Browsing by Subject "Procedures"

Now showing 1 - 18 of 18

Open Access
Accelerated phase-cycled SSFP imaging with compressed sensing
(Institute of Electrical and Electronics Engineers Inc., 2015) Çukur, T.
Balanced steady-state free precession (SSFP) imaging suffers from irrecoverable signal losses, known as banding artifacts, in regions of large B0 field inhomogeneity. A common solution is to acquire multiple phase-cycled images each with a different frequency sensitivity, such that the location of banding artifacts are shifted in space. These images are then combined to alleviate signal loss across the entire field-of-view. Although high levels of artifact suppression are viable using a large number of images, this is a time costly process that limits clinical utility. Here, we propose to accelerate individual acquisitions such that the overall scan time is equal to that of a single SSFP acquisition. Aliasing artifacts and noise are minimized by using a variable-density random sampling pattern in k-space, and by generating disjoint sampling patterns for separate acquisitions. A sparsity-enforcing method is then used for image reconstruction. Demonstrations on realistic brain phantom images, and in vivo brain and knee images are provided. In all cases, the proposed technique enables robust SSFP imaging in the presence of field inhomogeneities without prolonging scan times. © 2014 IEEE.
Open Access
Atomic force microscopy for the investigation of molecular and cellular behavior
(Elsevier, 2016-10) Ozkan A.D.; Topal, A. E.; Dana, A.; Güler, Mustafa O.; Tekinay, A. B.
The present review details the methods used for the measurement of cells and their exudates using atomic force microscopy (AFM) and outlines the general conclusions drawn by the mechanical characterization of biological materials through this method. AFM is a material characterization technique that can be operated in liquid conditions, allowing its use for the investigation of the mechanical properties of biological materials in their native environments. AFM has been used for the mechanical investigation of proteins, nucleic acids, biofilms, secretions, membrane bilayers, tissues and bacterial or eukaryotic cells; however, comparison between studies is difficult due to variances between tip sizes and morphologies, sample fixation and immobilization strategies, conditions of measurement and the mechanical parameters used for the quantification of biomaterial response. Although standard protocols for the AFM investigation of biological materials are limited and minor differences in measurement conditions may create large discrepancies, the method is nonetheless highly effective for comparatively evaluating the mechanical integrity of biomaterials and can be used for the real-time acquisition of elasticity data following the introduction of a chemical or mechanical stimulus. While it is currently of limited diagnostic value, the technique is also useful for basic research in cancer biology and the characterization of disease progression and wound healing processes.
Open Access
BRAPH: A graph theory software for the analysis of brain connectivity
(Public Library of Science, 2017) Mijalkov, M.; Kakaei, E.; Pereira, J. B.; Westman, E.; Volpe, G.
The brain is a large-scale complex network whose workings rely on the interaction between its various regions. In the past few years, the organization of the human brain network has been studied extensively using concepts from graph theory, where the brain is represented as a set of nodes connected by edges. This representation of the brain as a connectome can be used to assess important measures that reflect its topological architecture. We have developed a freeware MatLab-based software (BRAPH–BRain Analysis using graPH theory) for connectivity analysis of brain networks derived from structural magnetic resonance imaging (MRI), functional MRI (fMRI), positron emission tomography (PET) and electroencephalogram (EEG) data. BRAPH allows building connectivity matrices, calculating global and local network measures, performing non-parametric permutations for group comparisons, assessing the modules in the network, and comparing the results to random networks. By contrast to other toolboxes, it allows performing longitudinal comparisons of the same patients across different points in time. Furthermore, even though a user-friendly interface is provided, the architecture of the program is modular (object-oriented) so that it can be easily expanded and customized. To demonstrate the abilities of BRAPH, we performed structural and functional graph theory analyses in two separate studies. In the first study, using MRI data, we assessed the differences in global and nodal network topology in healthy controls, patients with amnestic mild cognitive impairment, and patients with Alzheimer’s disease. In the second study, using resting-state fMRI data, we compared healthy controls and Parkinson’s patients with mild cognitive impairment. © 2017 Mijalkov et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Open Access
Data mining experiments on the Angiotensin II-Antagonist in Paroxysmal Atrial Fibrillation (ANTIPAF-AFNET 2) trial: ‘exposing the invisible’
(Oxford University Press, 2016) Okutucu, S.; Katircioglu-Öztürk, D.; Oto, E.; Güvenir, H. A.; Karaagaoglu, E.; Oto, A.; Meinertz, T.; Goette, A.
