Showing papers by "Utrecht University published in 2001"

Minimum information about a microarray experiment (MIAME)-toward standards for microarray data.

Abstract: Microarray analysis has become a widely used tool for the generation of gene expression data on a genomic scale. Although many significant results have been derived from microarray studies, one limitation has been the lack of standards for presenting and exchanging such data. Here we present a proposal, the Minimum Information About a Microarray Experiment (MIAME), that describes the minimum information required to ensure that microarray data can be easily interpreted and that results derived from its analysis can be independently verified. The ultimate goal of this work is to establish a standard for recording and reporting microarray-based gene expression data, which will in turn facilitate the establishment of databases and public repositories and enable the development of data analysis tools. With respect to MIAME, we concentrate on defining the content and structure of the necessary information rather than the technical format for capturing it.

Holographic reconstruction of spacetime and renormalization in the AdS/CFT correspondence

Abstract: We develop a systematic method for renormalizing the AdS/CFT prescription for computing correlation functions. This involves regularizing the bulk on-shell supergravity action in a covariant way, computing all divergences, adding counterterms to cancel them and then removing the regulator. We explicitly work out the case of pure gravity up to six dimensions and of gravity coupled to scalars. The method can also be viewed as providing a holographic reconstruction of the bulk spacetime metric and of bulk fields on this spacetime, out of conformal field theory data. Knowing which sources are turned on is sufficient in order to obtain an asymptotic expansion of the bulk metric and of bulk fields near the boundary to high enough order so that all infrared divergences of the on-shell action are obtained. To continue the holographic reconstruction of the bulk fields one needs new CFT data: the expectation value of the dual operator. In particular, in order to obtain the bulk metric one needs to know the expectation value of stress-energy tensor of the boundary theory. We provide completely explicit formulae for the holographic stress-energy tensors up to six dimensions. We show that both the gravitational and matter conformal anomalies of the boundary theory are correctly reproduced. We also obtain the conformal transformation properties of the boundary stress-energy tensors.

Mass-loss predictions for O and B stars as a function of metallicity

Abstract: We have calculated a grid of massive star wind models and mass-loss rates for a wide range of metal abundances between 1=100 Z=Z 10. The calculation of this grid completes the Vink et al. (2000) mass-loss recipe with an additional parameter Z. We have found that the exponent of the power law dependence of mass loss vs. metallicity is constant in the range between 1/30 Z=Z 3. The mass-loss rate scales as _ M / Z 0:85 v1 p with p = 1:23 for stars with Te > 25 000 K, and p = 1:60 for the B supergiants with Te 25 000 K, and _ M / Z 0:64 for B supergiants with Te < 25 000 K. Although it is derived that the exponent of the mass loss vs. metallicity dependence is constant over a large range in Z, one should be aware of the presence of bi-stability jumps at specic temperatures. Here the character of the line driving changes drastically due to recombinations of dominant metal species resulting in jumps in the mass loss. We have investigated the physical origins of these jumps and have derived formulae that combine mass loss recipes for both sides of such jumps. As observations of dierent galaxies show that the ratio Fe/O varies with metallicity, we make a distinction between the metal abundance Z derived on the basis of iron or oxygen lines. Our mass-loss predictions are successful in explaining the observed mass-loss rates for Galactic and Small Magellanic Cloud O- type stars, as well as in predicting the observed Galactic bi-stability jump. Hence, we believe that our predictions are reliable and suggest that our mass-loss recipe be used in future evolutionary calculations of massive stars at dierent metal abundance. A computer routine to calculate mass loss is publicly available.

