Intrinsic dimension of data representations in deep neural networks

Deep neural networks progressively transform their inputs across multiple processing layers. What are the geometrical properties of the representations learned by these networks? Here we study the intrinsic dimensionality (ID) of data-representations, i.e. the minimal number of parameters needed to describe a representation. We find that, in a trained network, the ID is orders of magnitude smaller than the number of units in each layer. Across layers, the ID first increases and then progressively decreases in the final layers. Remarkably, the ID of the last hidden layer predicts classification accuracy on the test set. These results can neither be found by linear dimensionality estimates (e.g., with principal component analysis), nor in representations that had been artificially linearized. They are neither found in untrained networks, nor in networks that are trained on randomized labels. This suggests that neural networks that can generalize are those that transform the data into low-dimensional, but not necessarily flat manifolds

Accuracy of Rats in Discriminating Visual Objects Is Explained by the Complexity of Their Perceptual Strategy

Despite their growing popularity as models of visual functions, it remains unclear whether rodents are capable of deploying advanced shape-processing strategies when engaged in visual object recognition. In rats, for instance, pattern vision has been reported to range from mere detection of overall object luminance to view-invariant processing of discriminative shape features. Here we sought to clarify how refined object vision is in rodents, and how variable the complexity of their visual processing strategy is across individuals. To this aim, we measured how well rats could discriminate a reference object from 11 distractors, which spanned a spectrum of image-level similarity to the reference. We also presented the animals with random variations of the reference, and processed their responses to these stimuli to derive subject-specific models of rat perceptual choices. Our models successfully captured the highly variable discrimination performance observed across subjects and object conditions. In particular, they revealed that the animals that succeeded with the most challenging distractors were those that integrated the wider variety of discriminative features into their perceptual strategies. Critically, these strategies were largely preserved when the rats were required to discriminate outlined and scaled versions of the stimuli, thus showing that rat object vision can be characterized as a transformation-tolerant, feature-based filtering process. Overall, these findings indicate that rats are capable of advanced processing of shape information, and point to the rodents as powerful models for investigating the neuronal underpinnings of visual object recognition and other high-level visual functions

Site directed biotinylation of filamentous phage structural proteins

Filamentous bacteriophages have been used in numerous applications for the display of antibodies and random peptide libraries. Here we describe the introduction of a 13 amino acid sequence LASIFEAQKIEWR (designated BT, which is biotinylated in vivo by E. coli) into the N termini of four of the five structural proteins of the filamentous bacteriophage fd (Proteins 3, 7, 8 and 9). The in vivo and in vitro biotinylation of the various phages were compared. The production of multifunctional phages and their application as affinity reagents are demonstrated

The cognitive neuroscience of prehension: recent developments

Prehension, the capacity to reach and grasp, is the key behavior that allows humans to change their environment. It continues to serve as a remarkable experimental test case for probing the cognitive architecture of goal-oriented action. This review focuses on recent experimental evidence that enhances or modifies how we might conceptualize the neural substrates of prehension. Emphasis is placed on studies that consider how precision grasps are selected and transformed into motor commands. Then, the mechanisms that extract action relevant information from vision and touch are considered. These include consideration of how parallel perceptual networks within parietal cortex, along with the ventral stream, are connected and share information to achieve common motor goals. On-line control of grasping action is discussed within a state estimation framework. The review ends with a consideration about how prehension fits within larger action repertoires that solve more complex goals and the possible cortical architectures needed to organize these actions

Validation of a low-cost virtual reality system for training street-crossing. A comparative study in healthy, neglected and non-neglected stroke individuals

