Miracle-dz/UniFAR-FTUs huggingface dataset:
Quantitative optical measurement of mitochondrial superoxide dynamics in pulmonary artery endothelial cells

Reactive oxygen species (ROS) play a vital role in cell signaling and redox regulation, but when present in excess, lead to numerous pathologies. Detailed quantitative characterization of mitochondrial superoxide anion ( O2•-) production in fetal pulmonary artery endothelia cells (PAECs) has never been reported. The aim of this study is to assess mitochondrial O2•- production in cultured PAECs over time using a novel quantitative optical approach. The rate, the sources, and the dynamics of O2•- production were assessed using targeted metabolic modulators of the mitochondrial electron transport chain (ETC) complexes, specifically an uncoupler and inhibitors of the various ETC complexes, and inhibitors of extra-mitochondrial sources of O2•-. After stabilization, the cells were loaded with nanomolar mitochondrial-targeted hydroethidine (Mito-HE, MitoSOX) online during the experiment without washout of the residual dye. Time-lapse fluorescence microscopy was used to monitor the dynamic changes in O2•- fluorescence intensity over time in PAECs. The transient behaviors of the fluorescence time course showed exponential increases in the rate of O2•- production in the presence of the ETC uncoupler or inhibitors. The most dramatic and the fastest increase in O2•- production was observed when the cells were treated with the uncoupling agent, PCP. We also showed that only the complex IV inhibitor, KCN, attenuated the marked surge in O2•- production induced by PCP. The results showed that mitochondrial respiratory complexes I, III and IV are sources of O2•- production in PAECs, and a new observation that ROS production during uncoupling of mitochondrial respiration is mediated in part via complex IV. This novel method can be applied in other studies that examine ROS production under stress condition and during ROS-mediated injuries in vitro.
Cholesteryl ester transfer protein: at the heart of the action of lipid-modulating therapy with statins, fibrates, niacin, and cholesteryl ester transfer protein inhibitors

Subnormal plasma levels of high-density lipoprotein cholesterol (HDL-C) constitute a major cardiovascular risk factor; raising low HDL-C levels may therefore reduce the residual cardiovascular risk that frequently presents in dyslipidaemic subjects despite statin therapy. Cholesteryl ester transfer protein (CETP), a key modulator not only of the intravascular metabolism of HDL and apolipoprotein (apo) A-I but also of triglyceride (TG)-rich particles and low-density lipoprotein (LDL), mediates the transfer of cholesteryl esters from HDL to pro-atherogenic apoB-lipoproteins, with heterotransfer of TG mainly from very low-density lipoprotein to HDL. Cholesteryl ester transfer protein activity is elevated in the dyslipidaemias of metabolic disease involving insulin resistance and moderate to marked hypertriglyceridaemia, and is intimately associated with premature atherosclerosis and high cardiovascular risk. Cholesteryl ester transfer protein inhibition therefore presents a preferential target for elevation of HDL-C and reduction in atherosclerosis. This review appraises recent evidence for a central role of CETP in the action of current lipid-modulating agents with HDL-raising potential, i.e. statins, fibrates, and niacin, and compares their mechanisms of action with those of pharmacological agents under development which directly inhibit CETP. New CETP inhibitors, such as dalcetrapib and anacetrapib, are targeted to normalize HDL/apoA-I levels and anti-atherogenic activities of HDL particles. Further studies of these CETP inhibitors, in particular in long-term, large-scale outcome trials, will provide essential information on their safety and efficacy in reducing residual cardiovascular risk.
A Stringent Limit on a Drifting Proton-to-Electron Mass Ratio from Alcohol in the Early Universe

Varying Constant? Searches for time-varying fundamental constants provide a means to look beyond the standard model of particle physics. Bagdonaite et al. (p. 46, published online 13 December) set an improved limit on the possible timevariation of the proton-to-electron mass ratio by comparing the frequencies of methanol transitions observed in a galaxy at a look-back time of 7 billion years with those measured in the laboratory. The values agree within 10−7, consistent with no variation over cosmic time. The proton-to-electron mass ratio inferred from methanol lines in a distant galaxy is in accord with the laboratory value. The standard model of physics is built on the fundamental constants of nature, but it does not provide an explanation for their values, nor require their constancy over space and time. Here we set a limit on a possible cosmological variation of the proton-to-electron mass ratio μ by comparing transitions in methanol observed in the early universe with those measured in the laboratory. From radio-astronomical observations of PKS1830-211, we deduced a constraint of ∆μ/μ = (0.0 ± 1.0) × 10−7 at redshift z = 0.89, corresponding to a look-back time of 7 billion years. This is consistent with a null result.
Sense-Aaware Semantic Analysis: A Multi-Prototype Word Representation Model Using Wikipedia

