Challenges of supply chain visibility in distribution logistics – a literature review

Purpose: Complex supply chains characterise today\u27s economic life, which is determined by uncertainties and risks. Managing those successfully requires the development of resilient and flexible structures and processes based on information transparency, which enables better decision-making, especially in times of global crises. In this context, supply chain visibility (SCV) is defined as the stakeholders\u27 capability to have access to accurate and timely information about the flow of goods. Although the importance of SCV has been discussed in scientific literature and practice, challenges still inhibit improved SCV, particularly in distribution logistics. These have been scarcely investigated. The purpose of this study is to identify the challenges of SCV in distribution logistics and to provide implications to address them. Methodology: A qualitative content analysis (QCA) spanning 26 scientific articles was used. Results: We found evidence of challenges inhibiting SCV in distribution logistics within the three aggregated dimensions of inappropriate processes & technologies and information systems, lack of communication & trust, and insufficient monitoring & decision-making metrics. The findings show that trust can be seen as both a challenge and a prerequisite. Despite the possibilities of digitalisation, there exist trade-offs between manual processes and new technology implementation. Decision-making can be based on individual experiences, and monitoring can be difficult due to undefined metrics. Conclusion: Practitioners may use the findings to better identify and address the challenges of SCV in distribution logistics. Further studies could extend the findings through empirical studies, which would allow practitioners to assess their level of SCV and derive initial solutions

Layer-by-layer biofabrication of coronary covered stents with clickable elastin-like recombinamers

Producción CientíficaCoronary artery disease is the leading cause of death around the world. Endovascular stenting is the preferred treatment option to restore blood flow in the coronary arteries due to the lower perioperative morbidity when compared with more invasive treatment options. However, stent failure is still a major clinical problem, and further technological solutions are required to improve the performance of current stents. Here, we developed coronary stents covered with elastin-like recombinamers (ELRs) by exploiting a layer-by-layer technique combined with catalyst-free click chemistry. The resulting ELR-covered stents were intact after an in vitro simulated implantation procedure by balloon dilatation, which evidenced the elastic performance of the membrane. Additionally, the stents were mechanically stable under high flow conditions, which is in agreement with the covalent and stable nature of the click chemistry crosslinking strategy exploited during the ELR-membrane manufacturing and the successful embedding of the stent. Minimal platelet adhesion was detected after blood exposure in a Chandler loop as shown by scanning electron microscopy. The seeding of human endothelial progenitor cells (EPCs) on the ELR-membranes resulted in a confluent endothelial layer. These results prove the potential of this strategy to develop an advanced generation of coronary stents, with a stable and bioactive elastin-like membrane to exclude the atherosclerotic plaque from the blood stream or to seal coronary perforations and aneurysms, while providing a luminal surface with minimal platelet adhesion and favouring endothelialization.German federal and state governments (project StUpPD_330-18)Ministerio de Economía, Industria y Competitividad (projects PCIN-2015-010 / MAT2016-78903-R)Junta de Castilla y León (project VA317P18

Results of Operational Sea-Wave Monitoring with Radar Gauges

The German Federal Institute of Hydrology (BfG) developed a low-cost, non-contact sea-wave monitoring system based on a single radar sensor. A short description of the measuring system and the analysis of wave parameters is given. Furthermore, long-term wave measurements with this system, in combination with wind-measurements and statistics, are used to analyse possible future changes in wave heights. The results are in good agreement with those of other methods. Due to the good results achieved with the single radar sensor, an extension of the system which will be capable of recording directional information, is now under development. First results are presented in this study.El Instituto Federal Alemán de Hidrología (BfG) ha desarrollado un sistema de seguimiento de bajo coste, que no tiene contacto con la ola, basado en un sensor con un único radar. Se proporciona en el presente artículo una breve descripción del sistema de medición y del análisis de los parámetros de las olas. Además, las mediciones de olas por periodos largos efectuadas con este sistema, en combinación con las medidas del viento y las estadísti-cas, se utilizan para analizar los posibles cambios futuros en las alturas de las olas. Los resultados concuerdan con aquellos obtenidos mediante otros métodos. Debido a los buenos resultados obtenidos con el sensor de radar único, una extensión del sistema, que está ahora en fase de desarrollo, podrá registrar la información direccional. En este estudio se presentan los primeros resultados.L’Institut fédéral allemand d’hydrologie (BfG) a élaboré un système peu onéreux de surveillance à distance des vagues à partir d’un unique sondeur radar. Une brève description du système de mesure ainsi que l’analyse des paramètres des vagues est donnée. De plus, les mesures à long-terme des vagues avec ce système, combinées avec les mesures du vent et les statistiques sont utilisées pour analyser les changements futurs possibles des hauteurs de vagues. Les résultats concordent avec ceux établis au moyen d’autres méthodes. Du fait des bons résultats de l’unique sondeur radar, une extension du système qui pourrait enregistrer des informations relatives à la direction, est actuellement en cours de développement. Les premiers résultats sont présentés dans cette étud

