Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification of regulatory role of DNA methylation in colon cancer gene expression via systematic bioinformatics analysis

Abstract Colon cancer arises from the accumulations of genetic and epigenetic changes. Currently, profiles of DNA methylation and gene expression of colon cancer have not been elucidated clearly. This articles aims to characterize the profile of DNA methylation and gene expression of colon cancer systemically, and acquire candidate genes potentially regulated by altered methylation for this disease. Data were downloaded from The Cancer Genome Atlas database. Differentially methylated CpG sites (DMCs) and differentially methylated regions (DMRs) were calculated via COHCAP. Differentially expressed genes (DEGs) were identified by DESeq2. Weighted gene co-expression network analysis (WGCNA) package in R was applied for WGCNA. Data of 275 solid tumor tissues and 19 adjacent tumor tissues of colon cancer were obtained. A total of 1828 DMCs, including 1390 hypermethylated and 438 hypomethylated CpG sites, were identified between tumor and normal groups. A total of 789 DEGs, containing 435 upregulated genes and 354 downregulated genes were observed. It revealed that 8 DMRs-DEGs and 95 DMCs-DEGs pairs were significantly correlated. Furthermore, genes of yellow and brown modules from WGCNA were significantly correlated with tumor/normal status, and significantly enriched in peroxisome proliferator activated receptor signaling pathway, glutamatergic synapse, and neuroactive ligand-receptor interaction. Genes in the above 2 modules were also significantly enriched in DMCs or DMRs-associated genes. Specifically, ADHFE1, HAND2, and GNAO1 were hypermethylated and downregulated in colon cancer, suggesting that the low expression levels of these genes may be regulated by DNA hypermethylation. In addition, the 3 genes were involved in brown module of WGCNA, indicating their important roles in colon cancer. The investigation of the relationship between DNA methylation and gene expression may help to understand the effect of DNA methylation alteration on genes expression, especially gene co-expression network in the development of colon cancer. Genes such as ADHFE1, HAND2, and GNAO1 may be served as potential candidates for diagnosis and therapy targets in colon cancer.
Bond-orientational order and Frank’s constant in two-dimensional colloidal hard spheres

Recently, the full phase behaviour of 2D colloidal hard spheres was experimentally established, and found to involve a first order liquid to hexatic transition and a continuous hexatic to crystal transition (Thorneywork et al 2017 Phys. Rev. Lett. 118 158001). Here, we expand upon this work by considering the behaviour of the bond-orientational correlation time and Frank’s constant in the region of these phase transitions. We also consider the excess entropy, as calculated from the radial distribution functions, for a wide range of area fractions covering the liquid, hexatic and crystal phases. In all cases, the behaviour of these quantities further corroborates the previously reported melting scenario of 2D colloidal hard spheres.
C-Store: A Column-oriented DBMS

This paper presents the design of a read-optimized relational DBMS that contrasts sharply with most current systems, which are write-optimized. Among the many differences in its design are: storage of data by column rather than by row, careful coding and packing of objects into storage including main memory during query processing, storing an overlapping collection of column-oriented projections, rather than the current fare of tables and indexes, a non-traditional implementation of transactions which includes high availability and snapshot isolation for read-only transactions, and the extensive use of bitmap indexes to complement B-tree structures.We present preliminary performance data on a subset of TPC-H and show that the system we are building, C-Store, is substantially faster than popular commercial products. Hence, the architecture looks very encouraging.
SeqGAN: Sequence Generative Adversarial Nets with Policy Gradient

As a new way of training generative models, Generative Adversarial Net (GAN) that uses a discriminative model to guide the training of the generative model has enjoyed considerable success in generating real-valued data. However, it has limitations when the goal is for generating sequences of discrete tokens. A major reason lies in that the discrete outputs from the generative model make it difficult to pass the gradient update from the discriminative model to the generative model. Also, the discriminative model can only assess a complete sequence, while for a partially generated sequence, it is non-trivial to balance its current score and the future one once the entire sequence has been generated. In this paper, we propose a sequence generation framework, called SeqGAN, to solve the problems. Modeling the data generator as a stochastic policy in reinforcement learning (RL), SeqGAN bypasses the generator differentiation problem by directly performing gradient policy update. The RL reward signal comes from the GAN discriminator judged on a complete sequence, and is passed back to the intermediate state-action steps using Monte Carlo search. Extensive experiments on synthetic data and real-world tasks demonstrate significant improvements over strong baselines.
The Work-Rate of Elite Hurling Match-Play