Mass-loss predictions for O and B stars as a function of metallicity

Abstract: We have calculated a grid of massive star wind models and mass-loss rates for a wide range of metal abundances between 1/100 and 10 Z/Zsun. The calculation of this grid completes the Vink et al. (2000) mass-loss recipe with an additional parameter Z. We have found that the exponent of the power law dependence of mass loss vs. metallicity is constant in the range between 1/30 and 3 Z/Zsun. The mass-loss rate scales as Mdot \propto Z^0.85 Vinf^p with p = -1.23 for stars with Teff \ga 25000 K, and p = -1.60 for the B supergiants with Teff \la 25000 K. Taking also into account the metallicity dependence of Vinf, using the power law dependence Vinf \propto Z^0.13 from Leitherer et al. (1992), the overall result of mass loss as a function of metallicity can be represented by Mdot \propto Z^0.69 for stars with Teff \ga 25000 K, and Mdot \propto Z^0.64 for B supergiants with Teff \la 25000 K. Our mass-loss predictions are successful in explaining the observed mass-loss rates for Galactic and Small Magellanic Cloud O-type stars, as well as in predicting the observed Galactic bi-stability jump. Hence, we believe that our predictions are reliable and suggest that our mass-loss recipe be used in future evolutionary calculations of massive stars at different metal abundance. A computer routine to calculate mass loss is publicly available.

Platinum Group Organometallics Based on “Pincer” Complexes: Sensors, Switches, and Catalysts

Abstract: Since the first reports in the late 1970s on transition metal complexes contain- ing pincer-type ligands—named after the particular coordination mode of these ligands—these systems have at- tracted increasing interest owing to the unusual properties of the metal centers imparted by the pincer ligand. Typical- ly, such a ligand comprises an anionic aryl ring which is ortho,ortho-disubsti- tuted with heteroatom substituents, for example, CH2NR2 ,C H 2PR2 or CH2SR, which generally coordinate to the met- al center, and therefore support the MC s bond. This commonly results in a terdentate and meridional coordina- tion mode consisting of two metalla- cycles which share the MC bond. Detailed studies of the formation and the properties of a large variety of pincers containing platinum group metal complexes have provided direct access to both a fundamental under- standing of a variety of reactions in organometallic chemistry and to a range of new applications of these complexes. The discovery of alkane dehydrogenation catalysts, the mecha- nistic elucidation of fundamental transformations (for example, CC bond activation), the construction of the first metallodendrimers for sustain- able homogeneous catalysis, and the engineering of crystalline switches for materials processing represent only a few of the many highlights which have emanated from these numerous inves- tigations. This review discusses the synthetic methodologies that are cur- rently available for the preparation of platinum group metal complexes con- taining pincer ligands and especially emphasizes different applications that have been realized in materials science such as the development and engineer- ing of sensors, switches, and catalysts.

Sorption of veterinary pharmaceuticals in soils: a review.

Abstract: Veterinary pharmaceuticals (VPs) are used in large amounts in modern husbandry. Due to their use pattern, they possess a potential for reaching the soil environment. To assess their mobility in soil, the literature on sorption of chemicals used as VPs is reviewed and put into perspective of their physicochemical properties. The compilation of sorption coefficients to soil solids (Kd,solid) demonstrates that these chemicals display a wide range of mobility (0.2 < Kd,solid < 6,000 L/kg). Partition coefficients for association of tetracycline and quinolone carboxylic acid VPs to dissolved organic matter (Kd,DOM) vary between 100 and 50,000 L/kg. The variation in Kd,solid for a given compound in different soils can be significant. For most of the compounds, the variation is not considerably lower for the organic carbon-normalized sorption coefficient Koc. In addition, prediction of log Koc by log Kow leads to significant underestimation of log Koc and log Kd,DOM values. This suggests that mechanisms other than hydrophobic partitioning play a significant role in sorption of VPs. A number of hydrophobicity-independent mechanisms such as cation exchange, cation bridging at clay surfaces, surface complexation, and hydrogen bonding appear to be involved. These processes are not accounted for by organic carbon normalization, suggesting that this data treatment is conceptually inappropriate and fails to describe the sorption behavior. Moreover, prediction of log Koc based on the hydrophobicity parameter log Kow is not successful.

