Alkylation of ketones by use of solid KOH in dimethyl sulfoxide

A mixture of solid KOH in dimethyl sulfoxide has a strong basicity, but only a low nucleophilicity and is used for methylation of ketones. With this simple and inexpensive reagent complete methylation with yields up to 90% can be achieved

A field study of an EU antidumping proceeding. - The case of Vietnamese footwear.

This thesis describes the antidumping duty imposed towards Vietnam on certain footwear and the implications that follows the measure. In an antidumping investigation it is of great importance to establish whether the exporting country is a market economy or not. The EC decision to impose a provisional antidumping duty on imports of certain footwear with uppers of leather originating in Vietnam was based on the conclusion that Vietnam is a Non-Market Economy. The idea of Non-Market Economy (NME) treatment is based on the system where free trade only works if the trading is maintained on a free market. A company can be granted Market Economy Treatment (MET) by the EU and when granted this treatment it will be considered as situated in a market economy even though the country is treated as a Non-Market Economy. No company was granted such treatment in the described case based on the fact that the Vietnamese companies did not pay market rent for the land on which their facilities are situated. The term Non-Market Economy is not widely used which also complicates the implementation. Member States within the European Union (EU) have agreed on a common commercial policy in trade with non Member States (third countries). Articles 131- 134 of the EC Treaty provide for the legal basis for this policy. The EU and its Member States are all Members of the World Trade Organization, WTO, and consequently need to follow the regulations in several international trade agreements (WTO law). EC Courts have however so far sustained that GATT and WTO law does not have direct effect in the EC legal system. Vietnam was recently accessed to the WTO and became the 150th Member. When accessing WTO the main challenge is that it will force the enterprises in the Member state to increase their competiveness and that is especially due to small and medium sized enterprises as the footwear companies. The companies have to meet the demands on international standards and the implementation of certain legislation will increase. The predictability is also an important issue and how the importers and exporters can predict the tariffs on certain goods. Within the WTO there is a right to dispute trial and the AD Agreement also states that all national legislation includes rules that all members should have a trial organ when it comes to final decisions on anti dumping tariffs. In the WTO dispute settlement procedure there is a huge difference though and that is that individual companies cannot have their cases tried, only member states. But this is further complicated by the fact that the EU does not give direct effect to the WTO Law. The EU also gives contradictory conclusions on trade since it embraces free trade but at the same time use trade defence instruments. It is difficult to estimate the effects on exports of Vietnamese footwear but according to the Leather and Footwear Association, LEFASO and the Ministry of Trade in Vietnam, the export will decline. There are also risks that foreign investors will move their production to other countries. The costs for the companies will be much higher for the producing companies in Vietnam that have made investments than the actual positive effects from measures for the Common Industry in the EU

Role of urokinase plasminogen cascade for the progression of chronic kidney disease

