Prospects for high-resolution microwave spectroscopy of methanol in a Stark-deflected molecular beam

Recently, the extremely sensitive torsion-rotation transitions in methanol have been used to set a tight constraint on a possible variation of the proton-to-electron mass ratio over cosmological time scales. In order to improve this constraint, laboratory data of increased accuracy will be required. Here, we explore the possibility for performing high-resolution spectroscopy on methanol in a Stark-deflected molecular beam. We have calculated the Stark shift of the lower rotational levels in the ground torsion-vibrational state of CH3OH and CD3OH molecules, and have used this to simulate trajectories through a typical molecular beam resonance setup. Furthermore, we have determined the efficiency of non-resonant multi-photon ionization of methanol molecules using a femtosecond laser pulse. The described setup is in principle suited to measure microwave transitions in CH3OH at an accuracy below 10^{-8}

Signal processing in the TGF-beta superfamily ligand-receptor network

The TGF-beta pathway plays a central role in tissue homeostasis and morphogenesis. It transduces a variety of extracellular signals into intracellular transcriptional responses that control a plethora of cellular processes, including cell growth, apoptosis, and differentiation. We use computational modeling to show that coupling of signaling with receptor trafficking results in a highly versatile signal-processing unit, able to sense by itself absolute levels of ligand, temporal changes in ligand concentration, and ratios of multiple ligands. This coupling controls whether the response of the receptor module is transient or permanent and whether or not different signaling channels behave independently of each other. Our computational approach unifies seemingly disparate experimental observations and suggests specific changes in receptor trafficking patterns that can lead to phenotypes that favor tumor progression.Comment: 33 pages, 7 figure

Genetic Variation in FADS Genes and Plasma Cholesterol Levels in 2-Year-Old Infants

Single nucleotide polymorphisms (SNPs) in genes involved in fatty acid metabolism (FADS1 FADS2 gene cluster) are associated with plasma lipid levels. We aimed to investigate whether these associations are already present early in life and compare the relative contribution of FADS SNPs vs traditional (non-genetic) factors as determinants of plasma lipid levels. Information on infants' plasma total cholesterol levels, genotypes of five FADS SNPs (rs174545, rs174546, rs174556, rs174561, and rs3834458), anthropometric data, maternal characteristics, and breastfeeding history was available for 521 2-year-old children from the KOALA Birth Cohort Study. For 295 of these 521 children, plasma HDLc and non-HDLc levels were also known. Multivariable linear regression analysis was used to study the associations of genetic and non-genetic determinants with cholesterol levels. All FADS SNPs were significantly associated with total cholesterol levels. Heterozygous and homozygous for the minor allele children had about 4% and 8% lower total cholesterol levels than major allele homozygotes. In addition, homozygous for the minor allele children had about 7% lower HDLc levels. This difference reached significance for the SNPs rs174546 and rs3834458. The associations went in the same direction for non-HDLc, but statistical significance was not reached. The percentage of total variance of total cholesterol levels explained by FADS SNPs was relatively low (lower than 3%) but of the same order as that explained by gender and the non-genetic determinants together. FADS SNPs are associated with plasma total cholesterol and HDLc levels in preschool children. This brings a new piece of evidence to explain how blood lipid levels may track from childhood to adulthood. Moreover, the finding that these SNPs explain a similar amount of variance in total cholesterol levels as the non-genetic determinants studied reveals the potential importance of investigating the effects of genetic variations in early life

Competenties voor relatiemanagement: tussen ministerie en uitvoeringsorganisaties in

Na de scheiding van beleid en uitvoering moeten ministeries hun relatie met (verzelfstandigde) uitvoeringsorganisaties opnieuw inrichten. Aan de hand van diverse voorbeelden en de uitkomsten van een kleine enquête blijkt dat ze dat op dit moment nog zeer verschillend doen. Er kan een aantal modellen worden onderscheiden, waarbij contracten, contactpersonen of speciale afdelingen worden ingezet, om de opdrachtgever-en/of eigenaarrol van het departement te vervullen. Met behulp van theorie over accountmanagement worden in dit artikel de vereiste competenties voor relatiemanagement afgeleid evenals enkele aandachtspunten voor de organisatorische in-bedding van deze functie. Op basis daarvan wordt een profiel geschetst van de ideale relatiemanager