Aims: The aims of this study include (i) pursuing data-mining experiments on the Angiotensin II-Antagonist in Paroxysmal Atrial Fibrillation (ANTIPAF-AFNET 2) trial dataset containing atrial fibrillation (AF) burden scores of patients with many clinical parameters and (ii) revealing possible correlations between the estimated risk factors of AF and other clinical findings or measurements provided in the dataset. Methods: Ranking Instances by Maximizing the Area under a Receiver Operating Characteristics (ROC) Curve (RIMARC) is used to determine the predictive weights (Pw) of baseline variables on the primary endpoint. Chi-square automatic interaction detector algorithm is performed for comparing the results of RIMARC. The primary endpoint of the ANTIPAF-AFNET 2 trial was the percentage of days with documented episodes of paroxysmal AF or with suspected persistent AF. Results: By means of the RIMARC analysis algorithm, baseline SF-12 mental component score (Pw = 0.3597), age (Pw = 0.2865), blood urea nitrogen (BUN) (Pw = 0.2719), systolic blood pressure (Pw = 0.2240), and creatinine level (Pw = 0.1570) of the patients were found to be predictors of AF burden. Atrial fibrillation burden increases as baseline SF-12 mental component score gets lower; systolic blood pressure, BUN and creatinine levels become higher; and the patient gets older. The AF burden increased significantly at age >76. Conclusions: With the ANTIPAF-AFNET 2 dataset, the present data-mining analyses suggest that a baseline SF-12 mental component score, age, systolic blood pressure, BUN, and creatinine level of the patients are predictors of AF burden. Additional studies are necessary to understand the distinct kidney-specific pathophysiological pathways that contribute to AF burden. Published on behalf of the European Society of Cardiology.
Open Access
Differences in illumination estimation in #thedress
(Association for Research in Vision and Ophthalmology Inc., 2017) Toscani, M.; Gegenfurtner, K. R.; Doerschner, K.
We investigated whether people who report different colors for #thedress do so because they have different assumptions about the illumination in #thedress scene. We introduced a spherical illumination probe (Koenderink, Pont, van Doorn, Kappers, & Todd, 2007) into the original photograph, placed in fore-, or background of the scene and-for each location-let observers manipulate the probe's chromaticity, intensity and the direction of the illumination. Their task was to adjust the probe such that it would appear as a white sphere in the scene. When the probe was located in the foreground, observers who reported the dress to be white (white perceivers) tended to produce bluer adjustments than observers who reported it as blue (blue perceivers). Blue perceivers tended to perceive the illumination as less chromatic. There were no differences in chromaticity settings between perceiver types for the probe placed in the background. Perceiver types also did not differ in their illumination intensity and direction estimates across probe locations. These results provide direct support for the idea that the ambiguity in the perceived color of the dress can be explained by the different assumptions that people have about the illumination chromaticity in the foreground of the scene. In a second experiment we explore the possibility that blue perceivers might overall be less sensitive to contextual cues, and measure white and blue perceivers' dress color matches and labels for manipulated versions of the original photo. Results indeed confirm that contextual cues predominantly affect white perceivers.
Open Access
Drug delivery system based on cyclodextrin-naproxen inclusion complex incorporated in electrospun polycaprolactone nanofibers
(Elsevier, 2014) Canbolat, M. F.; Celebioglu A.; Uyar, Tamer
In this study, we select naproxen (NAP) as a reference drug and electrospun poly (e-caprolactone) (PCL) nanofibers as a fibrous matrix for our drug-delivery system. NAP was complexed with beta-cyclodextrin (βCD) to form inclusion complex (NAP-βCD-IC) and then NAP-βCD-IC was incorporated into PCL nanofibers via electrospinning. The incorporation of NAP without CD-IC into electrospun PCL was also carried out for a comparative study. Our aim is to analyze the release profiles of NAP from PCL/NAP and PCL/NAP-βCD-IC nanofibers and we investigate the effect of CD-IC on the release behavior of NAP from the nanofibrous PCL matrix. The characterization of NAP-βCD-IC and the presence of CD-IC in PCL/NAP-βCD-IC nanofibers were studied by FTIR, XRD, TGA, NMR and SEM. The SEM imaging of the electrospun PCL/NAP and PCL/NAP-βCD-IC nanofibers reveal that the average fiber diameter of these nanofibers is around 300. nm, in addition, the aggregates of CD-IC in PCL/NAP-βCD-IC nanofibers is observed. The release study of NAP in buffer solution elucidate that the PCL/NAP-βCD-IC nanofibers have higher release amount of NAP than the PCL/NAP nanofibers due to the solubility enhancement of NAP by CD-IC.
