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Metabolomics studies identify novel diagnostic and prognostic indicators in patients with alcoholic hepatitis

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World journal of Hepatology 2016年第10期8卷 499-508页

作者： Mona Ascha Zeneng Wang Mustafa S Ascha Raed Dweik Nizar N Zein David Grove j mark brown Stephanie Marshall Rocio Lopez Ibrahim A Hanouneh Department of Gastroenterology and Hepatology Cleveland Clinic Department of Cellular and Molecular Medicine Cleveland Clinic Department of Pulmonary Allergy and Critical Care Medicine/Respiratory Institute Cleveland Clinic Department of Quantitative Health Science Cleveland Clinic Minnesota Gastroenterology Min- neapolis

AIM: To identify plasma analytes using metabolomics that correlate with the diagnosis and severity of liver disease in patients with alcoholic hepatitis(AH).METHODS: We prospectively recruited patients with cirrhosis from AH(n = 23) and those with cirrhosis with acute decompensation(AD) from etiologies other than alcohol(n = 25). We used mass spectrometry to identify 29 metabolic compounds in plasma samples from fasted subjects. A receiver operating characteristics analysis was performed to assess the utility of biomarkers in distinguishing acute AH from alcoholic cirrhosis. Logistic regression analysis was performed to build a predictive model for AH based on clinical characteristics. A survival analysis was used to construct Kaplan Meier curves evaluating transplant-free ***: A comparison of model for end-stage liver disease(MELD)-adjusted metabolomics levels between cirrhosis patients who had AD or AH showed that patients with AH had significantly higher levels of betaine, and lower creatinine, phenylalanine, homocitrulline, citrulline, tyrosine, octenoyl-carnitine, and symmetric dimethylarginine. When considering combined levels, betaine and citrulline were highly accurate predictors for differentiation between AH and AD(area under receiver operating characteristics curve = 0.84). The plasma levels of carnitine [0.54(0.18, 0.91); P = 0.005], homocitrulline [0.66(0.34, 0.99); P markers(carnitine P = 0.005, butyrobetaine P = 0.32, homocitrulline P = 0.002, leucine P = 0.027, valine P = 0.024, phenylalanine P = 0.037, tyrosine P = 0.012, acetyl-carnitine P = 0.006, propionyl-carnitine P = 0.03, butyryl-carnitine P = 0.03, trimethyl-lisine P = 0.034, pentanoyl-carnitine P = 0.03, hexanoyl-carnitine P = 0.026) were associated with increased mortality in patients with AH. CONCLUSION: Metabolomics plasma anal

关键词： Metabolomics Biomarkers Liver disease Model for end-stage liver disease Cirrhosis Alcoholic hepatitis Liver biopsy

Emerging role of A-kinase anchoring protein 5 signaling in reward circuit function

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Neural Regeneration Research 2025年第10期20卷 2913-2914页

作者： William j.Flerlage mark L.Dell’Acqua Brian M.Cox Fereshteh S.Nugent Uniformed Services University of the Health Sciences Department of Pharmacology and Molecular TherapeuticsBethesdaMDUSA Department of Pharmacology University of Colorado School of MedicineAnschutz Medical CampusAuroraCOUSA

There is a strong evidence supporting the hypothesis of synaptic dysfunction as a major contributor to neural circuit and network disruption underlying emotional and mood dysregulation in psychiatric disorders(Simmons et al.,2024).Diverse sets of distinct molecular signaling pathways converge on the synapse to regulate synaptogenesis,synaptic function,and synaptic plasticity in brain regions and circuits through complex interactions organized by numerous multivalent protein scaffolds,including the family of proteins known as A-kinase anchoring proteins(AKAPs).