Abstract Collins, DK, McRobert, A, Morton, JP, O'Sullivan, D, and Doran, DA. The work-rate of elite hurling match-play. J Strength Cond Res 32(3): 805–811, 2018—This study describes the global work-rate of elite hurling match-play and the influence which positional difference has on work-rate is considered. The movement of ninety-four players was recorded using global positioning system, sampling at 4 Hz in a total of 12 games. Data were classified according to the positional line on the field and period of the match. The total and high-speed distance of match-play was 7,617 ± 1,219 m (95% confidence interval [CI], 7,367–7,866) and 1,134 ± 358 m (95% CI, 1,060–1,206), respectively. The maximum speed attained was 29.8 ± 2.3 km·h−1 with a mean speed of 6.1 ± 1 km·h−1. The second {271 ± 107 m (p = 0.001; effect size [ES] = 0.25)}, third (278 ± 118 m [p = 0.001; ES = 0.21]), and fourth quarter (255 ± 108 m [p = 0.001; ES = 0.31]) high-speed running distance differed significantly from that of the first quarter (330 ± 120 m). There was a significant difference in total (p = 0.001; ES = 0.01–0.85), high-speed running (p = 0.001; ES = 0.21–0.76), and sprint (p = 0.013; ES = 0.01–0.39) distance across the positions, with midfielders undertaking the highest volume of work, followed by the half-forward and half-back lines and finally the full-forward and full-back lines. A decrease in high-speed running distance seems to occur through out the game and in particular at the latter stages of each half. Distinct positional work profiles are evident. The present finding provide a context on which training which replicates the work-rate of match-play may be formulated, thus helping to improve the physical preparation of elite players.
The Complement C3a–C3aR Axis Promotes Development of Thoracic Aortic Dissection via Regulation of MMP2 Expression

Thoracic aortic dissection (TAD), once ruptured, is devastating to patients, and no effective pharmaceutical therapy is available. Anaphylatoxins released by complement activation are involved in a variety of diseases. However, the role of the complement system in TAD is unknown. We found that plasma levels of C3a, C4a, and C5a were significantly increased in patients with TAD. Elevated circulating C3a levels were also detected in the developmental process of mouse TAD, which was induced by β-aminopropionitrile monofumarate (BAPN) treatment, with enhanced expression of C1q and properdin in mouse dissected aortas. These findings indicated activation of classical and alternative complement pathways. Further, expression of C3aR was obviously increased in smooth muscle cells of human and mouse dissected aortas, and knockout of C3aR notably inhibited BAPN-induced formation and rupture of TAD in mice. C3aR antagonist administered pre- and post-BAPN treatment attenuated the development of TAD. We found that C3aR knockout decreased matrix metalloproteinase 2 (MMP2) expression in BAPN-treated mice. Additionally, recombinant C3a stimulation enhanced MMP2 expression and activation in smooth muscle cells that were subjected to mechanical stretch. Finally, we generated MMP2-knockdown mice by in vivo MMP2 short hairpin RNA delivery using recombinant adeno-associated virus and found that MMP2 deficiency significantly reduced the formation of TAD. Therefore, our study suggests that the C3a–C3aR axis contributes to the development of TAD via regulation of MMP2 expression. Targeting the C3a–C3aR axis may represent a strategy for inhibiting the formation of TAD.
Finding Alternatives and Reduced Formulations for Process-Based Models

