Complementation Classes Research Articles

The Taxon Concept: Is it Taxonic?

The question of whether the concept of a "taxon" (a nonarbitrary latent category) is itself categorical, or is a matter of degree, has lain dormant within taxometrics. I analyze the problem conceptually. Part of the meaning of "taxon," I hold, goes beyond the manifest statistical properties of admixed probability distributions; any of certain forms of causal nexus leading to admixed distributions are involved as well. I defend the thesis that the threshold question, "Is there a taxon?" has a yes-or-no answer, establishing that "taxonicity" is categorical (taxonic), but also that as some taxa are much more readily distinguished from their complement classes than are others, the taxon question is also quantitative. It is on this basis that Meehl and others held the view that taxonicity is a matter of degree; however, they were wrong to hold that it is only a matter of degree.

Complements of the socle in monolithic groups

We show that if H is a finite group with a unique minimal normal subgroup N, which is not abelian, then the number of conjugacy classes of complements of N in H is strictly smaller than |N|.

Comprehensive Analysis of Genetic Alterations in Acute Myeloid Leukemia According to the WHO Classification.

Acute myeloid leukemia (AML) is a heterogeneous clonal disorder of hematopoietic progenitor cells, and is thought to be the consequence of two broad complementation classes of mutations: those that confer a proliferative and/or survival advantage to hematopoietic progenitors, and those that impair hematopoietic differentiation and confer properties of self-renewal. To date, several genetic alterations, which are involved in the pathophysiology of the AML development, have been apparent, and some of them have been disclosed to have an impact on the clinical management. Therefore, it is required to establish the detailed classification of AML according to the genetic status. In this study, we comprehensively analyzed the genetic alterations in AML patients in comparison with the WHO classification. The study population included 115 newly diagnosed AML patients consisting of 25 recurrent genetic abnormalities, 25 multilineage dysplasia, 7 therapy-related and 56 not otherwise categorized WHO subcategories. Bone marrow samples were obtained from the patients after obtaining informed consent for banking and molecular analyses. Mutations in FLT3, cKIT, NPM1, N-RAS, p53, C/EBPa, AML1 and AKT1 genes were analyzed as previously described. In consistent with previous reports, FLT3 (20.9%), NPM1 (14.8%) and C/EBPa (13.0%) mutations were frequently observed, while no AKT1 mutation was found. Furthermore, NPM1 mutation was not found in AML with recurrent genetic abnormalities and C/EBPa mutation was not found in AML with recurrent genetic abnormalities or therapy related. Nine cases have double mutations of FLT3 and NPM1 genes, and 3 have FLT3 and C/EBPa mutations. Of note is that 15 of 25 (60%) AML with multilineage dysplasia cases have at least one mutation in p53, NPM1, C/EBPa, FLT3, N-RAS and AML1 genes and that p53 mutation was selectively found in the cases with complex karyotype. However, 4 AML with multilineage dysplasia cases with normal karyotype did not have any mutations in the analyzed genes. Comprehensive genetic analysis clarifies the detailed molecular base of AML and could make the subdivision of the WHO classification by combining the analysis for clinical impacts. Especially, mutation status in p53, NPM1 and C/EBPa genes seems to be useful for the subdivision of the AML with multilineage dysplasia, which is the most heterogeneous subcategory in the WHO classification.

Dimensional Analyses of Taxonic Data

Principal component analysis (PCA) and common factor analysis are often used to model latent data structures. Typically, such analyses assume a single population whose correlation or covariance matrix is modelled. However, data may sometimes be unwittingly sampled from mixed populations containing a taxon (nonarbitrary subpopulation) and its complement class. One derives relations between values of PCA parameters within subpopulations and their values in the mixed population. These results are then extended to factor analysis in mixed populations. As relationships between subpopulation and mixed-population principal components and factors sensitively depend on within-subpopulation structures and between-subpopulation differences, naive interpretation of PCA or factor analytic findings can potentially mislead. Several analyses, better suited to the dimensional analysis of admixture data structures, are presented and compared.