Carbon dioxide emissions from the global cement industry

Abstract: ▪ Abstract The cement industry contributes about 5% to global anthropogenic CO2 emissions, making the cement industry an important sector for CO2-emission mitigation strategies. CO2 is emitted from the calcination process of limestone, from combustion of fuels in the kiln, as well as from power generation. In this paper, we review the total CO2 emissions from cement making, including process and energy-related emissions. Currently, most available data only includes the process emissions. We also discuss CO2 emission mitigation options for the cement industry. Estimated total carbon emissions from cement production in 1994 were 307 million metric tons of carbon (MtC), 160 MtC from process carbon emissions, and 147 MtC from energy use. Overall, the top 10 cement-producing countries in 1994 accounted for 63% of global carbon emissions from cement production. The average intensity of carbon dioxide emissions from total global cement production is 222 kg of C/t of cement. Emission mitigation options include en...

APC , Signal transduction and genetic instability in colorectal cancer

Abstract: Colorectal cancer arises through a gradual series of histological changes, each of which is accompanied by a specific genetic alteration. In general, an intestinal cell needs to comply with two essential requirements to develop into a cancer: it must acquire selective advantage to allow for the initial clonal expansion, and genetic instability to allow for multiple hits in other genes that are responsible for tumour progression and malignant transformation. Inactivation of APC — the gene responsible for most cases of colorectal cancer — might fulfil both requirements.

Handbook of bereavement research: Consequences, coping, and care

Abstract: New research continues to challenge our assumptions about the fundamental nature and course of grief: its roots in our biology, our emotions, and our social interactions. The "Handbook of Bereavement Research" provides a broad view of diverse contemporary approaches to bereavement, examining both normal adaptation and complicated manifestations of grief. In this volume, leading interdisciplinary scholars focus on three important themes in bereavement research: consequences, coping and care. In exploring the consequences of bereavement, authors examine developmental factors that influence grief both for the individual and the family at different phases of the life cycle. In exploring coping, they describe exciting new empirical studies about how people can and do cope with grief, without professional intervention. People do not grieve alone, so chapters on coping present new ways to understand grief at an interpersonal level as well. Until recently, intervention for the bereaved has not been scientifically guided and has become the subject of challenging differences of opinion and approach. Chapters in the care section of the volume critically examine interventions to date and provide guidance for assessment and more empirically guided treatment strategies. The "Handbook" provides an up-to-date comprehensive review of scientific knowledge about bereavement in an authoritative yet accessible way that should be useful reading for researchers, practitioners and health care professionals in the 21st century.

Fractional Flow Reserve to Determine the Appropriateness of Angioplasty in Moderate Coronary Stenosis A Randomized Trial

Abstract: Background—PTCA of a coronary stenosis without documented ischemia at noninvasive stress testing is often performed, but its benefit is unproven. Coronary pressure–derived fractional flow reserve (FFR) is an invasive index of stenosis severity that is a reliable substitute for noninvasive stress testing. A value of 0.75 identifies stenoses with hemodynamic significance. Methods and Results—In 325 patients for whom PTCA was planned and who did not have documented ischemia, FFR of the stenosis was measured. If FFR was >0.75, patients were randomly assigned to deferral (deferral group; n=91) or performance (performance group; n=90) of PTCA. If FFR was <0.75, PTCA was performed as planned (reference group; n=144). Clinical follow-up was obtained at 1, 3, 6, 12, and 24 months. Event-free survival was similar between the deferral and performance groups (92% versus 89% at 12 months and 89% versus 83% at 24 months) but was significantly lower in the reference group (80% at 12 months and 78% at 24 months). In addi...

Staphylococcus aureus resistance to human defensins and evasion of neutrophil killing via the novel virulence factor MprF is based on modification of membrane lipids with L-lysine

