Miracle-dz/UniFAR-FTUs huggingface dataset:
Down-regulation of extracellular signal-regulated kinase 1/2 activity in P-glycoprotein-mediated multidrug resistant hepatocellular carcinoma cells.

AIM To study the expression and phosphorylation of extracellular signal-regulated kinase (ERK) 1 and ERK2 in multidrug resistant (MDR) hepatocellular carcinoma (HCC) cells. METHODS MDR HCC cell lines, HepG2/adriamycin (ADM) and SMMC7721/ADM, were developed by exposing parental cells to stepwise increasing concentrations of ADM. MTT assay was used to determine drug sensitivity. Flow cytometry was employed to analyze cell cycle distribution and measure cell P-glycoprotein (P-gp) and multidrug resistant protein 1 (MRP1) expression levels. ERK1 and ERK2 mRNA expression levels were measured by quantitative real-time PCR (QRT-PCR). Expression and phosphorylation of ERK1 and ERK2 were analyzed by Western blot. RESULTS MTT assay showed that HepG2/ADM and SMMC7721/ADM were resistant not only to ADM, but also to multiple anticancer drugs. The P-gp expression was over 10-fold higher in HepG2/ADM cells than in HepG2 cells (8.92% +/- 0.22% vs 0.88% +/- 0.05%, P < 0.001) and over 4-fold higher in SMMC7721/ADM cells than in SMMC7721 cells (7.37% +/- 0.26% vs 1.74% +/- 0.25%, P < 0.001). However, the MRP1 expression was not significantly higher in HepG2/ADM and SMMC7721/ADM cells than in parental cells. In addition, the percentage of MDR HepG2/ADM and SMMC7721/ADM cells was significantly decreased in the G0/G1 phase and increased in the the S phase or G2/M phase. QRT-PCR analysis demonstrated that the ERK1 and ERK2 mRNA expression increased apparently in HepG2/ADM cells and decreased significantly in SMMC7721/ADM cells. Compared with the expression of parental cells, ERK1 and ERK2 protein expressions were markedly decreased in SMMC7721/ADM cells. However, ERK2 protein expression was markedly increased while ERK1 protein expression had no significant change in HepG2/ADM cells. Phosphorylation of ERK1 and ERK2 was markedly decreased in both HepG2/ADM and SMMC7721/ADM MDR cells. CONCLUSION ERK1 and ERK2 activities are down-regulated in P-gp-mediated MDR HCC cells. ERK1 or ERK2 might be a potential drug target for circumventing MDR HCC cells.
Retroviral gene transfer of signaling molecules into murine fetal hepatocytes defines distinct roles for the STAT3 and ras pathways during hepatic development

We recently demonstrated that oncostatin M (OSM) in the presence of glucocorticoid promotes development of fetal hepatic cells in a primary culture system. Our results also suggested that OSM transduces differentiation signals through gp130, a common subunit of the interleukin (IL)‐6 family cytokine receptors. However, an essential downstream pathway required for hepatic development remains unknown. To address this issue, we expressed signal molecules by a retroviral expression vector in primary fetal hepatic cells and investigated a signaling pathway essential for OSM‐mediated hepatic development. Expression of a dominant‐negative form of STAT3 (ΔSTAT3), but not ΔSTAT5, suppressed differentiated phenotypes of hepatocytes induced by OSM. On the other hand, dominant‐negative forms of Ras (RasN17) and SHP‐2(C463A) rather augmented the expression of hepatic differentiation markers, suggesting that the Ras pathway negatively regulates hepatic development. Consistently, expression of a constitutively activated form of Ras (RasV12) inhibited cellular responses to OSM. Our results indicate that STAT3 is an essential signaling component for OSM‐induced hepatic development, while activation of Ras appears to negatively regulate this process. Thus, retrovirus‐mediated gene transfer is an effective means to analyze function of a gene in primary fetal hepatic culture.
Machine learning models in breast cancer survival prediction.

