Miracle-dz/UniFAR-FTUs huggingface dataset:
Epigenetic Signatures of Cigarette Smoking

Background—DNA methylation leaves a long-term signature of smoking exposure and is one potential mechanism by which tobacco exposure predisposes to adverse health outcomes, such as cancers, osteoporosis, lung, and cardiovascular disorders. Methods and Results—To comprehensively determine the association between cigarette smoking and DNA methylation, we conducted a meta-analysis of genome-wide DNA methylation assessed using the Illumina BeadChip 450K array on 15 907 blood-derived DNA samples from participants in 16 cohorts (including 2433 current, 6518 former, and 6956 never smokers). Comparing current versus never smokers, 2623 cytosine–phosphate–guanine sites (CpGs), annotated to 1405 genes, were statistically significantly differentially methylated at Bonferroni threshold of P<1×10−7 (18 760 CpGs at false discovery rate <0.05). Genes annotated to these CpGs were enriched for associations with several smoking-related traits in genome-wide studies including pulmonary function, cancers, inflammatory diseases, and heart disease. Comparing former versus never smokers, 185 of the CpGs that differed between current and never smokers were significant P<1×10−7 (2623 CpGs at false discovery rate <0.05), indicating a pattern of persistent altered methylation, with attenuation, after smoking cessation. Transcriptomic integration identified effects on gene expression at many differentially methylated CpGs. Conclusions—Cigarette smoking has a broad impact on genome-wide methylation that, at many loci, persists many years after smoking cessation. Many of the differentially methylated genes were novel genes with respect to biological effects of smoking and might represent therapeutic targets for prevention or treatment of tobacco-related diseases. Methylation at these sites could also serve as sensitive and stable biomarkers of lifetime exposure to tobacco smoke.
Ubiquitin Depletion as a Key Mediator of Toxicity by Translational Inhibitors

ABSTRACT Cycloheximide acts at the large subunit of the ribosome to inhibit translation. Here we report that ubiquitin levels are critical for the survival of Saccharomyces cerevisiae cells in the presence of cycloheximide: ubiquitin overexpression confers resistance to cycloheximide, while a reduced ubiquitin level confers sensitivity. Consistent with these findings, ubiquitin is unstable in yeast (t 1/2 = 2 h) and is rapidly depleted upon cycloheximide treatment. Cycloheximide does not noticeably enhance ubiquitin turnover, but serves principally to block ubiquitin synthesis. Cycloheximide also induces UBI4, the polyubiquitin gene. The cycloheximide-resistant phenotype of ubiquitin overexpressors is also characteristic of partial-loss-of-function proteasome mutants. Ubiquitin is stabilized in these mutants, which may account for their cycloheximide resistance. Previous studies have reported that ubiquitin is destabilized in the absence of Ubp6, a proteasome-associated deubiquitinating enzyme, and that ubp6 mutants are hypersensitive to cycloheximide. Consistent with the model that cycloheximide-treated cells are ubiquitin deficient, the cycloheximide sensitivity of ubp6 mutants can be rescued either by ubiquitin overexpression or by mutations in proteasome subunit genes. These results also show that ubiquitin wasting in ubp6 mutants is proteasome mediated. Ubiquitin overexpression rescued cells from additional translational inhibitors such as anisomycin and hygromycin B, suggesting that ubiquitin depletion may constitute a widespread mechanism for the toxicity of translational inhibitors.
On the function of BMP‐4 in patterning the marginal zone of the Xenopus embryo.

