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Novel polysaccharide-protein conjugates provide an immunogenic 13-valent pneumococcal conjugate vaccine for ***

Synthetic and Systems biotechnology 2017年第1期2卷 49-58页

作者： allison e.b.turner Jonas e.Gerson Helen Y.So Daniel J.Krasznai Adrienne J.St.Hilaire Donald F.Gerson Vaccine Research and Development PnuVax Incorporated Headquarters134 Albert St.KingstonOntarioK7L 3V2Canada Vaccine Research and Development PnuVax Incorporated Laboratories6000 Royalmount Ave.MontrealQuebecH4P 2T1Canada

Pneumonia remains the single leading cause of childhood death *** the commercial availability of multiple pneumococcal conjugate vaccines(PCVs),high dosage cost and supply shortages prevent PCV delivery to much of the developing *** current work presents high-yield pneumococcal conjugates that are immunogenic in animals and suitable for use in human vaccine *** 13-valent pneumococcal conjugate vaccine(PCV-13)investigated in this research incorporated serotypes 1,3,4,5,6A,6b,7F,9V,14,18C,19A,19F,and *** polysaccharides(PnPSs)and CRM197 carrier protein were produced and purified in-house,and used to prepare PnPS-CRM conjugates using unique,cyanide-free,in vacuo glycation conjugation *** vitro characterization confirmed the generation of higher molecular weight PnPS-CRM conjugates low in free *** vivo animal studies were performed to compare PnuVax's PCV-13 to the commercially available PCV-13,Prevnar®13(Pfizer,USA).A boost dose was provided to all groups post-dose 1 at t?14 ***-dose 2 results at t?28 days showed that all 13 serotypes in PnuVax's PCV-13 were *** serotype IgG GMCs demonstrated that PnuVax's PCV-13 is immunogenic for all 13 serotypes,with 10 of the 13 serotypes statistically the same or higher than Prevnar®13 post-dose *** a result,the novel polysaccharideprotein conjugates developed in this work are highly promising for use in human PCV *** in vacuo conjugation technique applied in this work could also be readily adapted to develop many other conjugate vaccines.

关键词： Pneumonia Vaccine development PCV Pneumococcal conjugate vaccine Polysaccharide Carrier protein In vacuo glycation

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Wildfire severity alters soil microbial exoenzyme production and fungal abundances in the southern Appalachian Mountains

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Pedosphere 2024年第5期34卷 865-878页

作者： Megan L.SCHILL Richard bAIRD Shawn P.bROWN allison M.VeACH Department of Integrative biology University of Texas at San Antonio biochemistry Molecular Biology Entomology and Plant Pathology Department Mississippi State University Department of biological Sciences The University of Memphis

Climate change has increased drought frequency and duration that are exacerbated by increased temperatures globally. This effect has, and will continue,to increase fire occurrence across many regions of North America. In the southern Appalachian Mountains, wildfires with high burn severity occurred in 2016due to increased drought and human activity. To investigate the effects of burn severity on soil physicochemical properties, microbial extracellular enzyme production, and microbial abundances in a temperate region, surface soils (0–15 cm) were collected from two sites (the Great Smoky Mountains National Park in Tennessee and the Nantahala National Forest in North Carolina, USA) spanning lightly, moderately, and severely burned areas, accompanied by adjacent unburned locations that act as controls. The soil samples were collected at three time points between 2017 and 2019 (i.e., 0.5, 1, and 2.5 years post-fire)among burn severity plots. Total hydrolytic enzyme production varied over time, with severe burn plots having significantly lower enzyme production at 2.5years post-fire. Individual enzymes varied among burn severities and across time post-fire. Light burn plots showed greater carbon-specific (β-glucosidase and β-xylosidase) and phosphorus-specific (acid phosphatase) enzyme activities at 0.5 years post-fire, but this effect was transient. At 2.5 years post-fire, theβ-xylosidase and acid phosphatase activities were lower in severe or moderate burn plots relative to the controls. In contrast, the activity of nitrogen-specific enzyme leucyl aminopeptidase was the lowest in severe burn plots at 0.5 years post-fire, but was the lowest in light burn plots at 2.5 years post-fire. The fungi:bacteria ratio declined with burn severity, indicating that fungi are sensitive or less resilient to high burn severity during recovery. These results suggest that wildfires alter trajectories for soil microbial structure and function within a 2.5-year timeframe, which potentially

关键词： 16S rRNA burn severity extracellular enzyme fungi:bacteria ratio internal transcribed spacer microbial structure

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Autism spectrum disorders in adolescence and adulthood: Long-term outcomes and relevant issues for treatment and research

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Science China(Life Sciences) 2015年第10期58卷 1010-1015页

