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Peginterferon Lambda-1a, a New Therapeutic for Hepatitis C Infection, from Bench to Clinic

Journal of Clinical and Translational Hepatology 2013年第2期1卷 116-124页

作者： Henrik Andersen Jeff meyer Jeremy Freeman Sean E.Doyle Kevin Klucher dennis m.miller Diana Hausman Jan L.Hillson ZymoGenetics/Bristol-myers Squibb Seattle WA 98102 USA EmD Serono Billerica MA USA Oncothyreon Inc. Seattle WA USA CPTxBio Woodinville WA USA

Chronic infection with hepatitis C virus (HCV) is estimated to affect approximately 3% of the world's population and cause 350,000 deaths each *** number of years,the standard of care has been combination therapy with recombinant alfa interferons—originally as native proteins but more recently as polyethyleneglycol-modified derivatives—and ribavirin,with the recent addition of an NS3 protease inhibitor for HCV genotype ***,therapeutic alfa interferons are associated with a significant burden of treatment-limiting adverse events,including musculoskeletal and influenza-like symptoms,hematologic cytopenias,autoimmune disease,fatigue,and other neurologic *** 2003,a team at ZymoGenetics (now a fully owned subsidiary of Bristol-myers Squibb) and a second,independent group simultaneously identified a new class of interferons—the type Ⅲ lambda interferons—with near-identical activity to the type Ⅰ alfa interferons in hepatocytes but with an unrelated and less ubiquitous *** evaluation of the type Ⅲ interferon system demonstrated antiviral activity against HCV in vitro with limited activity in peripheral blood mononuclear cells and other nonhepatocyte cell types,supporting its development as a potentially better-tolerated therapy for viral *** lambda-1a (Lambda) is an investigational type Ⅲ therapeutic agent originally developed at ZymoGenetics that is currently in Phase 3 studies for the treatment of *** this review,we describe the selection of the Lambda molecule and its preclinical and early clinical development,and how the resulting data have helped to establish the differentiated safety profile for Lambda—with fewer influenza-like and musculoskeletal symptoms and less hematologic toxicity than the alfa interferons—that was seen in later studies.

关键词： Discovery HCV Interferonλ

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movie therapy for children with amblyopia:restoring binocular vision with brain plasticity

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Science China(Life Sciences) 2022年第3期65卷 654-656页

作者： Bernhard A.Sabel dennis m.Levi Institute of medical Psychology Medical FacultyOtto-v.-Guericke University of MagdeburgMagdeburg 39120Germany Herbert Wertheim School of Optometry&Vision Science and Helen Wills Neuroscience Institute University of CaliforniaBerkeley CA 94720USA

Amblyopia is a common neurodevelopmental disorder that occurs when the two eyes do not send well matched visual signals to the brain early in *** mismatch of the information coming from both eyes can have different causes:it may be due to differences in image clarity or contrast(called"anisometropia")because the two eyes require different corrective lens powers.

关键词： movie matched visual

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Inverse-designed spinodoid metamaterials

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npj Computational materials 2020年第1期6卷 1029-1038页

作者： Siddhant Kumar Stephanie Tan Li Zheng dennis m.Kochmann mechanics&materials Lab Department of Mechanical and Process EngineeringETH Zürich8092 ZürichSwitzerland Faculty of Electrical Engineering Mathematics and Computer ScienceDelft University of Technology2628 CD DelftNetherlands Graduate Aerospace Laboratories California Institute of TechnologyPasadenaCA 91125USA

After a decade of periodic truss-,plate-,and shell-based architectures having dominated the design of metamaterials,we introduce the non-periodic class of spinodoid *** by natural self-assembly processes,spinodoid metamaterials are a close approximation of microstructures observed during spinodal phase *** theoretical parametrization is so intriguingly simple that one can bypass costly phase-field simulations and obtain a rich and seamlessly tunable property ***,breaking with the periodicity of classical metamaterials is the enabling factor to the large property space and the ability to introduce seamless functional *** introduce an efficient and robust machine learning technique for the inverse design of(meta-)materials which,when applied to spinodoid topologies,enables us to generate uniform and functionally graded cellular mechanical metamaterials with tailored direction-dependent(anisotropic)stiffness and *** specifically present biomimetic artificial bone architectures that not only reproduce the properties of trabecular bone accurately but also even geometrically resemble natural bone.

