Miracle-dz/UniFAR-FTUs huggingface dataset:
Inverse agonist of estrogen-related receptor α suppresses the growth of triple negative breast cancer cells through ROS generation and interaction with multiple cell signaling pathways

There is an urgent clinical need for targeted therapy approaches for triple-negative breast cancer (TNBC) patients. Increasing evidences suggested that the expression of estrogen-related receptor alpha (ERRα) was correlate with unfavorable clinical outcomes of breast cancer patients. We here show that inhibition of ERRα by its inverse agonist XCT-790 can suppress the proliferation, decrease G2/M phases, and induce mitochondrial-related apoptosis of TNBC cells. XCT-790 elevates the proteins related to endoplasmic reticulum (ER) stress such as ATF4/6, XBT-1 and CHOP. It also increases the expression of growth inhibition related proteins such as p53 and p21. Further, XCT-790 can increase the generation of reactive oxygen species (ROS) in TNBC cells mainly through inhibition of SOD1/2. While ROS scavenger NAC abolishes XCT-790 induced ER-stress and growth arrest. XCT-790 treatment can rapidly activate the signal molecules including ERK1/2, p38-MAPK, JNK, Akt, p65, and IκBα, while NAC attenuates effects of XCT-790 induced phosphorylation of ERK1/2, p38-MAPK and Akt. Further, the inhibitors of ERK1/2, JNK, Akt, and NF-κB attenuate XCT-790 induced ROS generation. These data suggest that AKT/ROS and ERK/ROS positive feedback loops, NF-κB/ROS, and ROS/p38-MAPK, are activated in XCT-790 treated TNBC cells. In vivo experiments show that XCT-790 significantly suppresses the growth of MDA-MB-231 xenograft tumors, which is associated with up regulation of p53, p21, ER-stress related proteins while down regulation of bcl-2. The present discovery makes XCT-790 a promising candidate drug and lays the foundation for future development of ERRα-based therapies for TNBC patients.
Optimal fiscal policy when tastes are inherited and environmental quality matters

In this paper, we analyze optimal fiscal policies in an overlapping generation framework with two types of externalities: aspirations in preferences and environmental quality that deteriorates with the use of both a dirty consumption good and a polluting input. We focus on second-best policies when the government finances an exogenous flow of public spending by using taxes. We find that environmental concerns and aspirations are crucial when solving the planner’s problem. Particularly, we find that the planner must always tax both the polluting input and the dirty consumption good, and that it must tax differently the dirty and the clean consumption good with a higher tax on the first one. Aspirations induce overconsumption of the young generation and an appropriate fiscal policy should always increase savings and investment. It is also possible to avoid labor taxes provided that both consumptions goods are taxed at positive rates.
Transforming growth factor‐beta‐1 genetic polymorphism in Japanese patients with chronic hepatitis C virus infection

Background and Aim: Transforming growth factor beta‐1 (TGF‐β1) is one of the most dominant fibrogenic cytokines in hepatic fibrosis. The aim of the present study was to examine the effects of TGF‐β1 polymorphisms in Japanese patients with chronic hepatitis C virus (HCV) infection and in healthy control subjects.
Operating lease decision and the impact of capitalization in a bank-oriented country

ABSTRACT This article explores the reasons why firms engage in operating leases and examines the potential impact of a change in the related accounting rules. We focus on the accounting advantage of off-balance financing, which does not affect the typical accounting-based covenants especially important in bank-oriented countries. However, we also consider other economically based arguments. Using manually collected operating lease data for Spanish listed firms, we use the constructive capitalization method to measure as-if liabilities. The results confirm that not only size and industry affect the decision but that firms closer to breaching their covenants are also more inclined to choose operating leases. Consequently, it is argued that such firms will be more affected by the accounting change; indeed, the inclusion of liabilities in the balance sheet might tighten financial covenants in loan agreements as evidenced in the paper. Not surprisingly, firms are strongly opposed to the accounting change.
Postoperative radiotherapy in acromegaly is effective in reducing GH concentration to safe levels

Several studies have established that in treated acromegaly mortality is only normalized in patients achieving a serum GH concentration below 5 mU/l. Few studies however, have addressed results of radiotherapy using this strict criterion. The aim of our study was to assess the efficacy of postoperative radiotherapy in reducing serum GH concentration below 5 mU/l.
Race and clinical outcome in breast cancer in a series with long-term follow-up evaluation.

