Miracle-dz/UniFAR-FTUs huggingface dataset:
NF-κB Site Interacts with Sp Factors and Up-regulates the NR1 Promoter during Neuronal Differentiation*

The NR1 gene undergoes induction in neurogenesis mainly via promoter de-repression, and up-regulation during neuronal differentiation by undefined mechanism(s). Here, we show that in the distal region the NR1 promoter has an active NF-κB site sharing the consensus with the immunoglobulin (Ig)/human immunodeficiency virus NF-κB site. Mutation of this site significantly reduced NR1 promoter up-regulation during neuronal differentiation of P19 cells. Electrophoretic mobility shift assays revealed that P19 nuclei constitutively contained p50 and that neuronal differentiation not only increased nuclear p50 but also induced p65 nuclear translocation. Responding to this change was an up-regulation of NF-κB-dependent promoter activity. However, inhibition of NF-κB nuclear translocation by an IκBα super-repressor or decoy DNA only moderately inhibited NR1 promoter up-regulation. Interestingly, the NR1 NF-κB site strongly interacted with Sp3/Sp1, instead of NF-κB factors, in P19 nuclear extracts. This interaction was reduced for Sp3 following neuronal differentiation, accompanied by dynamic expression of Sp factors. Cotransfection of Sp factors (Sp1, 3, or 4) upregulated the NR1 NF-κB site dramatically in differentiated neurons, but only moderately in undifferentiated P19 cells. This up-regulation was strong for Sp1 in differentiated cells and for Sp3 in undifferentiated cells. Chromatin-immunoprecipitation assays further demonstrated that Sp1 and Sp3 interacted with the NR1 NF-κB site in situ, and Sp3 lost its interaction after neuronal differentiation. We conclude that the NF-κB site positively regulates the NR1 promoter during neuronal differentiation via interacting mainly with Sp factors and neuronal differentiation reduces the effect of Sp3 factor on this site.
Blockade of amino acid‐induced depolarizations and inhibition of excitatory post‐synaptic potentials in rat dentate gyrus.

Excitatory post‐synaptic potentials (e.p.s.p.s) evoked by stimulation of the medial perforant path and depolarizations induced by excitatory amino acids were recorded from granule cells in the preparation of the hippocampal slice from the rat. The effects of (+/‐)‐2‐amino‐5‐phosphonovalerate (APV), gamma‐D‐glutamylglycine (gamma DGG) and cis‐2,3‐piperidinedicarboxylate (PDA), antagonists of excitatory amino acids on these phenomena were compared. gamma DGG was the most effective antagonist of the e.p.s.p. Its action was reversible and not associated with any change in the passive membrane properties of the granule cells or in the apparent reversal potential of the e.p.s.p. Quantal analysis showed that the reduction in the e.p.s.p. paralleled the decrease in quantal size rather than quantal content, confirming a post‐synaptic site of the action of gamma DGG. The potency of gamma DGG against the exogenous agonists was N‐methyl‐D‐aspartate greater than kainate greater than or equal to quisqualate. APV had very little effect on the e.p.s.p. but was a selective antagonist of N‐methyl‐D‐aspartate‐induced depolarizations. PDA depolarized granule cells and increased their membrane input resistance. Although gamma DGG was a potent antagonist of both glutamate‐ and aspartate‐induced depolarizations, no clear pattern of specificity could be found. The action of glutamate was unaffected by APV. These results indicate that the receptor for the transmitter at the synapses formed by the fibres of the perforant path with the granule cells is of the quisqualate and/or kainate type. The present data are consistent with the biochemical evidence that glutamate may be the endogenous transmitter at his synapse.
The Framework for the Selection of Personnel Based on the SWARA and ARAS Methods Under Uncertainties

In the hiring process at companies, decision makers have underused the methods of the multi-criteria decision-making processes of selection of personnel. Therefore, this paper aims to establish a framework for the selection of candidates during the process of the recruitment and selection of personnel based on the SWARA and ARAS methods under uncertainties. The usability and efficiency of the proposed framework is considered in the conducted case study of the selection of candidate for the position of the sales manager.
Rotor Walks on General Trees

