Clustering via kernel decomposition

Spectral clustering methods were proposed recently which rely on the eigenvalue decomposition of an affinity matrix. In this letter, the affinity matrix is created from the elements of a nonparametric density estimator and then decomposed to obtain posterior probabilities of class membership. Hyperparameters are selected using standard cross-validation methods

The aspartic proteinase family of three Phytophthora species

Background - Phytophthora species are oomycete plant pathogens with such major social and economic impact that genome sequences have been determined for Phytophthora infestans, P. sojae and P. ramorum. Pepsin-like aspartic proteinases (APs) are produced in a wide variety of species (from bacteria to humans) and contain conserved motifs and landmark residues. APs fulfil critical roles in infectious organisms and their host cells. Annotation of Phytophthora APs would provide invaluable information for studies into their roles in the physiology of Phytophthora species and interactions with their hosts. Results - Genomes of Phytophthora infestans, P. sojae and P. ramorum contain 11-12 genes encoding APs. Nine of the original gene models in the P. infestans database and several in P. sojae and P. ramorum (three and four, respectively) were erroneous. Gene models were corrected on the basis of EST data, consistent positioning of introns between orthologues and conservation of hallmark motifs. Phylogenetic analysis resolved the Phytophthora APs into 5 clades. Of the 12 sub-families, several contained an unconventional architecture, as they either lacked a signal peptide or a propart region. Remarkably, almost all APs are predicted to be membrane-bound. Conclusions - One of the twelve Phytophthora APs is an unprecedented fusion protein with a putative G-protein coupled receptor as the C-terminal partner. The others appear to be related to well-documented enzymes from other species, including a vacuolar enzyme that is encoded in every fungal genome sequenced to date. Unexpectedly, however, the oomycetes were found to have both active and probably-inactive forms of an AP similar to vertebrate BACE, the enzyme responsible for initiating the processing cascade that generates the Aß peptide central to Alzheimer's Disease. The oomycetes also encode enzymes similar to plasmepsin V, a membrane-bound AP that cleaves effector proteins of the malaria parasite Plasmodium falciparum during their translocation into the host red blood cell. Since the translocation of Phytophthora effector proteins is currently a topic of intense research activity, the identification in Phytophthora of potential functional homologues of plasmepsin V would appear worthy of investigation. Indeed, elucidation of the physiological roles of the APs identified here offers areas for future study. The significant revision of gene models and detailed annotation presented here should significantly facilitate experimental design

A coupling prescription for post-Newtonian corrections in Quantum Mechanics

The interplay between quantum theory and general relativity remains one of the main challenges of modern physics. A renewed interest in the low-energy limit is driven by the prospect of new experiments that could probe this interface. Here we develop a covariant framework for expressing post-Newtonian corrections to Schr\"odinger's equation on arbitrary gravitational backgrounds based on a $1/c^2$ expansion of Lorentzian geometry, where $c$ is the speed of light. Our framework provides a generic coupling prescription of quantum systems to gravity that is valid in the intermediate regime between Newtonian gravity and General Relativity, and that retains the focus on geometry. At each order in $1/c^2$ this produces a nonrelativistic geometry to which quantum systems at that order couple. By considering the gauge symmetries of both the nonrelativistic geometries and the $1/c^2$ expansion of the complex Klein--Gordon field, we devise a prescription that allows us to derive the Schr\"odinger equation and its post-Newtonian corrections on a gravitational background order-by-order in $1/c^2$. We also demonstrate that these results can be obtained from a $1/c^2$ expansion of the complex Klein--Gordon Lagrangian. We illustrate our methods by performing the $1/c^2$ expansion of the Kerr metric up to $\mathcal{O}(c^{-2})$, which leads to a special case of the Hartle--Thorne metric. The associated Schr\"odinger equation captures novel and potentially measurable effects.Comment: 43 pages incl. 1 appendix, 1 figur

The bile duct ligated rat : a relevant model to study muscle mass loss in cirrhosis

Muscle mass loss and hepatic encephalopathy (complex neuropsychiatric disorder) are serious complications of chronic liver disease (cirrhosis) which impact negatively on clinical outcome and quality of life and increase mortality. Liver disease leads to hyperammonemia and ammonia toxicity is believed to play a major role in the pathogenesis of hepatic encephalopathy. However, the effects of ammonia are not brain-specific and therefore may also affect other organs and tissues including muscle. The precise pathophysiological mechanisms underlying muscle wasting in chronic liver disease remains to be elucidated. In the present study, we characterized body composition as well as muscle protein synthesis in cirrhotic rats with hepatic encephalopathy using the 6-week bile duct ligation (BDL) model which recapitulates the main features of cirrhosis. Compared to sham-operated control animals, BDL rats display significant decreased gain in body weight, altered body composition, decreased gastrocnemius muscle mass and circumference as well as altered muscle morphology. Muscle protein synthesis was also significantly reduced in BDL rats compared to control animals. These findings demonstrate that the 6-week BDL experimental rat is a relevant model to study liver disease-induced muscle mass loss

