Miracle-dz/UniFAR-FTUs huggingface dataset:
Down-regulation of survivin expression by small interfering RNA induces pancreatic cancer cell apoptosis and enhances its radiosensitivity.

AIM To investigate the inhibitory effect of small interfering RNA (siRNA) on the expression of survivin in pancreatic cancer cell line PC-2 and the role of siRNA in inducing PC-2 cell apoptosis and enhancing its radiosensitivity. METHODS A siRNA plasmid expression vector against survivin was constructed and transfected into PC-2 cells with Lipofectamine 2000. The down regulation of survivin expression was detected by semi-quantitative RT-PCR and immunohistochemical SP method and the role of siRNA in inducing PC-2 cell apoptosis and enhancing its radiosensitivity was detected by flow cytometry. RESULTS The sequence-specific siRNA efficiently and specifically down-regulated the expression of survivin at both mRNA and protein levels. The expression inhibition ratio was 81.25% at mRNA level detected by semi-quantitative RT-PCR and 74.24% at protein level detected by immunohistochemical method. Forty-eight hours after transfection,apoptosis was induced in 7.03% cells by siRNA and in 14.58% cells by siRNA combined with radiation. CONCLUSION The siRNA plasmid expression vector against survivin can inhibit the expression of survivin in PC-2 cells efficiently and specifically. Inhibiting the expression of survivin can induce apoptosis of PC-2 cells and enhance its radiosensitivity significantly. RNAi against survivin is of potential value in gene therapy of pancreatic cancer.
Thiol-based redox signaling in the nitrogen-fixing symbiosis

In nitrogen poor soils legumes establish a symbiotic interaction with rhizobia that results in the formation of root nodules. These are unique plant organs where bacteria differentiate into bacteroids, which express the nitrogenase enzyme complex that reduces atmospheric N 2 to ammonia. Nodule metabolism requires a tight control of the concentrations of reactive oxygen and nitrogen species (RONS) so that they can perform useful signaling roles while avoiding nitro-oxidative damage. In nodules a thiol-dependent regulatory network that senses, transmits and responds to redox changes is starting to be elucidated. A combination of enzymatic, immunological, pharmacological and molecular analyses has allowed us to conclude that glutathione and its legume-specific homolog, homoglutathione, are abundant in meristematic and infected cells, that their spatio-temporally distribution is correlated with the corresponding (homo)glutathione synthetase activities, and that they are crucial for nodule development and function. Glutathione is at high concentrations in the bacteroids and at moderate amounts in the mitochondria, cytosol and nuclei. Less information is available on other components of the network. The expression of multiple isoforms of glutathione peroxidases, peroxiredoxins, thioredoxins, glutaredoxins and NADPH-thioredoxin reductases has been detected in nodule cells using antibodies and proteomics. Peroxiredoxins and thioredoxins are essential to regulate and in some cases to detoxify RONS in nodules. Further research is necessary to clarify the regulation of the expression and activity of thiol redox-active proteins in response to abiotic, biotic and developmental cues, their interactions with downstream targets by disulfide-exchange reactions, and their participation in signaling cascades. The availability of mutants and transgenic lines will be crucial to facilitate systematic investigations into the function of the various proteins in the legume-rhizobial symbiosis.
3-D time-accurate CFD simulations of wind turbine rotor flow fields

This paper presents the results of three-dimensional and time-accurate Computational Fluid Dynamics (CFD) simulations of the flow field around the National Renewable Energy Laboratory (NREL) Phase VI horizontal axis wind turbine rotor. The 3-D, unsteady, parallel, finite volume flow solver, PUMA2, is used for the simulations. The solutions are obtained using unstructured moving grids rotating with the turbine blades. Three different flow cases with different wind speeds and wind yaw angles are investigated: 7 m/s with 0◦ yaw (pre-stall case I), 7 m/s with 30◦ yaw (prestall, yawed case II), and 15 m/s with 0◦ yaw (post-stall case III). Results from the inviscid simulations for these three cases and comparisons with the experimental data are presented. Some information on the current work in progress towards Large Eddy Simulations (LES), including details about the viscous grid and the implementation of wall-functions, are also discussed. The inviscid results show that the flow is attached for cases I and II, with the latter having an asymmetrical wake structure, whereas there is massive separation over the entire blade span in case III. There are considerable spanwise pressure variations in addition to the chordwise variations, in all three cases. Comparisons of sectional pressure coefficient distributions with experimental data show good agreement. These threedimensional and time-accurate CFD results can be used for the far-field noise predictions based on the Ffowcs Williams Hawkings method (FWH), which can provide a first-principles prediction of both the noise and the underlying turbulent flow that generates the noise, in the context of the wind turbine application.
Utilizing RADseq data for phylogenetic analysis of challenging taxonomic groups: A case study in Carex sect. Racemosae.

PREMISE OF THE STUDY Relationships among closely related and recently diverged taxa can be especially difficult to resolve. Here we use both Sanger sequencing and next-generation RADseq data sets to estimate phylogenetic relationships among species of Carex section Racemosae (Cyperaceae), a clade largely restricted to high latitudes and elevations. Interest in relationships among these taxa derives from questions about the species' biogeographic histories and possible links between diversification and Pleistocene glaciations. METHODS A combination of approaches and molecular markers were used to estimate relationships among Carex species within sect. Racemosae and taxa from closely related sections. Nuclear and chloroplast loci generated by Sanger sequencing were analyzed with *BEAST, and SNP data from RADseq loci were analyzed as a concatenated data set using maximum likelihood and as independent loci using SVDquartets. KEY RESULTS Sanger sequencing data sets resolved relationships among taxa at intermediate phylogenetic depths (albeit with low levels of support). Only the RADseq data resolved relationships with strong support at all phylogenetic depths. Moreover, different methods and data partitions of the RADseq data resulted in nearly identical topologies. Carex sect. Racemosae is a strongly supported clade, although a handful of species were found to group with closely related sections. Herbarium specimens up to 35 yr old successfully produced informative RADseq data. CONCLUSIONS Despite the short read lengths of RADseq data, they nevertheless resolved relationships that Sanger sequencing data did not. Resolution of the phylogenetic relationships among recently and rapidly diversifying taxa within sect. Racemosae clades suggest a role for the Pleistocene glaciations in clade diversification.
Threshold Bipower Variation and the Impact of Jumps on Volatility Forecasting

This study reconsiders the role of jumps for volatility forecasting by showing that jumps have a positive and mostly significant impact on future volatility. This result becomes apparent once volatility is separated into its continuous and discontinuous components using estimators which are not only consistent, but also scarcely plagued by small sample bias. With the aim of achieving this, we introduce the concept of threshold bipower variation, which is based on the joint use of bipower variation and threshold estimation. We show that its generalization (threshold multipower variation) admits a feasible central limit theorem in the presence of jumps and provides less biased estimates, with respect to the standard multipower variation, of the continuous quadratic variation in finite samples. We further provide a new test for jump detection which has substantially more power than tests based on multipower variation. Empirical analysis (on the S&P500 index, individual stocks and US bond yields) shows that the proposed techniques improve significantly the accuracy of volatility forecasts especially in periods following the occurrence of a jump.
The school playground experience: opportunities and challenges for children and school staff

The school playground experience is an inevitable part of school life for primary school children. For most children, the experience is a positive and enjoyable one that contributes to their physical and social well-being and has been associated with enhanced attention and learning in the classroom. For some children, however, the playground can be a frightening and dangerous place in which aggressive behaviour and bullying can be experienced and/or witnessed. The recognition of this fact has, in some cases, led to the reduction or elimination of playground time. Many intervention programmes aimed at promoting positive in-school behaviour and preventing negative behaviours, including bullying, have been developed and used with positive results in schools. This paper provides a research-based commentary on some of the positive and negative features of playground life for children and some of the successful intervention programmes that have been developed and used. It is argued that facing the issues and problems presented by negative playground behaviour and dealing with them in a positive way, rather than avoiding them with policies that restrict the freedom of children to interact and engage with peers in the playground, is essential for the well-being of children and school staff. The paper calls for further research to inform school policy and action in this area.
Hybrid aligned zinc oxide nanowires array on CVD graphene for hydrogen sensing

A novel seedless floating growth scheme has been developed to grow vertically aligned ZnO nanowires array on single layer CVD graphene in solution at low temperatures (<;100 °C). The obtained hybrid ZnO-graphene nanostructures are ideal for chemical and gas sensing applications considering the advantages of high sensitivity due to large sensing surface area on the ZnO nanowire array and fast response and recovery due to high charge mobility of graphene. High-quality single-crystallinity of ZnO nanowires, a key parameter for high-performance sensors, has been confirmed using transmission electron microscopy. In addition, the well-formed interface between graphene and ZnO obtained is important to achieve high signal-to-noise ratio. Hydrogen sensors were fabricated using the hybrid ZnO-graphene nanostructure on interdigitated electrodes, and responses to hydrogen with different concentration were characterized. This floating growth process provides a low-cost and robust scheme for large-scale fabrication of semiconductor nanostructures on graphene for chemical and gas sensing applications.
The ecological validity of tests of executive function

