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      • Modification and reformulation of chitosan-DNA nanoparticles for vaginal DNA vaccination

        Kiang, Tina The Johns Hopkins University 2005 해외박사(DDOD)

        RANK : 247343

        Gene therapy applications have moved away from replacement or augmentation therapy to the treatment of acquired diseases in recent years. This shift in focus allows for a wider range of vectors since integration and permanent expression of genes are not necessarily required. Non-viral vectors for gene delivery offer biological safety and versatility that most viral vectors cannot afford. Chitosan has previously shown promise as a non-viral gene carrier, particularly in mucosal vaccination strategies. The goal of this work was to evaluate the potential of this gene carrier in vaginal DNA vaccination. Chitosans over a range of degrees of deacetylation and molecular weights were synthesized by two different reactions: via heterogeneous acetylation of highly deacetylated chitosan and by homogeneous deacetylation of chitin. The synthesized chitosans were evaluated for the ability to effectively complex with DNA. After characterization of the size, zeta potential, and DNAse protection ability of the chitosan-DNA nanoparticles, high molecular weight (390 kDa) chitosan with degrees of deacetylation 90, 70 and 62% and +/- ratios 3.3, 5.0 and 9.0, respectively, were chosen for subsequent experimentation. While nanoparticle formulations formed by lower deacetylation chitosan failed to produce higher levels of gene expression in vitro as previously seen with 90% DA chitosan nanoparticles, gene expression levels in vivo were found to be significantly higher. Since modifications in chitosan deacetylation alter the physical properties of the polymer itself; cellular attachment and trafficking experiments were performed to evaluate these changes, with both plain and transferrin-conjugated nanoparticles. FACScan experiments showed a decrease in cellular attachment as the degree of deacetylation of chitosan used to form the nanoparticles decreased. Confocal microscopy experiments revealed that, at later time points, nanoparticles of 70 and 62% deacetylation were more frequently co-localized to acidic and transferrin-containing vesicles versus nanoparticles formed from 90% deacetylated chitosan. Although transferrin conjugation imparted specificity to the nanoparticles, as observed via confocal microscopy, it did not necessarily translate to increased cellular attachment or gene expression. Inclusion of an endosomalytic polymer, PPAA, to nanoparticles formed with 90% deacetylated chitosan increased gene expression levels and resulted in increased intracellular release of DNA from the nanoparticles. Biodistribution and cellular morphology were evaluated after instillation of chitosan-DNA nanoparticles into the vagina of mice. Nanoparticles formed with 90% DA chitosan were found to attach to the vaginal wall surface and cause disruption in intercellular tight junctions more readily than nanoparticles formed with 70 or 62% DA chitosan. Nanoparticles composed of chitosan with lower degrees of deacetylation more readily dissociated in the vaginal environment, while 90% DA chitosan nanoparticles remained intact and were transported away from the instillation site. The differences in the uptake and transport properties translated to differences in the gene expression in vivo . When these nanoparticles were evaluated for efficacy in eliciting immune response to HIV-gag1, however, no significant response occurred. Although the immunization application did not produce a positive result, a firm groundwork for continued study has been laid. Initial gene expression results, as well as vaginal biodistribution and transport studies point to the possibility of the using these nanoparticle formulations in future application to the vaginal mucosal route.

      • Event-related brain potential studies of semantic processing in schizophrenia and schizotypal personality

        Kiang, Michael Wai Jong University of California, San Diego 2007 해외박사(DDOD)