Abstract: Defensins, antimicrobial peptides of the innate immune system, protect human mucosal epithelia and skin against microbial infections and are produced in large amounts by neutrophils. The bacterial pathogen Staphylococcus aureus is insensitive to defensins by virtue of an unknown resistance mechanism. We describe a novel staphylococcal gene, mprF, which determines resistance to several host defense peptides such as defensins and protegrins. An mprF mutant strain was killed considerably faster by human neutrophils and exhibited attenuated virulence in mice, indicating a key role for defensin resistance in the pathogenicity of S. aureus. Analysis of membrane lipids demonstrated that the mprF mutant no longer modifies phosphatidylglycerol with l-lysine. As this unusual modification leads to a reduced negative charge of the membrane surface, MprF-mediated peptide resistance is most likely based on repulsion of the cationic peptides. Accordingly, inactivation of mprF led to increased binding of antimicrobial peptides by the bacteria. MprF has no similarity with genes of known function, but related genes were identified in the genomes of several pathogens including Mycobacterium tuberculosis, Pseudomonas aeruginosa, and Enterococcus faecalis. MprF thus constitutes a novel virulence factor, which may be of general relevance for bacterial pathogens and represents a new target for attacking multidrug resistant bacteria.

Mutations in the APC tumour suppressor gene cause chromosomal instability

Abstract: Two forms of genetic instability have been described in colorectal cancer: microsatellite instability and chromosomal instability. Microsatellite instability results from mutations in mismatch repair genes; chromosomal instability is the hallmark of many colorectal cancers, although it is not completely understood at the molecular level. As truncations of the Adenomatous Polyposis Coli (APC) gene are found in most colorectal tumours, we thought that mutations in APC might be responsible for chromosomal instability. To test this hypothesis, we examined mouse embryonic stem (ES) cells homozygous for Min (multiple intestinal neoplasia) or Apc1638T alleles. Here we show that Apc mutant ES cells display extensive chromosome and spindle aberrations, providing genetic evidence for a role of APC in chromosome segregation. Consistent with this, APC accumulates at the kinetochore during mitosis. Apc mutant cells form mitotic spindles with an abundance of microtubules that inefficiently connect with kinetochores. This phenotype is recapitulated by the induced expression of a 253-amino-acid carboxy-terminal fragment of APC in microsatellite unstable colorectal cancer cells. We conclude that loss of APC sequences that lie C-terminal to the beta-catenin regulatory domain contributes to chromosomal instability in colorectal cancer.

The Indian Ocean Experiment: Widespread Air Pollution from South and Southeast Asia

Abstract: The Indian Ocean Experiment (INDOEX) was an international, multiplatform field campaign to measure long-range transport of air pollution from South and Southeast Asia toward the Indian Ocean during the dry monsoon season in January to March 1999. Surprisingly high pollution levels were observed over the entire northern Indian Ocean toward the Intertropical Convergence Zone at about 6°S. We show that agricultural burning and especially biofuel use enhance carbon monoxide concentrations. Fossil fuel combustion and biomass burning cause a high aerosol loading. The growing pollution in this region gives rise to extensive air quality degradation with local, regional, and global implications, including a reduction of the oxidizing power of the atmosphere.

High-Resolution X-ray Emission and X-ray Absorption Spectroscopy

Abstract: In this review, high-resolution X-ray emission and X-ray absorption spectroscopy will be discussed. The focus is on the 3d transition-metal systems. To understand high-resolution X-ray emission and reso-nant X-ray emission, it is first necessary to spend some time discussing the X-ray absorption process. Section II discusses 1s X-ray absorption, i.e., the K edges, and section III deals with 2p X-ray absorption, the L edges. X-ray emission is discussed in, respectively, the L edges. X-ray emission is discussed in, respec-tively, and section V on 2p3s and 2p3d X-ray emission. Section VI focuses on magnetic dichroism effects, and in section VII selective X-ray absorption experiments are discussed. To limit the scope of this review paper, many related topics (for example, EELS, XPS, and resonant photoemission, phonon-oriented inelastic X-ray scat-tering, and X-ray microscopy) will not be discussed. In addition, many aspects of X-ray absorption, such as reflection experiments, diffraction absorption fine structure, and related experiments, will remain untouched. EXAFS will be discussed very briefly, and its X-ray emission analogue EXEFS 69,71 will not be discussed.

