223 research outputs found
Multiple‐Path Technique for the Determination of Physico‐Chemical Data Behind Shock Fronts
Application of photogrammetry to generate quantitative geobody data in ephemeral fluvial systems
Outcrop studies are often used as analogues to subsurface sedimentary reservoirs, with photogrammetry representing a useful technique to obtain quantitative geometrical data of sedimentary architectures. Digital photogrammetry techniques were used to study fluvial sediments of the Lower Jurassic Kayenta Formation of the western USA, and model-extracted statistics for channel and sheetflood elements, relevant to reservoir modelling, were compared to 1D and 2D datasets from the same outcrops. Results suggest that the 1D/2D data significantly underestimated element dimensions and ranges in ephemeral-fluvial systems. Consequently, this study demonstrates the value of photogrammetric techniques for obtaining statistically relevant and more accurate reservoir modelling input data from outcrop
Functional Diffusion Tensor Imaging: Measuring Task-Related Fractional Anisotropy Changes in the Human Brain along White Matter Tracts
Functional neural networks in the human brain can be studied from correlations between activated gray matter regions measured with fMRI. However, while providing important information on gray matter activation, no information is gathered on the co-activity along white matter tracts in neural networks.We report on a functional diffusion tensor imaging (fDTI) method that measures task-related changes in fractional anisotropy (FA) along white matter tracts. We hypothesize that these fractional anisotropy changes relate to morphological changes of glial cells induced by axonal activity although the exact physiological underpinnings of the measured FA changes remain to be elucidated. As expected, these changes are very small as compared to the physiological noise and a reliable detection of the signal change would require a large number of measurements. However, a substantial increase in signal-to-noise ratio was achieved by pooling the signal over the complete fiber tract. Adopting such a tract-based statistics enabled us to measure the signal within a practically feasible time period. Activation in the sensory thalamocortical tract and optic radiation in eight healthy human subjects was found during tactile and visual stimulation, respectively.The results of our experiments indicate that these FA changes may serve as a functional contrast mechanism for white matter. This noninvasive fDTI method may provide a new approach to study functional neural networks in the human brain
Argyrin B a non-competitive inhibitor of the human immunoproteasome exhibiting preference for β1i
Inhibitors of the proteasome have found broad therapeutic applications however, they show severe toxicity due to the abundance of proteasomes in healthy cells. In contrast, inhibitors of the immunoproteasome, which is upregulated during disease states, are less toxic and have increased therapeutic potential including against autoimmune disorders. In this project, we report argyrin B, a natural product cyclic peptide to be a reversible, non-competitive inhibitor of the immunoproteasome. Argyrin B showed selective inhibition of the β5i and β1i sites of the immunoproteasome over the β5c and β1c sites of the constitutive proteasome with nearly 20-fold selective inhibition of β1i over the homologous β1c. Molecular modelling attributes the β1i over β1c selectivity to the small hydrophobic S1 pocket of β1i and β5i over β5c to site-specific amino acid variations that enable additional bonding interactions and stabilization of the binding conformation. These findings facilitate the design of immunoproteasome selective and reversible inhibitors that may have a greater therapeutic potential and lower toxicity
Interventions for families affected by HIV
Family-based interventions are efficacious for human immunodeficiency virus (HIV) detection, prevention, and care, but they are not broadly diffused. Understanding intervention adaptation and translation processes can support evidence-based intervention (EBI) diffusion processes. This paper provides a narrative review of a series of EBI for families affected by HIV (FAH) that were adapted across five randomized controlled trials in the US, Thailand, and South Africa over 15 years. The FAH interventions targeted parents living with HIV and their children or caregiver supports. Parents with HIV were primarily mothers infected through sexual transmission. The EBIs for FAH are reviewed with attention to commonalities and variations in risk environments and intervention features. Frameworks for common and robust intervention functions, principles, practice elements, and delivery processes are utilized to highlight commonalities and adaptations for each location, time period, and intervention delivery settings. Health care, housing, food, and financial security vary dramatically in each risk environment. Yet, all FAH face common health, mental health, transmission, and relationship challenges. The EBIs efficaciously addressed these common challenges and were adapted across contexts with fidelity to robust intervention principles, processes, factors, and practices. Intervention adaptation teams have a series of structural decision points: mainstreaming HIV with other local health priorities or not; selecting an optimal delivery site (clinics, homes, community centers); and how to translate intervention protocols to local contexts and cultures. Replication of interventions with fidelity must occur at the level of standardized functions and robust principles, processes, and practices, not manualized protocols. Adopting a continuous quality improvement paradigm will enhance rapid and global diffusion of EBI for FAH
