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We report and analyze the results of our computational testing of branchand-cut for piecewise linear optimization using the cutting planes given recently by Zhao and de Farias. Besides evaluating the performance of the cuts, we ev...
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We report and analyze the results of our computational testing of branchand-cut for piecewise linear optimization using the cutting planes given recently by Zhao and de Farias. Besides evaluating the performance of the cuts, we evaluate the effect of formulation on the performance of branch-and-cut. Finally, we report and analyze results on piecewise linear optimization problems with semi-continuous constraints.
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Because virtual computing platforms are dynamically changing, it is difficult to build high-quality intrusion detection system. In this paper, we present an automated approach to intrusions detection in order to maintain sufficien...
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Because virtual computing platforms are dynamically changing, it is difficult to build high-quality intrusion detection system. In this paper, we present an automated approach to intrusions detection in order to maintain sufficient performance and reduce dependence on execution environment. We discuss a hidden Markov model strategy for abnormality detection using frequent system call sequences, letting us identify attacks and intrusions automatically and efficiently. We also propose an automated mining algorithm, named AGAS, to generate frequent system call sequences. In our approach, the detection performance is adaptively tuned according to the execution state every period. To improve performance, the period value is also under self-adjustment.
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Information services on the Internet are being used as an important tool to facilitate discovery of the information that is of user interests. Many approaches have been proposed to discover the information on the Internet, while t...
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Information services on the Internet are being used as an important tool to facilitate discovery of the information that is of user interests. Many approaches have been proposed to discover the information on the Internet, while the search engines are the most common ones. However, most of the current approaches of information discovery can discover the keyword-matching information only but cannot recommend the most recent and relative information to users automatically. Sometimes users can give only a fuzzy keyword instead of an accurate one. Thus, some desired information would be ignored by the search engines. Moreover, the current search engines cannot discover the latent but logically relevant information or services for users. This paper measures the semantic-similarity and link-similarity between keywords. Based on that, it introduces the concept of similarity of web pages, and presents a method for information recommendation. The experimental evaluation and comparisons with the existing studies are finally performed.
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Obesity and associated comorbidities are a major health burden, and novel therapeutics to help treat obesity are urgently needed. There is increasing evidence that targeting the amylin receptors (AMYRs), heterodimers of the calcit...
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Obesity and associated comorbidities are a major health burden, and novel therapeutics to help treat obesity are urgently needed. There is increasing evidence that targeting the amylin receptors (AMYRs), heterodimers of the calcitonin G protein–coupled receptor (CTR) and receptor activity-modifying proteins, improves weight control and has the potential to act additively with other treatments such as glucagon-like peptide-1 receptor agonists. Recent data indicate that AMYR agonists, which can also independently activate the CTR, may have improved efficacy for treating obesity, even though selective activation of CTRs is not efficacious. AM833 (cagrilintide) is a novel lipidated amylin analog that is undergoing clinical trials as a nonselective AMYR and CTR agonist. In the current study, we have investigated the pharmacology of AM833 across 25 endpoints and compared this peptide with AMYR selective and nonselective lipidated analogs (AM1213 and AM1784), and the clinically used peptide agonists pramlintide (AMYR selective) and salmon CT (nonselective). We also profiled human CT and rat amylin as prototypical selective agonists of CTR and AMYRs, respectively. Our results demonstrate that AM833 has a unique pharmacological profile across diverse measures of receptor binding, activation, and regulation. SIGNIFICANCE STATEMENT AM833 is a novel nonselective agonist of calcitonin family receptors that has demonstrated efficacy for the treatment of obesity in phase 2 clinical trials. This study demonstrates that AM833 has a unique pharmacological profile across diverse measures of receptor binding, activation, and regulation when compared with other selective and nonselective calcitonin receptor and amylin receptor agonists. The present data provide mechanistic insight into the actions of AM833. Copyright ? 2021 by The Author(s).
