Smaller,Stronger, More Stable: Peptide Variants of a SARS-CoV-2 Neutralizing Miniprotein

Based on the structure of a de novo designed miniprotein (LCB1) in complex with the receptor binding domain (RBD) of the SARS-CoV-2 spike protein, we have generated and characterized truncated peptide variants of LCB1, which present only two of the three LCB1 helices, and which fully retained the virus neutralizing potency against different SARS-CoV-2 variants of concern (VOC). This antiviral activity was even 10-fold stronger for a cyclic variant of the two-helix peptides, as compared to the full-length peptide. Furthermore, the proteolytic stability of the cyclic peptide was substantially improved, rendering it a better potential candidate for SARS-CoV-2 therapy. In a more mechanistic approach, the peptides also served as tools to dissect the role of individual mutations in the RBD for the susceptibility of the resulting virus variants to neutralization by the peptides. As the peptides reported here were generated through chemical synthesis, rather than recombinant protein expression, they are amenable to further chemical modification, including the incorporation of a wide range of non-proteinogenic amino acids, with the aim to further stabilize the peptides against proteolytic degradation, as well as to improve the strength, as well the breadth, of their virus neutralizing capacity.     

Downstream environmental effects of dam operations: Changes in habitat quality for native fish species

Hydropeaking dam operation and water extractions for irrigation have been broadly stated as alterations to natural flow regimes, which have also been noticed in the Biobío Watershed, in Central Chile, since 1996. In the Biobío River, most of native fish species are endemic and very little is known about them. Their ecological and social values have never been estimated, and there is lack of information about their habitat preferences. Furthermore, changes on fish habitat availability due to natural and/or man‐made causes have not been evaluated. In this study, eight native fish species, in a representative reach of the Biobío River, were studied and their preferred habitats were surveyed and characterized. A hydrodynamic model was built and linked to the fish habitat simulation model CASiMiR. Fuzzy rules and fuzzy sets were developed for describing habitat preference of the native fish species. CASiMiR was then used to simulate how physical habitat conditions vary due to flow control (i.e. upstream dams). Results show how overall habitat quality, expressed as weighted usable area (WUA) and hydraulic habitat suitability (HHS), changes and fluctuates due to the dam operation and how the daily hydropeaking is influencing quantity, quality and location of different habitats. The study suggests that the analysed fish are highly susceptible to flow control, as dams are currently operated, and fish habitat improvement suggestions are proposed. Copyright © 2010 John Wiley & Sons, Ltd.     

Mismatch Modeling and Simulation—A Comprehensive Approach

This article describes a comprehensive approach to mismatch simulation and modeling as needed for integrated circuit design. Local device mismatch as well as global process variations and parameter correlations are regarded. A method for mismatch modeling based on spatial frequencies is described, which enables to overcome insufficiencies of the first order models. Measurement results are presented to demonstrate the achieved modeling precision. All models and methods mentioned here are commercially available in the simulation tool GAME (General Analysis of Mismatch Effects) which is used in the semiconductor industry since 1998.     

Tumor Infiltration with CD20+CD73+ B Cells Correlates with Better Outcome in Colorectal Cancer

Immunotherapy has become increasingly important in the treatment of colorectal cancer (CRC). Currently, CD73, also known as ecto-5′-nucleotidase (NT5E), has gained considerable interest as a potential therapeutic target. CD73 is one of the key enzymes catalyzing the conversion of extracellular ATP into adenosine, which in turn exerts potent immune suppressive effects. However, the role of CD73 expression on various cell types within the CRC tumor microenvironment remains unresolved. The expression of CD73 on various cell types has been described recently, but the role of CD73 on B-cells in CRC remains unclear. Therefore, we analyzed CD73 on B-cells, especially on tumor-infiltrating B-cells, in paired tumor and adjacent normal tissue samples from 62 eligible CRC patients. The highest expression of CD73 on tumor-infiltrating B-cells was identified on class-switched memory B-cells, followed by naive B-cells, whereas no CD73 expression was observed on plasmablasts. Clinicopathological correlation analysis revealed that higher CD73⁺ B-cells infiltration in the CRC tumors was associated with better overall survival. Moreover, metastasized patients showed a significantly decreased number of tumor-infiltrating CD73⁺ B-cells. Finally, neoadjuvant therapy correlated with reduced CD73⁺ B-cell numbers and CD73 expression on B-cells in the CRC tumors. As promising new immune therapies are being developed, the role of CD73⁺ B-cells and their subsets in the development of colorectal cancer should be further explored to find new therapeutic options.     

