question:Given an abstract from a research paper, your task is to identify and label relationships between chemical compounds and genes mentioned in the abstract.The relationship type must be one of ['DOWNREGULATOR', 'SUBSTRATE', 'INDIRECT-REGULATOR', 'PART-OF', 'MODULATOR-ACTIVATOR', 'REGULATOR', 'INHIBITOR', 'COFACTOR', 'UPREGULATOR', 'ACTIVATOR', 'ANTAGONIST', 'NOT', 'INDIRECT-DOWNREGULATOR', 'SUBSTRATE_PRODUCT-OF', 'INDIRECT-UPREGULATOR', 'AGONIST', 'PRODUCT-OF', 'MODULATOR', 'DIRECT-REGULATOR', 'UNDEFINED', 'AGONIST-INHIBITOR', 'AGONIST-ACTIVATOR', 'MODULATOR-INHIBITOR'].Please format your output as a JSON array. Each entry in the array should express a single relation, formatted as ["<Entity_A>", "<RELATION_A_B>", "<Entity_B>"]. If no relations can be found, please output an empty JSON array [].Abstract:Anti-inflammatory effect of essential oil and its constituents from fingered citron (Citrus medica L. var. sarcodactylis) through blocking JNK, ERK and NF-κB signaling pathways in LPS-activated RAW 264.7 cells. We investigated the composition of essential oil from fingered citron (Citrus medica L. var. sarcodactylis) (FCEO) peels by GC-MS and its anti-inflammatory effects on lipopolysaccharide (LPS) -stimulated mouse macrophage (RAW 264.7) cells. Fifteen compounds, representing 98.97% of the essential oil, were tentatively identified; the main constituents were limonene (52.44%) and γ-terpinene (28.41%). FCEO significantly inhibited nitric oxide (NO) and prostaglandin E2 (PGE2) by suppressing the protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX) -2, respectively. Additionally, FCEO suppressed the production of tumor necrosis factor-α (TNF-α), interleukin (IL) -1β, and IL-6. FCEO attenuated LPS-induced nuclear factor-κB (NF-κB) activation via inhibition of inhibitor κB-α phosphorylation. Furthermore, FCEO blocked activation of c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) but not that of p38 mitogen-activated protein kinase. These results indicate that FCEO inhibits LPS-stimulated inflammation by blocking the NF-κB, JNK, and ERK pathways in macrophages, and demonstrate that FCEO possesses anti-inflammatory properties.