FishSizer: Software solution for efficiently measuring larval fish size

Length and depth of fish larvae are part of the fundamental measurements in many marine ecology studies involving early fish life history. Until now, obtaining these measurements has required intensive manual labor and the risk of inter- and intra-observer variability. We developed an open-source software solution to semi-automate the measurement process and thereby reduce both time consumption and technical variability. Using contrast-based edge detection, the software segments images of a fish larva into “larva” and “background.” Length and depth are extracted from the “larva” segmentation while taking curvature of the larva into consideration. The graphical user interface optimizes workflow and ease of usage, thereby reducing time consumption for both training and analysis. The software allows for visual verification of all measurements. A comparison of measurement methods on a set of larva images showed that this software reduces measurement time by 66%–78% relative to commonly used software. Using this software instead of the commonly used manual approach has the potential to save researchers from many hours of monotonous work. No adjustment was necessary for 89% of the images regarding length (70% for depth). Hence, the only workload on most images was the visual inspection. As the visual inspection and manual dimension extraction works in the same way as currently used software, we expect no loss in accuracy.publishedVersio

Parent-child interaction in Nigerian families: conversation analysis, context and culture

This paper uses a conversation analysis (CA) approach to explore parent child interaction (PCI) within Nigerian families. We illustrate how speech and language therapists (SLTs), by using CA, can tailor recommendations according to the interactional style of each individual family that are consonant with the family’s cultural beliefs. Three parent-child dyads were videoed playing and talking together in their home environments. The analysis uncovered a preference for instructional talk similar to that used in the classroom. Closer examination revealed that this was not inappropriate when considering the context of the activities and their perceived discourse role. Furthermore, this was not necessarily at the expense of responsivity or semantic contingency. The preference for instructional talk appeared to reflect deeply held cultural beliefs about the role of adults and children within the family and it is argued that the cultural paradigm is vitally important to consider when evaluating PCI. Given a potential risk that such young children may be vulnerable in terms of language difficulties, we offer an example of how PCI can be enhanced to encourage language development without disrupting the naturally occurring talk or the underlying purpose of the interaction

The Botrytis cinerea endopolygalacturonase gene family

C ell w all d egrading e nzyme s (CWDEs) secreted by microbial plant pathogens have been suggested to function as virulence factors. Evidence that particular bacterial CWDEs contribute to virulence has emerged in the last two decades. Targeted gene replacement of different genes encoding CWDEs resulted in mutants with reduced virulence on a number of host plants. Similar molecular genetic approaches in plant pathogenic fungi have, until recently, been unsuccessful in elucidating a role for fungal CWDEs in pathogenesis. This thesis describes molecular genetic analyses of CWDEs secreted by the necrotrophic plant pathogenic fungus Botrytis cinerea , the causal agent of gray mould.From literature it was known that B. cinerea secretes many CWDEs when grown in liquid culture. The number of CWDE encoding genes present in the B. cinerea genome was unknown and detailed expression studies were lacking. In order to fill this knowledge gap we used the following strategy:Cloning of genes encoding CWDEsStudy of the expression of CWDE genes both in liquid cultures and in plantaTargeted deletion of CWDE genes that have expression patterns that indicate a function in the infection processChapter 1 introduces the research area and gives an outline of the thesis. It describes a model of the chemical and structural composition of the plant cell wall and reviews various classes of microbial CWDEs. It summarises previously published data on the role of bacterial and fungal CWDEs in pathogenesis in general and on the CWDEs secreted by B. cinerea in particular. B. cinerea has a wide host range but prefers hosts that contain high amounts of pectin. Therefore the focus was on endo p oly g alacturonases (endoPGs), enzymes that cleave homogalacturonan, a major constituent of pectin.In order to study gene expression of B. cinereain planta , it was essential to develop a standardised inoculation procedure that enables reproducible infections both in time and space. The development of this inoculation procedure for tomato leaves is described in Chapter 2. The expression of two fungal genes and a number of plant PR-protein genes was investigated in time course experiments performed at two different incubation temperatures.Subsequently, we set out to clone the genes of interest, analysed their expression and studied the effect in pathogenesis by targeted gene replacement. The genes were isolated by hybridisation with heterologous probes. The first gene that was cloned and characterised, Bcpg 1, is constitutively expressed. Targeted replacement of this gene resulted in a mutant with reduced virulence on apple fruits and tomato (Chapter 3). Subsequently, five additional endoPG genes were isolated (Chapter 4). The gene products were compared with other fungal endoPGs and it was shown that the members of the B. cinereaBcpg gene family fall into at least three distinct monophyletic groups (Chapter 4).The members of the endoPG gene family, denoted as Bcpg 1-6, are differentially expressed in liquid cultures that differed in carbon source or pH (Chapters 4). The constitutive expression pattern of Bcpg 1, as found in Chapter 3, was further confirmed. Bcpg 2 is expressed under all circumstances tested except when B. cinerea is grown in glucose-containing medium at low pH. Bcpg 3 is expressed at low ambient pH. Bcpg 4 is induced by the pectin breakdown end-product galacturonic acid, and is repressed by glucose. Bcpg 5 expression can be induced by a yet unknown factor present in apple pectin. Bcpg 6 is, like Bcpg 4, induced by galacturonic acid but is, unlike Bcpg 4, not repressed by glucose. The expression of the endoPG gene family enables the fungus to degrade pectate in a flexible manner. It enables the fungus to respond to environmental signals like nutrient availability and pH.The expression of the endoPG gene family during infection of tomato leaf, broad bean leaf, apple fruit and courgette fruit was studied (Chapter 5). Expression of the genes in planta is differential and most expression patterns can be explained by the results of expression studies in liquid cultures. Bcpg 1 is expressed in all host tissues tested, whereas expression of Bcpg 2 is evident in tomato, broad bean and courgette. Bcpg 3 and Bcpg 5 are expressed in apple fruit. Bcpg 4 and Bcpg 6 are expressed in all host tissues tested.Chapter 6 discusses the results in a broader context. It is hypothesised that, besides Bcpg 1, additional members of the Bcpg gene family contribute to virulence, albeit likely under specific circumstances. It is suggested that fungal CWDEs can play a role in plant pathogenesis but that this role also strongly depends on the lifestyle of the fungus. It is postulated that B. cinerea depends strongly on endoPGs for successful infection. The research described in this thesis may lead to novel disease control strategies that rely on P oly G alacturonase I nhibiting P rotein (PGIP) expression in transgenic host plants.</p

