Miracle-dz/UniFAR-FTUs huggingface dataset:
Changes in diet and lifestyle and long-term weight gain in women and men.

BACKGROUND Specific dietary and other lifestyle behaviors may affect the success of the straightforward-sounding strategy "eat less and exercise more" for preventing long-term weight gain. METHODS We performed prospective investigations involving three separate cohorts that included 120,877 U.S. women and men who were free of chronic diseases and not obese at baseline, with follow-up periods from 1986 to 2006, 1991 to 2003, and 1986 to 2006. The relationships between changes in lifestyle factors and weight change were evaluated at 4-year intervals, with multivariable adjustments made for age, baseline body-mass index for each period, and all lifestyle factors simultaneously. Cohort-specific and sex-specific results were similar and were pooled with the use of an inverse-variance-weighted meta-analysis. RESULTS Within each 4-year period, participants gained an average of 3.35 lb (5th to 95th percentile, -4.1 to 12.4). On the basis of increased daily servings of individual dietary components, 4-year weight change was most strongly associated with the intake of potato chips (1.69 lb), potatoes (1.28 lb), sugar-sweetened beverages (1.00 lb), unprocessed red meats (0.95 lb), and processed meats (0.93 lb) and was inversely associated with the intake of vegetables (-0.22 lb), whole grains (-0.37 lb), fruits (-0.49 lb), nuts (-0.57 lb), and yogurt (-0.82 lb) (P≤0.005 for each comparison). Aggregate dietary changes were associated with substantial differences in weight change (3.93 lb across quintiles of dietary change). Other lifestyle factors were also independently associated with weight change (P<0.001), including physical activity (-1.76 lb across quintiles); alcohol use (0.41 lb per drink per day), smoking (new quitters, 5.17 lb; former smokers, 0.14 lb), sleep (more weight gain with <6 or >8 hours of sleep), and television watching (0.31 lb per hour per day). CONCLUSIONS Specific dietary and lifestyle factors are independently associated with long-term weight gain, with a substantial aggregate effect and implications for strategies to prevent obesity. (Funded by the National Institutes of Health and others.).
Monolignol Pathway 4-Coumaric Acid:Coenzyme A Ligases in Populus. trichocarpa: Novel Specificity, Metabolic Regulation, and Simulation of Coenzyme A Ligation Fluxes1[W]

Two 4-coumaric acid:CoA ligases regulate CoA flux with novel specificity. 4-Coumaric acid:coenzyme A ligase (4CL) is involved in monolignol biosynthesis for lignification in plant cell walls. It ligates coenzyme A (CoA) with hydroxycinnamic acids, such as 4-coumaric and caffeic acids, into hydroxycinnamoyl-CoA thioesters. The ligation ensures the activated state of the acid for reduction into monolignols. In Populus spp. , it has long been thought that one monolignol-specific 4CL is involved. Here, we present evidence of two monolignol 4CLs, Ptr4CL3 and Ptr4CL5, in Populus trichocarpa. Ptr4CL3 is the ortholog of the monolignol 4CL reported for many other species. Ptr4CL5 is novel. The two Ptr4CLs exhibited distinct Michaelis-Menten kinetic properties. Inhibition kinetics demonstrated that hydroxycinnamic acid substrates are also inhibitors of 4CL and suggested that Ptr4CL5 is an allosteric enzyme. Experimentally validated flux simulation, incorporating reaction/inhibition kinetics, suggested two CoA ligation paths in vivo: one through 4-coumaric acid and the other through caffeic acid. We previously showed that a membrane protein complex mediated the 3-hydroxylation of 4-coumaric acid to caffeic acid. The demonstration here of two ligation paths requiring these acids supports this 3-hydroxylation function. Ptr4CL3 regulates both CoA ligation paths with similar efficiencies, whereas Ptr4CL5 regulates primarily the caffeic acid path. Both paths can be inhibited by caffeic acid. The Ptr4CL5-catalyzed caffeic acid metabolism, therefore, may also act to mitigate the inhibition by caffeic acid to maintain a proper ligation flux. A high level of caffeic acid was detected in stem-differentiating xylem of P. trichocarpa. Our results suggest that Ptr4CL5 and caffeic acid coordinately modulate the CoA ligation flux for monolignol biosynthesis.
Enhancement frequency decreases with increasing age in relapsing-remitting multiple sclerosis

