Miracle-dz/UniFAR-FTUs huggingface dataset:
Beyond Unfractionated Heparin and Warfarin: Current and Future Advances

Anticoagulants are widely used by cardiologists. Unfractionated heparin (UFH) and coumarins were discovered more than 60 years ago, and for more than 40 years, they have been the sole anticoagulant drugs available to clinicians.1,2 Now, in 2007, several new anticoagulants have been introduced, and many more are under clinical development. Will these new anticoagulants replace the established drugs, and if so, how will these new anticoagulants fit into the therapeutic armamentarium of the practicing cardiologist? Both UFH and coumarins were in clinical use long before their mechanism of action was completely understood. Both were also discovered by chance: UFH from extracts of dog liver and coumarins from extracts of vegetable matter (spoiled sweet clover). Low-molecular-weight heparin (LMWH) was also discovered by chance in the late 1970s and early 1980s and was in clinical use for at least a decade before its mechanistic advantages over UFH were identified.3 In the quest for new anticoagulants, scientists often turned to extracting natural anticoagulants from hemophagic animals and insects and from snake venoms.4 Defibrinating enzymes, factor Xa inhibitors, and thrombin inhibitors were isolated, purified, and in some cases synthesized by recombinant techniques. Of these anticoagulants, recombinant hirudin (from leeches) and recombinant NAPC2 (from hookworm) have been tested clinically. A few new anticoagulants (thrombomodulin, activated protein C) are synthesized by recombinant techniques, but with advances in structure-based design, most new anticoagulants are small molecules designed specifically to block the activity of coagulation enzymes either by fitting into their catalytic pockets, like a key into a lock, or by interacting with and activating anticoagulant proteins such as antithrombin (AT; eg, fondaparinux). On the basis of these technological advances, it is now possible to modulate the coagulation process at almost every step. The first wave of new anticoagulants was not orally active, thereby limiting …
Wild Card Queries for Searching Resources on the Web

We propose a domain-independent framework for searching and retrieving facts and relationships within natural language text sources. In this framework, an extraction task over a text collection is expressed as a query that combines text fragments with wild cards, and the query result is a set of facts in the form of unary, binary and general $n$-ary tuples. A significance of our querying mechanism is that, despite being both simple and declarative, it can be applied to a wide range of extraction tasks. A problem in querying natural language text though is that a user-specified query may not retrieve enough exact matches. Unlike term queries which can be relaxed by removing some of the terms (as is done in search engines), removing terms from a wild card query without ruining its meaning is more challenging. Also, any query expansion has the potential to introduce false positives. In this paper, we address the problem of query expansion, and also analyze a few ranking alternatives to score the results and to remove false positives. We conduct experiments and report an evaluation of the effectiveness of our querying and scoring functions.
Acidic Nucleoplasmic DNA-binding Protein (And-1) Controls Chromosome Congression by Regulating the Assembly of Centromere Protein A (CENP-A) at Centromeres*

Background: The incorporation of CENP-A at centromeres is important for chromosome segregation during mitosis. Results: And-1 together with HJURP regulates the assembly of new CENP-A onto centromeres. Conclusion: And-1 facilitates the recruitment of CENP-A to centromeres. Significance: These studies reveal a novel role of And-1 in the regulation of chromosome congression during mitosis. The centromere is an epigenetically designated chromatin domain that is essential for the accurate segregation of chromosomes during mitosis. The incorporation of centromere protein A (CENP-A) into chromatin is fundamental in defining the centromeric loci. Newly synthesized CENP-A is loaded at centromeres in early G1 phase by the CENP-A-specific histone chaperone Holliday junction recognition protein (HJURP) coupled with other chromatin assembly factors. However, it is unknown whether there are additional HJURP-interacting factor(s) involving in this process. Here we identify acidic nucleoplasmic DNA-binding protein 1 (And-1) as a new factor that is required for the assembly of CENP-A nucleosomes. And-1 interacts with both CENP-A and HJURP in a prenucleosomal complex, and the association of And-1 with CENP-A is increased during the cell cycle transition from mitosis to G1 phase. And-1 down-regulation significantly compromises chromosome congression and the deposition of HJURP-CENP-A complexes at centromeres. Consistently, overexpression of And-1 enhances the assembly of CENP-A at centromeres. We conclude that And-1 is an important factor that functions together with HJURP to facilitate the cell cycle-specific recruitment of CENP-A to centromeres.
Structural and Functional Analysis of Laninamivir and its Octanoate Prodrug Reveals Group Specific Mechanisms for Influenza NA Inhibition