Open Access
Dynamic tuning of plasmon resonance in the visible using graphene
(The Optical Society, 2016) Balci, S.; Balci, O.; Kakenov, N.; Atar, F. B.; Kocabas, C.
We report active electrical tuning of plasmon resonance of silver nanoprisms (Ag NPs) in the visible spectrum. Ag NPs are placed in close proximity to graphene which leads to additional tunable loss for the plasmon resonance. The ionic gating of graphene modifies its Fermi level from 0.2 to 1 eV, which then affects the absorption of graphene due to Pauli blocking. Plasmon resonance frequency and linewidth of Ag NPs can be reversibly shifted by 20 and 35 meV, respectively. The coupled graphene-Ag NPs system can be classically described by a damped harmonic oscillator model. Atomic layer deposition allows for controlling the graphene-Ag NP separation with atomic-level precision to optimize coupling between them.
Open Access
Glycosaminoglycan-Mimetic Signals Direct the Osteo/Chondrogenic Differentiation of Mesenchymal Stem Cells in a Three-Dimensional Peptide Nanofiber Extracellular Matrix Mimetic Environment
(American Chemical Society, 2016-02) Arslan, E.; Güler, Mustafa O.; Tekinay, A. B.
Recent efforts in bioactive scaffold development focus strongly on the elucidation of complex cellular responses through the use of synthetic systems. Designing synthetic extracellular matrix (ECM) materials must be based on understanding of cellular behaviors upon interaction with natural and artificial scaffolds. Hence, due to their ability to mimic both the biochemical and mechanical properties of the native tissue environment, supramolecular assemblies of bioactive peptide nanostructures are especially promising for development of bioactive ECM-mimetic scaffolds. In this study, we used glycosaminoglycan (GAG) mimetic peptide nanofiber gel as a three-dimensional (3D) platform to investigate how cell lineage commitment is altered by external factors. We observed that amount of fetal bovine serum (FBS) presented in the cell media had synergistic effects on the ability of GAG-mimetic nanofiber gel to mediate the differentiation of mesenchymal stem cells into osteogenic and chondrogenic lineages. In particular, lower FBS concentration in the culture medium was observed to enhance osteogenic differentiation while higher amount FBS promotes chondrogenic differentiation in tandem with the effects of the GAG-mimetic 3D peptide nanofiber network, even in the absence of externally administered growth factors. We therefore demonstrate that mesenchymal stem cell differentiation can be specifically controlled by the combined influence of growth medium components and a 3D peptide nanofiber environment.
Open Access
Inter-varietal structural variation in grapevine genomes
(Wiley-Blackwell Publishing Ltd., 2016) Cardone, M. F.; D'Addabbo, P.; Alkan C.; Bergamini, C.; Catacchio, C. R.; Anaclerio, F.; Chiatante, G.; Marra, A.; Giannuzzi, G.; Perniola, R.; Ventura M.; Antonacci, D.
Grapevine (Vitis vinifera L.) is one of the world's most important crop plants, which is of large economic value for fruit and wine production. There is much interest in identifying genomic variations and their functional effects on inter-varietal, phenotypic differences. Using an approach developed for the analysis of human and mammalian genomes, which combines high-throughput sequencing, array comparative genomic hybridization, fluorescent inï¿½situ hybridization and quantitative PCR, we created an inter-varietal atlas of structural variations and single nucleotide variants (SNVs) for the grapevine genome analyzing four economically and genetically relevant table grapevine varieties. We found 4.8 million SNVs and detected 8% of the grapevine genome to be affected by genomic variations. We identified more than 700 copy number variation (CNV) regions and more than 2000 genes subjected to CNV as potential candidates for phenotypic differences between varieties
Open Access
Ischemic stroke phenotype in patients with nonsustained atrial fibrillation
(Lippincott Williams and Wilkins, 2015) Arsava, E. M.; Bas, D. F.; Atalar, Ergin; Has, A. C.; Oguz, K. K.; Topcuoglu, M. A.