关键词： function supporting

Assessing ecological and physiological costs of melanism in North American Papilio glaucus females: two decades of dark morph frequency declines

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Insect Science 2020年第3期27卷 583-612页

作者： j.mark Scriber Department of Entomology Michigan State UniversityEast LansingMichiganUSA McGuire Center for Lepidoptera and Biodiversity Florida Museum of Natural HistoryUniversity of FloridaGainesvilleFloridaUSA

Polymorphisms for melanic form of insects may provide various selective ***,melanic alleles may have significant/subtle pleiotrophic“costs.”Several potential pleiotrophic effects of the W(=Y)‐linked melanism gene in Papilio glaucus L.(Lepidoptera)showed no costs for melanic versus yellow in adult size,oviposition preferences,fecundity,egg viability,larval survival/growth rates,cold stress tolerance,or postdiapause emergence *** selection(males choosing yellow rather than mimetic dark females)had been suggested to provide a balanced polymorphism in ***,but spermatophore counts in wild females and direct field tethering studies of size‐matched pairs of virgin females(dark and yellow),show that male preferences are random or frequency‐dependent from Florida to Michigan,providing no yellow counter‐*** frequency declines of dark(melanic/mimetic)females in *** populations are shown in several major populations from Florida(27.3°N latitude)to Ohio(38.5°N).Summer temperatures have increased significantly at all these locations during this time(1999–2018),but whether dark morphs may be more vulnerable(in any stage)to such climate warming remains to be *** potential reasons for the frequency declines in mimetic females are discussed:(i)genetic introgression of Z‐linked melanism suppressor genes from ***(R&j)and the hybrid species,***(Pavulaan&Wright),(ii)differential developmental incompatibilities,or Haldane effects,known to occur in hybrids,(iii)selection against intermediately melanic(“dusty”)females(with the W‐linked melanic gene,b+)which higher temperatures can cause.

关键词： climate warming ecology of melanism incomplete mimicry pleiotrophic costs

Integrating ancient patterns and current dynamics of insect-plant interactions＂ Taxonomic and geographic variation in herbivore specialization

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Insect Science 2010年第6期17卷 471-507页

作者： j. mark Scriber Department of Entomology Michigan State University East Lansing Michigan McGuire Center for Lepidoptera and Biodiversity Florida Museum of Natural History University of Florida Gainesville Florida USA

The search for pattern in the ecology and evolutionary biology of insect-plant associations has fascinated biologists for centuries. High levels of tropical （tow-latitude） plant and insect diversity relative to poleward latitudes and the disproportionate abundance of host-specialized insect herbivores have been noted. This review addresses several aspects of local insect specialization, host use abilities （and loss of these abilities with specialization）, host-associated evolutionary divergence, and ecological （including ＂hybrid＂） speciation, with special reference to the generation of biodiversity and the geographic and taxonomic identification of ＂species borders＂ for swallowtail butterflies （Papilionidae）. From ancient phytochemically defined angiosperm affiliations that trace back millions of years to recent and very local specialized populations, the Papilionidae （swallowtail butterflies） have provided a model for enhanced tmderstanding of localized ecological patterns and genetically based evolutionary processes. They have served as a useful group for evaluating the feeding specialization/physiological efficiency hypothesis. They have shown how the abiotic （thermal） environment interacts with host nutritional suitability to generate ＂voltinisrn/suitability＂ gradients in specialization or preference latitudinally, and geographical mosaics locally. Several studies reviewed here suggest strongly that the oscillation hypothesis for speciation does have considerable merit, but at the same time, some species-level host specializations may lead to evolutionary dead-ends, especially with rapid environmental/habitat changes involving their host plants. Latitudinal gradients in species richness and degree of herbivore feeding specialization have been impacted by recent developments in ecological genetics and evolutionary ecology. Localized insect- plant associations that span the biospectrum from polyphenisms, polymorphisms, biotypes, demes, host races, to cryptic speci

关键词： evolutionary dead-ends key innovations latitudinal gradients oscillation hypothesis of speciation polyspecialists preference/performance specialization/physiological efficiency hypothesis voltinism-suitability hypothesis

Impacts of climate warming on hybrid zone movement： Geographically diffuse and biologically porous ＂species borders＂

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Insect Science 2011年第2期18卷 121-159页

