Blocking of LFA-1 enhances expansion of Th17 cells induced by human CD14(+) CD16(++) nonclassical monocytes.

Among human peripheral blood (PB) monocyte (Mo) subsets, the classical CD14(++) CD16(-) (cMo) and intermediate CD14(++) CD16(+) (iMo) Mos are known to activate pathogenic Th17 responses, whereas the impact of nonclassical CD14(+) CD16(++) Mo (nMo) on T-cell activation has been largely neglected. The aim of this study was to obtain new mechanistic insights on the capacity of Mo subsets from healthy donors (HDs) to activate IL-17(+) T-cell responses in vitro, and assess whether this function was maintained or lost in states of chronic inflammation. When cocultured with autologous CD4(+) T cells in the absence of TLR-2/NOD2 agonists, PB nMos from HDs were more efficient stimulators of IL-17-producing T cells, as compared to cMo. These results could not be explained by differences in Mo lifespan and cytokine profiles. Notably, however, the blocking of LFA-1/ICAM-1 interaction resulted in a significant increase in the percentage of IL-17(+) T cells expanded in nMo/T-cell cocultures. As compared to HD, PB Mo subsets of patients with rheumatoid arthritis were hampered in their T-cell stimulatory capacity. Our new insights highlight the role of Mo subsets in modulating inflammatory T-cell responses and suggest that nMo could become a critical therapeutic target against IL-17-mediated inflammatory diseases.

Control of Vertical Dimension During Rapid Palatal Expansion Using a High Pull Chin

Submitted in partial fulfillment of the requirements for a Certificate in Orthodontics, Dept. of Orthodontics, University of Connecticut Health Center, 1986

Detecting the signature of natural selection with microsatellites

Natural selection is one of the major factors in the evolution of all organisms. Detecting the signature of natural selection has been a central theme in evolutionary genetics. With the availability of microsatellite data, it is of interest to study how natural selection can be detected with microsatellites. ^ The overall aim of this research is to detect signatures of natural selection with data on genetic variation at microsatellite loci. The null hypothesis to be tested is the neutral mutation theory of molecular evolution, which states that different alleles at a locus have equivalent effects on fitness. Currently used tests of this hypothesis based on data on genetic polymorphism in natural populations presume that mutations at the loci follow the infinite allele/site models (IAM, ISM), in the sense that at each site at most only one mutation event is recorded, and each mutation leads to an allele not seen before in the population. Microsatellite loci, which are abundant in the genome, do not obey these mutation models, since the new alleles at such loci can be created either by contraction or expansion of tandem repeat sizes of core motifs. Since the current genome map is mainly composed of microsatellite loci and this class of loci is still most commonly studied in the context of human genome diversity, this research explores how the current test procedures for testing the neutral mutation hypothesis should be modified to take into account a generalized model of forward-backward stepwise mutations. In addition, recent literature also suggested that past demographic history of populations, presence of population substructure, and varying rates of mutations across loci all have confounding effects for detecting signatures of natural selection. ^ The effects of the stepwise mutation model and other confounding factors on detecting signature of natural selection are the main results of the research. ^

Stability of Rapid Maxillary Expansion

Submitted in partial fulfillment of the requirements for a Certificate in Orthodontics, Dept. of Orthodontics, University of Connecticut Health Center, 1993

Na 1 Nachlass Max Horkheimer, 694 - "German Economy, Politics and Culture, 1900-1933", "The Collapse of German Democracy and the Expansion of National Socialism" (p. IX 168e - IX 169a)

"German Economy, Politics and Culture, 1900-1933. A Research Project of the International Institute of Social Research" (1940):; 1. Umriß des Forschungsprojekts: e)-g) Fassung vom 25.5.1940: e) Typoskript, 63 Blatt, f) Typoskript mit handschriftlichen Korrekturen, 61 Blatt, g) Typoskript, 61 Blatt, h)-k) "Introduction": h) Typoskript, 21 Blatt, i) Typoskript, 15 Blatt, k) D.V. Glass: Entwurf, Manuskript, 17 Blatt; 2. Kostenschätzung zum Forschungsprojekt. 1 Blatt; "The Collapse of German Democracy and the Expansion of National Socialism" (1940):; 1. Darstellung des Forschungsprojekts (15.9.1940), a) als Typoskript vervielfältigt, 70 Blatt;

