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New Improved cGMP Analogues to Target Rod Photoreceptor Degeneration
No full textRetinitis pigmentosa (RP) is a form of retinal degeneration affecting a young population with an unmet medical need. Photoreceptor degeneration has been associated with increased guanosine 3′,5′-cyclic monophosphate (cGMP), which reaches toxic levels for photoreceptors. Therefore, inhibitory cGMP analogues attract interest for RP treatments. Here we present the synthesis of dithio-CN03, a phosphorodithioate analogue of cGMP, prepared using the H-phosphonothioate route. Two crystal modifications were identified as a trihydrate and a tetrahydrofuran monosolvates. Dithio-CN03 featured a lower aqueous solubility than its RP-phosphorothioate counterpart CN03, a drug candidate, and this characteristic might be favorable for sustained-release formulations aimed at retinal delivery. Dithio-CN03 was tested in vitro for its neuroprotective effects in photoreceptor models of RP. The comparison of dithio-CN03 to CN03 and its diastereomer SP-CN03, and to their phosphate derivative oxo-CN03 identifies dithio-CN03 as the compound with the highest efficacy in neuroprotection and thus as a promising new candidate for the treatment of RP. European Union: MSCA-ITN-2017−765441 (transMed) andEuropean Union’s Horizon 2020 research and innovationprogramme under the EJP RD COFUND-EJP N° 825575,grant # 101 (TreatRP).</p
Tunnel fire safety management and systems thinking : Adapting engineering practice through regulations and education
No full textSociety is changing ever faster, and tunnels are complex systems where performance is affected by many different stakeholders. These conditions suggest that safety management needs to be proactive and based on a systems perspective that acknowledges socio-technical theories. Although systems thinking principles are foundational in overarching European regulations and goals, system principles generally don’t affect tunnel fire safety design principles or engineering practice. In the countries investigated in this study, tunnel fire safety management (TFSM) builds on experience-based and risk management-based principles that are optimized independently system by system. This is usually done with limited consideration of how these systems are interconnected and affect the overall tunnel system. The purpose of this paper is to investigate how systems thinking could support existing engineering practice. The work presented in this article is the outcome of a collaboration between fire safety researchers and practitioners from five countries and three continents. Through three workshops, current TFSM principles have been compiled and discussed. It is suggested that tunnel safety regulations be redesigned to strengthen the ability of engineers to work in design teams using systems thinking principles. The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jonatan Gehandler reports financial support was provided by Research Council of Norway. Ricky Carvel is Editorial Board Member. Jose L. Torero previously was Editor for Fire Safety Journal.The authors would like to thank the following for useful discussions during the writing of this paper: Peter Woodburn, Arup, UK; John Aldridge, London Bridge Associates, UK; Ieuan Rickard, OFR Consultants, UK; Karl Fridolf, Swedish Transport Administration; Johan Lundin, BSL, Sweden; Jaime Cadena Gomez, Transurban, Australia. Dr. Francine Amon is acknowledged for proofreading. Work on this paper has been partly funded by the Research Council of Norway (NRC), through the FORREGION research program and the Capacity Boost Tunnel Safety project. The financial support from NRC and the in-kind contribution from our respective organizations is gratefully acknowledged.</p
Effects of breathing variables on modelled particle lung deposition at physical activity for children and adults
No full textThe respiratory tract deposited fraction (DF) is the link between exposure and health effects of airborne particles. Here, we investigate how breathing pattern alterations at increasing physical activity affect DF in different regions of the respiratory tract and compare DF between adults and children (5 and 10 years old). We performed a literature review on the alteration of tidal volume with minute ventilation at increasing physical activity and used the results to model the size resolved (0.001–10 µm) DF, primarily using the deposition models from NCRP and Yeh and Schum (1980), but also MPPD. We found a shift in the deposited size distribution with increasing physical activity—DF of ultrafine particles increased in the alveolar region and decreased in the other regions, while DF of coarser particles decreased in the alveolar region and increased in the extra-thoracic region. Children had a 10–20% higher DF of ultrafine particles in the alveolar region compared to adults. We also present parametrizations of the daily average size resolved (0.005–5 µm) DF, accounting for varying physical activity throughout the day and oral/nasal breathing. These can be applied to any size distribution to estimate deposited doses. We found that deposited mass and number doses were more than twice as high for 5-year-olds compared to adults when normalized for body weight, primarily caused by their higher weight normalized minute ventilation. This demonstrates the importance of studying children’s exposure to air pollution and not only rely on data from adults. Open access funding provided by Lund University. This research was supported by Formas (prn 2018–00693), with contributions from the Swedish Research Council (2021–03265) and the Swedish Heart Lung Foundation (2020–0855).</p
