From DNA sequence to application: possibilities and complications

The development of sophisticated genetic tools during the past 15 years have facilitated a tremendous increase of fundamental and application-oriented knowledge of lactic acid bacteria (LAB) and their bacteriophages. This knowledge relates both to the assignments of open reading frames (ORF’s) and the function of non-coding DNA sequences. Comparison of the complete nucleotide sequences of several LAB bacteriophages has revealed that their chromosomes have a fixed, modular structure, each module having a set of genes involved in a specific phase of the bacteriophage life cycle. LAB bacteriophage genes and DNA sequences have been used for the construction of temperature-inducible gene expression systems, gene-integration systems, and bacteriophage defence systems. The function of several LAB open reading frames and transcriptional units have been identified and characterized in detail. Many of these could find practical applications, such as induced lysis of LAB to enhance cheese ripening and re-routing of carbon fluxes for the production of a specific amino acid enantiomer. More knowledge has also become available concerning the function and structure of non-coding DNA positioned at or in the vicinity of promoters. In several cases the mRNA produced from this DNA contains a transcriptional terminator-antiterminator pair, in which the antiterminator can be stabilized either by uncharged tRNA or by interaction with a regulatory protein, thus preventing formation of the terminator so that mRNA elongation can proceed. Evidence has accumulated showing that also in LAB carbon catabolite repression in LAB is mediated by specific DNA elements in the vicinity of promoters governing the transcription of catabolic operons. Although some biological barriers have yet to be solved, the vast body of scientific information presently available allows the construction of tailor-made genetically modified LAB. Today, it appears that societal constraints rather than biological hurdles impede the use of genetically modified LAB.

Building nonparametric nn-body force fields using Gaussian process regression

Constructing a classical potential suited to simulate a given atomic system is a remarkably difficult task. This chapter presents a framework under which this problem can be tackled, based on the Bayesian construction of nonparametric force fields of a given order using Gaussian process (GP) priors. The formalism of GP regression is first reviewed, particularly in relation to its application in learning local atomic energies and forces. For accurate regression it is fundamental to incorporate prior knowledge into the GP kernel function. To this end, this chapter details how properties of smoothness, invariance and interaction order of a force field can be encoded into corresponding kernel properties. A range of kernels is then proposed, possessing all the required properties and an adjustable parameter $n$ governing the interaction order modelled. The order $n$ best suited to describe a given system can be found automatically within the Bayesian framework by maximisation of the marginal likelihood. The procedure is first tested on a toy model of known interaction and later applied to two real materials described at the DFT level of accuracy. The models automatically selected for the two materials were found to be in agreement with physical intuition. More in general, it was found that lower order (simpler) models should be chosen when the data are not sufficient to resolve more complex interactions. Low $n$ GPs can be further sped up by orders of magnitude by constructing the corresponding tabulated force field, here named "MFF".Comment: 31 pages, 11 figures, book chapte

Temporal networks of face-to-face human interactions

The ever increasing adoption of mobile technologies and ubiquitous services allows to sense human behavior at unprecedented levels of details and scale. Wearable sensors are opening up a new window on human mobility and proximity at the finest resolution of face-to-face proximity. As a consequence, empirical data describing social and behavioral networks are acquiring a longitudinal dimension that brings forth new challenges for analysis and modeling. Here we review recent work on the representation and analysis of temporal networks of face-to-face human proximity, based on large-scale datasets collected in the context of the SocioPatterns collaboration. We show that the raw behavioral data can be studied at various levels of coarse-graining, which turn out to be complementary to one another, with each level exposing different features of the underlying system. We briefly review a generative model of temporal contact networks that reproduces some statistical observables. Then, we shift our focus from surface statistical features to dynamical processes on empirical temporal networks. We discuss how simple dynamical processes can be used as probes to expose important features of the interaction patterns, such as burstiness and causal constraints. We show that simulating dynamical processes on empirical temporal networks can unveil differences between datasets that would otherwise look statistically similar. Moreover, we argue that, due to the temporal heterogeneity of human dynamics, in order to investigate the temporal properties of spreading processes it may be necessary to abandon the notion of wall-clock time in favour of an intrinsic notion of time for each individual node, defined in terms of its activity level. We conclude highlighting several open research questions raised by the nature of the data at hand.Comment: Chapter of the book "Temporal Networks", Springer, 2013. Series: Understanding Complex Systems. Holme, Petter; Saram\"aki, Jari (Eds.

