Opposite Roles of B7.1 and CD28 Costimulatory Molecules for Protective Immunity against HSV-2 Challenge in a gD DNA Vaccine Model

David B. Weiner,신정임 대한면역학회 2005 Immune Network Vol.5 No.2

Background: Costimulation is a critical process in Ag-specific immune responses. Both B7.1 and CD28 molecules have been reported to stimulate T cell responses during antigen presentation. Therefore, we tested whether Ag-specific immune responses as well as protective immunity are influenced by coinjecting with B7.1 and CD28 cDNAs in a mouse HSV-2 challenge model system. Methods: ELISA was used to detect levels of antibodies, cytokines and chemokines while thymidine incorporation assay was used to evaluate T cell proliferation levels. Results: Ag-specific antibody responses were enhanced by CD28 coinjection but not by B7.1 coinjection. Furthermore, CD28 coinjection increased IgG1 production to a significant level, as compared to pgD pcDNA3, suggesting that CD28 drives Th2 type responses. In contrast, B7.1 coinjection showed the opposite, suggesting a Th1 bias. B7.1 coinjection also enhanced Ag-specific Th cell proliferative responses as well as production of Th1 type cytokines and chemokines significantly higher than pgD pcDNA3. However, CD28 coinjection decreased Ag-specific Th cell proliferative responses as well as production of Th1 types of cytokines and chemokine significantly lower than pgD pcDNA3. Only MCP-1 production was enhanced by CD28. B7.1 coimmunized animals exhibited an enhanced survival rate as well as decreased herpetic lesion formation, as compared to pgD pcDNA3. In contrast, CD28 vaccinated animals exhibited decreased survival from lethal challenge. Conclusion: This study shows that B7.1 enhances protective Th1 type cellular immunity against HSV-2 challenge while CD28 drives a more detrimental Th2 type immunity against HSV-2 challenge, supporting an opposite role of B7.1 and CD28 in Ag-specific immune responses to a Th1 vs Th2 type.

Opposite Roles of B7.1 and CD28 Costimulatory Molecules for Protective Immunity against HSV-2 Challenge in a gD DNA Vaccine Model

Weiner, David B.,Sin, Jeong-Im The Korean Association of Immunobiologists 2005 Immune Network Vol.5 No.2

Background: Costimulation is a critical process in Ag-specific immune responses. Both B7.1 and CD28 molecules have been reported to stimulate T cell responses during antigen presentation. Therefore, we tested whether Ag-specific immune responses as well as protective immunity are influenced by coinjecting with B7.1 and CD28 cDNAs in a mouse HSV-2 challenge model system. Methods: ELISA was used to detect levels of antibodies, cytokines and chemokines while thymidine incorporation assay was used to evaluate T cell proliferation levels. Results: Ag-specific antibody responses were enhanced by CD28 coinjection but not by B7.1 coinjection. Furthermore, CD28 coinjection increased IgG1 production to a significant level, as compared to pgD+pcDNA3, suggesting that CD28 drives Th2 type responses. In contrast, B7.1 coinjection showed the opposite, suggesting a Th1 bias. B7.1 coinjection also enhanced Ag-specific Th cell proliferative responses as well as production of Th1 type cytokines and chemokines significantly higher than pgD+pcDNA3. However, CD28 coinjection decreased Ag-specific Th cell proliferative responses as well as production of Th1 types of cytokines and chemokine significantly lower than pgD+pcDNA3. Only MCP-1 production was enhanced by CD28. B7.1 coimmunized animals exhibited an enhanced survival rate as well as decreased herpetic lesion formation, as compared to pgD+pcDNA3. In contrast, CD28 vaccinated animals exhibited decreased survival from lethal challenge. Conclusion: This study shows that B7.1 enhances protective Th1 type cellular immunity against HSV-2 challenge while CD28 drives a more detrimental Th2 type immunity against HSV-2 challenge, supporting an opposite role of B7.1 and CD28 in Ag-specific immune responses to a Th1 vs Th2 type.

