Miracle-dz/UniFAR-FTUs huggingface dataset:
The Inability of Wild-Type Rabies Virus To Activate Dendritic Cells Is Dependent on the Glycoprotein and Correlates with Its Low Level of the De Novo-Synthesized Leader RNA

ABSTRACT Dendritic cells (DCs) are the most efficient antigen-presenting cells, playing a key role in the adaptive immune responses to viral infections. Our studies demonstrate that wild-type (wt) rabies virus (RABV) does not activate DCs. Adoptive transfer of DCs primed with wt RABV did not activate DCs, stimulate virus neutralizing antibodies (VNA), or protect recipients against challenge. However, adoptive transfer of DCs primed with laboratory-attenuated RABV resulted in DC activation, production of VNA, and protection against challenge. In vitro studies with recombinant RABV (laboratory-attenuated RABV expressing the glycoprotein or the phosphoprotein from wt RABV) demonstrate that DC activation is dependent on the glycoprotein and involves the IPS-1 pathway. Furthermore, binding to and entry into DCs by wt RABV is severely blocked, and the copy number of de novo-synthesized leader RNA was two logs lower in DCs infected with the wt than in DCs treated with laboratory-attenuated RABV. However, transient transfection of DCs with synthesized leader RNA from either wt or attenuated RABV is capable of activating DCs in a dose-dependent manner. Thus, the inability of wt RABV to activate DCs correlates with its low level of the de novo-synthesized leader RNA. IMPORTANCE Rabies remains a public health threat, with more than 55,000 fatalities each year around the world. Since DCs play a key role in the adaptive immune responses to viral infections, we investigated the ability of rabies virus (RABV) to activate DCs. It was found that the adoptive transfer of DCs primed with wt RABV did not activate DCs, stimulate VNA, or protect mice against lethal challenge. However, laboratory-attenuated RABV mediates the activation of DCs via the IPS-1 pathway and is glycoprotein dependent. We further show that wt RABV evades DC-mediated immune activation by inefficient binding/entry into DCs and as a result of a reduced level of de novo-synthesized leader RNA. These findings may have important implications in the development of efficient rabies vaccines.
Regulation of the rhaEWRBMA Operon Involved in l-Rhamnose Catabolism through Two Transcriptional Factors, RhaR and CcpA, in Bacillus subtilis

ABSTRACT The Bacillus subtilis rhaEWRBMA (formerly yuxG-yulBCDE) operon consists of four genes encoding enzymes for l-rhamnose catabolism and the rhaR gene encoding a DeoR-type transcriptional regulator. DNase I footprinting analysis showed that the RhaR protein specifically binds to the regulatory region upstream of the rhaEW gene, in which two imperfect direct repeats are included. Gel retardation analysis revealed that the direct repeat farther upstream is essential for the high-affinity binding of RhaR and that the DNA binding of RhaR was effectively inhibited by l-rhamnulose-1-phosphate, an intermediate of l-rhamnose catabolism. Moreover, it was demonstrated that the CcpA/P-Ser-HPr complex, primarily governing the carbon catabolite control in B. subtilis, binds to the catabolite-responsive element, which overlaps the RhaR binding site. In vivo analysis of the rhaEW promoter-lacZ fusion in the background of ccpA deletion showed that the l-rhamnose-responsive induction of the rhaEW promoter was negated by the disruption of rhaA or rhaB but not rhaEW or rhaM, whereas rhaR disruption resulted in constitutive rhaEW promoter activity. These in vitro and in vivo results clearly indicate that RhaR represses the operon by binding to the operator site, which is detached by l-rhamnulose-1-phosphate formed from l-rhamnose through a sequence of isomerization by RhaA and phosphorylation by RhaB, leading to the derepression of the operon. In addition, the lacZ reporter analysis using the strains with or without the ccpA deletion under the background of rhaR disruption supported the involvement of CcpA in the carbon catabolite repression of the operon. IMPORTANCE Since l-rhamnose is a component of various plant-derived compounds, it is a potential carbon source for plant-associating bacteria. Moreover, it is suggested that l-rhamnose catabolism plays a significant role in some bacteria-plant interactions, e.g., invasion of plant pathogens and nodulation of rhizobia. Despite the physiological importance of l-rhamnose catabolism for various bacterial species, the transcriptional regulation of the relevant genes has been poorly understood, except for the regulatory system of Escherichia coli. In this study, we show that, in Bacillus subtilis, one of the plant growth-promoting rhizobacteria, the rhaEWRBMA operon for l-rhamnose catabolism is controlled by RhaR and CcpA. This regulatory system can be another standard model for better understanding the regulatory mechanisms of l-rhamnose catabolism in other bacterial species.
Behavioral heterogeneity in the Australian housing market

