Quantum tomography of electrical currents.

In quantum nanoelectronics, time-dependent electrical currents are built from few elementary excitations emitted with well-defined wavefunctions. However, despite the realization of sources generating quantized numbers of excitations, and despite the development of the theoretical framework of time-dependent quantum electronics, extracting electron and hole wavefunctions from electrical currents has so far remained out of reach, both at the theoretical and experimental levels. In this work, we demonstrate a quantum tomography protocol which extracts the generated electron and hole wavefunctions and their emission probabilities from any electrical current. It combines two-particle interferometry with signal processing. Using our technique, we extract the wavefunctions generated by trains of Lorentzian pulses carrying one or two electrons. By demonstrating the synthesis and complete characterization of electronic wavefunctions in conductors, this work offers perspectives for quantum information processing with electrical currents and for investigating basic quantum physics in many-body systems.

Gasoline cars produce more carbonaceous particulate matter than modern filter-equipped diesel cars.

Carbonaceous particulate matter (PM), comprising black carbon (BC), primary organic aerosol (POA) and secondary organic aerosol (SOA, from atmospheric aging of precursors), is a highly toxic vehicle exhaust component. Therefore, understanding vehicle pollution requires knowledge of both primary emissions, and how these emissions age in the atmosphere. We provide a systematic examination of carbonaceous PM emissions and parameterisation of SOA formation from modern diesel and gasoline cars at different temperatures (22, -7 °C) during controlled laboratory experiments. Carbonaceous PM emission and SOA formation is markedly higher from gasoline than diesel particle filter (DPF) and catalyst-equipped diesel cars, more so at -7 °C, contrasting with nitrogen oxides (NOX). Higher SOA formation from gasoline cars and primary emission reductions for diesels implies gasoline cars will increasingly dominate vehicular total carbonaceous PM, though older non-DPF-equipped diesels will continue to dominate the primary fraction for some time. Supported by state-of-the-art source apportionment of ambient fossil fuel derived PM, our results show that whether gasoline or diesel cars are more polluting depends on the pollutant in question, i.e. that diesel cars are not necessarily worse polluters than gasoline cars.

Secondary organic aerosol origin in an urban environment: influence of biogenic and fuel combustion precursors.

Source contributions of organic aerosol (OA) are still not fully understood, especially in terms of quantitative distinction between secondary OA formed from anthropogenic precursors vs. that formed from natural precursors. In order to investigate the OA origin, a field campaign was carried out in Barcelona in summer 2013, including two periods characterized by low and high traffic conditions. Volatile organic compound (VOC) concentrations were higher during the second period, especially aromatic hydrocarbons related to traffic emissions, which showed a marked daily cycle peaking during traffic rush hours, similarly to black carbon (BC) concentrations. Biogenic VOC (BVOC) concentrations showed only minor changes from the low to the high traffic period, and their intra-day variability was related to temperature and solar radiation cycles, although a decrease was observed for monoterpenes during the day. The organic carbon (OC) concentrations increased from the first to the second period, and the fraction of non-fossil OC as determined by (14)C analysis increased from 43% to 54% of the total OC. The combination of (14)C analysis and Aerosol Chemical Speciation Monitor (ACSM) OA source apportionment showed that the fossil OC was mainly secondary (>70%) except for the last sample, when the fossil secondary OC only represented 51% of the total fossil OC. The fraction of non-fossil secondary OC increased from 37% of total secondary OC for the first sample to 60% for the last sample. This enhanced formation of non-fossil secondary OA (SOA) could be attributed to the reaction of BVOC precursors with NOx emitted from road traffic (or from its nocturnal derivative nitrate that enhances night-time semi-volatile oxygenated OA (SV-OOA)), since NO2 concentrations increased from 19 to 42 µg m(-3) from the first to the last sample.

White-to-brite conversion in human adipocytes promotes metabolic reprogramming towards fatty acid anabolic and catabolic pathways.