Proteinuri er en tilstand som forekommer ved en række nyresygdomme og er karakteriseret ved at nyrerne ”lækker” protein så det kan måles i urinen. Det er en selvstændig prædiktor for forværring af nyrefunktion, øget sygelighed og død. Meget tyder på at det er proteinerne selv, der er skadelige for nyren, men mekanismen er ikke kendt. Proteiner fra koagulationssystemet, herunder plasminogen, og komplementsystemet (del af det medfødte immunforsvar) findes i urin ved defekt filtrationsbarriere, men ikke i urin fra raske. Fra in vitro studier vides, at plasmin kan aktivere og kløve de kritiske komponenter C3 og C5 i komplementsystemet. Derved dannes de proinflammatoriske molekyler C3a og C5a samt under visse omstændigheder ”membran attak” komplekser (MAC, C5b-9). Plasmin aktiveres fra inaktivt plasminogen i proteinurisk urin via urokinase-type plasminogen aktivator (uPA), som findes i urin fra raske. I studierne undersøges en række hypoteser: plasminogen og komplement filtreres sammen ved proteinuri; at aktiveret plasmin driver komplementaktivering og inflammation fra nyrernes tubulussystem; samt at dette kan forhindres helt eller delvist ved at hæmme uPA med amilorid.Studie I undersøger udskillelsen af komplementaktiveringsprodukter i urinen hos nyretransplanterede med albuminuri som er en særlig høj-risikogruppe for tab af nyrefunktion og død og i en mindre gruppe ikke transplanterede nyresyge patienter, ligeledes med albuminuri. Endvidere undersøges ekstracellulære vesikler i urin for at lokalisere hvor henne i nyre komplement slår ned. Vi fandt at udskillelsen af splitprodukterne C3c, C3dg, og sC5b-9 associeret C9 neoantigen, normaliseret for kreatinin i spoturinprøver, var stærkt og signifikant øget ved albuminuri hos nyretransplanterede og ikke i urin fra transplanterede uden proteinuri. Samtidig sås der ikke forskelle i plasmakoncentrationer mellem de 2 grupper. Produkterne var også øget i urin fra patienter med proteinuri der ikke var transplanteret sammenlignet med raske kontroller. I ekstracellulære vesikler fra urin påvistes C9 neoantigenet kun ved albuminuri og yderligere undersøgelse via lektinaffinitetsisolering viste at både C3dg og C5b-9 var bundet til vesikler som stammede fra cellemembraner i proximale tubulus.Studie II tager konceptet videre og undersøger en eventuel aktiveringsmekanisme via uPA-plasminogen ved eksperimenter in vitro med kommercielt tilgængelige rene komplement- og koagulations proteiner samt hvorvidt dette kunne hæmmes med amilorid. Vi undersøgte også to kohorter med patienter med albuminuri som behandles med amilorid, samt et studie med mus med inducerbar progressiv proteinuri. I proteinurisk fase blev mus behandlet med enten amilorid eller saltvandsinjektion. Vi fandt en signifikant aktivering af både C3 og C5 direkte via uPA-plasmin i buffere in vitro og i urin ex vivo. C3 og C5 aktivering kunne hæmmes på en gradueret måde ved at hæmme uPA med amilorid in vitro. C3 kunne aktiveres ved at inkubere normal rask urin ved samtidig tilsættelse af eksogent plasminogen på en amiloridfølsom måde. Patientundersøgelserne viste at en dags amiloridbehandling kun tenderede til at nedbringe C3a i urinen hos nyretransplanterede. To dages amilorid behandling i patienter med diabetisk nyresygedom og proteinuri nedsatte C3dg og C9 neoantigen udskillelse. I dyreforsøget viste vi at amilorid i 4 dage signifikant sænkede døgnudskillelsen af C3a og C5a i urinen. Specifik hæmning af uPA i 11 dage i podocin (-/-) mus med et monoklonalt hæmmende antistof der modvirkede aktivering af plasminogen medførte også en signifikant reduktion i C3a og C5a udskillelseshastighed.I Studie III undersøges C3dg og sC5b-9 associeret C9 neoantigen i urin og plasma i konsekutive prøver opsamlet under graviditeten i en gruppe gravide med type 1 diabetes, n = 88 deltagere, hvoraf n = 14 udviklede preeklamspsi. Vi viste en signifikant stigning i både C3dg og C9 neoantigen i urinen mod slutningen af graviditeten som fulgte albuminudskillelsen hos de patienter der udviklede præeklampsi. Både C3dg og C9 neoantigen relaterede signifikant til albumin i urin men korrelationen til C9 total plasmin(ogen) var stærkere. Ekstracellulære vesikler blev også undersøgt og C3dg og C9 neoantigen blev kun påvist hos preeklampsipatienter ved gestationsuge 36, men ikke i kontroller eller ved 12 uger.De tre studier viser at udskillelsen af aktiveringsprodukter fra komplementsystemet i urinen følger graden af proteinuri men ikke plasmakoncentrationer og at aktiveringen derfor mest sandsynligt sker i tubulussytemet efter filtrering. Endvidere kan komplement membran-attak kompleks bindes specifikt men ikke eksklusivt til proximale tubulus apikale membraner vist via ekstracellulære vesikler i urin. Korrelationen mellem komplementfaktorer til plasmin(ogen) i urin var stærkere end til albumin, foreneligt med at plasminogen kan være medvirkende til aktivering. Amilorid har in vitro en hæmmende effekt på uPA i lav mikromolærområdet, som kan eftervises in vivo i patienter med proteinuri. Den signifikante afsvækkelse men ikke fulde blokering skyldes formentlig at det findes yderligere pleiotrope aktiveringsveje som også kan drive komplementaktivering intratubulært. Resultaterne tyder på en mekanistisk kobling mellem uPAplasminogenkaskaden og komplementaktivering som alene eller sammen med andre mekanismer kan drive inflammation og vævsskade i nyrerne ved proteinuri. Dette kan også være en forklaring på hvorfor proteinuri over lang tid er associeret med fald i nyrefunktionen og kunne give ophav til nye farmakologiske mål. Amilorid og/eller stoffer med plasmin- eller komplementhæmmende effekt og som når tubulussystemet kan have en nyrebeskyttende virkning ved nyresygedom med proteinuri. Dette bør testes i fremtidige studier. Proteinuria is a common feature in chronic kidney disease (CKD) and an independent risk factor for accelerated disease progression. CKD affects approximately 10% of the global population and leads to hypertension, cardiovascular