Serial Stages Research Articles

Automated test of behavioral flexibility in mice using a behavioral sequencing task in IntelliCage

There has been a long-standing need to develop efficient and standardized behavioral test methods for evaluating higher-order brain functions in mice. Here, we developed and validated a behavioral flexibility test in mice using IntelliCage, a fully automated behavioral analysis system for mice in a group-housed environment. We first developed a “behavioral sequencing task” in the IntelliCage that enables us to assess the learning ability of place discrimination and behavioral sequence for reward acquisition. In the serial reversal learning using the task, the discriminated spatial patterns of the rewarded and never-rewarded places were serially reversed, and thus, mice were accordingly expected to realign the previously acquired behavioral sequence. In general, the tested mice showed rapid acquisition of the behavioral sequencing task and behavioral flexibility in the subsequent serial reversal stages both in intra- and inter-session analyses. It was found that essentially the same results were obtained among three different laboratories, which confirm the high stability of the present test protocol in different strains of mice (C57BL/6, DBA/2, and ICR). In particular, the most trained cohort of C57BL/6 mice achieved a markedly rapid adaptation to the reversal task in the final phase of the long-term serial reversal test, which possibly indicated that the mice adapted to the “reversal rule” itself. In conclusion, the newly developed behavioral test was shown to be a valid assay of behavioral flexibility in mice, and is expected to be utilized in tests of mouse models of cognitive deficits.

Mathematical Modeling of the Human Cognitive System in Two Serial Processing Stages With Its Applications in Adaptive Workload-Management Systems

With the increasing usage of in-vehicle systems, drivers have to frequently perceive and respond to messages from these in-vehicle systems. In addition, previous studies have found that the interval between the messages (arrival rate) presented to a driver becomes one of the factors affecting driver workload. To reduce driver workload, researchers on adaptive workload-management systems have found that adding extra delay time into the interval of messages can significantly reduce driver workload. However, it is unknown whether this extra delay time added by an adaptive workload-management system will increase the performance time of drivers or not. To answer this important question, using closed-form mathematical equations, the current work quantifies human performance time (total task completion time and reaction time of each task) when there are two serial processing stages in the human cognitive system. The mathematical model developed in this work provides solutions of the optimal interval of messages that generate the lowest workload without deteriorating drivers' performance time to respond to multiple messages from in-vehicle systems. This is one of a few closed-form deterministic mathematical models with analytic solutions that can predict average reaction time when there are two multiple serial stages in the cognitive system in dual tasks. With relatively simple equations, the mathematical model can still capture the major patterns of simulation results with stochastic properties and human behavioral experimental results. The mathematical equations developed in this study can be used in the design of adaptive workload-management systems and other driver assistance systems.

Top-down modulation of ventral occipito-temporal responses during visual word recognition

Although interactivity is considered a fundamental principle of cognitive (and computational) models of reading, it has received far less attention in neural models of reading that instead focus on serial stages of feed-forward processing from visual input to orthographic processing to accessing the corresponding phonological and semantic information. In particular, the left ventral occipito-temporal (vOT) cortex is proposed to be the first stage where visual word recognition occurs prior to accessing nonvisual information such as semantics and phonology. We used functional magnetic resonance imaging (fMRI) to investigate whether there is evidence that activation in vOT is influenced top-down by the interaction of visual and nonvisual properties of the stimuli during visual word recognition tasks. Participants performed two different types of lexical decision tasks that focused on either visual or nonvisual properties of the word or word-like stimuli. The design allowed us to investigate how vOT activation during visual word recognition was influenced by a task change to the same stimuli and by a stimulus change during the same task. We found both stimulus- and task-driven modulation of vOT activation that can only be explained by top-down processing of nonvisual aspects of the task and stimuli. Our results are consistent with the hypothesis that vOT acts as an interface linking visual form with nonvisual processing in both bottom up and top down directions. Such interactive processing at the neural level is in agreement with cognitive and computational models of reading but challenges some of the assumptions made by current neuro-anatomical models of reading.

