Superconductor-insulator quantum phase transition in a single Josephson junction

The superconductor-to-insulator quantum phase transition in resistively shunted Josephson junctions is investigated by means of path-integral Monte Carlo simulations. This numerical technique allows us to directly access the (previously unexplored) regime of the Josephson-to-charging energy ratios E_J/E_C of order one. Our results unambiguously support an earlier theoretical conjecture, based on renormalization-group calculations, that at T -> 0 the dissipative phase transition occurs at a universal value of the shunt resistance R_S = h/4e^2 for all values E_J/E_C. On the other hand, finite-temperature effects are shown to turn this phase transition into a crossover, which position depends significantly on E_J/E_C, as well as on the dissipation strength and on temperature. The latter effect needs to be taken into account in order to reconcile earlier theoretical predictions with recent experimental results.Comment: 7 pages, 6 figure

Chemical modeling for pH prediction of acidified musts with gypsum and tartaric acid in warm regions

Winemaking of musts acidified with up to 3 g/L of gypsum (CaSO4 2H2O) and tartaric acid, both individually and in combination, as well as a chemical modeling have been carried out to study the behaviour of these compounds as acidifiers. Prior to fermentation gypsum and tartaric acid reduce the pH by 0.12 and 0.17 pH units/g/L, respectively, but while gypsum does not increase the total acidity and reduces buffering power, tartaric acid shows the opposite behaviour. When these compounds were used in combination, the doses of tartaric acid necessary to reach a suitable pH were reduced. Calcium concentrations increase considerably in gypsum-acidified must, although they fell markedly after fermentation over time. Sulfate concentrations also increased, although with doses of 2 g/L they were lower than the maximum permitted level (2.5 g/L). Chemical modeling gave good results and the errors in pH predictions were less than 5% in almost all case

Burning questions in burnout research

Despite the fact that burnout has been around for almost half a century, various topics are still hotly debated. Although over one million publications appeared on the subject, scholars still do not agree about many issues. This chapter discusses these issues and attempts to take stock by answering six burning questions: (1) What is the nature of burnout?; (2) Is burnout also a medical diagnosis?; (3) How can burnout be assessed?; (4) Is there a burnout pandemic?; (5) Is burnout rooted in the person and the body?; and (6) Are burnout interventions successful? Not surprisingly, these questions can only be answered preliminary. However, directions for future research are proposed to overcome the paradox between the countless number of burnout publications on the one hand and the piecemeal and incomplete knowledge on the other. Overall, the chapter contributes to the ongoing debate on the nature of burnout by placing it on an empirical footing

Coulomb Blockade and Coherent Single-Cooper-Pair Tunneling in Single Josephson Junctions

We have measured the current-voltage characteristics of small-capacitance single Josephson junctions at low temperatures (T < 0.04 K), where the strength of the coupling between the single junction and the electromagnetic environment was controlled with one-dimensional arrays of dc SQUIDs. We have clearly observed Coulomb blockade of Cooper-pair tunneling and even a region of negative differential resistance, when the zero-bias resistance of the SQUID arrays is much higher than the quantum resistance h/e^2 = 26 kohm. The negative differential resistance is evidence of coherent single-Cooper-pair tunneling in the single Josephson junction.Comment: RevTeX, 4 pages with 6 embedded figure

Export of functional Streptomyces coelicolor alditol oxidase to the periplasm or cell surface of Escherichia coli and its application in whole-cell biocatalysis

Streptomyces coelicolor A3(2) alditol oxidase (AldO) is a soluble monomeric flavoprotein in which the flavin cofactor is covalently linked to the polypeptide chain. AldO displays high reactivity towards different polyols such as xylitol and sorbitol. These characteristics make AldO industrially relevant, but full biotechnological exploitation of this enzyme is at present restricted by laborious and costly purification steps. To eliminate the need for enzyme purification, this study describes a whole-cell AldO biocatalyst system. To this end, we have directed AldO to the periplasm or cell surface of Escherichia coli. For periplasmic export, AldO was fused to endogenous E. coli signal sequences known to direct their passenger proteins into the SecB, signal recognition particle (SRP), or Twin-arginine translocation (Tat) pathway. In addition, AldO was fused to an ice nucleation protein (INP)-based anchoring motif for surface display. The results show that Tat-exported AldO and INP-surface-displayed AldO are active. The Tat-based system was successfully employed in converting xylitol by whole cells, whereas the use of the INP-based system was most likely restricted by lipopolysaccharide LPS in wild-type cells. It is anticipated that these whole-cell systems will be a valuable tool for further biological and industrial exploitation of AldO and other cofactor-containing enzymes.

