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Sample records for system tissues identified

  1. Improved system for identifying biological tissue temperature using electrical impedance tomography

    Directory of Open Access Journals (Sweden)

    Korolyuk Evgeniy

    2018-01-01

    Full Text Available This paper proposes a cheap and compact medical system that determines the temperature of an object using broadband impedance tomography. This system can be used in medicine to visualize ice structure in tissue during cryosurgical operations, as well as for fault diagnosis and location in studied industrial objects. These effects are achieved by measuring electrical impedance between electrode pairs in the measuring chamber. The assembled prototype is compact, consumes little power, and allows to non-invasively determine the impedance of a target object in real time. The research included experimental studies to determine the dependence of the impedance spectrum of saline water and muscle tissue on temperature in broad band spectrum, which allowed to obtain the dependence of total electrical impedance of target objects on temperature.

  2. Integrative systems analysis of diet-induced obesity identified a critical transition in the transcriptomes of the murine liver and epididymal white adipose tissue.

    Science.gov (United States)

    Kim, J; Kwon, E-Y; Park, S; Kim, J-R; Choi, S-W; Choi, M-S; Kim, S-J

    2016-02-01

    It is well known that high-fat diet (HFD) can cause immune system-related pathological alterations after a significant body weight gain. The mechanisms of the delayed pathological alterations during the development of diet-induced obesity (DIO) are not fully understood. To elucidate the mechanisms underlying DIO development, we analyzed time-course microarray data obtained from a previous study. First, differentially expressed genes (DEGs) were identified at each time point by comparing the hepatic transcriptome of mice fed HFD with that of mice fed normal diet. Next, we clustered the union of DEGs and identified annotations related to each cluster. Finally, we constructed an 'integrated obesity-associated gene regulatory network (GRN) in murine liver'. We analyzed the epididymal white adipose tissue (eWAT) transcriptome usig the same procedure. Based on time-course microarray data, we found that the genes associated with immune responses were upregulated with an oscillating expression pattern between weeks 2 and 8, relatively downregulated between weeks 12 and 16, and eventually upregulated after week 20 in the liver of the mice fed HFD. The genes associated with immune responses were also upregulated at late stage, in the eWAT of the mice fed HFD. These results suggested that a critical transition occurred in the immune system-related transcriptomes of the liver and eWAT around week 16 of the DIO development, and this may be associated with the delayed pathological alterations. The GRN analysis suggested that Maff may be a key transcription factor for the immune system-related critical transition thatoccurred at week 16. We found that transcription factors associated with immune responses were centrally located in the integrated obesity-associated GRN in the liver. In this study, systems analysis identified regulatory network modules underlying the delayed immune system-related pathological changes during the development of DIO and could suggest possible

  3. Pigmented Creatine Deposits in Amyotrophic Lateral Sclerosis Central Nervous System Tissues Identified by Synchrotron Fourier Transform Infrared Microspectroscopy and X-ray Fluorescence Spectromicroscopy

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    Kastyak, M.; Szczerbowska-Boruchowska, M; Adamek, D; Tomik, B; Lankosz, M; Gough, K

    2010-01-01

    Amyotrophic Lateral Sclerosis (ALS) is an untreatable, neurodegenerative disease of motor neurons characterized by progressive muscle atrophy, limb paralysis, dysarthria, dysphagia, dyspnae and finally death. Large motor neurons in ventral horns of spinal cord and motor nuclei in brainstem, large pyramidal neurons of motor cortex and/or large myelinated axons of corticospinal tracts are affected. In recent synchrotron Fourier Transform Infrared microspectroscopy (sFTIR) studies of ALS CNS autopsy tissue, we discovered a small deposit of crystalline creatine, which has a crucial role in energy metabolism. We have now examined unfixed, snap frozen, post-autopsy tissue sections of motor cortex, brain stem, spinal cord, hippocampus and substantia nigra from six ALS and three non-degenerated cases with FTIR and micro-X-ray fluorescence (XRF). Heterogeneous pigmented deposits were discovered in spinal cord, brain stem and motor neuron cortex of two ALS cases. The FTIR signature of creatine has been identified in these deposits and in numerous large, non-pigmented deposits in four of the ALS cases. Comparable pigmentation and creatine deposits were not found in controls or in ALS hippocampus and substantia nigra. Ca, K, Fe, Cu and Zn, as determined by XRF, were not correlated with the pigmented deposits; however, there was a higher incidence of hot spots (Ca, Zn, Fe and Cu) in the ALS cases. The identity of the pigmented deposits remains unknown, although the absence of Fe argues against both erythrocytes and neuromelanin. We conclude that elevated creatine deposits may be indicators of dysfunctional oxidative processes in some ALS cases.

  4. Near Identifiability of Dynamical Systems

    Science.gov (United States)

    Hadaegh, F. Y.; Bekey, G. A.

    1987-01-01

    Concepts regarding approximate mathematical models treated rigorously. Paper presents new results in analysis of structural identifiability, equivalence, and near equivalence between mathematical models and physical processes they represent. Helps establish rigorous mathematical basis for concepts related to structural identifiability and equivalence revealing fundamental requirements, tacit assumptions, and sources of error. "Structural identifiability," as used by workers in this field, loosely translates as meaning ability to specify unique mathematical model and set of model parameters that accurately predict behavior of corresponding physical system.

  5. Distributed Persistent Identifiers System Design

    Directory of Open Access Journals (Sweden)

    Pavel Golodoniuc

    2017-06-01

    Full Text Available The need to identify both digital and physical objects is ubiquitous in our society. Past and present persistent identifier (PID systems, of which there is a great variety in terms of technical and social implementation, have evolved with the advent of the Internet, which has allowed for globally unique and globally resolvable identifiers. PID systems have, by in large, catered for identifier uniqueness, integrity, and persistence, regardless of the identifier’s application domain. Trustworthiness of these systems has been measured by the criteria first defined by Bütikofer (2009 and further elaborated by Golodoniuc 'et al'. (2016 and Car 'et al'. (2017. Since many PID systems have been largely conceived and developed by a single organisation they faced challenges for widespread adoption and, most importantly, the ability to survive change of technology. We believe that a cause of PID systems that were once successful fading away is the centralisation of support infrastructure – both organisational and computing and data storage systems. In this paper, we propose a PID system design that implements the pillars of a trustworthy system – ensuring identifiers’ independence of any particular technology or organisation, implementation of core PID system functions, separation from data delivery, and enabling the system to adapt for future change. We propose decentralisation at all levels — persistent identifiers and information objects registration, resolution, and data delivery — using Distributed Hash Tables and traditional peer-to-peer networks with information replication and caching mechanisms, thus eliminating the need for a central PID data store. This will increase overall system fault tolerance thus ensuring its trustworthiness. We also discuss important aspects of the distributed system’s governance, such as the notion of the authoritative source and data integrity

  6. Soft tissue anchor systems.

    Science.gov (United States)

    Yu, G V; Chang, T; White, J M

    1994-04-01

    The concept of soft tissue attachment and reattachment has been addressed over the years through a variety of surgical techniques. This includes tendons and ligaments that have been detached both surgically and traumatically from their osseous origins or insertions. This study is designed to provide the reader with a comprehensive overview of current commercially available devices. Detailed descriptions of the various devices are provided along with a discussion of the advantages and disadvantages of each. Their application and use in reconstructive foot and ankle surgery are also discussed.

  7. Human tissue in systems medicine.

    Science.gov (United States)

    Caie, Peter D; Schuur, Klaas; Oniscu, Anca; Mullen, Peter; Reynolds, Paul A; Harrison, David J

    2013-12-01

    Histopathology, the examination of an architecturally artefactual, two-dimensional and static image remains a potent tool allowing diagnosis and empirical expectation of prognosis. Considerable optimism exists that the advent of molecular genetic testing and other biomarker strategies will improve or even replace this ancient technology. A number of biomarkers already add considerable value for prediction of whether a treatment will work. In this short review we argue that a systems medicine approach to pathology will not seek to replace traditional pathology, but rather augment it. Systems approaches need to incorporate quantitative morphological, protein, mRNA and DNA data. A significant challenge for clinical implementation of systems pathology is how to optimize information available from tissue, which is frequently sub-optimal in quality and amount, and yet generate useful predictive models that work. The transition of histopathology to systems pathophysiology and the use of multiscale data sets usher in a new era in diagnosis, prognosis and prediction based on the analysis of human tissue. © 2013 The Authors. FEBS Journal published by John Wiley & Sons Ltd on behalf of FEBS.

  8. Guided genetic screen to identify genes essential in the regeneration of hair cells and other tissues.

    Science.gov (United States)

    Pei, Wuhong; Xu, Lisha; Huang, Sunny C; Pettie, Kade; Idol, Jennifer; Rissone, Alberto; Jimenez, Erin; Sinclair, Jason W; Slevin, Claire; Varshney, Gaurav K; Jones, MaryPat; Carrington, Blake; Bishop, Kevin; Huang, Haigen; Sood, Raman; Lin, Shuo; Burgess, Shawn M

    2018-01-01

    Regenerative medicine holds great promise for both degenerative diseases and traumatic tissue injury which represent significant challenges to the health care system. Hearing loss, which affects hundreds of millions of people worldwide, is caused primarily by a permanent loss of the mechanosensory receptors of the inner ear known as hair cells. This failure to regenerate hair cells after loss is limited to mammals, while all other non-mammalian vertebrates tested were able to completely regenerate these mechanosensory receptors after injury. To understand the mechanism of hair cell regeneration and its association with regeneration of other tissues, we performed a guided mutagenesis screen using zebrafish lateral line hair cells as a screening platform to identify genes that are essential for hair cell regeneration, and further investigated how genes essential for hair cell regeneration were involved in the regeneration of other tissues. We created genetic mutations either by retroviral insertion or CRISPR/Cas9 approaches, and developed a high-throughput screening pipeline for analyzing hair cell development and regeneration. We screened 254 gene mutations and identified 7 genes specifically affecting hair cell regeneration. These hair cell regeneration genes fell into distinct and somewhat surprising functional categories. By examining the regeneration of caudal fin and liver, we found these hair cell regeneration genes often also affected other types of tissue regeneration. Therefore, our results demonstrate guided screening is an effective approach to discover regeneration candidates, and hair cell regeneration is associated with other tissue regeneration.

  9. Quality system in Malaysian National Tissue Bank

    International Nuclear Information System (INIS)

    Go Boon Thong; Firdaus, M. N.; Abd Rani Shamsudin

    1999-01-01

    Quality System in Malaysian National Tissue Bank is based on the Quality Manual which has been drawn up by the chairman, who is the Dean, School of Medical Sciences. The Quality Manual include general standard for Tissue Banking in University Science of Malaysia which describe and explain a set of general standard similar to the EATB standard. The primary aim of the quality system is to produce a safe and effective tissue graft for successful clinical use and to ensure the safety of tissue bank operators. The Quality Manual also related the role of a Technical Manual, which explain the standard of technical aspect of tissue bank in a Quality Assurance. The safe working environment and Good Laboratory Practice is highlight in Quality System. Documentation of tissue bank activities is the key to the administration to tissue bank. Finally Quality System in tissue banking will never be complete without a Tissue Bank Auditing System which allow the tissue bank coordinator and staff to look into the problem and further enhance the progress of the tissue bank

  10. Parameter identifiability of linear dynamical systems

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    Glover, K.; Willems, J. C.

    1974-01-01

    It is assumed that the system matrices of a stationary linear dynamical system were parametrized by a set of unknown parameters. The question considered here is, when can such a set of unknown parameters be identified from the observed data? Conditions for the local identifiability of a parametrization are derived in three situations: (1) when input/output observations are made, (2) when there exists an unknown feedback matrix in the system and (3) when the system is assumed to be driven by white noise and only output observations are made. Also a sufficient condition for global identifiability is derived.

  11. KLC1-ALK: a novel fusion in lung cancer identified using a formalin-fixed paraffin-embedded tissue only.

    Directory of Open Access Journals (Sweden)

    Yuki Togashi

    Full Text Available The promising results of anaplastic lymphoma kinase (ALK inhibitors have changed the significance of ALK fusions in several types of cancer. These fusions are no longer mere research targets or diagnostic markers, but they are now directly linked to the therapeutic benefit of patients. However, most available tumor tissues in clinical settings are formalin-fixed and paraffin-embedded (FFPE, and this significantly limits detailed genetic studies in many clinical cases. Although recent technical improvements have allowed the analysis of some known mutations in FFPE tissues, identifying unknown fusion genes by using only FFPE tissues remains difficult. We developed a 5'-rapid amplification of cDNA ends-based system optimized for FFPE tissues and evaluated this system on a lung cancer tissue with ALK rearrangement and without the 2 known ALK fusions EML4-ALK and KIF5B-ALK. With this system, we successfully identified a novel ALK fusion, KLC1-ALK. The result was confirmed by reverse transcription-polymerase chain reaction and fluorescence in situ hybridization. Then, we synthesized the putative full-length cDNA of KLC1-ALK and demonstrated the transforming potential of the fusion kinase with assays using mouse 3T3 cells. To the best of our knowledge, KLC1-ALK is the first novel oncogenic fusion identified using only FFPE tissues. This finding will broaden the potential value of archival FFPE tissues and provide further biological and clinical insights into ALK-positive lung cancer.

  12. Identifying intelligent Building Management Systems (BMS) in ...

    African Journals Online (AJOL)

    Identifying intelligent Building Management Systems (BMS) in sustainable housing. ... Journal of Fundamental and Applied Sciences ... attention to the principles of sustainability of energy and organized approach to sustainable development.

  13. IDENTIFIABILITY VERSUS HETEROGENEITY IN GROUNDWATER MODELING SYSTEMS

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    A M BENALI

    2003-06-01

    Full Text Available Review of history matching of reservoirs parameters in groundwater flow raises the problem of identifiability of aquifer systems. Lack of identifiability means that there exists parameters to which the heads are insensitive. From the guidelines of the study of the homogeneous case, we inspect the identifiability of the distributed transmissivity field of heterogeneous groundwater aquifers. These are derived from multiple realizations of a random function Y = log T  whose probability distribution function is normal. We follow the identifiability of the autocorrelated block transmissivities through the measure of the sensitivity of the local derivatives DTh = (∂hi  ∕ ∂Tj computed for each sample of a population N (0; σY, αY. Results obtained from an analysis of Monte Carlo type suggest that the more a system is heterogeneous, the less it is identifiable.

  14. Distributed design approach in persistent identifiers systems

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    Golodoniuc, Pavel; Car, Nicholas; Klump, Jens

    2017-04-01

    The need to identify both digital and physical objects is ubiquitous in our society. Past and present persistent identifier (PID) systems, of which there is a great variety in terms of technical and social implementations, have evolved with the advent of the Internet, which has allowed for globally unique and globally resolvable identifiers. PID systems have catered for identifier uniqueness, integrity, persistence, and trustworthiness, regardless of the identifier's application domain, the scope of which has expanded significantly in the past two decades. Since many PID systems have been largely conceived and developed by small communities, or even a single organisation, they have faced challenges in gaining widespread adoption and, most importantly, the ability to survive change of technology. This has left a legacy of identifiers that still exist and are being used but which have lost their resolution service. We believe that one of the causes of once successful PID systems fading is their reliance on a centralised technical infrastructure or a governing authority. Golodoniuc et al. (2016) proposed an approach to the development of PID systems that combines the use of (a) the Handle system, as a distributed system for the registration and first-degree resolution of persistent identifiers, and (b) the PID Service (Golodoniuc et al., 2015), to enable fine-grained resolution to different information object representations. The proposed approach solved the problem of guaranteed first-degree resolution of identifiers, but left fine-grained resolution and information delivery under the control of a single authoritative source, posing risk to the long-term availability of information resources. Herein, we develop these approaches further and explore the potential of large-scale decentralisation at all levels: (i) persistent identifiers and information resources registration; (ii) identifier resolution; and (iii) data delivery. To achieve large-scale decentralisation

  15. Trustworthy persistent identifier systems of the future

    Science.gov (United States)

    Golodoniuc, Pavel; Klump, Jens; Car, Nicholas

    2016-04-01

    Over the last two decades, persistent identifier (PID) systems have seen some significant changes in their governance policies, system capabilities, and technology. The development of most systems was driven by two main application areas, namely archives and libraries. Guidelines and criteria for trustworthy PID systems have been clearly devised (Bütikofer, 2009) and many PID system implementations for the identification of static digital objects have been built (e.g., PURL). However systems delivering persistent identifiers for dynamic datasets are not yet mature. There has been a rapid proliferation of different PID systems caused by the specific technical or organisational requirements of various communities that could not be met by existing systems such as DOI, ISBN, and EAN. Many of these different systems were limited by their inability to provide native means of persistent identifier resolution. This has prompted a decoupling of PID-associated data from the resolution service and this is where the Handle system has played a significant role. The Handle allowed to build a distributed system of independently managed resolver services. A trustworthy PID system must be designed to outlive the objects it provides persistent identifiers for, which may cease to exist or otherwise be deprecated, and the technology used to implement it, which will certainly need to change with time. We propose that such a system should rest on four pillars of agreements - (i) definitions, (ii) policies, (iii) services, and (iv) data services, to ensure longevity. While we believe all four pillars are equally important, we intentionally leave regulating aspects of issuing of identifiers and their registration out of the scope of this paper and focus on the agreements that have to be established between PID resolver services and the data sources indicated by the persistent identifiers. We propose an approach to development of PID systems that combines the use of (a) the Handle system

  16. Structural Identifiability of Dynamic Systems Biology Models.

    Science.gov (United States)

    Villaverde, Alejandro F; Barreiro, Antonio; Papachristodoulou, Antonis

    2016-10-01

    A powerful way of gaining insight into biological systems is by creating a nonlinear differential equation model, which usually contains many unknown parameters. Such a model is called structurally identifiable if it is possible to determine the values of its parameters from measurements of the model outputs. Structural identifiability is a prerequisite for parameter estimation, and should be assessed before exploiting a model. However, this analysis is seldom performed due to the high computational cost involved in the necessary symbolic calculations, which quickly becomes prohibitive as the problem size increases. In this paper we show how to analyse the structural identifiability of a very general class of nonlinear models by extending methods originally developed for studying observability. We present results about models whose identifiability had not been previously determined, report unidentifiabilities that had not been found before, and show how to modify those unidentifiable models to make them identifiable. This method helps prevent problems caused by lack of identifiability analysis, which can compromise the success of tasks such as experiment design, parameter estimation, and model-based optimization. The procedure is called STRIKE-GOLDD (STRuctural Identifiability taKen as Extended-Generalized Observability with Lie Derivatives and Decomposition), and it is implemented in a MATLAB toolbox which is available as open source software. The broad applicability of this approach facilitates the analysis of the increasingly complex models used in systems biology and other areas.

  17. Identifying Effectiveness Criteria for Internet Payment Systems.

    Science.gov (United States)

    Shon, Tae-Hwan; Swatman, Paula M. C.

    1998-01-01

    Examines Internet payment systems (IPS): third-party, card, secure Web server, electronic token, financial electronic data interchange (EDI), and micropayment based. Reports the results of a Delphi survey of experts identifying and classifying IPS effectiveness criteria and classifying types of IPS providers. Includes the survey invitation letter…

  18. European quality system for tissue banking.

    Science.gov (United States)

    Manyalich, M; Navarro, A; Koller, J; Loty, B; de Guerra, A; Cornu, O; Vabels, G; Fornasari, P M; Costa, A N; Siska, I; Hirn, M; Franz, N; Miranda, B; Kaminski, A; Uhrynowska, I; Van Baare, J; Trias, E; Fernández, C; de By, T; Poniatowski, S; Carbonell, R

    2009-01-01

    The aims of this project were to analyze the factors that influence quality and safety of tissues for transplantation and to develop the method to ensure standards of quality and safety in relation to tissue banking as demanded by European Directive 2004/23/EC and its technical annexes. It is organized in 4 Working Groups, the objectives of each one being focused in a specific area. The Guide of Recommendations for Tissue Banking is structured into 4 parts: (1) quality systems that apply to tissue banking and general quality system requirements, (2) regulatory framework in Europe, (3) standards available, and (4) recommendations of the fundamental quality and safety keypoints. This Working Group handled design of a multinational musculoskeletal tissue registry prototype. This Working Group handled design and validation of a specialized training model structured into online and face-to-face courses. The model was improved with suggestions from students, and 100% certification was obtained. The Guide for Auditing Tissue Establishments provides guidance for auditors, a self-assessment questionnaire, and an audit report form. The effectiveness and sustainability of the outputs were assessed. Both guides are useful for experienced tissue establishments and auditors and also for professionals that are starting in the field. The registry prototype proves it is possible to exchange tissues between establishments throughout Europe. The training model has been effective in educating staff and means having professionals with excellent expertise. Member states could adapt/adopt it. The guides should be updated periodically and perhaps a European organization should take responsibility for this and even create a body of auditors.

  19. Radiological approach to systemic connective tissue diseases

    International Nuclear Information System (INIS)

    Wiesmann, W.; Schneider, M.

    1988-01-01

    Systemic lupus erythematosus (SLE) and progressive systemic sclerosis (PSS) represent the most frequent manifestations of systemic connective tissue diseases (collagen diseases). Radiological examinations are employed to estimate the extension and degree of the pathological process. In addition, progression of the disease can be verified. In both of the above collagen diseases, specific radiological findings can be observed that permit them to be differentiated from other entities. An algorithm for the adequate radiological work-up of collagen diseases is presented. (orig.) [de

  20. Radiological approach to systemic connective tissue diseases

    Energy Technology Data Exchange (ETDEWEB)

    Wiesmann, W; Schneider, M

    1988-07-01

    Systemic lupus erythematosus (SLE) and progressive systemic sclerosis (PSS) represent the most frequent manifestations of systemic connective tissue diseases (collagen diseases). Radiological examinations are employed to estimate the extension and degree of the pathological process. In addition, progression of the disease can be verified. In both of the above collagen diseases, specific radiological findings can be observed that permit them to be differentiated from other entities. An algorithm for the adequate radiological work-up of collagen diseases is presented.

  1. Genome-wide strategies identify downstream target genes of chick connective tissue-associated transcription factors.

    Science.gov (United States)

    Orgeur, Mickael; Martens, Marvin; Leonte, Georgeta; Nassari, Sonya; Bonnin, Marie-Ange; Börno, Stefan T; Timmermann, Bernd; Hecht, Jochen; Duprez, Delphine; Stricker, Sigmar

    2018-03-29

    Connective tissues support organs and play crucial roles in development, homeostasis and fibrosis, yet our understanding of their formation is still limited. To gain insight into the molecular mechanisms of connective tissue specification, we selected five zinc-finger transcription factors - OSR1, OSR2, EGR1, KLF2 and KLF4 - based on their expression patterns and/or known involvement in connective tissue subtype differentiation. RNA-seq and ChIP-seq profiling of chick limb micromass cultures revealed a set of common genes regulated by all five transcription factors, which we describe as a connective tissue core expression set. This common core was enriched with genes associated with axon guidance and myofibroblast signature, including fibrosis-related genes. In addition, each transcription factor regulated a specific set of signalling molecules and extracellular matrix components. This suggests a concept whereby local molecular niches can be created by the expression of specific transcription factors impinging on the specification of local microenvironments. The regulatory network established here identifies common and distinct molecular signatures of limb connective tissue subtypes, provides novel insight into the signalling pathways governing connective tissue specification, and serves as a resource for connective tissue development. © 2018. Published by The Company of Biologists Ltd.

  2. Fourier transform infrared imaging and infrared fiber optic probe spectroscopy identify collagen type in connective tissues.

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    Arash Hanifi

    Full Text Available Hyaline cartilage and mechanically inferior fibrocartilage consisting of mixed collagen types are frequently found together in repairing articular cartilage. The present study seeks to develop methodology to identify collagen type and other tissue components using Fourier transform infrared (FTIR spectral evaluation of matrix composition in combination with multivariate analyses. FTIR spectra of the primary molecular components of repair cartilage, types I and II collagen, and aggrecan, were used to develop multivariate spectral models for discrimination of the matrix components of the tissues of interest. Infrared imaging data were collected from bovine bone, tendon, normal cartilage, meniscus and human repair cartilage tissues, and composition predicted using partial least squares analyses. Histology and immunohistochemistry results were used as standards for validation. Infrared fiber optic probe spectral data were also obtained from meniscus (a tissue with mixed collagen types to evaluate the potential of this method for identification of collagen type in a minimally-invasive clinical application. Concentration profiles of the tissue components obtained from multivariate analysis were in excellent agreement with histology and immunohistochemistry results. Bone and tendon showed a uniform distribution of predominantly type I collagen through the tissue. Normal cartilage showed a distribution of type II collagen and proteoglycan similar to the known composition, while in repair cartilage, the spectral distribution of both types I and II collagen were similar to that observed via immunohistochemistry. Using the probe, the outer and inner regions of the meniscus were shown to be primarily composed of type I and II collagen, respectively, in accordance with immunohistochemistry data. In summary, multivariate analysis of infrared spectra can indeed be used to differentiate collagen type I and type II, even in the presence of proteoglycan, in

  3. Cardiac tissue engineering using perfusion bioreactor systems

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    Radisic, Milica; Marsano, Anna; Maidhof, Robert; Wang, Yadong; Vunjak-Novakovic, Gordana

    2009-01-01

    This protocol describes tissue engineering of synchronously contractile cardiac constructs by culturing cardiac cell populations on porous scaffolds (in some cases with an array of channels) and bioreactors with perfusion of culture medium (in some cases supplemented with an oxygen carrier). The overall approach is ‘biomimetic’ in nature as it tends to provide in vivo-like oxygen supply to cultured cells and thereby overcome inherent limitations of diffusional transport in conventional culture systems. In order to mimic the capillary network, cells are cultured on channeled elastomer scaffolds that are perfused with culture medium that can contain oxygen carriers. The overall protocol takes 2–4 weeks, including assembly of the perfusion systems, preparation of scaffolds, cell seeding and cultivation, and on-line and end-point assessment methods. This model is well suited for a wide range of cardiac tissue engineering applications, including the use of human stem cells, and high-fidelity models for biological research. PMID:18388955

  4. Network-Based Method for Identifying Co- Regeneration Genes in Bone, Dentin, Nerve and Vessel Tissues.

    Science.gov (United States)

    Chen, Lei; Pan, Hongying; Zhang, Yu-Hang; Feng, Kaiyan; Kong, XiangYin; Huang, Tao; Cai, Yu-Dong

    2017-10-02

    Bone and dental diseases are serious public health problems. Most current clinical treatments for these diseases can produce side effects. Regeneration is a promising therapy for bone and dental diseases, yielding natural tissue recovery with few side effects. Because soft tissues inside the bone and dentin are densely populated with nerves and vessels, the study of bone and dentin regeneration should also consider the co-regeneration of nerves and vessels. In this study, a network-based method to identify co-regeneration genes for bone, dentin, nerve and vessel was constructed based on an extensive network of protein-protein interactions. Three procedures were applied in the network-based method. The first procedure, searching, sought the shortest paths connecting regeneration genes of one tissue type with regeneration genes of other tissues, thereby extracting possible co-regeneration genes. The second procedure, testing, employed a permutation test to evaluate whether possible genes were false discoveries; these genes were excluded by the testing procedure. The last procedure, screening, employed two rules, the betweenness ratio rule and interaction score rule, to select the most essential genes. A total of seventeen genes were inferred by the method, which were deemed to contribute to co-regeneration of at least two tissues. All these seventeen genes were extensively discussed to validate the utility of the method.

  5. Structural identifiability of polynomial and rational systems

    NARCIS (Netherlands)

    J. Nemcová (Jana)

    2010-01-01

    htmlabstractSince analysis and simulation of biological phenomena require the availability of their fully specified models, one needs to be able to estimate unknown parameter values of the models. In this paper we deal with identifiability of parametrizations which is the property of one-to-one

  6. Diagnostic value of MRS-quantified brain tissue lactate level in identifying children with mitochondrial disorders

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    Lunsing, Roelineke J.; Strating, Kim [University Medical Centre Groningen, University of Groningen, Department of Child Neurology, Groningen (Netherlands); Koning, Tom J. de [University Medical Centre Groningen, University of Groningen, Department of Pediatric Metabolic Diseases, Groningen (Netherlands); Sijens, Paul E. [University Medical Centre Groningen, University of Groningen, Department of Radiology, Groningen (Netherlands)

    2017-03-15

    Magnetic resonance spectroscopy (MRS) of children with or without neurometabolic disease is used for the first time for quantitative assessment of brain tissue lactate signals, to elaborate on previous suggestions of MRS-detected lactate as a marker of mitochondrial disease. Multivoxel MRS of a transverse plane of brain tissue cranial to the ventricles was performed in 88 children suspected of having neurometabolic disease, divided into 'definite' (n = 17, ≥1 major criteria), 'probable' (n = 10, ≥2 minor criteria), 'possible' (n = 17, 1 minor criterion) and 'unlikely' mitochondrial disease (n = 44, none of the criteria). Lactate levels, expressed in standardized arbitrary units or relative to creatine, were derived from summed signals from all voxels. Ten 'unlikely' children with a normal neurological exam served as the MRS reference subgroup. For 61 of 88 children, CSF lactate values were obtained. MRS lactate level (>12 arbitrary units) and the lactate-to-creatine ratio (L/Cr >0.22) differed significantly between the definite and the unlikely group (p = 0.015 and p = 0.001, respectively). MRS L/Cr also differentiated between the probable and the MRS reference subgroup (p = 0.03). No significant group differences were found for CSF lactate. MRS-quantified brain tissue lactate levels can serve as diagnostic marker for identifying mitochondrial disease in children. (orig.)

  7. Diagnostic value of MRS-quantified brain tissue lactate level in identifying children with mitochondrial disorders

    International Nuclear Information System (INIS)

    Lunsing, Roelineke J.; Strating, Kim; Koning, Tom J. de; Sijens, Paul E.

    2017-01-01

    Magnetic resonance spectroscopy (MRS) of children with or without neurometabolic disease is used for the first time for quantitative assessment of brain tissue lactate signals, to elaborate on previous suggestions of MRS-detected lactate as a marker of mitochondrial disease. Multivoxel MRS of a transverse plane of brain tissue cranial to the ventricles was performed in 88 children suspected of having neurometabolic disease, divided into 'definite' (n = 17, ≥1 major criteria), 'probable' (n = 10, ≥2 minor criteria), 'possible' (n = 17, 1 minor criterion) and 'unlikely' mitochondrial disease (n = 44, none of the criteria). Lactate levels, expressed in standardized arbitrary units or relative to creatine, were derived from summed signals from all voxels. Ten 'unlikely' children with a normal neurological exam served as the MRS reference subgroup. For 61 of 88 children, CSF lactate values were obtained. MRS lactate level (>12 arbitrary units) and the lactate-to-creatine ratio (L/Cr >0.22) differed significantly between the definite and the unlikely group (p = 0.015 and p = 0.001, respectively). MRS L/Cr also differentiated between the probable and the MRS reference subgroup (p = 0.03). No significant group differences were found for CSF lactate. MRS-quantified brain tissue lactate levels can serve as diagnostic marker for identifying mitochondrial disease in children. (orig.)

  8. Identifying optimal models to represent biochemical systems.

    Directory of Open Access Journals (Sweden)

    Mochamad Apri

    Full Text Available Biochemical systems involving a high number of components with intricate interactions often lead to complex models containing a large number of parameters. Although a large model could describe in detail the mechanisms that underlie the system, its very large size may hinder us in understanding the key elements of the system. Also in terms of parameter identification, large models are often problematic. Therefore, a reduced model may be preferred to represent the system. Yet, in order to efficaciously replace the large model, the reduced model should have the same ability as the large model to produce reliable predictions for a broad set of testable experimental conditions. We present a novel method to extract an "optimal" reduced model from a large model to represent biochemical systems by combining a reduction method and a model discrimination method. The former assures that the reduced model contains only those components that are important to produce the dynamics observed in given experiments, whereas the latter ensures that the reduced model gives a good prediction for any feasible experimental conditions that are relevant to answer questions at hand. These two techniques are applied iteratively. The method reveals the biological core of a model mathematically, indicating the processes that are likely to be responsible for certain behavior. We demonstrate the algorithm on two realistic model examples. We show that in both cases the core is substantially smaller than the full model.

  9. Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems

    CERN Document Server

    Thiriet, Marc

    2013-01-01

    The volumes in this authoritative series present a multidisciplinary approach to modeling and simulation of flows in the cardiovascular and ventilatory systems, especially multiscale modeling and coupled simulations. Volume 5 is devoted to cells, tissues, and organs of the cardiovascular and ventilatory systems with an emphasis on mechanotransduction-based regulation of flow. The blood vessel wall is a living tissue that quickly reacts to loads applied on it by the flowing blood. In any segment of a blood vessel, the endothelial and smooth muscle cells can sense unusual time variations in small-magnitude wall shear stress and large-amplitude wall stretch generated by abnormal hemodynamic stresses. These cells respond with a short-time scale (from seconds to hours) to adapt the vessel caliber. Since such adaptive cell activities can be described using mathematical models, a key objective of this volume is to identify the mesoscopic agents and nanoscopic mediators required to derive adequate mathematical models...

  10. Lung involvement in systemic connective tissue diseases

    Directory of Open Access Journals (Sweden)

    Plavec Goran

    2008-01-01

    Full Text Available Background/Aim. Systemic connective tissue diseases (SCTD are chronic inflammatory autoimmune disorders of unknown cause that can involve different organs and systems. Their course and prognosis are different. All of them can, more or less, involve the respiratory system. The aim of this study was to find out the frequency of respiratory symptoms, lung function disorders, radiography and high-resolution computerized tomography (HRCT abnormalities, and their correlation with the duration of the disease and the applied treatment. Methods. In 47 non-randomized consecutive patients standard chest radiography, HRCT, and lung function tests were done. Results. Hypoxemia was present in nine of the patients with respiratory symptoms (20%. In all of them chest radiography was normal. In five of these patients lung fibrosis was established using HRCT. Half of all the patients with SCTD had symptoms of lung involvement. Lung function tests disorders of various degrees were found in 40% of the patients. The outcome and the degree of lung function disorders were neither in correlation with the duration of SCTD nor with therapy used (p > 0.05 Spearmans Ro. Conclusion. Pulmonary fibrosis occurs in about 10% of the patients with SCTD, and possibly not due to the applied treatment regimens. Hypoxemia could be a sing of existing pulmonary fibrosis in the absence of disorders on standard chest radiography.

  11. Tissue-type-specific transcriptome analysis identifies developing xylem-specific promoters in poplar.

    Science.gov (United States)

    Ko, Jae-Heung; Kim, Hyun-Tae; Hwang, Ildoo; Han, Kyung-Hwan

    2012-06-01

    Plant biotechnology offers a means to create novel phenotypes. However, commercial application of biotechnology in crop improvement programmes is severely hindered by the lack of utility promoters (or freedom to operate the existing ones) that can drive gene expression in a tissue-specific or temporally controlled manner. Woody biomass is gaining popularity as a source of fermentable sugars for liquid fuel production. To improve the quantity and quality of woody biomass, developing xylem (DX)-specific modification of the feedstock is highly desirable. To develop utility promoters that can drive transgene expression in a DX-specific manner, we used the Affymetrix Poplar Genome Arrays to obtain tissue-type-specific transcriptomes from poplar stems. Subsequent bioinformatics analysis identified 37 transcripts that are specifically or strongly expressed in DX cells of poplar. After further confirmation of their DX-specific expression using semi-quantitative PCR, we selected four genes (DX5, DX8, DX11 and DX15) for in vivo confirmation of their tissue-specific expression in transgenic poplars. The promoter regions of the selected DX genes were isolated and fused to a β-glucuronidase (GUS)-reported gene in a binary vector. This construct was used to produce transgenic poplars via Agrobacterium-mediated transformation. The GUS expression patterns of the resulting transgenic plants showed that these promoters were active in the xylem cells at early seedling growth and had strongest expression in the developing xylem cells at later growth stages of poplar. We conclude that these DX promoters can be used as a utility promoter for DX-specific biomass engineering. © 2012 The Authors. Plant Biotechnology Journal © 2012 Society for Experimental Biology, Association of Applied Biologists and Blackwell Publishing Ltd.

  12. Test systems to identify reproductive toxicants.

    Science.gov (United States)

    Riecke, K; Stahlmann, R

    2000-09-01

    Experience with drugs and other xenobiotics indicates that both animal testing and epidemiological studies are necessary to provide adequate data for an estimation of risks that might be associated with exposure to a chemical substance. In this review, the pros and cons of test systems for reproductive toxicity are discussed. Usually, several studies are performed to cover the different phases of the reproductive cycle. In the preclinical development of drugs, the three so-called 'segment testing protocols' have been used for several decades now. More recently, new testing concepts have been accepted internationally which include more flexibility in implementation. Several examples of compounds with the potential for reproductive toxicity are presented in more detail in a discussion of some pitfalls of the tests for fertility (phthalates and fluoroquinolones), teratogenicity (acyclovir and protease inhibitors) and postnatal developmental toxicity (fluoroquinolones). In addition, important aspects of kinetics and metabolism as a prerequisite for a rational interpretation of results from toxicological studies are briefly discussed. In vitro assays are useful for supplementing the routinely used in vivo approaches or for studying an expected or defined effect, but they are not suitable for revealing an unknown effect of a chemical on the complex reproductive process.

  13. A Kinome RNAi Screen in Drosophila Identifies Novel Genes Interacting with Lgl, aPKC, and Crb Cell Polarity Genes in Epithelial Tissues.

    Science.gov (United States)

    Parsons, Linda M; Grzeschik, Nicola A; Amaratunga, Kasun; Burke, Peter; Quinn, Leonie M; Richardson, Helena E

    2017-08-07

    In both Drosophila melanogaster and mammalian systems, epithelial structure and underlying cell polarity are essential for proper tissue morphogenesis and organ growth. Cell polarity interfaces with multiple cellular processes that are regulated by the phosphorylation status of large protein networks. To gain insight into the molecular mechanisms that coordinate cell polarity with tissue growth, we screened a boutique collection of RNAi stocks targeting the kinome for their capacity to modify Drosophila "cell polarity" eye and wing phenotypes. Initially, we identified kinase or phosphatase genes whose depletion modified adult eye phenotypes associated with the manipulation of cell polarity complexes (via overexpression of Crb or aPKC). We next conducted a secondary screen to test whether these cell polarity modifiers altered tissue overgrowth associated with depletion of Lgl in the wing. These screens identified Hippo, Jun kinase (JNK), and Notch signaling pathways, previously linked to cell polarity regulation of tissue growth. Furthermore, novel pathways not previously connected to cell polarity regulation of tissue growth were identified, including Wingless (Wg/Wnt), Ras, and lipid/Phospho-inositol-3-kinase (PI3K) signaling pathways. Additionally, we demonstrated that the "nutrient sensing" kinases Salt Inducible Kinase 2 and 3 ( SIK2 and 3 ) are potent modifiers of cell polarity phenotypes and regulators of tissue growth. Overall, our screen has revealed novel cell polarity-interacting kinases and phosphatases that affect tissue growth, providing a platform for investigating molecular mechanisms coordinating cell polarity and tissue growth during development. Copyright © 2017 Parsons et al.

  14. Identifying cis-mediators for trans-eQTLs across many human tissues using genomic mediation analysis.

    Science.gov (United States)

    Yang, Fan; Wang, Jiebiao; Pierce, Brandon L; Chen, Lin S

    2017-11-01

    The impact of inherited genetic variation on gene expression in humans is well-established. The majority of known expression quantitative trait loci (eQTLs) impact expression of local genes ( cis -eQTLs). More research is needed to identify effects of genetic variation on distant genes ( trans -eQTLs) and understand their biological mechanisms. One common trans -eQTLs mechanism is "mediation" by a local ( cis ) transcript. Thus, mediation analysis can be applied to genome-wide SNP and expression data in order to identify transcripts that are " cis -mediators" of trans -eQTLs, including those " cis -hubs" involved in regulation of many trans -genes. Identifying such mediators helps us understand regulatory networks and suggests biological mechanisms underlying trans -eQTLs, both of which are relevant for understanding susceptibility to complex diseases. The multitissue expression data from the Genotype-Tissue Expression (GTEx) program provides a unique opportunity to study cis -mediation across human tissue types. However, the presence of complex hidden confounding effects in biological systems can make mediation analyses challenging and prone to confounding bias, particularly when conducted among diverse samples. To address this problem, we propose a new method: Genomic Mediation analysis with Adaptive Confounding adjustment (GMAC). It enables the search of a very large pool of variables, and adaptively selects potential confounding variables for each mediation test. Analyses of simulated data and GTEx data demonstrate that the adaptive selection of confounders by GMAC improves the power and precision of mediation analysis. Application of GMAC to GTEx data provides new insights into the observed patterns of cis -hubs and trans -eQTL regulation across tissue types. © 2017 Yang et al.; Published by Cold Spring Harbor Laboratory Press.

  15. Identifying and exploiting trait-relevant tissues with multiple functional annotations in genome-wide association studies

    Science.gov (United States)

    Zhang, Shujun

    2018-01-01

    Genome-wide association studies (GWASs) have identified many disease associated loci, the majority of which have unknown biological functions. Understanding the mechanism underlying trait associations requires identifying trait-relevant tissues and investigating associations in a trait-specific fashion. Here, we extend the widely used linear mixed model to incorporate multiple SNP functional annotations from omics studies with GWAS summary statistics to facilitate the identification of trait-relevant tissues, with which to further construct powerful association tests. Specifically, we rely on a generalized estimating equation based algorithm for parameter inference, a mixture modeling framework for trait-tissue relevance classification, and a weighted sequence kernel association test constructed based on the identified trait-relevant tissues for powerful association analysis. We refer to our analytic procedure as the Scalable Multiple Annotation integration for trait-Relevant Tissue identification and usage (SMART). With extensive simulations, we show how our method can make use of multiple complementary annotations to improve the accuracy for identifying trait-relevant tissues. In addition, our procedure allows us to make use of the inferred trait-relevant tissues, for the first time, to construct more powerful SNP set tests. We apply our method for an in-depth analysis of 43 traits from 28 GWASs using tissue-specific annotations in 105 tissues derived from ENCODE and Roadmap. Our results reveal new trait-tissue relevance, pinpoint important annotations that are informative of trait-tissue relationship, and illustrate how we can use the inferred trait-relevant tissues to construct more powerful association tests in the Wellcome trust case control consortium study. PMID:29377896

  16. Identifying and exploiting trait-relevant tissues with multiple functional annotations in genome-wide association studies.

    Directory of Open Access Journals (Sweden)

    Xingjie Hao

    2018-01-01

    Full Text Available Genome-wide association studies (GWASs have identified many disease associated loci, the majority of which have unknown biological functions. Understanding the mechanism underlying trait associations requires identifying trait-relevant tissues and investigating associations in a trait-specific fashion. Here, we extend the widely used linear mixed model to incorporate multiple SNP functional annotations from omics studies with GWAS summary statistics to facilitate the identification of trait-relevant tissues, with which to further construct powerful association tests. Specifically, we rely on a generalized estimating equation based algorithm for parameter inference, a mixture modeling framework for trait-tissue relevance classification, and a weighted sequence kernel association test constructed based on the identified trait-relevant tissues for powerful association analysis. We refer to our analytic procedure as the Scalable Multiple Annotation integration for trait-Relevant Tissue identification and usage (SMART. With extensive simulations, we show how our method can make use of multiple complementary annotations to improve the accuracy for identifying trait-relevant tissues. In addition, our procedure allows us to make use of the inferred trait-relevant tissues, for the first time, to construct more powerful SNP set tests. We apply our method for an in-depth analysis of 43 traits from 28 GWASs using tissue-specific annotations in 105 tissues derived from ENCODE and Roadmap. Our results reveal new trait-tissue relevance, pinpoint important annotations that are informative of trait-tissue relationship, and illustrate how we can use the inferred trait-relevant tissues to construct more powerful association tests in the Wellcome trust case control consortium study.

  17. Automated local bright feature image analysis of nuclear protein distribution identifies changes in tissue phenotype

    International Nuclear Information System (INIS)

    Knowles, David; Sudar, Damir; Bator, Carol; Bissell, Mina

    2006-01-01

    The organization of nuclear proteins is linked to cell and tissue phenotypes. When cells arrest proliferation, undergo apoptosis, or differentiate, the distribution of nuclear proteins changes. Conversely, forced alteration of the distribution of nuclear proteins modifies cell phenotype. Immunostaining and fluorescence microscopy have been critical for such findings. However, there is an increasing need for quantitative analysis of nuclear protein distribution to decipher epigenetic relationships between nuclear structure and cell phenotype, and to unravel the mechanisms linking nuclear structure and function. We have developed imaging methods to quantify the distribution of fluorescently-stained nuclear protein NuMA in different mammary phenotypes obtained using three-dimensional cell culture. Automated image segmentation of DAPI-stained nuclei was generated to isolate thousands of nuclei from three-dimensional confocal images. Prominent features of fluorescently-stained NuMA were detected using a novel local bright feature analysis technique, and their normalized spatial density calculated as a function of the distance from the nuclear perimeter to its center. The results revealed marked changes in the distribution of the density of NuMA bright features as non-neoplastic cells underwent phenotypically normal acinar morphogenesis. In contrast, we did not detect any reorganization of NuMA during the formation of tumor nodules by malignant cells. Importantly, the analysis also discriminated proliferating non-neoplastic cells from proliferating malignant cells, suggesting that these imaging methods are capable of identifying alterations linked not only to the proliferation status but also to the malignant character of cells. We believe that this quantitative analysis will have additional applications for classifying normal and pathological tissues

  18. Automated local bright feature image analysis of nuclear proteindistribution identifies changes in tissue phenotype

    Energy Technology Data Exchange (ETDEWEB)

    Knowles, David; Sudar, Damir; Bator, Carol; Bissell, Mina

    2006-02-01

    The organization of nuclear proteins is linked to cell and tissue phenotypes. When cells arrest proliferation, undergo apoptosis, or differentiate, the distribution of nuclear proteins changes. Conversely, forced alteration of the distribution of nuclear proteins modifies cell phenotype. Immunostaining and fluorescence microscopy have been critical for such findings. However, there is an increasing need for quantitative analysis of nuclear protein distribution to decipher epigenetic relationships between nuclear structure and cell phenotype, and to unravel the mechanisms linking nuclear structure and function. We have developed imaging methods to quantify the distribution of fluorescently-stained nuclear protein NuMA in different mammary phenotypes obtained using three-dimensional cell culture. Automated image segmentation of DAPI-stained nuclei was generated to isolate thousands of nuclei from three-dimensional confocal images. Prominent features of fluorescently-stained NuMA were detected using a novel local bright feature analysis technique, and their normalized spatial density calculated as a function of the distance from the nuclear perimeter to its center. The results revealed marked changes in the distribution of the density of NuMA bright features as non-neoplastic cells underwent phenotypically normal acinar morphogenesis. In contrast, we did not detect any reorganization of NuMA during the formation of tumor nodules by malignant cells. Importantly, the analysis also discriminated proliferating non-neoplastic cells from proliferating malignant cells, suggesting that these imaging methods are capable of identifying alterations linked not only to the proliferation status but also to the malignant character of cells. We believe that this quantitative analysis will have additional applications for classifying normal and pathological tissues.

  19. Micro-Raman spectroscopy a powerful technique to identify crocidolite and erionite fibers in tissue sections

    Science.gov (United States)

    Rinaudo, C.; Croce, A.; Allegrina, M.; Baris, I. Y.; Dogan, A.; Powers, A.; Rivera, Z.; Bertino, P.; Yang, H.; Gaudino, G.; Carbone, M.

    2013-05-01

    Exposure to mineral fibers such asbestos and erionite is widely associated with the development of lung cancer and pleural malignant mesothelioma (MM). Pedigree and mineralogical studies indicated that genetics may influence mineral fiber carcinogenesis. Although dimensions strongly impact on the fiber carcinogenic potential, also the chemical composition and the fiber is relevant. By using micro-Raman spectroscopy we show here persistence and identification of different mineral phases, directly on histopathological specimens of mice and humans. Fibers of crocidolite asbestos and erionite of different geographic areas (Oregon, US and Cappadocia, Turkey) were injected in mice intra peritoneum. MM developed in 10/15 asbestos-treated mice after 5 months, and in 8-10/15 erionite-treated mice after 14 months. The persistence of the injected fibers was investigated in pancreas, liver, spleen and in the peritoneal tissue. The chemical identification of the different phases occurred in the peritoneal cavity or at the organ borders, while only rarely fibers were localized in the parenchyma. Raman patterns allow easily to recognize crocidolite and erionite fibers. Microscopic analysis revealed that crocidolite fibers were frequently coated by ferruginous material ("asbestos bodies"), whereas erionite fibers were always free from coatings. We also analyzed by micro-Raman spectroscopy lung tissues, both from MM patients of the Cappadocia, where a MM epidemic developed because of environmental exposure to erionite, and from Italian MM patients with occupational exposure to asbestos. Our findings demonstrate that micro-Raman spectroscopy is technique able to identify mineral phases directly on histopathology specimens, as routine tissue sections prepared for diagnostic purpose. REFERENCES A.U. Dogan, M. Dogan. Environ. Geochem. Health 2008, 30(4), 355. M. Carbone, S. Emri, A.U. Dogan, I. Steele, M. Tuncer, HI. Pass, et al. Nat. Rev. Cancer. 2007, 7 (2),147. M. Carbone, Y

  20. Differential proteomic and tissue expression analyses identify valuable diagnostic biomarkers of hepatocellular differentiation and hepatoid adenocarcinomas.