Unilateral spatial neglect is a common consequence of stroke that directly affects the performance of activities of daily living. This impairment is traditionally assessed with paper-and-pencil tests that can lack correspondence to real life and are easily compensated. Virtual reality can immerse patients in more ecological scenarios, thus providing therapists with new tools to assess and train the effects of this impairment in simulated real tasks. This paper presents the clinical validation and convergent validity of a low-cost virtual reality system for training street-crossing in stroke patients with and without neglect. The performance of neglect patients was significantly worse than the performance of non-neglect and healthy participants. In addition, several correlations between the scores in the system and in the traditional scales were detected.This study was funded in part by Ministerio de Educacion y Ciencia Spain, Projects Consolider-C (SEJ2006-14301/PSIC), "CIBER of Physiopathology of Obesity and Nutrition, an initiative of ISCIII" and the Excellence Research Program PROMETEO (Generalitat Valenciana. Conselleria de Educacion, 2008-157).Navarro, MD.; Llorens Rodríguez, R.; Noé, E.; Ferri, J.; Alcañiz Raya, ML. (2013). Validation of a low-cost virtual reality system for training street-crossing. A comparative study in healthy, neglected and non-neglected stroke individuals. Neuropsychological Rehabilitation. 23(4):597-618. https://doi.org/10.1080/09602011.2013.806269S597618234Allegri, R. F. (2000). Atención y negligencia: bases neurológicas, evaluación y trastornos. Revista de Neurología, 30(05), 491. doi:10.33588/rn.3005.99645Appelros, P., Karlsson, G. M., Seiger, Åke, & Nydevik, I. (2002). Neglect and Anosognosia After First-Ever Stroke: Incidence and Relationship to Disability. Journal of Rehabilitation Medicine, 34(5), 215-220. doi:10.1080/165019702760279206Baheux, K., Yoshizawa, M., & Yoshida, Y. (2007). Simulating hemispatial neglect with virtual reality. Journal of NeuroEngineering and Rehabilitation, 4(1). doi:10.1186/1743-0003-4-27Boian, R. F., Burdea, G. C., Deutsch, J. E. and Winter, S. H. Street crossing using a virtual environment mobility simulator.Paper presented at 3rd Annual International Workshop on Virtual Reality. Lausanne, Switzerland.Broeren, J., Samuelsson, H., Stibrant-Sunnerhagen, K., Blomstrand, C., & Rydmark, M. (2007). Neglect assessment as an application of virtual reality. Acta Neurologica Scandinavica, 116(3), 157-163. doi:10.1111/j.1600-0404.2007.00821.xBuxbaum, L. J., Ferraro, M. K., Veramonti, T., Farne, A., Whyte, J., Ladavas, E., … Coslett, H. B. (2004). Hemispatial neglect: Subtypes, neuroanatomy, and disability. Neurology, 62(5), 749-756. doi:10.1212/01.wnl.0000113730.73031.f4Buxbaum, L. J., Palermo, M. A., Mastrogiovanni, D., Read, M. S., Rosenberg-Pitonyak, E., Rizzo, A. A., & Coslett, H. B. (2008). Assessment of spatial attention and neglect with a virtual wheelchair navigation task. Journal of Clinical and Experimental Neuropsychology, 30(6), 650-660. doi:10.1080/13803390701625821Castiello, U., Lusher, D., Burton, C., Glover, S., & Disler, P. (2004). Improving left hemispatial neglect using virtual reality. Neurology, 62(11), 1958-1962. doi:10.1212/01.wnl.0000128183.63917.02Conners, C. K., Epstein, J. N., Angold, A., & Klaric, J. (2003). Journal of Abnormal Child Psychology, 31(5), 555-562. doi:10.1023/a:1025457300409Folstein, M. F., Folstein, S. E., & McHugh, P. R. (1975). «Mini-mental state». Journal of Psychiatric Research, 12(3), 189-198. doi:10.1016/0022-3956(75)90026-6Fordell, H., Bodin, K., Bucht, G., & Malm, J. (2011). A virtual reality test battery for assessment and screening of spatial neglect. Acta Neurologica Scandinavica, 123(3), 167-174. doi:10.1111/j.1600-0404.2010.01390.xGupta, V., Knott, B. A., Kodgi, S., & Lathan, C. E. (2000). Using the «VREye» System for the Assessment of Unilateral Visual Neglect: Two Case Reports. Presence: Teleoperators and Virtual Environments, 9(3), 268-286. doi:10.1162/105474600566790Hartman-Maeir, A., & Katz, N. (1995). Validity of the Behavioral Inattention Test (BIT): Relationships With Functional Tasks. American Journal of Occupational Therapy, 49(6), 507-516. doi:10.5014/ajot.49.6.507Jannink, M. J. A., Aznar, M., de Kort, A. C., van de Vis, W., Veltink, P., & van der Kooij, H. (2009). Assessment of visuospatial neglect in stroke patients using virtual reality: a pilot study. International Journal of Rehabilitation Research, 32(4), 280-286. doi:10.1097/mrr.0b013e3283013b1cJehkonen, M., Laihosalo, M., & Kettunen, J. (2006). Anosognosia after stroke: assessment, occurrence, subtypes and