OBJECTIVE: Fat depots with thermogenic activity have been identified in humans. In mice, the appearance of thermogenic adipocytes within white adipose depots (so-called brown-in-white i.e., brite or beige adipocytes) protects from obesity and insulin resistance. Brite adipocytes may originate from direct conversion of white adipocytes. The purpose of this work was to characterize the metabolism of human brite adipocytes. METHODS: Human multipotent adipose-derived stem cells were differentiated into white adipocytes and then treated with peroxisome proliferator-activated receptor (PPAR)γ or PPARα agonists between day 14 and day 18. Gene expression profiling was determined using DNA microarrays and RT-qPCR. Variations of mRNA levels were confirmed in differentiated human preadipocytes from primary cultures. Fatty acid and glucose metabolism was investigated using radiolabelled tracers, Western blot analyses and assessment of oxygen consumption. Pyruvate dehydrogenase kinase 4 (PDK4) knockdown was achieved using siRNA. In vivo, wild type and PPARα-null mice were treated with a ß3-adrenergic receptor agonist (CL316,243) to induce appearance of brite adipocytes in white fat depot. Determination of mRNA and protein levels was performed on inguinal white adipose tissue. RESULTS: PPAR agonists promote a conversion of white adipocytes into cells displaying a brite molecular pattern. This conversion is associated with transcriptional changes leading to major metabolic adaptations. Fatty acid anabolism i.e., fatty acid esterification into triglycerides, and catabolism i.e., lipolysis and fatty acid oxidation, are increased. Glucose utilization is redirected from oxidation towards glycerol-3-phophate production for triglyceride synthesis. This metabolic shift is dependent on the activation of PDK4 through inactivation of the pyruvate dehydrogenase complex. In vivo, PDK4 expression is markedly induced in wild-type mice in response to CL316,243, while this increase is blunted in PPARα-null mice displaying an impaired britening response. CONCLUSIONS: Conversion of human white fat cells into brite adipocytes results in a major metabolic reprogramming inducing fatty acid anabolic and catabolic pathways. PDK4 redirects glucose from oxidation towards triglyceride synthesis and favors the use of fatty acids as energy source for uncoupling mitochondria.

Anxiolytic activity and active principles of Piper amalago (Piperaceae), a medicinal plant used by the Q'eqchi' Maya to treat susto, a culture-bound illness.

ETHNOPHARMACOLOGICAL RELEVANCE: The medicinal plant, Piper amalago L. (Piperaceae), is used traditionally by Q'eqchi' Maya healers for the treatment of "susto" a culture-bound syndrome. Previous research suggests that susto symptoms may be a manifestation of anxiety. The objectives were to characterize the effect of ethanolic extract of P. amalago in behavioral assays of anxiety at doses representative of traditional use and to isolate active principles. MATERIALS AND METHODS: Rats treated orally with low dose ethanolic extracts of P. amalago leaves (8-75mg/kg) were tested in several behavioral paradigms including the elevated plus maze (EPM), social interaction (SI), and conditioned emotional response (CER) tests, and compared to diazepam, a positive control. The active anxiolytic principle was isolated by bioassay guided isolation using an in vitro GABAA competitive binding assay. RESULTS: Extracts had significant anxiolytic activity in all behavioral tests, with the strongest activity in the SI and the CER paradigms. In an in vitro GABAA competitive binding assay, a 66.5µg/mL concentration of P. amalago ethanol extract displaced 50% of the GABAA-BZD receptor ligand [(3)H]-Flunitrazepam. Bioassay-guided fractionation identified a furofuran lignan, a molecule with structural similarity to yangambin, with high affinity for the GABAA-BZD receptor as the principle bioactive. CONCLUSION: The results suggest that the ethnobotanical use of this plant may have a pharmacological basis in its anxiolytic activity, as demonstrated in animal behaviour tests.

Adaptive preconditioning in neurological diseases - therapeutic insights from proteostatic perturbations.

