Miracle-dz/UniFAR-FTUs huggingface dataset:
DNA-Encoded Flagellin Activates Toll-Like Receptor 5 (TLR5), Nod-like Receptor Family CARD Domain-Containing Protein 4 (NRLC4), and Acts as an Epidermal, Systemic, and Mucosal-Adjuvant

Eliciting effective immune responses using non-living/replicating DNA vaccines is a significant challenge. We have previously shown that ballistic dermal plasmid DNA-encoded flagellin (FliC) promotes humoral as well as cellular immunity to co-delivered antigens. Here, we observe that a plasmid encoding secreted FliC (pFliC(-gly)) produces flagellin capable of activating two innate immune receptors known to detect flagellin; Toll-like Receptor 5 (TLR5) and Nod-like Receptor family CARD domain-containing protein 4 (NRLC4). To test the ability of pFliC(-gly) to act as an adjuvant we immunized mice with plasmid encoding secreted FliC (pFliC(-gly)) and plasmid encoding a model antigen (ovalbumin) by three different immunization routes representative of dermal, systemic, and mucosal tissues. By all three routes we observed increases in antigen-specific antibodies in serum as well as MHC Class I-dependent cellular immune responses when pFliC(-gly) adjuvant was added. Additionally, we were able to induce mucosal antibody responses and Class II-dependent cellular immune responses after mucosal vaccination with pFliC(-gly). Humoral immune responses elicited by heterologus prime-boost immunization with a plasmid encoding HIV-1 from gp160 followed by protein boosting could be enhanced by use of pFliC(-gly). We also observed enhancement of cross-clade reactive IgA as well as a broadening of B cell epitope reactivity. These observations indicate that plasmid-encoded secreted flagellin can activate multiple innate immune responses and function as an adjuvant to non-living/replicating DNA immunizations. Moreover, the capacity to elicit mucosal immune responses, in addition to dermal and systemic properties, demonstrates the potential of flagellin to be used with vaccines designed to be delivered by various routes.
Modeling a User’s Culture

Localizing user interfaces has been proven beneficial for both user satisfaction and work efficiency; however, current localization methods disregard the many facets in the cultural background of today‘s typical user by simply adapting to a certain country. The chapter proposes a new approach to localization by modeling the user’s culture according to its understanding in cultural anthropology. Contrasting this view with cultural influences on user interface perception and preferences, the authors obtain an intersection of aspects that need to be included in a cultural user model, and deduce which user interface aspects have to be adaptable. With this, the chapter turns towards the application of their approach with the help of adaptive user interfaces, which allow the flexible composition of different user interface elements. The authors describe one possibility for implementing such culturally adaptive systems, and exemplify the design of different gradations of user interface aspects with the help of their MOCCA system.
Plasma MicroRNA Levels Differ between Endurance and Strength Athletes

Aim MicroRNAs (miRNAs) are stable in the circulation and are likely to function in inter-organ communication during a variety of metabolic responses that involve changes in gene expression, including exercise training. However, it is unknown whether differences in circulating-miRNA (c-miRNA) levels are characteristic of training modality. Methods We investigated whether levels of candidate c-miRNAs differ between elite male athletes of two different training modalities (n = 10 per group) - endurance (END) and strength (STR) - and between these groups and untrained controls (CON; n = 10). Fasted, non-exercised, morning plasma samples were analysed for 14 c-miRNAs (miR-1, miR-16-2, miR-20a-1, miR-21, miR-93, miR-103a, miR-133a, miR-146a, miR-192, miR-206, miR-221, miR-222, miR-451, miR-499). Moreover, we investigated whether c-miRNA levels were associated with quantitative performance-related phenotypes within and between groups. Results miR-222 was present at different levels in the three participant groups (p = 0.028) with the highest levels being observed in END and the lowest in STR. A number of other c-miRNAs were present at higher levels in END than in STR (relative to STR, ± 1 SEM; miR-222: 1.94 fold (1.73-2.18), p = 0.011; miR-21: 1.56 fold (1.39-1.74), p = 0.013; miR-146a: 1.50 fold (1.38-1.64), p = 0.019; miR-221: 1.51 fold (1.34-1.70), p = 0.026). Regression analyses revealed several associations between candidate c-miRNA levels and strength-related performance measures before and after adjustment for muscle or fat mass, but not following adjustment for group. Conclusion Certain c-miRNAs (miR-222, miR-21, miR-146a and miR-221) differ between endurance- and resistance-trained athletes and thus have potential as useful biomarkers of exercise training and / or play a role in exercise mode-specific training adaptations. However, levels of these c-miRNAs are probably unrelated to muscle bulk or fat reserves.
High‐Fat High‐Energy Feeding Impairs Fasting Glucose and Increases Fasting Insulin Levels in the Göttingen Minipig

