The concept of servitization is well established in the literature, and yet the processes of organisational change that manufacturers undergo to compete through services have received much less ...attention. Therefore, this paper develops a model that enables a description of the servitization processes, the principal stages of organisational change, and the forces impacting these processes. It is based on a series of 14 case studies of the process of servitization over time in multinational manufacturers. Evidence and analysis from these cases are used to establish that manufacturers undergo four stages of organisational maturity (Exploration, Engagement, Expansion and Exploitation), through which an organisation progresses according to the pressures of five principal forces (customer pull, technology push, value network positioning, organisational readiness, and organisational commitment). This progression can be characterised as a business growth model with multiple crises or tipping points. This research contributes to our understanding of the process of servitization and proposes a model which can be used to explain progression. It also forms the basis to better prepare manufacturers as to what to expect as they embark on a servitization journey.
Researchers have many times turned their attention to nature and biological processes to develop novel technologies and materials. In a medical perspective, nature-based products are believed to be a ...strategic alternative approach to the use of fully synthetic materials, particularly in the design of medical devices. In the past decades, marine organisms have become the focus of considerable attention as potential sources of valuable materials. The sustainable exploitation and valorisation of natural marine resources constitutes a highly attractive and strategic platform for the development of novel biomaterials, with both economic and environmental benefits. In this context, algae are known to synthesise large quantities of polysaccharides and are well established sources of these particularly interesting molecules, many of which are known for their applicability in the design of biomaterials. Agar, carrageenan and alginates are some of the most known examples, and their uses can range from food to biomedical applications. However, few of the world’s available seaweed species are used commercially. Among the three main divisions of macroalgae (Chlorophyta, Phaeophyta and Rhodophyta), the green algae remain largely unexploited in this biomedical arena. While the demand for novel materials and technologies increases, so does the research of unexploited marine green algae including its unique polysaccharide ulvan.
The development of sensors for pH monitoring is of extreme importance in the monitoring of concrete and reinforced concrete structures. Imidazole derivatives are promising probes for pH sensing due ...to the amphoteric nature of their heterocyclic ring, which can be protonated/deprotonated upon pH changes. In this work, a triarylimidazole was synthesised and used as a dopant in an organic-inorganic hybrid (OIH) sol-gel matrix to obtain a pH-sensitive membrane for further application in optical fibre sensors (OFS). The triarylimidazole probe shows fluorimetric response in pH between 9 and 13, which is the desired range for monitoring carbonation of concrete. This degradation process lowers the highly alkaline pH of concrete (12.5-13) to values below 9, which creates favourable conditions for corrosion of concrete reinforcement. The OIH membranes used were based on Jeffamine THF170 and 3-glycidoxypropytrimethoxysilane precursors, which had already been shown to be suitable and resistant in contact with cement-based materials. The OIHs were doped with three different contents of the triarylimidazole and the structural, dielectric, thermal and optical properties of the pure and doped OIH materials were evaluated. The structural analysis showed that the presence of the triarylimidazole did not change the structural properties of the OIH material. Electrochemical impedance spectroscopy showed that in the doped samples the conductivity increased with the imidazole concentration. The
r
obtained for the doped samples ranged approximately from 11 to 19 and for the pure matrices was 8. Thermal analysis showed that these materials are stable up to 350 °C and that the presence of the probe did not change that feature. The optical properties showed that the prepared OIH materials have promising properties to be used as pH sensitive fluorimetric probes.
OIH sol-gel materials based on Jeffamine THF-170 and GPTMS, doped with triarylimidazole, were synthesized. The
r
obtained for the OIH doped samples ranged between 11 and 19. The OIHs are thermally stable for fresh concrete purposes.
Water security and industrial wastewater treatment are significant global concerns. One of the main issues with environmental contamination has been the discharge of dye wastewater from the textile ...and dye industries, contributing to an ever-growing problem with water pollution, poisoning water supplies, and harming the ecosystem. The traditional approach to wastewater treatment has been found to be inefficient, and biosorption techniques and mechanisms have been proven to be a successful replacement for conventional methods. Recent developments have led to the recognition of fibrous materials as an environmentally friendly option with broad application in several industries, including wastewater treatment. This review explores the potential of fibrous materials produced by the electrospinning technique as adsorbents for wastewater treatment, while at the same time, for the removal of adsorbates such as oil, dyes, heavy metals, and other substances, as reported in the literature. Textile wastewater filtering structures, produced by electrospinning, are summarized and the use of synthetic and natural polymers for this purpose is discussed. The limitations of electrospun textile wastewater filtering structures are also mentioned. Electrospun nanofibrous membranes appear to be a very promising route to filter textile wastewater and therefore contribute to water reuse and to reducing the contamination of water courses.
