In Vivo Albumin-Binding of a C-Functionalized Cyclam Platform for 64Cu-PET/CT Imaging in Breast Cancer Model

An improved glucose-chelator-albumin bioconjugate (GluCAB) derivative, GluCAB-2^Mal, has been synthesized and studied for in vivo ⁶⁴Cu-PET/CT imaging in breast cancer mice models together with its first-generation analogue GluCAB-1^Mal. The radioligand works on the principle of tumor targeting through the enhanced permeability and retention (EPR) effect with a supportive role played by glucose metabolism. [⁶⁴Cu]Cu-GluCAB-2^Mal (99 % RCP) exhibited high serum stability with immediate binding to serum proteins. In vivo experiments for comparison between tumor targeting of [⁶⁴Cu]Cu-GluCAB-2^Mal and previous-generation [⁶⁴Cu]Cu-GluCAB-1^Mal encompassed microPET/CT imaging and biodistribution analysis in an allograft E0771 breast cancer mouse model. Tumor uptake of [⁶⁴Cu]Cu-GluCAB-2^Mal was clearly evident with twice as much accumulation as compared to its predecessor and a tumor/muscle ratio of up to 5 after 24 h. Further comparison indicated a decrease in liver accumulation for [⁶⁴Cu]Cu-Glu-CAB-2^Mal.     

Linking entrepreneurial orientation to project success

Entrepreneurial orientation (EO) is a strategic posture of an organization, and it is related to basic policies and practices for the development of entrepreneurial actions looking for creating competitive advantages. This study develops and tests a model of the relationship between entrepreneurial orientation and project success in Brazilian context. As quantitative research, a survey was used to collect data. A sample of 100 valid answers from project practitioners was treated through the structural equation modeling method. As research implications, the main result points out the positive correlation between the entrepreneurial orientation and the project success, contributing to the development of this research subject and helping to minimize the gap in the literature that addresses the relationship between project success and EO. In practical terms, understanding that innovativeness, risk taking, proactiveness, autonomy and competitive aggressiveness (the dimensions of the EO) can contribute to project success and can also indirectly impact on organizational performance, could help organizations get competitive advantage when developing correlate factors. Finally, the results suggest that practices of project management can be aligned to the firm's entrepreneurial orientation to enable firms to attain better results in their projects and generate a competitive advantage. On other hand, given the proportion of the impact of EO on project success (20.3%) identified in this study, it is critical that project management professionals expand their horizon to recognize other factors that affect project success.     

Forest governance and REDD+ in Central Africa: towards a participatory model to increase stakeholder involvement in carbon markets

Forests play a significant role in the global carbon budget, and can help to mitigate climate change impacts. Tropical forests which experience high rates of deforestation and forest degradation are particularly important, as they are the most active in winter. Based on academic research into global environmental policies in Central Africa, this study finds that REDD+ policies can succeed when there is a carbon market mechanism that increases participation by developing countries, with better integration of forest management and community forestry. Incentives should be based on an appropriate baseline, accurate carbon stocks and fluxes estimation, a suitable silvicultural system and regular monitoring.     

R2D2: A scalable deep learning toolkit for medical imaging segmentation

Deep learning has gained a significant popularity in recent years thanks to its tremendous success across a wide range of relevant fields of applications, including medical image analysis domain in particular. Although convolutional neural networks (CNNs) based medical applications have been providing powerful solutions and revolutionizing medicine, efficiently training of CNNs models is a tedious and challenging task. It is a computationally intensive process taking long time and rare system resources, which represents a significant hindrance to scientific research progress. In order to address this challenge, we propose in this article, R2D2, a scalable intuitive deep learning toolkit for medical imaging semantic segmentation. To the best of our knowledge, the present work is the first that aims to tackle this issue by offering a novel distributed versions of two well-known and widely used CNN segmentation architectures [ie, fully convolutional network (FCN) and U-Net]. We introduce the design and the core building blocks of R2D2. We further present and analyze its experimental evaluation results on two different concrete medical imaging segmentation use cases. R2D2 achieves up to 17.5× and 10.4× speedup than single-node based training of U-Net and FCN, respectively, with a negligible, though still unexpected segmentation accuracy loss. R2D2 offers not only an empirical evidence and investigates in-depth the latest published works but also it facilitates and significantly reduces the effort required by researchers to quickly prototype and easily discover cutting-edge CNN configurations and architectures.     