Beyond detuning: 10 years of progress and new challenges in the development and application of assays for HIV incidence estimation

Beyond detuning: 10 years of progress and new challenges in the development and application of assays for HIV incidence estimation

The Velocity Characteristics of a Serial-Staged EHD Gas Pump in Air

The application of the ionic wind in the fields of aerodynamic control and heat transfer is limited by its low velocity and small active area. This paper deals with the experimental and theoretical analysis of the ionic-wind velocity in serial-staged electrohydrodynamic gas pumps under a negative corona discharge in air. Each stage consists of a pair of needle array-to-ring or needle array-to-mesh electrodes. It was observed that the active area of the gas pump can be enlarged by using a needle array electrode where the negative corona discharge started simultaneously and that the needle array-to-mesh electrode can generate a higher ionic wind velocity compared to that of the needle array-to-ring electrode. The flow velocity of the ionic wind is dependent on both the number of serial stages and the pressure loss. A maximum average flow velocity of 7.39 m/s, volumetric flow rate of 140 L/min, and energy conversion efficiency of 0.8% were achieved experimentally in this paper.

Practical Design for Energy-Saving EDM Supply System

In this paper a kind of architecture for an energy-saving EDM supply composed of three serial stages in the topology and its practical design are discussed. Various special controllers and its assisted circuits are introduced in the each of the three serial stages. The PFC controller UC3854 placed on the front stage provides satisfactory input power factor of the system. The PWM controller UC3875 mounted on the middle stage realize the closed control of the current of the inductance limiting machining current. An embedded controller PIC16F877 on the final stage is chosen to setting such machining variables as peak current, discharge duration and pulse interval. The communication with host PC is also realized by the same embedded controller. The architecture based on model of multi-controller parallel working guarantees capacity of the system real-time process. The prototype of the energy-saving EDM pulse supply using MOSFET power device is developed. A lot of experiments have demonstrated the feasibility and stability of the practical design.

Neural Mechanisms for Interacting with a World Full of Action Choices

The neural bases of behavior are often discussed in terms of perceptual, cognitive, and motor stages, defined within an information processing framework that was originally inspired by models of human abstract problem solving. Here, we review a growing body of neurophysiological data that is difficult to reconcile with this influential theoretical perspective. As an alternative foundation for interpreting neural data, we consider frameworks borrowed from ethology, which emphasize the kinds of real-time interactive behaviors that animals have engaged in for millions of years. In particular, we discuss an ethologically-inspired view of interactive behavior as simultaneous processes that specify potential motor actions and select between them. We review how recent neurophysiological data from diverse cortical and subcortical regions appear more compatible with this parallel view than with the classical view of serial information processing stages.

Computational modeling of stochastic processes in electron amplifiers

A computational method for simulation of stochastic processes of an electron multiplication in microchannel electron amplifiers is developed. The method is based on 3D Monte Carlo (MC) simulations and theorems about serial and parallel amplification stages proposed here. Splitting a stochastic process into a number of different stages, enables a contribution of each stage to the entire process to be easily investigated. The method preserves all advantages of the MC simulations which are used only once for one simple stage. The use of the theorems allows to conduct any further investigations and optimizations without additional MC simulations. The method provides a high calculation accuracy with minimal cost of computations. The model is relevant to unsaturated operation of the amplifier with exponential output distribution. The mean gain and the variance of the amplitude distribution at the output of the amplifier are predicted. In this paper the method is used to show how the input ratio of the signal to the noise is transforming to the output one, and how different multiplication stages contribute to the noise factor of the system. Finally, the effect of variations in channel diameters on noise characteristics of microchannel electron amplifiers is investigated.

Building the developmental oculome: systems biology in vertebrate eye development and disease

The vertebrate eye is a sophisticated multicomponent organ that has been actively studied for over a century, resulting in the identification of the major embryonic and molecular events involved in its complex developmental program. Data gathered so far provides sufficient information to construct a rudimentary network of the various signaling molecules, transcription factors, and their targets for several key stages of this process. With the advent of genomic technologies, there has been a rapid expansion in our ability to collect and process biological information, and the use of systems-level approaches to study specific aspects of vertebrate eye development has already commenced. This is beginning to result in the definition of the dynamic developmental networks that operate in ocular tissues, and the interactions of such networks between coordinately developing ocular tissues. Such an integrative understanding of the eye by a comprehensive systems-level analysis can be termed the 'oculome', and that of serial developmental stages of the eye as it transits from its initiation to a fully formed functional organ represents the 'developmental oculome'. Construction of the developmental oculome will allow novel mechanistic insights that are essential for organ regeneration-based therapeutic applications, and the generation of computational models for eye disease states to predict the effects of drugs. This review discusses our present understanding of two of the individual components of the developing vertebrate eye--the lens and retina--at both the molecular and systems levels, and outlines the directions and tools required for construction of the developmental oculome.