ABSTRACT We propose a heterogeneous agent model (HAM) of four groups of investors with Markov chain regime-dependent beliefs for the housing market. Within the Markov switching framework, we take into account how heterogeneous investors shift their trading behaviour in response to changes in housing market conditions. The model is estimated and compared with the benchmark rational expectation models using the Australian housing market data from 1982Q1 to 2013Q2. We find evidence of within- and between-group heterogeneity in the Australian housing market. We show that HAM with Markov switching beliefs provides a better in-sample estimation efficiency and outperforms the conventional rational expectation models in terms of out-of-sample prediction.
Sizn1 Is a Novel Protein That Functions as a Transcriptional Coactivator of Bone Morphogenic Protein Signaling

ABSTRACT Bone morphogenic proteins (BMPs) play pleotrophic roles in nervous system development, and their signaling is highly regulated at virtually every step in the pathway. We have cloned a novel gene, Sizn1 (Smad-interacting zinc finger protein), which functions as a transcriptional coactivator of BMP signaling. It positively modulates BMP signaling by interacting with Smad family members and associating with CBP in the transcription complex. Sizn1 is expressed in the ventral embryonic forebrain, where, as we will show, it contributes to BMP-dependent, cholinergic-neuron-specific gene expression. These data indicate that Sizn1 is a positive modulator of BMP signaling and provide further insight into how BMP signaling can be modulated in neuronal progenitor subsets to influence cell-type-specific gene expression and development.
Space-time spectra of complex cell filters in the macaque monkey: A comparison of results obtained with pseudowhite noise and grating stimuli

Abstract White noise stimuli were used to estimate second-order kernels for complex cells in cortical area VI of the macaque monkey, and drifting grating stimuli were presented to the same sample of neurons to obtain orientation and spatial-frequency tuning curves. Using these data, we quantified how well second-order kernels predict the normalized tuning of the average response of complex cells to drifting gratings. The estimated second-order kernel of each complex cell was transformed into an interaction function defined over all spatial and temporal lags without regard to absolute position or delay. The Fourier transform of each interaction function was then computed to obtain an interaction spectrum. For a cell that is well modeled by a second-order system, the cell’s interaction spectrum is proportional to the tuning of its average spike rate to drifting gratings. This result was used to obtain spatial-frequency and orientation tuning predictions for each cell based on its second-order kernel. From the spatial-frequency and orientation tuning curves, we computed peaks and bandwidths, and an index for directional selectivity. We found that the predictions derived from second-order kernels provide an accurate description of the change in the average spike rate of complex cells to single drifting sine–wave gratings. These findings are consistent with a model for complex cells that has a quadratic spectral energy operator at its core but are inconsistent with a spectral amplitude model.
Rotman Lens-Based Retrodirective Array

A new type of broadband retrodirective array, which has been constructed using a microstrip Rotman lens, is presented. Automatic tracking of targets is obtained by exploiting the conjugate phase response of the beamforming network which is exhibited when the input ports are terminated with either open or short circuits. In addition, the true time-delay property of the Rotman lens gives broadband operation of the self-tracking array when used in conjunction with Vivaldi antennas. The simulated and measured bistatic and monostatic radar cross-section (RCS) patterns of a structure consisting of 13 beamports and 12 array ports are presented at frequencies in the range 8-12 GHz. Significantly enhanced RCS within the scan coverage ±40° is demonstrated by comparing the retrodirective behavior of a 12-element Vivaldi array terminated with and without the Rotman lens.
Gender-specific association of psychological distress with cardiovascular risk scores

