Miracle-dz/UniFAR-FTUs huggingface dataset:
κ-Opioid Receptor Activation Modulates Ca2+Currents and Secretion in Isolated Neuroendocrine Nerve Terminals

Whole-cell patch-clamp recordings were performed together with time-resolved measurements of membrane capacitance (Cm) in nerve terminals acutely dissociated from neurohypophysis of adult rats to investigate modulation of Ca2+ currents and secretion by activation of opioid receptors. Bath superfusion of the κ-opioid agonists U69,593 (0.3–1 μm), dynorphin A (1 μm), or U50,488H (1–3 μm) reversibly suppressed the peak amplitude of Ca2+ currents 32.7 ± 2.7% (in 41 of 56 terminals), 37.4 ± 5.3% (in 5 of 8 terminals), and 33.5 ± 8.1% (in 5 of 10 terminals), respectively. In contrast, tests in 11 terminals revealed no effect of the μ-opioid agonist [d-Pen2,5]-enkephalin (1–3 μm; n = 7) or of the δ-agonist Tyr-d-Ala-Gly-N-Me-Phe-Gly-ol (1 μm; n = 4) on Ca2+currents. Three components of high-threshold current were distinguished on the basis of their sensitivity to blockade by ω-conotoxin GVIA, nicardipine, and ω-conotoxin MVIIC: N-, L-, and P/Q-type current, respectively. Administration of U69,593 inhibited N-type current in these nerve terminals on average 32%, whereas L-type current was reduced 64%, and P/Q-type current was inhibited 28%. Monitoring of changes in Cm in response to brief depolarizing steps revealed that the κ-opioid-induced reductions in N-, L-, or P/Q-type currents were accompanied by attenuations in two kinetically distinct components of Ca2+-dependent exocytotic release. These data provide strong evidence of a functional linkage between blockade of Ca2+ influx through voltage-dependent Ca2+ channels and inhibitory modulation of release by presynaptic opioid receptors in mammalian central nerve endings.
Evolution and Dynamics of Regulatory Architectures Controlling Polymyxin B Resistance in Enteric Bacteria

Complex genetic networks consist of structural modules that determine the levels and timing of a cellular response. While the functional properties of the regulatory architectures that make up these modules have been extensively studied, the evolutionary history of regulatory architectures has remained largely unexplored. Here, we investigate the transition between direct and indirect regulatory pathways governing inducible resistance to the antibiotic polymyxin B in enteric bacteria. We identify a novel regulatory architecture—designated feedforward connector loop—that relies on a regulatory protein that connects signal transduction systems post-translationally, allowing one system to respond to a signal activating another system. The feedforward connector loop is characterized by rapid activation, slow deactivation, and elevated mRNA expression levels in comparison with the direct regulation circuit. Our results suggest that, both functionally and evolutionarily, the feedforward connector loop is the transitional stage between direct transcriptional control and indirect regulation.
Quantitative assessment of brain microvascular and tissue oxygenation during cardiac arrest and resuscitation in pigs

Cardiac arrest is associated with a very high rate of mortality, in part due to inadequate tissue perfusion during attempts at resuscitation. Parameters such as mean arterial pressure and end‐tidal carbon dioxide may not accurately reflect adequacy of tissue perfusion during cardiac resuscitation. We hypothesised that quantitative measurements of tissue oxygen tension would more accurately reflect adequacy of tissue perfusion during experimental cardiac arrest. Using oxygen‐dependent quenching of phosphorescence, we made measurements of oxygen in the microcirculation and in the interstitial space of the brain and muscle in a porcine model of ventricular fibrillation and cardiopulmonary resuscitation. Measurements were performed at baseline, during untreated ventricular fibrillation, during resuscitation and after return of spontaneous circulation. After achieving stable baseline brain tissue oxygen tension, as measured using an Oxyphor G4‐based phosphorescent microsensor, ventricular fibrillation resulted in an immediate reduction in all measured parameters. During cardiopulmonary resuscitation, brain oxygen tension remained unchanged. After the return of spontaneous circulation, all measured parameters including brain oxygen tension recovered to baseline levels. Muscle tissue oxygen tension followed a similar trend as the brain, but with slower response times. We conclude that measurements of brain tissue oxygen tension, which more accurately reflect adequacy of tissue perfusion during cardiac arrest and resuscitation, may contribute to the development of new strategies to optimise perfusion during cardiac resuscitation and improve patient outcomes after cardiac arrest.
Assessing the Feasibility of Poly-(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) and Poly-(lactic acid) for Potential Food Packaging Applications