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As the Earth's population approaches nine billion people in the upcoming decades, food production must increase by nearly 70% to satisfy this global need (Reytar et al. 2014). To quell global food demands, productivity has increas...
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As the Earth's population approaches nine billion people in the upcoming decades, food production must increase by nearly 70% to satisfy this global need (Reytar et al. 2014). To quell global food demands, productivity has increased in recent years through agrotechnological advances (e.g., Fisher et al. 2014) and crop breeding (Klumper and Qaim 2014), but the ramp-up of production and associated intensive management are degrading agroecosystems (Lal 2004), thereby threatening their sustainability (Karlen et al. 2014).Ecosystem degradation due to intensive agriculture is seen vividly in Iowa, which has become a world-leading, commodity-based agroecosystem due to its overall fertile soils. However, the enhanced erosion triggered by accelerating production levels, in conjunction with more frequent shifts between high intensity rainfall and deep droughts, is so extreme that two-thirds of the farmland in Iowa is losing soil at a rate over 11 Mt/ha/yr, which is equivalent to a little over a dump truck load per hectare per year (Tevis 2015). During a week of intense storms in 2014, Iowa farmers lost an estimated $1 billion in yield due to erosion (Eller 2014).Additionally, intensive management has depleted the soils of essential nutrients (Pimentel et al. 1995) making Iowa a “nutrient-hungry system.” To maintain high production, artificial fertilizers are broadly applied in mass quantities, but nearly half of these applied fertilizers are lost through leaching, runoff, and erosion (Burkart et al. 2005). As a result, recent record nitrate levels in the Raccoon and Des Moines Rivers in Iowa, predominantly from agricultural runoff, are taxing the aging infrastructure of the Des Moines Water Works and have even prompted lawsuits against three upstream, agricultural counties (Eller 2014). Further downstream, the problems persist as nutrient fluxes from the Upper Mississippi River Basin have been linked to hypoxia in the Gulf of Mexico (Porter et al. 2015).The widespread ramifications of this ecosystem degradation have pushed the development of adaptive, watershed-scale management plans for improving the sustainability of agroecosystems like those in Iowa. But, do we have the necessary tools to assess accurately at the watershed scale the performance of the different practices currently in use or possible alternatives (e.g., Robertson et al. 2014)? As a substitute to extensive field monitoring studies, computer models can work as an indirect form of adaptive management (Prato 2003) to evaluate watershed-scale responses to different combinations of current and projected practices.One factor to consider in developing these assessment modeling tools is that intensive land management and the resulting soil redistribution can augment the natural heterogeneity observed in agroecosystems along a hillslope for properties like Soil Organic Carbon (SOC) and other nutrients by dictating flowpath development and soil erodibility (e.g., Wilson et al. 2009; Dlugoβ et al. 2010; Stavi and Lal 2011; Papanicolaou et al. 2015b). Hence, the selective entrainment and resulting fluxes of these constituents may differ significantly in areas where erosion dominates relative to areas where deposition occurs (Van Oost et al. 2006; Wang et al. 2015), resulting in the increased variability across the landscape.Since most biogeochemical models (e.g., ROTH-C, DNDC, CENTURY) used to quantify changes in SOC or other nutrients focus within a soil column, it is unlikely that they will capture this augmented, field-level heterogeneity. As a result, existing models will either overestimate or underestimate stock predictions depending on the location within a field, since they do not consider selective mobilization (e.g., Parton et al. 1987; Paustian et al. 1992; Harden et al. 1999; Manies et al. 2001).The majority of studies that have attempted field-scale assessments of SOC linked these existing biogeochemical models with lumped erosion models, such as those based on the Un
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As the momentum behind Chip Multi-Processors (CMPs) continues to grow, Last Level Cache (LLC) management becomes a crucial issue to CMPs because off-chip accesses often involve a big latency. Private cache design is distinguished ...
