Miracle-dz/UniFAR-FTUs huggingface dataset:
Toll-Like Receptor 8 Is a Major Sensor of Group B Streptococcus But Not Escherichia coli in Human Primary Monocytes and Macrophages

TLR8 is the major endosomal sensor of degraded RNA in human monocytes and macrophages. It has been implicated in the sensing of viruses and more recently also bacteria. We previously identified a TLR8-IFN regulatory factor 5 (IRF5) signaling pathway that mediates IFNβ and interleukin-12 (IL-12) induction by Staphylococcus aureus and is antagonized by TLR2. The relative importance of TLR8 for the sensing of various bacterial species is however still unclear. We here compared the role of TLR8 and IRF5 for the sensing of Group B Streptococcus (GBS), S. aureus, and Escherichia coli in human primary monocytes and monocyte-derived macrophages (MDM). GBS induced stronger IFNβ and TNF production as well as IRF5 nuclear translocation compared to S. aureus grown to the stationary phase, while S. aureus in exponential growth appeared similarly potent to GBS. Cytokine induction in primary human monocytes by GBS was not dependent on hemolysins, and induction of IFNβ and IL-12 as well as IRF5 activation were reduced with TLR2 ligand costimulation. Heat inactivation of GBS reduced IRF5 and NF-kB translocation, while only the viable E. coli activated IRF5. The attenuated stimulation correlated with loss of bacterial RNA integrity. The E. coli-induced IRF5 translocation was not inhibited by TLR2 costimulation, suggesting that IRF5 was activated via a TLR8-independent mechanism. Gene silencing of MDM using siRNA revealed that GBS-induced IFNβ, IL-12-p35, and TNF production was dependent on TLR8 and IRF5. In contrast, cytokine induction by E. coli was TLR8 independent but still partly dependent on IRF5. We conclude that TLR8-IRF5 signaling is more important for the sensing of GBS than for stationary grown S. aureus in human primary monocytes and MDM, likely due to reduced resistance of GBS to phagosomal degradation and to a lower production of TLR2 activating lipoproteins. TLR8 does not sense viable E. coli, while IRF5 still contributes to E. coli-induced cytokine production, possibly via a cytosolic nucleic acid sensing mechanism.
Cell Entry and Trafficking of Human Adenovirus Bound to Blood Factor X Is Determined by the Fiber Serotype and Not Hexon:Heparan Sulfate Interaction

Human adenovirus serotype 5 (HAdV5)-based vectors administered intravenously accumulate in the liver as the result of their direct binding to blood coagulation factor X (FX) and subsequent interaction of the FX-HAdV5 complex with heparan sulfate proteoglycan (HSPG) at the surface of liver cells. Intriguingly, the serotype 35 fiber-pseudotyped vector HAdV5F35 has liver transduction efficiencies 4-logs lower than HAdV5, even though both vectors carry the same hexon capsomeres. In order to reconcile this apparent paradox, we investigated the possible role of other viral capsid proteins on the FX/HSPG-mediated cellular uptake of HAdV5-based vectors. Using CAR- and CD46-negative CHO cells varying in HSPG expression, we confirmed that FX bound to serotype 5 hexon protein and to HAdV5 and HAdV5F35 virions via its Gla-domain, and enhanced the binding of both vectors to surface-immobilized hypersulfated heparin and cellular HSPG. Using penton mutants, we found that the positive effect of FX on HAdV5 binding to HSPG and cell transduction did not depend on the penton base RGD and fiber shaft KKTK motifs. However, we found that FX had no enhancing effect on the HAdV5F35-mediated cell transduction, but a negative effect which did not involve the cell attachment or endocytic step, but the intracellular trafficking and nuclear import of the FX-HAdV5F35 complex. By cellular imaging, HAdV5F35 particles were observed to accumulate in the late endosomal compartment, and were released in significant amounts into the extracellular medium via exocytosis. We showed that the stability of serotype 5 hexon∶FX interaction was higher at low pH compared to neutral pH, which could account for the retention of FX-HAdV5F35 complexes in the late endosomes. Our results suggested that, despite the high affinity interaction of hexon capsomeres to FX and cell surface HSPG, the adenoviral fiber acted as the dominant determinant of the internalization and trafficking pathway of HAdV5-based vectors.
An investigation of user perceptions and attitudes towards learning objects