BACKGROUND Breast cancer is one of the most common cancers with a high mortality rate among women. With the early diagnosis of breast cancer survival will increase from 56% to more than 86%. Therefore, an accurate and reliable system is necessary for the early diagnosis of this cancer. The proposed model is the combination of rules and different machine learning techniques. Machine learning models can help physicians to reduce the number of false decisions. They try to exploit patterns and relationships among a large number of cases and predict the outcome of a disease using historical cases stored in datasets. OBJECTIVE The objective of this study is to propose a rule-based classification method with machine learning techniques for the prediction of different types of Breast cancer survival. METHODS We use a dataset with eight attributes that include the records of 900 patients in which 876 patients (97.3%) and 24 (2.7%) patients were females and males respectively. Naive Bayes (NB), Trees Random Forest (TRF), 1-Nearest Neighbor (1NN), AdaBoost (AD), Support Vector Machine (SVM), RBF Network (RBFN), and Multilayer Perceptron (MLP) machine learning techniques with 10-cross fold technique were used with the proposed model for the prediction of breast cancer survival. The performance of machine learning techniques were evaluated with accuracy, precision, sensitivity, specificity, and area under ROC curve. RESULTS Out of 900 patients, 803 patients and 97 patients were alive and dead, respectively. In this study, Trees Random Forest (TRF) technique showed better results in comparison to other techniques (NB, 1NN, AD, SVM and RBFN, MLP). The accuracy, sensitivity and the area under ROC curve of TRF are 96%, 96%, 93%, respectively. However, 1NN machine learning technique provided poor performance (accuracy 91%, sensitivity 91% and area under ROC curve 78%). CONCLUSIONS This study demonstrates that Trees Random Forest model (TRF) which is a rule-based classification model was the best model with the highest level of accuracy. Therefore, this model is recommended as a useful tool for breast cancer survival prediction as well as medical decision making.
Hyperosmotic Urea Reversibly Opens the Tight Junctions Between Brain Capillary Endothelial Cells in Cell Culture

The effect of hyperosmotic solutions of urea on primary cultures of bovine brain microvessel endothelial cells was examined. Confluent monolayers of cells positive for Factor VIII-related antigen were obtained by seven days in culture. The cells were: (a) incubated in media containing 1 M, 2 M or 3 M urea and horseradish peroxidase (HRP) for various periods of time and then examined by transmission electron microscopy. (b) Exposed to hypertonic urea solutions and 14C-3-O-methyl-D-glucose for determination of the intracellular water space. In control cultures endothelial cells were bound together by tight junctional complexes over 91% of which excluded HRP. In experimental cultures 82% of the interendothelial clefts became permeable to HRP after one minute of incubation with 3 M urea. The degree of cell shrinkage corresponded well with the extent of junctional opening. In monolayers examined 24 hours following removal of urea from the media more than 63% of the intercellular clefts were impermeable to HRP. These observations indicate that hyperosmotic solutions of urea reversibly open the tight junctions between brain microvessel endothelial cells in tissue culture. Decrease in cell volume appears to be linked to the increased junctional permeability.
Modèles réduits pour l'étude des mécanismes et de la modulation de l'oscillation australe El Niño

