Number of Attractors in the Critical Kauffman Model Is Exponential.

The Kauffman model is the archetypal model of genetic computation. It highlights the importance of criticality, at which many biological systems seem poised. In a series of advances, researchers have honed in on how the number of attractors in the critical regime grows with network size. But a definitive answer has remained elusive. We prove that, for the critical Kauffman model with connectivity one, the number of attractors grows at least, and at most, as (2/sqrt[e])^{N}. This is the first proof that the number of attractors in a critical Kauffman model grows exponentially.

Removal of micropollutants with coarse-ground activated carbon for enhanced separation with hydrocyclone classifiers.

One key technology to eliminate organic micropollutants (OMP) from wastewater effluent is adsorption using powdered activated carbon (PAC). To avoid a discharge of highly loaded PAC particles into natural water bodies a separation stage has to be implemented. Commonly large settling tanks and flocculation filters with the application of coagulants and flocculation aids are used. In this study, a multi-hydrocyclone classifier with a downstream cloth filter has been investigated on a pilot plant as a space-saving alternative with no need for a dosing of chemical additives. To improve the separation, a coarser ground PAC type was compared to a standard PAC type with regard to elimination results of OMP as well as separation performance. With a PAC dosing rate of 20 mg/l an average of 64.7 wt% of the standard PAC and 79.5 wt% of the coarse-ground PAC could be separated in the hydrocyclone classifier. A total average separation efficiency of 93-97 wt% could be reached with a combination of both hydrocyclone classifier and cloth filter. Nonetheless, the OMP elimination of the coarse-ground PAC was not sufficient enough to compete with the standard PAC. Further research and development is necessary to find applicable coarse-grained PAC types with adequate OMP elimination capabilities.

Critical steps in the isolation and expansion of adipose-derived stem cells for translational therapy.

Since the discovery of adipose-derived stem cells (ASCs), there have been high expectations of their putative clinical use. Recent advances support these expectations, and it is expected that the transition from pre-clinical and clinical studies to implementation as a standard treatment modality is imminent. However ASCs must be isolated and expanded according to good manufacturing practice guidelines and a basic assurance of quality, safety, and medical effectiveness is needed for authorisation by regulatory agencies, such as European Medicines Agency and US Food and Drug Administration. In this review, a collection of studies investigating the influence of different steps of the isolation and expansion protocol on the yield and functionality of ASCs has been presented in an attempt to come up with best recommendations that ensure potential beneficial clinical outcome of using ASCs in any therapeutic setting. If the findings confirm the initial observations of beneficial effects of ASCs, the path is paved for implementing these ASC-based therapies as standard treatment options.

[ESC guidelines 2015 for ventricular arrhythmias and prevention of sudden cardiac death. What is new?]. / ESC-Leitlinien 2015 zu ventrikulären Arrhythmien und zur Prävention des plötzlichen Herztodes. Was ist neu?

The new European Society of Cardiology (ESC) guidelines for the management of patients with ventricular arrhythmia and the prevention of sudden cardiac death, recently published at the annual ESC meeting in London, contain an extensive update of the recommendations for the diagnostics, drug therapy, interventional and device therapy of ventricular arrhythmia. The new recommendations for implantable cardioverter defibrillator (ICD) treatment for primary and secondary prophylaxis of sudden cardiac death can be seen as a focused update of the previously published guidelines. Pre-existing recommendations for catheter ablation of ventricular arrhythmias have been partly extensively expanded with respect to the results of recent clinical trials. The guideline committee also adapted their recommendations regarding the hereditary arrhythmia syndromes to the 2013 consensus report of the American Heart Association (AHA), the European Heart Rhythm Association (EHRA) and the Asia Pacific Heart Rhythm Society (APHRS).

[Innovative techniques in atrial fibrillation therapy]. / Innovative Verfahren der Vorhofflimmertherapie.

