The algebraic dichotomy conjecture for infinite domain Constraint Satisfaction Problems

We prove that an $\omega$-categorical core structure primitively positively interprets all finite structures with parameters if and only if some stabilizer of its polymorphism clone has a homomorphism to the clone of projections, and that this happens if and only if its polymorphism clone does not contain operations $\alpha$, $\beta$, $s$ satisfying the identity $\alpha s(x,y,x,z,y,z) \approx \beta s(y,x,z,x,z,y)$. This establishes an algebraic criterion equivalent to the conjectured borderline between P and NP-complete CSPs over reducts of finitely bounded homogenous structures, and accomplishes one of the steps of a proposed strategy for reducing the infinite domain CSP dichotomy conjecture to the finite case. Our theorem is also of independent mathematical interest, characterizing a topological property of any $\omega$-categorical core structure (the existence of a continuous homomorphism of a stabilizer of its polymorphism clone to the projections) in purely algebraic terms (the failure of an identity as above).Comment: 15 page

On Backdoors to Tractable Constraint Languages

International audienceIn the context of CSPs, a strong backdoor is a subset of variables such that every complete assignment yields a residual instance guaranteed to have a specified property. If the property allows efficient solving, then a small strong backdoor provides a reasonable decomposition of the original instance into easy instances. An important challenge is the design of algorithms that can find quickly a small strong backdoor if one exists. We present a systematic study of the parameterized complexity of backdoor detection when the target property is a restricted type of constraint language defined by means of a family of polymor-phisms. In particular, we show that under the weak assumption that the polymorphisms are idempotent, the problem is unlikely to be FPT when the parameter is either r (the constraint arity) or k (the size of the backdoor) unless P = NP or FPT = W[2]. When the parameter is k + r, however, we are able to identify large classes of languages for which the problem of finding a small backdoor is FPT

Congruence modularity implies cyclic terms for finite algebras

An n-ary operation f : A(n) -> A is called cyclic if it is idempotent and f(a(1), a(2), a(3), ... , a(n)) = f(a(2), a(3), ... , a(n), a(1)) for every a(1), ... , a(n) is an element of A. We prove that every finite algebra A in a congruence modular variety has a p-ary cyclic term operation for any prime p greater than vertical bar A vertical bar

Use of Di- and Tripropionate substrate analogs to probe the active site of human recombinant coproporphyrinogen oxidase

Background: Defects in the enzyme coproporphyrinogen oxidase result in accumulation of porphyrins which may affect the severity of a subset of porphyrias. Thus evaluation of this enzyme for substrate selectivity is of value. Kinetic evaluations of recombinant human coproporphyrinogen oxidase have been undertaken using six di- and tripropionate analogs of the natural substrate coproporphyrinogen-III. These Substrate analogs were modified by having alkyl groups in place of one or both of the ring 13- or 17-propionate moieties. Material/Methods: Cloned human enzyme was incubated with analogs under apparent first order conditions and with various substrate concentrations. The kinetic values, K-m and V-max, were determined. Results: Relative to the authentic substrate, the K-m values for the 13-ethyl, dimethyl and diethyl porphyrinogens were very comparable whereas the K-m values were much higher using dipropyl and dibutyl porphyrinogen and much lower for the 17-ethyl analog. For the dipropionate analogs, the V-max values were an apparent function of the carbon length of the substituent. on the C and D rings, with longer carbon length severely reducing product formation by some 4-5 orders of magnitude. Also, the two isomeric tripropionates that were tested indicated that it was more detrimental to have an ethyl group at the 13-position for both binding and catalysis. Conclusions: This work extends our understanding of porphyrin ring substituent effects reported by Cooper et al. (2005). The substituents on both the C and D rings have significant effects on both the substrate binding and catalysis by this important enzyme

Constraint Satisfaction with Counting Quantifiers

We initiate the study of constraint satisfaction problems (CSPs) in the presence of counting quantifiers, which may be seen as variants of CSPs in the mould of quantified CSPs (QCSPs). We show that a single counting quantifier strictly between exists^1:=exists and exists^n:=forall (the domain being of size n) already affords the maximal possible complexity of QCSPs (which have both exists and forall), being Pspace-complete for a suitably chosen template. Next, we focus on the complexity of subsets of counting quantifiers on clique and cycle templates. For cycles we give a full trichotomy -- all such problems are in L, NP-complete or Pspace-complete. For cliques we come close to a similar trichotomy, but one case remains outstanding. Afterwards, we consider the generalisation of CSPs in which we augment the extant quantifier exists^1:=exists with the quantifier exists^j (j not 1). Such a CSP is already NP-hard on non-bipartite graph templates. We explore the situation of this generalised CSP on bipartite templates, giving various conditions for both tractability and hardness -- culminating in a classification theorem for general graphs. Finally, we use counting quantifiers to solve the complexity of a concrete QCSP whose complexity was previously open