作者： allison b.RATTO Gary b.MeSIbOV Department of Psychology University of North Carolina at Chapel Hill Department of Psychiatry University of North Carolina at Chapel Hill

The advances in research and treatment of autism spectrum disorders(ASD) over the past three decades have focused largely on early childhood and school-age years. Although ASD is a lifelong condition, there has been relatively little attention paid to ASD during the adolescent and adulthood periods. As the population of those with ASD continues to rise and age, the need to provide research and treatment for this group has become increasingly evident. This paper reviews the current literature available on symptoms, functioning, and treatment of adolescents and adults with ASD, as well as the unique issues that arise for individuals with ASD after childhood. Adulthood outcomes for ASD are generally poor, even for those with average to above average cognitive ability. Further research and additional clinical resources are needed for this rapidly increasing group.

关键词： autism spectrum disorder (ASD) adolescence adulthood developmental trajectory

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Infectious causation of chronic disease:examining the relationship between Giardia lamblia infection and irritable bowel syndrome

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World Journal of Gastroenterology 2007年第34期13卷 4574-4578页

作者： Alice S Penrose eden V Wells allison e Aiello Preventive Medicine University of Michigan Ann Arbor MI 48109-2029 United States Michigan Department of Community Health Lansing MI United States Department of epidemiology University of Michigan Ann Arbor MI 48109-2029 United States

AIM: To evaluate whether a higher prevalence of Giardia lamblia infection is associated with an increase in irritable bowel syndrome (IbS) prescriptions at the county level in Michigan. MeTHODS: The Michigan Disease Surveillance System (MDSS) was used to ascertain both the numbers of Giardia lamblia infections as well as the total number of foodborne illnesses per population by county in Michigan during 2005. This was compared with blue Cross blue Shield (bCbS) of Michigan numbers of drug prescriptions for IbS per one thousand members per county in 2005. These data were also analyzed for associations with per capita income by county and the number of refugees entering each county in 2005. ReSULTS: There were a total of 786 confirmed cases of Giardia lamblia reported to MDSS in 2005. During the same time period, the number of prescriptions for IbS varied from 0.5 per 1000 members up to 6.0 per 1000 members per month. There was no trend towards higher numbers of IbS prescriptions in the counties with more Giardia lamblia infections. Per capita income was not associated with either IbS prescriptions or Giardiasis. There was a significant linear association between the number of refugees entering each county, and the number of Giardia lamblia cases per 100 000 population. CONCLUSION: In this ecological study, there was no association found between bCbS prescriptions for IbS and Giardia lamblia infections in Michigan counties. Our findings may have been influenced by the disparate number of refugees admitted per county.

关键词： Foodborne Gastrointestinal Giardia lamblia Irritable bowel syndrome Parasite Prescription Refugees

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Understanding of the influence of process parameters on the heat transfer behavior at the metal/die interface in high pressure die casting process

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Science China(Technological Sciences) 2009年第1期52卷 172-175页

作者： allison John Research & Advanced engineering Department Scientific Research Laboratory Ford Motor Company

The current paper focuses on the influence of the process parameters on the peak values of the inter-facial heat transfer coefficient (IHTC) at metal/die interface during high pressure die casting (HPDC) process. A "step shape" casting and AM50 alloy were used during the experiment. The IHTC was de-termined by solving the inverse thermal problem based on the measured temperature inside the die. Results show that the initial die surface temperature (IDST, TDI) has a dominant influence while the casting pressure and fast shot velocity have a secondary influence on the IHTC peak values. by curve fitting, it was found that the IHTC peak value (hmax) changes as a function of the IDST in a manner of hmax =eαTγDI. Such relationship between the IHTC peak value and the IDST can also be found when the casting alloy is ADC12, indicating that this phenomenon is a common characteristic in the HPDC process.

关键词： high pressure die casting interfacial heat transfer coefficient AM50 ADC12

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A precise monitoring of snow surface height in the region of Lambert Glacier basin-Amery Ice Shelf,east Antarctica

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Science China earth Sciences 2005年第1期48卷 100-111页

作者： I.allison Australian Antarctic Division and Antarctic Climate and ecosystems CRC

