Principles of motor learning in ecological dynamics : a comment on functions of learning and the acquisition of motor skills (with reference to sport)

This paper provides a commentary on the contribution by Dr Chow who questioned whether the functions of learning are general across all categories of tasks or whether there are some task-particular aspects to the functions of learning in relation to task type. Specifically, they queried whether principles and practice for the acquisition of sport skills are different than what they are for musical, industrial, military and human factors skills. In this commentary we argue that ecological dynamics contains general principles of motor learning that can be instantiated in specific performance contexts to underpin learning design. In this proposal, we highlight the importance of conducting skill acquisition research in sport, rather than relying on empirical outcomes of research from a variety of different performance contexts. Here we discuss how task constraints of different performance contexts (sport, industry, military, music) provide different specific information sources that individuals use to couple their actions when performing and acquiring skills. We conclude by suggesting that his relationship between performance task constraints and learning processes might help explain the traditional emphasis on performance curves and performance outcomes to infer motor learning.

Lattice-free models of cell invasion : discrete simulations and travelling waves

Invasion waves of cells play an important role in development, disease and repair. Standard discrete models of such processes typically involve simulating cell motility, cell proliferation and cell-to-cell crowding effects in a lattice-based framework. The continuum-limit description is often given by a reaction–diffusion equation that is related to the Fisher–Kolmogorov equation. One of the limitations of a standard lattice-based approach is that real cells move and proliferate in continuous space and are not restricted to a predefined lattice structure. We present a lattice-free model of cell motility and proliferation, with cell-to-cell crowding effects, and we use the model to replicate invasion wave-type behaviour. The continuum-limit description of the discrete model is a reaction–diffusion equation with a proliferation term that is different from lattice-based models. Comparing lattice based and lattice-free simulations indicates that both models lead to invasion fronts that are similar at the leading edge, where the cell density is low. Conversely, the two models make different predictions in the high density region of the domain, well behind the leading edge. We analyse the continuum-limit description of the lattice based and lattice-free models to show that both give rise to invasion wave type solutions that move with the same speed but have very different shapes. We explore the significance of these differences by calibrating the parameters in the standard Fisher–Kolmogorov equation using data from the lattice-free model. We conclude that estimating parameters using this kind of standard procedure can produce misleading results.

Quantifying spatial structure in experimental observations and agent-based simulations using pair-correlation functions

We define a pair-correlation function that can be used to characterize spatiotemporal patterning in experimental images and snapshots from discrete simulations. Unlike previous pair-correlation functions, the pair-correlation functions developed here depend on the location and size of objects. The pair-correlation function can be used to indicate complete spatial randomness, aggregation or segregation over a range of length scales, and quantifies spatial structures such as the shape, size and distribution of clusters. Comparing pair-correlation data for various experimental and simulation images illustrates their potential use as a summary statistic for calibrating discrete models of various physical processes.

Expression, regulation and putative nutrient-sensing function of taste GPCRs in the heart

G protein-coupled receptors (GPCRs) are critical for cardiovascular physiology. Cardiac cells express >100 nonchemosensory GPCRs, indicating that important physiological and potential therapeutic targets remain to be discovered. Moreover, there is a growing appreciation that members of the large, distinct taste and odorant GPCR families have specific functions in tissues beyond the oronasal cavity, including in the brain, gastrointestinal tract and respiratory system. To date, these chemosensory GPCRs have not been systematically studied in the heart. We performed RT-qPCR taste receptor screens in rodent and human heart tissues that revealed discrete subsets of type 2 taste receptors (TAS2/Tas2) as well as Tas1r1 and Tas1r3 (comprising the umami receptor) are expressed. These taste GPCRs are present in cultured cardiac myocytes and fibroblasts, and are enriched in myocytes, which we corroborated using in situ hybridization. Tas1r1 gene-targeted mice (Tas1r1Cre/Rosa26tdRFP) strikingly recapitulated these data. In vivo taste receptor expression levels were developmentally regulated in the postnatal period. Intriguingly, several Tas2rs were upregulated in cultured rat myocytes and in mouse heart in vivo following starvation. The discovery of taste GPCRs in the heart opens an exciting new field of cardiac research. We predict that these taste receptors may function as nutrient sensors in the heart.