Newton{Cartan Submanifolds and Fluid Membranes

We develop the geometric description of submanifolds in Newton--Cartan spacetime. This provides the necessary starting point for a covariant spacetime formulation of Galilean-invariant hydrodynamics on curved surfaces. We argue that this is the natural geometrical framework to study fluid membranes in thermal equilibrium and their dynamics out of equilibrium. A simple model of fluid membranes that only depends on the surface tension is presented and, extracting the resulting stresses, we show that perturbations away from equilibrium yield the standard result for the dispersion of elastic waves. We also find a generalisation of the Canham--Helfrich bending energy for lipid vesicles that takes into account the requirements of thermal equilibrium.Comment: 56 pages including appendices, v2: updated to published versio

The aspartic proteinase family of three Phytophthora species

Background: Phytophthora species are oomycete plant pathogens with such major social and economic impact that genome sequences have been determined for Phytophthora infestans, P. sojae and P. ramorum. Pepsin-like aspartic proteinases (APs) are produced in a wide variety of species (from bacteria to humans) and contain conserved motifs and landmark residues. APs fulfil critical roles in infectious organisms and their host cells. Annotation of Phytophthora APs would provide invaluable information for studies into their roles in the physiology of Phytophthora species and interactions with their hosts. Results: Genomes of Phytophthora infestans, P. sojae and P. ramorum contain 11-12 genes encoding APs. Nine of the original gene models in the P. infestans database and several in P. sojae and P. ramorum (three and four, respectively) were erroneous. Gene models were corrected on the basis of EST data, consistent positioning of introns between orthologues and conservation of hallmark motifs. Phylogenetic analysis resolved the Phytophthora APs into 5 clades. Of the 12 sub-families, several contained an unconventional architecture, as they either lacked a signal peptide or a propart region. Remarkably, almost all APs are predicted to be membrane-bound. Conclusions: One of the twelve Phytophthora APs is an unprecedented fusion protein with a putative G-protein coupled receptor as the C-terminal partner. The others appear to be related to well-documented enzymes from other species, including a vacuolar enzyme that is encoded in every fungal genome sequenced to date. Unexpectedly, however, the oomycetes were found to have both active and probably-inactive forms of an AP similar to vertebrate BACE, the enzyme responsible for initiating the processing cascade that generates the Aβ peptide central to Alzheimer's Disease. The oomycetes also encode enzymes similar to plasmepsin V, a membrane-bound AP that cleaves effector proteins of the malaria parasite Plasmodium falciparum during their translocation into the host red blood cell. Since the translocation of Phytophthora effector proteins is currently a topic of intense research activity, the identification in Phytophthora of potential functional homologues of plasmepsin V would appear worthy of investigation. Indeed, elucidation of the physiological roles of the APs identified here offers areas for future study. The significant revision of gene models and detailed annotation presented here should significantly facilitate experimental design.Fil: Kay, John. Cardiff University; Reino UnidoFil: Meijer, Harold J. G.. Wageningen University; Reino UnidoFil: Ten Have, Arjen. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mar del Plata. Instituto de Investigaciones Biológicas; Argentina. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales; ArgentinaFil: van Kan, Jan A. L.. Wageningen University; Reino Unid