Abstract: High‐fat diet and obesity are known to be of major importance for development of type 2 diabetes in humans. High‐fat feeding can induce syndromes of glucose intolerance and/or insulin resistance in several species, and the Göttingen minipig might be a useful model for studying the effect of dietary high‐fat intake and obesity on glucose homeostasis and the susceptibility to diabetes. The present study was designed as a pilot study to investigate the effects of obesity caused by high‐fat high‐energy feeding on oral and intravenous glucose tolerance. Male Göttingen minipigs were fed a control diet (CD) or a high‐fat high‐energy diet (HFD) for 3 months. Body weight (32.6 ± 2.4 kg vs. 24.9 ± 0.5 kg, p < 0.001) and total (13.2 ± 3.2% vs. 6.1 ± 0.5%, p= 0.002) and truncal (11.0 ± 3.9% vs. 1.8 ± 1.1%, p= 0.001) fat percent were increased significantly, whereas relative lean body mass was decreased (84.8 ± 3.3% vs. 91.9 ± 0.5%, p= 0.002) in the HFD group compared to CD. Fasting plasma glucose (4.3 ± 0.4 mM vs. 3.6 ± 0.3 mM, p= 0.023) and insulin (80 ± 23 pM vs. 23 ± 21 pM, p= 0.012) were increased in the HFD group compared to CD, but oral glucose tolerance was not significantly changed. Insulin responses to intravenous glucose were increased (6741 ± 2538 vs. 3938 ± 771 pM 3 min, p= 0.050), while glucose clearance was not changed by HFD vs. CD, thus indicating insulin resistance. In conclusion, changes in body weight and composition, resulting in minor abnormalities in glucose tolerance and insulin sensitivity, characterized by slight hyperglycemia and compensatory hyperinsulinemia, can be induced in the male Göttingen minipig by high‐fat high‐energy feeding for 3 months. This approach seems to be an interesting and promising method for establishment of a nonrodent model of insulin resistance or type 2 diabetes.
Toward Unsupervised Whole-Corpus Tagging

We present a system for unsupervised tagging of words into classes produced by a distributional clustering technique called co-clustering. A hidden Markov model (HMM), trained on the high-frequency terms in the lexicon, is used to "tag" occurrences of low-frequency terms. In experiments using the Wall Street Journal portion of the Penn Treebank, we show that previously reported problems in using Baum-Welch estimation for part-of-speech tagging do not occur in this context. We also show how state-level term emission models can be augmented to account for morphological patterns using features automatically derived from the output of co-clustering. Finally, we consider an alternative means of extending the coverage of the lexicon, in which low-frequency terms are added to the lexicon as types, and compare this approach with the token-level assignments made by the HMM.
Presurgical and postsurgical mental and psychomotor development of infants with sagittal synostosis.