Na 1 Nachlass Max Horkheimer, 695 - "The Collapse of German Democracy and the Expansion of National Socialism", "Cultural Aspects of National Socialism" u.a. (p. IX 169.1a - IX 170.1-4)

"The Collapse of German Democracy and the Expansion of National Socialism" (1940):; 1. Darstellung des Forschungsprojekts (15.9.1940), b. Typoskript mit handschriftlichen Korrekturen, 78 Blatt; 2. "Research work on recent trends in the history of ideas (parts of the Research project on the Collapse of German Democracy would be included)". Als Memorandum zur Eröffnung zur Eröffnung einer Zweigstelle des Instituts in Los Angeles (12.12.1940): a) Typoskript, 2 Blatt, b) Teilstück, Typoskript mit handschriftlichen Korrekturen, 1 Blatt, c) Teilstück, Typoskript mit handschriftlichen Korrekturen, 1 Blatt, d) Teilstück, Typoskript, 1 Blatt, e) Teilstück, Typoskript, 1 Blatt, f) Entwurf, Typoskript mit handschriftlichen Korrekturen und Manuskript, 3 Blatt; 3. University of California, Los Angeles: 2 Briefe (Abschrift) von Max Horkheimer, o.O., 1940, 2 Briefe (Abschrift) an Max Horkheimer, 1940, 2 Blatt; A.R.L. Gurland: "Survey of Structural Changes in the German Economy, 1933 to 1939. Technological Bases and Organizational Forms of the National Socialist Economic System". Typoskript mit handschriftlichen Korrekturen unter anderem von Theodor W. Adorno, 48 Blatt (formal nicht identisch mit "Technological Trends and Economic Structure under National Socialism", Studies in Philosophy and Social Science, Bd. IX, 1941, S. 226ff.); "Cultural Aspects of National Socialism. A Research Project" (1941):; 1. Institute of Social Research: Mitteilung über das Forschungsprojekt und das 'Supplementary Statement', Typoskript, englisch, 4 Blatt; 2. Supplementary Statement to the Research Project, a) Typoskript, 14.4.1941, 63 Blatt, b) Typoskript, 12.4.1941, mit handschriftlichen Korrekturen, 35 Blatt; 3. "Cultural Aspects of National Socialism. A Research Project" (24.2.1941), a) als Typoskript vervielfältigt, 54 Blatt, b) Typoskript mit handschriftlichen Korrekturen, 34 Blatt, c) Fassung Januar 1941, Typoskript mit handschriftlichen Korrekturen, 40 Blatt; 4. Inhaltsverzeichnisse, mit handschriftlichen Korrekturen, 3 Blatt;

Texas Department of Health organizational structure changes: A reflection of public health policy and agency expansion, September 1, 1946--June 30, 1994

The premise of this study is that changes in the agency's organizational structure reflect changes in government public health policy. Based on this premise, this study tracks the changes in the organizational structure and the overall expansion of the Texas Department of Health to understand the evolution of changing public health priorities in state policy from September 1, 1946 through June 30, 1994, a period of growth and new responsibilities. It includes thirty-seven observations of organizational structure as depicted by organizational charts of the agency and/or adapted from public documents. ^ The major questions answered are, what are the changes in the organizational structure, why did they occur and, what are the policy priorities reflected in these changes in and across the various time periods. ^ The analysis of the study included a thorough review of the organizational structure of the agency for the time-span of the study, the formulation of the criteria to be used in ascertaining the changes, the delineation of the changes in the organizational structure and comparison of the observations sequentially to characterize the change, the discovery of reasons for the structural changes (financial, statutory - federal and state, social and political factors), and the determination of policy priorities for each time period and their relation to the expansion and evolution of the agency. ^ The premise that the organizational structure of the agency and the changes over time reflect government public health policy and agency expansion was found to be true. ^

Proteomic identification and functional characterization of prohibitin 1 and 2 in T cell activation, expansion, survival and disease