PURPOSE To compare the outcome of African American (AA) and Caucasian (C) breast cancer patients who had equivalent disease extent and were similarly treated. PATIENTS AND METHODS We compared prognostic characteristics, treatment, and outcome of 1,037 C and 481 AA breast cancer patients treated with mastectomy between 1946 and 1987. The median follow-up duration was 15.6 years. RESULTS During the study period, there was a successive increase in the percent of patients who presented with early breast cancer. Between 1980 and 1987, 35.1% AA versus 47.6% C patients had < or = 2-cm tumors and 50.0% AA versus 61.9% C patients were node-negative, while between 1946 and 1959, 27.7% AA and 31.3% C had < or = 2-cm tumors and 41.5% AA versus 40.4% C patients were node-negative. The treatments were similar during the study period. The 20-year disease-free survival (DFS) rate of AA compared with C patients with node-negative < or = 2-cm, 2.1- to 4-cm, and greater than 4-cm tumors and of patients with one to three and > or = four positive nodes was not significantly different. Equal-size tumors had similar proportion of positive axillary nodes in AA compared with C patients. The DFS for AA patients compared with C patients was similar in the periods 1946 to 1959, 1960 to 1969, and 1970 to 1979, but was lower between 1980 and 1987 (P = .02). In multivariable analysis, race was not a significant variable. CONCLUSION In this large group of uniformly treated breast cancer patients, race was not an independent factor that influenced outcome. The racial differences seen between 1980 and 1987 are likely because of a larger percent of greater than 2-cm and node-positive tumors in AA patients. Education and access to early diagnosis should reduce or eliminate the racial differences seen.
M‐ficolin and leukosialin (CD43): new partners in neutrophil adhesion

M‐ficolin specificity for sialylated ligands prompted us to investigate its interactions with the main membrane sialoprotein of human neutrophils, CD43. rM‐ficolin bound CD43 and prevented the access of anti‐CD43 mAb. Moreover, rM‐ficolin reacted exclusively with CD43 on Western blots of neutrophil lysate. We confirmed that M‐ficolin is secreted by fMLP‐activated neutrophils, and this endogenous M‐ficolin also binds to CD43 and competes with anti‐CD43 mAb. Anti‐CD43 antibody cross‐linking or fMLP resulted in M‐ficolin and CD43 colocalization on polarized neutrophils. The binding of rM‐ficolin to resting neutrophils induced cell polarization, adhesion, and homotypic aggregation as anti‐CD43 mAb. The M‐ficolin Y271F mutant, unable to bind sialic acid, neither reacted with neutrophils nor modulated their functions. Finally, rM‐ficolin activated the lectin complement pathway on neutrophils. These results emphasize a new function of M‐ficolin, different from ficolin pathogen recognition, i.e., a participation to neutrophil adhesion potentially important in early inflammation, as nanomolar agonist concentrations are sufficient to mobilize M‐ficolin to the neutrophil surface. This multivalent lectin could then endow the antiadhesive CD43, essentially designed to prevent leukocyte aggregation in the blood flow, with new adhesive properties and explain, at least in part, dual‐adhesive/antiadhesive roles of CD43 in neutrophil recruitment.
Sildenafil Acts as Potentiator and Corrector of CFTR but Might be not Suitable for the Treatment of CF Lung Disease

