Showing papers by "University of Amsterdam published in 2002"

The polycomb group protein EZH2 is involved in progression of prostate cancer

Abstract: Prostate cancer is a leading cause of cancer-related death in males and is second only to lung cancer. Although effective surgical and radiation treatments exist for clinically localized prostate cancer, metastatic prostate cancer remains essentially incurable. Here we show, through gene expression profiling, that the polycomb group protein enhancer of zeste homolog 2 (EZH2) is overexpressed in hormone-refractory, metastatic prostate cancer. Small interfering RNA (siRNA) duplexes targeted against EZH2 reduce the amounts of EZH2 protein present in prostate cells and also inhibit cell proliferation in vitro. Ectopic expression of EZH2 in prostate cells induces transcriptional repression of a specific cohort of genes. Gene silencing mediated by EZH2 requires the SET domain and is attenuated by inhibiting histone deacetylase activity. Amounts of both EZH2 messenger RNA and EZH2 protein are increased in metastatic prostate cancer; in addition, clinically localized prostate cancers that express higher concentrations of EZH2 show a poorer prognosis. Thus, dysregulated expression of EZH2 may be involved in the progression of prostate cancer, as well as being a marker that distinguishes indolent prostate cancer from those at risk of lethal progression.

Transition-metal-based magnetic refrigerants for room-temperature applications

Abstract: Magnetic refrigeration techniques based on the magnetocaloric effect (MCE) have recently been demonstrated as a promising alternative to conventional vapour-cycle refrigeration1. In a material displaying the MCE, the alignment of randomly oriented magnetic moments by an external magnetic field results in heating. This heat can then be removed from the MCE material to the ambient atmosphere by heat transfer. If the magnetic field is subsequently turned off, the magnetic moments randomize again, which leads to cooling of the material below the ambient temperature. Here we report the discovery of a large magnetic entropy change in MnFeP0.45As0.55, a material that has a Curie temperature of about 300 K and which allows magnetic refrigeration at room temperature. The magnetic entropy changes reach values of 14.5 J K-1 kg-1 and 18 J K-1 kg-1 for field changes of 2 T and 5 T, respectively. The so-called giant-MCE material Gd5Ge2Si2 (ref. 2) displays similar entropy changes, but can only be used below room temperature. The refrigerant capacity of our material is also significantly greater than that of Gd (ref. 3). The large entropy change is attributed to a field-induced first-order phase transition enhancing the effect of the applied magnetic field.

TRANSITION PATH SAMPLING: Throwing Ropes Over Rough Mountain Passes, in the Dark

Abstract: This article reviews the concepts and methods of transition path sampling. These methods allow computational studies of rare events without requiring prior knowledge of mechanisms, reaction coordinates, and transition states. Based upon a statistical mechanics of trajectory space, they provide a perspective with which time dependent phenomena, even for systems driven far from equilibrium, can be examined with the same types of importance sampling tools that in the past have been applied so successfully to static equilibrium properties.

Extended transthoracic resection compared with limited transhiatal resection for adenocarcinoma of the esophagus.

Abstract: Background Controversy exists about the best surgical treatment for esophageal carcinoma. Methods We randomly assigned 220 patients with adenocarcinoma of the mid-to-distal esophagus or adenocarcinoma of the gastric cardia involving the distal esophagus either to transhiatal esophagectomy or to transthoracic esophagectomy with extended en bloc lymphadenectomy. Principal end points were overall survival and disease-free survival. Early morbidity and mortality, the number of quality-adjusted life-years gained, and cost effectiveness were also determined. Results A total of 106 patients were assigned to undergo transhiatal esophagectomy, and 114 to undergo transthoracic esophagectomy. Demographic characteristics and characteristics of the tumor were similar in the two groups. Perioperative morbidity was higher after transthoracic esophagectomy, but there was no significant difference in in-hospital mortality (P=0.45). After a median follow-up of 4.7 years, 142 patients had died — 74 (70 percent) after transh...