The Role of Cell Cycle Regulators in Cell Survival—Dual Functions of Cyclin-Dependent Kinase 20 and p21Cip1/Waf1

The mammalian cell cycle is important in controlling normal cell proliferation and the development of various diseases. Cell cycle checkpoints are well regulated by both activators and inhibitors to avoid cell growth disorder and cancerogenesis. Cyclin dependent kinase 20 (CDK20) and p21^Cip1/Waf1 are widely recognized as key regulators of cell cycle checkpoints controlling cell proliferation/growth and involving in developing multiple cancers. Emerging evidence demonstrates that these two cell cycle regulators also play an essential role in promoting cell survival independent of the cell cycle, particularly in those cells with a limited capability of proliferation, such as cardiomyocytes. These findings bring new insights into understanding cytoprotection in these tissues. Here, we summarize the new progress of the studies on these two molecules in regulating cell cycle/growth, and their new roles in cell survival by inhibiting various cell death mechanisms. We also outline their potential implications in cancerogenesis and protection in heart diseases. This information renews the knowledge in molecular natures and cellular functions of these regulators, leading to a better understanding of the pathogenesis of the associated diseases and the discovery of new therapeutic strategies.     

Divide-and-Conquer Matrisome Protein (DC-MaP) Strategy: An MS-Friendly Approach to Proteomic Matrisome Characterization

Currently, the extracellular matrix (ECM) is considered a pivotal complex meshwork of macromolecules playing a plethora of biomolecular functions in health and disease beyond its commonly known mechanical role. Only by unraveling its composition can we leverage related tissue engineering and pharmacological efforts. Nevertheless, its unbiased proteomic identification still encounters some limitations mainly due to partial ECM enrichment by precipitation, sequential fractionation using unfriendly-mass spectrometry (MS) detergents, and resuspension with harsh reagents that need to be entirely removed prior to analysis. These methods can be technically challenging and labor-intensive, which affects the reproducibility of ECM identification and induces protein loss. Here, we present a simple new method applicable to tissue fragments of 10 mg and more. The technique has been validated on human ovarian tissue and involves a standardized procedure for sample processing with an MS-compatible detergent and combined centrifugation. This two-step protocol eliminates the need for laborious sample clarification and divides our samples into 2 fractions, soluble and insoluble, successively enriched with matrisome-associated (ECM-interacting) and core matrisome (structural ECM) proteins.     

Centrifuge modeling of the geotextile reinforced slope subject to drawdown

Geotextile is an effective reinforcement approach of slopes that experiences various loads such as drawdown. The geotextile reinforcement mechanism is essential to effectively evaluate the safety of geotextile-reinforced slopes under drawdown conditions. A series of drawdown centrifuge model tests were performed to investigate the deformation and failure behaviors of slopes reinforced with different geotextile layouts. The deformation and failure of unreinforced and reinforced slopes were compared and the geotextile reinforcement was indicated to significantly increase the safety limit and the ductility, reduce the displacement, and change the failure feature of slopes under drawdown conditions. The slopes exhibited remarkable progressive failure, downward from the slope top, under drawdown conditions. The progressive failure was induced by coupling of deformation localization and local failure based on full-field measurements of displacement of slopes subjected to drawdown. The geotextile reinforced the slope by decreasing and uniformizing the slope deformation by the soil-geotextile interaction. Through geotextile displacement analysis, the geotextile-reinforced slope was divided into the anchoring zone and the restricting zone by a boundary that was independent of the decrease of water level. The geotextile restrained the soil in the anchoring zone and the soil restrained the geotextile in the restricting zone. The reinforcement effect was distinct only when the geotextile was long enough to cross the slip surface of the unreinforced slope under drawdown conditions.     

Modified Galacto- or Fuco-Clusters Exploiting the Siderophore Pathway to Inhibit the LecA- or LecB-Associated Virulence of Pseudomonas aeruginosa

Galacto- and fuco-clusters conjugated with one to three catechol or hydroxamate motifs were synthesised to target LecA and LecB lectins of Pseudomonas aeruginosa (PA) localised in the outer membrane and inside the bacterium. The resulting glycocluster–pseudosiderophore conjugates were evaluated as Trojan horses to cross the outer membrane of PA by iron transport. The data suggest that glycoclusters with catechol moieties are able to hijack the iron transport, whereas those with hydroxamates showed strong nonspecific interactions. Mono- and tricatechol galactoclusters ( G1C and G3C ) were evaluated as inhibitors of infection by PA in comparison with the free galactocluster ( G0 ). All of them exhibited an inhibitory effect between 46 to 75 % at 100 μM, with a higher potency than G0 . This result shows that LecA localised in the outer membrane of PA is involved in the infection mechanism.