ii Dedication . v Acknowledgments . vii Vita . viii List of Tables . xiv List of Figures . xvi Chapter 1: Introduction. 1 Chapter 2: Statement of the Problem . 4 Chapter 3: Literature Review . 6 3.1: Introduction to thermoplastic polymer . 6 3.1. 1: Problems with thermoplastics . 8 3.2: Introduction to biodegradable polymer . 9 3.3 Polyhydroxyalkanoates (PHA) . 10 3.3.1 Polyhydroxyalkanoates (PHA) synthesis . 12 3.3.2: Physicochemical properties of PHA, specifically PHB . 15 3.3.3: PHB plasticized with Poly-(3-hydroxyvalerate) (HV) . 17 3.4: Introduction to Poly(lactic acid) (PLA) . 19 3.4. 1: Poly(lactic acid) (PLA) production . 20
Novel functions of silver on superconducting properties for RE123 melt-solidified bulks

The intrinsic effects of Ag-addition on crystal structure and superconducting properties of Y123 melt-solidified bulks have been investigated. Increased c-axis length and decreases of maximum Tc and carrier density caused by Ag-addition suggested the incorporation of Ag into the Y123 matrix, in which Ag+ was considered to substitute for Cu ion of Cu-O chain. It was also found that Ag-addition enhanced Jc properties all applied fields at 77 K. The distinct second peak of Jc observed for the Ag-added bulk suggested that the Ag-incorporated regions acted as effective pinning centers under disordered vortex lattice.
Improved Laboratory Transition Probabilities for Hf II and Hafnium Abundances in the Sun and 10 Metal-poor Stars

Radiative lifetimes from laser-induced fluorescence measurements, accurate to ~±5%, are reported for 41 odd-parity levels of Hf II. The lifetimes are combined with branching fractions measured using Fourier transform spectrometry to determine transition probabilities for 150 lines of Hf II. Approximately half of these new transition probabilities overlap with recent independent measurements using a similar approach. The two sets of measurements are found to be in good agreement for lines in common. Our new laboratory data are applied to refine the hafnium photospheric solar abundance and to determine hafnium abundances in 10 metal-poor giant stars with enhanced r-process abundances. For the Sun we derive log ε(Hf) = 0.88 ± 0.08 from four lines; the uncertainty is dominated by the weakness of the lines and their blending by other spectral features. Within the uncertainties of our analysis, the r-process-rich stars possess constant Hf/La and Hf/Eu abundance ratios, log ε(Hf/La) = -0.13 ± 0.02(σ = 0.06) and log ε(Hf/Eu) = +0.04 ± 0.02 (σ = 0.06). The observed average stellar abundance ratio of Hf/Eu and La/Eu is larger than previous estimates of the solar system r-process-only value, suggesting a somewhat larger contribution from the r-process to the production of Hf and La. The newly determined Hf values could be employed as part of the chronometer pair, Th/Hf, to determine radioactive stellar ages.
Multi-objective ACO virtual machine placement in cloud computing environments

Cloud computing systems provide services to users based on a pay-as-you-go model. The more services that data centers deliver to users, the more those centers need to be prepared. However, data centers consume huge amounts of energy from the environment. In order to improve data-center efficiency, resource consolidation using virtualization technology is becoming important for the reduction of the environmental impact caused by the data centers. One of the important keys in resource consolidation is the mapping of virtual machines to suitable physical machines, a procedure called virtual machine placement. The present paper focuses on this problem of virtual machine placement and proposes a multi-objective optimization approach to minimize both power consumption and resource wastage and to minimize energy communication cost between network elements within a data center. An Ant Colony Optimization (ACO) algorithm is proposed to obtain a Pareto set for a multi-objective problem. The proposed algorithms are tested using Cloudsim tools. The performances of these algorithms are compared with three well-known single-objective approaches and a multi-objective Genetic Algorithm (GA). The results demonstrate that the proposed algorithms can seek and find solutions that exhibit balance between different objectives. However, ACO is able to And better solutions than GA in terms of our objectives.
Co-delivery of hydrophilic and hydrophobic anticancer drugs using biocompatible pH-sensitive lipid-based nano-carriers for multidrug-resistant cancers

