Miracle-dz/UniFAR-FTUs huggingface dataset:
Cytochrome P450 Architecture and Cysteine Nucleophile Placement Impact Raloxifene-Mediated Mechanism-Based Inactivation

The propensity for cytochrome P450 (P450) enzymes to bioactivate xenobiotics is governed by the inherent chemistry of the xenobiotic itself and the active site architecture of the P450 enzyme(s). Accessible nucleophiles in the active site or egress channels of the P450 enzyme have the potential of sequestering reactive metabolites through covalent modification, thereby limiting their exposure to other proteins. Raloxifene, a drug known to undergo CYP3A-mediated reactive metabolite formation and time-dependent inhibition in vitro, was used to explore the potential for bioactivation and enzyme inactivation of additional P450 enzymes (CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A5). Every P450 tested except CYP2E1 was capable of raloxifene bioactivation, based on glutathione adduct formation. However, raloxifene-mediated time-dependent inhibition only occurred in CYP2C8 and CYP3A4. Comparable inactivation kinetics were achieved with KI and kinact values of 0.26 μM and 0.10 min−1 and 0.81 μM and 0.20 min−1 for CYP2C8 and CYP3A4, respectively. Proteolytic digests of CYP2C8 and CYP3A4 Supersomes revealed adducts to Cys225 and Cys239 for CYP2C8 and CYP3A4, respectively. For each P450 enzyme, proposed substrate/metabolite access channels were mapped and active site cysteines were identified, which revealed that only CYP2C8 and CYP3A4 possess accessible cysteine residues near the active site cavities, a result consistent with the observed kinetics. The combined data suggest that the extent of bioactivation across P450 enzymes does not correlate with P450 inactivation. In addition, multiple factors contribute to the ability of reactive metabolites to form apo-adducts with P450 enzymes.
Slow Co-Evolution of the MAGO and Y14 Protein Families Is Required for the Maintenance of Their Obligate Heterodimerization Mode

The exon junction complex (EJC) plays important roles in RNA metabolisms and the development of eukaryotic organisms. MAGO (short form of MAGO NASHI) and Y14 (also Tsunagi or RBM8) are the EJC core components. Their biological roles have been well investigated in various species, but the evolutionary patterns of the two gene families and their protein-protein interactions are poorly known. Genome-wide survey suggested that the MAGO and Y14 two gene families originated in eukaryotic organisms with the maintenance of a low copy. We found that the two protein families evolved slowly; however, the MAGO family under stringent purifying selection evolved more slowly than the Y14 family that was under relative relaxed purifying selection. MAGO and Y14 were obliged to form heterodimer in a eukaryotic organism, and this obligate mode was plesiomorphic. Lack of binding of MAGO to Y14 as functional barrier was observed only among distantly species, suggesting that a slow co-evolution of the two protein families. Inter-protein co-evolutionary signal was further quantified in analyses of the Tol-MirroTree and co-evolution analysis using protein sequences. About 20% of the 41 significantly correlated mutation groups (involving 97 residues) predicted between the two families was clade-specific. Moreover, around half of the predicted co-evolved groups and nearly all clade-specific residues fell into the minimal interaction domains of the two protein families. The mutagenesis effects of the clade-specific residues strengthened that the co-evolution is required for obligate MAGO-Y14 heterodimerization mode. In turn, the obliged heterodimerization in an organism serves as a strong functional constraint for the co-evolution of the MAGO and Y14 families. Such a co-evolution allows maintaining the interaction between the proteins through large evolutionary time scales. Our work shed a light on functional evolution of the EJC genes in eukaryotes, and facilitates to understand the co-evolutionary processes among protein families.
Learning Convolutional Feature Hierarchies for Visual Recognition