    Science.gov (United States)

    Reis, Henning; Padden, Juliet; Ahrens, Maike; Pütter, Carolin; Bertram, Stefanie; Pott, Leona L; Reis, Anna-Carinna; Weber, Frank; Juntermanns, Benjamin; Hoffmann, Andreas-C; Eisenacher, Martin; Schlaak, Joörg F; Canbay, Ali; Meyer, Helmut E; Sitek, Barbara; Baba, Hideo A

    2015-10-01

    The exact discrimination of lesions with true hepatocellular differentiation from secondary tumours and neoplasms with hepatocellular histomorphology like hepatoid adenocarcinomas (HAC) is crucial. Therefore, we aimed to identify ancillary protein biomarkers by using complementary proteomic techniques (2D-DIGE, label-free MS). The identified candidates were immunohistochemically validated in 14 paired samples of hepatocellular carcinoma (HCC) and non-tumourous liver tissue (NT). The candidates and HepPar1/Arginase1 were afterwards tested for consistency in a large cohort of hepatocellular lesions and NT (n = 290), non-hepatocellular malignancies (n = 383) and HAC (n = 13). Eight non-redundant, differentially expressed proteins were suitable for further immunohistochemical validation and four (ABAT, BHMT, FABP1, HAOX1) for further evaluation. Sensitivity and specificity rates for HCC/HAC were as follows: HepPar1 80.2%, 94.3% / 80.2%, 46.2%; Arginase1 82%, 99.4% / 82%, 69.2%; BHMT 61.4%, 93.8% / 61.4%, 100%; ABAT 84.4%, 33.7% / 84.4%, 30.8%; FABP1 87.2%, 95% / 87.2%, 69.2%; HAOX1 95.5%, 36.3% / 95.5%, 46.2%. The best 2×/3× biomarker panels for the diagnosis of HCC consisted of Arginase1/HAOX1 and BHMT/Arginase1/HAOX1 and for HAC consisted of Arginase1/FABP1 and BHMT/Arginase1/FABP1. In summary, we successfully identified, validated and benchmarked protein biomarker candidates of hepatocellular differentiation. BHMT in particular exhibited superior diagnostic characteristics in hepatocellular lesions and specifically in HAC. BHMT is therefore a promising (panel based) biomarker candidate in the differential diagnostic process of lesions with hepatocellular aspect.

  1. Tissue

    Directory of Open Access Journals (Sweden)

    David Morrissey

    2012-01-01

    Full Text Available Purpose. In vivo gene therapy directed at tissues of mesenchymal origin could potentially augment healing. We aimed to assess the duration and magnitude of transene expression in vivo in mice and ex vivo in human tissues. Methods. Using bioluminescence imaging, plasmid and adenoviral vector-based transgene expression in murine quadriceps in vivo was examined. Temporal control was assessed using a doxycycline-inducible system. An ex vivo model was developed and optimised using murine tissue, and applied in ex vivo human tissue. Results. In vivo plasmid-based transgene expression did not silence in murine muscle, unlike in liver. Although maximum luciferase expression was higher in muscle with adenoviral delivery compared with plasmid, expression reduced over time. The inducible promoter cassette successfully regulated gene expression with maximum levels a factor of 11 greater than baseline. Expression was re-induced to a similar level on a temporal basis. Luciferase expression was readily detected ex vivo in human muscle and tendon. Conclusions. Plasmid constructs resulted in long-term in vivo gene expression in skeletal muscle, in a controllable fashion utilising an inducible promoter in combination with oral agents. Successful plasmid gene transfection in human ex vivo mesenchymal tissue was demonstrated for the first time.

  2. Near Infrared Spectroscopy Systems for Tissue Oximetry

    DEFF Research Database (Denmark)

    Petersen, Søren Dahl

    for other medical applications. The tissue oximeters are realised by incorporation of pn-diodes into the silicon in order to form arrays of infrared detectors. These arrays can then be used for spatially resolved spectroscopy measurements, with the targeted end user being prematurely born infant children...

  3. Tissue doses in X-ray examinations of osteoarticular system

    International Nuclear Information System (INIS)

    Rabkin, I.Kh.; Stavitskij, R.V.; Blinov, N.N.; Vasil'ev, Yu.D.

    1985-01-01

    The X-ray method in diagnosis of the osteoarticular system disease is described. Problems on tissue dose distribution in X-ray examinations of a skeleton, a skull, humeral articulation, cervical, thoracic and lumbar vertebrae, hip joint, hipbones are considered. The values of specific tissue doses in roentgenography of the osteoarticular system are given

  4. Gene expression profiles help identify the Tissue of Origin for metastatic brain cancers

    Directory of Open Access Journals (Sweden)

    VandenBerg Scott R

    2010-04-01

    Full Text Available Abstract Background Metastatic brain cancers are the most common intracranial tumor and occur in about 15% of all cancer patients. In up to 10% of these patients, the primary tumor tissue remains unknown, even after a time consuming and costly workup. The Pathwork® Tissue of Origin Test (Pathwork Diagnostics, Redwood City, CA, USA is a gene expression test to aid in the diagnosis of metastatic, poorly differentiated and undifferentiated tumors. It measures the expression pattern of 1,550 genes in these tumors and compares it to the expression pattern of a panel of 15 known tumor types. The purpose of this study was to evaluate the performance of the Tissue of Origin Test in the diagnosis of primary sites for metastatic brain cancer patients. Methods Fifteen fresh-frozen metastatic brain tumor specimens of known origins met specimen requirements. These specimens were entered into the study and processed using the Tissue of Origin Test. Results were compared to the known primary site and the agreement between the two results was assessed. Results Fourteen of the fifteen specimens produced microarray data files that passed all quality metrics. One originated from a tissue type that was off-panel. Among the remaining 13 cases, the Tissue of Origin Test accurately predicted the available diagnosis in 12/13 (92.3% cases. Discussion This study demonstrates the accuracy of the Tissue of Origin Test when applied to predict the tissue of origin of metastatic brain tumors. This test could be a very useful tool for pathologists as they classify metastatic brain cancers.

  5. Tissue plasminogen activator; identifying major barriers related to intravenous injection in ischemic acute cerebral infraction

    Directory of Open Access Journals (Sweden)

    Fariborz Khorvash

    2017-01-01

    Full Text Available Background: According to previous publications, in patients with acute ischemic cerebral infarction, thrombolytic therapy using intravenous tissue plasminogen activator (IV-tPA necessitates precise documentation of symptoms' onset. The aim of this study was to identify major barriers related to the IV-tPA injection in such patients. Materials and Methods: Between the year 2014-2015, patients with definitive diagnosis of acute cerebral infarction (n = 180 who attended the neurology ward located at the Isfahan Alzahra Hospital were studied. To investigate barriers related to door to IV-tPA needle time, personal reasons, and criteria for inclusion or exclusion of patients, three questionnaire forms were designed based on the Food and Drug Administration-approved indications or contraindications. Results: The mean age of males versus females was 60 versus 77.5 years (ranged 23–93 vs. 29–70 years, respectively. Out of total population, only 10.7% transferred to hospital in <4.5 h after the onset of symptoms. Regarding to eligibility for IV-tPA, 68.9% of total population have had criteria for such treatment. Concerning to both items such as transferring to hospital in <4.5 h after the onset of symptoms and eligibility for IV-tPA, only 6.6% of total population met the criteria for such management. There was ignorance or inattention to symptoms in 75% of population studied. There was a mean of 195.92 ± 6.65 min (182.8–209.04 min for door to IV-tPA needle time. Conclusion: Despite the international guidelines for IV-tPA injection within 3–4.5 h of ischemic stroke symptoms' onset, the results of this study revealed that falling time due to ignorance of symptoms, literacy, and living alone might need further attention. As a result, to decrease death and disability, educational programs related to the symptoms' onset by consultant neurologist in Isfahan/Iran seem to be advantageous.

  6. Thrombomodulin Expression in Tissues From Dogs With Systemic Inflammatory Disease.

    Science.gov (United States)

    Kim, S D; Baker, P; DeLay, J; Wood, R D

    2016-07-01

    Thrombomodulin (TM) is a membrane glycoprotein expressed on endothelial cells, which plays a major role in the protein C anticoagulation pathway. In people with inflammation, TM expression can be down-regulated on endothelial cells and a soluble form released into circulation, resulting in increased risk of thrombosis and disseminated intravascular coagulation. TM is present in dogs; however, there has been minimal investigation of its expression in canine tissues, and the effects of inflammation on TM expression in canine tissues have not been investigated. The objective of this study was to evaluate endothelial TM expression in tissues from dogs with systemic inflammatory diseases. A retrospective evaluation of tissue samples of lung, spleen, and liver from dogs with and without systemic inflammatory diseases was performed using immunohistochemistry (IHC) and a modified manual IHC scoring system. TM expression was significantly reduced in all examined tissues in dogs diagnosed with septic peritonitis or acute pancreatitis. © The Author(s) 2016.

  7. A stratified transcriptomics analysis of polygenic fat and lean mouse adipose tissues identifies novel candidate obesity genes.

    Directory of Open Access Journals (Sweden)

    Nicholas M Morton

    Full Text Available Obesity and metabolic syndrome results from a complex interaction between genetic and environmental factors. In addition to brain-regulated processes, recent genome wide association studies have indicated that genes highly expressed in adipose tissue affect the distribution and function of fat and thus contribute to obesity. Using a stratified transcriptome gene enrichment approach we attempted to identify adipose tissue-specific obesity genes in the unique polygenic Fat (F mouse strain generated by selective breeding over 60 generations for divergent adiposity from a comparator Lean (L strain.To enrich for adipose tissue obesity genes a 'snap-shot' pooled-sample transcriptome comparison of key fat depots and non adipose tissues (muscle, liver, kidney was performed. Known obesity quantitative trait loci (QTL information for the model allowed us to further filter genes for increased likelihood of being causal or secondary for obesity. This successfully identified several genes previously linked to obesity (C1qr1, and Np3r as positional QTL candidate genes elevated specifically in F line adipose tissue. A number of novel obesity candidate genes were also identified (Thbs1, Ppp1r3d, Tmepai, Trp53inp2, Ttc7b, Tuba1a, Fgf13, Fmr that have inferred roles in fat cell function. Quantitative microarray analysis was then applied to the most phenotypically divergent adipose depot after exaggerating F and L strain differences with chronic high fat feeding which revealed a distinct gene expression profile of line, fat depot and diet-responsive inflammatory, angiogenic and metabolic pathways. Selected candidate genes Npr3 and Thbs1, as well as Gys2, a non-QTL gene that otherwise passed our enrichment criteria were characterised, revealing novel functional effects consistent with a contribution to obesity.A focussed candidate gene enrichment strategy in the unique F and L model has identified novel adipose tissue-enriched genes contributing to obesity.

  8. Microfluidic systems for stem cell-based neural tissue engineering.

    Science.gov (United States)

    Karimi, Mahdi; Bahrami, Sajad; Mirshekari, Hamed; Basri, Seyed Masoud Moosavi; Nik, Amirala Bakhshian; Aref, Amir R; Akbari, Mohsen; Hamblin, Michael R

    2016-07-05

    Neural tissue engineering aims at developing novel approaches for the treatment of diseases of the nervous system, by providing a permissive environment for the growth and differentiation of neural cells. Three-dimensional (3D) cell culture systems provide a closer biomimetic environment, and promote better cell differentiation and improved cell function, than could be achieved by conventional two-dimensional (2D) culture systems. With the recent advances in the discovery and introduction of different types of stem cells for tissue engineering, microfluidic platforms have provided an improved microenvironment for the 3D-culture of stem cells. Microfluidic systems can provide more precise control over the spatiotemporal distribution of chemical and physical cues at the cellular level compared to traditional systems. Various microsystems have been designed and fabricated for the purpose of neural tissue engineering. Enhanced neural migration and differentiation, and monitoring of these processes, as well as understanding the behavior of stem cells and their microenvironment have been obtained through application of different microfluidic-based stem cell culture and tissue engineering techniques. As the technology advances it may be possible to construct a "brain-on-a-chip". In this review, we describe the basics of stem cells and tissue engineering as well as microfluidics-based tissue engineering approaches. We review recent testing of various microfluidic approaches for stem cell-based neural tissue engineering.

  9. Biomaterials in co-culture systems: towards optimizing tissue integration and cell signaling within scaffolds.

    Science.gov (United States)

    Battiston, Kyle G; Cheung, Jane W C; Jain, Devika; Santerre, J Paul

    2014-05-01

    Most natural tissues consist of multi-cellular systems made up of two or more cell types. However, some of these tissues may not regenerate themselves following tissue injury or disease without some form of intervention, such as from the use of tissue engineered constructs. Recent studies have increasingly used co-cultures in tissue engineering applications as these systems better model the natural tissues, both physically and biologically. This review aims to identify the challenges of using co-culture systems and to highlight different approaches with respect to the use of biomaterials in the use of such systems. The application of co-culture systems to stimulate a desired biological response and examples of studies within particular tissue engineering disciplines are summarized. A description of different analytical co-culture systems is also discussed and the role of biomaterials in the future of co-culture research are elaborated on. Understanding the complex cell-cell and cell-biomaterial interactions involved in co-culture systems will ultimately lead the field towards biomaterial concepts and designs with specific biochemical, electrical, and mechanical characteristics that are tailored towards the needs of distinct co-culture systems. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. ABCD2 identifies a subclass of peroxisomes in mouse adipose tissue

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Xiaoxi, E-mail: xiaoxi.liu@uky.edu; Liu, Jingjing, E-mail: jingjing.liu0@gmail.com; Lester, Joshua D., E-mail: joshua.lester@uky.edu; Pijut, Sonja S., E-mail: srhee2@uky.edu; Graf, Gregory A., E-mail: Gregory.Graf@uky.edu

    2015-01-02

    Highlights: • We examined the D2 localization and the proteome of D2-containing compartment in mouse adipose tissue. • We confirmed the presence of D2 on a subcellular compartment that has typical structure as a microperoxisome. • We demonstrated the scarcity of peroxisome markers on D2-containing compartment. • The D2-containing compartment may be a subpopulation of peroxisome in mouse adipose tissue. • Proteomic data suggests potential association between D2-containing compartment and mitochondria and ER. - Abstract: ATP-binding cassette transporter D2 (D2) is an ABC half transporter that is thought to promote the transport of very long-chain fatty acyl-CoAs into peroxisomes. Both D2 and peroxisomes increase during adipogenesis. Although peroxisomes are essential to both catabolic and anabolic lipid metabolism, their function, and that of D2, in adipose tissues remain largely unknown. Here, we investigated the D2 localization and the proteome of D2-containing organelles, in adipose tissue. Centrifugation of mouse adipose homogenates generated a fraction enriched with D2, but deficient in peroxisome markers including catalase, PEX19, and ABCD3 (D3). Electron microscopic imaging of this fraction confirmed the presence of D2 protein on an organelle with a dense matrix and a diameter of ∼200 nm, the typical structure and size of a microperoxisome. D2 and PEX19 antibodies recognized distinct structures in mouse adipose. Immunoisolation of the D2-containing compartment confirmed the scarcity of PEX19 and proteomic profiling revealed the presence of proteins associated with peroxisome, endoplasmic reticulum (ER), and mitochondria. D2 is localized to a distinct class of peroxisomes that lack many peroxisome proteins, and may associate physically with mitochondria and the ER.

  11. Can MRI diffusion-weighted imaging identify postoperative residual/recurrent soft-tissue sarcomas?

    Directory of Open Access Journals (Sweden)

    Mai Maher ElDaly

    2018-01-01

    Full Text Available Purpose: The aim of this study was to evaluate contrast-enhanced magnetic resonance imaging (CE-MRI and quantitative diffusion-weighted imaging (DWI with apparent diffusion coefficient (ADC mapping in the detection of recurrent/residual postoperative soft tissue sarcomas. Materials and Methods: This study included 36 patients; 27 patients had postoperative recurrent/residual soft tissue sarcomas and 9 patients had postoperative and treatment-related changes (inflammation/fibrosis. The DWI was obtained with 3 b values including 0, 400, and 800 s/mm2. Calculation of the ADC value of the lesion was done via placing the region of interest (ROI to include the largest area of the lesion. ADC values were compared to histopathology. Results: Our results showed that including CE-MRI improved the diagnostic accuracy and sensitivity in recurrence detection compared to conventional non-enhanced sequences. However, it showed low specificity (55.56% with a high false-positive rate that may lead to an unnecessary biopsy of a mass such as region of postoperative scar tissue. Conclusion: The joint use of gadolinium-enhanced MRI and quantitative DWI with ADC mapping offer added value in the detection of recurrent/residual postoperative soft tissue sarcoma. This combined use increased both the diagnostic sensitivity and specificity with a cut-off average ADC value for detecting nonmyxoid recurrent/residual lesions ≤1.3 × 10−3 mm2/s (100% specificity and 90.48% sensitivity. Our results showed limited value of DWI with ADC mapping in assessing myxoid sarcomatous tumor recurrences.

  12. Systems Engineering-Based Tool for Identifying Critical Research Systems

    Science.gov (United States)

    Abbott, Rodman P.; Stracener, Jerrell

    2016-01-01

    This study investigates the relationship between the designated research project system independent variables of Labor, Travel, Equipment, and Contract total annual costs and the dependent variables of both the associated matching research project total annual academic publication output and thesis/dissertation number output. The Mahalanobis…

  13. Identifying digital records in business systems: the definition of a ...

    African Journals Online (AJOL)

    Before digital records can be preserved or managed, they need to be identified first. However, records identification is not a clearly defined process. Given the multi-faceted information system environment in organisations, large quantities of potential records are created and stored in systems not designed for records ...

  14. 5 CFR 838.611 - Identifying the retirement system.

    Science.gov (United States)

    2010-01-01

    ... order must contain language identifying the retirement system to be affected. For example, “CSRS,” “FERS... in paragraphs (b)(1) and (b)(2) of this section, language referring to benefits under another retirement system, such as military retired pay, Foreign Service retirement benefits or Central Intelligence...

  15. From control system security indices to attack identifiability

    NARCIS (Netherlands)

    Herdeiro Teixeira, A.M.; Sandberg, H

    2016-01-01

    In this paper, we investigate detectability and identifiability of attacks on linear dynamical systems that are subjected to external disturbances. We generalize a concept for a security index, which was previously introduced for static systems. The index exactly quantifies the resources

  16. Adaptive process triage system cannot identify patients with gastrointestinal perforation

    DEFF Research Database (Denmark)

    Bohm, Aske Mathias; Tolstrup, Mai-Britt; Gögenur, Ismail

    2017-01-01

    INTRODUCTION: Adaptive process triage (ADAPT) is a triage tool developed to assess the severity and address the priority of emergency patients. In 2009-2011, ADAPT was the most frequently used triage system in Denmark. Until now, no Danish triage system has been evaluated based on a selective group...... triaged as green or yellow had a GIP that was not identified by the triage system. CONCLUSION: ADAPT is incapable of identifying one of the most critically ill patient groups in need of emergency abdominal surgery. FUNDING: none. TRIAL REGISTRATION: HEH-2013-034 I-Suite: 02336....

  17. Microfluidic system for enhanced cardiac tissue formation

    Directory of Open Access Journals (Sweden)

    Busek Mathias

    2017-09-01

    Full Text Available Hereby a microfluidic system for cell cultivation is presented in which human pluripotent stem cell-derived cardiomyocytes were cultivated under perfusion. Besides micro-perfusion this system is also capable to produce well-defined oxygen contents, apply defined forces and has excellent imaging characteristics. Cardiomyocytes attach to the surface, start spontaneous beating and stay functional for up to 14 days under perfusion. The cell motion was subsequently analysed using an adapted video analysis script to calculate beating rate, beating direction and contraction or relaxation speed.

  18. Safe Exploration for Identifying Linear Systems via Robust Optimization

    OpenAIRE

    Lu, Tyler; Zinkevich, Martin; Boutilier, Craig; Roy, Binz; Schuurmans, Dale

    2017-01-01

    Safely exploring an unknown dynamical system is critical to the deployment of reinforcement learning (RL) in physical systems where failures may have catastrophic consequences. In scenarios where one knows little about the dynamics, diverse transition data covering relevant regions of state-action space is needed to apply either model-based or model-free RL. Motivated by the cooling of Google's data centers, we study how one can safely identify the parameters of a system model with a desired ...

  19. A novel CpG island set identifies tissue-specific methylation at developmental gene loci.

    Directory of Open Access Journals (Sweden)

    Robert Illingworth

    2008-01-01

    Full Text Available CpG islands (CGIs are dense clusters of CpG sequences that punctuate the CpG-deficient human genome and associate with many gene promoters. As CGIs also differ from bulk chromosomal DNA by their frequent lack of cytosine methylation, we devised a CGI enrichment method based on nonmethylated CpG affinity chromatography. The resulting library was sequenced to define a novel human blood CGI set that includes many that are not detected by current algorithms. Approximately half of CGIs were associated with annotated gene transcription start sites, the remainder being intra- or intergenic. Using an array representing over 17,000 CGIs, we established that 6%-8% of CGIs are methylated in genomic DNA of human blood, brain, muscle, and spleen. Inter- and intragenic CGIs are preferentially susceptible to methylation. CGIs showing tissue-specific methylation were overrepresented at numerous genetic loci that are essential for development, including HOX and PAX family members. The findings enable a comprehensive analysis of the roles played by CGI methylation in normal and diseased human tissues.

  20. Structural identifiability analysis of a cardiovascular system model.

    Science.gov (United States)

    Pironet, Antoine; Dauby, Pierre C; Chase, J Geoffrey; Docherty, Paul D; Revie, James A; Desaive, Thomas

    2016-05-01

    The six-chamber cardiovascular system model of Burkhoff and Tyberg has been used in several theoretical and experimental studies. However, this cardiovascular system model (and others derived from it) are not identifiable from any output set. In this work, two such cases of structural non-identifiability are first presented. These cases occur when the model output set only contains a single type of information (pressure or volume). A specific output set is thus chosen, mixing pressure and volume information and containing only a limited number of clinically available measurements. Then, by manipulating the model equations involving these outputs, it is demonstrated that the six-chamber cardiovascular system model is structurally globally identifiable. A further simplification is made, assuming known cardiac valve resistances. Because of the poor practical identifiability of these four parameters, this assumption is usual. Under this hypothesis, the six-chamber cardiovascular system model is structurally identifiable from an even smaller dataset. As a consequence, parameter values computed from limited but well-chosen datasets are theoretically unique. This means that the parameter identification procedure can safely be performed on the model from such a well-chosen dataset. Thus, the model may be considered suitable for use in diagnosis. Copyright © 2016 IPEM. Published by Elsevier Ltd. All rights reserved.

  1. Promoting tissue regeneration by modulating the immune system.

    Science.gov (United States)

    Julier, Ziad; Park, Anthony J; Briquez, Priscilla S; Martino, Mikaël M

    2017-04-15

    The immune system plays a central role in tissue repair and regeneration. Indeed, the immune response to tissue injury is crucial in determining the speed and the outcome of the healing process, including the extent of scarring and the restoration of organ function. Therefore, controlling immune components via biomaterials and drug delivery systems is becoming an attractive approach in regenerative medicine, since therapies based on stem cells and growth factors have not yet proven to be broadly effective in the clinic. To integrate the immune system into regenerative strategies, one of the first challenges is to understand the precise functions of the different immune components during the tissue healing process. While remarkable progress has been made, the immune mechanisms involved are still elusive, and there is indication for both negative and positive roles depending on the tissue type or organ and life stage. It is well recognized that the innate immune response comprising danger signals, neutrophils and macrophages modulates tissue healing. In addition, it is becoming evident that the adaptive immune response, in particular T cell subset activities, plays a critical role. In this review, we first present an overview of the basic immune mechanisms involved in tissue repair and regeneration. Then, we highlight various approaches based on biomaterials and drug delivery systems that aim at modulating these mechanisms to limit fibrosis and promote regeneration. We propose that the next generation of regenerative therapies may evolve from typical biomaterial-, stem cell-, or growth factor-centric approaches to an immune-centric approach. Most regenerative strategies have not yet proven to be safe or reasonably efficient in the clinic. In addition to stem cells and growth factors, the immune system plays a crucial role in the tissue healing process. Here, we propose that controlling the immune-mediated mechanisms of tissue repair and regeneration may support

  2. Structural and practical identifiability analysis of S-system.

    Science.gov (United States)

    Zhan, Choujun; Li, Benjamin Yee Shing; Yeung, Lam Fat

    2015-12-01

    In the field of systems biology, biological reaction networks are usually modelled by ordinary differential equations. A sub-class, the S-systems representation, is a widely used form of modelling. Existing S-systems identification techniques assume that the system itself is always structurally identifiable. However, due to practical limitations, biological reaction networks are often only partially measured. In addition, the captured data only covers a limited trajectory, therefore data can only be considered as a local snapshot of the system responses with respect to the complete set of state trajectories over the entire state space. Hence the estimated model can only reflect partial system dynamics and may not be unique. To improve the identification quality, the structural and practical identifiablility of S-system are studied. The S-system is shown to be identifiable under a set of assumptions. Then, an application on yeast fermentation pathway was conducted. Two case studies were chosen; where the first case is based on a larger state trajectories and the second case is based on a smaller one. By expanding the dataset which span a relatively larger state space, the uncertainty of the estimated system can be reduced. The results indicated that initial concentration is related to the practical identifiablity.

  3. Advances in polymeric systems for tissue engineering and biomedical applications.

    Science.gov (United States)

    Ravichandran, Rajeswari; Sundarrajan, Subramanian; Venugopal, Jayarama Reddy; Mukherjee, Shayanti; Ramakrishna, Seeram

    2012-03-01

    The characteristics of tissue engineered scaffolds are major concerns in the quest to fabricate ideal scaffolds for tissue engineering applications. The polymer scaffolds employed for tissue engineering applications should possess multifunctional properties such as biocompatibility, biodegradability and favorable mechanical properties as it comes in direct contact with the body fluids in vivo. Additionally, the polymer system should also possess biomimetic architecture and should support stem cell adhesion, proliferation and differentiation. As the progress in polymer technology continues, polymeric biomaterials have taken characteristics more closely related to that desired for tissue engineering and clinical needs. Stimuli responsive polymers also termed as smart biomaterials respond to stimuli such as pH, temperature, enzyme, antigen, glucose and electrical stimuli that are inherently present in living systems. This review highlights the exciting advancements in these polymeric systems that relate to biological and tissue engineering applications. Additionally, several aspects of technology namely scaffold fabrication methods and surface modifications to confer biological functionality to the polymers have also been discussed. The ultimate objective is to emphasize on these underutilized adaptive behaviors of the polymers so that novel applications and new generations of smart polymeric materials can be realized for biomedical and tissue engineering applications. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. 5 CFR 838.911 - Identifying the retirement system.

    Science.gov (United States)

    2010-01-01

    .... (a) To satisfy the requirements of § 838.804(b)(1), a court order must contain language identifying...) and (b)(2) of this section, language referring to benefits under another retirement system, such as military retired pay, Foreign Service retirement benefits and Central Intelligence Agency retirement...

  5. Kinase Gene Expression Profiling of Metastatic Clear Cell Renal Cell Carcinoma Tissue Identifies Potential New Therapeutic Targets.

    Directory of Open Access Journals (Sweden)

    Pooja Ghatalia

    Full Text Available Kinases are therapeutically actionable targets. Kinase inhibitors targeting vascular endothelial growth factor receptors (VEGFR and mammalian target of rapamycin (mTOR improve outcomes in metastatic clear cell renal cell carcinoma (ccRCC, but are not curative. Metastatic tumor tissue has not been comprehensively studied for kinase gene expression. Paired intra-patient kinase gene expression analysis in primary tumor (T, matched normal kidney (N and metastatic tumor tissue (M may assist in identifying drivers of metastasis and prioritizing therapeutic targets. We compared the expression of 519 kinase genes using NanoString in T, N and M in 35 patients to discover genes over-expressed in M compared to T and N tissue. RNA-seq data derived from ccRCC tumors in The Cancer Genome Atlas (TCGA were used to demonstrate differential expression of genes in primary tumor tissue from patients that had metastasis at baseline (n = 79 compared to those that did not develop metastasis for at least 2 years (n = 187. Functional analysis was conducted to identify key signaling pathways by using Ingenuity Pathway Analysis. Of 10 kinase genes overexpressed in metastases compared to primary tumor in the discovery cohort, 9 genes were also differentially expressed in TCGA primary tumors with metastasis at baseline compared to primary tumors without metastasis for at least 2 years: EPHB2, AURKA, GSG2, IKBKE, MELK, CSK, CHEK2, CDC7 and MAP3K8; p<0.001. The top pathways overexpressed in M tissue were pyridoxal 5'-phosphate salvage, salvage pathways of pyrimidine ribonucleotides, NF-kB signaling, NGF signaling and cell cycle control of chromosomal replication. The 9 kinase genes validated to be over-expressed in metastatic ccRCC may represent currently unrecognized but potentially actionable therapeutic targets that warrant functional validation.

  6. Optical redox imaging of fixed unstained tissue slides to identify biomarkers for breast cancer diagnosis/prognosis: feasibility study

    Science.gov (United States)

    Xu, He N.; Tchou, Julia; Li, Yusheng; Feng, Min; Zhang, Paul; Quinn, William J.; Baur, Joseph A.; Li, Lin Z.

    2018-02-01

    We previously showed that optical redox imaging (ORI) of snap-frozen breast biopsies by the Chance redox scanner readily discriminates cancer from normal tissue. Moreover, indices of redox heterogeneity differentiate among tumor xenografts with different metastatic potential. These observations suggest that ORI of fluorescence of NADH and oxidized flavoproteins (Fp) may provide diagnostic/prognostic value for clinical applications. In this work, we investigate whether ORI of formalin-fixed-paraffin-embedded (FFPE) unstained clinical tissue slides of breast tumors is feasible and comparable to ORI of snap-frozen tumors. If ORI of FFPE is validated, it will enhance the versatility of ORI as a novel diagnostic/prognostic assay as FFPE samples are readily available. ORI of fixed tissue slides was performed using a fluorescence microscope equipped with a precision automated stage and appropriate optical filters. We developed a vignette correction algorithm to remove the tiling effect of stitched-images. The preliminary data from imaging fixed slides of breast tumor xenografts showed intratumor redox heterogeneity patterns similar to that of the frozen tissues imaged by the Chance redox scanner. From ORI of human breast tissue slides we identified certain redox differences among normal, ductal carcinoma in situ, and invasive carcinoma. We found paraformaldehyde fixation causes no change in NADH signals but enhances Fp signals of fresh muscle fibers. We also investigated the stability of the fluorescence microscope and reproducibility of tissue slide fluorescence signals. We plan to validate the diagnostic/prognostic value of ORI using clinically annotated breast cancer sample set from patients with long-term follow-up data.

  7. Tissue Equivalent Phantom Design for Characterization of a Coherent Scatter X-ray Imaging System

    Science.gov (United States)

    Albanese, Kathryn Elizabeth

    Scatter in medical imaging is typically cast off as image-related noise that detracts from meaningful diagnosis. It is therefore typically rejected or removed from medical images. However, it has been found that every material, including cancerous tissue, has a unique X-ray coherent scatter signature that can be used to identify the material or tissue. Such scatter-based tissue-identification provides the advantage of locating and identifying particular materials over conventional anatomical imaging through X-ray radiography. A coded aperture X-ray coherent scatter spectral imaging system has been developed in our group to classify different tissue types based on their unique scatter signatures. Previous experiments using our prototype have demonstrated that the depth-resolved coherent scatter spectral imaging system (CACSSI) can discriminate healthy and cancerous tissue present in the path of a non-destructive x-ray beam. A key to the successful optimization of CACSSI as a clinical imaging method is to obtain anatomically accurate phantoms of the human body. This thesis describes the development and fabrication of 3D printed anatomical scatter phantoms of the breast and lung. The purpose of this work is to accurately model different breast geometries using a tissue equivalent phantom, and to classify these tissues in a coherent x-ray scatter imaging system. Tissue-equivalent anatomical phantoms were designed to assess the capability of the CACSSI system to classify different types of breast tissue (adipose, fibroglandular, malignant). These phantoms were 3D printed based on DICOM data obtained from CT scans of prone breasts. The phantoms were tested through comparison of measured scatter signatures with those of adipose and fibroglandular tissue from literature. Tumors in the phantom were modeled using a variety of biological tissue including actual surgically excised benign and malignant tissue specimens. Lung based phantoms have also been printed for future

  8. Gene expression profiling of prostate tissue identifies chromatin regulation as a potential link between obesity and lethal prostate cancer.

    Science.gov (United States)

    Ebot, Ericka M; Gerke, Travis; Labbé, David P; Sinnott, Jennifer A; Zadra, Giorgia; Rider, Jennifer R; Tyekucheva, Svitlana; Wilson, Kathryn M; Kelly, Rachel S; Shui, Irene M; Loda, Massimo; Kantoff, Philip W; Finn, Stephen; Vander Heiden, Matthew G; Brown, Myles; Giovannucci, Edward L; Mucci, Lorelei A

    2017-11-01

    Obese men are at higher risk of advanced prostate cancer and cancer-specific mortality; however, the biology underlying this association remains unclear. This study examined gene expression profiles of prostate tissue to identify biological processes differentially expressed by obesity status and lethal prostate cancer. Gene expression profiling was performed on tumor (n = 402) and adjacent normal (n = 200) prostate tissue from participants in 2 prospective cohorts who had been diagnosed with prostate cancer from 1982 to 2005. Body mass index (BMI) was calculated from the questionnaire immediately preceding cancer diagnosis. Men were followed for metastases or prostate cancer-specific death (lethal disease) through 2011. Gene Ontology biological processes differentially expressed by BMI were identified using gene set enrichment analysis. Pathway scores were computed by averaging the signal intensities of member genes. Odds ratios (ORs) for lethal prostate cancer were estimated with logistic regression. Among 402 men, 48% were healthy weight, 31% were overweight, and 21% were very overweight/obese. Fifteen gene sets were enriched in tumor tissue, but not normal tissue, of very overweight/obese men versus healthy-weight men; 5 of these were related to chromatin modification and remodeling (false-discovery rate 7, 41% vs 17%; P = 2 × 10 -4 ) and an increased risk of lethal disease that was independent of grade and stage (OR, 5.26; 95% confidence interval, 2.37-12.25). This study improves our understanding of the biology of aggressive prostate cancer and identifies a potential mechanistic link between obesity and prostate cancer death that warrants further study. Cancer 2017;123:4130-4138. © 2017 American Cancer Society. © 2017 American Cancer Society.

  9. A Framework for Identifying and Understanding Enterprise Systems Benefits

    DEFF Research Database (Denmark)

    Schubert, Petra; Williams, Susan P.

    2011-01-01

    Purpose – Identifying the benefits arising from implementations of enterprise systems and realizing business value remains a significant challenge for both research and industry. This paper aims to consolidate previous work. It presents a framework for investigating enterprise systems benefits...... into aspects and criteria plus an attributed appraisal value. The resulting scheme for the “three-level benefit codes” provides a greater level of detail about the nature of expected and realized benefits. Practical implications – The high level of detail and the code scheme comprising 60 different codes...... and the method for deriving the codes allows companies to identify and define benefits as well as to assess the outcome of enterprise systems implementation projects. Originality/value – The paper empirically develops an applicable benefits framework, which addresses the lack of detail of previous frameworks....

  10. TissueCypher™: A systems biology approach to anatomic pathology

    Directory of Open Access Journals (Sweden)

    Jeffrey W Prichard

    2015-01-01

    Full Text Available Background: Current histologic methods for diagnosis are limited by intra- and inter-observer variability. Immunohistochemistry (IHC methods are frequently used to assess biomarkers to aid diagnoses, however, IHC staining is variable and nonlinear and the manual interpretation is subjective. Furthermore, the biomarkers assessed clinically are typically biomarkers of epithelial cell processes. Tumors and premalignant tissues are not composed only of epithelial cells but are interacting systems of multiple cell types, including various stromal cell types that are involved in cancer development. The complex network of the tissue system highlights the need for a systems biology approach to anatomic pathology, in which quantification of system processes is combined with informatics tools to produce actionable scores to aid clinical decision-making. Aims: Here, we describe a quantitative, multiplexed biomarker imaging approach termed TissueCypher™ that applies systems biology to anatomic pathology. Applications of TissueCypher™ in understanding the tissue system of Barrett's esophagus (BE and the potential use as an adjunctive tool in the diagnosis of BE are described. Patients and Methods: The TissueCypher™ Image Analysis Platform was used to assess 14 epithelial and stromal biomarkers with known diagnostic significance in BE in a set of BE biopsies with nondysplastic BE with reactive atypia (RA, n = 22 and Barrett's with high-grade dysplasia (HGD, n = 17. Biomarker and morphology features were extracted and evaluated in the confirmed BE HGD cases versus the nondysplastic BE cases with RA. Results: Multiple image analysis features derived from epithelial and stromal biomarkers, including immune biomarkers and morphology, showed significant differences between HGD and RA. Conclusions: The assessment of epithelial cell abnormalities combined with an assessment of cellular changes in the lamina propria may serve as an adjunct to conventional

  11. Serial analysis of gene expression identifies connective tissue growth factor expression as a prognostic biomarker in gallbladder cancer.

    Science.gov (United States)

    Alvarez, Hector; Corvalan, Alejandro; Roa, Juan C; Argani, Pedram; Murillo, Francisco; Edwards, Jennifer; Beaty, Robert; Feldmann, Georg; Hong, Seung-Mo; Mullendore, Michael; Roa, Ivan; Ibañez, Luis; Pimentel, Fernando; Diaz, Alfonso; Riggins, Gregory J; Maitra, Anirban

    2008-05-01

    Gallbladder cancer (GBC) is an uncommon neoplasm in the United States, but one with high mortality rates. This malignancy remains largely understudied at the molecular level such that few targeted therapies or predictive biomarkers exist. We built the first series of serial analysis of gene expression (SAGE) libraries from GBC and nonneoplastic gallbladder mucosa, composed of 21-bp long-SAGE tags. SAGE libraries were generated from three stage-matched GBC patients (representing Hispanic/Latino, Native American, and Caucasian ethnicities, respectively) and one histologically alithiasic gallbladder. Real-time quantitative PCR was done on microdissected epithelium from five matched GBC and corresponding nonneoplastic gallbladder mucosa. Immunohistochemical analysis was done on a panel of 182 archival GBC in high-throughput tissue microarray format. SAGE tags corresponding to connective tissue growth factor (CTGF) transcripts were identified as differentially overexpressed in all pairwise comparisons of GBC (P Cancer Genome Anatomy Project web site and should facilitate much needed research into this lethal neoplasm.

  12. Identifying Potential Weapon Systems That Can Be Divested

    Science.gov (United States)

    2016-04-08

    sustainment cost mitigation strategies include reduce supply chain by maximizing multi-role equipment, reduce divestiture obstacles/friction points...question. Extensive search of the internet government websites were used to find government information and open access articles related to the research...they did not use it, and if they use anything thing else to identify these low priority systems. The intent of the survey was not to get into

  13. SECONDARY PULMONARY ARTERIAL HYPERTENSION IN SYSTEMIC DISEASES OF CONNECTIVE TISSUE

    Directory of Open Access Journals (Sweden)

    N. A. Shostak

    2016-01-01

    Full Text Available Modern definition of pulmonary arterial hypertension (PAH as well as data on prevalence and incidence of secondary PAH in systemic disease of connective tissue is presented,  including data of USA, France and Scotland registers. The main chains of pathogenesis, classification approaches, clinical features and diagnostics are described. 

  14. SECONDARY PULMONARY ARTERIAL HYPERTENSION IN SYSTEMIC DISEASES OF CONNECTIVE TISSUE

    Directory of Open Access Journals (Sweden)

    N. A. Shostak

    2009-01-01

    Full Text Available Modern definition of pulmonary arterial hypertension (PAH as well as data on prevalence and incidence of secondary PAH in systemic disease of connective tissue is presented,  including data of USA, France and Scotland registers. The main chains of pathogenesis, classification approaches, clinical features and diagnostics are described. 

  15. A photoacoustic tomography system for imaging of biological tissues

    International Nuclear Information System (INIS)

    Su Yixiong; Zhang Fan; Xu Kexin; Yao Jianquan; Wang, Ruikang K

    2005-01-01

    Non-invasive laser-induced photoacoustic tomography (PAT) is a promising imaging modality in the biomedical optical imaging field. This technology, based on the intrinsic optical properties of tissue and ultrasonic detection, overcomes the resolution disadvantage of pure-optical imaging caused by strong light scattering and the contrast and speckle disadvantages of pure ultrasonic imaging. Here, we report a PAT experimental system constructed in our laboratory. In our system, a Q-switched Nd : YAG pulse laser operated at 532 nm with a 8 ns pulse width is used to generate a photoacoustic signal. By using this system, the two-dimensional distribution of optical absorption in the tissue-mimicking phantom is reconstructed and has an excellent agreement with the original ones. The spatial resolution of the imaging system approaches 100 μm through about 4 cm of highly scattering medium

  16. The PAXgene(® tissue system preserves phosphoproteins in human tissue specimens and enables comprehensive protein biomarker research.

    Directory of Open Access Journals (Sweden)

    Sibylle Gündisch

    Full Text Available Precise quantitation of protein biomarkers in clinical tissue specimens is a prerequisite for accurate and effective diagnosis, prognosis, and personalized medicine. Although progress is being made, protein analysis from formalin-fixed and paraffin-embedded tissues is still challenging. In previous reports, we showed that the novel formalin-free tissue preservation technology, the PAXgene Tissue System, allows the extraction of intact and immunoreactive proteins from PAXgene-fixed and paraffin-embedded (PFPE tissues. In the current study, we focused on the analysis of phosphoproteins and the applicability of two-dimensional gel electrophoresis (2D-PAGE and enzyme-linked immunosorbent assay (ELISA to the analysis of a variety of malignant and non-malignant human tissues. Using western blot analysis, we found that phosphoproteins are quantitatively preserved in PFPE tissues, and signal intensities are comparable to that in paired, frozen tissues. Furthermore, proteins extracted from PFPE samples are suitable for 2D-PAGE and can be quantified by ELISA specific for denatured proteins. In summary, the PAXgene Tissue System reliably preserves phosphoproteins in human tissue samples, even after prolonged fixation or stabilization times, and is compatible with methods for protein analysis such as 2D-PAGE and ELISA. We conclude that the PAXgene Tissue System has the potential to serve as a versatile tissue fixative for modern pathology.

  17. Artery Soft-Tissue Modelling for Stent Implant Training System

    Directory of Open Access Journals (Sweden)

    Giovanni Aloisio

    2004-08-01

    Full Text Available Virtual reality technology can be utilised to provide new systematic training methods for surgical procedures. Our aim is to build a simulator that allows medical students to practice the coronary stent implant procedure and avoids exposing patients to risks. The designed simulation system consists of a virtual environment and a haptic interface, in order to provide both the visualization of the coronary arteries and the tactile and force feedback generated during the interactions of the surgical instruments in the virtual environment. Since the arteries are soft tissues, their shape may change during an operation; for this reason physical modelling of the organs is necessary to render their behaviour under the influence of surgeon's instruments. The idea is to define a model that computes the displacement of the tissue versus time; from the displacement it is possible to calculate the response of the tissue to the surgical tool external stimuli. Information about tools displacements and tissue responses are also used to graphically model the artery wall and virtual surgical instrument deformations generated as a consequence of their coming into contact. In order to obtain a realistic simulation, the Finite Element Method has been used to model the soft tissues of the artery, using linear elasticity to reduce computational time and speed up interaction rates.

  18. Identifying inaccuracy of MS Project using system analysis

    Science.gov (United States)

    Fachrurrazi; Husin, Saiful; Malahayati, Nurul; Irzaidi

    2018-05-01

    The problem encountered in project owner’s financial accounting report is the difference in total project costs of MS Project to the Indonesian Standard (Standard Indonesia Standard / Cost Estimating Standard Book of Indonesia). It is one of the MS Project problems concerning to its cost accuracy, so cost data cannot be used in an integrated way for all project components. This study focuses on finding the causes of inaccuracy of the MS Projects. The aim of this study, which is operationally, are: (i) identifying cost analysis procedures for both current methods (SNI) and MS Project; (ii) identifying cost bias in each element of the cost analysis procedure; and (iii) analysing the cost differences (cost bias) in each element to identify what the cause of inaccuracies in MS Project toward SNI is. The method in this study is comparing for both the system analysis of MS Project and SNI. The results are: (i) MS Project system in Work of Resources element has limitation for two decimal digits only, have led to its inaccuracy. Where the Work of Resources (referred to as effort) in MS Project represents multiplication between the Quantities of Activities and Requirements of resources in SNI; (ii) MS Project and SNI have differences in the costing methods (the cost estimation methods), in which the SNI uses the Quantity-Based Costing (QBC), meanwhile MS Project uses the Time-Based Costing (TBC). Based on this research, we recommend to the contractors who use SNI should make an adjustment for Work of Resources in MS Project (with correction index) so that it can be used in an integrated way to the project owner’s financial accounting system. Further research will conduct for improvement the MS Project as an integrated tool toward all part of the project participant.

  19. Identifying gene coexpression networks underlying the dynamic regulation of wood-forming tissues in Populus under diverse environmental conditions.

    Science.gov (United States)

    Zinkgraf, Matthew; Liu, Lijun; Groover, Andrew; Filkov, Vladimir

    2017-06-01

    Trees modify wood formation through integration of environmental and developmental signals in complex but poorly defined transcriptional networks, allowing trees to produce woody tissues appropriate to diverse environmental conditions. In order to identify relationships among genes expressed during wood formation, we integrated data from new and publically available datasets in Populus. These datasets were generated from woody tissue and include transcriptome profiling, transcription factor binding, DNA accessibility and genome-wide association mapping experiments. Coexpression modules were calculated, each of which contains genes showing similar expression patterns across experimental conditions, genotypes and treatments. Conserved gene coexpression modules (four modules totaling 8398 genes) were identified that were highly preserved across diverse environmental conditions and genetic backgrounds. Functional annotations as well as correlations with specific experimental treatments associated individual conserved modules with distinct biological processes underlying wood formation, such as cell-wall biosynthesis, meristem development and epigenetic pathways. Module genes were also enriched for DNase I hypersensitivity footprints and binding from four transcription factors associated with wood formation. The conserved modules are excellent candidates for modeling core developmental pathways common to wood formation in diverse environments and genotypes, and serve as testbeds for hypothesis generation and testing for future studies. No claim to original US government works. New Phytologist © 2017 New Phytologist Trust.

  20. Evolution of NASA's Earth Science Digital Object Identifier Registration System

    Science.gov (United States)

    Wanchoo, Lalit; James, Nathan

    2017-01-01

    NASA's Earth Science Data and Information System (ESDIS) Project has implemented a fully automated system for assigning Digital Object Identifiers (DOIs) to Earth Science data products being managed by its network of 12 distributed active archive centers (DAACs). A key factor in the successful evolution of the DOI registration system over last 7 years has been the incorporation of community input from three focus groups under the NASA's Earth Science Data System Working Group (ESDSWG). These groups were largely composed of DOI submitters and data curators from the 12 data centers serving the user communities of various science disciplines. The suggestions from these groups were formulated into recommendations for ESDIS consideration and implementation. The ESDIS DOI registration system has evolved to be fully functional with over 5,000 publicly accessible DOIs and over 200 DOIs being held in reserve status until the information required for registration is obtained. The goal is to assign DOIs to the entire 8000+ data collections under ESDIS management via its network of discipline-oriented data centers. DOIs make it easier for researchers to discover and use earth science data and they enable users to provide valid citations for the data they use in research. Also for the researcher wishing to reproduce the results presented in science publications, the DOI can be used to locate the exact data or data products being cited.

  1. Identifying The Most Applicable Renewable Energy Systems Of Iran

    Directory of Open Access Journals (Sweden)

    Nasibeh Mousavi

    2017-03-01

    Full Text Available These years because of energy crisis all of country try to find a new way to reduce energy consumptions and obtain maximum use of renewable energy. Iran also is not an exception of this progress. Renewable energy is energy that is provided by renewable sources such as the sun or wind. In general renewable energies are not adaptable to every single community. Because of location and special climate conditions of Iran most applicable renewable energy systems in Iran are solar and wind energy. Main purpose of this paper is to review and identify most applicable renewable energy systems of Iran and also review on traditional and current methods that utilized to obtain maximum use of these renewable energies.

  2. Using HFACS-Healthcare to Identify Systemic Vulnerabilities During Surgery.

    Science.gov (United States)

    Cohen, Tara N; Francis, Sarah E; Wiegmann, Douglas A; Shappell, Scott A; Gewertz, Bruce L

    2018-03-01

    The Human Factors Analysis and Classification System for Healthcare (HFACS-Healthcare) was used to classify surgical near miss events reported via a hospital's event reporting system over the course of 1 year. Two trained analysts identified causal factors within each event narrative and subsequently categorized the events using HFACS-Healthcare. Of 910 original events, 592 could be analyzed further using HFACS-Healthcare, resulting in the identification of 726 causal factors. Most issues (n = 436, 60.00%) involved preconditions for unsafe acts, followed by unsafe acts (n = 257, 35.39%), organizational influences (n = 27, 3.72%), and supervisory factors (n = 6, 0.82%). These findings go beyond the traditional methods of trending incident data that typically focus on documenting the frequency of their occurrence. Analyzing near misses based on their underlying contributing human factors affords a greater opportunity to develop process improvements to reduce reoccurrence and better provide patient safety approaches.

  3. A computer model for identifying security system upgrades

    International Nuclear Information System (INIS)

    Lamont, A.