종족음악학의 전통의 의미

데이비드코플랜 세계음악학회 1999 음악과 문화 Vol.1 No.-

Presynaptic Regulation of Astroglial Excitatory Neurotransmitter Transporter GLT1

Yang, Yongjie,Gozen, Oguz,Watkins, Andrew,Lorenzini, Ileana,Lepore, Angelo,Gao, Yuanzheng,Vidensky, Svetlana,Brennan, Jean,Poulsen, David,Won Park, Jeong,Li Jeon, Noo,Robinson, Michael B.,Rothstein, J Elsevier 2009 Neuron Vol.61 No.6

<P><B>Summary</B></P><P>The neuron-astrocyte synaptic complex is a fundamental operational unit of the nervous system. Astroglia regulate synaptic glutamate, via neurotransmitter transport by GLT1/EAAT2. Astroglial mechanisms underlying this essential neuron-glial communication are not known. We now show that presynaptic terminals regulate astroglial synaptic functions, GLT1/EAAT2, via kappa B-motif binding phosphoprotein (KBBP), the mouse homolog of human heterogeneous nuclear ribonucleoprotein K (hnRNP K), which binds the GLT1/EAAT2 promoter. Neuron-stimulated KBBP is required for GLT1/EAAT2 transcriptional activation and is responsible for astroglial alterations in neural injury. Denervation of neuron-astrocyte signaling by corticospinal tract transection, ricin-induced motor neuron death, or neurodegeneration in amyotrophic lateral sclerosis all result in reduced astroglial KBBP expression and transcriptional dysfunction of astroglial transporter expression. Presynaptic elements dynamically coordinate normal astroglial function and also provide a fundamental signaling mechanism by which altered neuronal function and injury leads to dysregulated astroglia in CNS disease.</P>

Long-term Outcomes of Sacral Nerve Stimulation in Pelvic Floor Dysfunctions

David Hernández-Hernández,Bárbara Padilla-Fernández,Milagros Castro Romera,Stephany Hess Medler,David Castro-Díaz 대한배뇨장애요실금학회 2021 International Neurourology Journal Vol.25 No.4

Purpose: The aim of this study was to analyze the long-term outcomes of sacral nerve stimulation (SNS) in both idiopathic and neurogenic pelvic floor disorders in patients treated at a referral center. Methods: This retrospective observational study analyzed the records of 106 patients tested at our department from December 1999 to January 2017. The efficacy variables evaluated were the Global Response Assessment (range, 0%–100%) and, according to the clinical indication, other specific variables such International Consultation on Incontinence Questionnaire- Short Form, number of catheterizations or pads/day, and the numerical pain scale. The safety variables analyzed were complications (pain, migration, infection), reinterventions and explants. Patients’ quality of life (QoL) and satisfaction with the procedure were evaluated through telephone interviews. Results: The clinical indications were overactive bladder (OAB) (n=36), urinary retention (UR) (n=37), bladder pain syndrome/ interstitial cystitis (BPS/IC) (n=19), fecal incontinence (FI) (n=8), and double incontinence (DI) (n=6). The implant rates according to the clinical indication were as follows: OAB, 55.6%; UR, 56.8%; BPS/IC, 63.15%; FI, 87.5%; and DI, 66.7%. Clinical and/or statistically significant improvements in all efficacy variables were observed. Loss of therapeutic effect at 75 months of follow-up was observed in 34% of patients. Device-related pain appeared in 25 patients (39%); in 20 patients, it was resolved by reprogramming and 5 patients required device removal. An overall improvement in QoL and high levels of satisfaction with the procedure were observed. More than 90% of patients would recommend SNS to a friend or relative. Conclusions: SNS is a minimally invasive procedure that offers a real alternative to patients with refractory pelvic floor dysfunction. Its safety profile is very favorable and it provides a long-lasting improvement in symptoms and QoL.