question:You will be presented with the abstract, introduction, and discussion section from a biomedical research article. Your task is to create a summary that a layperson can understand, capturing the essence of the research article. Keep essential scientific terms, but ensure that the language remains clear and the concepts are explained in an uncomplicated manner.Title: Determining the genetic basis of anthracycline-cardiotoxicity by molecular response QTL mapping in induced cardiomyocytes}Article:Abstract:Anthracycline-induced cardiotoxicity( ACT) is a key limiting factor in setting optimal chemotherapy regimes, with almost half of patients expected to develop congestive heart failure given high doses. However, the genetic basis of sensitivity to anthracyclines remains unclear. We created a panel of iPSC-derived cardiomyocytes from 45 individuals and performed RNA-seq after 24 hr exposure to varying doxorubicin dosages. The transcriptomic response is substantial: the majority of genes are differentially expressed and over 6000 genes show evidence of differential splicing, the later driven by reduced splicing fidelity in the presence of doxorubicin. We show that inter-individual variation in transcriptional response is predictive of in vitro cell damage, which in turn is associated with in vivo ACT risk. We detect 447 response-expression quantitative trait loci( QTLs) and 42 response-splicing QTLs, which are enriched in lower ACT GWAS p-values, supporting the in vivo relevance of our map of genetic regulation of cellular response to anthracyclines.Introduction:Anthracyclines, including the prototypical doxorubicin, continue to be used as chemotherapeutic agents treating a wide range of cancers, particularly leukemia, lymphoma, multiple myeloma, breast cancer, and sarcoma. A well-known side-effect of doxorubicin treatment is anthracycline-induced cardiotoxicity( ACT). For some patients ACT manifests as an asymptomatic reduction in cardiac function, as measured by left ventricular ejection fraction( LVEF), but in more extreme cases ACT can lead to congestive heart failure( CHF). The risk of CHF is dosage-dependent: an early study( Von Hoff et al., 1979) estimated 3% of patients at 400 mg/m2, 7% of patients at 550 mg/m2, and 18% of patients at 700 mg/m2 develop CHF, where a more recent study puts these numbers at 5%, 26% and 48% respectively( Swain et al., 2003). Reduced LVEF shows a similar dosage-dependent pattern, but is not fully predictive of CHF. Perhaps most daunting for patients is that CHF can occur years after treatment: out of 1807 cancer survivors followed for 7 years in a recent survey a third died of heart diseases compared to 51% of cancer recurrence( Vejpongsa and Yeh, 2014). Various candidate gene studies have attempted to find genetic determinants of ACT, but are plagued by small sample sizes and unclear endpoint definitions, resulting in limited replication between studies. Two ACT genome-wide association studies( GWAS) have been published( Aminkeng et al., 2015; Schneider et al., 2017). While neither found genome-wide significant associations using their discovery cohorts, both found one variant that they were able to replicate in independent cohorts. A nonsynonymous coding variant, rs2229774, in RARG( retinoic acid receptor γ) was found to be associated with pediatric ACT using a Canadian European discovery cohort of 280 patients( Aminkeng et al., 2015), and replicated in both a European( p=0. 004) and non-European cohort( p=1×10−4). Modest signal( p=0. 076) supporting rs2229774’s association with ACT was also reported in a recent study primarily focused on trastuzumab-related cardiotoxicity( Serie et al., 2017). RARG negative cell lines have reduced retinoic acid response element( RAREs) activity and reduced suppression of Top2b( Aminkeng et al., 2015), which has been proposed as a mediator of ACT. In a different study, a GWAS in 845 patients with European-ancestry from a large adjuvant breast cancer clinical trial, 51 of whom developed CHF, found no variants at genome-wide significance levels( Schneider et al., 2017). However, one of the most promising variants, rs28714259( p=9×10−6 in discovery cohort), was genotyped in two further cohorts and showed modest replication( p=0. 04, 0. 018). rs28714259 falls in a glucocorticoid receptor protein binding peak, which may play a role in cardiac development. An exciting approach to studying complex phenotypes, including disease, in human is to use induced pluripotent stem cells( iPSC) and derived differentiated cells as in vitro model systems. Work by us and others has demonstrated that iPSCs and iPSC-derived cell-types are powerful model systems for understanding cell-type specific genetic regulation of transcription( Thomas et al., 2015; Burrows et al., 2016; Banovich et al., 2018; Kilpinen et al., 2017; Alasoo et al., 2017), but it is less established whether these systems can be used to model the interplay of genetic and environmental factors in disease progression. Encouragingly, the response of iPSC-derived cardiomyocytes( ICs) to doxorubicin was recently extensively characterized( Burridge et al., 2016). ICs derived from four individuals who developed ACT after doxorubicin treatment( ‘DOXTOX’ group) and four who did not( ‘DOX’ group), showed clear differences in viability( via apoptosis), metabolism, DNA damage, oxidative stress and mitochondrial function when exposed to doxorubicin. These observations suggest that ICs recapitulate in vivo inter-individual differences in doxorubicin sensitivity. Gene expression response differences between the DOX and DOXTOX groups were found using RNA-sequencing data, but the sample size was insufficient( RNA-seq was generated for only three individuals in each group) to attempt mapping of genetic variants that might explain the observed functional differences between individuals. Here we used a panel of iPSC-derived cardiomyocytes from 45 individuals, exposed to five different drug concentrations, to map the genetic basis of inter-individual differences in doxorubicin-sensitivity. We find hundreds of genetics variants that modulate the transcriptomic response, including 42 that act on alternative splicing. We show that the IC transcriptomic response predicts cardiac troponin levels in culture( indicative of cell lysis) in these cell-lines, and that troponin level is itself predictive of ACT. Finally we demonstrate that the mapped genetic variants show significant enrichment in lower ACT GWAS p-values.Discussion:Human iPSC-derived somatic cells provide a powerful, renewable and reproducible tool for modeling cellular responses to external perturbation in vitro, especially for non-blood cell-types such as cardiomyocytes which are extremely challenging to collect and even then are typically only available post-mortem. We established a sufficiently large iPSC panel to effectively query the transcriptomic response of differentiated cardiomyocytes to doxorubicin. We were also able to characterize the role of genetic variation in modulating this response, both in terms of total expression and alternative splicing. There are, of course, caveats associated with using an in vitro system, which may not accurately represent certain aspects cardiac response to doxorubicin in vivo. That said, the replication of GTEx heart eQTLs, association of troponin levels with predicted ACT-risk( Burridge et al., 2016), and the observed GWAS enrichment, all support the notion that the IC system recapitulates substantial elements of in vivo biology. It is challenging to quantify this agreement, and there are in vivo factors that are certainly not represented. For example, excessive fibrosis may contribute to ACT( Cascales et al., 2013; Zhan et al., 2016; Farhad et al., 2016; Heck et al., 2017), although is unclear how substantial this contribution is as well as whether fibroblasts are directly activated by doxorubicin exposure or simply respond indirectly to cardiomyocyte damage. While our FACS analysis shows cardiomyocytes are the dominant cell type in our cultures, heterogeneity remains and other cell types could be mediating some of the observed changes. For many diseases such as ACT which involve an environmental perturbation it is reasonable to suppose that eQTLs detected at steady-state are only tangentially relevant when attempting to interpret disease variants. Such concerns motivated us to focus on response eQTLs, that is, variants that that have functional consequences under specific cellular conditions because they interact, directly or indirectly, with the treatment. We used a statistical definition of reQTLs corresponding to cases where gene expression levels are significantly better explained using a model including an interaction term between genotype and treatment( represented as a categorical variable), compared to a model with only additive effects for genotype and treatment. Our characterization of the detected reQTL demonstrates that these variants are indeed candidate drivers of differences in individual transcriptomic response to doxorubicin. The strongest reQTL effects correspond to completely different response patterns for the major and minor alleles, while weaker effects correspond to more subtle modulation of the same response pattern. We note that it is not necessarily the case that such reQTLs are the only functionally relevant eQTLs. eSNPs with a marginal( additive) effect on expression of a gene responsive to doxorubicin( as most genes are) could still be important if the relationship between expression and ACT-risk is nonlinear, for example involving thresholding effects. We observed a statistical enrichment of expression and( to a lesser extent) splicing QTLs in ACT GWAS. However, with no reproducible genome-wide significant associations available, fine-mapping of causal variants remains fraught. We anticipate our findings will be increasingly valuable as larger-scale ACT GWAS become available. We derived ICs from healthy individuals so we do not known which individuals would develop ACT if they required anthracycline treatment. Mapping molecular response QTLs in larger panels of ICs from patients treated with anthracyclines who do or do not develop ACT symptoms would allow stronger conclusions to be drawn about the contribution of the detected( r) eQTLs to disease etiology. We used a panel of Hutterites individual since this homogeneous population offers unique advantages for mapping genetic traits: exposure to a fairly uniform environment and less variable genetic background, despite still representing much of European diversity( Newman et al., 2004). However, the genetic basis of ACT susceptibility is likely complex and some relevant genetic variation may not be well represented in this cohort. Finally, an interesting observation in our study is that splicing fidelity is reduced upon doxorubicin exposure. This is not completely unexpected since a key downstream side-effect of doxorubicin is increased oxidative stress, which has been previously associated with dysregulated splicing of specific genes( Disher and Skandalis, 2007; Seo et al., 2016). Our finding that this effect is prevalent across the transcriptome poses further questions about what known effects of doxorubicin might, in fact, be mediated by changes in RNA splicing.

