Miracle-dz/UniFAR-FTUs huggingface dataset:
Human Papillomavirus Genotypes and Cofactors Causing Cervical Intraepithelial Neoplasia and Cervical Cancer in Korean Women

Objective Infection with human papillomavirus (HPV) is a necessary cause of cervical cancer, but the risk associated with the various viral types and related cofactors have not been adequately assessed in Korean women. This study aimed to investigate the genotype distribution of HPV and cofactors related to cervical carcinogenesis in Korean women. Materials and Methods We conducted a hospital-based case-control study in 215 women with histologically confirmed cervical neoplasia (111 cases of cervical intraepithelial neoplasia [CIN] and 104 cases of invasive cervical cancer [ICC]) and 1214 healthy control women. Polymerase chain reaction–based dot blot assays were used for detection of 16 high-risk HPV types. To clarify the cofactors, we administered questionnaires evaluating smoking, drinking, and sexual and reproductive history from women infected with HPV. Results Human papillomavirus was detected in 86.5% of the women with CIN and 96.2% of the women with ICC compared to 14.6% of the control women. The most common HPV types were, in descending order of frequency, types 16, 58, 18, 33, and 66 for CIN, and types 16, 18, 31, and 33 for ICC. Among the control women, HPV 16, 66, 33, 58, 18, and 31 were the most common types. Smoking and higher number of births (≥3) were associated with CIN (odds ratio [OR], 2.49; 95% confidence interval [CI], 1.21–5.15, and OR, 2.67; 95% CI, 1.36–5.28, respectively). This relationship was also found in the women with ICC (OR, 3.42; 95% CI, 1.59–7.38, and OR, 2.17; 95% CI, 1.08–4.38, respectively) compared to controls. In addition, the circumcision of sexual partner and the sexual habit of condom use were protective factors for ICC (OR, 0.47; 95% CI, 0.24–0.90, and OR, 0.19; 95% CI, 0.06–0.57, respectively). Conclusion Human papillomavirus types 16, 18, 31, 33, and 58 are the major causative genotypes for cervical carcinogenesis in Korean women. Smoking and multiparity seem to be the most significant cofactors.
Modeling the Appearance of Fluorescent Colors

The advent of improved durability pigments has resulted in the increased use of fluorescent colored materials in safety and warning applications (e.g., high-priority traffic signs; safety vests). Yet, little is known about the relationship between the visual effectiveness of fluorescent colored materials and their photometric properties. Archival data sets were reanalyzed to assess the appropriateness of an elegant psychophysical model of the appearance of fluorescent colors first introduced by Schultze (1953). The results indicated that the expression Y/MacAdam Limit (x,y) provided an excellent prediction of the suprathreshold appearance of fluorescent color (x,y); where (x,y) represented the color of the test stimulus in 1931 CIE chromaticity coordinates. These findings have important implications for design using fluorescent colors and may also contribute significantly to our understanding of related color phenomena.
Advanced Fluorescence Microscopy Techniques—FRAP, FLIP, FLAP, FRET and FLIM

Fluorescence microscopy provides an efficient and unique approach to study fixed and living cells because of its versatility, specificity, and high sensitivity. Fluorescence microscopes can both detect the fluorescence emitted from labeled molecules in biological samples as images or photometric data from which intensities and emission spectra can be deduced. By exploiting the characteristics of fluorescence, various techniques have been developed that enable the visualization and analysis of complex dynamic events in cells, organelles, and sub-organelle components within the biological specimen. The techniques described here are fluorescence recovery after photobleaching (FRAP), the related fluorescence loss in photobleaching (FLIP), fluorescence localization after photobleaching (FLAP), Förster or fluorescence resonance energy transfer (FRET) and the different ways how to measure FRET, such as acceptor bleaching, sensitized emission, polarization anisotropy, and fluorescence lifetime imaging microscopy (FLIM). First, a brief introduction into the mechanisms underlying fluorescence as a physical phenomenon and fluorescence, confocal, and multiphoton microscopy is given. Subsequently, these advanced microscopy techniques are introduced in more detail, with a description of how these techniques are performed, what needs to be considered, and what practical advantages they can bring to cell biological research.
Obesity is Associated with Genetic Variants That Alter Dopamine Availability