On the clinical validity of the Maslach Burnout Inventory and the Burnout Measure

Abstract: Current knowledge about burnout suffers from a healthy worker bias since only working - and thus relatively healthy - employees have been investigated. The main objective of this study is to examine - for the first time among employees who sought psychological treatment - the validity of the two most widely used burnout instruments; the Maslach Burnout Inventory (MBI) and the Burnout Measure (BM). Two groups were distinguished: a “burned out” group (n = 71) that suffers from work-related neurasthenia (according to ICD-10 criteria), and a “non-burned out” group (n = 68). Results show that: (1) the validity of the three-factor structure of the MBI and the BM is confirmed; (2) burnout can partly be differentiated from other mental syndromes (e.g., anxiety and depression); and (3) two MBI-scales (Emotional Exhaustion and Depersonalization) and one BM-scale (Exhaustion) are able to discriminate between burned out and non-burned out employees. The practical implications of these results are discussed.

Sox9 induces testis development in XX transgenic mice.

Abstract: Mutations in SOX9 are associated with male-to-female sex reversal in humans. To analyze Sox9 function during sex determination, we ectopically expressed this gene in XX gonads. Here, we show that Sox9 is sufficient to induce testis formation in mice, indicating that it can substitute for the sex-determining gene Sry.

Microalbuminuria is common, also in a nondiabetic, nonhypertensive population, and an independent indicator of cardiovascular risk factors and cardiovascular morbidity

Abstract: Objectives. To assess the prevalence of microalbuminuria in the general population, especially in nondiabetic and nonhypertensive subjects, and its association with known cardiovascular risk factors and cardiovascular morbidity. Design. Cross-sectional cohort study. Setting. Inhabitants of the city of Groningen, the Netherlands. Subjects. All inhabitants, aged between 28 and 75 years, were send a postal questionnaire and a vial to collect an early morning urine sample (n = 85 421). Of these 40 856 subjects (47.8%) responded. Cardiovascular risk factors and morbidity were validated in a well defined nondiabetic and nonhypertensive group of 5241 subjects. Main outcome measures. Microalbuminuria, self-reported cardiovascular risk and cardiovascular morbidity in the total study cohort, and additionally more detailed measurements in a subset of the total population. Results. Microalbuminuria (20-200 mg L-1) was present in 7.2% of the subjects and independently associated with age, gender, hypertension, diabetes, smoking, previous myocardial infarction and stroke. Some of these associations were already observed at albuminuria levels of 10-20 mg L-1. After exclusion of the diabetic and hypertensive subjects, microalbuminuria was still prevalent in 6.6% of the subjects. Conclusions. Microalbuminuria appears to be common not only in the general population but also in a nondiabetic, nonhypertensive population and is independently associated with increased cardiovascular risk factors and cardio-vascular morbidity. Importantly, some of these associations are present at urinary albumin levels currently considered to be normal. These findings suggest that urinary albumin measurements may be useful in early risk profiling and prevention of cardiovascular disease in the population at large.

Three-dimensional modeling for functional analysis of cardiac images, a review

Abstract: Three-dimensional (3-D) imaging of the heart is a rapidly developing area of research in medical imaging. Advances in hardware and methods for fast spatio-temporal cardiac imaging are extending the frontiers of clinical diagnosis and research on cardiovascular diseases. In the last few years, many approaches have been proposed to analyze images and extract parameters of cardiac shape and function from a variety of cardiac imaging modalities. In particular, techniques based on spatio-temporal geometric models have received considerable attention. This paper surveys the literature of two decades of research on cardiac modeling. The contribution of the paper is three-fold: (1) to serve as a tutorial of the field for both clinicians and technologists, (2) to provide an extensive account of modeling techniques in a comprehensive and systematic manner, and (3) to critically review these approaches in terms of their performance and degree of clinical evaluation with respect to the final goal of cardiac functional analysis. From this review it is concluded that whereas 3-D model-based approaches have the capability to improve the diagnostic value of cardiac images, issues as robustness, 3-D interaction, computational complexity and clinical validation still require significant attention.