Abstract Objective. To examine the gender differences in the association of psychological distress with cardiovascular disease (CVD) risk scores using two different CVD risk assessment models. Design and setting. A cross-sectional, population-based study from 1997 to 1998 in Pieksämäki, Finland. Subjects. A population sample of 899 (399 male and 500 female) middle-aged subjects. Main outcome measures. The 10-year risk for CVD events was calculated using the European SCORE model and the Framingham CVD risk prediction model. Psychological distress was measured using the 12-item General Health Questionnaire (GHQ-12). Study subjects were allocated into three groups according to their global GHQ-12 -scores: 0 points, 1–2 points, and 3–12 points. Results. Psychological distress was associated with higher mean CVD risk scores in men. Men in the highest GHQ group (3–12 points) had significantly higher mean European CVD risk score (3.6 [SD 3.3]) compared with men in the lowest group (0 points) (2.5 [SD 2.6]), the difference being 1.1 (95% CI 0.4 to 1.9). The p-value for linearity between the three GHQ groups was 0.003. The Framingham CVD risk prediction model yielded similar results: 15.7 (SD 10.2) vs. 12.3 (SD 9.6), the difference 3.4 (95% CI 1.0 to 6.0) and p-value for linearity 0.008. No significant association was observed in women. Conclusion. A gender-specific association was found betwen psychological distress and cardiovascular risk scores. These results highlight the importance of identifying men with psychological distress when assessing CVD risk.
Not in our park! Local community perceptions of recreational activities in peri-urban national parks

ABSTRACT Increased pressure to allow more recreational activities in peri-urban national parks may impact local communities. We surveyed residents living in local communities near six peri-urban national parks (IUCN Category II) in Queensland, Australia. We assessed their sense of place, their perceptions of different types of visitors’ activities, and interactions between attitudes and perceptions. Most respondents, including national park users and non-users, perceived non-motorised recreational activities as appropriate but perceived motorised activities negatively. Overall, negative perceptions were related to a respondent's sense of place. Respondents with a stronger sense of place had more positive perceptions of non-motorised activities but more negative perceptions of motorised activities than respondents reporting a weaker sense of place. Results suggest that people identifying with their local national park may have a small ‘latitude of acceptance’ for motorised activities. We found limited displacement due to recreational conflicts; most respondents still visited these parks. The methods used here, if applied to other peri-urban national parks, could help determine a local community's recreational activity thresholds, offering park managers a way to potentially diminish conflict and enhance visitors’ experiences.
Students' Learning through Hypermedia

This study assessed the effectiveness of hypermedia software in the learning and retention, association, and structuring of biological knowledge by using fifth grade students (ages 9 to 11 years) from three urban schools in Southern Chile. Four groups of 24 subjects each were exposed to either hypermedia software presentation on basic functions of the human body (Group 1), the same information in linear, electronic book mode (Group 2), the same information on a printed brochure (Group 3), or no experimental treatment but exposure (as were students in the other three groups) to regular lectures and materials (control group or Group 4). Six students from each school were randomly assigned to the treatment and control groups; thus 24 students from each school (N = 72) participated. Students in all groups increased their retention of information. They also improved their performance on remote concept associations and on consttuction of conceptual maps. However, the groups who used the software presentation obtained significantly better scores on remote association of concepts. There were correlations for the users' hypermedia navigational patterns with the richness of the students' conceptual maps, and the students' remote association. In general, results support the use of similar software in education wherein the goals are remote associations and rich conceprual maps, and, more specifically, they indicate that the students' navigational pattern through information could serve them better to structure and relate conceptual information.
Presence of the IL‐1RA Allele 2 (IL1RN*2) is Associated with Enhanced IL‐1β Production In Vitro

