Surface Binding of TOTAPOL Assists Structural Investigations of Amyloid Fibrils by Dynamic Nuclear Polarization NMR Spectroscopy

Dynamic nuclear polarization (DNP) NMR can enhance sensitivity but often comes at the price of a substantial loss of resolution. Two major factors affect spectral quality: low‐temperature heterogeneous line broadening and paramagnetic relaxation enhancement (PRE) effects. Investigations by NMR spectroscopy, isothermal titration calorimetry (ITC), and EPR revealed a new substantial affinity of TOTAPOL to amyloid surfaces, very similar to that shown by the fluorescent dye thioflavin‐T (ThT). As a consequence, DNP spectra with remarkably good resolution and still reasonable enhancement could be obtained at very low TOTAPOL concentrations, typically 400 times lower than commonly employed. These spectra yielded several long‐range constraints that were difficult to obtain without DNP. Our findings open up new strategies for structural studies with DNP NMR spectroscopy on amyloids that can bind the biradical with affinity similar to that shown towards ThT.     

Inhibitors against Fungal Cell Wall Remodeling Enzymes

Fungal β‐1,3‐glucan glucanosyltransferases are glucan‐remodeling enzymes that play important roles in cell wall integrity, and are essential for the viability of pathogenic fungi and yeasts. As such, they are considered possible drug targets, although inhibitors of this class of enzymes have not yet been reported. Herein we report a multidisciplinary approach based on a structure‐guided design using a highly conserved transglycosylase from Sacharomyces cerevisiae, that leads to carbohydrate derivatives with high affinity for Aspergillus fumigatus Gel4. We demonstrate by X‐ray crystallography that the compounds bind in the active site of Gas2/Gel4 and interact with the catalytic machinery. The topological analysis of noncovalent interactions demonstrates that the combination of a triazole with positively charged aromatic moieties are important for optimal interactions with Gas2/Gel4 through unusual pyridinium cation–π and face‐to‐face π–π interactions. The lead compound is capable of inhibiting AfGel4 with an IC₅₀ value of 42 μm .     

Digitally reconstructing Van Gogh's Field with Irises near Arles part 3: Determining the original colors

In earlier articles, we determined the spatial distributions and concentrations of all pigments used by Van Gogh in his painting Field with Irises near Arles. The colors of some pigments are expected to have changed over time, especially those of chrome yellow, cochineal, and eosin lake. For all pigments in this painting, we made physical paint reconstructions by following historical sources on raw materials and production processes, and we determined their optical properties. We combined this with pigment concentration maps to reconstruct the original colors of the painting digitally. When substituting the reconstruction paints into the calculations, we found that technical‐scientific data was not sufficient to resolve several issues. In those cases, discussions within the broad interdisciplinary team allowed us to make informed decisions. These issues refer to the representation of the sky area, and the original contributions of the red lake pigments to local colors. The digitally reconstructed colors of the painting show that due to discoloring of red lake pigments, the irises in the field have changed from a warm purple to purplish blue, and many pink spots in the field have turned to white. The range of yellows in the field has decreased and partly turned to dark brown. The digital reconstruction gives a better understanding of the color scheme used by Van Gogh when compared to remarks the artist made in letters when describing this painting. Also, the original color composition is seen to be aligned with color theories on which Van Gogh based his work.     

Biaxial Orientation of Poly(ethylene 2,5‐furandicarboxylate): An Explorative Study

The biaxial orientation behavior of poly(ethylene 2,5‐furandicarboxylate) (PEF) is studied in comparison to poly(ethylene terephthalate) (PET). PEF is a polyester that can be produced through similar steps as PET but using 100% biobased 2,5‐furandicarboxylic acid instead of terephthalic acid. This work highlights the stress–strain behavior of PEF during biaxial orientation at various temperatures. Strain hardening and strain‐induced crystallization in the oriented PEF samples generally appeared at higher stretch ratios for PEF than for PET at comparable molecular weight, while somewhat lower degrees of crystallinity are reached in PEF. Shrinkage in oriented PEF is found to be on par with PET in the region of the glass transition. Higher modulus and improved barrier properties, compared to PET, are found in the oriented materials when sufficiently high stretch ratios are applied in biaxial orientation.     

Analysis of mixed motion in deterministic ratchets via experiment and particle simulation

Deterministic lateral displacement (DLD) ratchets are microfluidic devices, which are used for size-based sorting of cells or DNA. Based on their size, particles are showing different kinds of motion, leading to their fractionation. In earlier studies, so-called zigzag and displacement motions are observed, and in recent study by our group (Kulrattanarak et al., Meas Sci Technol, 2010a; J Colloid Interface Sci, 2010b), we have shown that also mixed motion occurs, which is an irregular alternation of zigzag and displacement motion. We have shown that the mixed motion is due to asymmetry of the flow lane distribution, induced by the symmetry breaking of the oblique primitive lattice cell (Kulrattanarak et al. 2010b). In this study, we investigate mixed motion in depth by numerical and experimental analysis. Via 3D simulations, we have computed explicit particle trajectories in DLD, and are able to show that there are two critical length scales determining the type of motion. The first length scale d _f,1 is the first flow lane width, which determines the transition between zigzag motion and mixed motion. The other length scale, d _f,c , determines the transition between mixed motion and displacement motion. Based on our experimental and numerical results we have been able to correlate the migration angle of particles showing mixed motion to the particle size, relative to the two critical length scales d _f,1 and d _f,c .     

