Importance of drilling-related processes on the origin of borehole breakouts — Insights from LWD observations

Logging while drilling (LWD) images are widely used for the analysis of borehole stability. In this context, borehole breakouts are a crucial indication of rock failure developing when the circumferential stress around the borehole exceeds the yield value of the rock. This study investigates the impact of drilling-related processes (DRPs) on the origin of borehole breakouts. DRPs, for instance, include connections or tripping operations. For this purpose, we analyze data from 12 boreholes in different geological settings throughout the Norwegian and Danish North Sea, containing a total of 208 borehole breakouts. The extensive data acquisition of LWD offers the unique possibility to link the imaging to real-time drilling operations and to monitor anomalies of e.g., bottom hole pressure. These records allow us to connect any thermal, hydraulic, or mechanical interaction next to the borehole wall to perturbations of the stress field. This analysis resulted in an apparent strong coincidence of borehole breakouts, representing major stress perturbations, with DRPs. The causal relationship is highlighted by one order of magnitude higher occurrence of DRPs in depth sections containing breakouts. Major pressure reductions in the annulus of the borehole seem to be the most significant cause of drilling-related wellbore failures. This applies in particular to shutting off the pumps during connections, where pressure reductions of up to 16 % of the annulus pressure led to higher circumferential stresses. This process will increase the likelihood of compressive and shear failure, therefore causing borehole breakouts. These observations further open the perspective of counteracting wellbore instabilities by pressure modification. In addition to the initiation of breakouts, their temporal evolution – as seen in relogs – can also be ascribed to DRPs. This study indicates that not only plasticity but also mechanical interaction from DRPs is a key driver of the temporal growth of borehole breakouts

A mini-module with built-in spacers for high-throughput ultrafiltration

Ultrafiltration membrane modules suffer from a permeate flow decrease arising during filtration and caused by concentration polarization and fouling in, e.g., fermentation broth purification. Such performance losses are frequently mitigated by manipulating the hydrodynamic conditions at the membrane-fluid interface using, e.g., mesh spacers acting as static mixers. This additional element increases manufacturing complexity while improving mass transport in general, yet accepting their known disadvantages such as less transport in dead zones. However, the shape of such spacers is limited to the design of commercially available spacer geometries. Here, we present a methodology to design an industrially relevant mini-module with an optimized built-in 3D spacer structure in a flat-sheet ultrafiltration membrane module to eliminate the spacer as a separate part. Therefore, the built-in structures have been conceptually implemented through an in-silico design in compliance with the specifications for an injection molding process. Ten built-in structures were investigated in a digital twin of the mini-module by 3D-CFD simulations to select two options, which were then compared to the empty feed channel regarding mass transfer. Subsequently, the simulated flux increase was experimentally verified during bovine serum albumin (BSA) filtration. The new built-in sinusoidal corrugation outperforms conventional mesh spacer inlays by up to 30% higher permeation rates. The origin of these improvements is correlated to the flow characteristics inside the mini-module as visualized online and in-situ by low-field and high-field magnetic resonance imaging velocimetry (flow-MRI) during pure water permeation

Transformative Materials to Create 3D Functional Human Tissue Models In Vitro in a Reproducible Manner

Recreating human tissues and organs in the petri dish to establish models as tools in biomedical sciences has gained momentum. These models can provide insight into mechanisms of human physiology, disease onset, and progression, and improve drug target validation, as well as the development of new medical therapeutics. Transformative materials play an important role in this evolution, as they can be programmed to direct cell behavior and fate by controlling the activity of bioactive molecules and material properties. Using nature as an inspiration, scientists are creating materials that incorporate specific biological processes observed during human organogenesis and tissue regeneration. This article presents the reader with state-of-the-art developments in the field of in vitro tissue engineering and the challenges related to the design, production, and translation of these transformative materials. Advances regarding (stem) cell sources, expansion, and differentiation, and how novel responsive materials, automated and large-scale fabrication processes, culture conditions, in situ monitoring systems, and computer simulations are required to create functional human tissue models that are relevant and efficient for drug discovery, are described. This paper illustrates how these different technologies need to converge to generate in vitro life-like human tissue models that provide a platform to answer health-based scientific questions.</p

Fabrication of cell container arrays with overlaid surface topographies

This paper presents cell culture substrates in the form of microcontainer arrays with overlaid surface topographies, and a technology for their fabrication. The new fabrication technology is based on microscale thermoforming of thin polymer films whose surfaces are topographically prepatterned on a micro- or nanoscale. For microthermoforming, we apply a new process on the basis of temporary back moulding of polymer films and use the novel concept of a perforated-sheet-like mould. Thermal micro- or nanoimprinting is applied for prepatterning. The novel cell container arrays are fabricated from polylactic acid (PLA) films. The thin-walled microcontainer structures have the shape of a spherical calotte merging into a hexagonal shape at their upper circumferential edges. In the arrays, the cell containers are arranged densely packed in honeycomb fashion. The inner surfaces of the highly curved container walls are provided with various topographical micro- and nanopatterns. For a first validation of the microcontainer arrays as in vitro cell culture substrates, C2C12 mouse premyoblasts are cultured in containers with microgrooved surfaces and shown to align along the grooves in the three-dimensional film substrates. In future stem-cell-biological and tissue engineering applications, microcontainers fabricated using the proposed technology may act as geometrically defined artificial microenvironments or niches

Point Mutations in GLI3 Lead to Misregulation of its Subcellular Localization

Background Mutations in the transcription factor GLI3, a downstream target of Sonic Hedgehog (SHH) signaling, are responsible for the development of malformation syndromes such as Greig-cephalopolysyndactyly-syndrome (GCPS), or Pallister-Hall-syndrome (PHS). Mutations that lead to loss of function of the protein and to haploinsufficiency cause GCPS, while truncating mutations that result in constitutive repressor function of GLI3 lead to PHS. As an exception, some point mutations in the C-terminal part of GLI3 observed in GCPS patients have so far not been linked to loss of function. We have shown recently that protein phosphatase 2A (PP2A) regulates the nuclear localization and transcriptional activity a of GLI3 function. Principal Findings We have shown recently that protein phosphatase 2A (PP2A) and the ubiquitin ligase MID1 regulate the nuclear localization and transcriptional activity of GLI3. Here we show mapping of the functional interaction between the MID1-α4-PP2A complex and GLI3 to a region between amino acid 568-1100 of GLI3. Furthermore we demonstrate that GCPS-associated point mutations, that are located in that region, lead to misregulation of the nuclear GLI3-localization and transcriptional activity. GLI3 phosphorylation itself however appears independent of its localization and remains untouched by either of the point mutations and by PP2A-activity, which suggests involvement of an as yet unknown GLI3 interaction partner, the phosphorylation status of which is regulated by PP2A activity, in the control of GLI3 subcellular localization and activity. Conclusions The present findings provide an explanation for the pathogenesis of GCPS in patients carrying C-terminal point mutations, and close the gap in our understanding of how GLI3-genotypes give rise to particular phenotypes. Furthermore, they provide a molecular explanation for the phenotypic overlap between Opitz syndrome patients with dysregulated PP2A-activity and syndromes caused by GLI3-mutations

UV Reactor

Tubular UV-LED Reacto