A variant of the breast cancer type 2 susceptibility protein (BRC) repeat is essential for the RECQL5 Helicase to interact with RAD51 Recombinase for genome stabilization

The BRC repeat is a structural motif in the tumor suppressor BRCA2 (breast cancer type 2 susceptibility protein), which promotes homologous recombination (HR) by regulating RAD51 recombinase activity. To date, the BRC repeat has not been observed in other proteins, so that its role in HR is inferred only in the context of BRCA2. Here, we identified a BRC repeat variant, named BRCv, in the RECQL5 helicase, which possesses anti-recombinase activity in vitro and suppresses HR and promotes cellular resistance to camptothecin-induced replication stress in vivo. RECQL5-BRCv interacted with RAD51 through two conserved motifs similar to those in the BRCA2-BRC repeat. Mutations of either motif compromised functions of RECQL5, including association with RAD51, inhibition of RAD51-mediated D-loop formation, suppression of sister chromatid exchange, and resistance to camptothecin-induced replication stress. Potential BRCvs were also found in other HR regulatory proteins, including Srs2 and Sgs1, which possess anti-recombinase activities similar to that of RECQL5. A point mutation in the predicted Srs2-BRCv disrupted the ability of the protein to bind RAD51 and to inhibit D-loop formation. Thus, BRC is a common RAD51 interaction module that can be utilized by different proteins to either promote HR, as in the case of BRCA2, or to suppress HR, as in RECQL5.

Homogeneous bent functions of degree n in 2n variables do not exist for n>3

We prove that homogeneous bent functions f:GF(2)^2n --> GF(2) of degree n do not exist for n>3. Consequently homogeneous bent functions must have degree 3.

The eight variable homogeneous degree three bent functions

We determine the affine equivalence classes of the eight variable degree three homogeneous bent functions using a new algorithm. Our algorithm applies to general bent functions and can systematically determine the automorphism groups. We provide a partial verification of the enumeration of eight variable degree three homogeneous bent functions obtained by Meng et al. We determine the affine equivalence classes of these functions.

Universal designated-verifier signatures

Motivated by privacy issues associated with dissemination of signed digital certificates, we define a new type of signature scheme called a ‘Universal Designated-Verifier Signature’ (UDVS). A UDVS scheme can function as a standard publicly-verifiable digital signature but has additional functionality which allows any holder of a signature (not necessarily the signer) to designate the signature to any desired designated-verifier (using the verifier’s public key). Given the designated-signature, the designated-verifier can verify that the message was signed by the signer, but is unable to convince anyone else of this fact. We propose an efficient deterministic UDVS scheme constructed using any bilinear group-pair. Our UDVS scheme functions as a standard Boneh-Lynn-Shacham (BLS) signature when no verifier-designation is performed, and is therefore compatible with the key-generation, signing and verifying algorithms of the BLS scheme. We prove that our UDVS scheme is secure in the sense of our unforgeability and privacy notions for UDVS schemes, under the Bilinear Diffie-Hellman (BDH) assumption for the underlying group-pair, in the random-oracle model. We also demonstrate a general constructive equivalence between a class of unforgeable and unconditionally-private UDVS schemes having unique signatures (which includes the deterministic UDVS schemes) and a class of ID-Based Encryption (IBE) schemes which contains the Boneh-Franklin IBE scheme but not the Cocks IBE scheme.

