Knowledge modeling for software design

This paper develops a modeling framework for systems engineering that encompasses systems modeling, task modeling, and knowledge modeling, and allows knowledge engineering and software engineering to be seen as part of a unified developmental process. This framework is used to evaluate what novel contributions the 'knowledge engineering' paradigm has made and how these impact software engineering

Effects of Ponderosa Pine Ecological Restoration on Forest Soils and Understory Vegetation in Northern Arizona

The human exclusion of wildfire and overgrazing by livestock since settlement have caused dramatic changes in ponderosa pine (Pinus ponderosa Dougl ex Laws) forest ecosystems. These changes include increased numbers of tree stems, reduced understory cover and diversity, and the introduction of invasive, non-native understory species. This study evaluated the coverage and species composition of understory vegetation present in the “cool-season” (late spring and early summer) in a ponderosa pine forest on grazed and ungrazed plots that had undergone restoration treatments on three different soil/geologic parent material types near Flagstaff, Arizona, twelve years after tree thinning and grazing exclosure treatments were applied. Several measured soil properties, such as soil respiration and temperature, were also evaluated in this study. Species richness of “cool-season” vegetation was influenced more by grazing practices than restoration treatments. Differences could be less or greater when vegetation that is active later in the season is measured. Vegetative cover was significantly influenced by restoration treatments (9.3% cover under open canopies and 6.5% under dense canopies), probably due to differences in competition for light and other resources (i.e. soil moisture and nutrients). Unlike finding by Abella et al. (2015), who studied “warm-season” vegetation, “cool-season” understory cover was not influenced by soil parent material type in this study, which might suggest that differences in understory cover due to soil properties are only seen shortly after restoration treatments are applied, or the time of year vegetation is evaluated may play a role in the differences seen. Soil respiration was highest on limestone soil parent material type (3.3 g C-CO2 m-2 day-1), and soil temperature was lowest under closed canopy treatments (15°C)

IFN-γ-producing CD4+ T cells promote experimental cerebral malaria by modulating CD8+ T cell accumulation within the brain.

It is well established that IFN-γ is required for the development of experimental cerebral malaria (ECM) during Plasmodium berghei ANKA infection of C57BL/6 mice. However, the temporal and tissue-specific cellular sources of IFN-γ during P. berghei ANKA infection have not been investigated, and it is not known whether IFN-γ production by a single cell type in isolation can induce cerebral pathology. In this study, using IFN-γ reporter mice, we show that NK cells dominate the IFN-γ response during the early stages of infection in the brain, but not in the spleen, before being replaced by CD4(+) and CD8(+) T cells. Importantly, we demonstrate that IFN-γ-producing CD4(+) T cells, but not innate or CD8(+) T cells, can promote the development of ECM in normally resistant IFN-γ(-/-) mice infected with P. berghei ANKA. Adoptively transferred wild-type CD4(+) T cells accumulate within the spleen, lung, and brain of IFN-γ(-/-) mice and induce ECM through active IFN-γ secretion, which increases the accumulation of endogenous IFN-γ(-/-) CD8(+) T cells within the brain. Depletion of endogenous IFN-γ(-/-) CD8(+) T cells abrogates the ability of wild-type CD4(+) T cells to promote ECM. Finally, we show that IFN-γ production, specifically by CD4(+) T cells, is sufficient to induce expression of CXCL9 and CXCL10 within the brain, providing a mechanistic basis for the enhanced CD8(+) T cell accumulation. To our knowledge, these observations demonstrate, for the first time, the importance of and pathways by which IFN-γ-producing CD4(+) T cells promote the development of ECM during P. berghei ANKA infection

No Fall Too Small: Assessing Barriers to Fall Prevention Programs

In Vermont, 1/3 of adults 45 years or older fell in the year 2018, statistically above the national average, which has not changed since 2012. Of those who fell, 34% experienced an injury after their fall. Evidence-based interventions and fall prevention programs effectively reduce falls, and these programs aimed at reducing falls appear to reduce fractures. In fact, it has been shown that exercise intervention reduces fall risk by 30%. Our review of the literature highlighted that there are numerous barriers to accessing fall prevention programs, including loss of independence, transportation, cost, and lack of interest. With this in mind, we investigated the potential barriers to accessing and attending fall prevention programs in Vermont.https://scholarworks.uvm.edu/comphp_gallery/1311/thumbnail.jp

Clinically Silent Alzheimer\u27s and Vascular Pathologies Influence Brain Networks Supporting Executive Function in Healthy Older Adults