This paper addresses the problem of model complexity commonly arising in constructing and using process-based models with intricate interactions. Apart from complex process details the dynamic behavior of such systems is often limited to a discrete number of typical states. Thus, models reproducing the system's processes in all details are often too complex and over-parameterized. In order to reduce simulation times and to get a better impression of the important mechanisms, simplified formulations are desirable. In this work a data adaptive model reduction scheme that automatically builds simple models from complex ones is proposed. The method can be applied to the transformation and reduction of systems of ordinary differential equations. It consists of a multistep approach using a low dimensional projection of the model data followed by a Genetic Programming/Genetic Algorithm hybrid to evolve new model systems. As the resulting models again consist of differential equations, their process-based interpretation in terms of new state variables becomes possible. Transformations of two simple models with oscillatory dynamics, simulating a mathematical pendulum and predator-prey interactions respectively, serve as introductory examples of the method's application. The resulting equations of force indicate the predator-prey system's equivalence to a nonlinear oscillator. In contrast to the simple pendulum it contains driving and damping forces that produce a stable limit cycle.
Mycophenolate Mofetil Therapy in Children With Idiopathic Nephrotic Syndrome: Does Therapeutic Drug Monitoring Make a Difference?

Background: Idiopathic nephrotic syndrome (INS) necessitates administration of corticosteroids or corticoid-sparing agents in 60% of the cases for prolonged periods resulting in serious adverse effects. Methods: To avoid these complications, we investigated the efficacy and safety of mycophenolate mofetil (MMF) in our retrospective single-center study with 15 patients presenting with complicated courses of INS and aspired to estimate a cutoff level for mycophenolic acid–area under the curve (MPA-AUC) values, which can predict relapses with high sensitivity. Results: Seven of 15 patients stayed in remission while receiving MMF. Average frequency of relapses was 1.39 (0.28–2.5) per year. In case of relapses, patients had lower predose and estimated AUC0–12 levels of MPA (P = 0.02 and 0.001, respectively). Based on the results of receiver operating characteristic analysis, we consider an estimated MPA-AUC0–12 lower than 44.6 mg·h·L−1 as a risk factor for future relapses (91% sensitivity, 57% specificity, P = 0.06) because the prevalence of relapse is significantly lower (0.07 versus 0.5, P = 0.02), if the estimated MPA-AUC0–12 is >44.6 mg·h·L−1. During MMF administration, we did not detect any adverse event requiring discontinuation of treatment. Conclusions: In conclusion, we demonstrate MMF as an alternative treatment for children with complicated INS to maintain remission without serious side effects. Furthermore, we propose a higher therapeutic target range of MPA-AUC0–12 (>45 mg·h·L−1) than used in transplanted children underlining the crucial role of therapeutic drug monitoring.
Prediction of Hot Spots at Myeloid Cell Leukemia-1–Inhibitor Interface Using Energy Estimation and Alanine Scanning Mutagenesis

Myeloid cell leukemia 1 (Mcl1) is an antiapoptotic protein that plays central role in apoptosis regulation. Also, Mcl1 has the potency to resist apoptotic cues resulting in up-regulation and cancer cell protection. A molecular probe that has the potential to specifically target Mcl1 and thereby provoke its down-regulatory activity is very essential. The aim of the current study is to probe the internal conformational dynamics of protein motions and potential binding mechanism in response to a series of picomolar range Mcl1 inhibitors using explicit-solvent molecular dynamics (MD) simulations. Subsequently, domain cross-correlation and principal component analysis was performed on the snapshots obtained from the MD simulations. Our results showed significant differences in the internal conformational dynamics of Mcl1 with respect to binding affinity values of inhibitors. Further, the binding free energy estimation, using three different samples, was performed on the MD simulations and revealed that the predicted energies (ΔGmmgbsa) were in good correlation with the experimental values (ΔGexpt). Also, the energies obtained using all sampling models were efficiently ranked. Subsequently, the decomposition energy analysis highlighted the major energy-contributing residues at the Mcl1 binding pocket. Computational alanine scanning performed on high energy-contributing residues predicted the hot spot residues. The dihedral angle analysis using MD snapshots on the predicted hot spot residue exhibited consistency in side chain conformational motion that ultimately led to strong binding affinity values. The findings from the present study might provide valuable guidelines for the design of novel Mcl1 inhibitors that might significantly improve the specificity for new-generation chemotherapeutic agents.
Peripheral arterial disease: an underestimated aetiology of exercise intolerance in chronic obstructive pulmonary disease patients