Abstract Doxorubicin (Adriamycin® ) is a potent and broad-spectrum antineoplastic agent, the clinical utility of which is restricted by a cumulative and progressive cardiomyopathy that develops with ...repeated dosing. Fundamental to the cardiac failure is an interference with mitochondrial respiration and inhibition of oxidative phosphorylation. Global gene expression arrays in cardiac tissue indicate that inhibition of mitochondrial oxidative phosphorylation by doxorubicin (DOX) is accompanied by a decreased expression of genes related to aerobic fatty acid oxidation and a corresponding increase in expression of genes involved in anaerobic glycolysis, possibly as an alternate source for ATP production. The aim of this investigation was to determine whether this is also manifest at the metabonomic level as a switch in metabolic flux in cardiac tissue, and whether this can be averted by co-administering the cardioprotective drug, dexrazoxane (DZR).13 C-isotopomer analysis of isolated perfused hearts from male Sprague–Dawley rats receiving 6 weekly s.c. injections of 2 mg/kg DOX demonstrated a shift from the preferential oxidation of fatty acids to enhanced oxidation of glucose and lactate plus pyruvate, indicative of a compensatory shift towards increased pyruvate dehydrogenase activity. Substrate-selective isotopomer analysis combined with western blots indicate an inhibition of long-chain fatty acid oxidation and not MCAD activity or fatty acyl-carnitine transport. Co-administering DZR averted many treatment-related changes in cardiac substrate metabolism, consistent with DZR being an effective cardioprotective agent against DOX-induced cardiomyopathy. This switch in substrate metabolism resembles that described for other models of cardiac failure; accordingly, this change in metabolic flux may represent a general compensatory response of cardiac tissue to imbalances in bioenergetic demand and supply, and not a characteristic unique to DOX-induced cardiac failure itself.
Tissue engineering provides unique opportunities for regenerating diseased or damaged tissues using cells obtained from tissue biopsies. Tissue engineered grafts can also be used as high fidelity ...models to probe cellular and molecular interactions underlying developmental processes. In this study, we co-cultured human umbilical vein endothelial cells (HUVECs) and human mesenchymal stem cells (MSCs) under various environmental conditions to elicit synergistic interactions leading to the colocalized development of capillary-like and bone-like tissues. Cells were encapsulated at the 1:1 ratio in fibrin gel to screen compositions of endothelial growth medium (EGM) and osteogenic medium (OM). It was determined that, to form both tissues, co-cultures should first be supplied with EGM followed by a 1:1 cocktail of the two media types containing bone morphogenetic protein-2. Subsequent studies of HUVECs and MSCs cultured in decellularized, trabecular bone scaffolds for 6 weeks assessed the effects on tissue construct of both temporal variations in growth-factor availability and addition of fresh cells. The resulting grafts were implanted subcutaneously into nude mice to determine the phenotype stability and functionality of engineered vessels. Two important findings resulted from these studies: (i) vascular development needs to be induced prior to osteogenesis, and (ii) the addition of additional hMSCs at the osteogenic induction stage improves both tissue outcomes, as shown by increased bone volume fraction, osteoid deposition, close proximity of bone proteins to vascular networks, and anastomosis of vascular networks with the host vasculature. Interestingly, these observations compare well with what has been described for native development. We propose that our cultivation system can mimic various aspects of endothelial cell-osteogenic precursor interactions in vivo, and could find utility as a model for studies of heterotypic cellular interactions that couple blood vessel formation with osteogenesis.
The demand for new fluorophores for different biological target imaging is increasing. Benzo
phenoxazine derivatives are fluorochromophores that show promising optical properties for bioimaging, ...namely fluorescent emission at the NIR of the visible region, where biological samples have minimal fluorescence emission. In this study, six new benzo
phenoxazinium chlorides possessing sulfonamide groups at 5-amino-positions were synthesized and their optical and biological properties were tested. Compared with previous probes evaluated using fluorescence microscopy, using different
strains, these probes, with sulfonamide groups, stained the vacuole membrane and/or the perinuclear membrane of the endoplasmic reticulum with great specificity, with some fluorochromophores capable of even staining the plasma membrane. Thus, the addition of a sulfonamide group to the benzo
phenoxazinium core increases their specificity and attributes for the fluorescent labeling of cell applications and fractions, highlighting them as quite valid alternatives to commercially available dyes.