Aging is associated with declines in executive function. We examined how executive functional brain systems are influenced by clinically silent Alzheimer’s disease (AD) pathology and cerebral white matter hyperintensities (WMHs). Twenty-nine younger adults and thirty-four cognitively normal older adults completed a working memory paradigm while functional magnetic resonance imaging (fMRI) was performed. Older adults further underwent lumbar cerebrospinal fluid (CSF) draw for assessment of AD pathology and FLAIR imaging for assessment of WMHs. Accurate working memory performance in both age groups was associated with high fronto-visual functional connectivity (fC). However, in older adults, higher expression of fronto-visual fC was linked with lower levels of clinically silent AD pathology. In addition, AD pathology and WMHs were each independently related to increased fMRI response in the left dorsolateral prefrontal cortex, a pattern associated with slower task performance. Our results suggest that clinically silent AD pathology is related to lower expression of a fronto-visual fC pattern supporting executive task performance. Further, our findings suggest that AD pathology and WMHs appear to be linked with ineffective increases in frontal response in CN older adults

Brief Report: HIV-1 gp120 T-Cell Responses Correspond to Infection Outcomes in the Global iPrEx Chemoprophylaxis Trial.

Association of HIV-1-specific T-cell responses to infection risk in seronegative individuals is controversial. We quantified and phenotypically characterized gp120-specific T-cell responses in HIV-1 exposed, but uninfected subjects enrolled in the global Pre-exposure Prophylaxis Initiative (iPrEx) chemoprophylaxis trial. IFNγ ELISpot responses were detected in 24% of subjects irrespective of infection outcome. HIV-1 gp120 envelope-specific T-cell responses were more uniformly IFN-γ+TNF-α+Mip-1β+ in persistently seronegative subjects relative to subjects who later seroconverted (median frequency of 76.5% and 66.5%, respectively). IFNγ responses targeted the V2 loop for subjects who remained seronegative. HIV-1 gp120 envelope V2 loop-specific CD8 T-cell responses may help to protect against HIV-1 acquisition

Discs large (Dlg1) complexes in lymphocyte activation

T cell antigen recognition involves the formation of a structured interface between antigen-presenting and T cells that facilitates the specific transmission of activating and desensitizing stimuli. The molecular machinery that organizes the signaling molecules and controls their disposition in response to activation remains poorly understood. We show here that in T cells Discs large (Dlg1), a PDZ domain-containing protein, is recruited upon activation to cortical actin and forms complexes with early participants in T cell activation. Transient overexpression of Dlg1 attenuates basal and Vav1-induced NFAT reporter activation. Reduction of Dlg1 expression by RNA interference enhances both CD3- and superantigen-mediated NFAT activation. Attenuation of antigen receptor signaling appears to be a complex, highly orchestrated event that involves the mutual segregation of important elements of the early signaling complex

Comparison of Mycobacterium tuberculosis genomes reveals frequent deletions in a 20 kb variable region in clinical isolates. Yeast 17:272–282

Abstract The Mycobacterium tuberculosis complex is associated with a remarkably low level of structural gene polymorphism. As part of a search for alternative forms of genetic variation that may act as a source of biological diversity in M. tuberculosis, we have identi®ed a region of the genome that is highly variable amongst a panel of unrelated clinical isolates. Fifteen of 24 isolates examined contained one or more copies of the M. tuberculosis-speci®c IS6110 insertion element within this 20 kb variable region. In nine of the isolates, including the laboratory-passaged strain H37Rv, genomic deletions were identi®ed, resulting in loss of between two and 13 genes. In each case, deletions were associated with the presence of a copy of the IS6110 element. Absence of¯anking tri-or tetra-nucleotide repeats identi®ed homologous recombination between adjacent IS6110 elements as the most likely mechanism of the deletion events. IS6110 insertion into hotspots within the genome of M. tuberculosis provides a mechanism for generation of genetic diversity involving a high frequency of insertions and deletions

Effective Mitigation of Anchoring Bias, Projection Bias, and Representativeness Bias from Serious Game-based Training

AbstractAlthough human use of heuristics can result in ‘fast and frugal’ decision-making, those prepotent tendencies can also impair our ability to make optimal choices. Previous work had suggested such cognitive biases are resistant to mitigation training. Serious games offer a method to incorporate desirable elements into a training experience, and allow the use of mechanisms that enhance learning and retention. We developed a game to train recognition and mitigation of three forms of cognitive bias: anchoring, a tendency to be inordinately influenced by one piece of information; projection, an implicit assumption that others think or know what you do; and representativeness, judging the likelihood of a hypothesis by how much the available data resembles it. Participants were randomly assigned to play the training game once, twice spaced by 10 to 12 days, or a control condition that used a training video. External questionnaire-based assessments were given immediately post-training and 12 weeks later. Superior training was seen from the game. An independent group using our training game with their own novel bias assessment instruments (to which the researchers and game-developers had no access or content information) validated the key finding. These results demonstrate the viability and high value of using serious computer games to train mitigation of cognitive biases