The genes of the interleukin‐1 (IL‐1) complex code for three proteins: IL‐1α, IL‐1β and the IL‐1 receptor antagonist (IL‐1RA). Each of these genes is polymorphic and there is increasing evidence that certain alleles are associated with increased susceptibility to a given disease of inflammatory nature. In the IL‐1β gene there are two base‐exchange polymorphisms in positions −511 and +3953, and IL‐1RA gene has a penta‐allelic polymorphic site in intron 2 containing variable numbers of an 86‐bp tandem repeat sequence. As the IL‐1β/IL‐1RA ratio may be critical in the regulation of inflammation, we examined whether there are allelic associations between these loci (thus suggesting co‐ordinate regulation) and whether these have an effect on the in vitro production of IL‐1β. We found that the IL‐1RA allele 2 (IL1RN*2) is associated with the presence of allele 2 of the IL‐1β gene (position −511) and with the absence of allele 2 of the IL‐1β gene (position +3953). Mononuclear cells from carriers of allele 2 (position −511) and non‐carriers of allele 2 (position +3953) had a slight, but non‐significant, elevated capacity to produce IL‐1βin vitro. However, IL‐1RA allele 2 strongly increased in vitro production of IL‐1β, regardless of the presence or absence of these alleles. Taken together, these data suggest that the known allelisms in the IL‐1β gene are not major regulators of the in vitro IL‐1β production, but the IL‐1RA allele 2 (or an unknown allele strongly associated with it) has a decisive role.
Selective Regulation of Gαq/11 by an RGS Domain in the G Protein-coupled Receptor Kinase, GRK2*

G protein-coupled receptor kinases (GRKs) are well characterized regulators of G protein-coupled receptors, whereas regulators of G protein signaling (RGS) proteins directly control the activity of G protein α subunits. Interestingly, a recent report (Siderovski, D. P., Hessel, A., Chung, S., Mak, T. W., and Tyers, M. (1996) Curr. Biol. 6, 211–212) identified a region within the N terminus of GRKs that contained homology to RGS domains. Given that RGS domains demonstrate AlF4 −-dependent binding to G protein α subunits, we tested the ability of G proteins from a crude bovine brain extract to bind to GRK affinity columns in the absence or presence of AlF4 −. This revealed the specific ability of bovine brain Gαq/11 to bind to both GRK2 and GRK3 in an AlF4 −-dependent manner. In contrast, Gαs, Gαi, and Gα12/13 did not bind to GRK2 or GRK3 despite their presence in the extract. Additional studies revealed that bovine brain Gαq/11 could also bind to an N-terminal construct of GRK2, while no binding of Gαq/11, Gαs, Gαi, or Gα12/13 to comparable constructs of GRK5 or GRK6 was observed. Experiments using purified Gαq revealed significant binding of both GαqGDP/AlF4 − and Gαq(GTPγS), but not Gαq(GDP), to GRK2. Activation-dependent binding was also observed in both COS-1 and HEK293 cells as GRK2 significantly co-immunoprecipitated constitutively active Gαq(R183C) but not wild type Gαq. In vitro analysis revealed that GRK2 possesses weak GAP activity toward Gαq that is dependent on the presence of a G protein-coupled receptor. However, GRK2 effectively inhibited Gαq-mediated activation of phospholipase C-β both in vitro and in cells, possibly through sequestration of activated Gαq. These data suggest that a subfamily of the GRKs may be bifunctional regulators of G protein-coupled receptor signaling operating directly on both receptors and G proteins.
Fungal CYP51 Inhibitors VT-1161 and VT-1129 Exhibit Strong In Vitro Activity against Candida glabrata and C. krusei Isolates Clinically Resistant to Azole and Echinocandin Antifungal Compounds

ABSTRACT The in vitro activities of fungal CYP51 inhibitors VT-1161 and VT-1129 were determined for Candida glabrata (n = 34) and C. krusei (n = 50). C. glabrata isolates were screened for FKS gene mutations. All isolates were resistant clinically and/or in vitro to at least one standard antifungal compound. VT-1161 and VT-1129 MICs for all isolates were at least 5-fold below achievable human plasma levels for VT-1161. VT-1161 and VT-1129 are promising for the treatment of resistant C. glabrata and C. krusei infections.
Behavior of bacteria and antibiotics under space conditions.

