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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

The organization of societal conflicts by pavement ants Tetramorium caespitum： an agent-based model of amine-mediated decision making

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Current Zoology 2016年第3期62卷 277-284页

作者： Kevin M. hoover Andrew N. BUBAK Isaac j. LAw jazmine D. w. YAEGER Kenneth j. RENNER john G. SwALLOw Michael j. GREENE Department of Integrative Biology University of Colorado Denver Denver CO 80217-3364 USA Neuroscience Program University of Colorado Anschutz Medical Campus Aurora CO 80045 USA Department of Biology University of South Dakota Vermillion South Dakota 57069 USA

Ant colonies self-organize to solve complex problems despite the simplicity of an individual ant＇s brain. Pavement ant Tetramorium caespitum colonies must solve the problem of defending the ter- ritory that they patrol in search of energetically rich forage. when members of 2 colonies randomly interact at the territory boundary a decision to fight occurs when： 1） there is a mismatch in nest- mate recognition cues and 2） each ant has a recent history of high interaction rates with nestmate ants. Instead of fighting, some ants will decide to recruit more workers from the nest to the fighting location, and in this way a positive feedback mediates the development of colony wide wars. In ants, the monoamines serotonin （5-HT） and octopamine （OA） modulate many behaviors associated with colony organization and in particular behaviors associated with nestmate recognition and ag- gression. In this article, we develop and explore an agent-based model that conceptualizes how in- dividual changes in brain concentrations of 5-HT and OA, paired with a simple threshold-based de- cision rule, can lead to the development of colony wide warfare. Model simulations do lead to the development of warfare with 91% of ants fighting at the end of 1 h. when conducting a sensitivity analysis, we determined that uncertainty in monoamine concentration signal decay influences the behavior of the model more than uncertainty in the decision-making rule or density. we conclude that pavement ant behavior is consistent with the detection of interaction rate through a single timed interval rather than integration of multiple interactions.

关键词： agent-based model aggressive behavior ants decision making monoamines octopamine serotonin.

Identification of proteins involved in lignocellulose degradation using in gel zymogram analysis combined with mass spectroscopy-based peptide analysis of gut proteins from larval Asian Ionghorned beetles, Anoplophora glabripennis

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Insect Science 2010年第3期17卷 253-264页

作者： Scott M. Geib Ming Tien Kelli hoover Departments of Biochemistry and Molecular Biology Departments of Entomology The Pennsylvania State University University Park Pennsylvania USA

Enzyme activities toward lignocellulose substrates were analyzed in the gut of larval Asian longhorned beetle （Anoplophora glabripennis）. Total protein was extracted from gut contents of wild collected larvae from an invasive population in worchester, MA, USA. From these protein extracts, lignocellulolytic activities were measured （β-1,4- endoglucanase,β-1,4-glucosidase and birch wood xylanase）.β-1,4-glucosidase activity was 0.075 μmol glucose/mg protein per min, endoglucanase activity was measured at 0.41/zmol glucose/mg protein per min and xylanase activity was 0.058μmol xylose/mg protein per min. To identify specific enzymes that may provide these activities, zymogram analysis was performed to detect enzymes active toward carboxymethyl cellulose （CMC）, 4-methylumbelliferyl-β-D-glueopyranoside and birch wood xylan. Three protein bands were found to be active toward CMC, three displayed β-1,4-glucosidase, and one displayed xylanase activity. Proteins from active bands from these zymograms were then identified by in-gel trypsin digestions followed by peptide identification by matrix-assisted laser desorption ionization - time of flight - time of flight mass spectrometry （MS）. A custom A. glabripennis transcriptome database was used for peptide identification, giving highly significant matches in all MS analyses. These matches were then searched against the National Center for Biotechnology Information database to provide annotation to the transcripts and provide possible classification. From these analyses, we were able to detect enzymes active toward cellulose and xylan, and proteins putatively involved in lignocellulose degradation in the gut of this wood-feeding insect. Future research will be focused on characterizing these enzymes through cloning and expression experiments and understanding how the lignocellulose degradation system functions in the gut of this insect.