In neurological disorders, both acute and chronic neural stress can disrupt cellular proteostasis, resulting in the generation of pathological protein. However in most cases, neurons adapt to these proteostatic perturbations by activating a range of cellular protective and repair responses, thus maintaining cell function. These interconnected adaptive mechanisms comprise a 'proteostasis network' and include the unfolded protein response, the ubiquitin proteasome system and autophagy. Interestingly, several recent studies have shown that these adaptive responses can be stimulated by preconditioning treatments, which confer resistance to a subsequent toxic challenge - the phenomenon known as hormesis. In this review we discuss the impact of adaptive stress responses stimulated in diverse human neuropathologies including Parkinson׳s disease, Wolfram syndrome, brain ischemia, and brain cancer. Further, we examine how these responses and the molecular pathways they recruit might be exploited for therapeutic gain. This article is part of a Special Issue entitled SI:ER stress.

Measurements of VOC/SVOC emission factors from burning incenses in an environmental test chamber: influence of temperature, relative humidity, and air exchange rate.

This study investigates the influence of three environmental indoor parameters (i.e., temperature, relative humidity, and air exchange rate) on the emission of 13 volatile organic compounds (VOCs) and semi-volatile organic compounds (SVOCs) during incense burning. Experiments have been carried out using an environmental test chamber. Statistical results from a classical two-level full factorial design highlight the predominant effect of ventilation on emission factors. The higher the ventilation, the higher the emission factor. Moreover, thanks to these results, an estimation of the concentration range for the compounds under study can be calculated and allows a quick look of indoor pollution induced by incense combustion. Carcinogenic substances (i.e., benzene, benzo(a)pyrene, and formaldehyde) produced from the incense combustion would be predicted in typical living indoors conditions to reach instantaneous concentration levels close to or higher than air quality exposure threshold values.

French intensive training course in laparoscopic surgery (HUGOFirst) on live porcine models: Validation of a performance assessment scale and residents' satisfaction in a prospective study.

INTRODUCTION: Simulation as a method for practical teaching of surgical residents requires objective evaluation in order to measure the student's acquisition of knowledge and skills. The objectives of this article are to publish our evaluation and validation grids and also the measure of student satisfaction. METHOD: A teaching platform based on practical exercises with a porcine model was created in 2009 at seven French University Hospitals. Three times a year, 31 Diplôme d'Études Spécialisées Complémentaires (DESC) surgical residents underwent timed assessment of the performance of five surgical tasks: trocar insertion (trocars) testing the convergence of instruments (convergence), intra-corporeal knot tying (knots), running of the small intestine to find a lesion (exploration), and performance of a running suture closure of the peritoneum (closure). Two experts evaluated performances prospectively on grid score sheets specifically designed and validated for these exercises. We measured time, scores on a rating scale, and the interest and satisfaction of the residents. RESULTS: Data for 31 residents between May 2011 and March 2012 were analyzed. Rating scales were statistically validated and correlated (Kappa correlation coefficient K>0.69) for each task. The performance times of the most experienced residents decreased significantly for all tasks except for small bowel exploration (P=0.2). After four sessions, times were significantly improved with better quality (fewer errors and higher average scores [>88%]), regardless of the residents' experience. Of the participants, 92% were satisfied, 86% thought that the sessions improved their technical skills and 74% thought it had a favorable impact on their clinical practice. CONCLUSION: This study shows that the performance of surgical techniques can be improved through simulation, that HUFEG grids are valid, and that this teaching program is popular with surgical residents.

Normalization of Reverse Transcription Quantitative PCR Data During Ageing in Distinct Cerebral Structures.

Reverse transcription quantitative-polymerase chain reaction (RT-qPCR) has become a routine method in many laboratories. Normalization of data from experimental conditions is critical for data processing and is usually achieved by the use of a single reference gene. Nevertheless, as pointed by the Minimum Information for Publication of Quantitative Real-Time PCR Experiments (MIQE) guidelines, several reference genes should be used for reliable normalization. Ageing is a physiological process that results in a decline of many expressed genes. Reliable normalization of RT-qPCR data becomes crucial when studying ageing. Here, we propose a RT-qPCR study from four mouse brain regions (cortex, hippocampus, striatum and cerebellum) at different ages (from 8 weeks to 22 months) in which we studied the expression of nine commonly used reference genes. With the use of two different algorithms, we found that all brain structures need at least two genes for a good normalization step. We propose specific pairs of gene for efficient data normalization in the four brain regions studied. These results underline the importance of reliable reference genes for specific brain regions in ageing.

