The cardiovascular interaction between caffeine and nicotine in humans

In a placebo-controlled, double-blind randomized design, we investigated the cardiovascular interaction between caffeine (250 mg intravenously) and nicotine (4 mg chewing gum) in 10 healthy volunteers, both under baseline conditions and during physical and mental stress (standing up and mental arithmetic). Caffeine alone induced a significant increase in blood pressure associated with a decrease in heart rate, whereas nicotine alone increased both blood pressure and heart rate. The combination of caffeine and nicotine increased systolic and diastolic blood pressure by 10.8 +/- 2.0 and 12.4 +/- 1.9 mm Hg, respectively. This pressor response did not differ significantly from the calculated additive effects of caffeine and nicotine on blood pressure, measuring 12.9 +/- 2.0 and 14.2 +/- 2.1 mm Hg, respectively. Heart rate and forearm blood flow also showed a similar response when the combination of caffeine and nicotine was compared with the calculated sum. During physical stress (standing up), blood pressure, heart rate, and plasma catecholamines increased in the placebo test. The pressor response to standing up was less pronounced after the combination of caffeine and nicotine compared with the sum of the separate effects (combination versus sum: delta diastolic blood pressure, 24.7 +/- 1.9 versus 35.2 +/- 2.6 mm Hg [p < 0.01]; delta mean arterial pressure, 22.1 +/- 2.0 mm Hg versus 28.6 +/- 1.6 mm Hg [p < 0.05]). The plasma catecholamine response did not differ between the combination and the sum of both drugs. During mental arithmetic, blood pressure, heart rate, and forearm blood flow increased in the placebo test. The forearm vasodilator response to mental stress was attenuated by the combination of caffeine and nicotine compared with the sum of both drugs (combination versus sum: delta forearm blood flow, -0.1 +/- 0.3 versus 1.4 +/- 0.5 ml/100 ml/min [p < 0.05]). We conclude that the combined administration of caffeine and nicotine shows additive effects on cardiovascular parameters during baseline conditions but less than additive effects during sympathoadrenal stimulation.     

Social comparison and affiliation under threat: Going beyond the affiliate-choice paradigm.

Examined the emotional similarity hypothesis, a derivation from social comparison theory, which predicts that increasing fear should lead to greater affiliation with someone who is awaiting the same threat (and who therefore is of relatively similar emotional status) relative to someone who has already experienced the threat (and who therefore is of relatively dissimilar emotional status). Results failed to support the emotional similarity hypothesis and in so doing challenged the importance of emotional comparison as a determinant of verbal affiliation under threat. Cognitive clarity concerns instead seemed to account better for the observed effects on verbal affiliation. Supplementary analyses of nonverbal affiliation (facial glances) likewise ran counter to an emotional similarity prediction. Effects of affiliation on anxiety were also examined. Previous conclusions regarding the pattern and causes of affiliation under threat that have relied on the affiliate-choice paradigm are considered. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Polycyclic Aromatic Hydrocarbons Activate the Aryl Hydrocarbon Receptor and the Constitutive Androstane Receptor to Regulate Xenobiotic Metabolism in Human Liver Cells

Polycyclic aromatic hydrocarbons (PAHs) are environmental pollutants produced by incomplete combustion of organic matter. They induce their own metabolism by upregulating xenobiotic-metabolizing enzymes such as cytochrome P450 monooxygenase 1A1 (CYP1A1) by activating the aryl hydrocarbon receptor (AHR). However, previous studies showed that individual PAHs may also interact with the constitutive androstane receptor (CAR). Here, we studied ten PAHs, different in carcinogenicity classification, for their potential to activate AHR- and CAR-dependent luciferase reporter genes in human liver cells. The majority of investigated PAHs activated AHR, while non-carcinogenic PAHs tended to activate CAR. We further characterized gene expression, protein abundancies and activities of the AHR targets CYP1A1 and 1A2, and the CAR target CYP2B6 in human HepaRG hepatoma cells. Enzyme induction patterns strongly resembled the profiles obtained at the receptor level, with AHR-activating PAHs inducing CYP1A1/1A2 and CAR-activating PAHs inducing CYP2B6. In summary, this study provides evidence that beside well-known activation of AHR, some PAHs also activate CAR, followed by subsequent expression of respective target genes. Furthermore, we found that an increased PAH ring number is associated with AHR activation as well as the induction of DNA double-strand breaks, whereas smaller PAHs activated CAR but showed no DNA-damaging potential.     