关键词： beta-glucosidase cellulase Cerambycidae endoglucanase proteomics xylanase

Preparation and Characterization of TaN ALD Precursors

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半导体技术 2004年第7期29卷 82-85,91页

作者： Tracy Yund Cynthia A. hoover Praxair Inc. 175 E. Park Dr. Tonawanda NY 14150Praxair Inc. 175 E. Park Dr. Tonawanda NY 14150

High purity organic-tantalum precursors forthin film ALD TaN were synthesized andcharacterized. Vapor pressure and thermal stabilityof these precursors were studied. From the vaporpressure analysis, it was found that TBTEMT has ahigher vapor pressure than any other published liq-uid TaN precursor, including TBTDET,TAITMATA,and IPTDET. Thermal stability of the alkyl groupson the precursors was investigated using a 1H NMRtechnique. The results indicated that the tert-butylimino group is the most stable group onTBTDET and TBTEMT as compared to thedialkylamido groups. Thermal stability of TaN pre-cursors decreased in the following order: TBTDET> PDMAT > TBTEMT. In conclusion, precursor va-por pressure and thermal stability were tuned bymaking slight variations in the ligand sphere aroundthe metal center.

关键词：热稳定性汽压分析 TBTDET PDMAT TBTEMT TaN ALD

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Specificity of Developmental Resistance in Gypsy Moth (Lymantria dispar) to two DNA-Insect Viruses

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Virologica Sinica 2009年第5期24卷 493-500页

作者： Kelli hoover Michael j. Grove The Pennsylvania State University Department of Entomology 501 ASI Building University Park PA 16802 USA

Gypsy moth （Lymantria dispar） larvae displayed marked developmental resistance within an instar to L dispar M nucleopolyhedrovirus （LdMNPV） regardless of the route of infection （oral or intrahemocoelic） in a previous study, indicating that in gypsy moth, this resistance has a systemic component. In this study, gypsy moth larvae challenged with the Amsacta moorei entomopoxvirus （AMEV） showed developmental resistance within the fourth instar to oral, but not intrahemocoelic, inoculation. In general, gypsy moth is considered refractory to oral challenge with AMEV, but in this study, 43% mortality occurred in newly molted fourth instars fed a dose of 5×10^6 large spheroids of AMEV; large spheroids were found to be more infectious than small spheroids when separated by a sucrose gradient. Developmental resistance within the fourth instar was reflected by a 2-fold reduction in mortality （18%-21%） with 5 X 106 large spheroids in larvae orally challenged at 24, 48 or 72 h post-molt. Fourth instars were highly sensitive to intrahemocoelic challenge with AMEV; 1PFU produced approximately 80% mortality regardless of age within the instar. These results indicate that in gypsy moth, systemic developmental resistance may be specific to LdMNPV, reflecting a co-evolutionary relationship between the baculovirus and its host.

关键词： Resistance Co-evolution Baculovirus Entomopoxvirus Gypsy moth

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Hydrodynamic instability experiments with three-dimensional modulations at the National Ignition Facility

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High Power Laser Science and Engineering 2015年第2期3卷 1-8页

作者： V.A.Smalyuk S.V.weber D.T.Casey D.S.Clark j.E.Field S.w.Haan A.V.Hamza D.E.hoover O.L.Landen A.Nikroo H.F.Robey C.R.weber Lawrence Livermore National Laboratory NIF Directorate General Atomics