    1988-01-01

    This paper describes a prototype safeguards analysis tool that automatically identifies system weaknesses against an insider adversary and suggest possible upgrades to improve the probability that the adversary will be detected. The tool is based on this premise: as the adversary acts, he or she creates a set of facts that can be detected by safeguards components. Whenever an adversary's planned set of actions create a set of facts which the security personnel would consider irregular or unusual, we can improve the security system by implementing safeguards that detect those facts. Therefore, an intelligent computer program can suggest upgrades to the facility if we construct a knowledge base that contains information about: (1) the facts created by each possible adversary action, (2) the facts that each possible safeguard can detect, and (3) groups of facts which will be considered irregular whenever they occur together. The authors describe the structure of the knowledge base and show how the above information can be represented in it. They also describe the procedures that a computer program can use to identify missing or weak safeguards and to suggest upgrades

  4. System for tissue characterization using synchronous detection of diffuse reflectance

    International Nuclear Information System (INIS)

    Morales Lopez, Orestes M.; Stolik Isakina, Suren; La Rosa Vazquez, Jose Manuel de; Valor Reed, Alma

    2016-01-01

    The development of a system for the characterization of tissues optical properties in-vivo by synchronous detection of diffuse reflectance is presented. The system comprises an exploring probe with a linear spatial arrangement of optical fibers coupled to six lasers of 650 nm wavelength and a photodiode. The system also includes a preamplifier circuit for the photodiode, a driver for the amplitude modulation of the light signal of the lasers with optical power monitoring, a digital phase splitter for reference signal generation, an amplifying circuit with digitally switch able gain, a double phase demodulation circuit, an Arduino, and a control interface developed in LabVIEW. (Author)

  5. Metabolic labeling of sialic acids in tissue culture cell lines: methods to identify substituted and modified radioactive neuraminic acids

    International Nuclear Information System (INIS)

    Diaz, S.; Varki, A.

    1985-01-01

    The parent sialic acid N-acetylneuraminic acid can be modified or substituted in various ways, giving rise to a family of more than 25 compounds. The definitive identification of these compounds has previously required isolation of nanomole amounts for mass spectrometry or NMR. We have explored the possibility of using the known metabolic precursors of the sialic acids, particularly N-acetyl-[6-3H]mannosamine, to label and identify various forms of sialic acids in tissue culture cells. Firstly, we defined several variables that affect the labeling of sialic acids with N-acetyl-[6-3H]mannosamine. Secondly, we have devised a simple screening method to identify cell lines that synthesize substituted or modified sialic acids. We next demonstrate that it is possible to definitively identify the natures of the various labeled sialic acids without the use of mass spectrometry, even though they are present only in tracer amounts. The methods used include paper chromatography, analytical de-O-acetylation, periodate release of the 9-3H as [3H]formaldehyde (which is subsequently converted to a specific 3H-labeled chromophore), acylneuraminate pyruvate lyase treatment with identification of [3H]acylmannosamines, gas-liquid chromatography with radioactive detection, and two new high-pressure liquid chromatography methods utilizing the amine-adsorption:ion suppression and ion-pair principles. The use of an internal N-acetyl-[4-14C]neuraminic acid standard in each of these methods assures precision and accuracy. The combined use of these methods now allows the identification of radioactive tracer amounts of the various types of sialic acids in well-defined populations of tissue culture cells; it may also allow the identification of hitherto unknown forms of sialic acids

  6. Multi-Stream Saline-Jet Dissection Using a Simple Irrigation System Defines Difficult Tissue Planes

    Science.gov (United States)

    Ng, Philip CH

    2010-01-01

    Introduction: Single-stream hydro-jet dissection is increasingly used in various laparoscopic procedures, but its use requires special equipment. We describe a simple method for using an irrigation system for saline-jet tissue dissection as a useful adjunct prior to adhesiolysis. Material and Methods: Intraabdominal adhesions prolong laparoscopic procedures, because tissue planes are difficult to identify. We performed multi-jet saline dissection (MSSJ) between 2000 and 2009 in more than 500 patients during laparoscopy involving hernias, gallbladders, appendices, and intestinal obstructions. We use a standard suction irrigation probe, which is attached to a 1-liter saline bag with an inflatable cuff around to create a pressure of 250mm Hg to 300mm Hg. In effect, this is the standard setup generally used for irrigation. After using saline dissection, tissue planes can be better defined and the structures can then be separated. Result and Discussion: Using this method, we have successfully identified tissue planes in spite of dense adhesions, and our conversion rates to open have been reduced dramatically. This method is relatively safer than other modalities of tissue dissection, such as diathermy, ultrasonic, blunt or sharp dissection. The disadvantage is that with tissues saturated with saline it becomes more difficult to use diathermy hemostasis. Care has to be exercised in monitoring the temperature and volume of the fluid used. PMID:20529528

  7. Combined gene expression analysis of whole-tissue and microdissected pancreatic ductal adenocarcinoma identifies genes specifically overexpressed in tumor epithelia.

    Science.gov (United States)

    Badea, Liviu; Herlea, Vlad; Dima, Simona Olimpia; Dumitrascu, Traian; Popescu, Irinel

    2008-01-01

    The precise details of pancreatic ductal adenocarcinoma (PDAC) pathogenesis are still insufficiently known, requiring the use of high-throughput methods. However, PDAC is especially difficult to study using microarrays due to its strong desmoplastic reaction, which involves a hyperproliferating stroma that effectively "masks" the contribution of the minoritary neoplastic epithelial cells. Thus it is not clear which of the genes that have been found differentially expressed between normal and whole tumor tissues are due to the tumor epithelia and which simply reflect the differences in cellular composition. To address this problem, laser microdissection studies have been performed, but these have to deal with much smaller tissue sample quantities and therefore have significantly higher experimental noise. In this paper we combine our own large sample whole-tissue study with a previously published smaller sample microdissection study by Grützmann et al. to identify the genes that are specifically overexpressed in PDAC tumor epithelia. The overlap of this list of genes with other microarray studies of pancreatic cancer as well as with the published literature is impressive. Moreover, we find a number of genes whose over-expression appears to be inversely correlated with patient survival: keratin 7, laminin gamma 2, stratifin, platelet phosphofructokinase, annexin A2, MAP4K4 and OACT2 (MBOAT2), which are all specifically upregulated in the neoplastic epithelia, rather than the tumor stroma. We improve on other microarray studies of PDAC by putting together the higher statistical power due to a larger number of samples with information about cell-type specific expression and patient survival.

  8. Systemic connective tissue features in women with fibromuscular dysplasia.

    Science.gov (United States)

    O'Connor, Sarah; Kim, Esther Sh; Brinza, Ellen; Moran, Rocio; Fendrikova-Mahlay, Natalia; Wolski, Kathy; Gornik, Heather L

    2015-10-01

    Fibromuscular dysplasia (FMD) is a non-atherosclerotic disease associated with hypertension, headache, dissection, stroke, and aneurysm. The etiology is unknown but hypothesized to involve genetic and environmental components. Previous studies suggest a possible overlap of FMD with other connective tissue diseases that present with dissections and aneurysms. The aim of this study was to investigate the prevalence of connective tissue physical features in FMD. A total of 142 FMD patients were consecutively enrolled at a single referral center (97.9% female, 92.1% of whom had multifocal FMD). Data are reported for 139 female patients. Moderately severe myopia (29.1%), high palate (33.1%), dental crowding (29.7%), and early-onset arthritis (15.6%) were prevalent features. Classic connective features such as hypertelorism, cleft palate, and hypermobility were uncommon. The frequency of systemic connective tissue features was compared between FMD patients with a high vascular risk profile (having had ⩾1 dissection and/or ⩾2 aneurysms) and those with a standard vascular risk profile. A history of spontaneous pneumothorax (5.9% high risk vs 0% standard risk) and atrophic scarring (17.6% high risk vs 6.8% standard risk) were significantly more prevalent in the high risk group, pconnective tissue features such as high palate and pneumothorax were more prominent among FMD patients with a high vascular risk profile. © The Author(s) 2015.

  9. Genetic differences in transcript responses to low-dose ionizing radiation identify tissue functions associated with breast cancer susceptibility.

    Science.gov (United States)

    Snijders, Antoine M; Marchetti, Francesco; Bhatnagar, Sandhya; Duru, Nadire; Han, Ju; Hu, Zhi; Mao, Jian-Hua; Gray, Joe W; Wyrobek, Andrew J

    2012-01-01

    High dose ionizing radiation (IR) is a well-known risk factor for breast cancer but the health effects after low-dose (LD, differences in their sensitivity to radiation-induced mammary cancer (BALB/c and C57BL/6) for the purpose of identifying mechanisms of mammary cancer susceptibility. Unirradiated mammary and blood tissues of these strains differed significantly in baseline expressions of DNA repair, tumor suppressor, and stress response genes. LD exposures of 7.5 cGy (weekly for 4 weeks) did not induce detectable genomic instability in either strain. However, the mammary glands of the sensitive strain but not the resistant strain showed early transcriptional responses involving: (a) diminished immune response, (b) increased cellular stress, (c) altered TGFβ-signaling, and (d) inappropriate expression of developmental genes. One month after LD exposure, the two strains showed opposing responses in transcriptional signatures linked to proliferation, senescence, and microenvironment functions. We also discovered a pre-exposure expression signature in both blood and mammary tissues that is predictive for poor survival among human cancer patients (p = 0.0001), and a post-LD-exposure signature also predictive for poor patient survival (pidentify genetic features that predispose or protect individuals from LD-induced breast cancer.

  10. Identifying clinically relevant drug resistance genes in drug-induced resistant cancer cell lines and post-chemotherapy tissues.

    Science.gov (United States)

    Tong, Mengsha; Zheng, Weicheng; Lu, Xingrong; Ao, Lu; Li, Xiangyu; Guan, Qingzhou; Cai, Hao; Li, Mengyao; Yan, Haidan; Guo, You; Chi, Pan; Guo, Zheng

    2015-12-01

    Until recently, few molecular signatures of drug resistance identified in drug-induced resistant cancer cell models can be translated into clinical practice. Here, we defined differentially expressed genes (DEGs) between pre-chemotherapy colorectal cancer (CRC) tissue samples of non-responders and responders for 5-fluorouracil and oxaliplatin-based therapy as clinically relevant drug resistance genes (CRG5-FU/L-OHP). Taking CRG5-FU/L-OHP as reference, we evaluated the clinical relevance of several types of genes derived from HCT116 CRC cells with resistance to 5-fluorouracil and oxaliplatin, respectively. The results revealed that DEGs between parental and resistant cells, when both were treated with the corresponding drug for a certain time, were significantly consistent with the CRG5-FU/L-OHP as well as the DEGs between the post-chemotherapy CRC specimens of responders and non-responders. This study suggests a novel strategy to extract clinically relevant drug resistance genes from both drug-induced resistant cell models and post-chemotherapy cancer tissue specimens.

  11. A combined structural dynamics approach identifies a putative switch in factor VIIa employed by tissue factor to initiate blood coagulation

    DEFF Research Database (Denmark)

    Olsen, Ole H; Rand, Kasper D; Østergaard, Henrik

    2007-01-01

    Coagulation factor VIIa (FVIIa) requires tissue factor (TF) to attain full catalytic competency and to initiate blood coagulation. In this study, the mechanism by which TF allosterically activates FVIIa is investigated by a structural dynamics approach that combines molecular dynamics (MD......) simulations and hydrogen/deuterium exchange (HX) mass spectrometry on free and TF-bound FVIIa. The differences in conformational dynamics from MD simulations are shown to be confined to regions of FVIIa observed to undergo structural stabilization as judged by HX experiments, especially implicating activation...... in the presence of TF or an active-site inhibitor. Based on MD simulations, a key switch of the TF-induced structural changes is identified as the interacting pair Leu305{163} and Phe374{225} in FVIIa, whose mutual conformations are guided by the presence of TF and observed to be closely linked to the structural...

  12. Identifying Conventionally Sub-Seismic Faults in Polygonal Fault Systems

    Science.gov (United States)

    Fry, C.; Dix, J.

    2017-12-01

    Polygonal Fault Systems (PFS) are prevalent in hydrocarbon basins globally and represent potential fluid pathways. However the characterization of these pathways is subject to the limitations of conventional 3D seismic imaging; only capable of resolving features on a decametre scale horizontally and metres scale vertically. While outcrop and core examples can identify smaller features, they are limited by the extent of the exposures. The disparity between these scales can allow for smaller faults to be lost in a resolution gap which could mean potential pathways are left unseen. Here the focus is upon PFS from within the London Clay, a common bedrock that is tunnelled into and bears construction foundations for much of London. It is a continuation of the Ieper Clay where PFS were first identified and is found to approach the seafloor within the Outer Thames Estuary. This allows for the direct analysis of PFS surface expressions, via the use of high resolution 1m bathymetric imaging in combination with high resolution seismic imaging. Through use of these datasets surface expressions of over 1500 faults within the London Clay have been identified, with the smallest fault measuring 12m and the largest at 612m in length. The displacements over these faults established from both bathymetric and seismic imaging ranges from 30cm to a couple of metres, scales that would typically be sub-seismic for conventional basin seismic imaging. The orientations and dimensions of the faults within this network have been directly compared to 3D seismic data of the Ieper Clay from the offshore Dutch sector where it exists approximately 1km below the seafloor. These have typical PFS attributes with lengths of hundreds of metres to kilometres and throws of tens of metres, a magnitude larger than those identified in the Outer Thames Estuary. The similar orientations and polygonal patterns within both locations indicates that the smaller faults exist within typical PFS structure but are

  13. Cyclic AMP system in muscle tissue during prolonged hypokinesia

    Science.gov (United States)

    Antipenko, Y. A.; Bubeyev, Y. A.; Korovkin, B. F.; Mikhaleva, N. P.

    1980-01-01

    Components of the cyclic Adenosine-cyclic-35-monophosphate (AMP) system in the muscle tissue of white rats were studied during 70-75 days of hypokinesia, created by placing the animals in small booths which restricted their movements, and during the readaptation period. In the initial period, cyclic AMP levels and the activities of phosphodiesterase and adenylate cyclase in muscle tissue were increased. The values for these indices were roughly equal for controls and experimental animals during the adaptation period, but on the 70th day of the experiment cAMP levels dropped, phosphodiesterase activity increased, and the stimulative effect of epinephrine on the activity of adenylate cyclase decreased. The indices under study normalized during the readaptation period.

  14. Can tissue spectrophotometry and laser Doppler flowmetry help to identify patients at risk for wound healing disorders after neck dissection?

    Science.gov (United States)

    Rohleder, Nils H; Flensberg, Sandra; Bauer, Florian; Wagenpfeil, Stefan; Wales, Craig J; Koerdt, Steffen; Wolff, Klaus D; Hölzle, Frank; Steiner, Timm; Kesting, Marco R

    2014-03-01

    Microcirculation and oxygen supply in cervical skin were measured with an optical, noninvasive method in patients with or without radiotherapy before neck dissection. The course of wound healing was monitored after the surgical procedure to identify predictive factors for postoperative wound healing disorders. Tissue spectrophotometry and laser Doppler flowmetry were used to determine capillary oxygen saturation, hemoglobin concentration, blood flow, and blood velocity at 2-mm and 8-mm depths in the cervical skin of 91 patients before neck dissection in a maxillofacial unit of a university hospital in Munich, Germany. Parameters were evaluated for differences between patients with irradiation (24) and without (67) and patients with wound healing disorders (25) and without (66) (univariate or multivariate statistical analyses). Velocity at 2 mm was lower in irradiated skin (P = .016). Flow at 2 mm was higher in patients with wound healing disorders (P = .018). High flow values could help to identify patients at risk for cervical wound healing disorders. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Tissue hypoxygenation activates the adrenomedullin system in vivo

    DEFF Research Database (Denmark)

    Hofbauer, K H; Jensen, B L; Kurtz, A

    2000-01-01

    Our study aimed to investigate the influence of tissue hypo-oxygenation on the adrenomedullin (ADM) system in vivo. For this purpose, male Sprague-Dawley rats were exposed to normobaric hypoxia (8% oxygen) or to functional anemia [0.1% carbon monoxide (CO)] or to cobalt chloride (60 mg/kg) for 6 h......-fold in all organs examined. Similarly, ADM-R mRNA abundance increased during hypoxia and CO inhalation in all organs examined with exception of the liver. The effects of hypoxia and of CO inhalation on ADM and ADM-R mRNAs were mimicked by injection of cobaltous chloride. Hypoxia also significantly...

  16. Differential expression patterns in chemosensory and non-chemosensory tissues of putative chemosensory genes identified by transcriptome analysis of insect pest the purple stem borer Sesamia inferens (Walker.

    Directory of Open Access Journals (Sweden)

    Ya-Nan Zhang

    Full Text Available BACKGROUND: A large number of insect chemosensory genes from different gene subfamilies have been identified and annotated, but their functional diversity and complexity are largely unknown. A systemic examination of expression patterns in chemosensory organs could provide important information. METHODOLOGY/PRINCIPAL FINDINGS: We identified 92 putative chemosensory genes by analysing the transcriptome of the antennae and female sex pheromone gland of the purple stem borer Sesamia inferens, among them 87 are novel in this species, including 24 transcripts encoding for odorant binding proteins (OBPs, 24 for chemosensory proteins (CSPs, 2 for sensory neuron membrane proteins (SNMPs, 39 for odorant receptors (ORs and 3 for ionotropic receptors (IRs. The transcriptome analyses were validated and quantified with a detailed global expression profiling by Reverse Transcription-PCR for all 92 transcripts and by Quantitative Real Time RT-PCR for selected 16 ones. Among the chemosensory gene subfamilies, CSP transcripts are most widely and evenly expressed in different tissues and stages, OBP transcripts showed a clear antenna bias and most of OR transcripts are only detected in adult antennae. Our results also revealed that some OR transcripts, such as the transcripts of SNMP2 and 2 IRs were expressed in non-chemosensory tissues, and some CSP transcripts were antenna-biased expression. Furthermore, no chemosensory transcript is specific to female sex pheromone gland and very few are found in the heads. CONCLUSION: Our study revealed that there are a large number of chemosensory genes expressed in S. inferens, and some of them displayed unusual expression profile in non-chemosensory tissues. The identification of a large set of putative chemosensory genes of each subfamily from a single insect species, together with their different expression profiles provide further information in understanding the functions of these chemosensory genes in S. inferens as

  17. Differential expression patterns in chemosensory and non-chemosensory tissues of putative chemosensory genes identified by transcriptome analysis of insect pest the purple stem borer Sesamia inferens (Walker).

    Science.gov (United States)

    Zhang, Ya-Nan; Jin, Jun-Yan; Jin, Rong; Xia, Yi-Han; Zhou, Jing-Jiang; Deng, Jian-Yu; Dong, Shuang-Lin

    2013-01-01

    A large number of insect chemosensory genes from different gene subfamilies have been identified and annotated, but their functional diversity and complexity are largely unknown. A systemic examination of expression patterns in chemosensory organs could provide important information. We identified 92 putative chemosensory genes by analysing the transcriptome of the antennae and female sex pheromone gland of the purple stem borer Sesamia inferens, among them 87 are novel in this species, including 24 transcripts encoding for odorant binding proteins (OBPs), 24 for chemosensory proteins (CSPs), 2 for sensory neuron membrane proteins (SNMPs), 39 for odorant receptors (ORs) and 3 for ionotropic receptors (IRs). The transcriptome analyses were validated and quantified with a detailed global expression profiling by Reverse Transcription-PCR for all 92 transcripts and by Quantitative Real Time RT-PCR for selected 16 ones. Among the chemosensory gene subfamilies, CSP transcripts are most widely and evenly expressed in different tissues and stages, OBP transcripts showed a clear antenna bias and most of OR transcripts are only detected in adult antennae. Our results also revealed that some OR transcripts, such as the transcripts of SNMP2 and 2 IRs were expressed in non-chemosensory tissues, and some CSP transcripts were antenna-biased expression. Furthermore, no chemosensory transcript is specific to female sex pheromone gland and very few are found in the heads. Our study revealed that there are a large number of chemosensory genes expressed in S. inferens, and some of them displayed unusual expression profile in non-chemosensory tissues. The identification of a large set of putative chemosensory genes of each subfamily from a single insect species, together with their different expression profiles provide further information in understanding the functions of these chemosensory genes in S. inferens as well as other insects.

  18. An international eDelphi study identifying the research and education priorities in wound management and tissue repair.

    Science.gov (United States)

    Cowman, Seamus; Gethin, Georgina; Clarke, Eric; Moore, Zena; Craig, Gerardine; Jordan-O'Brien, Julie; McLain, Niamh; Strapp, Helen

    2012-02-01

    To incorporate an international and multidisciplinary consensus in the determination of the research and education priorities for wound healing and tissue repair. A compelling reason for the study is the lack of an agreed list of priorities for wound care research and education. Furthermore, there is a growth in the prevalence of chronic wounds, a growth in wound care products and marketing, and an increase in clinician attendance at conferences and education programmes. The study used a survey method. A four-round eDelphi technique was used to collect responses from an international population of health professionals across 24 countries. Responses were obtained from 360 professionals representing many health care settings. The top education priorities related to the standardisation of all foundation education programmes in wound care, the inclusion of wound care in all professional undergraduate and postgraduate education programmes, selecting dressings and the prevention of pressure ulcers. The top research priorities related to the dressing selection, pressure ulcer prevention and wound infection. conclusion: Professionals from different backgrounds and countries who are engaged in wound management share a common set of priorities for research and education. Most notably, the priorities identified relate to long-established clinical challenges in wound care and underpin the principles of good patient care practices. The priorities are closely allied to an ageing population and identify many challenges ahead for practitioners engaged in wound management services. The provision of wound care is a major investment of health service resources and remains a clinical challenge today. Research is essential to building evidence-based practice and fundamental to development of quality in standards of practice; education is central to achieving competence to deliver effective care. The determination of research and education priorities is therefore an absolute requirement

  19. Using Ambystoma mexicanum (Mexican axolotl) embryos, chemical genetics, and microarray analysis to identify signaling pathways associated with tissue regeneration.

    Science.gov (United States)

    Ponomareva, Larissa V; Athippozhy, Antony; Thorson, Jon S; Voss, S Randal

    2015-12-01

    Amphibian vertebrates are important models in regenerative biology because they present exceptional regenerative capabilities throughout life. However, it takes considerable effort to rear amphibians to juvenile and adult stages for regeneration studies, and the relatively large sizes that frogs and salamanders achieve during development make them difficult to use in chemical screens. Here, we introduce a new tail regeneration model using late stage Mexican axolotl embryos. We show that axolotl embryos completely regenerate amputated tails in 7days before they exhaust their yolk supply and begin to feed. Further, we show that axolotl embryos can be efficiently reared in microtiter plates to achieve moderate throughput screening of soluble chemicals to investigate toxicity and identify molecules that alter regenerative outcome. As proof of principle, we identified integration 1 / wingless (Wnt), transforming growth factor beta (Tgf-β), and fibroblast growth factor (Fgf) pathway antagonists that completely block tail regeneration and additional chemicals that significantly affected tail outgrowth. Furthermore, we used microarray analysis to show that inhibition of Wnt signaling broadly affects transcription of genes associated with Wnt, Fgf, Tgf-β, epidermal growth factor (Egf), Notch, nerve growth factor (Ngf), homeotic gene (Hox), rat sarcoma/mitogen-activated protein kinase (Ras/Mapk), myelocytomatosis viral oncogene (Myc), tumor protein 53 (p53), and retinoic acid (RA) pathways. Punctuated changes in the expression of genes known to regulate vertebrate development were observed; this suggests the tail regeneration transcriptional program is hierarchically structured and temporally ordered. Our study establishes the axolotl as a chemical screening model to investigate signaling pathways associated with tissue regeneration. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. An international eDelphi study identifying the research and education priorities in wound management and tissue repair.

    LENUS (Irish Health Repository)

    2012-02-01

    Aim. To incorporate an international and multidisciplinary consensus in the determination of the research and education priorities for wound healing and tissue repair. Background. A compelling reason for the study is the lack of an agreed list of priorities for wound care research and education. Furthermore, there is a growth in the prevalence of chronic wounds, a growth in wound care products and marketing, and an increase in clinician attendance at conferences and education programmes. Design. The study used a survey method. Methods. A four-round eDelphi technique was used to collect responses from an international population of health professionals across 24 countries. Results. Responses were obtained from 360 professionals representing many health care settings. The top education priorities related to the standardisation of all foundation education programmes in wound care, the inclusion of wound care in all professional undergraduate and postgraduate education programmes, selecting dressings and the prevention of pressure ulcers. The top research priorities related to the dressing selection, pressure ulcer prevention and wound infection. Conclusion. Professionals from different backgrounds and countries who are engaged in wound management share a common set of priorities for research and education. Most notably, the priorities identified relate to long-established clinical challenges in wound care and underpin the principles of good patient care practices. The priorities are closely allied to an ageing population and identify many challenges ahead for practitioners engaged in wound management services. Relevance to clinical practice. The provision of wound care is a major investment of health service resources and remains a clinical challenge today. Research is essential to building evidence-based practice and fundamental to development of quality in standards of practice; education is central to achieving competence to deliver effective care. The

  1. A novel C-type lectin identified by EST analysis in tissue migratory larvae of Ascaris suum.

    Science.gov (United States)

    Yoshida, Ayako; Nagayasu, Eiji; Horii, Yoichiro; Maruyama, Haruhiko

    2012-04-01

    C-type lectins (CTLs) are a group of proteins which bind to carbohydrate epitopes in the presence of Ca(2+), which have been described in a wide range of species. In this study, a cDNA sequence coding a putative CTL has been identified from the cDNA library constructed from the pig round worm Ascaris suum lung L3 (LL3) larvae, which was designated as A. suum C-type lectin-1 (As-CTL-1). The 510 nucleotide open reading frame of As-CTL-1 cDNA encoded the predicted 169 amino acid protein including a putative signal peptide of 23 residues and C-type lectin/C-type lectin-like domain (CLECT) at residue 26 to 167. As-CTL-1 was most similar to Toxocara canis C-type lectin-1 and 4 (Tc-CTL-1 and 4), and highly homologous to namatode CTLs and mammalian CTLs as well, such as human C-type lectin domain family 4 member G (CLECG4). In addition, As-CTL-1 was strongly expressed in tissue migrating LL3 and the L4 larvae, which were developmental larvae stages within the mammalian host. These results suggest that A. suum larvae might utilize As-CTL-1 to avoid pathogen recognition mechanisms in mammalian hosts due to it is similarity to host immune cell receptors.

  2. Thoracic and abdominal SPECT imaging in systemic amyloidosis in identifying multiorgan involvement

    International Nuclear Information System (INIS)

    Wellman, H.N.; Benson, M.D.; Park, H.M.; Siddiqui, A.R.; Krepshaw, J.D.

    1988-01-01

    Thirty-three patients with systemic amyloidosis have been studied. Thoracic single photon emission computed tomography (SPECT) for myocardial involvement and skeletal imaging were performed with Tc-99m PYP, and abdominal SPECT with TcS colloid. Myocardial wall involvement was easily discernible with SPECT in 17 cases, and in many with normal ultrasonography. PYP uptake was also observed in liver (five patients), kidneys (four patients), and soft tissues (two patients). Most patients had widespread degenerative joint disease. With TcS colloid, intrinsic liver abnormalities were found in four patients, hepatomegaly in seven, and splenic infiltration in two. Nuclear SPECT and planar imaging characterize the distribution of systemic amyloidosis in organs, distribution not readily identified with other diagnostic modalities

  3. Systemic Aspects of Soft Tissue Rheumatic Disorders (STRDs)

    International Nuclear Information System (INIS)

    Owlia, M. B.; Mehrpoor, G.

    2014-01-01

    Objective: To determine the markers of systemic inflammation in soft tissue rheumatic disorders (STRDs). Study Design: Case series. Place and Duration of Study: Rheumatology Clinic, Yazd, Iran, from November 2010 to December 2011. Methodology: Patients aged 20 years or above with known diagnosis of STRD according to clinical criteria and/ or paraclinical investigations for at least 3 weeks duration were longitudinally followed. Patients with diagnosis of rheumatoid arthritis, hypothyroidism, or any other known systemic conditions (other than diabetes mellitus) were excluded. After careful and detailed history taking, laboratory tests indicating systemic inflammation including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and routine screening rheumatologic tests were assessed. Results: Of the 90 patients, 75% were female and 25% were male and 28 (31.1%) of patients had diabetes mellitus. Fifty six (62%) and 49 (54%) of all studies cases had some degrees of morning stiffness and remarkable fatigue respectively. Twenty two (24%) had elevated CRP and 5 (5.5%) had abnormal ESR. Rheumatoid factor (RF) and anti-CCP was positive in 5 (5.5%) and 12 (13.3%) of patients accordingly. Three (3.3%) patients suffered from anemia of chronic disease. Mean ESR was 48 A +- 7.34 (hl) and mean CRP was 10.06 A +- 1.96 mg/dl. Mean RF was 10.8 A +- 1.64 U/ml and mean anti- CCP was 18.5 A +- 2.71 U/ml. Mean hemoglobin was between 10.4 A +- 1.01 g/dl. Conclusion: Features of subtle systemic inflammation are positive in some cases of soft tissue rheumatism. (author)

  4. Newly Identified Wild Rice Accessions Conferring High Salt Tolerance Might Use a Tissue Tolerance Mechanism in Leaf

    Science.gov (United States)

    Prusty, Manas R.; Kim, Sung-Ryul; Vinarao, Ricky; Entila, Frederickson; Egdane, James; Diaz, Maria G. Q.; Jena, Kshirod K.

    2018-01-01

    Cultivated rice (Oryza sativa L.) is very sensitive to salt stress. So far a few rice landraces have been identified as a source of salt tolerance and utilized in rice improvement. These tolerant lines primarily use Na+ exclusion mechanism in root which removes Na+ from the xylem stream by membrane Na+ and K+ transporters, and resulted in low Na+ accumulation in shoot. Identification of a new donor source conferring high salt tolerance is imperative. Wild relatives of rice having wide genetic diversity are regarded as a potential source for crop improvement. However, they have been less exploited against salt stress. Here, we simultaneously evaluated all 22 wild Oryza species along with the cultivated tolerant lines including Pokkali, Nona Bokra, and FL478, and sensitive check varieties under high salinity (240 mM NaCl). Based on the visual salt injury score, three species (O. alta, O. latifolia, and O. coarctata) and four species (O. rhizomatis, O. eichingeri, O. minuta, and O. grandiglumis) showed higher and similar level of tolerance compared to the tolerant checks, respectively. All three CCDD genome species exhibited salt tolerance, suggesting that the CCDD genome might possess the common genetic factors for salt tolerance. Physiological and biochemical experiments were conducted using the newly isolated tolerant species together with checks under 180 mM NaCl. Interestingly, all wild species showed high Na+ concentration in shoot and low concentration in root unlike the tolerant checks. In addition, the wild-tolerant accessions showed a tendency of a high tissue tolerance in leaf, low malondialdehyde level in shoot, and high retention of chlorophyll in the young leaves. These results suggest that the wild species employ tissue tolerance mechanism to manage salt stress. Gene expression analyses of the key salt tolerance-related genes suggested that high Na+ in leaf of wild species might be affected by OsHKT1;4-mediated Na+ exclusion in leaf and the following Na

  5. Chronic toxicity risk after radiotherapy for patients with systemic sclerosis (systemic scleroderma) or systemic lupus erythematosus: Association with connective tissue disorder severity

    International Nuclear Information System (INIS)

    Gold, Douglas G.; Miller, Robert C.; Pinn, Melva E.; Osborn, Thomas G.; Petersen, Ivy A.; Brown, Paul D.

    2008-01-01

    No method reliably identifies which patients with connective tissue disorders are at greatest risk of radiotherapy-related complications. Building on our prior experience, we postulated that disease severity, as measured by the number of organ systems involved, may predict chronic radiation toxicity risk

  6. Methods and systems for identifying ligand-protein binding sites

    KAUST Repository

    Gao, Xin; Naveed, Hammad

    2016-01-01

    The invention provides a novel integrated structure and system-based approach for drug target prediction that enables the large-scale discovery of new targets for existing drugs Novel computer-readable storage media and computer systems are also

  7. Identifying bottlenecks in manufacturing systems using stochastic criticality analysis

    NARCIS (Netherlands)

    Nogueira Bastos, J.P.; van der Sanden, L.J.; Donk, O.; Voeten, J.P.M.; Stuijk, S.; Schiffelers, R.R.H.; Corporaal, H.

    2018-01-01

    System design is a difficult process with many design-choices for which the impact may be difficult to foresee. Manufacturing system design is no exception to this. Increased use of flexible manufacturing systems which are able to perform different operations/use-cases further raises the design

  8. Establishment of the optimum two-dimensional electrophoresis system of ovine ovarian tissue.

    Science.gov (United States)

    Jia, J L; Zhang, L P; Wu, J P; Wang, J; Ding, Q

    2014-08-26

    Lambing performance of sheep is the most important economic trait and is regarded as a critic factoring affecting the productivity in sheep industry. Ovary plays the most roles in lambing trait. To establish the optimum two-dimensional electrophoresis system (2-DE) of ovine ovarian tissue, the common protein extraction methods of animal tissue (trichloroacetic acid/acetone precipitation and direct schizolysis methods) were used to extract ovine ovarian protein, and 17-cm nonlinear immobilized PH 3-10 gradient strips were used for 2-DE. The sample handling, loading quantity of the protein sample, and isoelectric focusing (IEF) steps were manipulated and optimized in this study. The results indicate that the direct schizolysis III method, a 200-μg loading quantity of the protein sample, and IEF steps II (20°C active hydration, 14 h→500 V, 1 h→1000 V 1 h→1000-9000 V, 6 h→80,000 VH→500 V 24 h) are optimal for 2-DE analysis of ovine ovarian tissue. Therefore, ovine ovarian tissue proteomics 2-DE was preliminarily established by the optimized conditions in this study; meanwhile, the conditions identified herein could provide a reference for ovarian sample preparation and 2-DE using tissues from other animals.

  9. Systems constellations : A better way to identify branding opportunities?

    NARCIS (Netherlands)

    Jurg, W.; Bloemer, J.; Doorewaard, H.; Peelen, E.

    2008-01-01

    Building strong brands has become one of the main marketing priorities for brand-supportive companies. The leading positivist paradigm in marketing may not be, however, the most-effective perspective in identifying branding opportunities. This paper offers an alternative phenomenological point of

  10. Identifying the Determinants of Chronic Absenteeism: A Bioecological Systems Approach

    Science.gov (United States)

    Gottfried, Michael A.; Gee, Kevin A.

    2017-01-01

    Background/Context: Chronic school absenteeism is a pervasive problem across the US; in early education, it is most rampant in kindergarten and its consequences are particularly detrimental, often leading to poorer academic, behavioral and developmental outcomes later in life. Though prior empirical research has identified a broad range of…

  11. Transverse vibration technique to identify deteriorated wood floor systems

    Science.gov (United States)

    R.J. Ross; X. Wang; M.O. Hunt; L.A. Soltis

    2002-01-01

    The Forest Products Laboratory, USDA Forest Service, has been developing nondestructive evaluation (NDE) techniques to identify degradation of wood in structures and the performance characteristics that remain in the structure. This work has focused on using dynamic testing techniques, particularly stress wave and ultrasonic transmission NDE techniques for both...

  12. Pairwise comparisons of ten porcine tissues identify differential transcriptional regulation at the gene, isoform, promoter and transcription start site level

    International Nuclear Information System (INIS)

    Farajzadeh, Leila; Hornshøj, Henrik; Momeni, Jamal; Thomsen, Bo; Larsen, Knud; Hedegaard, Jakob; Bendixen, Christian; Madsen, Lone Bruhn

    2013-01-01

    Highlights: •Transcriptome sequencing yielded 223 mill porcine RNA-seq reads, and 59,000 transcribed locations. •Establishment of unique transcription profiles for ten porcine tissues including four brain tissues. •Comparison of transcription profiles at gene, isoform, promoter and transcription start site level. •Highlights a high level of regulation of neuro-related genes at both gene, isoform, and TSS level. •Our results emphasize the pig as a valuable animal model with respect to human biological issues. -- Abstract: The transcriptome is the absolute set of transcripts in a tissue or cell at the time of sampling. In this study RNA-Seq is employed to enable the differential analysis of the transcriptome profile for ten porcine tissues in order to evaluate differences between the tissues at the gene and isoform expression level, together with an analysis of variation in transcription start sites, promoter usage, and splicing. Totally, 223 million RNA fragments were sequenced leading to the identification of 59,930 transcribed gene locations and 290,936 transcript variants using Cufflinks with similarity to approximately 13,899 annotated human genes. Pairwise analysis of tissues for differential expression at the gene level showed that the smallest differences were between tissues originating from the porcine brain. Interestingly, the relative level of differential expression at the isoform level did generally not vary between tissue contrasts. Furthermore, analysis of differential promoter usage between tissues, revealed a proportionally higher variation between cerebellum (CBE) versus frontal cortex and cerebellum versus hypothalamus (HYP) than in the remaining comparisons. In addition, the comparison of differential transcription start sites showed that the number of these sites is generally increased in comparisons including hypothalamus in contrast to other pairwise assessments. A comprehensive analysis of one of the tissue contrasts, i

  13. A Kinome RNAi Screen in Drosophila Identifies Novel Genes Interacting with Lgl, aPKC, and Crb Cell Polarity Genes in Epithelial Tissues

    NARCIS (Netherlands)

    Parsons, Linda M.; Grzeschik, Nicola A; Amaratunga, Kasun; Burke, Peter; Quinn, Leonie M; Richardson, Helena E

    2017-01-01

    In both Drosophila melanogaster and mammalian systems, epithelial structure and underlying cell polarity are essential for proper tissue morphogenesis and organ growth. Cell polarity interfaces with multiple cellular processes that are regulated by the phosphorylation status of large protein

  14. Automated systems to identify relevant documents in product risk management

    Science.gov (United States)

    2012-01-01

    Background Product risk management involves critical assessment of the risks and benefits of health products circulating in the market. One of the important sources of safety information is the primary literature, especially for newer products which regulatory authorities have relatively little experience with. Although the primary literature provides vast and diverse information, only a small proportion of which is useful for product risk assessment work. Hence, the aim of this study is to explore the possibility of using text mining to automate the identification of useful articles, which will reduce the time taken for literature search and hence improving work efficiency. In this study, term-frequency inverse document-frequency values were computed for predictors extracted from the titles and abstracts of articles related to three tumour necrosis factors-alpha blockers. A general automated system was developed using only general predictors and was tested for its generalizability using articles related to four other drug classes. Several specific automated systems were developed using both general and specific predictors and training sets of different sizes in order to determine the minimum number of articles required for developing such systems. Results The general automated system had an area under the curve value of 0.731 and was able to rank 34.6% and 46.2% of the total number of 'useful' articles among the first 10% and 20% of the articles presented to the evaluators when tested on the generalizability set. However, its use may be limited by the subjective definition of useful articles. For the specific automated system, it was found that only 20 articles were required to develop a specific automated system with a prediction performance (AUC 0.748) that was better than that of general automated system. Conclusions Specific automated systems can be developed rapidly and avoid problems caused by subjective definition of useful articles. Thus the efficiency of

  15. Extension Systems in Tanzania: Identifying Gaps in Research

    African Journals Online (AJOL)

    in Tanzania on agricultural extension systems; review research globally on agricultural ... cal techniques, unique results and major recommendations. .... participation in decision-making, natural .... soil and water management technologies in.

  16. Identifying niche-mediated regulatory factors of stem cell phenotypic state: a systems biology approach.

    Science.gov (United States)

    Ravichandran, Srikanth; Del Sol, Antonio

    2017-02-01

    Understanding how the cellular niche controls the stem cell phenotype is often hampered due to the complexity of variegated niche composition, its dynamics, and nonlinear stem cell-niche interactions. Here, we propose a systems biology view that considers stem cell-niche interactions as a many-body problem amenable to simplification by the concept of mean field approximation. This enables approximation of the niche effect on stem cells as a constant field that induces sustained activation/inhibition of specific stem cell signaling pathways in all stem cells within heterogeneous populations exhibiting the same phenotype (niche determinants). This view offers a new basis for the development of single cell-based computational approaches for identifying niche determinants, which has potential applications in regenerative medicine and tissue engineering. © 2017 The Authors. FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.

  17. Identifying Vulnerabilities and Hardening Attack Graphs for Networked Systems

    Energy Technology Data Exchange (ETDEWEB)

    Saha, Sudip; Vullinati, Anil K.; Halappanavar, Mahantesh; Chatterjee, Samrat

    2016-09-15

    We investigate efficient security control methods for protecting against vulnerabilities in networked systems. A large number of interdependent vulnerabilities typically exist in the computing nodes of a cyber-system; as vulnerabilities get exploited, starting from low level ones, they open up the doors to more critical vulnerabilities. These cannot be understood just by a topological analysis of the network, and we use the attack graph abstraction of Dewri et al. to study these problems. In contrast to earlier approaches based on heuristics and evolutionary algorithms, we study rigorous methods for quantifying the inherent vulnerability and hardening cost for the system. We develop algorithms with provable approximation guarantees, and evaluate them for real and synthetic attack graphs.

  18. Methods and systems for identifying ligand-protein binding sites

    KAUST Repository

    Gao, Xin

    2016-05-06

    The invention provides a novel integrated structure and system-based approach for drug target prediction that enables the large-scale discovery of new targets for existing drugs Novel computer-readable storage media and computer systems are also provided. Methods and systems of the invention use novel sequence order-independent structure alignment, hierarchical clustering, and probabilistic sequence similarity techniques to construct a probabilistic pocket ensemble (PPE) that captures even promiscuous structural features of different binding sites for a drug on known targets. The drug\\'s PPE is combined with an approximation of the drug delivery profile to facilitate large-scale prediction of novel drug- protein interactions with several applications to biological research and drug development.

  19. Identified problems in fabricating Mobile Radioscopy System (MRS)

    International Nuclear Information System (INIS)

    Arshad Yassin; Khairul Anuar Mohd Salleh; Ab Razak Hamzah; Khari Che Ros; Hasni Hashim

    2009-01-01

    This paper describes problems found and solving method in our effort to fabricate the first up to standard mobile radioscopy system (MRS). The MRS is expected to solve problems faced by small and medium local industries to have their own digital industrial radiography system (DIR) i.e. expensive cost, lack of experience in handling radiation electronic detector, etc. Most of the problems occurred give the challenge to obtain the best radiographic image quality in terms of quantitative evaluation. With the upcoming developments, the MRS is expected to acceptable to be us in oil and gas industry and power generation plant. (Author)

  20. The Mice Drawer System Tissue Sharing Program (MDS-TSP)

    Science.gov (United States)

    Biticchi, Roberta; Cancedda, Ranieri; Cilli, Michele; Cotronei, Vittorio; Costa, Delfina; Liu, Yi; Piccardi, Federica; Pignataro, Salvatore; Ruggiu, Alessandra; Tasso, Roberta; Tavella, Sara

    Several organs and apparatus are affected by weightless conditions and in particular by the weightless experienced during space flights. Therefore space missions are good opportunities to investigate in a whole organism the controlling cellular and molecular mechanisms. For this type of studies mice represent an excellent animal model for several reasons: reduced body size, relatively short time needed to reach adulthood, availability of strains with different genetic background and of different transgenic lines, etc. In line with the International Space Station (ISS) development, the Italian Space Agency (ASI) contracted Thales Alenia Space Italia, the largest Italian aerospace industry, to design and build a spaceflight payload for rodent research on ISS, the Mouse Drawer System (MDS -see abstract P. Cipparelli et al.). This payload meets NIH guideline for several physical parameters to maintain 6 animals in good health conditions in a space environment. Given the interest of our laboratory in the microgravity induced skeleton alterations, we focused our attention on transgenic mice over-expressing pleiotrophin (PTN) under the control of the human bone specific osteocalcin promoter. This protein is a heparin-binding cytokine with different functions. PTN is expressed by the cells in an early differentiation stage and is upregulated in tissue injury and wound repair. PTN is specifically involved in bone formation, neurite outgrowth and angiogenesis. As PTN-transgenic mice show an increased bone mass and mineralization, we decided to use this mouse model in the flight experiment and to study its potential role in counteracting bone loss in microgravity. Not all mouse strains are equally suitable for flight. After preliminary tests in the MDS breadboard at our animal facility on the behavior of different mouse strains, PTN-transgenic mice originally obtained in the BDF strain were backcrossed in the C57Bl/J10 strain before being used in this study. In order to

  1. Immunochip Analysis Identifies Multiple Susceptibility Loci for Systemic Sclerosis

    NARCIS (Netherlands)

    Mayes, Maureen D.; Bossini-Castillo, Lara; Gorlova, Olga; Martin, Jose Ezequiel; Zhou, Xiaodong; Chen, Wei V.; Assassi, Shervin; Ying, Jun; Tan, Filemon K.; Arnett, Frank C.; Reveille, John D.; Guerra, Sandra; Terue, Maria; Carmona, Francisco David; Gregersen, Peter K.; Lee, Annette T.; Lopez-Isac, Elena; Ochoa, Eguzkine; Carreira, Patricia; Simeon, Carmen Pilar; Castellvi, Ivan; Angel Gonzalez-Gay, Miguel; Zhernakova, Alexandra; Padyukov, Leonid; Aarcon-Riquelme, Marta; Wijmenga, Cisca; Beretta, Lorenzo; Riemekasten, Gabriela; Witte, Torsten; Hunzelmann, Nicolas; Kreuter, Alexander; Distler, Jorg H. W.; Voskuy, Alexandre E.; Schuerwegh, Annemie J.; Hesselstrand, Roger; Nordin, Annika; Airo, Paolo; Lunardi, Claudio; Shiels, Paul; van Laar, Jacob M.; Herrick, Ariane; Worthington, Jane; Denton, Christopher; Wigley, Fredrick M.; Hummers, Laura K.; Varga, John; Hinchcliff, Monique E.; Baron, Murray; Hudson, Marie; Pope, Janet E.

    2014-01-01

    In this study, 1,833 systemic sclerosis (SSc) cases and 3,466 controls were genotyped with the Immunochip array. Classical alleles, amino acid residues, and SNPs across the human leukocyte antigen (HLA) region were imputed and tested. These analyses resulted in a model composed of six polymorphic

  2. Identifying Experts and Authoritative Documents in Social Bookmarking Systems

    Science.gov (United States)

    Grady, Jonathan P.

    2013-01-01

    Social bookmarking systems allow people to create pointers to Web resources in a shared, Web-based environment. These services allow users to add free-text labels, or "tags", to their bookmarks as a way to organize resources for later recall. Ease-of-use, low cognitive barriers, and a lack of controlled vocabulary have allowed social…

  3. Identifying Employer Needs from Accounting Information Systems Programs

    Science.gov (United States)

    Dillon, Thomas W.; Kruck, S. E.

    2008-01-01

    As the need for new hires with accounting and information technology knowledge increases, a new major in accounting information systems (AIS) has emerged. This new AIS degree is a hybrid of accounting concepts and common business subjects combined with key information technology issues. Employers were presented with 56 core content areas found in…

  4. Differential N-glycan patterns identified in lung adenocarcinoma by N-glycan profiling of formalin-fixed paraffin-embedded (FFPE) tissue sections.

    Science.gov (United States)

    Wang, Xiaoning; Deng, Zaian; Huang, Chuncui; Zhu, Tong; Lou, Jiatao; Wang, Lin; Li, Yan

    2018-02-10

    N-glycan profiling is a powerful approach for analyzing the functional relationship between N-glycosylation and cancer. Current methods rely on either serum or fresh tissue samples; however, N-glycan patterns may differ between serum and tissue, as the proteins of serum originate from a variety of tissues. Furthermore, fresh tissue samples are difficult to ship and store. Here, we used a profiling method based on formalin-fixed paraffin-embedded (FFPE) tissue sections from lung adenocarcinoma patients. We found that our method was highly reproducible. We identified 58 N-glycan compositions from lung adenocarcinoma FFPE samples, 51 of which were further used for MS n -based structure prediction. We show that high mannose type N-glycans are upregulated, while sialylated N-glycans are downregulated in our FFPE lung adenocarcinoma samples, compared to the control samples. Our receiver operating characteristic (ROC) curve analysis shows that high mannose type and sialylated N-glycans are useful discriminators to distinguish between lung adenocarcinoma and control tissue. Together, our results indicate that expression levels of specific N-glycans correlate well with lung adenocarcinoma, and strongly suggest that our FFPE-based method will be useful for N-glycan profiling of cancer tissues. Glycosylation is one of the most important post-translational protein modifications, and is associated with several physiopathological processes, including carcinogenesis. In this study, we tested the feasibility of using formalin-fixed paraffin-embedded (FFPE) tissue sections to identify changes in N-glycan patterns and identified the differentially expressed N-glycans of lung adenocarcinoma. Our study shows that the FFPE-based N-glycan profiling method is useful for clinical diagnosis as well as identification of potential biomarkers, and our data expand current knowledge of differential N-glycan patterns of lung adenocarcinoma. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Methylcellulose Based Thermally Reversible Hydrogel System for Tissue Engineering Applications

    Directory of Open Access Journals (Sweden)

    Ram V. Devireddy

    2013-06-01

    Full Text Available The thermoresponsive behavior of a Methylcellulose (MC polymer was systematically investigated to determine its usability in constructing MC based hydrogel systems in cell sheet engineering applications. Solution-gel analyses were made to study the effects of polymer concentration, molecular weight and dissolved salts on the gelation of three commercially available MCs using differential scanning calorimeter and rheology. For investigation of the hydrogel stability and fluid uptake capacity, swelling and degradation experiments were performed with the hydrogel system exposed to cell culture solutions at incubation temperature for several days. From these experiments, the optimal composition of MC-water-salt that was able to produce stable hydrogels at or above 32 °C, was found to be 12% to 16% of MC (Mol. wt. of 15,000 in water with 0.5× PBS (~150mOsm. This stable hydrogel system was then evaluated for a week for its efficacy to support the adhesion and growth of specific cells in culture; in our case the stromal/stem cells derived from human adipose tissue derived stem cells (ASCs. The results indicated that the addition (evenly spread of ~200 µL of 2 mg/mL bovine collagen type -I (pH adjusted to 7.5 over the MC hydrogel surface at 37 °C is required to improve the ASC adhesion and proliferation. Upon confluence, a continuous monolayer ASC sheet was formed on the surface of the hydrogel system and an intact cell sheet with preserved cell–cell and cell–extracellular matrix was spontaneously and gradually detached when the grown cell sheet was removed from the incubator and exposed to room temperature (~30 °C within minutes.

