We have characterized a cold-induced, boiling stable antifreeze protein. This highly active ice recrystallization inhibition protein shows a much lower thermal hysteresis effect and displays binding ...behavior that is uncharacteristic of any AFP from fish or insects. Ice-binding studies show it binds to the (
1
0
1
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) plane of ice and FTIR studies reveal that it has an unusual type of highly β-sheeted secondary structure. Ice-binding studies of both glycosylated and nonglycosylated expressed forms indicate that it adsorbs to ice through the protein backbone. These results are discussed in light of the currently proposed mechanisms of AFP action.
Cystine-dense peptides (CDPs) are a miniprotein class that can drug difficult targets with high affinity and low immunogenicity. Tools for their design, however, are not as developed as those for ...small-molecule and antibody drugs. CDPs have diverse taxonomic origins, but structural characterization is lacking. Here, we adapted Iterative Threading ASSEmbly Refinement (I-TASSER) and Rosetta protein modeling software for structural prediction of 4298 CDP scaffolds and performed in silico prescreening for CDP binders to targets of interest. Mammalian display screening of a library of docking-enriched, methionine and tyrosine scanned (DEMYS) CDPs against PD-L1 yielded binders from four distinct CDP scaffolds. One was affinity-matured, and cocrystallography yielded a high-affinity (
= 202 pM) PD-L1-binding CDP that competes with PD-1 for PD-L1 binding. Its subsequent incorporation into a CD3-binding bispecific T cell engager produced a molecule with pM-range in vitro T cell killing potency and which substantially extends survival in two different xenograft tumor-bearing mouse models. Both in vitro and in vivo, the CDP-incorporating bispecific molecule outperformed a comparator antibody-based molecule. This CDP modeling and DEMYS technique can accelerate CDP therapeutic development.
NASA's Wide-field Infrared Survey Explorer(WISE) spacecraft has been brought out of hibernation and has resumed surveying the sky at 3.4 and 4.6 mu m. The scientific objectives of the NEOWISE ...reactivation mission are to detect, track, and characterize near-Earth asteroids and comets. The search for minor planets resumed on 2013 December 23, and the first new near-Earth object (NEO) was discovered 6 days later. As an infrared survey, NEOWISE detects asteroids based on their thermal emission and is equally sensitive to high and low albedo objects; consequently, NEOWISE-discovered NEOs tend to be large and dark. Over the course of its three-year mission, NEOWISE will determine radiometrically derived diameters and albedos for ~2000 NEOs and tens of thousands of Main Belt asteroids. The 32 months of hibernation have had no significant effect on the mission's performance. Image quality, sensitivity, photometric and astrometric accuracy, completeness, and the rate of minor planet detections are all essentially unchanged from the prime mission's post-cryogenic phase.
This paper presents a monitoring method for on-line detection and indication of the occurrence of a cutting tool failure during high-speed face milling. The method consists of processing of the ...vibration signal using a reconfigurable infinite impulse response (IIR) bandpass digital filter and statistical techniques. The healthy tool threshold and the filter passband are adjusted and configured based on the cutting parameters that were set up during the machining process. For this process, sets of filter coefficients are pre-calculated for a number of defined insert passing frequencies ranges. The method is verified on-line during machining tests that are carried out at different tool failure levels and using various cutting parameters. In all experimental tests, the method allows the tool condition to be detected and indicated correctly. The proposed method is therefore shown to be simple, fast, computationally efficient, and reliable for the detection and indication of the presence of several types of tool failures for various cutting parameters, and the use of this method does not require any modification of the machine tool structure.
This study aims to improve the osseointegration of titanium implants through surface immobilization of peptides that induce a beneficial biological response. This was carried out biofunctionalizating ...titanium surfaces by silanization and subsequent covalent binding of a peptide with a sequence that promotes cell adhesion. Objective: The development of a new technique of immobilization of oligopeptides on the surface of titanium by using 3-chloropropyltrietoxisilane (CPTES) as bonding agent between the surface of titanium and the peptide. Materials and methods: A physicochemical characterization of the surfaces through the techniques of XPS, ToF-SIMS and contact angle was performed. Also cell adhesion studies have been conducted to evaluate in vitro biological response. Results: Through the process of silanization the titanium surface is completely covered with CPTES, which allows the subsequent accession of oligopeptides. The cell adhesion results show a higher cell adhesion and cell extension on biofunctionalized samples. Conclusions: We developed a system of covalent binding of oligopeptides on titanium surfaces that can modify the biological response of the attached cells.
In the last decade, there has been an increasing interest in the role of space in the learning process. However, there is limited research about how different Learning Spaces (LS) can lead to ...Sustainable Development (SD). Therefore, this paper presents a systematic literature review aimed to identify how physical, virtual, and hybrid LS have been designed and used to support SD. From an initial sample of 204 articles between 2009 and 2021 found in the Scopus database, 33 were included after inclusion criteria were applied. Findings show a wide variety of focus in the uses of LS (e.g., promote education quality, accessibility, or environmental sustainability). In general, the design process of LS implies a top-bottom approach, where students remain as passive actors. Nevertheless, it has been identified a growing interest in codesign processes that promote broader participation and bottom-top perspectives. This study contributes to orientate the understanding of the concept of LS, and looks towards inspiring new teaching and learning practices.
316L Stainless steel is one of the most used metallic material in orthopedical prosthesis, osteosinthesis plates, and cardiovascular stents. One of the main problems this material presents is the ...nickel and chromium release, specially the Ni ion release that provokes allergy in a high number of patients. Recently, experimental applications in vitro and in vivo seem to indicate that the thickness of the nature oxide of the stainless steel results in very strong reinforcement of the biological response and reduce the ion release due to the thicker surface oxide. It is possible to grow the natural chromium oxide layer by electrolytic method such anodization. In this study, two main anodization methods to grow chromium oxide on the 316L stainless steel have been evaluated. Nickel and Chromium ions release in human blood at 37 degrees C were detected at times of 1, 6, 11, and 15 days by means of atomic absorption in a graphite furnace (GAAF). Moreover, cytocompatibility tests were carried out. Perfusion experiments were performed to evaluate morphometrically platelet interaction with the material and to explore the potential thrombogenicity. The results showed a good cytocompatibility between the material and the osteoblast-like cells. However, these anodization methods released between 2 and 10 times more nickel and chromium than the original stainless steel, depending on the method used. Besides, anodized samples shown an increase of the percentage of surface covered by platelets. Consequently, the anodization methods studied do not improve the long-term behavior of the stainless steel for its application as cardiovascular stents.
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