Auto-induction Screening Protocol for Ranking Clonal Libraries of Pichia pastoris MutS Strains

David Wollborn,Rebecca Luise Müller,Lara Pauline Munkler,Rebekka Horstmann,Andrea Germer,Lars Mathias Blank,Jochen Büchs 한국생물공학회 2022 Biotechnology and Bioprocess Engineering Vol.27 No.4

Screening Pichia pastoris (Komagataella phaffii) strain libraries utilizing the methanol inducible alcohol oxidase 1 (AOX1) promoter requires addition of methanol as an inducer during cultivation. As the AOX1 promoter is repressed in the presence of glucose or glycerol, common screening procedures include long incubation times before methanol induction by successive multiple additions. In this study, a P. pastoris MutS strain, secreting a green fluorescent protein (GFP), was used to characterize a standard screening protocol in complex medium. Based on these results, an auto-induction screening method for P. pastoris strains was developed using mineral SYN6 medium, where methanol was added from the beginning. To gain more insight into growth and production behavior, the cultures were online-monitored, using the Respiration Activity Monitoring System and the BioLector system. Monitoring the oxygen transfer rate indicated that prolonged cultivation phases before induction can be avoided and that high glucose concentrations hinder inducible protein production. The results show the effects of using 20 g/L glucose, and the resulting ethanol formation on the screening process. The newly developed auto-induction method was then used to screen and rank a strain library of high, medium, and low GFP producers. These results demonstrate that the auto-induction method facilitates the identification of high producers during primary screening. It is significantly less time consuming and labor intensive. Nonetheless, it leads to the same conclusion as the conventional screening with manual methanol additions.

The Perspectives and Alerters on Request for EFL Learners of English

David B. Kim 한국영미어문학회 2015 영미어문학 Vol.- No.116

David B. Kim. 2015. The Perspectives and Alerters on Request for EFL Learners of English. Studies in British and American Language and Literature 116, 209-232. This study investigates the different types of perspective and alerter on request, and the relation of the two features for Korean EFL learners of English. After studying request strategies for one semester, the 64 participants studying general English conversation were presented with six different pragmatic situations on request and asked to write request strategies including four types of perspective and eight types of alerter as they would like to use in the natural speaking context. First, in the results of perspectives, the participants frequently used the speaker oriented and the hearer oriented perspectives in the socially intimate situation. Most of them used the patterns of the textbook in the socially distant situation and employed the two perspectives for their major strategies in socially equal situation, Second, the cross tabulation analysis summarized the relationship between perspective and alerter. In the socially intimate situation, the participants preferred to use the hearer oriented or the speaker oriented strategies. The participants used suitable strategies to meet the socially distant situation. However, the participants used different types of perspectives with different alerters in socially equal situation. In conclusion, though some results in each category did not show any consistencies, the use of learners’ strategies was similar to those of previous studies.

Concrete structures under combined mechanical and environmental actions: Modelling of durability and reliability

Dita Vořechovská,Martina Šomodíková,Jan Podroužek,David Lehký,Břetislav Teplý 사단법인 한국계산역학회 2017 Computers and Concrete, An International Journal Vol.20 No.1

Service life assessments which do not include the synergy between mechanical and environmental loading are neglecting a factor that can have a significant impact on structural safety and durability assessment. The degradation of concrete structure is a result of the combined effect of environmental and mechanical factors. In order to make service life design realistic it is necessary to consider both of these factors acting simultaneously. This paper deals with the advanced modelling of concrete carbonation and chloride ingress into concrete using stochastic 1D and 2D models. Widely accepted models incorporated into the new fib Model Code 2010 are extended to include factors that reflect the coupled effects of mechanical and environmental loads on the durability and reliability of reinforced concrete structures. An example of cooling tower degradation by carbonation and an example of a bended reinforced concrete beam kept for several years in salt fog are numerically studied to show the capability of the stochastic approach. The modelled degradation measures are compared with experimental results, leading to good agreement.

