Miracle-dz/UniFAR-FTUs huggingface dataset:
Depressed light emission by symbiotic Vibrio fischeri of the sepiolid squid Euprymna scolopes

Bioluminescent marine bacteria of the species Vibrio fischeri are the specific light organ symbionts of the sepiolid squid Euprymna scolopes. Although they share morphological and physiological characteristics with other strains of V. fischeri, when cultured away from the light organ association the E. scolopes symbionts depress their maximal luminescence over 1,000-fold. The primary cause of this reduced luminescence is the underproduction by these bacteria of luciferase autoinducer, a molecule involved in the positive transcriptional regulation of the V. fischeri lux operon. Such an absence of visible light production outside of the symbiotic association has not been previously reported among light organ symbionts of this or any other species of luminous bacteria. Levels of luminescence approaching those of the E. scolopes bacteria in the intact association can be restored by the addition of exogenous autoinducer to bacteria in laboratory culture and are affected by the presence of cyclic AMP. We conclude that some condition(s) specific to the internal environment of the light organ is necessary for maximal autoinduction of luminescence in the symbionts of this squid-bacterial association.
Corneal hysteresis but not corneal thickness correlates with optic nerve surface compliance in glaucoma patients.

PURPOSE To investigate relationships between acute intraocular pressure (IOP)-induced optic nerve head surface deformation and corneal hysteresis and thickness in glaucomatous and nonglaucomatous human eyes. METHODS This was a prospective experimental study of 100 subjects (38 with glaucoma, 62 without glaucoma). Data collected included spherical equivalent, optic disc diameter, central corneal thickness (CCT), axial length, cylinder, Goldmann IOP, Pascal IOP, and ocular pulse amplitude and ocular response analyzer (ORA) measurements of corneal hysteresis (CH). Elevation of IOP was induced in the right eye of each subject with a modified LASIK suction ring to an average of 64 mm Hg for less than 30 seconds. Heidelberg Retina Tomography II (HRT) was used to map the optic nerve surface before and during IOP elevation. Mean cup depth was calculated using built-in HRT data analysis software. Change in optic disc depth during IOP elevation was calculated for all right eyes, and tests for correlation with the parameters listed were performed. RESULTS Both CH and CCT were lower in the glaucoma group (8.8 mm Hg and 532 microm) than in the control group (9.6 mm Hg, P = 0.012; 551 microm, P = 0.011, respectively). There were no statistically significant differences in spherical equivalent, cylinder, axial length, optic disc size, or ocular pulse amplitude between the glaucoma and the control groups. There was no difference between the amount of IOP elevation between the two groups (P = 0.41), and the average difference in mean cup depth between baseline (mean cup depth, 247 microm) and during IOP elevation was 33 microm (29.8 microm in glaucoma and 36.1 microm in control; P = 0.5). Multiple variable analysis, controlling for age and sex, showed that CH was correlated with mean cup depth increase (P = 0.032). This relationship persisted (P = 0.032) after controlling for glaucoma status in addition to age and sex. Other factors, including CCT (P = 0.3), axial length (P = 0.9), ocular pulse amplitude (P = 0.22), and spherical equivalent (P = 0.38), were not significant in this model. CONCLUSIONS In the glaucoma patients but not the control patients, CH but not CCT or other anterior segment parameters was associated with increased deformation of the optic nerve surface during transient elevations of IOP. (ClinicalTrials.gov number, NCT00328835.).
QoE Based P2P Scalable Video Streaming over Mobile Ad Hoc Networks

This paper studies the resource allocation problem for efficiently utilizing network resources for distributing video over a peer to peer mobile ad hoc network. We define an NP complete linear optimization problem to handle the upload bandwidth available across each node. Scalable video coding is used to maximize the quality of experience among users and to distribute the load and reduce the consumed power across different nodes. We propose a QoE based energy efficient (QEE) model that provides an approximation algorithm and compare with other previously proposed models [18][19]. Furthermore, the model is also compared with non-quality of experience plus non-energy efficient (NQNE) and a quality of experience plus non-energy efficient (QNE) models. Simulation results show that the proposed model achieves better quality of experience, a lower power consumption and performs better under network churn.
Improving principal practice: Addressing teacher evaluation through data analysis and strategic professional development