Bone morphogenetic protein 4 (BMP‐4) is expressed in the ventral marginal zone of the gastrulating embryo. At late gastrula stage this gene is expressed in the ventral‐most part of the slit blastopore and in tissues that derive from it. At tailbud stages BMP‐4 is expressed in the spinal cord roof plate, neural crest, eye and auditory vesicle. The interactions of BMP‐4 with dorsal genes such as goosecoid (gsc) and Xnot‐2 were studied in vivo. In embryos ventralized by UV irradiation and suramin treatment, BMP‐4 zygotic transcripts accumulate prematurely and the entire marginal zone expresses this gene. The patterning effect of BMP‐4 on ventro‐posterior development can be revealed by a sensitive assay involving the injection of BMP‐4 mRNA in the ventral marginal zone of embryos partially dorsalized with LiCl, which leads to the complete rescue of trunk and tail structures. The experiments presented here argue that BMP‐4 may act in vivo as a ventral signal for the proper patterning of the marginal zone, actively interacting with dorsal genes such as gsc and Xnot‐2. A model is proposed in which the timing of expression of various marginal zone‐specific genes plays a central role in patterning the mesoderm.
High Quality Monolithic 8-Shaped Inductors for Silicon RF IC Design

In this paper, RF characterization results of 8-shaped inductors on high resistivity silicon (HRS) substrate are presented. Electrical performances reported to area occupation of 8-shaped inductors are compared to those of classical octagonal/rectangular inductors. It is observed that 8-shaped inductors lead to inductance values 60% higher than what could be expected from classical octagonal/rectangular devices. A predictive electrical model is proposed based on previous investigations. Correlations between measurements and simulation data are found satisfactory.
Hispanics' use of Internet health information: an exploratory study.

PURPOSE The research examined use of the Internet to seek health information among Hispanics in the United States. METHODS A secondary analysis used the Impact of the Internet and Advertising on Patients and Physicians, 2000-2001, survey data. Pearson's chi(2) test, multivariate analysis of variance (MANOVA), analysis of variance (ANOVA), and independent samples t tests were conducted to test for relationships and differences between facets of Hispanic and non-Hispanic white online health information seeking. RESULTS Findings indicated lower Internet health information seeking among Hispanics (28.9%, n=72) than non-Hispanic whites (35.6%, n=883). On a scale of 1 (strongly agree) to 4 (strongly disagree), Hispanics were likely to agree that Internet health information improves understanding of medical conditions and treatments (M=1.65), gives patients confidence to talk to doctors about health concerns (M=1.67), and helps patients get treatment they would not otherwise receive (M=2.23). Hispanics viewed their skills in assessing Internet health information as good. Overall ratings were also positive for items related to sharing Internet health information with a doctor. Conflicting with these findings, Hispanics (M=3.33) and non-Hispanic whites (M=3.46) reported that physician-patient relationships worsened as a result of bringing online health information to a visit (scale 1=a lot better to 5=a lot worse). CONCLUSION This study provides further evidence of differences in Internet health information seeking among Hispanics and non-Hispanic whites. Cultural discordance may be a possible explanation for Hispanics' view that the Internet negatively impacts physician-patient relationships. Strategies to increase Hispanics' access to Internet health information will likely help them become empowered and educated consumers, potentially having a favorable impact on health outcomes.
The predictive value of cytogenetic diagnosis after CVS based on 4860 cases with both direct and culture methods

Cytogenetic analysis was performed in 4860 chorionic villus samples by means of both direct preparation and long‐term culture. The results of the analysis were compared with a classification including all theoretical types of combinations between the chromosomal constitution of the cytotrophoblast, extraembryonal mesoderm, and fetus, with the aim of evaluating the cytogenetic variability along the trophoblast—embryo axis. Eighteen of 29 possible combinations were found demonstrating a considerable heterogeneity. A mosaic conceptus was found in 1·5 per cent of cases, with generalized mosaicisms and confined mosaicisms in 0·2 and 1·3 per cent, respectively. Cytogenetic variability along the trophoblast—embryo axis was found in 1·42 per cent of cases. Results possibly leading to diagnostic errors (false‐positive and false‐negative results) were found in only 1·38 per cent. False‐positive results of direct preparation were the most commonly observed discrepancy (0·8 per cent), while the incidence of false‐positive results of the culture method and of both methods was 0·31 and 0·16 per cent respectively. The incidence of false‐negative results was 0·1 per cent, with false‐negative results of direct preparation 0·08 per cent and false‐negative results of both methods 0·02 per cent. False‐negative results of the culture method were not found. Our data confirm the high diagnostic accuracy of chorionic villus sampling and the utility of the combined use of the two methods in minimizing diagnostic errors and in reducing the need for follow‐up amniocentesis.
Use of the International Classification of Functioning, Disability and Health (ICF) to identify preliminary comprehensive and brief core sets for multiple sclerosis

