Hedging and standard - MRP

In standard-MRP packages it is possible to use safety stocknorms. In none of the standard-MRP packages however, it is possible to use hedging as an alternative technique for safety stocknorras, although this technique has several advantages from a theoretical point of view. At Eindhoven University of Technology an attempt is made to incorporate hedging in an existing MRP-package.From the functional design it appeared, that what originally seemed to be a simple addition to the options available in an MRP-package, turned out to have a rather large impact on many of the MRP-modules.<br/

Regional geothermal aquifer architecture of the fluvial Lower Cretaceous Nieuwerkerk Formation – a palynological analysis

The primary challenge for efficient geothermal doublet design and deployment is the adequate prediction of the size, shape, lateral extent and thickness (or aquifer architecture) of aquifers. In the West Netherlands Basin, fluvial Lower Cretaceous sandstone-rich successions form the main aquifers for geothermal heat exploitation. Large variations in the thickness of these successions are recognised in currently active doublet systems that cannot be explained. This creates an uncertainty in aquifer thickness prediction, which increases the uncertainty in doublet lifetime prediction as it has an impact on net aquifer volume. The goal of this study was to improve our understanding of the thickness variations and regional aquifer architecture of the Nieuwerkerk Formation geothermal aquifers. For this purpose, new palynological data were evaluated to correlate aquifers in currently active doublet systems based on their chronostratigraphic position and regional Maximum Flooding Surfaces. Based on the palynological cuttings analysis, the fluvial interval of the Nieuwerkerk Formation was subdivided into two successions: a Late Ryazanian to Early Valanginian succession and a Valanginian succession. Within these successions trends were identified in sandstone content. In combination with seismic interpretation, maps were constructed that predict aquifer thickness and their lateral extent in the basin. The study emphasises the value of palynological analyses to reduce the uncertainty of fluvial hot sedimentary aquifer exploitation

Extracellular matrix formation after transplantation of human embryonic stem cell-derived cardiomyocytes

Transplantation of human embryonic stem cell-derived cardiomyocytes (hESC-CM) for cardiac regeneration is hampered by the formation of fibrotic tissue around the grafts, preventing electrophysiological coupling. Investigating this process, we found that: (1) beating hESC-CM in vitro are embedded in collagens, laminin and fibronectin, which they bind via appropriate integrins; (2) after transplantation into the mouse heart, hESC-CM continue to secrete collagen IV, XVIII and fibronectin; (3) integrin expression on hESC-CM largely matches the matrix type they encounter or secrete in vivo; (4) co-transplantation of hESC-derived endothelial cells and/or cardiac progenitors with hESC-CM results in the formation of functional capillaries; and (5) transplanted hESC-CM survive and mature in vivo for at least 24 weeks. These results form the basis of future developments aiming to reduce the adverse fibrotic reaction that currently complicates cell-based therapies for cardiac disease, and to provide an additional clue towards successful engraftment of cardiomyocytes by co-transplanting endothelial cells

A broad-spectrum macrocyclic peptide inhibitor of the SARS-CoV-2 spike protein

The ongoing COVID-19 pandemic has had great societal and health consequences. Despite the availability of vaccines, infection rates remain high due to immune evasive Omicron sublineages. Broad-spectrum antivirals are needed to safeguard against emerging variants and future pandemics. We used mRNA display under a reprogrammed genetic code to find a spike-targeting macrocyclic peptide that inhibits SARS-CoV-2 Wuhan strain infection and pseudoviruses containing spike proteins of SARS-CoV-2 variants or related sarbecoviruses. Structural and bioinformatic analyses reveal a conserved binding pocket between the receptor binding domain, N-terminal domain and S2 region, distal to the ACE2 receptor-interaction site. Our data reveal a hitherto unexplored site of vulnerability in sarbecoviruses that peptides and potentially other drug-like molecules can target

A broad-spectrum macrocyclic peptide inhibitor of the SARS-CoV-2 spike protein

The ongoing COVID-19 pandemic has had great societal and health consequences. Despite the availability of vaccines, infection rates remain high due to immune evasive Omicron sublineages. Broad-spectrum antivirals are needed to safeguard against emerging variants and future pandemics. We used messenger RNA (mRNA) display under a reprogrammed genetic code to find a spike-targeting macrocyclic peptide that inhibits SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) Wuhan strain infection and pseudoviruses containing spike proteins of SARS-CoV-2 variants or related sarbecoviruses. Structural and bioinformatic analyses reveal a conserved binding pocket between the receptor-binding domain, N-terminal domain, and S2 region, distal to the angiotensin-converting enzyme 2 receptor-interaction site. Our data reveal a hitherto unexplored site of vulnerability in sarbecoviruses that peptides and potentially other drug-like molecules can target