  6. Methylcellulose based thermally reversible hydrogel system for tissue engineering applications.

    Science.gov (United States)

    Thirumala, Sreedhar; Gimble, Jeffrey M; Devireddy, Ram V

    2013-06-25

    The thermoresponsive behavior of a Methylcellulose (MC) polymer was systematically investigated to determine its usability in constructing MC based hydrogel systems in cell sheet engineering applications. Solution-gel analyses were made to study the effects of polymer concentration, molecular weight and dissolved salts on the gelation of three commercially available MCs using differential scanning calorimeter and rheology. For investigation of the hydrogel stability and fluid uptake capacity, swelling and degradation experiments were performed with the hydrogel system exposed to cell culture solutions at incubation temperature for several days. From these experiments, the optimal composition of MC-water-salt that was able to produce stable hydrogels at or above 32 °C, was found to be 12% to 16% of MC (Mol. wt. of 15,000) in water with 0.5× PBS (~150mOsm). This stable hydrogel system was then evaluated for a week for its efficacy to support the adhesion and growth of specific cells in culture; in our case the stromal/stem cells derived from human adipose tissue derived stem cells (ASCs). The results indicated that the addition (evenly spread) of ~200 µL of 2 mg/mL bovine collagen type -I (pH adjusted to 7.5) over the MC hydrogel surface at 37 °C is required to improve the ASC adhesion and proliferation. Upon confluence, a continuous monolayer ASC sheet was formed on the surface of the hydrogel system and an intact cell sheet with preserved cell-cell and cell-extracellular matrix was spontaneously and gradually detached when the grown cell sheet was removed from the incubator and exposed to room temperature (~30 °C) within minutes.

  7. Identifying behaviour patterns of construction safety using system archetypes.

    Science.gov (United States)

    Guo, Brian H W; Yiu, Tak Wing; González, Vicente A

    2015-07-01

    Construction safety management involves complex issues (e.g., different trades, multi-organizational project structure, constantly changing work environment, and transient workforce). Systems thinking is widely considered as an effective approach to understanding and managing the complexity. This paper aims to better understand dynamic complexity of construction safety management by exploring archetypes of construction safety. To achieve this, this paper adopted the ground theory method (GTM) and 22 interviews were conducted with participants in various positions (government safety inspector, client, health and safety manager, safety consultant, safety auditor, and safety researcher). Eight archetypes were emerged from the collected data: (1) safety regulations, (2) incentive programs, (3) procurement and safety, (4) safety management in small businesses (5) production and safety, (6) workers' conflicting goals, (7) blame on workers, and (8) reactive and proactive learning. These archetypes capture the interactions between a wide range of factors within various hierarchical levels and subsystems. As a free-standing tool, they advance the understanding of dynamic complexity of construction safety management and provide systemic insights into dealing with the complexity. They also can facilitate system dynamics modelling of construction safety process. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Role of the immune system in cardiac tissue damage and repair following myocardial infarction.

    Science.gov (United States)

    Saparov, Arman; Ogay, Vyacheslav; Nurgozhin, Talgat; Chen, William C W; Mansurov, Nurlan; Issabekova, Assel; Zhakupova, Jamilya

    2017-09-01

    The immune system plays a crucial role in the initiation, development, and resolution of inflammation following myocardial infarction (MI). The lack of oxygen and nutrients causes the death of cardiomyocytes and leads to the exposure of danger-associated molecular patterns that are recognized by the immune system to initiate inflammation. At the initial stage of post-MI inflammation, the immune system further damages cardiac tissue to clear cell debris. The excessive production of reactive oxygen species (ROS) by immune cells and the inability of the anti-oxidant system to neutralize ROS cause oxidative stress that further aggravates inflammation. On the other hand, the cells of both innate and adaptive immune system and their secreted factors are critically instrumental in the very dynamic and complex processes of regulating inflammation and mediating cardiac repair. It is important to decipher the balance between detrimental and beneficial effects of the immune system in MI. This enables us to identify better therapeutic targets for reducing the infarct size, sustaining the cardiac function, and minimizing the likelihood of heart failure. This review discusses the role of both innate and adaptive immune systems in cardiac tissue damage and repair in experimental models of MI.

  9. Systems Genetics Analysis to Identify the Genetic Modulation of a Glaucoma-Associated Gene.

    Science.gov (United States)

    Chintalapudi, Sumana R; Jablonski, Monica M

    2017-01-01

    Loss of retinal ganglion cells (RGCs) is one of the hallmarks of retinal neurodegenerative diseases, glaucoma being one of the most common. Recently, γ-synuclein (SNCG) was shown to be highly expressed in the somas and axons of RGCs. In various mouse models of glaucoma, downregulation of Sncg gene expression correlates with RGC loss. To investigate the regulation of Sncg in RGCs, we used a systems genetics approach to identify a gene that modulates the expression of Sncg, followed by confirmatory studies in both healthy and diseased retinas. We found that chromosome 1 harbors an eQTL that modulates the expression of Sncg in the mouse retina and identified Pfdn2 as the candidate upstream modulator of Sncg expression. Downregulation of Pfdn2 in enriched RGCs causes a concomitant reduction in Sncg. In this chapter, we describe our strategy and methods for identifying and confirming a genetic modulation of a glaucoma-associated gene. A similar method can be applied to other genes expressed in other tissues.

  10. Cataloging the Praesepe Cluster: Identifying Interlopers and Binary Systems

    Science.gov (United States)

    Lucey, Madeline R.; Gosnell, Natalie M.; Mann, Andrew; Douglas, Stephanie

    2018-01-01

    We present radial velocity measurements from an ongoing survey of the Praesepe open cluster using the WIYN 3.5m Telescope. Our target stars include 229 early-K to mid-M dwarfs with proper motion memberships that have been observed by the repurposed Kepler mission, K2. With this survey, we will provide a well-constrained membership list of the cluster. By removing interloping stars and determining the cluster binary frequency we can avoid systematic errors in our analysis of the K2 findings and more accurately determine exoplanet properties in the Praesepe cluster. Obtaining accurate exoplanet parameters in open clusters allows us to study the temporal dimension of exoplanet parameter space. We find Praesepe to have a mean radial velocity of 34.09 km/s and a velocity dispersion of 1.13 km/s, which is consistent with previous studies. We derive radial velocity membership probabilities for stars with ≥3 radial velocity measurements and compare against published membership probabilities. We also identify radial velocity variables and potential double-lined spectroscopic binaries. We plan to obtain more observations to determine the radial velocity membership of all the stars in our sample, as well as follow up on radial velocity variables to determine binary orbital solutions.

  11. Nitrogen-15 studies on identifying fertilizer excess in environmental systems

    International Nuclear Information System (INIS)

    Freyer, H.D.; Aly, A.I.M.

    1975-01-01

    The feasibility of identifying fertilizer excesses in surface and ground waters on the basis of variations in the isotope ratio of nitrogen has been studied. The isotope ratio of the commonly used ammonium and nitrate fertilizers is similar to that of atmospheric nitrogen. These ratios are shifted when fertilizers are added to the soil. In the soil, fertilizer ammonium is oxidized and the nitrate formed is reduced in the heavy isotope. The fractionation factors are calculated. This artificially added nitrate becomes mixed with natural nitrate which, in general, is enriched in the heavy isotope. Only 50% (or even less) of the nitrate formed may stem from the added fertilizer. The mixing ratios are time-dependent, and different for various types and conditions of soil. In spite of this complexity, information on this isotopic process should be obtainable, if the isotope ratios of artificial and natural nitrate, respectively, are substantially different. Surface waters, in general, show no significant correlation between nitrate content and isotope ratio due to additions of sewage waters. Some data on ground waters from agricultural areas, however, where the nitrate content apparently resulted from fertilizers, gave a negative correlation of lower isotope ratios with higher nitrate contents. An inverse correlation was found in the isotope ratios of nitrate in untouched surface waters, and they even reflect the composition of the total soil nitrogen. (author)

  12. Weight-dependent changes of immune system in adipose tissue: Importance of leptin

    International Nuclear Information System (INIS)

    Caspar-Bauguil, S.; Cousin, B.; Andre, M.; Nibbelink, M.; Galinier, A.; Periquet, B.; Casteilla, L.; Penicaud, L.

    2006-01-01

    Ancestral lymphoid cells reside in adipose tissues, and their numbers are highly altered in obesity. Leptin, production of which is correlated to fat mass, is strongly involved in the relationships between adipose tissues and immune system. We investigated in epididymal (EPI) and inguinal (ING) fat pads to determine whether 1) lymphocyte phenotypes were correlated to the tissue weight and 2) leptin was involved in such relationships. Immunohistological analyses revealed a tight relationship between the T and NK lymphocytes of the stromal vascular fraction and adipocytes. We identified a significant negative and positive correlation between EPI weight and the percentage of NK and total T cells respectively by cytofluorometric analyses. The NK and ancestral γδ T cell contents were directly dependent of leptin since they increased significantly in high-fat (HF) diet mice but not in leptin-deficient (ob/ob) mice as compared to control. By contrast, the αβ T cell content seemed independent of leptin because their percentages increased significantly with the EPI weight whatever the type of mice (control, HF, ob/ob). The present study suggests that adipose tissues present, according to their localization, different immunological mechanisms that might be involved in the regulation of adipose cells functions and proliferations

  13. Identifying User Experience Goals for Interactive Climate Management Business Systems

    DEFF Research Database (Denmark)

    Clemmensen, Torkil; Barlow, Stephanie

    2013-01-01

    This paper presents findings from interpretative phenomenological interviews about the user experience of interactive climate management with six growers and crop consultants. The focus of user experience research has been on quantitative studies of consumers’ initial usage experiences, for example...... of mobile phones or e-commerce websites. In contrast, this empirical paper provides an example of how to capture user experience in work contexts and with a qualitative methodology. We present a model of the essence of the emotional user experience of interactive climate management. Then we suggest...... of interactive climate management in this and other domains. The overall aim with the paper is to take the concept of user experience into the IS community and to describe and understand what are individual workers’ positive emotional use experiences when interacting with workplace systems....

  14. Pairwise comparisons of ten porcine tissues identify differential transcriptional regulation at the gene, isoform, promoter and transcription start site level

    DEFF Research Database (Denmark)

    Farajzadeh, Leila; Hornshøj, Henrik; Momeni, Jamal

    2013-01-01

    , isoform, and transcription start site (TSS), and promoter level showed that several of the genes differed at all four levels. Interestingly, these genes were mainly annotated to the "electron transport chain" and neuronal differentiation, emphasizing that "tissue important" genes are regulated at several...

  15. Modeling light–tissue interaction in optical coherence tomography systems

    DEFF Research Database (Denmark)

    Andersen, Peter E.; Jørgensen, Thomas Martini; Thrane, Lars

    2015-01-01

    Optical coherence tomography (OCT) performs high-resolution, cross-sectional tomographic imaging of the internal tissue microstructure by measuring backscattered or backreflected light. The scope of this chapter is to present analytical and numerical models that are able to describe light-tissue ...

  16. Vehicle systems and payload requirements evaluation. [computer programs for identifying launch vehicle system requirements

    Science.gov (United States)

    Rea, F. G.; Pittenger, J. L.; Conlon, R. J.; Allen, J. D.

    1975-01-01

    Techniques developed for identifying launch vehicle system requirements for NASA automated space missions are discussed. Emphasis is placed on development of computer programs and investigation of astrionics for OSS missions and Scout. The Earth Orbit Mission Program - 1 which performs linear error analysis of launch vehicle dispersions for both vehicle and navigation system factors is described along with the Interactive Graphic Orbit Selection program which allows the user to select orbits which satisfy mission requirements and to evaluate the necessary injection accuracy.

  17. Flowering of Woody Bamboo in Tissue Culture Systems

    Directory of Open Access Journals (Sweden)

    Jin-Ling Yuan

    2017-09-01

    Full Text Available Flowering and subsequent seed set are not only normal activities in the life of most plants, but constitute the very reason for their existence. Woody bamboos can take a long time to flower, even over 100 years. This makes it difficult to breed bamboo, since flowering time cannot be predicted and passing through each generation takes too long. Another unique characteristic of woody bamboo is that a bamboo stand will often flower synchronously, both disrupting the supply chain within the bamboo industry and affecting local ecology. Therefore, an understanding of the mechanism that initiates bamboo flowering is important not only for biology research, but also for the bamboo industry. Induction of flowering in vitro is an effective way to both shorten the flowering period and control the flowering time, and has been shown for several species of bamboo. The use of controlled tissue culture systems allows investigation into the mechanism of bamboo flowering and facilitates selective breeding. Here, after a brief introduction of flowering in bamboo, we review the research on in vitro flowering of bamboo, including our current understanding of the effects of plant growth regulators and medium components on flower induction and how in vitro bamboo flowers can be used in research.

  18. Metabolomics and transcriptomics identify pathway differences between visceral and subcutaneous adipose tissue in colorectal cancer patients: the ColoCare study.

    Science.gov (United States)

    Liesenfeld, David B; Grapov, Dmitry; Fahrmann, Johannes F; Salou, Mariam; Scherer, Dominique; Toth, Reka; Habermann, Nina; Böhm, Jürgen; Schrotz-King, Petra; Gigic, Biljana; Schneider, Martin; Ulrich, Alexis; Herpel, Esther; Schirmacher, Peter; Fiehn, Oliver; Lampe, Johanna W; Ulrich, Cornelia M

    2015-08-01

    Metabolic and transcriptomic differences between visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) compartments, particularly in the context of obesity, may play a role in colorectal carcinogenesis. We investigated the differential functions of their metabolic compositions. Biochemical differences between adipose tissues (VAT compared with SAT) in patients with colorectal carcinoma (CRC) were investigated by using mass spectrometry metabolomics and gene expression profiling. Metabolite compositions were compared between VAT, SAT, and serum metabolites. The relation between patients' tumor stage and metabolic profiles was assessed. Presurgery blood and paired VAT and SAT samples during tumor surgery were obtained from 59 CRC patients (tumor stages I-IV) of the ColoCare cohort. Gas chromatography time-of-flight mass spectrometry and liquid chromatography quadrupole time-of-flight mass spectrometry were used to measure 1065 metabolites in adipose tissue (333 identified compounds) and 1810 metabolites in serum (467 identified compounds). Adipose tissue gene expression was measured by using Illumina's HumanHT-12 Expression BeadChips. Compared with SAT, VAT displayed elevated markers of inflammatory lipid metabolism, free arachidonic acid, phospholipases (PLA2G10), and prostaglandin synthesis-related enzymes (PTGD/PTGS2S). Plasmalogen concentrations were lower in VAT than in SAT, which was supported by lower gene expression of FAR1, the rate-limiting enzyme for ether-lipid synthesis in VAT. Serum sphingomyelin concentrations were inversely correlated (P = 0.0001) with SAT adipose triglycerides. Logistic regression identified lipids in patients' adipose tissues, which were associated with CRC tumor stage. As one of the first studies, we comprehensively assessed differences in metabolic, lipidomic, and transcriptomic profiles between paired human VAT and SAT and their association with CRC tumor stage. We identified markers of inflammation in VAT, which

  19. A robust approach to identifying tissue-specific gene expression regulatory variants using personalized human induced pluripotent stem cells.

    Directory of Open Access Journals (Sweden)

    Je-Hyuk Lee

    2009-11-01

    Full Text Available Normal variation in gene expression due to regulatory polymorphisms is often masked by biological and experimental noise. In addition, some regulatory polymorphisms may become apparent only in specific tissues. We derived human induced pluripotent stem (iPS cells from adult skin primary fibroblasts and attempted to detect tissue-specific cis-regulatory variants using in vitro cell differentiation. We used padlock probes and high-throughput sequencing for digital RNA allelotyping and measured allele-specific gene expression in primary fibroblasts, lymphoblastoid cells, iPS cells, and their differentiated derivatives. We show that allele-specific expression is both cell type and genotype-dependent, but the majority of detectable allele-specific expression loci remains consistent despite large changes in the cell type or the experimental condition following iPS reprogramming, except on the X-chromosome. We show that our approach to mapping cis-regulatory variants reduces in vitro experimental noise and reveals additional tissue-specific variants using skin-derived human iPS cells.

  20. Review of vascularised bone tissue-engineering strategies with a focus on co-culture systems.

    Science.gov (United States)

    Liu, Yuchun; Chan, Jerry K Y; Teoh, Swee-Hin

    2015-02-01

    Poor angiogenesis within tissue-engineered grafts has been identified as a main challenge limiting the clinical introduction of bone tissue-engineering (BTE) approaches for the repair of large bone defects. Thick BTE grafts often exhibit poor cellular viability particularly at the core, leading to graft failure and lack of integration with host tissues. Various BTE approaches have been explored for improving vascularisation in tissue-engineered constructs and are briefly discussed in this review. Recent investigations relating to co-culture systems of endothelial and osteoblast-like cells have shown evidence of BTE efficacy in increasing vascularization in thick constructs. This review provides an overview of key concepts related to bone formation and then focuses on the current state of engineered vascularized co-culture systems using bone repair as a model. It will also address key questions regarding the generation of clinically relevant vascularized bone constructs as well as potential directions and considerations for research with the objective of pursuing engineered co-culture systems in other disciplines of vascularized regenerative medicine. The final objective is to generate serious and functional long-lasting vessels for sustainable angiogenesis that will enable enhanced cellular survival within thick voluminous bone grafts, thereby aiding in bone formation and remodelling in the long term. However, more evidence about the quality of blood vessels formed and its associated functional improvement in bone formation as well as a mechanistic understanding of their interactions are necessary for designing better therapeutic strategies for translation to clinical settings. Copyright © 2012 John Wiley & Sons, Ltd.

  1. Systemic Lupus Erythematosus and Systemic Autoimmune Connective Tissue Disorders behind Recurrent Diastolic Heart Failure

    Directory of Open Access Journals (Sweden)

    Luis Miguel Blasco Mata

    2012-01-01

    Full Text Available Diastolic heart failure (DHF remains unexplained in some patients with recurrent admissions after full investigation. A study was directed for screening SLE and systemic autoimmune connective tissue disorders in recurrent unexplained DHF patients admitted at a short-stay and intermediate care unit. It was found that systemic autoimmune conditions explained 11% from all of cases. Therapy also prevented new readmissions. Autoimmunity should be investigated in DHF.

  2. Occurrence and Tissue Distribution of Porcine Circovirus Type 2 Identified by Immunohistochemistry in Danish Finishing Pigs at Slaughter

    DEFF Research Database (Denmark)

    Hansen, Mette Sif; Pors, S. E.; Bille-Hansen, Vivi

    2010-01-01

    Infection with porcine circovirus type 2 (PCV2) may be subclinical or lead to the development of porcine circovirus disease (PCVD), which includes the entities of post-weaning multisystemic wasting syndrome (PMWS) and the porcine respiratory disease complex (PRDC). PCV2 infection and PMWS occur...... or more tissues of 61% of the pigs were positive for PCV2 antigen. Up to 78% of the pigs had mild lymphoid depletion, indistinct lymphoid follicles and/or histiocytic Infiltration of the lymph nodes, but these lesions were not associated with PCV2. No association was found between the presence of lung...

  3. Qualitative tissue differentiation by analysing the intensity ratios of atomic emission lines using laser induced breakdown spectroscopy (LIBS): prospects for a feedback mechanism for surgical laser systems.

    Science.gov (United States)

    Kanawade, Rajesh; Mahari, Fanuel; Klämpfl, Florian; Rohde, Maximilian; Knipfer, Christian; Tangermann-Gerk, Katja; Adler, Werner; Schmidt, Michael; Stelzle, Florian

    2015-01-01

    The research work presented in this paper focuses on qualitative tissue differentiation by monitoring the intensity ratios of atomic emissions using 'Laser Induced Breakdown Spectroscopy' (LIBS) on the plasma plume created during laser tissue ablation. The background of this study is to establish a real time feedback control mechanism for clinical laser surgery systems during the laser ablation process. Ex-vivo domestic pig tissue samples (muscle, fat, nerve and skin) were used in this experiment. Atomic emission intensity ratios were analyzed to find a characteristic spectral line for each tissue. The results showed characteristic elemental emission intensity ratios for the respective tissues. The spectral lines and intensity ratios of these specific elements varied among the different tissue types. The main goal of this study is to qualitatively and precisely identify different tissue types for tissue specific laser surgery. © 2015 The Authors. Journal of Biophotonics published by WILEY-VCH Verlag.

  4. Development of a model system to identify differences in spring and winter oat.

    Science.gov (United States)

    Chawade, Aakash; Lindén, Pernilla; Bräutigam, Marcus; Jonsson, Rickard; Jonsson, Anders; Moritz, Thomas; Olsson, Olof

    2012-01-01

    Our long-term goal is to develop a Swedish winter oat (Avena sativa). To identify molecular differences that correlate with winter hardiness, a winter oat model comprising of both non-hardy spring lines and winter hardy lines is needed. To achieve this, we selected 294 oat breeding lines, originating from various Russian, German, and American winter oat breeding programs and tested them in the field in south- and western Sweden. By assaying for winter survival and agricultural properties during four consecutive seasons, we identified 14 breeding lines of different origins that not only survived the winter but also were agronomically better than the rest. Laboratory tests including electrolytic leakage, controlled crown freezing assay, expression analysis of the AsVrn1 gene and monitoring of flowering time suggested that the American lines had the highest freezing tolerance, although the German lines performed better in the field. Finally, six lines constituting the two most freezing tolerant lines, two intermediate lines and two spring cultivars were chosen to build a winter oat model system. Metabolic profiling of non-acclimated and cold acclimated leaf tissue samples isolated from the six selected lines revealed differential expression patterns of 245 metabolites including several sugars, amino acids, organic acids and 181 hitherto unknown metabolites. The expression patterns of 107 metabolites showed significant interactions with either a cultivar or a time-point. Further identification, characterisation and validation of these metabolites will lead to an increased understanding of the cold acclimation process in oats. Furthermore, by using the winter oat model system, differential sequencing of crown mRNA populations would lead to identification of various biomarkers to facilitate winter oat breeding.

  5. Antibodies against deamidated gliadin peptides identify adult coeliac disease patients negative for antibodies against endomysium and tissue transglutaminase.

    Science.gov (United States)

    Dahle, C; Hagman, A; Ignatova, S; Ström, M

    2010-07-01

    This study was done to evaluate the diagnostic utility of antibodies against deamidated gliadin peptides compared to traditional markers for coeliac disease. To evaluate diagnostic utility of antibodies against deamidated gliadin peptide (DGP). Sera from 176 adults, referred for endoscopy without previous analysis of antibodies against tissue transglutaminase (tTG) or endomysium (EmA), were retrospectively analysed by ELISAs detecting IgA/IgG antibodies against DGP or a mixture of DGP and tTG, and compared with IgA-tTG and EmA. Seventy-nine individuals were diagnosed with coeliac disease. Receiver operating characteristic analyses verified the manufacturers' cut-off limits except for IgA/IgG-DGP/tTG. In sera without IgA deficiency, the sensitivity was higher for IgA/IgG-DGP (0.85-0.87) compared with IgA-tTg (0.76) and EmA (0.61). All tests showed high specificity (0.95-1.00). Eighteen coeliac disease-sera were negative regarding IgA-tTG, nine of which were positive for IgA/IgG-DGP. Sera from coeliac disease-patients >70 years were more often negative for IgA-tTG (50%) and IgA/IgG-DGP (36%) than younger patients (15% and 8% respectively) (P adult coeliac disease patients negative for antibodies against endomysium and tissue transglutaminase. Serology is often negative in elderly patients with coeliac disease; a small bowel biopsy should therefore be performed generously before coeliac disease is excluded.

  6. Proteomic profiling of antibody-inducing immunogens in tumor tissue identifies PSMA1, LAP3, ANXA3, and maspin as colon cancer markers

    Science.gov (United States)

    Yang, Qian; Roehrl, Michael H.; Wang, Julia Y.

    2018-01-01

    We hypothesized that cancer tissue immunogens – antigens capable of inducing specific antibody production in patients – are promising targets for development of precision diagnostics and humoral immunotherapies. We developed an innovative immuno-proteomic strategy and identified new immunogenic markers of colon cancer. Proteins from cancers and matched normal tissues were separated by 2D gel electrophoresis and blotted with serum antibodies from the same patients. Antibody-reactive proteins were sequenced by mass spectrometry and validated by Western blotting and immunohistochemistry. 170 serum antibody-reactive proteins were identified only in cancerous but not matched normal. Among these, proteasome subunit alpha type 1 (PSA1), leucine aminopeptidase 3 (LAP3), annexin A3 (ANXA3), and maspin (serpin B5) were reproducibly found in tissues from three patients. Differential expression patterns were confirmed in samples from eight patients with various stages of colon adenocarcinoma and liver metastases. These tumor-resident proteins and/or their associated serum antibodies may be promising markers for colon cancer screening and early diagnosis. Furthermore, tumor tissue-specific antibodies could potentially be exploited as immunotherapeutic targets against cancer. More generally, proteomic profiling of antibody-inducing cancer-associated immunogens represents a powerful generic method for uncovering the tumor antigen-ome, i.e., the totality of immunogenic tumor-associated proteins. PMID:29423100

  7. Greenlandic water and sanitation systems-identifying system constellation and challenges

    DEFF Research Database (Denmark)

    Hendriksen, Kåre; Hoffmann, Birgitte

    2017-01-01

    " (United Nations 2015). This obviously raises the question of how this can be achieved considering the very different conditions and cultures around the globe. This article presents the Greenlandic context and elucidates the current Greenland water supply system and wastewater management system from......A good water supply and wastewater management is essential for a local sustainable community development. This is emphasized in the new global goals of the UN Sustainable Development, where the sixth objective is to: "Ensure availability and sustainable management of water and sanitation for all...... a socio-technical approach, focusing on the geographic, climatic and cultural challenges. The article identifies a diverse set of system constellations in different parts of Greenland and concludes with a discussion of health and quality of life implications....

  8. A Systems Biology Framework Identifies Molecular Underpinnings of Coronary Heart Disease

    Science.gov (United States)

    Huan, Tianxiao; Zhang, Bin; Wang, Zhi; Joehanes, Roby; Zhu, Jun; Johnson, Andrew D.; Ying, Saixia; Munson, Peter J.; Raghavachari, Nalini; Wang, Richard; Liu, Poching; Courchesne, Paul; Hwang, Shih-Jen; Assimes, Themistocles L.; McPherson, Ruth; Samani, Nilesh J.; Schunkert, Heribert; Meng, Qingying; Suver, Christine; O'Donnell, Christopher J.; Derry, Jonathan; Yang, Xia; Levy, Daniel

    2013-01-01

    Objective Genetic approaches have identified numerous loci associated with coronary heart disease (CHD). The molecular mechanisms underlying CHD gene-disease associations, however, remain unclear. We hypothesized that genetic variants with both strong and subtle effects drive gene subnetworks that in turn affect CHD. Approach and Results We surveyed CHD-associated molecular interactions by constructing coexpression networks using whole blood gene expression profiles from 188 CHD cases and 188 age- and sex-matched controls. 24 coexpression modules were identified including one case-specific and one control-specific differential module (DM). The DMs were enriched for genes involved in B-cell activation, immune response, and ion transport. By integrating the DMs with altered gene expression associated SNPs (eSNPs) and with results of GWAS of CHD and its risk factors, the control-specific DM was implicated as CHD-causal based on its significant enrichment for both CHD and lipid eSNPs. This causal DM was further integrated with tissue-specific Bayesian networks and protein-protein interaction networks to identify regulatory key driver (KD) genes. Multi-tissue KDs (SPIB and TNFRSF13C) and tissue-specific KDs (e.g. EBF1) were identified. Conclusions Our network-driven integrative analysis not only identified CHD-related genes, but also defined network structure that sheds light on the molecular interactions of genes associated with CHD risk. PMID:23539213

  9. Transthoracic ultrasonic tissue indices identify patients with severe left anterior descending artery stenosis. Correlation with fractional flow reserve. Pilot study.

    Science.gov (United States)

    Dobrowolski, Piotr; Kowalski, Mirosław; Rybicka, Justyna; Lech, Agnieszka; Tyczyński, Paweł; Witkowski, Adam; Hoffman, Piotr

    2016-01-01

    The aim of this study was to evaluate the potential clinical application of ultrasonic tissue indices, with a focus on systolic strain (SS) and systolic strain rate (SSR) parameters derived from transthoracic echocardiography, in the assessment of left anterior descending artery (LAD) stenosis. The data of 30 patients with significant LAD stenosis were analysed. All patients underwent transthoracic echocardiography to obtain systolic myocardial velocity (Sm), longitudinal SS, and SSR from basal, mid, and apical segments of anterior and inferior walls in two-chamber apical view. Severity of LAD obstruction was measured by means of fractional flow reserve (FFR) during coronary catheterisation. Systolic velocities, strain, and strain rate measured in basal, middle, and apical segments of the anterior left ventricular (LV) wall were lower when compared to those obtained from the corresponding, i.e. unaffected, inferior LV wall. There was a significant correlation between FFR and the value of SS, SSR characterising the apical LV segment of the anterior wall (r = -0.583, p = 0.01; r = -0.598, p = 0.01, respectively). Moreover, we found significant correlation between FFR and Sm in the mid-segment of the LV anterior wall (r = 0.611, p = 0.009). We conclude that SS and SSR obtained from the apical segment of the anterior LV wall may be related to the severity of LAD stenosis.

  10. Systems genetic analysis of brown adipose tissue function

    Czech Academy of Sciences Publication Activity Database

    Pravenec, Michal; Saba, L. M.; Zídek, Václav; Landa, Vladimír; Mlejnek, Petr; Šilhavý, Jan; Šimáková, Miroslava; Strnad, Hynek; Trnovská, J.; Škop, V.; Hüttl, M.; Marková, I.; Oliyarnyk, O.; Malínská, H.; Kazdová, L.; Smith, H.; Tabakoff, B.

    2018-01-01

    Roč. 50, č. 1 (2018), s. 52-66 ISSN 1094-8341 R&D Projects: GA ČR(CZ) GA13-04420S Institutional support: RVO:67985823 Keywords : brown adipose tissue * coexpression modules * quantitative trait locus * recombinant inbred strains * spontaneously hypertensive rat Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Human genetics Impact factor: 3.044, year: 2016

  11. CXCR6, a newly defined biomarker of tissue-specific stem cell asymmetric self-renewal, identifies more aggressive human melanoma cancer stem cells.

    Directory of Open Access Journals (Sweden)

    Rouzbeh Taghizadeh

    2010-12-01

    Full Text Available A fundamental problem in cancer research is identifying the cell type that is capable of sustaining neoplastic growth and its origin from normal tissue cells. Recent investigations of a variety of tumor types have shown that phenotypically identifiable and isolable subfractions of cells possess the tumor-forming ability. In the present paper, using two lineage-related human melanoma cell lines, primary melanoma line IGR39 and its metastatic derivative line IGR37, two main observations are reported. The first one is the first phenotypic evidence to support the origin of melanoma cancer stem cells (CSCs from mutated tissue-specific stem cells; and the second one is the identification of a more aggressive subpopulation of CSCs in melanoma that are CXCR6+.We defined CXCR6 as a new biomarker for tissue-specific stem cell asymmetric self-renewal. Thus, the relationship between melanoma formation and ABCG2 and CXCR6 expression was investigated. Consistent with their non-metastatic character, unsorted IGR39 cells formed significantly smaller tumors than unsorted IGR37 cells. In addition, ABCG2+ cells produced tumors that had a 2-fold greater mass than tumors produced by unsorted cells or ABCG2- cells. CXCR6+ cells produced more aggressive tumors. CXCR6 identifies a more discrete subpopulation of cultured human melanoma cells with a more aggressive MCSC phenotype than cells selected on the basis of the ABCG2+ phenotype alone.The association of a more aggressive tumor phenotype with asymmetric self-renewal phenotype reveals a previously unrecognized aspect of tumor cell physiology. Namely, the retention of some tissue-specific stem cell attributes, like the ability to asymmetrically self-renew, impacts the natural history of human tumor development. Knowledge of this new aspect of tumor development and progression may provide new targets for cancer prevention and treatment.

  12. A novel multi-network approach reveals tissue-specific cellular modulators of fibrosis in systemic sclerosis.

    Science.gov (United States)

    Taroni, Jaclyn N; Greene, Casey S; Martyanov, Viktor; Wood, Tammara A; Christmann, Romy B; Farber, Harrison W; Lafyatis, Robert A; Denton, Christopher P; Hinchcliff, Monique E; Pioli, Patricia A; Mahoney, J Matthew; Whitfield, Michael L

    2017-03-23

    Systemic sclerosis (SSc) is a multi-organ autoimmune disease characterized by skin fibrosis. Internal organ involvement is heterogeneous. It is unknown whether disease mechanisms are common across all involved affected tissues or if each manifestation has a distinct underlying pathology. We used consensus clustering to compare gene expression profiles of biopsies from four SSc-affected tissues (skin, lung, esophagus, and peripheral blood) from patients with SSc, and the related conditions pulmonary fibrosis (PF) and pulmonary arterial hypertension, and derived a consensus disease-associate signature across all tissues. We used this signature to query tissue-specific functional genomic networks. We performed novel network analyses to contrast the skin and lung microenvironments and to assess the functional role of the inflammatory and fibrotic genes in each organ. Lastly, we tested the expression of macrophage activation state-associated gene sets for enrichment in skin and lung using a Wilcoxon rank sum test. We identified a common pathogenic gene expression signature-an immune-fibrotic axis-indicative of pro-fibrotic macrophages (MØs) in multiple tissues (skin, lung, esophagus, and peripheral blood mononuclear cells) affected by SSc. While the co-expression of these genes is common to all tissues, the functional consequences of this upregulation differ by organ. We used this disease-associated signature to query tissue-specific functional genomic networks to identify common and tissue-specific pathologies of SSc and related conditions. In contrast to skin, in the lung-specific functional network we identify a distinct lung-resident MØ signature associated with lipid stimulation and alternative activation. In keeping with our network results, we find distinct MØ alternative activation transcriptional programs in SSc-associated PF lung and in the skin of patients with an "inflammatory" SSc gene expression signature. Our results suggest that the innate immune

  13. Development of a computational system for management of risks in radiosterilization processes of biological tissues

    International Nuclear Information System (INIS)

    Montoya, Cynara Viterbo

    2009-01-01

    Risk management can be understood to be a systematic management which aims to identify record and control the risks of a process. Applying risk management becomes a complex activity, due to the variety of professionals involved. In order to execute risk management the following are requirements of paramount importance: the experience, discernment and judgment of a multidisciplinary team, guided by means of quality tools, so as to provide standardization in the process of investigating the cause and effects of risks and dynamism in obtaining the objective desired, i.e. the reduction and control of the risk. This work aims to develop a computational system of risk management (software) which makes it feasible to diagnose the risks of the processes of radiosterilization of biological tissues. The methodology adopted was action-research, according to which the researcher performs an active role in the establishment of the problems found, in the follow-up and in the evaluation of the actions taken owing to the problems. The scenario of this action-research was the Laboratory of Biological Tissues (LTB) in the Radiation Technology Center IPEN/CNEN-SP - Sao Paulo/Brazil. The software developed was executed in PHP and Flash/MySQL language, the server (hosting), the software is available on the Internet (www.vcrisk.com.br), which the user can access from anywhere by means of the login/access password previously sent by email to the team responsible for the tissue to be analyzed. The software presents friendly navigability whereby the user is directed step-by-step in the process of investigating the risk up to the means of reducing it. The software 'makes' the user comply with the term and present the effectiveness of the actions taken to reduce the risk. Applying this system provided the organization (LTB/CTR/IPEN) with dynamic communication, effective between the members of the multidisciplinary team: a) in decision-making; b) in lessons learned; c) in knowing the new risk

  14. Upregulation of Mrps18a in breast cancer identified by selecting phage antibody libraries on breast tissue sections

    DEFF Research Database (Denmark)

    Sørensen, Karen Marie Juul; Meldgaard, Theresa; Melchjorsen, Connie Jenning

    2017-01-01

    BACKGROUND: One of the hallmarks of cancer is an altered energy metabolism, and here, mitochondria play a central role. Previous studies have indicated that some mitochondrial ribosomal proteins change their expression patterns upon transformation. METHOD: In this study, we have used the selection...... of recombinant antibody libraries displayed on the surface of filamentous bacteriophage as a proteomics discovery tool for the identification of breast cancer biomarkers. A small subpopulation of breast cells expressing both cytokeratin 19 and cytokeratin 14 was targeted using a novel selection procedure....... RESULTS: We identified the mitochondrial ribosomal protein s18a (Mrps18a) as a protein which is upregulated in breast cancer. However, Mrps18a was not homogeneously upregulated in all cancer cells, suggesting the existence of sub-populations within the tumor. The upregulation was not confined...

  15. TumorTracer: a method to identify the tissue of origin from the somatic mutations of a tumor specimen

    DEFF Research Database (Denmark)

    Marquard, Andrea Marion; Birkbak, Nicolai Juul; Thomas, Cecilia Engel

    2015-01-01

    A substantial proportion of cancer cases present with a metastatic tumor and require further testing to determine the primary site; many of these are never fully diagnosed and remain cancer of unknown primary origin (CUP). It has been previously demonstrated that the somatic point mutations......-copy-number classifier on three independent data sets: 1669 newly available public tumors of various types, a cohort of 91 breast metastases, and a set of 24 specimens from 9 lung cancer patients subjected to multiregion sequencing. The cross-validation accuracy was highest when all three types of information were used...... detected in a tumor can be used to identify its site of origin with limited accuracy. We hypothesized that higher accuracy could be achieved by a classification algorithm based on the following feature sets: 1) the number of nonsynonymous point mutations in a set of 232 specific cancer-associated genes, 2...

  16. A focused air-pulse system for optical-coherence-tomography-based measurements of tissue elasticity

    International Nuclear Information System (INIS)

    Wang, Shang; Larin, K V; Li, Jiasong; Vantipalli, S; Twa, M D; Manapuram, R K; Aglyamov, S; Emelianov, S

    2013-01-01

    Accurate non-invasive assessment of tissue elasticity in vivo is required for early diagnostics of many tissue abnormalities. We have developed a focused air-pulse system that produces a low-pressure and short-duration air stream, which can be used to excite transient surface waves (SWs) in soft tissues. System characteristics were studied using a high-resolution analog pressure transducer to describe the excitation pressure. Results indicate that the excitation pressure provided by the air-pulse system can be easily controlled by the air source pressure, the angle of delivery, and the distance between the tissue surface and the port of the air-pulse system. Furthermore, we integrated this focused air-pulse system with phase-sensitive optical coherence tomography (PhS-OCT) to make non-contact measurements of tissue elasticity. The PhS-OCT system is used to assess the group velocity of SW propagation, which can be used to determine Young’s modulus. Pilot experiments were performed on gelatin phantoms with different concentrations (10%, 12% and 14% w/w). The results demonstrate the feasibility of using this focused air-pulse system combined with PhS-OCT to estimate tissue elasticity. This easily controlled non-contact technique is potentially useful to study the biomechanical properties of ocular and other tissues in vivo. (letter)

  17. Transcriptome analysis of skeletal muscle tissue to identify genes involved in pre-slaughter stress response in pigs

    Directory of Open Access Journals (Sweden)

    Vincenzo Russo

    2010-01-01

    Full Text Available The knowledge of genes and molecular processes controlling stress reactions and involved in the genetic system determining resistance to stress in pigs could be important for the improvement of meat quality. This research aimed to compare the expression profiles of skeletal muscle between physically stressed and not stressed pigs of different breeds immediately before slaughter. DNA microarray analysis showed that different functional categories of genes are up-regulated in stressed compared to not stressed pigs and relevant differences among breeds were found.

  18. Digital gene expression profiling of flax (Linum usitatissimum L.) stem peel identifies genes enriched in fiber-bearing phloem tissue.

    Science.gov (United States)

    Guo, Yuan; Qiu, Caisheng; Long, Songhua; Chen, Ping; Hao, Dongmei; Preisner, Marta; Wang, Hui; Wang, Yufu

    2017-08-30

    To better understand the molecular mechanisms and gene expression characteristics associated with development of bast fiber cell within flax stem phloem, the gene expression profiling of flax stem peels and leaves were screened, using Illumina's Digital Gene Expression (DGE) analysis. Four DGE libraries (2 for stem peel and 2 for leaf), ranging from 6.7 to 9.2 million clean reads were obtained, which produced 7.0 million and 6.8 million mapped reads for flax stem peel and leave, respectively. By differential gene expression analysis, a total of 975 genes, of which 708 (73%) genes have protein-coding annotation, were identified as phloem enriched genes putatively involved in the processes of polysaccharide and cell wall metabolism. Differential expression genes (DEGs) was validated using quantitative RT-PCR, the expression pattern of all nine genes determined by qRT-PCR fitted in well with that obtained by sequencing analysis. Cluster and Gene Ontology (GO) analysis revealed that a large number of genes related to metabolic process, catalytic activity and binding category were expressed predominantly in the stem peels. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of the phloem enriched genes suggested approximately 111 biological pathways. The large number of genes and pathways produced from DGE sequencing will expand our understanding of the complex molecular and cellular events in flax bast fiber development and provide a foundation for future studies on fiber development in other bast fiber crops. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Preparation and in vivo evaluation of radioiodinated closo-decaborate(2-) derivatives to identify structural components that provide low retention in tissues

    International Nuclear Information System (INIS)

    Wilbur, D. Scott; Chyan, M.-K.; Hamlin, Donald K.; Perry, Matthew A.

    2010-01-01

    Introduction: In vivo deastatination of 211 At-labeled biomolecules can severely limit their use in endoradiotherapy. Our studies have shown that the use of closo-decaborate(2-) moiety for 211 At-labeling of biomolecules provides high in vivo stability towards deastatination. However, data from those studies have also been suggestive that some astatinated closo-decaborate(2-) catabolites may be retained in tissues. In this study, we investigated the in vivo distributions of several structurally simple closo-decaborate(2-) derivatives to gain information on the effects of functional groups if catabolites are released into the blood system from the carrier biomolecule. Methods: Thirteen closo-decaborate(2-) derivatives were synthesized and radioiodinated for evaluation. Tissue concentrations of the radioiodinated compounds were obtained in groups of five mice at 1 and 4 h postinjection (pi). Dual-label ( 125 I and 131 I) experiments permitted evaluation of two compounds in each set of mice. Results: All of the target compounds were readily synthesized. Radioiodination reactions were conducted with chloramine-T and Na[ 125/131 I]I in water to give high yields (75-96%) of the desired compounds. Biodistribution data at 1 and 4 h pi (representing catabolites released into the blood system) showed small differences in tissue concentrations for some compounds, but large differences for others. The results indicate that formal (overall) charge on the compounds could not be used as a predictor of tissue localization or retention. However, derivatives containing carboxylate groups generally had lower tissue concentrations. Acid cleavable hydrazone functionalities appeared to be the best candidates for further study. Conclusions: Further studies incorporating hydrazone functionalities into pendant groups for biomolecule radiohalogenation are warranted.

  20. Central nervous system tissue heterotopia of the nose: case report and review of the literature

    Science.gov (United States)

    Altissimi, G; Ascani, S; Falcetti, S; Cazzato, C; Bravi, I

    2009-01-01

    Summary The Authors present a case of heterotopic central nervous system tissue observed in an 81-year-old male in the form of an ethmoidal polyp. A review of the literature indicates that this is a rare condition characterised by a connective tissue lesion with astrocytic and oligodendrocytic glial cells, which may be located outside the nasal pyramid in some cases and inside the nasal cavity in others. The most important diagnostic aspect involves differentiating these from meningoencephalocele, which maintains an anatomical connection with central nervous system tissue. Contrast-enhanced imaging is essential for diagnosis, as in cases of heterotopic central nervous system tissue, it will demonstrate that there are no connections with intra-cranial tissue. Endoscopic excision is the treatment of choice. PMID:20161881

  1. A Genome-Wide mQTL Analysis in Human Adipose Tissue Identifies Genetic Variants Associated with DNA Methylation, Gene Expression and Metabolic Traits.

    Directory of Open Access Journals (Sweden)

    Petr Volkov

    Full Text Available Little is known about the extent to which interactions between genetics and epigenetics may affect the risk of complex metabolic diseases and/or their intermediary phenotypes. We performed a genome-wide DNA methylation quantitative trait locus (mQTL analysis in human adipose tissue of 119 men, where 592,794 single nucleotide polymorphisms (SNPs were related to DNA methylation of 477,891 CpG sites, covering 99% of RefSeq genes. SNPs in significant mQTLs were further related to gene expression in adipose tissue and obesity related traits. We found 101,911 SNP-CpG pairs (mQTLs in cis and 5,342 SNP-CpG pairs in trans showing significant associations between genotype and DNA methylation in adipose tissue after correction for multiple testing, where cis is defined as distance less than 500 kb between a SNP and CpG site. These mQTLs include reported obesity, lipid and type 2 diabetes loci, e.g. ADCY3/POMC, APOA5, CETP, FADS2, GCKR, SORT1 and LEPR. Significant mQTLs were overrepresented in intergenic regions meanwhile underrepresented in promoter regions and CpG islands. We further identified 635 SNPs in significant cis-mQTLs associated with expression of 86 genes in adipose tissue including CHRNA5, G6PC2, GPX7, RPL27A, THNSL2 and ZFP57. SNPs in significant mQTLs were also associated with body mass index (BMI, lipid traits and glucose and insulin levels in our study cohort and public available consortia data. Importantly, the Causal Inference Test (CIT demonstrates how genetic variants mediate their effects on metabolic traits (e.g. BMI, cholesterol, high-density lipoprotein (HDL, hemoglobin A1c (HbA1c and homeostatic model assessment of insulin resistance (HOMA-IR via altered DNA methylation in human adipose tissue. This study identifies genome-wide interactions between genetic and epigenetic variation in both cis and trans positions influencing gene expression in adipose tissue and in vivo (dysmetabolic traits associated with the development of

  2. Heat generation caused by ablation of dental hard tissues with an ultrashort pulse laser (USPL) system.

    Science.gov (United States)

    Braun, Andreas; Krillke, Raphael Franz; Frentzen, Matthias; Bourauel, Christoph; Stark, Helmut; Schelle, Florian

    2015-02-01

    Heat generation during the removal of dental hard tissues may lead to a temperature increase and cause painful sensations or damage dental tissues. The aim of this study was to assess heat generation in dental hard tissues following laser ablation using an ultrashort pulse laser (USPL) system. A total of 85 specimens of dental hard tissues were used, comprising 45 specimens of human dentine evaluating a thickness of 1, 2, and 3 mm (15 samples each) and 40 specimens of human enamel with a thickness of 1 and 2 mm (20 samples each). Ablation was performed with an Nd:YVO4 laser at 1,064 nm, a pulse duration of 9 ps, and a repetition rate of 500 kHz with an average output power of 6 W. Specimens were irradiated for 0.8 s. Employing a scanner system, rectangular cavities of 1-mm edge length were generated. A temperature sensor was placed at the back of the specimens, recording the temperature during the ablation process. All measurements were made employing a heat-conductive paste without any additional cooling or spray. Heat generation during laser ablation depended on the dental hard tissue (enamel or dentine) and the thickness of the respective tissue (p dental hard tissues, heat generation has to be considered. Especially during laser ablation next to pulpal tissues, painful sensations and potential thermal injury of pulp tissue might occur.

  3. Thicker three-dimensional tissue from a "symbiotic recycling system" combining mammalian cells and algae.

    Science.gov (United States)

    Haraguchi, Yuji; Kagawa, Yuki; Sakaguchi, Katsuhisa; Matsuura, Katsuhisa; Shimizu, Tatsuya; Okano, Teruo

    2017-01-31

    In this paper, we report an in vitro co-culture system that combines mammalian cells and algae, Chlorococcum littorale, to create a three-dimensional (3-D) tissue. While the C2C12 mouse myoblasts and rat cardiac cells consumed oxygen actively, intense oxygen production was accounted for by the algae even in the co-culture system. Although cell metabolism within thicker cardiac cell-layered tissues showed anaerobic respiration, the introduction of innovative co-cultivation partially changed the metabolism to aerobic respiration. Moreover, the amount of glucose consumption and lactate production in the cardiac tissues and the amount of ammonia in the culture media decreased significantly when co-cultivated with algae. In the cardiac tissues devoid of algae, delamination was observed histologically, and the release of creatine kinase (CK) from the tissues showed severe cardiac cell damage. On the other hand, the layered cell tissues with algae were observed to be in a good histological condition, with less than one-fifth decline in CK release. The co-cultivation with algae improved the culture condition of the thicker tissues, resulting in the formation of 160 μm-thick cardiac tissues. Thus, the present study proposes the possibility of creating an in vitro "symbiotic recycling system" composed of mammalian cells and algae.