Combustion Processes as a Source of High Levels of Indoor Hydroxyl Radicals through the Photolysis of Nitrous Acid.

Hydroxyl radicals (OH) are known to control the oxidative capacity of the atmosphere but their influence on reactivity within indoor environments is believed to be of little importance. Atmospheric direct sources of OH include the photolysis of ozone and nitrous acid (HONO) and the ozonolysis of alkenes. It has been argued that the ultraviolet light fraction of the solar spectrum is largely attenuated within indoor environments, thus, limiting the extent of photolytic OH sources. Conversely, the ozonolysis of alkenes has been suggested as the main pathway of OH formation within indoor settings. According to this hypothesis the indoor OH radical concentrations span in the range of only 10(4) to 10(5) cm(-3). However, recent direct OH radical measurements within a school classroom yielded OH radical peak values at moderate light intensity measured at evenings of 1.8 × 10(6) cm(-3) that were attributed to the photolysis of HONO. In this work, we report results from chamber experiments irradiated with varying light intensities in order to mimic realistic indoor lighting conditions. The exhaust of a burning candle was introduced in the chamber as a typical indoor source causing a sharp peak of HONO, but also of nitrogen oxides (NOx). The photolysis of HONO yields peak OH concentration values, that for the range of indoors lightning conditions were estimated in the range 5.7 ×· 10(6) to 1.6 × 10(7) cm(-3). Excellent agreement exists between OH levels determined by a chemical clock and those calculated by a simple PSS model. These findings suggest that significant OH reactivity takes place at our dwellings and the consequences of this reactivity-that is, formation of secondary oxidants-ought to be studied hereafter.

Molecular pathogenesis of alpha-1-antitrypsin deficiency.

Alpha-1 antitrypsin (α1-AT) is the most abundant circulating protease inhibitor. The common severe Z allele of α1-AT (Glu342Lys) causes the protein to form ordered polymers that are retained within the endoplasmic reticulum of hepatocytes. These polymers form the periodic acid-Schiff positive inclusions that are associated with cirrhosis. The lack of circulating α1-AT predisposes the Z α1-AT homozygote to early onset emphysema. We review here the molecular basis of α1-AT deficiency and show how understanding the liver disease provides new insights in the pathobiology of the associated emphysema. The mechanism of α1-AT deficiency provides a paradigm for a wider group of conditions that we have termed the serpinopathies. We also examine the strategies that are being pursued to develop novel therapies for α1-AT deficiency. This review considers our understanding of the pathobiology of α1-AT deficiency and then illustrate the therapeutic possibilities that can ensue once we understand basic mechanisms of disease.

Real-time decoherence of Landau and Levitov quasiparticles in quantum Hall edge channels.

Quantum Hall edge channels at integer filling factor provide a unique test bench to understand the decoherence and relaxation of single-electron excitations in a ballistic quantum conductor. In this Letter, we obtain a full visualization of the decoherence scenario of energy (Landau)- and time (Levitov)-resolved single-electron excitations at filling factor ν = 2. We show that the Landau excitation exhibits a fast relaxation followed by spin-charge separation whereas the Levitov excitation only experiences spin-charge separation. We finally suggest to use Hong-Ou-Mandel-type experiments to probe specific signatures of these different scenarios.

Two-stroke scooters are a dominant source of air pollution in many cities.

Fossil fuel-powered vehicles emit significant particulate matter, for example, black carbon and primary organic aerosol, and produce secondary organic aerosol. Here we quantify secondary organic aerosol production from two-stroke scooters. Cars and trucks, particularly diesel vehicles, are thought to be the main vehicular pollution sources. This needs re-thinking, as we show that elevated particulate matter levels can be a consequence of 'asymmetric pollution' from two-stroke scooters, vehicles that constitute a small fraction of the fleet, but can dominate urban vehicular pollution through organic aerosol and aromatic emission factors up to thousands of times higher than from other vehicle classes. Further, we demonstrate that oxidation processes producing secondary organic aerosol from vehicle exhaust also form potentially toxic 'reactive oxygen species'.

