Miracle-dz/UniFAR-FTUs huggingface dataset:
A meta-analysis of levetiracetam for randomized placebo-controlled trials in patients with refractory epilepsy

Objective The objective of this study was to investigate the efficacy and safety profile of levetiracetam as add-on therapy in patients with refractory epilepsy. Methods Web of Science, MEDLINE (Ovid and PubMed), Cochrane Library, EMBASE, and Google Scholar were systematically searched to identify potential eligible randomized controlled trials by two reviewers independently. Pooled estimates of risk ratios (RRs) for 50%, 75%, and 100% reduction from baseline were calculated using the fixed-effect model or random-effect model. Quality of included studies was assessed with the Cochrane Collaboration’s Risk of Bias tool. Serious adverse events and withdrawals induced by interventions and the most common side effects were analyzed. Results Seventeen trials with a total of 3,205 participants were included in this meta-analysis, including 14 trials for adulthood and three trials for children. Pooled estimates suggested that levetiracetam was an effective anti-epileptic drug at 1,000–3,000 mg/day (RR =2.00 for 1,000 mg/day, RR =2.68 for 2,000 mg/day, RR =2.18 for 3,000 mg/day) for adults and 60 mg/kg/day (RR =2.00) for children compared to placebo in terms of 50% reduction from baseline. Likewise, as for seizure freedom rate, levetiracetam had an advantage over placebo at 1,000–3,000 mg/day (RR =5.84 for 1,000 mg/day, RR =4.55 for 2,000 mg/day, RR =4.57 for 3,000 mg/day, respectively) for adults and 60 mg/kg/day (RR =4.52) for children. Regarding safety profile, patients treated with levetiracetam had significantly higher occurrence than placebo for somnolence, asthenia, dizziness, infection, nasopharyngitis, anxiety, and irritability; however, most studies reported that these adverse events were mild and transient. Conclusion Levetiracetam is an effective anti-epileptic drug for both adults and children with generalized or partial-onset refractory seizures at 1,000–3,000 or 60 mg/kg/day, with a favorable adverse event profile.
Elimination of Impulsive Disturbances From Archive Audio Signals Using Bidirectional Processing

In this application-oriented paper we consider the problem of elimination of impulsive disturbances, such as clicks, pops and record scratches, from archive audio recordings. The proposed approach is based on bidirectional processing-noise pulses are localized by combining the results of forward-time and backward-time signal analysis. Based on the results of specially designed empirical tests (rather than on the results of theoretical analysis), incorporating real audio files corrupted by real impulsive disturbances, we work out a set of local, case-dependent fusion rules that can be used to combine forward and backward detection alarms. This allows us to localize noise pulses more accurately and more reliably, yielding noticeable performance improvements, compared to the traditional methods, based on unidirectional processing. The proposed approach is carefully validated using both artificially corrupted audio files and real archive gramophone recordings.
A Test of the Law of Demand in a Virtual World: Exploring the Petri Dish Approach to Social Science

We report results of an experiment on prices and demand in a fantasy-based virtual world. A virtual world is a persistent, synthetic, online environment that can be accessed by many users at the same time. Because most virtual worlds are built around a fantasy theme, complete with magic, monsters, and treasure, there is considerable skepticism that human behavior in such environments is in any way "normal". Our world, "Arden", was designed to test whether players in a typical fantasy environment were economically "normal. " Specifically, we tested whether fantasy gamers conform to the Law of Demand, which states that increasing the price of a good, all else equal, will reduce the quantity demanded. We created two exactly equivalent worlds, and randomly assigned players to one or the other. The only difference in the two worlds was that the price of a single good, a health potion, was twice as high in the experimental world than in the control. We allowed players (N = 43) to enter and play the environment for a month. We found that players in the experimental condition purchased 43.1 percent fewer of the potions, implying a demand elasticity of -0.431. This finding is well within the range one expects for normal economic agents. We take this as evidence that the Law of Demand holds in fantasy environments, which suggests in turn that fantasy gamers may well be economically normal. If so, it may be worthwhile to conduct controlled economic and social experiments in virtual worlds at greater scales of both population (thousands of users) and time (many months).
Bounce Rock—A shergottite‐like basalt encountered at Meridiani Planum, Mars

Abstract– The Opportunity rover of the Mars Exploration Rover mission encountered an isolated rock fragment with textural, mineralogical, and chemical properties similar to basaltic shergottites. This finding was confirmed by all rover instruments, and a comprehensive study of these results is reported here. Spectra from the miniature thermal emission spectrometer and the Panoramic Camera reveal a pyroxene‐rich mineralogy, which is also evident in Mössbauer spectra and in normative mineralogy derived from bulk chemistry measured by the alpha particle X‐ray spectrometer. The correspondence of Bounce Rock’s chemical composition with the composition of certain basaltic shergottites, especially Elephant Moraine (EET) 79001 lithology B and Queen Alexandra Range (QUE) 94201, is very close, with only Cl, Fe, and Ti exhibiting deviations. Chemical analyses further demonstrate characteristics typical of Mars such as the Fe/Mn ratio and P concentrations. Possible shock features support the idea that Bounce Rock was ejected from an impact crater, most likely in the Meridiani Planum region. Bopolu crater, 19.3 km in diameter, located 75 km to the southwest could be the source crater. To date, no other rocks of this composition have been encountered by any of the rovers on Mars. The finding of Bounce Rock by the Opportunity rover provides further direct evidence for an origin of basaltic shergottite meteorites from Mars.
Transparent Live Code Offloading on FPGA

Even though it seems that FPGAs have finally made the transition from research labs to the consumer devices' market, programming them remains challenging. Despite the improvements made by High-Level Synthesis (HLS), which removed the language and paradigm barriers that prevented many computer scientists from working with them, producing a new design typically requires at least several hours, making data- and context-dependent adaptations virtually impossible. In this paper we present a new framework that off-loads, on-the-fly and transparently to both the user and the developer, computationally-intensive code fragments to FPGAs. While the performance should not surpass that of hand-crafted HDL code, or even code produced by HLS, our results come with no additional development costs and do not require producing and deploying a new bit-stream to the FPGA each time a change is made. Moreover, since optimizations are made at run-time, they may fit particular datasets or usage scenarios, something which is rarely foreseeable at design or compile time. Our proposal revolves around an overlay architecture that is pre-programmed on the FPGA and dynamically reconfigured by our framework to execute code fragments extracted from the Data Flow Graph (DFG) of computational intensive routines. We validated our solution using standard benchmarks and proved we are able to off-load to FPGAs without developer's intervention.
Continua of biliteracy: An ecological framework for educational policy, research, and practice in multilingual settings

Nancy H. Hornberger (ed.), Continua of biliteracy: An ecological framework for educational policy, research, and practice in multilingual settings (Bilingual Education and Biliteracy 41). Clevedon: Multilingual Matters, 2003. Pp. 370. Pb $39.95. The collection of articles in Nancy Hornberger's edited book Continua of biliteracy provides a notion of historical development and a sampling of research applications for a specific conceptualization of the phenomenon of biliteracy and multiliteracy. The collection reviews 13 years of theoretical and qualitative research generated by Hornberger's (1989) initial presentation of the continua of biliteracy. The book includes three chapters by Hornberger: the original article, the revision and development of the continua of biliteracy in light of developments in literacy research through the 1990s, written with Skilton-Sylvester (Hornberger & Skilton-Sylvester 2000), and finally an extension of the themes developed in the original model through the metaphor of ecology (Hornberger 2002). These three articles function as a theoretical framework consisting of the past, present, and future directions in research generated through this conceptualization. The other chapters report on research that utilizes Hornberger's framework, covering the issues of language policy, literate identities, teacher roles, and pedagogical practice in various locations, such as the United States, Latin America, Wales, South Africa, and India. This range of issues in a variety of settings demonstrates the robustness of the theory and exemplifies for the reader some of the options of application that it offers.
A novel double-negative feedback loop between miR-489 and the HER2-SHP2-MAPK signaling axis regulates breast cancer cell proliferation and tumor growth