  4. Study of the optical properties of solid tissue phantoms using single and double integrating sphere systems

    CSIR Research Space (South Africa)

    Monem, S

    2015-12-01

    Full Text Available light propagation mechanisms inside the tissues. In this work, two calibration models based on measurements adopting integrating sphere systems have been used to determine the optical properties of the studied solid phantoms. Integrating sphere...

  5. Evaluation of histological scoring systems for tissue-engineered, repaired and osteoarthritic cartilage

    NARCIS (Netherlands)

    Rutgers, M.; van Pelt, M.J.; Dhert, W.J.A.; Creemers, L.B.; Saris, D.B.F.

    2010-01-01

    Osteoarthritis and Cartilage Volume 18, Issue 1, January 2010, Pages 12-23 -------------------------------------------------------------------------------- Review Evaluation of histological scoring systems for tissue-engineered, repaired and osteoarthritic cartilage M. Rutgers†, M.J.P. van Pelt†,

  6. 20 Years of persistent identifiers - Which systems are here to stay?

    Science.gov (United States)

    Klump, Jens; Huber, Robert; Lehnert, Kerstin

    2016-04-01

    Web-based persistent identifiers have been around for more than 20 years, a period long enough to start observing patterns of success and failure. Persistent identifiers were invented to address challenges arising from the distributed and disorganised nature of the internet, which not only allowed new technologies to emerge, it also made it difficult to maintain a persistent record of science. Persistent identifiers now allow unambiguous identification of resources on the net. The expectations were that persistent identifiers would lead to greater accessibility, transparency and reproducibility of research results. Over the past two decades a number of persistent identifier systems have been built, one of them being Digital Object Identifiers (DOI). While DOI were originally invented by the publishing industry, they quickly became an established way for the identification of research resources. At first, these resources referred to scholarly literature and related resources. Other identifier systems, some of them using DOI as an example, were developed as grass-roots efforts by the scientific community. The concept of using persistent identifiers has since been expanded to other, non-textual resources, like datasets (DOI, EPIC) and geological specimens (IGSN), and more recently to authors and contributors of scholarly works (ORCID), and to software and instruments. A common witticism states that "a great thing about standards is that there are so many to choose from." Setting up identifier systems is technically trivial. The real challenge lies in creating a governance system for the respective identifiers. Which systems will stand the test of time? Drawing on data from the Registry of Research Data Repositories (re3data.org) and our own experience in the field, this presentation looks at the history and adoption of existing identifier systems and how this gives us some indications towards factors influencing sustainability of these systems.

  7. Quantitative multiplex quantum dot in-situ hybridisation based gene expression profiling in tissue microarrays identifies prognostic genes in acute myeloid leukaemia

    Energy Technology Data Exchange (ETDEWEB)

    Tholouli, Eleni [Department of Haematology, Manchester Royal Infirmary, Oxford Road, Manchester, M13 9WL (United Kingdom); MacDermott, Sarah [The Medical School, The University of Manchester, Oxford Road, M13 9PT Manchester (United Kingdom); Hoyland, Judith [School of Biomedicine, Faculty of Medical and Human Sciences, The University of Manchester, Oxford Road, M13 9PT Manchester (United Kingdom); Yin, John Liu [Department of Haematology, Manchester Royal Infirmary, Oxford Road, Manchester, M13 9WL (United Kingdom); Byers, Richard, E-mail: richard.byers@cmft.nhs.uk [School of Cancer and Enabling Sciences, Faculty of Medical and Human Sciences, The University of Manchester, Stopford Building, Oxford Road, M13 9PT Manchester (United Kingdom)

    2012-08-24

    Highlights: Black-Right-Pointing-Pointer Development of a quantitative high throughput in situ expression profiling method. Black-Right-Pointing-Pointer Application to a tissue microarray of 242 AML bone marrow samples. Black-Right-Pointing-Pointer Identification of HOXA4, HOXA9, Meis1 and DNMT3A as prognostic markers in AML. -- Abstract: Measurement and validation of microarray gene signatures in routine clinical samples is problematic and a rate limiting step in translational research. In order to facilitate measurement of microarray identified gene signatures in routine clinical tissue a novel method combining quantum dot based oligonucleotide in situ hybridisation (QD-ISH) and post-hybridisation spectral image analysis was used for multiplex in-situ transcript detection in archival bone marrow trephine samples from patients with acute myeloid leukaemia (AML). Tissue-microarrays were prepared into which white cell pellets were spiked as a standard. Tissue microarrays were made using routinely processed bone marrow trephines from 242 patients with AML. QD-ISH was performed for six candidate prognostic genes using triplex QD-ISH for DNMT1, DNMT3A, DNMT3B, and for HOXA4, HOXA9, Meis1. Scrambled oligonucleotides were used to correct for background staining followed by normalisation of expression against the expression values for the white cell pellet standard. Survival analysis demonstrated that low expression of HOXA4 was associated with poorer overall survival (p = 0.009), whilst high expression of HOXA9 (p < 0.0001), Meis1 (p = 0.005) and DNMT3A (p = 0.04) were associated with early treatment failure. These results demonstrate application of a standardised, quantitative multiplex QD-ISH method for identification of prognostic markers in formalin-fixed paraffin-embedded clinical samples, facilitating measurement of gene expression signatures in routine clinical samples.

  8. Multi-tissue analysis of co-expression networks by higher-order generalized singular value decomposition identifies functionally coherent transcriptional modules.

    Science.gov (United States)

    Xiao, Xiaolin; Moreno-Moral, Aida; Rotival, Maxime; Bottolo, Leonardo; Petretto, Enrico

    2014-01-01

    Recent high-throughput efforts such as ENCODE have generated a large body of genome-scale transcriptional data in multiple conditions (e.g., cell-types and disease states). Leveraging these data is especially important for network-based approaches to human disease, for instance to identify coherent transcriptional modules (subnetworks) that can inform functional disease mechanisms and pathological pathways. Yet, genome-scale network analysis across conditions is significantly hampered by the paucity of robust and computationally-efficient methods. Building on the Higher-Order Generalized Singular Value Decomposition, we introduce a new algorithmic approach for efficient, parameter-free and reproducible identification of network-modules simultaneously across multiple conditions. Our method can accommodate weighted (and unweighted) networks of any size and can similarly use co-expression or raw gene expression input data, without hinging upon the definition and stability of the correlation used to assess gene co-expression. In simulation studies, we demonstrated distinctive advantages of our method over existing methods, which was able to recover accurately both common and condition-specific network-modules without entailing ad-hoc input parameters as required by other approaches. We applied our method to genome-scale and multi-tissue transcriptomic datasets from rats (microarray-based) and humans (mRNA-sequencing-based) and identified several common and tissue-specific subnetworks with functional significance, which were not detected by other methods. In humans we recapitulated the crosstalk between cell-cycle progression and cell-extracellular matrix interactions processes in ventricular zones during neocortex expansion and further, we uncovered pathways related to development of later cognitive functions in the cortical plate of the developing brain which were previously unappreciated. Analyses of seven rat tissues identified a multi-tissue subnetwork of co

  9. Multi-tissue analysis of co-expression networks by higher-order generalized singular value decomposition identifies functionally coherent transcriptional modules.

    Directory of Open Access Journals (Sweden)

    Xiaolin Xiao

    2014-01-01

    Full Text Available Recent high-throughput efforts such as ENCODE have generated a large body of genome-scale transcriptional data in multiple conditions (e.g., cell-types and disease states. Leveraging these data is especially important for network-based approaches to human disease, for instance to identify coherent transcriptional modules (subnetworks that can inform functional disease mechanisms and pathological pathways. Yet, genome-scale network analysis across conditions is significantly hampered by the paucity of robust and computationally-efficient methods. Building on the Higher-Order Generalized Singular Value Decomposition, we introduce a new algorithmic approach for efficient, parameter-free and reproducible identification of network-modules simultaneously across multiple conditions. Our method can accommodate weighted (and unweighted networks of any size and can similarly use co-expression or raw gene expression input data, without hinging upon the definition and stability of the correlation used to assess gene co-expression. In simulation studies, we demonstrated distinctive advantages of our method over existing methods, which was able to recover accurately both common and condition-specific network-modules without entailing ad-hoc input parameters as required by other approaches. We applied our method to genome-scale and multi-tissue transcriptomic datasets from rats (microarray-based and humans (mRNA-sequencing-based and identified several common and tissue-specific subnetworks with functional significance, which were not detected by other methods. In humans we recapitulated the crosstalk between cell-cycle progression and cell-extracellular matrix interactions processes in ventricular zones during neocortex expansion and further, we uncovered pathways related to development of later cognitive functions in the cortical plate of the developing brain which were previously unappreciated. Analyses of seven rat tissues identified a multi-tissue

  10. Spatial transcriptomics: paving the way for tissue-level systems biology.

    Science.gov (United States)

    Moor, Andreas E; Itzkovitz, Shalev

    2017-08-01

    The tissues in our bodies are complex systems composed of diverse cell types that often interact in highly structured repeating anatomical units. External gradients of morphogens, directional blood flow, as well as the secretion and absorption of materials by cells generate distinct microenvironments at different tissue coordinates. Such spatial heterogeneity enables optimized function through division of labor among cells. Unraveling the design principles that govern this spatial division of labor requires techniques to quantify the entire transcriptomes of cells while accounting for their spatial coordinates. In this review we describe how recent advances in spatial transcriptomics open the way for tissue-level systems biology. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Methodology for identifying boundaries of systems important to safety in CANDU nuclear power plants

    International Nuclear Information System (INIS)

    Therrien, S.; Komljenovic, D.; Therrien, P.; Ruest, C.; Prevost, P.; Vaillancourt, R.

    2007-01-01

    This paper presents a methodology developed to identify the boundaries of the systems important to safety (SIS) at the Gentilly-2 Nuclear Power Plant (NPP), Hydro-Quebec. The SIS boundaries identification considers nuclear safety only. Components that are not identified as important to safety are systematically identified as related to safety. A global assessment process such as WANO/INPO AP-913 'Equipment Reliability Process' will be needed to implement adequate changes in the management rules of those components. The paper depicts results in applying the methodology to the Shutdown Systems 1 and 2 (SDS 1, 2), and to the Emergency Core Cooling System (ECCS). This validation process enabled fine tuning the methodology, performing a better estimate of the effort required to evaluate a system, and identifying components important to safety of these systems. (author)

  12. Five-dimensional ultrasound system for soft tissue visualization.

    Science.gov (United States)

    Deshmukh, Nishikant P; Caban, Jesus J; Taylor, Russell H; Hager, Gregory D; Boctor, Emad M

    2015-12-01

    A five-dimensional ultrasound (US) system is proposed as a real-time pipeline involving fusion of 3D B-mode data with the 3D ultrasound elastography (USE) data as well as visualization of these fused data and a real-time update capability over time for each consecutive scan. 3D B-mode data assist in visualizing the anatomy of the target organ, and 3D elastography data adds strain information. We investigate the feasibility of such a system and show that an end-to-end real-time system, from acquisition to visualization, can be developed. We present a system that consists of (a) a real-time 3D elastography algorithm based on a normalized cross-correlation (NCC) computation on a GPU; (b) real-time 3D B-mode acquisition and network transfer; (c) scan conversion of 3D elastography and B-mode volumes (if acquired by 4D wobbler probe); and (d) visualization software that fuses, visualizes, and updates 3D B-mode and 3D elastography data in real time. We achieved a speed improvement of 4.45-fold for the threaded version of the NCC-based 3D USE versus the non-threaded version. The maximum speed was 79 volumes/s for 3D scan conversion. In a phantom, we validated the dimensions of a 2.2-cm-diameter sphere scan-converted to B-mode volume. Also, we validated the 5D US system visualization transfer function and detected 1- and 2-cm spherical objects (phantom lesion). Finally, we applied the system to a phantom consisting of three lesions to delineate the lesions from the surrounding background regions of the phantom. A 5D US system is achievable with real-time performance. We can distinguish between hard and soft areas in a phantom using the transfer functions.

  13. Tissue Renin-Angiotensin Systems: A Unifying Hypothesis of Metabolic Disease

    Directory of Open Access Journals (Sweden)

    Jeppe eSkov

    2014-02-01

    Full Text Available The actions of angiotensin peptides are diverse and locally acting tissue renin-angiotensin systems (RAS are present in almost all tissues of the body. An activated RAS strongly correlates to metabolic disease (e.g. diabetes and its complications and blockers of RAS have been demonstrated to prevent diabetes in humans.Hyperglycemia, obesity, hypertension, and cortisol are well-known risk factors of metabolic disease and all stimulate tissue RAS whereas glucagon-like peptide-1, vitamin D, and aerobic exercise are inhibitors of tissue RAS and to some extent can prevent metabolic disease. Furthermore, an activated tissue RAS deteriorates the same risk factors creating a system with several positive feedback pathways. The primary effector hormone of the RAS, angiotensin II, stimulates reactive oxygen species, induces tissue damage, and can be associated to most diabetic complications. Based on these observations we hypothesize that an activated tissue RAS is the principle cause of metabolic syndrome and type 2 diabetes, and additionally is mediating the majority of the metabolic complications. The involvement of positive feedback pathways may create a self-reinforcing state and explain why metabolic disease initiate and progress. The hypothesis plausibly unify the major predictors of metabolic disease and places tissue RAS regulation in the center of metabolic control.

  14. The skeletal vascular system - Breathing life into bone tissue.

    Science.gov (United States)

    Stegen, Steve; Carmeliet, Geert

    2017-08-26

    During bone development, homeostasis and repair, a dense vascular system provides oxygen and nutrients to highly anabolic skeletal cells. Characteristic for the vascular system in bone is the serial organization of two capillary systems, each typified by specific morphological and physiological features. Especially the arterial capillaries mediate the growth of the bone vascular system, serve as a niche for skeletal and hematopoietic progenitors and couple angiogenesis to osteogenesis. Endothelial cells and osteoprogenitor cells interact not only physically, but also communicate to each other by secretion of growth factors. A vital angiogenic growth factor is vascular endothelial growth factor and its expression in skeletal cells is controlled by osteogenic transcription factors and hypoxia signaling, whereas the secretion of angiocrine factors by endothelial cells is regulated by Notch signaling, blood flow and possibly hypoxia. Bone loss and impaired fracture repair are often associated with reduced and disorganized blood vessel network and therapeutic targeting of the angiogenic response may contribute to enhanced bone regeneration. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. System reliability analysis using dominant failure modes identified by selective searching technique

    International Nuclear Information System (INIS)

    Kim, Dong-Seok; Ok, Seung-Yong; Song, Junho; Koh, Hyun-Moo

    2013-01-01

    The failure of a redundant structural system is often described by innumerable system failure modes such as combinations or sequences of local failures. An efficient approach is proposed to identify dominant failure modes in the space of random variables, and then perform system reliability analysis to compute the system failure probability. To identify dominant failure modes in the decreasing order of their contributions to the system failure probability, a new simulation-based selective searching technique is developed using a genetic algorithm. The system failure probability is computed by a multi-scale matrix-based system reliability (MSR) method. Lower-scale MSR analyses evaluate the probabilities of the identified failure modes and their statistical dependence. A higher-scale MSR analysis evaluates the system failure probability based on the results of the lower-scale analyses. Three illustrative examples demonstrate the efficiency and accuracy of the approach through comparison with existing methods and Monte Carlo simulations. The results show that the proposed method skillfully identifies the dominant failure modes, including those neglected by existing approaches. The multi-scale MSR method accurately evaluates the system failure probability with statistical dependence fully considered. The decoupling between the failure mode identification and the system reliability evaluation allows for effective applications to larger structural systems

  16. Tissue P Systems With Channel States Working in the Flat Maximally Parallel Way.

    Science.gov (United States)

    Song, Bosheng; Perez-Jimenez, Mario J; Paun, Gheorghe; Pan, Linqiang

    2016-10-01

    Tissue P systems with channel states are a class of bio-inspired parallel computational models, where rules are used in a sequential manner (on each channel, at most one rule can be used at each step). In this work, tissue P systems with channel states working in a flat maximally parallel way are considered, where at each step, on each channel, a maximal set of applicable rules that pass from a given state to a unique next state, is chosen and each rule in the set is applied once. The computational power of such P systems is investigated. Specifically, it is proved that tissue P systems with channel states and antiport rules of length two are able to compute Parikh sets of finite languages, and such P systems with one cell and noncooperative symport rules can compute at least all Parikh sets of matrix languages. Some Turing universality results are also provided. Moreover, the NP-complete problem SAT is solved by tissue P systems with channel states, cell division and noncooperative symport rules working in the flat maximally parallel way; nevertheless, if channel states are not used, then such P systems working in the flat maximally parallel way can solve only tractable problems. These results show that channel states provide a frontier of tractability between efficiency and non-efficiency in the framework of tissue P systems with cell division (assuming P ≠ NP ).

  17. Independent bottlenecks characterize colonization of systemic compartments and gut lymphoid tissue by salmonella.

    Science.gov (United States)

    Lim, Chee Han; Voedisch, Sabrina; Wahl, Benjamin; Rouf, Syed Fazle; Geffers, Robert; Rhen, Mikael; Pabst, Oliver

    2014-07-01

    Vaccination represents an important instrument to control typhoid fever in humans and protects mice from lethal infection with mouse pathogenic serovars of Salmonella species. Mixed infections with tagged Salmonella can be used in combination with probabilistic models to describe the dynamics of the infection process. Here we used mixed oral infections with tagged Salmonella strains to identify bottlenecks in the infection process in naïve and vaccinated mice. We established a next generation sequencing based method to characterize the composition of tagged Salmonella strains which offers a fast and reliable method to characterise the composition of genome-tagged Salmonella strains. We show that initial colonization of Salmonella was distinguished by a non-Darwinian selection of few bacteria setting up the infection independently in gut associated lymphoid tissue and systemic compartments. Colonization of Peyer's patches fuels the sustained spread of bacteria into mesenteric lymph nodes via dendritic cells. In contrast, infection of liver and spleen originated from an independent pool of bacteria. Vaccination only moderately reduced invasion of Peyer's patches but potently uncoupled bacterial populations present in different systemic compartments. Our data indicate that vaccination differentially skews the capacity of Salmonella to colonize systemic and gut immune compartments and provide a framework for the further dissection of infection dynamics.

  18. Independent bottlenecks characterize colonization of systemic compartments and gut lymphoid tissue by salmonella.

    Directory of Open Access Journals (Sweden)

    Chee Han Lim

    2014-07-01

    Full Text Available Vaccination represents an important instrument to control typhoid fever in humans and protects mice from lethal infection with mouse pathogenic serovars of Salmonella species. Mixed infections with tagged Salmonella can be used in combination with probabilistic models to describe the dynamics of the infection process. Here we used mixed oral infections with tagged Salmonella strains to identify bottlenecks in the infection process in naïve and vaccinated mice. We established a next generation sequencing based method to characterize the composition of tagged Salmonella strains which offers a fast and reliable method to characterise the composition of genome-tagged Salmonella strains. We show that initial colonization of Salmonella was distinguished by a non-Darwinian selection of few bacteria setting up the infection independently in gut associated lymphoid tissue and systemic compartments. Colonization of Peyer's patches fuels the sustained spread of bacteria into mesenteric lymph nodes via dendritic cells. In contrast, infection of liver and spleen originated from an independent pool of bacteria. Vaccination only moderately reduced invasion of Peyer's patches but potently uncoupled bacterial populations present in different systemic compartments. Our data indicate that vaccination differentially skews the capacity of Salmonella to colonize systemic and gut immune compartments and provide a framework for the further dissection of infection dynamics.

  19. Tissue distribution of enrofloxacin after intramammary or simulated systemic administration in isolated perfused sheep udders.

    Science.gov (United States)

    López Cadenas, Cristina; Fernández Martínez, Nélida; Sierra Vega, Matilde; Diez Liébana, Maria J; Gonzalo Orden, Jose M; Sahagún Prieto, Ana M; García Vieitez, Juan J

    2012-11-01

    To determine the tissue distribution of enrofloxacin after intramammary or simulated systemic administration in isolated perfused sheep udders by measuring its concentration at various sample collection sites. 26 udders (obtained following euthanasia) from 26 healthy lactating sheep. For each isolated udder, 1 mammary gland was perfused with warmed, gassed Tyrode solution. Enrofloxacin (1 g of enrofloxacin/5 g of ointment) was administered into the perfused gland via the intramammary route or systemically via the perfusion fluid (equivalent to a dose of 5 mg/kg). Samples of the perfusate were obtained every 30 minutes for 180 minutes; glandular tissue samples were obtained at 2, 4, 6, and 8 cm from the teat base after 180 minutes. The enrofloxacin content of the perfusate and tissue samples was analyzed via high-performance liquid chromatography with UV detection. After intramammary administration, maximun perfusate enrofloxacin concentration was detected at 180 minutes and, at this time, mean tissue enrofloxacin concentration was detected and mean tissue enrofloxacin concentration was 123.80, 54.48, 36.72, and 26.42 μg/g of tissue at 2, 4, 6, and 8 cm from the teat base, respectively. Following systemic administration, perfusate enrofloxacin concentration decreased with time and, at 180 minutes, tissue enrofloxacin concentrations ranged from 40.38 to 35.58 μg/g of tissue. By 180 minutes after administration via the intramammary or systemic route in isolated perfused sheep mammary glands, mean tissue concentration of enrofloxacin was greater than the minimum inhibitory concentration required to inhibit growth of 90% of many common mastitis pathogens in sheep. Use of either route of administration (or in combination) appears suitable for the treatment of acute mastitis in sheep.

  20. Identifying the Goal, User model and Conditions of Recommender Systems for Formal and Informal Learning

    NARCIS (Netherlands)

    Drachsler, Hendrik; Hummel, Hans; Koper, Rob

    2008-01-01

    Drachsler, H., Hummel, H. G. K., & Koper, R. (2009). Identifying the Goal, User model and Conditions of Recommender Systems for Formal and Informal Learning. Journal of Digital Information, 10(2), 4-24.

  1. A precision isotonic measuring system for isolated tissues.

    Science.gov (United States)

    Mellor, P M

    1984-12-01

    An isotonic measuring system is described which utilizes an angular position transducer of the linear differential voltage transformer type. Resistance to corrosion, protection against the ingress of solutions, and ease of mounting and setting up were the mechanical objectives. Accuracy, linearity, and freedom from drift were essential requirements of the electrical specification. A special housing was designed to accommodate the transducer to overcome these problems. A control unit incorporating a power supply and electronic filtering components was made to serve up to four such transducers. The transducer output voltage is sufficiently high to drive directly even low sensitivity chart recorders. Constructional details and a circuit diagram are included. Fifty such transducers have been in use for up to four years in these laboratories. Examples of some of the published work done using this transducer system are referenced.

  2. Multicompartment Drug Release System for Dynamic Modulation of Tissue Responses.

    Science.gov (United States)

    Morris, Aaron H; Mahal, Rajwant S; Udell, Jillian; Wu, Michelle; Kyriakides, Themis R

    2017-10-01

    Pharmacological modulation of responses to injury is complicated by the need to deliver multiple drugs with spatiotemporal resolution. Here, a novel controlled delivery system containing three separate compartments with each releasing its contents over different timescales is fabricated. Core-shell electrospun fibers create two of the compartments in the system, while electrosprayed spheres create the third. Utility is demonstrated by targeting the foreign body response to implants because it is a dynamic process resulting in implant failure. Sequential delivery of a drug targeting nuclear factor-κB (NF-κB) and an antifibrotic is characterized in in vitro experiments. Specifically, macrophage fusion and p65 nuclear translocation in the presence of releasate or with macrophages cultured on the surfaces of the constructs are evaluated. In addition, releasate from pirfenidone scaffolds is shown to reduce transforming growth factor-β (TGF-β)-induced pSMAD3 nuclear localization in fibroblasts. In vivo, drug eluting constructs successfully mitigate macrophage fusion at one week and fibrotic encapsulation in a dose-dependent manner at four weeks, demonstrating effective release of both drugs over different timescales. Future studies can employ this system to improve and prolong implant lifetimes, or load it with other drugs to modulate other dynamic processes. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Identifying the Return on Investment for Army Migration to a Modular Open Systems Approach for Future and Legacy Systems

    Science.gov (United States)

    2017-04-05

    Identifying the Return on Investment for Army Migration to a Modular Open Systems Approach for Future and Legacy Systems Phillip Minor...Authorization Act (NDAA) of 2015, cites the modular open systems approach (MOSA) as both a business and technical strategy to reduce the cost of system ...access the service over the network. Combine the advances cited above with the emergence of systems developed using the modular open systems approach

  4. Nitrogen assimilation system in maize is regulated by developmental and tissue-specific mechanisms

    KAUST Repository

    Plett, Darren

    2016-08-10

    Key message: We found metabolites, enzyme activities and enzyme transcript abundances vary significantly across the maize lifecycle, but weak correlation exists between the three groups. We identified putative genes regulating nitrate assimilation. Abstract: Progress in improving nitrogen (N) use efficiency (NUE) of crop plants has been hampered by the complexity of the N uptake and utilisation systems. To understand this complexity we measured the activities of seven enzymes and ten metabolites related to N metabolism in the leaf and root tissues of Gaspe Flint maize plants grown in 0.5 or 2.5 mM NO3 − throughout the lifecycle. The amino acids had remarkably similar profiles across the lifecycle except for transient responses, which only appeared in the leaves for aspartate or in the roots for asparagine, serine and glycine. The activities of the enzymes for N assimilation were also coordinated to a certain degree, most noticeably with a peak in root activity late in the lifecycle, but with wide variation in the activity levels over the course of development. We analysed the transcriptional data for gene sets encoding the measured enzymes and found that, unlike the enzyme activities, transcript levels of the corresponding genes did not exhibit the same coordination across the lifecycle and were only weakly correlated with the levels of various amino acids or individual enzyme activities. We identified gene sets which were correlated with the enzyme activity profiles, including seven genes located within previously known quantitative trait loci for enzyme activities and hypothesise that these genes are important for the regulation of enzyme activities. This work provides insights into the complexity of the N assimilation system throughout development and identifies candidate regulatory genes, which warrant further investigation in efforts to improve NUE in crop plants. © 2016, Springer Science+Business Media Dordrecht.

  5. Nitrogen assimilation system in maize is regulated by developmental and tissue-specific mechanisms

    KAUST Repository

    Plett, Darren; Holtham, Luke; Baumann, Ute; Kalashyan, Elena; Francis, Karen; Enju, Akiko; Toubia, John; Roessner, Ute; Bacic, Antony; Rafalski, Antoni; Dhugga, Kanwarpal S.; Tester, Mark A.; Garnett, Trevor; Kaiser, Brent N.

    2016-01-01

    Key message: We found metabolites, enzyme activities and enzyme transcript abundances vary significantly across the maize lifecycle, but weak correlation exists between the three groups. We identified putative genes regulating nitrate assimilation. Abstract: Progress in improving nitrogen (N) use efficiency (NUE) of crop plants has been hampered by the complexity of the N uptake and utilisation systems. To understand this complexity we measured the activities of seven enzymes and ten metabolites related to N metabolism in the leaf and root tissues of Gaspe Flint maize plants grown in 0.5 or 2.5 mM NO3 − throughout the lifecycle. The amino acids had remarkably similar profiles across the lifecycle except for transient responses, which only appeared in the leaves for aspartate or in the roots for asparagine, serine and glycine. The activities of the enzymes for N assimilation were also coordinated to a certain degree, most noticeably with a peak in root activity late in the lifecycle, but with wide variation in the activity levels over the course of development. We analysed the transcriptional data for gene sets encoding the measured enzymes and found that, unlike the enzyme activities, transcript levels of the corresponding genes did not exhibit the same coordination across the lifecycle and were only weakly correlated with the levels of various amino acids or individual enzyme activities. We identified gene sets which were correlated with the enzyme activity profiles, including seven genes located within previously known quantitative trait loci for enzyme activities and hypothesise that these genes are important for the regulation of enzyme activities. This work provides insights into the complexity of the N assimilation system throughout development and identifies candidate regulatory genes, which warrant further investigation in efforts to improve NUE in crop plants. © 2016, Springer Science+Business Media Dordrecht.

  6. Differential Expression Patterns in Chemosensory and Non-Chemosensory Tissues of Putative Chemosensory Genes Identified by Transcriptome Analysis of Insect Pest the Purple Stem Borer Sesamia inferens (Walker)

    OpenAIRE

    Zhang, Ya-Nan; Jin, Jun-Yan; Jin, Rong; Xia, Yi-Han; Zhou, Jing-Jiang; Deng, Jian-Yu; Dong, Shuang-Lin

    2013-01-01

    BACKGROUND: A large number of insect chemosensory genes from different gene subfamilies have been identified and annotated, but their functional diversity and complexity are largely unknown. A systemic examination of expression patterns in chemosensory organs could provide important information. METHODOLOGY/PRINCIPAL FINDINGS: We identified 92 putative chemosensory genes by analysing the transcriptome of the antennae and female sex pheromone gland of the purple stem borer Sesamia inferens, am...

  7. Co-culture systems-based strategies for articular cartilage tissue engineering.

    Science.gov (United States)

    Zhang, Yu; Guo, Weimin; Wang, Mingjie; Hao, Chunxiang; Lu, Liang; Gao, Shuang; Zhang, Xueliang; Li, Xu; Chen, Mingxue; Li, Penghao; Jiang, Peng; Lu, Shibi; Liu, Shuyun; Guo, Quanyi

    2018-03-01

    Cartilage engineering facilitates repair and regeneration of damaged cartilage using engineered tissue that restores the functional properties of the impaired joint. The seed cells used most frequently in tissue engineering, are chondrocytes and mesenchymal stem cells. Seed cells activity plays a key role in the regeneration of functional cartilage tissue. However, seed cells undergo undesirable changes after in vitro processing procedures, such as degeneration of cartilage cells and induced hypertrophy of mesenchymal stem cells, which hinder cartilage tissue engineering. Compared to monoculture, which does not mimic the in vivo cellular environment, co-culture technology provides a more realistic microenvironment in terms of various physical, chemical, and biological factors. Co-culture technology is used in cartilage tissue engineering to overcome obstacles related to the degeneration of seed cells, and shows promise for cartilage regeneration and repair. In this review, we focus first on existing co-culture systems for cartilage tissue engineering and related fields, and discuss the conditions and mechanisms thereof. This is followed by methods for optimizing seed cell co-culture conditions to generate functional neo-cartilage tissue, which will lead to a new era in cartilage tissue engineering. © 2017 Wiley Periodicals, Inc.

  8. Evaluation of impedance on biological Tissues using automatic control measurement system

    Energy Technology Data Exchange (ETDEWEB)

    Kil, Sang Hyeong; Shin, Dong Hoon; Lee, Seong Mo [Pusan National University, Yangsan (Korea, Republic of); Lee, Moo Seok; Kim, Sang Sik [Pusan National University, Busan (Korea, Republic of); Kim, Gun FDo; Lee, Jong Kyu [Pukyung National University, Busan (Korea, Republic of)

    2015-08-15

    Each biological tissue has endemic electrical characteristics owing to various differences such as those in cellular arrangement or organization form. The endemic electrical characteristics change when any biological change occurs. This work is a preliminary study surveying the changes in the electrical characteristics of biological tissue caused by radiation exposure. For protection against radiation hazards, therefore the electrical characteristics of living tissue were evaluated after development of the automatic control measurement system using LabVIEW. No alteration of biological tissues was observed before and after measurement of the electrical characteristics, and the biological tissues exhibited similar patterns. Through repeated measurements using the impedance/gain-phase analyzer, the coefficient of variation was determined as within 10%. The reproducibility impedance phase difference in electrical characteristics of the biological tissue did not change, and the tissue had resistance. The absolute value of impedance decreased constantly in proportion to the frequency. It has become possible to understand the electrical characteristics of biological tissues through the measurements made possible by the use of the developed.

  9. Evaluation of impedance on biological Tissues using automatic control measurement system

    International Nuclear Information System (INIS)

    Kil, Sang Hyeong; Shin, Dong Hoon; Lee, Seong Mo; Lee, Moo Seok; Kim, Sang Sik; Kim, Gun FDo; Lee, Jong Kyu

    2015-01-01

    Each biological tissue has endemic electrical characteristics owing to various differences such as those in cellular arrangement or organization form. The endemic electrical characteristics change when any biological change occurs. This work is a preliminary study surveying the changes in the electrical characteristics of biological tissue caused by radiation exposure. For protection against radiation hazards, therefore the electrical characteristics of living tissue were evaluated after development of the automatic control measurement system using LabVIEW. No alteration of biological tissues was observed before and after measurement of the electrical characteristics, and the biological tissues exhibited similar patterns. Through repeated measurements using the impedance/gain-phase analyzer, the coefficient of variation was determined as within 10%. The reproducibility impedance phase difference in electrical characteristics of the biological tissue did not change, and the tissue had resistance. The absolute value of impedance decreased constantly in proportion to the frequency. It has become possible to understand the electrical characteristics of biological tissues through the measurements made possible by the use of the developed.

  10. An integrative transcriptomic approach to identify depot differences in genes and microRNAs in adipose tissues from high fat fed mice.

    Science.gov (United States)

    Wijayatunga, Nadeeja N; Pahlavani, Mandana; Kalupahana, Nishan S; Kottapalli, Kameswara Rao; Gunaratne, Preethi H; Coarfa, Cristian; Ramalingam, Latha; Moustaid-Moussa, Naima

    2018-02-06

    Obesity contributes to metabolic disorders such as diabetes and cardiovascular disease. Characterization of differences between the main adipose tissue depots, white (WAT) [including subcutaneous (SAT) and visceral adipose tissue (VAT)] and brown adipose tissue (BAT) helps to identify their roles in obesity. Thus, we studied depot-specific differences in whole transcriptome and miRNA profiles of SAT, VAT and BAT from high fat diet (HFD/45% of calories from fat) fed mice using RNA sequencing and small RNA-Seq. Using quantitative real-time polymerase chain reaction, we validated depot-specific differences in endoplasmic reticulum (ER) stress related genes and miRNAs using mice fed a HFD vs. low fat diet (LFD/10% of calories from fat). According to the transcriptomic analysis, lipogenesis, adipogenesis, inflammation, endoplasmic reticulum (ER) stress and unfolded protein response (UPR) were higher in VAT compared to BAT, whereas energy expenditure, fatty acid oxidation and oxidative phosphorylation were higher in BAT than in VAT of the HFD fed mice. In contrast to BAT, ER stress marker genes were significantly upregulated in VAT of HFD fed mice than the LFD fed mice. For the first time, we report depot specific differences in ER stress related miRNAs including; downregulation of miR-125b-5p, upregulation miR-143-3p, and miR-222-3p in VAT following HFD and upregulation of miR-30c-2-3p only in BAT following a HFD in mice than the LFD mice. In conclusion, HFD differentially regulates miRNAs and genes in different adipose depots with significant induction of genes related to lipogenesis, adipogenesis, inflammation, ER stress, and UPR in WAT compared to BAT.

  11. A Lindenmayer system-based approach for the design of nutrient delivery networks in tissue constructs

    Energy Technology Data Exchange (ETDEWEB)

    Yasar, Ozlem; Starly, Binil [School of Industrial Engineering, University of Oklahoma, Norman, OK 73019 (United States); Lan, S-F [University of Oklahoma Bioengineering Center, University of Oklahoma, Norman, OK 73019 (United States)

    2009-12-15

    Large thick tissue constructs have reported limited success primarily due to the inability of cells to survive deep within the scaffold. Without access to adequate nutrients, cells placed deep within the tissue construct will die out, leading to non-uniform tissue regeneration. Currently, there is a necessity to design nutrient conduit networks within the tissue construct to enable cells to survive in the matrix. However, the design of complex networks within a tissue construct is challenging. In this paper, we present the Lindenmayer system, an elegant fractal-based language algorithm framework, to generate conduit networks in two- and three-dimensional architecture with several degrees of complexity. The conduit network maintains a parent-child relationship between each branch of the network. Several L-system parameters have been studied-branching angle, branch length, ratio of parent to child branch diameter, etc-to simulate several architectures under a given L-system notation. We have also presented a layered manufacturing-based UV-photopolymerization process using the Texas Instruments DLP(TM) system to fabricate the branched structures. This preliminary work showcases the applicability of L-system-based construct designs to drive scaffold fabrication systems.

  12. A Lindenmayer system-based approach for the design of nutrient delivery networks in tissue constructs

    International Nuclear Information System (INIS)

    Yasar, Ozlem; Starly, Binil; Lan, S-F

    2009-01-01

    Large thick tissue constructs have reported limited success primarily due to the inability of cells to survive deep within the scaffold. Without access to adequate nutrients, cells placed deep within the tissue construct will die out, leading to non-uniform tissue regeneration. Currently, there is a necessity to design nutrient conduit networks within the tissue construct to enable cells to survive in the matrix. However, the design of complex networks within a tissue construct is challenging. In this paper, we present the Lindenmayer system, an elegant fractal-based language algorithm framework, to generate conduit networks in two- and three-dimensional architecture with several degrees of complexity. The conduit network maintains a parent-child relationship between each branch of the network. Several L-system parameters have been studied-branching angle, branch length, ratio of parent to child branch diameter, etc-to simulate several architectures under a given L-system notation. We have also presented a layered manufacturing-based UV-photopolymerization process using the Texas Instruments DLP(TM) system to fabricate the branched structures. This preliminary work showcases the applicability of L-system-based construct designs to drive scaffold fabrication systems.

  13. The Immune System in Tissue Environments Regaining Homeostasis after Injury: Is "Inflammation" Always Inflammation?

    Science.gov (United States)

    Kulkarni, Onkar P; Lichtnekert, Julia; Anders, Hans-Joachim; Mulay, Shrikant R

    2016-01-01

    Inflammation is a response to infections or tissue injuries. Inflammation was once defined by clinical signs, later by the presence of leukocytes, and nowadays by expression of "proinflammatory" cytokines and chemokines. But leukocytes and cytokines often have rather anti-inflammatory, proregenerative, and homeostatic effects. Is there a need to redefine "inflammation"? In this review, we discuss the functions of "inflammatory" mediators/regulators of the innate immune system that determine tissue environments to fulfill the need of the tissue while regaining homeostasis after injury.

  14. Artificial neural net system for interactive tissue classification with MR imaging and image segmentation

    International Nuclear Information System (INIS)

    Clarke, L.P.; Silbiger, M.; Naylor, C.; Brown, K.

    1990-01-01

    This paper reports on the development of interactive methods for MR tissue classification that permit mathematically rigorous methods for three-dimensional image segmentation and automatic organ/tumor contouring, as required for surgical and RTP planning. The authors investigate a number of image-intensity based tissue- classification methods that make no implicit assumptions on the MR parameters and hence are not limited by image data set. Similarly, we have trained artificial neural net (ANN) systems for both supervised and unsupervised tissue classification

  15. Dimethadione embryotoxicity in the rat is neither correlated with maternal systemic drug concentrations nor embryonic tissue levels

    Energy Technology Data Exchange (ETDEWEB)

    Ozolinš, Terence R.S., E-mail: ozolinst@queensu.ca [Department of Biomedical and Molecular Sciences, Program in Pharmacology and Toxicology, Queen’s University, Botterell Hall, Kingston, ON K7L 3N6 (Canada); Weston, Andrea D. [Currently at Applied Biotechnology/Lead Discovery, Bristol-Myers Squibb, 5 Research Pkwy Wallingford, CT 06492-1996 (United States); Perretta, Anthony [Currently at Pfizer Research and Development, Eastern Point Road, Groton, CT 06340 (United States); Thomson, Jason J. [Currently at Yale Stem Cell Center, Yale School of Medicine, PO Box 208073, New Haven, CT 06520-8073 (United States); Brown, Nigel A. [Division of Basic Medical Sciences, St. George’s University of London, UK SW17 0RE (United Kingdom)

    2015-11-15

    Pregnant rats treated with dimethadione (DMO), the N-demethylated metabolite of the anticonvulsant trimethadione, produce offspring having a 74% incidence of congenital heart defects (CHD); however, the incidence of CHD has high inter-litter variability (40–100%) that presents a challenge when studying the initiating events prior to the presentation of an abnormal phenotype. We hypothesized that the variability in CHD incidence was the result of differences in maternal systemic concentrations or embryonic tissue concentrations of DMO. To test this hypothesis, dams were administered 300 mg/kg DMO every 12 h from the evening of gestational day (GD) 8 until the morning of GD 11 (six total doses). Maternal serum levels of DMO were assessed on GD 11, 12, 13, 14, 15, 18 and 21. Embryonic tissue concentrations of DMO were assessed on GD 11, 12, 13 and 14. In a separate cohort of GD 12 embryos, DMO concentrations and parameters of growth and development were assessed to determine if tissue levels of DMO were correlated with these endpoints. Embryos were exposed directly to different concentrations of DMO with whole embryo culture (WEC) and their growth and development assessed. Key findings were that neither maternal systemic concentrations nor tissue concentrations of DMO identified embryos that were sensitive or resistant to DMO in vivo. Direct exposure of embryos to DMO via WEC also failed to show correlations between embryonic concentrations of DMO with developmental outcomes in vitro. We conclude that neither maternal serum nor embryonic tissue concentrations of DMO predict embryonic outcome. - Highlights: • Dimethadione (DMO) induces septation defects (VSD) in rat offspring. • Despite high rate of VSD defects inter-litter variability is 40–100%. • Maternal and embryonic concentrations of DMO were assessed. • Neither serum nor tissue levels of DMO were correlated with embryotoxicity.

  16. Dimethadione embryotoxicity in the rat is neither correlated with maternal systemic drug concentrations nor embryonic tissue levels

    International Nuclear Information System (INIS)

    Ozolinš, Terence R.S.; Weston, Andrea D.; Perretta, Anthony; Thomson, Jason J.; Brown, Nigel A.

    2015-01-01

    Pregnant rats treated with dimethadione (DMO), the N-demethylated metabolite of the anticonvulsant trimethadione, produce offspring having a 74% incidence of congenital heart defects (CHD); however, the incidence of CHD has high inter-litter variability (40–100%) that presents a challenge when studying the initiating events prior to the presentation of an abnormal phenotype. We hypothesized that the variability in CHD incidence was the result of differences in maternal systemic concentrations or embryonic tissue concentrations of DMO. To test this hypothesis, dams were administered 300 mg/kg DMO every 12 h from the evening of gestational day (GD) 8 until the morning of GD 11 (six total doses). Maternal serum levels of DMO were assessed on GD 11, 12, 13, 14, 15, 18 and 21. Embryonic tissue concentrations of DMO were assessed on GD 11, 12, 13 and 14. In a separate cohort of GD 12 embryos, DMO concentrations and parameters of growth and development were assessed to determine if tissue levels of DMO were correlated with these endpoints. Embryos were exposed directly to different concentrations of DMO with whole embryo culture (WEC) and their growth and development assessed. Key findings were that neither maternal systemic concentrations nor tissue concentrations of DMO identified embryos that were sensitive or resistant to DMO in vivo. Direct exposure of embryos to DMO via WEC also failed to show correlations between embryonic concentrations of DMO with developmental outcomes in vitro. We conclude that neither maternal serum nor embryonic tissue concentrations of DMO predict embryonic outcome. - Highlights: • Dimethadione (DMO) induces septation defects (VSD) in rat offspring. • Despite high rate of VSD defects inter-litter variability is 40–100%. • Maternal and embryonic concentrations of DMO were assessed. • Neither serum nor tissue levels of DMO were correlated with embryotoxicity.

  17. A systems biology strategy to identify molecular mechanisms of action and protein indicators of traumatic brain injury.

    Science.gov (United States)

    Yu, Chenggang; Boutté, Angela; Yu, Xueping; Dutta, Bhaskar; Feala, Jacob D; Schmid, Kara; Dave, Jitendra; Tawa, Gregory J; Wallqvist, Anders; Reifman, Jaques

    2015-02-01

    The multifactorial nature of traumatic brain injury (TBI), especially the complex secondary tissue injury involving intertwined networks of molecular pathways that mediate cellular behavior, has confounded attempts to elucidate the pathology underlying the progression of TBI. Here, systems biology strategies are exploited to identify novel molecular mechanisms and protein indicators of brain injury. To this end, we performed a meta-analysis of four distinct high-throughput gene expression studies involving different animal models of TBI. By using canonical pathways and a large human protein-interaction network as a scaffold, we separately overlaid the gene expression data from each study to identify molecular signatures that were conserved across the different studies. At 24 hr after injury, the significantly activated molecular signatures were nonspecific to TBI, whereas the significantly suppressed molecular signatures were specific to the nervous system. In particular, we identified a suppressed subnetwork consisting of 58 highly interacting, coregulated proteins associated with synaptic function. We selected three proteins from this subnetwork, postsynaptic density protein 95, nitric oxide synthase 1, and disrupted in schizophrenia 1, and hypothesized that their abundance would be significantly reduced after TBI. In a penetrating ballistic-like brain injury rat model of severe TBI, Western blot analysis confirmed our hypothesis. In addition, our analysis recovered 12 previously identified protein biomarkers of TBI. The results suggest that systems biology may provide an efficient, high-yield approach to generate testable hypotheses that can be experimentally validated to identify novel mechanisms of action and molecular indicators of TBI. © 2014 The Authors. Journal of Neuroscience Research Published by Wiley Periodicals, Inc.

  18. Micro fluidic System for Culturing and Monitoring of Neuronal Cells and Tissue

    DEFF Research Database (Denmark)

    Bakmand, Tanya; Waagepetersen, Helle S.

    The aim of this Ph.D. project was to combine experience within cell and tissue culturing, electrochemistry and microfabrication in order to develop an in vivo-like fluidic culturing platform, challenging the traditional culturing methods. The first goal was to develope a fluidic system for cultur...... with mass production. The last part of this thesis also includes perspectives on how to expand the latest designed device to facilitate culturing of tissue and co-culturing of cells....

  19. Designing an Adaptive Web-Based Learning System Based on Students' Cognitive Styles Identified Online

    Science.gov (United States)

    Lo, Jia-Jiunn; Chan, Ya-Chen; Yeh, Shiou-Wen

    2012-01-01

    This study developed an adaptive web-based learning system focusing on students' cognitive styles. The system is composed of a student model and an adaptation model. It collected students' browsing behaviors to update the student model for unobtrusively identifying student cognitive styles through a multi-layer feed-forward neural network (MLFF).…

  20. Creation of a system of signs to identify the user on the dynamics of ...

    African Journals Online (AJOL)

    Describes a method of creating a system of signs to identify the user for authentication on the dynamics of ink handwriting using a multi-touch sensor. The result is a reduction of the computational complexity of classification when creating access control systems. Keywords: analysis and classification of signals, user ...

  1. Identifying and Quantifying Emergent Behavior Through System of Systems Modeling and Simulation

    Science.gov (United States)

    2015-09-01

    the similarities and differences between Agent Based Modeling ( ABM ) and Equation Based Modeling (EBM). Both modeling approaches “simulate a system by...entities. For the latter difference, EBM focuses on the system level observables, while ABM defines behaviors at the individual agent level and observes...EMERGENT BEHAVIOR THROUGH SYSTEM OF SYSTEMS MODELING AND SIMULATION by Mary Ann Cummings September 2015 Dissertation Supervisor: Man-Tak Shing

  2. Genome-wide analysis of the CCCH zinc finger family identifies tissue specific and stress responsive candidates in chickpea (Cicer arietinum L.).

    Science.gov (United States)

    Pradhan, Seema; Kant, Chandra; Verma, Subodh; Bhatia, Sabhyata

    2017-01-01

    The CCCH zinc finger is a group of proteins characterised by a typical motif consisting of three cysteine residues and one histidine residue. These proteins have been reported to play important roles in regulation of plant growth, developmental processes and environmental responses. In the present study, genome wide analysis of the CCCH zinc finger gene family was carried out in the available chickpea genome. Various bioinformatics tools were employed to predict 58 CCCH zinc finger genes in chickpea (designated CarC3H1-58), which were analysed for their physio-chemical properties. Phylogenetic analysis classified the proteins into 12 groups in which members of a particular group had similar structural organization. Further, the numbers as well as the types of CCCH motifs present in the CarC3H proteins were compared with those from Arabidopsis and Medicago truncatula. Synteny analysis revealed valuable information regarding the evolution of this gene family. Tandem and segmental duplication events were identified and their Ka/Ks values revealed that the CarC3H gene family in chickpea had undergone purifying selection. Digital, as well as real time qRT-PCR expression analysis was performed which helped in identification of several CarC3H members that expressed preferentially in specific chickpea tissues as well as during abiotic stresses (desiccation, cold, salinity). Moreover, molecular characterization of an important member CarC3H45 was carried out. This study provides comprehensive genomic information about the important CCCH zinc finger gene family in chickpea. The identified tissue specific and abiotic stress specific CCCH genes could be potential candidates for further characterization to delineate their functional roles in development and stress.

  3. The necessity of a theory of biology for tissue engineering: metabolism-repair systems.

    Science.gov (United States)

    Ganguli, Suman; Hunt, C Anthony

    2004-01-01

    Since there is no widely accepted global theory of biology, tissue engineering and bioengineering lack a theoretical understanding of the systems being engineered. By default, tissue engineering operates with a "reductionist" theoretical approach, inherited from traditional engineering of non-living materials. Long term, that approach is inadequate, since it ignores essential aspects of biology. Metabolism-repair systems are a theoretical framework which explicitly represents two "functional" aspects of living organisms: self-repair and self-replication. Since repair and replication are central to tissue engineering, we advance metabolism-repair systems as a potential theoretical framework for tissue engineering. We present an overview of the framework, and indicate directions to pursue for extending it to the context of tissue engineering. We focus on biological networks, both metabolic and cellular, as one such direction. The construction of these networks, in turn, depends on biological protocols. Together these concepts may help point the way to a global theory of biology appropriate for tissue engineering.

