Miracle-dz/UniFAR-FTUs huggingface dataset:
Nanoscale polysaccharide derivative as an AEG-1 siRNA carrier for effective osteosarcoma therapy

Background Nanomedicine, which is the application of nanotechnology in medicine to make medical diagnosis and treatment more accurate, has great potential for precision medicine. Despite some improvements in nanomedicine, the lack of efficient and low-toxic vectors remains a major obstacle. Objective The aim of this study was to prepare an efficient and low-toxic vector which could deliver astrocyte elevated gene-1 (AEG-1) small interfering RNA (siRNA; siAEG-1) into osteosarcoma cells effectively and silence the targeted gene both in vitro and in vivo. Materials and methods We prepared a novel polysaccharide derivative by click conjugation of azidized chitosan with propargyl focal point poly (L-lysine) dendrons (PLLD) and subsequent coupling with folic acid (FA; Cs-g-PLLD-FA). We confirmed the complexation of siAEG-1and Cs-g-PLLD or Cs-g-PLLD-FA by gel retardation assay. We examined the cell cytotoxicity, cell uptake, cell proliferation and invasion abilities of Cs-g-PLLD-FA/siAEG-1 in osteosarcoma cells. In osteosarcoma 143B cells tumor-bearing mice models, we established the therapeutic efficacy and safety of Cs-g-PLLD-FA/siAEG-1. Results Cs-g-PLLD-FA could completely encapsulate siAEG-1 and showed low cytotoxicity in osteosarcoma cells and tumour-bearing mice. The Cs-g-PLLD-FA/siAEG-1 nanocomplexes were capable of transferring siAEG-1 into osteosarcoma cells efficiently, and the knockdown of AEG-1 resulted in the inhibition of tumour cell proliferation and invasion. In addition, caudal vein injecting of Cs-g-PLLD-FA/siAEG-1 complexes inhibited tumor growth and lung metastasis in tumor-bearing mice by silencing AEG-1 and regulating MMP-2/9. Conclusion In summary, Cs-g-PLLD-FA nanoparticles are a promising system for the effective delivery of AEG-1 siRNA for treating osteosarcoma.
Pharmacokinetic/pharmacodynamic modelling of the antimalarial effect of Actelion‐451840 in an induced blood stage malaria study in healthy subjects

Aims The aim of this study was to use data from an experimental induced blood stage malaria clinical trial to characterize the antimalarial activity of the new compound Actelion‐451840 using pharmacokinetic/pharmacodynamic (PK/PD) modelling. Then, using simulations from the model, the dose and dosing regimen necessary to achieve cure of infection were derived. Methods Eight healthy male subjects were infected with blood stage P. falciparum. After 7 days, a single dose of 500 mg of Actelion‐451840 was administered under fed conditions. Parasite and drug concentrations were sampled frequently. Parasite growth and the relation to drug exposure were estimated using PK/PD modelling. Simulations were then undertaken to derive estimates of the likelihood of achieving cure in different scenarios. Results Actelion‐451840 was safe and well tolerated. Single dose treatment markedly reduced the level of P. falciparum parasitaemia, with a weighted average parasite reduction rate of 73.6 (95% CI 56.1, 96.5) and parasite clearance half‐life of 7.7 h (95% CI 7.3, 8.3). A two compartment PK/PD model with a steep concentration−kill effect predicted maximum effect with a sustained concentration of 10–15 ng ml−1 and cure achieved in 90% of subjects with six once daily doses of 300 mg once daily. Conclusions Actelion‐451840 shows clinical efficacy against P. falciparum infections. The PK/PD model developed from a single proof‐of‐concept study with eight healthy subjects enabled prediction of therapeutic effects, with cure rates with seven daily doses predicted to be equivalent to artesunate monotherapy. Larger doses or more frequent dosing are not predicted to achieve more rapid cure.
Determinants of Nationalization in the Oil Sector: A Theory and Evidence from Panel Data

In this paper we study nationalizations in the oil industry around the world in 1960-2002. We show, both theoretically and empirically, that governments are more likely to nationalize when oil prices are high and when political institutions are weak. We consider a simple dynamic model of the interaction between a government and a foreign oil company. The government cannot commit to abstain from expropriation and the company cannot commit to pay high taxes. Even though nationalization is inefficient it does occur in equilibrium when oil prices are high. The model's predictions are consistent with the panel analysis of a comprehensive dataset on nationalizations in the oil industry since 1960. Nationalization is more likely to happen when oil prices are high and the quality of institutions is low even when controlling for country fixed effects.
Comment on The Ecstasy and Agony of Assay Interference Compounds