The rotor walk on a graph is a deterministic analogue of random walk. Each vertex is equipped with a rotor, which routes the walker to the neighboring vertices in a fixed cyclic order on successive visits. We consider rotor walk on an infinite rooted tree, restarted from the root after each escape to infinity. We prove that the limiting proportion of escapes to infinity equals the escape probability for random walk, provided only finitely many rotors send the walker initially toward the root. For independently and identically distributed random initial rotor directions on a regular tree, the limiting proportion of escapes is either zero or the random walk escape probability, and undergoes a discontinuous phase transition between the two as the distribution is varied. In the critical case there are no escapes, but the walker's maximum distance from the root grows doubly exponentially with the number of visits to the root. We also prove that there exist trees of bounded degree for which the proportion of escapes eventually exceeds the escape probability by arbitrarily large $o(1)$ functions. No larger discrepancy is possible, while for regular trees, the discrepancy is at most logarithmic.
Simultaneous Subcutaneous and Intranasal Administration of a CAF01-Adjuvanted Chlamydia Vaccine Elicits Elevated IgA and Protective Th1/Th17 Responses in the Genital Tract

The selection of any specific immunization route is critical when defining future vaccine strategies against a genital infection like Chlamydia trachomatis (C.t.). An optimal Chlamydia vaccine needs to elicit mucosal immunity comprising both neutralizing IgA/IgG antibodies and strong Th1/Th17 responses. A strategic tool to modulate this immune profile and mucosal localization of vaccine responses is to combine parenteral and mucosal immunizations routes. In this study, we investigate whether this strategy can be adapted into a two-visit strategy by simultaneous subcutaneous (SC) and nasal immunization. Using a subunit vaccine composed of C.t. antigens (Ags) adjuvanted with CAF01, a Th1/Th17 promoting adjuvant, we comparatively evaluated Ag-specific B and T cell responses and efficacy in mice following SC and simultaneous SC and nasal immunization (SIM). We found similar peripheral responses with regard to interferon gamma and IL-17 producing Ag-specific splenocytes and IgG serum levels in both vaccine strategies but in addition, the SIM protocol also led to Ag-specific IgA responses and increased B and CD4+ T cells in the lung parenchyma, and in lower numbers also in the genital tract (GT). Following vaginal infection with C.t. , we observed that SIM immunization gave rise to an early IgA response and IgA-secreting plasma cells in the GT in contrast to SC immunization, but we were not able to detect more rapid recruitment of mucosal T cells. Interestingly, although SIM vaccination in general improved mucosal immunity we observed no improved efficacy against genital infection compared to SC, a finding that warrants for further investigation. In conclusion, we demonstrate a novel vaccination strategy that combines systemic and mucosal immunity in a two-visit strategy.
Natural Vocalizations in the Mammalian Inferior Colliculus are Broadly Encoded by a Small Number of Independent Multi-Units

How complex natural sounds are represented by the main converging center of the auditory midbrain, the central inferior colliculus, is an open question. We applied neural discrimination to determine the variation of detailed encoding of individual vocalizations across the best frequency gradient of the central inferior colliculus. The analysis was based on collective responses from several neurons. These multi-unit spike trains were recorded from guinea pigs exposed to a spectrotemporally rich set of eleven species-specific vocalizations. Spike trains of disparate units from the same recording were combined in order to investigate whether groups of multi-unit clusters represent the whole set of vocalizations more reliably than only one unit, and whether temporal response correlations between them facilitate an unambiguous neural representation of the vocalizations. We found a spatial distribution of the capability to accurately encode groups of vocalizations across the best frequency gradient. Different vocalizations are optimally discriminated at different locations of the best frequency gradient. Furthermore, groups of a few multi-unit clusters yield improved discrimination over only one multi-unit cluster between all tested vocalizations. However, temporal response correlations between units do not yield better discrimination. Our study is based on a large set of units of simultaneously recorded responses from several guinea pigs and electrode insertion positions. Our findings suggest a broadly distributed code for behaviorally relevant vocalizations in the mammalian inferior colliculus. Responses from a few non-interacting units are sufficient to faithfully represent the whole set of studied vocalizations with diverse spectrotemporal properties.
AERODYNAMIC COUPLING EFFECTS ON FLUTTER AND BUFFETING OF BRIDGES