Role of the N-terminal region in G protein-coupled receptor functions : negative modulation revealed by 5-HT2B receptor polymorphisms

The putative role of the N-terminal region of rhodopsin-like 7 transmembrane biogenic amine receptors in agonist-induced signaling has not yet been clarified despite recent advances in 7 transmembrane receptor structural biology. Given the existence of N-terminal nonsynonymous polymorphisms (R6G;E42G) within the HTR2B gene in a drug-abusing population, we assessed whether these polymorphisms affect 5-hydroxytryptamine 2B (5-HT2B) receptor in vitro pharmacologic and coupling properties in transfected COS-7 cells. Modification of the 5-HT2B receptor N terminus by the R6G;E42G polymorphisms increases such agonist signaling pathways as inositol phosphate accumulation as assessed by either classic or operational models. The N-terminal R6G;E42G mutations of the 5-HT2B receptor also increase cell proliferation and slow its desensitization kinetics compared with the wild-type receptor, further supporting a role for the N terminus in transduction efficacy. Furthermore, by coexpressing a tethered wild-type 5-HT2B receptor N terminus with a 5-HT2B receptor bearing a N-terminal deletion, we were able to restore original coupling. This reversion to normal activity of a truncated 5-HT2B receptor by coexpression of the membrane-tethered wild-type 5-HT2B receptor N terminus was not observed using a membrane-tethered 5-HT2B receptor R6G;E42G N terminus. These data suggest that the N terminus exerts a negative control over basal as well as agonist-stimulated receptor activity that is lost in the R6G;E42G mutant. Our findings reveal a new and unanticipated role of the 5-HT2B receptor N terminus as a negative modulator, affecting both constitutive and agonist-stimulated activity. Moreover, our data caution against excluding the N terminus and extracellular loops in structural studies of this 7 transmembrane receptor family

Decision support system for age-related macular degeneration using discrete wavelet transform

Age-related macular degeneration (AMD) affects the central vision and subsequently may lead to visual loss in people over 60 years of age. There is no permanent cure for AMD, but early detection and successive treatment may improve the visual acuity. AMD is mainly classified into dry and wet type; however, dry AMD is more common in aging population. AMD is characterized by drusen, yellow pigmentation, and neovascularization. These lesions are examined through visual inspection of retinal fundus images by ophthalmologists. It is laborious, time-consuming, and resource-intensive. Hence, in this study, we have proposed an automated AMD detection system using discrete wavelet transform (DWT) and feature ranking strategies. The first four-order statistical moments (mean, variance, skewness, and kurtosis), energy, entropy, and Gini index-based features are extracted from DWT coefficients. We have used five (t test, Kullback–Lieber Divergence (KLD), Chernoff Bound and Bhattacharyya Distance, receiver operating characteristics curve-based, and Wilcoxon) feature ranking strategies to identify optimal feature set. A set of supervised classifiers namely support vector machine (SVM), decision tree, k -nearest neighbor ( k -NN), Naive Bayes, and probabilistic neural network were used to evaluate the highest performance measure using minimum number of features in classifying normal and dry AMD classes. The proposed framework obtained an average accuracy of 93.70 %, sensitivity of 91.11 %, and specificity of 96.30 % using KLD ranking and SVM classifier. We have also formulated an AMD Risk Index using selected features to classify the normal and dry AMD classes using one number. The proposed system can be used to assist the clinicians and also for mass AMD screening programs.

On the Collision and Preimage Resistance of Certain Two-Call Hash Functions

In this paper we present concrete collision and preimage attacks on a large class of compression function constructions making two calls to the underlying ideal primitives. The complexity of the collision attack is above the theoretical lower bound for constructions of this type, but below the birthday complexity; the complexity of the preimage attack, however, is equal to the theoretical lower bound. We also present undesirable properties of some of Stam’s compression functions proposed at CRYPTO ’08. We show that when one of the n-bit to n-bit components of the proposed 2n-bit to n-bit compression function is replaced by a fixed-key cipher in the Davies-Meyer mode, the complexity of finding a preimage would be 2 n/3. We also show that the complexity of finding a collision in a variant of the 3n-bits to 2n-bits scheme with its output truncated to 3n/2 bits is 2 n/2. The complexity of our preimage attack on this hash function is about 2 n . Finally, we present a collision attack on a variant of the proposed m + s-bit to s-bit scheme, truncated to s − 1 bits, with a complexity of O(1). However, none of our results compromise Stam’s security claims.