OBJECTIVE The current study compared the mental and psychomotor development of infants with nonsyndromic sagittal synostosis (SS) with a demographically matched comparison group without congenital defects. Within the SS group, we tested the hypothesis that age of cranial release would be inversely correlated with mental development. DESIGN The design was prospective and longitudinal. Participants were assessed at 4, 12, and 24 months of age. SETTING The study was conducted in a craniofacial clinic at an urban children's hospital. PARTICIPANTS Participants were 19 infants with SS (consecutive craniofacial program referrals) and 19 demographically matched comparison infants recruited from the community. One infant with SS did not attend the 24-month assessment. MAIN OUTCOME MEASURES Mental and Psychomotor Indices from the Bayley Scales of Infant Development were the primary outcome measures. Subdomains of development were created using Kohen-Raz scoring procedures. All measures were determined a priori. RESULTS Repeated-measures MANOVAs revealed no statistically significant differences in the developmental trajectories of the two groups. None of the SS group infants received Mental Development Index (MDI) scores in the mentally retarded or borderline range of intellectual functioning (i.e., below 78). An inverse correlation (r = -.30) was found between the age at surgery and Bayley growth curve coefficients; however, this association was not statistically significant (p = .10, one-tailed). CONCLUSIONS Results are consistent with previous studies of the mental and psychomotor development of infants with nonsyndromic craniosynostoses in relation to normative test data. The relation between surgery age and developmental outcome merits further study in a larger sample with a greater range of surgery ages.
Electrophysiological actions of GABAB agonists and antagonists in rat dorso‐lateral septal neurones in vitro

1 The actions of GABAB‐receptor agonists and antagonists on rat dorso‐lateral septal neurones in vitro were recorded with intracellular microelectrodes. 2 In the presence of 1 μm tetrodotoxin to prevent indirect neuronal effects caused by action potential‐dependent neurotransmitter release, bath application of baclofen (0.1–30 μm) or SK&F 97541 (0.01–3 μm) evoked concentration‐dependent hyperpolarizations which reversed close to the potassium equilibrium potential; the EC50s were 0.55 and 0.05 μm, respectively. No significant desensitization was observed during prolonged agonist exposure (≤ 10 min). 3 Hyperpolarizations induced by baclofen were antagonized in a competitive manner by the following GABAB‐receptors antagonists (calculated pA2 values in parentheses): CGP 36742 (4.0), 2‐OH saclofen (4.2), CGP 35348 (4.5), CGP 52432 (6.7) and CGP 55845A (8.3). Responses to SK&F 97541 were also antagonized by CGP 55845A (pA2 = 8.4). 4 The amplitude of the late, GABAB receptor‐mediated inhibitory postsynaptic potential (i.p.s.p.) was reduced by the GABAB antagonists as follows (means ± s.e.mean): CGP 55845A (1 μm) 91 ± 5%, CGP 52432 (1 μm) 64 ± 5%, CGP 35348 (100 μm) 82 ± 5%, CGP 36742 (100 μm) 76 ± 8%, and 2‐OH saclofen (100 μm) 68 ± 3%. 5 It is concluded that neurones in the rat dorso‐lateral septal nucleus express conventional GABAB receptors, which are involved in the generation of slow inhibitory postsynaptic potentials. CGP 55845A is the most potent GABAB receptor antagonist described in this brain area.
On the Impact of Virtual Traffic Lights on Carbon Emissions Mitigation

Considering that the transport sector is responsible for an increasingly important share of current environmental problems, we look at Intelligent Transportation Systems (ITS) as a feasible means of helping in solving this issue. In particular, we evaluate the impact in terms of Carbon Dioxide (CO2)emissions of Virtual Traffic Light (VTL), which is a recently proposed infrastructureless traffic control system solely based on Vehicle-to-Vehicle (V2V) communication. Our evaluation uses a real-city scenario in a complex simulation framework, involving microscopic traffic, wireless communication, and emission models. Compared with an approximation of the physical traffic light system deployed in the city, our results show a significant reduction on CO2 emissions when using VTLs, reaching nearly 20% under high-density traffic.
QUANTITATIVE INVESTIGATIONS OF I D I O T Y P I C ANTIBODIES I. ANALYSIS OF PRECIPrrATING ANTIBODY POPULATIONS* BY HARRY DAUGHARTY,$ PH.D.,