An exploratory study to examine intentions to adopt an evidence-based HIV linkage-to-care intervention among state health department AIDS directors in the United States
<p>Abstract</p> <p>Background</p> <p>Widespread dissemination and implementation of evidence-based human immunodeficiency virus (HIV) linkage-to-care (LTC) interventions is essential for improving HIV-positive patients' health outcomes and reducing transmission to uninfected others. To date, however, little work has focused on identifying factors associated with intentions to adopt LTC interventions among policy makers, including city, state, and territory health department AIDS directors who play a critical role in deciding whether an intervention is endorsed, distributed, and/or funded throughout their region.</p> <p>Methods</p> <p>Between December 2010 and February 2011, we administered an online questionnaire with state, territory, and city health department AIDS directors throughout the United States to identify factors associated with intentions to adopt an LTC intervention. Guided by pertinent theoretical frameworks, including the Diffusion of Innovations and the "push-pull" capacity model, we assessed participants' attitudes towards the intervention, perceived organizational and contextual demand and support for the intervention, likelihood of adoption given endorsement from stakeholder groups (<it>e.g</it>., academic researchers, federal agencies, activist organizations), and likelihood of enabling future dissemination efforts by recommending the intervention to other health departments and community-based organizations.</p> <p>Results</p> <p>Forty-four participants (67% of the eligible sample) completed the online questionnaire. Approximately one-third (34.9%) reported that they intended to adopt the LTC intervention for use in their city, state, or territory in the future. Consistent with prior, related work, these participants were classified as LTC intervention "adopters" and were compared to "nonadopters" for data analysis. Overall, adopters reported more positive attitudes and greater perceived demand and support for the intervention than did nonadopters. Further, participants varied with their intention to adopt the LTC intervention in the future depending on endorsement from different key stakeholder groups. Most participants indicated that they would support the dissemination of the intervention by recommending it to other health departments and community-based organizations.</p> <p>Conclusions</p> <p>Findings from this exploratory study provide initial insight into factors associated with public health policy makers' intentions to adopt an LTC intervention. Implications for future research in this area, as well as potential policy-related strategies for enhancing the adoption of LTC interventions, are discussed.</p
Non invasive in vivo investigation of hepatobiliary structure and function in STII medaka (Oryzias latipes): methodology and applications
Differential roles of epigenetic changes and Foxp3 expression in regulatory T cell-specific transcriptional regulation
Naturally occurring regulatory T (Treg) cells, which specifically express the transcription factor forkhead box P3 (Foxp3), are engaged in the maintenance of immunological self-tolerance and homeostasis. By transcriptional start site cluster analysis, we assessed here how genome-wide patterns of DNA methylation or Foxp3 binding sites were associated with Treg-specific gene expression. We found that Treg-specific DNA hypomethylated regions were closely associated with Treg up-regulated transcriptional start site clusters, whereas Foxp3 binding regions had no significant correlation with either up- or down-regulated clusters in nonactivated Treg cells. However, in activated Treg cells, Foxp3 binding regions showed a strong correlation with down-regulated clusters. In accordance with these findings, the above two features of activation-dependent gene regulation in Treg cells tend to occur at different locations in the genome. The results collectively indicate that Treg-specific DNA hypomethylation is instrumental in gene up-regulation in steady state Treg cells, whereas Foxp3 down-regulates the expression of its target genes in activated Treg cells. Thus, the two events seem to play distinct but complementary roles in Treg-specific gene expression
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