The net surface snow accumulation on the Antarctic ice sheet is determined by a combination of precipitation, sublimation and wind redistribution. We present a one-year record of hourly snow-height measurements at LGb69 (70°50'S, 77°04'e, 1850 m a.s.l.). east side of Lambert Glacier basin (LGb), and 4 year record at G3 (70°53'S, 69°52'e, 84 m a.s.l.), Amery Ice Shelf (AIS). The measurements were made with ultrasonic sensors mounted on automatic weather stations installed at two sites. The snow accumulation at LGb69 is approximately 70 cm. Throughout the winter, between April and September, there was little change in surface snow height (SSH) at the two sites. The negative SSH change is due to densification at LGb69, and is due to both ablation and densification at G3. The strongest accumulation at two sites occurred during the period between October and March (accounting for 101.6% at LGb69), with four episodic increasing events occurring during 2002 for LGb69, and eight events during 1999-2002 for G3 (2 to 3 events per year). At LGb69, these episodic events coincided with obvious humidity 'pulses' and decreases of incoming solar radiation as recorded by the AWS. Observations of the total cloud amount at Davis station, 160 km NNe of LGb69, showed good correlation with major accumulation events recorded at LGb69. There was an obvious anti-correlation between the lowest cloud height at Davis and the daily accumulation rate at LGb69. Although there was no correlation over the total year between wind speed and accumulation at LGb69, large individual accumulation events are associated with episodes of strong wind (>7 m/s), we estimate drift snow may contribute to total SSH up to 35%. Strong accumulation events at LGb69 are associated with major storms in the region and inland transport of moist air masses from the coast.

关键词： Antarctica, Lambert Glacier basin, Amery Ice Shelf, accumulation, katabatic wind.

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Macrophage polarization in response to wear particles in vitro

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Cellular & Molecular Immunology 2013年第6期10卷 471-482页

作者： Joseph K Antonios Zhenyu Yao Chenguang Li allison J Rao Stuart b Goodman Orthopaedic Research Laboratories Department of Orthopaedic Surgery Stanford University School of Medicine Stanford CA USA

Total joint replacement is a highly successful surgical procedure for treatment of patients with disabling arthritis and joint dysfunction. However, over time, with high levels of activity and usage of the joint, implant wear particles are generated from the articulating surfaces. These wear particles can lead to activation of an inflammatory reaction, and subsequent bone resorption around the implant （periprosthetic osteolysis）. Cells of the monocyte/macrophage lineage orchestrate this chronic inflammatory response, which is dominated by a pro-inflammatory （M 1） macrophage phenotype rather than an anti-inflammatory pro-tissue healing （M2） macrophage phenotype. While it has been shown that interleukin-4 （IL-4） selectively polarizes macrophages towards an M2 anti-inflammatory phenotype which promotes bone healing, rather than inflammation, little is known about the time course in which this occurs or conditions in which repolarization through I L-4 is most effective. The goal of this work was to study the time course of murine macrophage polarization and cytokine release in response to challenge with combinations of polymethyl methacrylate （PMMA） particles, lipopolysaccharide （LPS） and IL-4 in vitro. Treatment of particle-challenged monocyte/macrophages with IL-4 led to an initial suppression of pro-inflammatory cytokines and inducible nitric oxide synthase （iNOS） production and subsequent polarization into an M2 anti-inflammatory phenotype. This result was optimized when IL-4 was delivered before PMMA particle challenge, to an M 1 phenotype rather than to uncommitted （MO） macrophages. The effects of this polarization were sustained over a 5-day time course. Polarization of M1 macrophages into an M2 phenotype may be a strategy to mitigate wear particle associated periprosthetic osteolysis.

关键词： IL-4 macrophage polarization osteolysis PMMA particles total joint replacement

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PLGA nanodepots co-encapsulating prostratin and anti-CD25 enhance primary natural killer cell antiviral and antitumor function

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Nano Research 2020年第3期13卷 736-744页

作者： elizabeth e.Sweeney Preethi b.balakrishnan allison b.Powell Allan bowen Indra Sarabia Rachel A.burga R.brad Jones Alberto bosque C.Russell Y.Cruz Rohan Fernandes The George Washington Cancer Center The George Washington UniversityWashingtonDC20052USA Center for Cancer and Immunology Research Children’s National Health SystemWashingtonDC20010USA Department of Microbiology Immunologyand Tropical MedicineThe George Washington UniversityWashingtonDC20052USA Infectious Disease Division Weill Cornell Medical CollegeNew YorkNY10065USA View author publications Department of Medicine The George Washington UniversityWashingtonDC20052USA

