A Knowledge-based Approach for Automatic Generation of Summaries of Behavior

Effective automatic summarization usually requires simulating human reasoning such as abstraction or relevance reasoning. In this paper we describe a solution for this type of reasoning in the particular case of surveillance of the behavior of a dynamic system using sensor data. The paper first presents the approach describing the required type of knowledge with a possible representation. This includes knowledge about the system structure, behavior, interpretation and saliency. Then, the paper shows the inference algorithm to produce a summarization tree based on the exploitation of the physical characteristics of the system. The paper illustrates how the method is used in the context of automatic generation of summaries of behavior in an application for basin surveillance in the presence of river floods.

VHDL-based system design of a cognitive sensorimotor loop (CSL) for haptic Human-Machine Interaction (HMI)

This document is a summary of the Bachelor thesis titled “VHDL-Based System Design of a Cognitive Sensorimotor Loop (CSL) for Haptic Human-Machine Interaction (HMI)” written by Pablo de Miguel Morales, Electronics Engineering student at the Universidad Politécnica de Madrid (UPM Madrid, Spain) during an Erasmus+ Exchange Program at the Beuth Hochschule für Technik (BHT Berlin, Germany). The tutor of this project is Dr. Prof. Hild. This project has been developed inside the Neurobotics Research Laboratory (NRL) in close collaboration with Benjamin Panreck, a member of the NRL, and another exchange student from the UPM Pablo Gabriel Lezcano. For a deeper comprehension of the content of the thesis, a deeper look in the document is needed as well as the viewing of the videos and the VHDL design. In the growing field of automation, a large amount of workforce is dedicated to improve, adapt and design motor controllers for a wide variety of applications. In the specific field of robotics or other machinery designed to interact with humans or their environment, new needs and technological solutions are often being discovered due to the existing, relatively unexplored new scenario it is. The project consisted of three main parts: Two VHDL-based systems and one short experiment on the haptic perception. Both VHDL systems are based on a Cognitive Sensorimotor Loop (CSL) which is a control loop designed by the NRL and mainly developed by Dr. Prof. Hild. The CSL is a control loop whose main characteristic is the fact that it does not use any external sensor to measure the speed or position of the motor but the motor itself. The motor always generates a voltage that is proportional to its angular speed so it does not need calibration. This method is energy efficient and simplifies control loops in complex systems. The first system, named CSL Stay In Touch (SIT), consists in a one DC motor system controller by a FPGA Board (Zynq ZYBO 7000) whose aim is to keep contact with any external object that touches its Sensing Platform in both directions. Apart from the main behavior, three features (Search Mode, Inertia Mode and Return Mode) have been designed to enhance the haptic interaction experience. Additionally, a VGA-Screen is also controlled by the FPGA Board for the monitoring of the whole system. This system has been completely developed, tested and improved; analyzing its timing and consumption properties. The second system, named CSL Fingerlike Mechanism (FM), consists in a fingerlike mechanical system controlled by two DC motors (Each controlling one part of the finger). The behavior is similar to the first system but in a more complex structure. This system was optional and not part of the original objectives of the thesis and it could not be properly finished and tested due to the lack of time. The haptic perception experiment was an experiment conducted to have an insight into the complexity of human haptic perception in order to implement this knowledge into technological applications. The experiment consisted in testing the capability of the subjects to recognize different objects and shapes while being blindfolded and with their ears covered. Two groups were done, one had full haptic perception while the other had to explore the environment with a plastic piece attached to their finger to create a haptic handicap. The conclusion of the thesis was that a haptic system based only on a CSL-based system is not enough to retrieve valuable information from the environment and that other sensors are needed (temperature, pressure, etc.) but that a CSL-based system is very useful to control the force applied by the system to interact with haptic sensible surfaces such as skin or tactile screens. RESUMEN. Este documento es un resumen del proyecto fin de grado titulado “VHDL-Based System Design of a Cognitive Sensorimotor Loop (CSL) for Haptic Human-Machine Interaction (HMI)” escrito por Pablo de Miguel, estudiante de Ingeniería Electrónica de Comunicaciones en la Universidad Politécnica de Madrid (UPM Madrid, España) durante un programa de intercambio Erasmus+ en la Beuth Hochschule für Technik (BHT Berlin, Alemania). El tutor de este proyecto ha sido Dr. Prof. Hild. Este proyecto se ha desarrollado dentro del Neurorobotics Research Laboratory (NRL) en estrecha colaboración con Benjamin Panreck (un miembro del NRL) y con Pablo Lezcano (Otro estudiante de intercambio de la UPM). Para una comprensión completa del trabajo es necesaria una lectura detenida de todo el documento y el visionado de los videos y análisis del diseño VHDL incluidos en el CD adjunto. En el creciente sector de la automatización, una gran cantidad de esfuerzo está dedicada a mejorar, adaptar y diseñar controladores de motor para un gran rango de aplicaciones. En el campo específico de la robótica u otra maquinaria diseñada para interactuar con los humanos o con su entorno, nuevas necesidades y soluciones tecnológicas se siguen desarrollado debido al relativamente inexplorado y nuevo escenario que supone. El proyecto consta de tres partes principales: Dos sistemas basados en VHDL y un pequeño experimento sobre la percepción háptica. Ambos sistemas VHDL están basados en el Cognitive Sesnorimotor Loop (CSL) que es un lazo de control creado por el NRL y cuyo desarrollador principal ha sido Dr. Prof. Hild. El CSL es un lazo de control cuya principal característica es la ausencia de sensores externos para medir la velocidad o la posición del motor, usando el propio motor como sensor. El motor siempre genera un voltaje proporcional a su velocidad angular de modo que no es necesaria calibración. Este método es eficiente en términos energéticos y simplifica los lazos de control en sistemas complejos. El primer sistema, llamado CSL Stay In Touch (SIT), consiste en un sistema formado por un motor DC controlado por una FPGA Board (Zynq ZYBO 7000) cuyo objetivo es mantener contacto con cualquier objeto externo que toque su plataforma sensible en ambas direcciones. Aparte del funcionamiento básico, tres modos (Search Mode, Inertia Mode y Return Mode) han sido diseñados para mejorar la interacción. Adicionalmente, se ha diseñado el control a través de la FPGA Board de una pantalla VGA para la monitorización de todo el sistema. El sistema ha sido totalmente desarrollado, testeado y mejorado; analizando su propiedades de timing y consumo energético. El segundo sistema, llamado CSL Fingerlike Mechanism (FM), consiste en un mecanismo similar a un dedo controlado por dos motores DC (Cada uno controlando una falange). Su comportamiento es similar al del primer sistema pero con una estructura más compleja. Este sistema no formaba parte de los objetivos iniciales del proyecto y por lo tanto era opcional. No pudo ser plenamente desarrollado debido a la falta de tiempo. El experimento de percepción háptica fue diseñado para profundizar en la percepción háptica humana con el objetivo de aplicar este conocimiento en aplicaciones tecnológicas. El experimento consistía en testear la capacidad de los sujetos para reconocer diferentes objetos, formas y texturas en condiciones de privación del sentido del oído y la vista. Se crearon dos grupos, en uno los sujetos tenían plena percepción háptica mientras que en el otro debían interactuar con los objetos a través de una pieza de plástico para generar un hándicap háptico. La conclusión del proyecto fue que un sistema háptico basado solo en sistemas CSL no es suficiente para recopilar información valiosa del entorno y que debe hacer uso de otros sensores (temperatura, presión, etc.). En cambio, un sistema basado en CSL es idóneo para el control de la fuerza aplicada por el sistema durante la interacción con superficies hápticas sensibles tales como la piel o pantallas táctiles.