For decades, multi-drug resistance (MDR) to chemotherapeutic drugs has been a serious challenge for researchers and has limited the use of anticancer drugs in malignancy treatment. Combination therapy has been considered as one of the most promising methods to address this problem. In the current study, we optimized niosome nanoparticles containing chemotherapeutic agent doxorubicin and chemosensitizer curcumin in term of surfactant content. Then, a new biocompatible structure (LipoNiosome, combination of niosome and liposome) containing Tween 60: cholesterol: DPPC (at 55 : 30 : 15 : 3) with 3% DSPE-mPEG was designed and developed to serve as a model for selective co-delivery of hydrophilic and hydrophobic drugs to cancerous cells. The proposed formulation provided potential benefits, including pH-sensitive sustained release, smooth globular surface morphology, high entrapment efficiency (∼80% for both therapeutic agents) and small diameter (42 nm). Exposure of cancer cells to LipoNiosome-doxorubicin–curcumin has shown an excellent performance of specific cellular internalization and synergistic toxic effect (>40%; as compared to free drugs and >23% when compared to single doxorubicin delivery) against Saos-2, MG-63 and KG-1 cell lines. A new cationic formulation (zeta potential: +35.26 mV; diameter: 52.2 nm) was also designed for co-delivery of above-mentioned drugs and gene as well. Finely, we suggested a kinetic model (Korsmeyer–Peppa with R2 = 93% near cancer cells) for in vitro drug release of the co-delivery system. The presently formulated nano-based systems would provide researchers with a more obvious understanding of new LipoNiosome formulation as a successful lipid-based nano-carriers for co-delivery of doxorubicin, curcumin and other anticancer agents.
Inwardly Permeating Na Ions Generate the Voltage Dependence of Resurgent Na Current in Cerebellar Purkinje Neurons

Voltage-gated Na channels of cerebellar Purkinje neurons express an endogenous open-channel blocking protein. This blocker binds channels at positive potentials and unbinds at negative potentials, generating a resurgent Na current and permitting rapid firing. The macroscopic voltage dependence of resurgent current raises the question of whether the blocker directly senses membrane potential or whether voltage dependence is conferred indirectly. Because we previously found that inwardly permeating Na ions facilitate dissociation of the blocker, we measured voltage-clamped currents in different Na gradients to test the role of permeating ions in generating the voltage dependence of unblock. In reverse gradients, outward resurgent currents were tiny or absent, suggesting that unblock normally requires “knockoff” by Na. Inward resurgent currents at strongly negative potentials, however, were larger in reverse than in control gradients. Moreover, occupancy of the blocked state was prolonged both in reverse gradients and in control gradients with reduced Na concentrations, indicating that block is more stable when inward currents are small. Accordingly, reverse gradients shifted the voltage dependence of block, such that resurgent currents were evoked even after conditioning at negative potentials. Additionally, in control gradients, peak resurgent currents decreased linearly with driving force during the conditioning step, suggesting that the stability of block varies directly with inward Na current amplitude. Thus, the voltage dependence of blocker unbinding results almost entirely from repulsion by Na ions occupying the external pore. The lack of voltage sensitivity of the blocking protein suggests that the blocker's binding site lies outside the membrane field, in the permeation pathway.
Clinical ef fi cacy and neuroprotective effects of brimonidine in the management of glaucoma and ocular hypertension

