Spectroscopic and in vitro Investigations of Fe2+/α-Ketoglutarate-Dependent Enzymes Involved in Nucleic Acid Repair and Modification

The activation of molecular oxygen for the highly selective functionalization and repair of DNA and RNA nucleobases is achieved by α-ketoglutarate (α-KG)/iron-dependent dioxygenases. Of special interest are the human homologues AlkBH of Escherichia coli EcAlkB and ten-eleven translocation (TET) enzymes. These enzymes are involved in demethylation or dealkylation of DNA and RNA, although additional physiological functions are continuously being found. Given their importance, studying enzyme-substrate interactions, turnover and kinetic parameters is pivotal for the understanding of the mode of action of these enzymes. Diverse analytical methods, including X-ray crystallography, UV/Vis absorption, electron paramagnetic resonance (EPR), circular dichroism (CD) and nuclear magnetic resonance (NMR) spectroscopy have been employed to study the changes in the active site and the overall enzyme structure upon substrate, cofactor, and inhibitor addition. Several methods are now available to assess the activity of these enzymes. By discussing limitations and possibilities of these techniques for EcAlkB, AlkBH and TET we aim to give a comprehensive synopsis from a bioinorganic point-of-view, addressing researchers from different disciplines working in the highly interdisciplinary and rapidly evolving field of epigenetic processes and DNA/RNA repair and modification.     

Composition and properties of bovine milk: A study from dairy farms in northern Sweden; Part II. Effect of monthly variation

This study investigated the influence of monthly variation on the composition and properties of raw farm milk collected as part of a full-scale cheese-making trial in a region in northern Sweden. In our companion paper, the contribution of on-farm factors to the variation in milk quality attributes is described. In total, 42 dairy farms were recruited for the study, and farm milk samples were collected monthly over 1 yr and characterized for quality attributes of importance for cheese making. Principal component analysis suggested that milk samples collected during the outdoor period (June–September) were different from milk samples collected during the indoor period. Despite the interaction with the milking system, the results showed that fat and protein concentrations were lower in milk collected during May through August, and lactose concentration was higher in milk collected during April through July than for the other months. Concentrations of free fatty acids were generally low, with the highest value (0.86 mmol/100 g of fat) observed in February and the lowest (0.70 mmol/100 g of fat) observed in June. Plasmin and plasminogen-derived activities varied with sampling month without a clear seasonal pattern. The pH of farm tank milk ranged from 6.60 to 6.82, with the lowest and highest values in September and February, respectively. The highest somatic cell count was observed in August (201 × 10³ cells/mL) and the lowest in April (143 × 10³ cells/mL). The highest value of gel strength, was recorded in December (88 Pa) and the lowest in July (64 Pa). Rennet coagulation time and gel strength were inversely correlated, with the lowest rennet coagulation time value observed in December. Orthogonal projections to latent structures (OPLS) and discriminant analysis adaptation of OPLS identified casein micelle size and total proteolysis as the milk quality attributes with major responses to sampling month, with smaller casein micelle size and higher total proteolysis associated with the outdoor months. Using discriminant analysis adaptation of OPLS to further investigate causes behind the variation in milk traits revealed that there were factors in addition to feeding on pasture that differed between outdoor and indoor months. Because fresh grass was seldom the primary feed in the region during the outdoor period, grazing was not considered the sole reason for the observed difference between outdoor and indoor periods in raw milk quality attributes.     

Site-Specific Isotopic Labeling (SSIL): Access to High-Resolution Structural and Dynamic Information in Low-Complexity Proteins

Remarkable technical progress in the area of structural biology has paved the way to study previously inaccessible targets. For example, large protein complexes can now be easily investigated by cryo-electron microscopy, and modern high-field NMR magnets have challenged the limits of high-resolution characterization of proteins in solution. However, the structural and dynamic characteristics of certain proteins with important functions still cannot be probed by conventional methods. These proteins in question contain low-complexity regions (LCRs), compositionally biased sequences where only a limited number of amino acids is repeated multiple times, which hamper their characterization. This Concept article describes a site-specific isotopic labeling (SSIL) strategy, which combines nonsense suppression and cell-free protein synthesis to overcome these limitations. An overview on how poly-glutamine tracts were made amenable to high-resolution structural studies is used to illustrate the usefulness of SSIL. Furthermore, we discuss the potential of this methodology to give further insights into the roles of LCRs in human pathologies and liquid–liquid phase separation, as well as the challenges that must be addressed in the future for the popularization of SSIL.     