Human languages are naturally ambiguous, which makes it difficult to automatically understand the semantics of text. Most vector space models (VSM) treat all occurrences of a word as the same and build a single vector to represent the meaning of a word, which fails to capture any ambiguity. We present sense-aware semantic analysis (SaSA), a multi-prototype VSM for word representation based on Wikipedia, which could account for homonymy and polysemy. The "sense-specific'' prototypes of a word are produced by clustering Wikipedia pages based on both local and global contexts of the word in Wikipedia. Experimental evaluations on semantic relatedness for both isolated words and words in sentential contexts and word sense induction demonstrate its effectiveness.
Relay Broadcast Channel With Confidential Messages

In this paper, we investigate the effects of a trusted relay node on the secrecy of the broadcast channel by considering the model of relay broadcast channel with confidential messages (RBC-CM). Inner and outer bounds on the capacity-equivocation region of the RBC-CM are provided, and the capacity results are further explained via a degraded Gaussian example, which we call the degraded Gaussian relay broadcast channel with one common and one confidential messages. Numerical results show that this trusted relay node helps to enhance the security of the Gaussian broadcast channel with one common and one confidential messages.
Enhancing the spatial resolution of presence detection in a PIR based wireless surveillance network

Pyroelectric sensors are low-cost, low-power small components commonly used only to trigger alarm in presence of humans or moving objects. However, the use of an array of pyroelectric sensors can lead to extraction of more features such as direction of movements, speed, number of people and other characteristics. In this work a low-cost pyroelectric infrared sensor based wireless network is set up to be used for tracking people motion. A novel technique is proposed to distinguish the direction of movement and the number of people passing. The approach has low computational requirements, therefore it is well-suited to limited-resources devices such as wireless nodes. Tests performed gave promising results.
Cirrus clouds and their geoengineering potential

This thesis evaluates the option of modifying cirrus clouds in order to counteract part of the anthropogenic global warming, also known as cirrus seeding. The feasibility of cirrus seeding is assessed with the general circulation model ECHAM6-HAM with coupled aerosol-cloud interactions. The warming effect of cirrus clouds on climate led part of the research community to the idea of artificially decreasing their frequency and optical thickness by seeding them with ice nucleating particles. Cirrus seeding relies on the competition between two distinct cirrus formation pathways: homogeneous nucleation of soluble aerosols and heterogeneous ice crystal nucleation with the help of solid ice nucleating particles. Seeding attempts to transform optically thicker, longer lived homogeneously nucleated cirrus clouds to thinner and shorter lived heterogeneously nucleated cirrus clouds. The cirrus seeding effectiveness depends on the correct representation of cirrus clouds in climate models. We evaluated the ECHAM6-HAM model against CALIPSO satellite data and found that the model reproduces the cirrus cloud occurrence fraction and ice water content well, but overestimates their extinction. Most importantly, we found that a large fraction of cirrus clouds formed in environments with liquid water, which cannot be modified by cirrus seeding. Moreover, modelled in situ cirrus formed by heterogenous ice nucleation on dust aerosols in most of the world, limiting the cirrus geoengineering potential. Meanwhile, homogeneous cirrus were dominant only in the tropical tropopause layer and over mountain regions. Seeding cirrus clouds with ice nucleating particles of radii below 10 μm did not lead to a significant cooling effect on climate, due to radiative warming effects of increasing cirrus cloud cover and decreasing ice crystal radius, which neutralized the cooling gained by the ice crystal number decrease. However, when seeding with larger ice nucleating particles, cirrus cloud cover, ice crystal number concentration, and ice water content decreased, due to increased ice crystal sedimentation velocity, leading to a cooling of up to 0.7◦C globally. In addition, an idealized cirrus geoengineering setup with increased ice crystal sedimentation velocities at temperatures colder than -35◦C could fully counteract the temperature increase by 1.5 x CO2 concentrations. Furthermore, seeding with ice nucleating particles larger than 10 μm could counteract up to 55% of the temperature and precipitation damage caused by a 1.5 x CO2 increase, without causing negative side effects in any of the analysed regions. Thus, cirrus geoengineering was found to be, not considering its problematic engineering details and large modelling uncertainties, an attractive method to counteract part of the anthropogenic warming.
MR imaging and T2 mapping of femoral cartilage: in vivo determination of the magic angle effect.