We have previously reported an increase of the "resistance" to antibiotics of bacteria during space missions. In the present experiment, we studied the growth of Escherichia coli cultured in vitro in space in the presence of dihydrostreptomycin: tritiated and nontritiated. This experiment was carried out during the STS 42 mission aboard the U.S. Space Shuttle Discovery (IML-1 program). Cells were cultured in plastic bags and growth was stopped at six different time points by lowering the temperature to 5 degrees C. Several methods were used: viable cell counting by Colony Forming Units; total cell number by optical densitometry; electron microscopy; radioactivity measurements. The investigations show no difference between flight and ground experiments for the cultures without antibiotic. The growth rate with antibiotic was accelerated in flight, the growth yield was not changed, and there were no differences in the ultrastructures. The results suggest some changes in antibiotic binding in space. We did not observe any differences between the cultures developed in flight in the 1-g centrifuge and the cultures placed in the static rack in microgravity.
Discriminative Joint-Feature Topic Model With Dual Constraints for WCE Classification

Wireless capsule endoscopy (WCE) enables clinicians to examine the digestive tract without any surgical operations, at the cost of a large amount of images to be analyzed. The main challenge for automatic computer-aided diagnosis arises from the difficulty of robust characterization of these images. To tackle this problem, a novel discriminative joint-feature topic model (DJTM) with dual constraints is proposed to classify multiple abnormalities in WCE images. We first propose a joint-feature probabilistic latent semantic analysis (PLSA) model, where color and texture descriptors extracted from same image patches are jointly modeled with their conditional distributions. Then the proposed dual constraints: visual words importance and local image manifold are embedded into the joint-feature PLSA model simultaneously to obtain discriminative latent semantic topics. The visual word importance is proposed in our DJTM to guarantee that visual words with similar importance come from close latent topics while the local image manifold constraint enforces that images within the same category share similar latent topics. Finally, each image is characterized by distribution of latent semantic topics instead of low level features. Our proposed DJTM showed an excellent overall recognition accuracy 90.78%. Comprehensive comparison results demonstrate that our method outperforms existing multiple abnormalities classification methods for WCE images.
Corporate Governance and Its Impact on R&D Investment in Emerging Markets

ABSTRACT Corporate R&D activities are inherently risky but also difficult to monitor. Against this background, we examine the impact of ownership concentration and legal shareholder rights protection on corporate R&D investments in emerging markets. Based on a comprehensive sample of publicly listed firms from 24 countries, we find that R&D intensity is lower in firms with (strategic) block ownership, and this effect is more pronounced in countries with stronger shareholder rights protection. This suggests that, similar to the situation in developed economies, dispersed ownership, which allows shareholders to diversify their investment risks, is beneficial for corporate R&D and that this effect is intensified by more developed institutions.
Radiolabeled lipid nanoparticles for diagnostic imaging.

BACKGROUND Nanoparticles are increasingly being incorporated into the design of diagnostic imaging agents. Significant research efforts have been conducted with one class of lipid nanoparticle (liposomes) radiolabeled with gamma-emitting radionuclides as radiopharmaceuticals for scintigraphic imaging of cancer, inflammation/infection and sentinel lymph node detection. OBJECTIVE This article reviews the current literature with special emphasis on the clinical studies performed with liposome radiopharmaceuticals for detection of tumors, infectious/inflammatory sites or metastatic lymph nodes. Future uses of liposome radiopharmaceuticals are also described. METHODS Characteristics required of the radionuclide, liposome formulation and radiolabeling method for an effective radiopharmaceutical are discussed. A description of the procedures and instrumentation for conducting an imaging study with liposome radiopharmaceutical is included. Clinical studies using liposome radiopharmaceuticals are summarized. Future imaging applications of first- and second-generation radiolabeled liposomes for chemodosimetry and the specific targeting of a disease process are also described. RESULTS/CONCLUSION The choice of radionuclide, liposome formulation and radiolabeling method must be carefully considered during the design of a liposome radiopharmaceutical for a given application. After-loading and surface chelation methods are the most efficient and practical. Clinical studies with liposome radiopharmaceuticals demonstrated that a wide variety of tumors could be detected with good sensitivity and specificity. Liposome radiopharmaceuticals could also clearly detect various soft tissue and bone inflammatory/infectious lesions, and performed equal to or better than infection imaging agents that are approved at present. Yet, despite these favorable results, no liposome radiopharmaceutical has been approved for any indication. Some of the reasons for this can be attributed to reports of an unexpected infusion-related adverse reaction in two studies, the requirement of more complex liposome manufacturing procedures, and the adoption of other competing imaging procedures. Continued research of liposome radiopharmaceutical design based on a better understanding of liposome biology, improved radiolabeling methodologies and advances in gamma camera technology is warranted.