        RANK : 247343

        Existing hypotheses propose that abnormal spread of activation in semantic long-term memory causes disorganized speech in schizophrenia. There is in fact behavioral and event-related brain potential (ERP) evidence that schizophrenia patients are deficient in using meaningful contextual stimuli to pre-activate related concepts and thereby facilitate, or prime, their processing. In contrast, results from other behavioral studies suggest that, following meaningful stimuli, schizophrenia patients activate weakly related concepts in particular to a greater than normal degree. In order to account for these different results, some researchers have proposed that the former abnormality may occur at shorter intervals and the latter at longer intervals following a meaningful stimulus. The present studies examined in finer detail how relatedness and time course modulate activation of concepts in semantic memory in schizophrenia patients, and in healthy individuals as a function of schizotypal personality, which may be genetically linked to schizophrenia. As a measure of semantic activation, these studies used the amplitude of the N400 ERP component elicited by meaningful stimuli. N400 amplitude is normally reduced by factors thought to pre-activate the eliciting stimulus, such as its relatedness to preceding context. We found evidence that schizophrenia patients have deficits in using meaningful contextual stimuli to pre-activate related concepts in general, over both a short and a long time course. The apparent discrepancy between these results and those of previous behavioral studies of schizophrenia patients suggesting increased spread of activation to weakly related items may stem from response-related factors affecting behavioral reaction time but not N400 amplitude. In addition, we found that patients' N400 abnormalities were specifically correlated not with disorganized language production, but with positive psychotic symptoms (i.e., delusions and hallucinations). Thus, semantic priming abnormalities may play a causal role in the development of delusions. Analogous to what we observed in schizophrenia patients, N400 data in healthy individuals were consistent with an association between higher schizotypy and decreased use of context to activate relate items and/or to inhibit unrelated items. This finding supports the view that decreased semantic priming may be one of a number of neurophysiological markers common to schizophrenia and schizotypal personality.

      • Savannas and seasonal drought: The landscape-leaf connection through optimal stomatal control

        Kiang, Nancy Yao-Lan University of California, Berkeley 2002 해외박사(DDOD)

        RANK : 247343

        At a California blue oak savanna site, this research performs the first, full continuous partitioning for a savanna of evapotranspiration from the understory and tree layers through sap flow and eddy covariance measurements over seasonal cycles. Advanced statistics are used to identify the non-linearities in responses of canopy stomatal conductance, G<italic><sub>V</sub></italic>, to meteorological drivers, and in particular the critical soil moisture points for blue oak water stress are identified. Apparent coordination in the seasonal use of water and energy resources in the out-of-phase phenology of the grasses and trees hints at optimization between growth forms for the annual useage of water in this Mediterrean ecosystem. Applying the probabilistic ecohydrological optimality model of hydrologists Rodriguez-Iturbe and co-workers (2001), the different levels of statistical water stress experienced by the grasses and trees are differentiated during the different seasons helps explain their out-of-phase growth periods. However, this hydrologists' model's lack of inclusion of the role of energy, the driver of transpiration, motivates an examination of the question of optimality as developed by plant ecophysiologists in leaf gas exchange models. It is found that their complementary lack of inclusion of a soil moisture budget in turn limits their leaf level optimality models, since there is no clearly specified constraint for the optimality criterion. Thus, this research proposes a complete optimality model that clarifies the necessity of linking both leaf and landscape scales, the work of both ecophysiologists and hydrologists. A new mathematical framework is required, that of stochastic optimal control, in which the plant's stomatal conductance is steered by expectations of future water availability at the landscape scale, which have been made by natural selection. Thus, this framework incorporates adaptation to climate as well as response to immediate environmental conditions. This research adds to the database one of the more complete budgets of ecosystem fluxes of water vapor, increases coverage of arid and savanna ecosystems in the flux measurement community, and clarifies the meaning of optimality of water useage at leaf and landscape scales.

      • Structure, reactivity and tailoring of porous organic solids based on phenylacetylene silver coordination networks

        Kiang, Yuan-Hon Cornell University 2000 해외박사(DDOD)

