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Therapeutics to harness the immune microenvironment in multiple myeloma

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Cancer Drug Resistance 2022年第3期5卷 647-661页

作者： james j.Ignatz-Hoover james j.Driscoll University Hospitals Seidman Cancer CenterClevelandOH 44106USA Department of Biochemistry Case Western Reserve UniversityClevelandOH 44106USA Hematopoietic and Immune Cancer Biology Program Case Comprehensive Cancer CenterCase Western Reserve UniversityClevelandOH 44106USA

Multiple myeloma(MM)remains an incurable,genetically heterogeneous disease characterized by the uncontrolled proliferation of transformed plasma cells nurtured within a permissive bone marrow(BM)*** therapies leverage the unique biology of MM cells and target the immune microenvironment that drives tumor growth and facilitates immune *** inhibitors and immunomodulatory drugs were initially introduced to complement and have now supplanted cytotoxic chemotherapy as frontline anti-myeloma ***,monoclonal antibodies,bispecific antibodies,and chimeric antigen receptor T cells were developed to revamp the immune system to overcome immune suppression and improve patient *** current MM therapies have markedly extended patient survival,acquired drug resistance inevitably emerges and drives disease *** logical progression for the next generation of MM therapies would be to design and validate agents that prevent and/or overcome acquired resistance to *** complex BM microenvironment promotes resistance to both current anti-myeloma agents and emerging *** cells are intertwined with a complex BM immune microenvironment that contributes to the development of adaptive drug ***,we describe recently FDA-approved and investigational anti-myeloma agents that directly or indirectly target the BM microenvironment to prevent or overcome drug *** effects of anti-myeloma agents may foster the development of rationally-designed drug cocktails that prevent BM-mediated resistance to immunotherapies.

关键词： Multiple myeloma drug resistance proteasome inhibitors immunomodulators immunotherapeutics adaptive resistance bone marrow microenvironment

Weak mismatch epitaxy and structural feedback in graphene growth on copper foil

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Nano Research 2013年第2期6卷 99-112页

作者： Neil R. Wilson Alexander j. Marsden Mohammed Saghir Catherine j. Bromley Renald Schaub Giovanni Costantini Thomas W. White Cerianne Partridge Alexei Barinov Pavel Dudin Ana M. Sanchez james j. Mudd Marc Walker Gavin R. Bell Department of Physics University of Warwick Coventry CV4 7AL UK EaStCHEM School of Chemistry University of St Andrews St Andrews KY16 9ST UK Department of Chemistry University of Warwick Coventry CV4 7AL UK Sincrotrone Trieste S.Cp.A. Area Science Park 1-34012 Basovizza Trieste Italy

Graphene growth by low-pressure chemical vapor deposition on low cost copper foils shows great promise for large scale applications. It is known that the local crystallography of the foil influences the graphene growth rate. Here we find an epitaxial relationship between graphene and copper foil. Interfacial restructuring between graphene and copper drives the formation of （nl0） facets on what is otherwise a mostly Cu（100） surface, and the facets in turn influence the graphene orientations from the onset of growth. Angle resolved photoemission shows that the electronic structure of the graphene is decoupled from the copper indicating a weak interaction between them. Despite this, two preferred orientations of graphene are found, ±8° from the Cu[010] direction, creating a non-uniform distribution of graphene grain boundary misorientation angles. Comparison with the model system of graphene growth on single crystal Cu（110） indicates that this orientational alignment is due to mismatch epitaxy. Despite the differences in symmetry the orientation of the graphene is defined by that of the copper. We expect these observations to not only have importance for controlling and understanding the growth process for graphene on copper, but also to have wider implications for the growth of two-dimensional materials on low cost metal substrates.

关键词： graphene chemical vapordeposition mismatch epitaxy structural feedback low energy electrondiffraction angle resolvedphoto-emissionspectroscopy (ARPES)

Intraspecific temporal resource partitioning at white-tailed deer feeding sites

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Current Zoology 2019年第2期65卷 139-146页

作者： David B. STONE james A. MARTIN Bradley S. COHEN Thomas j. PREBYL Charlie KILLMASTER Karl V. MILLER Warnell School of Forestry and Natural Resources University of Georgia Athens GA USA Savannah River Ecology Lab University of Georgia Aiken SC USA Department of Biology Tennessee Technological University Cookeville TN USA Georgia Department of Natural Resources Atlanta GA USA