The 2009 H1N1 influenza pandemic (pH1N1) led to record sales of neuraminidase (NA) inhibitors, which has contributed significantly to the recent increase in oseltamivir-resistant viruses. Therefore, development and careful evaluation of novel NA inhibitors is of great interest. Recently, a highly potent NA inhibitor, laninamivir, has been approved for use in Japan. Laninamivir is effective using a single inhaled dose via its octanoate prodrug (CS-8958) and has been demonstrated to be effective against oseltamivir-resistant NA in vitro. However, effectiveness of laninamivir octanoate prodrug against oseltamivir-resistant influenza infection in adults has not been demonstrated. NA is classified into 2 groups based upon phylogenetic analysis and it is becoming clear that each group has some distinct structural features. Recently, we found that pH1N1 N1 NA (p09N1) is an atypical group 1 NA with some group 2-like features in its active site (lack of a 150-cavity). Furthermore, it has been reported that certain oseltamivir-resistant substitutions in the NA active site are group 1 specific. In order to comprehensively evaluate the effectiveness of laninamivir, we utilized recombinant N5 (typical group 1), p09N1 (atypical group 1) and N2 from the 1957 pandemic H2N2 (p57N2) (typical group 2) to carry out in vitro inhibition assays. We found that laninamivir and its octanoate prodrug display group specific preferences to different influenza NAs and provide the structural basis of their specific action based upon their novel complex crystal structures. Our results indicate that laninamivir and zanamivir are more effective against group 1 NA with a 150-cavity than group 2 NA with no 150-cavity. Furthermore, we have found that the laninamivir octanoate prodrug has a unique binding mode in p09N1 that is different from that of group 2 p57N2, but with some similarities to NA-oseltamivir binding, which provides additional insight into group specific differences of oseltamivir binding and resistance.
Heuristic-Based Multi-Agent Monte Carlo Tree Search

Monte Carlo Tree Search (MCTS) is a relatively new sampling best-first method to search for optimal decisions. The MCTS' popularity is based on its extraordinary results in the challenging two-player based game Go, a game considered much harder than Chess and that until very recently was considered unfeasible for Artificial Intelligence methods. Different MCTS variants have been proposed, mainly to enhance its capabilities. Perhaps, one of the main limitations of this approach is its applicability in scenarios where multiple agents (more than two) are required. Some works have made an attempt to overcome this limitation by using a vector of reward values for each agent and allowing the algorithm to find an optimal equilibrium strategy. Inspired by these approaches, in this work we make an effort to explore a new proposal for handling multiple agents in MCTS by using a vector of values of what the agents need to do (defined tasks) instead of a vector of rewards for each agent. To achieve this we use a rather simple, but powerful heuristic that estimates the desired values of this vector. That is, a set of values that could lead to the optimal completion of the task. We tested this idea in a real-world scenario rather than using it in games as traditionally done. The results achieved by our proposed approach, named Heuristic-Based Multi-Agent Monte Carlo Tree Search, indicate the feasibility of using heuristics in the MCTS algorithm in situations where more than two agents are required.
Evaluating Online Global Recovery with Fenix Using Application-Aware In-Memory Checkpointing Techniques

Exascale systems promise the potential for computation at unprecedented scales and resolutions, but achieving exascale by the end of this decade presents significant challenges. A key challenge is due to the very large number of cores and components and the resulting mean time between failures (MTBF) in the order of hours or minutes. Since the typical run times of target scientific applications are longer than this MTBF, fault tolerance techniques will be essential. An important class of failures that must be addressed is process or node failures. While checkpoint/restart (C/R) is currently the most widely accepted technique for addressing processor failures, coordinated, stable-storage-based global C/R might be unfeasible at exascale when the time to checkpoint exceeds the expected MTBF. This paper explores transparent recovery via implicitly coordinated, diskless, application-driven checkpointing as a way to tolerate process failures in MPI applications at exascale. The discussed approach leverages User Level Failure Mitigation (ULFM), which is being proposed as an MPI extension to allow applications to create policies for tolerating process failures. Specifically, this paper demonstrates how different implementations of application-driven in-memory checkpoint storage and recovery compare in terms of performance and scalability. We also experimentally evaluate the effectiveness and scalability of the Fenix online global recovery framework on a production system -the Titan Cray XK7 at ORNL- and demonstrate the ability of Fenix to tolerate dynamically injected failures using the execution of four benchmarks and mini-applications with different behaviors.
A Conceptual Framework for Object Composition and Behavior Description 3. a Framework for Object Composition

After providing a model for composite objects, we propose a model for the composition process. A composition process helps to construct composite objects. Our starting point is the basic idea that a composite object is formed by superposing three kinds of properties. Intuitively, superposition of properties means to put together a set of properties in such a way that the interrelations between these properties are kept minimal and the whole remains coherent. If the composition process has to support this principle, then a stepwise process to composition is recommended. This reasoning is also backed by observing that some composite object descriptions may be too complex and we need to focus on certain aspects of composition. We therefore implement separation of concerns in the composition process, allowing different aspects of a composite object to be treated separately. This has the advantage of localizing related aspects. Some aspects of a composite object are built upon others. This is the case for inherent and aggregate properties. The general principle of cohesion dictates that closely related ideas should be kept together and unrelated ideas be kept separated. Thus inherent and aggregate properties should not be treated independently. Also, following the idea of cohesion, the interactions among the component objects and the overall properties of the composite object should be treated distinctly. A composite object may have properties which are not attributable to component objects. Taking into account the aspects of composite objects presented above, there appears to be three distinct aspects of a composite object: (1) its internal activity, (2) its relationship with its component objects and resulting properties, and (3) the properties non attributable to its component objects. For the definition of each aspect, we assign a specific step. The proposed process consists of the three consecutive steps. 3.1. The composition process We will now give an overview of each step and explain how they are interrelated. The first step has to handle the interactions among the component objects. In other words, it has to deal with the internal activity of a composite object. We call this step configuration of component objects (or configuration for short). The second step, which we call juxtaposition, has to describe the resultant properties. It has to deal with the way the composite object is handled as a unit, i.e., it concerns the identity of the composite object,
BRANDS: A Marketing Game

0. BRANDSaA A Quick-Start Instructions. 1. Overview of BRANDSaA A . 2. BRANDSaA A Teaching Strategy and Tactics. 3. The BRANDMAPSaA A Memos. 4. Performance Evaluation in BRANDSaA A . 5. The BRANDSaA A Market Model. 6. The BRANDSaA A Parameter File. 7. The BRANDSaA A Software. 8. Managing BRANDSaA A Output. 9. Undocumented BRANDSaA A Marketing Research Studies. Index.
Georgia Computes!: an alliance to broaden participation across the state of Georgia

Designers of computing systems are also predominantly white or Asian and male. When only one demographic group makes up the design pool, the pool of ideas and possibilities is constrained. For example, some voice recognition systems in cars don't recognize female voices. 1 How could a product be released that doesn't work with more than half of the population? Perhaps because there were not enough women involved in the design and development process to make that a priority? ■ Computing jobs are among the best-paid jobs in the US economy. When women and members of under-represented minorities don't get those jobs, it depresses their income and their ability to raise their standard of living. Insuring equal opportunity access to computing careers is an issue of equity and economic justice. How do we broaden participation to computing? The National Science Founda-The lack of diversity in computer science is a significant problem for several reasons: ■ We need more workers in computing disciplines. The US Bureau of Labor Statistics and NCWIT have both tracked a growing gap between jobs available in computing disciplines and graduates in those disciplines. In the United States, white and Asian males are a decreasing proportion of the overall population. We currently rely on a shrinking demographic group for workers in one of the most significant and growing segments of our economy. Computing is a critical part of our modern world, and computer science is the key to understanding and using computing effectively. Yet, computer science in the United States and across much of the developed world is predominantly male, and in the United States, predominantly white or Asian.
Weighted inequalities and vector-valued Calderón-Zygmund operators on non-homogeneous spaces

Recently, F. Nazarov, S. Treil and A. Volberg (and independently X. Tolsa) have extended the classical theory of Calderon-Zygmund operators to the context of a "non-homogeneous" space $(\mathbb {X},d,\mu )$, where, in particular, the measure $\mu $ may be non-doubling. In the present work we study weighted inequalities for these operators. Specifically, for $1 < p < \infty $, we identify sufficient conditions for the weight on one side, which guarantee the existence of another weight in the other side, so that the weighted $L^p$ inequality holds. We deal with this problem by developing a vector-valued theory for Calderon-Zygmund operators on non-homogeneous spaces which is interesting in its own right. For the case of the Cauchy integral operator, which is the most important example, we even prove that the conditions for the weights are also necessary.
Damage Modes in Dental Layer Structures

