Miracle-dz/UniFAR-FTUs huggingface dataset:
Regulation of Hepatic UGT2B15 by Methylation in Adults of Asian Descent

The hepatic uridine 5′-diphosphate-glucuronosyl transferases (UGTs) are critical for detoxifying endo- and xenobiotics. Since UGTs are also dynamically responsive to endogenous and exogenous stimuli, we examined whether epigenetic DNA methylation can regulate hepatic UGT expression and differential effects of ethnicity, obesity, and sex. The methylation status of UGT isoforms was determined with Illumina Methylation 450 BeadChip arrays, with genotyping confirmed by sequencing and gene expression confirmed with quantitative reverse transcriptase polymerase chain reaction (q-RT-PCR). The UGT1A3 mRNA was 2-fold higher in females than males (p < 0.05), while UGT1A1 and UGT2B7 mRNA were significantly higher in Pacific Islanders than Caucasians (both p < 0.05). Differential mRNA or methylation did not occur with obesity. The methylation of the UGT2B15 locus cg09189601 in Caucasians was significantly lower than the highly methylated locus in Asians (p < 0.001). Three intergenic loci between UGT2B15 and 2B17 (cg07973162, cg10632656, and cg07952421) showed higher rates of methylation in Caucasians than in Asians (p < 0.001). Levels of UGT2B15 and UGT2B17 mRNA were significantly lower in Asians than Caucasians (p = 0.01 and p < 0.001, respectively). Genotyping and sequencing indicated that only UGT2B15 is regulated by methylation, and low UGT2B17 mRNA is due to a deletion genotype common to Asians. Epigenetic regulation of UGT2B15 may predispose Asians to altered drug and hormone metabolism and begin to explain the increased risks for adverse drug reactions and some cancers in this population.
Tameness in least fixed-point logic and McColm's conjecture

We investigate fundamental model-theoretic dividing lines (the order property, the independence property, the strict order property, and the tree property 2) in the context of least fixed-point (LFP) logic over families of finite structures. We show that, unlike the first-order (FO) case, the order property and the independence property are equivalent, but all of the other natural implications are strict. We identify the LFP strict order property with proficiency, a well-studied notion in finite model theory. Gregory McColm conjectured that FO and LFP definability coincide over a family C of finite structures exactly when C is non-proficient. McColm's conjecture is false in general, but as an application of our results, we show that it holds under standard FO tameness assumptions adapted to families of finite structures.
Development of a dose verification system for Vero4DRT using Monte Carlo method

Vero4DRT is an innovative image‐guided radiotherapy system employing a C‐band X‐ray head with gimbal mechanics. The purposes of this study were to propose specific MC models of the linac head and multileaf collimator (MLC) for the Vero4DRT and to verify their accuracy. For a 6 MV photon beam delivered by the Vero4DRT, a simulation code was implemented using EGSnrc. The linac head model and the MLC model were simulated based on its specification. Next, the percent depth dose (PDD) and beam profiles at depths of 15, 100, and 200 mm were simulated under source‐to‐surface distance of 900 and 1000 mm. Field size was set to 150×150mm2 at a depth of 100 mm. Each of the simulated dosimetric metrics was then compared with the corresponding measurements by a 0.125 cc ionization chamber. After that, intra‐ and interleaf leakage, tongue‐and‐groove, and rounded‐leaf profiles were simulated for the static MLC model. Meanwhile, film measurements were performed using EDR2 films under similar conditions to simulation. The measurement for the rounded‐leaf profile was performed using the water phantom and the ionization chamber. The leaf physical density and abutting leaf gap were adjusted to obtain good agreement between the simulated intra‐ and interleaf leakage profiles and measurements. For the MLC model in step‐and‐shoot cases, a pyramid and a prostate IMRT field were simulated, while film measurements were performed using EDR2. For the linac head, exclusive of MLC, the difference in PDD was <1.0% after the buildup region. The simulated beam profiles agreed to within 1.3% at each depth. The MLC model has been shown to reproduce dose measurements within 2.5% for static tests. The MLC is made of tungsten alloy with a purity of 95%. The leaf gap of 0.015 cm and the MLC physical density of 18.0g/cm3, which provided the best agreement between the simulated and measured leaf leakage, were assigned to our MC model. As a result, the simulated step‐and‐shoot IMRT dose distributions agreed with the film measurements to within 3.3%, with exception of the penumbra region. We have developed specific MC models of the linac head and the MLC in the Vero4DRT system. The results have demonstrated that our MC models have high accuracy. PACS numbers: 87.55. K‐, 87.56. nk, 87.56. bd
Characteristics of Fly ash Produced at Power and Water Desalination Plants Firing Fuel Oil