Taxometric and Factor Analytic Models of Anxiety Sensitivity Among Youth: Exploring the Latent Structure of Anxiety Psychopathology Vulnerability

This study represents an effort to better understand the latent structure of anxiety sensitivity (AS), a well-established affect-sensitivity individual difference factor, among youth by employing taxometric and factor analytic approaches in an integrative manner. Taxometric analyses indicated that AS, as indexed by the Child Anxiety Sensitivity Index (CASI; Silverman, Flesig, Rabian, & Peterson, 1991), demonstrates taxonic latent class structure in a large sample of youth from North America ( N = 4,462; M age = 15.6 years; SD = 1.3). Subsequent confirmatory factor analyses indicated that the latent continuous, multidimensional, 4-factor model of AS among youth (Silverman, Goedhart, Barrett, & Turner, 2003) provided good fit for the CASI data among the complement class (“normative form” of AS), but not among the taxon class (“high-risk form” of AS). EFAs supported the prediction that the AS taxon demonstrates a unique, heretofore unexplored latent continuous, unidimensional factor structure among youth. Findings are discussed in relation to refining our understanding of the latent structure of AS and the clinical implications that arise from it.

Paroxysmal Nocturnal Hemoglobinuria in Children

Paroxysmal nocturnal hemoglobinuria (PNH), an acquired hematologic disorder characterized by intravascular hemolysis, nocturnal hemoglobinuria, thrombotic events, serious infections, and bone marrow failure, is very rare in children. PNH is caused by a somatic mutation of the phosphatidylinositol glycan (GPI) complementation class A (PIGA) gene, followed by a survival advantage of the PNH clone, which results in a deficiency of GPI-anchored proteins on hematopoietic cells. Currently, immunophenotypic GPI-linked anchor protein analysis has replaced the acid Ham and sucrose lysis test, as it provides a reliable diagnostic tool for this disease. The presence of PNH clones should be considered in every child with an acquired bone marrow failure syndrome, for example (hypoplastic) myelodysplastic syndrome and aplastic anemia, and/or unexpected serious thrombosis. Treatment of PNH in children is dependent on the clinical presentation. In cases of severe bone marrow failure, stem cell transplantation should be seriously considered as a therapeutic option even if no matched sibling donor is available. This article reviews the reported cases of PNH in children using the recently published guidelines for classification, diagnostics, and treatment.

Taxometric and factor analytic models of anxiety sensitivity: Integrating approaches to latent structural research.

This study represents an effort to better understand the latent structure of anxiety sensitivity (AS), as indexed by the 16-item Anxiety Sensitivity Index (ASI; S. Reiss, R. A. Peterson, M. Gursky, & R. J. McNally, 1986), by using taxometric and factor-analytic approaches in an integrative manner. Taxometric analyses indicated that AS has a taxonic latent class structure (i.e., a dichotomous latent class structure) in a large sample of North American adults (N=2,515). As predicted, confirmatory factor analyses indicated that a multidimensional 3-factor model of AS provided a good fit for the AS complement class (normative or low-risk form) but not the AS taxon class (high-risk form). Exploratory factor analytic results suggested that the AS taxon may demonstrate a unique, unidimensional factor solution, though there are alternative indications that it may be characterized by a 2-factor solution. Findings suggest that the latent structural nature of AS can be conceptualized as a taxonic latent class structure composed of 2 types or forms of AS, each of these forms characterized by its own unique latent continuity and dimensional structure.

A mutation in Arabidopsis cytochrome b5 reductase identified by high‐throughput screening differentially affects hydroxylation and desaturation

As a model for analyzing the production of novel fatty acids in oilseeds, we used the genetic and molecular techniques available for Arabidopsis to characterize modifying mutations affecting the accumulation of hydroxy fatty acids in the seeds of Arabidopsis plants that express a transgene for the castor bean fatty acid hydroxylase, FAH12. We developed a high-throughput analytical system and used it to identify three complementation classes of mutations with reduced hydroxy fatty acid accumulation from among Arabidopsis M3 seed samples derived from chemical mutagenesis. We identified one of the mutations by positional cloning as a single base pair change in a gene encoding NADH:cytochrome b5 reductase (CBR1, At5g17770). When expressed in yeast, the mutant form of the enzyme was less active and less stable than the wild-type enzyme. Characterization of homozygous mutant lines with and without the FAH12 transgene (FAH12 cbr1-1 and cbr1-1, respectively) indicated that the only detectable consequence of the cbr1-1 mutation was on desaturase and hydroxylase reactions in the developing seed. The leaf and root fatty compositions, as well as the growth, development and seed production of mutant plants were indistinguishable from wild type. Interestingly, while the cbr1-1 mutation reduced the accumulation of hydroxy fatty acids in seeds by 85%, the effects on 18:1 and 18:2 desaturation reactions were much less (<25% and <60%, respectively). These results suggest that there is competition in developing seeds among the several reactions that utilize reduced cytochrome b5.