Hydrogen storage using physisorption – materials demands

Abstract: A survey is presented of the storage capacities of a large number of different adsorbents for hydrogen at 77 K and 1 bar. Results are evaluated to examine the feasibility and perspectives of transportable and reversible storage systems based on physisorption of hydrogen on adsorbents. It is concluded that microporousadsorbents, e.g. zeolites and activated carbons, display appreciable sorption capacities. Based on their micropore volume (∼1 ml/g) carbon-based sorbents display the largest adsorption, viz. 238 ml (STP)/g, at the prevailing conditions. Optimization of sorbent and adsorption conditions is expected to lead to adsorption of ∼560 ml (STP)/g, close to targets set for mobile applications.

International surveillance of bloodstream infections due to Candida species: frequency of occurrence and in vitro susceptibilities to fluconazole, ravuconazole, and voriconazole of isolates collected from 1997 through 1999 in the SENTRY antimicrobial surveillance program.

Abstract: A surveillance program (SENTRY) of bloodstream infections (BSI) in the United States, Canada, Latin America, and Europe from 1997 through 1999 detected 1,184 episodes of candidemia in 71 medical centers (32 in the United States, 23 in Europe, 9 in Latin America, and 7 in Canada). Overall, 55% of the yeast BSIs were due to Candida albicans, followed by Candida glabrata and Candida parapsilosis (15%), Candida tropicalis (9%), and miscellaneous Candida spp. (6%). In the United States, 45% of candidemias were due to non-C. albicans species. C. glabrata (21%) was the most common non-C. albicans species in the United States, and the proportion of non-C. albicans BSIs was highest in Latin America (55%). C. albicans accounted for 60% of BSI in Canada and 58% in Europe. C. parapsilosis was the most common non-C. albicans species in Latin America (25%), Canada (16%), and Europe (17%). Isolates of C. albicans, C. parapsilosis, and C. tropicalis were all highly susceptible to fluconazole (97 to 100% at ≤8 μg/ml). Likewise, 97 to 100% of these species were inhibited by ≤1 μg/ml of ravuconazole (concentration at which 50% were inhibited [MIC50], 0.007 to 0.03 μg/ml) or voriconazole (MIC50, 0.007 to 0.06 μg/ml). Both ravuconazole and voriconazole were significantly more active than fluconazole against C. glabrata (MIC90s of 0.5 to 1.0 μg/ml versus 16 to 32 μg/ml, respectively). A trend of increased susceptibility of C. glabrata to fluconazole was noted over the three-year period. The percentage of C. glabrata isolates susceptible to fluconazole increased from 48% in 1997 to 84% in 1999, and MIC50s decreased from 16 to 4 μg/ml. A similar trend was documented in both the Americas (57 to 84% susceptible) and Europe (22 to 80% susceptible). Some geographic differences in susceptibility to triazole were observed with Canadian isolates generally more susceptible than isolates from the United States and Europe. These observations suggest susceptibility patterns and trends among yeast isolates from BSI and raise additional questions that can be answered only by continued surveillance and clinical investigations of the type reported here (SENTRY Program).

The Structure and Stability of Common Mental Disorders: The NEMESIS Study

Abstract: Background We analyzed the underlying latent structure of 12-month DSM-III-R diagnoses of 9 common disorders for the general population in the Netherlands. In addition, we sought to establish (1) the stability of the latent structure underlying mental disorders across a 1-year period (structural stability) and (2) the stability of individual differences in mental disorders at the level of the latent dimensions (differential stability). Methods Data were obtained from the first and second measurement of the Netherlands Mental Health Survey and Incidence Study (NEMESIS) (response rate at baseline: 69.7%, n = 7076; 1 year later, 79.4%, n = 5618). Nine common DSM-III-R diagnoses were assessed twice with the Composite International Diagnostic Interview with a time lapse of 1 year. Using structural equation modeling, the number of latent dimensions underlying these diagnoses was determined, and the structural and differential stability were assessed. Results A 3-dimensional model was established as having the best fit: a first dimension underlying substance use disorders (alcohol dependence, drug dependence); a second dimension for mood disorders (major depression, dysthymia), including generalized anxiety disorder; and a third dimension underlying anxiety disorders (simple phobia, social phobia, agoraphobia, and panic disorder). The structural stability of this model during a 1-year period was substantial, and the differential stability of the 3 latent dimensions was considerable. Conclusions Our results confirm the 3-dimensional model for 12-month prevalence of mental disorders. Results underline the argument for focusing on core psychopathological processes rather than on their manifestation as distinguished disorders in future population studies on common mental disorders.