Cellulose gelation in aqueous hydroxide solutions by CO2(g) : Fact and theory
No full textUnderstanding how the solvent structure affects the stability of the dissolved state and the following precipitation is important for designing future dissolution-coagulation systems for cellulose processing. In this study, two morpholinium hydroxides with different alkyl chain lengths, namely N,N-dimethylmorpholinium hydroxide (NDMMOH(aq)) and N‑butyl‑N-methyl morpholinium hydroxide (BMMorOH(aq)), were studied and compared with the previously thoroughly investigated cellulose solvent benzyltriemethylammonium hydroxide (Triton B(aq)) which is well-known for its superior ability to stabilize the dissolved state. Cellulose solutions in each solvent were characterized by NMR, flow and frequency sweeps, while cellulose coagulation by CO2(g) was followed by in situ FTIR, pH and temperature measurements. The coagulated systems were characterized by CP/MAS 13C NMR, flow, and frequency sweep measurements. Complementary molecular dynamic (MD) simulations were performed to gain a deeper insight into the observed gelation behavior. The intrinsic viscosity indicated more extended cellulose chains in the solvents with more hydrophobic moieties (Triton B and BMMorOH). Even though the course of coagulation did not show any significant differences during monitoring, both the properties of the obtained gels and the MD simulations indicated differences in formation and properties of the coagulated materials that could be related both to the choice of solvent and coagulant. The Knut and Allice Wallenberg Foundation is gratefully acknowledged for financial support within Wallenberg Wood Science Center and the Swedish NMR Centre is acknowledged for providing spectrometer time.</p
Progressive Induction Hardening : Measurement and Alteration of Residual Stresses
No full textProgressive induction hardening is an in-line steel heat treatment method commonly used to surface harden powertrain components. It produces a martensitic case layer with a sharp transition zone to the base material. This rapid process will induce large residual stresses, where a compressive state in the case layer will shift to a tensile state in the transition zone. For fatigue performance, it is important to quantify the magnitude and distribution of these stresses, and moreover how they depend on material and processing parameters. In this work, x-ray diffraction in combination with a layer removal method is used for efficient and robust quantification of the subsurface stress state, which combines electropolishing with either turning or milling. Characterization is done on C45E steel samples that were progressively induction hardened using either a fast or slow (27.5 or 5 mm/s, respectively) scanning speed. The results show that although the hardening procedures will meet arbitrary requirements on surface hardness, case depth and microstructure, the subsurface tensile stress peak magnitude is doubled when using a fast scanning speed. However, the near-surface compressive residual stresses are comparable. In addition, the subsurface tensile residual stress peak is compared with the on-surface tensile stresses in the fade-out zone.The authors would like to thank RISE Research Institutes of Sweden AB and the members of the Swedish Heat Treatment Centre for financing support of this study.</p
How aligned are industry strategy and government policy for the decarbonization of energy-intensive process industries?
No full textDecarbonization of energy-intensive process industries (EPIs) is a central unresolved challenge for limiting global warming to 1.5°C or well-below 2°C. In this article, we investigate the alignment between government policy and applicable industry strategy in decarbonization efforts across six European countries–Denmark, Germany, Netherlands, Norway, Sweden and the United Kingdom. We distinguish between ‘target alignment’ (How comparable are the size of the emission reduction commitments?), ‘temporal alignment’ (How closely do the timelines match?) and ‘solution alignment’ (Are the same types of solutions prioritized?). Based on an analysis of national policy documents, company strategies of the 10 largest emitting EPI plants in each country, as well as secondary sources, we find high target alignment. However, we find substantially lower temporal alignment as emitters are reluctant to commit to intermediate targets that match the decarbonization timelines laid out in national government policy. Solution alignment is intermediate across all six countries as emitters generally pursue the decarbonization options prioritized in policy, but with most emitters remaining at the level of ambitions or plans and few examples of commercial investments so far.This work was funded by the Research Council of Norway, via grants 326410 (CaptureX – Socio-technical drivers, opportunities andchallenges for large-scale CCUS), 29605 (FME NTRANS – Norwegian Centre for Energy Transition Strategies) and 295021 (INTRANSIT –Innovation Policy for Industrial Transformation, Sustainability and Digitalization) as well as by Innovation Fund Denmark, via theVALCCAP project, part of InnoMission 1 and the Swedish Energy Agency, via grant 48508-1.</p