c-Jun phosphorylation by the human vaccinia-related kinase 1 (VRK1) and its cooperation with the N-terminal kinase of c-Jun (JNK)

The VRK1 kinase is a novel Ser-Thr kinase in the human kinome that diverged from the casein kinase 1 branch. These kinases phosphorylate transcription factors related to stress responses, such as p53. In this report we have studied the phosphorylation of the transcription factor c-Jun in its N-terminal region. The VRK1 protein phosphorylates c-Jun with a Km of 0.4 lM, and is not inhibited by SP600125. VRK1 phosphorylates c-Jun in Ser63 and Ser73 in vitro, the same residues targeted by the N-terminal kinase of c-Jun (JNK). This phosphorylation induces the stabilization and accumulation of the c- Jun protein. VRK1 phosphorylates the endogenous c-Jun in Ser63. VRK1 activates c-Jun dependent transcription, which is dependent on phosphorylation of Ser63 and Ser73. The c-Jun with Ser63Ala and Ser73Ala substitutions is not transcriptionally active when cotransfected with VRK1. VRK1 interacts with c-Jun but not with JNK. The cotransfection of VRK1 and JNK has an additive effect on the transcriptional activation of c-Jun indicating that they can cooperate when both are at suboptimal dose; otherwise, maximum effect by one of them prevents the effect of the other. The VRK1-c-Jun connection represents a component of a new signaling pathway whose upstream elements remain to be identified.Peer reviewe

Macroporous click-elastin-like hydrogels for tissue engineering applications

Producción CientíficaElastin is a key extracellular matrix (ECM) protein that imparts functional elasticity to tissues and therefore an attractive candidate for bioengineering materials. Genetically engineered elastin-like recombinamers (ELRs) maintain inherent properties of the natural elastin (e.g. elastic behavior, bioactivity, low thrombogenicity, inverse temperature transition) while featuring precisely controlled composition, the possibility for biofunctionalization and non-animal origin. Recently the chemical modification of ELRs to enable their crosslinking via a catalyst-free click chemistry reaction, has further widened their applicability for tissue engineering. Despite these outstanding properties, the generation of macroporous click-ELR scaffolds with controlled, interconnected porosity has remained elusive so far. This significantly limits the potential of these materials as the porosity has a crucial role on cell infiltration, proliferation and ECM formation. In this study we propose a strategy to overcome this issue by adapting the salt leaching/gas foaming technique to click-ELRs. As result, macroporous hydrogels with tuned pore size and mechanical properties in the range of many native tissues were reproducibly obtained as demonstrated by rheological measurements and quantitative analysis of fluorescence, scanning electron and two-photon microscopy images. Additionally, the appropriate size and interconnectivity of the pores enabled smooth muscle cells to migrate into the click-ELR scaffolds and deposit extracellular matrix. The macroporous structure together with the elastic performance and bioactive character of ELRs, the specificity and non-toxic character of the catalyst-free click-chemistry reaction, make these scaffolds promising candidates for applications in tissue regeneration. This work expands the potential use of ELRs and click chemistry systems in general in different biomedical fields.Ministerio de Economía, Industria y Competitividad (Projects MAT2013-42473-R, MAT2015-68901-R, MAT2016- 78903-R)Junta de Castilla y León (programa de apoyo a proyectos de investigación - Ref. VA313U14, VA015U16 y PCIN-2015-010)gobierno federal y estatal de Alemania en el marco del Programa de Posición Rotacional i³tm (2014-R4-01) y del Programa START de la Facultad de Medicina de la Universidad de Aachen (proyecto nº 691713),el centro de imágenes del Centro Interdisciplinario de Investigación Clínica (IZKF) de la Facultad de Medicina de la Universidad de Aache