Pulmonary vein isolation (PVI) is the established cornerstone in most catheter-based ablation treatment strategies for atrial fibrillation (AF); however, it is still a challenge to create contiguous, transmural and permanent ablation lesions using radiofrequency current in combination with three-dimensional mapping systems. To overcome these limitations, innovative spiral mapping and ablation catheters as well as balloon-based ablation catheters incorporating alternative energy sources, such as cryoenergy and laser were developed and evaluated and have proved their potential for safe and clinically effective PVI. In addition, novel ablation strategies, such as identification and ablation of AF-inducing foci and/or AF-perpetuating rotors using either endocardial or epicardial mapping systems were introduced and are currently under clinical evaluation. The identification and modulation of atrial ganglionic plexi (GP) and, therefore, of the autonomous nervous system is another additive ablation approach which requires further clinical evaluation.

Inline classification of polymer films using Machine learning methods.

Improving the sortability of plastic packaging film waste (PPFW) is crucial for increasing the recycling rate in Austria as they account for 150,000 t of the annually produced 300,000 t of plastic packaging waste. Currently PPFW is thermally recovered, as it is impossible to separate the mechanically recyclable monomaterial films from the non mechanically-recyclable multimaterial films. In this study, machine learning models capable of classifying inline into monolayer and multilayer films of PPFW according to their spectral fingerprint taken in transflection were created. Feature selection methods, like PCA and MRMR F-Tests, identified the most relevant spectral ranges for classification, that show the least redundancy and highest relevance. This effective subset of features decreases the required complexity of the model while reducing prediction time without compromising accuracy. The resulting models achieved a prediction accuracy of 85 % on unseen specimens with minimal prediction latency, effectively showing the inline applicability of these models in sorting aggregates.

Noise spectroscopy using correlations of single-shot qubit readout.

A better understanding of the noise causing qubit decoherence is crucial for improving qubit performance. The noise spectrum affecting the qubit may be extracted by measuring dephasing under the application of pulse sequences but requires accurate qubit control and sufficiently long relaxation times, which are not always available. Here, we describe an alternative method to extract the spectrum from correlations of single-shot measurement outcomes of successive free induction decays. This method only requires qubit initialization and readout with a moderate fidelity and also allows independent tuning of both the overall sensitivity and the frequency region over which it is sensitive. Thus, it is possible to maintain a good detection contrast over a very wide frequency range. We discuss using our method for measuring both 1/f noise and the fluctuation spectrum of the nuclear bath of GaAs spin qubits.

Transcriptional signature of human adipose tissue-derived stem cells (hASCs) preconditioned for chondrogenesis in hypoxic conditions.

Hypoxia is an important factor involved in the control of stem cells. To obtain a better insight into the phenotypical changes brought about by hypoxic preconditioning prior to chondrogenic differentiation; we have investigated growth, colony-forming and chondrogenic capacity, and global transcriptional responses of six adipose tissue-derived stem cell lines expanded at oxygen concentrations ranging from ambient to 1%. The assessment of cell proliferation and colony-forming potential revealed that the hypoxic conditions corresponding to 1% oxygen played a major role. The chondrogenic inducibility, examined by high-density pellet model, however, did not improve on hypoxic preconditioning. While the microarray analysis revealed a distinctive inter-donor variability, the exposure to 1% hypoxia superseded the biological variability and produced a specific expression profile with 2581 significantly regulated genes and substantial functional enrichment in the pathways of cell proliferation and apoptosis. Additionally, exposure to 1% oxygen resulted in upregulation of factors related to angiogenesis and cell growth. In particular, leptin (LEP), the key regulator of body weight and food intake was found to be highly upregulated. In conclusion, the results of this investigation demonstrate the significance of donor demographics and the importance of further studies into the use of regulated oxygen tension as a tool for preparation of ASCs in order to exploit their full potential.

Fire ant alate wing motion data and numerical reconstruction.

The wing motions of a male and a female fire ant alate, which beat their wings at 108 and 96 Hz, respectively, were captured with a stereo imaging system at a high frame rate of 8,000 frames per second. By processing the high-speed image frames, the three-dimensional wingtip positions and the wing surface orientation angles were determined with a high phase resolution, i.e. 74 and 83 phases per period for the male and the female, respectively. A numerical reconstruction of the stereo wingbeat images demonstrated that the data collected described almost all the details of the wing surface motion, so that further computational fluid dynamic simulations are possible for fire ant alate flight.

Beach cusps as self-organized patterns.