Contrast enhancement found on MRI of patients with MS demonstrates areas of blood–brain barrier damage and inflammation. Contrast enhanced MRI shows evidence of disease activity five to 10 times more frequently than is indicated by clinically apparent relapse. However, the frequency of enhancement differs significantly among the different clinical MS phenotypes. It is much lower in patients with primary progressive MS (PPMS) than in those with secondary progressive MS (SPMS). 1 Enhancement frequency is highest in relapsing-remitting MS (RRMS). 2,3⇓ These differences in enhancement frequency among the clinical MS phenotypes has been interpreted as an indication that different mechanisms are responsible for disease evolution in the different phases or manifestations of the disease. However, recent experimental work has shown that clinical and pathologic manifestations of autoimmune demyelination are age dependent.4 This suggests that increasing age might also be responsible for the reduced frequency of enhancement seen in patients with PPMS or SPMS, who are typically older than those with RRMS. To address whether increasing age …
A Model Theory Approach to Structural Limits

The goal of this paper is to unify two lines in a particular area of graph limits. First, we generalize and provide unified treatment of various graph limit concepts by means of a combination of model theory and analysis. Then, as an example, we generalize limits of bounded degree graphs from subgraph testing to finite model testing.
The effect of adaptive bone remodeling threshold levels on resorption around noncemented hip stems.

• A submitted manuscript is the author's version of the article upon submission and before peer-review. There can be important differences between the submitted version and the official published version of record. People interested in the research are advised to contact the author for the final version of the publication, or visit the DOI to the publisher's website. • The final author version and the galley proof are versions of the publication after peer review. • The final published version features the final layout of the paper including the volume, issue and page numbers.
Binocular combination of luminance profiles

We develop and test a new two-dimensional model for binocular combination of the two eyes' luminance profiles. For first-order stimuli, the model assumes that one eye's luminance profile first goes through a luminance compressor, receives gain-control and gain-enhancement from the other eye, and then linearly combines the other eye's output profile. For second-order stimuli, rectification is added in the signal path of the model before the binocular combination site. Both the total contrast and luminance energies, weighted sums over both the space and spatial-frequency domains, were used in the interocular gain-control, while only the total contrast energy was used in the interocular gain-enhancement. To challenge the model, we performed a binocular brightness matching experiment over a large range of background and target luminances. The target stimulus was a dichoptic disc with a sharp edge that has an increment or decrement luminance from its background. The disk's interocular luminance ratio varied from trial to trial. To refine the model we tested three luminance compressors, five nested binocular combination models (including the Ding–Sperling and the DSKL models), and examined the presence or absence of total luminance energy in the model. We found that (1) installing a luminance compressor, either a logarithmic luminance function or luminance gain-control, (2) including both contrast and luminance energies, and (3) adding interocular gain-enhancement (the DSKL model) to a combined model significantly improved its performance. The combined model provides a systematic account of binocular luminance summation over a large range of luminance input levels. It gives a unified explanation of Fechner's paradox observed on a dark background, and a winner-take-all phenomenon observed on a light background. To further test the model, we conducted two additional experiments: luminance summation of discs with asymmetric contour information (Experiment 2), similar to Levelt (1965) and binocular combination of second-order contrast-modulated gratings (Experiment 3). We used the model obtained in Experiment 1 to predict the results of Experiments 2 and 3 and the results of our previous studies. Model simulations further refined the contrast space weight and contrast sensitivity functions that are installed in the model, and provide a reasonable account for rebalancing of imbalanced binocular vision by reducing the mean luminance in the dominant eye.
Multi-targeting NGR-modified liposomes recognizing glioma tumor cells and vasculogenic mimicry for improving anti-glioma therapy