Human and animal studies have implicated dopamine in appetite regulation, and family studies have shown that BMI has a strong genetic component. Dopamine availability is controlled largely by three enzymes: COMT, MAOA and MAOB, and by the dopamine transporter SLC6A3, and each gene has a well‐characterized functional variant. Here we look at these four functional polymorphisms together, to investigate how heritable variation in dopamine levels influences the risk of obesity in a cohort of 1150, including 240 defined as obese (BMI ≥ 30). The COMT and SLC6A3 polymorphisms showed no association with either weight, BMI or obesity risk. We found, however, that both MAOA and MAOB show an excess of the low‐activity genotypes in obese individuals (MAOA:χ2= 15.45, p = 0.004; MAOB:χ2= 8.05, p = 0.018). Additionally, the MAOA genotype was significantly associated with both weight (p = 0.0005) and BMI (p = 0.001). When considered together, the ‘at risk genotype’ ‐ low activity genotypes at both the MAOA and MAOB loci ‐ shows a relative risk for obesity of 5.01. These results have not been replicated and, given the experience of complex trait genetics, warrant caution in interpretation. In implicating both the MAOA and MOAB variants, however, this study provides the first indication that dopamine availability (as opposed to other effects of MAOA) is involved in human obesity. It is therefore a priority to assess the associations in replication datasets.
Cost-Effectiveness of Oral Anticoagulants for Treatment of Atrial Fibrillation

Background— New anticoagulants may improve health outcomes in patients with atrial fibrillation, but it is unclear whether their use is cost-effective. Methods and Results— A Markov state transition was created to compare 4 therapies: dabigatran 150 mg BID, apixaban 5 mg BID, rivaroxaban 20 mg QD, and warfarin therapy. The population included those with newly diagnosed atrial fibrillation who were eligible for treatment with warfarin. Compared with warfarin, apixaban, rivaroxaban, and dabigatran, costs were $93 063, $111 465, and $140 557 per additional quality-adjusted life year gained, respectively. At a threshold of $100 000 per quality-adjusted life year, apixaban provided the greatest absolute benefit while still being cost-effective, although warfarin would be superior if apixaban was 2% less effective than expected. Although apixaban was the optimal strategy in our base case, in probabilistic sensitivity analysis, warfarin was optimal in an equal number of iterations at a cost-effectiveness threshold of $100 000 per quality-adjusted life year. Conclusions— While at a standard cost-effectiveness threshold of $100 000 per quality-adjusted life year, apixaban seems to be the optimal anticoagulation strategy; this finding is sensitive to assumptions about its efficacy and cost. In sensitivity analysis, warfarin seems to be the optimal choice in an equal number of simulations. As a result, although all the novel oral anticoagulants produce greater quality-adjusted life expectancy than warfarin, they may not represent good value for money.
High dietary niacin intake is associated with decreased chromosome translocation frequency in airline pilots

Experimental studies suggest that B vitamins such as niacin, folate, riboflavin, vitamin B6 and vitamin B12 may protect against DNA damage induced by ionising radiation (IR). However, to date, data from IR-exposed human populations are not available. We examined the intakes of these B vitamins and their food sources in relation to the frequency of chromosome translocations as a biomarker of cumulative DNA damage, in eighty-two male airline pilots. Dietary intakes were estimated by using a self-administered semi-quantitative FFQ. Translocations in peripheral blood lymphocytes were scored by using fluorescence in situ hybridisation whole-chromosome painting. Negative binomial regression was used to estimate rate ratios and 95 % CI, adjusted for age and occupational and lifestyle factors. We observed a significant inverse association between translocation frequency and dietary intake of niacin (P = 0·02): adjusted rate ratio for subjects in the highest tertile compared with the lowest tertile was 0·58 (95 % CI 0·40, 0·83). Translocation frequency was not associated with total niacin intake from food and supplements as well as dietary or total intake of folate, riboflavin or vitamin B6 or B12. However, the adjusted rate ratios were significant for subjects with ≥ median compared with < median intake of whole grains (P = 0·03) and red and processed meat (P = 0·01): 0·69 (95 % CI 0·50, 0·96) and 1·56 (95 % CI 1·13, 2·16), respectively. Our data suggest that a high intake of niacin from food or a diet high in whole grains but low in red and processed meat may protect against cumulative DNA damage in IR-exposed persons.
Hepatitis B screening before chemotherapy: a survey of practitioners' knowledge, beliefs, and screening practices.

