Bepalen van het elutiepatroon van diethylstilbestrol (DES) op een Chromatolithe A kolom

Er is onderzoek verricht naar het elutiepatroon voor DES op verschillende batches Chromatolithe A. De hier gerapporteerde onderzoeken hebben geleid tot een aangepaste versie van het RIKILT-intern analysevoorschrift A 270 (2e oplage) voor het bepalen van diëthylstilbestrol (DES) in runderurine met betrekking tot de kolomzuiveringsstap

Apoptosis induction by Bid requires unconventional ubiquitination and degradation of its N-terminal fragment

Bcl-2 family member Bid is subject to autoinhibition; in the absence of stimuli, its N-terminal region sequesters the proapoptotic Bcl-2 homology 3 (BH3) domain. Upon proteolytic cleavage in its unstructured loop, Bid is activated, although structural data reveal no apparent resulting conformational change. We found that, upon Bid cleavage, the N-terminal fragment (tBid-N) is ubiquitinated and degraded, thus freeing the BH3 domain in the C-terminal fragment (tBid-C). Ubiquitination of tBid-N is unconventional because acceptor sites are neither lysines nor the N terminus. Chemical approaches implicated thioester and hydroxyester linkage of ubiquitin and mutagenesis implicated serine and possibly threonine as acceptor residues in addition to cysteine. Acceptor sites reside predominantly but not exclusively in helix 1, which is required for ubiquitination and degradation of tBid-N. Rescue of tBid-N from degradation blocked Bid's ability to induce mitochondrial outer membrane permeability but not mitochondrial translocation of the cleaved complex. We conclude that unconventional ubiquitination and proteasome-dependent degradation of tBid-N is required to unleash the proapoptotic activity of tBid-C

Statistiek in de chemometrie : deel 1: theoretisch gedeelte

In april - juni 1990 werd op het RIKILT een interne cursus over de toepassing van statistiek in de chemometrie gegeven. De cursus bestond uit een theoretisch gedeelte en de behandeling van praktische toepassingen met behulp van SPSS. Cursusleider voor het theoretische deel was dr. W.G. de Ruig, voor het praktische deel dr. ir. A.B. Cramwinckel. Bij het opzetten en geven van de cursus werd veel medewerking ondervonden van ir. A.A.M . Jansen en drs. J.A. Oude Voshaar van de Groep Landbouwwiskunde. Dit rapport omvat het theoretische gedeelte van de cursus. Hierbij zijn een aantal basisbegrippen uit de statistiek, die in de chemometrie van pas komen, behandeld. Aan de orde zijn gekomen: populaties, steekproeven, eigenschappen en toepassing van de normale verdeling, steekproefgemiddelde, standaardafwijking, betrouwbaarheidsinterval, toetsen van hypothesen, ringonderzoek, proefopzetten, variantieanalyse, lineaire-regressieanalyse, calibratie, multipele lineaire regressie en met deze onderwerpen gerelateerde begrippen

Can decision transparency increase citizen trust in regulatory agencies? Evidence from a representative survey experiment

Decision transparency is often proposed as a way to maintain or even increase citizen trust, yet this assumption is still untested in the context of regulatory agencies. We test the effect of transparency of a typical decision tradeoff in regulatory enforcement: granting forbearance or imposing a sanction. We employed a representative survey experiment (n = 1,546) in which we test the effect of transparency in general (providing information about a decision or not) and the effect of specific types of transparency (process or rationale transparency). We do this for agencies supervising financial markets, education, and health care. We find that overall decision transparency significantly increases citizen trust in only two of the three agencies. Rationale transparency has a more pronounced positive effect only for the Education Inspectorate. We conclude that the overall effect of decision transparency is positive but that the nature of the regulatory domain may weaken or strengthen this effect