Purpose. To identify the preliminary comprehensive and brief core sets for multiple sclerosis (MS), in a Delphi process using the International Classification of Functioning, Disability and Health (ICF). Method. Focus groups and a consensus process were used to identify ICF core sets for MS. This included: preliminary ICF studies; empirical patient data collection for 101 MS participants; review of the evidence base and treatment in MS literature followed by a Delphi exercise with 23 physicians and allied health professionals in Melbourne, Australia. Results. One hundred and forty-four (40%) second level ICF categories were selected by 23 participants in three rounds. The comprehensive MS ICF core set includes 34 (24%) categories from the component ‘body function’, six (4%) categories from ‘body structures’, 68 (47%) from ‘activities and participation’ and 36 (25%) from the component ‘environmental’ factors. Ten categories in ‘personal factors’ in MS were also suggested by the participants after intensive discussions. The brief set comprises 30 categories, 21% of categories in the comprehensive core set. Conclusion. Consensus expert opinion can use ICF categories to identify the core set for MS which reflects disease complexity and care burden for persons' with MS. Further research is needed to identify ICF categories of relevant personal factors to improve our understanding of the large social and cultural variance associated with them.
Bootstrapping coreference resolution using word associations

In this paper, we present an unsupervised framework that bootstraps a complete coreference resolution (CoRe) system from word associations mined from a large unlabeled corpus. We show that word associations are useful for CoRe -- e.g., the strong association between Obama and President is an indicator of likely coreference. Association information has so far not been used in CoRe because it is sparse and difficult to learn from small labeled corpora. Since unlabeled text is readily available, our unsupervised approach addresses the sparseness problem. In a self-training framework, we train a decision tree on a corpus that is automatically labeled using word associations. We show that this unsupervised system has better CoRe performance than other learning approaches that do not use manually labeled data.
Analysis of cis- and trans-Acting Factors Involved in Regulation of the Streptococcus mutans Fructanase Gene (fruA)

ABSTRACT There are two primary levels of control of the expression of the fructanase gene (fruA) of Streptococcus mutans: induction by levan, inulin, or sucrose and repression in the presence of glucose and other readily metabolized sugars. The goals of this study were to assess the functionality of putative cis-acting regulatory elements and to begin to identify the trans-acting factors involved in induction and catabolite repression of fruA. The fruA promoter and its derivatives generated by deletions and/or site-directed mutagenesis were fused to a promoterless chloramphenicol acetyltransferase (CAT) gene as a reporter, and strains carrying the transcriptional fusions were then analyzed for CAT activities in response to growth on various carbon sources. A dyadic sequence, ATGACA(TC)TGTCAT, located at −72 to −59 relative to the transcription initiation site was shown to be essential for expression of fruA. Inactivation of the genes that encode fructose-specific enzymes II resulted in elevated expression from the fruA promoter, suggesting negative regulation of fruA expression by the fructose phosphotransferase system. Mutagenesis of a terminator-like structure located in the 165-base 5′ untranslated region of the fruA mRNA or insertional inactivation of antiterminator genes revealed that antitermination was not a mechanism controlling induction or repression of fruA, although the untranslated leader mRNA may play a role in optimal expression of fructanase. Deletion or mutation of a consensus catabolite response element alleviated glucose repression of fruA, but interestingly, inactivation of the ccpA gene had no discernible effect on catabolite repression of fruA. Accumulating data suggest that expression of fruA is regulated by a mechanism that has several unique features that distinguish it from archetypical polysaccharide catabolic operons of other gram-positive bacteria.
Assessing the effectiveness of peer-facilitated interventions addressing high-risk drinking among judicially mandated college students.