Analysis of human cytochrome P450 3A4 cooperativity: Construction and characterization of a site-directed mutant that displays hyperbolic steroid hydroxylation kinetics

Cytochrome P450 3A4 is generally considered to be the most important human drug-metabolizing enzyme and is known to catalyze the oxidation of a number of substrates in a cooperative manner. An allosteric mechanism is usually invoked to explain the cooperativity. Based on a structure–activity study from another laboratory using various effector–substrate combinations and on our own studies using site-directed mutagenesis and computer modeling of P450 3A4, the most likely location of effector binding is in the active site along with the substrate. Our study was designed to test this hypothesis by replacing residues Leu-211 and Asp-214 with the larger Phe and Glu, respectively. These residues were predicted to constitute a portion of the effector binding site, and the substitutions were designed to mimic the action of the effector by reducing the size of the active site. The L211F/D214E double mutant displayed an increased rate of testosterone and progesterone 6β-hydroxylation at low substrate concentrations and a decreased level of heterotropic stimulation elicited by α-naphthoflavone. Kinetic analyses of the double mutant revealed the absence of homotropic cooperativity with either steroid substrate. At low substrate concentrations the steroid 6β-hydroxylase activity of the wild-type enzyme was stimulated by a second steroid, whereas L211F/D214E displayed simple substrate inhibition. To analyze L211F/D214E at a more mechanistic level, spectral binding studies were carried out. Testosterone binding by the wild-type enzyme displayed homotropic cooperativity, whereas substrate binding by L211F/D214E displayed hyperbolic behavior.

