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Root infinitives on Twitter
(2017)
Editorial
(2017)
We develop a simple two-zone interpretation of the broadband baseline Crab nebula spectrum between 10(-5) eV and similar to 100 TeV by using two distinct log-parabola energetic electrons distributions. We determine analytically the very-high energy photon spectrum as originated by inverse-Compton scattering of the far-infrared soft ambient photons within the nebula off a first population of electrons energized at the nebula termination shock. The broad and flat 200 GeV peak jointly observed by Fermi/LAT and MAGIC is naturally reproduced. The synchrotron radiation from a second energetic electron population explains the spectrum from the radio range up to similar to 10 keV. We infer from observations the energy dependence of the microscopic probability of remaining in proximity of the shock of the accelerating electrons.
Since the Shallow Structure Hypothesis (SSH) was first put forward in 2006, it has inspired a growing body of research on grammatical processing in nonnative (L2) speakers. More than 10 years later, we think it is time for the SSH to be reconsidered in the light of new empirical findings and current theoretical assumptions about human language processing. The purpose of our critical commentary is twofold: to clarify some issues regarding the SSH and to sketch possible ways in which this hypothesis might be refined and improved to better account for L1 and L2 speakers’ performance patterns.
Photonic sensing in highly concentrated biotechnical processes by photon density wave spectroscopy
(2017)
Photon Density Wave (PDW) spectroscopy is introduced as a new approach for photonic sensing in highly concentrated biotechnical processes. It independently quantifies the absorption and reduced scattering coefficient calibration-free and as a function of time, thus describing the optical properties in the vis/NIR range of the biomaterial during their processing. As examples of industrial relevance, enzymatic milk coagulation, beer mashing, and algae cultivation in photo bioreactors are discussed.
Background: Infliximab (IFX), an anti-TNF monoclonal antibody approved for the treatment of inflammatory bowel disease, is dosed per kg body weight (BW). However, the rationale for body size adjustment has not been unequivocally demonstrated [1], and first attempts to improve IFX therapy have been undertaken [2]. The aim of our study was to assess the impact of different dosing strategies (i.e. body size-adjusted and fixed dosing) on drug exposure and pharmacokinetic (PK) target attainment. For this purpose, a comprehensive simulation study was performed, using patient characteristics (n=116) from an in-house clinical database.
Methods: IFX concentration-time profiles of 1000 virtual, clinically representative patients were generated using a previously published PK model for IFX in patients with Crohn's disease [3]. For each patient 1000 profiles accounting for PK variability were considered. The IFX exposure during maintenance treatment after the following dosing strategies was compared: i) fixed dose, and per ii) BW, iii) lean BW (LBW), iv) body surface area (BSA), v) height (HT), vi) body mass index (BMI) and vii) fat-free mass (FFM)). For each dosing strategy the variability in maximum concentration Cmax, minimum concentration Cmin (= C8weeks) and area under the concentration-time curve (AUC), as well as percent of patients achieving the PK target, Cmin=3 μg/mL [4] were assessed.
Results: For all dosing strategies the variability of Cmin (CV ≈110%) was highest, compared to Cmax and AUC, and was of similar extent regardless of dosing strategy. The proportion of patients reaching the PK target (≈⅓ was approximately equal for all dosing strategies.
As a potentially toxic agent on nervous system and bone, the safety of aluminium exposure from adjuvants in vaccines and subcutaneous immune therapy (SCIT) products has to be continuously reevaluated, especially regarding concomitant administrations. For this purpose, knowledge on absorption and disposition of aluminium in plasma and tissues is essential. Pharmacokinetic data after vaccination in humans, however, are not available, and for methodological and ethical reasons difficult to obtain. To overcome these limitations, we discuss the possibility of an in vitro-in silico approach combining a toxicokinetic model for aluminium disposition with biorelevant kinetic absorption parameters from adjuvants. We critically review available kinetic aluminium-26 data for model building and, on the basis of a reparameterized toxicokinetic model (Nolte et al., 2001), we identify main modelling gaps. The potential of in vitro dissolution experiments for the prediction of intramuscular absorption kinetics of aluminium after vaccination is explored. It becomes apparent that there is need for detailed in vitro dissolution and in vivo absorption data to establish an in vitro-in vivo correlation (IVIVC) for aluminium adjuvants. We conclude that a combination of new experimental data and further refinement of the Nolte model has the potential to fill a gap in aluminium risk assessment. (C) 2017 Elsevier Inc. All rights reserved.