A recent editorial (Aldrich et al. The Ecstasy and Agony of Assay Interference Compounds . J. Chem. Inf. MODEL 2017 , 57 , 387 - 390 ) is examined critically. When assessing assay hits from screening, it is important to draw a distinction between false positives, that have no effect on target function, and compounds that affect target function through an undesirable mechanism of action. Observation of frequent-hitter behavior for a compound should be regarded as circumstantial evidence, rather than definitive proof, that the compound has interfered with assay readouts or acted through an undesirable mechanism of action. The applicability domain of published (Baell and Holloway J. Med. Chem. 2010 , 53 , 2719 - 2740 ) Pan Assay INterference compoundS (PAINS) filters is limited by the narrow scope of the proprietary data used to derive them. It is suggested that journal guidelines for authors should not prescribe, as those for the Journal of Medicinal Chemistry appear to do, that activity in assays reported for compounds that match PAINS filters be treated any differently from that for compounds that do not match PAINS filters. It is argued that use of models based on proprietary data in the evaluation of manuscripts would contradict the editorial policy of any journal that deemed the use of proprietary data to be unacceptable in modeling studies.
Gene Ontology-Based Analysis of Zebrafish Omics Data Using the Web Tool Comparative Gene Ontology.

Gene Ontology (GO) analysis is a powerful tool in systems biology, which uses a defined nomenclature to annotate genes/proteins within three categories: "Molecular Function," "Biological Process," and "Cellular Component. " GO analysis can assist in revealing functional mechanisms underlying observed patterns in transcriptomic, genomic, and proteomic data. The already extensive and increasing use of zebrafish for modeling genetic and other diseases highlights the need to develop a GO analytical tool for this organism. The web tool Comparative GO was originally developed for GO analysis of bacterial data in 2013 ( www.comparativego.com ). We have now upgraded and elaborated this web tool for analysis of zebrafish genetic data using GOs and annotations from the Gene Ontology Consortium.
Characterization of carotenoids in Rhodothermus marinus

Rhodothermus marinus, a marine aerobic thermophile, was first isolated from an intertidal hot spring in Iceland. In recent years, the R. marinus strain PRI 493 has been genetically modified, which opens up possibilities for targeted metabolic engineering of the species, such as of the carotenoid biosynthetic pathway. In this study, the carotenoids of the R. marinus type‐strain DSM 4252T, strain DSM 4253, and strain PRI 493 were characterized. Bioreactor cultivations were used for pressurized liquid extraction and analyzed by ultra‐high performance supercritical fluid chromatography with diode array and quadropole time‐of‐flight mass spectrometry detection (UHPSFC‐DAD‐QTOF/MS). Salinixanthin, a carotenoid originally found in Salinibacter ruber and previously detected in strain DSM 4253, was identified in all three R. marinus strains, both in the hydroxylated and nonhydroxylated form. Furthermore, an additional and structurally distinct carotenoid was detected in the three strains. MS/MS fragmentation implied that the mass difference between salinixanthin and the novel carotenoid structure corresponded to the absence of a 4‐keto group on the ß‐ionone ring. The study confirmed the lack of carotenoids for the strain SB‐71 (ΔtrpBΔpurAcrtBI’::trpB) in which genes encoding two enzymes of the proposed pathway are partially deleted. Moreover, antioxidant capacity was detected in extracts of all the examined R. marinus strains and found to be 2–4 times lower for the knock‐out strain SB‐71. A gene cluster with 11 genes in two operons in the R. marinusDSM 4252T genome was identified and analyzed, in which several genes were matched with carotenoid biosynthetic pathway genes in other organisms.
Ten‐year immune persistence and safety of the HPV‐16/18 AS04‐adjuvanted vaccine in females vaccinated at 15–55 years of age

