Miracle-dz/UniFAR-FTUs huggingface dataset:
Sustained immunogenicity of the HPV-16/18 AS04-adjuvanted vaccine administered as a two-dose schedule in adolescent girls: Five-year clinical data and modeling predictions from a randomized study

In this randomized, partially-blind study (clinicaltrials.gov; NCT00541970), the licensed formulation of the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine (20 μg each of HPV-16/18 antigens) was found highly immunogenic up to 4 y after first vaccination, whether administered as a 2-dose (2D) schedule in girls 9–14 y or 3-dose (3D) schedule in women 15–25 y. This end-of-study analysis extends immunogenicity and safety data until Month (M) 60, and presents antibody persistence predictions estimated by piecewise and modified power law models. Healthy females (age stratified: 9–14, 15–19, 20–25 y) were randomized to receive 2D at M0,6 (N = 240 ) or 3D at M0,1,6 (N = 239). Here, results are reported for girls 9–14 y (2D) and women 15–25 y (3D). Seropositivity rates, geometric mean titers (by enzyme-linked immunosorbent assay) and geometric mean titer ratios (GMRs; 3D/2D; post-hoc exploratory analysis) were calculated. All subjects seronegative pre-vaccination in the according-to-protocol immunogenicity cohort were seropositive for anti-HPV-16 and −18 at M60. Antibody responses elicited by the 2D and 3D schedules were comparable at M60, with GMRs close to 1 (anti-HPV-16: 1.13 [95% confidence interval: 0.82–1.54]; anti-HPV-18: 1.06 [0.74–1.51]). Statistical modeling predicted that in 95% of subjects, antibodies induced by 2D and 3D schedules could persist above natural infection levels for ≥ 21 y post-vaccination. The vaccine had a clinically acceptable safety profile in both groups. In conclusion, a 2D M0,6 schedule of the HPV-16/18 AS04-adjuvanted vaccine was immunogenic for up to 5 y in 9–14 y-old girls. Statistical modeling predicted that 2D-induced antibodies could persist for longer than 20 y.
Tracking an RGB-D Camera Using Points and Planes

Planes are dominant in most indoor and outdoor scenes and the development of a hybrid algorithm that incorporates both point and plane features provides numerous advantages. In this regard, we present a tracking algorithm for RGB-D cameras using both points and planes as primitives. We show how to extend the standard prediction-and-correction framework to include planes in addition to points. By fitting planes, we implicitly take care of the noise in the depth data that is typical in many commercially available 3D sensors. In comparison with the techniques that use only points, our tracking algorithm has fewer failure modes, and our reconstructed model is compact and more accurate. The tracking algorithm is supported by relocalization and bundle adjustment processes to demonstrate a real-time simultaneous localization and mapping (SLAM) system using a hand-held or robot-mounted RGB-D camera. Our experiments show large-scale indoor reconstruction results as point-based and plane-based 3D models, and demonstrate an improvement over the point-based tracking algorithms using a benchmark for RGB-D cameras.
Specific Binding of Nisin to the Peptidoglycan Precursor Lipid II Combines Pore Formation and Inhibition of Cell Wall Biosynthesis for Potent Antibiotic Activity*

Unlike numerous pore-forming amphiphilic peptide antibiotics, the lantibiotic nisin is active in nanomolar concentrations, which results from its ability to use the lipid-bound cell wall precursor lipid II as a docking molecule for subsequent pore formation. Here we use genetically engineered nisin variants to identify the structural requirements for the interaction of the peptide with lipid II. Mutations affecting the conformation of the N-terminal part of nisin comprising rings A through C, e.g.[S3T]nisin, led to reduced binding and increased the peptide concentration necessary for pore formation. The binding constant for the S3T mutant was 0.043 × 107 m −1 compared with 2 × 107 m −1 for the wild-type peptide, and the minimum concentration for pore formation increased from the 1 nm to the 50 nm range. In contrast, peptides mutated in the flexible hinge region, e.g. [ΔN20/ΔM21]nisin, were completely inactive in the pore formation assay, but were reduced to some extent in their in vivo activity. We found the remaining in vivo activity to result from the unaltered capacity of the mutated peptide to bind to lipid II and thus to inhibit its incorporation into the peptidoglycan network. Therefore, through interaction with the membrane-bound cell wall precursor lipid II, nisin inhibits peptidoglycan synthesis and forms highly specific pores. The combination of two killing mechanisms in one molecule potentiates antibiotic activity and results in nanomolar MIC values, a strategy that may well be worth considering for the construction of novel antibiotics.
Adaptive packet marking for providing differentiated services in the Internet

