472 research outputs found
The State of Theory in LGBTQ Aging: Implications for Gerontological Scholarship
Social research in lesbian, gay, bisexual, transgender, and queer (LGBTQ) aging is a rapidly growing field, but an examination of the use of theory has not yet been conducted for its impact on the fieldâs direction. We conducted a systematic review of empirical articles published in LGBTQ aging in the years 2009â2017 (N = 102). Using a typology of theory use in scholarly articles, we analyzed these articles for the types of theories being used, the degree to which theories were used in each article, and the analytical function they served. We found that 52% of articles consistently applied theory, 23% implied or partially applied theory, and 25% presented as atheoretical. A wide range of theories were used and served multiple analytical functions such as concept development and explanation of findings. We discuss the strengths and weaknesses of theory use in this body of literature, especially with respect to implications for future knowledge development in the field
Accounting Problems Under the Excess Profits Tax
DNA vaccines based on subunits from pathogens have several advantages over other vaccine strategies. DNA vaccines can easily be modified, they show good safety profiles, are stable and inexpensive to produce, and the immune response can be focused to the antigen of interest. However, the immunogenicity of DNA vaccines which is generally quite low needs to be improved. Electroporation and co-delivery of genetically encoded immune adjuvants are two strategies aiming at increasing the efficacy of DNA vaccines. Here, we have examined whether targeting to antigen-presenting cells (APC) could increase the immune response to surface envelope glycoprotein (Env) gp120 from Human Immunodeficiency Virus type 1 (HIV- 1). To target APC, we utilized a homodimeric vaccine format denoted vaccibody, which enables covalent fusion of gp120 to molecules that can target APC. Two molecules were tested for their efficiency as targeting units: the antibody-derived single chain Fragment variable (scFv) specific for the major histocompatilibility complex (MHC) class II I-E molecules, and the CC chemokine ligand 3 (CCL3). The vaccines were delivered as DNA into muscle of mice with or without electroporation. Targeting of gp120 to MHC class II molecules induced antibodies that neutralized HIV-1 and that persisted for more than a year after one single immunization with electroporation. Targeting by CCL3 significantly increased the number of HIV-1 gp120-reactive CD8(+) T cells compared to non-targeted vaccines and gp120 delivered alone in the absence of electroporation. The data suggest that chemokines are promising molecular adjuvants because small amounts can attract immune cells and promote immune responses without advanced equipment such as electroporation.Funding Agencies|Research Council of Norway; Odd Fellow</p
Estimating Remaining Carbon Budgets Using Temperature Responses Informed by CMIP6
A remaining carbon budget (RCB) estimates how much CO2 we can emit and still reach a specific temperature target. The RCB concept is attractive since it easily communicates to the public and policymakers, but RCBs are also subject to uncertainties. The expected warming levels for a given carbon budget has a wide uncertainty range, which increases with less ambitious targets, i.e., with higher CO2 emissions and temperatures. Leading causes of RCB uncertainty are the future non-CO2 emissions, Earth system feedbacks, and the spread in the climate sensitivity among climate models. The latter is investigated in this paper, using a simple carbon cycle model and emulators of the temperature responses of the Earth System Models in the Coupled Model Intercomparison Project Phase 6 (CMIP6) ensemble. Driving 41 CMIP6 emulators with 127 different emission scenarios for the 21st century, we find almost perfect linear relationship between maximum global surface air temperature and cumulative carbon emissions, allowing unambiguous estimates of RCB for each CMIP6 model. The range of these estimates over the model ensemble is a measure of the uncertainty in the RCB arising from the range in climate sensitivity over this ensemble, and it is suggested that observational constraints imposed on the transient climate response in the model ensemble can reduce uncertainty in RCB estimates
Comparison of bulk milk antibody and youngstock serology screens for determining herd status for Bovine Viral Diarrhoea Virus
BACKGROUND: This paper examines the use of Bulk Milk antibody (BM Ab), Youngstock (YS) serology (Check Tests) and Bulk Milk PCR (BM PCR) for determining the presence or absence of animals persistently infected (PI) with Bovine Viral Diarrhoea Virus (BVDV) within a herd. Data is presented from 26 herds where average herd sizes were 343 and 98 animals for dairy and beef units respectively. Seventeen herds had sufficient data to analyse using Receiver Operating Characteristic (ROC) and probability curves enabling calculation of the sensitivity and specificity of BM Ab and YS Check tests for determining the presence of PI animals within herds in this dataset. RESULTS: Using BM Ab to screen a herd for the presence of PI animals, achieved a herd level sensitivity and specificity of 80.00Â % (44.39â97.48Â %) and 85.71Â % (42.13â99.64Â %) respectively (95Â % confidence intervals quoted). Sensitivity and specificity of YS Check Tests at a cut off of 3/10 Ab positive YS were 81.82Â % (48.22â97.72Â %) and 66.67Â % (22.28â95.67Â %) respectively (95Â % confidence interval). These results were achieved by comparing the screening tests to whole herd PI searches that took place 