Generalized element load method for first- and second-order element solutions with element load effect

The finite element method in principle adaptively divides the continuous domain with complex geometry into discrete simple subdomain by using an approximate element function, and the continuous element loads are also converted into the nodal load by means of the traditional lumping and consistent load methods, which can standardise a plethora of element loads into a typical numerical procedure, but element load effect is restricted to the nodal solution. It in turn means the accurate continuous element solutions with the element load effects are merely restricted to element nodes discretely, and further limited to either displacement or force field depending on which type of approximate function is derived. On the other hand, the analytical stability functions can give the accurate continuous element solutions due to element loads. Unfortunately, the expressions of stability functions are very diverse and distinct when subjected to different element loads that deter the numerical routine for practical applications. To this end, this paper presents a displacement-based finite element function (generalised element load method) with a plethora of element load effects in the similar fashion that never be achieved by the stability function, as well as it can generate the continuous first- and second-order elastic displacement and force solutions along an element without loss of accuracy considerably as the analytical approach that never be achieved by neither the lumping nor consistent load methods. Hence, the salient and unique features of this paper (generalised element load method) embody its robustness, versatility and accuracy in continuous element solutions when subjected to the great diversity of transverse element loads.

A new twist on mode indicator functions

Mode indicator functions (MIFs) are used in modal testing and analysis as a means of identifying modes of vibration, often as a precursor to modal parameter estimation. Various methods have been developed since the MIF was introduced four decades ago. These methods are quite useful in assisting the analyst to identify genuine modes and, in the case of the complex mode indicator function, have even been developed into modal parameter estimation techniques. Although the various MIFs are able to indicate the existence of a mode, they do not provide the analyst with any descriptive information about the mode. This paper uses the simple summation type of MIF to develop five averaged and normalised MIFs that will provide the analyst with enough information to identify whether a mode is longitudinal, vertical, lateral or torsional. The first three functions, termed directional MIFs, have been noted in the literature in one form or another; however, this paper introduces a new twist on the MIF by introducing two MIFs, termed torsional MIFs, that can be used by the analyst to identify torsional modes and, moreover, can assist in determining whether the mode is of a pure torsion or sway type (i.e., having a rigid cross-section) or a distorted twisting type. The directional and torsional MIFs are tested on a finite element model based simulation of an experimental modal test using an impact hammer. Results indicate that the directional and torsional MIFs are indeed useful in assisting the analyst to identify whether a mode is longitudinal, vertical, lateral, sway, or torsion.