This improvement project was developed to address the discrepancy between how principals rate and evaluate teachers and the value-added measures teachers receive based on student growth data from standardized tests. Specifically, this project engaged a group of principals in a professional development program designed to improve their rater agreement against criterion measures in a commercially developed program. Employing improvement science methods, a multi-tiered process of interventions was designed and implemented with the goals of improving target agreement, decreasing discrepancy, and eliminating scoring bias among the twelve evaluators who participated in the study in the Concordia School District. After each intervention, data were analyzed to determine appropriate subsequent interventions. Through collaboration with leaders from the North Carolina Department of Public Instruction (NCDPI) the project was enhanced and extended through face-to-face opportunities and follow-up sessions. Qualitative and quantitative data from the project indicate that evaluation ratings improved among the participants. Due to the collaborative nature of the project between a district and the state department of education, this prototype for improving the quality of evaluations has implications to serve as a statewide model.
A PhoPQ-Regulated ABC Transporter System Exports Tetracycline in Pseudomonas aeruginosa

ABSTRACT Pseudomonas aeruginosa is an important human pathogen whose infections are difficult to treat due to its high intrinsic resistance to many antibiotics. Here, we show that the disruption of PA4456, encoding the ATP binding component of a putative ATP-binding cassette (ABC) transporter, increased the bacterium's susceptible to tetracycline and other antibiotics or toxic chemicals. Fluorescence spectroscopy and antibiotic accumulation tests showed that the interruption of the ABC transporter caused increased intracellular accumulation of tetracycline, demonstrating a role of the ABC transporter in tetracycline expulsion. Site-directed mutagenesis proved that the conserved residues of E170 in the Walker B motif and H203 in the H-loop, which are important for ATP hydrolysis, were essential for the function of PA4456. Through a genome-wide search, the PhoPQ two-component system was identified as a regulator of the computationally predicted PA4456-4452 operon that encodes the ABC transporter system. A >5-fold increase of the expression of this operon was observed in the phoQ mutant. The results obtained also show that the expression of the phzA1B1C1D1E1 operon and the production of pyocyanin were significantly higher in the ABC transporter mutant, signifying a connection between the ABC transporter and pyocyanin production. These results indicated that the PhoPQ-regulated ABC transporter is associated with intrinsic resistance to antibiotics and other adverse compounds in P. aeruginosa, probably by extruding them out of the cell.
Defective remodeling of cardiolipin and phosphatidylglycerol in Barth syndrome.

Cardiolipin (CL) and phosphatidylglycerol (PG) are the major polyglycerophospholipids observed in mammalian tissues. CL is exclusively found in the inner mitochondrial membrane and is required for optimal function of many of the respiratory and ATP-synthesizing enzymes. The role of CL in oxidative phosphorylation is, however, not fully understood and although reduced CL content leads to aberrant cell function, no human disorders with a primary defect in cardiolipin metabolism have been described. In this paper we present evidence that patients with the rare disorder X-linked cardioskeletal myopathy and neutropenia (Barth syndrome, MIM 302060) have a primary defect in CL and PG remodeling. We investigated phospholipid metabolism in cultured skin fibroblasts of patients and show that the biosynthesis rate of PG and CL is normal but that the CL pool size is 75% reduced, indicating accelerated degradation. Moreover, the incorporation of linoleic acid, which is the characteristic acyl side chain found in mammalian CL, into both PG and CL is significantly reduced, whereas the incorporation of other fatty acids into these phospholipids is normal. We show that this defect was only observed in Barth syndrome patients' cells and not in cells obtained from patients with primary defects in the respiratory chain, demonstrating that the observed defect is not secondary to respiratory chain dysfunction. These results imply that the G4.5 gene product, which is mutated in Barth syndrome patients, is specifically involved in the remodeling of PG and CL and for the first time identify an essential factor in this important cellular process.
Developmental nicotine exposure disrupts dendritic arborization patterns of hypoglossal motoneurons in the neonatal rat