The design of embedded systems is becoming continuously more complex such that efficient system-level design methods are becoming crucial. Recently, combined Answer Set Programming (ASP) and Quantifier Free Integer Difference Logic (QF-IDL) solving has been shown to be a promising approach in system synthesis. However, this approach still has several restrictions limiting its applicability. In the paper at hand, we propose a novel ASP modulo Theories (ASPmT) system synthesis approach, which (i) supports more sophisticated system models, (ii) tightly integrates the QF-IDL solving into the ASP solving, and (iii) makes use of partial assignment checking. As a result, more realistic systems are considered and an early exclusion of infeasible solutions improves the entire system synthesis.
It has been observationally established that winds of hot massive stars have highly variable characteristics. The variability evident in the winds is believed to be caused by structures on a broad range of spatial scales. Small-scale structures (clumping) in stellar winds of hot stars are possible consequence of an instability appearing in their radiation hydrodynamics. To understand how clumping may influence calculation of theoretical spectra, different clumping properties and their 3D nature have to be taken into account. Properties of clumping have been examined using our 3D radiative transfer calculations. Effects of clumping for the case of the B[e] phenomenon are discussed.
Conclusion
(2016)
This chapter revisits the role of the new modes of governance in areas of limited statehood. First, it states that there is no linear relationship between degrees of statehood and the overall effectiveness of new modes of sustainability governance. Second, the chapter states that, in most of the cases, national governments are hesitant or even actively hamper the development of new modes of governance. Third, it shows that the absence of the shadow of hierarchy can indeed lead to ineffective new modes of governance. However, the shadow of hierarchy does not necessarily need to be cast by states. Finally, the author reviews the complexities involved in participatory practices, stressing the importance of institutional structures and knowledgeable brokers. The chapter concludes by outlining fields for future research.
Introduction
(2016)
The Paris Agreement for Climate Change or the Sustainable Development Goals (SDGs) rely on new modes of governance for implementation. Indeed, new modes of governance such as market-based instruments, public-private partnerships or multi-stakeholder initiatives have been praised for playing a pivotal role in effective and legitimate sustainability governance. Yet, do they also deliver in areas of limited statehood? States such as Malaysia or the Dominican Republic partly lack the ability to implement and enforce rules; their statehood is limited. This introduction provides the analytical framework of this volume and critically examines the performance of new modes of governance in areas of limited statehood, drawing on the book’s in-depth case studies on issues of climate change, biodiversity, and health.
This chapter investigates the trajectory of establishing the Forest Stewardship Council (FSC) in the early 1990s as the first private transnational certification organization with an antagonistic stakeholder body. Its main contribution is a micro-analysis of the founding assembly in 1993. By investigating the role of brokers within the negotiation as one institutional scope condition for ‘arguing’ having occurred, the chapter adopts a dramaturgical approach. It contends that the authority of brokers is not necessarily institutionally given, but needs to be gained: brokers have to prove situationally that their knowledge is relevant and that they are speaking impartially in the interest of progress rather than their own. The chapter stresses the importance of procedural knowledge which brokers provide in contrast to policy knowledge.
Gilbert et al. conclude that evidence from the Open Science Collaboration’s Reproducibility Project: Psychology indicates high reproducibility, given the study methodology. Their very optimistic assessment is limited by statistical misconceptions and by causal inferences from selectively interpreted, correlational data. Using the Reproducibility Project: Psychology data, both optimistic and pessimistic conclusions about reproducibility are possible, and neither are yet warranted.
Harmonized data file as the basis for comparative analysis of quality of life in the Candidate Countries and the European Union member states, based on seven different data sets, one Eurobarometer survey covering 13 Candidate Countries with an identical set of variables conducted in April 2002, the other six Standard Eurobarometer of different subjects and fielded in different years, each with another set of questions identical with the CC Eurobarometer. Selected aggregate indicators of quality of life ... describing the social situation in the EU15 and Candidate Countries.
