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Generation of Human Microglia from Induced Pluripotent Stem Cells to Study Innate Immunity in Neurological Diseases.
No full textMicroglia play an important role in developmental and homeostatic brain function. They profoundly influence the development and progression of neurological disorders, including Alzheimer’s disease (AD). In AD, microglia respond to degenerating neurons, beta-amyloid (Aβ) and tau pathology, and CNS inflammation. AD-etiology involves complex interactions between age, genetic, and environmental risk factors. Recently, GWAS studies in large AD cohorts have identified numerous SNPs present in innate immune genes, many expressed in microglia. These SNPs confer an elevated risk in developing AD, and harboring of these SNPS is considered a risk factor. While the genes themselves are not risk factors, SNPs in these genes may impair the normal function of microglia, such as cytokine production and phagocytosis. Furthermore, many of these genes are involved in the detection or clearance of Aβ, and therefore these SNPs may collectively influence microglia function or influence dysfunction.Studying human microglia is challenging because of the rarity and difficulty in acquiring cells from human CNS tissue. A methodology for generating human microglia from a renewable source has long remained elusive despite success in generating the other cell-types of the CNS. This elusiveness existed due to the ontogeny of microglia and their unique transcriptome and functional differences versus other myeloid cells. The goal of my dissertation was to generate human induced pluripotent stem cell (iPSC)-derived microglia (iMGLs) to study their molecular and physiological function in neurological disease. To accomplish this goal, I developed a fully-defined protocol to generate large number of pure (>95%) iMGLs under 40 days. iMGLs are highly like primary human microglia as assessed via whole-transcriptome and functional analyses. iMGL studies, in vitro and in vivo, highly suggest that they can be used as surrogates for human p microglia. Using iMGLs, I showed how AD-GWAS related microglial genes were influenced by two hallmark AD proteins—Aβ and Tau. In addition, I showed that iMGLs populate mouse brains and develop microglial-like arborized morphology and respond to Aβ in an AD transgenic mice. Together, this protocol represents an important advance in our ability to study human microglia in the context of development, health, and disease, such as A
A positron annihilation study of crystalline, quasicrystalline and amorphous Al-Mn-Si alloys
No full textPT: J; CR: BANCEL PA, 1985, PHYS REV LETT, V54, P2422 BANCEL PA, 1986, PHYS REV B, V33, P7917 BRANDT W, 1967, POSITRON ANNIHILATIO, P155 CASSADA WA, 1986, PHYS REV LETT, V56, P2276 CHEN CH, 1986, PHYS REV B, V33, P2814 COOPER M, 1966, ACTA CRYSTALLOGR, V20, P614 DINI K, 1986, J PHYS F MET PHYS, V16, P1917 DUNLAP RA, 1986, J MATER RES, V1, P415 DUNLAP RA, 1986, J PHYS F MET PHYS, V16, P11 DUNLAP RA, 1986, J PHYS F MET PHYS, V16, P1247 ELSER V, 1985, PHYS REV LETT, V55, P2883 FOLLSTAEDT DM, 1986, PHYS REV LETT, V56, P1827 KAJCSOS Z, 1982, NUCL INSTRUM METHODS, V199, P327 POON SJ, 1985, PHYS REV LETT, V55, P2324 RAMACHANDRARAO P, 1985, PRAMANA, V25, L225 SCHECHTMAN D, 1984, PHYS REV LETT, V53, P1951 SIEGEL RW, 1980, ANNU REV MATER SCI, V10, P393 ZHANG Z, 1985, PHILOS MAG A, V52, L49; NR: 18; TC: 11; J9: J PHYS-F-METAL PHYS; PG: 5; GA: G5443Source type: Electronic(1
Air quality during the 2008 Beijing Olympics : secondary pollutants and regional impact
No full textAuthor name used in this publication: Wang T.Author name used in this publication: Nie, W.Author name used in this publication: Gao, J.Author name used in this publication: Xue, L. K.Author name used in this publication: Gao, X. M.Author name used in this publication: Wang, X. F.Author name used in this publication: Qiu, J.Author name used in this publication: Poon, C. N.Author name used in this publication: Meinardi, S.Author name used in this publication: Blake, D.Author name used in this publication: Wang, S. L.Author name used in this publication: Ding, A. J.Author name used in this publication: Chai, F. H.Author name used in this publication: Zhang, Q. Z.Author name used in this publication: Wang, W. X.2010-2011 > Academic research: refereed > Publication in refereed journalVersion of RecordPublishedC