Phase Behavior of Bent-Core Molecules

Recently, a new class of smectic liquid crystal phases (SmCP phases) characterized by the spontaneous formation of macroscopic chiral domains from achiral bent-core molecules has been discovered. We have carried out Monte Carlo simulations of a minimal hard spherocylinder dimer model to investigate the role of excluded volume interations in determining the phase behavior of bent-core materials and to probe the molecular origins of polar and chiral symmetry breaking. We present the phase diagram as a function of pressure or density and dimer opening angle $\psi$. With decreasing $\psi$, a transition from a nonpolar to a polar smectic phase is observed near $\psi = 167^{\circ}$, and the nematic phase becomes thermodynamically unstable for $\psi < 135^{\circ}$. No chiral smectic or biaxial nematic phases were found.Comment: 4 pages Revtex, 3 eps figures (included

Hypothermic machine perfusion in liver transplantation: a randomized trial

BACKGROUNDTransplantation of livers obtained from donors after circulatory death is associated with an increased risk of nonanastomotic biliary strictures. Hypothermic oxygenated machine perfusion of livers may reduce the incidence of biliary complications, but data from prospective, controlled studies are limited.METHODSIn this multicenter, controlled trial, we randomly assigned patients who were undergoing transplantation of a liver obtained from a donor after circulatory death to receive that liver either after hypothermic oxygenated machine perfusion (machine-perfusion group) or after conventional static cold storage alone (control group). The primary end point was the incidence of nonanastomotic biliary strictures within 6 months after transplantation. Secondary end points included other graft-related and general complications.RESULTSA total of 160 patients were enrolled, of whom 78 received a machine-perfused liver and 78 received a liver after static cold storage only (4 patients did not receive a liver in this trial). Nonanastomotic biliary strictures occurred in 6% of the patients in the machine-perfusion group and in 18% of those in the control group (risk ratio, 0.36; 95% confidence interval [CI], 0.14 to 0.94; P=0.03). Postreperfusion syndrome occurred in 12% of the recipients of a machine-perfused liver and in 27% of those in the control group (risk ratio, 0.43; 95% CI, 0.20 to 0.91). Early allograft dysfunction occurred in 26% of the machine-perfused livers, as compared with 40% of control livers (risk ratio, 0.61; 95% CI, 0.39 to 0.96). The cumulative number of treatments for nonanastomotic biliary strictures was lower by a factor of almost 4 after machine perfusion, as compared with control. The incidence of adverse events was similar in the two groups.CONCLUSIONSHypothermic oxygenated machine perfusion led to a lower risk of nonanastomotic biliary strictures following the transplantation of livers obtained from donors after circulatory death than conventional static cold storage.Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Study protocol for a multicenter randomized controlled trial to compare the efficacy of end-ischemic dual hypothermic oxygenated machine perfusion with static cold storage in preventing non-anastomotic biliary strictures after transplantation of liver grafts donated after circulatory death: DHOPE-DCD trial

Background: The major concern in liver transplantation of grafts from donation after circulatory death (DCD) donors remains the high incidence of non-anastomotic biliary strictures (NAS). Machine perfusion has been proposed as an alternative strategy for organ preservation which reduces ischemia-reperfusion injury (IRI). Experimental studies have shown that dual hypothermic oxygenated machine perfusion (DHOPE) is associated with less IRI, improved hepatocellular function, and better preserved mitochondrial and endothelial function compared to conventional static cold storage (SCS). Moreover, DHOPE was safely applied with promising results in a recently performed phase-1 study. The aim of the current study is to determine the efficacy of DHOPE in reducing the incidence of NAS after DCD liver transplantation. Methods: This is an international multicenter randomized controlled trial. Adult patients (≥18 yrs. old) undergoing transplantation of a DCD donor liver (Maastricht category III) will be randomized between the intervention and control group. In the intervention group, livers will be subjected to two hours of end-ischemic DHOPE after SCS and before implantation. In the control group, livers will be subjected to care as usual with conventional SCS only. Primary outcome is the incidence of symptomatic NAS diagnosed by a blinded adjudication committee. In all patients, magnetic resonance cholangiography will be obtained at six months after transplantation. Discussion: DHOPE is associated with reduced IRI of the bile ducts. Whether reduced IRI of the bile ducts leads to lower incidence of NAS after DCD liver transplantation can only be examined in a randomized controlled trial. Trial registration: The trial was registered in Clinicaltrials.gov in September 2015 with the identifier NCT02584283