This study empirically evaluates the technology acceptance model drawn from Information Systems (IS) literature to investigate how user beliefs and attitudes influence learning-object use among higher education learners by evaluating the relationships between perceived usefulness, perceived ease of use, attitude, behavioural intentions and actual use. In the study, 601 potential learning-object users were presented with an introductory demonstration of learning objects for a Digital Systems course. Following the demonstration and practice, data on user beliefs, attitudes and intention to use learning objects were gathered, while data on actual use of learning objects was collected at the end of the semester. Subjects with prior experience using the learning objects were eliminated from further analysis, resulting in a final sample of 481 users. structural equation modelling was employed to test the hypothesised study model. The analysis showed that both the user beliefs and attitudes have significant positive relationships with behavioural intention and that behavioural intention accurately predicted the actual use of learning objects. The results extend the validity of the TAM into a learning object context and clearly pointed out that it can be used to predict users’ future behaviour.
Goal Setting as a Strategy for Dietary and Physical Activity Behavior Change: A Review of the Literature

Objective. Estimate effectiveness of goal setting for nutrition and physical activity behavior change, review the effect of goal-setting characteristics on behavior change, and investigate effectiveness of interventions containing goal setting. Data source. For this review, a literature search was conducted for the period January 1977 through December 2003 that included a Current Contents, Biosis Previews, Medline, PubMed, PsycINFO, and ERIC search of databases and a reference list search. Key words were goal, goal setting, nutrition, diet, dietary, physical activity, exercise, behavior change, interventions, and fitness. Study inclusion and exclusion criteria. The search identified 144 studies, of which 28 met inclusion criteria for being published in a peer reviewed journal and using goal setting in an intervention to modify dietary or physical activity behaviors. Excluded from this review were those studies that (1) evaluated goal setting cross-sectionally without an intervention; (2) used goal setting for behavioral disorders, to improve academic achievement, or in sports performance; (3) were reviews. Data extraction and synthesis. The articles were categorized by target audience and secondarily by research focus. Data extracted included outcome measure, research rating, purpose, sample, sample description, assignment, findings, and goal-setting support. Results. Thirteen of the 23 adult studies used a goal-setting effectiveness study design and eight produced positive results supporting goal setting. No adolescent or child studies used this design. The results were inconclusive for the studies investigating goal-setting characteristics (n = 7). Four adult and four child intervention evaluation studies showed positive outcomes. No studies reported power calculations, and only 32% of the studies were rated as fully supporting goal setting. Conclusions. Goal setting has shown some promise in promoting dietary and physical activity behavior change among adults, but methodological issues still need to be resolved. The literature with adolescents and children is limited, and the authors are not aware of any published studies with this audience investigating the independent effect of goal setting on dietary or physical activity behavior. Although, goal setting is widely used with children and adolescents in nutrition interventions, its effectiveness has yet to be reported.
Running Head : TEMPORAL PREPARATION AND AGING TEMPORAL PREPARATION IN AGING : A FUNCTIONAL MRI STUDY

Young and elderly adults performed a choice-RT task while scanned with functional Magnetic Resonance Imaging. A foreperiod separated warning and a response signal. In the variable condition, the foreperiod varied rando mly between 1 and 3 sec. In the fixed conditions, it was kept constant at either 1 or 3 s ec. Elderly subjects responded slower than controls in both task conditions. An interacti on was observed between age and foreperiod in the variable condition only: in the y oung group, RT decreased with longer foreperiods, whereas the elderly participants showe d th opposite tendency. This was accompanied by difference in brain activation. Righ t lateral prefrontal regions were more activated in the young than in the elderly group in the variable vs. fixed foreperiod contrast. These findings unveil the neural substrat e of age-related preparation deficits, and confirm that the involvement of right lateral p refrontal cortex is essential for strategic preparation under uncertain timing conditions.
Triple Junction Solutions for a Singularly Perturbed Neumann Problem