Women remain at risk of human papillomavirus (HPV) infection for most of their lives. The duration of protection against HPV‐16/18 from prophylactic vaccination remains unknown. We investigated the 10‐year immune response and long‐term safety profile of the HPV‐16/18 AS04‐adjuvanted vaccine (AS04‐HPV‐16/18 vaccine) in females aged between 15 and 55 years at first vaccination. Females who received primary vaccination with three doses of AS04‐HPV‐16/18 vaccine in the primary phase‐III study (NCT00196937) were invited to attend annual evaluations for long‐term immunogenicity and safety. Anti‐HPV‐16/18 antibodies in serum and cervico‐vaginal secretions (CVS) were measured using enzyme‐linked immunosorbent assay (ELISA). Serious adverse events (SAEs) were recorded throughout the follow‐up period. Seropositivity rates for anti‐HPV‐16 remained high (≥96.3%) in all age groups 10 years after first vaccination. It was found that 99.2% of 15–25‐year olds remained seropositive for anti‐HPV‐18 compared to 93.7% and 83.8% of 26–45‐year olds and 45–55‐year olds, respectively. Geometric mean titers (GMT) remained above natural infection levels in all age groups. Anti‐HPV‐16 and anti‐HPV‐18 titers were at least 5.3‐fold and 3.1‐fold higher than titers observed after natural infection, respectively, and were predicted to persist above natural infection levels for ≥30 years in all age groups. At Year 10, anti‐HPV‐16/18 antibody titers in subjects aged 15–25 years remained above plateau levels observed in previous studies. Correlation coefficients for antibody titers in serum and CVS were 0.64 (anti‐HPV‐16) and 0.38 (anti‐HPV‐18). This study concluded that vaccinated females aged 15–55 years elicited sustained immunogenicity with an acceptable safety profile up to 10 years after primary vaccination, suggesting long‐term protection against HPV.
Moment reconstruction and moment‐adjusted imputation when exposure is generated by a complex, nonlinear random effects modeling process

For the classical, homoscedastic measurement error model, moment reconstruction (Freedman et al., 2004, 2008) and moment‐adjusted imputation (Thomas et al., 2011) are appealing, computationally simple imputation‐like methods for general model fitting. Like classical regression calibration, the idea is to replace the unobserved variable subject to measurement error with a proxy that can be used in a variety of analyses. Moment reconstruction and moment‐adjusted imputation differ from regression calibration in that they attempt to match multiple features of the latent variable, and also to match some of the latent variable's relationships with the response and additional covariates. In this note, we consider a problem where true exposure is generated by a complex, nonlinear random effects modeling process, and develop analogues of moment reconstruction and moment‐adjusted imputation for this case. This general model includes classical measurement errors, Berkson measurement errors, mixtures of Berkson and classical errors and problems that are not measurement error problems, but also cases where the data‐generating process for true exposure is a complex, nonlinear random effects modeling process. The methods are illustrated using the National Institutes of Health–AARP Diet and Health Study where the latent variable is a dietary pattern score called the Healthy Eating Index‐2005. We also show how our general model includes methods used in radiation epidemiology as a special case. Simulations are used to illustrate the methods.
Female High School Students’ Perceptions and Experiences of Gender Roles and Stereotypes in Dating Relationships

Female high school students’ experiences and perceptions of gender roles and gender stereotypes is largely missing from research on sexual health and dating violence. The aim of this study was to examine how adolescent females perceive of and experience gender roles and gender inequity in dating relationships. A secondary data analysis of seventy in-depth interviews from a larger study on adolescent females’ perceptions of healthy and unhealthy dating relationships was conducted. The majority of participants were 16 or 17-year-old, almost 80% self-identified as Caucasian or African American, and the majority were 11th or 12th graders. Five themes emerged: 1) Biology, socialization or what? with subthemes 1a) Biology and 1b) Socialization; 2) Experiences and perceptions of power and control in relationships; 3) The conundrum of stereotypes: challenges, confrontations, confusions; 4) The importance and motivation of sex; 5) Communication, caring, commitment, with subthemes, 5a) Males not wanting committed relationships, females wanting them, 5b) Who cares? Males do not care and females care deeply, and 5c) Role reversals. Public health programs can be strengthened by inclusion of the voices of adolescent females. Programs promoting healthy adolescent relationships should engage adolescent males and females, utilize role models, and focus on collective action.
The Course of Emotion in Three Centuries of German Text-A Methodological Framework