The effects of aerodynamic coupling among modes of vibration on the flutter and buffeting re- sponse of long-span bridges are investigated. By introducing the unsteady, self-excited aerodynamic forces in terms of rational function approximations, the equations of motion in generalized modal coordinates are transformed into a frequency-independent state-space format. The frequencies, damping ratios, and complex mode shapes at a prescribed wind velocity, and the critical flutter conditions, are identified by solving a complex eigenvalue problem. A significant feature of this approach is that an iterative solution for determining the flutter conditions is not necessary, because the equations of motion are independent of frequency. The energy increase in each flutter motion cycle is examined using the work done by the generalized aerodynamic forces or by the self-excited forces along the bridge axis. Accordingly, their contribution to the aerodynamic damping can be clearly identified. The multimode flutter generation mechanism and the roles of flutter derivatives are investigated. Finally, the coupling effects on the buffeting response due to self-excited forces are also discussed.
MixMir: microRNA motif discovery from gene expression data using mixed linear models

microRNAs (miRNAs) are a class of ∼22nt non-coding RNAs that potentially regulate over 60% of human protein-coding genes. miRNA activity is highly specific, differing between cell types, developmental stages and environmental conditions, so the identification of active miRNAs in a given sample is of great interest. Here we present a novel computational approach for analyzing both mRNA sequence and gene expression data, called MixMir. Our method corrects for 3′ UTR background sequence similarity between transcripts, which is known to correlate with mRNA transcript abundance. We demonstrate that after accounting for kmer sequence similarities in 3’ UTRs, a statistical linear model based on motif presence/absence can effectively discover active miRNAs in a sample. MixMir utilizes fast software implementations for solving mixed linear models which are widely-used in genome-wide association studies (GWAS). Essentially we use 3’ UTR sequence similarity in place of population cryptic relatedness in the GWAS problem. Compared to similar methods such as miReduce, Sylamer and cWords, we found that MixMir performed better at discovering true miRNA motifs in three mouse Dicer knockout experiments from different tissues, two of which were collected by our group. We confirmed these results on protein and mRNA expression data obtained from miRNA transfection experiments in human cell lines. MixMir can be freely downloaded from https://github.com/ldiao/MixMir.
Why do parents' education level and income affect the amount of fruits and vegetables adolescents eat?

BACKGROUND There are large socioeconomic disparities in food behaviours. The objective of the present study is to longitudinally explore socioeconomic disparities in adolescents' fruit and vegetable (FV) intake and to assess mediators of the disparity. METHODS A longitudinal study containing 896 adolescents from 20 randomly selected elementary schools within two Norwegian counties (response rate 84%). Questionnaires were administered in May 2002 (mean age 12.5 years) and again in May 2005. FV intake was measured by four food frequency questions (times/week). Socioeconomic status was based on parents' reports of their own educational level and family income (both dichotomized). Data were analysed with repeated mixed models. RESULTS A disparity in adolescents' FV intake was observed with family income (1.1 times/week, P = 0.05). An interaction between parental education and time (survey) was found for parental education (P = 0.04) and the educational disparity was greater in 2005 (2.4 times/week, P < 0.001) than in 2002 (1.3 times/week, P = 0.03). In multiple mediation analyses, a total of 92% (2002) and 60% (2005) of the educational disparity and 89% of the income disparity, were explained. For both, the adolescents' reports of the accessibility of FV at home explained most of the disparity. CONCLUSIONS Perceived accessibility appears to be the strongest mediator of the relationship between adolescents' FV intake and their parents' educational level and income and may therefore be an important target for future interventions that aim to reduce socioeconomic disparities in adolescents' FV intake.
Mixing Time of Exponential Random Graphs