We consider the singularly perturbed Neumann problem $\varepsilon^2 \Delta u -u +u^p = 0$, $u>0$ in $\Omega$, ${\partial u \over \partial \nu}=0$ on $\partial \Omega$, where $p>1$ and $\Omega$ is a smooth and bounded domain in $\mathbb{R}^2$. We construct a class of solutions which consist of large number of spikes concentrated on three line segments with a common endpoint which intersect $\partial \Omega$ orthogonally.
Superstructure of the centromeric complex of TubZRC plasmid partitioning systems

Bacterial plasmid partitioning systems segregate plasmids into each daughter cell. In the well-understood ParMRC plasmid partitioning system, adapter protein ParR binds to centromere parC, forming a helix around which the DNA is externally wrapped. This complex stabilizes the growth of a filament of actin-like ParM protein, which pushes the plasmids to the poles. The TubZRC plasmid partitioning system consists of two proteins, tubulin-like TubZ and TubR, and a DNA centromere, tubC, which perform analogous roles to those in ParMRC, despite being unrelated in sequence and structure. We have dissected in detail the binding sites that comprise Bacillus thuringiensis tubC, visualized the TubRC complex by electron microscopy, and determined a crystal structure of TubR bound to the tubC repeat. We show that the TubRC complex takes the form of a flexible DNA–protein filament, formed by lateral coating along the plasmid from tubC, the full length of which is required for the successful in vitro stabilization of TubZ filaments. We also show that TubR from Bacillus megaterium forms a helical superstructure resembling that of ParR. We suggest that the TubRC DNA–protein filament may bind to, and stabilize, the TubZ filament by forming such a ring-like structure around it. The helical superstructure of this TubRC may indicate convergent evolution between the actin-containing ParMRC and tubulin-containing TubZRC systems.
Spatiotemporal activation of the two visual pathways in form discrimination and spatial location: A brain mapping study

To address the question of the relationship between the two visual pathways, a ventral stream for object and form vision and a dorsal stream for spatial and motion vision, we measured the spatiotemporal activation patterns in the two pathways responding to an integrated visuospatial task to which form discrimination and spatial location were assigned simultaneously. The two cognitive components of form discrimination and spatial location were interwoven in the task; however, the fMRI data demonstrated that such a task still activated both ventral GTi/GF (the inferior temporal gyrus/the fusiform gyrus) and dorsal Ga/PCu (the angular gyrus/Precuneus), which are supposed to mediate form discrimination and spatial location, respectively. In addition, the source waveforms of the fMRI foci based on the source analysis of the fMRI‐seeded dipole modeling and the moving dipole modeling indicated that in responding to the task combining simultaneously form perception and spatial location, the activity in Ga/PCu begins earlier than that in GTi/GF, but it peaks later and lasts longer. Hum. Brain Mapping 18:79–89, 2003. © 2002 Wiley‐Liss, Inc.
The Glutamate–Glutamine (GABA) Cycle: Importance of Late Postnatal Development and Potential Reciprocal Interactions between Biosynthesis and Degradation