1â19 months after the initial screen with a mean interval of 8Â months. Removal of this delay by taking BM samples on the day of a whole herd test and simulating a YS Check Test from the herd test data produced improvements in the reliability of the Check Tests. BM Ab sensitivity and specificity remained unchanged. However, the Check Test sensitivity and specificity improved to 90.9Â % (58.72â99.77Â %) and 100Â % (54.07â100Â %) respectively (95Â % confidence interval) at a cut of off 2.5/10 Ab positive animals. Our limited BM PCR results identified 5/23 dairy farms with a positive BM PCR result; two contained milking PIs, two had non-milking PIs and another had no PIs identified. CONCLUSIONS: Delaying a PI search following an initial herd screen decreased the diagnostic accuracy and relevance of our results. With careful interpretation, longitudinal surveillance using a combination of the techniques discussed can successfully determine farm status and therefore allow changes in BVDV status to be detected early, thus enabling prompt action in the event of a BVDV incursion
Lactobacillus plantarum displaying CCL3 chemokine in fusion with HIV-1 Gag derived antigen causes increased recruitment of T cells
Background Chemokines are attractive candidates for vaccine adjuvants due to their ability to recruit the immune cells. Lactic acid bacteria (LAB)-based delivery vehicles have potential to be used as a cheap and safe option for vaccination. Chemokine produced on the surface of LAB may potentially enhance the immune response to an antigen and this approach can be considered in development of future mucosal vaccines.
Results We have constructed strains of Lactobacillus plantarum displaying a chemokine on their surface. L. plantarum was genetically engineered to express and anchor to the surface a protein called CCL3Gag. CCL3Gag is a fusion protein comprising of truncated HIV-1 Gag antigen and the murine chemokine CCL3, also known as MIP-1Îą. Various surface anchoring strategies were explored: (1) a lipobox-based covalent membrane anchor, (2) sortase-mediated covalent cell wall anchoring, (3) LysM-based non-covalent cell wall anchoring, and (4) an N-terminal signal peptide-based transmembrane anchor. Protein production and correct localization were confirmed using Western blotting, flow cytometry and immunofluorescence microscopy. Using a chemotaxis assay, we demonstrated that CCL3Gag-producing L. plantarum strains are able to recruit immune cells in vitro.
Conclusions The results show the ability of engineered L. plantarum to produce a functional chemotactic protein immobilized on the bacterial surface. We observed that the activity of surface-displayed CCL3Gag differed depending on the type of anchor used. The chemokine which is a part of the bacteria-based vaccine may increase the recruitment of immune cells and, thereby, enhance the reaction of the immune system to the vaccine
The Structure of Climate Variability Across Scales
One of the most intriguing facets of the climate system is that it exhibits variability across all temporal and spatial scales; pronounced examples are temperature and precipitation. The structure of this variability, however, is not arbitrary. Over certain spatial and temporal ranges it can be described by scaling relationships in the form of powerâlaws in probability density distributions and autocorrelation functions. These scaling relationships can be quantified by scaling exponents which measure how the variability changes across scales and how the intensity changes with frequency of occurrence. Scaling determines the relative magnitudes and persistence of natural climate fluctuations. Here, we review various scaling mechanisms and their relevance for the climate system. We show observational evidence of scaling and discuss the application of scaling properties and methods in trend detection, climate sensitivity analyses, and climate predictio
A new method of inferring the size, number density, and charge of mesospheric dust from its in situ collection by the DUSTY probe
The linguocultural image of hand in Polish folk languageThe goal of this paper is a reconstruction of the linguocultural image of rÄka (hand) in the Polish folk language, as defined by a cognitive model proposed by BartmiĹski in the 1980âs. Among the sources considered here are the linguistic system itself (as exemplified by dictionaries of the Polish language, etymological dictionaries, dialect dictionaries) as well as literary texts, including folk songs and prose (e.g. riddles, sayings, fairy tales), and folk traditions and beliefs, recorded in the FOLBAS computer base and in the UMCS Ethnolinguistic Archives. From all these sources there emerges a rich and complex image showing this part of the body mainly from a functional perspective and appreciation of its role in Polish folk culture
A new method of inferring the size, number density, and charge of mesospheric dust from its in situ collection by the DUSTY probe
We present a new method of analyzing measurements of mesospheric
dust made with DUSTY rocket-borne Faraday cup probes. It can yield the
variation in fundamental dust parameters through a mesospheric cloud with an
altitude resolution down to 10 cm or less if plasma probes give the plasma
density variations with similar height resolution. A DUSTY probe was the
first probe that unambiguously detected charged dust and aerosol particles in
the Earth's mesosphere. DUSTY excluded the ambient plasma by various biased
grids, which however allowed dust particles with radii above a few nanometers
to enter, and it measured the flux of charged dust particles. The flux
measurements directly yielded the total ambient dust charge density.