Like the anti-angiogenic strategy, anti-vascular mimicry is considered as a novel targeting strategy for glioma. In the present study, we used NGR as a targeting ligand and prepared NGR-modified liposomes containing combretastatin A4 (NGR-SSL-CA4) in order to evaluate their potential targeting of glioma tumor cells and vasculogenic mimicry (VM) formed by glioma cells as well as their anti-VM activity in mice with glioma tumor cells. NGR-SSL-CA4 was prepared by a thin-film hydration method. The in vitro targeting of U87-MG (human glioma tumor cells) by NGR-modified liposomes was evaluated. The in vivo targeting activity of NGR-modified liposomes was tested in U87-MG orthotopic tumor-bearing nude mice. The anti-VM activity of NGR-SSL-CA4 was also investigated in vitro and in vivo. The targeting activity of the NGR-modified liposomes was demonstrated by in vitro flow cytometry and in vivo biodistribution. The in vitro anti-VM activity of NGR-SSL-CA4 was indicated in a series of cell migration and VM channel experiments. NGR-SSL-CA4 produced very marked anti-tumor and anti-VM activity in U87-MG orthotopic tumor-bearing mice in vivo. Overall, the NGR-SSL-CA4 has great potential in the multi-targeting therapy of glioma involving U87-MG cells, and the VM formed by U87-MG cells as well as endothelial cells producing anti-U87-MG cells, and anti-VM formed by U87-MG cells as well as anti-endothelial cell activity.
Interleukin-4 and interferon- γ levels in Epstein-Barr virus-associated infectious mononucleosis and nasopharyngeal carcinoma

Background: Cytokines have been suggested to participate in the pathogenesis of infectious mononucleosis (IM) and nasopharyngeal carcinoma (NPC). METHODS: Serum levels and gene expression of interleukin-4 (IL-4) and interferon-γ (IFN-γ) were assessed by immunologic and PCR assays, respectively in patients with Epstein-Barr virus (EBV)-associated IM and NPC and EBV nega-tive controls. RESULTS: The serum levels of IFN- γ were elevated, but those of IL-4 were decreased in IM and NPC patients as compared with those of the control group (p < 0.05). CONCLUSIONS: These results suggest that serum levels of IFN-γ may be predominant over those of IL-4 during the course of IM and NPC.
Distinct Gene Number-Genome Size Relationships for Eukaryotes and Non-Eukaryotes: Gene Content Estimation for Dinoflagellate Genomes

The ability to predict gene content is highly desirable for characterization of not-yet sequenced genomes like those of dinoflagellates. Using data from completely sequenced and annotated genomes from phylogenetically diverse lineages, we investigated the relationship between gene content and genome size using regression analyses. Distinct relationships between log10-transformed protein-coding gene number (Y′) versus log10-transformed genome size (X′, genome size in kbp) were found for eukaryotes and non-eukaryotes. Eukaryotes best fit a logarithmic model, Y′ = ln(-46.200+22.678X′, whereas non-eukaryotes a linear model, Y′ = 0.045+0.977X′, both with high significance (p<0.001, R2>0.91). Total gene number shows similar trends in both groups to their respective protein coding regressions. The distinct correlations reflect lower and decreasing gene-coding percentages as genome size increases in eukaryotes (82%–1%) compared to higher and relatively stable percentages in prokaryotes and viruses (97%–47%). The eukaryotic regression models project that the smallest dinoflagellate genome (3×106 kbp) contains 38,188 protein-coding (40,086 total) genes and the largest (245×106 kbp) 87,688 protein-coding (92,013 total) genes, corresponding to 1.8% and 0.05% gene-coding percentages. These estimates do not likely represent extraordinarily high functional diversity of the encoded proteome but rather highly redundant genomes as evidenced by high gene copy numbers documented for various dinoflagellate species.
A childhood acute lymphoblastic leukemia genome-wide association study identifies novel sex-specific risk variants