        RANK : 247343

        This thesis studies the preparation of covalently crosslinked porous organic solids <italic>via</italic> phenylacetylene nitrile ligands and silver(I) ions coordination networks. A prototype of three-fold symmetric phenylacetylene nitrile ligand, 1,3,5-tris(4-ethynyl benzonitrile) (<bold>1</bold>) has been found to crystallize with silver(I) trifluoromethansulfonate to form a three dimensional channel structure. The extended channels found in this coordination network are of honeycomb type 15 Å in diameter. Properties such as guest removal and exchange within this host crystal have been investigated. The honeycomb channels in the crystal structure are retained through both guest exchange and complete guest removal. The apohost (defined as a host without occluded guests) exhibits selectivity for new guests by absorbing aromatic molecules and not aliphatic molecules from the vapor phase. Repeated removal and reintroduction of benzyl alcohol guests is demonstrated to occur with the retention of crystallinity and without the macroscopic reformation of the crystallites. Investigations on molecular variants of the prototypic ligand <bold> 1</bold> crystallized with silver(I) trifluoromethansulfonate have revealed a nearly invariant honeycomb porous structure type. Modifications involved both the attachment of pendant groups on the central aromatic ring of the parent molecule and the addition of elongated spacer unit between the central benzene ring and the peripheral nitrile groups. Single crystal refinements for five silver(I) salts of modified organic ligands as well as powder studies of 15 crystalline phases showed the consistent formation of the honeycomb channels, demonstrating that the parent porous architecture is stable both to functional modification as well as to size change. It was found in the case of a host with alcohol functionality that trifluoroacetic anhydride and silyl triflate both reacted with the host to form respectively an ester and a siloxane with retention of the porous structure type. In the case of a phenylacetylene nitrile molecule with three alcohol side chains, the introduction and subsequent reaction with di-<italic>t</italic>-butylsilyl bis(triflate) resulted in the formation of low polymers. This polymerized materials shows increased chemical robustness in contrast to the unpolymerized materials.

      • A School-Based Group Intervention for Immigrant Adolescents: Addressing Acculturative Stress and Facilitating Ethnic Identity Development, School Connectedness, and Related Psychosocial Outcomes

        Kiang, Mark Montclair State University ProQuest Dissertations 2020 해외박사(DDOD)

        RANK : 247343

        Immigrant adolescents account for an ever-increasing portion of middle school and high school populations. In addition to experiencing stress related to typical adolescent development, immigrant adolescents are exposed to immigration-related and acculturative stress, which can lead to compromised mental health (Takeuchi, Alegria, Jackson, & Williams, 2007). Unfortunately, immigrants as a group tend to underutilize mental health services due to a number of cultural and economic factors (Saechao et al., 2012). Schools offer an ideal setting for services that address immigrant student stress (Gonzalez, Eades, & Supple, 2014). Ethnic identity and school connectedness are two constructs that have been linked to positive psychosocial outcomes for immigrant and minority adolescents. In this study, I investigated the effectiveness of a school-based, short-term group counseling intervention for immigrant adolescents, consisting of five 60 minute sessions, that addressed acculturative stress and ethnic identity development in comparison to a non-intervention control group, based on measures of participants’ school connectedness, ethnic identity, and psychological adjustment (i.e., self-esteem and general distress). Additionally, I explored the role that an immigrant adolescent’s ethnic identity played in predicting psychological adjustment outcomes and in moderating intervention versus control group assignment. In total, 89 immigrant adolescents (44 in the intervention group and 35 in the non-treatment control group) from a variety of ethnic backgrounds at a single public high school in the Northeast participated in the study. One-way ANCOVA results indicated significantly better posttest measurements for both psychological adjustment measures (self-esteem and general distress) in the intervention group as compared to the control group, after adjusting for pretest measurements, however this was not the case for ethnic identity or school connectedness. A hierarchical multiple regression indicated that pretest ethnic identity was a significant predictor of higher posttest general distress, but that it did not significantly moderate the relationship between group assignment and posttest general distress. The results of this study suggest that the group counseling intervention is promising, particularly in terms of improving psychological adjustment above and beyond non-treatment. Further investigation regarding how counselors and educators can address and improve school connectedness is recommended. Ethnic identity appears to have important links to positive psychological adjustment, but it is a complex construct that may require more holistic and culturally-appropriate forms of measurement for immigrant adolescents. I have delineated the goals and strategies of the intervention so that they may inform future practice.