impact on functional outcome reviewed. Acta Neurologica Scandinavica, 114(5), 293-306. doi:10.1111/j.1600-0404.2006.00723.xKatz, N., Ring, H., Naveh, Y., Kizony, R., Feintuch, U., & Weiss, P. L. (2005). Interactive virtual environment training for safe street crossing of right hemisphere stroke patients with Unilateral Spatial Neglect. Disability and Rehabilitation, 27(20), 1235-1244. doi:10.1080/09638280500076079Kim, D. Y., Ku, J., Chang, W. H., Park, T. H., Lim, J. Y., Han, K., … Kim, S. I. (2010). Assessment of post-stroke extrapersonal neglect using a three-dimensional immersive virtual street crossing program. Acta Neurologica Scandinavica, 121(3), 171-177. doi:10.1111/j.1600-0404.2009.01194.xKim, J., Kim, K., Kim, D. Y., Chang, W. H., Park, C.-I., Ohn, S. H., … Kim, S. I. (2007). Virtual Environment Training System for Rehabilitation of Stroke Patients with Unilateral Neglect: Crossing the Virtual Street. CyberPsychology & Behavior, 10(1), 7-15. doi:10.1089/cpb.2006.9998Kim, K., Kim, J., Ku, J., Kim, D. Y., Chang, W. H., Shin, D. I., … Kim, S. I. (2004). A Virtual Reality Assessment and Training System for Unilateral Neglect. CyberPsychology & Behavior, 7(6), 742-749. doi:10.1089/cpb.2004.7.742Kim, Y. M., Chun, M. H., Yun, G. J., Song, Y. J., & Young, H. E. (2011). The Effect of Virtual Reality Training on Unilateral Spatial Neglect in Stroke Patients. Annals of Rehabilitation Medicine, 35(3), 309. doi:10.5535/arm.2011.35.3.309Krakauer, J. W. (2006). Motor learning: its relevance to stroke recovery and neurorehabilitation. Current Opinion in Neurology, 19(1), 84-90. doi:10.1097/01.wco.0000200544.29915.ccMcComas, J., MacKay, M., & Pivik, J. (2002). Effectiveness of Virtual Reality for Teaching Pedestrian Safety. CyberPsychology & Behavior, 5(3), 185-190. doi:10.1089/109493102760147150Myers, R. L., & Bierig, T. A. (2000). Virtual Reality and Left Hemineglect: A Technology for Assessment and Therapy. CyberPsychology & Behavior, 3(3), 465-468. doi:10.1089/10949310050078922Peskine, A., Rosso, C., Box, N., Galland, A., Caron, E., Rautureau, G., … Pradat-Diehl, P. (2010). Virtual reality assessment for visuospatial neglect: importance of a dynamic task. Journal of Neurology, Neurosurgery & Psychiatry, 82(12), 1407-1409. doi:10.1136/jnnp.2010.217513Romero, M., Sánchez, A., Marín, C., Navarro, M. D., Ferri, J., & Noé, E. (2012). Utilidad clínica de la versión en castellano del Mississippi Aphasia Screening Test (MASTsp): validación en pacientes con ictus. Neurología, 27(4), 216-224. doi:10.1016/j.nrl.2011.06.006Rose, F. D., Brooks, B. M., & Rizzo, A. A. (2005). Virtual Reality in Brain Damage Rehabilitation: Review. CyberPsychology & Behavior, 8(3), 241-262. doi:10.1089/cpb.2005.8.241Schwebel, D. C., & McClure, L. A. (2010). Using virtual reality to train children in safe street-crossing skills. Injury Prevention, 16(1), e1-e1. doi:10.1136/ip.2009.025288Simpson, G., Johnston, L., & Richardson, M. (2003). An investigation of road crossing in a virtual environment. Accident Analysis & Prevention, 35(5), 787-796. doi:10.1016/s0001-4575(02)00081-7Smith, J., Hebert, D., & Reid, D. (2007). Exploring the effects of virtual reality on unilateral neglect caused by stroke: Four case studies. Technology and Disability, 19(1), 29-40. doi:10.3233/tad-2007-19104Sugarman, H., Weisel-Eichler, A., Burstin, A. and Brown, R.Use of novel virtual reality system for the assessment and treatment of unilateral spatial neglect: A feasibility study. Paper presented at International Conference on Virtual Rehabilitation. Zürich.Tanaka, T., Sugihara, S., Nara, H., Ino, S., & Ifukube, T. (2005). Journal of NeuroEngineering and Rehabilitation, 2(1), 31. doi:10.1186/1743-0003-2-31Thomson, J. A., Tolmie, A. K., Foot, H. C., Whelan, K. M., Sarvary, P., & Morrison, S. (2005). Influence of Virtual Reality Training on the Roadside Crossing Judgments of Child Pedestrians. Journal of Experimental Psychology: Applied, 11(3), 175-186. doi:10.1037/1076-898x.11.3.175Weiss, P. L. (Tamar), Naveh, Y., & Katz, N. (2003). Design and testing of a virtual environment to train stroke patients with unilateral spatial neglect to cross a street safely. Occupational Therapy International, 10(1), 39-55. doi:10.1002/oti.176Witmer, B. G., & Singer, M. J. (1998). Measuring Presence in Virtual Environments: A Presence Questionnaire. Presence: Teleoperators and Virtual Environments, 7(3), 225-240. doi:10.1162/105474698565686Wu, H., Ashmead, D. H. and Bodenheimer, B.Using immersive virtual reality to evaluate pedestrian street crossing decisions at a roundabout. Paper presented at 6th Symposium on appied perception in Graphics and Visualization. Chania