The gold standard for studies of glutamate–glutamine (GABA) cycling and its connections to brain biosynthesis from glucose of glutamate and GABA and their subsequent metabolism are the elegant in vivo studies by 13C magnetic resonance spectroscopy (NMR), showing the large fluxes in the cycle. However, simpler experiments in intact brain tissue (e.g., immunohistochemistry), brain slices, cultured brain cells, and mitochondria have also made important contributions to the understanding of details, mechanisms, and functional consequences of glutamate/GABA biosynthesis and degradation. The purpose of this review is to attempt to integrate evidence from different sources regarding (i) the enzyme(s) responsible for the initial conversion of α-ketoglutarate to glutamate; (ii) the possibility that especially glutamate oxidation is essentially confined to astrocytes; and (iii) the ontogenetically very late onset and maturation of glutamine–glutamate (GABA) cycle function. Pathway models based on the functional importance of aspartate for glutamate synthesis suggest the possibility of interacting pathways for biosynthesis and degradation of glutamate and GABA and the use of transamination as the default mechanism for initiation of glutamate oxidation. The late development and maturation are related to the late cortical gliogenesis and convert brain cortical function from being purely neuronal to becoming neuronal-astrocytic. This conversion is associated with huge increases in energy demand and production, and the character of potentially incurred gains of function are discussed. These may include alterations in learning mechanisms, in mice indicated by lack of pairing of odor learning with aversive stimuli in newborn animals but the development of such an association 10–12 days later. The possibility is suggested that analogous maturational changes may contribute to differences in the way learning is accomplished in the newborn human brain and during later development.
Convex Risk Minimization and Conditional Probability Estimation

This paper proves, in very general settings, that convex risk minimization is a procedure to select a unique conditional probability model determined by the classification problem. Unlike most previous work, we give results that are general enough to include cases in which no minimum exists, as occurs typically, for instance, with standard boosting algorithms. Concretely, we first show that any sequence of predictors minimizing convex risk over the source distribution will converge to this unique model when the class of predictors is linear (but potentially of infinite dimension). Secondly, we show the same result holds for \emph{empirical} risk minimization whenever this class of predictors is finite dimensional, where the essential technical contribution is a norm-free generalization bound.
Gamification for Word Sense Labeling

Obtaining gold standard data for word sense disambiguation is important but costly. We show how it can be done using a “Game with a Purpose” (GWAP) called Wordrobe. This game consists of a large set of multiple-choice questions on word senses generated from the Groningen Meaning Bank. The players need to answer these questions, scoring points depending on the agreement with fellow players. The working assumption is that the right sense for a word can be determined by the answers given by the players. To evaluate our method, we gold-standard tagged a portion of the data that was also used in the GWAP. A comparison yielded promising results, ranging from a precision of 0.88 and recall of 0.83 for relative majority agreement, to a precision of 0.98 and recall of 0.35 for questions that were answered unanimously.
THL-100 Multi-Terawatt Laser System of Visible Range

Results of investigation of the parameters of the THL-100 hybrid laser system of visible range developed at the IHCE SB RAS in collaboration with the LPI RAS are presented. The laser system consists of the Ti:Sa Start-480M starting complex and the photodissociation XeF(C-A) amplifier with aperture of 24 cm. The starting complex provides 50-fs spectrally limited radiation pulses with energy of the second harmonic (475 nm) up to 20 mJ and 50-ps positively chirped radiation pulses with energy up to 5 mJ. The active medium of the XeF(CA) amplifier is created in the XeF2/N2 mixture upon exposure to VUV radiation of xenon excited by a highpower electron beam. It is demonstrated that record power of 14 TW is attained by amplification of negatively chirped radiation pulse with duration of 1.6 ps in the XeF(C-A) amplifier, and maximum energy of ~3.2 J is realized by amplification of positively chirped radiation pulse.
Mossy Fiber Long-Term Potentiation Deficits in BACE1 Knock-Outs Can Be Rescued by Activation of α7 Nicotinic Acetylcholine Receptors

β-Site amyloid precursor protein-cleaving enzyme 1 (BACE1)—the neuronal β-secretase responsible for producing β-amyloid (Aβ) peptides—emerged as one of the key therapeutic targets of Alzheimer's disease (AD). Although complete ablation of the BACE1 gene prevents Aβ formation, we reported that BACE1 knock-out mice display severe presynaptic deficits at mossy fiber (MF)-to-CA3 synapses in the hippocampus, a major locus of BACE1 expression. We also found that the deficits are likely due to abnormal presynaptic Ca2+ regulation. Cholinergic system has been implicated in AD, in some cases involving Ca2+-permeable α7-nicotinic acetylcholine receptors (nAChRs). Here we report that brief application of nicotine, via α7-nAChRs, can restore MF long-term potentiation in BACE1 knock-outs. Our data suggest that activating α7-nAChRs can recover the presynaptic deficits in BACE1 knock-outs.
Natural Disease Resistance in Threatened Staghorn Corals