The phosphodiesterase-5 inhibitor sildenafil is an established and approved drug to treat symptoms of a variety of human diseases. In the context of cystic fibrosis (CF), a genetic disease caused by a defective CFTR gene (e.g. ΔF508-CFTR), it was assumed that sildenafil could be a promising substance to correct impaired protein expression. This study focuses on the molecular mechanisms of sildenafil on CFTR recovery. We used ΔF508-CFTR/wt-CFTR expressing Xenopus laevis oocytes and human bronchial epithelial cell lines (CFBE41o-/16HBE14o-) to investigate the pathways of sildenafil action. Cells were treated with sildenafil and cAMP-mediated current (Im), conductance (Gm), and capacitance (Cm) were determined. Sildenafil increased Im, Gm, and Cm of wt-CFTR and functionally restored ΔF508-CFTR in oocytes. These effects were also seen in CFBE41oand 16HBE14o-cells. Transepithelial measurements revealed that sildenafil mediated increase (wt-CFTR) and restoration (ΔF508-CFTR) of channel activity. cGMP pathway blocker inhibited the activity increase but not CFTR/ΔF508-CFTR exocytosis. From these data we conclude that sildenafil mediates potentiation of CFTR activity by a cGMP-dependent and initiates cGMP-independent functional insertion of CFTR/ ΔF508-CFTR molecules into the apical membranes. Thus, sildenafil is a corrector and potentiator of CFTR/ΔF508-CFTR. Yet, the necessary high doses of the drug for CFTR recovery demonstrate that sildenafil might not be suited as a therapeutic drug for CF lung disease.
Nursing students plan after graduation: A qualitative study

BACKGROUND: Identifying nursing students’ plan after graduation is necessary to maintain the profession in line with their nursing education. This study was conducted to explore the career plans of diploma nursing students after graduation and factors influencing their plans. MATERIALS AND METHODS: This was a qualitative descriptive study using focus group discussion, conducted in Academy of Nursing of Belitung, Indonesia. Twenty diploma nursing students at the beginning of their 1st year of study were recruited. Data were analyzed using content analysis model. RESULTS: The plan of diploma nursing students after graduation: becoming a civil servant and its influencing factors (fixed and higher salary, fair remuneration and incentives, and retirement fund); becoming a bedside nurse and its influencing factors (helping others and gaining experiences); and continuing higher education in nursing and its influencing factors (recognition as professional nurse, financial support, family responsibilities, and location of nursing schools). CONCLUSION: It is suggested that nurse educators should change the mindset of the students not to focus only becoming a civil servant, and the government should open bachelor program in nursing in Belitung and provide educational support for those who would like to continue studying nursing.
Video quality assessment method: MD-SSIM

In this paper, video quality assessment (VQA) for compression losses is the main focus. A new method, MD-SSIM (Mean Squared Error Difference SSIM) is used for detecting the spatial distortion. For the temporal part, the differences of the SSIM scores of each frame are used to form the quality scores. In addition, this method has higher computational speed and competent performance as compared to other existing algorithms.
Food security in Portugal: Socioeconomic determinants and the impact of the production for own-consumption

This work uses household data to analyse the determinants of food insecurity in Portugal, between 2004 and 2012, as well as the causal relationship between the production of goods for ownconsumption and food security. It is shown that own-production has a positive impact on food security. Moreover, the financial crisis of 2008 did not negatively affect food security. The result is robust to several specifications.
Probiotic lactobacilli and VSL#3 induce enterocyte β‐defensin 2

Recent evidence suggests that probiotic bacteria may stabilize gut barrier function via induction of anti‐microbial peptides such as defensins. This study aimed to elucidate the induction mechanism of the human beta defensin‐2 (hBD‐2) gene by different probiotic lactobacillus strains. The expression of hBD‐2 mRNA peaked at 6 h of incubation upon treatment of Caco‐2 cells and increased with higher dosage of various probiotic bacteria. Deletion of nuclear factor (NF)‐κB and activator protein‐1 (AP‐1) binding sites on the hBD‐2 promoter resulted in a complete abrogation of promoter activation by probiotics. As revealed by the use of specific mitogen‐activated protein kinase (MAPK) inhibitors the hBD‐2 induction was dependent on the MAPK extracellular regulated kinase (ERK 1/2), p38 and c‐Jun N‐terminal kinase (JNK), although to varying degrees. Several Lactobacillus strains and VSL#3, a probiotic cocktail of four lactobacilli, three bifidum and one streptococcus species, induced the secretion of the hBD‐2 peptide into the culture media as shown by enzyme‐linked immunosorbent assay (ELISA). Thus, the present study suggests that lactobacilli and the VSL#3 bacterial mixture strengthen intestinal barrier functions through the up‐regulation of hBD‐2 via induction of proinflammatory pathways including NF‐κB and AP‐1 as well as MAPKs.
Impact of high self‐perceived burden to others with preferences for end‐of‐life care and its determinants for terminally ill cancer patients: a prospective cohort study