Egocentric Social Network Structure, Health, and Pro-Social Behaviors in a National Panel Study of Americans

Using a population-based, panel survey, we study how egocentric social networks change over time, and the relationship between egocentric network properties and health and pro-social behaviors. We find that the number of prosocial activities is strongly positively associated with having more friends, or an increase in degree, with approximately 0.04 more prosocial behaviors expected for every friend added. Moreover, having more friends is associated with an improvement in health, while being healthy and prosocial is associated with closer relationships. Specifically, a unit increase in health is associated with an expected 0.45 percentage-point increase in average closeness, while adding a prosocial activity is associated with a 0.46 percentage-point increase in the closeness of one’s relationships. Furthermore, a tradeoff between degree and closeness of social contacts was observed. As the number of close social contacts increases by one, the estimated average closeness of each individual contact decreases by approximately three percentage-points. The increased awareness of the importance of spillover effects in health and health care makes the ascertainment of egocentric social networks a valuable complement to investigations of the relationship between socioeconomic factors and health

Performance of adenosine “stress-only” perfusion MRI in patients without a history of myocardial infarction: a clinical outcome study

To assess the diagnostic value of adenosine “stress-only” myocardial perfusion MR for ischemia detection as an indicator for coronary angiography in patients without a prior myocardial infarction and a necessity to exclude ischemia. Adenosine perfusion MRI was performed at 1.5 T in 139 patients with a suspicion of ischemia and no prior myocardial infarction. After 3 min of adenosine infusion a perfusion sequence was started. Patients with a perfusion defect were referred to coronary angiography (CAG). Patients with a normal perfusion were enrolled in follow-up. Fourteen out of 139 patients (10.1%) had a perfusion defect indicative of ischemia. These patients underwent a coronary angiogram, which showed complete agreement with the perfusion images. 125 patients with a normal myocardial perfusion entered follow-up (median 672 days, range 333–1287 days). In the first year of follow-up one Major Adverse Coronary Event (MACE) occurred and one patient had new onset chest pain with a confirmed coronary stenosis. Reaching a negative predictive value for MACE of 99.2% and for any coronary event of 98.4%. At 2 year follow-up no additional MACE occurred. Sensitivity of adenosine perfusion MR for MACE is 93.3% and specificity and positive predictive value are 100%. Adenosine myocardial perfusion MR for the detection of myocardial ischemia in a “stress-only” protocol in patients without prior myocardial infarctions, has a high diagnostic accuracy. This fast examination can play an important role in the evaluation of patients without prior myocardial infarctions and a necessity to exclude ischemia

Chlorine Dioxide Is a Size-Selective Antimicrobial Agent

Background / Aims: ClO2, the so-called "ideal biocide", could also be applied as an antiseptic if it was understood why the solution killing microbes rapidly does not cause any harm to humans or to animals. Our aim was to find the source of that selectivity by studying its reaction-diffusion mechanism both theoretically and experimentally. Methods: ClO2 permeation measurements through protein membranes were performed and the time delay of ClO2 transport due to reaction and diffusion was determined. To calculate ClO2 penetration depths and estimate bacterial killing times, approximate solutions of the reaction-diffusion equation were derived. In these calculations evaporation rates of ClO2 were also measured and taken into account. Results: The rate law of the reaction-diffusion model predicts that the killing time is proportional to the square of the characteristic size (e. g. diameter) of a body, thus, small ones will be killed extremely fast. For example, the killing time for a bacterium is on the order of milliseconds in a 300 ppm ClO2 solution. Thus, a few minutes of contact time (limited by the volatility of ClO2) is quite enough to kill all bacteria, but short enough to keep ClO2 penetration into the living tissues of a greater organism safely below 0.1 mm, minimizing cytotoxic effects when applying it as an antiseptic. Additional properties of ClO2, advantageous for an antiseptic, are also discussed. Most importantly, that bacteria are not able to develop resistance against ClO2 as it reacts with biological thiols which play a vital role in all living organisms. Conclusion: Selectivity of ClO2 between humans and bacteria is based not on their different biochemistry, but on their different size. We hope initiating clinical applications of this promising local antiseptic

Cancellations of (helicopter-transported) mobile medical team dispatches in the Netherlands