Plants firing fuel oil produce huge quantities of fly ash as solid waste, which needs to be characterized prior to its proper management. It is worth mentioning that the published literature lack comprehensive information on the characteristics of such fly ash. Characteristics of fuel oil fly ash produced at selected power (PP) and water desalination (DP) plants were determined. The results showed that grain size of the DP fly ash (66.87 µm) is slightly larger than that of PP fly ash (63.09 µm). The PP fly ash is mostly carbon while DP has a larger percent of metal oxide ashes. Ash content in PP and DP fly ash were 4.8 and 43.3 percent, respectively. Moreover, metal concentrations are higher in DP fly ash than that in PP fly ash. As an example, average vanadium concentrations were 15619 and 40879 mg/kg in PP and DP fly ash samples, respectively. Generally, fly ash samples produced at the two plants are different in their physical and chemical characteristics, which could be attributed to the different fuels and additives being used at the two plants.
Anticancer Potentials of Phytochemicals from Some Indigenous Food and Medicinal Plants of West Africa

A selected number of potential anticancer agents in phytochemicals isolated from some indigenous food and medicinal plants of the West African sub-region, has been reviewed. The attempt has benefited from a store of knowledge on the characterized and identified phytochemicals from indigenous plants by organic chemists, in the past six or so decades. Such compounds as satisfied the structure-activity-relationships with known anticancer active agents were selected and profiled and cover phytochemical classes as: alkaloids, flavonoids, terpenoids, and ‘miscellaneous’, the latter class comprising compounds considered chemically inappropriate for the previous classes. Anticancer activities covered include: induction of carcinogen-metabolizing enzymes, selective cytotoxicity to tumor cells, reversal of multidrug resistance in cancer cells, and inhibition of metastasis. Food and medicinal uses of the source plants have also been described.
Physical and dosimetric characteristic of high‐definition multileaf collimator (HDMLC) for SRS and IMRT

Physical and dosimetric characteristics of HDMLC were studied for SRS6, 6, and 10 MV X‐rays from Novalis Tx. This in‐built tertiary collimator consists of 60 pairs (32×0.25 cm; 26×0.5 cm and 2×0.7 cm) of leaves. Properties of HDMLC studied included alignment, readout and radiation field congruence, radiation penumbra, accuracy and reproducibility of leaf position and gap width, static and dynamic leaf shift, tongue‐and‐groove effect, leaf transmission and leakage, leaf travel speed, and delivery of dynamic conformal arc and IMRT. All tests were performed using a calibrated ionization chamber, film dosimetry and DynaLog file analysis. Alignment of leaves with isocenter plane was better than 0.03 cm at all gantry and collimator positions. The congruence of HDMLC readout and radiation field agreed to within ± 0.03cm for filed sizes ranging from 1×1 to 20×20 cm2. Mean 80% to 20% penumbra width parallel (perpendicular) to leaf motion was 0.24±0.05(0.21±0.02) cm, 0.37±0.12(0.29±0.07) cm, and 0.51±0.13(0.43±0.07) cm for SRS6, 6, and 10 MV X‐rays, respectively. Circular field penumbra was comparable to corresponding square field. Average penumbra of 1×20 cm2 field was effectively constant over off‐axis positions of up to 12 cm with mean value of 0.16 (± 0.01)cm at 1.5 cm depth and 0.38 (± 0.04)cm at 10 cm depth. Minimum and maximum effective penumbra along the straight diagonal edge of irregular fields increased from 0.3 and 0.32 cm at 70° steep angle to 0.35 and 0.56 cm at 20° steep angle. Modified Picket Fence test showed average FWHM of 0.18 cm and peak‐to‐peak distance of 1.99 cm for 0.1 cm band and 2 cm interband separation. Dynamic multileaf collimation (DMLC) output factor remained within ± 1% for 6 MV and ± 0.5% for 10 MV X‐rays at all gantry positions, and was reproducible within ± 0.5% over a period of 14 months. The static leaf shift was 0.03 cm for all energies, while dynamic leaf shift was 0.044 cm for 10 MV and 0.039 cm for both SRS6 and 6 MV X‐rays. The dose depression and corresponding tongue‐and‐groove size were 24% and 0.17 cm for 6 MV and 19% and 0.20 cm for 10 MV X‐rays. Average transmission through HDMLC was 1.09%, 1.14% and 1.34% for SRS6, 6 and 10 MV X‐rays. Analysis of DynaLog files for leaf speed test in arc dynamic mode, delivery test of dynamic conformal arc, and step‐and‐shoot and sliding window IMRT showed at least 95% or more of the error counts had misplacements < 0.2cm, with maximum root mean square (RMS) error value calculated at 0.13 cm. Accurate and reproducible leaf position and gap width, and less leakage and small consistent penumbra over the fields demonstrate HDMLC suitable for high‐dose resolution SRS and IMRT. PACS number: 87.56. N‐, 87.55. Qr, 87.50. cm, 87.55. de, 87.53. Ly
The Microtubule Network and Cell Death Are Regulated by an miR-34a/Stathmin 1/βIII-Tubulin Axis