Disease epidemics have caused extensive damage to tropical coral reefs and to the reef-building corals themselves, yet nothing is known about the abilities of the coral host to resist disease infection. Understanding the potential for natural disease resistance in corals is critically important, especially in the Caribbean where the two ecologically dominant shallow-water corals, Acropora cervicornis and A. palmata, have suffered an unprecedented mass die-off due to White Band Disease (WBD), and are now listed as threatened under the US Threatened Species Act and as critically endangered under the IUCN Red List criteria. Here we examine the potential for natural resistance to WBD in the staghorn coral Acropora cervicornis by combining microsatellite genotype information with in situ transmission assays and field monitoring of WBD on tagged genotypes. We show that six percent of staghorn coral genotypes (3 out of 49) are resistant to WBD. This natural resistance to WBD in staghorn corals represents the first evidence of host disease resistance in scleractinian corals and demonstrates that staghorn corals have an innate ability to resist WBD infection. These resistant staghorn coral genotypes may explain why pockets of Acropora have been able to survive the WBD epidemic. Understanding disease resistance in these corals may be the critical link to restoring populations of these once dominant corals throughout their range.
A geometric analysis of diffusion tensor measurements of the human brain

The degree of diffusion tensor anisotropy is often associated with the organization of structural tissues such as white matter. Numerous measures of diffusion anisotropy have been proposed, which could lead to confusion in interpreting and comparing results from different studies. In this study, a new method for representing the diffusion tensor shape, called the three‐phase (3P) plot, is described. This is a graphical technique based upon a barycentric coordinate system, which weights the tensor shape by a combination of linear, cylindrical, and spherical shape factors. This coordinate system can be used to map and potentially segment different tissues based upon the tensor shape. In addition, the 3P plot can be used to examine the shape properties of existing measures of diffusion anisotropy. In this paper, the 3P plot is used to compare four well‐known anisotropy measures: the anisotropy index, the fractional anisotropy, the relative anisotropy, and the volume fraction. Computer simulations and diffusion tensor images of normal brains were obtained to study the properties of this new mapping technique. Magn Reson Med 44:283–291, 2000. © 2000 Wiley‐Liss, Inc.
ABO blood type A is associated with increased risk of ARDS in whites following both major trauma and severe sepsis.

BACKGROUND ABO glycosyltransferases catalyze antigen modifications on various glycans and glycoproteins and determine the ABO blood types. Blood type A has been associated with increased risk of vascular diseases and differential circulating levels of proteins related to inflammation and endothelial function. The objective of this study was to determine the association of ABO blood types with ARDS risk in patients with major trauma and severe sepsis. METHODS We conducted prospective cohort studies in two populations at an urban tertiary referral, level I trauma center. Critically ill patients (n 5 732) presenting after major trauma were followed for 5 days for ARDS development. Additionally, 976 medical patients with severe sepsis were followed for 5 days for ARDS. Multivariable logistic regression was used to adjust for confounders. RESULTS ARDS developed in 197 of the 732 trauma patients (27%). Blood type A was associated with increased ARDS risk among whites (37% vs 24%; adjusted OR, 1.88; 95% CI, 1.14-3.12; P 5 .014), but not blacks (adjusted OR, 0.61; 95% CI, 0.33-1.13; P=.114). ARDS developed in 222 of the 976 patients with severe sepsis (23%). Blood type A was also associated with an increased ARDS risk among whites (31% vs 21%; adjusted OR, 1.67; 95% CI, 1.08-2.59; P=.021) but, again, not among blacks (adjusted OR, 1.17; 95% CI, 0.59-2.33; P=.652). CONCLUSIONS Blood type A is associated with an increased risk of ARDS in white patients with major trauma and severe sepsis. These results suggest a role for ABO glycans and glycosyltransferases in ARDS susceptibility.