the abundance of intolerant species. Aquatic macroinvertebrates are specialized feeders, falling into five functional feeding groups which affect ecosystem processes such as the decomposition of organic matter. Through a reduction of intolerant taxa, functional feeding diversity will be reduced because the functional feeding groups are not equally distributed across all tolerance levels. This alteration in functional feeding diversity may affect ecosystem processes within the stream. I hypothesized that the degradation of streams from the Urban Stream Syndrome would result in a decrease in macroinvertebrate diversity and the diversity of the functional feeding groups, altering organic matter processing. To evaluate this hypothesis, I quantified the taxonomic and functional diversity of macroinvertebrate assemblages in an urban and non-urban stream. I then developed a model for organic matter processing using macroinvertebrate consumption rates from the literature and predicted organic matter processing rates in the urban and non-urban stream. I found that there was a reduction in the intolerant macroinvertebrates in the urban stream when compared to the non-urban stream. There was also a reduction in taxonomic and functional diversity in the urban stream. The modeled consumption rates indicated that in the urban stream, Collectors were responsible for the most consumption, whereas in the non-urban stream Shredders were predicted to process the most organic matter. These results support my hypothesis that the Urban Stream Syndrome alters organic matter processing in streams through a shift in macroinvertebrate functional diversity
A Marriage By Any Other Sign: Social Signification in The Way of the World
Full text linkThis paper analyzes William Congreve’s The Way of the World through the lens of Derrida’s theory of différance, arguing that the play destabilizes the fixed social categories of marriage and identity through linguistic performance. While many critics read Congreve’s portrayal of marriage as either reinforcing or satirizing Restoration social structures, this analysis emphasizes how language itself resists fixed meaning. Drawing on key scenes between Mirabell and Millamant, Waitwell’s reflections on autonomy, and Fainall’s contradictory claims of masculine selfhood, the paper demonstrates how the signs “husband,” “wife,” and “man” shift and defer meaning rather than affirm static roles. Characters do not simply reflect legal or economic structures—they reshape them through ironic and strategic language. By exposing how identity is produced relationally, not essentially, Congreve turns marriage from a social institution into a field of rhetorical play. Ultimately, this reading reveals that The Way of the World enacts not just social critique but linguistic subversion, showing how even love and resentment are performed through unstable signs
Simone de Beauvoir’s Influence on “The Handmaid’s Tale”
No full textUsing the theories that Simone de Beauvoir presents in The Second Sex, this paper will analyze Margaret Atwood’s The Handmaid’s Tale. Discussing how Gilead reflects the oppression women face, and the idea of women as “other,” and Beauvoir describes. She spends much time discussing the Hegelian master-slave dialectic, which is seen in The Handmaid’s Tale through Gilead’s laws. Forcing the Handmaids to not only be an incubator for the commander, but also forcing them to do the shopping for the household, and not allowing them basic human rights such as reading. Mussett analyzes this and gives further analysis on women as a tool for mediation to men. In the novel, Handmaids were used by the men as a vessel for carrying babies, forcing them to be defined by biology, as Beauvoir gives criticism to. Russell’s critique on reproductive technologies allows capitalist societies to profit, similarly the Handmaids are used for their fertility, profiting the commander’s families. Beauvoir also critiques patriarchal marriage, stating that it takes away from the autonomy of women. This is present in The Handmaid’s Tale, by showing that Serena is unhappy with the situation that she is in with her husband. Beauvoir\u27s feminist critiques reflect in The Handmaid’s Tale in a multitude of ways that have been built upon by multiple scholars
Macro-financial models of Canadian dollar interest rate swap yields
No full textThis paper analyzes the dynamics of Canadian dollar–denominated (CAD) interest rate swap yields. It applies autoregressive distributive lag (ARDL) models, using monthly time series data, to estimate the effects of the current short-term interest rate on interest rate swap yields after controlling for relevant macro-financial variables. It shows that the current short-term interest rate is a crucial driver of the CAD swap yields of different maturity tenors. Previous empirical research testing the Keynesian hypothesis, which maintains that the current short-term interest rate has a decisive influence on the long-term interest rate, has discerned similar patterns for interest rate swaps denominated in other currencies. Thus, the findings of this paper lend additional support to the Keynesian hypothesis by showing that the same pattern holds for CAD interest rate swap yields
Euro Interest Rate Swap Yields: A GARCH Analysis
No full textThis paper models the month-over-month change in euro-denominated (EUR) long-term interest rate swap yields. It shows that the change in the short-term interest rate has an economically and statistically significant effect on the change in EUR swap yields of different maturity tenors in the subsequent period, after controlling for various macroeconomic and financial variables, such as the month-over-month change in inflation or core inflation and the growth of industrial production, and the percentage change in the equity price index, the exchange rate, and the size of the European Central Bank’s (ECB) balance sheet. It uses a generalised autoregressive conditional heteroskedasticity (GARCH) approach to model the dynamics of the monthly change in EUR swap yields and their volatility. The results of the estimated models of EUR swap yields of different maturity tenors extend the Keynesian view that the central bank’s monetary policy actions have a decisive influence on long-term government bond yields and long-term market interest rates, primarily through their effects on the current short-term interest rate
Blockade of chPD1 T cell derived cytokines decreases inflammatory molecules related to cytokine release syndrome in acute lymphocytic leukemia
Full text linkAcute lymphocytic leukemia (ALL) is a common pediatric cancer that is characterized by its high incidence of relapsed and refractory (R/R) cases. This brings about a need for new treatments that are safe and effective. One type of novel cancer immunotherapy uses chimeric antigen receptor (CAR) expressing T cells. CARs target tumor-associated antigens and enhance T cell responses. CAR T cell therapy has been successful in treating ALL, however there are associated toxicities such as cytokine release syndrome (CRS). One potential way to reduce CRS is to inhibit cytokine secretion and to alter the costimulatory domain in the CAR T cell. Therefore, we developed CAR T cells containing different costimulatory domains to test the role of costimulation in CRS induction. We used a chimeric-PD1 (chPD1) receptor with the Programmed Death 1 receptor as the tumor-targeting domain. The purpose of this study was to evaluate whether T cell secretion of inflammatory cytokines was required for tumor cell cytotoxicity and release of CRS-inducing inflammatory molecules. Additionally, if inclusion of costimulatory domains, CD28, 4-1BB, and Dap10, in the chPD1 receptor altered tumor cell cytotoxicity and cytokine secretion was evaluated. ChPD1 T cells had significant tumor cell killing compared to control T cells. Compared to 4-1BB and Dap10, inclusion of CD28 in the chPD1 receptor increased secretion of CRS-related cytokines. Blocking antibodies were used to test the requirement of T-cell cytokine secretion in CRS induction. Blockade of IFN-γ, GM-CSF, and IL-10 alone or in combination did not decrease tumor cell death. However, blockade of these cytokines did alter release of CRS-related molecules NO, TNF-α, and IL-6 from activated leukocytes. Therefore, blocking chPD1 derived cytokines could reduce the induction of CRS, and the inclusion of 4-1BB and Dap10 could provide safer costimulation for chPD1 CAR T cell therapy used against ALL