Several immune pathologies are the result of aberrant regulation of T lymphocytes. Pronounced T cell proliferation can result in autoimmunity or hematologic malignancy, whereas loss of T cell activity can manifest as immunodeficiency. Thus, there is a critical need to characterize the signal transduction pathways that mediate T cell activation so that novel and rational strategies to detect and effectively control T cell mediated disease can be achieved. ^ The first objective of this dissertation was to identify and characterize novel T cell regulatory proteins that are differentially expressed upon antigen induced activation. Using a functional proteomics approach, two members of the prohibitin (Phb) family of proteins, Phb1 and Phb2, were determined to be upregulated upon activation of primary human T cells. Furthermore, their regulated expression was dependent upon CD3 and CD28 signaling pathways which synergistically increased their expression. In contrast to previous reports of Phb nuclear localization, both proteins were determined to localize to the mitochondrial inner membrane of human T cells. Additionally, novel Phb phosphorylation sites were identified and characterized using mass spectrometry, phosphospecific antibodies and site directed mutagenesis. ^ Prohibitins have been proposed to play important roles in cancer development however the mechanism of action has not been elucidated. The second objective of this dissertation was to define the functional role of Phbs in T cell activity, survival and disease. Compared to levels in normal human T cells, Phb expression was higher in the human tumor T cell line Kit225 and subcellularly localized to the mitochondrion. Ablation of Phb expression by siRNA treatment of Kit225 cells resulted in disruption of mitochondrial membrane potential and significantly enhanced their sensitivity to cell death, suggesting they serve a protective function in T cells. Furthermore, Q-RT-PCR analysis of human oncology cDNA expression libraries indicated the Phbs may represent hematological cancer biomarkers. Indeed, Phb1 and Phb2 protein levels were 6-10 fold higher in peripheral blood mononuclear cells isolated from malignant lymphoma and multiple myeloma patients compared to healthy individuals. ^ Taken together, Phb1 and Phb2 are novel phosphoproteins upregulated during T cell activation and transformation to function in the maintenance of mitochondrial integrity and perhaps energy metabolism, thus representing previously unrecognized intracellular biomarkers and therapeutic targets for regulating T cell activation and hematologic malignancies. ^

A Su Salud Injury Prevention expansion: Analysis of injury prevention perceptions in a Hispanic community

Unintentional injury is the leading cause of death for American ages one to 44 and is ranked in the top ten causes of death for all age groups (CDC, 2006a). A Su Salud Injury Prevention was developed to address injury prevention awareness and education. The program is a mass media education campaign that uses role models, mass media, and community outreach to prevent injury. In 2009, University Health System (UHS) expanded the program. Baseline data were collected from 426 residents in targeted neighborhoods northwest of downtown San Antonio to support the expansion. The purpose of this study was to explore injury perceptions, knowledge, and behaviors of adults living in the expansion area, and define the predominant factors associated with these perceptions. A secondary aim was to assess community awareness and willingness to participate in the program.^ Survey results showed motor vehicle crashes (MVC), falls, drinking and driving, and guns and assaults were considered the most serious injures for adults. The most serious child injuries were MVC, abuse and neglect, falls, and head injuries. Residents were knowledgeable of state seatbelt policy, and over 90% responded as compliant for seatbelt and child car seat use. Most were knowledgeable about drinking and driving state policy and negative outcomes. However, 70% of those reporting driving under the influence of alcohol within the last year engaged in repeat high risk behavior. Men and residents under the age of 55 were more likely to engage in repeat drinking and driving (OR= 3.6, 7.0 respectively). Residents consider injury prevention an important issue, and have interest in a local injury prevention program. Younger women are the most likely to participate in a local program as potential role models and volunteers.^ Results from the study are summarized into an injury prevention and demographic profile of the community that will be used to develop tailored injury prevention messages to create a more effective program, and support program coordinators in effective community engagement. Results will also be used as a comparative basis for future evaluation of a behavioral injury prevention program focused on a predominantly Mexican-American community.^

Regulation of phosphatidylinositide turnover in the myometrium by cAMP: Implications for the control of uterine contraction

