Neural Basis of Scientific Innovation Induced by Heuristic Prototype

A number of major inventions in history have been based on bionic imitation. Heuristics, by applying biological systems to the creation of artificial devices and machines, might be one of the most critical processes in scientific innovation. In particular, prototype heuristics propositions that innovation may engage automatic activation of a prototype such as a biological system to form novel associations between a prototype''s function and problem-solving. We speculated that the cortical dissociation between the automatic activation and forming novel associations in innovation is critical point to heuristic creativity. In the present study, novel and old scientific innovations (NSI and OSI) were selected as experimental materials in using learning-testing paradigm to explore the neural basis of scientific innovation induced by heuristic prototype. College students were required to resolve NSI problems (to which they did not know the answers) and OSI problems (to which they knew the answers). From two fMRI experiments, our results showed that the subjects could resolve NSI when provided with heuristic prototypes. In Experiment 1, it was found that the lingual gyrus (LG; BA18) might be related to prototype heuristics in college students resolving NSI after learning a relative prototype. In Experiment 2, the LG (BA18) and precuneus (BA31) were significantly activated for NSI compared to OSI when college students learned all prototypes one day before the test. In addition, the mean beta-values of these brain regions of NSI were all correlated with the behavior accuracy of NSI. As our hypothesis indicated, the findings suggested that the LG might be involved in forming novel associations using heuristic information, while the precuneus might be involved in the automatic activation of heuristic prototype during scientific innovation.     

Protein sequences yield a proteomic code

Analysis of crystallized protein structures suggests that globular proteins are organized as consecutively connected units of 25-35 residues. These units are closed loops, that is returns of the polypeptide chain trajectory to a close contact with itself. This universal feature of apparently polymer-statistical nature is a basis for a principally novel view on the globular proteins as loop fold structures. The same unit size has been detected in protein sequences translated from complete prokaryotic genomes by positional autocorrelation analysis, which strongly indicates the evolutionary connection of the units. The units are further characterized by prototype sequences matching to their numerous derivatives in the translated genomes. The matches to five strongest prokaryotic prototypes and three prototypes of C. elegans are identified in the sequences of crystallized proteins, and their structures analyzed. Corresponding segments of the polypeptide chains in majority of cases form closed loops, though evolutionary fate of every prototype element is shown to be rather diverse. Then loop ends can be separated by a sequence-wise distant segments and stabilized by the spatial interactions in the context of the overall globular structure. The units belong to a presumably limited spectrum of the sequence prototypes, full repertoire of which would constitute a proteomic code.     

Avian detection and identification of perceptual organization in random noise

Recent research has suggested that pigeons may have difficulty globally integrating visual information in hierarchically arranged stimuli. To isolate and understand the mechanisms responsible for processing emergent perceptual structure, three pigeons were tested in a two alternative choice task that required the global integration of organized local information. They were reinforced for localizing, on randomized distractor backgrounds of black and white square elements, different types of structured targets (e.g., stripes, squares, checkerboards) arranged from these same elements. These hierarchical stimuli were tested at four different levels of spatial granularity (i.e., different element sizes). Experiment 1 found rapid acquisition for the vertical and horizontal stripes or square targets and somewhat slower learning with the checkerboard pattern. Experiment 2 demonstrated successful transfer to a novel target types (alternating bars and "diagonal" stripes). In both experiments, displays with the greatest spatial granularity (smallest elements and most repetitive structure) monotonically supported the best discrimination. These results indicate pigeons can perceive and discriminate emergent visual structure under the right circumstances and suggest they do so with a generalized rule for detecting patterns of non-random perceptual structure.     

A further study of choice and percentage reinforcement

In Experiment I four pigeons were trained in a concurrent chains procedure with fixed-ratio schedules (FR1) in the initial components and fixed-time schedules in the terminal components. Pecking one of the keys when both keys were white initiated a fixed time schedule on that key. A peck to the left key produced three stripes on the key. At the termination of the fixed-time component food always occurred. Pecking the other key produced either a circle or a triangle. If a circle appeared, reinforcement occurred. If a triangle appeared a brief timeout was given. Initially the stripes appeared on the left key and the circle and triangle on the left. This was reversed during the course of the experiment. In addition, sessions were conducted in which both circle and triangle sometimes preceded reinforcement and sometimes timeout. For most birds under most conditions there was a preference for the key that produced the circle and triangle. When these were uncorrelated with reinforcement and time out three of the birds preferred the key producing 100% reinforcement.

In Experiment II three factors were varied and VI 20 sec schedules were used in the initial links instead of FR1. The results showed that pigeons preferred the 50% condition more 1) the greater the duration of the terminal links, 2) the smaller the value on the initial link VI schedules and 3) the less the probability of food in the terminal link with stripes on the key.     