Objective To assess the prevalence of peripheral arterial disease and its implications for exercise limitation in chronic obstructive pulmonary disease (COPD) patients. Method One hundred and fifty-one moderate-to-severe COPD patients (forced expiratory volume in 1s: 37 ± 6 SD% predicted) and 73 healthy age-matched control individuals (divided into 31 smokers and 42 nonsmokers) participated in this study. All COPD patients were either exsmokers or current smokers and their tobacco-smoking history was similar to that of healthy smokers. To evaluate the existence of arterial disease, lower limb perfusion pressure impairment was assessed using the ankle brachial index, whereas arterial stiffness was assessed by the pulse wave velocity (PWV). The definition of peripheral arterial disease required an ankle brachial index value of 0.90 or less, whereas the PWV increment was considered to be a direct witness of arterial stiffness increase. A 6-min walk test was performed to assess physical exercise capacity. Results Prevalence of peripheral arterial disease was higher in COPD patients than in healthy participants (81 ±3 SD; 49 ± 5 SD and 9 ± 2 SD%, respectively, in COPD, healthy smokers and nonsmokers). PWV mean values were significantly higher in COPD patients compared with healthy smokers and nonsmokers (10.3 ±2.1 SD m/s; 9.2 ±1.3 SD m/s and 8.7 ± 2.2 SD m/s, respectively). The distance covered during the 6-min-walk test was associated positively with the degree of peripheral arterial disease (r = 0.78; P = 0.05) and negatively with the PWV values (r = –0.74; P = 0.05). Not only tobacco-smoking history but also COPD severity was shown to influence these associations. Conclusion The effect of peripheral arterial disease on exercise intolerance in COPD seems to be considerable. Therefore, COPD patients participating in a pulmonary rehabilitation programme should profit from a systematic search for arterial disease. Arterial dysfunction has to be taken into account in the multidisciplinary treatment of these patients.
Calibration adjustments to address bias in mortality analyses due to informative sampling—a census-linked survey analysis in Switzerland

Background Sampling bias, like survey participants’ nonresponse, needs to be adequately addressed in the analysis of sampling designs. Often survey weights will be calibrated on specific covariates related to the probability of selection and nonresponse to get representative population estimates. However, such calibrated survey (CS) weights are usually constructed for cross-sectional results, but not for longitudinal analyses. For example, when the outcome of interest is time to death, and sampling selection is related to time to death and censoring, sampling is informative. Then, unweighted or CS weighted inferential statistical analyses may be biased. In 2010, Switzerland changed from a decennial full enumeration census to a yearly registry-based (i.e., data from harmonised community registries) and a survey-based census system. In the present study, we investigated the potential bias due to informative sampling when time to death is the outcome of interest, using data from the new Swiss census system. Methods We analysed more than 6.5 million individuals aged 15 years or older from registry-based census data from years 2010 to 2013, linked with mortality records up to end of 2014. Out of this population, a target sample of 3.5% was sampled from the Swiss Federal Statistical Office (SFSO) in a stratified yearly micro census. The SFSO calculated CS weights to enable representative population estimates from the micro census. We additionally constructed inverse probability (IP) weights, where we used survival information in addition to known sampling covariates. We compared CS and IP weighted mortality rates (MR) and life expectancy (LE) with estimates from the underlying population. Additionally, we performed a simulation study under different sampling and nonresponse scenarios. Results We found that individuals who died in 2011, had a 0.67 (95% CI [0.64–0.70]) times lower odds of participating in the 2010 micro census, using a multivariable logistic regression model with covariates age, gender, nationality, civil status, region and survival information. IP weighted MR were comparable to estimates from the total population, whereas CS weighted MR underestimated the population MR in general. The IP weighted LE estimates at age 30 years for men were 50.9 years (95% CI [50.2–51.6] years), whereas the CS weighted overestimated LE by 2.5 years. Our results from the simulation study confirmed that IP weighted models are comparable to population estimates. Conclusion Mortality analyses based on the new Swiss survey-based census system may be biased, because of informative sampling. We conclude that mortality analyses based on census-linked survey data have to be carefully conducted, and if possible, validated by registry information to allow for unbiased interpretation and generalisation.
Establishing an Ultrasound Curriculum in Undergraduate Medical Education: How Much Time Does It Take?