The emission spectrum and the radiative lifetime of Eu3+ in luminescent lanthanide complexes

Abstract: Although luminescent complexes of lanthanide ions and organic ligands have been studied intensively, relatively little attention has been paid to the natural (or ‘radiative’) lifetime of the lanthanide centered luminescent state in these systems. Here, the applicability of the well-known Judd–Ofelt theory to the emissive properties of Eu3+ complexes is investigated. Moreover, it is demonstrated experimentally that the radiative lifetime of the 5D0 excited state of Eu3+ can be calculated directly from its corrected emission spectrum, without using Judd–Ofelt theory. We also discuss briefly the possibility of finding the natural lifetimes of lanthanide ions other than Eu3+.

Systema Porifera. A Guide to the Classification of Sponges

Abstract: Why write a book on sponge taxonomy; who would read such a book; what is the relevance of sponges; and what are sponges anyway?

Cortical Focus Drives Widespread Corticothalamic Networks during Spontaneous Absence Seizures in Rats

Abstract: Absence seizures are the most pure form of generalized epilepsy. They are characterized in the electroencephalogram by widespread bilaterally synchronous spike-wave discharges (SWDs), which are the reflections of highly synchronized oscillations in thalamocortical networks. To reveal network mechanisms responsible for the initiation and generalization of the discharges, we studied the interrelationships between multisite cortical and thalamic field potentials recorded during spontaneous SWDs in the freely moving WAG/Rij rat, a genetic model of absence epilepsy. Nonlinear association analysis revealed a consistent cortical "focus" within the peri-oral region of the somatosensory cortex. The SWDs recorded at other cortical sites consistently lagged this focal site, with time delays that increased with electrode distance (corresponding to a mean propagation velocity of 1.4 m/sec). Intra-thalamic relationships were more complex and could not account for the observed cortical propagation pattern. Cortical and thalamic sites interacted bi-directionally, whereas the direction of this coupling could vary throughout one seizure. However, during the first 500 msec, the cortical focus was consistently found to lead the thalamus. These findings argue against the existence of one common subcortical pacemaker for the generation of generalized spike-wave discharges characteristic for absence seizures in the rat. Instead, the results suggest that a cortical focus is the dominant factor in initiating the paroxysmal oscillation within the corticothalamic loops, and that the large-scale synchronization is mediated by ways of an extremely fast intracortical spread of seizure activity. Analogous mechanisms may underlie the pathophysiology of human absence epilepsy.

Dynamics of cell wall structure in Saccharomyces cerevisiae.

Abstract: The cell wall of Saccharomyces cerevisiae is an elastic structure that provides osmotic and physical protection and determines the shape of the cell. The inner layer of the wall is largely responsible for the mechanical strength of the wall and also provides the attachment sites for the proteins that form the outer layer of the wall. Here we find among others the sexual agglutinins and the flocculins. The outer protein layer also limits the permeability of the cell wall, thus shielding the plasma membrane from attack by foreign enzymes and membrane-perturbing compounds. The main features of the molecular organization of the yeast cell wall are now known. Importantly, the molecular composition and organization of the cell wall may vary considerably. For example, the incorporation of many cell wall proteins is temporally and spatially controlled and depends strongly on environmental conditions. Similarly, the formation of specific cell wall protein–polysaccharide complexes is strongly affected by external conditions. This points to a tight regulation of cell wall construction. Indeed, all five mitogen-activated protein kinase pathways in bakers’ yeast affect the cell wall, and additional cell wall-related signaling routes have been identified. Finally, some potential targets for new antifungal compounds related to cell wall construction are discussed.

Financial Development, Property Rights, and Growth

Abstract: The authors analyze how property rights affect the allocation of firms' available resources among different types of assets. In particular, they investigate empirically for a large number of countries whether firms in environments with more secure property rights allocate available resources more toward intangible assets and consequentially grow faster. The authors find that improved asset allocation due to better property rights has an effect on growth in sectoral value added equal to improved access to financing arising from greater financial development. The results are robust, using various samples and specifications, including controlling for growth opportunities.

