Experience-driven formation of parts-based representations in a model of layered visual memory

Growing neuropsychological and neurophysiological evidence suggests that the visual cortex uses parts-based representations to encode, store and retrieve relevant objects. In such a scheme, objects are represented as a set of spatially distributed local features, or parts, arranged in stereotypical fashion. To encode the local appearance and to represent the relations between the constituent parts, there has to be an appropriate memory structure formed by previous experience with visual objects. Here, we propose a model how a hierarchical memory structure supporting efficient storage and rapid recall of parts-based representations can be established by an experience-driven process of self-organization. The process is based on the collaboration of slow bidirectional synaptic plasticity and homeostatic unit activity regulation, both running at the top of fast activity dynamics with winner-take-all character modulated by an oscillatory rhythm. These neural mechanisms lay down the basis for cooperation and competition between the distributed units and their synaptic connections. Choosing human face recognition as a test task, we show that, under the condition of open-ended, unsupervised incremental learning, the system is able to form memory traces for individual faces in a parts-based fashion. On a lower memory layer the synaptic structure is developed to represent local facial features and their interrelations, while the identities of different persons are captured explicitly on a higher layer. An additional property of the resulting representations is the sparseness of both the activity during the recall and the synaptic patterns comprising the memory traces.Comment: 34 pages, 12 Figures, 1 Table, published in Frontiers in Computational Neuroscience (Special Issue on Complex Systems Science and Brain Dynamics), http://www.frontiersin.org/neuroscience/computationalneuroscience/paper/10.3389/neuro.10/015.2009

Superficial characteristics of titanium after treatment of chorreated surface, passive acid, and decontamination with argon plasma

Background. Titanium is characterized by its biocompatibility, resistance to maximum stress, and fatigue and non-toxicity. The composition, surface structure, and roughness of titanium have a key and direct influence on the osseointegration processes when it is used in the form of dental implants. The objective of the present study is to characterize, at chemical, superficial, and biological levels, the result of the application of the sandblasted with large-grit and acid-etched (SLA) treatment consisting of coarse-grained and double-passivated acid blasting with subsequent decontamination with argon plasma on the surface of titanium implants type IV. (2) Methods. Four Oxtein® dental implants (Zaragoza, Spain) were investigated with the following coding: Code L63713T (titanium grade IV, 3.75 mm in diameter, and 13 mm in length). The surface of the implants was SLA type obtained from coarse-grained, double passivated acid, and decontaminated with argon plasma. The samples were in their sealed packages and were opened in our laboratory. The X-ray photoelectron spectroscopy (XPS) technique was used to characterize the chemical composition of the surface, and the scanning electronic microscope (SEM) technique was used to perform topographic surface evaluation. Cell cultures were also performed on both surfaces. (3) Results. The superficial chemical analysis of the studied samples presented the following components, approximately, expressed in atomic percentage: O: 39%; Ti: 18%; C: 39%; N: 2%; and Si: 1%. In the same way, the topographic analysis values were obtained in the evaluated roughness parameters: Ra: 1.5 μm ± 0.02%; Rq: 1.31 μm ± 0.33; Rz: 8.98 μm ± 0.73; Rp: 5.12 μm ± 0.48; Rv: 3.76 μm ± 0.51; and Rc: 4.92 μm ± 0.24. At a biological level, the expression of osteocalcin was higher (p < 0.05) on the micro-rough surface compared to that machined at 48 and 96 h of culture. (4) Conclusions. The data obtained in our study indicate that the total carbon content, the relative concentration of titanium, and the roughness of the treatment performed on the implants are in agreement with those found in the literature. Further, the roughness of the treatment performed on the implants throws a spongy, three-dimensional surface suitable for bone growth on it. The biological results found are compatible with the clinical use of the surface tested

Improving treatment of glioblastoma: new insights in targeting cancer stem cells effectively