Random locomotion and chemotaxis of human blood polymorphonuclear leukocytes (PMN) in the presence of EDTA: PMN in close quarters require neither leukocyte integrins nor external divalent cations

Divalent cations are thought essential for motile function of leukocytes in general, and for the function of critical adhesion molecules in particular. In the current study, under direct microscopic observation with concomitant time-lapse video recording, we examined the effects of 10 mM EDTA on locomotion of human blood polymorphonuclear leukocytes (PMN). In very thin slide preparations, EDTA did not impair either random locomotion or chemotaxis; motile behavior appeared to benefit from the close approximation of slide and coverslip (“chimneying”). In preparations twice as thick, PMN in EDTA first exhibited active deformability with little or no displacement, then rounded up and became motionless. However, on creation of a chemotactic gradient, the same cells were able to orient and make their way to the target, often, however, losing momentarily their purchase on the substrate. In either of these preparations without EDTA, specific antibodies to β2 integrins did not prevent random locomotion or chemotaxis, even when we added antibodies to β1 and αvβ3 integrins and to integrin-associated protein, and none of these antibodies added anything to the effects of EDTA. In the more turbulent environment of even more media, effects of anti-β2 integrins became evident: PMN still could locomote but adhered to substrate largely by their uropods and by uropod-associated filaments. We relate these findings to the reported independence from integrins of PMN in certain experimental and disease states. Moreover, we suggest that PMN locomotion in close quarters is not only integrin-independent, but independent of external divalent cations as well.

A hierarchical neuronal network for planning behavior

Planning a goal-directed sequence of behavior is a higher function of the human brain that relies on the integrity of prefrontal cortical areas. In the Tower of London test, a puzzle in which beads sliding on pegs must be moved to match a designated goal configuration, patients with lesioned prefrontal cortex show deficits in planning a goal-directed sequence of moves. We propose a neuronal network model of sequence planning that passes this test and, when lesioned, fails in a way that mimics prefrontal patients’ behavior. Our model comprises a descending planning system with hierarchically organized plan, operation, and gesture levels, and an ascending evaluative system that analyzes the problem and computes internal reward signals that index the correct/erroneous status of the plan. Multiple parallel pathways connecting the evaluative and planning systems amend the plan and adapt it to the current problem. The model illustrates how specialized hierarchically organized neuronal assemblies may collectively emulate central executive or supervisory functions of the human brain.

Social transmission of reproductive behavior increases frequency of inherited disorders in a young-expanding population

The observation of high frequencies of certain inherited disorders in the population of Saguenay–Lac Saint Jean can be explained in terms of the variance and the correlation of effective family size (EFS) from one generation to the next. We have shown this effect by using the branching process approach with real demographic data. When variance of EFS is included in the model, despite its profound effect on mutant allele frequency, any mutant introduced in the population never reaches the known carrier frequencies (between 0.035 and 0.05). It is only when the EFS correlation between generations is introduced into the model that we can explain the rise of the mutant alleles. This correlation is described by a c parameter that reflects the dependency of children’s EFS on their parents’ EFS. The c parameter can be considered to reflect social transmission of demographic behavior. We show that such social transmission dramatically reduces the effective population size. This could explain particular distributions in allele frequencies and unusually high frequency of certain inherited disorders in some human populations.

Androgen-repressed phenotype in human prostate cancer

An androgen-repressed human prostate cancer cell line, ARCaP, was established and characterized. This cell line was derived from the ascites fluid of a patient with advanced metastatic disease. In contrast to the behavior of androgen-dependent LNCaP and its androgen-independent C4-2 subline, androgen and estrogen suppress the growth of ARCaP cells in a dose-dependent manner in vivo and in vitro. ARCaP is tumorigenic and highly metastatic. It metastasizes to the lymph node, lung, pancreas, liver, kidney, and bone, and forms ascites fluid in athymic hosts. ARCaP cells express low levels of androgen receptor mRNA and prostate-specific antigen mRNA and protein. Immunohistochemical staining shows that ARCaP cells stain intensely for epidermal growth factor receptor, c-erb B2/neu, and c-erb B3. Staining is negative for chromogranin A and positive for bombesin, serotonin, neuron-specific enolase, and the c-met protooncogene (a hepatic growth factor/scatter factor receptor). ARCaP cells also secrete high levels of gelatinase A and B and some stromelysin, which suggests that this cell line may contain markers representing invasive adenocarcinoma with selective neuronendocrine phenotypes. Along with its repression of growth, androgen is also found to repress the expression of prostate-specific antigen in ARCaP cells as detected by a prostate-specific antigen promoter–β-galactosidase reporter assay. Our results suggest that the androgen-repressed state may be central to prostate cancer progression and that advanced prostate cancer can progress from an androgen-independent to an androgen-repressed state.