Searching for DNA - protein Interactions by Lambda Phage Display

We applied phage display technology to DNA-protein interaction studies. A cDNA expression library displayed on the surface of bacteriophage lambda was generated from the highly differentiated MMH E14 murine hepatic cell line. Selection of this library using the promoter sequence of the liver-enriched transcription factor HNF1alpha gene as ligate identified DNA-binding domains specifically interacting with different regions of this regulatory sequence. One of the selected phage showed 100% identity to a DNA-binding domain shared by differentiation specific element-binding protein, vasoactive intestinal peptide receptor-repressor protein and replication factor C and was further investigated. Specific binding of the selected protein domain was confirmed in a phage-independent context. By combining ELISA and South-Western assays using the selected phage and a bacterially expressed glutathione-S-transferase protein fused to the encoded DNA-binding domain, an array of multiple adjacent DNA-binding sites sharing a common consensus motif was identified. The strategy described represents a powerful tool to identify proteins that bind to DNA regulatory elements

Neutrophil proteases can inactivate human PAR3 and abolish the co-receptor function of PAR3 on murine platelets

Three members of the protease-activated receptor family, PAR1, PAR3 and PAR4, are activated when thrombin Cleaves the receptor N-terminus, exposing a tethered ligand. Proteases other than thrombin can also cleave PAR family members and, depending upon whether this exposes or removes the tethered ligand, either activate or disable the receptor. For example, on human platelets PAR1 is disabled by cathepsin G, although aggregation still occurs because cathepsin G can activate PARA The present studies examine the interaction of cathepsin G and a second neutrophil protease, elastase, with PAR3 using two model systems: COS-7 cells transfected with human PAR3 and mouse plate lets, which express PAR3 and PAR4, but not PAR1. In contrast to human platelets, cathepsin G did not aggregate murine platelets, and prevented their activation only at low thrombin concentrations. Elastase had no effect on thrombin responses in mouse platelets, but when added to COS cells expressing human PAR3, both cathepsin G and elastase prevented activation of phospholipase C by thrombin. Notably, this inhibition occurred without loss of the binding sites for two monoclonal antibodies that flank the tethered ligand on human PAR3; We therefore conclude that 1) exposure to cathepsin G disables signaling through human PAR3, and prevents murine PAR3 from serving its normal role, which is to facilitate PAR4 cleavage at low thrombin concentrations, 2) elastase disables human, but not murine, PAR3, 3) in contrast to human PAR4, mouse PAR4 will not support platelet aggregation in response to cathepsin G, and 4) the inactivation of human PAR3 by cathepsin G and elastase involves a mechanism other than amputation of the tethered ligand domain. These results extend the range of possible interactions between PAR family members and proteases, and provide further support for species-specific differences in the interaction of these receptors with proteases other than thrombin