Emission characteristics of air pollutants from incense and candle burning in indoor atmospheres.

Volatile organic compounds (VOCs) and particles emitted by incense sticks and candles combustion in an experimental room have been monitored on-line and continuously with a high time resolution using a state-of-the-art high sensitivity-proton transfer reaction-mass spectrometer (HS-PTR-MS) and a condensation particle counter (CPC), respectively. The VOC concentration-time profiles, i.e., an increase up to a maximum concentration immediately after the burning period followed by a decrease which returns to the initial concentration levels, were strongly influenced by the ventilation and surface interactions. The obtained kinetic data set allows establishing a qualitative correlation between the elimination rate constants of VOCs and their physicochemical properties such as vapor pressure and molecular weight. The emission of particles increased dramatically during the combustion, up to 9.1(±0.2) × 10(4) and 22.0(±0.2) × 10(4) part cm(-3) for incenses and candles, respectively. The performed kinetic measurements highlight the temporal evolution of the exposure level and reveal the importance of ventilation and deposition to remove the particles in a few hours in indoor environments.

Parastomal hernia.

Despite advances in surgery including new prosthetic materials and the advent of laparoscopy, the treatment of parastomal hernias remains a challenge for the surgeon. This is mainly due to the very high recurrence rate. Adequate management requires preoperative multidisciplinary consultation to offer the most appropriate surgical solution to each patient. We propose a review of current knowledge about this complication.

The impact of obesity on secretion of adiponectin multimeric isoforms differs in visceral and subcutaneous adipose tissue.

OBJECTIVE: Hypoadiponectinemia observed in obesity is associated with insulin resistance, diabetes and atherosclerosis. The aim of the present study was to investigate secretion of adiponectin and its multimeric isoforms by explants derived from subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) in obese and non-obese subjects. DESIGN: Paired samples of SAT and VAT and blood samples were obtained from 23 subjects (10 non-obese and 13 obese) undergoing elective abdominal surgery. Total adiponectin quantities and adiponectin isoforms were measured in conditioned media of explants derived from SAT and VAT using enzyme-linked immunosorbent assay and non-denaturing western blot, respectively. RESULTS: Total adiponectin plasma levels were lower in obese than in non-obese subjects (P<0.05). Secretion of total adiponectin in adipose tissue (AT) explants was lower in obese than in non-obese subjects in SAT (P<0.05) but not in VAT. In both, SAT and VAT, the most abundant isoform released into conditioned media was the high-molecular weight (HMW) form. Its relative proportion in relation to total adiponectin was higher in conditioned media of explants from both fat depots when compared with plasma (P<0.001). The proportion of secreted HMW vs total adiponectin was higher in VAT than in SAT explants in the group of non-obese individuals (49.3±3.1% in VAT vs 40.6±2.8% in SAT; P<0.01), whereas no difference between the two depots was found in obese subjects (46.2±3.0 % in VAT vs 46.0±2.4 % in SAT). CONCLUSION: Obesity is associated with the decrease of total adiponectin secretion in SAT. The profile of adiponectin isoforms secreted by SAT and VAT explants differs from that in plasma. Secretion of total adiponectin and HMW isoform of adiponectin are different in obese and non-obese subjects in relation to AT depot.

Macrophage gene expression is related to obesity and the metabolic syndrome in human subcutaneous fat as well as in visceral fat.