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As the momentum behind Chip Multi-Processors (CMPs) continues to grow, Last Level Cache (LLC) management becomes a crucial issue to CMPs because off-chip accesses often involve a big latency. Private cache design is distinguished by smaller local access latency, good performance isolation and easy scalability, thus is becoming an attractive design alternative for LLC of CMPs. This paper proposes Balanced Private Non-Uniform Cache Architecture (BP-NUCA), a new LLC architecture that starts from private cache design for smaller local access latency and good performance isolation, then introduces a low cost mechanism to dynamically migrate private blocks among peer private caches of LLC to improve the overall space utilization. BP-NUCA achieves this by measuring the cache access pressure level that each cache set experiences at runtime and then using the information to guide block migration among different private caches of LLC. A heavily accessed set, namely a set with high access pressure level, is allowed to migrate its evicted blocks to peer private caches, replacing blocks of sets which are with the same index and have low access pressure level. By migrating blocks from heavily accessed cache sets to less accessed cache sets, BP-NUCA effectively balances space utilization of LLC among different cores. Experimental results using a full system CMP simulator show that BP-NUCA improves the overall throughput by as much as 20.3 %, 12.4 %, 14.5 % and 18.0 % (on average 7.7 %, 4.4 %, 4.0 % and 6.1 %) over private cache, shared cache, shared cache management scheme UCP and private cache organization CC respectively on a 4-core CMP for SPEC CPU2006 benchmarks.
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Given a graph G=(V, E) and k source-sink pairs (s1, t1), …, (sk, tk) with each si, ti V, the Min-Sum Disjoint Paths problem asks to find k disjoint paths connecting all the source-sink pairs with minimized total length, while the...
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Given a graph G=(V, E) and k source-sink pairs (s1, t1), …, (sk, tk) with each si, ti V, the Min-Sum Disjoint Paths problem asks to find k disjoint paths connecting all the source-sink pairs with minimized total length, while the Min-Max Disjoint Paths problem asks for k disjoint paths connecting all the source-sink pairs with minimized length of the longest path. We show that the weighted Min-Sum Disjoint Paths problem is FPNP-complete in general graphs, and the unweighted Min-Sum Disjoint Paths problem and the unweighted Min-Max Disjoint Paths problem cannot be approximated within m(m1-1) for any constant > 0 even in planar graphs, assuming P P NP, where m is the number of edges in G. We give for the first time a simple bicriteria approximation algorithm for the unweighted Min-Max Edge-Disjoint Paths problem and the weighted Min-Sum Edge-Disjoint Paths problem, wi
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Four estimators of the directed information rate between a pair of jointly stationary ergodic finite-alphabet processes are proposed, based on universal probability assignments. The first one is a Shannon–McMillan–Breiman-type e...
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Four estimators of the directed information rate between a pair of jointly stationary ergodic finite-alphabet processes are proposed, based on universal probability assignments. The first one is a Shannon–McMillan–Breiman-type estimator, similar to those used by Verdú in 2005 and Cai in 2006 for estimation of other information measures. We show the almost sure and $L_{1}$ convergence properties of the estimator for any underlying universal probability assignment. The other three estimators map universal probability assignments to different functionals, each exhibiting relative merits such as smoothness, nonnegativity, and boundedness. We establish the consistency of these estimators in almost sure and $L_{1}$ senses, and derive near-optimal rates of convergence in the minimax sense under mild conditions. These estimators carry over directly to estimating other information measures of stationary ergodic finite-alphabet processes, such as entropy rate and mutual information rate, with near-optimal performance and provide alternatives to classical approaches in the existing literature. Guided by these theoretical results, the proposed estimators are implemented using the context-tree weighting algorithm as the universal probability assignment. Experiments on synthetic and real data are presented, demonstrating the potential of the proposed schemes in practice and the utility of directed information estimation in detecting and measuring causal influence and delay.
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The aim of the study is to provide an up-to-date review of studies that used preclinical animal models for the evaluation of tissue engineering treatments for spinal cord injury (SCI), which involved the use of biomaterials with o...