作者： j. mark Scriber Department of Entomology Michigan State University East Lansing Michigan McGuire Center for Lepidoptera and Biodiversity Flonda Museum of Natural History University of Florida Gainesville Florida USA

The ecology and evolutionary biology of insect-plant associations has real- ized extensive attention, especially during the past 60 years. The classifications （categorical designations） of continuous variation in biodiversity, ranging from global patterns （e.g., lat- itudinal gradients in species richness/diversity and degree of herbivore feeding specialization） to localized insect-plant associations that span the biospectrum from polyphenisms, polymorphisms, biotypes, demes, host races, to cryptic species, remain academically contentious. Semantic and biosystematic （taxonomical） disagreements sometimes detract from more important ecological and evolutionary processes that drive diversification, the dynamics of gene flow and local extinctions. This review addresses several aspects of insect specialization, host-associated divergence and ecological （including ＂hybrid＂） speciation, with special reference to the climate warming impacts on species borders of hybridiz- ing swallowtail butterflies （Papilionidae）. Interspecific hybrid introgression may result in collapse of multi-species communities or increase species numbers via homoploid hybrid speciation. We may see diverging, merging, or emerging genotypes across hybrid zones, all part of the ongoing processes of evolution. Molecular analyses of genetic mosaics and genomic dynamics with ＂divergence hitchhiking＂, combined with ecological, ethological and physiological studies of＂species porosity＂, have already begun to unveil some answers for some important ecological/evolutionary questions. （i） How rapidly can host-associated divergence lead to new species （and why doesn＇t it always do so, e.g., resulting in ＂incom- plete＂ speciation）？（ii） How might ＂speciation genes＂ function, and how/where would we find them？（iii） Can oscillations from specialists to generalists and back to specialists help explain global diversity in herbivorous insects？（iv） How could recombinant interspecific hybridization lead to divergence an

关键词： cryptic species divergence hitchhiking ecologiealspeciation host associateddivergence mosaic genomes range limits recombinant hybrid species phylogeography,polyspecialists species boundaries

A review of refinery complexity applications

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Petroleum Science 2017年第1期14卷 167-194页

作者： mark j. Kaiser Center for Energy Studies Louisiana State UniversityEnergy Coast and Environment Building Baton RougeLA 70803 USA

Refinery complexity quantifies the sophistication and capital intensity of a refinery and has found widespread application in facility classification, cost estimation, sales price models, and other uses. Despite the ubiquity and widespread use of refining complexity, however, surprisingly little material has been written on its applications. The pur- pose of this review is to describe the primary applications of refinery complexity and some recent extensions. A secondary purpose of this review is to provide a framework that unifies complexity applications and suggests avenues for future research. Examples illustrate the applications considered.

关键词： Cost estimation Functional complexityInverse problem Replacement cost Refineryclassification Sales price models

Segregation of F-2 interspecific hybrid growth performance and wing color patterns relative to parental species in the Papilio machaon species group （Lepidoptera： Papilionidae）

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Insect Science 2007年第5期14卷 389-400页

作者： j. mark SCRIBER Department of Entomology Michigan State University East Lansing Michigan USA

A strange Papilio female specimen with a prominent yellow wing band type very much like P. brevicauda （and also seen in P. machaon, and P. zelicaon） was captured in the forested mountains of southwest Vermont, USA. Despite its brevicauda-like appearance, it had mt-DNA of P. polyxenes. In eastern North America the P. brevicauda （Maritime Provinces of Canada） is currently believed to reflect previous （ancient） hybridization between ancestral P. machaon and P. polyxenes. It is uncertain whether the brevicauda-like wing trait features in the odd Vermont female may be a result of some introgression of P. machaon or P. brevicauda with P. polyxenes in eastern North America as seen also in the Ozark Mountains with P. joanae. Nonetheless, the significance of wing trait analyses in relation to hybrid zones with P. polyxenes remains relevant. The segregation of wing color patterns and hostplant use abilities （efficiencies and growth rates） were examined for laboratory hand-paired F-2 hybrids of P. zelicaon ~ Papilio polyxenes relative to the parental species and primary hybrids. The black adult color pattern characterizing P. polyxenes is presumed to be inherited as a simple autosomal dominant. These hybrids were examined to determine：（i） how F-1 primary hybrid offspring perform relative to the parental types in survival, growth rates, and growth efficiencies; and （ii） whether these larval traits and the adult color patterns might be linked with wing morphology in the F-2 hybrids. While the F-1 hybrids grew as well as the P. polyxenes parent （P. zelicaon was significantly less efficient and slower in growth than either of these）, we could not convincingly determine whether the growth performances of the F-2 segregants were linked with the parental wing patterns.