We propose an unsupervised method for learning multi-stage hierarchies of sparse convolutional features. While sparse coding has become an increasingly popular method for learning visual features, it is most often trained at the patch level. Applying the resulting filters convolutionally results in highly redundant codes because overlapping patches are encoded in isolation. By training convolutionally over large image windows, our method reduces the redudancy between feature vectors at neighboring locations and improves the efficiency of the overall representation. In addition to a linear decoder that reconstructs the image from sparse features, our method trains an efficient feed-forward encoder that predicts quasi-sparse features from the input. While patch-based training rarely produces anything but oriented edge detectors, we show that convolutional training produces highly diverse filters, including center-surround filters, corner detectors, cross detectors, and oriented grating detectors. We show that using these filters in multistage convolutional network architecture improves performance on a number of visual recognition and detection tasks.
Performance improvement of TCP on a wireless ad hoc network

We describe a new technique for improving TCP performance in an ad hoc network that uses a table-driven type of routing protocol paying attention to short-duration link failure. We took as the object of research a flexible radio network (FRN), which is an ad hoc network for data collection. We also evaluated the case in which the effect of the collision of a data packet and an ACK packet is suppressed by delayed ACK and resending the ACK packet preferentially. We showed through simulation the combination of these improvements could increase TCP throughput about 20%.
Matrix Metallopeptidase 14 Plays an Important Role in Regulating Tumorigenic Gene Expression and Invasion Ability of HeLa Cells

Objectives The objectives of this study were to investigate the functional effect of matrix metallopeptidase 14 (MMP14) on cell invasion in cervical cancer cells (HeLa line) and to study the underlying molecular mechanisms. Methods Expression vector of short hairpin RNA targeting MMP14 was treated in HeLa cells, and then, transfection efficiency was verified by a florescence microscope. Transwell assay was used to investigate cell invasion ability in HeLa cells. Quantitative polymerase chain reaction and Western blotting analysis were used to detect the expression of MMP14 and relative factors in messenger RNA and protein levels, respectively. Results Matrix metallopeptidase 14 short hairpin RNA expression vector transfection obviously decreased MMP14 expression in messenger RNA and protein levels. Down-regulation of MMP14 suppressed invasion ability of HeLa cells and reduced transforming growth factor &bgr;1 and vascular endothelial growth factor B expressions. Furthermore, MMP14 knockdown decreased bone sialoprotein and enhanced forkhead box protein L2 expression in both RNA and protein levels. Conclusion Matrix metallopeptidase 14 plays an important role in regulating invasion of HeLa cells. Matrix metallopeptidase 14 knockdown contributes to attenuating the malignant phenotype of cervical cancer cell.
Genetic Mapping of Quantitative Trait Loci Underlying Flowering Time in Chrysanthemum (Chrysanthemum morifolium)

Flowering time is an important trait in chrysanthemum, but its genetic basis remains poorly understood. An intra-specific mapping population bred from the cross between the autumn-flowering cultivar ‘Yuhualuoying’ and the summer-flowering ‘Aoyunhanxiao’ was used to determine the number and relative effect of QTL segregating for five measures of flowering time. From flowering time data recorded over two consecutive seasons, 35 additive QTL were detected, each explaining between 5.8% and 22.7% of the overall phenotypic variance. Of these, 13 were detected in both years. Nine genomic regions harboring QTL for at least two of the five traits were identified. Ten pairs of loci epistatically determined the flowering time, but their contribution to the overall phenotypic variance was less than for the additive QTL. The results suggest that flowering time in chrysanthemum is principally governed by main effect QTL but that epistasis also contributes to the genetic architecture of the trait, and the major QTL identified herein are useful in our ongoing efforts to streamline the improvement of chrysanthemum via the use of molecular methodology.
Power Control for Cellular Communications with Time‐Varying Channel Uncertainties