The production of antibodies specifically directed to other antibody molecules from an individual donor was discovered by Kunkel, Mannik, and Williams (1), who prepared such antibodies in rabbits against human antibodies to A substance, dextran, and levan, and, independently, by Oudin and Michel (2), who used Salmonella typhi coated with rabbit antibody to immunize recipient rabbits. The designation of the ~mmunogenic portion of the donor population as "idiotypic antibody" (3) reflects the fact that the anti-antibodies are, with certain exceptions (4, 5), reactive only with the antibody injected, and not with antibody of the same specificity from another animal. Kelus and Geli (6) were able to produce anti-idiotypic antibodies against antiProteus vulgaris from a number of different rabbits in almost every recipient tested. Anti-Proteus from different animals, including members of a family group, were not cross-reactive with anti-idiotypic antisera. Individual antigenic specificity in specifically purified rabbit antibody to streptococcal carbohydrate was demonstrated by Braun and Krause (4), who utilized goat antisera to the rabbit antibodies. Idiotypic determinants have been localized to Fragment Fab of IgG donor molecules (1, 4, 6). These findings demonstrate that antibodies of the same specificity from different animals differ sufficiently in their antigenic structure to be distinguishable by antiantibody. Furthermore, they suggest that at least portions of the idiotypic, donor antibody populations are homogeneous; otherwise one might not expect to find concentrations of unique antigenic determinants sufficiently great to induce the formation of precipitating antibody in another animal. I t is of interest in this connection that donor antibodies utilized by Braun and Krause exhibited limited electrophoretic heterogeneity (4), and that myeloma proteins possess individual antigenic specificities (7-9) which are localized in Fragment Fab.
Comparative Proteomic Analysis of Liver Steatosis and Fibrosis after Oral Hepatotoxicant Administration in Sprague-Dawley Rats

The past decade has seen an increase in the development and clinical use of biomarkers associated with histological features of liver disease. Here, we conduct a comparative histological and global proteomics analysis to identify coregulated modules of proteins in the progression of hepatic steatosis or fibrosis. We orally administered the reference chemicals bromobenzene (BB) or 4,4′-methylenedianiline (4,4′-MDA) to male Sprague-Dawley rats for either 1 single administration or 5 consecutive daily doses. Livers were preserved for histopathology and global proteomics assessment. Analysis of liver sections confirmed a dose- and time-dependent increase in frequency and severity of histopathological features indicative of lipid accumulation after BB or fibrosis after 4,4′-MDA. BB administration resulted in a dose-dependent increase in the frequency and severity of inflammation and vacuolation. 4,4′-MDA administration resulted in a dose-dependent increase in the frequency and severity of periportal collagen accumulation and inflammation. Pathway analysis identified a time-dependent enrichment of biological processes associated with steatogenic or fibrogenic initiating events, cellular functions, and toxicological states. Differentially expressed protein modules were consistent with the observed histology, placing physiologically linked protein networks into context of the disease process. This study demonstrates the potential for protein modules to provide mechanistic links between initiating events and histopathological outcomes.
Effect of Exercise on the Relationship between Myocardial Blood Flow and Systolic Wall Thickening in Dogs with Acute Coronary Stenosis

Relationships between regional myocardial perfusion and transmural function, both during treadmill exercise and at rest, were examined in conscious dogs with varying degrees of coronary stenosis produced by a hydraulic occluder. In 13 dogs we measured myocardial blood flow with microspheres (10–12 μm in diameter) and regional systolic wall thickening (%). During exercise with coronary stenosis, myocardial blood flow was characterized by nonuniform distribution, and associated with regional dysfunction. The relationships between normalized myocardial blood flow and normalized %wall thickening during exercise with coronary stenosis were linear, with signifi-cantly different slopes (mean myocardial blood flow: y = 1.23x −0.16, r = 0.93; subendocardial myocardial blood flow: y = 1.50x −0.02, r = 0.86; subepicardial myocardial blood flow: y = 0.83x −0.18, r = 0.87). To fill the gap between available subendocardial and subepicardial data during exercise with coronary stenosis and control points, however, would require nonlinear components. In 10 of the dogs, coronary stenosis at rest was also produced to compare regional myocardial blood flow - %wall thickening relations at rest with those during steady state exercise. The absolute mean myocardial blood flow - %wall thickening relation during exercise with coronary stenosis (y = 11.6x - 1.9, r = 0.90) was significantly shifted rightward from the resting relation (y = 25.3x - 2.1, r = 0.80). However, when changes in %wall thickening were plotted vs. myocardial blood flow per beat, the relationships at rest and exercise were nearly superimposable. Likewise, relations between normalized myocardial blood flow and changes in %wall thickening at rest and exercise were not significantly different. We conclude: %wall thickening during exercise is directly related to changes in mean myocardial blood flow but is related in nonlinear fashion to changes in subepicardial and subendocardial myocardial blood flow; %wall thickening may provide a reliable index of the relative transmural flow distribution during exercise as well as at rest; during brief bouts (5–8 minutes) of exercise with coronary stenosis, the relationship between stabilized regional contractile dysfunction and level of myocardial blood flow per beat is the same as that during coronary stenosis at rest.
The O-Antigen Flippase Wzk Can Substitute for MurJ in Peptidoglycan Synthesis in Helicobacter pylori and Escherichia coli