Computer simulations of flow and sediment transport in the swash zone on a beach demonstrate that a model that couples local flow acceleration and alongshore surface gradient is sufficient to produce uniformly spaced beach cusps. The characteristics of the simulated cusps and the conditions under which they form are in reasonable agreement with observations of natural cusps. The self-organization mechanism in the model is incompatible with an accepted model in which standing alongshore waves drive the regular pattern of erosion and deposition that gives rise to beach cusps. Because the models make similar predictions, it is concluded that currently available observational data are insufficient for discrimination between them.

How much can we influence the rate of innovation?

Innovation is how organizations drive technological change, but the rate of innovation can vary considerably from one technological domain to another. To understand why some domains flourish more rapidly than others, we studied a model of innovation in which products are built out of components. We derived a conservation law for the average size of the product space as more components are acquired and tested our insights using historical data from language, gastronomy, mixed drinks, and technology. We find that the innovation rate is partly influenceable and partly predetermined, similar to how traits are partly set by nurture and partly set by nature. The predetermined aspect is fixed solely by the distribution of the complexity of products in each domain. Different distributions can produce markedly different innovation rates. This helps explain why some domains show faster innovation than others, despite similar efforts to accelerate them. Our insights also give a quantitative perspective on lean methodology, frugal innovation, and mechanisms to encourage tinkering.

Clustering signatures classify directed networks.

We use a clustering signature, based on a recently introduced generalization of the clustering coefficient to directed networks, to analyze 16 directed real-world networks of five different types: social networks, genetic transcription networks, word adjacency networks, food webs, and electric circuits. We show that these five classes of networks are cleanly separated in the space of clustering signatures due to the statistical properties of their local neighborhoods, demonstrating the usefulness of clustering signatures as a classifier of directed networks.

Acute aortic dissection--vascular emergency with numerous pitfalls.

Acute aortic syndrome comprises acute aortic dissection, aortic intramural haematoma and penetrating atherosclerotic ulcers of the aortic wall. It ranks, after acute coronary syndrome, as one of the most frequent acute life-threatening differential diagnoses of chest pain. Chances of survival would probably be good in the large majority of cases, assuming optimal therapeutic management including rapid diagnostic evaluation followed by immediate and appropriate treatment is provided. However, actual mortality rate in these patients is still currently higher than 40%, despite medical and surgical progress. This unfavourable prognosis for the most frequent variant of acute aortic syndrome--aortic dissection--is due to the wide variability of clinical symptoms. These are often initially unspecific and frequently lead to delays in establishing the correct diagnosis, possibly first recognised at autopsy. Even after a timely, correct diagnosis, there is still a considerably high mortality rate following surgery, even with younger patients. Whenever acute aortic dissection is suspected a diagnostic imaging study should immediately be obtained. In addition to CT angiography, transesophageal echocardiography is recommended, due to its flexibility, as the diagnostically most useful tool in this context. Based on three case reports of acute aortic dissection this paper critically discusses the problems in making a correct and timely diagnosis and also provides an overview of the current state of knowledge in the areas of pathophysiology, epidemiology, clinical symptomatology as well as appropriate case-related management and prognosis of acute aortic dissection.

Is prolactin a negative neuroendocrine regulator of human skin re-epithelisation after wounding?

Chronic wounds remain a major unmet healthcare challenge, associated with substantial morbidity and economic costs. Therefore, novel treatment strategies and therapeutic approaches need to be urgently developed. Yet, despite the increasingly recognized importance of neurohormonal signaling in skin physiology, the neuroendocrine regulation of cutaneous wound healing has received surprisingly little attention. Human skin, and its appendages, locally express the pleiotropic neurohormone prolactin (PRL), which not only regulates lactation but also hair follicle cycling, angiogenesis, keratinocyte proliferation, and epithelial stem cell functions. Therefore, we examined the effects of PRL in experimentally wounded female human skin organ culture. Overall, this revealed that PRL slightly, but significantly, inhibited epidermal regeneration (reepithelialisation), cytokeratin 6 protein expression and intraepidermal mitochondrial activity (MTCO1 expression), while it promoted keratinocyte terminal differentiation (i.e. involucrin expression) ex vivo. If the current pilot data are confirmed by further studies, PRL may serve as one of the-rarely studied-negative regulators of cutaneous wound healing that control excessive reepithelialisation. This raises the intriguing and clinically relevant question of whether PRL receptor antagonists could actually promote epidermal repair after human skin wounding.