A variety of random graph models have been developed in recent years to study a range of problems on networks, driven by the wide availability of data from many social, telecommunication, biochemical and other networks. A key model, extensively used in the sociology literature, is the exponential random graph model. This model seeks to incorporate in random graphs the notion of reciprocity, that is, the larger than expected number of triangles and other small subgraphs. Sampling from these distributions is crucial for parameter estimation hypothesis testing, and more generally for understanding basic features of the network model itself. In practice sampling is typically carried out using Markov chain Monte Carlo, in particular either the Glauber dynamics or the Metropolis-Hasting procedure.In this paper we characterize the high and low temperature regimes of the exponential random graph model. We establish that in the high temperature regime the mixing time of the Glauber dynamics is Theta(n2 log n), where n is the number of vertices in the graph; in contrast, we show that in the low temperature regime the mixing is exponentially slow for any local Markov chain. Our results, moreover, give a rigorous basis for criticisms made of such models. In the high temperature regime, where sampling with MCMC is possible, we show that any finite collection of edges are asymptotically independent; thus, the model does not possess the desired reciprocity property, and is not appreciably different from the Erdos-Renyi random graph.
A Large Scale Gene-Centric Association Study of Lung Function in Newly-Hired Female Cotton Textile Workers with Endotoxin Exposure

Background Occupational exposure to endotoxin is associated with decrements in pulmonary function, but how much variation in this association is explained by genetic variants is not well understood. Objective We aimed to identify single nucleotide polymorphisms (SNPs) that are associated with the rate of forced expiratory volume in one second (FEV1) decline by a large scale genetic association study in newly-hired healthy young female cotton textile workers. Methods DNA samples were genotyped using the Illumina Human CVD BeadChip. Change rate in FEV1 was modeled as a function of each SNP genotype in linear regression model with covariate adjustment. We controlled the type 1 error in study-wide level by permutation method. The false discovery rate (FDR) and the family-wise error rate (FWER) were set to be 0.10 and 0.15 respectively. Results Two SNPs were found to be significant (P<6.29×10−5), including rs1910047 (P = 3.07×10−5, FDR = 0.0778) and rs9469089 (P = 6.19×10−5, FDR = 0.0967), as well as other eight suggestive (P<5×10−4) associated SNPs. Gene-gene and gene-environment interactions were also observed, such as rs1910047 and rs1049970 (P = 0.0418, FDR = 0.0895); rs9469089 and age (P = 0.0161, FDR = 0.0264). Genetic risk score analysis showed that the more risk loci the subjects carried, the larger the rate of FEV1 decline occurred (P trend = 3.01×10−18). However, the association was different among age subgroups (P = 7.11×10−6) and endotoxin subgroups (P = 1.08×10−2). Functional network analysis illustrates potential biological connections of all interacted genes. Conclusions Genetic variants together with environmental factors interact to affect the rate of FEV1 decline in cotton textile workers.
Virological Characterization of Dual HIV-1/HIV-2 Seropositivity and Infections in Southern Ghana.

SUMMARY BACKGROUND Dual HIV-1/HIV-2 seropositivity (dual seropositivity) is common in West African countries including Ghana. The diagnosis of dual HIV-1/HIV-2 infections is however complicated as HIV-2 DNA is more often not detected in dual seropositive individuals. OBJECTIVES To detect the presence of HIV-1 and HIV-2 pro-viral DNA in dual seropositives and to determine the correlation between HIV-2 antibody titers and presence of HIV-2 DNA. The growth kinetics of HIV-1 and HIV-2 in vitro were also determined using plasma and lymphocyte cultures. DESIGN Cross-sectional study SETTING Urban and semi-rural HIV/AIDS clinics PARTICIPANTS 13 dual HIV-1/HIV-2 seropositives from Agomanya and Accra RESULTS HIV-1 DNA was detected in uncultured peripheral blood mononuclear cells of all 13 patients but HIV-2 DNA in 4 (30.8%). HIV-2 antibody titres were not useful in determining the presence or absence of HIV-2 DNA (P=0.28, Mann-Whitney U test). HIV-2 specific antibody was detected in 12 of the 13 dual seropositives by peptide-inhibition, the only patient with an Innolia gp36 band rating of 1+ was shown not to be reactive. HIV-2 grew efficiently in the presence or HIV-1 in vitro. CONCLUSION HIV-2 DNA may not be detected in all dual seropositives thus not all of such patients may need drugs effective against HIV-2. Peptide based assays will be useful for correctly diagnosing dual seropositivity. Since HIV-2 may grow efficiently in the presence of HIV-1 and no commercial HIV-2 HIV RNA tests are available, dual seropositives on HAART need to be monitored to determine if a lack of immune restoration may correspond to an efficient suppression of HIV-1 RNA levels.
Identifying Audiences and Messages for Nonformal Environmental Education– a Theoretical Framework for Interpreters