disease, and increased mortality. Aberrantly filtered plasma proteins, including zymogens and active proteases have potential activity in the tubular lumen. Our group previously demonstrated that plasminogen, a component of the fibrinolytic system, is abundantly present in urine and activated by urokinase-type plasminogen activator (uPA) in proteinuria. uPA is physiologically secreted to the tubular fluid and is significantly increased in urine in proteinuria. Complement factors are found in urine from patients with proteinuria. Plasmin cleaves the key components C3 and C5 in vitro and C5 in vivo during thrombus formation, generating biologically active C3a and C5a, which are potent proinflammatory anaphylatoxins. In the present project, it was hypothesized that i) complement factors are aberrantly filtered from plasma and activated in the tubular lumen via the uPA-plasminogen cascade in proteinuria, ii) complement activation split products are detectable in urine in relation to grade of proteinuria, and deposited in the apical membrane of tubular cells, and iii) uPA-plasmin driven complement activation can be attenuated pharmacologically by amiloride (an off target uPA inhibitor).Study I Complement proteins were measured in kidney transplant recipients (KTR) with albuminuria using in-house enzyme linked immunosorbent assays (ELISA) with neoepitope-specific monoclonal antibodies. Two cohorts were examined, one cross-sectional and one longitudinal. Urine excretion of mannose-binding lectin (MBL, 10-fold, p<0.001), C3c (2-fold, p<0.05), C3dg (3-fold, p<0.01), and sC5b-9 associated C9 neoantigen (20-fold, p<0.001) were significantly elevated in proteinuria, and C3dg and C9 neoantigen excretion followed changes in albuminuria over time, without changes in plasma concentrations. The fractional excretion of C9 neoantigen was significantly increased compared to albumin in cases, suggesting a net addition of sC5b-9 after filtration or preferential reabsorption of albumin. Nephron segment specific uEV-isolation documented an association of iC3b/C3dg and C5b-9 to proximal tubular apical membranes in albuminuria. The results strongly indicate intra tubular complement activation and deposition in the proximal tubular epithelium. In extension, suggesting that inhibiting complement in the intra tubular space could reduce the negative intra renal effects of proteinuria.Study II In vitro studies showed that C3 and C5 were activated by uPA-plasminogen but not by uPA or plasminogen alone in physiological and buffered solutions in an amiloride sensitive way. Pooled urine from healthy humans generated C3a from purified human C3 by addition of exogenous plasminogen (activated by endogenous uPA). Pre-incubation of urine with 2 mM amiloride or 500 KIU/ml aprotinin, but not 20 mM ethylenediaminetetraacetic acid (EDTA) inhibited C3a generation. C3a urine excretion was increased significantly KTRs with proteinuria (n = 7) compared to KTR controls (n = 7) but was not reduced by high dose amiloride for one day (p = 0.08). In patients with diabetes type-1 with (n = 16) or without (n = 14) diabetic nephropathy, high dose amiloride treatment for two days reduced C3dg (p < 0.05, n = 5) and C9 neoantigen (p < 0.05, n = 7) excretion rates in cases with detectable urine complement. In proteinuric podocin (-/-) mice, amiloride treatment for four days reduced 24 h urine C3a and C5a excretions (p < 0.05 for both) with no effect on albuminuria compared to vehicle. Inhibition of uPA for 11 days by a monoclonal α-uPA antibody reduced 24 h C5a and C3a excretions by ~50% (p = 0.012 and p = 0.019, respectively). uPAplasminogen play a significant role in intra tubular complement activation and uPA inhibition or direct complement inhibition might slow the progression to end stage kidney disease in proteinuria.Study III Preeclampsia (PE) is a severe complication of pregnancy with sudden onset of proteinuria and increased blood pressure. Since plasmin activated complement in urine and both complement and plasminogen excretion is elevated in PE, we sought to address the temporal association in an existing prospective cohort of 88 pregnant women with pregestational type-1 diabetes. Participants were included at gestational age (GA) 12 weeks and followed to parturition with urine and plasma sampling at GA 20, 28, 32, 36 and 38 weeks. 14 women developed preeclampsia in the study period and 8 controls with complete sample set were selected. Urine excretion of C3dg (p < 0.001) and C9 neoantigen (p = 0.002) increased gradually and in parallel to albumin in PE. C3dg and C9 neoantigen correlated to plasminogen (r = 0.51, p < 0.001 and r = 0.68, p < 0.001, respectively) and albumin (r = 0.44, p < 0.001 and C9 neoantigen, r = 0.59, p < 0.001, respectively) in urine. Receiver operating characteristic (ROC) analysis showed that C3dg and C9 neoantigen/creatinine ratios (AUC= 0.53 and 0.57 respectively) were inferior to albumin/creatinine ratio (ACR; AUC = 0.86) as biomarkers. uEVs were positive for C3dg in one of three and C9 neoantigen in three of three PE patients at GA 36 weeks but were absent in controls, suggesting tubular cell association. The temporal association is compatible with a direct relation between plasmin and complement activation, but complement was not a superior biomarker for PE.Conclusion Studies I-III demonstrate that 1) complement split products are aberrantly filtered in relation to albumin and plasminogen, 2) complement precursors are activated in the tubular lumen and deposited on proximal tubular apical cell membranes, 3) uPA-plasminogen activates complement in vitro and 4) uPAplasmin mediated complement activation is attenuated by uPA inhibition and in vitro and in vivo. The findings links proteinuria to intratubular proinflammatory signaling and complement deposition in tubular epithelial cells. This might lead to epithelial cell injury and progression of CKD and suggest a reno-protective effect of amiloride that goes beyond blood pressure reduction