Maternal smoking or use of other products containing nicotine during pregnancy can have significant adverse consequences for respiratory function in neonates. We have shown, in previous studies, that developmental nicotine exposure (DNE) in a model system compromises the normal function of respiratory circuits within the brainstem. The effects of DNE include alterations in the excitability and synaptic interactions of the hypoglossal motoneurons, which innervate muscles of the tongue. This study was undertaken to test the hypothesis that these functional consequences of DNE are accompanied by changes in the dendritic morphology of hypoglossal motoneurons. Hypoglossal motoneurons in brain stem slices were filled with neurobiotin during whole‐cell patch clamp recordings and subjected to histological processing to reveal dendrites. Morphometric analysis, including the Sholl method, revealed significant effects of DNE on dendritic branching patterns. In particular, whereas within the first five postnatal days there was significant growth of the higher‐order dendritic branches of motoneurons from control animals, the growth was compromised in motoneurons from neonates that were subjected to DNE. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 76: 1125–1137, 2016
Akt and Bcl-xL Promote Growth Factor-independent Survival through Distinct Effects on Mitochondrial Physiology*

A comparison of Akt- and Bcl-xL-dependent cell survival was undertaken using interleukin-3-dependent FL5.12 cells. Expression of constitutively active Akt allows cells to survive for prolonged periods following growth factor withdrawal. This survival correlates with the expression level of activated Akt and is comparable in magnitude to the protection provided by the anti-apoptotic geneBcl-x L . Although both genes prevent cell death, Akt-protected cells can be distinguished fromBcl-x L -protected cells on the basis of increased glucose transporter expression, glycolytic activity, mitochondrial potential, and cell size. In addition, Akt-expressing cells require high levels of extracellular nutrients to support cell survival. In contrast, Bcl-xL-expressing cells deprived of interleukin-3 survive in a more vegetative state, in which the cells are smaller, have lower mitochondrial potential, reduced glycolytic activity, and are less dependent on extracellular nutrients. Thus, Akt and Bcl-xL suppress mitochondrion-initiated apoptosis by distinct mechanisms. Akt-mediated survival is dependent on promoting glycolysis and maintaining a physiologic mitochondrial potential. In contrast, Bcl-xL maintains mitochondrial integrity in the face of a reduced mitochondrial membrane potential, which develops as a result of the low glycolytic rate in growth factor-deprived cells.
Understanding Variability in Posaconazole Exposure Using an Integrated Population Pharmacokinetic Analysis

ABSTRACT Posaconazole oral suspension is widely used for antifungal prophylaxis and treatment in immunocompromised patients, with highly variable pharmacokinetics reported in patients due to inconsistent oral absorption. This study aimed to characterize the pharmacokinetics of posaconazole in adults and investigate factors that influence posaconazole pharmacokinetics byusing a population pharmacokinetic approach. Nonlinear mixed-effects modeling was undertaken for two posaconazole studies in patients and healthy volunteers. The influences of demographic and clinical characteristics, such as mucositis, diarrhea, and drug-drug interactions, on posaconazole pharmacokinetics were investigated using a stepwise forward inclusion/backwards deletion procedure. A total of 905 posaconazole concentration measurements from 102 participants were analyzed. A one-compartment pharmacokinetic model with first-order oral absorption with lag time and first-order elimination best described posaconazole pharmacokinetics. Posaconazole relative bioavailability was 55% lower in patients who received posaconazole than in healthy volunteers. Coadministration of proton pump inhibitors (PPIs) or metoclopramide, as well as the occurrence of mucositis or diarrhea, reduced posaconazole relative bioavailability by 45%, 35%, 58%, and 45%, respectively, whereas concomitant ingestion of a nutritional supplement significantly increased bioavailability (129% relative increase). Coadministration of rifampin or phenytoin increased apparent posaconazole clearance by more than 600%, with a smaller increase observed with fosamprenavir (34%). Participant age, weight, or sex did not significantly affect posaconazole pharmacokinetics. Posaconazole absorption was reduced by a range of commonly coadministered medicines and clinical complications, such as mucositis and diarrhea. Avoidance of PPIs and metoclopramide and administration with food or a nutritional supplement are effective strategies to increase posaconazole absorption.
DC electrical tree growth in epoxy resin and the influence of the size of inceptive AC trees