Guiding cell adhesion and motility by modulating cross-linking and topographic properties of microgel arrays

Biomaterial-driven modulation of cell adhesion and migration is a challenging aspect of tissue engineering. Here, we investigated the impact of surface-bound microgel arrays with variable geometry and adjustable cross-linking properties on cell adhesion and migration. We show that cell migration is inversely correlated with microgel array spacing, whereas directionality increases as array spacing increases. Focal adhesion dynamics is also modulated by microgel topography resulting in less dynamic focal adhesions on surface-bound microgels. Microgels also modulate the motility and adhesion of Sertoli cells used as a model for cell migration and adhesion. Both focal adhesion dynamics and speed are reduced on microgels. Interestingly, Gas2L1, a component of the cytoskeleton that mediates the interaction between microtubules and microfilaments, is dispensable for the regulation of cell adhesion and migration on microgels. Finally, increasing microgel cross-linking causes a clear reduction of focal adhesion turnover in Sertoli cells. These findings not only show that spacing and rigidity of surface-grafted microgels arrays can be effectively used to modulate cell adhesion and motility of diverse cellular systems, but they also form the basis for future developments in the fields of medicine and tissue engineering

A Dexamethasone-Loaded Polymeric Electrospun Construct as a Tubular Cardiovascular Implant

Cardiovascular tissue engineering is providing many solutions to cardiovascular diseases. The complex disease demands necessitating tissue-engineered constructs with enhanced functionality. In this study, we are presenting the production of a dexamethasone (DEX)-loaded electrospun tubular polymeric poly(l-lactide) (PLA) or poly(d,l-lactide-co-glycolide) (PLGA) construct which contains iPSC-CMs (induced pluripotent stem cell cardiomyocytes), HUVSMCs (human umbilical vein smooth muscle cells), and HUVECs (human umbilical vein endothelial cells) embedded in fibrin gel. The electrospun tube diameter was calculated, as well as the DEX release for 50 days for 2 different DEX concentrations. Furthermore, we investigated the influence of the polymer composition and concentration on the function of the fibrin gels by imaging and quantification of CD31, alpha-smooth muscle actin (aSMA), collagen I (col I), sarcomeric alpha actinin (SAA), and Connexin 43 (Cx43). We evaluated the cytotoxicity and cell proliferation of HUVECs and HUVSMCs cultivated in PLA and PLGA polymeric sheets. The immunohistochemistry results showed efficient iPSC-CM marker expression, while the HUVEC toxicity was higher than the respective HUVSMC value. In total, our study emphasizes the combination of fibrin gel and electrospinning in a functionalized construct, which includes three cell types and provides useful insights of the DEX release and cytotoxicity in a tissue engineering perspective

Physiological Mineralization during In Vitro Osteogenesis in a Biomimetic Spheroid Culture Model

Bone health-targeting drug development strategies still largely rely on inferior 2D in vitro screenings. We aimed at developing a scaffold-free progenitor cell-based 3D biomineralization model for more physiological high-throughput screenings. MC3T3-E1 pre-osteoblasts were cultured in α-MEM with 10% FCS, at 37 °C and 5% CO2 for up to 28 days, in non-adherent V-shaped plates to form uniformly sized 3D spheroids. Osteogenic differentiation was induced by 10 mM β-glycerophosphate and 50 µg/mL ascorbic acid. Mineralization stages were assessed through studying expression of marker genes, alkaline phosphatase activity, and calcium deposition by histochemistry. Mineralization quality was evaluated by Fourier transformed infrared (FTIR) and scanning electron microscopic (SEM) analyses and quantified by micro-CT analyses. Expression profiles of selected early- and late-stage osteoblast differentiation markers indicated a well-developed 3D biomineralization process with strongly upregulated Col1a1, Bglap and Alpl mRNA levels and type I collagen- and osteocalcin-positive immunohistochemistry (IHC). A dynamic biomineralization process with increasing mineral densities was observed during the second half of the culture period. SEM–Energy-Dispersive X-ray analyses (EDX) and FTIR ultimately confirmed a native bone-like hydroxyapatite mineral deposition ex vivo. We thus established a robust and versatile biomimetic, and high-throughput compatible, cost-efficient spheroid culture model with a native bone-like mineralization for improved pharmacological ex vivo screenings