Background and Purpose: The widespread use of ambulatory cardiac monitoring has not only increased the detection of high-risk arrhythmias like persistent and paroxysmal atrial fibrillation (AF), but also made it possible to identify other aberrations such as short-lasting (<30 seconds) irregular runs of supraventricular tachycardia. Ischemic stroke phenotype might be helpful in understanding whether these nonsustained episodes play a similar role in stroke pathophysiology like their persistent and paroxysmal counterparts. Methods: In a consecutive series of patients with ischemic stroke, we retrospectively determined clinical and imaging features associated with nonsustained AF (n=126), defined as <30-second-lasting supraventricular tachyarrhythmias with irregular RR interval on 24-hour Holter monitoring, and compared them to patients with persistent/paroxysmal AF (n=239) and no AF (n=246). Results: Patients with persistent/paroxysmal AF significantly differed from patients with nonsustained AF by a higher prevalence of female sex (odds ratio [95% confidence interval], 1.8 [1.1-2.9]), coronary artery disease (1.9 [1.1-3.0]), and embolic imaging features (2.7 [1.1-6.5]), and lower frequency of smoking (0.4 [0.2-0.8]) and hyperlipidemia (0.5 [0.3-0.8]). In contrast, patients with no AF were younger (0.5 [0.4-0.6] per decade) and more likely to be male (1.7 [1.0-2.8]) in comparison with nonsustained AF population. The prevalence of nonsustained AF was similar among cryptogenic and noncryptogenic stroke patients (32% versus 29%). Voxel-wise comparison of lesion probability maps revealed no significant difference between cryptogenic stroke patients with and without nonsustained AF. Conclusions: Clinical features of patients with nonsustained AF exhibited an intermediary phenotype in between patients with persistent/paroxysmal AF and no AF. Furthermore, imaging features did not entirely resemble patterns observed in patients with longer durations of AF.
Open Access
Iterative H-minima-based marker-controlled watershed for cell nucleus segmentation
(John Wiley & Sons, Inc., 2016) Koyuncu, Can Fahrettin; Akhan, Ece; Ersahin, T.; Cetin Atalay, R.; Gunduz Demir, Çiğdem
Automated microscopy imaging systems facilitate high-throughput screening in molecular cellular biology research. The first step of these systems is cell nucleus segmentation, which has a great impact on the success of the overall system. The marker-controlled watershed is a technique commonly used by the previous studies for nucleus segmentation. These studies define their markers finding regional minima on the intensity/gradient and/or distance transform maps. They typically use the h-minima transform beforehand to suppress noise on these maps. The selection of the h value is critical; unnecessarily small values do not sufficiently suppress the noise, resulting in false and oversegmented markers, and unnecessarily large ones suppress too many pixels, causing missing and undersegmented markers. Because cell nuclei show different characteristics within an image, the same h value may not work to define correct markers for all the nuclei. To address this issue, in this work, we propose a new watershed algorithm that iteratively identifies its markers, considering a set of different h values. In each iteration, the proposed algorithm defines a set of candidates using a particular h value and selects the markers from those candidates provided that they fulfill the size requirement. Working with widefield fluorescence microscopy images, our experiments reveal that the use of multiple h values in our iterative algorithm leads to better segmentation results, compared to its counterparts.
Open Access
MaterialVis: material visualization tool using direct volume and surface rendering techniques
(Elsevier Inc., 2014) Okuyan, E.; Güdükbay, Uğur; Bulutay, C.; Heinig, Karl-Heinz
Visualization of the materials is an indispensable part of their structural analysis. We developed a visualization tool for amorphous as well as crystalline structures, called MaterialVis. Unlike the existing tools, MaterialVis represents material structures as a volume and a surface manifold, in addition to plain atomic coordinates. Both amorphous and crystalline structures exhibit topological features as well as various defects. MaterialVis provides a wide range of functionality to visualize such topological structures and crystal defects interactively. Direct volume rendering techniques are used to visualize the volumetric features of materials, such as crystal defects, which are responsible for the distinct fingerprints of a specific sample. In addition, the tool provides surface visualization to extract hidden topological features within the material. Together with the rich set of parameters and options to control the visualization, MaterialVis allows users to visualize various aspects of materials very efficiently as generated by modern analytical techniques such as the Atom Probe Tomography.
Open Access
Patrolling monocytes control tumor metastasis to the lung
(American Association for the Advancement of Science, 2015) Hanna, R. N.; Cekic, C.; Sag, D.; Tacke, R.; Thomas, G. D.; Nowyhed, H.; Herrley, E.; Rasquinha, N.; McArdle, S.; Wu, R.; Peluso, E.; Metzger, D.; Ichinose, H.; Shaked, I.; Chodaczek, G.; Biswas, S. K.; Hedrick, C. C.