Electrical tree propagation is a precursor to dielectric failure in high voltage polymeric insulation. Tree growth has been widely studied under AC conditions, but its behavior under DC is not well understood. The aim of this work was to examine the importance of polarity and initiating defect size on DC tree propagation. Electrical tree propagation in epoxy resin under constant DC voltages of +60 kV and −60 kV was measured in samples with classical needle-plane electrodes, but with small initial trees (< 100 μm) incepted under lower AC voltages before the DC tests. Experimental results showed strong polarity dependence. In either polarity, the length of the initial AC tree had a major influence on the inception of the subsequent DC tree. The effect was attributed to the defect being influential if it is larger than the space charge injection region. As a consequence, there is a critical defect size that will accelerate failure of DC insulation dependent on space charge injection behavior of the polymer/electrode system in question — a critical finding for high voltage asset management.
Differential expression of alpha-GAL epitopes (Galalpha1-3Galbeta1-4GlcNAc-R) on pig and mouse organs.

BACKGROUND Expression of the alpha-gal epitope in mice can be completely eliminated by disruption of the alpha1,3 galactosyltransferase gene. As an initial step for assessing the feasibility of this approach in the pig, it was of interest to compare the expression of alpha-gal epitopes in pig and mouse organs. METHODS Membranes from pig and mouse organ homogenates were analyzed for alpha-gal epitope expression by Western blots, enzyme-linked immunosorbent assay (ELISA), immunostaining of tissues, and ELISA inhibition assay. RESULTS Immunostaining of Western blots with human anti-Gal detected alpha-gal epitopes on glycoproteins from pig organs but not on glycoproteins from the corresponding mouse organs. ELISA with membrane homogenates and immunostaining of tissue sections demonstrated a much higher binding of human anti-Gal to alpha-gal epitopes on pig membranes than on mouse membranes. ELISA inhibition assay with monoclonal anti-Gal indicated that alpha-gal epitope expression in pig organs is up to 500-fold higher than in mouse organs. CONCLUSION Expression of alpha-gal epitopes in pig organs is many fold higher than in mouse organs. The abundance of these epitopes in pigs raises the question of whether pigs can properly develop without expression of alpha-gal epitopes.
Lycopene Effects Contributing to Prostate Health

Epidemiological evidence links lycopene consumption with decreased prostate cancer risk. Several signaling pathways have been identified as players in prostate cancer development. Chronic prostatitis, for example, due to infections, is a suggested risk factor for prostate cancer. Endogenous production of reactive oxygen species during inflammation may lead to oxidative DNA damage, which can be mutagenic, if unrepaired. Androgen signaling, cytokine (IL-6, IL-4) and growth factor signaling (e.g., IGF, Wnt/β-catenin) cross-talk via PI3K/Akt, MAPK, and Jak/STAT pathways have been identified as major controllers of prostate growth. During disease progression, and after androgen ablation therapy, the remaining operational pathways are upregulated to compensate for the lost growth signal, finally resulting in androgen-independent prostate cancer. Lycopene modulates several of the aforementioned pathways, providing a promising rationale for prostate cancer risk reduction by lycopene: In many experimental setups, lycopene reduced inflammatory signals, prevented oxidative DNA damage, modulated the expression or activity of IGF axis members, of Wnt/β-catenin and androgen signalling, and enhanced gap junctional communication. Lycopene's influence on these pathways likely contributes to the observed cell growth inhibition and apoptosis induction by lycopene. A substantial part of the lycopene effects can be explained by its antioxidant action, but other mechanisms might also be involved.
Morphometric analysis of intraluminal mucus in airways in chronic obstructive pulmonary disease.