AbstractChildhood acute lymphoblastic leukemia (ALL) occurs more frequently in males. Reasons behind sex differences in childhood ALL risk are unknown. In the present genome-wide association study (GWAS), we explored the genetic basis of sex differences by comparing genotype frequencies between male and female cases in a case-only study to assess effect-modification by sex.The case-only design included 236 incident cases of childhood ALL consecutively recruited at the Texas Children's Cancer Center in Houston, Texas from 2007 to 2012. All cases were non-Hispanic whites, aged 1 to 10 years, and diagnosed with confirmed B-cell precursor ALL. Genotyping was performed using the Illumina HumanCoreExome BeadChip on the Illumina Infinium platform. Besides the top 100 statistically most significant results, results were also analyzed by the top 100 highest effect size with a nominal statistical significance (P <0.05). The statistically most significant sex-specific association (P = 4 × 10−6) was with the single nucleotide polymorphism (SNP) rs4813720 (RASSF2), an expression quantitative trait locus (eQTL) for RASSF2 in peripheral blood. rs4813720 is also a strong methylation QTL (meQTL) for a CpG site (cg22485289) within RASSF2 in pregnancy, at birth, childhood, and adolescence. cg22485289 is one of the hypomethylated CpG sites in ALL compared with pre-B cells. Two missense SNPs, rs12722042 and 12722039, in the HLA-DQA1 gene yielded the highest effect sizes (odds ratio [OR] ∼ 14; P <0.01) for sex-specific results. The HLA-DQA1 SNPs belong to DQA1*01 and confirmed the previously reported male-specific association with DQA1*01. This finding supports the proposed infection-related etiology in childhood ALL risk for males. Further analyses revealed that most SNPs (either direct effect or through linkage disequilibrium) were within active enhancers or active promoter regions and had regulatory effects on gene expression levels.Cumulative data suggested that RASSF2 rs4813720, which correlates with increased RASSF2 expression, may counteract the suppressor effect of estrogen-regulated miR-17-92 on RASSF2 resulting in protection in males. Given the amount of sex hormone-related mechanisms suggested by our findings, future studies should examine prenatal or early postnatal programming by sex hormones when hormone levels show a large variation.
Cooperative Epistemic Multi-Agent Planning for Implicit Coordination

Epistemic planning can be used for decision making in multi-agent situations with distributed knowledge and capabilities. Recently, Dynamic Epistemic Logic (DEL) has been shown to provide a very natural and expressive framework for epistemic planning. We extend the DEL-based epistemic planning framework to include perspective shifts, allowing us to define new notions of sequential and conditional planning with implicit coordination. With these, it is possible to solve planning tasks with joint goals in a decentralized manner without the agents having to negotiate about and commit to a joint policy at plan time. First we define the central planning notions and sketch the implementation of a planning system built on those notions. Afterwards we provide some case studies in order to evaluate the planner empirically and to show that the concept is useful for multi-agent systems in practice.
The K-bZIP Protein from Kaposi's Sarcoma-Associated Herpesvirus Interacts with p53 and Represses Its Transcriptional Activity

ABSTRACT Kaposi's sarcoma-associated herpesvirus (KSHV) is a gammaherpesvirus that has been implicated in the pathogenesis of Kaposi's sarcoma. KSHV encodes K-bZIP (open reading frame K8), a protein that belongs to the basic region-leucine zipper (bZIP) family of transcription factors. Here we show that K-bZIP associates with the cellular transcription factor p53 directly in vitro and in vivo. This interaction requires the bZIP domain of K-bZIP and the carboxy-terminal region (amino acids 300 to 393) of p53. We also show that K-bZIP represses the transcriptional activity of p53 which is required for apoptosis of the host cell. These results imply that K-bZIP blocks p53-mediated host cell death through its interaction with p53.
TASTE: Testability Analysis Engine and Opened Libraries for Digital Data Path

Testability is one of the most important factors that are considered during design cycle along with reliability, speed, power consumption, cost and other factors important for a customer. Estimation of testability parameter strongly depends on how accurate information utilized for the estimation by a testability analysis method is. In the paper, two results of our previous, long-term research in the area of digital circuit testability analysis are summarized: principle of our testability analysis engine and libraries used to store the information outgoing from transparency models. The engine is general and accuracy of its results strongly depends on the information stored in the libraries. If simple transparency model is utilized, information about circuit testability could be far away from real state of the circuit. Otherwise, testability information can approximate so serious parameter such as fault-coverage factor.
Minimum Free Energy Path of Ligand-Induced Transition in Adenylate Kinase

Large-scale conformational changes in proteins involve barrier-crossing transitions on the complex free energy surfaces of high-dimensional space. Such rare events cannot be efficiently captured by conventional molecular dynamics simulations. Here we show that, by combining the on-the-fly string method and the multi-state Bennett acceptance ratio (MBAR) method, the free energy profile of a conformational transition pathway in Escherichia coli adenylate kinase can be characterized in a high-dimensional space. The minimum free energy paths of the conformational transitions in adenylate kinase were explored by the on-the-fly string method in 20-dimensional space spanned by the 20 largest-amplitude principal modes, and the free energy and various kinds of average physical quantities along the pathways were successfully evaluated by the MBAR method. The influence of ligand binding on the pathways was characterized in terms of rigid-body motions of the lid-shaped ATP-binding domain (LID) and the AMP-binding (AMPbd) domains. It was found that the LID domain was able to partially close without the ligand, while the closure of the AMPbd domain required the ligand binding. The transition state ensemble of the ligand bound form was identified as those structures characterized by highly specific binding of the ligand to the AMPbd domain, and was validated by unrestrained MD simulations. It was also found that complete closure of the LID domain required the dehydration of solvents around the P-loop. These findings suggest that the interplay of the two different types of domain motion is an essential feature in the conformational transition of the enzyme.
An Approximation Algorithm for the Discrete Team Decision Problem