A biological meaningful classification in child psychiatry that is based upon ethological methods

An ethological approach to behavior quantification and classification in child psychiatry is described using the prototype approach to concept formation, in which examples are considered exemplars of concepts. Data are based on a large number of psychiatric evaluations. A number of behaviors was selected and their occurrence recorded and quantified. This resulted in a number of parameters for which values were determined per child. Classification of parameters was based on a number of explicit criteria that varied in their usefulness. It appeared that a classification on the basis of biological function was most useful. This biologically meaningful classification reasonably paralleled traditional child psychiatric diagnoses. The resulting prototypes may be useful during psychiatric evaluation of children.     

Better living by not completing: a wonderful peculiarity of pigeon vision?

Whereas many non-human species have been demonstrated to visually complete partly occluded figures, pigeons have been repeatedly failed to do so. We asked whether this failure reflected the pigeons' lack of perceptual process for completion or their decision among completed and non-completed figures. Four pigeons searched for a red lozenge target having one of its four contours punched in a rectangular edge out among three intact lozenges. All of these four stimuli had a white square next to them. After obtaining consistent search performances, the pigeons were tested with the punched target in a variety of locations relative to the white square, including right at the edges. Humans tested in the same task needed longer times before detecting the target when the square was placed right at the punched edge, suggesting automatic completion in humans. In contrast, the pigeons showed no similar difficulty. This result has two important suggestions: first, pigeons fail to complete partially occluded objects at the perceptual level, and second, this lack of completion is sometimes advantageous for them.     

Pigeons (Columba livia) as Trainable Observers of Pathology and Radiology Breast Cancer Images

Pathologists and radiologists spend years acquiring and refining their medically essential visual skills, so it is of considerable interest to understand how this process actually unfolds and what image features and properties are critical for accurate diagnostic performance. Key insights into human behavioral tasks can often be obtained by using appropriate animal models. We report here that pigeons (Columba livia)—which share many visual system properties with humans—can serve as promising surrogate observers of medical images, a capability not previously documented. The birds proved to have a remarkable ability to distinguish benign from malignant human breast histopathology after training with differential food reinforcement; even more importantly, the pigeons were able to generalize what they had learned when confronted with novel image sets. The birds’ histological accuracy, like that of humans, was modestly affected by the presence or absence of color as well as by degrees of image compression, but these impacts could be ameliorated with further training. Turning to radiology, the birds proved to be similarly capable of detecting cancer-relevant microcalcifications on mammogram images. However, when given a different (and for humans quite difficult) task—namely, classification of suspicious mammographic densities (masses)—the pigeons proved to be capable only of image memorization and were unable to successfully generalize when shown novel examples. The birds’ successes and difficulties suggest that pigeons are well-suited to help us better understand human medical image perception, and may also prove useful in performance assessment and development of medical imaging hardware, image processing, and image analysis tools.     

Spelling protein structure

Recent sequence analysis of complete prokaryotic proteomes suggests that in early evolutionary stages proteins were rather small, of the size 25-35 amino acids. Corroborating evidence comes from protein crystal data, which indicate this size for closed loops--universal structural units of globular proteins. In the latest development we were able to derive and structurally characterize several sequence/structure prototypes apparently representing early protein units. Structurally the prototypes appear as closed loops stabilized by end-to-end van der Waals interactions. While nearly standard in size the loops are highly diverse in terms of their secondary structure. A presentation of the protein as an assembly of descendants of the prototypes, the first of its kind, is described in detail here. The sequence and structure of the ATP-binding subunit of histidine permease of S. typhimurium is shown to contain several modified copies of different prototype elements, closed loops, and, thus, can be spelled as: x-PI-x-PIV-PVI-PII-PVII-x, where PI-PVII are the prototype elements. This study sets up the basic principles for the sequence/structure prototype spelling of globular proteins.     

Self-organization of neurons described by the maximum-entropy principle

In the article the maximum-entropy principle and Parzen windows are applied to derive an optimal mapping of a continuous into a descrete random variable. The mapping can be performed by a network of self-organizing information processing units similar to biological neurons. Each neuron is selectively sensitized to one prototype from the sample space of the discrete random variable. The continuous random variable is applied as the input signal exciting the neurons. The response of the network is described by the excitation vector which represents the encoded input signal. Due to the interaction between neurons adaptive changes of prototypes are caused by the excitations. The derived mathematical model explains this interaction in detail; a simplified self-organization rule derived from it corresponds to that of Kohonen. One and two-dimensional examples of self-organization simulated on a computer are shown in the article.     