Proposed diagnostic criteria for the Brugada syndrome: consensus report.

Abstract: Asyndrome characterized by ST-segment elevation in right precordial leads (V1 to V3) that is unrelated to ischemia, electrolyte disturbances, or obvious structural heart disease was reported as early as 1953,1 but was first described as a distinct clinical entity associated with a high risk of sudden cardiac death in 1992.2–4⇓⇓ The Brugada syndrome is a familial disease that displays an autosomal dominant mode of transmission, with incomplete penetrance and an incidence ranging between 5 and 66 per 10 000. In regions of Southeast Asia where it is endemic, the clinical presentation of Brugada syndrome is distinguished by a male predominance (8:1 ratio of male:female) and the appearance of arrhythmic events at an average age of 40 years (range: 1 to 77 years).2,5⇓ Although a number of candidate genes are considered plausible, thus far the syndrome has been linked only to mutations in SCN5A , the gene encoding for the α subunit of the sodium channel.6 A number of ambiguities exist concerning the diagnosis of Brugada syndrome. The electrocardiographic signature of the syndrome is dynamic and often concealed, but can be unmasked by potent sodium channel blockers such as flecainide, ajmaline, and procainamide,7 although the specificity of this effect for uncovering patients at risk for sudden death has been an issue of concern. A recent report by Remme et al8 has shown that the number of idiopathic ventricular fibrillation patients diagnosed as having Brugada syndrome is a sensitive function of the diagnostic criteria applied. What are the proper diagnostic criteria for identifying Brugada syndrome? A definitive answer to this question has been out of reach and is the reason for the establishment of a special Arrhythmia Working Group of the European Society of Cardiology that met from August 31 to …

Molecular Dynamics Simulations

Abstract: Molecular Dynamics (MD) simulations are in many respects very similar to real experiments. In MD, first, sample is prepared, a model system consisting of N particles is selected, and then Newton's equations of motion are solved for the system until the properties of the system no longer change with time. To measure an observable quantity in a MD simulation, one must first of all be able to express this observable as a function of the positions and momenta of the particles in the system. The best introduction to MD simulations is to consider a simple program. To start the simulation, one should assign initial positions and velocities to all particles in the system. The particle positions should be chosen compatible with the structure that one is aiming to simulate. A good MD program requires a good algorithm to integrate Newton's equations of motion. Accuracy for large time steps is more important because the longer the time step that one can use, the fewer evaluations of the forces are needed per unit of simulation time. For most MD applications, Verlet-like algorithms are perfectly adequate. However, sometimes it is convenient to employ a higher-order algorithm.

Self-organization of vegetation in arid ecosystems

Abstract: Scientists are still searching for possible unifying mechanisms to explain this range of spatial patterns (Tongway and Ludwig 2001), and an important question of this research is whether this range is the result of preexisting environmental heterogeneity, the result of spatial selforganization, or both (Klausmeier 1999; Couteron and Lejeune 2001; HilleRisLambers et al. 2001; Von Hardenberg et al. 2001). Here, we contribute to the ongoing debate about vegetation pattern formation in arid ecosystems by presenting novel, spatially explicit model analyses and results, extending on the work of HilleRisLambers et al. (2001). Our results show that these different vegetation patterns observed in arid ecosystems might all be the result of spatial self-organization, caused by one single mechanism: water infiltrates faster into vegetated ground than into bare soil, leading to net displacement of surface water to vegetated patches. This model differs from earlier model results (Klausmeier 1999; Couteron and Lejeune 2001; HilleRisLambers et al. 2001; Von Hardenberg et al. 2001) primarily in two ways: it is fully mechanistic, and it treats the lateral flow of water above and below the soil as separate, not independent, variables. Although the current model greatly simplifies the biophysics of arid systems, it can reproduce the whole range of distinctive vegetation patterns as observed in arid ecosystems, indicating that the proposed mechanism might be generally applicable. We further show that self-organized vegetation patterns can persist far into regions of high aridity, where plants would become extinct if homogeneously distributed, pointing to the importance of this mechanism for maintaining productivity of arid ecosystems (Noy-Meir 1973). Our analyses are based on the model first developed in HilleRisLambers et al. (2001)

Carnitine biosynthesis in mammals.