MicroRNA-34a (miR-34a) is a master regulator of signaling networks that maintains normal physiology and disease and is currently in development as a miRNA-based therapy for cancer. Prior studies have reported low miR-34a expression in osteosarcoma; however, the molecular mechanisms underlying miR-34a activity in osteosarcoma are not well-defined. Therefore, this study evaluated the role of miR-34a in regulating signal transduction pathways that influence cell death in osteosarcoma. Levels of miR-34a were attenuated in human osteosarcoma cells and xenografts of the Pediatric Preclinical Testing Consortium (PPTC). Bioinformatics predictions identified stathmin 1 (STMN1) as a potential miR-34a target. Biotin pull-down assay and luciferase reporter analysis confirmed miR-34a target interactions within the STMN1 mRNA 3′-untranslated region. Overexpression of miR-34a in osteosarcoma cells suppressed STMN1 expression and reduced cell growth in vitro. Restoration of miR-34a led to microtubule destabilization and increased βIII-tubulin expression, with corresponding G1–G2 phase cell-cycle arrest and apoptosis. Knockdown of the Sp1 transcription factor, by siRNA silencing, also upregulated βIII-tubulin expression in osteosarcoma cells, suggesting that miR-34a indirectly affects Sp1. Validating the coordinating role of miR-34a in microtubule destabilization, when miR-34a was combined with either microtubule inhibitors or chemotherapy, STMN1 phosphorylation was suppressed and there was greater cytotoxicity in osteosarcoma cells. These results demonstrate that miR-34a directly represses STMN1 gene and protein expression and upregulates βIII-tubulin, leading to disruption of the microtubule network and cell death. Implications: The miR-34a/STMN1/βIII-tubulin axis maintains the microtubule cytoskeleton in osteosarcoma, and combining miR-34a with microtubule inhibitors can be investigated as a novel therapeutic strategy. Mol Cancer Res; 15(7); 953–64. ©2017 AACR.
Multi-scale Location-Aware Kernel Representation for Object Detection

Although Faster R-CNN and its variants have shown promising performance in object detection, they only exploit simple first-order representation of object proposals for final classification and regression. Recent classification methods demonstrate that the integration of high-order statistics into deep convolutional neural networks can achieve impressive improvement, but their goal is to model whole images by discarding location information so that they cannot be directly adopted to object detection. In this paper, we make an attempt to exploit high-order statistics in object detection, aiming at generating more discriminative representations for proposals to enhance the performance of detectors. To this end, we propose a novel Multi-scale Location-aware Kernel Representation (MLKP) to capture high-order statistics of deep features in proposals. Our MLKP can be efficiently computed on a modified multi-scale feature map using a low-dimensional polynomial kernel approximation. Moreover, different from existing orderless global representations based on high-order statistics, our proposed MLKP is location retentive and sensitive so that it can be flexibly adopted to object detection. Through integrating into Faster R-CNN schema, the proposed MLKP achieves very competitive performance with state-of-the-art methods, and improves Faster R-CNN by 4.9% (mAP), 4.7% (mAP) and 5.0% (AP at IOU=[0.5:0.05:0.95]) on PASCAL VOC 2007, VOC 2012 and MS COCO benchmarks, respectively. Code is available at: https://github.com/Hwang64/MLKP.
Quantitative comparison of automatic and manual IMRT optimization for prostate cancer: the benefits of DVH prediction