The first hydrodynamic instability growth measurements with three-dimensional(3D) surface-roughness modulations were performed on CH shell spherical implosions at the National Ignition Facility(NIF) [G. H. Miller, E. I. Moses, and C. R. wuest, Opt. Eng. 43, 2841(2004)]. The initial capsule outer-surface amplitudes were increased approximately four times, compared with the standard specifications, to increase the signal-to-noise ratio, helping to qualify a technique for measuring small 3D modulations. The instability growth measurements were performed using x-ray through-foil radiography based on time-resolved pinhole imaging. Averaging over 15 similar images significantly increased the signal-to-noise ratio, making possible a comparison with 3D simulations. At a convergence ratio of～2.4, the measured modulation levels were～3 times larger than those simulated based on the growth of the known imposed initial surface modulations. Several hypotheses are discussed, including increased instability growth due to modulations of the oxygen content in the bulk of the capsule. Future experiments will be focused on measurements with standard 3D ‘nativeroughness' capsules as well as with deliberately imposed oxygen modulations.

关键词： Hydrodynamic instabilities

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Targeted quantitative profiling of metabolites and gene transcripts associated with 4-aminobutyrate (GABA) in apple fruit stored under multiple abiotic stresses

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Horticulture Research 2018年第1期5卷 66-79页

作者： Carolyne j.Brikis Adel Zarei Greta Z.Chiu Kristen L.Deyman jingyun Liu Christopher P.Trobacher Gordon j.hoover Sanjeena Subedi jennifer R.DeEll Gale G.Bozzo Barry j.Shelp Department of Plant Agriculture University of GuelphGuelphOntarioN1G 2W1Canada Department of Mathematical Sciences Binghamton UniversityBinghamtonNY13902USA Ontario Ministry of Agriculture Food and Rural AffairsBox 5871283 Blueline Rd.at Highway 3SimcoeOntarioN3Y 4N5Canada

4-Aminobutyrate accumulates in plants under abiotic ***,targeted quantitative profiling of metabolites and transcripts was conducted to monitor glutamate-and polyamine-derived 4-aminobutyrate production and its subsequent catabolism to succinate or 4-hydroxybutyrate in apple(Malus x domestica Borkh.)fruit stored at 0°C with 2.5 kPa O2 and 0.03 or 5 kPa CO2 for 16 ***-temperature-induced protein hydrolysis appeared to be responsible for the enhanced availability of amino acids during early storage,and the resulting higher glutamate level stimulated 4-aminobutyrate levels more than *** CO2 increased the levels of polyamines,as well as succinate and 4-hydroxybutyrate,during early storage,and 4-aminobutyrate and 4-hydroxybutyrate over the longer *** of all of the genes likely involved in 4-aminobutyrate metabolism from glutamate/polyamines to succinate/4-hydroxybutyrate was induced in a co-ordinated ***2-regulated expression of apple GLUTAMATE DECARBOXYLASE 2,AMINE OXIDASE 1,ALDEHYDE DEHYDROGENASE 10A8 and POLYAMINE OXIDASE 2 was evident with longer term *** suggested that respiratory activities were restricted by the elevated CO2/O2 environment,and that decreasing NAD+availability and increasing NADPH and NADPH/NADP+,respectively,played key roles in the regulation of succinate and 4-hydroxybutyate ***,these findings suggest that both transcriptional and biochemical mechanisms are associated with 4-aminobutyrate and 4-hydroxybutyrate metabolism in apple fruit stored under multiple abiotic stresses.

关键词： hydrolysis subsequent restricted

A test of two mechanisms proposed to optimize grassland aboveground primary productivity in response to grazing

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journal of Plant Ecology 2012年第4期5卷 357-365页

