Study on the replication quality of micro-structures in the injection molding process with dynamical tool tempering systems

The injection molding of micro-structures is a promising mass-production method for a broad range of materials. However, the replication quality of these structures depends significantly on the heat flow during the filling stage. In this paper, the filling and heat transfer of v-groove and random structures below 5 μm is investigated with the help of an AFM (atomic force microscope) and thermo couples. A numerical model is developed to predict the filling of surface structures during the filling and packing stage. The model implies the use of simple fully developed flow models taking the power-law material model into account. This permits investigation into which ways several processing parameters affect the polymer flow in the surface structures. The mold wall temperature, which has significant effects on the polymer flow, is varied by using a variothermal mold temperature control system to validate the model proposed.     

Fluid dynamics of a quantized vortex filament in a hole

The behavior of nucleated vortex loops and of remanent vortex filaments in idealized circular and slit-like orifices has been investigated by direct computation. It is found that such vortices can be stretched by the diverging flow on the exit side of the orifice. The energy needed to stretch the vortex is abstracted from the flow field and observed as dissipation. This occurs in the form of discrete phase-slip events in the case of nucleated vortex loops, and in the form of multiple-phase-slip cascades when a remanent vortex is involved.     

Sources of failure in the public switched telephone network

What makes a distributed system reliable? A study of failures in the US public switched telephone network (PSTN) shows that human intervention is one key to this large system's reliability. Software is not the weak link in the PSTN system's dependability. Extensive use of built-in self-test and recovery mechanisms in major system components (switches) contributed to software dependability and are significant design features in the PSTN. The network's high dependability indicates that the trade-off between dependability gains and complexity introduced by built-in self-test and recovery mechanisms can be positive. Likewise, the tradeoff between complex interactions and the loose coupling of system components has been positive, permitting quick human intervention in most system failures and resulting in an extremely reliable system     

Nanobody Paratope Ensembles in Solution Characterized by MD Simulations and NMR

Variable domains of camelid antibodies (so-called nanobodies or V_HH) are the smallest antibody fragments that retain complete functionality and therapeutic potential. Understanding of the nanobody-binding interface has become a pre-requisite for rational antibody design and engineering. The nanobody-binding interface consists of up to three hypervariable loops, known as the CDR loops. Here, we structurally and dynamically characterize the conformational diversity of an anti-GFP-binding nanobody by using molecular dynamics simulations in combination with experimentally derived data from nuclear magnetic resonance (NMR) spectroscopy. The NMR data contain both structural and dynamic information resolved at various timescales, which allows an assessment of the quality of protein MD simulations. Thus, in this study, we compared the ensembles for the anti-GFP-binding nanobody obtained from MD simulations with results from NMR. We find excellent agreement of the NOE-derived distance maps obtained from NMR and MD simulations and observe similar conformational spaces for the simulations with and without NOE time-averaged restraints. We also compare the measured and calculated order parameters and find generally good agreement for the motions observed in the ps–ns timescale, in particular for the CDR3 loop. Understanding of the CDR3 loop dynamics is especially critical for nanobodies, as this loop is typically critical for antigen recognition.     

Transparent, conductive graphene electrodes for dye-sensitized solar cells

Transparent, conductive, and ultrathin graphene films, as an alternative to the ubiquitously employed metal oxides window electrodes for solid-state dye-sensitized solar cells, are demonstrated. These graphene films are fabricated from exfoliated graphite oxide, followed by thermal reduction. The obtained films exhibit a high conductivity of 550 S/cm and a transparency of more than 70% over 1000-3000 nm. Furthermore, they show high chemical and thermal stabilities as well as an ultrasmooth surface with tunable wettability.     

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.     

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...