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A variety of visualization techniques can be utilized to compare multiple Spatial 3D or time-varying Spatial 3D data instances (e.g., comparing pre- versus post-treatment volumetric medical images). However, despite the fact that comparative visualization is frequently needed – scientists, engineers, and even humanists must routinely compare such data – visualization users and practitioners suffer from a lack of adequate Spatial 3D comparative visualization tools and guidelines. Here we survey the field and present a taxonomy for classifying existing and new comparison visualization techniques for such data into four fundamental approaches: Juxtaposition, Superimposition, Interchangeable, and Explicit Encoding. The results clarify the key design decisions and tradeoffs that designers must make to create an effective comparative Spatial 3D data visualization and suggest the potential of emerging hybrid approaches, ones creatively combining aspects of the four fundamental approaches. [ABSTRACT FROM AUTHOR]

Abstract: Image database extensions for functional brain images were assessed by asking clinicians questions about (i) diagnosis confidence level before and after using the software; (ii) expected and unexpected differences between patient and control images; and (iii) an overall rating of the future usefulness of this application in an everyday clinical setting. Examining the difference image of a patient compared to a normative group affects the clinicians’ initial diagnosis of the patient in two-thirds of the cases. All three clinicians stated that the interface would be a useful tool when added to the clinical workup of a patient. [Copyright &y& Elsevier]

Researchers face many challenges in representing biological data, including: (1) inherent complexity of biological data, (2) domain knowledge barrier, (3) constantly evolving knowledge, and (4) lack of expert data-modeling skills. We have studied how to represent biological sequences and sequence-related genomics concepts using logical data structure. From our multiple experiences in genomic data modeling, we present results in three areas: genomic schema elements, genomic schema fragments, and genomic data modeling lessons. A genomic schema element is a data model that contains only one basic biological sequence notion. Genomic schema elements provide biology data modelers with baseline thoughts in genomic data modeling. A genomic schema fragment is a data model that contains only one genomic topic area. Genomic schema fragments provide biology data modelers with successful design solutions that they can adapt to fit their own problem''s needs. Genomic data modeling lessons address issues particularly important to genomic data modeling such as modeling contextual information, modeling intermediate and derived data, modeling inconsistent data, and modeling categorical rules. Genomic data modeling lessons provide novice biology data modelers with enriched principles from content-neutral data modeling techniques. In all, we have demonstrated how to manage evolving genomic knowledge concepts and discovery results using data modeling techniques extended into the genomics domain. [Copyright &y& Elsevier]

Focuses on the knowledge of engineers to use expert system shells to develop production-rule-based expert system applications. Problems explored on the use of data-based management; Identification of the features of this system; Examination of basic syntactic components in relation to this topic; Exploration of similarities and differences in syntax in relation to this topic. INSET: Related work..

Summary: RIPPER is a framework for mass-spectrometry-based label-free relative quantification for proteomics and metabolomics studies. RIPPER combines a series of previously described algorithms for pre-processing, analyte quantification, retention time alignment, and analyte grouping across runs. It is also the first software framework to implement proximity-based intensity normalization. RIPPER produces lists of analyte signals with their unnormalized and normalized intensities that can serve as input to statistical and directed mass spectrometry (MS) methods for detecting quantitative differences between biological samples using MS. Availability and implementation: http://www.z.umn.edu/ripper. [ABSTRACT FROM AUTHOR]

Male chimpanzees, Pan troglodytes, cooperate to defend a community range within which resident females range in smaller core areas. There has been debate over exactly what males are defending, whether mates, territory or both. One hypothesis holds that males are defending mates, and that an increase in community range size will lead directly to the acquisition of more females. However, males frequently attack females as well as males at the edge of the community range. We examined 18 years of observational data on the Gombe chimpanzees to determine the behaviour of males during extragroup encounters, and the consequences of changes in community range size on the number of adult females and indirect measures of food availability. Males were always aggressive to males from other communities, and often attacked adult females, especially those that were not sexually receptive, were older, and/or had more than one offspring. The number of females did not increase with range size, but several measures suggested an increase in food availability with range size. These measures include more time spent in large foraging parties, higher encounter rates with resident females, more encounters with sexually receptive females and higher female reproductive rates. These findings suggest that males defend a feeding territory for their resident females and protect them from sexual harassment. Although a large range may eventually attract more females, this is not an immediate consequence of range expansion. Male number was not correlated with community range size. [Copyright &y& Elsevier]

Studies female competition and male territorial behavior influence female chimpanzee in Gombe Park, Tanzania. Investigation of relationship between female space use patterns and female feeding competition; Variability of space use patterns of individual females; Female range patterns by both feeding competition and male territorial behavior.

Live attenuated vaccines such as SIV with a deleted nef gene have provided the most robust protection against subsequent vaginal challenge with wild-type (WT) SIV in the SIV-rhesus macaque model of HIV-1 transmission to women. Hence, identifying correlates of this protection could enable design of an effective HIV-1 vaccine. One such prechallenge correlate of protection from vaginal challenge has recently been identified as a system with three components: 1) IgG Abs reacting with the viral envelope glycoprotein trimeric gp41; 2) produced by plasma cells in the submucosa and ectopic tertiary lymphoid follicles in the ectocervix and vagina; and 3) concentrated on the path of virus entry by the neonatal FcR in the overlying epithelium. We now examine the mucosal production of the Ab component of this system after vaginal challenge. We show that vaginal challenge immediately elicits striking increases in plasma cells not only in the female reproductive tract but also at other mucosal sites, and that these increases correlate with low but persistent replication at mucosal sites. We describe vaginal ectopic follicles that are structurally and functionally organized similar to follicles in secondary lymphoid organs, and we provide inferential evidence for a key role of the female reproductive tract epithelium in facilitating Ab production, affinity maturation, and class switch recombination. Vaccination thus accesses an epithelial-immune system axis in the female reproductive tract to respond to exposure to mucosal pathogens. Designing strategies to mimic this system could advance development of an effective HIV-1 vaccine. [ABSTRACT FROM AUTHOR]

Principles to guide design of an effective vaccine against HIV are greatly needed, particularly to protect women in the pandemic’s epicenter in Africa. We have been seeking these principles by identifying correlates of the robust protection associated with SIVmac239Δnef vaccination in the SIV-rhesus macaque animal model of HIV-1 transmission to women. We identified one correlate of SIVmac239Δnef protection against vaginal challenge as a resident mucosal system for SIV-gp41 trimer Ab production and neonatal FcR-mediated concentration of these Abs on the path of virus entry to inhibit establishment of infected founder populations at the portal of entry. In this study, we identify blocking CD4+ T cell recruitment to thereby inhibit local expansion of infected founder populations as a second correlate of protection. Virus-specific immune complex interactions with the inhibitory FcγRIIb receptor in the epithelium lining the cervix initiate expression of genes that block recruitment of target cells to fuel local expansion. Immune complex–FcγRIIb receptor interactions at mucosal frontlines to dampen the innate immune response to vaginal challenge could be a potentially general mechanism for the mucosal immune system to sense and modulate the response to a previously encountered pathogen. Designing vaccines to provide protection without eliciting these transmission-promoting innate responses could contribute to developing an effective HIV-1 vaccine. [ABSTRACT FROM AUTHOR]

We sought design principles for a vaccine to prevent HIV transmission to women by identifying correlates of protection conferred by a highly effective live attenuated SIV vaccine in the rhesus macaque animal model. We show that SIVmac239Δnef vaccination recruits plasma cells and induces ectopic lymphoid follicle formation beneath the mucosal epithelium in the rhesus macaque female reproductive tract. The plasma cells and ectopic follicles produce IgG Abs reactive with viral envelope glycoprotein gp41 trimers, and these Abs are concentrated on the path of virus entry by the neonatal FcR in cervical reserve epithelium and in vaginal epithelium. This local Ab production and delivery system correlated spatially and temporally with the maturation of local protection against high-dose pathogenic SIV vaginal challenge. Thus, designing vaccines to elicit production and concentration of Abs at mucosal frontlines could aid in the development of an effective vaccine to protect women against HIV-1. [ABSTRACT FROM AUTHOR]