This paper examines the use of adaptable priority marking for providing soft bandwidth guarantees to individual connections or connection groups over the Internet. In contrast to other proposals for service differentiation which focus on providing firm performance guarantees, the proposed scheme does not require resource reservation for individual connections and can be supported with minimal changes to the network infrastructure. It uses modest support from the network in the form of priority handling for appropriately marked packets and relies on intelligent transmission control mechanisms at the edges of the network to achieve the desired throughput levels. The paper describes the control mechanisms and evaluates their behaviour in various network environments. These mechanisms are shown to have several salient features which make them suitable for deployment in an evolving Internet.
Differential Transcriptional Analysis of the Cyanobacterium Cyanothece sp. Strain ATCC 51142 during Light-Dark and Continuous-Light Growth

ABSTRACT We analyzed the metabolic rhythms and differential gene expression in the unicellular, diazotrophic cyanobacterium Cyanothece sp. strain ATCC 51142 under N2-fixing conditions after a shift from normal 12-h light-12-h dark cycles to continuous light. We found that the mRNA levels of ∼10% of the genes in the genome demonstrated circadian behavior during growth in free-running (continuous light) conditions. The genes for N2 fixation displayed a strong circadian behavior, whereas photosynthesis and respiration genes were not as tightly regulated. One of our main objectives was to determine the strategies used by these cells to perform N2 fixation under normal day-night conditions, as well as under the greater stress caused by continuous light. We determined that N2 fixation cycled in continuous light but with a lower N2 fixation activity. Glycogen degradation, respiration, and photosynthesis were also lower; nonetheless, O2 evolution was about 50% of the normal peak. We also demonstrated that nifH (encoding the nitrogenase Fe protein), nifB, and nifX were strongly induced in continuous light; this is consistent with the role of these proteins during the assembly of the enzyme complex and suggested that the decreased N2 fixation activity was due to protein-level regulation or inhibition. Many soluble electron carriers (e.g., ferredoxins), as well as redox carriers (e.g., thioredoxin and glutathione), were strongly induced during N2 fixation in continuous light. We suggest that these carriers are required to enhance cyclic electron transport and phosphorylation for energy production and to maintain appropriate redox levels in the presence of elevated O2, respectively.
Bounds on Elasticities with Optimization Frictions: A Synthesis of Micro and Macro Evidence on Labor Supply

How can price elasticities be identified when agents face optimization frictions such as adjustment costs or inattention? I derive bounds on structural price elasticities that are a function of the observed effect of a price change on demand, the size of the price change, and the degree of frictions. The degree of frictions is measured by the utility losses agents tolerate to deviate from the frictionless optimum. The bounds imply that frictions affect intensive margin elasticities much more than extensive margin elasticities. I apply these bounds to the literature on labor supply. The utility costs of ignoring the tax changes used to identify intensive margin labor supply elasticities are typically less than 1% of earnings. As a result, small frictions can explain the differences between micro and macro elasticities, extensive and intensive margin elasticities, and other disparate findings. Pooling estimates from existing studies, I estimate a Hicksian labor supply elasticity of 0.33 on the intensive margin and 0.25 on the extensive margin after accounting for frictions.
A GABAergic, Strongly Inhibitory Projection to a Thalamic Nucleus in the Zebra Finch Song System