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The aim of the study is to provide an up-to-date review of studies that used preclinical animal models for the evaluation of tissue engineering treatments for spinal cord injury (SCI), which involved the use of biomaterials with or without the addition of cells or biomolecules. Electronic search of the PubMed, Web of Science, and Embase databases was performed for relevant studies published between January 2009 and December 2019. In total, 1579 articles were retrieved, of which 58 studies were included for analysis. Among the included studies, rats were the most common species used for animal models of SCI, while complete transection was the most commonly used injury pattern. Immediate intervention after injury was conducted in the majority of studies, and 8 weeks was the most common final time point of outcome assessment. A wide range of natural and synthetic biomaterials with different morphologies were used as a part of tissue engineering treatments for SCI, including scaffolds, hydrogels, and particles. Experimental parameters in studies using SCI animal models to evaluate tissue engineering treatments should be carefully considered to match the purpose of the study. Biomaterials that have functional modifications or are applied in combination with cells and biomolecules can be effective in creating a permissive environment for SCI repair in preclinical animal models. This review provides an up-to-date summary of the preclinical landscape where tissue engineering treatments involving biomaterials were tested in animal models of spinal cord injury (SCI). Using studies published within the last 10 years, novel perspectives were presented on the animal species used, injury pattern, timing of intervention and outcome measurement, and biomaterials selection, as well as a summary of the individual findings of each study. This review provides unique insight into biomaterials-based tissue engineering strategies that have progressed to testing in animal models of SCI, which will help shape future research in the field and propel the clinical translation of discoveries. ? Copyright 2022, Mary Ann Liebert, Inc.
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Background: Gout is the most common inflammatory arthritis, which, if left untreated or inadequately treated, will lead to joint destruction, bone erosion and disability due to the crystal deposition. Uric acid transporter 1 (URAT...
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Background: Gout is the most common inflammatory arthritis, which, if left untreated or inadequately treated, will lead to joint destruction, bone erosion and disability due to the crystal deposition. Uric acid transporter 1 (URAT1) was the promising therapeutic target for urate-lowering therapy. Objective: The goal of this work is to understand the structure-activity relationship (SAR) of a potent lesinurad-based hit, sodium 2-((5-bromo-4-((4-cyclopropyl-naphth-1-yl)methyl)-4H-1,2,4-triazol-3-yl)thio)acetate (1c), and based on that discover a more potent URAT1 inhibitor. Methods: The SAR of 1c was systematically explored and the in vitro URAT1 inhibitory activity of synthesized compounds 1a-1t was determined by the inhibition of URAT1-mediated [8-14C]uric acid uptake by human embryonic kidney 293 (HEK293) cells stably expressing human URAT1. Results: Twenty compounds 1a-1t were synthesized. SAR analysis was performed. Two highly active URAT1 inhibitors, sodium 2-((5-bromo-4-((4-n-propylnaphth-1-yl)methyl)-4H-1,2,4-triazol-3-yl)thio)acetate (1j) and sodium 2-((5-bromo-4-((4-bromonaphth-1-yl)methyl)-4H-1,2,4-triazol-3-yl)thio)acetate (1m), were identified, which were 78- and 76-fold more active than parent lesinurad in in vitro URAT1 inhibitory assay, respectively (IC50 values for 1j and 1m were 0.092 μM and 0.094 μM, respectively, against human URAT1 vs 7.18 μM for lesinurad). Conclusion: Two highly active URAT1 inhibitors were discovered. The SAR exploration also identified more flexible naphthyltriazolylmethane as a novel molecular skeleton that will be valuable for the design of URAT1 inhibitors, as indicated by the observation that many of the synthesized naphthyltriazolylmethane-bearing derivatives (1b-1d, 1g, 1j and 1m) showed significantly improved UART1 inhibitory activity (sub-micromolar IC50 values) as compared with lesinurad which has the rigid naphthyltriazole skeleton
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