Power control in a code‐division multiple access (CDMA) based cellular network is a challenging problem because the communication channels change rapidly because of multipath fading. These rapid fluctuations cause detrimental effects on the control efforts required to regulate the signal‐to‐interference plus noise ratios (SINRs) to the desired level. Thus, there is a need for power‐control algorithms that can adapt to rapid changes in the channel gain caused by multipath fading. Much of the previous work has either neglected the effects of fast fading, assumed that the fading is known, or assumed that all the link gains are known. In this paper, we model the effects of fast fading and develop practical strategies for robust power control based on SINR measurements in the presence of the fading. We develop a controller for the reverse link of a CDMA cellular system, and use a Lyapunov‐based analysis to prove that the SINR error is globally uniformly ultimately bounded. We also utilize a linear prediction filter that utilizes local SINR measurements and estimates of the Doppler frequency that can be derived from local SINR measurements to improve the estimate of the channel fading used in the controller. The power‐control algorithm is simulated for a cellular network with multiple cells, and the results indicate that the controller regulates the SINRs of all the mobile terminals (MTs) with low outage probability. In addition, a pulse‐code‐modulation technique is applied to allow the control command to be quantized for feedback to the transmitter. Simulation results indicate that the outage probabilities of all the MTs are still within the acceptable range if at least 3‐bit quantization is employed. Comparisons to a standard algorithm illustrate the improved performance of the predictive controller.
Comparison of Citrus tristeza virus (CTV) isolates by RFLP analysis of the coat protein nucleotide sequences and by the severity of the symptoms

Plants of Pera sweet orange on Rangpur lime rootstocks, from orchards of the northwest and north of Parana state, Brazil, were evaluated for severity of symptoms and genetic diversity of Citrus tristeza virus. The severity of symptoms was evaluated by the development of tree, fruit size and stem pitting symptoms. Isolates that infect these plants were compared with known mild and severe isolates by analysis of restriction fragments length polymorphism (RFLP) of the coat protein nucleotide sequences (CPNS), amplified by the polymerase chain reaction (PCR) and undergone digestion with the restriction enzymes Hinf I and Rsa I. The severity of symptoms showed that the analyzed plants from the northwest orchards presented mild to moderate tristeza symptoms, while the plants from the north orchards exhibited moderate to severe symptoms. The RFLP analysis revealed that the CTV isolates are constituted by haplotype mixtures. Rsa I was the enzyme that best discriminated the genetic diversity among the analyzed isolates of CTV. Two main groups were generated by the UPGMA analysis. The isolates from the northwest orchards grouped with most of the mild isolates used as control, and a great part of the isolates from the north orchards, was correlated with the severe isolate Capao Bonito. Correlation between the stem pitting intensity and RFLP patterns, was demonstrated with some exceptions. The failure of protection of some isolates and the contamination of the rootstocks by the severe isolates, in field nursery conditions, before grafting with scions with mild isolates, were the hypotheses considered to explain the occurrence of severe CTV isolates in the North area of Parana State.
A Plant Location Guide for the Unsure: Approximation Algorithms for Min-Max Location Problems

This paper studies an extension of the k-median problem under uncertain demand. We are given an n-vertex metric space (V, d) and m client sets \documentclass{aastex} \usepackage{amsbsy} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{bm} \usepackage{mathrsfs} \usepackage{pifont} \usepackage{stmaryrd} \usepackage{textcomp} \usepackage{portland,xspace} \usepackage{amsmath,amsxtra} \pagestyle{empty} \DeclareMathSizes{10}{9}{7}{6} \begin{document} $\{S_i \subseteq V\}_{i = 1}^m$ \end{document}. The goal is to open a set of k facilities F such that the worst-case connection cost over all the client sets is minimized, i.e., \documentclass{aastex} \usepackage{amsbsy} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{bm} \usepackage{mathrsfs} \usepackage{pifont} \usepackage{stmaryrd} \usepackage{textcomp} \usepackage{portland,xspace} \usepackage{amsmath,amsxtra} \pagestyle{empty} \DeclareMathSizes{10}{9}{7}{6} \begin{document} $$\min_{F \subseteq V, \,|F| = k}\max_{i \in [m]}\left \{\sum_{j \in S_i} d.
A A correct LR parser for C 11

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Synchronized gesture and speech production for humanoid robots