Modeling the dynamics of human hair cycles by a follicular automaton

The hair follicle cycle successively goes through the anagen, catagen, telogen, and latency phases, which correspond, respectively, to hair growth, arrest, shedding, and absence before a new anagen phase is initiated. Experimental observations collected over a period of 14 years in a group of 10 male volunteers, alopecic and nonalopecic, allowed us to determine the characteristics of scalp hair follicle cycles. On the basis of these observations, we propose a follicular automaton model to simulate the dynamics of human hair cycles. The automaton model is defined by a set of rules that govern the stochastic transitions of each follicle between the successive states anagen, telogen, and latency, and the subsequent return to anagen. The transitions occur independently for each follicle, after time intervals given stochastically by a distribution characterized by a mean and a variance. The follicular automaton model accounts both for the dynamical transitions observed in a single follicle and for the behavior of an ensemble of independently cycling follicles. Thus, the model successfully reproduces the evolution of the fractions of follicle populations in each of the three phases, which fluctuate around steady-state or slowly drifting values. We apply the follicular automaton model to the study of spatial patterns of follicular growth that result from a spatially heterogeneous distribution of parameters such as the mean duration of anagen phase. When considering that follicles die or miniaturize after going through a critical number of successive cycles, the model can reproduce the evolution to hair patterns similar to well known types of diffuse or androgenetic alopecia.

Isoform-specific effects of human apolipoprotein E on brain function revealed in ApoE knockout mice: Increased susceptibility of females

Apolipoprotein E (apoE) mediates the redistribution of lipids among cells and is expressed at highest levels in brain and liver. Human apoE exists in three major isoforms encoded by distinct alleles (ɛ2, ɛ3, and ɛ4). Compared with APOE ɛ2 and ɛ3, APOE ɛ4 increases the risk of cognitive impairments, lowers the age of onset of Alzheimer’s disease (AD), and decreases the response to AD treatments. Besides age, inheritance of the APOE ɛ4 allele is the most important known risk factor for the development of sporadic AD, the most common form of this illness. Although numerous hypotheses have been advanced, it remains unclear how APOE ɛ4 might affect cognition and increase AD risk. To assess the effects of distinct human apoE isoforms on the brain, we have used the neuron-specific enolase (NSE) promoter to express human apoE3 or apoE4 at similar levels in neurons of transgenic mice lacking endogenous mouse apoE. Compared with NSE-apoE3 mice and wild-type controls, NSE-apoE4 mice showed impairments in learning a water maze task and in vertical exploratory behavior that increased with age and were seen primarily in females. These findings demonstrate that human apoE isoforms have differential effects on brain function in vivo and that the susceptibility to apoE4-induced deficits is critically influenced by age and gender. These results could be pertinent to cognitive impairments observed in human APOE ɛ4 carriers. NSE-apoE mice and similar models may facilitate the preclinical assessment of treatments for apoE-related cognitive deficits.

Recovery of hearing and vocal behavior after hair-cell regeneration

Postmitotic hair-cell regeneration in the inner ear of birds provides an opportunity to study the effect of renewed auditory input on auditory perception, vocal production, and vocal learning in a vertebrate. We used behavioral conditioning to test both perception and vocal production in a small Australian parrot, the budgerigar. Results show that both auditory perception and vocal production are disrupted when hair cells are damaged or lost but that these behaviors return to near normal over time. Precision in vocal production completely recovers well before recovery of full auditory function. These results may have particular relevance for understanding the relation between hearing loss and human speech production especially where there is consideration of an auditory prosthetic device. The present results show, at least for a bird, that even limited recovery of auditory input soon after deafening can support full recovery of vocal precision.

Forming classes by stimulus frequency: Behavior and theory

Visual classification is the way we relate to different images in our environment as if they were the same, while relating differently to other collections of stimuli (e.g., human vs. animal faces). It is still not clear, however, how the brain forms such classes, especially when introduced with new or changing environments. To isolate a perception-based mechanism underlying class representation, we studied unsupervised classification of an incoming stream of simple images. Classification patterns were clearly affected by stimulus frequency distribution, although subjects were unaware of this distribution. There was a common bias to locate class centers near the most frequent stimuli and their boundaries near the least frequent stimuli. Responses were also faster for more frequent stimuli. Using a minimal, biologically based neural-network model, we demonstrate that a simple, self-organizing representation mechanism based on overlapping tuning curves and slow Hebbian learning suffices to ensure classification. Combined behavioral and theoretical results predict large tuning overlap, implicating posterior infero-temporal cortex as a possible site of classification.