OBJECTIVE The purpose of this study was to perform a quantitative evaluation of the effect of static magnetic field orientation on cartilage transverse (T2) relaxation time in the intact living joint and to determine the magnitude of the magic angle effect on in vivo femoral cartilage. MATERIALS AND METHODS Quantitative T2 maps of the femoral-tibial joint were obtained in eight asymptomatic male volunteers using a 3-T magnet. Cartilage T2 profiles (T2 vs normalized distance from subchondral bone) were evaluated as a function of orientation of the radial zone of cartilage with the applied static magnetic field (B(0)). RESULTS At a normalized distance of 0.3 from bone, cartilage T2 is 8.6% longer in cartilage oriented 55 degrees to B(0) compared with cartilage oriented parallel with B(0). Greater orientation variation is observed in more superficial cartilage. At a normalized distance of 0.6, cartilage T2 is 18.3% longer. The greatest orientation effect is observed near the articular surface where T2 is 29.1% longer at 55 degrees. CONCLUSION The effect of orientation on cartilage T2 is substantially less than that predicted from prior ex vivo studies. The greatest variation in cartilage T2 is observed in the superficial 20% of cartilage. Given the small orientation effect, it is unlikely that the "magic angle effect" accounts for regional differences in cartilage signal intensity observed in clinical imaging. We hypothesize that regional differences in the degree of cartilage compression are primarily responsible for the observed regional differences in cartilage T2.
Hepatitis C virus infection

Hepatitis C virus (HCV) results in more lost years of life and more illness than any infectious disease in Ontario. [1][1] Screening individuals born between 1945 and 1965 using an anti-HCV antibody test is currently recommended in the United States. [2][2] A similar approach appears to be cost-
Long-term memory, sleep, and the spacing effect

Many studies have shown that memory is enhanced when study sessions are spaced apart rather than massed. This spacing effect has been shown to have a lasting benefit to long-term memory when the study phase session follows the encoding session by 24 hours. Using a spacing paradigm we examined the impact of sleep and spacing gaps on long-term declarative memory for Swahili–English word pairs by including four spacing delay gaps (massed, 12 hours same-day, 12 hours overnight, and 24 hours). Results showed that a 12-hour spacing gap that includes sleep promotes long-term memory retention similar to the 24-hour gap. The findings support the importance of sleep to the long-term benefit of the spacing effect.
Cross-Platform Evaluation of Commercial Real-Time SYBR Green RT-PCR Kits for Sensitive and Rapid Detection of European Bat Lyssavirus Type 1

This study evaluates the performance of five two-step SYBR Green RT-qPCR kits and five one-step SYBR Green qRT-PCR kits using real-time PCR assays. Two real-time thermocyclers showing different throughput capacities were used. The analysed performance evaluation criteria included the generation of standard curve, reaction efficiency, analytical sensitivity, intra- and interassay repeatability as well as the costs and the practicability of kits, and thermocycling times. We found that the optimised one-step PCR assays had a higher detection sensitivity than the optimised two-step assays regardless of the machine used, while no difference was detected in reaction efficiency, R 2 values, and intra- and interreproducibility between the two methods. The limit of detection at the 95% confidence level varied between 15 to 981 copies/µL and 41 to 171 for one-step kits and two-step kits, respectively. Of the ten kits tested, the most efficient kit was the Quantitect SYBR Green qRT-PCR with a limit of detection at 95% of confidence of 20 and 22 copies/µL on the thermocyclers Rotor gene Q MDx and MX3005P, respectively. The study demonstrated the pivotal influence of the thermocycler on PCR performance for the detection of rabies RNA, as well as that of the master mixes.
Observation of linear systems with unknown inputs via high-order sliding-modes

A high-order sliding-mode observer is designed for linear time invariant systems with single output and unknown bounded single input. It provides for the global observation of the state and the output under sufficient and necessary conditions of strong observability or strong detectability. The observation is finite-time-convergent and exact in the strong observability case. The accuracy of the proposed observation and identification schemes is estimated via the sampling step or magnitude of deterministic noises. The results are extended to the multi-input multi-output case.
Collaborating Globally: Culture and Organizational Computer-Mediated Communications

Culture shapes interpersonal communication. However, little is known about how culture interacts with computer-mediated communication (CMC) tools in a business context. We present a large-scale empirical study of cultural differences in computer mediated social interactions in a global company. Our dataset includes 9,000 volunteer users and more than 20 million records of their email and Instant Messaging conversations. We compared social network characteristics, preferences for CMC tools, and expression of sentiment across employees working in seven countries. Significant differences emerged and the patterns are consistent with the inherent cultural characteristics as suggested by cultural theories. In addition, we uncover the complex manner in which culture interacts with preference and use of different communication mediums. The existence of pervasive and complex cultural differences, points to the need to understand and account for such differences in designing cross-cultural collaborative systems.
A Bivariate Genome-Wide Approach to Metabolic Syndrome