The integrin inhibitor cilengitide enhances the anti-glioma efficacy of vasculostatin-expressing oncolytic virus

Oncolytic viral (OV) therapy has been considered as a promising treatment modality for brain tumors. Vasculostatin, the fragment of brain-specific angiogenesis inhibitor-1, shows anti-angiogenic activity against malignant gliomas. Previously, a vasculostatin-expressing oncolytic herpes simplex virus-1, Rapid Antiangiogenesis Mediated By Oncolytic virus (RAMBO), was reported to have a potent antitumor effect. Here, we investigated the therapeutic efficacy of RAMBO and cilengitide, an integrin inhibitor, combination therapy for malignant glioma. In vitro, tube formation was significantly decreased in RAMBO and cilengitide combination treatment compared with RAMBO or cilengitide monotherapy. Moreover, combination treatment induced a synergistic suppressive effect on endothelial cell migration compared with the control virus. RAMBO, combined with cilengitide, induced synergistic cytotoxicity on glioma cells. In the caspase-8 and -9 assays, the relative absorption of U87 Delta EGFR cell clusters treated with cilengitide and with RAMBO was significantly higher than that of those treated with control. In addition, the activity of caspase 3/7 was significantly increased with combination therapy. In vivo, there was a significant increase in the survival of mice treated with combination therapy compared with RAMBO or cilengitide monotherapy. These results indicate that cilengitide enhanced vasculostatin-expressing OV therapy for malignant glioma and provide a rationale for designing future clinical trials combining these two agents

Long-term dopamine neurochemical monitoring in primates

Many debilitating neuropsychiatric and neurodegenerative disorders are characterized by dopamine neurotransmitter dysregulation. Monitoring subsecond dopamine release accurately and for extended, clinically relevant timescales is a critical unmet need. Especially valuable has been the development of electrochemical fast-scan cyclic voltammetry implementing microsized carbon fiber probe implants to record fast millisecond changes in dopamine concentrations. Nevertheless, these well-established methods have only been applied in primates with acutely (few hours) implanted sensors. Neurochemical monitoring for long timescales is necessary to improve diagnostic and therapeutic procedures for a wide range of neurological disorders. Strategies for the chronic use of such sensors have recently been established successfully in rodents, but new infrastructures are needed to enable these strategies in primates. Here we report an integrated neurochemical recording platform for monitoring dopamine release from sensors chronically implanted in deep brain structures of nonhuman primates for over 100 days, together with results for behavior-related and stimulation-induced dopamine release. From these chronically implanted probes, we measured dopamine release from multiple sites in the striatum as induced by behavioral performance and reward-related stimuli, by direct stimulation, and by drug administration. We further developed algorithms to automate detection of dopamine. These algorithms could be used to track the effects of drugs on endogenous dopamine neurotransmission, as well as to evaluate the long-term performance of the chronically implanted sensors. Our chronic measurements demonstrate the feasibility of measuring subsecond dopamine release from deep brain circuits of awake, behaving primates in a longitudinally reproducible manner. Keywords: striatum; voltammetry; neurotransmitters; chronic implantsNational Institute of Neurological Diseases and Stroke (U.S.) (Grant R01 NS025529)National Institute of Neurological Diseases and Stroke (U.S.) (Grant F32 NS093897)United States. Army Research Office (Contract W911NF-16-1-0474)National Institute of Biomedical Imaging and Bioengineering (U.S.) (Grant R01 EB016101

Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine: Brussels, Belgium. 15-18 March 2016.

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]

Progressive transformation of a flux rope to an ICME

The solar wind conditions at one astronomical unit (AU) can be strongly disturbed by the interplanetary coronal mass ejections (ICMEs). A subset, called magnetic clouds (MCs), is formed by twisted flux ropes that transport an important amount of magnetic flux and helicity which is released in CMEs. At 1 AU from the Sun, the magnetic structure of MCs is generally modeled neglecting their expansion during the spacecraft crossing. However, in some cases, MCs present a significant expansion. We present here an analysis of the huge and significantly expanding MC observed by the Wind spacecraft during 9 and 10 November, 2004. After determining an approximated orientation for the flux rope using the minimum variance method, we precise the orientation of the cloud axis relating its front and rear magnetic discontinuities using a direct method. This method takes into account the conservation of the azimuthal magnetic flux between the in- and out-bound branches, and is valid for a finite impact parameter (i.e., not necessarily a small distance between the spacecraft trajectory and the cloud axis). Moreover, using the direct method, we find that the ICME is formed by a flux rope (MC) followed by an extended coherent magnetic region. These observations are interpreted considering the existence of a previous larger flux rope, which partially reconnected with its environment in the front. These findings imply that the ejected flux rope is progressively peeled by reconnection and transformed to the observed ICME (with a remnant flux rope in the front part).Comment: Solar Physics (in press