  4. Fitting tissue chips and microphysiological systems into the grand scheme of medicine, biology, pharmacology, and toxicology.

    Science.gov (United States)

    Watson, David E; Hunziker, Rosemarie; Wikswo, John P

    2017-10-01

    ; and mechanism of action of drug candidates. Impact statement Microphysiological systems (MPS), which include engineered organoids and both individual and coupled organs-on-chips and tissue chips, are a rapidly growing topic of research that addresses the known limitations of conventional cellular monoculture on flat plastic - a well-perfected set of techniques that produces reliable, statistically significant results that may not adequately represent human biology and disease. As reviewed in this article and the others in this thematic issue, MPS research has made notable progress in the past three years in both cell sourcing and characterization. As the field matures, currently identified challenges are being addressed, and new ones are being recognized. Building upon investments by the Defense Advanced Research Projects Agency, National Institutes of Health, Food and Drug Administration, Defense Threat Reduction Agency, and Environmental Protection Agency of more than $200 million since 2012 and sizable corporate spending, academic and commercial players in the MPS community are demonstrating their ability to meet the translational challenges required to apply MPS technologies to accelerate drug development and advance toxicology.

  5. [Research progress of co-culture system for constructing vascularized tissue engineered bone].

    Science.gov (United States)

    Fu, Weili; Xiang, Zhou

    2014-02-01

    To review the research progress of the co-culture system for constructing vascularized tissue engineered bone. The recent literature concerning the co-culture system for constructing vascularized tissue engineered bone was reviewed, including the selection of osteogenic and endothelial lineages, the design and surface modification of scaffolds, the models and dimensions of the co-culture system, the mechanism, the culture conditions, and their application progress. The construction of vascularized tissue engineered bone is the prerequisite for their survival and further clinical application in vivo. Mesenchymal stem cells (owning the excellent osteogenic potential) and endothelial progenitor cells (capable of directional differentiation into endothelial cell) are considered as attractive cell types for the co-culture system to construct vascularized tissue engineered bone. The culture conditions need to be further optimized. Furthermore, how to achieve the clinical goals of minimal invasion and autologous transplantation also need to be further studied. The strategy of the co-culture system for constructing vascularized tissue engineered bone would have a very broad prospects for clinical application in future.

  6. Hydrogel-laden paper scaffold system for origami-based tissue engineering.

    Science.gov (United States)

    Kim, Su-Hwan; Lee, Hak Rae; Yu, Seung Jung; Han, Min-Eui; Lee, Doh Young; Kim, Soo Yeon; Ahn, Hee-Jin; Han, Mi-Jung; Lee, Tae-Ik; Kim, Taek-Soo; Kwon, Seong Keun; Im, Sung Gap; Hwang, Nathaniel S

    2015-12-15

    In this study, we present a method for assembling biofunctionalized paper into a multiform structured scaffold system for reliable tissue regeneration using an origami-based approach. The surface of a paper was conformally modified with a poly(styrene-co-maleic anhydride) layer via initiated chemical vapor deposition followed by the immobilization of poly-l-lysine (PLL) and deposition of Ca(2+). This procedure ensures the formation of alginate hydrogel on the paper due to Ca(2+) diffusion. Furthermore, strong adhesion of the alginate hydrogel on the paper onto the paper substrate was achieved due to an electrostatic interaction between the alginate and PLL. The developed scaffold system was versatile and allowed area-selective cell seeding. Also, the hydrogel-laden paper could be folded freely into 3D tissue-like structures using a simple origami-based method. The cylindrically constructed paper scaffold system with chondrocytes was applied into a three-ring defect trachea in rabbits. The transplanted engineered tissues replaced the native trachea without stenosis after 4 wks. As for the custom-built scaffold system, the hydrogel-laden paper system will provide a robust and facile method for the formation of tissues mimicking native tissue constructs.

  7. Tissue simulant response at projectile impact on flexible fabric armour systems

    NARCIS (Netherlands)

    Bree, J.L.M.J. van; Volker, A.; Heiden, N. van der

    2006-01-01

    Behind Armour Blunt Trauma is a phenomenon which has been studied extensively for rigid personal protective armour systems. These systems used in e.g. bullet proof vests manage to defeat high velocity small arms projectiles. Tissue simulants are used to study behind armour effects. At high velocity

  8. Estradiol Synthesis in Gut-Associated Lymphoid Tissue: Leukocyte Regulation by a Sexually Monomorphic System.

    Science.gov (United States)

    Oakley, Oliver R; Kim, Kee Jun; Lin, Po-Ching; Barakat, Radwa; Cacioppo, Joseph A; Li, Zhong; Whitaker, Alexandra; Chung, Kwang Chul; Mei, Wenyan; Ko, CheMyong

    2016-12-01

    17β-estradiol is a potent sex hormone synthesized primarily by gonads in females and males that regulates development and function of the reproductive system. Recent studies show that 17β-estradiol is locally synthesized in nonreproductive tissues and regulates a myriad of events, including local inflammatory responses. In this study, we report that mesenteric lymph nodes (mLNs) and Peyer's patches (Pps) are novel sites of de novo synthesis of 17β-estradiol. These secondary lymphoid organs are located within or close to the gastrointestinal tract, contain leukocytes, and function at the forefront of immune surveillance. 17β-estradiol synthesis was initially identified using a transgenic mouse with red fluorescent protein coexpressed in cells that express aromatase, the enzyme responsible for 17β-estradiol synthesis. Subsequent immunohistochemistry and tissue culture experiments revealed that aromatase expression was localized to high endothelial venules of these lymphoid organs, and these high endothelial venule cells synthesized 17β-estradiol when isolated and cultured in vitro. Both mLNs and Pps contained 17β-estradiol with concentrations that were significantly higher than those of peripheral blood. Furthermore, the total amount of 17β-estradiol in these organs exceeded that of the gonads. Mice lacking either aromatase or estrogen receptor-β had hypertrophic Pps and mLNs with more leukocytes than their wild-type littermates, demonstrating a role for 17β-estradiol in leukocyte regulation. Importantly, we did not observe any sex-dependent differences in aromatase expression, 17β-estradiol content, or steroidogenic capacity in these lymphoid organs.

  9. Leveraging Diverse Data Sources to Identify and Describe U.S. Health Care Delivery Systems.

    Science.gov (United States)

    Cohen, Genna R; Jones, David J; Heeringa, Jessica; Barrett, Kirsten; Furukawa, Michael F; Miller, Dan; Mutti, Anne; Reschovsky, James D; Machta, Rachel; Shortell, Stephen M; Fraze, Taressa; Rich, Eugene

    2017-12-15

    Health care delivery systems are a growing presence in the U.S., yet research is hindered by the lack of universally agreed-upon criteria to denote formal systems. A clearer understanding of how to leverage real-world data sources to empirically identify systems is a necessary first step to such policy-relevant research. We draw from our experience in the Agency for Healthcare Research and Quality's Comparative Health System Performance (CHSP) initiative to assess available data sources to identify and describe systems, including system members (for example, hospitals and physicians) and relationships among the members (for example, hospital ownership of physician groups). We highlight five national data sources that either explicitly track system membership or detail system relationships: (1) American Hospital Association annual survey of hospitals; (2) Healthcare Relational Services Databases; (3) SK&A Healthcare Databases; (4) Provider Enrollment, Chain, and Ownership System; and (5) Internal Revenue Service 990 forms. Each data source has strengths and limitations for identifying and describing systems due to their varied content, linkages across data sources, and data collection methods. In addition, although no single national data source provides a complete picture of U.S. systems and their members, the CHSP initiative will create an early model of how such data can be combined to compensate for their individual limitations. Identifying systems in a way that can be repeated over time and linked to a host of other data sources will support analysis of how different types of organizations deliver health care and, ultimately, comparison of their performance.

  10. Which Doctor to Trust: A Recommender System for Identifying the Right Doctors.

    Science.gov (United States)

    Guo, Li; Jin, Bo; Yao, Cuili; Yang, Haoyu; Huang, Degen; Wang, Fei

    2016-07-07

    Key opinion leaders (KOLs) are people who can influence public opinion on a certain subject matter. In the field of medical and health informatics, it is critical to identify KOLs on various disease conditions. However, there have been very few studies on this topic. We aimed to develop a recommender system for identifying KOLs for any specific disease with health care data mining. We exploited an unsupervised aggregation approach for integrating various ranking features to identify doctors who have the potential to be KOLs on a range of diseases. We introduce the design, implementation, and deployment details of the recommender system. This system collects the professional footprints of doctors, such as papers in scientific journals, presentation activities, patient advocacy, and media exposure, and uses them as ranking features to identify KOLs. We collected the information of 2,381,750 doctors in China from 3,657,797 medical journal papers they published, together with their profiles, academic publications, and funding. The empirical results demonstrated that our system outperformed several benchmark systems by a significant margin. Moreover, we conducted a case study in a real-world system to verify the applicability of our proposed method. Our results show that doctors' profiles and their academic publications are key data sources for identifying KOLs in the field of medical and health informatics. Moreover, we deployed the recommender system and applied the data service to a recommender system of the China-based Internet technology company NetEase. Patients can obtain authority ranking lists of doctors with this system on any given disease.

  11. Deep Coverage Proteomics Identifies More Low-Abundance Missing Proteins in Human Testis Tissue with Q-Exactive HF Mass Spectrometer.

    Science.gov (United States)

    Wei, Wei; Luo, Weijia; Wu, Feilin; Peng, Xuehui; Zhang, Yao; Zhang, Manli; Zhao, Yan; Su, Na; Qi, YingZi; Chen, Lingsheng; Zhang, Yangjun; Wen, Bo; He, Fuchu; Xu, Ping

    2016-11-04

    Since 2012, missing proteins (MPs) investigation has been one of the critical missions of Chromosome-Centric Human Proteome Project (C-HPP) through various biochemical strategies. On the basis of our previous testis MPs study, faster scanning and higher resolution mass-spectrometry-based proteomics might be conducive to MPs exploration, especially for low-abundance proteins. In this study, Q-Exactive HF (HF) was used to survey proteins from the same testis tissues separated by two separating methods (tricine- and glycine-SDS-PAGE), as previously described. A total of 8526 proteins were identified, of which more low-abundance proteins were uniquely detected in HF data but not in our previous LTQ Orbitrap Velos (Velos) reanalysis data. Further transcriptomics analysis showed that these uniquely identified proteins by HF also had lower expression at the mRNA level. Of the 81 total identified MPs, 74 and 39 proteins were listed as MPs in HF and Velos data sets, respectively. Among the above MPs, 47 proteins (43 neXtProt PE2 and 4 PE3) were ranked as confirmed MPs after verifying with the stringent spectra match and isobaric and single amino acid variants filtering. Functional investigation of these 47 MPs revealed that 11 MPs were testis-specific proteins and 7 MPs were involved in spermatogenesis process. Therefore, we concluded that higher scanning speed and resolution of HF might be factors for improving the low-abundance MP identification in future C-HPP studies. All mass-spectrometry data from this study have been deposited in the ProteomeXchange with identifier PXD004092.

  12. The role of the endocrine system in feeding-induced tissue-specific circadian entrainment.

    Science.gov (United States)

    Sato, Miho; Murakami, Mariko; Node, Koichi; Matsumura, Ritsuko; Akashi, Makoto

    2014-07-24

    The circadian clock is entrained to environmental cycles by external cue-mediated phase adjustment. Although the light input pathway has been well defined, the mechanism of feeding-induced phase resetting remains unclear. The tissue-specific sensitivity of peripheral entrainment to feeding suggests the involvement of multiple pathways, including humoral and neuronal signals. Previous in vitro studies with cultured cells indicate that endocrine factors may function as entrainment cues for peripheral clocks. However, blood-borne factors that are well characterized in actual feeding-induced resetting have yet to be identified. Here, we report that insulin may be involved in feeding-induced tissue-type-dependent entrainment in vivo. In ex vivo culture experiments, insulin-induced phase shift in peripheral clocks was dependent on tissue type, which was consistent with tissue-specific insulin sensitivity, and peripheral entrainment in insulin-sensitive tissues involved PI3K- and MAPK-mediated signaling pathways. These results suggest that insulin may be an immediate early factor in feeding-mediated tissue-specific entrainment. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  13. New perspectives in cell delivery systems for tissue regeneration: natural-derived injectable hydrogels.

    Science.gov (United States)

    Munarin, Fabiola; Petrini, Paola; Bozzini, Sabrina; Tanzi, Maria Cristina

    2012-09-27

    Natural polymers, because of their biocompatibility, availability, and physico-chemical properties have been the materials of choice for the fabrication of injectable hydrogels for regenerative medicine. In particular, they are appealing materials for delivery systems and provide sustained and controlled release of drugs, proteins, gene, cells, and other active biomolecules immobilized.In this work, the use of hydrogels obtained from natural source polymers as cell delivery systems is discussed. These materials were investigated for the repair of cartilage, bone, adipose tissue, intervertebral disc, neural, and cardiac tissue. Papers from the last ten years were considered, with a particular focus on the advances of the last five years. A critical discussion is centered on new perspectives and challenges in the regeneration of specific tissues, with the aim of highlighting the limits of current systems and possible future advancements.

  14. Osteoimmunology: the study of the relationship between the immune system and bone tissue.

    Science.gov (United States)

    Arboleya, Luis; Castañeda, Santos

    2013-01-01

    Bone tissue is a highly regulated structure, which plays an essential role in various physiological functions. Through autocrine and paracrine mechanisms, bone tissue is involved in hematopoiesis, influencing the fate of hematopoietic stem cells. There are a number of molecules shared by bone cells and immune system cells indicating that there are multiple connections between the immune system and bone tissue. In order to pool all the knowledge concerning both systems, a new discipline known under the term «osteoimmunology» has been developed. Their progress in recent years has been exponential and allowed us to connect and increase our knowledge in areas not seemingly related such as rheumatoid erosion, postmenopausal osteoporosis, bone metastases or periodontal disease. In this review, we have tried to summarize the most important advances that have occurred in the last decade, especially in those areas of interest related to rheumatology. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  15. Electromagnetic effects on the biological tissue surrounding a transcutaneous transformer for an artificial anal sphincter system*

    Science.gov (United States)

    Zan, Peng; Yang, Bang-hua; Shao, Yong; Yan, Guo-zheng; Liu, Hua

    2010-01-01

    This paper reports on the electromagnetic effects on the biological tissue surrounding a transcutaneous transformer for an artificial anal sphincter. The coupling coils and human tissues, including the skin, fat, muscle, liver, and blood, were considered. Specific absorption rate (SAR) and current density were analyzed by a finite-length solenoid model. First, SAR and current density as a function of frequency (10–107 Hz) for an emission current of 1.5 A were calculated under different tissue thickness. Then relations between SAR, current density, and five types of tissues under each frequency were deduced. As a result, both the SAR and current density were below the basic restrictions of the International Commission on Non-Ionizing Radiation Protection (ICNIRP). The results show that the analysis of these data is very important for developing the artificial anal sphincter system. PMID:21121071

  16. Identifying Stakeholders and Their Preferences about NFR by Comparing Use Case Diagrams of Several Existing Systems

    Science.gov (United States)

    Kaiya, Haruhiko; Osada, Akira; Kaijiri, Kenji

    We present a method to identify stakeholders and their preferences about non-functional requirements (NFR) by using use case diagrams of existing systems. We focus on the changes about NFR because such changes help stakeholders to identify their preferences. Comparing different use case diagrams of the same domain helps us to find changes to be occurred. We utilize Goal-Question-Metrics (GQM) method for identifying variables that characterize NFR, and we can systematically represent changes about NFR using the variables. Use cases that represent system interactions help us to bridge the gap between goals and metrics (variables), and we can easily construct measurable NFR. For validating and evaluating our method, we applied our method to an application domain of Mail User Agent (MUA) system.

  17. An Ontology for Identifying Cyber Intrusion Induced Faults in Process Control Systems

    Science.gov (United States)

    Hieb, Jeffrey; Graham, James; Guan, Jian

    This paper presents an ontological framework that permits formal representations of process control systems, including elements of the process being controlled and the control system itself. A fault diagnosis algorithm based on the ontological model is also presented. The algorithm can identify traditional process elements as well as control system elements (e.g., IP network and SCADA protocol) as fault sources. When these elements are identified as a likely fault source, the possibility exists that the process fault is induced by a cyber intrusion. A laboratory-scale distillation column is used to illustrate the model and the algorithm. Coupled with a well-defined statistical process model, this fault diagnosis approach provides cyber security enhanced fault diagnosis information to plant operators and can help identify that a cyber attack is underway before a major process failure is experienced.

  18. On the identifiability of linear dynamical systems. [parameters observation in presence of white noise

    Science.gov (United States)

    Glover, K.; Willems, J. C.

    1973-01-01

    Consider the situation in which the unknown parameters of a stationary linear system may be parametrized by a set of unknown parameters. The question thus arises of when such a set of parameters can be uniquely identified on the basis of observed data. This problem is considered here both in the case of input and output observations and in the case of output observations in the presence of a white noise input. Conditions for local identifiability are derived for both situations and a sufficient condition for global identifiability is given for the former situation, i.e., when simultaneous input and output observations are available.

  19. An Active Type I-E CRISPR-Cas System Identified in Streptomyces avermitilis.

    Directory of Open Access Journals (Sweden)

    Yi Qiu

    Full Text Available CRISPR-Cas systems, the small RNA-dependent immune systems, are widely distributed in prokaryotes. However, only a small proportion of CRISPR-Cas systems have been identified to be active in bacteria. In this work, a naturally active type I-E CRISPR-Cas system was found in Streptomyces avermitilis. The system shares many common genetic features with the type I-E system of Escherichia coli, and meanwhile shows unique characteristics. It not only degrades plasmid DNA with target protospacers, but also acquires new spacers from the target plasmid DNA. The naive features of spacer acquisition in the type I-E system of S. avermitilis were investigated and a completely conserved PAM 5'-AAG-3' was identified. Spacer acquisition displayed differential strand bias upstream and downstream of the priming spacer, and irregular integrations of new spacers were observed. In addition, introduction of this system into host conferred phage resistance to some extent. This study will give new insights into adaptation mechanism of the type I-E systems in vivo, and meanwhile provide theoretical foundation for applying this system on the genetic modification of S. avermitilis.

  20. Learn the Lagrangian: A Vector-Valued RKHS Approach to Identifying Lagrangian Systems.

    Science.gov (United States)

    Cheng, Ching-An; Huang, Han-Pang

    2016-12-01

    We study the modeling of Lagrangian systems with multiple degrees of freedom. Based on system dynamics, canonical parametric models require ad hoc derivations and sometimes simplification for a computable solution; on the other hand, due to the lack of prior knowledge in the system's structure, modern nonparametric models in machine learning face the curse of dimensionality, especially in learning large systems. In this paper, we bridge this gap by unifying the theories of Lagrangian systems and vector-valued reproducing kernel Hilbert space. We reformulate Lagrangian systems with kernels that embed the governing Euler-Lagrange equation-the Lagrangian kernels-and show that these kernels span a subspace capturing the Lagrangian's projection as inverse dynamics. By such property, our model uses only inputs and outputs as in machine learning and inherits the structured form as in system dynamics, thereby removing the need for the mundane derivations for new systems as well as the generalization problem in learning from scratches. In effect, it learns the system's Lagrangian, a simpler task than directly learning the dynamics. To demonstrate, we applied the proposed kernel to identify the robot inverse dynamics in simulations and experiments. Our results present a competitive novel approach to identifying Lagrangian systems, despite using only inputs and outputs.

  1. Identifying compromised systems through correlation of suspicious traffic from malware behavioral analysis

    Science.gov (United States)

    Camilo, Ana E. F.; Grégio, André; Santos, Rafael D. C.

    2016-05-01

    Malware detection may be accomplished through the analysis of their infection behavior. To do so, dynamic analysis systems run malware samples and extract their operating system activities and network traffic. This traffic may represent malware accessing external systems, either to steal sensitive data from victims or to fetch other malicious artifacts (configuration files, additional modules, commands). In this work, we propose the use of visualization as a tool to identify compromised systems based on correlating malware communications in the form of graphs and finding isomorphisms between them. We produced graphs from over 6 thousand distinct network traffic files captured during malware execution and analyzed the existing relationships among malware samples and IP addresses.

  2. Integration and Interoperability: An Analysis to Identify the Attributes for System of Systems

    Science.gov (United States)

    2008-09-01

    divisions of the enterprise. Examples of the current I2 are: • a nightly feed of elearning information is captured through an automated and...standardized process throughout the enterprise and • the LMS has been integrated with SkillSoft, a third party elearning software system, (http...Command (JITC) is responsible to test all programs that utilize standard interfaces to specific global nets or systems. Many times programs that

  3. The Challenge of Ensuring Persistency of Identifier Systems in the World of Ever-Changing Technology

    Directory of Open Access Journals (Sweden)

    Nicholas J. Car

    2017-04-01

    Full Text Available The identification of information objects has always been important with library collections with indexes having been created in the most ancient times. Since the digital age, many specialised and generic persistent identifier (PID systems have been used to identify digital objects. Just as many ancient indexes have died over time, so too PID systems have had a lifecycle from inception to active phase to paralysis, and eventually a fall into oblivion. Where the indexes within the Great Library at Alexandria finally succumbed to fire, technology change has been the destroyer of more recent digital indexes. We distil four PID system design principles from observations over the years that we think should be implemented by PID system architects to ensure that their systems survive change. The principles: describe how to ensure identifiers’ system and organisation independence; codify the delivery of essential PID system functions; mandate a separation of PID functions from data delivery mechanisms; and require generation of policies detailing how change is handled. In addition to suggesting specific items for each principle, we propose that a platform-independent model (PIM be established for persistent identifiers – of any sort and with any resolver technology – in order to enable transition between present and future systems and the preservation of the identifiers’ functioning. We detail our PID system—the PID Service—that implements the proposed principles and a data model to some extent and we describe an implementation case study of an organisation’s implementation of PID systems that implement the Pillars further but still not completely. Penultimately, we describe in a Future Work section, an opportunity for the use of both the Pillars and the PIM; that of the World Wide Web Consortium’s Permanent Identifier Community Group who is seeking to “set up and maintain a secure permanent, URL re-direction service for the web”.

  4. The Great Irish Famine: Identifying Starvation in the Tissues of Victims Using Stable Isotope Analysis of Bone and Incremental Dentine Collagen.

    Directory of Open Access Journals (Sweden)

    Julia Beaumont

    Full Text Available The major components of human diet both past and present may be estimated by measuring the carbon and nitrogen isotope ratios (δ13C and δ15N of the collagenous proteins in bone and tooth dentine. However, the results from these two tissues differ substantially: bone collagen records a multi-year average whilst primary dentine records and retains time-bound isotope ratios deriving from the period of tooth development. Recent studies harnessing a sub-annual temporal sampling resolution have shed new light on the individual dietary histories of our ancestors by identifying unexpected radical short-term dietary changes, the duration of breastfeeding and migration where dietary change occurs, and by raising questions regarding factors other than diet that may impact on δ13C and δ15N values. Here we show that the dentine δ13C and δ15N profiles of workhouse inmates dating from the Great Irish Famine of the 19th century not only record the expected dietary change from C3 potatoes to C4 maize, but when used together they also document prolonged nutritional and other physiological stress resulting from insufficient sustenance. In the adults, the influence of the maize-based diet is seen in the δ13C difference between dentine (formed in childhood and rib (representing an average from the last few years of life. The demonstrated effects of stress on the δ13C and δ15N values will have an impact on the interpretations of diet in past populations even in slow-turnover tissues such as compact bone. This technique also has applicability in the investigation of modern children subject to nutritional distress where hair and nails are unavailable or do not record an adequate period of time.

  5. Analyses of Tissue Culture Adaptation of Human Herpesvirus-6A by Whole Genome Deep Sequencing Redefines the Reference Sequence and Identifies Virus Entry Complex Changes.

    Science.gov (United States)

    Tweedy, Joshua G; Escriva, Eric; Topf, Maya; Gompels, Ursula A

    2017-12-31

    Tissue-culture adaptation of viruses can modulate infection. Laboratory passage and bacterial artificial chromosome (BAC)mid cloning of human cytomegalovirus, HCMV, resulted in genomic deletions and rearrangements altering genes encoding the virus entry complex, which affected cellular tropism, virulence, and vaccine development. Here, we analyse these effects on the reference genome for related betaherpesviruses, Roseolovirus, human herpesvirus 6A (HHV-6A) strain U1102. This virus is also naturally "cloned" by germline subtelomeric chromosomal-integration in approximately 1% of human populations, and accurate references are key to understanding pathological relationships between exogenous and endogenous virus. Using whole genome next-generation deep-sequencing Illumina-based methods, we compared the original isolate to tissue-culture passaged and the BACmid-cloned virus. This re-defined the reference genome showing 32 corrections and 5 polymorphisms. Furthermore, minor variant analyses of passaged and BACmid virus identified emerging populations of a further 32 single nucleotide polymorphisms (SNPs) in 10 loci, half non-synonymous indicating cell-culture selection. Analyses of the BAC-virus genome showed deletion of the BAC cassette via loxP recombination removing green fluorescent protein (GFP)-based selection. As shown for HCMV culture effects, select HHV-6A SNPs mapped to genes encoding mediators of virus cellular entry, including virus envelope glycoprotein genes gB and the gH/gL complex. Comparative models suggest stabilisation of the post-fusion conformation. These SNPs are essential to consider in vaccine-design, antimicrobial-resistance, and pathogenesis.

  6. Strain-time cell death threshold for skeletal muscle in a tissue-engineered model system for deep tissue injury

    NARCIS (Netherlands)

    Gefen, A.; Nierop, van B.J.; Bader, D.L.; Oomens, C.W.J.

    2008-01-01

    Deep tissue injury (DTI) is a severe pressure ulcer that results from sustained deformation of muscle tissue overlying bony prominences. In order to understand the etiology of DTI, it is essential to determine the tolerance of muscle cells to large mechanical strains. In this study, a new

  7. Late effects of normal tissues (lent) scoring system: the soma scale

    International Nuclear Information System (INIS)

    Mornex, F.; Pavy, J.J.; Denekamp, J.

    1997-01-01

    Radiation tolerance of normal tissues remains the limiting factor for delivering tumoricidal dose. The late toxicity of normal tissues is the most critical element of an irradiation: somatic, functional and structural alterations occur during the actual treatment itself, but late effects manifest months to years after acute effects heal, and may progress with time. The optimal therapeutic ratio ultimately requires not only complete tumor clearance, but also minimal residual injury to surrounding vital normal tissues. The disparity between the intensity of acute and late effects and the inability to predict the eventual manifestation of late normal tissue injury has made radiation oncologists recognize the importance of careful patient follow-up. There is so far no uniform toxicity scoring system to compare several clinical studies in the absence of a 'common toxicity language'. This justifies the need to establish a precise evaluation system for the analysis of late effects of radiation on normal tissues. The SOMA/LENT scoring system results from an international collaboration. European Organization Treatment of Cancer (EORTC) and Radiation Therapy Oncology Group (RTOG) have created subcommittees with the aim of addressing the question of standardized toxic effects criteria. This effort appeared as a necessity to standardize and improve the data recording, to then describe and evaluate uniform toxicity at regular time intervals. The current proposed scale is not yet validated, and should be used cautiously. (authors)

  8. Control Points To Reduce Movement of Central Nervous System Tissue during Beef Slaughter.

    Science.gov (United States)

    Aalhus, J L; Thacker, R D; Larsen, I L; Roberts, J C; Price, M A; Juárez, M

    2017-02-01

    Consumption of central nervous system tissue (CNST) from cattle with bovine spongiform encephalopathy (BSE) is thought to cause the human neurological disease, variant Creutzfeldt-Jacob disease. To identify points of cross-contamination of beef carcasses with CNST, 55 young beef cattle were slaughtered and processed through a federally inspected multispecies abattoir. The objectives of this study were to evaluate CNST spread following the placement of a plug in the penetration site of the skull after captive bolt stunning, to evaluate cross-contamination of carcasses before and after splitting, to compare the effects of hot water pasteurization (84°C for 10 s) versus cold water wash (10°C for 30 s) for reducing CNST on the carcass, and to examine other possible sources of cross-contamination in the abattoir. Results indicated that the use of a plastic plug reduced CNST contamination near the bolt penetration site. This study also confirmed that carcass splitting resulted in an increase in CNST contamination at various areas of the carcass. Hot water pasteurization appeared to be an effective means of removing CNST contamination from carcasses in most of the areas sampled.

  9. Elastin Cables Define the Axial Connective Tissue System in the Murine Lung.

    Science.gov (United States)

    Wagner, Willi; Bennett, Robert D; Ackermann, Maximilian; Ysasi, Alexandra B; Belle, Janeil; Valenzuela, Cristian D; Pabst, Andreas; Tsuda, Akira; Konerding, Moritz A; Mentzer, Steven J

    2015-11-01

    The axial connective tissue system is a fiber continuum of the lung that maintains alveolar surface area during changes in lung volume. Although the molecular anatomy of the axial system remains undefined, the fiber continuum of the lung is central to contemporary models of lung micromechanics and alveolar regeneration. To provide a detailed molecular structure of the axial connective tissue system, we examined the extracellular matrix of murine lungs. The lungs were decellularized using a 24 hr detergent treatment protocol. Systematic evaluation of the decellularized lungs demonstrated no residual cellular debris; morphometry demonstrated a mean 39 ± 7% reduction in lung dimensions. Scanning electron microscopy (SEM) demonstrated an intact structural hierarchy within the decellularized lung. Light, fluorescence, and SEM of precision-cut lung slices demonstrated that alveolar duct structure was defined by a cable line element encased in basement membrane. The cable line element arose in the distal airways, passed through septal tips and inserted into neighboring blood vessels and visceral pleura. The ropelike appearance, collagenase resistance and anti-elastin immunostaining indicated that the cable was an elastin macromolecule. Our results indicate that the helical line element of the axial connective tissue system is composed of an elastin cable that not only defines the structure of the alveolar duct, but also integrates the axial connective tissue system into visceral pleura and peripheral blood vessels. © 2015 Wiley Periodicals, Inc.

  10. Restoring nervous system structure and function using tissue engineered living scaffolds

    Institute of Scientific and Technical Information of China (English)

    Laura A Struzyna; James P Harris; Kritika S Katiyar; H Isaac Chen; D KacyCullen

    2015-01-01

    Neural tissue engineering is premised on the integration of engineered living tissue with the host nervous system to directly restore lost function or to augment regenerative capacity following ner-vous system injury or neurodegenerative disease. Disconnection of axon pathways – the long-distance ifbers connecting specialized regions of the central nervous system or relaying peripheral signals – is a common feature of many neurological disorders and injury. However, functional axonal regenera-tion rarely occurs due to extreme distances to targets, absence of directed guidance, and the presence of inhibitory factors in the central nervous system, resulting in devastating effects on cognitive and sensorimotor function. To address this need, we are pursuing multiple strategies using tissue engi-neered “living scaffolds”, which are preformed three-dimensional constructs consisting of living neural cells in a deifned, often anisotropic architecture. Living scaffolds are designed to restore function by serving as a living labeled pathway for targeted axonal regeneration – mimicking key developmental mechanisms– or by restoring lost neural circuitry via direct replacement of neurons and axonal tracts. We are currently utilizing preformed living scaffolds consisting of neuronal clusters spanned by long axonal tracts as regenerative bridges to facilitate long-distance axonal regeneration and for targeted neurosurgical reconstruction of local circuits in the brain. Although there are formidable challenges in preclinical and clinical advancement, these living tissue engineered constructs represent a promising strategy to facilitate nervous system repair and functional recovery.

  11. Restoring nervous system structure and function using tissue engineered living scaffolds

    Directory of Open Access Journals (Sweden)

    Laura A Struzyna

    2015-01-01

    Full Text Available Neural tissue engineering is premised on the integration of engineered living tissue with the host nervous system to directly restore lost function or to augment regenerative capacity following nervous system injury or neurodegenerative disease. Disconnection of axon pathways - the long-distance fibers connecting specialized regions of the central nervous system or relaying peripheral signals - is a common feature of many neurological disorders and injury. However, functional axonal regeneration rarely occurs due to extreme distances to targets, absence of directed guidance, and the presence of inhibitory factors in the central nervous system, resulting in devastating effects on cognitive and sensorimotor function. To address this need, we are pursuing multiple strategies using tissue engineered "living scaffolds", which are preformed three-dimensional constructs consisting of living neural cells in a defined, often anisotropic architecture. Living scaffolds are designed to restore function by serving as a living labeled pathway for targeted axonal regeneration - mimicking key developmental mechanisms- or by restoring lost neural circuitry via direct replacement of neurons and axonal tracts. We are currently utilizing preformed living scaffolds consisting of neuronal clusters spanned by long axonal tracts as regenerative bridges to facilitate long-distance axonal regeneration and for targeted neurosurgical reconstruction of local circuits in the brain. Although there are formidable challenges in preclinical and clinical advancement, these living tissue engineered constructs represent a promising strategy to facilitate nervous system repair and functional recovery.

  12. Identifying a system of predominant negative symptoms: Network analysis of three randomized clinical trials.

    Science.gov (United States)

    Levine, Stephen Z; Leucht, Stefan

    2016-12-01

    Reasons for the recent mixed success of research into negative symptoms may be informed by conceptualizing negative symptoms as a system that is identifiable from network analysis. We aimed to identify: (I) negative symptom systems; (I) central negative symptoms within each system; and (III) differences between the systems, based on network analysis of negative symptoms for baseline, endpoint and change. Patients with chronic schizophrenia and predominant negative symptoms participated in three clinical trials that compared placebo and amisulpride to 60days (n=487). Networks analyses were computed from the Scale for the Assessment of Negative Symptoms (SANS) scores for baseline and endpoint for severity, and estimated change based on mixed models. Central symptoms to each network were identified. The networks were contrasted for connectivity with permutation tests. Network analysis showed that the baseline and endpoint symptom severity systems formed symptom groups of Affect, Poor responsiveness, Lack of interest, and Apathy-inattentiveness. The baseline and endpoint networks did not significantly differ in terms of connectivity, but both significantly (Psymptom group split into three other groups. The most central symptoms were Decreased Spontaneous Movements at baseline and endpoint, and Poverty of Speech for estimated change. Results provide preliminary evidence for: (I) a replicable negative symptom severity system; and (II) symptoms with high centrality (e.g., Decreased Spontaneous Movement), that may be future treatment targets following replication to ensure the curent results generalize to other samples. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. DAISY: a new software tool to test global identifiability of biological and physiological systems.

    Science.gov (United States)

    Bellu, Giuseppina; Saccomani, Maria Pia; Audoly, Stefania; D'Angiò, Leontina

    2007-10-01

    A priori global identifiability is a structural property of biological and physiological models. It is considered a prerequisite for well-posed estimation, since it concerns the possibility of recovering uniquely the unknown model parameters from measured input-output data, under ideal conditions (noise-free observations and error-free model structure). Of course, determining if the parameters can be uniquely recovered from observed data is essential before investing resources, time and effort in performing actual biomedical experiments. Many interesting biological models are nonlinear but identifiability analysis for nonlinear system turns out to be a difficult mathematical problem. Different methods have been proposed in the literature to test identifiability of nonlinear models but, to the best of our knowledge, so far no software tools have been proposed for automatically checking identifiability of nonlinear models. In this paper, we describe a software tool implementing a differential algebra algorithm to perform parameter identifiability analysis for (linear and) nonlinear dynamic models described by polynomial or rational equations. Our goal is to provide the biological investigator a completely automatized software, requiring minimum prior knowledge of mathematical modelling and no in-depth understanding of the mathematical tools. The DAISY (Differential Algebra for Identifiability of SYstems) software will potentially be useful in biological modelling studies, especially in physiology and clinical medicine, where research experiments are particularly expensive and/or difficult to perform. Practical examples of use of the software tool DAISY are presented. DAISY is available at the web site http://www.dei.unipd.it/~pia/.

  14. A system for the obtention and analysis of diffuse reflection spectra from biological tissue

    International Nuclear Information System (INIS)

    La Cadena, A. de; La Rosa, J. de; Stolik, S.

    2012-01-01

    The diffuse reflection spectroscopy is a technique with is possible to study biological tissue. In the field of the biomedical applications is useful for diagnostic purposes, since is possible to analyze biological tissue in a non invasive way. also, can be used with therapeutical purposes, for example in photodynamic therapy or laser surgery because with this technique it can be determined the biological effects produced by these treatments. In this paper is shown the development of a system to obtain and analyze diffuse reflection spectra of biological tissues, using a LED as a light source, that emits light between 400-700nm. The system has an interface for the regulation of the emittance of the LED. For diffuse reflectance spectra analysis, we use an HR4000CG-UV-NIR spectrometer. (Author)

  15. Transcriptome analysis reveals mucin 4 to be highly associated with periodontitis and identifies pleckstrin as a link to systemic diseases

    Science.gov (United States)

    Lundmark, Anna; Davanian, Haleh; Båge, Tove; Johannsen, Gunnar; Koro, Catalin; Lundeberg, Joakim; Yucel-Lindberg, Tülay

    2015-01-01

    The multifactorial chronic inflammatory disease periodontitis, which is characterized by destruction of tooth-supporting tissues, has also been implicated as a risk factor for various systemic diseases. Although periodontitis has been studied extensively, neither disease-specific biomarkers nor therapeutic targets have been identified, nor its link with systemic diseases. Here, we analyzed the global transcriptome of periodontitis and compared its gene expression profile with those of other inflammatory conditions, including cardiovascular disease (CVD), rheumatoid arthritis (RA), and ulcerative colitis (UC). Gingival biopsies from 62 patients with periodontitis and 62 healthy subjects were subjected to RNA sequencing. The up-regulated genes in periodontitis were related to inflammation, wounding and defense response, and apoptosis, whereas down-regulated genes were related to extracellular matrix organization and structural support. The most highly up-regulated gene was mucin 4 (MUC4), and its protein product was confirmed to be over-expressed in periodontitis. When comparing the expression profile of periodontitis with other inflammatory diseases, several gene ontology categories, including inflammatory response, cell death, cell motion, and homeostatic processes, were identified as common to all diseases. Only one gene, pleckstrin (PLEK), was significantly overexpressed in periodontitis, CVD, RA, and UC, implicating this gene as an important networking link between these chronic inflammatory diseases. PMID:26686060

  16. 76 FR 4823 - Hazardous Waste Management System; Identifying and Listing Hazardous Waste Exclusion

    Science.gov (United States)

    2011-01-27

    ... Waste Management System; Identifying and Listing Hazardous Waste Exclusion AGENCY: Environmental... hazardous wastes. The Agency has decided to grant the petition based on an evaluation of waste-specific... excludes the petitioned waste from the requirements of hazardous waste regulations under the Resource...

  17. Identifying Students' Characteristic Learning Behaviors in an Intelligent Tutoring System Fostering Self-Regulated Learning

    Science.gov (United States)

    Bouchet, Francois; Azevedo, Roger; Kinnebrew, John S.; Biswas, Gautam

    2012-01-01

    Identification of student learning behaviors, especially those that characterize or distinguish students, can yield important insights for the design of adaptation and feedback mechanisms in Intelligent Tutoring Systems (ITS). In this paper, we analyze trace data to identify distinguishing patterns of behavior in a study of 51 college students…

  18. Using an Educational Electronic Documentation System to Help Nursing Students Accurately Identify Nursing Diagnoses

    Science.gov (United States)

    Pobocik, Tamara J.

    2013-01-01

    The use of technology and electronic medical records in healthcare has exponentially increased. This quantitative research project used a pretest/posttest design, and reviewed how an educational electronic documentation system helped nursing students to identify the accurate related to statement of the nursing diagnosis for the patient in the case…

  19. Barriers to installing innovative energy systems in existing housing stock identified

    NARCIS (Netherlands)

    Hoppe, Thomas

    2013-01-01

    Several barriers to upgrading existing social housing with innovative energy systems (IES) have been identified by a study of eight large-scale renovation projects in the Netherlands. These include a lack of trust between stakeholders, opposition from tenants on grounds of increased costs or delays,

  20. Adipose tissue endocannabinoid system gene expression: depot differences and effects of diet and exercise

    Directory of Open Access Journals (Sweden)

    Yang Rongze

    2011-10-01

    Full Text Available Abstract Background Alterations of endocannabinoid system in adipose tissue play an important role in lipid regulation and metabolic dysfunction associated with obesity. The purpose of this study was to determine whether gene expression levels of cannabinoid type 1 receptor (CB1 and fatty acid amide hydrolase (FAAH are different in subcutaneous abdominal and gluteal adipose tissue, and whether hypocaloric diet and aerobic exercise influence subcutaneous adipose tissue CB1 and FAAH gene expression in obese women. Methods Thirty overweight or obese, middle-aged women (BMI = 34.3 ± 0.8 kg/m2, age = 59 ± 1 years underwent one of three 20-week weight loss interventions: caloric restriction only (CR, N = 9, caloric restriction plus moderate-intensity aerobic exercise (CRM, 45-50% HRR, N = 13, or caloric restriction plus vigorous-intensity aerobic exercise (CRV, 70-75% HRR, N = 8. Subcutaneous abdominal and gluteal adipose tissue samples were collected before and after the interventions to measure CB1 and FAAH gene expression. Results At baseline, FAAH gene expression was higher in abdominal, compared to gluteal adipose tissue (2.08 ± 0.11 vs. 1.78 ± 0.10, expressed as target gene/β-actin mRNA ratio × 10-3, P Conclusions There are depot differences in subcutaneous adipose tissue endocannabinoid system gene expression in obese individuals. Aerobic exercise training may preferentially modulate abdominal adipose tissue endocannabinoid-related gene expression during dietary weight loss. Trial Registration ClinicalTrials.gov: NCT00664729.

  1. Bioactive Molecule-loaded Drug Delivery Systems to Optimize Bone Tissue Repair.

    Science.gov (United States)

    Oshiro, Joao Augusto; Sato, Mariana Rillo; Scardueli, Cassio Rocha; Lopes de Oliveira, Guilherme Jose Pimentel; Abucafy, Marina Paiva; Chorilli, Marlus

    2017-01-01

    Bioactive molecules such as peptides and proteins can optimize the repair of bone tissue; however, the results are often unpredictable when administered alone, owing to their short biological half-life and instability. Thus, the development of bioactive molecule-loaded drug delivery systems (DDS) to repair bone tissue has been the subject of intense research. DDS can optimize the repair of bone tissue owing to their physicochemical properties, which improve cellular interactions and enable the incorporation and prolonged release of bioactive molecules. These characteristics are fundamental to favor bone tissue homeostasis, since the biological activity of these factors depends on how accessible they are to the cell. Considering the importance of these DDS, this review aims to present relevant information on DDS when loaded with osteogenic growth peptide and bone morphogenetic protein. These are bioactive molecules that are capable of modulating the differentiation and proliferation of mesenchymal cells in bone tissue cells. Moreover, we will present different approaches using these peptide and protein-loaded DDS, such as synthetic membranes and scaffolds for bone regeneration, synthetic grafts, bone cements, liposomes, and micelles, which aim at improving the therapeutic effectiveness, and we will compare their advantages with commercial systems. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  2. NRC Information No. 91-29: Deficiencies identified during electrical distribution system functional inspections

    International Nuclear Information System (INIS)

    Rossi, C.E.

    1992-01-01

    During multidisciplinary inspections, the US Nuclear Regulatory Commission (NRC) has identified many deficiencies related to the electrical distribution system. To address these deficiencies, the NRC has developed an inspection to specifically evaluate the electrical distribution system. During the last year, the NRC completed eight EDSFIs, performing at least one in each of the several common deficiencies in the licensees' programs and in the electrical distribution systems as designed and configured at each plant. These deficiencies included inadequate ac voltages at the 480 Vac and 120 Vac distribution levels, inadequate procedures to test circuit breakers, and inadequate determinations and evaluations of setpoints

  3. Optical Characterization of Tissue Phantoms Using a Silicon Integrated fdNIRS System on Chip.

    Science.gov (United States)

    Sthalekar, Chirag C; Miao, Yun; Koomson, Valencia Joyner

    2017-04-01

    An interface circuit with signal processing and digitizing circuits for a high frequency, large area avalanche photodiode (APD) has been integrated in a 130 nm BiCMOS chip. The system enables the absolute oximetry of tissue using frequency domain Near Infrared Spectroscopy (fdNIRS). The system measures the light absorbed and scattered by the tissue by measuring the reduction in the amplitude of signal and phase shift introduced between the light source and detector which are placed a finite distance away from each other. The received 80 MHz RF signal is downconverted to a low frequency and amplified using a heterodyning scheme. The front-end transimpedance amplifier has a 3-level programmable gain that increases the dynamic range to 60 dB. The phase difference between an identical reference channel and the optical channel is measured with a 0.5° accuracy. The detectable current range is [Formula: see text] and with a 40 A/W reponsivity using the APD, power levels as low as 500 pW can be detected. Measurements of the absorption and reduced scattering coefficients of solid tissue phantoms using this system are compared with those using a commercial instrument with differences within 30%. Measurement of a milk based liquid tissue phantom show an increase in absorption coefficient with addition of black ink. The miniaturized circuit serves as an efficiently scalable system for multi-site detection for applications in neonatal cerebral oximetry and optical mammography.

  4. NBAS mutations cause a multisystem disorder involving bone, connective tissue, liver, immune system, and retina

    NARCIS (Netherlands)

    Segarra, Nuria Garcia; Ballhausen, Diana; Crawford, Heather; Perreau, Matthieu; Campos-Xavier, Belinda; van Spaendonck-Zwarts, Karin; Vermeer, Cees; Russo, Michel; Zambelli, Pierre-Yves; Stevenson, Brian; Royer-Bertrand, Beryl; Rivolta, Carlo; Candotti, Fabio; Unger, Sheila; Munier, Francis L.; Superti-Furga, Andrea; Bonafé, Luisa

    2015-01-01

    We report two unrelated patients with a multisystem disease involving liver, eye, immune system, connective tissue, and bone, caused by biallelic mutations in the neuroblastoma amplified sequence (NBAS) gene. Both presented as infants with recurrent episodes triggered by fever with vomiting,

  5. Effects of tissue impedance on heat generation during RF delivery with the Thermage system

    Science.gov (United States)

    Tomkoria, Sara; Pope, Karl

    2005-04-01

    The Thermage ThermaCool TC system is a non-ablative RF device designed to promote tissue tightening and contouring. The system delivers RF energy to a target area under the skin, with volumetric tissue heating in that area. While the amount of energy delivered to a patient can be controlled by ThermaCool system settings, the distribution of energy to the treatment area and underlying layers is variable from individual to individual due to differences in body composition. The present study investigated how local tissue impedance affects the amount of discomfort experienced by patients during RF energy delivery. Discomfort results from heat generation in the treatment area. By using features of the ThermaCool TC System, local impedance (impedance of the treatment area), bulk impedance (impedance of the underlying tissue layers), and total impedance (the sum of local and bulk impedance) were measured for 35 patients. For each patient, impedance measurements were compared to discomfort levels expressed during treatment. Analysis of whole body, local, and bulk impedance values indicate that the percent of total body impedance in the local treatment area contributes to discomfort levels expressed by patients during treatment.

  6. A decision support system for identifying abnormal operating procedures in a nuclear power plant

    International Nuclear Information System (INIS)

    Hsieh, Min-Han; Hwang, Sheue-Ling; Liu, Kang-Hong; Liang, Sheau-Farn Max; Chuang, Chang-Fu

    2012-01-01

    Highlights: ► A decision support system has been constructed and verified. ► The operator's decision-making time was decreased by about 25%. ► The accuracy was increased by about 18%. ► The system prevents overlooking important information. ► Fewer erroneous solutions were implemented, and the mental workload was reduced. - Abstract: In order to prevent safety hazards that can result from inappropriate decisions made by the operators of a nuclear power plant (NPP), this study was undertaken to develop a decision support system to reduce the complexity of the decision-making process by aiding operators’ cognitive activities, integrating unusual symptoms, and identifying the most suitable abnormal operating procedure (AOP) for operators. The study was conducted from the perspective of human factors engineering in order to compare the process that operators originally used to select an AOP with a process that included a support system for AOP identification. The results of the study indicated that the existence of a support system reduces errors by quickly suggesting likely AOPs. With such a support system in place, there were clear improvements in human performance, i.e., decision-making time decreased by about 25%, and the accuracy of the operators’ decisions, judged by the successful resolution of specific problems, increased by about 18%. In addition, there were fewer erroneous solutions implemented, and the mental workload was reduced. Hence, the decision support system is proposed as a training tool in identifying AOPs in the main control room (MCR).