Regulation of uterine quiescence involves the integration of the signaling pathways regulating uterine contraction and relaxation. Uterine contractants increase intracellular calcium through receptor/GαqPLC coupling, resulting in contraction of the myometrium. Elevation of cAMP concentration has been correlated with relaxation of the myometrium. However, the mechanism of cAMP action in the uterus is unclear. ^ Both endogenous and exogenous increases in cAMP inhibited oxytocin-stimulated phosphatidylinositide turnover in an immortalized pregnant human myometrial cell line (PHM1-41). This inhibition was reversed by cAMP-dependent protein kinase (PKA) inhibitors, suggesting the involvement of PKA. cAMP inhibited phosphatidyinositide turnover stimulated by different agonists in different cell lines. These data suggest that the cAMP inhibitory mechanism is neither cell nor receptor dependent, and inhibits Gαq/PLCβ1 and PLCβ3 coupling. ^ The subcellular localization of PKA occurs via PKA binding to A-Kinase-Anchoring-Proteins (AKAP), and peptides that inhibit this association have been developed (S-Ht31). S-Ht31 blocked cAMP-stimulated PKA activity and decreased PKA concentration in PHM1-41 cell plasma membranes. S-Ht31 reversed the ability of CPT-cAMP, forskolin and relaxin to inhibit phosphatidylinositide turnover in PHM1-41 cells. Overlay analysis of both PHM1-41 cell and nonpregnant rat myometrium found an AKAPs of 86 kDa and 150 kDa associated with the plasma membrane, respectively. These data suggest that PKA anchored to the plasma membrane via AKAP150/PKA anchoring is involved in the cAMP inhibitory mechanism. ^ CPT-cAMP and isoproterenol inhibited phosphatidylinositide turnover in rat myometrium from days 12 through 20 of gestation. In contrast, neither agent was effective in the 21 day pregnant rat myometrium. The decrease in the cAMP inhibitory mechanism was correlated with a decrease in PKA and an increase in protein phosphatase 2B (PP2B) concentration in rat myometrial plasma membranes on day 21 of gestation. In myometrial total cell homogenates, both PKA and PP2B concentration increased on day 21. S-Ht31 inhibited cAMP inhibition of phosphatidylinositide turnover in day 19 pregnant rat myometrium. Both PKA and PP2B coimmunoprecipitated with an AKAP150 in a gestational dependent manner, suggesting this AKAP localizes PKA and PP2B to the plasma membrane. ^ These data presented demonstrate the importance of the cAMP inhibitory mechanism in regulating uterine contractility. ^

Description and chemical and mineral composition of iron oxide samples from two Finnish lakes

Fifteen iron oxide accumulations from the bottoms of two Finnish lakes ("lake ores") were found to contain as much as 50% Fe. Differential X-ray powder diffraction and selective dissolution by oxalate showed that the samples consisted of poorly crystallized goethite and ferrihydrite. The crust ores of one lake had higher ferrihydrite to goethite ratios than the nodular ores of the other lake. The higher ferrihydrite proportion was attributed to a higher rate of Fe2+ supply from the ground water and/or a higher rate of oxidation as a function of water depth and bottom-sediment permeability. Values of Al-for-Fe substitution of the goethites determined from unit-cell dimensions agreed with those obtained from chemical extraction if the unit-cell volume rather than the c dimension was used. In very small goethite crystals a slight expansion of the a unit-cell dimension is probaby compensated by a corresponding contraction of the c dimension, so that a contraction of the c dimension need not necessarily be caused by Al substitution. The goethites of the two lakes differed significantly in their Al-for-Fe substitutions and hence in their unit-cell sizes, OH-bending characteristics, dehydroxylation temperatures, dissolution kinetics, and Mössbauer parameters. The difference in Al substitution (0 vs. 7 mole %) is attributed to the Al-supplying power of the bottom sediments: the silty-clayey sediments in one lake appear to have supplied A1 during goethite formation, whereas the gravelly-sandy sediments in the other lake did not. The compositions of the goethites thus reflect their environments of formation.