Mucus volume in both central and peripheral airways was assessed in 13 patients, six with chronic bronchitis (CB) and seven with chronic pulmonary emphysema (CPE), by morphologic quantitative measurement in autopsied lungs, and the results were compared with those from four control lungs (NL). The patients with CB and CPE had severe obstructive impairment that did not differ significantly between the two groups (FEV1%, mean 45% in CB and mean 49% in CPE). Mucous hypersecretion during clinical remission differed significantly between the CB and CPE groups (mean 80 ml/day in CB and mean 8 ml/day in CPE). The length of the airway basement membrane and the area of mucus were measured with a digitizing computer. The volume ratio of mucus to airway lumen, which was defined as the volume ratio of mucus to airway lumen calculated as a cylinder by the length of basement membrane, was regarded as the mucus occupying ratio (MOR). MOR was significantly higher in CB lungs (4.1 +/- 1.0% in central airways and 19.6 +/- 3.8% in peripheral airways, mean +/- SE) than in NL (0.3 +/- 0.1% in central airways and 0.6 +/- 0.3% in peripheral airways, respectively) in both central and peripheral airways (p less than 0.05 and p less than 0.01, respectively), whereas no significant increase in MOR was found in CPE lungs, compared with NL. Furthermore, peripheral airway MOR was significantly higher than that of central airways in CB lungs (p less than 0.05). (ABSTRACT TRUNCATED AT 250 WORDS)
Autoinhibited proteins as promising drug targets

Current drug discovery efforts generally focus on a limited number of protein classes, typically including proteins with well‐defined catalytic active sites (e.g., kinases) or ligand binding sites (e.g., G protein‐coupled receptors). Nevertheless, many clinically important pathways are mediated by proteins with no such obvious targets for small molecule inhibitors. Allosteric inhibitors offer an alternative approach to inhibition of protein activities, particularly for proteins that undergo conformational changes as part of their activity cycle. Proteins regulated by autoinhibitory domains represent one broad class of proteins that meets this criterion. In this article, we discuss the potential of autoinhibited proteins as targets for allosteric inhibitors and describe two examples of small molecules that act by stabilizing native autoinhibited conformations of their targets. We propose that proteins regulated by autoinhibition may be generally amenable to allosteric inhibition by small molecules that stabilize the native, autoinhibited fold. © 2004 Wiley‐Liss, Inc.
Effect of vaccine administration modality on immunogenicity and efficacy

The many factors impacting the efficacy of a vaccine can be broadly divided into three categories: features of the vaccine itself, including immunogen design, vaccine type, formulation, adjuvant and dosing; individual variations among vaccine recipients and vaccine administration-related parameters. While much literature exists related to vaccines, and recently systems biology has started to dissect the impact of individual subject variation on vaccine efficacy, few studies have focused on the role of vaccine administration-related parameters on vaccine efficacy. Parenteral and mucosal vaccinations are traditional approaches for licensed vaccines; novel vaccine delivery approaches, including needless injection and adjuvant formulations, are being developed to further improve vaccine safety and efficacy. This review provides a brief summary of vaccine administration-related factors, including vaccination approach, delivery route and method of administration, to gain a better understanding of their potential impact on the safety and immunogenicity of candidate vaccines.
Serengeti Birds Maintain Forests by Inhibiting Seed Predators

Fruit-eating birds inhibit seed predation by beetles, a mechanism that is destabilized when disturbance opens the forest canopy. Of fundamental interest in conservation ecology are the regulatory mechanisms that maintain communities. We document a mechanism that maintains forests in the Serengeti ecosystem, Tanzania, and the destabilization when disturbance opens forest canopy. Forest birds, by consuming seeds, protected them from beetle attack. Consumption increased the germination rate and the density of seedlings and recruits, which was sufficient to maintain the forest. Opening of the canopy resulted in loss of birds, increased beetle attack, and loss of germination. Thus, frugivorous birds are necessary for the maintenance of forests. Their absence could have resulted in the observed forest decline since 1966.