L'Oscillation Australe El Nino (ENSO pour El Nino Southern Oscillation) est la fluctuation climatique la plus intense sur Terre apres le cycle saisonnier. L'observation, la comprehension et la prevision de cette fluctuation aux retombees mondiales sont des enjeux scientifiques majeurs. Cette these documente divers aspects d'ENSO tels que ses mecanismes, sa modulation et sa prevision. Ces divers aspects sont abordes en developpant une hierarchie de modeles du Pacifique equatorial, de complexite croissante, qui s'etend de modeles conceptuels a une methode d'assimilation de donnees dans un modele de complexite intermediaire. Nous etudions dans un premier temps les mecanismes de formation d'ENSO. Nous developpons une derivation alternative du modele conceptuel de recharge/decharge ou ENSO resulte d'un ajustement de la thermocline equatoriale a echelle de bassin. Nous implementons par ailleurs un diagnostic original dans un modele d'instabilites couplees equatoriales, ce qui met en avant un nouveau mecanisme de formation d'ENSO ou les reflexions aux frontieres oceaniques jouent un role secondaire. La stratification moyenne de l'ocean contribue a la modulation decenalle des caracteristiques d'ENSO. Cette relation est abordee dans un nouveau modele reduit qui prend en compte les premiers modes baroclines d'un ocean continument stratifie. L'espace des solutions du modele est explore, indiquant un controle de la stabilite d'ENSO par les caracteristiques de la thermocline equatoriale. La sensibilite a la stratification au cours des dernieres decennies est mise en perspective avec la sensibilite aux retroactions thermodynamiques et atmospheriques. Nous soulignons en particulier certaines limitations des methodes usuelles d'estimation de la retroaction de thermocline dans le Pacifique central. Finalement, nous implementons une methode de Filtre de Kalman d'Ensemble dans un modele intermediaire du Pacifique equatorial deja existant, afin d'assimiler des observations de niveau de la mer et d'initialiser des previsions retrospectives d'ENSO. Nous montrons que la contrainte majeure du modele porte sur les modes de bassin qui sont associes au processus de recharge/decharge du Pacifique equatorial. Notre travail fournit un formalisme pour diagnostiquer la modulation des caracteristiques d'ENSO dans les observations, les previsions et projections climatiques. Les resultats soutiennent la necessite d'etendre la comprehension des mecanismes d'ENSO, afin de rendre compte de la diversite des regimes observes et d'ameliorer les previsions.
Effects of postmilking teat treatment on the colonization of Staphylococcus aureus on chapped teat skin.

Sixteen Holstein cows were used to test the effect of postmilking teat treatment on colonization and intramammary infection by Staphylococcus aureus on chapped teats. Treatments were (1) chapping the teat and using 1% I2/10% glycerin postdip solution, (2) 1% I2/10% glycerin postdip solution on nonchapped teats, (3) chapping the teat and using 10% glycerin postdip solution, (4) chapping the teat and not using a postdip solution. All mammary glands were free of S aureus teat skin colonization and intramammary infection at the start of the study. Teats selected for chapping were dipped in 1N NaOH prior to 3 applications of S aureus broth culture; cultures were applied at 12-hour intervals on all teats. Treatments were applied after each milking for 30 days and were initiated after the second broth dip. Teat skin swab specimens and milk samples were collected before treatment application. Teat skin condition was scored daily. Nonchapped teats (treatment 2) did not support skin or orifice colonization by S aureus. Treatment-1 teats healed most rapidly and supported less colonization in skin and orifice than did treatment-3 and -4 teats. Teat skin scores and skin colonization were lower for treatment-3 than treatment-4 teats. A correlation between teat skin colonization and teat skin conditions was found. Two intramammary infections were found in treatment-4 quarters and 1 in a treatment-3 quarter. (ABSTRACT TRUNCATED AT 250 WORDS)
Spatiotemporal patterns of primary productivity derived from remote sensing and flux measurements

Summary form only given. Forest ecosystem plays an important role in regulating the global climate by serving as the primary carbon pool for atmospheric carbon dioxide. Deforestation and forest degradation could pose a serious threat on the global emission of greenhouse gases, and this has been declared as the critical issue for United Nation's REDD programme. Under the threat of global warming and climate change, it is critical to quantify the mechanism of carbon flux in order to locate the so-called missing carbon sink and to identify potential strategies for mitigation. With complex ecosystem functions and uncertainty of climate change, both the micro-and macroscopic behavior of carbon flow and its influencing factors have to be systematically studied. There are consequently significant national and international efforts to develop a carbon monitoring system, such as the National Forest Carbon Monitoring, Accounting and Reporting System developed by Canada government, and National Carbon Accounting System by Australian government. These systems aims to tracking and forecasting land based emissions and removals of greenhouse gases from land-use changes, livestock and crop production, and disturbance events such as deforestation, afforestation, and natural disturbances. Based on synergic analysis of data from detailed forest inventory, remote sensing, and ecosystem modeling, the accounting results are used to monitor forest and carbon cycles, and are reported internationally. This study aims to incorporating data with complementary characteristics, such that MODIS provides GPP/PSNnet with consistent spatial coverage, and flux towers provides time-series measurements of NEE and basis for the validation of remote sensed data. With synergic analysis of data from different platforms, both the spatial and temporal behavior of carbon flux can be better delineated in terms of multi-scaled perspectives. Specifically, a description of MODIS GPP/PSNnet algorithm logic and eddy covariance technique will be summarized, followed by an inter-comparison of GPP from both platforms, and an attempt to describe the spatial and temporal pattern of primary productivity and examine the contributing factors for such variation. Finally, the constraints for application of both methods in a heterogeneous landscape like Taiwan will be discussed.
Impact of an aggressive invasive catheterization and revascularization strategy on mortality in patients with cardiogenic shock in the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO-I) trial. An observational study.