Correspondence: Ivan Goldberg c/Eye Associates, Floor 4, 187 Macquarie Street, Sydney NSW 2000, Australia Tel +61 2 9231 1833 Fax +61 2 9232 3086 Email eyegoldberg@gmail.com Abstract: Elevated intraocular pressure (IOP) is a signifi cant risk factor for the development and progression of glaucomatous optic neuropathy, but increasingly we appreciate that non-pressure dependent factors, are key to our understanding of the pathophysiology of these neurodegenerative diseases, that target the retinal ganglion cell. As we try to expand therapy beyond IOP control, medications are being assessed for their neuroprotective abilities. Brimonidine is an effective ocular hypotensive treatment both as a fi rst and second line agent, in the management of glaucoma and ocular hypertension. Brimonidine tartrate 0.2% is generally safe and well tolerated, with its safety profi le further enhanced in the altered formulation brimonidine-Purite 0.1%. Beyond brimonidine’s pressure lowering capacity, laboratory and early clinical evidence supports its neuroprotective potential. We await validation of this in human clinical trials.
A built-in self-repair design for RAMs with 2-D redundancy

This brief presents a built-in self-repair (BISR) scheme for semiconductor memories with two-dimensional (2-D) redundancy structures, i.e., spare rows and spare columns. The BISR design is composed of a built-in self-test module and a built-in redundancy analysis (BIRA) module. The BIRA module executes the proposed RA algorithm for RAM with a 2-D redundancy structure. The BIRA module also serves as the reconfiguration unit in the normal mode. Experimental results show that a high repair rate (i.e., the ratio of the number of repaired memories to the number of defective memories) is achieved with the BISR scheme. The BISR circuit has a low area overhead-about 4.6% for an 8 K /spl times/ 64 SRAM.
Extraction of social context and application to personal multimedia exploration

Personal media collections are often viewed and managed along the social dimension, the places we spend time at and the people we see, thus tools for extracting and using this information are required. We present novel algorithms for identifying socially significant places termed social spheres unobtrusively from GPS traces of daily life, and label them as one of Home, Work, or Other, with quantitative evaluation of 9 months taken from 5 users. We extract locational co-presence of these users and formulate a novel measure of social tie strength based on frequency of interaction, and the nature of spheres it occurs within. Comparative user studies of a multimedia browser designed to demonstrate the utility of social metadata indicate the usefulness of a simple interface allowing navigation and filtering in these terms. We note the application of social context is potentially much broader than personal media management, including context-aware device behaviour, life logs, social networks, and location-aware information services.
Plastics recycling: challenges and opportunities

Plastics are inexpensive, lightweight and durable materials, which can readily be moulded into a variety of products that find use in a wide range of applications. As a consequence, the production of plastics has increased markedly over the last 60 years. However, current levels of their usage and disposal generate several environmental problems. Around 4 per cent of world oil and gas production, a non-renewable resource, is used as feedstock for plastics and a further 3–4% is expended to provide energy for their manufacture. A major portion of plastic produced each year is used to make disposable items of packaging or other short-lived products that are discarded within a year of manufacture. These two observations alone indicate that our current use of plastics is not sustainable. In addition, because of the durability of the polymers involved, substantial quantities of discarded end-of-life plastics are accumulating as debris in landfills and in natural habitats worldwide. Recycling is one of the most important actions currently available to reduce these impacts and represents one of the most dynamic areas in the plastics industry today. Recycling provides opportunities to reduce oil usage, carbon dioxide emissions and the quantities of waste requiring disposal. Here, we briefly set recycling into context against other waste-reduction strategies, namely reduction in material use through downgauging or product reuse, the use of alternative biodegradable materials and energy recovery as fuel. While plastics have been recycled since the 1970s, the quantities that are recycled vary geographically, according to plastic type and application. Recycling of packaging materials has seen rapid expansion over the last decades in a number of countries. Advances in technologies and systems for the collection, sorting and reprocessing of recyclable plastics are creating new opportunities for recycling, and with the combined actions of the public, industry and governments it may be possible to divert the majority of plastic waste from landfills to recycling over the next decades.
Deep Sequencing Reveals Potential Antigenic Variants at Low Frequencies in Influenza A Virus-Infected Humans