Individuals may reduce competition by temporally partitioning their use of a shared resource. Behavioral differences between sexes in ungulates may encourage segregation as individuals attempt to avoid antagonistic interactions. However, dominant sex and age groups may reduce subordinates' access to food resources, regardless of the subordinate's sex. We hypothesized that white-tailed deer Odocoileus Virginian us temporally segregated at supplemental feedi ng sites based on social rank (subordinate: yearling males and adult females;dominant: adult males) and that segregation was affected by phase of the breeding season and diel cycle. If deer temporally segregate according to social rank, we predicted that the resulting activity patterns would manifest in one social class being relatively more susceptible to hunter-induced mortality. We used a multistate modeling approach to quantify temporal segregation and calculated the probability that a feeding site was in a particular state during diurnal and nocturnal hours for each of the 3 phases of the breeding season. We determined that transition probabilities differed by season and diel cycle and dominant and subordinate social classes clearly avoided each other, with <1% co-occurrenee at feedi ng sites. During the pre-breedi ng seas on, the probability of a subordi nate being present during diurnal hours was *** more likely than a dominant being present, but did not differ during nocturnal hours. There was no difference for dominants and subordinates during diurnal or no cturnal hours during the breedi ng season .In the post-breedi ng season, subordi nates were 1.7x more likely to occur at the feeding site than a dominant during diurnal hours but they did not differ during nocturnal hours. Our results indicate that dominance status influences temporal segregation at feeding sites and is affected by the phase of the breeding season. Therefore, the resulti ng activity patterns may in crease subordi nates' risk to human

关键词： competition multistate modeling predation risk supplemental feeding sites intraspecific temporal resource partitioning white-tailed deer

Guidelines for the use of accelerated pavement testing data in autonomous vehicle infrastructure research

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j.urnal of Traffic and Transportation Engineering(English Edition) 2019年第3期6卷 273-281页

作者： WynAND j.vdM.Steyn james W.Maina Department of Civil Engineering University of Pretoria

There is much research conducted on the vehicle technologies required for operation of autonomous vehicles(AV) on public roads, as well as analysis of the interaction between AV and the road environment. However, limited research exists on the impact of AV on road pavement structures. The research includes issues such as the effect of more channelized traffic loading, shorter inter-vehicle following distances and potential higher traffic volumes of more uniform vehicle types and loads. This paper discusses the application of existing and generation of new, relevant accelerated pavement testing(APT) data in understanding the effects of AV on pavement infrastructure. The paper presents development of provisional guidelines for the use and application of APT data to ensure that road pavement structures cope with anticipated increase in AV use. It is concludes that the use of AV fleets on existing road pavement infrastructure may lead to different behaviors and responses than what became the norm under non-autonomous vehicle fleets;appropriate analysis of existing APT data will contribute to the improved understanding of these expected changes in behaviors and responses; appropriate planning of AV operations-focused APT is possible with existing technology to contribute to the provision of economic and durable road pavement infrastructure in future.

关键词： Autonomous vehicles Accelerated pavement testing Vehicle-pavement interaction Road infrastructure

Burrowing Richardson's ground squirrels affect plant seedling assemblages via environmental but not seed bank changes

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Current Zoology 2020年第3期66卷 219-226页

作者： Levi j.Newediuk james F.Hare Department of Biological Sciences University of ManitobaWinnipegManitobaCanada R3T 2N2

In grassland ecosystems,burrowing mammals create disturbances,providing habitat for animal species and increasing plant community *** investigated whether seedling assemblages on Richardson's ground squirrel Urocitellus richardsonii mounds result from seed rearrangement or environmental changes that favor germination of certain species over *** test whether ground squirrels rearrange the seed bank by burrowing,we compared seed compositions among mounds,burrows,and undisturbed *** test whether ground squirrels change environmental conditions,we compared soil nitrate and bare ground cover on and off *** also compared seedlings that germinated on mounds with seedlings that germinated on artificial disturbances from which we removed aboveground *** nitrate and bare ground cover were significantly higher on mounds than artificial *** seed richness and abundance did not differ among mounds,burrows,and undisturbed soil,seedling richness was reduced on mounds relative to artificial *** disturbance favors seedlings that can capitalize on bare ground availability but are less able to immobilize nitrate,as opposed to perennial species that immobilize more nitrate but take longer to *** results suggest that Richardson's ground squirrels act as ecosystem engineers,although future research following succession on ground squirrel mounds is necessary to understand how they influence plant communities past the seedling stage.

关键词： burrowing disturbance ecosystem engineering Richardsons ground squirrel seed bank seedling species composition

The importance of large-diameter trees to the creation of snag and deadwood biomass

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Ecological Processes 2021年第1期10卷 380-393页

作者： james A.Lutz Soren Struckman Sara j.Germain Tucker j.Furniss Department of Wildland Resources S.J.and Jessie E.Quinney College of Natural ResourcesUtah State University5230 Old Main HillLoganUT 84322-5230USA