Running a Digital Design Agency in Rural Kenya: A Working Process to Foster Teamwork and Ownership
No full textThis graduation project aimed to support Digital Lions, a digital design agency in rural Kenya, in improving their working process on client projects. Digital Lions is a Fair Trade agency that delivers digital products in the areas of graphic design and web development to international clientele. The agency is a sister organization of an NGO that provides IT education in rural areas. Digital Lions serves as a stepping stone for some of the graduates from this IT education program. The mission of Digital Lions is to create jobs and skills development opportunities to these talents through real client projects. Digital Lions’ context and working process were researched through interviews, observations, and informal interactions with key stakeholders, during a 7-week field research phase. This research consisted of living and working on the campus where Digital LIons is hosted in Loropio, Turkana, Kenya. The main findings from this field research were that Digital Lions’ founder desired to have a team that is self-managing. However, the employees of Digital LIons still lacked knowledge and experience in teamwork within an agency. Moreover, due to remote working arrangements and colliding activities outside of the agency, it was difficult for the team to align their schedules and collaborate synchronously. Consequently, there was little responsibility and ownership to address important matters that could improve the agency. Thus, the design goal for this project was to enhance collaboration within the Digital Lions team, in order to initiate their transition from a collective of freelancers to a self-managing agency. A list of design requirements was generated from an exploratory prototyping phase. This consisted of rapidly creating prototypes of possible interventions and testing them with subjects in close proximity. This provided quick insights into what could and could not work, as well as new design requirements. The final design solution was three-fold. 1. The team of 7 employees are divided into two subteams, called the Think&Do Teams. This makes aligning schedules to communicate and collaborate synchronously significantly easier. 2. The Think&Do Teams are provided with Action Sheets that guide them through a series of outlined activities or tasks within a given strategy to address an important agency matter. An example of such matter is to collaboratively create a coherent Instagram content strategy for the agency. The Action Sheets provide high level instructions and links to useful resources, serving as a catalyst for effective teamwork on real tasks. 3. The Think&Do teams are facilitated by the agency leader and foreign volunteers that support the agency. They are provided with an Action Sheets template and a filled in example, as well as a handbook on how to prepare the Action Sheets, so that the team is enabled to address important agency matters effectively. By implementing this solution, the team slowly transitions from working like a collective of freelancers to a collaborative team. Over time the employees gain ownership of important agency matters and experience in truly working as a team. This solution accelerates the team in becoming a self-managing agency. Strategic Product Desig
Low Nonlinearity Optical Fibers for Broadband and Long-Distance Communications
No full textA class of low nonlinearity dispersion-shifted and dispersion-flattened fibers for broadband and long haul applications is presented. The refractive index profiles of these fibers assume a depressed-core multi-clad geometry in order to achieve effective-areas much larger than those in conventional optical fibers.
A systematic approach for designing large effective-area dispersion-shifted fibers, using a reference W-index profile to initiate the design, is presented. Transmission properties, including effective-area, mode-field-diameter, dispersion, dispersion slope, cutoff wavelength, and bending, microbending and splice losses are evaluated for several design examples. To ascertain that the proposed fibers can be practically fabricated, the effects of varying fiber dimensions and indices on effective-area, mode-field-diameter and dispersion are assessed.