Similarly, in natural language processing (NLP), emotion analytics have developed into an active area of research (Liu, 2015). Nevertheless, there is little previous work explicitly addressing emotion in historical language and the specific methodological problems this raises. Hamilton et al. (2016) as well as Cook and Stevenson (2010) presented methods for identifying amelioration and pejoration of words. Acerbi et al. (2013) and Bentley et al. (2014) demonstrated the potential of emotion analysis for the Digital Humanities (DH) by linking temporal emotion patterns in texts to major sociopolitical events and trends in the 20 century.
A cross-sectional assessment of food- and nutrient-based standards applied to British schoolchildren’s packed lunches

Abstract Objective In England, standards for school meals included both foods and nutrients until 2015. School policies for packed lunches are generally food based; research is needed to determine whether these are adequate or whether a small number of nutrients would potentially improve their quality. Design From dietary data obtained using a weighed dietary assessment tool, a diet quality score (DQS) for packed lunches was calculated using the number of standards met out of twenty-one (eight foods and thirteen nutrients). Multilevel regression analysis determined the foods and nutrients contributing to variation in the DQS. Setting Eighty-nine primary schools across the four regions of the UK (England, Wales, Scotland and Northern Ireland). Subjects British schoolchildren (n 1294), aged 8–9 years, taking a packed lunch. Results The optimal model included all eight foods and seven of the thirteen nutrients, explaining 72 % of the variance in DQS. Folate, Fe and vitamin C, together with the eight food groups, explained 70 % of DQS variation. Conclusions Ideally, policies for school packed lunches should include food-based standards plus recommendations based on a small number of nutrients.
Advantages of diapause in Trichogramma dendrolimi mass production on eggs of the Chinese silkworm, Antheraea pernyi.

BACKGROUND Trichogramma dendrolimi Matsumura is widely used as a biological control agent for control of lepidopteran agricultural pests in China and can be successfully reared using the large eggs of the Chinese silkworm, Antheraea pernyi. In this study, biological parameters of diapaused, non-diapaused, and cold-stored T. dendrolimi were investigated for two generations on host eggs of A. pernyi under laboratory conditions. RESULTS The cold-stored T. dendrolimi performed more poorly than diapaused and non-diapaused T. dendrolimi based on biological parameters. In the F1 generation, the non-diapaused T. dendrolimi had a higher emergence rate, longer longevity, and a lower proportion of deformed individuals than diapaused T. dendrolimi. In the F2 generation, the diapaused T. dendrolimi had a lower proportion of unemerged parasitoids than non-diapaused T. dendrolimi. However, the diapaused T. dendrolimi had a higher number of parasitized hosts than non-diapaused T. dendrolimi in both generations. In the F1 generation, the index of population trend (I) was found to be similar for diapaused (140.792) and non-diapaused (141.542) T. dendrolimi and was approximately 3.4 times that of cold-stored T. dendrolimi (41.698). In the F2 generation, the diapaused T. dendrolimi showed the largest I (146.791), followed by non-diapaused (136.859) and cold-stored T. dendrolimi (59.607). CONCLUSION In a 3-year augmentative field release from 2014 to 2016, diapaused T. dendrolimi showed effective parasitism on eggs of the Asian corn borer, Ostrinia furnacalis. These results indicated that diapaused T. dendrolimi can be an efficient alternative method for mass rearing of T. dendrolimi for long-term cold storage. © 2017 Society of Chemical Industry.
Aerobic degradation of buprofezin via novel degradationintermediates by Rhodococcus sp. strain RX-3

Buprofezin is a commonly used chemical with satisfactory efficacy against sucking insect pests, but its disposal causes serious environmental problems. In this study, a bacterial strain RX-3 isolated by continuous enrichment from buprofezin-treated soil was tested for biodegradation of buprofezin. The bacteria were most similar to Rhodococcus sp. based on their morphological, physiological and biochemical characteristics, as well as phylogenetic placement inferred from 16S rRNA gene sequence. Strain RX-3 was found capable of utilizing buprofezin as the sole source of carbon for growth over a wide range of temperature (25-45°C) and pH (5.0-9.0) conditions. It could completely degrade 60 mg/L of buprofezin within 80 h, and in the presence of metals such as Ba2+, Zn2+ and Cu2+. In addition, six newly identified metabolites formed during buprofezin degradation were detected and identified by gas chromatography-mass spectrometry (GC-MS), from which we proposed a novel degradation pathway. Our results suggest that Rhodococcus sp. RX-3 could be a potential bioremediation agent of buprofezin-contaminated environments.
Structural Materials. Properties of Classified Fly Ashes by Using of Electrostatic Precipitator and the Modification of Fly Ashes by the Removal of Carbon.