关键词： density property periodic

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Deep learning for visualization and novelty detection in large X-ray diffraction datasets

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npj Computational materials 2021年第1期7卷 942-947页

作者： Lars Banko Phillip m.maffettone dennis Naujoks Daniel Olds Alfred Ludwig materials Discovery and Interfaces Institute for MaterialsRuhr University BochumBochumGermany National Synchrotron Light Source II Brookhaven National LaboratoryUptonNYUSA ZGH Center for Interface-Dominated High Performance MaterialsRuhr University BochumBochumGermany

We apply variational autoencoders(VAE)to X-ray diffraction(XRD)data analysis on both simulated and experimental thin-film *** show that crystal structure representations learned by a VAE reveal latent information,such as the structural similarity of textured diffraction *** other artificial intelligence(AI)agents are effective at classifying XRD data into known phases,a similarly conditioned VAE is uniquely effective at knowing what it doesn’t know:it can rapidly identify data outside the distribution it was trained on,such as novel phases and *** capabilities demonstrate that a VAE is a valuable AI agent for aiding materials discovery and understanding XRD measurements both‘on-the-fly’and during post hoc analysis.

关键词： VAE uniquely latent

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SYSTEmS ENGINEERING RESEARCH

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Journal of Systems Science and Systems Engineering 2008年第3期17卷 319-333页

作者： Abd-El-Kader SAHRAOUI dennis m.BUEDE Andrew P.SAGE LAAS-CNRS and Universitéde Toulouse 7 Avenue du Colonel Roche Toulouse31077France Innovative Decisions Inc.2139 Golf Course Dr.RestonVA 20191 USA Dept.of Systems Engineering and Operations Research George Mason UniversityFairfaxVA 22030 USA

In this paper, we propose selected research topics that are believed central to progress and growth in the application of systems engineering （SE）. As a professional activity, and as an intellectual activity, systems engineering has strong links to such associated disciplines as decision analysis, operation research, project management, quality management, and systems design. When focussing on systems engineering research, we should distinguish between subjects that are of systems engineering essence and others that more closely correspond to those that are more relevant for related disciplines.

关键词： Systems engineering systems of systems requirements engineering systems families

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Review of coal and gas outburst in Australian underground coal mines

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International Journal of mining Science and Technology 2019年第6期29卷 815-824页

作者： dennis J.Black CoalGAS Department of Civil Mining and Environmental Engineering University of Wollongong

Outburst of coal and gas represents a significant risk to the health and safety of mine personnel working in development and longwall production face *** have been over 878 outburst events recorded in twenty-two Australian underground coal *** outburst incidents have been associated with abnormal geological *** of Australian outburst incidents and mining experience in conditions where gas content was above current threshold levels are presented and *** experience suggests that for gas con-tent below 9.0 m^3/t,mining in carbon dioxide(CO2)rich seam gas conditions does not pose a greater risk of outburst than mining in CH4 rich seam gas *** experience also suggests that where no abnormal geological structures are present that mining in areas with gas content greater than the current accepted threshold levels can be undertaken with no discernible increase in outburst *** current approach to determining gas content threshold limits in Australian mines has been effective in prevent-ing injury from outburst,however operational experience suggests the current method is overly conser-vative and in some cases the threshold limits are low to the point that they provide no significant reduction in outburst *** factors that affect outburst risk,such as gas pressure,coal toughness and stress and geological structures are presently not incorporated into outburst threshold limits adopted in Australian *** factors and the development of an outburst risk index applicable to Australian underground coal mining conditions are the subject of ongoing research.

关键词： Outburst Desorption rate DRI Threshold limit

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Spatially-graded 3D-printed viscoelastic truss metamaterials for impact trajectory control and energy absorption

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Theoretical & Applied mechanics Letters 2024年第5期14卷 378-385页

作者： Kaoutar Radi Raphaël N.Glaesener Siddhant Kumar dennis m.Kochmann mechanics&materials Lab Department of Mechanical and Process EngineeringETH Zürich 8092Switzerland mechanics&materials Computing Lab Department of Materials Science&EngineeringTU Delft 2628 CNNetherlands

This study demonstrates that two-and three-dimensional spatially graded,truss-based polymeric-material metamaterials can be designed for beneficial impact mitigation and energy absorption *** a combination of numerical and experimental techniques,we highlight the broad property space of periodic viscoelastic trusses,realized using 3D printing via selective laser *** beyond periodic designs,we investigate the impact response of spatially variant viscoelastic lattices in both two and three *** result reveal that introducing spatial variations in lattice topology allows for redirecting of the impact trajectory,opening new opportunities for engineering and tailoring lightweight materials with target impact *** is achieved through the combined selection of base material and metamaterial design.

关键词： metamaterial 3D Printing Viscoelasticity Impact Truss Finite element method

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Evaluation of steroidogenic capacity after follicle stimulating hormone stimulation in bovine granulosa cells of Revalor 200~ implanted heifers

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Journal of Animal Science and Biotechnology 2014年第3期5卷 280-285页

作者： ANDrea D Stapp Craig A Gifford dennis m Hallford Jennifer A Hernandez Gifford Department of Animal Science Oklahoma State University Department of Animal and Range Science New Mexico State University Department of Animal Science 114B Animal Science BuildingOklahoma State University