  7. An information-theoretic approach to assess practical identifiability of parametric dynamical systems.

    Science.gov (United States)

    Pant, Sanjay; Lombardi, Damiano

    2015-10-01

    A new approach for assessing parameter identifiability of dynamical systems in a Bayesian setting is presented. The concept of Shannon entropy is employed to measure the inherent uncertainty in the parameters. The expected reduction in this uncertainty is seen as the amount of information one expects to gain about the parameters due to the availability of noisy measurements of the dynamical system. Such expected information gain is interpreted in terms of the variance of a hypothetical measurement device that can measure the parameters directly, and is related to practical identifiability of the parameters. If the individual parameters are unidentifiable, correlation between parameter combinations is assessed through conditional mutual information to determine which sets of parameters can be identified together. The information theoretic quantities of entropy and information are evaluated numerically through a combination of Monte Carlo and k-nearest neighbour methods in a non-parametric fashion. Unlike many methods to evaluate identifiability proposed in the literature, the proposed approach takes the measurement-noise into account and is not restricted to any particular noise-structure. Whilst computationally intensive for large dynamical systems, it is easily parallelisable and is non-intrusive as it does not necessitate re-writing of the numerical solvers of the dynamical system. The application of such an approach is presented for a variety of dynamical systems--ranging from systems governed by ordinary differential equations to partial differential equations--and, where possible, validated against results previously published in the literature. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. On the identifiability of inertia parameters of planar Multi-Body Space Systems

    Science.gov (United States)

    Nabavi-Chashmi, Seyed Yaser; Malaek, Seyed Mohammad-Bagher

    2018-04-01

    This work describes a new formulation to study the identifiability characteristics of Serially Linked Multi-body Space Systems (SLMBSS). The process exploits the so called "Lagrange Formulation" to develop a linear form of Equations of Motion w.r.t the system Inertia Parameters (IPs). Having developed a specific form of regressor matrix, we aim to expedite the identification process. The new approach allows analytical as well as numerical identification and identifiability analysis for different SLMBSSs' configurations. Moreover, the explicit forms of SLMBSSs identifiable parameters are derived by analyzing the identifiability characteristics of the robot. We further show that any SLMBSS designed with Variable Configurations Joint allows all IPs to be identifiable through comparing two successive identification outcomes. This feature paves the way to design new class of SLMBSS for which accurate identification of all IPs is at hand. Different case studies reveal that proposed formulation provides fast and accurate results, as required by the space applications. Further studies might be necessary for cases where planar-body assumption becomes inaccurate.

  9. Interlaced photoacoustic and ultrasound imaging system with real-time coregistration for ovarian tissue characterization

    Science.gov (United States)

    Alqasemi, Umar; Li, Hai; Yuan, Guangqian; Kumavor, Patrick; Zanganeh, Saeid; Zhu, Quing

    2014-07-01

    Coregistered ultrasound (US) and photoacoustic imaging are emerging techniques for mapping the echogenic anatomical structure of tissue and its corresponding optical absorption. We report a 128-channel imaging system with real-time coregistration of the two modalities, which provides up to 15 coregistered frames per second limited by the laser pulse repetition rate. In addition, the system integrates a compact transvaginal imaging probe with a custom-designed fiber optic assembly for in vivo detection and characterization of human ovarian tissue. We present the coregistered US and photoacoustic imaging system structure, the optimal design of the PC interfacing software, and the reconfigurable field programmable gate array operation and optimization. Phantom experiments of system lateral resolution and axial sensitivity evaluation, examples of the real-time scanning of a tumor-bearing mouse, and ex vivo human ovaries studies are demonstrated.

  10. Brief Communication: Tissue-engineered Microenvironment Systems for Modeling Human Vasculature

    Science.gov (United States)

    Tourovskaia, Anna; Fauver, Mark; Kramer, Gregory; Simonson, Sara; Neumann, Thomas

    2015-01-01

    The high attrition rate of drug candidates late in the development process has led to an increasing demand for test assays that predict clinical outcome better than conventional 2D cell culture systems and animal models. Government agencies, the military, and the pharmaceutical industry have started initiatives for the development of novel in-vitro systems that recapitulate functional units of human tissues and organs. There is growing evidence that 3D cell arrangement, co-culture of different cell types, and physico-chemical cues lead to improved predictive power. A key element of all tissue microenvironments is the vasculature. Beyond transporting blood the microvasculature assumes important organ-specific functions. It is also involved in pathologic conditions, such as inflammation, tumor growth, metastasis, and degenerative diseases. To provide a tool for modeling this important feature of human tissue microenvironments, we developed a microfluidic chip for creating tissue-engineered microenvironment systems (TEMS) composed of tubular cell structures. Our chip design encompasses a small chamber that is filled with an extracellular matrix (ECM) surrounding one or more tubular channels. Endothelial cells seeded into the channels adhere to the ECM walls and grow into perfusable tubular tissue structures that are fluidically connected to upstream and downstream fluid channels in the chip. Using these chips we created models of angiogenesis, the blood-brain-barrier (BBB), and tumor-cell extravasation. Our angiogenesis model recapitulates true angiogenesis, in which sprouting occurs from a “parent” vessel in response to a gradient of growth factors. Our BBB model is composed of a microvessel generated from brain-specific endothelial cells (ECs) within an ECM populated with astrocytes and pericytes. Our tumor-cell extravasation model can be utilized to visualize and measure tumor-cell migration through vessel walls into the surrounding matrix. The described

  11. Structural identifiability of systems biology models: a critical comparison of methods.

    Directory of Open Access Journals (Sweden)

    Oana-Teodora Chis

    Full Text Available Analysing the properties of a biological system through in silico experimentation requires a satisfactory mathematical representation of the system including accurate values of the model parameters. Fortunately, modern experimental techniques allow obtaining time-series data of appropriate quality which may then be used to estimate unknown parameters. However, in many cases, a subset of those parameters may not be uniquely estimated, independently of the experimental data available or the numerical techniques used for estimation. This lack of identifiability is related to the structure of the model, i.e. the system dynamics plus the observation function. Despite the interest in knowing a priori whether there is any chance of uniquely estimating all model unknown parameters, the structural identifiability analysis for general non-linear dynamic models is still an open question. There is no method amenable to every model, thus at some point we have to face the selection of one of the possibilities. This work presents a critical comparison of the currently available techniques. To this end, we perform the structural identifiability analysis of a collection of biological models. The results reveal that the generating series approach, in combination with identifiability tableaus, offers the most advantageous compromise among range of applicability, computational complexity and information provided.

  12. Unitary input DEA model to identify beef cattle production systems typologies

    Directory of Open Access Journals (Sweden)

    Eliane Gonçalves Gomes

    2012-08-01

    Full Text Available The cow-calf beef production sector in Brazil has a wide variety of operating systems. This suggests the identification and the characterization of homogeneous regions of production, with consequent implementation of actions to achieve its sustainability. In this paper we attempted to measure the performance of 21 livestock modal production systems, in their cow-calf phase. We measured the performance of these systems, considering husbandry and production variables. The proposed approach is based on data envelopment analysis (DEA. We used unitary input DEA model, with apparent input orientation, together with the efficiency measurements generated by the inverted DEA frontier. We identified five modal production systems typologies, using the isoefficiency layers approach. The results showed that the knowledge and the processes management are the most important factors for improving the efficiency of beef cattle production systems.

  13. Interactions between adipose tissue and the immune system in health and malnutrition.

    Science.gov (United States)

    Wensveen, Felix M; Valentić, Sonja; Šestan, Marko; Wensveen, Tamara Turk; Polić, Bojan

    2015-09-01

    Adipose tissue provides the body with a storage depot of nutrients that is drained during times of starvation and replenished when food sources are abundant. As such, it is the primary sensor for nutrient availability in the milieu of an organism, which it communicates to the body through the excretion of hormones. Adipose tissue regulates a multitude of body functions associated with metabolism, such as gluconeogenesis, feeding and nutrient uptake. The immune system forms a vital layer of protection against micro-organisms that try to gain access to the nutrients contained in the body. Because infections need to be resolved as quickly as possible, speed is favored over energy-efficiency in an immune response. Especially when immune cells are activated, they switch to fast, but energy-inefficient anaerobic respiration to fulfill their energetic needs. Despite the necessity for an effective immune system, it is not given free rein in its energy expenditure. Signals derived from adipose tissue limit immune cell numbers and activity under conditions of nutrient shortage, whereas they allow proper immune cell activity when food sources are sufficiently available. When excessive fat accumulation occurs, such as in diet-induced obesity, adipose tissue becomes the site of pathological immune cell activation, causing chronic low-grade systemic inflammation. Obesity is therefore associated with a number of disorders in which the immune system plays a central role, such as atherosclerosis and non-alcoholic steatohepatitis. In this review, we will discuss the way in which adipose tissue regulates activity of the immune system under healthy and pathological conditions. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. How to Identify Possible Applications of Product Configuration Systems in Engineer-to-Order Companies

    DEFF Research Database (Denmark)

    Kristjansdottir, Katrin; Shafiee, Sara; Hvam, Lars

    2017-01-01

    -toorder (ETO) companies that support gradual implementation of PCS due to large product variety and, several times, higher complexity of products and processes. The overall PCS process can thereby be broken down, and the risk minimised. This paper provides a three-step framework to identify different......Product configuration systems (PCS) play an essential role when providing customised and engineered products efficiently. Literature in the field describes numerous strategies to develop PCS but neglects to identify different application areas. This topic is particularly important for engineer...

  15. A multimodal image sensor system for identifying water stress in grapevines

    Science.gov (United States)

    Zhao, Yong; Zhang, Qin; Li, Minzan; Shao, Yongni; Zhou, Jianfeng; Sun, Hong

    2012-11-01

    Water stress is one of the most common limitations of fruit growth. Water is the most limiting resource for crop growth. In grapevines, as well as in other fruit crops, fruit quality benefits from a certain level of water deficit which facilitates to balance vegetative and reproductive growth and the flow of carbohydrates to reproductive structures. A multi-modal sensor system was designed to measure the reflectance signature of grape plant surfaces and identify different water stress levels in this paper. The multi-modal sensor system was equipped with one 3CCD camera (three channels in R, G, and IR). The multi-modal sensor can capture and analyze grape canopy from its reflectance features, and identify the different water stress levels. This research aims at solving the aforementioned problems. The core technology of this multi-modal sensor system could further be used as a decision support system that combines multi-modal sensory data to improve plant stress detection and identify the causes of stress. The images were taken by multi-modal sensor which could output images in spectral bands of near-infrared, green and red channel. Based on the analysis of the acquired images, color features based on color space and reflectance features based on image process method were calculated. The results showed that these parameters had the potential as water stress indicators. More experiments and analysis are needed to validate the conclusion.

  16. SMM-system: A mining tool to identify specific markers in Salmonella enterica.

    Science.gov (United States)

    Yu, Shuijing; Liu, Weibing; Shi, Chunlei; Wang, Dapeng; Dan, Xianlong; Li, Xiao; Shi, Xianming

    2011-03-01

    This report presents SMM-system, a software package that implements various personalized pre- and post-BLASTN tasks for mining specific markers of microbial pathogens. The main functionalities of SMM-system are summarized as follows: (i) converting multi-FASTA file, (ii) cutting interesting genomic sequence, (iii) automatic high-throughput BLASTN searches, and (iv) screening target sequences. The utility of SMM-system was demonstrated by using it to identify 214 Salmonella enterica-specific protein-coding sequences (CDSs). Eighteen primer pairs were designed based on eighteen S. enterica-specific CDSs, respectively. Seven of these primer pairs were validated with PCR assay, which showed 100% inclusivity for the 101 S. enterica genomes and 100% exclusivity of 30 non-S. enterica genomes. Three specific primer pairs were chosen to develop a multiplex PCR assay, which generated specific amplicons with a size of 180bp (SC1286), 238bp (SC1598) and 405bp (SC4361), respectively. This study demonstrates that SMM-system is a high-throughput specific marker generation tool that can be used to identify genus-, species-, serogroup- and even serovar-specific DNA sequences of microbial pathogens, which has a potential to be applied in food industries, diagnostics and taxonomic studies. SMM-system is freely available and can be downloaded from http://foodsafety.sjtu.edu.cn/SMM-system.html. Copyright © 2011 Elsevier B.V. All rights reserved.

  17. Bim: guardian of tissue homeostasis and critical regulator of the immune system, tumorigenesis and bone biology.

    Science.gov (United States)

    Akiyama, Toru; Tanaka, Sakae

    2011-08-01

    One of the most important roles of apoptosis is the maintenance of tissue homeostasis. Impairment of apoptosis leads to a number of pathological conditions. In response to apoptotic signals, various proteins are activated in a pathway and signal-specific manner. Recently, the pro-apoptotic molecule Bim has attracted increasing attention as a pivotal regulator of tissue homeostasis. The Bim expression level is strictly controlled in both transcriptional and post-transcriptional levels. This control is dependent on cell, tissue and apoptotic stimuli. The phenotype of Bim-deficient mice is a systemic lupus erythematosus-like autoimmune disease with an abnormal accumulation of hematopoietic cells. Bim is thus a critical regulator of hematopoietic cells and immune system. Further studies have revealed the critical roles of Bim in various normal and pathological conditions, including bone homeostasis and tumorigenesis. The current understanding of Bim signaling and roles in the maintenance of tissue homeostasis is reviewed in this paper, focusing on the immune system, bone biology and tumorigenesis to illustrate the diversified role of Bim.

  18. Application of the ultrasound hyperthermia model for a multi-layered tissue system

    International Nuclear Information System (INIS)

    Loerincz, A

    2004-01-01

    This work models the thermal effect of several planar transducers targeting the tumour interactively in a ceramics-coupling-skin-muscle-tumour system. The most important inputs of the model include the following: emitted electric output, J/s; mechanical efficiency, %; number of transducers, pieces; surface area of the transducer, m 2 ; area, m 2 and temperature, K of the cooling surface, attenuation coefficients, Np/cm MHz; specific heats, J/gK; densities, g/cm 3 ; heat conductivities, J/msK; sound velocities m/s; flow rate of blood in the tissues, ml/gtissue/min; sound path in the tissues and in the blood flowing through the tissues, m. From the inputs, a number of intermediate data are determined, e.g. the geometry of the irradiated bodies that are in the path of ultrasound, acoustic hardness, Pas/m; sound reflection and sound transmission occurring at the interfaces, Np; heat exchanger wall thickness of the irradiated bodies, m; heat dissipation and heat exchanger surface areas, m 2 ; flow rate of blood in the tissues located in the path of ultrasound, ml/tissue mass in g/min; and the sound attenuation of the tissues, Np. The amount of generated heat, K/s decreased by the heat energy transported, J/s to the surrounding tissues by blood and heat conductivity, and the actual temperature, K of the irradiated tissue are the output parameters calculated by the model. The output results are available in the form of functions. The expected temperature of the target area, K can be set to either the denaturation temperature or to the respiratory decomposition temperature (43.5 deg. C) without damaging the surrounding tissues by setting in the following parameters properly: electric output power, W; the number and surface area, m 2 of the transducers; the area, m 2 and temperature, K of the cooling surfaces. After further development, the model will be suitable for handling more than three tissue layers, increased blood flow rates different angles of incidence, and

  19. A Wearable Goggle Navigation System for Dual-Mode Optical and Ultrasound Localization of Suspicious Lesions: Validation Studies Using Tissue-Simulating Phantoms and an Ex Vivo Human Breast Tissue Model.

    Directory of Open Access Journals (Sweden)

    Zeshu Zhang

    Full Text Available Surgical resection remains the primary curative treatment for many early-stage cancers, including breast cancer. The development of intraoperative guidance systems for identifying all sites of disease and improving the likelihood of complete surgical resection is an area of active ongoing research, as this can lead to a decrease in the need of subsequent additional surgical procedures. We develop a wearable goggle navigation system for dual-mode optical and ultrasound imaging of suspicious lesions. The system consists of a light source module, a monochromatic CCD camera, an ultrasound system, a Google Glass, and a host computer. It is tested in tissue-simulating phantoms and an ex vivo human breast tissue model. Our experiments demonstrate that the surgical navigation system provides useful guidance for localization and core needle biopsy of simulated tumor within the tissue-simulating phantom, as well as a core needle biopsy and subsequent excision of Indocyanine Green (ICG-fluorescing sentinel lymph nodes. Our experiments support the contention that this wearable goggle navigation system can be potentially very useful and fully integrated by the surgeon for optimizing many aspects of oncologic surgery. Further engineering optimization and additional in vivo clinical validation work is necessary before such a surgical navigation system can be fully realized in the everyday clinical setting.

  20. Lacrimal drainage-associated lymphoid tissue (LDALT): a part of the human mucosal immune system.

    Science.gov (United States)

    Knop, E; Knop, N

    2001-03-01

    Mucosa-associated lymphoid tissue (MALT) specifically protects mucosal surfaces. In a previous study of the human conjunctiva, evidence was also found for the presence of MALT in the lacrimal sac. The present study, therefore, aims to investigate its morphology and topographical distribution in the human lacrimal drainage system. Lacrimal drainage systems (n = 51) obtained from human cadavers were investigated by clearing flat wholemounts or by serial sections of tissue embedded in paraffin, OCT compound, or epoxy resin. These were further analyzed by histology, immunohistochemistry, and electron microscopy. All specimens showed the presence of lymphocytes and plasma cells as a diffuse lymphoid tissue in the lamina propria, together with intraepithelial lymphocytes and occasional high endothelial venules (HEV). It formed a narrow layer along the canaliculi that became thicker in the cavernous parts. The majority of lymphocytes were T cells, whereas B cells were interspersed individually or formed follicular centers. T cells were positive for CD8 and the human mucosa lymphocyte antigen (HML-1). Most plasma cells were positive for IgA and the overlying epithelium expressed its transporter molecule secretory component (SC). Basal mucous glands were present in the lacrimal canaliculi and in the other parts accompanied by alveolar and acinar glands, all producing IgA-rich secretions. Primary and secondary lymphoid follicles possessing HEV were present in about half of the specimens. The term lacrimal drainage-associated lymphoid tissue (LDALT) is proposed here to describe the lymphoid tissue that is regularly present and belongs to the common mucosal immune system and to the secretory immune system. It is suggested that it may form a functional unit together with the lacrimal gland and conjunctiva, connected by tear flow, lymphocyte recirculation, and probably the neural reflex arc, and play a major role in preserving ocular surface integrity.

  1. Microbiological Features of KPC-Producing Enterobacter Isolates Identified in a U.S. Hospital System

    Science.gov (United States)

    Ahn, Chulsoo; Syed, Alveena; Hu, Fupin; O’Hara, Jessica A.; Rivera, Jesabel I.; Doi, Yohei

    2014-01-01

    Microbiological data regarding KPC-producing Enterobacter spp. are scarce. In this study, 11 unique KPC-producing Enterobacter isolates were identified among 44 ertapenem-non-susceptible Enterobacter isolates collected between 2009 and 2013 at a hospital system in Western Pennsylvania. All cases were healthcare-associated and occurred in medically complex patients. While pulsed-field gel electrophoresis (PFGE) showed diverse restriction patterns overall, multilocus sequence typing (MLST) identified Enterobacter cloacae isolates with sequence types (STs) 93 and 171 from two hospitals each. The levels of carbapenem minimum inhibitory concentrations were highly variable. All isolates remained susceptible to colistin, tigecycline, and the majority to amikacin and doxycycline. A blaKPC-carrying IncN plasmid conferring trimethoprim-sulfamethoxazole resistance was identified in three of the isolates. Spread of blaKPC in Enterobacter spp. appears to be due to a combination of plasmid-mediated and clonal processes. PMID:25053203

  2. Cell and biomolecule delivery for tissue repair and regeneration in the central nervous system.

    Science.gov (United States)

    Elliott Donaghue, Irja; Tam, Roger; Sefton, Michael V; Shoichet, Molly S

    2014-09-28

    Tissue engineering frequently involves cells and scaffolds to replace damaged or diseased tissue. It originated, in part, as a means of effecting the delivery of biomolecules such as insulin or neurotrophic factors, given that cells are constitutive producers of such therapeutic agents. Thus cell delivery is intrinsic to tissue engineering. Controlled release of biomolecules is also an important tool for enabling cell delivery since the biomolecules can enable cell engraftment, modulate inflammatory response or otherwise benefit the behavior of the delivered cells. We describe advances in cell and biomolecule delivery for tissue regeneration, with emphasis on the central nervous system (CNS). In the first section, the focus is on encapsulated cell therapy. In the second section, the focus is on biomolecule delivery in polymeric nano/microspheres and hydrogels for the nerve regeneration and endogenous cell stimulation. In the third section, the focus is on combination strategies of neural stem/progenitor cell or mesenchymal stem cell and biomolecule delivery for tissue regeneration and repair. In each section, the challenges and potential solutions associated with delivery to the CNS are highlighted. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Central and peripheral mechanisms of the NPY system in the regulation of bone and adipose tissue.

    Science.gov (United States)

    Shi, Yan-Chuan; Baldock, Paul A

    2012-02-01

    Skeletal research is currently undergoing a period of marked expansion. The boundaries of "bone" research are being re-evaluated and with this, a growing recognition of a more complex and interconnected biology than previously considered. One aspect that has become the focus of particular attention is the relationship between bone and fat homeostasis. Evidence from a number of avenues indicates that bone and adipose regulation are both related and interdependent. This review examines the neuropeptide Y (NPY) system, known to exert powerful control over both bone and fat tissue. The actions of this system are characterized by signaling both within specific nuclei of the hypothalamus and also the target tissues, mediated predominantly through two G-protein coupled receptors (Y1 and Y2). In bone tissue, elevated NPY levels act consistently to repress osteoblast activity. Moreover, both central Y2 receptor and osteoblastic Y1 receptor signaling act similarly to repress bone formation. Conversely, loss of NPY expression or receptor signaling induces increased osteoblast activity and bone mass in both cortical and cancellous envelopes. In fat tissue, NPY action is more complex. Energy homeostasis is powerfully altered by elevations in hypothalamic NPY, resulting in increases in fat accretion and body-wide energy conservation, through the action of locally expressed Y1 receptors, while local Y2 receptors act to inhibit NPY-ergic tone. Loss of central NPY expression has a markedly reduced effect, consistent with a physiological drive to promote fat accretion. In fat tissue, NPY and Y1 receptors act to promote lipogenesis, consistent with their roles in the brain. Y2 receptors expressed in adipocytes also act in this manner, showing an opposing action to their role in the hypothalamus. While direct investigation of these processes has yet to be completed, these responses appear to be interrelated to some degree. The starvation-based signal of elevated central NPY inducing

  4. Systems-based analysis of the Sarcocystis neurona genome identifies pathways that contribute to a heteroxenous life cycle.

    Science.gov (United States)

    Blazejewski, Tomasz; Nursimulu, Nirvana; Pszenny, Viviana; Dangoudoubiyam, Sriveny; Namasivayam, Sivaranjani; Chiasson, Melissa A; Chessman, Kyle; Tonkin, Michelle; Swapna, Lakshmipuram S; Hung, Stacy S; Bridgers, Joshua; Ricklefs, Stacy M; Boulanger, Martin J; Dubey, Jitender P; Porcella, Stephen F; Kissinger, Jessica C; Howe, Daniel K; Grigg, Michael E; Parkinson, John

    2015-02-10

    Sarcocystis neurona is a member of the coccidia, a clade of single-celled parasites of medical and veterinary importance including Eimeria, Sarcocystis, Neospora, and Toxoplasma. Unlike Eimeria, a single-host enteric pathogen, Sarcocystis, Neospora, and Toxoplasma are two-host parasites that infect and produce infectious tissue cysts in a wide range of intermediate hosts. As a genus, Sarcocystis is one of the most successful protozoan parasites; all vertebrates, including birds, reptiles, fish, and mammals are hosts to at least one Sarcocystis species. Here we sequenced Sarcocystis neurona, the causal agent of fatal equine protozoal myeloencephalitis. The S. neurona genome is 127 Mbp, more than twice the size of other sequenced coccidian genomes. Comparative analyses identified conservation of the invasion machinery among the coccidia. However, many dense-granule and rhoptry kinase genes, responsible for altering host effector pathways in Toxoplasma and Neospora, are absent from S. neurona. Further, S. neurona has a divergent repertoire of SRS proteins, previously implicated in tissue cyst formation in Toxoplasma. Systems-based analyses identified a series of metabolic innovations, including the ability to exploit alternative sources of energy. Finally, we present an S. neurona model detailing conserved molecular innovations that promote the transition from a purely enteric lifestyle (Eimeria) to a heteroxenous parasite capable of infecting a wide range of intermediate hosts. Sarcocystis neurona is a member of the coccidia, a clade of single-celled apicomplexan parasites responsible for major economic and health care burdens worldwide. A cousin of Plasmodium, Cryptosporidium, Theileria, and Eimeria, Sarcocystis is one of the most successful parasite genera; it is capable of infecting all vertebrates (fish, reptiles, birds, and mammals-including humans). The past decade has witnessed an increasing number of human outbreaks of clinical significance associated with

  5. Beacon-based tourist information system to identify visiting trends of tourists

    Directory of Open Access Journals (Sweden)

    Akihiro Yamaguchi

    2017-11-01

    Full Text Available In this study, we propose a system that provides tourist information and obtains trends of visiting tourists using beacons and cloud service. As part of our research, we are working on the promotion of local area tourism in cooperation with a local community. A low energy Bluetooth device is used as a beacon to transmit a universally unique identifier. In addition, beacons are placed at sightseeing spots and tourist facilities. Our proposed system comprises two application programs; one is a client-side application program that provides area-specific tourist information corresponding to the detected beacon. The other is a server-side application to record time and location information of the detected beacons. In this paper, we describe the scheme of our system, and present the results of experiments conducted using the prototype system in the local tourist area. In addition, we discuss an open platform for information collection services using beacons.

  6. Identifying critical constraints for the maximum loadability of electric power systems - analysis via interior point method

    Energy Technology Data Exchange (ETDEWEB)

    Barboza, Luciano Vitoria [Sul-riograndense Federal Institute for Education, Science and Technology (IFSul), Pelotas, RS (Brazil)], E-mail: luciano@pelotas.ifsul.edu.br

    2009-07-01

    This paper presents an overview about the maximum load ability problem and aims to study the main factors that limit this load ability. Specifically this study focuses its attention on determining which electric system buses influence directly on the power demand supply. The proposed approach uses the conventional maximum load ability method modelled by an optimization problem. The solution of this model is performed using the Interior Point methodology. As consequence of this solution method, the Lagrange multipliers are used as parameters that identify the probable 'bottlenecks' in the electric power system. The study also shows the relationship between the Lagrange multipliers and the cost function in the Interior Point optimization interpreted like sensitivity parameters. In order to illustrate the proposed methodology, the approach was applied to an IEEE test system and to assess its performance, a real equivalent electric system from the South- Southeast region of Brazil was simulated. (author)

  7. Control-based method to identify underlying delays of a nonlinear dynamical system.

    Science.gov (United States)

    Yu, Dongchuan; Frasca, Mattia; Liu, Fang

    2008-10-01

    We suggest several stationary state control-based delay identification methods which do not require any structural information about the controlled systems and are applicable to systems described by delayed ordinary differential equations. This proposed technique includes three steps: (i) driving a system to a steady state; (ii) perturbing the control signal for shifting the steady state; and (iii) identifying all delays by detecting the time that the system is abruptly drawn out of stationarity. Some aspects especially important for applications are discussed as well, including interaction delay identification, stationary state convergence speed, performance comparison, and the influence of noise on delay identification. Several examples are presented to illustrate the reliability and robustness of all delay identification methods suggested.

  8. Anterior temporal artery tap to identify systemic interference using short-separation NIRS measurements

    DEFF Research Database (Denmark)

    Sood, Mehak; Jindal, Utkarsh; Chowdhury, Shubhajit Roy

    2015-01-01

    that are also affected by tDCS. An approach may be to use short optode separations to measure systemic hemodynamic fluctuations occurring in the superficial layers which can then be used as regressors to remove the systemic contamination. Here, we demonstrate that temporal artery tap may be used to better...... of neural activity is possible with a measure of cerebral hemoglobin oxygenation using near-infrared spectroscopy (NIRS). In principal accordance, NIRS can capture the hemodynamic response to tDCS but the challenge remains in removing the systemic interference occurring in the superficial layers of the head...... identify systemic interference using this short-separation NIRS. Moreover, NIRS-EEG joint-imaging during anodal tDCS was used to measure changes in mean cerebral haemoglobin oxygen saturation (rSO2) along with changes in the log-transformed mean-power of EEG within 0.5 Hz-11.25 Hz. We found that percent...

  9. Information sensitivity functions to assess parameter information gain and identifiability of dynamical systems.

    Science.gov (United States)

    Pant, Sanjay

    2018-05-01

    A new class of functions, called the 'information sensitivity functions' (ISFs), which quantify the information gain about the parameters through the measurements/observables of a dynamical system are presented. These functions can be easily computed through classical sensitivity functions alone and are based on Bayesian and information-theoretic approaches. While marginal information gain is quantified by decrease in differential entropy, correlations between arbitrary sets of parameters are assessed through mutual information. For individual parameters, these information gains are also presented as marginal posterior variances, and, to assess the effect of correlations, as conditional variances when other parameters are given. The easy to interpret ISFs can be used to (a) identify time intervals or regions in dynamical system behaviour where information about the parameters is concentrated; (b) assess the effect of measurement noise on the information gain for the parameters; (c) assess whether sufficient information in an experimental protocol (input, measurements and their frequency) is available to identify the parameters; (d) assess correlation in the posterior distribution of the parameters to identify the sets of parameters that are likely to be indistinguishable; and (e) assess identifiability problems for particular sets of parameters. © 2018 The Authors.

  10. Integrating the nursing management minimum data set into the logical observation identifier names and codes system.

    Science.gov (United States)

    Subramanian, Amarnath; Westra, Bonnie; Matney, Susan; Wilson, Patricia S; Delaney, Connie W; Huff, Stan; Huff, Stanley M; Huber, Diane

    2008-11-06

    This poster describes the process used to integrate the Nursing Management Minimum Data Set (NMMDS), an instrument to measure the nursing context of care, into the Logical Observation Identifier Names and Codes (LOINC) system to facilitate contextualization of quality measures. Integration of the first three of 18 elements resulted in 48 new codes including five panels. The LOINC Clinical Committee has approved the presented mapping for their next release.

  11. Systems and methods for automatically identifying and linking names in digital resources

    Science.gov (United States)

    Parker, Charles T.; Lyons, Catherine M.; Roston, Gerald P.; Garrity, George M.

    2017-06-06

    The present invention provides systems and methods for automatically identifying name-like-strings in digital resources, matching these name-like-string against a set of names held in an expertly curated database, and for those name-like-strings found in said database, enhancing the content by associating additional matter with the name, wherein said matter includes information about the names that is held within said database and pointers to other digital resources which include the same name and it synonyms.

  12. Capacity of milk composition to identify the feeding system used to feed dairy cows.

    Science.gov (United States)

    Vicente, Fernando; Santiago, Carme; Jiménez-Calderón, José D; Martínez-Fernández, Adela

    2017-08-01

    This Research Paper addresses the hypothesis that is possible to identify the type of feed used for dairy cows by means of the analysis of milk composition and the fatty acid profile of milk fat. Sixteen dairy farms were monitored during 1 year with quarterly visits between summer 2014 and spring 2015. Rations varied throughout the year due to annual dynamic change of forage production, forage rotation, variation of nutrient requirements according to physiological state of the animal, etc. The ingredients of the rations were analysed by cluster identifying five feeding systems based on the main ingredient of the diet: grazing, maize silage, grass silage, dry forage and concentrate. Milk composition could explain up to 91·3% of the total variability among feeding systems, while fatty acid profile could explain only up to 61·2% of total variability. However, when the sum of types of fatty acids and their ratios are taken, up to 93·5% of total variability could be explained. The maize silage system had the greatest milk yield, protein, solid non-fat and urea proportions, as well as the highest proportion of saturated fatty acid and lowest concentration of trans11 18 : 1, cis9 18 : 1 and 18 : 3 n3. Principal component analysis distinguishes the maize silage system from other feeding systems, both from milk composition and milk fatty acid profile. Concentrate system overlapped partially with the grazing, grass silage and dry forage systems. The latter systems had the highest concentrations of cis9 18 : 1, trans11 18 : 1 and 18 : 3, but there was no clear differentiation among them.

  13. Methodology to explore interactions between the water system and society in order to identify adaptation strategies

    Science.gov (United States)

    Offermans, A. G. E.; Haasnoot, M.

    2009-04-01

    Development of sustainable water management strategies involves analysing current and future vulnerability, identification of adaptation possibilities, effect analysis and evaluation of the strategies under different possible futures. Recent studies on water management often followed the pressure-effect chain and compared the state of social, economic and ecological functions of the water systems in one or two future situations with the current situation. The future is, however, more complex and dynamic. Water management faces major challenges to cope with future uncertainties in both the water system as well as the social system. Uncertainties in our water system relate to (changes in) drivers and pressures and their effects on the state, like the effects of climate change on discharges. Uncertainties in the social world relate to changing of perceptions, objectives and demands concerning water (management), which are often related with the aforementioned changes in the physical environment. The methodology presented here comprises the 'Perspectives method', derived from the Cultural Theory, a method on analyzing and classifying social response to social and natural states and pressures. The method will be used for scenario analysis and to identify social responses including changes in perspectives and management strategies. The scenarios and responses will be integrated within a rapid assessment tool. The purpose of the tool is to provide users with insight about the interaction of the social and physical system and to identify robust water management strategies by analysing the effectiveness under different possible futures on the physical, social and socio-economic system. This method allows for a mutual interaction between the physical and social system. We will present the theoretical background of the perspectives method as well as a historical overview of perspective changes in the Dutch Meuse area to show how social and physical systems interrelate. We

  14. Clustering analysis of water distribution systems: identifying critical components and community impacts.

    Science.gov (United States)

    Diao, K; Farmani, R; Fu, G; Astaraie-Imani, M; Ward, S; Butler, D

    2014-01-01

    Large water distribution systems (WDSs) are networks with both topological and behavioural complexity. Thereby, it is usually difficult to identify the key features of the properties of the system, and subsequently all the critical components within the system for a given purpose of design or control. One way is, however, to more explicitly visualize the network structure and interactions between components by dividing a WDS into a number of clusters (subsystems). Accordingly, this paper introduces a clustering strategy that decomposes WDSs into clusters with stronger internal connections than external connections. The detected cluster layout is very similar to the community structure of the served urban area. As WDSs may expand along with urban development in a community-by-community manner, the correspondingly formed distribution clusters may reveal some crucial configurations of WDSs. For verification, the method is applied to identify all the critical links during firefighting for the vulnerability analysis of a real-world WDS. Moreover, both the most critical pipes and clusters are addressed, given the consequences of pipe failure. Compared with the enumeration method, the method used in this study identifies the same group of the most critical components, and provides similar criticality prioritizations of them in a more computationally efficient time.

  15. Novel high-throughput screening system for identifying STAT3-SH2 antagonists

    International Nuclear Information System (INIS)

    Uehara, Yutaka; Mochizuki, Masato; Matsuno, Kenji; Haino, Takeharu; Asai, Akira

    2009-01-01

    Constitutive activation of the oncogenic transcription factor STAT3 frequently occurs in various human malignancies. STAT3 activation involves dimerization via intermolecular pTyr-SH2 interaction. Thus, antagonizing this interaction is a feasible approach to inhibit STAT3 activation for cancer therapy. In order to identify selective STAT3 inhibitors, we developed a biochemical HTS system based on AlphaScreen technology, which measures the abilities of test compounds to antagonize pTyr-SH2 interactions. We screened our chemical libraries using this system and identified 5,15-diphenylporphyrin (5,15-DPP) as a selective STAT3-SH2 antagonist. Selective inhibition of STAT3 nuclear translocation and DNA biding activity was observed in cells treated with 5,15-DPP. IL-6-dependent dimerization of STAT3, c-myc promoter binding and c-myc protein expression were all suppressed by 5,15-DPP, whereas no decrement in either expression or phosphorylation level of STAT3 was observed. Thus, the HTS assay system represented herein may be useful for identifying novel STAT3-SH2 antagonists.

  16. Stereo camera based virtual cane system with identifiable distance tactile feedback for the blind.

    Science.gov (United States)

    Kim, Donghun; Kim, Kwangtaek; Lee, Sangyoun

    2014-06-13

    In this paper, we propose a new haptic-assisted virtual cane system operated by a simple finger pointing gesture. The system is developed by two stages: development of visual information delivery assistant (VIDA) with a stereo camera and adding a tactile feedback interface with dual actuators for guidance and distance feedbacks. In the first stage, user's pointing finger is automatically detected using color and disparity data from stereo images and then a 3D pointing direction of the finger is estimated with its geometric and textural features. Finally, any object within the estimated pointing trajectory in 3D space is detected and the distance is then estimated in real time. For the second stage, identifiable tactile signals are designed through a series of identification experiments, and an identifiable tactile feedback interface is developed and integrated into the VIDA system. Our approach differs in that navigation guidance is provided by a simple finger pointing gesture and tactile distance feedbacks are perfectly identifiable to the blind.

  17. Stereo Camera Based Virtual Cane System with Identifiable Distance Tactile Feedback for the Blind

    Directory of Open Access Journals (Sweden)

    Donghun Kim

    2014-06-01

    Full Text Available In this paper, we propose a new haptic-assisted virtual cane system operated by a simple finger pointing gesture. The system is developed by two stages: development of visual information delivery assistant (VIDA with a stereo camera and adding a tactile feedback interface with dual actuators for guidance and distance feedbacks. In the first stage, user’s pointing finger is automatically detected using color and disparity data from stereo images and then a 3D pointing direction of the finger is estimated with its geometric and textural features. Finally, any object within the estimated pointing trajectory in 3D space is detected and the distance is then estimated in real time. For the second stage, identifiable tactile signals are designed through a series of identification experiments, and an identifiable tactile feedback interface is developed and integrated into the VIDA system. Our approach differs in that navigation guidance is provided by a simple finger pointing gesture and tactile distance feedbacks are perfectly identifiable to the blind.

  18. Alternative approaches for identifying acute systemic toxicity: Moving from research to regulatory testing.

    Science.gov (United States)

    Hamm, Jon; Sullivan, Kristie; Clippinger, Amy J; Strickland, Judy; Bell, Shannon; Bhhatarai, Barun; Blaauboer, Bas; Casey, Warren; Dorman, David; Forsby, Anna; Garcia-Reyero, Natàlia; Gehen, Sean; Graepel, Rabea; Hotchkiss, Jon; Lowit, Anna; Matheson, Joanna; Reaves, Elissa; Scarano, Louis; Sprankle, Catherine; Tunkel, Jay; Wilson, Dan; Xia, Menghang; Zhu, Hao; Allen, David

    2017-06-01

    Acute systemic toxicity testing provides the basis for hazard labeling and risk management of chemicals. A number of international efforts have been directed at identifying non-animal alternatives for in vivo acute systemic toxicity tests. A September 2015 workshop, Alternative Approaches for Identifying Acute Systemic Toxicity: Moving from Research to Regulatory Testing, reviewed the state-of-the-science of non-animal alternatives for this testing and explored ways to facilitate implementation of alternatives. Workshop attendees included representatives from international regulatory agencies, academia, nongovernmental organizations, and industry. Resources identified as necessary for meaningful progress in implementing alternatives included compiling and making available high-quality reference data, training on use and interpretation of in vitro and in silico approaches, and global harmonization of testing requirements. Attendees particularly noted the need to characterize variability in reference data to evaluate new approaches. They also noted the importance of understanding the mechanisms of acute toxicity, which could be facilitated by the development of adverse outcome pathways. Workshop breakout groups explored different approaches to reducing or replacing animal use for acute toxicity testing, with each group crafting a roadmap and strategy to accomplish near-term progress. The workshop steering committee has organized efforts to implement the recommendations of the workshop participants. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. High plasma apolipoprotein B identifies obese subjects who best ameliorate white adipose tissue dysfunction and glucose-induced hyperinsulinemia after a hypocaloric diet.

    Science.gov (United States)

    Bissonnette, Simon; Saint-Pierre, Nathalie; Lamantia, Valerie; Leroux, Catherine; Provost, Viviane; Cyr, Yannick; Rabasa-Lhoret, Remi; Faraj, May

    2018-06-18

    To optimize the prevention of type 2 diabetes (T2D), high-risk obese subjects with the best metabolic recovery after a hypocaloric diet should be targeted. Apolipoprotein B lipoproteins (apoB lipoproteins) induce white adipose tissue (WAT) dysfunction, which in turn promotes postprandial hypertriglyceridemia, insulin resistance (IR), and hyperinsulinemia. The aim of this study was to explore whether high plasma apoB, or number of plasma apoB lipoproteins, identifies subjects who best ameliorate WAT dysfunction and related risk factors after a hypocaloric diet. Fifty-nine men and postmenopausal women [mean ± SD age: 58 ± 6 y; body mass index (kg/m2): 32.6 ± 4.6] completed a prospective study with a 6-mo hypocaloric diet (-500 kcal/d). Glucose-induced insulin secretion (GIIS) and insulin sensitivity (IS) were measured by 1-h intravenous glucose-tolerance test (IVGTT) followed by a 3-h hyperinsulinemic-euglycemic clamp, respectively. Ex vivo gynoid WAT function (i.e., hydrolysis and storage of 3H-triolein-labeled triglyceride-rich lipoproteins) and 6-h postprandial plasma clearance of a 13C-triolein-labeled high-fat meal were measured in a subsample (n = 25). Postintervention first-phase GIISIVGTT and total C-peptide secretion decreased in both sexes, whereas second-phase and total GIISIVGTT and clamp IS were ameliorated in men (P hypocaloric diet. We propose that subjects with high plasma apoB represent an optimal target group for the primary prevention of T2D by hypocaloric diets. This trial was registered at BioMed Central as ISRCTN14476404.

  20. Evaluation of the WinROP system for identifying retinopathy of prematurity in Czech preterm infants.

    Science.gov (United States)

    Timkovic, Juraj; Pokryvkova, Martina; Janurova, Katerina; Barinova, Denisa; Polackova, Renata; Masek, Petr

    2017-03-01

    Retinopathy of Prematurity (ROP) is a potentially serious condition that can afflict preterm infants. Timely and correct identification of individuals at risk of developing a serious form of ROP is therefore of paramount importance. WinROP is an online system for predicting ROP based on birth weight and weight increments. However, the results vary significantly for various populations. It has not been evaluated in the Czech population. This study evaluates the test characteristics (specificity, sensitivity, positive and negative predictive values) of the WinROP system in Czech preterm infants. Data on 445 prematurely born infants included in the ROP screening program at the University Hospital Ostrava, Czech Republic, were retrospectively entered into the WinROP system and the outcomes of the WinROP and regular screening were compared. All 24 infants who developed high-risk (Type 1 or Type 2) ROP were correctly identified by the system. The sensitivity and negative predictive values for this group were 100%. However, the specificity and positive predictive values were substantially lower, resulting in a large number of false positives. Extending the analysis to low risk ROP, the system did not provide such reliable results. The system is a valuable tool for identifying infants who are not likely to develop high-risk ROP and this could help to substantially reduce the number of preterm infants in need of regular ROP screening. It is not suitable for predicting the development of less serious forms of ROP which is however in accordance with the declared aims of the WinROP system.

  1. Autoantibodies Recognizing Secondary NEcrotic Cells Promote Neutrophilic Phagocytosis and Identify Patients With Systemic Lupus Erythematosus

    Directory of Open Access Journals (Sweden)

    Mona H. C. Biermann

    2018-05-01

    Full Text Available Deficient clearance of apoptotic cells reportedly contributes to the etiopathogenesis of the autoimmune disease systemic lupus erythematosus (SLE. Based on this knowledge, we developed a highly specific and sensitive test for the detection of SLE autoantibodies (AAb utilizing secondary NEcrotic cell (SNEC-derived material as a substrate. The goal of the present study was to validate the use of SNEC as an appropriate antigen for the diagnosis of SLE in large cohort of patients. We confirmed the presence of apoptotically modified autoantigens on SNEC (dsDNA, high mobility group box 1 protein, apoptosis-associated chromatin modifications, e.g., histones H3-K27-me3; H2A/H4 AcK8,12,16; and H2B-AcK12. Anti-SNEC AAb were measured in the serum of 155 patients with SLE, 89 normal healthy donors (NHD, and 169 patients with other autoimmune connective tissue diseases employing SNEC-based indirect enzyme-linked immunosorbent assay (SNEC ELISA. We compared the test performance of SNEC ELISA with the routine diagnostic tests dsDNA Farr radioimmunoassay (RIA and nucleosome-based ELISA (anti-dsDNA-NcX-ELISA. SNEC ELISA distinguished patients with SLE with a specificity of 98.9% and a sensitivity of 70.6% from NHD clearly surpassing RIA and anti-dsDNA-NcX-ELISA. In contrast to the other tests, SNEC ELISA significantly discriminated patients with SLE from patients with rheumatoid arthritis, primary anti-phospholipid syndrome, spondyloarthropathy, psoriatic arthritis, and systemic sclerosis. A positive test result in SNEC ELISA significantly correlated with serological variables and reflected the uptake of opsonized SNEC by neutrophils. This stresses the relevance of SNECs in the pathogenesis of SLE. We conclude that SNEC ELISA allows for the sensitive detection of pathologically relevant AAb, enabling its diagnostic usage. A positive SNEC test reflects the opsonization of cell remnants by AAb, the neutrophil recruitment to tissues, and the enhancement of local

  2. Overview on zein protein: a promising pharmaceutical excipient in drug delivery systems and tissue engineering.

    Science.gov (United States)

    Labib, Gihan

    2018-01-01

    Natural pharmaceutical excipients have been applied extensively in the past decades owing to their safety and biocompatibility. Zein, a natural protein of plant origin offers great benefit over other synthetic polymers used in controlled drug and biomedical delivery systems. It was used in a variety of medical fields including pharmaceutical and biomedical drug targeting, vaccine, tissue engineering, and gene delivery. Being biodegradable and biocompatible, the current review focuses on the history and the medical application of zein as an attractive still promising biopolymer. Areas covered: The current review gives a broadscope on zein as a still promising protein excipient in different fields. Zein- based drug and biomedical delivery systems are discussed with special focus on current and potential application in controlled drug delivery systems, and tissue engineering. Expert opinion: Zein as a protein of natural origin can still be considered a promising polymer in the field of drug delivery systems as well as in tissue engineering. Although different researchers spotted light on zein application in different industrial fields extensively, the feasibility of its use in the field of drug delivery replenished by investigators in recent years has not yet been fully approached.

  3. Possibilities of identifying cyber attack in noisy space of n-dimensional abstract system

    Energy Technology Data Exchange (ETDEWEB)

    Jašek, Roman; Dvořák, Jiří; Janková, Martina; Sedláček, Michal [Tomas Bata University in Zlin Nad Stranemi 4511, 760 05 Zlin, Czech republic jasek@fai.utb.cz, dvorakj@aconte.cz, martina.jankova@email.cz, michal.sedlacek@email.cz (Czech Republic)

    2016-06-08

    This article briefly mentions some selected options of current concept for identifying cyber attacks from the perspective of the new cyberspace of real system. In the cyberspace, there is defined n-dimensional abstract system containing elements of the spatial arrangement of partial system elements such as micro-environment of cyber systems surrounded by other suitably arranged corresponding noise space. This space is also gradually supplemented by a new image of dynamic processes in a discreet environment, and corresponding again to n-dimensional expression of time space defining existence and also the prediction for expected cyber attacksin the noise space. Noises are seen here as useful and necessary for modern information and communication technologies (e.g. in processes of applied cryptography in ICT) and then the so-called useless noises designed for initial (necessary) filtering of this highly aggressive environment and in future expectedly offensive background in cyber war (e.g. the destruction of unmanned means of an electromagnetic pulse, or for destruction of new safety barriers created on principles of electrostatic field or on other principles of modern physics, etc.). The key to these new options is the expression of abstract systems based on the models of microelements of cyber systems and their hierarchical concept in structure of n-dimensional system in given cyberspace. The aim of this article is to highlight the possible systemic expression of cyberspace of abstract system and possible identification in time-spatial expression of real environment (on microelements of cyber systems and their surroundings with noise characteristics and time dimension in dynamic of microelements’ own time and externaltime defined by real environment). The article was based on a partial task of faculty specific research.

  4. Possibilities of identifying cyber attack in noisy space of n-dimensional abstract system

    International Nuclear Information System (INIS)

    Jašek, Roman; Dvořák, Jiří; Janková, Martina; Sedláček, Michal

    2016-01-01

    This article briefly mentions some selected options of current concept for identifying cyber attacks from the perspective of the new cyberspace of real system. In the cyberspace, there is defined n-dimensional abstract system containing elements of the spatial arrangement of partial system elements such as micro-environment of cyber systems surrounded by other suitably arranged corresponding noise space. This space is also gradually supplemented by a new image of dynamic processes in a discreet environment, and corresponding again to n-dimensional expression of time space defining existence and also the prediction for expected cyber attacksin the noise space. Noises are seen here as useful and necessary for modern information and communication technologies (e.g. in processes of applied cryptography in ICT) and then the so-called useless noises designed for initial (necessary) filtering of this highly aggressive environment and in future expectedly offensive background in cyber war (e.g. the destruction of unmanned means of an electromagnetic pulse, or for destruction of new safety barriers created on principles of electrostatic field or on other principles of modern physics, etc.). The key to these new options is the expression of abstract systems based on the models of microelements of cyber systems and their hierarchical concept in structure of n-dimensional system in given cyberspace. The aim of this article is to highlight the possible systemic expression of cyberspace of abstract system and possible identification in time-spatial expression of real environment (on microelements of cyber systems and their surroundings with noise characteristics and time dimension in dynamic of microelements’ own time and externaltime defined by real environment). The article was based on a partial task of faculty specific research.