Pancreatic secretory zymogen-granule membrane glycoprotein 2 (GP2) has been identified to be a major autoantigenic target in Crohn’s disease patients. It was discussed recently that a long and a short isoform of GP2 exists whereas the short isoform is often detected by GP2-specific autoantibodies. In the outcome of inflammatory bowel diseases, these GP2-specific autoantibodies are discussed as new serological markers for diagnosis and therapeutic monitoring. To investigate this further, camelid nanobodies were generated by phage display and selected against the short isoform of GP2 in order to isolate specific tools for the discrimination of both isoforms. Nanobodies are single domain antibodies derived from camelid heavy chain only antibodies and characterized by a high stability and solubility. The selected candidates were expressed, purified and validated regarding their binding properties in different enzyme-linked immunosorbent assays formats, immunofluorescence, immunohistochemistry and surface plasmon resonance spectroscopy. Four different nanobodies could be selected whereof three recognize the short isoform of GP2 very specifically and one nanobody showed a high binding capacity for both isoforms. The KD values measured for all nanobodies were between 1.3 nM and 2.3 pM indicating highly specific binders suitable for the application as diagnostic tool in inflammatory bowel disease.
Monoclonal antibodies are highly valuable tools in biomedicine but the generation by hybridoma technology is very time-consuming and elaborate. In order to circumvent the consisting drawbacks an in vitro immunization approach was established by which murine as well as human monoclonal antibodies against a viral coat protein could be developed. The in vitro immunization process was performed by isolation of murine hematopoietic stem cells or human monocytes and an in vitro differentiation into immature dendritic cells. After antigen loading the cells were co-cultivated with naive T and B lymphocytes for three days in order to obtain antigen-specific B lymphocytes in culture, followed by fusion with murine myeloma cells or human/murine heteromyeloma cells. Antigen-specific hybridomas were selected and the generated antibodies were purified and characterized in this study by ELISA, western blot, gene sequencing, affinity measurements. Further the characteristics were compared to a monoclonal antibody against the same target generated by conventional hybridoma technology. Isotype detection revealed a murine IgM and a human IgG4 antibody in comparison to an IgG1 for the conventionally generated antibody. The antibodies derived from in vitro immunization showed indeed a lower affinity for the antigen as compared to the conventionally generated one, which is probably based on the significantly shorter B cell maturation (3 days) during the immunization process. Nevertheless, they were suitable for building up a sandwich based detection system. Therefore, the in vitro immunization approach seems to be a good and particularly fast alternative to conventional hybridoma technology.
Preface to BPM 2014
(2016)
In this Comment, we review the results of pattern formation in a reaction-diffusion-advection system following the kinetics of the Gray-Scott model. A recent paper by Das [Phys. Rev. E 92, 052914 (2015)] shows that spatiotemporal chaos of the intermittency type can disappear as the advective flow is increased. This study, however, refers to a single point in the space of kinetic parameters of the original Gray-Scott model. Here we show that the wealth of patterns increases substantially as some of these parameters are changed. In addition to spatiotemporal intermittency, defect-mediated turbulence can also be found. In all cases, however, the chaotic behavior is seen to disappear as the advective flow is increased, following a scenario similar to what was reported in our earlier work [I. Berenstein and C. Beta, Phys. Rev. E 86, 056205 (2012)] as well as by Das. We also point out that a similar phenomenon can be found in other reaction-diffusion-advection models, such as the Oregonator model for the Belousov-Zhabotinsky reaction under flow conditions.
The origin of ambling horses
(2016)
Horseback riding is the most fundamental use of domestic horses and has had a huge influence on the development of human societies for millennia. Over time, riding techniques and the style of riding improved. Therefore, horses with the ability to perform comfortable gaits (e.g. ambling or pacing), so-called ‘gaited’ horses, have been highly valued by humans, especially for long distance travel. Recently, the causative mutation for gaitedness in horses has been linked to a substitution causing a premature stop codon in the DMRT3 gene (DMRT3_Ser301STOP) [1]. In mice, Dmrt3 is expressed in spinal cord interneurons and plays an important role in the development of limb movement coordination [1]. Genotyping the position in 4396 modern horses from 141 breeds revealed that nowadays the mutated allele is distributed worldwide with an especially high frequency in gaited horses and breeds used for harness racing [2]. Here, we examine historic horse remains for the DMRT3 SNP, tracking the origin of gaitedness to Medieval England between 850 and 900 AD. The presence of the corresponding allele in Icelandic horses (9th–11th century) strongly suggests that ambling horses were brought from the British Isles to Iceland by Norse people. Considering the high frequency of the ambling allele in early Icelandic horses, we believe that Norse settlers selected for this comfortable mode of horse riding soon after arrival. The absence of the allele in samples from continental Europe (including Scandinavia) at this time implies that ambling horses may have spread from Iceland and maybe also the British Isles across the continent at a later date.