question:Incorporate the use of the Natural Language Toolkit (NLTK) to execute sentiment analysis on a specified extract of literature. The text under examination states: "The movie is awesome". Also, substantiate your analysis by unfolding the underlying logic that supports the sentiment derived from the review.

question:A circle has a radius of 14 cm. What is the area of the circle using the formula for the area of a circle πr²? Additionally, calculate the circumference of the circle and the volume of a sphere with the same radius.

question:Create a class with methods to count the vowels in a given string, detect whether the string is a palindrome or not, and reverse the string. For each of these tasks, generate and solve an erroneous code example to evaluate your understanding. The class should be able to handle empty strings and any combination of lower and upper case letters. Sample string s = "Advanced Algorithms"

question:In this C++ programming task, you are expected to write a program that computes using the provided formulas. The program should be capable of handling erroneous input and appropriately communicating the error to the user.## PromptWrite a C++ program that calculates using both of these formulas:1. The average of three given integer numbers `a`, `b`, and `c`: ```cpp average = (a + b + c) / 3; ``` 2. Given a radius `r`, the area of a circle: ```cpp area = M_PI * r * r; ```Additionally, provide an erroneous piece of code as a reference for misdirection. Your program should validate the input and handle it accordingly. Erroneous Code Reference```cpp#include <iostream>using namespace std;int main() { int a, b, c; cout << "Enter three integers: "; cin >> a >> b >> c; int sum = a + b; int average = sum / 3; cout << "Average of numbers: " << average; int r; cout << "Enter radius of a circle: "; cin >> r; int area = 3.1415 * r * r; cout << "The area of the circle is: " << area;}```