PURPOSE Hepatitis B virus (HBV) reactivation is a potentially fatal complication of chemotherapy that can be largely prevented with medication, provided that asymptomatic HBV carriers are identified. We explored the knowledge, beliefs, and practices of Canadian oncologists/hematologists regarding HBV screening before chemotherapy. METHODS A novel questionnaire was mailed to all practicing hematologists/oncologists, where publicly accessible online physician registries facilitated identification of these specialists (71% of the Canadian physician population). RESULTS Of 504 potentially eligible practitioners, 311 (62%) responded, of whom 246 indicated that they administered chemotherapy and were thus included in final analyses. Respondents tended to underestimate the risk of HBV reactivation, and recognition of the major risk factor for HBV carriage (ie, birth in an endemic area) was low. Forty percent of respondents reported rarely or never testing for HBV before chemotherapy, and 36% reported screening only those patients with HBV risk factors. In multivariate analysis, having a predominantly hematologic practice, practitioner experience with HBV reactivation, ability to correctly estimate the risk of HBV reactivation, fewer years in practice, and female sex were independently associated with an increased likelihood of screening for HBV. CONCLUSION Canadian oncologists and hematologists tend to underestimate the risk of HBV reactivation and report relatively low HBV screening rates. Among those practitioners who do screen, the favored strategy is selective screening of patients with HBV risk factors. However, oncologists'/hematologists' knowledge regarding risk factors for HBV carriage seems to be low, potentially undermining the success of a selective screening strategy.
Quantitative high resolution mapping of HvMLH3 foci in barley pachytene nuclei reveals a strong distal bias and weak interference

In barley (Hordeum vulgare L.), chiasmata (the physical sites of genetic crossovers) are skewed towards the distal ends of chromosomes, effectively consigning a large proportion of genes to recombination coldspots. This has the effect of limiting potential genetic variability, and of reducing the efficiency of map-based cloning and breeding approaches for this crop. Shifting the sites of recombination to more proximal chromosome regions by forward and reverse genetic means may be profitable in terms of realizing the genetic potential of the species, but is predicated upon a better understanding of the mechanisms governing the sites of these events, and upon the ability to recognize real changes in recombination patterns. The barley MutL Homologue (HvMLH3), a marker for class I interfering crossovers, has been isolated and a specific antibody has been raised. Immunolocalization of HvMLH3 along with the synaptonemal complex transverse filament protein ZYP1, used in conjunction with fluorescence in situ hybridization (FISH) tagging of specific barley chromosomes, has enabled access to the physical recombination landscape of the barley cultivars Morex and Bowman. Consistent distal localization of HvMLH3 foci throughout the genome, and similar patterns of HvMLH3 foci within bivalents 2H and 3H have been observed. A difference in total numbers of HvMLH3 foci between these two cultivars has been quantified, which is interpreted as representing genotypic variation in class I crossover frequency. Discrepancies between the frequencies of HvMLH3 foci and crossover frequencies derived from linkage analysis point to the existence of at least two crossover pathways in barley. It is also shown that interference of HvMLH3 foci is relatively weak compared with other plant species.
Discovering New Agents Active against Methicillin-Resistant Staphylococcus aureus with Ligand-Based Approaches

To discover new agents active against methicillin-resistant Staphylococcus aureus (MRSA), in silico models derived from 5451 cell-based anti-MRSA assay data were developed using four machine learning methods, including naïve Bayesian, support vector machine (SVM), recursive partitioning (RP), and k-nearest neighbors (kNN). A total of 876 models have been constructed based on physicochemical descriptors and fingerprints. The overall predictive accuracies of the best models exceeded 80% for both training and test sets. The best model was employed for the virtual screening of anti-MRSA compounds, which were then validated by a cell-based assay using the broth microdilution method with three types of highly resistant MRSA strains (ST239, ST5, and 252). A total of 12 new anti-MRSA agents were confirmed, which had MIC values ranging from 4 to 64 mg/L. This work proves the capacity of combined multiple ligand-based approaches for the discovery of new agents active against MRSA with cell-based assays. We think this work may inspire other lead identification processes when cell-based assay data are available.
The period of the circadian oscillator is primarily determined by the balance between casein kinase 1 and protein phosphatase 1