In this paper we study a discrete version of the classical team decision problem. It has been shown previously that the general discrete team decision problem is NP-hard. Here we present an efficient approximation algorithm for this problem. For the maximization version of this problem with nonnegative rewards, this algorithm computes decision rules which are guaranteed to be within a fixed bound of optimal.
Gut Microbiota-Dependent Trimethylamine N-Oxide (TMAO) Pathway Contributes to Both Development of Renal Insufficiency and Mortality Risk in Chronic Kidney Disease

Rationale: Trimethylamine-N-oxide (TMAO), a gut microbial-dependent metabolite of dietary choline, phosphatidylcholine (lecithin), and L-carnitine, is elevated in chronic kidney diseases (CKD) and associated with coronary artery disease pathogenesis. Objective: To both investigate the clinical prognostic value of TMAO in subjects with versus without CKD, and test the hypothesis that TMAO plays a direct contributory role in the development and progression of renal dysfunction. Methods and Results: We first examined the relationship between fasting plasma TMAO and all-cause mortality over 5-year follow-up in 521 stable subjects with CKD (estimated glomerular filtration rate, <60 mL/min per 1.73 m2). Median TMAO level among CKD subjects was 7.9 &mgr;mol/L (interquartile range, 5.2–12.4 &mgr;mol/L), which was markedly higher (P<0.001) than in non-CKD subjects (n=3166). Within CKD subjects, higher (fourth versus first quartile) plasma TMAO level was associated with a 2.8-fold increased mortality risk. After adjustments for traditional risk factors, high-sensitivity C-reactive protein, estimated glomerular filtration rate, elevated TMAO levels remained predictive of 5-year mortality risk (hazard ratio, 1.93; 95% confidence interval, 1.13–3.29; P<0.05). TMAO provided significant incremental prognostic value (net reclassification index, 17.26%; P<0.001 and differences in area under receiver operator characteristic curve, 63.26% versus 65.95%; P=0.036). Among non-CKD subjects, elevated TMAO levels portend poorer prognosis within cohorts of high and low cystatin C. In animal models, elevated dietary choline or TMAO directly led to progressive renal tubulointerstitial fibrosis and dysfunction. Conclusions: Plasma TMAO levels are both elevated in patients with CKD and portend poorer long-term survival. Chronic dietary exposures that increase TMAO directly contributes to progressive renal fibrosis and dysfunction in animal models.
Human ganglion cells express the alpha-2 adrenergic receptor: relevance to neuroprotection

Background/aim: Alpha-2α adrenergic receptor (α2-AR) agonists are thought to be neuroprotective, preventing retinal ganglion cell death independent of pressure reduction. Previous studies have identified α2-ARs in rat retina. The authors aimed to demonstrate the presence and localisation of α2-ARs in human and rat retina and on the rat retinal ganglion cell line, RGC-5. Methods: Seven postmortem human and three postmortem rat eyes were paraformaldehyde fixed and frozen. RGC-5 cells were also paraformaldehyde fixed. The expression of α2A-ARs was determined by antibody immunofluorescence. Results: α2A-AR expression was identified in the human retina, on ganglion cells, and cells in the inner and outer nuclear layers (INL, ONL). Differential α2A-AR staining patterns in the INL and ONL suggest a further restriction to as yet unidentified neuronal subclasses. The RGC-5 cell line also expressed α2A-ARs in undifferentiated cells and an increased expression upon fully differentiated cells. Conclusion: α2-AR agonists in addition to their pressure lowering effects in the eye, may act directly upon retinal neurons, including retinal ganglion cells. The presence of α2-ARs on the RGC-5 cell line allows future investigation of these possible direct effects using in vitro glaucoma model systems.