Androgen receptor-dependent and independent functions of ARIP4

Androgen receptor (AR) is necessary for normal male phenotype development and essential for spermatogenesis. AR is a classical steroid receptor mediating actions of male sex steroids testosterone and 5-alpha-dihydrotestosterone. Numerous coregulators interact with the receptor and regulate AR activity on target genes. This study deals with the characterization of androgen receptor-interacting protein 4 (ARIP4). ARIP4 binds DNA, interacts with AR in vitro and in cultured yeast and mammalian cells, and modulates AR-dependent transactivation. ARIP4 is an active DNA-dependent ATPase, and this enzymatic activity is essential for the ability of ARIP4 to modulate AR function. On the basis of sequence homology in its ATPase domain, ARIP4 belongs to the SNF2 family of proteins involved in chromatin remodeling, DNA repair, and homologous recombination. Similar to its closest homologs ATRX and Rad54, ARIP4 does not seem to be a classical chromatin remodeling protein in that it does not appear to form large protein complexes in vivo or remodel mononucleosomes in vitro. However, ARIP4 is able to generate superhelical torsion on linear DNA fragments. ARIP4 is covalently modified by SUMO-1, and mutation of six potential SUMO attachment sites abolishes the ability of ARIP4 to bind DNA, hydrolyze ATP, and activate AR function. ARIP4 expression starts in early embryonic development. In mouse embryo ARIP4 is present mainly in the neural tube and limb buds. In adult mouse tissues ARIP4 expression is virtually ubiquitous. In mouse testis ARIP4 is expressed in the nuclei of Sertoli cells in a stage-dependent manner. ARIP4 is also present in the nuclei of Leydig cells, spermatogonia, pachytene and diplotene spermatocytes. Testicular expression pattern of ARIP4 does not differ significantly in wild-type, FSHRKO, and LuRKO mice. In the testis of hpg mice, ARIP4 is found mainly in interstitial cells and has very low, if any, expression in Sertoli and germ cells. Heterozygous Arip4+/ mice are fertile and appear normal; however, they are haploinsufficient with regard to androgen action in Sertoli cells. In contrast, Arip4 / embryos are not viable. They have significantly reduced body size at E9.5 and die by E11.5. Compared to wild-type littermates, Arip4 / embryos possess a higher percentage of apoptotic cells at E9.5 and E10.5. Fibroblasts derived from Arip4 / embryos cease growing after 2-3 passages and exhibit a significantly increased apoptosis and decreased proliferation rate than cells from wild-type embryos. Our findings demonstrate that ARIP4 plays an essential role in mouse embryonic development. In addition, testicular expression and AR coregulatory activity of ARIP4 suggest a role of ARIP4-AR interaction in the somatic cells of the testis.

The Functions and Regulation of Ornithine Decarboxylase

Ornithine decarboxylase (ODC) regulates the synthesis of polyamines which are involved in many cellular functions e.g. proliferation and differentiation. Due to its critical role, ODC is a tightly regulated enzyme by antizymes and antizyme inhibitors. If the regulation fails, the activity of ODC increases and may lead to malignant transformation of a cell. Increased ODC activity is found in many common cancers, including colon, prostate, and breast cancer. In a transformed cell, dynamics of the actin cytoskeleton is disturbed. A small G-protein, RhoA regulates organization of the cytoskeleton, and its overactivity increases malignant potential of the cell. The present results indicate that covalent attachment of polyamines by transglutaminase is a physiological means of regulating the activity of RhoA. The translocation of RhoA to the plasma membrane, where it exerts its activity is dependent on the presence of catalytically active ODC. As the overactivity of ODC and RhoA are implicated in cell transformation, the results provide a mechanistic explanation of the interrelationship between the polyamine metabolism and the reorganization of the actin cytoskeleton occurring in cancer cells. ODC and polyamines have also an important role in the function of central nervous system. They participate in the regulation of brain morphogenesis in embryos. In adult nervous tissue, polyamines regulate K+ and glutamate channels. K+ inward rectifying channels control membrane potentials and NMDA-type glutamate receptors (NMDAR) regulate synaptic plasticity. High ODC activity and polyamine levels are considered important in the development of ischemic brain damage and they are implicated in the pathogenesis of Alzheimer s disease (AD). A homolog of ODC was cloned from a human brain cDNA library, and several alternatively spliced variants were detected in human brain and testis. The novel protein was nevertheless devoid of ODC catalytic activity. It was subsequently found to be a novel inductor of ODC activity and polyamine synthesis, called antizyme inhibitor 2 (AZIN2). The accumulation of AZIN2 in vesicle-like formations along the axons and beneath the plasma membrane of neurons as well as in steroid hormone producing Leydig cells and luteal cells of the gonads implies that AZIN2 plays a role in secretion and vesicle trafficking. An accumulation of AZIN2 was detected also in specimens of AD brains. This increased expression of AZIN2 was specific for AD and was not found in brains with other neurodegenerative diseases including CADASIL or dementia with Lewy bodies.