Large-scale dataset from China gives new insights into leaf margin-temperature relationships

Chen, Wen-Yun,Su, Tao,Adams, Jonathan M.,Jacques, Fré,dé,ric M.B.,Ferguson, David K.,Zhou, Zhe-Kun Elsevier 2014 Palaeogeography, palaeoclimatology, palaeoecology Vol.402 No.-

Leaf margin analysis (LMA) is an important method of estimating paleotemperatures from fossil leaf floras or modern floras. Although some calibration has been carried out based upon large-scale studies of modern forests, most of this research has been in North America and Europe, with relatively little calibration work in East Asia. In the present study, we used species range maps of 3116 native dicot trees of China to derive synthetic local floras for each county from the Chinese humid region, and compared the percentage of untoothed leaf margined species with several temperature and precipitation related parameters. The results confirm the generally strong relationship between the proportion of species with untoothed leaf margins and climatic parameters within China. Leaf habit (deciduous vs. evergreen) does not strongly affect this relationship. The transfer function obtained from China, while not identical, is similar to those obtained from other regions, and is affected by regional restrictions, such as complex topography and relic taxa. As such it clarifies the potential range of error inherent in the LMA method as applied to paleodimate reconstruction. It is possible, however, that with the close similarity of the modern Chinese tree floras to Neogene floras in the Northern Hemisphere, the present estimate offers a better transfer function for reconstructing the Neogene paleoclimate in various regions without extremely cold conditions across the Northern Hemisphere. (C) 2014 Published by Elsevier B.V.

Predictors of durable immune responses six months after the last vaccination in preventive HIV vaccine trials

Huang, Yunda,Zhang, Lily,Janes, Holly,Frahm, Nicole,Isaacs, Abby,Kim, Jerome H.,Montefiori, David,McElrath, M. Julie,Tomaras, Georgia D.,Gilbert, Peter B. Elsevier 2017 Vaccine Vol.35 No.8

<P><B>Abstract</B></P> <P><B>Background</B></P> <P>The evaluation of durable immune responses is important in HIV vaccine research and development. The efficiency of such evaluation could be increased by incorporating predictors of the responses in the statistical analysis. In this paper, we investigated whether and how baseline demographic variables and immune responses measured two weeks after vaccination predicted durable immune responses measured six months later.</P> <P><B>Methods</B></P> <P>We included data from seven preventive HIV vaccine regimens evaluated in three clinical trials: a Phase 1 study of four DNA, NYVAC and/or AIDSVAX vaccine regimens (HVTN096), a Phase 2 study of two DNA and/or MVA vaccine regimens (HVTN205), and a Phase 3 study of a single ALVAC/AIDSVAX regimen (RV144). Regularized random forests and linear regression models were used to identify and evaluate predictors of the positivity and magnitude of durable immune responses.</P> <P><B>Results</B></P> <P>We analyzed 201 vaccine recipients with data from 10 to 127 immune response biomarkers, and 3–5 demographic variables. The best prediction of participants’ durable response positivity based on two-week responses rendered up to close-to-perfect accuracy; the best prediction of participants’ durable response magnitude rendered correlation coefficients between the observed and predicted responses ranging up to 0.91. Though prediction performances differed among biomarkers, durable immune responses were best predicted by the two-week response level of the same biomarker. Adding demographic information and two-week response levels of different biomarkers provided little or no improvement in the predictions.</P> <P><B>Conclusions</B></P> <P>For some biomarkers and for the vaccines we studied, two-week post-vaccination responses can well predict durable responses six months later. Therefore, if immune response durability is only assessed in a sub-sample of vaccine recipients, statistical analyses of durable responses will have increased efficiency by incorporating two-week response data. Further research is needed to generalize the findings to other vaccine regimens and biomarkers.</P> <P>Clinicaltrials.gov identifiers: NCT01799954, NCT00820846, NCT00223080.</P> <P><B>Highlights</B></P> <P> <UL> <LI> HIV vaccine-induced immune responses at 2weeks predict those 6months later. </LI> <LI> The former responses can increase evaluation efficiency of vaccine durability. </LI> <LI> The former responses of the same biomarker best predict the latter. </LI> <LI> Demographics and responses of other biomarkers add little for prediction. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>