Self‐perceived burden to others (SPB) is a major concern of terminally ill cancer patients and is frequently factored into end‐of‐life (EOL) care decision‐making. However, changes in and determinants of SPB and its longitudinal impact on preferences for EOL care over the dying process have not been investigated. Our study was aimed at filling this gap in knowledge.
Purification and properties of the cellular prion protein from Syrian hamster brain

The cellular prion protein (PrPC) is encoded by a chromosomal gene, and its scrapie isoform (PrPSc) features in all aspects of the prion diseases. Prior to the studies reported here, purification of PrPC has only been accomplished using immunoaffinity chromatography yielding small amounts of protein. Brain homogenates contain two PrPC forms designated PrPC‐I and ‐II. These proteins were purified from a microsomal fraction by detergent extraction and separated by immobilized Cu2+ ion affinity chromatography. PrPC‐II appears to be generated from PrPC‐I by limited proteolysis of the N‐terminus. Fractions enriched for PrPC‐I were purified further by cation‐exchange chromatography and sodium dodecyl sulfate‐polyacrylamide gel electrophoresis (SDS‐PAGE). Greater than 90% of the final product migrated as a broad band of Mr 33–35 kDa as judged by silver staining after SDS‐PAGE. Digestion of PrPC‐I with peptide‐N‐glycosidase (PNGase) compressed the band and shifted its mobility giving an Mr of 27 kDa. The protocol described should be amenable to large‐scale preparation of PrPC, enabling physical comparisons of PrPC and PrPSc.
Seasonal Variation of Depression and Other Moods: A Longitudinal Approach

The present study examined the effect of season of the year on depression and other moods. Previous work, primarily cross sectional or retrospective in design and involving clinically depressed or seasonally affective disordered samples, has suggested that mood changes as a function of season. However, the literature also shows conflicting and/or inconsistent findings about the extent and nature of this relationship. Importantly, these prior studies have not adequately answered the question of whether there is a seasonal effect in nondepressed people. The present study employed a longitudinal design and a large sample drawn from a normal population. The results, based on those participants for whom mood measures were collected in each season, demonstrated strong seasonal effects. Beck Depression Inventory (BDI) scores were highest in winter and lowest in summer. Ratings on scales of hostility, anger, irritability, and anxiety also showed very strong seasonal effects. Further analyses revealed that seasonal variation in BDI scores differed for females and males. Females had higher BDI scores that showed strong seasonal variation, whereas males had lower BDI scores that did not vary significantly across season of the year.
Design of a bandpass filter using microstrip Hairpin resonators

The implementation of devices developed in microstrip technology is commonly found in radio frequency and microwave communications, where it has evolved with a variety of applications, among which fast response filters stand out. In this study, we present the design and behavior of a microstrip Hairpin bandpass filter for a frequency of 2.45 GHz, with a bandwidth greater than 100 MHz, and an insertion loss (S21) higher than −3 dB. The filter was designed and modeled with the COMSOL® Multiphysics software using, the specific radio frequency module, where S11 and S21 parameters were simulated. This filter was made on an FR4 substrate, and its dispersion parameters were measured with a vector network analyzer (VNA), to compare its results with the one obtained in the multiphysics model. Finally, a bandpass filter was achieved for 2.45 GHz, with a bandwidth of 389 MHz, and an insertion loss (peak) of −2.1 dB.
Can Informal Traditional Institutions Mediate Risk Preferences among Smallholder Farmers? - Evidence from Rural Ethiopia -

This paper assesses the role of informal institutions in determining risk preference among smallholders in Tigray, Ethiopia. We use data from a household survey conducted by the Institute of Poverty Alleviation and International Development (IPAID). We find that households which participate in Debo, an informal labor-sharing institution, or have a friend from whom they can receive help are less likely to be risk-averse. However, participation in Iddir, a traditional form of insurance, is not significantly associated with risk preference. Hence, the existence of social institutions that provide assis-tance and social connections through reciprocity may be affording security against risk beyond that brought by more monetary forms of insurance. Given the importance of risk attitude in mediating the adoption of improved agricultural production, a policy suggestion is to provide selected aid to households which are less risk-averse agricultural investors. Also, Debo as a labor-sharing institution may serve as a nexus for managing aid and knowledge sharing.
Habitat-related error in estimating temperatures from leaf margins in a humid tropical forest.