Computer-aided diagnosis in chest radiography: a survey

Abstract: The traditional chest radiograph is still ubiquitous in clinical practice, and will likely remain so for quite some time. Yet, its interpretation is notoriously difficult. This explains the continued interest in computer-aided diagnosis for chest radiography. The purpose of this survey is to categorize and briefly review the literature on computer analysis of chest images, which comprises over 150 papers published in the last 30 years. Remaining challenges are indicated and some directions for future research are given.

Proliferation and differentiation of spermatogonial stem cells

Abstract: Spermatogonial stem cells (A s spermatogonia) are single cells that either renew themselves or produce A pr (paired) spermatogonia predestined to differentiate. In turn, the A pr divide into chains of A al (aligned) spermatogonia that also divide. The ratio between self-renewal and differentiation of the stem cells is regulated by glial cell line-derived neurotrophic factor produced by Sertoli cells, while the receptors are expressed in stem cells. A s , A pr and A al spermatogonia proliferate during part of the epithelial cycle forming many A al spermatogonia. During epithelial stage VIII, almost all A al spermatogonia, few A pr and very few A s spermatogonia differentiate into A1 spermatogonia. A number of molecules are involved in this differentiation step including the stem cell factor-c-kit system, the Dazl RNA binding protein, cyclin D 2 and retinoic acid. There is no fine regulation of the density of spermatogonial stem cells and consequently, in some areas, many A1 and, in other areas, few A1 spermatogonia are formed. An equal density of spermatocytes is then obtained by the apoptosis of A2, A3 or A4 spermatogonia to remove the surplus cells. The Bcl-2 family members Bax and Bcl-x L are involved in this density regulation. Several mechanisms are available to cope with major or minor shortages in germ cell production. After severe cell loss, stem cell renewal is preferred above differentiation and the period of proliferation of A s , A pr and A al spermatogonia is extended. Minor shortages are dealt with, at least in part, by less apoptosis among A2-A4 spermatogonia.

Molecular Detection of Antimicrobial Resistance

Abstract: The determination of antimicrobial susceptibility of a clinical isolate, especially with increasing resistance, is often crucial for the optimal antimicrobial therapy of infected patients. Nucleic acid-based assays for the detection of resistance may offer advantages over phenotypic assays. Examples are the detection of the methicillin resistance-encoding mecA gene in staphylococci, rifampin resistance in Mycobacterium tuberculosis, and the spread of resistance determinants across the globe. However, molecular assays for the detection of resistance have a number of limitations. New resistance mechanisms may be missed, and in some cases the number of different genes makes generating an assay too costly to compete with phenotypic assays. In addition, proper quality control for molecular assays poses a problem for many laboratories, and this results in questionable results at best. The development of new molecular techniques, e.g., PCR using molecular beacons and DNA chips, expands the possibilities for monitoring resistance. Although molecular techniques for the detection of antimicrobial resistance clearly are winning a place in routine diagnostics, phenotypic assays are still the method of choice for most resistance determinations. In this review, we describe the applications of molecular techniques for the detection of antimicrobial resistance and the current state of the art.

Shape matching: similarity measures and algorithms

Abstract: Shape matching is an important ingredient in shape retrieval, recognition and classification, alignment and registration, and approximation and simplification. This paper treats various aspects that are needed to solve shape matching problems: choosing the precise problem, selecting the properties of the similarity measure that are needed for the problem, choosing the specific similarity measure, and constructing the algorithm to compute the similarity. The focus is on methods that lie close to the field of computational geometry.