Mitochondrial vitamin B 12-binding proteins in patients with inborn errors of cobalamin metabolism

Inborn errors of vitamin B 12 (cobalamin, Cbl) metabolism are autosomal recessive disorders and have been classified into nine distinct complementation classes ( cblA- cblH and mut). Disorders affecting methylcobalamin metabolism cause megaloblastic anemia, which may be accompanied by leukopenia and thrombocytopenia, and a variety of neurological problems. Disorders affecting adenosylcobalamin cause methylmalonic acidemia and metabolic acidosis. Previous studies have shown that cobalamin binds to two enzymes in humans: methylmalonyl-CoA mutase in mitochondria and methionine synthase in the cytosol. In this study, cobalamin binding patterns were analyzed in crude mitochondrial fractions obtained from both control and patient fibroblasts that had been incubated with [ 57Co]cyanocobalamin. Crude mitochondrial fractions from control fibroblasts confirmed that the majority of [ 57Co]Cbl eluted with methylmalonyl-CoA mutase. However, in six of the nine disorders, at least one previously unidentified mitochondrial cobalamin binding protein was observed to bind [ 57Co]Cbl. The proportion of [ 57Co]Cbl that binds, is increased compared to controls when a deficiency in either adenosylcobalamin synthesis or utilization prevents binding to methylmalonyl-CoA mutase. Furthermore, unique cobalamin binding profiles emerged demonstrating how known mutations in these patients affect cobalamin binding to as yet unidentified proteins.

Learning verb complements for Modern Greek: balancing the noisy dataset

Attempting to automatically learn to identify verb complements from natural language corpora without the help of sophisticated linguistic resources like grammars, parsers or treebanks leads to a significant amount of noise in the data. In machine learning terms, where learning from examples is performed using class-labelled feature-value vectors, noise leads to an imbalanced set of vectors: assuming that the class label takes two values (in this work complement/non-complement), one class (complements) is heavily underrepresented in the data in comparison to the other. To overcome the drop in accuracy when predicting instances of the rare class due to this disproportion, we balance the learning data by applying one-sided sampling to the training corpus and thus by reducing the number of non-complement instances. This approach has been used in the past in several domains (image processing, medicine, etc) but not in natural language processing. For identifying the examples that are safe to remove, we use the value difference metric, which proves to be more suitable for nominal attributes like the ones this work deals with, unlike the Euclidean distance, which has been used traditionally in one-sided sampling. We experiment with different learning algorithms which have been widely used and their performance is well known to the machine learning community: Bayesian learners, instance-based learners and decision trees. Additionally we present and test a variation of Bayesian belief networks, the COr-BBN (Class-oriented Bayesian belief network). The performance improves up to 22% after balancing the dataset, reaching 73.7% f-measure for the complement class, having made use only a phrase chunker and basic morphological information for preprocessing.

Mutation and biochemical analysis of patients belonging to the cblB complementation class of vitamin B 12-dependent methylmalonic aciduria

Methylmalonic aciduria, cblB type (OMIM 251110) is an inborn error of vitamin B 12 metabolism that occurs due to mutations in the MMAB gene. MMAB encodes the enzyme ATP:cobalamin adenosyltransferase, which catalyzes the synthesis of the coenzyme adenosylcobalamin required for the activity of the mitochondrial enzyme methylmalonyl CoA mutase (MCM). MCM catalyzes the isomerization of methylmalonyl CoA to succinyl CoA. Deficient MCM activity results in methylmalonic aciduria and a susceptibility to life-threatening acidotic crises. The MMAB gene was sequenced from genomic DNA from a panel of 35 cblB patients, including five patients previously investigated. Nineteen MMAB mutations were identified, including 13 previously unknown mutations. These included 11 missense mutations, two duplications, one deletion, four splice-site mutations, and one nonsense mutation. None of these mutations was identified in 100 control alleles. Most of the missense mutations (9/11) were clustered in exon 7; many of these affected amino acid residues that are part of the probable active site of the enzyme. One previously described mutation, c.556C > T (p.R186W), was particularly common, accounting for 33% of pathogenic alleles. It was seen almost exclusively in patients of European background and was typically associated with presentation in the first year of life.