Abstract: Carnitine is indispensable for energy metabolism, since it enables activated fatty acids to enter the mitochondria, where they are broken down via beta-oxidation. Carnitine is probably present in all animal species, and in numerous micro-organisms and plants. In mammals, carnitine homoeostasis is maintained by endogenous synthesis, absorption from dietary sources and efficient tubular reabsorption by the kidney. This review aims to cover the current knowledge of the enzymological, molecular, metabolic and regulatory aspects of mammalian carnitine biosynthesis, with an emphasis on the human and rat.

Effects of early high-volume continuous venovenous hemofiltration on survival and recovery of renal function in intensive care patients with acute renal failure: A prospective, randomized trial

Abstract: ObjectiveTo study the effects of the initiation time of continuous venovenous hemofiltration and of the ultrafiltrate rate in patients with circulatory and respiratory insufficiency developing early oliguric acute renal failure. The primary end points were mortality at 28 days and recovery of renal

The Runaway Growth of Intermediate-Mass Black Holes in Dense Star Clusters

Abstract: We study the growth rate of stars via stellar collisions in dense star clusters, calibrating our analytic calculations with direct N-body simulations of up to 65,536 stars, performed on the GRAPE family of special-purpose computers. We find that star clusters with initial half-mass relaxation times 25 Myr are dominated by stellar collisions, the first collisions occurring at or near the point of core collapse, which is driven by the segregation of the most massive stars to the cluster center, where they end up in hard binaries. The majority of collisions occur with the same star, resulting in the runaway growth of a supermassive object. This object can grow up to ~0.1% of the mass of the entire star cluster and could manifest itself as an intermediate-mass black hole (IMBH). The phase of runaway growth lasts until mass loss by stellar evolution arrests core collapse. Star clusters older than about 5 Myr and with present-day half-mass relaxation times 100 Myr are expected to contain an IMBH.

Infliximab treatment induces apoptosis of lamina propria T lymphocytes in Crohn's disease.

Abstract: Background and aims: Treatment with infliximab induces remission in about 70% of patients with steroid refractory Crohn9s disease. Because Crohn9s disease is considered to be mediated by uncontrolled activation of mucosal T lymphocytes, we hypothesised that infliximab could induce apoptosis of T lymphocytes. Methods: Induction of apoptosis in vivo was studied in 10 patients with therapy refractory Crohn9s disease. In vitro, resting or stimulated Jurkat T cells were incubated with infliximab. Results: Infusion of infliximab (5 mg/kg) in steroid refractory patients with Crohn9s disease induced a clinical response in 9/10 patients but did not influence expression of activation markers, homing receptors, memory cells, Fas expression, or Bax/Bcl-2 expression on peripheral blood T lymphocytes. In contrast, a significant increase in CD3 and TUNEL positive cells within colonic biopsies was detected 24 hours after infusion of infliximab, suggesting that infliximab stimulates apoptosis of activated T lymphocytes but not of resting T cells. To test this hypothesis, the effects of infliximab on Jurkat T cells were investigated. We observed that infliximab induced apoptosis and an increase in the Bax/Bcl-2 ratio of CD3/CD28 stimulated Jurkat T cells but not of unstimulated Jurkat cells. Conclusions: Our data indicate that infliximab treatment causes a rapid and specific increase in apoptosis of T lymphocytes in the gut mucosa. These findings may explain the rapid and sustained therapeutic effects of infliximab in Crohn9s disease.