Structure–Transport Correlation Reveals Anisotropic Charge Transport in Coupled PbS Nanocrystal Superlattices

The assembly of colloidal semiconductive nanocrystals into highly ordered superlattices predicts novel structure-related properties by design. However, those structure–property relationships, such as charge transport depending on the structure or even directions of the superlattice, have remained unrevealed so far. Here, electric transport measurements and X-ray nanodiffraction are performed on self-assembled lead sulfide nanocrystal superlattices to investigate direction-dependent charge carrier transport in microscopic domains of these materials. By angular X-ray cross-correlation analysis, the structure and orientation of individual superlattices is determined, which are directly correlated with the electronic properties of the same microdomains. By that, strong evidence for the effect of superlattice crystallinity on the electric conductivity is found. Further, anisotropic charge transport in highly ordered monocrystalline domains is revealed, which is attributed to the dominant effect of shortest interparticle distance. This implies that transport anisotropy should be a general feature of weakly coupled nanocrystal superlattices.     

Process oriented industrial classification based on energy intensity

The Standard Industrial Classification (SIC) code has been used in the United States to categorize manufactured products. This classification is useful for many commercial and business related applications. However, when checked against energy use data collected through the Industrial Assessment Center (IAC) of San Diego State University (SDSU), the energy use profile of the SIC groups showed objectionable deviations within each group, rendering the code less than useful for overall energy based grouping and analyses. In this paper, a Process Oriented Energy Intensity Classification (POEIC) is introduced. When examined with data from about 270 plants of the IAC, this new classification offered more coherent and consistent energy use profile with smaller standard deviation for the selected energy intensity parameters than that of the SIC code.     

On the interaction between system and user characteristics

. The development of a representational framework, based on Moran's Command Language Grammar, for constructing adaptive computer systems is the main topic of this paper. A model of the user interface is developed of which two aspects are discussed: the mental model in the mind of the user and the perceptual model on the side of the machine. Cognitive style and personality factors are considered in their relation to the development of the mental model. The concept of metacommunication is analysed and discussed on all levels of Moran's CLG.     

Conceptualizing development in information and communication technology for development (ICT4D)

ABSTRACT

ICT4D research is faced with the challenge of rapidly changing technologies and increasingly complex social dynamics and development processes. We argue that ICT4D research requires a more acute sense of where our research is situated within a broader picture of development, e.g. with a better understanding of development processes, their ideological nature, the power structures and driving forces, and the mechanisms through which ICTs may be embedded in and shape these processes. Such a reflexivity is crucial not least in justifying our claims of contribution, but also in understanding the implications and potential impact of our research and practice. This editorial seeks to explore key conceptual components in ICT4D and their relationships, including dimensions of development, perspectives of development, conceptions of artefacts, and theory of change. A tentative conceptual schema is presented that connects these conceptual components.     

Strategic ramp-up planning in automotive production networks

In many industries, the frequency of production ramp-ups has increased due to shorter product life cycles and increased product variety. Production often takes place at globally dispersed facilities for customers in multiple markets, for example, in the automotive industry. Therefore, ramp-up planning must be carried out for a network. The planning problem at hand is to simultaneously optimise the allocation of products of a common product platform to plants, the timing of ramp-ups and ramp-downs, ramp-up duration and shape of capacity and production and transportation volumes with respect to the net present value of the profit. We develop a hierarchical planning framework and place strategic ramp-up planning therein. We provide a mixed integer programming model for this planning problem. Following the example of a German car manufacturer in the premium segment, we conduct a numerical analysis to obtain insights into optimal ramp-up and ramp-down decisions. The results show that it could be beneficial to use both steep and flat ramp-up curves. The impact of flexibility in the choice of ramp-up slots and the number of ramp-up curves provided on the objective value is substantial. The strategic ramp-up planning model outperforms sequential planning approaches.