This paper outlines a theoretically driven approach to identifying strategic audiences for nonformal environmental education and communication efforts, and offers a rationale for determining message content for site-based interpretive programs aimed at modifying the behaviors of two strategic audiences—on-site visitors and local communities. The role each of these audiences might play in resource protection and examples of theoretically derived messages that might be used to influence their behavior are discussed. Drawing on the Theory of Reasoned Action and the Theory of Planned Behavior, a framework is outlined for designing effective environmental education and communication interventions for replacing and modifying problematic environmental behaviors in and adjacent to protected areas. Representative research issues pertaining to both the design and the evaluation of communication interventions are also presented.
Multiple Criteria Comparative Evaluation of E-Learning Systems and Components

The main scientific problems investigated in this paper deal with the problem of multiple criteria evaluation of the quality of the main components of e-learning systems, i.e., learning objects (LOs) and virtual learning environments (VLEs). The aim of the paper is to analyse the existing LO and VLE quality evaluation methods, and to create more comprehensive methods based on learning individualisation approach. LOs and VLEs quality evaluation criteria are further investigated as the optimisation parameters and several optimisation methods are explored to be applied. Application of the experts' additive utility function using evaluation criteria ratings and their weights is explored in more detail. These new elements make the given work distinct from all the other earlier works in the area.
Synthesis, folding, and structure of the β‐turn mimic modified B1 domain of streptococcal protein G

The mechanism of β‐sheet formation remains a fundamental issue in our understanding of the protein folding process, but is hampered by the often encountered kinetic competition between folding and aggregation. The role of local versus nonlocal interactions has been probed traditionally by mutagenesis of both turn and strand residues. Recently, rigid organic molecules that impose a correct chain reversal have been introduced in several small peptides to isolate the importance of the long‐range interactions. Here, we present the incorporation of a well‐studied β‐turn mimic, designated as the dibenzofuran‐based (DBF) amino acid, in the B1 domain of streptococcal protein G (B1G), and compare our results with those obtained upon insertion of the same mimic into the N‐terminal β‐hairpin of B1G (O Melnyk et al., 1998, Lett Pept Sci 5:147–150). The DBF‐B1G domain conserves the structure and the functional and thermodynamical properties of the native protein, whereas the modified peptide does not adopt a native‐like conformation. The nature of the DBF flanking residues in the modified B1G domain prevents the β‐turn mimic from acting as a strong β‐sheet nucleator, which reinforces the idea that the native β‐hairpin formation is not driven by the β‐turn formation, but by tertiary interactions.
Genotype by environment interaction and genetic correlations among parities for somatic cell count and milk yield.

Lactation measures of somatic cell concentration and total SCC production were developed. Data were separated into three parity groups. Within parity, five data sets were created: four subsets by herd-year average SCC, and one with all records. Records on lactation SCC, total SCC production, and 305-d milk were analyzed by a sire model separately in each subset within parity. Variance components estimates were by REML. For SCC and total SCC production, heritability estimates averaged . 12 and were lowest in the highest level of herd-year average SCC. Estimates of genetic correlation between SCC and total SCC production were over . 95; between SCC and 305-d milk were around . 25 in first and -. 15 in later parities; between total SCC and 305-d milk were around . 50 in first and . 15 in later parities. Product-moment correlations between sire effects in different levels of herd-year average SCC were obtained. Ratios of product-moment correlations to their expected value were above . 80 for all traits in all parities. High ratios indicated little genotype by environment interaction. A sire by herd interaction was fitted in the model and accounted for less than 2% of total phenotypic variance for SCC and total SCC production, and 4% for 305-d milk. Estimates of genetic correlation of first with later parities were . 71 to . 86 for all traits. Between second and third parity genetic correlation estimates were around unity for all traits. Records from all parities should be used for sire evaluation.