The immune system plays an important role in regulating tumor growth and metastasis. Classical monocytes promote tumorigenesis and cancer metastasis, but how nonclassical "patrolling" monocytes (PMo) interact with tumors is unknown. Here we show that PMo are enriched in the microvasculature of the lung and reduce tumor metastasis to lung in multiple mouse metastatic tumor models. Nr4a1-deficient mice, which specifically lack PMo, showed increased lung metastasis in vivo. Transfer of Nr4a1-proficient PMo into Nr4a1-deficient mice prevented tumor invasion in the lung. PMo established early interactions with metastasizing tumor cells, scavenged tumor material from the lung vasculature, and promoted natural killer cell recruitment and activation. Thus, PMo contribute to cancer immunosurveillance and may be targets for cancer immunotherapy.
Open Access
A privacy-preserving solution for compressed storage and selective retrieval of genomic data
(Cold Spring Harbor Laboratory Press, 2016) Huang Z.; Ayday, E.; Lin, H.; Aiyar, R. S.; Molyneaux, A.; Xu, Z.; Fellay, J.; Steinmetz, L. M.; Hubaux, Jean-Pierre
In clinical genomics, the continuous evolution of bioinformatic algorithms and sequencing platforms makes it beneficial to store patients' complete aligned genomic data in addition to variant calls relative to a reference sequence. Due to the large size of human genome sequence data files (varying from 30 GB to 200 GB depending on coverage), two major challenges facing genomics laboratories are the costs of storage and the efficiency of the initial data processing. In addition, privacy of genomic data is becoming an increasingly serious concern, yet no standard data storage solutions exist that enable compression, encryption, and selective retrieval. Here we present a privacy-preserving solution named SECRAM (Selective retrieval on Encrypted and Compressed Reference-oriented Alignment Map) for the secure storage of compressed aligned genomic data. Our solution enables selective retrieval of encrypted data and improves the efficiency of downstream analysis (e.g., variant calling). Compared withBAM, thede factostandard for storing aligned genomic data, SECRAM uses 18%less storage. Compared with CRAM, one of the most compressed nonencrypted formats (using 34% less storage than BAM), SECRAM maintains efficient compression and downstream data processing, while allowing for unprecedented levels of security in genomic data storage. Compared with previous work, the distinguishing features of SECRAM are that (1) it is position-based insteadofread-based,and(2)itallowsrandomqueryingofasubregionfromaBAM-likefileinanencryptedform.Ourmethod thus offers a space-saving, privacy-preserving, and effective solution for the storage of clinical genomic data.
Open Access
Progesterone change in the late follicular phase affects pregnancy rates both agonist and antagonist protocols in normoresponders: a case-controlled study in ICSI cycles
(Taylor & Francis, 2016) Demir, B.; Kahyaoglu, I.; Guvenir, A.; Yerebasmaz, N.; Altinbas, S.; Dilbaz, B.; Dilbaz, S.; Mollamahmutoglu, L.
Objective: The aim of the presented study is to investigate the impact of progesterone change in the late follicular phase on the pregnancy rates of both agonist and antagonist protocols in normoresponders.Study design: A total of 201 normoresponder patients, who underwent embryo transfer were consecutively selected. 118 patients were stimulated using a long luteal GnRH agonist protocol and 83 using a flexible antagonist protocol. The level of change in late follicular phase progesterone was calculated according to the progesterone levels on the hCG day and pre-hCG day (1 or 2 days prior to hCG day) measurement.Results: Clinical pregnancy rates were comparable between long luteal and antagonist group (35.6 and 41%, respectively). The incidence of progesterone elevation on the hCG day was 11% in long luteal and 18% in antagonist group (p = 0.16). In pregnant cycles, p levels both on the hCG day and pre-hCG day measurement were significantly higher in antagonist than agonist cycles (p = 0.029, p = 0.038, respectively). The change of p level was statistically significant in non-pregnant cycles both for the agonist (-0.17 ± 0.07; 95% CI: -0.29 to -0.37) and antagonist groups (-0.18 ± 0.07; 95%CI: -0.31 to -0.04).Conclusions: Late follicular phase progesterone levels were stable during the cycles of pregnant patients irrespective of the protocols and were shown to be higher in pregnant patients in antagonist cycles when compared to agonist cycles.