Wavelet-based feature extraction and selection for classification of power system disturbances using support vector machines

This paper presents a new approach for the classification of the power system disturbances using support vector machines (SVMs). The proposed approach is carried out at three serial stages. Firstly, the features to be form the SVM classifier are obtained by using the wavelet transform and a few different feature extraction techniques. Secondly, the features exposing the best classification accuracy of these features are selected by a feature selection technique called as sequential forward selection. Thirdly, the best appropriate input vector for SVM classifier is rummaged. The input vector is started with the first best feature and incrementally added the chosen features. After the addition of each feature, the performance of the SVM is evaluated. The kernel and penalty parameters of the SVM are determined by cross-validation. The parameter set that gives the smallest misclassification error is retained. Finally, both the noisy and noiseless signals are applied to the classifier given above stages. Experimental results indicate that the proposed classifier is robust and has more high classification accuracy with regard to the other approaches in the literature for this problem.

Serial stages of gain control

Serial stages of gain control

2-layer based microfluidic concentration generator by hybrid serial and volumetric dilutions

We present a 2-layer based microfluidic concentration generator by a hybrid of a serial and a volumetric dilution for dose-response experiments in drug screening. The hybrid dilution method using 2-layer based microfluidic network significantly reduces the total number of cascaded serial dilution stages. The proposed strategy is capable of generating a large number of universal stepwise monotonic concentrations with a wide range of logarithmic and linear scales. We have studied an equivalent electrical circuit to that of the 2-layer based microfluidic network, where the only variable parameter is channel length. We have designed a microfluidic dilution generator simultaneously covering 14 doses with a combination of 4-order logarithmic and 4-point linear concentrations. The design has been verified by a commercial circuit analysis software (e.g., P-Spice) for the electrical circuit analysis and a computational fluid dynamics software (e.g., CFD-ACE+) for the microfluidic circuit analysis. As a real-life application of the proposed dilution generator, we have successfully performed a dose-response experiment using MCF-7 human breast cancer cells. We expect that the proposed dilution method will be useful to study not only high throughput drug screening but also optimization in biology, chemistry, medicine, and material sciences.

020. HORMONAL REGULATION OF SPERMATOGENESIS

Spermatogenesis is a spatially and temporally co-ordinated proliferation of the germinal epithelium in the semeniferous tubules. The germ cells are embedded in a scafolding formed by adjacent Sertoli cells linked tightly by intercellular junctions and with each germ cell enshrouded by elongations of Sertoli cell cytoplasm. Spermatogenesis comprises serial stages from the mitotic replication of the stem and early germ cells, followed by meiosis, the reductive division producing haploid, amorphous gametes which subsequently undergo spermiogenesis, the metamorphosis into terminally differentiated and functional spermatozoa. Although long known that all but the earliest stages are hormonally regulated by pituitary secretion of LH and FSH, it has remained difficult to separate gonadotrophin effects by classical endocrine ablate-replace methods as these two heterodimeric hormones have identical α and homologous β subunits, are secreted from the same pituitary gonadotrophs to target cognate receptors expressed on adjacent testicular cells as equally homologous, heptahelical G-coupled protein receptors. Over two decades our laboratory has developed a variety of complementary genetic and pharmacological approaches to dissect the individual and co-operative effects of LH, its main effector testosterone and FSH on spermatogenesis. Using the gonadotrophin and testosterone deficient hpg mouse, double transgenic human FSH secreting mouse and the androgen receptor knockout mouse lines together with steroidal depot homone delivery, we have explored systematically annd defined the individual primary actions of FSH and testosterone and their interactions in the regulation of testis growth, spermatogenesis and ultimately male fertility.

Process industry scheduling optimization using genetic algorithm and mathematical programming

This article addresses the problem of scheduling in oil refineries. The problem consists of a multi-product plant scheduling, with two serial machine stages--a mixer and a set of tanks--which have resource constraints and operate on a continuous flow basis. Two models were developed: the first using mixed-integer linear programming (MILP) and the second using genetic algorithms (GA). Their main objective was to meet the whole forecast demand, observing the operating constraints of the refinery and minimizing the number of operational changes. A real-life data-set related to the production of fuel oil and asphalt in a large refinery was used. The MILP and GA models proved to be good solutions for both primary objectives, but the GA model resulted in a smaller number of operational changes. The reason for this is that GA incorporates a multi-criteria approach, which is capable of adaptively updating the weights of the objective throughout the evolutionary process.