The anterior forebrain pathway (AFP) of the oscine song system is essential for song learning but not song production. Most cells recorded in this serially connected pathway show increased firing in response to song playback, suggesting largely excitatory connections among AFP nuclei. However, the neurons forming a key projection in this pathway, from area X to the medial nucleus of the dorsolateral thalamus (DLM), express glutamic acid decarboxylase in their somata and terminals, suggesting an inhibitory connection. To investigate the firing properties of DLM neurons and the functional influence of area X afferents in DLM, we made whole-cell recordings from DLM neurons in brain slices from adult male zebra finches. Most cells had intrinsic properties closely resembling those of mammalian thalamocortical cells, including a low-threshold Ca2+ spike and time-dependent, hyperpolarization-activated inward rectification. Activation of afferents from area X evoked a strong, all-or-none IPSP whose amplitude and latency were unchanged by application of glutamate antagonists, consistent with a monosynaptic contact. The IPSP had a reversal potential near −70 mV and was blocked by the GABAA receptor antagonist bicuculline methiodide. Post-inhibitory rebound firing occurred in DLM neurons with a delay near 50 msec. Strong inhibition can combine with the intrinsic properties of DLM neurons to allow signaling on disinhibition. Our data are consistent with the hypothesis that the AFP corresponds to the mammalian corticobasal ganglia–thalamocortical loop. The similar functional properties of avian and mammalian thalamic neurons suggest conserved forebrain mechanisms of sensorimotor information processing across vertebrate taxa.
Nonagonistic Dectin-1 ligand transforms CpG into a multitask nanoparticulate TLR9 agonist

Significance CpG oligodeoxynucleotide (ODN), a Toll-like receptor 9 ligand, is a promising immunotherapeutic agent; however, developing an IFN-inducing CpG ODN forming a stable nanoparticle without aggregation has been unsuccessful. Here we generated a nanoparticulate CpG ODN (K3) wrapped by the nonagonistic Dectin-1 ligand schizophyllan (SPG), K3-SPG. K3-SPG stimulates human peripheral blood mononuclear cells to produce large amounts of both type I and II IFN. K3-SPG thus became a potent adjuvant, especially for cytotoxic T-lymphocyte (CTL) induction to coadministered protein antigens without conjugation, which is attributable to its nanoparticulate nature rather than to targeting Dectin-1. Protective potency of K3-SPG as an influenza vaccine adjuvant was demonstrated in both murine and nonhuman primate models. K3-SPG may be used as an IFN inducer as well as a CTL inducer for immunotherapeutic applications. CpG DNA, a ligand for Toll-like receptor 9 (TLR9), has been one of the most promising immunotherapeutic agents. Although there are several types of potent humanized CpG oligodeoxynucleotide (ODN), developing “all-in-one” CpG ODNs activating both B cells and plasmacytoid dendritic cells forming a stable nanoparticle without aggregation has not been successful. In this study, we generated a novel nanoparticulate K CpG ODN (K3) wrapped by the nonagonistic Dectin-1 ligand schizophyllan (SPG), K3-SPG. In sharp contrast to K3 alone, K3-SPG stimulates human peripheral blood mononuclear cells to produce a large amount of both type I and type II IFN, targeting the same endosome where IFN-inducing D CpG ODN resides without losing its K-type activity. K3-SPG thus became a potent adjuvant for induction of both humoral and cellular immune responses, particularly CTL induction, to coadministered protein antigens without conjugation. Such potent adjuvant activity of K3-SPG is attributed to its nature of being a nanoparticle rather than targeting Dectin-1 by SPG, accumulating and activating antigen-bearing macrophages and dendritic cells in the draining lymph node. K3-SPG acting as an influenza vaccine adjuvant was demonstrated in vivo in both murine and nonhuman primate models. Taken together, K3-SPG may be useful for immunotherapeutic applications that require type I and type II IFN as well as CTL induction.
The hTERT Gene Is Embedded in a Nuclease-resistant Chromatin Domain*

Normal human cells rarely undergo spontaneous immortalization. Given that ectopic expression of the human telomerase catalytic subunit hTERT leads to cellular immortalization, the endogenous hTERT gene is likely constitutively repressed. Hence, we have examined the chromatin structure of the native hTERT locus and the neighboring loci, CRR9 and Xtrp2, in normal human fibroblasts and a set of immortal lines. Using generalized DNase I sensitivity assays, we revealed that the entire hTERT gene was embedded in a chromatin domain that was as resistant to the nuclease as the well studied β-globin loci in both telomerase-positive and -negative cells. This condensed domain was at least 100 kb in size and contained the intergenic region 5′ to the hTERT gene and the downstream Xtrp2 locus. A transition from the nuclease-sensitive CRR9 locus to the condensed region appeared near the 3′-end of the CRR9 gene. hTERT transcription was associated with the appearance of a major DNase I-hypersensitive site positioned around the hTERT transcription start site and several minor hypersensitive sites. In telomerase-negative cells, the inhibition of histone deacetylases by trichostatin A led to the opening of this chromatin domain, accompanied by transcription from the hTERT gene but not the Xtrp2 gene. In contrast, the inhibition of protein synthesis by cycloheximide induced transcription from both the hTERT and Xtrp2 genes, indicating that histone deacetylases and labile factors coordinate to silence this chromosomal region. Taken together, our data suggest a novel mechanism of hTERT regulation at the chromatin level and have important implications for studying telomerase expression.
Mixed-Forest Species Establishment in a Monodominant Forest in Central Africa: Implications for Tropical Forest Invasibility