Abstract: We present a mobile multi-touch interface for selecting, querying, and visually exploring data visualized on large, high-resolution displays. Although emerging large (e.g., ∼10m wide), high-resolution displays provide great potential for visualizing dense, complex datasets, their utility is often limited by a fundamental interaction problem – the need to interact with data from multiple positions around a large room. Our solution is a selection and querying interface that combines a hand-held multi-touch device with 6 degree-of-freedom tracking in the physical space that surrounds the large display. The interface leverages context from both the user''s physical position in the room and the current data being visualized in order to interpret multi-touch gestures. It also utilizes progressive refinement, favoring several quick approximate gestures as opposed to a single complex input in order to most effectively map the small mobile multi-touch input space to the large display wall. The approach is evaluated through two interdisciplinary visualization applications: a multi-variate data visualization for social scientists, and a visual database querying tool for biochemistry. The interface was effective in both scenarios, leading to new domain-specific insights and suggesting valuable guidance for future developers. [Copyright &y& Elsevier]

Abstract: Background: Proteomic studies in saliva have demonstrated its potential as a diagnostic biofluid, however the salivary peptidome is less studied. Here we study the effects of several sample collection and handling factors on salivary peptide abundance levels. Methods: Salivary peptides were isolated using an ultrafiltration device and analyzed by tandem mass spectrometry. A panel of 41 peptides common after various treatments were quantified and normalized. We evaluated the effects of freezing rate of the samples, nutritional status of the donors (fed vs. fasted), and room-temperature sample degradation on peptide abundance levels. Repeatability of our sample processing method and our instrumental analysis method were investigated. Results: Increased sample freezing rate produced higher levels of peptides. Donor nutritional status had no influence on the levels of measured peptides. No significant difference was detected in donors'' saliva following 5, 10 and 15min of room-temperature degradation. Sample processing and instrumental variability were relatively small, with median CVs of 9.6 and 6.6. Conclusions: Peptide abundance levels in saliva are rather forgiving towards variations in sample handling and donor nutritional status. Differences in freezing methods may affect peptide abundance, so consistency in freezing samples is preferred. Our results are valuable for standardizing sample collection and handling methods for peptidomic-based biomarker studies in saliva. [Copyright &y& Elsevier]

The hallmark of HIV-1 and SIV infections is CD4(+) T cell depletion. Both direct cell killing and indirect mechanisms related to immune activation have been suggested to cause the depletion of T cells. We have now identified a mechanism by which immune activation-induced fibrosis of lymphoid tissues leads to depletion of naive T cells in HIV-1 infected patients and SIV-infected rhesus macaques. The T regulatory cell response to immune activation increased procollagen production and subsequent deposition as fibrils via the TGF-β1 signaling pathway and chitinase 3-like-1 activity in fibroblasts in lymphoid tissues from patients infected with HIV-1. Collagen deposition restricted T cell access to the survival factor IL-7 on the fibroblastic reticular cell (FRC) network, resulting in apoptosis and depletion of T cells, which, in turn, removed a major source of lymphotoxin-β, a survival factor for FRCs during SIV infection in rhesus macaques. The resulting loss of FRCs and the loss of IL-7 produced by FRCs may thus perpetuate a vicious cycle of depletion of T cells and the FRC network. Because this process is cumulative, early treatment and antifibrotic therapies may offer approaches to moderate T cell depletion and improve immune reconstitution during HIV-1 infection. [ABSTRACT FROM AUTHOR]