Melatonin induces apoptotic death in LNCaP cells via p38 and JNK pathways: therapeutic implications for prostate cancer

Apoptosis, a form of cell death, is a fundamental process for the development and maintenance of multicellular organisms that promotes the removal of damaged, senescent or unwanted cells. Induction of cancer cell apoptosis is an important strategy of anticancer therapy. In this study, we examined if melatonin, the main secretory product of the pineal gland, inhibited the growth of prostate cancer cells (LNCaP) and promoted apoptosis via mitogen-activated protein kinases (MAPKs), which are closely associated with apoptosis and survival. Melatonin treatment significantly inhibited the growth of LNCaP cells in a dose- and time-dependent manner. It clearly induced both an early stage of apoptosis (propidium iodide(-), FITC Annexin-V(+)) and a late apoptosis/secondary necrosis (propidium iodide(+) and FITC Annexin-V(+)), which indicated induction of serial stages of apoptosis in cells. Moreover, melatonin markedly activated c-JUN N-terminal kinase (JNK) and p38 kinase, whereas extracellular signal-regulated kinase (ERK) was not responsive to melatonin. Treatment with MAPK inhibitors, PD98059 (ERK inhibitor), SP600125 (JNK inhibitor) and SB202190 (p38 inhibitor), confirmed that melatonin-induced apoptosis was JNK- and p38-dependent, but ERK-independent. In the presence of PD98059, caspase-3 activity increased, while levels of Bax/cytochrome c (Cyt c) and Bcl-2 decreased. These effects were opposite to those observed with SP600125 and SB202190 treatments. Together, these results strongly suggest that JNK and p38 activation directly participate in apoptosis induced by melatonin. Thus, melatonin may be of promise for anti-prostate cancer strategies.

Titration of hepatitis B virus infectivity in the sera of pre‐acute and late acute phases of HBV infection: Transmission experiments to chimeric mice with human liver repopulated hepatocytes

Studies of hepatitis B virus (HBV) infection in non-human primates such as chimpanzees are no longer possible due to ethical considerations and the endangered status of chimpanzees since April 2007 in Japan. A human hepatocyte transplanted chimeric mouse was used to characterize HBV infectivity in serial stages of acute infection. Chimeric mice were inoculated intravenously with serum samples obtained from an experimentally infected chimpanzee with HBV. Sera from the pre-acute phases (i.e., rump-up viremia prior to anti-HBc) and late acute phases (i.e., declining phase of HBsAg and anti-HBcAb positive) were collected from the chimpanzees 57 and 244 days after inoculation. These sera contained 2.6 x 10(6) and 2.8 x 10(6) copies/ml of HBV DNA, respectively. Three chimeric mice inoculated intravenously with 100 microl of pre-acute serum (equivalent to 10(0) copy of HBV DNA) developed an HBV infection. The three chimeric mice that received 100 microl of pre-acute serum (equivalent to 10(1) copies of HBV DNA), developed high levels of serum HBV DNA. None of the three chimeric mice inoculated with 100 microl of 1:10(4) dilution (equivalent to 10(1) copies of HBV DNA) of late-acute serum was infected, while only one of three chimeric mice inoculated with 100 microl of 1:10(3) dilution (equivalent to 10(2) copies of HBV DNA) of late-acute serum developed an HBV infection. Based on these results, chimeric mice can be used as animal models for the study of HBV infectivity, pathogenesis and control. The results show that pre-acute phase HBV serum is about 100-times more infectious than late acute phase serum.

Disconnection in prosopagnosia and face processing

Face perception is a function with significant complexity, reflected in cognitive models that propose a hierarchy of parallel and serial processing stages. Current neuroimaging data also show that face perception involves a core processing network of cortical modules, which are likely specialized for different functions involved in face processing. The core face processing network is further linked to an extended face processing network which is not solely involved in the perception of faces, but rather contains modules mediating the processing of semantic, biographic and emotional information about people. The segregation of these processes within discrete anatomic regions creates the potential for disconnection between regions to generate neuropsychological deficits involving faces. In this review we consider the types of disconnection possible both within the core face processing system and between the core and extended systems, the pattern of deficits that would be considered as evidence of such disconnections, the potential anatomy of lesions that would create them, and whether any cases exist that meet these criteria.