Spectrum of mutations inmutmethylmalonic acidemia and identification of a common Hispanic mutation and haplotype

Cobalamin nonresponsive methylmalonic acidemia (MMA, mut complementation class) results from mutations in the nuclear gene MUT, which codes for the mitochondrial enzyme methylmalonyl CoA mutase (MCM). To better elucidate the spectrum of mutations that cause MMA, the MUT gene was sequenced in 160 patients with mut MMA. Sequence analysis identified mutations in 96% of disease alleles. Mutations were found in all coding exons, but predominantly in exons 2, 3, 6, and 11. A total of 116 different mutations, 68 of which were novel, were identified. Of the 116 different mutations, 53% were missense mutations, 22% were deletions, duplications or insertions, 16% were nonsense mutations, and 9% were splice-site mutations. Sixty-one of the mutations have only been identified in one family. A novel mutation in exon 2, c.322C>T (p.R108C), was identified in 16 of 27 Hispanic patients. SNP genotyping data demonstrated that Hispanic patients with this mutation share a common haplotype. Three other mutations were seen exclusively in Hispanic patients: c.280G>A (p.G94R), c.1022dupA, and c.970G>A (p.A324T). Seven mutations were seen almost exclusively in black patients, including the previously reported c.2150G>T (p.G717V) mutation, which was identified in 12 of 29 black patients. Two mutations were seen only in Asian patients. Some frequently identified mutations were not population-specific and were identified in patients of various ethnic backgrounds. Some of these mutations were found in mutation clusters in exons 2, 3, 6, and 11, suggesting a recurrent mutation.

Tri-extraspecial groups

We classify the groups which are certain split extensions of special 2-groups of the form 23+3m, m ≥ 1, by the group L3(2). These groups behave very much like extraspecial 2-groups and we call them tri-extraspecial groups. A tri-extraspecial group of this form exists if and only if m is a positive even integer, and for every n ≥ 1 there are exactly two tri-extraspecial groups of the form 23+6n : L3(2). We denote these groups by T+(2n) and T−(2n). Let ε be + or −. Then the isomorphism type of Q (2n) ≔ O2(T ε(2n)) is independent of ε. The automorphism group Aε(2n) of T ε(2n) is a non-split extension of Q (2n) by the direct product L3 (2) × S2n (2) × 2. The group Aε(2n) permutes transitively the conjugacy classes of L3 (2)-complements to Q (2n) in T ε(2n). If S ε(2n) is the stabilizer in Aε(2n) of one of these classes of complements, then S ε(2n) is a split extension of Q (2n) by L3 (2) ×

Nitrogen metabolite repression in Hansenda polymorpha: the nmrl-l mutation.

In Hansenula polymorpha, the expression of the nitrate assimilation metabolism is subjected to re-pression-derepression mechanisms triggered by reduced nitrogen compounds such as ammonium. To further our knowledge on the genetics of these regulatory mechanisms, a screening strategy for the isolation of mutants exhibiting nitrate reductase activities in the presence of reduced nitrogen compounds was set up. This strategy makes use of a nitrate+ methylamine mutant to isolate suppressors of its characteristic phenotype--the inability to grow on a nitrate plus methylamine medium. A total of 21 regulatory mutants were isolated with this strategy and grouped into five complementation classes. One of these mutants harbours the recessive mutation nmr1-1, which determines the derepression of the nitrate assimilation metabolism in media containing nitrate plus a repressing nitrogen source (ammonium, methylamine, glutamate, urea or aspartate). Therefore, nitrate reductase activities are detected in the presence of reduced nitrogen sources, as long as nitrate is also in the medium. Our data indicate that the processes of repression-derepression and induction are controlled by elements which are distinct. Furthermore, they indicate that Nmrlp is involved in repressing circuits which control not only the nitrate-utilisation pathway, but also other pathways which are necessary for the utilisation of nitrogen sources alternative to ammonium. Of considerable interest is the fact that our nmr1-1 mutant is derepressed in glutamate but not in glutamine. Since the phenotype of this mutant seems to exclude a glutamine synthetase defect, we suggest that glutamate (or a derivative of this compound) might be involved in signalling nitrogen metabolite repression in H. polymorpha. Thus, in H. polymorpha, a glutamine-dependent circuit may co-exist with a glutamine-independent circuit.

COMMENSURABILITY CLASSES OF ARITHMETIC LINK COMPLEMENTS

In this paper, we exhibit three new commensurability classes of arithmetic link complements, bringing the known total to seventeen.