Open Access
Structural brain alterations of Down’s syndrome in early childhood evaluation by DTI and volumetric analyses
(Springer Verlag, 2017) Gunbey, H. P.; Bilgici, M. C.; Aslan, K.; Has, A. C.; Ogur, M. G.; Alhan, A.; Incesu, L.
Objectives: To provide an initial assessment of white matter (WM) integrity with diffusion tensor imaging (DTI) and the accompanying volumetric changes in WM and grey matter (GM) through volumetric analyses of young children with Down’s syndrome (DS). Methods: Ten children with DS and eight healthy control subjects were included in the study. Tract-based spatial statistics (TBSS) were used in the DTI study for whole-brain voxelwise analysis of fractional anisotropy (FA) and mean diffusivity (MD) of WM. Volumetric analyses were performed with an automated segmentation method to obtain regional measurements of cortical volumes. Results: Children with DS showed significantly reduced FA in association tracts of the fronto-temporo-occipital regions as well as the corpus callosum (CC) and anterior limb of the internal capsule (p < 0.05). Volumetric reductions included total cortical GM, cerebellar GM and WM volume, basal ganglia, thalamus, brainstem and CC in DS compared with controls (p < 0.05). Conclusion: These preliminary results suggest that DTI and volumetric analyses may reflect the earliest complementary changes of the neurodevelopmental delay in children with DS and can serve as surrogate biomarkers of the specific elements of WM and GM integrity for cognitive development. Key Points: • DS is the most common genetic cause of intellectual disability. • WM and GM structural alterations represent the neurological features of DS. • DTI may identify the earliest aging process changes. • DTI-volumetric analyses can serve as surrogate biomarkers of neurodevelopment in DS. © 2016, European Society of Radiology.
Open Access
Synthetic biogenesis of bacterial amyloid nanomaterials with tunable inorganic-organic interfaces and electrical conductivity
(American Chemical Society, 2017) Seker U.O.S.; Chen, A. Y.; Citorik, R. J.; Lu, T. K.
Amyloids are highly ordered, hierarchal protein nanoassemblies. Functional amyloids in bacterial biofilms, such as Escherichia coli curli fibers, are formed by the polymerization of monomeric proteins secreted into the extracellular space. Curli is synthesized by living cells, is primarily composed of the major curlin subunit CsgA, and forms biological nanofibers with high aspect ratios. Here, we explore the application of curli fibers for nanotechnology by engineering curli to mediate tunable biological interfaces with inorganic materials and to controllably form gold nanoparticles and gold nanowires. Specifically, we used cell-synthesized curli fibers as templates for nucleating and growing gold nanoparticles and showed that nanoparticle size could be modulated as a function of curli fiber gold-binding affinity. Furthermore, we demonstrated that gold nanoparticles can be preseeded onto curli fibers and followed by gold enhancement to form nanowires. Using these two approaches, we created artificial cellular systems that integrate inorganic-organic materials to achieve tunable electrical conductivity. We envision that cell-synthesized amyloid nanofibers will be useful for interfacing abiotic and biotic systems to create living functional materials.
Open Access
Two-tier tissue decomposition for histopathological image representation and classification
(Institute of Electrical and Electronics Engineers, 2015) Gultekin, T.; Koyuncu, C. F.; Sokmensuer, C.; Gunduz Demir, C.
In digital pathology, devising effective image representations is crucial to design robust automated diagnosis systems. To this end, many studies have proposed to develop object-based representations, instead of directly using image pixels, since a histopathological image may contain a considerable amount of noise typically at the pixel-level. These previous studies mostly employ color information to define their objects, which approximately represent histological tissue components in an image, and then use the spatial distribution of these objects for image representation and classification. Thus, object definition has a direct effect on the way of representing the image, which in turn affects classification accuracies. In this paper, our aim is to design a classification system for histopathological images. Towards this end, we present a new model for effective representation of these images that will be used by the classification system. The contributions of this model are twofold. First, it introduces a new two-tier tissue decomposition method for defining a set of multityped objects in an image. Different than the previous studies, these objects are defined combining texture, shape, and size information and they may correspond to individual histological tissue components as well as local tissue subregions of different characteristics. As its second contribution, it defines a new metric, which we call dominant blob scale, to characterize the shape and size of an object with a single scalar value. Our experiments on colon tissue images reveal that this new object definition and characterization provides distinguishing representation of normal and cancerous histopathological images, which is effective to obtain more accurate classification results compared to its counterparts.