Performance of masonry buildings and churches in the 22 february 2011 christchurch earthquake

As part of the „Project Masonry‟ Recovery Project funded by the New Zealand Natural Hazards Research Platform, commencing in March 2011, an international team of researchers was deployed to document and interpret the observed earthquake damage to masonry buildings and to churches as a result of the 22nd February 2011 Christchurch earthquake. The study focused on investigating commonly encountered failure patterns and collapse mechanisms. A brief summary of activities undertaken is presented, detailing the observations that were made on the performance of and the deficiencies that contributed to the damage to approximately 650 inspected unreinforced clay brick masonry (URM) buildings, to 90 unreinforced stone masonry buildings, to 342 reinforced concrete masonry (RCM) buildings, to 112 churches in the Canterbury region, and to just under 1100 residential dwellings having external masonry veneer cladding. In addition, details are provided of retrofit techniques that were implemented within relevant Christchurch URM buildings prior to the 22nd February earthquake and brief suggestions are provided regarding appropriate seismic retrofit and remediation techniques for stone masonry buildings.The authors acknowledge the financial support for Project Masonry from the New Zealand Natural Hazards Research Platform. The testing of adhesive anchors was undertaken in conjunction with the RAPID grant CMMI-1138614 from the US National Science Foundation. The investigation of the performance of residential brick veneers was financially supported by Brickworks Building Products Australia

Maldi matrices for the analysis of low molecular weight compounds: rational design, challenges and perspectives