Glioblastoma is the most common primary malignant brain tumour in the adult population. Despite multimodality treatment with surgery, radiotherapy and chemotherapy, outcomes are very poor, with less than 15% of patients alive after two years. Increasing evidence suggests that glioblastoma stem cells (GSCs) are likely to play an important role in the biology of this disease and are involved in treatment resistance and tumour recurrence following standard therapy. My thesis aims to address two main aspects of this research area: 1) optimization of methods to evaluate treatment responses of GSCs and their differentiated counterparts (non-GSCs), with a particular focus on a tissue culture model that resembles more closely the tumoral niche; 2) characterization of cell division and centrosome cycle of GSCs, investigating possible differences between these cells and non-GSCs, that would allow the identification of targets for new therapeutic strategies against glioblastomas. In the first part of my project, I optimized a clonogenic survival assay, to compare sensitivity of GSCs and non-GSCs to various treatments, and I developed the use of a 3-dimentional tissue culture system, that allows analysis of features and radiation responses of these two subpopulations in the presence of specific microenvironmental factors from the tumoral niche. In the second part, I show that GSCs display mitotic spindle abnormalities more frequently than non-GSCs and that they have distinctive features with regards to the centrosome cycle. I also demonstrate that GSCs are more sensitive than non-GSCs to subtle changes in Aurora kinase A activity, which result in a rapid increase in polyploidy and subsequently in senescence, with a consistent reduction in clonogenic survival. Based on these findings, I propose that kinases involved in the centrosome cycle need to be explored as a novel strategy to target GSCs effectively and improve outcomes of glioblastoma patients

A glance at imaging bladder cancer.

Purpose: Early and accurate diagnosis of Bladder cancer (BCa) will contribute extensively to the management of the disease. The purpose of this review was to briefly describe the conventional imaging methods and other novel imaging modalities used for early detection of BCa and outline their pros and cons. Methods: Literature search was performed on Pubmed, PMC, and Google scholar for the period of January 2014 to February 2018 and using such words as bladder cancer, bladder tumor, bladder cancer detection, diagnosis and imaging . Results: A total of 81 published papers were retrieved and are included in the review. For patients with hematuria and suspected of BCa, cystoscopy and CT are most commonly recommended. Ultrasonography, MRI, PET/CT using 18F-FDG or 11C-choline and recently PET/MRI using 18F-FDG also play a prominent role in detection of BCa. Conclusion: For initial diagnosis of BCa, cystoscopy is generally performed. However, cystoscopy can not accurately detect carcinoma insitu (CIS) and can not distinguish benign masses from malignant lesions. CT is used in two modes, CT and computed tomographic urography (CTU), both for dignosis and staging of BCa. However, they cannot differentiate T1 and T2 BCa. MRI is performed to diagnose invasive BCa and can differentiate muscle invasive bladder carcinoma (MIBC) from non-muscle invasive bladder carcinoma (NMIBC). However, CT and MRI have low sensitivity for nodal staging. For nodal staging PET/CT is preferred. PET/MRI provides better differentiation of normal and pathologic structures as compared with PET/CT. Nonetheless none of the approaches can address all issues related for the management of BCa. Novel imaging methods that target specific biomarkers, image BCa early and accurately, and stage the disease are warranted

Superficial characteristics of titanium after treatment of chorreated surface, passive acid, and decontamination with argon plasma