Ensemble approach to the analysis of weighted networks.

We present an approach to the analysis of weighted networks, by providing a straightforward generalization of any network measure defined on unweighted networks, such as the average degree of the nearest neighbors, the clustering coefficient, the "betweenness," the distance between two nodes, and the diameter of a network. All these measures are well established for unweighted networks but have hitherto proven difficult to define for weighted networks. Our approach is based on the translation of a weighted network into an ensemble of edges. Further introducing this approach we demonstrate its advantages by applying the clustering coefficient constructed in this way to two real-world weighted networks.

Seasonal variability in otariid energetics: implications for the effects of predators on localized prey resources.

Otariids, like other wild mammals, contend with a wide variety of energetic demands across seasons. However, due to the cryptic behaviors of this marine group, few studies have been able to examine longitudinal energetic costs or the potential impact of these costs on seasonal or annual prey requirements. Here we evaluated the changes in energy demand and intake of female California sea lions (Zalophus californianus) during reproductive (n=2 sea lions) and nonreproductive (n=3) periods. Monthly measurements included resting metabolic rate, blood hormone levels, body condition (blubber thickness and body mass), and caloric intake for adult sea lions throughout molting, late pregnancy, lactation, and postweaning. We found that maintenance energy demands decreased from 32.0 to 23.1 MJ d(-1) before pupping, remaining stable at 19.4+/-0.6 MJ d(-1) during lactation and postweaning. Energy intake rates to meet these demands showed marked changes with activity level and the reproductive cycle, reaching a peak intake of 3.6 times baseline levels during lactation. Translating this into prey demands, we find that 20,000 reproductively active females on San Nicolas Island rookeries would maximally require 4,950 metric tons of Pacific whiting during a month of the breeding season. This localized impact is reduced significantly with postbreeding dispersal and demonstrates the importance of considering spatial and temporal factors driving the energetic requirements of predators when designing marine protected areas.

Serendipity and strategy in rapid innovation.

Innovation is to organizations what evolution is to organisms: it is how organizations adapt to environmental change and improve. Yet despite advances in our understanding of evolution, what drives innovation remains elusive. On the one hand, organizations invest heavily in systematic strategies to accelerate innovation. On the other, historical analysis and individual experience suggest that serendipity plays a significant role. To unify these perspectives, we analysed the mathematics of innovation as a search for designs across a universe of component building blocks. We tested our insights using data from language, gastronomy and technology. By measuring the number of makeable designs as we acquire components, we observed that the relative usefulness of different components can cross over time. When these crossovers are unanticipated, they appear to be the result of serendipity. But when we can predict crossovers in advance, they offer opportunities to strategically increase the growth of the product space.

Characterization of a high copy number amplification at 6q24 in pancreatic cancer identifies c-myb as a candidate oncogene.

In a recent study designed to identify chromosomal aberrations in pancreatic cancer tissues using comparative genomic hybridization, a high copy number amplification on 6q was detected. To identify the most likely candidate oncogene, the extension of the amplification in pancreatic cancer tissues and cell lines was determined by Southern blot analysis. Exon trapping was performed with DNA from a yeast artificial chromosome clone containing the complete minimally amplified region. Only fragments from two genes, namely, the c-myb oncogene and a novel gene, were shown to be amplified. The c-myb proto-oncogene was amplified in 10% of the pancreatic carcinoma tissues and in the pancreatic cancer cell line PC2. Interestingly, the c-myb oncogene was overexpressed not only in the amplified samples but also in the majority of the examined pancreatic cancer tissues and cell lines, suggesting that amplification is only one of the mechanisms leading to overexpression. In contrast, the novel gene, which was called human eRF3b (eukaryotic release factor 3b), seems to be only coamplified with c-myb. Genetic alterations of c-myb were mainly found in advanced tumors, indicating a possible correlation to tumor progression and aggressive tumor phenotypes.