We present a model that is capable of synchronizing expressive gestures with speech. The model, implemented on a Honda humanoid robot, can generate a full range of gesture types, such as emblems, iconic and metaphoric gestures, deictic pointing and beat gestures. Arbitrary input text is analyzed with a part-of-speech tagger and a text-to-speech engine for timing information of spoken words. In addition, style tags can be optionally added to specify the level of excitement or topic changes. The text, combined with any tags, is then processed by several grammars, one for each gesture type to produce several candidate gestures for each word of the text. The model then selects probabilistically amongst the gesture types based on the desired degree of expressivity. Once a gesture type is selected, it coincides with a particular gesture template, consisting of trajectory curves that define the gesture. Speech timing patterns and style parameters are used to modulate the shape of the curve before it sent to the whole body control system on the robot. Evaluation of the model's parameters were performed, demonstrating the ability of observers to differentiate varying levels of expressiveness, excitement and speech synchronization. Modification of gesture speed for trajectory tracking found that positive associations like happiness and excitement accompanied faster speeds, with negative associations like sadness or tiredness occurred at slower speeds.
SHEF: Semantic Tagging and Summarization Techniques Applied to Cross-document Coreference

We describe experiments for the cross-document coreference task in SemEval 2007. Our cross-document coreference system uses an in-house agglomerative clustering implementation to group documents referring to the same entity. Clustering uses vector representations created by summarization and semantic tagging analysis components. We present evaluation results for four system configurations demonstrating the potential of the applied techniques.
Iterative Equalizer for OFDM-CDMA Multiple Access Communication Systems

In this paper, the receivers with adaptive equalizer and turbo decoder are investigated for orthogonal frequency division multiplexing-code division multiple access (OFDM-CDMA) systems in multipath channels. The de-spreading equalizer which combines de-spreading and equalization is used to mitigate the MAI and ISI. The stochastic gradient based LMS algorithm is used as the adaptive algorithm for the equalizer. Three receiver architectures are investigated: The first one is the traditional receiver called de-spreading equalizer disjointed with turbo decoder. In this scheme, the equalizer and turbo decoder operate independently and the equalizer relies on slicer output to adapt its filter coefficients. However, the extrinsic information from turbo decoder can provide more reliable information of the transmitted data. Hence the second receiver architecture is called as de-spreading equalizer jointed with turbo decoder, where turbo decoder gives the extrinsic information as feedback to the adaptive equalizer as the desired information. Finally, the equalizer jointed with turbo decoder is extended to differential coded signaling in OFDM-CDMA system and its performance is presented and discussed.
Checkpoint Kinase 1 Prevents Cell Cycle Exit Linked to Terminal Cell Differentiation

ABSTRACT Trophoblast stem (TS) cells proliferate in the presence of fibroblast growth factor 4, but in its absence, they differentiate into polyploid trophoblast giant (TG) cells that remain viable but nonproliferative. Differentiation is coincident with expression of the cyclin-dependent kinase (CDK)-specific inhibitors p21 and p57, of which p57 is essential for switching from mitotic cell cycles to endocycles. Here, we show that, in the absence of induced DNA damage, checkpoint kinase-1 (CHK1), an enzyme essential for preventing mitosis in response to DNA damage, functions as a mitogen-dependent protein kinase that prevents premature differentiation of TS cells into TG cells by suppressing expression of p21 and p57, but not p27, the CDK inhibitor that regulates mitotic cell cycles. CHK1 phosphorylates p21 and p57 proteins at specific sites, thereby targeting them for degradation by the 26S proteasome. TG cells lack CHK1, and restoring CHK1 activity in TG cells suppresses expression of p57 and restores mitosis. Thus, CHK1 is part of a “G2 restriction point” that prevents premature cell cycle exit in cells programmed for terminal differentiation, a role that CHK2 cannot play.
Predicting short interval tracking polls with online social media

The of behavioral patterns in online social media are often reflecting the happenings in our society. These patterns, which can be considered as opinions, are often correlated with public opinion polling. However, many correlation analyses done previously were for subsequent discoveries and not being able to handle short interval polling opinions. For opinions obtained from tracking polling with short opinion collection interval, like rolling polling, it cannot perform well in tracing the latest trends. This paper describes an extended correlation model for such kind of polling in examining the correlation between opinion in online social media and the public opinion from tracking poll. It has been tested with a recent rolling polling and it outperformed the previous correlation models.
A systematic review of the evidence on symptom management of cancer-related anorexia and cachexia.