Background Traits of non-dominant mixed-forest tree species and their synergies for successful co-occurrence in monodominant Gilbertiodendron dewevrei forest have not yet been investigated. Here we compared the tree species diversity of the monodominant forest with its adjacent mixed forest and then determined which fitness proxies and life history traits of the mixed-forest tree species were most associated with successful co-existence in the monodominant forest. Methodology/Principal Findings We sampled all trees (diameter in breast height [dbh]≥10 cm) within 6×1 ha topographically homogenous areas of intact central African forest in SE Cameroon, three independent patches of G. dewevrei-dominated forest and three adjacent areas (450–800 m apart). Monodominant G. dewevrei forest had lower sample-controlled species richness, species density and population density than its adjacent mixed forest in terms of stems with dbh≥10 cm. Analysis of a suite of population-level characteristics, such as relative abundance and geographical distribution, and traits such as wood density, height, diameter at breast height, fruit/seed dispersal mechanism and light requirement–revealed after controlling for phylogeny, species that co-occur with G. dewevrei tend to have higher abundance in adjacent mixed forest, higher wood density and a lower light requirement. Conclusions/Significance Our results suggest that certain traits (wood density and light requirement) and population-level characteristics (relative abundance) may increase the invasibility of a tree species into a tropical closed-canopy system. Such knowledge may assist in the pre-emptive identification of invasive tree species.
Increased &bgr;-Adrenergic Inotropy in Ventricular Myocardium From Trpm4−/− Mice

Rationale: The Trpm4 gene has recently been associated with several disorders, including cardiac conduction diseases and Brugada syndrome. Transient receptor potential member 4 (TRPM4) proteins constitute Ca2+-activated, but Ca2+-impermeable, nonselective cation channels and are expressed both in atrial and in ventricular cardiomyocytes. The physiological function of TRPM4 in the heart remains, however, incompletely understood. Objective: To establish the role of TRPM4 in cardiac muscle function. Methods and Results: We used TRPM4 knockout mice and performed patch-clamp experiments, membrane potential measurements, microfluorometry, contractility measurements, and in vivo pressure–volume loop analysis. We demonstrate that TRPM4 proteins are functionally present in mouse ventricular myocytes and are activated on Ca2+-induced Ca2+ release. In Trpm4−/− mice, cardiac muscle displays an increased &bgr;-adrenergic inotropic response both in vitro and in vivo. Measurements of action potential duration show a significantly decreased time for 50% and 90% repolarization in Trpm4−/− ventricular myocytes. We provide evidence that this change in action potential shape leads to an increased driving force for the L-type Ca2+ current during the action potential, which explains the altered contractility of the heart muscle. Conclusions: Our results show that functional TRPM4 proteins are novel determinants of the inotropic effect of &bgr;-adrenergic stimulation on the ventricular heart muscle.
Dry Matter Production, Nutrient Cycled and Removed, and Soil Fertility Changes in Yam-Based Cropping Systems with Herbaceous Legumes in the Guinea-Sudan Zone of Benin