It is shown that there is a trade-off between effective-area and mode-field-diameter and, generally, larger effective-areas are associated with larger mode-field-diameters. In other words, less signal distortion due to fiber nonlinearity (larger effective-area) is associated with higher power loss due to bending of fiber (larger mode-field-diameter). Thus, a large effective-area and low bending loss are conflicting requirements. A parameter Q is defined as a performance indicator, considering effective-area and mode-field-diameter. Dispersion-shifted single-mode fiber designs with effective-areas of 78 μm² to 210 μm² and the corresponding mode-field-diameter of 8.94 μm to 14.94 μm, dispersion less than 0.07 ps/nm.km, and dispersion slope of about 0.05 ps/ nm².km are presented. Numerical simulations for propagation of pulses in few designed fibers are performed.Designs of large effective-area dispersion-flattened fibers are also presented, for the first time we believe. These fibers provide large effective-area and low dispersion over an extended range of wavelengths. For our design, over the wavelength range of 1.48 μm < λ < 1.58 μm, the effective-area is 75 μm² to 100 μm², while the dispersion remains below 0.7 ps/nm.km.Ph. D
Durability and debond evaluation of high-rise concrete buildings using infrared thermography
No full textAuthor name used in this publication: W. L. LaiRefereed conference paper2012-2013 > Academic research: refereed > Refereed conference paperNot applicablePublishedCopyright retained by autho
Estimating selection pressures on HIV-1 using phylogenetic likelihood models
No full textHuman immunodeficiency virus (HIV-1) can rapidly evolve due to selection pressures exerted by HIV-specific immune responses, antiviral agents, and to allow the virus to establish infection in different compartments in the body. Statistical models applied to HIV-1 sequence data can help to elucidate the nature of these selection pressures through comparisons of non-synonymous (or amino acid changing) and synonymous (or amino acid preserving) substitution rates. These models also need to take into account the non-independence of sequences due to their shared evolutionary history. We review how we have developed these methods and have applied them to characterize the evolution of HIV-1 in vivo. To illustrate our methods, we present an analysis of compartment-specific evolution of HIV-1 em) in blood and cerebrospinal fluid and of site-to-site variation in the gag gene of subtype C HIV-1. Copyright (C) 2008 John Wiley & Sons, Ltd
South Asians in the United Kingdom and specialist services
No full textChapter one is a literature review of the psychosocial factors which influence
alcohol use in British South Asian men. Critical analysis of fourteen research articles
revealed differences between first and second-generation South Asian men. The
influence of religion, parental beliefs and acculturation were reported within the
literature to affect alcohol use. The literature highlighted the issue of stigma and lack
of awareness of services as barriers for treatment seeking. Additionally, the effect of
religious and cultural beliefs of alcohol use may also discourage support from
services.
Chapter two investigated the experiences of British South Asian women who
accessed psychological treatment within a cancer service using in-depth semistructured
interviews. Key informants participated in focus groups to gain
experiences of staff who had worked with South Asian communities. Using
Interpretative Phenomenological Analysis, the findings elicited themes which
illustrated that the South Asian women held pre-existing beliefs about psychological
services. They also described their psychological journey of cancer treatment and the
impact on their family, friends and differences between generations was reported.
Analysis of the key informants' focus group data highlighted the theme of challenges
faced by the South Asian patients and the staff. This article provided evidence for
better education and awareness for South Asian communities and staff.
Chapter three is a reflective article on the process of conducting the empirical
research. The article addressed the reasons that influenced the researcher to conduct
the study. Issues that had arisen were of the effect of 'sameness and difference'
between the researcher and participants and the impact of qualitative research
methodology and empowerment. A reflection of the impact from the interview
accounts was also discussed
Body mass, blood pressure, and cognitive functioning among octogenarians and centenarians
No full textAim: The purpose of this study was to examine the association among body mass, blood pressure (BP), and cognitive functioning for octogenarians and centenarians.
Methods: A total of 300 participants (221 centenarians and 79 octogenarians) from the Georgia Centenarian Study were included in this study. Demographic variables included age, gender, and ethnicity. Body mass was measured with the body mass index (BMI), and systolic and diastolic BP, as well as mean arterial pressure (MAP) and the Mini-Mental Status Examination (MMSE) were assessed.
Results: Results showed age differences indicating that centenarians had lower BMI and MMSE scores when compared to octogenarians. Women had lower cognitive functioning scores compared to men. Black Americans had higher BMI and BP as well as lower MMSE scores. Participants with low BMI values (< 18.5 kg/m2) and normal BP had a significantly lower MMSE score when compared to those with elevated BMI values (≥ 25 kg/m2 to < 30 kg/m2) and high BP. Multiple regression analyses determined that age, gender, ethnicity, and BMI were significantly associated with cognitive function in very late life.
Conclusions: The results suggest that extreme values of body mass (low and high) in combination with normal BP ( © The Author(s) 2023. This is an Open Access article licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were madeThe Georgia Centenarian Study was funded by [1P01AG17553] from the National Institute on Aging, a collaboration among The University of Georgia, Tulane University Health Sciences Center, Boston University, University of Kentucky, Emory University, Duke University, Wayne State University, Iowa State University, Temple University, and University of Michigan. Additional investigators of the Georgia Centenarian Study include S. M. Jazwinski, R. C. Green, M. MacDonald, M. Gearing, W. R. Markesbery (deceased), J. L. Woodard, M. A. Johnson, J. S. Tenover, I. C. Siegler, W. L. Rodgers, D. B. Hausman, C. Rott, A. Davey, and J. Arnold. The first author’s work on the project was supported by the Fulbright Commission and by United States Department of Agriculture, Hatch Project Grant, [IOW04116]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
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