A Novel Class of Anti-HIV Agents with Multiple Copies of Enfuvirtide Enhances Inhibition of Viral Replication and Cellular Transmission In Vitro

We constructed novel HIV-1 fusion inhibitors that may overcome the current limitations of enfuvirtide, the first such therapeutic in this class. The three prototypes generated by the Dock-and-Lock (DNL) technology to comprise four copies of enfuvirtide tethered site-specifically to the Fc end of different humanized monoclonal antibodies potently neutralize primary isolates (both R5-tropic and X4-tropic), as well as T-cell-adapted strains of HIV-1 in vitro. All three prototypes show EC(50) values in the subnanomolar range, which are 10- to 100-fold lower than enfuvirtide and attainable whether or not the constitutive antibody targets HIV-1. The potential of such conjugates to purge latently infected cells was also demonstrated in a cell-to-cell viral inhibition assay by measuring their efficacy to inhibit the spread of HIV-1(LAI) from infected human peripheral blood mononuclear cells to Jurkat T cells over a period of 30 days following viral activation with 100 nM SAHA (suberoylanilide hydroxamic acid). The IgG-like half-life was not significantly different from that of the parental antibody, as shown by the mean serum concentration of one prototype in mice at 72 h. These encouraging results provide a rationale to develop further novel anti-HIV agents by coupling additional antibodies of interest with alternative HIV-inhibitors via recombinantly-produced, self-assembling, modules.     

The role of edges in the selection of a jump target in Mantis religiosa

Before jumping to a landing object, praying mantids determine the distance, using information obtained from retinal image motion resulting from horizontal peering movements. The present study investigates the peering-jump behaviour of Mantis religiosa larvae with regard to jump targets differing in shape and size. The experimental animals were presented with square, triangular and round target objects with visual extensions of 20 degrees and 40 degrees. The cardboard objects, presented against a uniform white background, were solid black or shaded with a gradation from white to black. It was found that larger objects were preferred to smaller ones as jump targets, and that the square and triangle were preferred to the round disk. When two objects were presented, no preference was exhibited between square and triangular objects. However, when three objects were presented, the square was preferred. For targets with a visual angle of 40 degrees, the amplitude and velocity of the horizontal peering movements were greater for the round disk than for the square or triangle. This amplification of the peering movements suggests that weaker motion signals are generated in the case of curved edges. This may help to account for the preference for the square and triangle as jump targets.     

Molecular Cloning and Expression of Starfish Protein Kinase C Isoforms

To investigate the roles of protein kinase C (PKC) isoforms in Echinoderms, we cloned starfish cDNAs for novel, atypical, and conventional PKCs. They showed highest homology with PKCδ, ι, and α isoforms respectively. It was predicted from the whole genome sequence and by RT-PCR that sea urchin has only one isoform of each PKC subgroups. It is thus likely that these isoforms are the prototypes or ancestors of the PKC subgroups. The phylogenetic tree suggests that atypical PKC was first formed by evolution from the common prototype of AGC protein kinase family, and novel and conventional PKCs next. RT-PCR analysis indicated that novel and atypical PKC mRNAs are expressed ubiquitously in all tissues of adult starfish, whereas conventional PKC mRNA is expressed mainly in the ovary and oocytes, and only slightly in the tube foot and stomach. Upon heterologous expression, only atypical PKC was expressed in the functional form in insect cells.     

Long-term Retention of Many Visual Patterns by Pigeons

Using a simultaneous discrimination procedure it was shown that pigeons were capable of learning to discriminate 100 different black and white visual patterns from a further 625 similar stimuli, where responses to the former were rewarded and responses to the latter were not rewarded. Tests in which novel stimuli replaced either the rewarded or nonrewarded stimuli showed that the pigeons had not only learned about the 100 positive stimuli but also about the 625 negative stimuli. The fact that novel stimuli enhanced discrimination performance when they replaced the many negative stimuli indicated that the pigeons had categorized the stimuli into two classes, familiar and less familiar. Long-term retention was examined after a 6-month interval. To begin with it seemed poor but a recognition test performed after the subjects had been retrained with a subset of the stimuli after an interval of 7 months confirmed that pigeons are capable of retaining in memory several 100 visual items over an extended period. It is proposed that the initial retrieval weakness was due to a forgetting of the contingencies between stimulus categories and response outcomes. Further tests involving variously modified stimuli indicated that while stimulus size variations had a negative effect on performance, orientation changes did not interfere with recognition, supporting the view that small visual stimuli are memorized by pigeons largely free of orientation labels. The experiment generally confirms that pigeons have the capacity of storing information about a large number of visual stimuli over long periods of time.     