Background： Heifers not used as breeding stock are often implanted with steroids to increase growth efficiency thereby altering hormone profiles and potentially changing the environment in which ovarian follicles develop. Because bovine granulosa cell culture is a commonly used technique and often bovine ovaries are collected from abattoirs with no record of implant status, the objective of this study was to determine if the presence of an implant during bovine granulosa cell development impacts follicle stimulating hormone-regulated steroidogenic enzyme expression. Paired ovaries were collected from 16 feedlot heifers subjected to 1 of 3 treatments： non-implanted （n = 5）, Revalor 200 for 28 d （n = 5）, or Revalor 200 for 84 d （n = 6）. Small follicle （1 to 5 mm） granulosa cells were isolated from each pair and incubated with phosphate buffered saline （n = 16） or 100 ng/mL follicle stimulating hormone （n = 16） for 24 h. Results： Granulosa cells of implanted heifers treated with follicle stimulating hormone produced medium concentrations of progesterone similar （P = 0.22） to non-implanted heifers, while medium estradiol concentrations were increased （P 〈 0.10） at 28 and 84 d compared to non-implanted heifers indicating efficacy of treatment. Additionally, real-time PCR analysis in response to follicle stimulating hormone treatment demonstrated a decrease in steroidogenic acute regulatory protein （P = 0.05） mRNA expression in heifers implanted for 84 d and an increase in P450 side chain cleavage mRNA in granulosa cells of heifers implanted for 28 （P 〈 0.10） or 84 d （P 〈 0.05） compared to non-implanted females. However, no difference in expression of 3-beta-hydroxysteroid dehydrogenase （P= 0.57） and aromatase （P = 0.23） were demonstrated in implanted or non-implanted heifers. Conclusions： These results indicate follicles which develop in the presence of high concentrations of androgenic and estrogenic steroids via an implant tend to demonstrate an altered capacity to res

关键词： Bovine Follicle stimulating hormone Granulosa cells Implant Steroidogenesis

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Response of saproxylic insect communities to logging history, tree species, stage of decay, and wood posture in the central Nearctic boreal forest

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Journal of Forestry Research 2018年第5期29卷 1365-1377页

作者： R.W.James dennis Jay R.malcolm Sandy m.Smith m.Isabel Bellocq Faculty of Forestry University of Toronto 33 Willcocks St.Toronto ON M5S 3B3 Canada Departamento de Ecología Genética y EvoluciónFacultad de Ciencias Exactas y NaturalesUniversidad de Buenos Aires and IEGEBA (CONICET)Buenos Aires Argentina

Saproxylic insect assemblages are essential functional components of forest ecosystems that can be affected by forest *** used a split-plot ANOVA design to analyze differences in selected saproxylic insects（all arthropod orders and dipteran and parasitic hymenopteran families） emerging from dead wood of sites with different logging histories（horse-logged,mechanically-logged and unlogged）,tree species（Populus and Picea）,stage of decay（early-and late-decay stages） and posture（standing and downed logs） in the boreal forest of central *** clear effects of logging history were seen for the studied taxa; however,interaction between logging history and other dead wood features was *** consistently emerged more from Populus than from Picea dead *** of the studied saproxylic families were more abundant in late-decay than in early-decay *** of the Cecidomyiidae,Ceratopogonidae,Empididae,mycetophilidae and Sciaridae families,and hymenopterans of the Diapriidae and Ichneumonidae families were significantly more abundant in downed than in standing dead *** contrast,mymaridae was most abundant in standing dead *** study provides evidence that some insects at high taxonomic levels respond differently to dead wood quality,and this could inform future management strategies in the boreal forest for the conservation of saproxylic fauna and their ecological functions.

关键词： Boreal forest Dead wood quality Forest harvesting High-level taxa Saproxylic insects

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The development of *** erosion prediction and modeling

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International Soil and Water Conservation Research 2013年第2期1卷 1-11页

作者： John m.Laflen dennis C.Flanagan lowa State U. USDA-ARS National Soil Erosion Research Laboratory West LafayetteIN

Soil erosion prediction technology began over 70 years ago when Austin Zingg published a relationship between soil erosion(by water)and land slope and length,followed shortly by a relationship by Dwight Smith that expanded this equation to include conservation ***,it was nearly 20 years before this work's expansion resulted in the Universal Soil Loss Equation(USLE),perhaps the foremost achievement in soil erosion prediction in the last *** USLE has increased in application and complexity,and its usefulness and limitations have led to the development of additional technologies and new science in soil erosion research and *** among these new technologies is the Water Erosion Prediction Project(WEPP)model,which has helped to overcome many of the shortcomings of the USLE,and increased the scale over which erosion by water can be *** of application of erosion prediction include almost all land types:urban,rural,cropland,forests,rangeland,and construction *** applications of WEPP include prediction of radioactive material movement with soils at a superfund cleanup site,and near real-time daily estimation of soil erosion for the entire state of Iowa.

关键词： Universal Soil Loss Equation Water Erosion Prediction Project Soil erosion Erosion prediction History of erosion prediction

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