When do agents outperform centralized algorithms?

Multi-agent systems (MAS) literature often assumes decentralized MAS to be especially suited for dynamic and large scale problems. In operational research, however, the prevailing paradigm is the use of centralized algorithms. Present paper empirically evaluates whether a multi-agent system can outperform a centralized algorithm in dynamic and large scale logistics problems. This evaluation is novel in three aspects: (1) to ensure fairness both implementations are subject to the same constraints with respect to hardware resources and software limitations, (2) the implementations are systematically evaluated with varying problem properties, and (3) all code is open source, facilitating reproduction and extension of the experiments. Existing work lacks a systematic evaluation of centralized versus decentralized paradigms due to the absence of a real-time logistics simulator with support for both paradigms and a dataset of problem instances with varying properties. We extended an existing logistics simulator to be able to perform real-time experiments and we use a recent dataset of dynamic pickup-and-delivery problem with time windows instances with varying levels of dynamism, urgency, and scale. The OptaPlanner constraint satisfaction solver is used in a centralized way to compute a global schedule and used as part of a decentralized MAS based on the dynamic contract-net protocol (DynCNET) algorithm. The experiments show that the DynCNET MAS finds solutions with a relatively lower operating cost when a problem has all following three properties: medium to high dynamism, high urgency, and medium to large scale. In these circumstances, the centralized algorithm finds solutions with an average cost of 112.3% of the solutions found by the MAS. However, averaged over all scenario types, the average cost of the centralized algorithm is 94.2%. The results indicate that the MAS performs best on very urgent problems that are medium to large scale.     

Passively Q-switched 1.57-microm intracavity optical parametric oscillator

We demonstrate an eye-safe KTP-based optical parametric oscillator (OPO) driven intracavity by a diode-pumped 1064-nm Nd:YAG laser, passively Q-switched by a Cr4+:YAG crystal. The characteristics of this system, which operates at 1570 nm with a repetition rate as high as 50 Hz, are studied as a function of Cr4+:YAG optical density. Under optimum conditions the OPO generates 1.5-mJ, 3.4 +/- 0.1-ns pulses in a single transverse mode. For a Cr4+:YAG Q-switch element with an optical density of 0.5 the conversion efficiency of the intracavity energy is approximately 45% with the ratio of OPO to Nd:YAG peak-pulse intensity exceeding unity. These and other OPO characteristics compare favorably with a simple rate equation model of the OPO dynamics.     

Origin of Anomalous Bump at Low Temperatures in the c-Axis Optical Conductivity of High-T c Cuprates

The optical spectra of some high-Tc cuprates show anomalous bump around 450 cm ^–1 and dramatic phonon changes for E parallel to c axis, which grows at low temperatures. This phenomenon has been observed in Yba ₂ Cu ₃ O _6.6, YBa ₂ Cu ₄ O ₈ and Pb ₂ Sr ₂ RCu ₃ O ₈ , but not in (La,Sr) ₂ CuO ₄. In this study, we report the first observation of a similar anomaly in underdoped Bi ₂ Sr ₂ CaCu ₂ O ₈. The spectra were measured from two mosaics of Ba ₂ Sr ₂ CaCu ₂ O ₈ with T _c 80 K and 60 K. Considering that these spectral features seem to be common for all high-T _c cuprates with double CuO pyramids, we propose one plausible explanation that it is attributed to the second Josephson plasmon for intracell coupling in the Josephson coupled layer model.     

Grounded design: Design patterns as the link between theory and practice

The process of designing a networked learning environment can be characterized by a high degree of uncertainty. This is especially true when the design includes innovative technologies. It is difficult to design a networked learning environment that closely fits the requirements of the educational practice. Often the technology seems leading in the design process because it is the most tangible aspect of the e-learning environment. This brings along the risk that the technology becomes detached from its context of use.Design patterns are a means to overcome this problem of detachment between design and practice. Design patterns make the tight relationship between the two more explicit. In this paper we further elaborate on the relationship between design and practice. We will stress the importance of theory in the development of design patterns. Theory development is an essential aspect of our approach to the development of design patterns. The approach is oriented towards a systematic analysis of problems and the development of conceptual models that guide the definition and evaluation of design patterns. In this paper we present a case study of how the approach was used to develop design patterns for networked learning in the classroom.     

Process diagnostics using trace alignment: Opportunities, issues, and challenges

Business processes leave trails in a variety of data sources (e.g., audit trails, databases, and transaction logs). Hence, every process instance can be described by a trace, i.e., a sequence of events. Process mining techniques are able to extract knowledge from such traces and provide a welcome extension to the repertoire of business process analysis techniques. Recently, process mining techniques have been adopted in various commercial BPM systems (e.g., BPM|one, Futura Reflect, ARIS PPM, Fujitsu Interstage, Businesscape, Iontas PDF, and QPR PA). Unfortunately, traditional process discovery algorithms have problems dealing with less structured processes. The resulting models are difficult to comprehend or even misleading. Therefore, we propose a new approach based on trace alignment. The goal is to align traces in such a way that event logs can be explored easily. Trace alignment can be used to explore the process in the early stages of analysis and to answer specific questions in later stages of analysis. Hence, it complements existing process mining techniques focusing on discovery and conformance checking. The proposed techniques have been implemented as plugins in the ProM framework. We report the results of trace alignment on one synthetic and two real-life event logs, and show that trace alignment has significant promise in process diagnostic efforts.