Assessing a novel approach for predicting local 3D protein structures from sequence

We developed a novel approach for predicting local protein structure from sequence. It relies on the Hybrid Protein Model (HPM), an unsupervised clustering method we previously developed. This model learns three-dimensional protein fragments encoded into a structural alphabet of 16 protein blocks (PBs). Here, we focused on 11-residue fragments encoded as a series of seven PBs and used HPM to cluster them according to their local similarities. We thus built a library of 120 overlapping prototypes (mean fragments from each cluster), with good three-dimensional local approximation, i.e., a mean accuracy of 1.61 A Calpha root-mean-square distance. Our prediction method is intended to optimize the exploitation of the sequence-structure relations deduced from this library of long protein fragments. This was achieved by setting up a system of 120 experts, each defined by logistic regression to optimize the discrimination from sequence of a given prototype relative to the others. For a target sequence window, the experts computed probabilities of sequence-structure compatibility for the prototypes and ranked them, proposing the top scorers as structural candidates. Predictions were defined as successful when a prototype <2.5 A from the true local structure was found among those proposed. Our strategy yielded a prediction rate of 51.2% for an average of 4.2 candidates per sequence window. We also proposed a confidence index to estimate prediction quality. Our approach predicts from sequence alone and will thus provide valuable information for proteins without structural homologs. Candidates will also contribute to global structure prediction by fragment assembly.     

基于原型思维的城市边缘区景观格局演变研究——以北京市大兴区为例

城市边缘区是城市扩张过程中空间结构变化最大、土地利用转变最快的区域。以北京市大兴区为例,从原型思维出发,以2000、2010、2020年遥感影像解译数据、自然和社会经济等数据为基础,充分考虑地物地情及政策背景等因素,借助ArcGIS 10.5、Fragstats 4.2、SPSS等工具,对不同规划尺度和历时性维度下的景观格局指数进行分析、对比和验证,通过总体分析,场地切片和原型筛选三个步骤,筛选出大兴区6个空间原型组成框架,审视不同发展导向下的空间原型发展变化,探讨近20年间大兴区城市景观格局演变规律。旨在提出一种原型理论指导下的研究思路,尝试为城市转型、用地结构优化、区域规划等工作提供新的视角和一定的借鉴意义。     

Identification of images as a series of gradual transformations of geometrical figures

In the course of psychophysiological experiments with a tachistiscopic presentation of geometrical figures as transformations from a square into a triangle, the subjects worked out a distance scale for optical mouse movement depending on the degree of similarity between the presented figure and a square. This curve appears as a gradual decrease in the distance during the figure’s transformation from a square into a triangle. Significant variation in the shape of the curve was revealed upon exclusion of one of the images of the alphabet. The results are discussed in the context of the lateral inhibition phenomena and compared with the data of the theory of identification.     

Feasibility Study of the Elaboration of a Biodegradable and Bioactive Ligament Made of Poly(ε-caprolactone)-pNaSS Grafted Fibers for the Reconstruction of Anterior Cruciate Ligament: In Vivo Experiment

Background

The anterior cruciate ligament rupture is a common injury which mainly affects young and active population. Faced to this problem, the development of synthetic structures for ligament reconstruction is increasing. The most recent researches focused on the development of biodegradable structures that could be functionalized to enhance host integration. This work describes the elaboration of different poly(ε-caprolactone) prototypes for the rat anterior cruciate ligament replacement in order to found the best design for further in vivo assays.

12种鹅绒藤属（萝藦科）植物花粉器形态学研究

用光学显微镜对萝藦科（Asclepiadaceae）鹅绒藤属（Cynanchum）12种植物花粉器形态进行了观察。结果表明：花粉块的形态有3种类型：球形、长球形和超长球形。着粉腺的形态有6种类型：长圆形、方形、近方形、三角形、正三角形和近三角形。花粉器形态学结果对青羊参（Cynanchum otophyllum）在鹅绒藤属中的分类具有较大意义;支持《中国植物志》第63卷中对催吐白前组（Sect. Vincetoxicum）的分组处理;结合鹅绒藤属花粉块下垂,娃儿藤属（Tylophora）花粉块平展的特点,支持将娃儿藤属作为一个独特类群的观点。     

Evidence that pigeons orient to geomagnetic intensity during homing

The influence of the Earth's magnetic field on locomotory orientation has been studied in many taxa but is best understood for homing pigeons (Columba livia). Effects of experimentally induced and naturally occurring perturbations in the geomagnetic field suggest that pigeons are sensitive to changes in geomagnetic parameters. However, whether pigeons use the Earth's magnetic field for position determination remains unknown. Here we report an apparent orientation to the intensity gradient of the geomagnetic field observed in pigeons homing from sites in and around a magnetic anomaly. From flight trajectories recorded by GPS-based tracking devices, we noted that many pigeons released at unfamiliar sites initially flew, in some cases up to several kilometres, in directions parallel and/or perpendicular to the bearing of the local intensity field. This behaviour occurred irrespective of the homeward direction and significantly more often than what was expected by random chance. Our study describes a novel behaviour which provides strong evidence that pigeons when homing detect and respond to spatial variation in the Earth's magnetic field--information of potential use for navigation.