A recent publication indicated that the patient anatomical feature (PAF) model was capable of predicting optimal objectives based on past experience. In this study, the benefits of IMRT optimization using PAF‐predicted objectives as guidance for prostate were evaluated. Three different optimization methods were compared. 1) Expert Plan: Ten prostate cases (16 plans) were planned by an expert planner using conventional trial‐and‐error approach started with institutional modified OAR and PTV constraints. Optimization was stopped at 150 iterations and that plan was saved as Expert Plan. 2) Clinical Plan: The planner would keep working on the Expert Plan till he was satisfied with the dosimetric quality and the final plan was referred to as Clinical Plan. 3) PAF Plan: A third sets of plans for the same ten patients were generated fully automatically using predicted DVHs as guidance. The optimization was based on PAF‐based predicted objectives, and was continued to 150 iterations without human interaction. DMAX and D98% for PTV, DMAX for femoral heads, DMAX, D10cc, D25%/D17%, and D40% for bladder/rectum were compared. Clinical Plans are further optimized with more iterations and adjustments, but in general provided limited dosimetric benefits over Expert Plans. PTV D98% agreed within 2.31% among Expert, Clinical, and PAF plans. Between Clinical and PAF Plans, differences for DMAX of PTV, bladder, and rectum were within 2.65%, 2.46%, and 2.20%, respectively. Bladder D10cc was higher for PAF but <1.54% in general. Bladder D25% and D40% were lower for PAF, by up to 7.71% and 6.81%, respectively. Rectum D10cc, D17%, and D40% were 2.11%, 2.72%, and 0.27% lower for PAF, respectively. DMAX for femoral heads were comparable (<35 Gy on average). Compared to Clinical Plan (Primary+Boost), the average optimization time for PAF plan was reduced by 5.2 min on average, with a maximum reduction of 7.1 min. Total numbers of MUs per plan for PAF Plans were lower than Clinical Plans, indicating better delivery efficiency. The PAF‐guided planning process is capable of generating clinical‐quality prostate IMRT plans with no human intervention. Compared to manual optimization, this automatic optimization increases planning and delivery efficiency, while maintaining plan quality. PACS numbers: 87.55. D‐, 87.55. de, 87.53. Jw
Unleashing meiotic crossovers in hybrid plants

Significance In eukaryotes, meiotic recombination shuffles genetic information at each generation, making each offspring unique. In addition to its key role in heredity and evolution, this gene reshuffling is central in plant and animal breeding, which relies on the ability to combine desired alleles. However, the number of recombination events by generation is low, limiting the power of breeding programs. Here we showed that meiotic recombination can be massively increased in hybrid plants, up to almost eightfold. This opens the possibility of manipulating recombination to enhance the efficiency of plant breeding programs, which is important as we face the double challenge of ensuring food security while preserving natural resources. Meiotic crossovers shuffle parental genetic information, providing novel combinations of alleles on which natural or artificial selection can act. However, crossover events are relatively rare, typically one to three exchange points per chromosome pair. Recent work has identified three pathways limiting meiotic crossovers in Arabidopsis thaliana that rely on the activity of FANCM [Crismani W, et al. (2012) Science 336:1588–1590], RECQ4 [Séguéla-Arnaud M, et al. (2015) Proc Natl Acad Sci USA 112:4713–4718], and FIGL1 [Girard C, et al. (2015) PLoS Genet 11:e1005369]. Here we analyzed recombination in plants in which one, two, or all three of these pathways were disrupted in both pure line and hybrid contexts. The greatest effect was observed when combining recq4 and figl1 mutations, which increased the hybrid genetic map length from 389 to 3,037 cM. This corresponds to an unprecedented 7.8-fold increase in crossover frequency. Disrupting the three pathways did not further increase recombination, suggesting that some upper limit had been reached. The increase in crossovers is not uniform along chromosomes and rises from centromere to telomere. Finally, although in wild type recombination is much higher in male meiosis than in female meiosis (490 cM vs. 290 cM), female recombination is higher than male recombination in recq4 figl1 (3,200 cM vs. 2,720 cM), suggesting that the factors that make wild-type female meiosis less recombinogenic than male wild-type meiosis do not apply in the mutant context. The massive increase in recombination observed in recq4 figl1 hybrids opens the possibility of manipulating recombination to enhance plant breeding efficiency.
Is Self-Regard a Sociometer or a Hierometer? Self-Esteem Tracks Status and Inclusion, Narcissism Tracks Status