BACKGROUND Although retrospective analyses have revealed an association between survival and coronary angiography and angioplasty in patients with acute myocardial infarction complicated by cardiogenic shock, the degree to which bias in the selection of patients to undergo these procedures contributes to this observation remains unclear. METHODS AND RESULTS We studied 2200 patients in the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO-I) trial with acute myocardial infarction complicated by cardiogenic shock (systolic blood pressure < 90 mm Hg for > or = 1 hour) who survived > or = 1 hour after the onset of shock to determine the influence of an aggressive strategy of early angiography (within 24 hours of shock onset) and coronary angioplasty or bypass surgery, if appropriate, on survival. Revascularization was not protocol mandated but was selected by the attending physicians. Shock was present on admission in 11% and developed after admission in 89% of shock patients. The 30-day mortality was 38% in the 406 patients who underwent early angiography and were referred within 24 hours for angioplasty (n = 175), bypass surgery (n = 36), angioplasty and bypass surgery (n = 22), or neither (late or no revascularization, n = 173) compared with 62% in the 1794 patients who did not (P = .0001). However, there were important differences in the baseline characteristics of the two groups, including younger age (63 versus 68 years, P = .0001), less prior infarction (19% versus 27%, P = .001), and a shorter time to thrombolytic therapy (2.9 versus 3.2 hours, P = .0001) in patients treated with an aggressive strategy. Using multivariate logistic regression analysis to adjust for differences in baseline characteristics, an aggressive strategy was independently associated with reduced 30-day mortality (odds ratio, 0.43 [confidence interval, 0.34 to 0.54], P = .0001). CONCLUSIONS An aggressive strategy of early angiography (and revascularization when appropriate) is associated with a reduction in mortality in patients with acute myocardial infarction and cardiogenic shock who receive thrombolytic therapy.
Pituitary-Thyroid State Correlates with Central Dopaminergic and Serotonergic Activity in Healthy Humans

Data from lower animals suggest anatomic and physiological interactions between brain dopamine and serotonin (5-hydroxytryptamine, 5-HT) systems and the hypothalamic-pituitary-thyroid axis. However, in humans, investigations of interactions between these central neurochemical systems (especially the dopaminergic system) and thyroid function are rare; in healthy humans they are practically nonexistent. Using cerebrospinal fluid (CSF) and blood samples simultaneously obtained from indwelling subarachnoid and venous catheters in healthy humans, we determined the CSF concentrations of homovanillic acid (HVA) and 5-hydroxyindolacetic acid, the major metabolites of dopamine and 5-HT, and plasma concentrations of TSH, total triiodothyronine (T3), free T3, total thyroxine (T4) and free T4. CSF HVA concentrations were significantly and negatively correlated with plasma TSH and T3 (free and total), but not with T4 (free or total). CSF 5-HIAA concentrations were significantly and negatively correlated with plasma TSH and total T3 but not with free T3 or T4 (free or total). These results indicate that CNS monoamine-thyroid interactions are of physiological significance in the normal, euthyroid human.
Effects of missense mutations on rat aquaporin-2 in LLC-PK1 porcine kidney cells.