A Route for Bioenergy in the Sahara Region : Date Palm Waste Valorization through Updraft Gasification
No full textThe Adrar region (Algeria) has a total of 397,800 date palm trees (Phoenix dactylifera L.). Due to annual palm cleaning, large quantities of lignocellulosic biomass are produced. Depending on the variety, an average of 65 kg of biowaste is obtained per palm tree. Since the value of this biowaste is underrated, most of the palms are burned outdoors, causing air and visual pollution. This work explores the gasification potential of lignocellulosic waste from date palms (Phoenix dactylifera L. Takarbouche variety) into useful energy. The technology investigated is air updraft fixed-bed gasification, thanks to an originally designed and built reactor, with the capability to process 1 kg of feedstock. Four types of palm waste—namely, palms, petioles, bunch, and bunch peduncles—are first characterized (bulk density, proximate analysis, fixed carbon, elemental composition, and calorific value) and then used as feedstock for two gasification tests each. The syngas produced for the four date palm wastes is combustible, with an outlet temperature between 200 and 400 °C. The operating temperature inside the gasifier varies according to the feature of the biomass cuts (from 174 °C for the peduncles to 557 °C for palms). The experimental setup is also equipped with a cyclone, allowing for the recovery of some of the tar produced during the tests. Finally, the results show that the residence time has a positive effect on the conversion rate of date palm waste, which can significantly increase it to values of around 95%. Project: 177/2017 (Bio-fuel production from Saharan biomass in a continuous system using solar energy)\u2014General Directorate of Scientific Research and Technological Development (DGRSDT), Ministry of higher Education, Algeria.</p
ASKOR FRÅN SÅGVERK INOM TCN OCH MÖJLIGA TILLÄMPNINGAR : Slutrapport
No full textResultat angående ett antal utvalda TCN-företag (Stenvalls, Setra, Bergkvist Siljan, Holmen, Norra Timber och Derome) om deras produktion av aska och hanteringen av aska från förbränning av sågverksavfall har gjorts med hjälp av utskickat frågepaket. Produktionen av aska varierar men sammanslagen våtaska dominerade vidare hantering av askavfall. Askhanteringen sköttes såväl i egen regi som av återvinningsföretag beroende på sågverk och deras produktion. Egen hantering som material för utfyllnad eller ljudvall gör att kostnaden kan hållas låg men för företag där återvinningsföretag är iblandande kan kostnad för ett normalstort sågverk ligga på kring 800 kkr per år. Slutligen så visade studier av brandskyddande förmåga av fraktionerade asktillsatser vid tillverkning av spånskivematerial lovande resultat och att tillväxten av mögel-svampar kan hämmas vid tillsatser över 5%
Synthesis and stability studies of bicyclo[6.1.0]nonyne scaffolds for automated solid-phase oligonucleotide synthesis
No full textTwo novel bicyclo[6.1.0]nonyne (BCN) linker derivatives, which can be directly incorporated into oligonucleotide sequences during standard automated solid-phase synthesis, are reported. Stabilities of BCN-carbinol and two BCN-oligonucleotides are evaluated under acidic conditions. In addition, derivatized BCN linkers (non-acidic and acid treated) are evaluated for strain-promoted alkyne-azide cycloaddition (SPAAC). This research was funded by European Union's Horizon 2020Research and Innovation Programme under the MarieSkłodowska-Curie grant agreement No. 721613 and 956070.</p
Round-Robin Study for Ice Adhesion Tests
No full textIce adhesion tests are widely used to assess the performance of potential icephobic surfaces and coatings. A great variety of test designs have been developed and used over the past decades due to the lack of formal standards for these types of tests. In many cases, the aim of the research was not only to determine ice adhesion values, but also to understand the key surface properties correlated to low ice adhesion surfaces. Data from different measurement techniques had low correspondence between the results: Values varied by orders of magnitude and showed different relative relationships to one another. This study sought to provide a broad comparison of ice adhesion testing approaches by conducting different ice adhesion tests with identical test surfaces. A total of 15 test facilities participated in this round-robin study, and the results of 13 partners are summarized in this paper. For the test series, ice types (impact and static) as well as test parameters were harmonized to minimize the deviations between the test setups. Our findings are presented in this paper, and the ice- and test-specific results are discussed. This study can improve our understanding of test results and support the standardization process for ice adhesion strength measurements.