ABSTRACT Influenza vaccines must be frequently reformulated to account for antigenic changes in the viral envelope protein, hemagglutinin (HA). The rapid evolution of influenza virus under immune pressure is likely enhanced by the virus's genetic diversity within a host, although antigenic change has rarely been investigated on the level of individual infected humans. We used deep sequencing to characterize the between- and within-host genetic diversity of influenza viruses in a cohort of patients that included individuals who were vaccinated and then infected in the same season. We characterized influenza HA segments from the predominant circulating influenza A subtypes during the 2012-2013 (H3N2) and 2013-2014 (pandemic H1N1; H1N1pdm) flu seasons. We found that HA consensus sequences were similar in nonvaccinated and vaccinated subjects. In both groups, purifying selection was the dominant force shaping HA genetic diversity. Interestingly, viruses from multiple individuals harbored low-frequency mutations encoding amino acid substitutions in HA antigenic sites at or near the receptor-binding domain. These mutations included two substitutions in H1N1pdm viruses, G158K and N159K, which were recently found to confer escape from virus-specific antibodies. These findings raise the possibility that influenza antigenic diversity can be generated within individual human hosts but may not become fixed in the viral population even when they would be expected to have a strong fitness advantage. Understanding constraints on influenza antigenic evolution within individual hosts may elucidate potential future pathways of antigenic evolution at the population level. IMPORTANCE Influenza vaccines must be frequently reformulated due to the virus's rapid evolution rate. We know that influenza viruses exist within each infected host as a “swarm” of genetically distinct viruses, but the role of this within-host diversity in the antigenic evolution of influenza has been unclear. We characterized here the genetic and potential antigenic diversity of influenza viruses infecting humans, some of whom became infected despite recent vaccination. Influenza virus between- and within-host genetic diversity was not significantly different in nonvaccinated and vaccinated humans, suggesting that vaccine-induced immunity does not exert strong selective pressure on viruses replicating in individual people. We found low-frequency mutations, below the detection threshold of traditional surveillance methods, in nonvaccinated and vaccinated humans that were recently associated with antibody escape. Interestingly, these potential antigenic variants did not reach fixation in infected people, suggesting that other evolutionary factors may be hindering their emergence in individual humans.
Fruit and vegetable consumption and mortality in Eastern Europe: Longitudinal results from the Health, Alcohol and Psychosocial Factors in Eastern Europe study

Background It is estimated that disease burden due to low fruit and vegetable consumption is higher in Central and Eastern Europe (CEE) and the former Soviet Union (FSU) than any other parts of the world. However, no large scale studies have investigated the association between fruit and vegetable (F&V) intake and mortality in these regions yet. Design The Health, Alcohol and Psychosocial Factors in Eastern Europe (HAPIEE) study is a prospective cohort study with participants recruited from the Czech Republic, Poland and Russia. Methods Dietary data was collected using food frequency questionnaire. Mortality data was ascertained through linkage with death registers. Multivariable adjusted hazard ratios were calculated by Cox regression models. Results Among 19,333 disease-free participants at baseline, 1314 died over the mean follow-up of 7.1 years. After multivariable adjustment, we found statistically significant inverse association between cohort-specific quartiles of F&V intake and stroke mortality: the highest vs lowest quartile hazard ratio (HR) was 0.52 (95% confidence interval (CI): 0.28–0.98). For total mortality, significant interaction (p = 0.008) between F&V intake and smoking was found. The associations were statistically significant in smokers, with HR 0.70 (0.53–0.91, p for trend: 0.011) for total mortality, and 0.62 (0.40–0.97, p for trend: 0.037) for cardiovascular disease (CVD) mortality. The association was appeared to be mediated by blood pressure, and F&V intake explained a considerable proportion of the mortality differences between the Czech and Russian cohorts. Conclusions Our results suggest that increasing F&V intake may reduce CVD mortality in CEE and FSU, particularly among smokers and hypertensive individuals.
Discriminative Unsupervised Feature Learning with Convolutional Neural Networks

Current methods for training convolutional neural networks depend on large amounts of labeled samples for supervised training. In this paper we present an approach for training a convolutional neural network using only unlabeled data. We train the network to discriminate between a set of surrogate classes. Each surrogate class is formed by applying a variety of transformations to a randomly sampled 'seed' image patch. We find that this simple feature learning algorithm is surprisingly successful when applied to visual object recognition. The feature representation learned by our algorithm achieves classification results matching or outperforming the current state-of-the-art for unsupervised learning on several popular datasets (STL-10, CIFAR-10, Caltech-101).