Potential Mechanisms Underlying TGF-β-mediated Complement Activation in Lung Fibrosis

While our previous studies suggest that limiting bleomycin-induced complement activation suppresses TGF-β signaling, the specific hierarchical interactions between TGF-β and complement in lung fibrosis are unclear. Herein, we investigated the mechanisms underlying TGF-β-induced complement activation in the pathogenesis of lung fibrosis. C57-BL6 mice were given intratracheal instillations of adenoviral vectors overexpressing TGF-β (Ad-TGFβ) or the firefly gene-luciferase (Ad-Luc; control). Two weeks later, mice with fibrotic lungs were instilled RNAi specific to receptors for C3a or C5a-C3ar or C5ar, and sacrificed at day 28. Histopathological analyses revealed that genetic silencing of C3ar or C5ar arrested the progression of TGF-β-induced lung fibrosis, collagen deposition and content (hydroxyproline, col1a1/2); and significantly suppressed local complement activation. With genetic silencing of either C3ar or C5ar, in Ad-TGFβ-injured lungs: we detected the recovery of Smad7 (TGF-β inhibitor) and diminished local release of DAF (membrane-bound complement inhibitor); in vitro: TGF-β-mediated loss of DAF was prevented. Conversely, blockade of the TGF-β receptor prevented C3a-mediated loss of DAF in both normal primary human alveolar and small airway epithelial cells. Of the 52 miRNAs analyzed as part of the Affymetrix array, normal primary human SAECs exposed to C3a, C5a or TGF-β caused discrete and overlapping miRNA regulation related to epithelial proliferation or apoptosis (miR-891A, miR-4442, miR-548, miR-4633), cellular contractility (miR-1197) and lung fibrosis (miR-21, miR-200C, miR-31HG, miR-503). Our studies present potential mechanisms by which TGF-β activates complement and promotes lung fibrosis

Scheduling surgical cases in a day-care environment: a branch-and-price approach.

In this paper we will investigate how to sequence surgical cases in a day-care facility so that multiple objectives are simultaneously optimized. The limited availability of resources and the occurrence of medical precautions, such as an additional cleaning of the operating room after the surgery of an infected patient, are taken into account. A branch-and-price methodology will be introduced in order to develop both exact and heuristic algorithms. In this methodology, column generation is used to optimize the linear programming formulation of the scheduling problem. Both a dynamic programming approach and an integer programming approach will be specified in order to solve the pricing problem. The column generation procedure will be combined with various branching schemes in order to guarantee the integrality of the solutions. The resulting solution procedures will be thoroughly tested and evaluated using real-life data of the surgical day-care center at the university hospital Gasthuisberg in Leuven (Belgium). Computational results will be summarized and conclusions will eventually be formulated.Branch-and-price; Column generation; Health care operations; Scheduling;

Combustion of a Solid Recovered Fuel (SRF) Produced from the Polymeric Fraction of Automotive Shredder Residue (ASR)

The use of alternative fuels derived from residues in energy-intensive industries that rely on fossil fuels can cause considerable energy cost savings, but also significant environmental benefits by conserving non-renewable resources and reducing waste disposal. However, the switching from conventional to alternative fuels is challenging for industries, which require a sound understanding of the properties and combustion characteristics of the alternative fuel, in order to adequately adapt their industrial processes and equipment for its utilization. In this work, a solid recovered fuel (SRF) obtained from the polymeric fraction of an automotive shredder residue is tested for use as an alternative fuel for scrap preheating in an aluminium refinery. The material and chemical composition of the SRF has been extensively characterized using proximate and ultimate analyses, calorific values and thermal degradation studies. Considering the calorific value and the chlorine and mercury contents measured, the SRF can be designated as class code NCV 1; Cl 2; Hg 2 (EN ISO 21640:2021). The combustion of the SRF was studied in a laboratory-scale pilot plant, where the effects of temperature, flow, and an oxidizer were determined. The ash remaining after combustion, the collected liquid, and the generated gas phase were analysed in each test. It was observed that increasing the residence time of the gas at a high temperature allowed for a better combustion of the SRF. The oxidizer type was important for increasing the total combustion of the vapour compounds generated during the oxidation of the SRF and for avoiding uncontrolled combustion.This research was conducted as part of the REVaMP project, which received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 869882. The authors want to thank the funding by the Basque Government for financing the activity of the “Sustainable Process Engineering” group as a consolidated research group (GIC15/13, IT993-16)

Formicamycin biosynthesis involves a unique reductive ring contraction

Fasamycin natural products are biosynthetic precursors of the formicamycins. Both groups of compounds are polyketide natural products that exhibit potent antibacterial activity despite displaying different three-dimensional topologies. We show here that transformation of fasamycin into formicamycin metabolites requires two gene products and occurs via a novel two-step ring expansion-ring contraction pathway. Deletion of forX, encoding a flavin dependent monooxygenase, abolished formicamycin production and leads to accumulation of fasamycin E. Deletion of the adjacent gene forY, encoding a flavin dependent oxidoreductase, also abolished formicamycin biosynthesis and led to the accumulation of new lactone metabolites that represent Baeyer–Villiger oxidation products of the fasamycins. These results identify ForX as a Baeyer–Villiger monooxygenase capable of dearomatizing ring C of the fasamycins. Through in vivo cross feeding and biomimetic semi-synthesis experiments we showed that these lactone products represent biosynthetic intermediates that are reduced to formicamycins in a unique reductive ring contraction reaction catalyzed by ForY

Oncologic and Safety Outcomes for Endoscopic Surgery Versus Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma: An Updated Systematic Review and Meta-analysis

We systematically reviewed the literature and summarized oncologic and safety outcomes for endoscopic management (EM) compared to radical nephroureterectomy (RNU) for patients with upper tract urothelial carcinoma (UTUC). Studies comparing oncologic and/or safety results for EM versus RNU in patients with UTUC were included in our review. Overall, 13 studies met the criteria, and five studies were included in a meta-analysis using adjusted hazard ratios (HRs) for overall survival (OS), cancer-specific survival (CSS), and bladder recurrence-free survival (BRFS). EM was associated similar OS (HR 1.27, 95% confidence interval [CI] 0.75–2.16), CSS (HR 1.37, 95% CI 0.99–1.91), and BRFS (HR 0.98, 95% CI 0.61–1.55) to RNU, while 28–85% of patients treated with EM experienced upper tract recurrence across the studies. EM required more interventions with a higher cumulative risk of complications and lower likelihood of renal preservation. In summary, EM for low-grade UTUC had comparable survival outcomes to RNU at the cost of higher local recurrence rates resulting in a need for long-term rigorous surveillance and repeated interventions

The inheritance of color and horns in Alaskan hybrid Galloway-Holstein cattle

Call number: LD2668 .T4 1934 W4

Cost benefit analysis of space communications technology. Volume 2: Final report

For abstract, see preceding accession