AIMS/HYPOTHESIS: Our goal was to identify a set of human adipose tissue macrophage (ATM)-specific markers and investigate whether their gene expression in subcutaneous adipose tissue (SAT) as well as in visceral adipose tissue (VAT) is related to obesity and to the occurrence of the metabolic syndrome. METHODS: ATM-specific markers were identified by DNA microarray analysis of adipose tissue cell types isolated from SAT of lean and obese individuals. We then analysed gene expression of these markers by reverse transcription quantitative PCR in paired samples of SAT and VAT from 53 women stratified into four groups (lean, overweight, obese and obese with the metabolic syndrome). Anthropometric measurements, euglycaemic-hyperinsulinaemic clamp, blood analysis and computed tomography scans were performed. RESULTS: A panel of 24 genes was selected as ATM-specific markers based on overexpression in ATM compared with other adipose tissue cell types. In SAT and VAT, gene expression of ATM markers was lowest in lean and highest in the metabolic syndrome group. mRNA levels in the two fat depots were negatively correlated with glucose disposal rate and positively associated with indices of adiposity and the metabolic syndrome. CONCLUSIONS/INTERPRETATION: In humans, expression of ATM-specific genes increases with the degree of adiposity and correlates with markers of insulin resistance and the metabolic syndrome to a similar degree in SAT and in VAT.

Light induced multiphase chemistry of gas-phase ozone on aqueous pyruvic and oxalic acids.

In this study for the first time it has been shown that pyruvic acid can affect the atmospheric multiphase reactions of ozone with oxalic acid due to its properties as a photosensitizer. To this end, the photochemical batch multiphase reactions of a mixture of pyruvic acid/oxalic acid (PA/OA) and gas-phase ozone under simulated sunlight were studied as a function of time using high pressure liquid chromatography equipped with a UV detector (HPLC-UV) and electrospray ionization mass spectrometry (ESI-MS) to investigate product formation. Following the simultaneous ozone and light irradiation the first peak for pyruvic and oxalic acids (retention time = 3.68 min) decreased to 67% of the initial intensity after a 12 h reaction while a broad and not well defined peak appeared at longer retention times. After prolonged exposure times this broad peak shifted to shorter retention times: from 14 min at 2 h reaction to 8 min at 12 h. The HPLC-UV analysis of the reaction mixture simultaneously exposed to ozone and irradiated by simulated sunlight for 6-12 h revealed the presence of high weight molecular mass products and formation at longer times of highly non-polar products. The results obtained from ESI-MS have clearly demonstrated that the distribution of high molecular weight products is consistent with an oligomer system. No evidence of oligomer formation was found after the sample (PA/OA) was exposed only to either ozone or irradiated with UV/Vis light using the same instrumental conditions.

Increased exposure to statins in patients developing chronic muscle diseases: a 2-year retrospective study.

OBJECTIVE: Case reports have suggested that lipid-lowering drugs (LLDs), especially statins, could induce or reveal chronic muscle diseases. We conducted a study to evaluate the association between chronic muscle diseases and prior exposure to LLDs. METHOD: This was a retrospective study of chronic primary muscle disease cases newly diagnosed at the Toulouse University Hospitals between January 2003 and December 2004 among patients living in the Midi-Pyrénées area, France. All patients remained symptomatic for more than 1 year after drug withdrawal, or required drugs for inflammatory myopathy. Data on the patient's exposure to LLDs and to other drugs were compared with that of matched controls (5/1) selected through the Midi-Pyrénées Health Insurance System database. RESULTS: A total of 37 patients were included in the study. Of those, 21 (56.8%) suffered from dermatomyositis (DM) or polymyositis (PM), 12 (32.4%) from genetic myopathy, and 4 (10.8%) from an unclassified disease. The prevalence of exposure to statins was 40.5% in patients and 20% in controls (odds ratio (OR) 2.73, 95% confidence interval (CI) 1.21-6.14; p<0.01). There was a significant positive interaction between statins and proton pump inhibitors exposure (weighted OR 3.3, 95% CI 1.37-7.54; p = 0.02). Statin exposure rate was 47.6% among patients with DM/PM (OR 3.86, 95% CI 1.30-11.57; p<0.01). There was no difference between patients and controls for exposure to fibrates. CONCLUSION: Patients who developed chronic muscle diseases after the age of 50, including DM/PM, had a higher than expected frequency of prior exposure to statins. Further studies are needed to confirm this association and the role of proton pump inhibitors.