Mounting evidence suggests that PERIOD (PER) proteins play a central role in setting the speed (period) and phase of the circadian clock. Pharmacological and genetic studies have shown that changes in PER phosphorylation kinetics are associated with changes in circadian rhythm period and phase, which can lead to sleep disorders such as Familial Advanced Sleep Phase Syndrome in humans. We and others have shown that casein kinase 1δ and ε (CK1δ/ε) are essential PER kinases, but it is clear that additional, unknown mechanisms are also crucial for regulating the kinetics of PER phosphorylation. Here we report that circadian periodicity is determined primarily through PER phosphorylation kinetics set by the balance between CK1δ/ε and protein phosphatase 1 (PP1). In CK1δ/ε-deficient cells, PER phosphorylation is severely compromised and nonrhythmic, and the PER proteins are constitutively cytoplasmic. However, when PP1 is disrupted, PER phosphorylation is dramatically accelerated; the same effect is not seen when PP2A is disrupted. Our work demonstrates that the speed and rhythmicity of PER phosphorylation are controlled by the balance between CK1δ/ε and PP1, which in turn determines the period of the circadian oscillator. Thus, our findings provide clear insights into the molecular basis of how the period and phase of our daily rhythms are determined.
Identification of Human Proteins That Modify Misfolding and Proteotoxicity of Pathogenic Ataxin-1

Proteins with long, pathogenic polyglutamine (polyQ) sequences have an enhanced propensity to spontaneously misfold and self-assemble into insoluble protein aggregates. Here, we have identified 21 human proteins that influence polyQ-induced ataxin-1 misfolding and proteotoxicity in cell model systems. By analyzing the protein sequences of these modifiers, we discovered a recurrent presence of coiled-coil (CC) domains in ataxin-1 toxicity enhancers, while such domains were not present in suppressors. This suggests that CC domains contribute to the aggregation- and toxicity-promoting effects of modifiers in mammalian cells. We found that the ataxin-1–interacting protein MED15, computationally predicted to possess an N-terminal CC domain, enhances spontaneous ataxin-1 aggregation in cell-based assays, while no such effect was observed with the truncated protein MED15ΔCC, lacking such a domain. Studies with recombinant proteins confirmed these results and demonstrated that the N-terminal CC domain of MED15 (MED15CC) per se is sufficient to promote spontaneous ataxin-1 aggregation in vitro. Moreover, we observed that a hybrid Pum1 protein harboring the MED15CC domain promotes ataxin-1 aggregation in cell model systems. In strong contrast, wild-type Pum1 lacking a CC domain did not stimulate ataxin-1 polymerization. These results suggest that proteins with CC domains are potent enhancers of polyQ-mediated protein misfolding and aggregation in vitro and in vivo.
Race-Based Shifting Standards and Racial Discrimination

Members of stereotyped groups tend to be judged relative to group-specific standards such that subjective descriptions (smart, aggressive, tall) mean something different when they are applied to members of different groups. A “shifting standards” effect is present when judgments of group members on objective rating scales show stronger evidence of assimilation to stereotypes than the same judgments on subjective scales. This research asks whether the tendency to shift standards when judging the academic competence of Black and White students is related to measures of racial prejudice and to race-relevant decisions. In three studies, the tendency to shift standards was uncorrelated with other measures of prejudice but predicted reduced allocation of funds to a Black student organization, an effect moderated by implicit prejudice. The importance of examining interactions among indicators as they predict behavioral outcomes and implications for the conceptualization of prejudice are discussed.
Hotspot: The Snake River Geothermal Drilling Project — An Overview