Natural teeth (enamel/dentin) and most restorations are essentially layered structures. This study examines the hypothesis that coating thickness and coating/substrate mismatch are key factors in the determination of contact-induced damage in clinically relevant bilayer composites. Accordingly, we study crack patterns in two model "coating/substrate" bilayer systems conceived to simulate crown and tooth structures, at opposite extremes of elastic/plastic mismatch: porcelain on glass-infiltrated alumina ("soft/hard"); and glass-ceramic on resin composite ("hard/soft). Hertzian contacts are used to investigate the evolution of fracture damage in the coating layers, as functions of contact load and coating thickness. The crack patterns differ radically in the two bilayer systems: In the porcelain coatings, cone cracks initiate at the coating top surface ; in the glass-ceramic coatings, cone cracks again initiate at the top surface, but additional, upward-extending transverse cracks initiate at the internal coating/substrate interface, with the latter dominant. The substrate is thereby shown to have a profound influence on the damage evolution to ultimate failure in the bilayer systems. However, the cracks are highly stabilized in both systems, with wide ranges between the loads to initiate first cracking and to cause final failure, implying damage-tolerant structures. Finite element modeling is used to evaluate the tensile stresses responsible for the different crack types. The clinical relevance of these observations is considered.
Exploiting Semantic and Visual Context for Effective Video Annotation

We propose a new method to refine the result of video annotation by exploiting the semantic and visual context of video. On one hand, semantic context mining is performed in a supervised way, using the manual concept labels of the training set. It is very useful for boosting video annotation performance, because semantic context is learned from labels given by people, indicating human intention. In this paper, we model the spatial and temporal context in video by using conditional random fields with different structures. Comparing with existing methods, our method could more accurately capture concept relationship in video and could more effectively improve the video annotation performance. On the other hand, visual context mining is performed in a semi-supervised way based on the visual similarities among video shots. It indicates the natural visual property of video, and could be considered as the compensation to semantic context, which generally could not be perfectly modeled. In this paper, we construct a graph based on the visual similarities among shots. Then a semi-supervised learning approach is adopt based on the graph to propagate probabilities of the reliable shots to others having similar visual features with them. Extensive experimental results on the widely used TRECVID datasets exhibit the effectiveness of our method for improving video annotation accuracy.
EL USO DE LÍPIDOS ESTRUCTURADOS EN LA NUTRICIÓN: UNA TECNOLOGÍA QUE ABRE NUEVAS PERSPECTIVAS EN EL DESARROLLO DE PRODUCTOS INNOVADORES

Los lipidos, junto con los carbohidratos y las proteinas son los principales componentes de la nutricion humana, y los trigliceridos son los principales lipidos presentes en los alimentos. Por lo tanto, toda modificacion en el patron de consumo de lipidos debe estar orientada a la modificacion de la composicion y estructura de los trigliceridos. La digestion de los trigliceridos por la lipasas bucal, gastrica e intestinal es altamente estereoespecifica en terminos del reconocimiento por parte de estas enzimas del tipo de acido graso que esta unido al glicerol. La lipasa ligual-gastrica, la lipasa pancreatica, y la lipasa lactea pueden liberar acidos grasos desde diferentes posiciones de los trigliceridos (sn-1, sn-2 o sn-3), permitiendo la formacion de acidos grasos libres, monogliceridos y glicerol. Los acidos grasos de cadenas superiores a C16 pueden formar jabones insolubles de calcio que precipitan en la cavidad intestinal facilitando la formacion de deposiciones de mucha consistencia, las que con frecuencia causan trastornos intestinales en ninos y adultos. La formulas que se han desarrollado para reemplazar a la leche materna, contienen lipidos de origen vegetal o animal que no simulan exactamente la estereoquimica de la leche materna, con lo cual la biodisponibilidad de los acidos grasos disminuye y se facilita la formacion a partir de estos de jabones de calcio insolubles. Esta es una causa comun de estrenimiento en lactantes que no reciben lactancia materna y que solo son alimentados con formulas. La tecnologia enzimatica permite la sintesis de trigliceridos con una composicion y estereoquimica de acidos grasos definida. Estos lipidos se conocen como lipidos estructurados y estan ahora disponibles para modificar la composicion de las formulas con el proposito de lograr una estereoquimica similar a la de la leche humana. La adicion de lipidos estructurados a las formulas permiten proveer un perfil nutricional similar al de la leche materna, evitando la formacion de jabones insolubles y disminuyendo considerablemente el estrenimiento en los lactantes