Beyond Hebb: Exclusive-OR and Biological Learning

A learning algorithm for multilayer neural networks based on biologically plausible mechanisms is studied. Motivated by findings in experimental neurobiology, we consider synaptic averaging in the induction of plasticity changes, which happen on a slower time scale than firing dynamics. This mechanism is shown to enable learning of the exclusive-OR (XOR) problem without the aid of error back-propagation, as well as to increase robustness of learning in the presence of noise.Comment: 4 pages RevTeX, 2 figures PostScript, revised versio

A two step algorithm for learning from unspecific reinforcement

We study a simple learning model based on the Hebb rule to cope with "delayed", unspecific reinforcement. In spite of the unspecific nature of the information-feedback, convergence to asymptotically perfect generalization is observed, with a rate depending, however, in a non- universal way on learning parameters. Asymptotic convergence can be as fast as that of Hebbian learning, but may be slower. Moreover, for a certain range of parameter settings, it depends on initial conditions whether the system can reach the regime of asymptotically perfect generalization, or rather approaches a stationary state of poor generalization.Comment: 13 pages LaTeX, 4 figures, note on biologically motivated stochastic variant of the algorithm adde

Physical, social and societal functioning of children with congenital adrenal hyperplasia (CAH) and their parents, in a Dutch population

<p>Abstract</p> <p>Background</p> <p>Most research concerning congenital adrenal hyperplasia (CAH) and related conditions caused by primary adrenal insufficiency, such as Addison's or Cushing's disease, has focused on medical aspects rather than on patients' quality of life. Therefore, our objective was to investigate the physical, social and societal functioning of children with CAH and their parents in a Dutch population.</p> <p>Methods</p> <p>The study is descriptive and cross-sectional. Self-designed questionnaires, based on questionnaires developed in the Netherlands for different patient groups, were sent to parents of children with CAH between 0 and 18 years old. Participants were recruited through the Dutch patient group for Adrenal Disease (NVACP) and six hospitals in the Netherlands. Three different questionnaires were designed for parents: for children aged 0 - 4, aged 4 - 12 and aged 12 - 18. Additionally, a fourth questionnaire was sent to adolescents with CAH aged 12 - 18. Main outcome measures were experienced burden of the condition, self-management and participation in several areas, such as school and leisure time.</p> <p>Results</p> <p>A total of 106 parents returned the questionnaire, 12 regarding pre-school children (0-4 years), 63 regarding primary school children (4-12 years), and 32 regarding secondary school children (12-18 years), combined response rate 69.7%. Also, 24 adolescents returned the questionnaire. Children and adolescents with CAH appear to be capable of self-management at a young age. Experienced burden of the condition is low, although children experience several health related problems on a daily basis. Children participate well in school and leisure time. Few children carry a crisis card or emergency injection with them.</p> <p>Conclusions</p> <p>Overall, our research shows that, according to their parents, children with CAH experience few negative effects of the condition and that they participate well in several areas such as school and leisure time. However, improvements can be made concerning the measures parents and children must take to prevent an adrenal crisis.</p

Decoupling the Effects of the Amyloid Precursor Protein From Amyloid-β Plaques on Axonal Transport Dynamics in the Living Brain

Amyloid precursor protein (APP) is the precursor to Aβ plaques. The cytoplasmic domain of APP mediates attachment of vesicles to molecular motors for axonal transport. In APP-KO mice, transport of Mn²⁺ is decreased. In old transgenic mice expressing mutated human (APP^(SwInd)) linked to Familial Alzheimer’s Disease, with both expression of APP^(SwInd) and plaques, the rate and destination of Mn²⁺ axonal transport is altered, as detected by time-lapse manganese-enhanced magnetic resonance imaging (MEMRI) of the brain in living mice. To determine the relative contribution of expression of APP^(SwInd) versus plaque on transport dynamics, we developed a Tet-off system to decouple expression of APP^(SwInd) from plaque, and then studied hippocampal to forebrain transport by MEMRI. Three groups of mice were compared to wild-type (WT): Mice with plaque and APP^(SwInd) expression; mice with plaque but suppression of APP^(SwInd) expression; and mice with APP^(SwInd) suppressed from mating until 2 weeks before imaging with no plaque. MR images were captured before at successive time points after stereotactic injection of Mn²⁺ (3–5 nL) into CA3 of the hippocampus. Mice were returned to their home cage between imaging sessions so that transport would occur in the awake freely moving animal. Images of multiple mice from the three groups (suppressed or expressed) together with C57/B6J WT were aligned and processed with our automated computational pipeline, and voxel-wise statistical parametric mapping (SPM) performed. At the conclusion of MR imaging, brains were harvested for biochemistry or histopathology. Paired T-tests within-group between time points (p = 0.01 FDR corrected) support the impression that both plaque alone and APP^(SwInd) expression alone alter transport rates and destination of Mn²⁺ accumulation. Expression of APP^(SwInd) in the absence of plaque or detectable Aβ also resulted in transport defects as well as pathology of hippocampus and medial septum, suggesting two sources of pathology occur in familial Alzheimer’s disease, from toxic mutant protein as well as plaque. Alternatively mice with plaque without APP^(SwInd) expression resemble the human condition of sporadic Alzheimer’s, and had better transport. Thus, these mice with APP^(SwInd) expression suppressed after plaque formation will be most useful in preclinical trials