The analysis of low molecular weight (LMW) compounds is of great interest to detect small pharmaceutical drugs rapidly and sensitively, or to trace and understand metabolic pathways. Matrix‐assisted laser desorption/ionization mass spectrometry (MALDI MS) plays a central role in the analysis of high molecular weight (bio)molecules. However, its application for LMW compounds is restricted by spectral interferences in the low m/z region, which are produced by conventional organic matrices. Several strategies regarding sample preparation have been investigated to overcome this problem. A different rationale is centred on developing new matrices which not only meet the fundamental requirements of good absorption and high ionization efficiency, but are also vacuum stable and “MALDI silent”, i. e., do not give matrix‐related signals in the LMW area. This review gives an overview on the rational design strategies used to develop matrix systems for the analysis of LMW compounds, focusing on (i) the modification of well‐known matrices, (ii) the search for high molecular weight matrices, (iii) the development of binary, hybrid and nanomaterial‐based matrices, (iv) the advance of reactive matrices and (v) the progress made regarding matrices for negative or dual polarity mode.To use MALDI MS and MS imaging for the analysis of low molecular weight (LMW) analytes, new matrix systems are needed which combine suitable absorption and high ionization efficiency in dual polarity mode with being vacuum stable and “MALDI silent”, i.e., enabling noise‐free measurements in the LMW area. This Minireview summarizes recent research regarding the design and synthesis of such matrices, and discusses recurring design strategies and motifs. imag

Addressing Covid-19 Challenges Through Multi-sectoral Collaboration: The Rural Rebound Case Studies

In early 2020, after the World Health Organization (WHO) characterized Covid-19 as a pandemic, several regional directors of this organization called all sectors of society to work together in supporting Covid-19 responses. In the past year, governments, businesses, not-for-profits, and citizens have been collaborating to mitigate the impacts of the pandemic. These impacts look different in rural areas than in large cities. The Rural Rebound case studies included in this paper highlight the experiences, learnings, and recommendations from selected stakeholders in rural Ontario, Canada, reflecting multi-sectoral collaboration. The underlying approach of the Rural Rebound Initiative, developed by the Rural Ontario Institute, is promoting peer-to-peer learning so other rural regions responding to similar concerns can take ideas from the case studies and adapt them to their own context. Multi-sectoral collaboration is not new or exclusive to Covid-19 responses, but it is a critical element that contributes to overcoming any crisis. The case studies, although different in nature, concurred on the importance of this type of collaboration to build on each other’s knowledge and generate solutions that respond to actual needs. Multi-sectoral collaboration also allows optimizing resources such as time, funds, and expertise. More than a year has passed since the pandemic started and there is still uncertainty about the future. Rural stakeholders, as do others, need to keep collaborating, working in partnerships, adapting, innovating, and learning from each other in order to navigate through the uncertainty. Keywords: rural, COVID-19, collaboration, peer learning ----------------------  Relever les défis de la Covid-19 grâce à une collaboration multisectorielle: études de cas sur le rebond rural Début 2020, après que l'Organisation mondiale de la santé (OMS) a qualifié la Covid-19 de pandémie, plusieurs directeurs régionaux de cette organisation ont appelé tous les secteurs de la société à travailler ensemble pour soutenir les réponses à la Covid-19. Au cours de la dernière année, les gouvernements, les entreprises, les organisations à but non lucratif et les citoyens ont collaboré pour atténuer les impacts de la pandémie. Ces impacts sont différents selon les zones, rurales ou urbaines. Les études de cas sur le rebond rural incluses dans cet article soulignent les expériences, les apprentissages et les recommandations de parties prenantes sélectionnées dans les régions rurales de l'Ontario, au Canada, reflétant une collaboration multisectorielle. L'approche sous-jacente de l'Initiative de rebond rural, développée par le Rural Ontario Institute, encourage l'apprentissage entre pairs afin que d'autres régions rurales répondant à des préoccupations similaires puissent s'inspirer des études de cas et les adapter à leur propre contexte. La collaboration multisectorielle n'est pas nouvelle ou exclusive aux réponses de la Covid-19, mais c'est un élément essentiel qui contribue à surmonter toute crise. Les études de cas, bien que de nature différente, ont concordé sur l'importance de ce type de collaboration pour s'appuyer sur les connaissances de chacun et générer des solutions qui répondent aux besoins réels. La collaboration multisectorielle permet également d'optimiser les ressources telles que le temps, les fonds et l'expertise. Plus d'un an s'est écoulé depuis le début de la pandémie et l'avenir demeure incertain. Les intervenants ruraux, comme les autres, doivent continuer à collaborer, à travailler en partenariat, à s'adapter, à innover et à apprendre les uns des autres afin de traverser les phases d’'incertitude. Mots clés: rural, COVID-19, collaboration, apprentissage entre pair