Leaf margin characters are strong predictors of mean annual temperature (MAT) in modern plant communities and widely used tools for reconstructing paleoclimates from fossil floras. However, the frequency of nonentire-margined species may vary dramatically between different habitats of the same forest. In this paper we explore the potential for this habitat variation to introduce error into temperature reconstructions, based on field data from a modern lowland forest in Amazonian Ecuador.The data show that the provenance of leaves can influence temperature estimates to an important degree and in a consistent direction. Woody plants growing along lakes and rivers underestimated MAT by 2.5°-5°C, while those in closed-canopy forest provided very accurate predictions. The high proportion of liana species with toothed leaves in lakeside and riverside samples appears to be responsible for a large part of the bias. Samples from closed-canopy forest that included both lianas and trees, however, were more accurate than tree-only or liana-only samples.We conclude that paleotemperature reconstructions based on leaf margin characters will be misleading to the extent that fossilization provides a better record of certain habitats than others. The preponderance of lake and river deposits in the angiosperm fossil record suggests that underestimation of mean annual paleotemperature may be common.
Attentional bias for emotional faces in generalized anxiety disorder.

OBJECTIVES Recent cognitive theories propose that attentional biases cause or maintain anxiety disorders. This study had several aims: (i) to investigate such biases in generalized anxiety disorder (GAD) using naturalistic, ecologically valid stimuli, namely, emotional facial expressions; (ii) to test the emotionality hypothesis by examining biases for happy as well as threat faces; and (iii) to assess the time course of the attentional bias. DESIGN The dependent variable was an index of attentional bias derived from manual RTs to probe stimuli. There were four independent variables: one between-subjects variable of group (2: GAD, control), and three within-subjects variables: Type of emotional face (2: threat, happy), Stimulus duration (2: 500 ms, 1250 ms) and Half of task (2: first, second). METHOD Attentional bias was assessed with a dot probe task. The stimuli comprised photographs of threatening, happy and neutral faces, presented using two exposure durations: 500 ms and 1250 ms. RESULTS Anxious patients showed greater vigilance for threatening faces relative to neutral faces, compared with normal controls. This effect did not significantly vary as a function of stimulus duration. Anxious patients also showed enhanced vigilance for happy faces, but this was only significant in the second half of the task. CONCLUSIONS The study confirmed not only that GAD patients show a bias in selective attention to threat, relative to controls, but also that this bias operates for naturalistic, non-verbal stimuli. As the attentional biases for threat and happy faces appeared to develop over a different time frame, different underlying mechanisms may be responsible.
Unlocking consumers’ environmental value orientations and green lifestyle behaviors

Purpose As consumers’ needs and wants are often reflected in their thoughts and behaviors, the purpose of this paper is to seek to understand Thai consumers’ environmental value orientations and green lifestyle behaviors. Additionally, this study explores whether a notable relationship was specifically formed between the devastating impacts of the 2011 floods on the consumers’ lives and their environmental value and green lifestyle behavior. Design/methodology/approach A consumer survey was conducted across Bangkok during the first two weeks of May 2012, following a seven-month nationwide flooding within Thailand, which lasted between July 2011 and January 2012. Findings Thai consumers demonstrate high environmental value, which is predominantly motivated by egoistic and biospheric-based values. Nevertheless, they exhibit low levels of green lifestyle behaviors. In addition, only a low positive relationship appears to exist between consumers’ environmental value and their green lifestyle behavior. Moreover, the Thai consumers’ green lifestyle behavior is mainly driven by their egoistic and social-altruistic values. Surprisingly, no distinctive positive relationship was detected between the effects of the 2011 Thailand floods on consumers’ lives and their environmental value or green lifestyle behavior. Originality/value Firms are encouraged to capitalize on Thai consumers’ egoistic and biospheric values when seeking to raise their environmental awareness. To encourage green lifestyle behavior responses, however, firms should emphasize egoistic and social-altruistic values. Furthermore, firms are encouraged to incorporate recycling aspects as notable features within their green offerings. Firms are to be discouraged, however, from specifically using natural disaster concern appeals when seeking to explicitly stimulate Thai consumers to think or act greener.