Background. Titanium is characterized by its biocompatibility, resistance to maximum stress, and fatigue and non-toxicity. The composition, surface structure, and roughness of titanium have a key and direct influence on the osseointegration processes when it is used in the form of dental implants. The objective of the present study is to characterize, at chemical, superficial, and biological levels, the result of the application of the sandblasted with large-grit and acid-etched (SLA) treatment consisting of coarse-grained and double-passivated acid blasting with subsequent decontamination with argon plasma on the surface of titanium implants type IV. (2) Methods. Four Oxtein® dental implants (Zaragoza, Spain) were investigated with the following coding: Code L63713T (titanium grade IV, 3.75 mm in diameter, and 13 mm in length). The surface of the implants was SLA type obtained from coarse-grained, double passivated acid, and decontaminated with argon plasma. The samples were in their sealed packages and were opened in our laboratory. The X-ray photoelectron spectroscopy (XPS) technique was used to characterize the chemical composition of the surface, and the scanning electronic microscope (SEM) technique was used to perform topographic surface evaluation. Cell cultures were also performed on both surfaces. (3) Results. The superficial chemical analysis of the studied samples presented the following components, approximately, expressed in atomic percentage: O: 39%; Ti: 18%; C: 39%; N: 2%; and Si: 1%. In the same way, the topographic analysis values were obtained in the evaluated roughness parameters: Ra: 1.5 μm ± 0.02%; Rq: 1.31 μm ± 0.33; Rz: 8.98 μm ± 0.73; Rp: 5.12 μm ± 0.48; Rv: 3.76 μm ± 0.51; and Rc: 4.92 μm ± 0.24. At a biological level, the expression of osteocalcin was higher (p < 0.05) on the micro-rough surface compared to that machined at 48 and 96 h of culture. (4) Conclusions. The data obtained in our study indicate that the total carbon content, the relative concentration of titanium, and the roughness of the treatment performed on the implants are in agreement with those found in the literature. Further, the roughness of the treatment performed on the implants throws a spongy, three-dimensional surface suitable for bone growth on it. The biological results found are compatible with the clinical use of the surface tested

Influence of Titanium Oxide Pillar Array Nanometric Structures and Ultraviolet Irradiation on the Properties of the Surface of Dental Implants: A Pilot Study

Aim: Titanium implants are commonly used as replacement therapy for lost teeth and much current research is focusing on the improvement of the chemical and physical properties of their surfaces in order to improve the osseointegration process. TiO2, when it is deposited in the form of pillar array nanometric structures, has photocatalytic properties and wet surface control, which, together with UV irradiation, provide it with superhydrophilic surfaces, which may be of interest for improving cell adhesion on the peri-implant surface. In this article, we address the influence of this type of surface treatment on type IV and type V titanium discs on their surface energy and cell growth on them. Materials and methods: Samples from titanium rods used for making dental implants were used. There were two types of samples: grade IV and grade V. In turn, within each grade, two types of samples were differentiated: untreated and treated with sand blasting and subjected to double acid etching. Synthesis of the film consisting of titanium oxide pillar array structures was carried out using plasma-enhanced chemical vapor deposition equipment. The plasma was generated in a quartz vessel by an external SLAN-1 microwave source with a frequency of 2.45 GHz. Five specimens from each group were used (40 discs in total). On the surfaces to be studied, the following determinations were carried out: (a) X-ray photoelectron spectroscopy, (b) scanning electron microscopy, (c) energy dispersive X-ray spectroscopy, (d) profilometry, (e) contact angle measurement or surface wettability, (f) progression of contact angle on applying ultraviolet irradiation, and (g) a biocompatibility test and cytotoxicity with cell cultures. Results: The application of ultraviolet light decreased the hydrophobicity of all the surfaces studied, although it did so to a greater extent on the surfaces with the studied modification applied, this being more evident in samples manufactured in grade V titanium. In samples made in grade IV titanium, this difference was less evident, and even in the sample manufactured with grade IV and SLA treatment, the application of the nanometric modification of the surface made the surface optically less active. Regarding cell growth, all the surfaces studied, grouped in relation to the presence or not of the nanometric treatment, showed similar growth. Conclusions. Treatment of titanium oxide surfaces with ultraviolet irradiation made them change temporarily into superhydrophilic ones, which confirms that their biocompatibility could be improved in this way, or at least be maintained

Evaluation of magnetic resonance imaging guidelines for differentiation between thoracolumbar intervertebral disk extrusions and intervertebral disk protrusions in dogs