Crystal cataracts: Human genetic cataract caused by protein crystallization

Several human genetic cataracts have been linked recently to point mutations in the γD crystallin gene. Here we provide a molecular basis for lens opacity in two genetic cataracts and suggest that the opacity occurs because of the spontaneous crystallization of the mutant proteins. Such crystallization of endogenous proteins leading to pathology is an unusual event. Measurements of the solubility curves of crystals of the Arg-58 to His and Arg-36 to Ser mutants of γD crystallin show that the mutations dramatically lower the solubility of the protein. Furthermore, the crystal nucleation rate of the mutants is enhanced considerably relative to that of the wild-type protein. It should be noted that, although there is a marked difference in phase behavior, there is no significant difference in protein conformation among the three proteins.

Hormones, genes, and behavior

With assays of hormone-sensitive behaviors, it is possible to demonstrate both direct and indirect actions of genes on mammalian social behaviors. Direct effects of estrogen receptor gene expression and progesterone receptor gene expression figure prominently in well analyzed neuroendocrine mechanisms for sex behavior, operating through a neural circuit that has been delineated. Indirect effects, notably the consequences of sexual differentiation, display complex dependencies. In a human condition, Kallmann syndrome, the data show a clear, indirect genetic influence on an important human social behavior, in which damage at chromosome Xp-22.3 works through at least six discrete steps to affect libido. Altogether, simplistic extrapolations from lower animals, especially during brief summaries for nonscientists, do not appear justified as we discover and conceptualize genetic influences on mammalian brain and behavior.

Mutations in copper-zinc superoxide dismutase that cause amyotrophic lateral sclerosis alter the zinc binding site and the redox behavior of the protein.

A series of mutant human and yeast copper-zinc superoxide dismutases has been prepared, with mutations corresponding to those found in familial amyotrophic lateral sclerosis (ALS; also known as Lou Gehrig's disease). These proteins have been characterized with respect to their metal-binding characteristics and their redox reactivities. Replacement of Zn2+ ion in the zinc sites of several of these proteins with either Cu2+ or Co2+ gave metal-substituted derivatives with spectroscopic properties different from those of the analogous derivative of the wild-type proteins, indicating that the geometries of binding of these metal ions to the zinc site were affected by the mutations. Several of the ALS-associated mutant copper-zinc superoxide dismutases were also found to be reduced by ascorbate at significantly greater rate than the wild-type proteins. We conclude that similar alterations in the properties of the zinc binding site can be caused by mutations scattered throughout the protein structure. This finding may help to explain what is perhaps the most perplexing question in copper-zinc superoxide dismutase-associated familial ALS-i.e., how such a diverse set of mutations can result in the same gain of function that causes the disease.

Cholesterol homeostasis in human brain: evidence for an age-dependent flux of 24S-hydroxycholesterol from the brain into the circulation.

We have investigated whether side chain-hydroxylated cholesterol species are important for elimination of cholesterol from the brain. Plasma concentrations of 24-hydroxycholesterol (24-OH-Chol) in the internal jugular vein and the brachial artery in healthy volunteers were consistent with a net flux of this steroid from the brain into the circulation, corresponding to elimination of approximately 4 mg cholesterol during a 24-h period in adults. Results of experiments with rats exposed to 18O2 were also consistent with a flux of 24-OH-Chol from the brain into the circulation. No other oxysterol measured showed a similar behavior as 24-OH-Chol. These results and the finding that the concentration of 24-OH-Chol was 30- to 1500-fold higher in the brain than in any other organ except the adrenals indicate that the major part of 24-OH-Chol present in the circulation originates from the brain. Both the 24-OH-Chol present in the brain and in the circulation were the 24S-stereoisomer. In contrast to other oxysterols, levels of plasma 24-OH-Chol were found to be markedly dependent upon age. The ratio between 24-OH-Chol and cholesterol in plasma was approximately 5 times higher during the first decade of life than during the sixth decade. There was a high correlation between levels of 24-OH-Chol in plasma and cerebrospinal fluid. It is suggested that the flux of 24-OH-Chol from the brain is important for cholesterol homeostasis in this organ.