Background: Oral cancer survival rates increase significantly when it is detected and treated early. Unfortunately, clinicians now lack tests which easily and reliably distinguish pre-malignant oral lesions from those already transitioned to malignancy. A test for proteins, ones found in non-invasively-collected whole saliva and whose abundances distinguish these lesion types, would meet this critical need. Methodology/Principal Findings: To discover such proteins, in a first-of-its-kind study we used advanced mass spectrometry-based quantitative proteomics analysis of the pooled soluble fraction of whole saliva from four subjects with pre-malignant lesions and four with malignant lesions. We prioritized candidate biomarkers via bioinformatics and validated selected proteins by western blotting. Bioinformatic analysis of differentially abundant proteins and initial western blotting revealed increased abundance of myosin and actin in patients with malignant lesions. We validated those results by additional western blotting of individual whole saliva samples from twelve other subjects with pre-malignant oral lesions and twelve with malignant oral lesions. Sensitivity/specificity values for distinguishing between different lesion types were 100%/75% (p = 0.002) for actin, and 67%/83% (p<0.00001) for myosin in soluble saliva. Exfoliated epithelial cells from subjects' saliva also showed increased myosin and actin abundance in those with malignant lesions, linking our observations in soluble saliva to abundance differences between pre-malignant and malignant cells. Conclusions/Significance: Salivary actin and myosin abundances distinguish oral lesion types with sensitivity and specificity rivaling other non-invasive oral cancer tests. Our findings provide a promising starting point for the development of noninvasive and inexpensive salivary tests to reliably detect oral cancer early. [ABSTRACT FROM AUTHOR]

Natural SIV infection of sooty mangabeys (SMs) is nonprogressive despite chronic virus replication. Strikingly, it is characterized by low levels of immune activation, while pathogenic SIV infection of rhesus macaques (RMs) is associated with chronic immune activation. To elucidate the mechanisms underlying this intriguing phenotype, we used high-density oligonucleotide microarrays to longitudinally assess host gene expression in SIV-infected SMs and RMs. We found that acute SIV infection of SMs was consistently associated with a robust innate immune response, including widespread upregulation of IFN-stimulated genes (ISGs) in blood and lymph nodes. While SMs exhibited a rapid resolution of ISG expression and immune activation, both responses were observed chronically in RMs. Systems biology analysis indicated that expression of the lymphocyte inhibitory receptor LAG3, a marker of T cell exhaustion, correlated with immune activation in SIV-infected RMs but not SMs. Our findings suggest that active immune regulatory mechanisms, rather than intrinsically attenuated innate immune responses, underlie the low levels of immune activation characteristic of SMs chronically infected with SIV. [ABSTRACT FROM AUTHOR]

Although there has been great progress in treating human immunodeficiency virus 1 (HIV-1) infection, preventing transmission has thus far proven an elusive goal. Indeed, recent trials of a candidate vaccine and microbicide have been disappointing, both for want of efficacy and concerns about increased rates of transmission. Nonetheless, studies of vaginal transmission in the simian immunodeficiency virus (SIV)–rhesus macaque (Macacca mulatta) model point to opportunities at the earliest stages of infection in which a vaccine or microbicide might be protective, by limiting the expansion of infected founder populations at the portal of entry. Here we show in this SIV–macaque model, that an outside-in endocervical mucosal signalling system, involving MIP-3α (also known as CCL20), plasmacytoid dendritic cells and CCR5+ cell-attracting chemokines produced by these cells, in combination with the innate immune and inflammatory responses to infection in both cervix and vagina, recruits CD4+ T cells to fuel this obligate expansion. We then show that glycerol monolaurate—a widely used antimicrobial compound with inhibitory activity against the production of MIP-3α and other proinflammatory cytokines—can inhibit mucosal signalling and the innate and inflammatory response to HIV-1 and SIV in vitro, and in vivo it can protect rhesus macaques from acute infection despite repeated intra-vaginal exposure to high doses of SIV. This new approach, plausibly linked to interfering with innate host responses that recruit the target cells necessary to establish systemic infection, opens a promising new avenue for the development of effective interventions to block HIV-1 mucosal transmission. [ABSTRACT FROM AUTHOR]