Four MRI variables have recently been suggested to be independently associated with a diagnosis of thoracolumbar intervertebral disk extrusion or protrusion. Midline intervertebral disk herniation, and partial intervertebral disk degeneration were associated with intervertebral disk protrusion, while presence of a single intervertebral disk herniation and disk material dispersed beyond the boundaries of the intervertebral disk space were associated with intervertebral disk extrusion. The aim of this retrospective, cross‐sectional study was to determine whether using these MRI variables improves differentiation between thoracolumbar intervertebral disk extrusions and protrusions. Eighty large breed dogs with surgically confirmed thoracolumbar intervertebral disk extrusions or protrusions were included. Randomized MRI studies were presented on two occasions to six blinded observers, which were divided into three experience categories. During the first assessment, observers made a presumptive diagnosis of thoracolumbar intervertebral disk extrusion or protrusion without guidelines. During the second assessment they were asked to make a presumptive diagnosis with the aid of guidelines. Agreement was evaluated by Kappa‐statistics. Diagnostic accuracy significantly improved from 70.8 to 79.6% and interobserver agreement for making a diagnosis of intervertebral disk extrusion or intervertebral disk protrusion improved from fair (κ = 0.27) to moderate (κ = 0.41) after using the proposed guidelines. Diagnostic accuracy was significantly influenced by degree of observer experience. Intraobserver agreement for the assessed variables ranged from fair to excellent and interobserver agreement ranged from fair to moderate. The results of this study suggest that the proposed imaging guidelines can aid in differentiating thoracolumbar intervertebral disk extrusions from protrusions

Non-contrast renal magnetic resonance imaging to assess perfusion and corticomedullary differentiation in health and chronic kidney disease

AIMS Arterial spin labelling (ASL) MRI measures perfusion without administration of contrast agent. While ASL has been validated in animals and healthy volunteers (HVs), application to chronic kidney disease (CKD) has been limited. We investigated the utility of ASL MRI in patients with CKD. METHODS We studied renal perfusion in 24 HVs and 17 patients with CKD (age 22-77 years, 40% male) using ASL MRI at 3.0T. Kidney function was determined using estimated glomerular filtration rate (eGFR). T1 relaxation time was measured using modified look-locker inversion and xFB02;ow-sensitive alternating inversion recovery true-fast imaging and steady precession was performed to measure cortical and whole kidney perfusion. RESULTS T1 was higher in CKD within cortex and whole kidney, and there was association between T1 time and eGFR. No association was seen between kidney size and volume and either T1, or ASL perfusion. Perfusion was lower in CKD in cortex (136 ± 37 vs. 279 ± 69 ml/min/100 g; p &#60; 0.001) and whole kidney (146 ± 24 vs. 221 ± 38 ml/min/100 g; p &#60; 0.001). There was significant, negative, association between T1 longitudinal relaxation time and ASL perfusion in both the cortex (r = -0.75, p &#60; 0.001) and whole kidney (r = -0.50, p &#60; 0.001). There was correlation between eGFR and both cortical (r = 0.73, p &#60; 0.01) and whole kidney (r = 0.69, p &#60; 0.01) perfusion. CONCLUSIONS Significant differences in renal structure and function were demonstrated using ASL MRI. T1 may be representative of structural changes associated with CKD; however, further investigation is required into the pathological correlates of reduced ASL perfusion and increased T1 time in CKD

Metabolic Profiling of IDH Mutation and Malignant Progression in Infiltrating Glioma.

Infiltrating low grade gliomas (LGGs) are heterogeneous in their behavior and the strategies used for clinical management are highly variable. A key factor in clinical decision-making is that patients with mutations in the isocitrate dehydrogenase 1 and 2 (IDH1/2) oncogenes are more likely to have a favorable outcome and be sensitive to treatment. Because of their relatively long overall median survival, more aggressive treatments are typically reserved for patients that have undergone malignant progression (MP) to an anaplastic glioma or secondary glioblastoma (GBM). In the current study, ex vivo metabolic profiles of image-guided tissue samples obtained from patients with newly diagnosed and recurrent LGG were investigated using proton high-resolution magic angle spinning spectroscopy (1H HR-MAS). Distinct spectral profiles were observed for lesions with IDH-mutated genotypes, between astrocytoma and oligodendroglioma histologies, as well as for tumors that had undergone MP. Levels of 2-hydroxyglutarate (2HG) were correlated with increased mitotic activity, axonal disruption, vascular neoplasia, and with several brain metabolites including the choline species, glutamate, glutathione, and GABA. The information obtained in this study may be used to develop strategies for in vivo characterization of infiltrative glioma, in order to improve disease stratification and to assist in monitoring response to therapy