The trauma centre of the Trauma Center Region North-West Netherlands (TRNWN) has consensus criteria for Mobile Medical Team (MMT) scene dispatch. The MMT can be dispatched by the EMS-dispatch centre or by the on-scene ambulance crew and is transported by helicopter or ground transport. Although much attention has been paid to improve the dispatch criteria, the MMT is often cancelled after being dispatched. The aim of this study was to assess the cancellation rate and the noncompliant dispatches of our MMT and to identify factors associated with this form of primary overtriage. By retrospective analysis of all MMT dispatches in the period from 1 July 2006 till 31 December 2006 using chart review, we conducted a consecutive case review of 605 dispatches. Four hundred and sixty seven of these were included for our study, collecting data related to prehospital triage, patient's condition on-scene and hospital course. Average age was 35.9 years; the majority of the patients were male (65.3%). Four hundred and thirty patients were victims of trauma, sustaining injuries in most cases from blunt trauma (89.3%). After being dispatched, the MMT was cancelled 203 times (43.5%). Statistically significant differences between assists and cancellations were found for overall mortality, mean RTS, GCS and ISS, mean hospitalization, length and amount of ICU admissions (p < 0.001). All dispatches were evaluated by using the MMT-dispatch criteria and mission appropriateness criteria. Almost 26% of all dispatches were neither appropriate, nor met the dispatch criteria. Fourteen missions were appropriate, but did not meet the dispatch criteria. The remaining 318 dispatches had met the dispatch criteria, of which 135 (30.3%) were also appropriate. The calculated additional costs of the cancelled dispatches summed up to a total of a,not sign 34,448, amounting to 2.2% of the total MMT costs during the study period. In our trauma system, the MMT dispatches are involved with high rates of overtriage. After being dispatched, the MMT is cancelled in almost 50% of all cases. We found an undertriage rate of 4%, which we think is acceptable. All cancellations were justified. The additional costs of the cancelled missions were within an acceptable range. According to this study, it seems to be possible to reduce the overtriage rate of the MMT dispatches, without increasing the undertriage rate to non-acceptable level

Better the devil you know:Threat effects and attachment to the European Union

The EU is facing unprecedented challenges and significant threats to its economic and political security. Austerity, the Eurozone crisis, rising immigration and heightened fear of terrorism all present serious challenges to the process of integration. How does this context of insecurity impact on what the EU means to its citizens? Will the public become increasingly Eurosceptic or will they discover a hitherto unrecognised attachment to the EU as the prospect of its collapse becomes real? Psychological research has demonstrated that individual exposure to threat decreases cognitive capacity, inducing a tendency towards rigidity or conservatism - a tendency to cling to the ‘devil you know’. So what might this mean for the European integration process? Using experimental techniques drawn from political psychology, the authors find a dual threat effect. The EU symbol has a negative (anti-EU) effect on EU-related attitudes when presented in neutral context. This is consonant with conceptualisations of the EU as a threat to national cultural and political norms. In contrast, however, visual priming of participants with EU symbols has a positive (pro-EU) effect on related attitudes when these are presented in a context that implies a subtle but imminent threat to the benefits of EU membership

Кинетика восстановления железа при восстановительной плавке рудоугольных окатышей

Исследовано влияние интенсивности теплообмена на кинетику восстановления железа в процессе плавки рудоугольных окатышей. Показано, что с ростом интенсивности теплообмена повышается скорость восстановительных процессов. Вследствие роста коэффициента теплообмена увеличивается глубина восстановленного слоя окатыша, существенно изменяются его структура и химический состав образующейся металлической фазы.Досліджено вплив інтенсивності теплообміну на кінетику відновлення заліза в процесі плавки рудовугільних окатишів. Показано, що при зростанні інтенсивності теплообміну підвищується швидкість відновлювальних процесів. Внаслідок зростання коефіцієнту теплообміну збільшується глибина відновленого шару окатиша, суттєво змінюються його структура та хімічний склад металевої фази, що утворюється.Influence of intensity of heat exchange is investigational on kinetics reduction of iron in the process of melting ore-coal pellets. It is rotined that speed of reduction processes rises with growth of intensity of heat exchange. Because of growth of coefficient of heat exchange the depth of the recovered layer of pellet is increased, his structure and chemical composition of appearing metallic phase changes substantially