Structural Basis for The Recognition of Deaminated Nucleobases by An Archaeal DNA Polymerase

With increasing temperature, nucleobases in DNA become increasingly damaged by hydrolysis of exocyclic amines. The most prominent damage includes the conversion of cytosine to uracil and adenine to hypoxanthine. These damages are mutagenic and put the integrity of the genome at risk if not repaired appropriately. Several archaea live at elevated temperatures and thus, are exposed to a higher risk of deamination. Earlier studies have shown that DNA polymerases of archaea have the property of sensing deaminated nucleobases in the DNA template and thereby stalling the DNA synthesis during DNA replication providing another layer of DNA damage recognition and repair. However, the structural basis of uracil and hypoxanthine sensing by archaeal B-family DNA polymerases is sparse. Here we report on three new crystal structures of the archaeal B-family DNA polymerase from Thermococcus kodakarensis (KOD) DNA polymerase in complex with primer and template strands that have extended single stranded DNA template 5’-overhangs. These overhangs contain either the canonical nucleobases as well as uracil or hypoxanthine, respectively, and provide unprecedented structural insights into their recognition by archaeal B-family DNA polymerases.     

A novel feature-based approach to characterize algorithm performance for the traveling salesperson problem

Meta-heuristics are frequently used to tackle NP-hard combinatorial optimization problems. With this paper we contribute to the understanding of the success of 2-opt based local search algorithms for solving the traveling salesperson problem (TSP). Although 2-opt is widely used in practice, it is hard to understand its success from a theoretical perspective. We take a statistical approach and examine the features of TSP instances that make the problem either hard or easy to solve. As a measure of problem difficulty for 2-opt we use the approximation ratio that it achieves on a given instance. Our investigations point out important features that make TSP instances hard or easy to be approximated by 2-opt.     

Non-encapsulated thermo-liquid crystals for digital particle tracking thermography/velocimetry in microfluidics

The ever accelerating state of technology has powered an increasing interest in heat transfer solutions and process engineering innovations in the microfluidics domain. In order to carry out such developments, reliable heat transfer diagnostic techniques are necessary. Thermo-liquid crystal (TLC) thermography, in combination with particle image velocimetry, has been a widely accepted and commonly used technique for the simultaneous measurement and characterization of temperature and velocity fields in macroscopic fluid flows for several decades. However, low seeding density, volume illumination, and low TLC particle image quality at high magnifications present unsurpassed challenges to its application to three-dimensional flows with microscopic dimensions. In this work, a measurement technique to evaluate the color response of individual non-encapsulated TLC particles is presented. A Shirasu porous glass membrane emulsification approach was used to produce the non-encapsulated TLC particles with a narrow size distribution and a multi-variable calibration procedure, making use of all three RGB and HSI color components, as well as the proper orthogonally decomposed RGB components, was used to achieve unprecedented low uncertainty levels in the temperature estimation of individual particles, opening the door to simultaneous temperature and velocity tracking using 3D velocimetry techniques.     

Compositional CSP Traces Refinement Checking

Compositional verification using assume-guarantee reasoning has recently seen an uprise due to the introduction of automatic techniques for learning assumptions. In this paper, we transfer this technique to a setting with CSP as modelling and property specification language, and present an approach to compositional traces refinement checking. The approach has been implemented using the CSP model checker FDR as teacher during learning. The implementation shows that the compositional approach can both drastically outperform as well as underperform FDR's performance, depending on the example at hand.