作者： A.K.Knapp D.L.hoover j.M.Blair G.Buis D.E.Burkepile A.Chamberlain S.L.Collins R.w.S.Fynn K.P.Kirkman M.D.Smith D.Blake N.Govender P.O'Neal T.Schreck A.Zinn Graduate Degree Program in Ecology and Department of Biology Colorado State UniversityFort CollinsCO 80526USA Division of Biology Kansas State UniversityManhattanKS 66506USA Department of Biological Sciences Florida International UniversityNorth MiamiFL 33181USA Department of Biology MSC03-2020University of New MexicoAlbuquerqueNM 87131USA Okavango Research Institute University of BotswanaPrivate Bag 285MaunBotswana School of Biological and Conservation Science University of KwaZulu-NatalPrivate Bag X01Scottsville 3209PietermaritzburgSouth Africa Department of Ecology and Evolutionary Biology Yale UniversityNew HavenCT 06520USA Scientific Services Kruger National ParkPrivate Bag X402Skukuza1350South Africa Department of Ecology and Evolutionary Biology University of CaliforniaIrvineCA 92697USA

Aims Mesic grasslands have a long evolutionary history of grazing by large herbivores and as a consequence,grassland species have numerous adaptations allowing them to respond favourably to *** empirical evidence has been equivocal,theory predicts that such adaptations combined with alterations in resources can lead to grazing-induced overcompensation in aboveground net primary production(ANPP;grazed ANPP>ungrazed ANPP)under certain *** tested two specific predictions from ***,overcompensation is more likely to occur in annually burned grasslands because limiting nutrients that would be lost with frequent fires are recycled through grazers and stimulate ***,overcompensation of biomass lost to grazers is more likely to occur in unburned sites where grazing has the greatest effect on increasing light availability through alterations in canopy *** we tested these nutrient versus light-based predictions in grazed grasslands that had been annually burned or protected from fire for>20 *** assessed responses in ANPP to grazing by large ungulates using both permanent and moveable grazing exclosures(252 exclosures from which biomass was harvested from 3192 quadrats)in a 2-year *** sites were located at the Konza Prairie Biological Station(KPBS)in North America and at Kruger National Park(KNP)in South *** KPBS,sites were grazed by North American bison whereas in KNP sites were grazed either by a diverse suite of herbivores(*** wildebeest,Burchell’s zebra,African buffalo)or by a single large ungulate(African buffalo).Important Findings we found no evidence for overcompensation in either burned or unburned sites,regardless of grazer ***,there was no support for either mechanism leading to ***,complete compensation of total biomass lost to grazers was the most common response characterizing grazing–ANPP relationships with,in some cases,undercompensation of grass ANPP being of

关键词： aboveground net primary production fire forbs herbivores savanna

Ponseti method treatment of neglected idiopathic clubfoot:Preliminary results of a multi-center study in Nigeria

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world journal of Orthopedics 2017年第8期8卷 624-630页

作者： Olayinka O Adegbehingbe Adeoye j Adetiloye Ladipo Adewole Dennis U Ajodo Nosirudeen Bello Oluwadare Esan Alex C hoover james Ior Omolade Lasebikan Owolabi Ojo Anthony Olasinde David Songden jose A Morcuende Department of Orthopedic Surgery and Traumatology Obafemi Awolowo University Gwarinpa General Hospital Federal Capital Territory Lagos State University College of Medicine Federal Medical Center Keffi Federal Medical Center Abeokuta Carver College of Medicine University of Iowa NKST Hospital Mkar National Orthopedic Hospital Federal Medical Center Owo Ekiti State Teaching Hospital

AIM To evaluate the effectiveness of the Ponseti method for initial correction of neglected clubfoot cases in multiple centers throughout *** Patient charts were reviewed through the International Clubfoot Registry for 12 different Ponseti clubfoot treatment centers and 328 clubfeet(225 patients) met inclusion criteria. All patients were treated by the method described by Ponseti including manipulation and casting with percutaneous Achilles tenotomy as *** A painless plantigrade foot was obtained in 255 feet(78%) without the need for extensive soft tissue release and/or bony *** we conclude that the Ponseti method is a safe, effective and low-cost treatment for initial correction of neglected idiopathic clubfoot presenting after walking age. Longterm follow-up will be required to assess outcomes.

关键词： Ponseti method Neglected clubfoot Nigeria walking age