Age model and color measurements of sediment cores from the eastern equatorial Pacific

High-resolution records of glacial-interglacial variations in biogenic carbonate, opal, and detritus (derived from non-destructive core log measurements of density, P-wave velocity and color; r >= 0.9) from 15 sediment sites in the eastern equatorial (sampling resolution is ~1 kyr) clear response to eccentricity and precession forcing. For the Peru Basin, we generate a high-resolution (21 kyr increment) orbitally-based chronology for the last 1.3 Ma. Spectral analysis indicates that the 100 kyr cycle became dominant at roughly 1.2 Ma, 200-300 kyr earlier than reported for other paleoclimatic records. The response to orbital forcing is weaker since the Mid-Brunhes Dissolution Event (at 400 ka). A west-east reconstruction of biogenic sedimentation in the Peru Basin (four cores; 91-85°W) distinguishes equatorial and coastal upwelling systems in the western and eastern sites, respectively. A north-south reconstruction perpendicular to the equatorial upwelling system (11 cores, 11°N-°3S) shows high carbonate contents (>= 50%) between 6°N and 4°S and highly variable opal contents between 2°N and 4°S. Carbonate cycles B-6, B-8, B-10, B-12, B-14, M-2, and M-6 are well developed with B-10 (430 ka) as the most prominent cycle. Carbonate highs during glacials and glacial-interglacial transitions extended up to 400 km north and south compared to interglacial or interglacial^glacial carbonate lows. Our reconstruction thus favors glacial-interglacial expansion and contraction of the equatorial upwelling system rather than shifting north or south. Elevated accumulation rates are documented near the equator from 6°N to 4°S and from 2°N to 4°S for carbonate and opal, respectively. Accumulation rates are higher during glacials and glacial-interglacial transitions in all cores, whereas increased dissolution is concentrated on Peru Basin sediments close to the carbonate compensation depth and occurred during interglacials or interglacial-glacial transitions.

Raster maps for 29 environmental variables in three geographical regions

Aim: Greater understanding of the processes underlying biological invasions is required to determine and predict invasion risk. Two subspecies of olive (Olea europaea subsp. europaea and Olea europaea subsp. cuspidata) have been introduced into Australia from the Mediterranean Basin and southern Africa during the 19th century. Our aim was to determine to what extent the native environmental niches of these two olive subspecies explain the current spatial segregation of the subspecies in their non-native range. We also assessed whether niche shifts had occurred in the non-native range, and examined whether invasion was associated with increased or decreased occupancy of niche space in the non-native range relative to the native range. Location: South-eastern Australia, Mediterranean Basin and southern Africa. Methods: Ecological niche models (ENMs) were used to quantify the similarity of native and non-native realized niches. Niche shifts were characterized by the relative contribution of niche expansion, stability and contraction based on the relative occupancy of environmental space by the native and non-native populations. Results: Native ENMs indicated that the spatial segregation of the two subspecies in their non-native range was partly determined by differences in their native niches. However, we found that environmentally suitable niches were less occupied in the non-native range relative to the native range, indicating that niche shifts had occurred through a contraction of the native niches after invasion, for both subspecies. Main conclusions: The mapping of environmental factors associated with niche expansion, stability or contraction allowed us to identify areas of greater invasion risk. This study provides an example of successful invasions that are associated with niche shifts, illustrating that introduced plant species are sometimes readily able to establish in novel environments. In these situations the assumption of niche stasis during invasion, which is implicitly assumed by ENMs, may be unreasonable.

Establishment, expansion and regeneration of aspen (Populus tremula) in the Torneträsk area, subarctic Sweden

In subarctic Sweden, recent decadal colonization and expansion of aspen (Populus tremula L.) were recorded. Over the past 100 years, aspen became c. 16 times more abundant, mainly as a result of increased sexual regeneration. Moreover, aspen now reach tree-size (>2 m) at the alpine treeline, an ecotone that has been dominated by mountain birch (Betula pubescens ssp. czerepanovii) for at least the past 4000 years. We found that sexual regeneration in aspen probably occurred seven times or more within the last century. Whereas sexual regeneration occurred during moist years following a year with an exceptionally high June-July temperature, asexual regeneration was favored by warm and dry summers. Disturbance to the birch forest by cyclic moth population outbreaks was critical in aspen establishment in the subalpine area. At the treeline, aspen colonization was less determined by these moth outbreaks, and was mainly restricted by summer temperature. If summer warming persists, aspen spread may continue in subarctic Sweden, particularly at the treeline. However, changing disturbance regimes, future herbivore population dynamics and the responses of aspen's competitors birch and pine to a changing climate may result in different outcomes.