Traditional yam-based cropping systems (shifting cultivation, slash-and-burn, and short fallow) often result in deforestation and soil nutrient depletion. The objective of this study was to determine the impact of yam-based systems with herbaceous legumes on dry matter (DM) production (tubers, shoots), nutrients removed and recycled, and the soil fertility changes. We compared smallholders' traditional systems (1-year fallow of Andropogon gayanus-yam rotation, maize-yam rotation) with yam-based systems integrated herbaceous legumes (Aeschynomene histrix/maize intercropping-yam rotation, Mucuna pruriens/maize intercropping-yam rotation). The experiment was conducted during the 2002 and 2004 cropping seasons with 32 farmers, eight in each site. For each of them, a randomized complete block design with four treatments and four replicates was carried out using a partial nested model with five factors: Year, Replicate, Farmer, Site, and Treatment. Analysis of variance (ANOVA) using the general linear model (GLM) procedure was applied to the dry matter (DM) production (tubers, shoots), nutrient contribution to the systems, and soil properties at depths 0–10 and 10–20 cm. DM removed and recycled, total N, P, and K recycled or removed, and soil chemical properties (SOM, N, P, K, and pH water) were significantly improved on yam-based systems with legumes in comparison with traditional systems.
Improve the mechanical property and flame retardant efficiency of the composites of poly(lactic acid) and resorcinol di(phenyl phosphate) (RDP) with ZnO‐coated kenaf

The kenaf coated with zinc oxide (ZnO) was prepared and characterized by X‐ray diffraction, scanning electron microscopy, and X‐ray photoelectron spectroscopy. The ZnO‐coated kenaf and the flame retardant resorcinol di(phenyl phosphate) were blended with poly(lactic acid) (PLA) by solution compounding and melt blending to prepare the flame‐retarded PLA composites. The thermal stability, the mechanical property, and the flame retardancy of the PLA composites were improved evidently. The tensile strength of the prepared PLA composites could reach up to 62.3 MPa in comparison with 55.4 MPa of the pure PLA. The dense and compact char residues were observed after the combustion of the PLA composites containing ZnO‐coated kenaf, whereas there were serious dripping phenomena and no char formation during the combustion of the pure PLA. The use of ZnO‐coated kenaf could increase flame retardant efficiency obviously. The mechanism of flame retardancy was discussed. Copyright © 2014 John Wiley & Sons, Ltd.
An Efficient Off-Line E-Cash System based on Signcryption without Bilinear Pairings

is an increased activity in research and development conducted to improve current payment systems in parallel with the progress of Internet. Signcryption combines the functionalities of encryption and digital signing in a single logical step. It is a cryptographic primitive that provides confidentiality, integrity, authentication and non-repudiation. Identity-based cryptography serves as an efficient alternative to the traditional certificate-based cryptosystems. This paper introduces an efficient electronic payment system based on signcryption without bilinear pairings. This e-cash system is more efficient than other schemes employing bilinear pairings and involves less computational cost. In the proposed protocol, the token is issued and authenticated by the bank to prevent double spending problem. The customer delegates his signing capability to the merchant. The bank verifies the identities of both the original signer (customer) and the proxy signer (merchant) and ensures the originality of the transaction. Unlike the existing e-payment systems, the problem of double spending of e-cash does not arise because each transaction is made uniquely identifiable. Hence, no separate protocol is needed to check double-spending. The performance and the security analysis of the proposed e-cash system are discussed revealing its strength from the viewpoint of security and efficiency with regard to computations required.
Whole Animal Automated Platform for Drug Discovery against Multi-Drug Resistant Staphylococcus aureus

Staphylococcus aureus, the leading cause of hospital-acquired infections in the United States, is also pathogenic to the model nematode Caenorhabditis elegans. The C. elegans-S. aureus infection model was previously carried out on solid agar plates where the bacteriovorous C. elegans feeds on a lawn of S. aureus. However, agar-based assays are not amenable to large scale screens for antibacterial compounds. We have developed a high throughput liquid screening assay that uses robotic instrumentation to dispense a precise amount of methicillin resistant S. aureus (MRSA) and worms in 384-well assay plates, followed by automated microscopy and image analysis. In validation of the liquid assay, an MRSA cell wall defective mutant, MW2ΔtarO, which is attenuated for killing in the agar-based assay, was found to be less virulent in the liquid assay. This robust assay with a Z’-factor consistently greater than 0.5 was utilized to screen the Biomol 4 compound library consisting of 640 small molecules with well characterized bioactivities. As proof of principle, 27 of the 30 clinically used antibiotics present in the library conferred increased C. elegans survival and were identified as hits in the screen. Surprisingly, the antihelminthic drug closantel was also identified as a hit in the screen. In further studies, we confirmed the anti-staphylococcal activity of closantel against vancomycin-resistant S. aureus isolates and other Gram-positive bacteria. The liquid C. elegans – S. aureus assay described here allows screening for anti-staphylococcal compounds that are not toxic to the host.