The Snake River volcanic province (SRP) overlies a thermal anomaly that extends deep into the mantle; it represents one of the highest heat flow provinces in North America, and an area with the highest calculated geothermal gradients. This makes the SRP one of the potentially highest producing geothermal districts in the United States. Elevated heat flow is typically highest along the margins of the topographic Snake River Plain and lowest along the axis of the plain, where thermal gradients are suppressed by the Snake River aquifer. Beneath this aquifer, however, thermal gradients rise again and may tap even higher heat flows associated with the intrusion of mafic magmas into a geophysically-imaged mid-crustal sill complex. The primary goal of this project is to evaluate geothermal potential in three distinct settings: (1) the high sub-aquifer geothermal gradient associated with the intrusion of mafic magmas and the release of crustal fluids from the associated wall rocks, (2) the valley-margin settings where surface heat flow may be driven by the up-flow of hot fluids along buried caldera ring-fault complexes, and (3) a more traditional fault-bounded basin with thick sedimentary cover. All settings are found within the central or western Snake River Plain and represent previously untested targets for geothermal exploration. Our first drill site tests the extent of geothermal resources along the axis of the plain, beneath the Snake River aquifer, in an area where elevated groundwater temperatures imply a significant flux of conductive or advective heat flow from below. Our second drill site assesses the geothermal potential of up-flow zones along a buried caldera margin, in an area of known geothermal potential (Twin Falls geothermal district). Further studies will include seismic reflection-refraction surveys, gravity-magnetic surveys, and downhole geophysical logs.
Molecular regulation of macrophages in unleashing cancer-related inflammation

It is unclear how tumor-associated macrophages (TAMs) contribute to the initiation of oncogenesis and how they are regulated at the molecular level. By using a lineage-specific deletion strategy, we found that heat shock protein 90kDa β (Grp94), member 1 (HSP90B1), a master chaperone for Toll-like receptors and integrins also known as GP96, critically endows TAMs with the ability to promote genotoxic stress and colitis-associated colon cancer.
Rubber‐like thermosetting epoxy asphalt composites exhibiting atypical yielding behaviors

Rubber-like thermosetting epoxy asphalt composites (REACs) were prepared by curing epoxy resin (diglycidyl ether of bisphenol A) with curing agents system made up of maleated petroleum asphalt, adipic acid, and methylhexahydrophthalic anhydride. REACs' glass transition temperatures (Tg) and mechanics performances were investigated by differential scanning calorimetry (DSC) and universal tester, respectively. DSC results indicated that REACs had homogeneous phase structures, and their Tg were lower than room temperature. Large elongation at break (eb), as high as 150–286%, and atypical yielding behaviors similar to so-called “hard elastic” thermoplastics were observed simultaneously for the first time as to thermosetting epoxy composites at room temperature. The striking characteristics of REACs were ascribed to the formation of unique asphalt-filled bimodal networks, consisting of simultaneous cured maleated asphalt short-chain and dicarboxylic acid long-chain interpenetrating bimodal networks and wherewith filled unmaleated asphalt. The experimental results suggest that these inexpensive REACs may find promising applications in many engineering fields. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010
The P66Shc/Mitochondrial Permeability Transition Pore Pathway Determines Neurodegeneration

Mitochondrial-mediated oxidative stress and apoptosis play a crucial role in neurodegenerative disease and aging. Both mitochondrial permeability transition (PT) and swelling of mitochondria have been involved in neurodegeneration. Indeed, knockout mice for cyclophilin-D (Cyc-D), a key regulatory component of the PT pore (PTP) that triggers mitochondrial swelling, resulted to be protected in preclinical models of multiple sclerosis (MS), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). However, how neuronal stress is transduced into mitochondrial oxidative stress and swelling is unclear. Recently, the aging determinant p66Shc that generates H2O2 reacting with cytochrome c and induces oxidation of PTP and mitochondrial swelling was found to be involved in MS and ALS. To investigate the role of p66Shc/PTP pathway in neurodegeneration, we performed experimental autoimmune encephalomyelitis (EAE) experiments in p66Shc knockout mice (p66Shc−/−), knock out mice for cyclophilin-D (Cyc-D−/−), and p66Shc Cyc-D double knock out (p66Shc/Cyc-D−/−) mice. Results confirm that deletion of p66Shc protects from EAE without affecting immune response, whereas it is not epistatic to the Cyc-D mutation. These findings demonstrate that p66Shc contributes to EAE induced neuronal damage most likely through the opening of PTP suggesting that p66Shc/PTP pathway transduces neurodegenerative stresses.