OBJECTIVE This study examined the effectiveness of three peer-facilitated brief alcohol interventions-small group motivational interviewing, motivationally enhanced peer theater, and an interactive alcohol-education program-with students engaging in high-risk drinking who were referred for alcohol policy violations. METHOD Undergraduate students referred for alcohol policy violations (N = 695) at a large northeastern public university were randomized to one of the three conditions. Six-month follow-up data were collected on drinking frequency and quantity, negative consequences, use of protective behaviors, and perceptions of peers' drinking norms. RESULTS There were no statistically significant overall pre-post effects or treatment effects. However, exploratory analyses indicated that decreases in perceived norms and increases in use of protective behavioral strategies were associated with reductions in alcohol use and alcohol-related problems at follow-up (p < .01). CONCLUSIONS The presence of nonsignificant pre-post or main effects is, in part, consistent with recent research indicating that sanctioned college students may immediately reduce drinking in response to citation and that brief interventions may not contribute to additional behavioral change. The presence of statistically significant correlations between alcohol use and related problems with corrections in norms misperceptions and increased use of protective behaviors at the individual level holds promise for both research and practice. The integration of elements addressing social norms and use of protective behaviors within brief cognitive-behavioral intervention protocols delivered by trained peer facilitators warrants further study using randomized clinical trials.
Sex-specific positive and negative consequences of avoidance training during childhood on adult active avoidance learning in mice

In humans and animals cognitive training during childhood plays an important role in shaping neural circuits and thereby determines learning capacity later in life. Using a negative feedback learning paradigm, the two-way active avoidance (TWA) learning, we aimed to investigate in mice (i) the age-dependency of TWA learning, (ii) the consequences of pretraining in childhood on adult learning capacity and (iii) the impact of sex on the learning paradigm in mice. Taken together, we show here for the first time that the beneficial or detrimental outcome of pretraining in childhood depends on the age during which TWA training is encountered, indicating that different, age-dependent long-term “memory traces” might be formed, which are recruited during adult TWA training and thereby either facilitate or impair adult TWA learning. While pretraining during infancy results in learning impairment in adulthood, pretraining in late adolescence improved avoidance learning. The experiments revealed a clear sex difference in the group of late-adolescent mice: female mice showed better avoidance learning during late adolescence compared to males, and the beneficial impact of late-adolescent pretraining on adult learning was more pronounced in females compared to males.
THE COMPLEMENT-DEPENDENT BACTERIOLYTIC ACTIVITY OF NORMAL HUMAN SERUM

The bacteriolytic activity of normal human serum on a rough strain of E. coli has been studied by a turbidimetric method. Bacteriolysis was found to be markedly dependent on ionic strength and pH, with optima at µ = 0.06 and pH 8.3–8.5, respectively. The method of cultivating the cells also influenced the rapidity of lysis. Lysis was temperature-dependent and was exhibited by all samples of human serum tested. Microscopically, organisms incubated with serum were observed to swell, loose their rod shape and eventually burst, leaving remnants of the cell membrane in suspension. Sphaeroplasts were obtained by brief exposure of cells to serum followed by dilution into 5 per cent sucrose. The bacteriolytic reaction was shown to require complement. No definite requirement for properdin or specific antibody in this system could be demonstrated by the absorption of serum with zymosan and with homologous cells respectively. The latter procedure was found to reduce bacteriolytic activity by removal of serum lysozyme. Absorption of serum with bentonite also led to loss of bacteriolytic activity which could be restored with lysozyme. The organism was not lysed by lysozyme alone, but lysis occurred with lysozyme + EDTA in tris buffer. The possibility of complement acting independently of antibody or properdin, in certain instances, is discussed in relation to bacterial cell wall structure. Data are presented supporting the hypothesis that the "substrate" of complement in cell membranes is a lipid or lipoprotein.
Adaptive-Size Meshes for Rigid and Nonrigid Shape Analysis and Synthesis