Über die Reaktion von [alpha]- und [beta]-Tetralon mit Kaliumsuperoxid

Lissel M. Über die Reaktion von [alpha]- und [beta]-Tetralon mit Kaliumsuperoxid. Tetrahedron Letters. 1984;25(21):2213-2214.The reaction of [alpha]- and [beta]-tetralone with potassium superoxide is described. In addition to 2-hydroxy-1,4-naphthoquinone [alpha]-naphthol is formed from [alpha]-tetralone and [beta]-naphthol and 2-carboxy-benzenepropionic acid from [beta]-tetralone

Evidence for a hopping mechanism in metal|single molecule|metal junctions involving conjugated metal–terpyridyl complexes; potential-dependent conductances of complexes [M(pyterpy)₂] ²⁺ (M = Co and Fe; pyterpy = 4′-(pyridin-4-yl)-2,2′:6′,2′′-terpyridine) in ionic liquid

Extensive studies of various families of conjugated molecules in metal|molecule|metal junctions suggest that the mechanism of conductance is usually tunnelling for molecular lengths < ca. 4 nm, and that for longer molecules, coherence is lost as a hopping element becomes more significant. In this work we present evidence that, for a family of conjugated, redox-active metal complexes, hopping may be a significant factor for even the shortest molecule studied (ca. 1 nm between contact atoms). The length dependence of conductance for two series of such complexes which differ essentially in the number of conjugated 1,4-C₆H₄- rings in the structures has been studied, and it is found that the junction conductances vary linearly with molecular length, consistent with a hopping mechanism, whereas there is significant deviation from linearity in plots of log(conductance) vs. length that would be characteristic of tunnelling, and the slopes of the log(conductance)–length plots are much smaller than expected for an oligophenyl system. Moreover, the conductances of molecular junctions involving the redox–active molecules, [M(pyterpy)₂] ²⁺/³⁺ (M = Co, Fe) have been studied as a function of electrochemical potential in ionic liquid electrolyte, and the conductance–overpotential relationship is found to fit well with the Kuznetsov–Ulstrup relationship, which is essentially a hopping description

Influencia del coaching educativo en las competencias profesionales de estudiantes del cuarto año de la Licenciatura en Inglés en el Centro Regional San Miguelito 2022

El propósito de la investigación fue analizar la influencia del coaching educativo en las competencias profesionales de estudiantes del cuarto año de la Licenciatura en Inglés del Centro Regional San Miguelito, para el año 2022. En cuanto a la metodología, el paradigma utilizado es cuantitativo, el tipo de investigación descriptiva y de campo, apoyado en un diseño no experimental, transversal y documental. La muestra objeto de estudio la conformaron (34) estudiantes. La técnica utilizada es la encuesta y el instrumento el cuestionario. Este fue validado a través de juicios de expertos y la confiabilidad se obtuvo por el coeficiente de Cronbach (Alfa). Como conclusiones se determinó que los estudiantes no tienen conocimiento sobre el coaching educativo. El asesoramiento está asociado a las prácticas tutoriales que desarrollan los docentes, por lo general de manera grupal. Por otra parte, las competencias profesionales relevantes desde el punto de vista de la profesión no se están desarrollando en el nivel deseado por los estudiantes. Se confirmó una influencia positiva entre las variables de estudio. Finalmente, se diseñó una propuesta con base a los resultados del diagnóstico orientados hacia tres áreas fundamentales: Escenario metodológico (aplicación en organizaciones inteligentes); Cognitivo (gestión del conocimiento) y, Desarrollo profesional y personal. Estas acciones de formación se desarrollan a través de una programación en la cual se consideran los elementos logísticos y operativos de recursos humanos, materiales y económicos