What adaptive function does self-regard serve? Sociometer theory predicts that it positively tracks social inclusion. A new theory, hierometer theory, predicts that it positively tracks social status. We tested both predictions with respect to two types of self-regard: self-esteem and narcissism. Study 1 (N = 940), featuring a cross-sectional design, found that both status and inclusion covaried positively with self-esteem, but that status alone covaried positively with narcissism. These links held independently of gender, age, and the Big Five personality traits. Study 2 (N = 627), a preregistered cross-sectional study, obtained similar results with alternative measures of self-esteem and narcissism. Studies 3–4 featured experimental designs in which status and inclusion were orthogonally manipulated. Study 3 (N = 104) found that both higher status and higher inclusion promoted higher self-esteem, whereas only higher status promoted higher narcissism. Study 4 (N = 259) obtained similar results with alternative measures of self-esteem and narcissism. The findings suggest that self-esteem operates as both sociometer and hierometer, positively tracking both status and inclusion, whereas narcissism operates primarily as a hierometer, positively tracking status.
Evaluación in vitro del efecto erosivo de tres bebidas carbonatadas sobre la superficie del esmalte dental

The aim of this in vitro study was to assess the effect of three erosive carbonated soft drinks over tooth enamel surface. Sixty enamel specimens were divided into four groups. Three groups were exposed to carbonated soft drinks for one minute, followed by three minutes of artificial saliva. This cycle was repeated every 20 minutes. The negative control group was immersed in distilled water. Vickers hardness method was used to determine the for erosive effect on specimens before and after they were exposed to soft drinks. , A significant difference (Student t-test p<0.05) was found between initial and final microhardness values of the specimens exposed to carbonated soft drinks. In conclusion, Kola Real® carbonated soft drink showed an erosive effect similar to Coca-Cola®, while Inca Kola® had the lowest erosive effect.
STAT3-enhancing germline mutations contribute to tumor-extrinsic immune evasion

Immune evasion and the suppression of antitumor responses during cancer progression are considered hallmarks of cancer and are typically attributed to tumor-derived factors. Although the molecular basis for the crosstalk between tumor and immune cells is an area of active investigation, whether host-specific germline variants can dictate immunosuppressive mechanisms has remained a challenge to address. A commonly occurring germline mutation (c.1162G>A/rs351855 G/A) in the FGFR4 (CD334) gene enhances signal transducer and activator of transcription 3 (STAT3) signaling and is associated with poor prognosis and accelerated progression of multiple cancer types. Here, using rs351855 SNP–knockin transgenic mice and Fgfr4-knockout mice, we reveal the genotype-specific gain of immunological function of suppressing the CD8/CD4+FOXP3+CD25+ regulatory T cell ratio in vivo. Furthermore, using knockin transgenic mouse models for lung and breast cancers, we establish the host-specific, tumor-extrinsic functions of STAT3-enhancing germline variants in impeding the tumor infiltration of CD8 T cells. Thus, STAT3-enhancing germline receptor variants contribute to immune evasion through their pleiotropic functions in immune cells.
Crimean-Congo Hemorrhagic Fever Virus Nucleocapsid Protein Augments mRNA Translation

ABSTRACT Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne Nairovirus of the Bunyaviridae family, causing severe illness with high mortality rates in humans. Here, we demonstrate that CCHFV nucleocapsid protein (CCHFV-NP) augments mRNA translation. CCHFV-NP binds to the viral mRNA 5′ untranslated region (UTR) with high affinity. It facilitates the translation of reporter mRNA both in vivo and in vitro with the assistance of the viral mRNA 5′ UTR. CCHFV-NP equally favors the translation of both capped and uncapped mRNAs, demonstrating the independence of this translation strategy on the 5′ cap. Unlike the canonical host translation machinery, inhibition of eIF4F complex, an amalgam of three initiation factors, eIF4A, eIF4G, and eIF4E, by the chemical inhibitor 4E1RCat did not impact the CCHFV-NP-mediated translation mechanism. However, the proteolytic degradation of eIF4G alone by the human rhinovirus 2A protease abrogated this translation strategy. Our results demonstrate that eIF4F complex formation is not required but eIF4G plays a critical role in this translation mechanism. Our results suggest that CCHFV has adopted a unique translation mechanism to facilitate the translation of viral mRNAs in the host cell cytoplasm where cellular transcripts are competing for the same translation apparatus. IMPORTANCE Crimean-Congo hemorrhagic fever, a highly contagious viral disease endemic to more than 30 countries, has limited treatment options. Our results demonstrate that NP favors the translation of a reporter mRNA harboring the viral mRNA 5′ UTR. It is highly likely that CCHFV uses an NP-mediated translation strategy for the rapid synthesis of viral proteins during the course of infection. Shutdown of this translation mechanism might selectively impact viral protein synthesis, suggesting that an NP-mediated translation strategy is a target for therapeutic intervention against this viral disease.