The peptidoglycan (PG) cell wall is an essential component of the cell envelope of most bacteria. Biogenesis of PG involves a lipid-linked disaccharide-pentapeptide intermediate called lipid II, which must be translocated across the cytoplasmic membrane after it is synthesized in the inner leaflet of this bilayer. Accordingly, it has been demonstrated that MurJ, the proposed lipid II flippase in Escherichia coli, is required for PG biogenesis, and thereby viability. In contrast, MurJ is not essential in Bacillus subtilis because this bacterium produces AmJ, an unrelated protein that is functionally redundant with MurJ. In this study, we investigated why MurJ is not essential in the prominent gastric pathogen, Helicobacter pylori. We found that in this bacterium, Wzk, the ABC (ATP-binding cassette) transporter that flips the lipid-linked O- or Lewis- antigen precursors across the inner membrane, is redundant with MurJ for cell viability. Heterologous expression of wzk in E. coli also suppresses the lethality caused by the loss of murJ. Furthermore, we show that this cross-species complementation is abolished when Wzk is inactivated by mutations that target a domain predicted to be required for ATPase activity. Our results suggest that Wzk can flip lipid II, implying that Wzk is the flippase with the most relaxed specificity for lipid-linked saccharides ever identified.
From Threat to Fear: The Neural Organization of Defensive Fear Systems in Humans

Postencounter and circa-strike defensive contexts represent two adaptive responses to potential and imminent danger. In the context of a predator, the postencounter reflects the initial detection of the potential threat, whereas the circa-strike is associated with direct predatory attack. We used functional magnetic resonance imaging to investigate the neural organization of anticipation and avoidance of artificial predators with high or low probability of capturing the subject across analogous postencounter and circa-strike contexts of threat. Consistent with defense systems models, postencounter threat elicited activity in forebrain areas, including subgenual anterior cingulate cortex (sgACC), hippocampus, and amygdala. Conversely, active avoidance during circa-strike threat increased activity in mid-dorsal ACC and midbrain areas. During the circa-strike condition, subjects showed increased coupling between the midbrain and mid-dorsal ACC and decreased coupling with the sgACC, amygdala, and hippocampus. Greater activity was observed in the right pregenual ACC for high compared with low probability of capture during circa-strike threat. This region showed decreased coupling with the amygdala, insula, and ventromedial prefrontal cortex. Finally, we found that locomotor errors correlated with subjective reports of panic for the high compared with low probability of capture during the circa-strike threat, and these panic-related locomotor errors were correlated with midbrain activity. These findings support models suggesting that higher forebrain areas are involved in early-threat responses, including the assignment and control of fear, whereas imminent danger results in fast, likely “hard-wired,” defensive reactions mediated by the midbrain.
Exploring the black box in Brazilian work groups: a study of diversity, conflict and performance

Over the last few decades, several studies have been conducted to examine the complex relationships between team diversity and individual and organizational outcomes. Although, in theory, team diversity can foster positive organizational synergies by increasing the variance of perspectives and approaches to work different members can bring, the same idiosyncratic characteristics can also engender significant difficulties resulting from problems in coordination, communication and conflict. This study used a sample of 44 work groups to examine the influence of five types of diversity on team outcomes and the mediating role of task and relational conflict on this relationship. A survey of 279 team members and interviews with the 44 team managers were used to examine these relationships. Findings suggest that different forms of diversity impact task conflict in different ways, which in turn is negatively associated with job satisfaction and team performance. Results further show that diversity is unrelated to relational conflict; however, this type of conflict seems to hinder both job satisfaction and team performance. Overall, these patterns suggest a complex link between team diversity and how work groups function.