In the early stages of viral infection, outcomes depend on a race between expansion of infection and the immune response generated to contain it. We combined in situ tetramer staining with in situ hybridization to visualize, map, and quantify relationships between immune effector cells and their targets in tissues. In simian immunodeficiency virus infections in macaques and lymphocytic choriomeningitis virus infections in mice, the magnitude and timing of the establishment of ah excess of effector cells versus targets were found to correlate with the extent of control and the infection outcome (i.e., control and clearance versus partial or poor control and persistent infection). This method highlights the importance of the location, timing, and magnitude of the immune response needed for a vaccine to be effective against agents of persistent infection, such as HIV-1. [ABSTRACT FROM AUTHOR]

The enteropathic manifestations of the human immunodeficiency virus (HIV) and the simian immunodeficiency virus (SIV) in late infection are usually due to infection by other microbes, but in early infection the viruses themselves cause an enteropathy by heretofore undetermined mechanisms. Here we report that SIV induces massive apoptosis of intestinal epithelial cells lining the small and large bowel, thus identifying apoptosis as the driving force behind the regenerative pathology of early infection. We found that apoptosis of gut epithelium paralleled the previously documented apoptosis and massive depletion of CD4 T cells in gut lamina propria, triggered by established mechanisms of gut epithelial cell apoptosis and, at peak, possibly by virus interactions with GPR15/Bob, an intestinal epithelial cell-associated alternative coreceptor for SIV and HIV-1. Apoptosis in early SIV infection is thus the common theme of the pathological processes that quickly afflict the innate as well as adaptive arms of the gut immune system. [ABSTRACT FROM AUTHOR]

Abstract: Even healthy adults worry about declines in mental efficiency with aging. Subjective changes in mental flexibility, self-regulation, processing speed, and memory are often cited. We show here that focal decreases in brain activity occur with normal aging as measured with fluorodeoxyglucose and positron emission tomography. The largest declines localize to a medial network including the anterior cingulate/medial prefrontal cortex, dorsomedial thalamus, and sugenual cingulate/basal forebrain. Declining metabolism in this network correlates with declining cognitive function. The medial prefrontal metabolic changes with aging are similar in magnitude to the hypometabolism found in Mild Cognitive Impairment or Alzheimer''s disease. These results converge with data from healthy elderly indicating dysfunction in the anterior attention system. The interaction of attention in the anterior cingulate cortex with memory in the medial temporal lobe may explain the global impairment that defines dementia. Despite the implications for an aging population, the neurophysiologic mechanisms of these metabolic decreases remain unknown. [Copyright &y& Elsevier]

In human immunodeficiency virus (HIV) infection, collagen deposition and fibrosis within the T cell zone disrupt the lymphatic tissue architecture, contributing to depletion of CD4+ T cells and limiting immune reconstitution. We used relevant animal and in vitro models to investigate the kinetics and possible underlying mechanism(s) of this process. In the lymphatic tissue of simian immunodeficiency virus (SIV)-infected rhesus macaques, we observed parallel increases in immune activation, transforming growth factor (TGF) β1-positive regulatory T (Treg) cells, and collagen type I deposition by 7 days after inoculation, consistent with the hypothesis that early immune activation elicits a countering Treg cell response associated with TGFβ1 expression and collagen deposition. In support of this hypothesis and the possible role of fibrosis in viral pathogenesis, we show (1) spatial colocalization and temporal concordance in levels of TGFβ1+ Treg cells and collagen deposition; (2) TGFβ1+ inducible Treg cell stimulation of primary lymphatic tissue fibroblasts to produce collagen type I in vitro; and (3) high levels of immune activation, TGFβ1+ Treg cells, and collagen deposition in pathogenic SIV infection of macaques, in contrast to apathogenic SIV infection in sooty mangabeys in which levels of immune activation, TGFβ1+ Treg cells, and collagen deposition were low. We thus conclude that the response of TGFβ1+ Treg cells to immune activation in early SIV/HIV infection is a double-edged sword: TGFβ1+ Treg cells normally have a positive effect by limiting immunopathological and autoreactive immune responses, but they also have a negative effect by dampening the antiviral immune response and, as we show here, causing deleterious effects on CD4+ T cell homeostasis by inducing collagen deposition in lymphatic tissues. [ABSTRACT FROM AUTHOR]