Absolute characterization of high numerical aperture microscope objectives utilizing a dipole scatterer

Measuring the aberrations of optical systems is an essential step in the fabrication of high precision optical components. Such a characterization is usually ba...     

The Internal Pressure Test in Experiment and Simulation—Influence of the Wall Thickness Variation and the Change of the Packaging Behavior after the Impact of Standard Liquids

The effect of the wall thickness variation of blow‐moulded bodies made of high‐density polyethylene on an internal pressure test after prestoring the packaging with standard liquids was evaluated in experiments and simulations. The objects of the investigation were jerrycans used for the transportation and storage of dangerous goods. The wall thickness was determined using two alternative methods to the magnetostatic measurement. These alternative methods are used for research purpose to get a volumetric model of the jerrycan wall as a geometric model for the simulation. The comparison of the experiments and the simulations of the internal pressure test were performed using the digital image correlation method. The integral strain and deformation of the whole jerrycan was detected by measuring the total mass of the jerrycan being filled with water during the internal pressure test. This is a suitable alternative to the optical measurements of local deformation by the digital image correlation method. Prestorage at 40 °C without the influence of chemicals strengthens the jerrycan, whereas the swelling effect of butyl acetate and hydrocarbon mixture softens the jerrycan. The comparison with the experiment is necessary to verify the accuracy of the simulation. It shows that the deformation can be simulated more precisely by using the actual measured geometry. The weakening of the high‐density polyethylene caused by a hydrocarbon mixture can be simulated using the Arrhenius equation. The aim of the simulation was to discover whether it is possible to use specimens to predict the behaviour of a packaging both after the influence of standard liquids. Copyright © 2012 John Wiley & Sons, Ltd.     

A cross‐cultural comparison of colour emotion for two‐colour combinations

Psychophysical experiments were conducted in the UK, Taiwan, France, Germany, Spain, Sweden, Argentina, and Iran to assess colour emotion for two‐colour combinations using semantic scales warm/cool, heavy/light, active/passive, and like/dislike. A total of 223 observers participated, each presented with 190 colour pairs as the stimuli, shown individually on a cathode ray tube display. The results show consistent responses across cultures only for warm/cool, heavy/light, and active/passive. The like/dislike scale, however, showed some differences between the observer groups, in particular between the Argentinian responses and those obtained from the other observers. Factor analysis reveals that the Argentinian observers preferred passive colour pairs to active ones more than the other observers. In addition to the cultural difference in like/dislike, the experimental results show some effects of gender, professional background (design vs. nondesign), and age. Female observers were found to prefer colour pairs with high‐lightness or low‐chroma values more than their male counterparts. Observers with a design background liked low‐chroma colour pairs or those containing colours of similar hue more than nondesign observers. Older observers liked colour pairs with high‐lightness or high‐chroma values more than young observers did. Based on the findings, a two‐level theory of colour emotion is proposed, in which warm/cool, heavy/light, and active/passive are identified as the reactive‐level responses and like/dislike the reflective‐level response. © 2010 Wiley Periodicals, Inc. Col Res Appl, 2012     

Problems and Benefits of Requirements Gathering With Focus Groups: A Case Study

Focus group interviews are considered as a rather weak, nonquantitative method of assessing user needs, ideas, and reactions in an early stage of the interface design process (Nielsen, 1993). Given this fact, it is relevant to reflect the practical use of focus groups step by step to determine their real strengths and limitations. In this article, we share our experience of planning, running, and analyzing focus groups within the design process of a home automation system. We describe the pre- and postwork in detail so that the pros and cons of gathering requirements with focus groups become apparent.