Ninety-two mixed etiology neurological patients and 216 control participants were assessed on a range of neuropsychological tests, including 10 neuropsychological measures of executive function derived from 6 different tests. People who knew the patients well (relatives or carers) completed a questionnaire about the patient's dysexecutive problems in everyday life, and this paper reports the extent to which the tests predicted the patients' everyday life problems. All of the tests were significantly predictive of at least some of the behavioral and cognitive deficits reported by patients' carers. However, factor analysis of the patients' dysexecutive symptoms suggested a fractionation of the dysexecutive syndrome, with neuropsychological tests loading differentially on 3 underlying cognitive factors (Inhibition, Intentionality, and Executive Memory), supporting the conclusions that different tests measure different cognitive processes, and that there may be limits to the fractionation of the executive system. (JINS, 1998, 4, 547–558.)
A Multimodal Human–Robot Interface to Drive a Neuroprosthesis for Tremor Management

Tremor is the most prevalent movement disorder, and its incidence is increasing with aging. In spite of the numerous therapeutic solutions available, 65% of those suffering from upper limb tremor report serious difficulties during their daily living. This gives rise to research on different treatment alternatives, amongst which wearable robots that apply selective mechanical loads constitute an appealing approach. In this context, the current work presents a multimodal human-robot interface to drive a neuroprosthesis for tremor management. Our approach relies on the precise characterization of the tremor to modulate a functional electrical stimulation system that compensates for it. The neuroprosthesis is triggered by the detection of the intention to move derived from the analysis of electroencephalographic activity, which provides a natural interface with the user. When a prediction is delivered, surface electromyography serves to detect the actual onset of the tremor in the presence of volitional activity. This information in turn triggers the stimulation, which relies on tremor parameters-amplitude and frequency-derived from a pair of inertial sensors that record the kinematics of the affected joint. Surface electromyography also yields a first characterization of the tremor, together with precise information on the preferred stimulation site. Apart from allowing for an optimized performance of the system, our multimodal approach permits the implementation of redundant methods to both enhance the reliability of the system and adapt to the specific needs of different users. Results with a representative group of patients illustrate the performance of the interface presented here and demonstrate its feasibility.
Spatial query processing for high resolutions

Modern database applications including computer-aided design (CAD), medical imaging, or molecular biology impose new requirements on spatial query processing. Particular problems arise from the need of high resolutions for very large spatial objects, including cars, space stations, planes and industrial plants, and from the design goal to use general purpose database management systems in order to guarantee industrial-strength. In the past two decades, various stand-alone spatial index structures have been proposed but their integration into fully-fledged database systems is problematic. Most of these approaches are based on decomposition of spatial objects leading to replicating index structures. In contrast to common black-and-white decompositions which suffer from the lack of intermediate solutions, we introduce grey approximations as a new and general concept. We demonstrate the benefits of grey approximations in the context of encoding spatial objects by space filling curves resulting in grey interval sequences. Spatial intersection queries are then processed by a filter and refine architecture which, as an important design goal, can purely be expressed by means of the SQL: 1999 standard. Our new High Resolution Indexing (HRI) method can easily be integrated into general purpose DBMSs. The experimental evaluation on real-world test data from car and plane design projects points out that our new concept outperforms competitive techniques that are implementable on top of a standard object-relational DBMS by an order of magnitude with respect to secondary storage space and overall query response time.
Aptamers as a Sensitive Tool to Detect Subtle Modifications in Therapeutic Proteins

