Instytut Podstawowych Problemów Techniki

Streszczenie:

The measurement and control of the heat transfer of sheet alloys in successive non-isothermal forming cycles is crucial to achieve the desired post-form properties and microstructure, which could not as of yet be realized by using traditional test facilities. In the present research, a novel heat transfer measurement facility was designed to generate and subsequently measure the in-situ heat transfer from a sheet alloy to multi-mediums such as forming tools, air, lubricant and coating. More importantly, the facility was able to use a single sheet alloy sample to perform successive non-isothermal forming cycles, and subsequently obtain high throughput experimental results including the temperature evolution, cooling rate, mechanical properties and microstructures of the alloy. The high throughput in-situ heat transfer measurement facility identified that the cooling rate of AA7075 was 152 °C/s and the mechanical strength was over 530 MPa in the 1st forming cycle. However, it decreased to less than the critical value of 100 °C/s in the successive 10th forming cycle, leading to a low mechanical strength of only 487 MPa. The identified variations that occur in the successive non-isothermal forming cycles would improve the consistency and accuracy of part performance in large-scale manufacturing.

Słowa kluczowe:

High throughput in-situ measurement,Heat transfer,Successive non-isothermal forming,Sheet alloys,Microstructure

Afiliacje autorów:

Streszczenie:

We used single-molecule AFM force spectroscopy (AFM-SMFS) in combination with click chemistry to mechanically dissociate anticalin, a non-antibody protein binding scaffold, from its target (CTLA-4), by pulling from eight different anchor residues. We found that pulling on the anticalin from residue 60 or 87 resulted in significantly higher rupture forces and a decrease in koff by 2–3 orders of magnitude over a force range of 50–200 pN. Five of the six internal anchor points gave rise to complexes significantly more stable than N- or C-terminal anchor points, rupturing at up to 250 pN at loading rates of 0.1–10 nN s^–1. Anisotropic network modeling and molecular dynamics simulations helped to explain the geometric dependency of mechanostability. These results demonstrate that optimization of attachment residue position on therapeutic binding scaffolds can provide large improvements in binding strength, allowing for mechanical affinity maturation under shear stress without mutation of binding interface residues.

Słowa kluczowe:

atomic force microscopy, protein engineering, single-molecule force spectroscopy, mechanical anisotropy, click chemistry, Go̅-Martini model, PCA

Afiliacje autorów:

Streszczenie:

In the present work, the compatibility relationship on the failure criteria between aluminium and polymer was established, and a mechanics-based model for a three-layered sandwich panel was developed based on the M-K model to predict its Forming Limit Diagram (FLD). A case study for a sandwich panel consisting of face layers from AA5754 aluminium alloy and a core layer from polyvinylidene difluoride (PVDF) was subsequently conducted, suggesting that the loading path of aluminium was linear and independent of the punch radius, while the risk for failure of PVDF increased with a decreasing radius and an increasing strain ratio. Therefore, the developed formability model would be conducive to the safety evaluation on the plastic forming and critical failure of composite sandwich panels.

Słowa kluczowe:

formability, M-K model, failure criteria, composite sandwich panel

Afiliacje autorów:

Streszczenie:

Anticalin is a non-immunoglobulin protein scaffold with potential as an alternative to monoclonal antibodies for nanoparticle-based drug delivery to cells displaying cytotoxic T-lymphocyte antigen 4 (CTLA-4). In this context, one limiting factor is the resistance of the anticalin:CTLA-4 complex to mechanical forces exerted by fluid shear stress. Here, we used single-molecule AFM force spectroscopy to screen residues along the anticalin backbone and determine the optimal pulling point that achieves maximum mechanical stability of the anticalin:CTLA-4 complex. We used non-canonical amino acid incorporation by amber suppression in the anticalin combined with click chemistry to attach an Fgβ peptide at internal residues of the anticalin. We then used the Fgβ peptide as a handle to mechanically dissociate anticalin from CTLA-4 by applying tension at 8 different anchor residues, and measure the unbinding energy landscape for each pulling geometry. We found that pulling from amino acid position 60 on the anticalin resulted in ∼100% higher mechanical stability of the complex as compared with either the N- or C-terminus. Molecular dynamics (MD) simulations using the coarse-grained Martini force field showed strong agreement with experiments and help explain the mechanisms underlying the geometric dependency of mechanical stability in this therapeutic molecular complex. These results demonstrate that the mechanical stability of receptor-ligand complexes can be optimized by controlling the loading geometry without making any changes to the binding interface.

Afiliacje autorów: