A Printable Photopolymerizable Thermosensitive p(HPMAm‐lactate)‐PEG Hydrogel for Tissue Engineering

Bioprinting is a new technology in regenerative medicine that allows the engineering of tissues by specific placement of cells in biomaterials. Importantly, the porosity and the relatively small dimensions of the fibers allow rapid diffusion of nutrients and metabolites. This technology requires the availability of hydrogels that ensure viability of encapsulated cells and have adequate mechanical properties for the preparation of structurally stable and well‐defined three‐dimensional constructs. The aim of this study is to evaluate the suitability of a biodegradable, photopolymerizable and thermosensitive A–B–A triblock copolymer hydrogel as a synthetic extracellular matrix for engineering tissues by means of three dimensional fiber deposition. The polymer is composed of poly(N‐(2‐hydroxypropyl)methacrylamide lactate) A‐blocks, partly derivatized with methacrylate groups, and hydrophilic poly(ethylene glycol) B‐blocks of a molecular weight of 10 kDa. Gels are obtained by thermal gelation and stabilized with additional chemical cross‐links by photopolymerization of the methacrylate groups coupled to the polymer. A power law dependence of the storage plateau modulus of the studied hydrogels on polymer concentration is observed for both thermally and chemically cross‐linked hydrogels. The hydrogels demonstrated mechanical characteristics similar to natural semi‐flexible polymers, including collagen. Moreover, the hydrogel shows suitable mechanical properties for bioprinting, allowing subsequent layer‐by‐layer deposition of gel fibers to form stable constructs up to at least 0.6 cm (height) with different patterns and strand spacing. The resulting constructs have reproducible vertical porosity and the ability to maintain separate localization of encapsulated fluorescent microspheres. Moreover, the constructs show an elastic modulus of 119 kPa (25 wt% polymer content) and a degradation time of approximately 190 days. Furthermore, high viability is observed for encapsulated chondrocytes after 1 and 3 days of culture. In summary, we conclude that the evaluated hydrogel is an interesting candidate for bioprinting applications.     

How fast do Chinese firms learn and catch up? Evidence from patent citations

There is a wealth of research on technological learning in developing countries, but few scholars have clearly addressed the issue of learning time in an empirical way. This paper aims to fill this void by presenting an empirical investigation of the time needed by Chinese firms to learn from the technologies that they have in-licensed. Furthermore, we analyzed in detail the antecedents leading to an acceleration or deceleration of the learning process among Chinese licensees. The results of an event history analysis indicate that recipient firms take on average 5.8 years to learn from their in-licensed technologies. The absorptive capacity and firm age of the licensees, the technology licensing scale, the age of the licensed technology, and the desorptive capability of the licensor firm all play a role in shortening the learning time.     

Potential and limits of FTIR methods for reclaimed asphalt characterisation

In recent years, as a result of both environmental policy and industrial economic strategy, the amount of asphalt pavement that has been recycled has risen dramatically. As a result of this, several international research projects have shown the need for improvements in reclaimed asphalt (RA) characterisation to support these higher recycling rates. During the life of a pavement, as well as the structural damage induced by traffic, the intrinsic properties of asphaltic materials are affected through the oxidative ageing of the bituminous binder. The molecular changes associated with this oxidation can be monitored via variations in Fourier transform infrared (FTIR) spectra. Therefore, if the relationships between binder properties, such as penetration, softening point and complex shear modulus and the spectra parameters can be established, the characterisation of RA produced by the milling of old pavements can be greatly improved. However, the interpretation of oxidation parameters from these spectra is not straightforward, and many different techniques are used to calculate them in the asphalt community. This paper gives a brief overview of asphalt oxidation and the FTIR principle. It then presents the results from four different calculation methods for the oxidation parameters applied to a set of more than 100 spectra obtained during the RILEM TC-ATB-TG5 round robin test. From this study, it is obvious that the conclusions of the analysis performed on the same set of raw spectra can differ considerably according to the FTIR oxidation index calculation method adopted. Using the RILEM database, the potential links between a given ageing index and the physical properties are then evaluated. As a result of this study it can be concluded that ageing comparison through FTIR should be considered as relative and restricted for use in measurements at different ageing steps on the same type of initial mixture. For FTIR spectra to be comparable between different laboratories, harmonisation of the data acquisition procedures is needed. Also the different calculation methods of the oxidation indicators seem to reflect different physical properties. So a first step toward harmonisation would be to agree on the relevant physical properties actually needed for efficient RA characterisation. This could then lead to a common FTIR index calculation method, which would reflect the properties of interest. For this, additional research is needed to improve knowledge of the relationship between the chemical oxidative process of a binder and the evolution of its physical properties.     

Cloning, characterization and functionality of the orotidine-5'-phosphate decarboxylase gene (URA3) of the glycolipid-producing yeast Candida bombicola

Candida bombicola is a yeast species known to synthesize glycolipids. Although these glycolipids find several industrial, cosmetic and pharmaceutical applications, very little is known about the genetics of C. bombicola. A basic tool for genetic study and modification is the availability of an efficient transformation and selection system. In order to develop such a system, the URA3 gene of Candida bombicola was isolated using degenerate PCR and genomic walking. The gene encodes for an enzyme of 262 amino acids and shows high homology with the known orotidine-5'-phosphate decarboxylases of several other yeast species. The functionality of the gene was proved by complementation of a URA3-negative Saccharomyces cerevisiae strain.     

Parental attachment, parental control, and early development of alcohol use: A longitudinal study.

The authors explored the predictive influence of both parental attachment and parental control on early onset of alcohol consumption in adolescence by use of a longitudinal sample of 1,012 young adolescents. Whether the relationship between parental control and adolescents' drinking is moderated by parental attachment was also examined. Consistent with other studies, attachment and strict control were cross-sectionally related to adolescents' alcohol use at all 3 measurements. However, the longitudinal results of structural equation modeling analyses suggest that a good attachment relationship between parent and child does not prevent adolescents from drinking. In addition, strict control was related to lower engagement in alcohol use. Furthermore, with regard to the moderating effect, parental attachment did not moderate longitudinally the association between parental control and an early development of alcohol use. Implications for further research are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Evaluation of Adverse Effects of Resorbable Hyaluronic Acid Fillers: Determination of Macrophage Responses

Resorbable tissue fillers for aesthetic purposes can induce severe complications including product migration, late swelling, and inflammatory reactions. The relation between product characteristics and adverse effects is not well understood. We hypothesized that the degree of cross-linking hyaluronic acid (HA) fillers was associated with the occurrence of adverse effects. Five experimental HA preparations similar to HA fillers were synthesized with an increasing degree of cross-linking. Furthermore, a series of commercial fillers (Perfectha^®) was obtained that differ in degradation time based on the size of their particulate HA components. Cytotoxic responses and cytokine production by human THP-1-derived macrophages exposed to extracts of the evaluated resorbable HA fillers were absent to minimal. Gene expression analysis of the HA-exposed macrophages revealed the responses related to cell cycle control and immune reactivity. Our results could not confirm the hypothesis that the level of cross-linking in our experimental HA fillers or the particulate size of commercial HA fillers is related to the induced biological responses. However, the evaluation of cytokine induction and gene expression in macrophages after biomaterial exposure presents promising opportunities for the development of methods to identify cellular processes that may be predictive for biomaterial-induced responses in patients.     

Transcriptomic Analysis in Human 3D Skin Model Injected with Resorbable Hyaluronic Acid Fillers Reveals Foreign Body Response

Usage of injectable dermal fillers applied for aesthetic purposes has extensively increased over the years. As such, the number of related adverse reactions has increased, including patients showing severe complications such as product migration, topical swelling and inflammatory reactions of the skin. In order to understand the underlying molecular events of these adverse reactions we performed a genome-wide gene expression study on the multi-cell type human Phenion^® Full-Thickness Skin Model exposed to five experimental hyaluronic acid (HA) preparations with increasing cross-linking degree, four commercial fillers from Perfectha^®, and non-resorbable filler Bio-Alcamid^®. In addition, we evaluated whether cross-linking degree or particle size of the HA-based fillers could be associated with the occurrence of adverse effects. In all cases, exposure to different HA fillers resulted in a clearly elevated gene expression of cytokines and chemokines related to acute inflammation as part of the foreign body response. Furthermore, for one experimental filler genes of OXPHOS complexes I-V were significantly down-regulated (adjusted p-value < 0.05), resulting in mitochondrial dysfunction which can be linked to over-expression of pro-inflammatory cytokines TNFα and IL-1β and chemokine CCL2. Our hypothesis that cross-linking degree or particle size of the HA-based fillers is related to the biological responses induced by these fillers could only partially be confirmed for particle size. In conclusion, our innovative approach resulted in gene expression changes from a human 3D skin model exposed to dermal fillers that mechanistically substantiate aforementioned adverse reactions, and thereby adds to the weight of evidence that these fillers may induce inflammatory and fibrotic responses.     

Trade-offs between mobility restrictions and transmission of SARS-CoV-2

In their response to the COVID-19 outbreak, governments face the dilemma to balance public health and economy. Mobility plays a central role in this dilemma because the movement of people enables both economic activity and virus spread. We use mobility data in the form of counts of travellers between regions, to extend the often-used SEIR models to include mobility between regions. We quantify the trade-off between mobility and infection spread in terms of a single parameter, to be chosen by policy makers, and propose strategies for restricting mobility so that the restrictions are minimal while the infection spread is effectively limited. We consider restrictions where the country is divided into regions, and study scenarios where mobility is allowed within these regions, and disallowed between them. We propose heuristic methods to approximate optimal choices for these regions. We evaluate the obtained restrictions based on our trade-off. The results show that our methods are especially effective when the infections are highly concentrated, e.g. around a few municipalities, as resulting from superspreading events that play an important role in the spread of COVID-19. We demonstrate our method in the example of the Netherlands. The results apply more broadly when mobility data are available.