Human epidermal growth factor receptor 2 (HER2 or ErBb2) is a receptor tyrosine kinase overexpressed in 20-30% of breast cancers and associated with poor prognosis and outcome. Dysregulation of several microRNAs (miRNAs) plays a key role in breast cancer progression and metastasis. In this study, we screened and identified miRNAs dysregualted in HER2-positive breast cancer cells. Our molecular study demonstrated that miR-489 was specifically downregulated by the HER2-downstream signaling, especially through the MAPK pathway. Restoration or overexpression of miR-489 in HER2-positive breast cancer cells significantly inhibited cell growth in vitro and decreased the tumorigenecity and tumor growth in xenograft mice. Mechanistically, we found that overexpression of miR-489 led to the decreased levels of HER2 and SHP2 and thus attenuated HER2-downstream signaling. Furthermore, we for the first time demonstrated that HER2 is a direct target of miR-489 and therefore HER2-SHP2-MAPK and miR-489 signaling pathways form a mutually inhibitory loop. Using quantitative real-time PCR analysis and Fluorescent in situ hybridization technique (FISH), we found that miR-489 was expressed at significantly lower level in tumor tissues compared to the adjacent normal tissues. Downregulation of miR-489 in breast cancers was associated with aggressive tumor phenotypes. Overall, our results define a double-negative feedback loop involving miR-489 and the HER2-SHP2-MAPK signaling axis that can regulate breast cancer cell proliferation and tumor progression and might have therapeutic relevance for HER2-positive breast cancer.
Lon protease: A key enzyme controlling mitochondrial bioenergetics in cancer

We have recently explored the in vivo functional and oncologic relevance of Lon protease (LONP1), an enzyme involved in mitochondrial quality control. We found that LONP1 is an essential protein for life and that it also performs a critical function in tumorigenesis by regulating the bioenergetics of cancer cells.
Using Search in Knowledge-Based Engineering

1 Freightliner Corporation, Enterprise Product Documentation, Portland/Oregon, USA, AndreasJunghanns@freightliner.com 2 Daimler-Chrysler AG, Research and Technology Department, Berlin, Germany, Ruediger.Klein@daimlerchrysler.com Abstract. Search has been instrumental in many well known successes of AI problem solving. These successes are currently mostly restricted to well structured domains like games or scheduling. The resulting search spaces can be searched using special purpose search heuristics and strategies. In this position paper we formulate the problems and challenges encountered when these successes are to be extended to more complex domains. Engineering provides a good test bed for these kinds of efforts: though quite complex and diverse, engineering applications have a clear structure and are (generally) well understood. Many different problem solving methods are typically used in combination. The resulting search spaces tend to be huge, they are typically dynamic, and include continuous as well as discrete dimensions. We analyze in which way current search techniques can be extended and modified in order to be applicable under these circumstances.
Workload evaluation of sectorized air traffic control and stream management

Stream management is a novel air traffic control operational concept in which controllers control streams of aircraft that are functionally equivalent, rather than being responsible for “aircraft in airspace. ” One of the potential benefits of stream management is workload reduction for the same amount of aircraft handled. An adaptation of the dynamic density workload measure was used to evaluate stream management operations against current sector based control. This evaluation is completed using FACET software and ASDI data. Stream visualizations and data analysis demonstrate the advantages of stream operations.
Identification and Characterization of Distinct C-Terminal Domains of the Human Hydroxycarboxylic Acid Receptor-2 That Are Essential for Receptor Export, Constitutive Activity, Desensitization, and Internalization

The human hydroxycarboxylic acid receptor 2 (HCA2), also known as GPR109A and HM74a, was first identified as a niacin receptor and has recently received significant attention because of its potential to clinically modify plasma lipids in a favorable manner. Our recent studies have demonstrated that the niacin-induced internalization of HCA2 receptors is regulated by G protein-coupled receptor kinase (GRK) 2 and arrestin3 and that internalized receptors rapidly recycle back to the cell surface. The investigation presented here used a combination of amino acid deletion and site-directed mutagenesis to identify structural and functional domains within the HCA2 C terminus and explore their potential roles in receptor phosphorylation, desensitization, and internalization. We first constructed four mutants with deletions of 10 to 15 amino acids each that were distinct from truncated mutants. We successfully identified different domains responsible for receptor export, constitutive activity, desensitization, phosphorylation, and internalization. We also generated a comprehensive series of alanine substitution mutants, replacing conserved serine and threonine residues in the C terminus with alanine residues to pinpoint the key residues that are essential for GRK2-mediated phosphorylation and arrestin3 association. Moreover, we found that a sequence from residues 329 to 343 in the C-terminal tail of HCA2 plays a crucial role in keeping HCA2 in an inactive conformation. These data demonstrate the importance of distinct domains within the C terminus of HCA2 for receptor cell surface expression, desensitization, and internalization and phosphorylation and stabilization of an inactive receptor conformation.
Piecewise parameter estimation for stochastic models in COPASI

MOTIVATION Computational modeling is widely used for deepening the understanding of biological processes. Parameterizing models to experimental data needs computationally efficient techniques for parameter estimation. Challenges for parameter estimation include in general the high dimensionality of the parameter space with local minima and in specific for stochastic modeling the intrinsic stochasticity. RESULTS We implemented the recently suggested multiple shooting for stochastic systems (MSS) objective function for parameter estimation in stochastic models into COPASI. This MSS objective function can be used for parameter estimation in stochastic models but also shows beneficial properties when used for ordinary differential equation models. The method can be applied with all of COPASI's optimization algorithms, and can be used for SBML models as well. AVAILABILITY AND IMPLEMENTATION The methodology is available in COPASI as of version 4.15. 95 and can be downloaded from http://www.copasi. org CONTACT frank.bergmann@bioquant.uni-heidelberg.de or fbergman@caltech.edu SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.
Three‐dimensional lithospheric structure below the New Zealand Southern Alps

Uppermost mantle seismic structure below the Southern Alps in South Island, New Zealand, is investigated by teleseismic P wave travel time residual inversion. The three-dimensional tomographic images show a near-vertical, high-velocity (2–4%) structure in the uppermost mantle that directly underlies thickened crust along the NNESSW axis of the Southern Alps. The center of the high-velocity anomaly lies to the east of the Alpine fault which bounds Pacific and Australian plate rocks. The oblique collision of these plates resulted in the uplift of the Southern Alps during the past 5–7 m.y. Also, a high-velocity anomaly (3–5%) corresponding to the Hikurangi subduction zone lies to the northeast of the Southern Alps anomaly, and low-velocity anomalies (-3%) underlying parts of northwestern and southern South Island may be signatures of late Tertiary extension and volcanism. The data consist of teleseismic arrival times from the New Zealand National Seismograph Network and arrival times recorded during the 1995–1996 Southern Alps Passive Seismic Experiment. Crustal heterogeneity was accounted for by back projecting the rays through an independently obtained three-dimensional crustal velocity and Moho depth model. The Southern Alps uppermost mantle velocity anomalies are most simply explained by lithospheric thickening below the center of convergence accompanied by thinning and asthenospheric upwelling adjacent to the region of convergence.
API Changes - How FarWould You Go?