A genomic perspective on human proteases

Over 400 human proteases documented in secondary databases can already be delineated in genomic sequence. A Genome Ontology annotation of 30 585 sequences in the provisional human proteome set recognises 498 proteases, i.e. 1.6%. Homology searches against finished sequence and comparisons between mouse and zebrafish are likely to increase this total. However, the data already indicate that the mechanistic class, sequence family and domain distribution of the genomic complement of proteases is unlikely to shift significantly from that already observed in the transcript data. Genomically derived novel sequences will require bioinformatic analysis and biochemical verification. The increasing availability of annotated genomic data will enable studies of splice variants, transcriptional control, polymorphisms, pseudogenes, inactive homologues and evolution. Comparative work on complete human protease families should produce a more integrated picture of their biochemistry and physiology. Genomic data will also lead to the identification of new protease involvement in disease processes and their evaluation as drug targets.

Complementation studies in the cblAclass of inborn error of cobalamin metabolism: evidence for interallelic complementation and for a new complementation class (cblH)

AIMTo investigate genetic heterogeneity within the cblA class of inborn error of cobalamin metabolism.CONTEXTThecblA disorder is characterised by vitamin B12 (cobalamin) responsive methylmalonic aciduria and deficient synthesis of adenosylcobalamin, required...

IMPLICATIONS OF RECENT INSIGHTS INTO THE PATHOPHYSIOLOGY OF PAROXYSMAL NOCTURNAL HAEMOGLOBINURIA

IMPLICATIONS OF RECENT INSIGHTS INTO THE PATHOPHYSIOLOGY OF PAROXYSMAL NOCTURNAL HAEMOGLOBINURIA

Vitamin B 12-responsive methylmalonic aciduria due to a new inborn error of adenosylcobalamin synthesis, cblH

Vitamin B12-responsive methylmalonic aciduria is characterized by deficient synthesis of adenosylcobalamin (AdoCbl) and decreased activity of the AdoCbl-dependent mitochondrial enzyme, methylmalonylCoA mutase. Two distinct disorders of AdoCbl synthesized have been characterized (cblA and cblB) and they can be distinguished on the basis of somatic cell complementation analysis. Such studies have clinical usefulness because in general cblA patients have a better prognosis than do cblB patients. We reported a patient whose fibroblasts had the clinical and biochemical features of the cblA class but complemented cells from all known inborn errors of cobalamin metabolism that cause methylmalonic aciduria, including cblA. The disorder in this patient was designated as cblA variant. Cells from this patient were tested against a panel of 29 cell lines from cblA patients and complemented all members of this panel. These studies strongly suggest that this patient represents a novel complementation class which we have called cblH. Detailed complementation analysis of a panel of 10 cblA lines provided evidence of interallelic complementation. The presence of this interallelic complementation indicates that care must be taken in the use of complementation analysis to identify cblA patients. These studies suggest that additional biochemical steps are required for the reduction and adenosylation of cobalamin. The full clinical spectrum of the new cblH class and its implications remains to be defined.

Coherent Infinitives in German, Polish, and Spanish

In this article I present a unified analysis of long scrambling (LS) (scrambling across sentence boundaries) out of infinitivals in German and Polish and clitic climbing (CC) (clitic movement across sentence boundaries) in Spanish. Infinitives exhibiting LS in German have been termed coherent infinitives by Bech (1955) whereas the phenomenon of infinitives allowing for clitic climbing (CC) in Spanish (and other Romance languages) is often named restructuring (see for example Napoli 1981, Bordelois 1986, Choe 1988). The terms coherent infinitives' and restructuring' refer to the observation that certain control verbs as well as ECM- and raising verbs can take infinitival complements that are not barriers for clause bounded processes. Although these infinitives are usually described in terms of a list of characteristics (see for example Haider 1986), it should be emphasized that a) empirical implications for other languages than German have not been discussed from a comparative perspective and b) the theoretical status of the concept of such infinitives is not clear. Restricting myself to control complements I will show that concerning a) LS in German and Polish and CC in Spanish show up with the same class of control complements, displaying an interesting parallel between the Slavic, Germanic and Romance languages from a typological point of view. Furthermore, concerning b), I will give a unified analysis of CC and LS by discussing lexically and structurally determined options, that make a bisentential representation behave syntactically like a monoclausal structure in German, Polish, and Spanish. I will argue that CC and LS are both licensed by the same mechanisms. To account for this fact I will introduce a theory of barriers and incorporation, apply it to the data presented and extend it to the impossibility of LS and CC in the presence of certain islands