HbA1c in Nondiabetic Dutch Infants Aged 8–12 Months: The GECKO-Drenthe birth cohort study

OBJECTIVE-An international committee of experts recommended using HbA(1c) for diagnostic testing for diabetes. Little is known about normal values of HbA(1c) in infants. The aim of this study is to describe the distribution of HbA(1c) in 8- to 12-month-old nondiabetic infants. RESEARCH DESIGN AND METHODS-HbA(1c) was measured in 86 infants participating in the Groningen Expert Center for Kids with Obesity (GECKO)-Drenthe birth cohort study. Anthropometric measurements were performed at Well Baby Clinics. Data on parents and children were collected prospectively using questionnaires. RESULTS-HbA(1c) was normally distributed with a mean (SD) HbA(1c) level of 5.38% (0.24), range 4.8-6.0% or 35.29 mmol/mol (2.65), range 29.1-42.1 mmol/mol. Age, sex, birth weight, duration of breastfeeding, anthropometric measurements, and maternal BMI were not associated with HbA(1c). CONCLUSIONS-We found a normal distribution of HbA(1c) with a relatively high mean HbA(1c) of 5.38%. No significant association between risk factors for type 2 diabetes and HbA(1c) levels was found

High Protein Intake Associates with Cardiovascular Events but not with Loss of Renal Function

The long-term effects of higher dietary protein intake on cardiovascular and renal outcomes in the general population are not clear. We analyzed data from 8461 individuals who did not have renal disease and participated in two or three subsequent screenings (6.4-yr follow-up) in a prospective, community-based cohort study (Prevention of Renal and Vascular ENd-stage Disease [PREVEND]). We calculated daily protein intake from 24-h urinary urea excretion (Maroni formula) and used Cox proportional hazard models to analyze the associations between protein intake, cardiovascular events, and mortality. We used mixed-effects models to investigate the association between protein intake and change in renal function over time. The mean ± SD daily protein intake was 1.20 ± 0.27 g/kg. Protein intake was significantly associated with cardiovascular events during follow-up. The associations seemed U-shaped; compared with intermediate protein intake, individuals with either higher or lower protein intake had higher event rates. All-cause mortality and noncardiovascular mortality also were significantly associated with protein intake; individuals with low protein intake had the highest event rates. We found no association between baseline protein intake and rate of renal function decline during follow-up. In summary, in the general population, high protein intake does not promote accelerated decline of renal function but does associate with an increased risk for cardiovascular events

Disasters in Abstracting Combinatorial Properties of Linear Dependence

A notion of geometric structure can be given to a set of points without using a coordinate system by instead describing geometric relations between finite combinations of elements. The fundamental problem is to then characterize when the points of such a “geometry” have a consistent coordinatization. Matroids are a first step in such a characterization as they require that geometric relations satisfy inherent abstract properties. Concretely, let E be a finite set and I be a collection of subsets of E. The problem is to characterize pairs (E,I) for which there exists a “representation” of E as vectors in a vector space over a field F where I corresponds to the linear independent subsets of E. Necessary conditions for such a representation to exist include: the empty set is independent, subsets of independent sets are also independent, and for each subset X, the maximal independent subsets of X have the same size. When these properties hold, we say that (E,I) describes a matroid. As a result of these properties, matroids provide many useful concepts and are an appropriate context in which to consider characterizations. Mayhew, Newman, and Whittle showed that there exist pathological obstructions to natural axiomatic and forbidden-substructure characterizations of real-representable matroids. Furthermore, an extension of a result of Seymour illustrates that there is high computational complexity in verifying that a representation exists. This thesis shows that such pathologies still persist even if it is known that there exists a coordinatization with complex numbers and a sense of orientation, both of which are necessary to have a coordinatization over the reals