Natural killer(NK)cells are attractive effector cells of the innate immune system against human immunodeficiency virus(HIV)and ***,NK cell therapies are limited by the fact that target cells evade NK cells,for example,in latent reservoirs(in HIV)or through upregulation of inhibitory signals(in cancer).To address this limitation,we describe a biodegradable nanoparticlebased“priming”approach to enhance the cytotoxic efficacy of peripheral blood mononuclear cell-derived NK *** present poly(lactic-co-glycolic acid)(PLGA)nanodepots(NDs)that co-encapsulate prostratin,a latency-reversing agent,and anti-CD25(aCD25),a cell surface binding antibody,to enhance primary NK cell function against HIV and *** utilize a nanoemulsion synthesis scheme to encapsulate both prostratin and aCD25 within the PLGA NDs(termed Pro-aCD25-NDs).Physicochemical characterization studies of the NDs demonstrated that our synthesis scheme resulted in stable and monodisperse *** NDs successfully released both active prostratin and anti-CD25,and with controllable release *** Pro-aCD25-NDs were administered in an in vitro model of latent HIV and acute T cell leukemia using J-Lat 10.6 cells,the NDs were observed to prime J-Lat cells resulting in significantly increased NK cell-mediated cytotoxicity compared to free prostratin plus anti-CD25,and other *** findings demonstrate the feasibility of using our Pro-aCD25-NDs to prime target cells for enhancing the cytotoxicity of NK cells as antiviral or antitumor agents.

关键词： poly(lactic-co-glycolic acid)(PLGA)nanodepots natural killer(NK)cells human immunodeficiency virus(HIV) cancer latency-reversing agent antibody

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Suicide transport blockade of motor neuron survival generates a focal graded injury and functional deficit

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Neural Regeneration Research 2021年第7期16卷 1281-1287页

作者： allison S.Liang Joanna e.Pagano Christopher A.Chrzan Randall D.McKinnon Department of Neurosurgery Rutgers-Robert Wood Johnson Medical SchoolPiscatawayNJUSA Member The Cancer Institute of New JerseyNew BrunswickNJUSA

We describe a pre-clinical spinal cord motor neuron injury model that is minimal invasive, reproducible, focal and easily applied to small *** axonal transport of a pro-apoptotic phosphatidylinosotol 3'-kinase inhibitor, wortmannin, via the sciatic nerve results in loss of ipsilateral lumbar motor neurons proportional to the level of drug *** neuron loss was detected by choline acetyltransferase(ChAT) immunostaining and with a transgenic thy1-eGFP *** short half-life of wortmannin generates minimal wound spread, and wortmannin does not affect axon transport, as determined by co-injection of a pseudorabies virus *** quantitative transcript analysis, we found that ChAT transcripts significantly decreased at 14 days post-delivery of 1 μg wortmannin, relative to sham controls, and remained low after 90 *** effects were observed with 200 ng and 100 ng *** also generated a transient and significant increase in astrocyte Gfap transcripts after 14 days with a return to control levels at 90 *** mice had hind limb spasticity and a forced motor function defect that was quantified using a water exit *** rapidly exit a shallow water tray, and wortmannin treated animals were up to 12-fold slower, a phenotype that persisted for at least 3 *** the focal delivery of wortmannin to motor neurons generates a reproducible and scalable injury that can facilitate quantitative studies on neural regeneration and *** efficacy of sciatic nerve suicide transport can also explain neurotoxin-mediated selective loss of motor neurons in diseases such as amyotrophic lateral *** procedures were performed at Rutgers under established Institutional Animal Care and Use protocols(eIACUC_TR201800022, approved on March 20, 2018).

关键词： amyotrophic lateral sclerosis injury motor function motor neuron PI3'kinase sciatic nerve suicide transport wortmannin

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PRISMS-Fatigue computational framework for fatigue analysis in polycrystalline metals and alloys

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npj Computational Materials 2021年第1期7卷 349-360页

作者： Mohammadreza Yaghoobi Krzysztof S.Stopka Aaditya Lakshmanan Veera Sundararaghavan John e.allison David L.McDowell Materials Science and engineering University of MichiganAnn ArborMIUSA Woodruff School of Mechanical engineering Georgia Institute of TechnologyAtlantaGAUSA Aerospace engineering University of MichiganAnn ArborMIUSA School of Materials Science and engineering Georgia Institute of TechnologyAtlantaGAUSA

The PRISMS-Fatigue open-source framework for simulation-based analysis of microstructural influences on fatigue resistance for polycrystalline metals and alloys is presented *** framework uses the crystal plasticity finite element method as its microstructure analysis tool and provides a highly efficient,scalable,flexible,and easy-to-use ICMe community *** PRISMS-Fatigue framework is linked to different open-source software to instantiate microstructures,compute the material response,and assess fatigue indicator *** performance of PRISMS-Fatigue is benchmarked against a similar framework implemented using *** indicate that the multilevel parallelism scheme of PRISMS-Fatigue is more efficient and scalable than AbAQUS for large-scale fatigue *** performance and flexibility of this framework is demonstrated with various examples that assess the driving force for fatigue crack formation of microstructures with different crystallographic textures,grain morphologies,and grain numbers,and under different multiaxial strain states,strain magnitudes,and boundary conditions.

关键词： fatigue alloys grain

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