Multisensory enhancement: gains in choice and in simple response times

Human observers can detect combinations of multisensory signals faster than each of the corresponding signals presented separately. In simple detection tasks, this facilitation in response times may reflect an enhancement in the perceptual processing stage or/and in the motor response stage. The current study compared the multisensory enhancements obtained in simple and choice response times (SRT and CRT, respectively) in bi- and tri-sensory (audio-visual-haptic) signal combinations using an identical experimental setup that differed only in the tasks--detecting the signals (SRT) or reporting the signals' location (CRT). Our measurements show that RTs were faster in the multisensory combinations conditions compared to the single stimulus conditions and that the absolute multisensory gains were larger in CRT than in SRT. These results can be interpreted in two ways. According to a serial stages model, the larger multisensory gains in CRT may suggest that when combinations of multisensory signals are presented, an additional enhancement occurs in the cognitive processing stages engaged in the CRT, beyond the enhancement in the perceptual and motor stages common to both SRT and CRT. Alternatively, the results suggest that multisensory enhancement reflect task-dependent interactions within and between multiple processing levels rather than facilitated processing modules. Thus, the larger absolute multisensory gains in CRT may reflect the inverse effectiveness principle, and Bayesian statistics, in that the maximal multisensory enhancements occur in the more difficult (less precise) uni-sensory conditions, i.e., in the CRT.

Neurogenic development of the auditory areas of the midbrain and diencephalon in the Xenopus laevis and evolutionary implications

To study whether the core-versus-shell pattern of neurogenesis occurred in the mesencephalic and diencephalic auditory areas of amniotes also appears in the amphibian, [ 3H]-thymidine was injected into tadpoles at serial developmental stages of Xenopus laevis. Towards the end of metamorphism, [ 3H]-thymidine labeling was examined and led to two main observations: 1) neuron generation in the principal nucleus (Tp) started at stage 50, and peaked at stage 53, whereas it began at stage 48.5, and peaked around stage 49 in the other two mesencephalic auditory areas, the laminar nucleus (Tl) and the magnocellular nucleus (Tmc). 2) Neuron generation appeared at stage 40, and peaked around stage 52 in the posterior thalamic nucleus (P) and the central thalamic nucleus (C). Our study revealed that, like the cores of mesencephalic auditory nuclei in amniotes, Tp showed differences from Tl and Tmc in the onset and the peak of neurogenesis. However, such differences did not occur in the P and C. Our neurogenetic data were consistent with anatomical and physiological reports indicating a clear distinction between the mesencephalic, but not the diencephalic auditory areas of the amphibian. Our data are helpful to get insights into the organization of auditory nuclei and its evolution in vertebrates.

Fibrosis quística: diagnóstico molecular en 93 pacientes argentinos y detección familiar de portadores. Impacto asistencial y proyección a nuevos avances terapéuticos

The cystic fibrosis is an autosomal recessive disease caused by more than 1500 mutations and variants in the cystic fibrosis transmembrane conductance regulator gene. To establish the spectrum and frequency of mutations on this gene in Argentinean patients.To detect heterozygotes in affected families. We investigated 91 clinical and biochemically confirmed patients with 2 elevated sweat tests and 2 sterile adults. We worked with 165 relatives. The molecular diagnosis was accomplished in 3 serial stages: a) determination of 29 frequent mutations; b) haplotypes for microsatellites; c) an extensive screening of gene through single strand conformation analysis and multiplex denaturing gradient gel electrophoresis with sequencing of abnormal patterns. Once patient's genotype was confirmed, we investigated the heterozygotes' state in the relatives. 1ST OBJECTIVE: Fourteen mutations were identified. Three more mutations were detected and other 11 mutations were characterized, 3 of them novel (p.G27R, c.622-2A>G, p.W277R). In total, we have identified 28 mutations responsible for 90.3% of the mutated alleles, 14 with a higher frequency than 1%. 2ND OBJECTIVE: From 165 investigated people, 143 were confirmed as heterozygotes and with normal genotype 22. This work contributed to the molecular characterization of patients with classic and atypical phenotypes and to the detection of great numbers of carriers. New pharmacological therapeutic investigations are based on the mutation type. Therefore, knowledge of patients, mutations (genotype) has significant importance for the future application of specific therapies.