Once a software library is deployed, it is extremely difficult to modify published types. Every new version has to preserve backward compatibility with existing applications. This limits the number of changes that may be applied to the public classes defined in the library. We present a tool that assists developers in maintaining the consistency of a shared library with the existing software. It allows for greater flexibility in evolving the library's functionality by supporting a wide range of changes
Sculpting the endomembrane system in deep time: high resolution phylogenetics of Rab GTPases

The presence of a nucleus and other membrane-bounded intracellular compartments is the defining feature of eukaryotic cells. Endosymbiosis accounts for the origins of mitochondria and plastids, but the evolutionary ancestry of the remaining cellular compartments is incompletely documented. Resolving the evolutionary history of organelle-identity encoding proteins within the endomembrane system is a necessity for unravelling the origins and diversification of the endogenously derived organelles. Comparative genomics reveals events after the last eukaryotic common ancestor (LECA), but resolution of events prior to LECA, and a full account of the intracellular compartments present in LECA, has proved elusive. We have devised and exploited a new phylogenetic strategy to reconstruct the history of the Rab GTPases, a key family of endomembrane-specificity proteins. Strikingly, we infer a remarkably sophisticated organellar composition for LECA, which we predict possessed as many as 23 Rab GTPases. This repertoire is significantly greater than that present in many modern organisms and unexpectedly indicates a major role for secondary loss in the evolutionary diversification of the endomembrane system. We have identified two Rab paralogues of unknown function but wide distribution, and thus presumably ancient nature; RabTitan and RTW. Furthermore, we show that many Rab paralogues emerged relatively suddenly during early metazoan evolution, which is in stark contrast to the lack of significant Rab family expansions at the onset of most other major eukaryotic groups. Finally, we reconstruct higher-order ancestral clades of Rabs primarily linked with endocytic and exocytic process, suggesting the presence of primordial Rabs associated with the establishment of those pathways and giving the deepest glimpse to date into pre-LECA history of the endomembrane system.
SOLVING CONVECTION AND CONVECTION REACTION PROBLEMS USING THE M.O.L.

The application of software based on the method of lines (m.o.l.) to convection and convection-reaction problems is considered. The components of a prototype software package, SPRINT2D, are unstructured mesh finite volume algorithms, coupled spatial and temporal error control algorithms and modified time integration techniques for the large systems of o.d. e.s. The software is applied to a realistic combustion problem and the lessons learned used to discuss the validity of the m.o. l. approach.
Parameter-free probabilistic API mining across GitHub

Existing API mining algorithms can be difficult to use as they require expensive parameter tuning and the returned set of API calls can be large, highly redundant and difficult to understand. To address this, we present PAM (Probabilistic API Miner), a near parameter-free probabilistic algorithm for mining the most interesting API call patterns. We show that PAM significantly outperforms both MAPO and UPMiner, achieving 69% test-set precision, at retrieving relevant API call sequences from GitHub. Moreover, we focus on libraries for which the developers have explicitly provided code examples, yielding over 300,000 LOC of hand-written API example code from the 967 client projects in the data set. This evaluation suggests that the hand-written examples actually have limited coverage of real API usages.
Online Semi-Supervised Multi-task Distance Metric Learning

Given several related tasks, multi-task learning can improve the performance of each task through sharing parameters or feature representations. In this paper, we apply multi-task learning to a particular case of distance metric learning, in which we have a small amount of labeled data. Consider the effectiveness of semi-supervised learning handling few labeled machine learning problems, we integrate semi-supervised learning with multi-task learning and distance metric learning. One of the defect of multi-task learning is its low training efficiency, as we need all the training examples from all tasks to train a model. We propose an online learning algorithm to overcome this drawback of multi-task learning. Experiments are conducted on one landmark multi-task learning dataset to demonstrate the efficiency and effectiveness of our online semi-supervised multi-task learning algorithm.
Infoseek's experiences searching the internet

This article recounts both amusing and useful data Infoseek has gathered over the past four years as a leading search site on the Internet. Topics include what people ask on the web, factors for relevance ranking web pages, techniques for searching an infinite number of web pages, and the reasons why Infoseek began writing a search engine in Java a year ago.