This paper discusses the chemical, physical and mineralogical properties of classified fly ashes by using of electrostatic precipitator and modified fly ashes by calcination at 500°C or plasma reactor. In addition, the influences of burning conditions and types of coals on the properties of fly ashes are investigated. It is proposed that the electrostatic precipitator can also be applied to the separator. The electrostatic precipitator in coal fired power plant has a number of hopper in the direction of flue gases. Blaine values of fly ashes collected at 1st, 2nd and 3rd hoppers are respectively about 3000 (ordinary), 5000 (fine) and 8000cm2/g (superfine), regardless of burning condition and types of coals. The glass contents of fly ashes become greater as their blaine values are raised. The adiabatic temperature rise of mortar containing fly ash is increased with the fineness of fly ash. The pozzolanic reactivity of fly ash at early stage and at later stage are respectively related to the fineness and the glass contents of fly ash. But, the early hydration of cement was retarded by addition of superfine fly ashes. The carbon content in fly ash influences on the paste fluidity. The carbon content in fly ash is decreased by calcination and plasma treatment and the fluidity of paste is improved by the removal of carbon, .
Diversity change during the rise of tetrapods and the impact of the ‘Carboniferous rainforest collapse’

The Carboniferous and early Permian were critical intervals in the diversification of early four-limbed vertebrates (tetrapods), yet the major patterns of diversity and biogeography during this time remain unresolved. Previous estimates suggest that global tetrapod diversity rose continuously across this interval and that habitat fragmentation following the ‘Carboniferous rainforest collapse’ (CRC) drove increased endemism among communities. However, previous work failed to adequately account for spatial and temporal biases in sampling. Here, we reassess early tetrapod diversity and biogeography with a new global species-level dataset using sampling standardization and network biogeography methods. Our results support a tight relationship between observed richness and sampling, particularly during the Carboniferous. We found that subsampled species richness initially increased into the late Carboniferous, then decreased substantially across the Carboniferous/Permian boundary before slowly recovering in the early Permian. Our analysis of biogeography does not support the hypothesis that the CRC drove endemism; instead, we found evidence for increased cosmopolitanism in the early Permian. While a changing environment may have played a role in reducing diversity in the earliest Permian, our results suggest that the CRC was followed by increased global connectivity between communities, possibly reflecting both reduced barriers to dispersal and the diversification of amniotes.
Therapeutic modulation of the bile acid pool by Cyp8b1 knockdown protects against nonalcoholic fatty liver disease in mice

Bile acids (BAs) are surfactant molecules that regulate the intestinal absorption of lipids. Thus, the modulation of BAs represents a potential therapy for nonalcoholic fatty liver disease (NAFLD), which is characterized by hepatic accumulation of fat and is a major cause of liver disease worldwide. Cyp8b1 is a critical modulator of the hydrophobicity index of the BA pool. As a therapeutic proof of concept, we aimed to determine the impact of Cyp8b1 inhibition in vivo on BA pool composition and as protection against NAFLD. Inhibition of Cyp8b1 expression in mice led to a remodeling of the BA pool, which altered its signaling properties and decreased intestinal fat absorption. In a model of cholesterol‐induced NAFLD, Cyp8b1 knockdown significantly decreased steatosis and hepatic lipid content, which has been associated with an increase in fecal lipid and BA excretion. Moreover, inhibition of Cyp8b1 not only decreased hepatic lipid accumulation, but also resulted in the clearance of previously accumulated hepatic cholesterol, which led to a regression in hepatic steatosis. Taken together, our data demonstrate that Cyp8b1 inhibition is a viable therapeutic target of crucial interest for metabolic diseases, such as NAFLD. —Chevre, R. , Trigueros‐Motos, L. , Castaño, D. , Chua, T. , Corliano, M. , Patankar, J. V. , Sng, L. , Sim, L. , Juin, T. L. , Carissimo, G. , Ng, L. F. P., Yi, C. N. J., Eliathamby, C. C. , Groen, A. K. , Hayden, M. R. , Singaraja, R. R. Therapeutic modulation of the bile acid pool by Cyp8b1 knockdown protects against nonalcoholic fatty liver disease in mice. FASEB J. 32, 3792–3802 (2018). www.fasebj. org