关键词： hybrid swarms feeding efficiencies autosomai trait genetics Papilio polyxenes,Papilio zelicaon Papilio brevicauda

Efficient ray casting of volumetric images using distance maps for empty space skipping

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Computational Visual Media 2020年第1期6卷 53-63页

作者： Lachlan j.Deakin mark A.Knackstedt Australian National University Canberra2601Australia

Volume and isosurface rendering are methods of projecting volumetric images to two dimensions for *** methods are common in medical imaging and scientific ***-mounted optical see-through displays have recently become an affordable technology and are a promising platform for volumetric image *** displayed on a head-mounted display must be presented at a high frame rate and with low latency to compensate for head *** latency can be jarring and may cause cybersickness which has similar symptoms to motion *** images can be very computationally expensive to render as they often have hundreds of millions of scalar ***,certain materials in images such as air surrounding an object boundary are often made transparent and need not be sampled,which improves rendering *** our previous work we introduced a novel ray traversal technique for rendering large sparse volumetric images at high frame *** method relied on the computation of an occupancy and distance map to speed up ray traversal through empty *** this work we achieve higher frame rates than our previous work with an improved method of resuming empty space skipping and the use of anisotropic Chebyshev distance *** optimised algorithm for computing Chebyshev distance maps on a graphical processing unit is introduced supporting real-time transfer function editing.

关键词： ray casting volume rendering isosurface rendering distance maps

Heart healthy equals prostate healthy and statins, aspirin, and/or metformin （S.A.M.） are the ideal recommendations for prostate cancer prevention

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Asian journal of Andrology 2015年第5期17卷 783-791,I0008页

作者： mark A Moyad Nicholas j Vogelzang Department of Urology University of Michigan Medical Center Ann Arbor Michigan USA Developmental Therapeutics Committee and Genitourinary Committee for US Oncology Research Comprehensive Cancer Centers of Nevada Las Vegas Nevada USA

Cardiovascular disease （CVD） has been the number one cause of death in the U.S. for 114 of the last 115 years. Lifestyle factors that promote CVD also appear to increase prostate cancer risk and those that reduce CVD risk also appear to reduce the risk of prostate cancer. The largest randomized trials utilizing dietary supplements or pharmacologic agents for prostate cancer prevention （Selenium and Vitamin E Cancer Prevention Trial [SELECT]） have also shed light on the problems and future solutions in this area. Dietary supplements that have not been found to be CVD protective, such as selenium and Vitamin E have not been found to be prostate protective. In addition, over exposure to specific anti-oxidants in nutritionally replete populations may be encouraging cancer growth. Futuretrials of dietary supplements to prevent prostate cancer could be problematic because by the time a definitive trial is initiated the participants will no longer be ＂deficient＂ in the nutrient being tested, which arguably occurred in the SELECT trial. It is also interesting that statins, aspirin, and/or metformin （S.A.M.） are 3 generic, low-cost, heart healthy agents derived from natural sources with separate mechanism of actions, which all appear to have the best benefit to risk ratio compared to any other agent available for prostate cancer prevention, especially aggressive disease, or as an ancillary agent （s） to conventional cancer treatment. It is time to focus on the forest over the trees and recommend proven CVD protective measures for men concerned about their risk of prostate cancer.

关键词： aspirin diet lifestyle metformin prostate cancer statins