BACKGROUND Mutations in the aquaporin-2 (AQP2) gene have been found in families with nephrogenic diabetes insipidus (NDI), but the pathophysiological mechanisms of how mutant AQP2 causes the disease are still not clear. METHODS Wild-type (WT) AQP2 and four mutants-T126M, A147T, R187C, and S216P-were transiently expressed in LLC-PK1 cells. The osmotic water permeability of LLC-PK1 cells expressing AQP2 mutants was determined by stopped-flow light-scattering microphotometry. Cell surface expression, subcellular localization, and effects of vasopressin stimulation were examined by surface biotin labeling and confocal immunohistochemistry. RESULTS The osmotic water permeability (Pf) of cells expressing WT increased significantly after vasopressin treatment, whereas the Pf of cells expressing T126M A147T, R187C, and S216P was not significantly different from that of the control even after vasopressin stimulation. Confocal immunohistochemistry demonstrated distribution of WT and A147T in early/recycling endosomal compartments and vasopressin-responsive translocation and surface expression. In contrast, stainings of T126M, R187C, and S216P were similar to that of Grp78, indicating that these mutants were misassembled and retarded in the endoplasmic reticulum. CONCLUSION Our results indicated that the intracellular distribution and vasopressin-regulated trafficking of A147T is intact, in contrast to the other three mutants, of which both were impaired. Thus, it is conceivable that the disruption of the AQP2 channel function accounts for the pathogenesis of A147T NDI, whereas trafficking defects account for that of the other types, suggesting that the pathophysiology of AQP2-related NDI is heterogeneous.
Safety and immunogenocity of a novel combined Haemophilus influenzae type b–Neisseria meningitidis serogroups A and C-tetanus-toxoid conjugate vaccine in healthy Chinese children aged 6 months to 5 years old

A novel combined Haemophilus influenzae type b-Neisseria meningitidis serogroups A and C-tetanus-toxoid conjugate vaccine (Hib-MenAC vaccine) has been developed to protect children against diseases caused by Hib, MenA, and MenC. This study investigated the safety and immunogenicity of the Hib-MenAC vaccine administered in 2-dose series to children aged 6–23 months and in a single dose to children aged 2–5 y. A randomized, positive-controlled, non-inferiority clinical trial was conducted for 1200 healthy participants in each age group. Within each age group, participants were randomly allocated to the Hib-MenAC group or the control group at a ratio of 1:1. Adverse reactions were recorded within 28 d after each dose. Blood samples were obtained to assess immunogenicity on day 0 and at 28 d after a complete vaccination course. For the investigational vaccine, the incidence of total adverse reactions in vaccinees aged 6–23 months was 46.8% and that in vaccinees aged 2–5 y was 29.8%. Most adverse reactions were mild or moderate. One non-fatal serious adverse event occurred in the Hib-MenAC group, but was unrelated to vaccination. The seroconversion rate to the 3 components reached 94.0%, and the proportion of vaccinees with rSBA titers ≥ 1:8 and PRP ≥ 0.15 g/mL reached 97.0% in both age groups. The safety and immunogenicity of the Hib-MenAC vaccine were non-inferior when compared to the licensed vaccines. It was concluded that the novel vaccine would be expected to protect children against all of the targeted diseases.
Cloning and expression of an adhesin (AIDA-I) involved in diffuse adherence of enteropathogenic Escherichia coli

The adherence of enteropathogenic Escherichia coli (EPEC) to the small bowel mucosa is an important step in the pathogenesis of diarrheal diseases. It has been shown that many EPEC strains adhere to HEp-2 and especially HeLa cells in characteristic patterns termed localized adherence (LA) and diffuse adherence (DA). A plasmid-derived DNA fragment encoding a factor specific for LA hybridized only to EPEC strains expressing LA, which demonstrated that LA and DA are mediated by two genetically distinct adhesins. EPEC strain 2787 (O127:H27), isolated from a case of infantile diarrhea, exhibited three major properties: (i) it showed DA to HeLa cells, (ii) it carried two large (ca. 100-kilobase [kb]) plasmids and one small plasmid of about 3 kb, and (iii) no fimbriae could be detected by electron microscopy in organisms grown on agar plates or in liquid cultures. Whole isolated plasmid DNA was partially digested with EcoRI and cloned into the vector pBR322. One recombinant clone (pIB6) was found to exhibit the same DA pattern on HeLa cells as did the parent strain. This clone contained an 11-kb DNA fragment derived from the largest of the three plasmids, as shown by Southern hybridization. By deletion analysis, a 6.0-kb DNA fragment was shown to be sufficient for expression of the DA phenotype. This insert encoded the production of a 100,000-dalton protein mediating adhesion to HeLa cells.