Therapeutic proteins are derived from complex expression/production systems, which can result in minor conformational changes due to preferential codon usage in different organisms, post-translational modifications, etc. Subtle conformational differences are often undetectable by bioanalytical methods but can sometimes profoundly impact the safety, efficacy and stability of products. Numerous bioanalytical methods exist to characterize the primary structure of proteins, post translational modifications; protein-substrate/protein/protein interactions and functional bioassays are available for most proteins that are developed as products. There are however few analytical techniques to detect changes in the tertiary structure of proteins suitable for use during drug development and quality control. For example, x-ray crystallography and NMR are impractical for routine use and do not capture the heterogeneity of the product. Conformation-sensitive antibodies can be used to map proteins. However the development of antibodies to represent sufficient epitopes can be challenging. Other limitations of antibodies include limited supply, high costs, heterogeneity and batch to batch variations in titer. Here we provide proof-of-principle that DNA aptamers to thrombin can be used as surrogate antibodies to characterize conformational changes. We show that aptamers can be used in assays using either an ELISA or a label-free platform to characterize different thrombin products. In addition we replicated a heat-treatment procedure that has previously been shown to not affect protein activity but can result in conformational changes that have serious adverse consequences. We demonstrate that a panel of aptamers (but not an antibody) can detect changes in the proteins even when specific activity is unaffected. Our results indicate a novel approach to monitor even small changes in the conformation of proteins which can be used in a routine drug-development and quality control setting. The technique can provide an early warning of structural changes during the manufacturing process that could have consequential outcomes downstream.
Peripubertal Administration of Icariin and Icaritin Advances Pubertal Development in Female Rats

Epimedii Herba is a traditional medicinal herb used in Korea and China and exerts estrogenic activity. In this study, we investigated the effect of peripubertal administration of Epimedii Herba on pubertal development in female rats using a modified protocol of the rodent 20-day pubertal female assay. Female Sprague-Dawley rats (21 days old after weaning, 10 rats per group) were divided into five groups: saline (Con), ethinyl estradiol (E2), Epimedii Herba ext (Ext), icariin (ICI), and icaritin (ICT), which were administered by oral gavage (E2 by subcutaneous injection) from postnatal day (PND) 21 through PND40. The time to vaginal opening (VO) was shorter for the Epimedii groups, particularly for the ICT group (p<0.05). Treatment with ICI and ICT significantly increased the duration of the estrus cycle (ICI, 2.78 days; ICT, 4.0 days; control, 1.78 days). Ovary weight was reduced by E2 treatment and increased by the Ext, ICI, and ICT treatments while the weight of the uterus and pituitary glands increased significantly only in the E2 and ICT groups. Although Epimedii Herba displayed relatively weak estrogenic activity, its repeated administration could affect pubertal development in female rats.
IL-21 Down-Regulates NKG2D/DAP10 Expression on Human NK and CD8+ T Cells1

IL-21 is a recently described cytokine, produced by activated Th cells, that shares significant homology with members of the IL-2 family of cytokines. IL-21 mediates its biological effects via the IL-21R in conjunction with the common receptor γ-chain that is also shared by members of the IL-2 family. We report that culture of human primary NK and CD8+ T cells with IL-21 in combination with IL-2 results in significant reduction of the cell surface expression of NKG2D, compared with that in cells treated with IL-2 alone. The reduced expression of NKG2D after IL-21 culture had functional consequences for NK cell function, as assessed by NKG2D-mediated redirected lysis assays and degranulation assays, compared with NK cells treated with IL-2 alone. IL-21-mediated NKG2D down-regulation in human NK cells correlated with a marked reduction of DNAX-activating protein of 10 kDa (DAP10) transcription in cells treated with IL-2 in combination with IL-21 compared with cells stimulated with only IL-2. This was attributed to a dramatic reduction in DAP10 promoter activity, as assessed by a DAP10 luciferase reporter construct. In contrast to NKG2D expression, IL-21 was able to induce the expression of the NK activation receptors NKp30 and 2B4 as well as the costimulatory receptor CD28 on CD8+ T cells. These data indicate that IL-21 is able to channel NK and CD8+ T cell function by altering the expression pattern of activation/costimulatory receptors.
Specification of individual Slouch muscle progenitors in Drosophila requires sequential Wingless signaling

The patterning of the Drosophila mesoderm requires Wingless (Wg), one of the founding members of a large family of secreted glycoproteins, the Wnt family. Little is known about how Wg provides patterning information to the mesoderm, which is neither an epithelium nor contains the site of Wg production. By studying specification of muscle founder cells as marked by the lineage-specific transcription factor Slouch, we asked how mesodermal cells interpret the steady flow of Wg. Through the manipulation of place, time and amount of Wg signaling, we have observed that Slouch founder cell cluster II is more sensitive to Wg levels than the other Slouch-positive founder cell clusters. To specify Slouch cluster I, Wg signaling is required to maintain high levels of the myogenic transcriptional regulator Twist. However, to specify cluster II, Wg not only maintains high Twist levels, but also provides a second contribution to activate Slouch expression. This dual requirement for Wg provides a paradigm for understanding how one signaling pathway can act over time to create a diverse array of patterning outcomes.