PURPOSE/OBJECTIVES To evaluate and synthesize the evidence regarding cancer-related anorexia and cachexia symptom management and make recommendations for future directions. DATA SOURCES Cochrane Library, MEDLINE, CANCERLIT, CINAHL, Dissertation Abstracts, EBM Reviews--Best Evidence, EMBASE, and the Computer Retrieval of Information on Scientific Projects. Current overviews, clinical trials, systematic research reviews, and meta-analyses. DATA SYNTHESIS All studies focused on increasing food intake. Nonpharmacologic clinical trials increased caloric and protein intake but resulted in no improvement in nutritional status, weight, tumor response, survival, or quality of life. Weight, appetite, and well-being were improved with megestrol acetate, but nutritional status was not improved. Some exercise studies demonstrated improvements in nutrition-related outcomes, but these were not primary research outcomes. CONCLUSIONS Symptom management of anorexia and cachexia should focus on decreasing energy expenditure or minimizing factors creating a negative energy balance, as well as improving food intake. Increased measurement sensitivity also is needed. IMPLICATIONS FOR NURSING Improved nutritional assessment skills are needed with an emphasis on anticipated problems and current status.
Pharmacokinetics of 3H-phenylephrine in man.

7-3H-phenylephrine was given to 15 volunteers by a short-infusion n = 4) or p.o. (10 volunteers, 1 patient with porto-caval anastomosis). Analysis of serum for free 3H-phenylephrine and fractionation of urinary radioactivity was performed by ion-exchange and thin-layer chromatography. As almost the same 3H-activity was excreted in urine after i.v. and p.o. administration, 86% and 80% of the dose respectively, complete enteral absorption can be assumed. A considerable difference was seen in the fraction of free phenylephrine, i.v. 16% of the dose versus p.o. 2.6%, which suggested reduced bioavailability. This was confirmed by comparison of the areas under the serum curve, which showed a bioavailability factor of 0.38. The result for the patient with porto-caval anastomosis was comparable to that in the normal volunteers. The biological half-life of 2 to 3h was comparable to that of structurally related amines, as were the total clearance of 2 l/h, and the volume of distribution of 340 l. Metabolism to phenolic conjugates mainly after oral ingestion, and to m-hydroxymandelic acid after i.v. injection, again demonstrated that m-hydroxylated amines are predominantly conjugated during the "first-pass" metabolism.
An Experimental Study of Surface Tension-Dependent Pool Boiling Characteristics of Carbon Nanotubes-Nanofluids

This paper reports an experimental investigation of the pool boiling heat transfer characteristics of single-walled carbon nanotubes (SWCNTs)-nanofluids. Two main characteristics were studied to identify their influence on boiling heat transfer: one is the surface tension through the addition of surfactant and the other is the chemical treatment of nanotubes sidewalls (i.e. oxidized and untreated sidewalls). A Transmission Electron Microscope was used to study the morphology of the functionalized nanotubes and their deposition on heater wire. The maximum enhancement of both the critical and burnout heat fluxes of this nanofluid over those of the pure deionized water are found to be 492% and 265%, respectively at a surfactant to carbon nanotubes concentration ratio of 1:5. This indicates that high enhancement of heat flux is possible and would depend on the concentration of the surfactants. Present results also demonstrate that CNT-nanofluids in a pool boiling environment can extend the saturated boiling regime and the burnout of the heated surface. The burnout heat flux is found to be a strong function of the relaxation of nanofluid surface tension with the base fluid. Based on the best fit of experimental data, an empirical correlation between the burnout heat flux of nanofluid and its relaxation of surface tension is introduced. © 2009 ASME