OBJECTIVE The metabolic syndrome (MetS) is defined as concomitant disorders of lipid and glucose metabolism, central obesity, and high blood pressure, with an increased risk of type 2 diabetes and cardiovascular disease. This study tests whether common genetic variants with pleiotropic effects account for some of the correlated architecture among five metabolic phenotypes that define MetS. RESEARCH DESIGN AND METHODS Seven studies of the STAMPEED consortium, comprising 22,161 participants of European ancestry, underwent genome-wide association analyses of metabolic traits using a panel of ∼2.5 million imputed single nucleotide polymorphisms (SNPs). Phenotypes were defined by the National Cholesterol Education Program (NCEP) criteria for MetS in pairwise combinations. Individuals exceeding the NCEP thresholds for both traits of a pair were considered affected. RESULTS Twenty-nine common variants were associated with MetS or a pair of traits. Variants in the genes LPL, CETP, APOA5 (and its cluster), GCKR (and its cluster), LIPC, TRIB1, LOC100128354/MTNR1B, ABCB11, and LOC100129150 were further tested for their association with individual qualitative and quantitative traits. None of the 16 top SNPs (one per gene) associated simultaneously with more than two individual traits. Of them 11 variants showed nominal associations with MetS per se. The effects of 16 top SNPs on the quantitative traits were relatively small, together explaining from ∼9% of the variance in triglycerides, 5.8% of high-density lipoprotein cholesterol, 3.6% of fasting glucose, and 1.4% of systolic blood pressure. CONCLUSIONS Qualitative and quantitative pleiotropic tests on pairs of traits indicate that a small portion of the covariation in these traits can be explained by the reported common genetic variants.
βη-complete models for System F

We show that Friedman's proof of the existence of non-trivial βη-complete models of λ→ can be extended to system F. We isolate a set of conditions that are sufficient to ensure βη-completeness for a model of F (and α-completeness at the level of types), and we discuss which class of models we get. In particular, the model introduced in Barbanera and Berardi (1997), having as polymorphic maps exactly all possible Scott continuous maps, is βη-complete, and is hence the first known complete non-syntactic model of F. In order to have a suitable framework in which to express the conditions and develop the proof, we also introduce the very natural notion of ‘polymax models’ of System F.
Immunonutrition and surgical practice

Immunonutrition generally refers to the effect of the provision of specific nutrients on the immune system. These nutrients typically have immunoenhancing properties, and recent advances in nutrition support involve studies designed to exploit the desirable biological properties of these nutrients. The term immunonutrition strictly implies that we are focusing on the effect of certain nutrients on aspects of the immune system. However, in reality immunonutrition also refers to studies that not only examine the function of lymphocytes and leucocytes, but which also study the influence of key nutrients on the acute-phase response, the inflammatory response and on gastrointestinal structure and function. The interest, therefore, is on the impact of immunonutrition on all aspects of host defence mechanisms in response to a catabolic stress. Major surgery evokes an acute-phase response, a transient immunosuppression and alterations in gastrointestinal function. Normal function is usually restored after a few days; however, in a subgroup of patients homeostasis may be lost and development of the systemic inflammatory response syndrome (SIRS) ensues. Results of recent clinical trials suggest that provision of immunomodulatory nutrients, including glutamine, arginine, n-3 polyunsaturated fatty acids and dietary nucleotides, may promote restoration of normal tissue function post-operatively and prevent the occurrence of SIRS.
Systems approaches and algorithms for discovery of combinatorial therapies

Effective therapy of complex diseases requires control of highly nonlinear complex networks that remain incompletely characterized. In particular, drug intervention can be seen as control of cellular network activity. Identification of control parameters presents an extreme challenge due to the combinatorial explosion of control possibilities in combination therapy and to the incomplete knowledge of the systems biology of cells. In this review paper, we describe the main current and proposed approaches to the design of combinatorial therapies, including the heuristic methods used now by clinicians and alternative approaches suggested recently by several authors. New approaches for designing combinations arising from systems biology are described. We discuss in special detail the design of algorithms that identify optimal control parameters in cellular networks based on a quantitative characterization of control landscapes, maximizing utilization of incomplete knowledge of the state and structure of intracellular networks. The use of new technology for high‐throughput measurements is key to these new approaches to combination therapy and essential for the characterization of control landscapes and implementation of the algorithms. Combinatorial optimization in medical therapy is also compared with the combinatorial optimization of engineering and materials science and similarities and differences are delineated. Copyright © 2009 John Wiley & Sons, Inc.
On the Capacity of Noncoherent Network Coding

We consider the problem of multicasting information from a source to a set of receivers over a network where intermediate network nodes perform randomized linear network coding operations on the source packets. We propose a channel model for the noncoherent network coding introduced by Koetter and Kschischang in , that captures the essence of such a network operation, and calculate the capacity as a function of network parameters. We prove that use of subspace coding is optimal, and show that, in some cases, the capacity-achieving distribution uses subspaces of several dimensions, where the employed dimensions depend on the packet length. This model and the results also allow us to give guidelines on when subspace coding is beneficial for the proposed model and by how much, in comparison to a coding vector approach, from a capacity viewpoint. We extend our results to the case of multiple source multicast that creates a virtual multiple access channel.