Modulation of gene expression in the liver: towards targeted correction of hyperlipidemia

Humane Genetica LUMC / Biofarmacie, LACDR ULNederlandse Hartstichting (NHF-98.144)Erfelijke aandoeningen, vroegdiagnostiek en behandelin

Affine term structure models : a time-changed approach with perfect fit to market curves

We address the so-called calibration problem which consists of fitting in a tractable way a given model to a specified term structure like, e.g., yield or default probability curves. Time-homogeneous jump-diffusions like Vasicek or Cox-Ingersoll-Ross (possibly coupled with compounded Poisson jumps, JCIR), are tractable processes but have limited flexibility; they fail to replicate actual market curves. The deterministic shift extension of the latter (Hull-White or JCIR++) is a simple but yet efficient solution that is widely used by both academics and practitioners. However, the shift approach is often not appropriate when positivity is required, which is a common constraint when dealing with credit spreads or default intensities. In this paper, we tackle this problem by adopting a time change approach. On the top of providing an elegant solution to the calibration problem under positivity constraint, our model features additional interesting properties in terms of implied volatilities. It is compared to the shift extension on various credit risk applications such as credit default swap, credit default swaption and credit valuation adjustment under wrong-way risk. The time change approach is able to generate much larger volatility and covariance effects under the positivity constraint. Our model offers an appealing alternative to the shift in such cases.Comment: 44 pages, figures and table

Znf202 Affects High Density Lipoprotein Cholesterol Levels and Promotes Hepatosteatosis in Hyperlipidemic Mice

Background: The zinc finger protein Znf202 is a transcriptional suppressor of lipid related genes and has been linked to hypoalphalipoproteinemia. A functional role of Znf202 in lipid metabolism in vivo still remains to be established. Methodology and Principal Findings: We generated mouse Znf202 expression vectors, the functionality of which was established in several in vitro systems. Next, effects of adenoviral znf202 overexpression in vivo were determined in normo- as well as hyperlipidemic mouse models. Znf202 overexpression in mouse hepatoma cells mhAT3F2 resulted in downregulation of members of the Apoe/c1/c2 and Apoa1/c3/a4 gene cluster. The repressive activity of Znf202 was firmly confirmed in an apoE reporter assay and Znf202 responsive elements within the ApoE promoter were identified. Adenoviral Znf202 transfer to Ldlr-/- mice resulted in downregulation of apoe, apoc1, apoa1, and apoc3 within 24 h after gene transfer. Interestingly, key genes in bile flux (abcg5/8 and bsep) and in bile acid synthesis (cyp7a1) were also downregulated. At 5 days post-infection, the expression of the aforementioned genes was normalized, but mice had developed severe hepatosteatosis accompanied by hypercholesterolemia and hypoalphalipoproteinemia. A much milder phenotype was observed in wildtype mice after 5 days of hepatic Znf202 overexpression. Interestingly and similar to Ldl-/- mice, HDL-cholesterol levels in wildtype mice were lowered after hepatic Znf202 overexpression. Conclusion/Significance: Znf202 overexpression in vivo reveals an important role of this transcriptional regulator in liver lipid homeostasis, while firmly establishing the proposed key role in the control of HDL levels

Abdominal Electrodes Analysis by Statistical Processing for Fetal Electrocardiogram Extraction

Obstetricians were asking the engineering support to study more extensively any technical possibility to electronically get some useful information from the whole PQRST complex of the fetal electrocardiogram (fECG) in order to identify eventual sign of fetal distress (FD). The latter should indeed be found as a more reliable information for the clinician with the potential benefit of increasing the sensibility as well as the specificity of the diagnosis of FD. A way to achieve this goal is Blind Source Separation. In this case, the extraction of an estimation of the fetal PQRST complex can be solved using Independent Component Analysis on signals recorded through electrodes located on the pregnant woman abdomen. Today, neither theoretical nor simulation considerations were investigated to determine an optimal number and location of these electrodes, despite possible important consequences on the extraction performances. We propose here a method to identify the location of electrodes (depending of the position of the fetus) that drive electrical components due to the fetus by analyzing the (joint and marginal) density functions of the recorded signals. This result allows to evaluate the ‘interesting’ sensors, therefore allowing electrode selection when many sensors are involved in the measure. We show several simulation results on artificial signals. Key Words Fetal electrocardiogram analysis, non-invasive measurement, mutual information, blind source separation.

Facing threat: Infants' and adults' visual scanning of faces with neutral, happy, sad, angry, and fearful emotional expressions

Contains fulltext : 99333.pdf (publisher's version ) (Closed access)Human faces are among the most important visual stimuli that we encounter at all ages. This importance partly stems from the face as a conveyer of information on the emotional state of other individuals. Previous research has demonstrated specific scanning patterns in response to threat-related compared to non-threat-related emotional expressions. This study investigated how visual scanning patterns toward faces which display different emotional expressions develop during infancy. The visual scanning patterns of 4-month-old and 7-month-old infants and adults when looking at threat-related (i.e., angry and fearful) versus non-threat-related (i.e., happy, sad, and neutral) emotional faces were examined. We found that infants as well as adults displayed an avoidant looking pattern in response to threat-related emotional expressions with reduced dwell times and relatively less fixations to the inner features of the face. In addition, adults showed a pattern of eye contact avoidance when looking at threat-related emotional expressions that was not yet present in infants. Thus, whereas a general avoidant reaction to threat-related facial expressions appears to be present from very early in life, the avoidance of eye contact might be a learned response toward others' anger and fear that emerges later during development.13 p

Apprentissage par projet en électricité : exemple et mise en oeuvre

La formation d’ingénieur à l’Université catholique de Louvain a été réorganisée selon un principe de pédagogie active (apprentissage par problèmes et par projets). Ainsi, il est proposé aux étudiants qui entament leur spécialisation en électricité ou en électromécanique, un projet leur permettant d’aborder à la fois les notions d’électromagnétisme et les notions de circuits électriques et de faire le lien entre ces deux matières. Dans cet article, nous présentons en détails un de ces projets, consistant pour les étudiants à réaliser un capteur de suivi de ligne, ainsi que son électronique de traitement. Des variantes sont également exposées, s’articulant autour de différents types de capteurs intégrés. Nous détaillons les moyens et l’approche mis en œuvre et tirons les conclusions relatives à l’organisation de ces projets