Background:Baseline levels of tree mortality can,over time,contribute to high snag densities and high levels of deadwood(down woody debris)if fire is infrequent and decomposition is *** can be important for tree recruitment,and it plays a maj.r role in terrestrial carbon cycling,but deadwood is rarely examined in a spatially explicit ***:Between 2011 and 2019,we annually tracked all trees and snags≥1 cm in diameter and mapped all pieces of deadwood≥10 cm diameter and≥1 m in length in 25.6 ha of Tsuga heterophylla/Pseudotsuga menziesii *** analyzed the amount,biomass,and spatial distribution of deadwood,and we assessed how various causes of mortality that contributed uniquely to deadwood ***:Compared to aboveground woody live biomass of 481 Mg ha^(−1)(from trees≥10 cm diameter),snag biomass was 74 Mg ha^(−1) and deadwood biomass was 109 Mg ha^(−1)(from boles≥10 cm diameter).Biomass from large-diameter trees(≥60 cm)accounted for 85%,88%,and 58%,of trees,snags,and deadwood,*** aboveground woody live and dead biomass was 668 Mg ha^(−1).The annual production of downed wood(≥10 cm diameter)from tree boles averaged 4 Mg ha^(−1) yr^(−1).Woody debris was spatially heterogeneous,varying more than two orders of magnitude from 4 to 587 Mg ha^(−1) at the scale of 20 m×20 m *** all causes of deadwood creation varied in importance between large-diameter trees and small-diameter *** of standing stems and deadwood had weak inverse distributions,reflecting the long period of time required for trees to reach large diameters following antecedent tree mortalities and the centennial scale time required for deadwood ***:Old-growth forests contain large stores of biomass in living trees,as well as in snag and deadwood biomass pools that are stable long after tree *** biomass(or carbon)in deadwood pools can lead to substantial underestimations of sequestration and stability.

关键词： Carbon sequestration Old-growth forest Pseudotsuga menziesii Tree mortality Tsuga heterophylla Wind River Forest Dynamics Plot

Effect of oxygen and nitrogen functionalization on the physical and electronic structure of graphene

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Nano Research 2015年第8期8卷 2620-2635页

作者： Alexander j. Marsden Peter Brommer james j. Mudd M. Adam Dyson Robert Cook Maria Asensio j.se Avila Ana Levy j.remy Sloan David Quigley Gavin R. Bell Neil R. Wilson Department of Physics University of Warwick Coventry UK Centre for Scientific Computing University of Warwick Coventry UK Synchrotron SOLEIL L'Orme des Merisiers Saint Aubin-BP 48 91192 Gifsur Yvette Cedex France

Covalent functionalization of graphene offers opportunities for tailoring its properties and is an unavoidable consequence of some graphene synthesis techniques. However, the changes induced by the functionalization are not well understood. By using atomic sources to control the extent of the oxygen and nitrogen functionalization, we studied the evolution in the structure and properties at the atomic scale. Atomic oxygen reversibly introduces epoxide groups whilst, under similar conditions, atomic nitrogen irreversibly creates diverse functionalities including substitutional, pyridinic, and pyrrolic nitrogen. Atomic oxygen leaves the Fermi energy at the Dirac point （i.e., undoped）, whilst atomic nitrogen results in a net n-doping; however, the experimental results are consistent with the dominant electronic effect for both being a transition from delocalized to localized states, and hence the loss of the signature electronic structure of graphene.

关键词： graphene functionalization chemical vapor deposition density functional theory

Investigation of alkaline-crude oil reaction

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Petroleum 2015年第1期1卷 31-39页

作者： james j.Sheng Texas Tech University

One of the mechanisms of alkaline flooding relies on alkaline reaction with organic acids(saponifiable components) in the crude oil to produce an in situ surfactant called soap that lowers interfacial tensions. However, this mechanism is not quantified in the literature. For example, what is the fraction of acid components which react with alkaline solution to generate soap? How much soap can be generated?In this paper, this mechanism and related issues are discussed, analyzed or quantified. In particular, the numerical simulation approach is used. The results show that only a fraction of acid components can be converted into soap; the amount of generated soap could be low. A minimum pH(e.g. 9) is needed for the acids to be converted to soap. The literature information on the effect of amount of acid components(total acid number) on oil recovery is also discussed.

关键词： Alkali Alkaline flooding Crude oil Acid number Soap Surfactant

Studies on Enzyme Kinetics by Microchip and Related Techniques

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高等学校化学学报 2004年第Z1期25卷 165-166页

作者： james j. Bao WANG Huai-Feng ZHOU Da-Wei Ken R. Wehmeyer College of Pharmaceuticals Tianjin University Tianjin 300072 China College of Pharmaceuticals Tianjin University Tianjin 300072 China College of Pharmaceuticals Tianjin University Tianjin 300072 China Procter & Gamble Pharmaceuticals 8700 Mason-Montgomery Road Mason OH 45040 USA

Both conventional and microchip-based capillary electrophoresis(CE) technologies have been used for the analysis of enzymes. Practical procedures of using CE to determine the Km and Vmax values of an enzyme have been developed. By studying the inhibition to the enzyme, it is possible to select a suitable drug candidate. When compared with the conventional CE method, single lane microchip-based method can improve the speed for the assay three times. By using multiple lane-based microchip, the speed can be further increased.

关键词： Enzyme Enzyme kinetics Inhibition Enzyme activity