Over the years, the use of ultrasound in the medical profession has become a common occurrence. As a result, many medical schools are considering an ultrasound curriculum for first‐ and second‐year medical students. The question posed by many of these programs is how much time and effort are required to establish such a curriculum. We at the University of Colorado School of Medicine sought to quantify the resources and time required.
A study of the planarity of the pyrrolone fragment in 2-isopropyl-2,3-dihydro-1H-isoindol-1-one.

Orthophthalaldehyde (o-phthalaldehyde, OPA) is an aromatic dialdehyde bearing two electron-withdrawing carbonyl groups. The reactions of OPA with primary amines are broadly applied for the synthesis of important heterocyclic compounds with biological relevance. A number of such reactions have been investigated recently and several structures of condensation products have been reported, however, the complex reaction mechanism is still not fully understood and comprises concurrent as well as consecutive reactions. The reaction products depend on the primary amine which reacts with OPA, the reaction environment (solvent) and the proportion of the reactants. The title molecule, C11H13NO, the product of the reaction of OPA with isopropylamine, contains a five-membered pyrrole C4N ring with a carbonyl substituent, which forms part of the isoindolinone unit. Though this pyrrole ring contains one C atom in the sp(3)-hybridized state, it is fairly planar. The title molecule has been compared with similar structures retrieved from the Cambridge Structural Database in order to study this phenomenon. The planarity of this fragment has been explained by the presence of partially delocalized C-C, C-N and C-O bonds, and by an inner angle in the planar pentagonal ring (∼108°), which is close to the ideal tetrahedral value for the sp(3)-hybridized state of the constituent C atom. Due to this propitious angle, this C atom can be present in states intermediate between sp(3)- and sp(2)-hybridized in different structures, while still maintaining the planarity of the ring. There are only weak intermolecular C-H.O hydrogen bonds and C-H. π-electron ring interactions in the structure. In particular, it is the pyrrole ring which is involved in these interactions.
Unmanned Aerial Vehicular System for Greenhouse Gas Measurement and Automatic Landing

This paper presents a reliable and low cost greenhouse gas measurement system. The system mainly consists of an unmanned aerial vehicle (UAV), a set of calibrated sensors, a wireless system, and a microcontroller. The system can measure the concentration of greenhouse gases namely carbon dioxide (CO 2 ), methane (CH 4 ), and ozone (O 3 ) at different altitudes. It can also measure temperature, humidity, and atmospheric pressure. The system is able to send data to a remote monitoring station. The UAV is equipped with image processing based navigation and landing system so that it can land autonomously on a designated place. To ensure safe landing the system uses a specially designed parachute. This paper also presents some data generated by the system.
Solid-State NMR H-N-(C)-H and H-N-C-C 3D/4D Correlation Experiments for Resonance Assignment of Large Proteins.

Solid-state NMR spectroscopy can provide insight into protein structure and dynamics at the atomic level without inherent protein size limitations. However, a major hurdle to studying large proteins by solid-state NMR spectroscopy is related to spectral complexity and resonance overlap, which increase with molecular weight and severely hamper the assignment process. Here the use of two sets of experiments is shown to expand the tool kit of 1 H-detected assignment approaches, which correlate a given amide pair either to the two adjacent CO-CA pairs (4D hCOCANH/hCOCAcoNH), or to the amide 1 H of the neighboring residue (3D HcocaNH/HcacoNH, which can be extended to 5D). The experiments are based on efficient coherence transfers between backbone atoms using INEPT transfers between carbons and cross-polarization for heteronuclear transfers. The utility of these experiments is exemplified with application to assemblies of deuterated, fully amide-protonated proteins from approximately 20 to 60 kDa monomer, at magic-angle spinning (MAS) frequencies from approximately 40 to 55 kHz. These experiments will also be applicable to protonated proteins at higher MAS frequencies. The resonance assignment of a domain within the 50.4 kDa bacteriophage T5 tube protein pb6 is reported, and this is compared to NMR assignments of the isolated domain in solution. This comparison reveals contacts of this domain to the core of the polymeric tail tube assembly.