      • (A) Study on the joining technology of automotive body using the nano-adhesives

        Feng, Kiang 성균관대학교 일반대학원 2010 국내석사

        RANK : 247342

        본 연구에서는 자동차 제조업에서 널리 사용하는 접착제(epoxy resin)로부터 개선한 두 종류의 나노 접착제 (nano-adhesive)를 소개한다. 이 나노 접착제들은 서로 다른 중량비율의 MWCNT (multi-wall carbon nano-tube)의 혼합을 통해 얻어진 것이다. 하이브리드 접착제의 품질과 성능의 최적화를 위해서는 재료의 전기적, 기계적 성질 및 접착제 레이어의 기하학적 변수 등이 모두 고려되어야 한다. 1) 먼저 나노 접착제 A(nano-adhesive A)는 NT(nano-tube)의 중량비율의 증가 및 접착제의 두께의 감소에 따라 저항이 감소하였다. CNT를 추가하지 않은 재료에서부터 CNT 추가 후의 접착경향을 분석하기 위하여 CNT 함량, 접착제 두께 및 겹침 길이가 다른 여러 가지 샘플에 대하여 인장 실험을 수행하였다. 그 결과, 나노 접착제 A에 2wt.%의 CNT가 포함되었을 때 최대 인장 강도(ultimate tensile strength)가 최고치에 도달하였다. 또한, 접착제 접착 전 플레이트에 대한 표면처리의 여부가 최대 인장 강도에 영향을 미쳤다. 2) 다음으로 나노 접착제 B에서는 두 가지 다른 종류의 CNT 혼합 방법을 사용하였다. 하나는 위에서와 동일한 기계적으로 교반하는 방법을 사용하였고, 다른 하나는 CNT를 먼저 DCE(dichloroethane)용액에 충분히 혼합한 후 이 용액과 접착제를 혼합하는 방법이다. 인장 실험 결과 0.5wt.%의 CNT와 DCE와의 혼합을 거친 0.3wt.% CNT가 포함되었을 때의 최대 인장 강도가 최고치에 도달하였다. 마지막으로 나노 접착제 B에 대하여 피로 실험을 한 결과 낮은 CNT혼합비율 및 CNT가 포함되지 않은 샘플들은 플레이트가 모두 파단 되였으며 이로 인해 구체적인 피로 강도의 강약을 판단하기 어려웠다. 하지만 CNT가 1%이상 포함되었을 때 피로 강도는 CNT의 중량비율의 증가에 따라 감소되었다.

      • The confluence of physical, organizational and informational space in academic communities

        Tan, Beng-Kiang Harvard University 2003 해외박사(DDOD)

        RANK : 247341

        As we move towards a knowledge economy, new skill sets will be demanded of the workforce. Studies have identified some of these skills as the ability to work in teams with people of different cultures, to think critically and to use a variety of technologies. In order to equip students with these skills, universities should consider a more active learning approach, requiring more collaborative, participative student involvement in their own learning. Universities also play a critical role in creating knowledge. Since new fields of knowledge often evolve from cross-disciplinary interaction, a vital and diverse learning community is critical both to fostering learning and to developing of new ideas. However, there is little research about what factors influence and sustain university learning communities or how to effectively design them. This thesis adopts a case study research method using five case studies and proposes a framework to guide the design or enhancement of university learning communities. After detailing each dimension of the framework: organization (which includes pedagogy and course program structure), physical space and information technology, it explains how individually and collectively these dimensions shape university learning communities. It then proposes three strategies for creating or enhancing university learning communities through active learning, cross discipline interaction and fostering communities of interest and demonstrates how they can be applied in different university environments.

      • Computational Approaches to Cell Type and Interindividual Variation in Autoimmune Disease

        Targ, Sasha Kiang ProQuest Dissertations & Theses University of Cali 2018 해외박사(DDOD)

        RANK : 247341

        Computational approaches offer substantial ability to improve annotation and interpretation of a range of genomic datasets collected with the advent of next generation sequencing technologies, providing an avenue to further understand the impact. We also develop a computational tool, demuxlet, for droplet-based single-cell RNA-sequencing (dscRNA-seq) that harnesses natural genetic variation to determine the sample identity of each cell and detect droplets containing two cells. These capa.

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