A physically based modeling method that uses adaptive-size meshes to model surfaces of rigid and nonrigid objects is presented. The initial model uses an a priori determined mesh size. However, the mesh size increases or decreases dynamically during surface reconstruction to locate nodes near surface areas of interest (like high curvature points) and to optimize the fitting error. Further, presented with multiple 3-D data frames, the mesh size varies as the data surface undergoes nonrigid motion. This model is used to reconstruct 3-D surfaces, analyze the nonrigid motion, track the corresponding points in nonrigid motion, and create graphic animation and visualization. The method was tested on real range data, on simulated nonrigid motion, and on real data for the left ventricular motion. >
COSMIC RAY TRANSPORT WITH MAGNETIC FOCUSING AND THE “TELEGRAPH” MODEL

Cosmic rays (CR), constrained by scattering on magnetic irregularities, are believed to propagate diffusively. However, a well-known defect of diffusive approximation, whereby some of the particles propagate unrealistically fast, has directed interest toward an alternative CR transport model based on the “telegraph” equation. Though, its derivations often lack rigor and transparency leading to inconsistent results. We apply the classic Chapman–Enskog method to the CR transport problem. We show that no “telegraph” (second order time derivative) term emerges in any order of a proper asymptotic expansion with systematically eliminated short timescales. Nevertheless, this term may formally be converted from the fourth order hyper-diffusive term of the expansion. However, both the telegraph and hyperdiffusive terms may only be important for a short relaxation period associated with either strong pitch-angle anisotropy or spatial inhomogeneity of the initial CR distribution. Beyond this period the system evolves diffusively in both cases. The term conversion, that makes the telegraph and Chapman–Enskog approaches reasonably equivalent, is possible only after this relaxation period. During this period, the telegraph solution is argued to be unphysical. Unlike the hyperdiffusion correction, it is not uniformly valid and introduces implausible singular components to the solution. These dominate the solution during the relaxation period. Because they are shown not to be inherent in the underlying scattering problem, we argue that the telegraph term is involuntarily acquired in an asymptotic reduction of the problem.
Cancer Stem Cells in Moderately Differentiated Buccal Mucosal Squamous Cell Carcinoma Express Components of the Renin–Angiotensin System

Aim We have recently identified and characterized cancer stem cell (CSC) subpopulations within moderately differentiated buccal mucosal squamous cell carcinoma (MDBMSCC). We hypothesized that these CSCs express components of the renin–angiotensin system (RAS). Methods 3,3′-Diaminobenzidine (DAB) immunohistochemical (IHC) staining was performed on formalin-fixed paraffin-embedded MDBMSCC samples to investigate the expression of the components of the RAS: (pro)renin receptor (PRR), angiotensin converting enzyme (ACE), angiotensin II receptor 1 (ATIIR1), and angiotensin II receptor 2 (ATIIR2). NanoString mRNA gene expression analysis and Western Blotting (WB) were performed on snap-frozen MDBMSCC samples to confirm gene expression and translation of these transcripts, respectively. Double immunofluorescent (IF) IHC staining of these components of the RAS with the embryonic stem cell markers OCT4 or SALL4 was performed to demonstrate their localization in relation to the CSC subpopulations within MDBMSCC. Results DAB IHC staining demonstrated expression of PRR, ACE, ATIIR1, and ATIIR2 in MDBMSCC. IF IHC staining showed that PRR was expressed by the CSC subpopulations within the tumor nests, the peri-tumoral stroma, and the endothelium of the microvessels within the peri-tumoral stroma. ATIIR1 and ATIIR2 were localized to the CSC subpopulations within the tumor nests and the peri-tumoral stroma, while ACE was localized to the endothelium of the microvessels within the peri-tumoral stroma. WB and NanoString analyses confirmed protein expression and transcription activation of PRR, ACE, and ATIIR1, but not of ATIIR2, respectively. Conclusion Our novel findings of the presence and localization of PRR, ACE, ATIIR1, and potentially ATIIR2 to the CSC subpopulations within MDBMSCC suggest CSC as a therapeutic target by modulation of the RAS.