Scaffolds produced by rapid prototyping (RP) techniques have proved their value for tissue engineering applications, due to their ability to produce predetermined forms and structures featuring fully ...interconnected pore architectures. Nevertheless, low cell seeding efficiency and non-uniform distribution of cells remain major limitations when using such types of scaffold. This can be mainly attributed to the inadequate pore architecture of scaffolds produced by RP and the limited efficiency of cell seeding techniques normally adopted. In this study we aimed at producing scaffolds with pore size gradients to enhance cell seeding efficiency and control the spatial organization of cells within the scaffold. Scaffolds based on blends of starch with poly(ε-caprolactone) featuring both homogeneously spaced pores (based on pore sizes of 0.75 and 0.1mm) and pore size gradients (based on pore sizes of 0.1–0.75–0.1 and 0.75–0.1–0.75mm) were designed and produced by three-dimensional plotting. The mechanical performance of the scaffolds was characterized using dynamic mechanical analysis (DMA) and conventional compression testing under wet conditions and subsequently characterized using scanning electron microscopy and micro-computed tomography. Osteoblast-like cells were seeded onto such scaffolds to investigate cell seeding efficiency and the ability to control the zonal distribution of cells upon seeding. Scaffolds featuring continuous pore size gradients were originally produced. These scaffolds were shown to have intermediate mechanical and morphological properties compared with homogenous pore size scaffolds. The pore size gradient scaffolds improved seeding efficiency from ∼35% in homogeneous scaffolds to ∼70% under static culture conditions. Fluorescence images of cross-sections of the scaffolds revealed that scaffolds with pore size gradients induce a more homogeneous distribution of cells within the scaffold.
Mammalian chromatin is the site of both RNA polymerase II (Pol II) transcription and coupled RNA processing. However, molecular details of such co-transcriptional mechanisms remain obscure, partly ...because of technical limitations in purifying authentic nascent transcripts. We present a new approach to characterize nascent RNA, called polymerase intact nascent transcript (POINT) technology. This three-pronged methodology maps nascent RNA 5′ ends (POINT-5), establishes the kinetics of co-transcriptional splicing patterns (POINT-nano), and profiles whole transcription units (POINT-seq). In particular, we show by depletion of the nuclear exonuclease Xrn2 that this activity acts selectively on cleaved 5′ P-RNA at polyadenylation sites. Furthermore, POINT-nano reveals that co-transcriptional splicing either occurs immediately after splice site transcription or is delayed until Pol II transcribes downstream sequences. Finally, we connect RNA cleavage and splicing with either premature or full-length transcript termination. We anticipate that POINT technology will afford full dissection of the complexity of co-transcriptional RNA processing.
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•POINT methodology dissects intact nascent RNA processing•Specificity of Xrn2 exonuclease in co-transcriptional RNA degradation•Splicing suppresses Xrn2-dependent premature termination•Different kinetic classes of co-transcriptional splicing in human genes
Sousa-Luís et al. describe tripartite methodology to purify and sequence RNA polymerase II-associated intact nascent transcripts (POINT) from mammalian genomes. POINT-5 distinguishes nascent RNA 5′ end caps from 5′ end cleavage, POINT-seq profiles full-length transcription units, and POINT-nano determines the kinetics of co-transcriptional splicing at a single-molecule level.
Background and Aim
The RHEMITT score (Renal disease; Heart failure; Endoscopic findings; Major bleeding; Incomplete SBCE; Tobacco; Treatment by enteroscopy) was the first score to accurately predict ...the individual risk of small bowel rebleeding after capsule endoscopy (SBCE). The aim of the study is on the prospective validation of the RHEMITT score.
Methods
Cohort of consecutive patients with mid‐gastrointestinal bleeding (MGIB) submitted to SBCE and followed prospectively, during at least 12 months, since 2017 until 2020. Rebleeding was defined as an overt bleeding event (melena or hematochezia) or a hemoglobin decrease of at least 2 g/dL. The RHEMITT score was calculated for each patient and the rebleeding rates compared. The performance of the score was tested by calculating the area under curve of the receiver operator characteristic curve. A rebleeding‐free survival was assessed, corresponding to the period between the date of SBCE and the date of the first post‐SBCE rebleeding event.
Results
We included 162 patients, 102 (62.9%) were female, with a mean age of 64 years old. The sensitivities and specificities of the score grades for predicting rebleeding were as following: for low‐risk patients, 0% (0–10%) and 28.8% (21.1–36.5%); for intermediate‐risk patients, 23.3% (8.2–38.4%) and 72% (64.3–79.7%); for high‐risk patients, 76.7% (61.6–91.8%) and 99.2% (97.7–100%), corresponding to an area under curve of the receiver operator characteristic of 0.988 (P < 0.001). Kaplan–Meyer plots were statistically different according to the attributed risk (log‐rank P value <0.001; Breslow–Wilcoxon P value <0.001).
Conclusion
The RHEMITT score performed with excellent discriminative power in predicting rebleeding risk, and we herewith propose a surveillance of MGIB patients guided by the RHEMITT score.
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