We extend the analysis of DUSTY data by using the impact currents on its main
grid and the bottom plate as before, together with a dust charging model and
a secondary charge production model, to allow the determination of
fundamental parameters, such as dust radius, charge number, and total dust
density. We demonstrate the utility of the new analysis technique by
considering observations made with the DUSTY probes during the MAXIDUSTY
rocket campaign in JuneâJuly 2016 and comparing the results with those of
other instruments (lidar and photometer) also used in the campaign. In the
present version we have used monodisperse dust size distributions.</p
The bodily presence of significant others: Intensive care patients' experiences in a situation of critical illness
This study is about intensive care patients and the bodily presence of significant others. The aim of the study is to inquire and understand the patients experience of the body in relation to their significant others during critical illness. Open, unstructured, in-depth interviews with six former intensive care patients provide the data for the study. The phenomenologicalâhermeneutical analysis points to a theme among ICU patients' experience of conflict between proximity and distance during the bodily presence of their relations. Patients experience different and conflicting forms of responses to the presence of their significant others. Patients experience significant positive confirmation but also negation through this presence. In the ICU situation, the reactions of significant others appear difficult to deal with, yet the physical presence is significant for establishing a sense of affinity. Patients seek to take some responsibility for themselves as well as for their relatives, and are met with a whole spectrum of reactions. Intensive care patients experience the need to be actively, physically present, which often creates sharp opposition between their personal needs and the needs of their significant others for active participation
Deletion of parasite immune modulatory sequences combined with immune activating signals enhances vaccine mediated protection against filarial nematodes
<p>Background: Filarial nematodes are tissue-dwelling parasites that can be killed by Th2-driven immune effectors, but that have evolved to withstand immune attack and establish chronic infections by suppressing host immunity. As a consequence, the efficacy of a vaccine against filariasis may depend on its capacity to counter parasite-driven immunomodulation.</p>
<p>Methodology and Principal Findings: We immunised mice with DNA plasmids expressing functionally-inactivated forms of two immunomodulatory molecules expressed by the filarial parasite Litomosoides sigmodontis: the abundant larval transcript-1 (LsALT) and cysteine protease inhibitor-2 (LsCPI). The mutant proteins enhanced antibody and cytokine responses to live parasite challenge, and led to more leukocyte recruitment to the site of infection than their native forms. The immune response was further enhanced when the antigens were targeted to dendritic cells using a single chain Fv-ÎąDEC205 antibody and co-administered with plasmids that enhance T helper 2 immunity (IL-4) and antigen-presenting cell recruitment (Flt3L, MIP-1Îą). Mice immunised simultaneously against the mutated forms of LsALT and LsCPI eliminated adult parasites faster and consistently reduced peripheral microfilaraemia. A multifactorial analysis of the immune response revealed that protection was strongly correlated with the production of parasite-specific IgG1 and with the numbers of leukocytes present at the site of infection.</p>
<p>Conclusions: We have developed a successful strategy for DNA vaccination against a nematode infection that specifically targets parasite-driven immunosuppression while simultaneously enhancing Th2 immune responses and parasite antigen presentation by dendritic cells.</p>
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