  5. Possibilities of identifying cyber attack in noisy space of n-dimensional abstract system

    Science.gov (United States)

    Jašek, Roman; Dvořák, Jiří; Janková, Martina; Sedláček, Michal

    2016-06-01

    This article briefly mentions some selected options of current concept for identifying cyber attacks from the perspective of the new cyberspace of real system. In the cyberspace, there is defined n-dimensional abstract system containing elements of the spatial arrangement of partial system elements such as micro-environment of cyber systems surrounded by other suitably arranged corresponding noise space. This space is also gradually supplemented by a new image of dynamic processes in a discreet environment, and corresponding again to n-dimensional expression of time space defining existence and also the prediction for expected cyber attacksin the noise space. Noises are seen here as useful and necessary for modern information and communication technologies (e.g. in processes of applied cryptography in ICT) and then the so-called useless noises designed for initial (necessary) filtering of this highly aggressive environment and in future expectedly offensive background in cyber war (e.g. the destruction of unmanned means of an electromagnetic pulse, or for destruction of new safety barriers created on principles of electrostatic field or on other principles of modern physics, etc.). The key to these new options is the expression of abstract systems based on the models of microelements of cyber systems and their hierarchical concept in structure of n-dimensional system in given cyberspace. The aim of this article is to highlight the possible systemic expression of cyberspace of abstract system and possible identification in time-spatial expression of real environment (on microelements of cyber systems and their surroundings with noise characteristics and time dimension in dynamic of microelements' own time and externaltime defined by real environment). The article was based on a partial task of faculty specific research.

  6. Portable, Fiber-Based, Diffuse Reflection Spectroscopy (DRS) Systems for Estimating Tissue Optical Properties.

    Science.gov (United States)

    Vishwanath, Karthik; Chang, Kevin; Klein, Daniel; Deng, Yu Feng; Chang, Vivide; Phelps, Janelle E; Ramanujam, Nimmi

    2011-02-01

    Steady-state diffuse reflection spectroscopy is a well-studied optical technique that can provide a noninvasive and quantitative method for characterizing the absorption and scattering properties of biological tissues. Here, we compare three fiber-based diffuse reflection spectroscopy systems that were assembled to create a light-weight, portable, and robust optical spectrometer that could be easily translated for repeated and reliable use in mobile settings. The three systems were built using a broadband light source and a compact, commercially available spectrograph. We tested two different light sources and two spectrographs (manufactured by two different vendors). The assembled systems were characterized by their signal-to-noise ratios, the source-intensity drifts, and detector linearity. We quantified the performance of these instruments in extracting optical properties from diffuse reflectance spectra in tissue-mimicking liquid phantoms with well-controlled optical absorption and scattering coefficients. We show that all assembled systems were able to extract the optical absorption and scattering properties with errors less than 10%, while providing greater than ten-fold decrease in footprint and cost (relative to a previously well-characterized and widely used commercial system). Finally, we demonstrate the use of these small systems to measure optical biomarkers in vivo in a small-animal model cancer therapy study. We show that optical measurements from the simple portable system provide estimates of tumor oxygen saturation similar to those detected using the commercial system in murine tumor models of head and neck cancer.

  7. Comparison of tissue damage caused by various laser systems with tissue tolerable plasma by light and laser scan microscopy

    International Nuclear Information System (INIS)

    Vandersee, Staffan; Lademann, Jürgen; Richter, Heike; Patzelt, Alexa; Lange-Asschenfeldt, Bernhard

    2013-01-01

    Tissue tolerable plasma (TTP) represents a novel therapeutic method with promising capabilities in the field of dermatological interventions, in particular disinfection but also wound antisepsis and regeneration. The energy transfer by plasma into living tissue is not easily educible, as a variety of features such as the medium’s actual molecule-stream, the ions, electrons and free radicals involved, as well as the emission of ultraviolet, visible and infrared light contribute to its increasingly well characterized effects. Thus, relating possible adversary effects, especially of prolonged exposure to a single component of the plasma’s mode of action, is difficult. Until now, severe adverse events connected to plasma exposure have not been reported when conducted according to existing therapeutic protocols. In this study, we have compared the tissue damage-potential of CO 2 and dye lasers with TTP in a porcine model. After exposure of pig ear skin to the three treatment modalities, all specimens were examined histologically and by means of laser scan microscopy (LSM). Light microscopical tissue damage could only be shown in the case of the CO 2 laser, whereas dye laser and plasma treatment resulted in no detectable impairment of the specimens. In the case of TTP, LSM examination revealed only an impairment of the uppermost corneal layers of the skin, thus stressing its safety when used in vivo. (letter)

  8. Development of a digital trigger system to identify recoil protons at COMPASS-II

    Energy Technology Data Exchange (ETDEWEB)

    Buechele, Maximilian; Fischer, Horst; Gorzellik, Matthias; Grussenmeyer, Tobias; Herrmann, Florian; Joerg, Philipp; Koenigsmann, Kay; Kremser, Paul; Schopferer, Sebastian [Albert-Ludwigs-Universitaet Freiburg (Germany)

    2014-07-01

    The GANDALF framework has been developed to deliver a high precision, high performance detector readout and trigger system for particle physics experiments such as the COMPASS-II experiment at CERN. Combining the high performance pulse digitization and feature extraction capabilities of twelve GANDALF modules, each comprising a Virtex-5 SX95T, with the strong computation power of a Virtex-6 SX315T FGPA operated on the TIGER module, we present a digital trigger system for a recoil proton detector. The trigger system was setup and commissioned successfully during a data taking period in 2012. It was mainly used for the calibration of the recoil proton detector and in tagging mode to identify proton tracks online.

  9. Simplified LCA and matrix methods in identifying the environmental aspects of a product system.

    Science.gov (United States)

    Hur, Tak; Lee, Jiyong; Ryu, Jiyeon; Kwon, Eunsun

    2005-05-01

    In order to effectively integrate environmental attributes into the product design and development processes, it is crucial to identify the significant environmental aspects related to a product system within a relatively short period of time. In this study, the usefulness of life cycle assessment (LCA) and a matrix method as tools for identifying the key environmental issues of a product system were examined. For this, a simplified LCA (SLCA) method that can be applied to Electrical and Electronic Equipment (EEE) was developed to efficiently identify their significant environmental aspects for eco-design, since a full scale LCA study is usually very detailed, expensive and time-consuming. The environmentally responsible product assessment (ERPA) method, which is one of the matrix methods, was also analyzed. Then, the usefulness of each method in eco-design processes was evaluated and compared using the case studies of the cellular phone and vacuum cleaner systems. It was found that the SLCA and the ERPA methods provided different information but they complemented each other to some extent. The SLCA method generated more information on the inherent environmental characteristics of a product system so that it might be useful for new design/eco-innovation when developing a completely new product or method where environmental considerations play a major role from the beginning. On the other hand, the ERPA method gave more information on the potential for improving a product so that it could be effectively used in eco-redesign which intends to alleviate environmental impacts of an existing product or process.

  10. Identifying Industry-Specific Components of Product Liability Response System Using Delphi-AHP Method

    Directory of Open Access Journals (Sweden)

    Seo JunHyeok

    2016-12-01

    Full Text Available PL (product liability response system is an enterprise-wide system that prevents company’s financial loss due to PL-related accidents. Existing researches on PL response system are mainly focused on preventive and/or defense strategies for the companies. Also, it is obvious that each industry has their original characteristics related on PL issues. It means industry-specific characteristics should be considered to adopt PL response strategies. Thus, this paper aims to discuss industry-specific PL response system and their components. Based on prior researches, we tried to reveal the possibility of its application to manufacturing companies of existing PL response strategies using Delphi method with PL experts. Based on first round results, we tried to classify existing PL strategies of manufacturing companies into several categories. To validate our suggestion for essential components of PL response system, second round Delphi method are applied. Analytic hierarchy process (AHP technique will be applied to identify a prioritized list of each components and strategies. Existing PL response strategies could be categorized with six components – strategy, technology, investment, training, awareness, and organization. Among six components, Technology – it represents the technology needed for improving the safety of all products – is the most important components to prepare PL accidents. The limitation of this paper is on the size of survey and variety of examples. However, the future study will enhance the potential of the proposed method. Regardless of rich research efforts to identify PL response strategies, there is no effort to categorize these strategies and prioritized them. Well-coordinated and actionable PL response strategies and their priorities could help small-and-medium sized enterprise (SME to develop their own PL response system with their limited resources.

  11. Analysis of the genetic phylogeny of multifocal prostate cancer identifies multiple independent clonal expansions in neoplastic and morphologically normal prostate tissue.

    Science.gov (United States)

    Cooper, Colin S; Eeles, Rosalind; Wedge, David C; Van Loo, Peter; Gundem, Gunes; Alexandrov, Ludmil B; Kremeyer, Barbara; Butler, Adam; Lynch, Andrew G; Camacho, Niedzica; Massie, Charlie E; Kay, Jonathan; Luxton, Hayley J; Edwards, Sandra; Kote-Jarai, ZSofia; Dennis, Nening; Merson, Sue; Leongamornlert, Daniel; Zamora, Jorge; Corbishley, Cathy; Thomas, Sarah; Nik-Zainal, Serena; O'Meara, Sarah; Matthews, Lucy; Clark, Jeremy; Hurst, Rachel; Mithen, Richard; Bristow, Robert G; Boutros, Paul C; Fraser, Michael; Cooke, Susanna; Raine, Keiran; Jones, David; Menzies, Andrew; Stebbings, Lucy; Hinton, Jon; Teague, Jon; McLaren, Stuart; Mudie, Laura; Hardy, Claire; Anderson, Elizabeth; Joseph, Olivia; Goody, Victoria; Robinson, Ben; Maddison, Mark; Gamble, Stephen; Greenman, Christopher; Berney, Dan; Hazell, Steven; Livni, Naomi; Fisher, Cyril; Ogden, Christopher; Kumar, Pardeep; Thompson, Alan; Woodhouse, Christopher; Nicol, David; Mayer, Erik; Dudderidge, Tim; Shah, Nimish C; Gnanapragasam, Vincent; Voet, Thierry; Campbell, Peter; Futreal, Andrew; Easton, Douglas; Warren, Anne Y; Foster, Christopher S; Stratton, Michael R; Whitaker, Hayley C; McDermott, Ultan; Brewer, Daniel S; Neal, David E

    2015-04-01

    Genome-wide DNA sequencing was used to decrypt the phylogeny of multiple samples from distinct areas of cancer and morphologically normal tissue taken from the prostates of three men. Mutations were present at high levels in morphologically normal tissue distant from the cancer, reflecting clonal expansions, and the underlying mutational processes at work in morphologically normal tissue were also at work in cancer. Our observations demonstrate the existence of ongoing abnormal mutational processes, consistent with field effects, underlying carcinogenesis. This mechanism gives rise to extensive branching evolution and cancer clone mixing, as exemplified by the coexistence of multiple cancer lineages harboring distinct ERG fusions within a single cancer nodule. Subsets of mutations were shared either by morphologically normal and malignant tissues or between different ERG lineages, indicating earlier or separate clonal cell expansions. Our observations inform on the origin of multifocal disease and have implications for prostate cancer therapy in individual cases.

  12. Integrated systems approach identifies risk regulatory pathways and key regulators in coronary artery disease.

    Science.gov (United States)

    Zhang, Yan; Liu, Dianming; Wang, Lihong; Wang, Shuyuan; Yu, Xuexin; Dai, Enyu; Liu, Xinyi; Luo, Shanshun; Jiang, Wei

    2015-12-01

    Coronary artery disease (CAD) is the most common type of heart disease. However, the molecular mechanisms of CAD remain elusive. Regulatory pathways are known to play crucial roles in many pathogenic processes. Thus, inferring risk regulatory pathways is an important step toward elucidating the mechanisms underlying CAD. With advances in high-throughput data, we developed an integrated systems approach to identify CAD risk regulatory pathways and key regulators. Firstly, a CAD-related core subnetwork was identified from a curated transcription factor (TF) and microRNA (miRNA) regulatory network based on a random walk algorithm. Secondly, candidate risk regulatory pathways were extracted from the subnetwork by applying a breadth-first search (BFS) algorithm. Then, risk regulatory pathways were prioritized based on multiple CAD-associated data sources. Finally, we also proposed a new measure to prioritize upstream regulators. We inferred that phosphatase and tensin homolog (PTEN) may be a key regulator in the dysregulation of risk regulatory pathways. This study takes a closer step than the identification of disease subnetworks or modules. From the risk regulatory pathways, we could understand the flow of regulatory information in the initiation and progression of the disease. Our approach helps to uncover its potential etiology. We developed an integrated systems approach to identify risk regulatory pathways. We proposed a new measure to prioritize the key regulators in CAD. PTEN may be a key regulator in dysregulation of the risk regulatory pathways.

  13. Biomarkers of systemic lupus erythematosus identified using mass spectrometry-based proteomics: a systematic review.

    Science.gov (United States)

    Nicolaou, Orthodoxia; Kousios, Andreas; Hadjisavvas, Andreas; Lauwerys, Bernard; Sokratous, Kleitos; Kyriacou, Kyriacos

    2017-05-01

    Advances in mass spectrometry technologies have created new opportunities for discovering novel protein biomarkers in systemic lupus erythematosus (SLE). We performed a systematic review of published reports on proteomic biomarkers identified in SLE patients using mass spectrometry-based proteomics and highlight their potential disease association and clinical utility. Two electronic databases, MEDLINE and EMBASE, were systematically searched up to July 2015. The methodological quality of studies included in the review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Twenty-five studies were included in the review, identifying 241 SLE candidate proteomic biomarkers related to various aspects of the disease including disease diagnosis and activity or pinpointing specific organ involvement. Furthermore, 13 of the 25 studies validated their results for a selected number of biomarkers in an independent cohort, resulting in the validation of 28 candidate biomarkers. It is noteworthy that 11 candidate biomarkers were identified in more than one study. A significant number of potential proteomic biomarkers that are related to a number of aspects of SLE have been identified using mass spectrometry proteomic approaches. However, further studies are required to assess the utility of these biomarkers in routine clinical practice. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  14. Identifying Ant-Mirid Spatial Interactions to Improve Biological Control in Cacao-Based Agroforestry System.

    Science.gov (United States)

    Bagny Beilhe, Leïla; Piou, Cyril; Tadu, Zéphirin; Babin, Régis

    2018-06-06

    The use of ants for biological control of insect pests was the first reported case of conservation biological control. Direct and indirect community interactions between ants and pests lead to differential spatial pattern. We investigated spatial interactions between mirids, the major cocoa pest in West Africa and numerically dominant ant species, using bivariate point pattern analysis to identify potential biological control agents. We assume that potential biological control agents should display negative spatial interactions with mirids considering their niche overlap. The mirid/ant data were collected in complex cacao-based agroforestry systems sampled in three agroecological areas over a forest-savannah gradient in Cameroon. Three species, Crematogaster striatula Emery (Hymenoptera: Formicidae), Crematogaster clariventris Mayr (Hymenoptera: Formicidae), and Oecophylla longinoda Latreille (Hymenoptera: Formicidae) with high predator and aggressive behaviors were identified as dominant and showed negative spatial relationships with mirids. The weaver ant, O. longinoda was identified as the only potential biological control agent, considering its ubiquity in the plots, the similarity in niche requirements, and the spatial segregation with mirids resulting probably from exclusion mechanisms. Combining bivariate point pattern analysis to good knowledge of insect ecology was an effective method to identify a potentially good biological control agent.

  15. An Automated Self-Learning Quantification System to Identify Visible Areas in Capsule Endoscopy Images.

    Science.gov (United States)

    Hashimoto, Shinichi; Ogihara, Hiroyuki; Suenaga, Masato; Fujita, Yusuke; Terai, Shuji; Hamamoto, Yoshihiko; Sakaida, Isao

    2017-08-01

    Visibility in capsule endoscopic images is presently evaluated through intermittent analysis of frames selected by a physician. It is thus subjective and not quantitative. A method to automatically quantify the visibility on capsule endoscopic images has not been reported. Generally, when designing automated image recognition programs, physicians must provide a training image; this process is called supervised learning. We aimed to develop a novel automated self-learning quantification system to identify visible areas on capsule endoscopic images. The technique was developed using 200 capsule endoscopic images retrospectively selected from each of three patients. The rate of detection of visible areas on capsule endoscopic images between a supervised learning program, using training images labeled by a physician, and our novel automated self-learning program, using unlabeled training images without intervention by a physician, was compared. The rate of detection of visible areas was equivalent for the supervised learning program and for our automatic self-learning program. The visible areas automatically identified by self-learning program correlated to the areas identified by an experienced physician. We developed a novel self-learning automated program to identify visible areas in capsule endoscopic images.

  16. The application of Fourier transform infrared microspectroscopy for the study of diseased central nervous system tissue.

    Science.gov (United States)

    Caine, Sally; Heraud, Philip; Tobin, Mark J; McNaughton, Donald; Bernard, Claude C A

    2012-02-15

    In the last two decades the field of infrared spectroscopy has seen enormous advances in both instrumentation and the development of bioinformatic methods for spectral analysis, allowing the examination of a large variety of healthy and diseased samples, including biological fluids, isolated cells, whole tissues, and tissue sections. The non-destructive nature of the technique, together with the ability to directly probe biochemical changes without the addition of stains or contrast agents, enables a range of complementary analyses. This review focuses on the application of Fourier transform infrared (FTIR) microspectroscopy to analyse central nervous system tissues, with the aim of understanding the biochemical and structural changes associated with neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, transmissible spongiform encephalopathies, multiple sclerosis, as well as brain tumours. Modern biospectroscopic methods that combine FTIR microspectroscopy with bioinformatic analysis constitute a powerful new methodology that can discriminate pathology from normal healthy tissue in a rapid, unbiased fashion, with high sensitivity and specificity. Notably, the ability to detect protein secondary structural changes associated with Alzheimer's plaques, neurons in Parkinson's disease, and in some spectra from meningioma, as well as in the animal models of Alzheimer's disease, transmissible spongiform encephalopathies, and multiple sclerosis, illustrates the power of this technology. The capacity to offer insight into the biochemical and structural changes underpinning aetio-pathogenesis of diseases in tissues provides both a platform to investigate early pathologies occurring in a variety of experimentally induced and naturally occurring central nervous system diseases, and the potential to evaluate new therapeutic approaches. Copyright © 2011 Elsevier Inc. All rights reserved.

  17. Evaluation of an automated connective tissue disease screening assay in Korean patients with systemic rheumatic diseases.

    Directory of Open Access Journals (Sweden)

    Seri Jeong

    Full Text Available This study aimed to evaluate the diagnostic utilities of the automated connective tissues disease screening assay, CTD screen, in patients with systemic rheumatic diseases. A total of 1093 serum samples were assayed using CTD screen and indirect immunofluorescent (IIF methods. Among them, 162 were diagnosed with systemic rheumatic disease, including rheumatoid arthritis (RA, systemic lupus erythematosus (SLE, and mixed connective tissue disease (MCT. The remaining 931 with non-systemic rheumatic disease were assigned to the control group. The median ratios of CTD screen tests were significantly higher in the systemic rheumatic disease group than in the control group. The positive likelihood ratios of the CTD screen were higher than those of IIF in patients with total rheumatic diseases (4.1 vs. 1.6, including SLE (24.3 vs. 10.7. The areas under the receiver operating characteristic curves (ROC-AUCs of the CTD screen for discriminating total rheumatic diseases, RA, SLE, and MCT from controls were 0.68, 0.56, 0.92 and 0.80, respectively. The ROC-AUCs of the combinations with IIF were significantly higher in patients with total rheumatic diseases (0.72 and MCT (0.85 than in those of the CTD screen alone. Multivariate analysis indicated that both the CTD screen and IIF were independent variables for predicting systemic rheumatic disease. CTD screen alone and in combination with IIF were a valuable diagnostic tool for predicting systemic rheumatic diseases, particularly for SLE.

  18. Evaluation of an automated connective tissue disease screening assay in Korean patients with systemic rheumatic diseases.

    Science.gov (United States)

    Jeong, Seri; Yang, Heeyoung; Hwang, Hyunyong

    2017-01-01

    This study aimed to evaluate the diagnostic utilities of the automated connective tissues disease screening assay, CTD screen, in patients with systemic rheumatic diseases. A total of 1093 serum samples were assayed using CTD screen and indirect immunofluorescent (IIF) methods. Among them, 162 were diagnosed with systemic rheumatic disease, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and mixed connective tissue disease (MCT). The remaining 931 with non-systemic rheumatic disease were assigned to the control group. The median ratios of CTD screen tests were significantly higher in the systemic rheumatic disease group than in the control group. The positive likelihood ratios of the CTD screen were higher than those of IIF in patients with total rheumatic diseases (4.1 vs. 1.6), including SLE (24.3 vs. 10.7). The areas under the receiver operating characteristic curves (ROC-AUCs) of the CTD screen for discriminating total rheumatic diseases, RA, SLE, and MCT from controls were 0.68, 0.56, 0.92 and 0.80, respectively. The ROC-AUCs of the combinations with IIF were significantly higher in patients with total rheumatic diseases (0.72) and MCT (0.85) than in those of the CTD screen alone. Multivariate analysis indicated that both the CTD screen and IIF were independent variables for predicting systemic rheumatic disease. CTD screen alone and in combination with IIF were a valuable diagnostic tool for predicting systemic rheumatic diseases, particularly for SLE.

  19. [A new approach to clinical and laboratory diagnosis of systemic and local soft tissue infections].

    Science.gov (United States)

    Barkhatova, N A

    2009-01-01

    Dynamic measurements of blood TNF-a, IL-IRA, CRP, oligopeptide, and lactoferrin levels in patients with systemic and local soft tissue infections revealed direct correlation between them which allowed to use these indicators for the diagnosis of systemic infections. Results of clinical and laboratory analyses provided a basis for distinguishing short-term systemic inflammatory response syndrome and sepsis and developing relevant diagnostic criteria. Sepsis combined with systemic inflammatory response syndrome persisting for more than 72 hours after the onset of adequate therapy was characterized by CRP levels > 30 mg/l, oligopeptides > 0.34 U, lactoferrin > 1900 ng/ml, TNF-a > 6 pg/ml, ILL-IRA systemic inflammatory response syndrome for less than 72 hours had lower TNF-a, CRP, oligopeptide, and lactoferrin levels with IL-IRA > 1500 pg/ml. This new approach to early diagnosis of systemic infections makes it possible to optimize their treatment and thereby enhance its efficiency.

  20. The Immune System in Tissue Environments Regaining Homeostasis after Injury: Is “Inflammation” Always Inflammation?

    OpenAIRE

    Kulkarni, Onkar P.; Lichtnekert, Julia; Anders, Hans-Joachim; Mulay, Shrikant R.

    2016-01-01

    Inflammation is a response to infections or tissue injuries. Inflammation was once defined by clinical signs, later by the presence of leukocytes, and nowadays by expression of “proinflammatory” cytokines and chemokines. But leukocytes and cytokines often have rather anti-inflammatory, proregenerative, and homeostatic effects. Is there a need to redefine “inflammation”? In this review, we discuss the functions of “inflammatory” mediators/regulators of the innate immune system that determine t...

  1. Three cases of systemic amyloidosis successfully diagnosed by subcutaneous fat tissue biopsy of the hip

    Directory of Open Access Journals (Sweden)

    Arahata M

    2016-08-01

    Full Text Available Masahisa Arahata,1 Shigeru Shimadoi,1 Satosi Yamatani,1 Shin-ichi Hayashi,2 Shigeharu Miwa,2 Hidesaku Asakura,3 Shinji Nakao4 1Department of Internal Medicine, Nanto Municipal Hospital, Nanto, 2Department of Diagnostic Pathology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, 3Department of Internal Medicine (III, 4Department of Cellular Transplantation Biology, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan Abstract: Fine-needle aspiration biopsy of the abdominal fat pad is considered to be a minimally invasive procedure for diagnosing systemic amyloidosis. However, this procedure is sometimes difficult and can be dangerous for elderly patients whose abdominal fat layer is thin because of malnutrition. In such cases, alternative diagnostic methods are required. We report three elderly patients with heart failure complicated by malnutrition. In all cases, electrocardiogram showed low voltage in the limb leads and a pseudoinfarct pattern in the chest leads, and echocardiography showed left ventricular wall thickening with granular sparkling appearance. These patients were suspected of having amyloid cardiomyopathy but could not undergo myocardial biopsies because of their poor conditions. After failed attempts at biopsy of the abdominal fat pad or the other organs, subcutaneous fat tissue biopsy over the hip led to the diagnosis of systemic amyloidosis with cardiomyopathy. The resultant diagnosis guided us to choose the appropriate treatment for the patients. This article illustrates that subcutaneous fat tissue biopsy of the hip could be a useful procedure for diagnosing systemic amyloidosis in elderly patients, particularly when a fat tissue biopsy of the abdomen is associated with a high risk of complications because of malnutrition. Keywords: systemic amyloidosis, amyloid cardiomyopathy, fine-needle aspiration biopsy, subcutaneous fat tissue, hip

  2. [Comparison of two different real-time PCR systems in postmortem diagnosis of tuberculosis in paraffin-embedded tissues].

    Science.gov (United States)

    Yağmur, Gülhan; Albayrak, Nurhan; Daş, Taner; Yıldırım, Muzaffer; Ozgün, Ayşe; Büyük, Yalçın

    2014-10-01

    Tuberculosis (TB) is one of those infections with high morbidity and mortality in all around the world. Hundreds of people died from this disease without diagnosed or due to resistant strains in Turkey. Therefore, it is important to identify postmortem cases who have died from tuberculosis. Molecular methods have been widely used as well as conventional methods in the diagnosis of tuberculosis. The aim of this study was to compare the two different real-time polymerase chain reaction (Rt-PCR) system in the postmortem diagnosis of Mycobacterium tuberculosis infections in paraffin-embedded tissues. A total of 40 paraffin-embedded tissue samples [lung (n= 35), brain (n= 2), heart (n= 2), lymph node (n= 1)] in which histopathologic findings consistent with TB (necrotizing granulomatous inflammation, gelatinous caseous pneumonia, necrotic fibrous nodul) obtained from 37 autopsy cases (31 male, 6 female; age range: 25-85 yrs) were included in the study. Paraffin-embedded tissues were deparafinized with xylene and ethyl alcohol and then DNA isolation was done with QIAsymphony DSP Virus/Pathogen Midi kit in the QIAsymphony device. DNA amplification process was performed by Rt-PCR using the kit Artus® M. tuberculosis RG-PCR in the Rotor-Gene® Q device (Qiagen, Germany). Likewise, after deparafinization process, samples placed in the cartridge and isolation and Rt-PCR was performed by Xpert® MTB/RIF (Cepheid, USA) system, simultaneosly. Seventeen and 20 out of the 40 paraffin-embedded tissues yielded positive results with Qiagen and Xpert system, respectively. M.tuberculosis DNA was found positive in 13 (32.5%) and negative in 16 (40%) of the samples by both of the systems, exhibiting 72.5% (29/40) of concordance. On the other hand, seven (17.5%) samples that were positive with Xpert system yielded negative result with the Qiagen, while four (10%) samples that were positive with Qiagen yielded negative result with the Xpert system. Of the 20 positive cases detected with

  3. Unit cell-based computer-aided manufacturing system for tissue engineering

    International Nuclear Information System (INIS)

    Kang, Hyun-Wook; Park, Jeong Hun; Kang, Tae-Yun; Seol, Young-Joon; Cho, Dong-Woo

    2012-01-01

    Scaffolds play an important role in the regeneration of artificial tissues or organs. A scaffold is a porous structure with a micro-scale inner architecture in the range of several to several hundreds of micrometers. Therefore, computer-aided construction of scaffolds should provide sophisticated functionality for porous structure design and a tool path generation strategy that can achieve micro-scale architecture. In this study, a new unit cell-based computer-aided manufacturing (CAM) system was developed for the automated design and fabrication of a porous structure with micro-scale inner architecture that can be applied to composite tissue regeneration. The CAM system was developed by first defining a data structure for the computing process of a unit cell representing a single pore structure. Next, an algorithm and software were developed and applied to construct porous structures with a single or multiple pore design using solid freeform fabrication technology and a 3D tooth/spine computer-aided design model. We showed that this system is quite feasible for the design and fabrication of a scaffold for tissue engineering. (paper)

  4. Tissue Specificity of a Response of the Pro- and Antioxidative System After Resuscitation

    Directory of Open Access Journals (Sweden)

    A. G. Zhukova

    2005-01-01

    Full Text Available This investigation was undertaken to study the resistance of membrane structures and the level of the intracellular defense systems of the heart, brain, and liver in animals with active versus passive behavior in different periods (days 7 and 30 after resuscitation made 10 minutes following systemic circulatory arrest. All the animals in which systemic circulation had been stopped were survivors with the cession of neurological deficit. The activity of antioxidative defense enzymes, such as cata-lase and superoxide dismutase, in cardiac, cerebral, and hepatic tissues was assayed by spectrophotometry using the conventional methods. The level of stress-induced protein HSP70 was measured in the tissue cytosolic fraction by the Western blotting assay. The activity of Ca2+ transport in the myocardial sarcoplasmic reticulum was determined on an Orion EA 940 ionomer («Orion Research», USA having a Ca2+-selective electrode. The findings show a significant tissue specificity in different postresuscitative periods (days 7 and 30 and varying (protective to damaging cardiac, cerebral, and hepatic responses in active and passive animals to hypoxia.

  5. Unit cell-based computer-aided manufacturing system for tissue engineering.

    Science.gov (United States)

    Kang, Hyun-Wook; Park, Jeong Hun; Kang, Tae-Yun; Seol, Young-Joon; Cho, Dong-Woo

    2012-03-01

    Scaffolds play an important role in the regeneration of artificial tissues or organs. A scaffold is a porous structure with a micro-scale inner architecture in the range of several to several hundreds of micrometers. Therefore, computer-aided construction of scaffolds should provide sophisticated functionality for porous structure design and a tool path generation strategy that can achieve micro-scale architecture. In this study, a new unit cell-based computer-aided manufacturing (CAM) system was developed for the automated design and fabrication of a porous structure with micro-scale inner architecture that can be applied to composite tissue regeneration. The CAM system was developed by first defining a data structure for the computing process of a unit cell representing a single pore structure. Next, an algorithm and software were developed and applied to construct porous structures with a single or multiple pore design using solid freeform fabrication technology and a 3D tooth/spine computer-aided design model. We showed that this system is quite feasible for the design and fabrication of a scaffold for tissue engineering.

  6. A logic programming and statistical systems approach for tissue characterization in magnetic resonance imaging

    International Nuclear Information System (INIS)

    Levy, G.C.; Dudewicz, E.J.; Harner, T.J.

    1989-01-01

    The main research goal has been to evalute significant factors affecting the in vivo magnetic resonance imaging (MRI) parameters R 1 , T 2 , and 1 H density. This approach differs significantly from other such projects in that the experimental data analysis is being performed while concurrently developing automated, computer-aided analysis software for such MRI tissue parameters. In the experimental portion of the project, statistical analyses, and a heuristic minimum/maximum discriminant analysis algorithm have been explored. Both methods have been used to classify tissue types from 1.5 Tesla transaxial MR images of the human brain. The developing program, written in the logic programming language Prolog, similar in a number of ways to many existing expert systems now in use for other medical applications; inclusion of the underlying statistical data base and advanced statistical analyses is the main differentiating feature of the current approach. First results indicate promising classification accuracy of various brain tissues such as gray and white matter, as well as differentiation of different types of gray matter and white matter (e.g.: caudate-nucleus vs. thalamus, both representatives of gray matter; and, cortical white matter vs. internal capsule as representative of white matter). Taking all four tissue types together, the percentage of correct classifications ranges from 73 to 87%. (author)

  7. Automated MALDI Matrix Coating System for Multiple Tissue Samples for Imaging Mass Spectrometry

    Science.gov (United States)

    Mounfield, William P.; Garrett, Timothy J.

    2012-03-01

    Uniform matrix deposition on tissue samples for matrix-assisted laser desorption/ionization (MALDI) is key for reproducible analyte ion signals. Current methods often result in nonhomogenous matrix deposition, and take time and effort to produce acceptable ion signals. Here we describe a fully-automated method for matrix deposition using an enclosed spray chamber and spray nozzle for matrix solution delivery. A commercial air-atomizing spray nozzle was modified and combined with solenoid controlled valves and a Programmable Logic Controller (PLC) to control and deliver the matrix solution. A spray chamber was employed to contain the nozzle, sample, and atomized matrix solution stream, and to prevent any interference from outside conditions as well as allow complete control of the sample environment. A gravity cup was filled with MALDI matrix solutions, including DHB in chloroform/methanol (50:50) at concentrations up to 60 mg/mL. Various samples (including rat brain tissue sections) were prepared using two deposition methods (spray chamber, inkjet). A linear ion trap equipped with an intermediate-pressure MALDI source was used for analyses. Optical microscopic examination showed a uniform coating of matrix crystals across the sample. Overall, the mass spectral images gathered from tissues coated using the spray chamber system were of better quality and more reproducible than from tissue specimens prepared by the inkjet deposition method.

  8. Mitochondrial function and tissue vitality: bench-to-bedside real-time optical monitoring system

    Science.gov (United States)

    Mayevsky, Avraham; Walden, Raphael; Pewzner, Eliyahu; Deutsch, Assaf; Heldenberg, Eitan; Lavee, Jacob; Tager, Salis; Kachel, Erez; Raanani, Ehud; Preisman, Sergey; Glauber, Violete; Segal, Eran

    2011-06-01

    Background: The involvement of mitochondria in pathological states, such as neurodegenerative diseases, sepsis, stroke, and cancer, are well documented. Monitoring of nicotinamide adenine dinucleotide (NADH) fluorescence in vivo as an intracellular oxygen indicator was established in 1950 to 1970 by Britton Chance and collaborators. We use a multiparametric monitoring system enabling assessment of tissue vitality. In order to use this technology in clinical practice, the commercial developed device, the CritiView (CRV), is tested in animal models as well as in patients. Methods and Results: The new CRV enables the optical monitoring of four different parameters, representing the energy balance of various tissues in vivo. Mitochondrial NADH is measured by surface fluorometry/reflectometry. In addition, tissue microcirculatory blood flow, tissue reflectance and oxygenation are measured as well. The device is tested both in vitro and in vivo in a small animal model and in preliminary clinical trials in patients undergoing vascular or open heart surgery. In patients, the monitoring is started immediately after the insertion of a three-way Foley catheter (urine collection) to the patient and is stopped when the patient is discharged from the operating room. The results show that monitoring the urethral wall vitality provides information in correlation to the surgical procedure performed.

  9. IDENTIFYING BRAȘOV COUNTY’S TOURISTIC VISITORS’ PROFILE USING EUROPEAN TOURISM INDICATORS SYSTEM

    Directory of Open Access Journals (Sweden)

    Gheorghita Dinca

    2017-05-01

    Full Text Available The need for sustainable development of regions is a current topic that concern both local authorities and academic experts, as demonstrated by this paper through case study in Brașov County, one of Romania’s main tourist regions. This paper is based on a research project meant to develop an original testing technique of European Tourism Indicators System of Sustainable Destinations (ETIS for Brașov County. The paper presents the results of a market survey carried out on a sample of 1,119 visitors and meant to identify travel characteristics of tourists from

  10. Identifying elementary iterated systems through algorithmic inference: The Cantor set example

    Energy Technology Data Exchange (ETDEWEB)

    Apolloni, Bruno [Dipartimento di Scienze dell' Informazione, Universita degli Studi di Milano, Via Comelico 39/41, 20135 Milan (Italy)]. E-mail: apolloni@dsi.unimi.it; Bassis, Simone [Dipartimento di Scienze dell' Informazione, Universita degli Studi di Milano, Via Comelico 39/41, 20135 Milan (Italy)]. E-mail: bassis@dsi.unimi.it

    2006-10-15

    We come back to the old problem of fractal identification within the new framework of algorithmic Inference. The key points are: (i) to identify sufficient statistics to be put in connection with the unknown values of the fractal parameters, and (ii) to manage the timing of the iterated process through spatial statistics. We fill these tasks successfully with the Cantor sets. We are able to compute confidence intervals for both the scaling parameter {theta} and the iteration number n at which we are observing a set. We both check numerically the coverage of these intervals and delineate a general strategy for affording more complex iterated systems.

  11. Micro-precise spatiotemporal delivery system embedded in 3D printing for complex tissue regeneration.

    Science.gov (United States)

    Tarafder, Solaiman; Koch, Alia; Jun, Yena; Chou, Conrad; Awadallah, Mary R; Lee, Chang H

    2016-04-25

    Three dimensional (3D) printing has emerged as an efficient tool for tissue engineering and regenerative medicine, given its advantages for constructing custom-designed scaffolds with tunable microstructure/physical properties. Here we developed a micro-precise spatiotemporal delivery system embedded in 3D printed scaffolds. PLGA microspheres (μS) were encapsulated with growth factors (GFs) and then embedded inside PCL microfibers that constitute custom-designed 3D scaffolds. Given the substantial difference in the melting points between PLGA and PCL and their low heat conductivity, μS were able to maintain its original structure while protecting GF's bioactivities. Micro-precise spatial control of multiple GFs was achieved by interchanging dispensing cartridges during a single printing process. Spatially controlled delivery of GFs, with a prolonged release, guided formation of multi-tissue interfaces from bone marrow derived mesenchymal stem/progenitor cells (MSCs). To investigate efficacy of the micro-precise delivery system embedded in 3D printed scaffold, temporomandibular joint (TMJ) disc scaffolds were fabricated with micro-precise spatiotemporal delivery of CTGF and TGFβ3, mimicking native-like multiphase fibrocartilage. In vitro, TMJ disc scaffolds spatially embedded with CTGF/TGFβ3-μS resulted in formation of multiphase fibrocartilaginous tissues from MSCs. In vivo, TMJ disc perforation was performed in rabbits, followed by implantation of CTGF/TGFβ3-μS-embedded scaffolds. After 4 wks, CTGF/TGFβ3-μS embedded scaffolds significantly improved healing of the perforated TMJ disc as compared to the degenerated TMJ disc in the control group with scaffold embedded with empty μS. In addition, CTGF/TGFβ3-μS embedded scaffolds significantly prevented arthritic changes on TMJ condyles. In conclusion, our micro-precise spatiotemporal delivery system embedded in 3D printing may serve as an efficient tool to regenerate complex and inhomogeneous tissues.

  12. Eating energy-Identifying possibilities for reduced energy use in the future food supply system

    International Nuclear Information System (INIS)

    Wallgren, Christine; Hoejer, Mattias

    2009-01-01

    This paper explores the possibilities for reducing future energy use for eating to a sustainable level. A backcasting approach is used to generate an image of the future where energy use for eating is 60% lower in 2050 than in 2000. The currently known potential to reduce energy use in the food supply system for producing, transporting, storing, cooking and eating food is explored and described in terms of a number of distinct changes that are numbered consecutively and presented in both a quantitative and qualitative way. Sweden is used as the case and all data regarding energy use apply for Swedish conditions. An exercise like this illustrates the possible outcome of taking sustainability seriously. If sustainability is to be achieved, some images of the future are needed so that potential targets can be identified. This paper does not present forecasts, but illustrates the kind of changes needed in order to achieve sustainable energy use in the food system.

  13. Storing files in a parallel computing system using list-based index to identify replica files

    Science.gov (United States)

    Faibish, Sorin; Bent, John M.; Tzelnic, Percy; Zhang, Zhenhua; Grider, Gary

    2015-07-21

    Improved techniques are provided for storing files in a parallel computing system using a list-based index to identify file replicas. A file and at least one replica of the file are stored in one or more storage nodes of the parallel computing system. An index for the file comprises at least one list comprising a pointer to a storage location of the file and a storage location of the at least one replica of the file. The file comprises one or more of a complete file and one or more sub-files. The index may also comprise a checksum value for one or more of the file and the replica(s) of the file. The checksum value can be evaluated to validate the file and/or the file replica(s). A query can be processed using the list.

  14. BLAT2DOLite: An Online System for Identifying Significant Relationships between Genetic Sequences and Diseases.

    Directory of Open Access Journals (Sweden)

    Liang Cheng

    Full Text Available The significantly related diseases of sequences could play an important role in understanding the functions of these sequences. In this paper, we introduced BLAT2DOLite, an online system for annotating human genes and diseases and identifying the significant relationships between sequences and diseases. Currently, BLAT2DOLite integrates Entrez Gene database and Disease Ontology Lite (DOLite, which contain loci of gene and relationships between genes and diseases. It utilizes hypergeometric test to calculate P-values between genes and diseases of DOLite. The system can be accessed from: http://123.59.132.21:8080/BLAT2DOLite. The corresponding web service is described in: http://123.59.132.21:8080/BLAT2DOLite/BLAT2DOLiteIDMappingPort?wsdl.

  15. Identifying Opportunities for Decision Support Systems in Support of Regional Resource Use Planning: An Approach Through Soft Systems Methodology.

    Science.gov (United States)

    Zhu; Dale

    2000-10-01

    / Regional resource use planning relies on key regional stakeholder groups using and having equitable access to appropriate social, economic, and environmental information and assessment tools. Decision support systems (DSS) can improve stakeholder access to such information and analysis tools. Regional resource use planning, however, is a complex process involving multiple issues, multiple assessment criteria, multiple stakeholders, and multiple values. There is a need for an approach to DSS development that can assist in understanding and modeling complex problem situations in regional resource use so that areas where DSSs could provide effective support can be identified, and the user requirements can be well established. This paper presents an approach based on the soft systems methodology for identifying DSS opportunities for regional resource use planning, taking the Central Highlands Region of Queensland, Australia, as a case study.

  16. The THUNDERBEAT system for tissue dissection and vascular control in laparoscopic splenectomy.

    Science.gov (United States)

    Ceccanti, Silvia; Falconi, Ilaria; Frediani, Simone; Boscarelli, Alessandro; Catani, Marco; Cozzi, Denis A

    2017-08-01

    The advent of new energy sources for hemostasis has greatly facilitated advanced laparoscopic procedures. We describe a straightforward technique of laparoscopic splenectomy (LS) accomplished using the THUNDERBEAT™ system (TS) (Olympus Medical Systems Corp., Tokyo, Japan) as the sole means of tissue dissection and hemostasis in two patients aged 19 and 6 years, respectively. The specimens were removed intact via a Pfannenstiel incision. Total operative time was 165 and 150 min, and length of hospital stay was three and 4 d, respectively. The TS is an appealing and reliable alternative to currently available energy devices, allowing fast dissection and secure hemostasis during laparoscopic splenectomy.

  17. An integrated system for identifying the hidden assassins in traditional medicines containing aristolochic acids

    Science.gov (United States)

    Wu, Lan; Sun, Wei; Wang, Bo; Zhao, Haiyu; Li, Yaoli; Cai, Shaoqing; Xiang, Li; Zhu, Yingjie; Yao, Hui; Song, Jingyuan; Cheng, Yung-Chi; Chen, Shilin

    2015-08-01

    Traditional herbal medicines adulterated and contaminated with plant materials from the Aristolochiaceae family, which contain aristolochic acids (AAs), cause aristolochic acid nephropathy. Approximately 256 traditional Chinese patent medicines, containing Aristolochiaceous materials, are still being sold in Chinese markets today. In order to protect consumers from health risks due to AAs, the hidden assassins, efficient methods to differentiate Aristolochiaceous herbs from their putative substitutes need to be established. In this study, 158 Aristolochiaceous samples representing 46 species and four genera as well as 131 non-Aristolochiaceous samples representing 33 species, 20 genera and 12 families were analyzed using DNA barcodes based on the ITS2 and psbA-trnH sequences. Aristolochiaceous materials and their non-Aristolochiaceous substitutes were successfully identified using BLAST1, the nearest distance method and the neighbor-joining (NJ) tree. In addition, based on sequence information of ITS2, we developed a Real-Time PCR assay which successfully identified herbal material from the Aristolochiaceae family. Using Ultra High Performance Liquid Chromatography-Mass Spectrometer (UHPLC-HR-MS), we demonstrated that most representatives from the Aristolochiaceae family contain toxic AAs. Therefore, integrated DNA barcodes, Real-Time PCR assays using TaqMan probes and UHPLC-HR-MS system provides an efficient and reliable authentication system to protect consumers from health risks due to the hidden assassins (AAs).

  18. An artificial neural network system to identify alleles in reference electropherograms.

    Science.gov (United States)

    Taylor, Duncan; Harrison, Ash; Powers, David

    2017-09-01

    Electropherograms are produced in great numbers in forensic DNA laboratories as part of everyday criminal casework. Before the results of these electropherograms can be used they must be scrutinised by analysts to determine what the identified data tells them about the underlying DNA sequences and what is purely an artefact of the DNA profiling process. This process of interpreting the electropherograms can be time consuming and is prone to subjective differences between analysts. Recently it was demonstrated that artificial neural networks could be used to classify information within an electropherogram as allelic (i.e. representative of a DNA fragment present in the DNA extract) or as one of several different categories of artefactual fluorescence that arise as a result of generating an electropherogram. We extend that work here to demonstrate a series of algorithms and artificial neural networks that can be used to identify peaks on an electropherogram and classify them. We demonstrate the functioning of the system on several profiles and compare the results to a leading commercial DNA profile reading system. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Rapid, computer vision-enabled murine screening system identifies neuropharmacological potential of two new mechanisms

    Directory of Open Access Journals (Sweden)

    Steven L Roberds

    2011-09-01

    Full Text Available The lack of predictive in vitro models for behavioral phenotypes impedes rapid advancement in neuropharmacology and psychopharmacology. In vivo behavioral assays are more predictive of activity in human disorders, but such assays are often highly resource-intensive. Here we describe the successful application of a computer vision-enabled system to identify potential neuropharmacological activity of two new mechanisms. The analytical system was trained using multiple drugs that are used clinically to treat depression, schizophrenia, anxiety, and other psychiatric or behavioral disorders. During blinded testing the PDE10 inhibitor TP-10 produced a signature of activity suggesting potential antipsychotic activity. This finding is consistent with TP-10’s activity in multiple rodent models that is similar to that of clinically used antipsychotic drugs. The CK1ε inhibitor PF-670462 produced a signature consistent with anxiolytic activity and, at the highest dose tested, behavioral effects similar to that of opiate analgesics. Neither TP-10 nor PF-670462 was included in the training set. Thus, computer vision-based behavioral analysis can facilitate drug discovery by identifying neuropharmacological effects of compounds acting through new mechanisms.

  20. Drug-Loadable Calcium Alginate Hydrogel System for Use in Oral Bone Tissue Repair.

    Science.gov (United States)

    Chen, Luyuan; Shen, Renze; Komasa, Satoshi; Xue, Yanxiang; Jin, Bingyu; Hou, Yepo; Okazaki, Joji; Gao, Jie

    2017-05-06

    This study developed a drug-loadable hydrogel system with high plasticity and favorable biological properties to enhance oral bone tissue regeneration. Hydrogels of different calcium alginate concentrations were prepared. Their swelling ratio, degradation time, and bovine serum albumin (BSA) release rate were measured. Human periodontal ligament cells (hPDLCs) and bone marrow stromal cells (BMSCs) were cultured with both calcium alginate hydrogels and polylactic acid (PLA), and then we examined the proliferation of cells. Inflammatory-related factor gene expressions of hPDLCs and osteogenesis-related gene expressions of BMSCs were observed. Materials were implanted into the subcutaneous tissue of rabbits to determine the biosecurity properties of the materials. The materials were also implanted in mandibular bone defects and then scanned using micro-CT. The calcium alginate hydrogels caused less inflammation than the PLA. The number of mineralized nodules and the expression of osteoblast-related genes were significantly higher in the hydrogel group compared with the control group. When the materials were implanted in subcutaneous tissue, materials showed favorable biocompatibility. The calcium alginate hydrogels had superior osteoinductive bone ability to the PLA. The drug-loadable calcium alginate hydrogel system is a potential bone defect reparation material for clinical dental application.

  1. ALERT. Adverse late effects of cancer treatment. Vol. 2. Normal tissue specific sites and systems

    Energy Technology Data Exchange (ETDEWEB)

    Rubin, Philip; Constine, Louis S. [Univ. Rochester Medical Center, NY (United States). Dept. of Radiation Oncology; Marks, Lawrence B. (ed.) [Univ. North Carolina and Lineberger, Comprehensive Cancer Center, Chapel Hill, NC (United States). Dept. of Radiation Oncology

    2014-09-01

    Comprehensively documents potential late effects in all the normal tissue sites in the human body. Considers in detail the detection, diagnosis, management and prevention of effects and discusses prognostic outcomes. Clearly presents radiation risk factors and interactions with chemotherapy effects. Provides the most current evidence-based medicine for cancer care survivorship guidelines. The literature on the late effects of cancer treatment is widely scattered in different journals since all major organ systems are affected and management is based on a variety of medical and surgical treatments. The aim of ALERT - Adverse Late Effects of Cancer Treatment is to offer a coherent multidisciplinary approach to the care of cancer survivors. The central paradigm is that cytotoxic multimodal therapy results in a perpetual cascade of events that affects each major organ system differently and is expressed continually over time. Essentially, radiation and chemotherapy are intense biologic modifiers that allow for cancer cure and cancer survivorship but accelerate senescence of normal tissues and increase the incidence of age-related diseases and second malignant tumors. Volume 2 of this two-volume work comprehensively documents potential late effects in all the normal tissue anatomic sites in the human body. The detection, diagnosis, management and prevention of effects are all considered in detail, and prognostic outcomes are discussed. Radiation risk factors and interactions with chemotherapy effects are clearly presented. The text is accompanied by numerous supportive illustrations and tables.

  2. Identifying and Visualizing Functional PAM Diversity across CRISPR-Cas Systems.

    Science.gov (United States)

    Leenay, Ryan T; Maksimchuk, Kenneth R; Slotkowski, Rebecca A; Agrawal, Roma N; Gomaa, Ahmed A; Briner, Alexandra E; Barrangou, Rodolphe; Beisel, Chase L

    2016-04-07

    CRISPR-Cas adaptive immune systems in prokaryotes boast a diversity of protein families and mechanisms of action, where most systems rely on protospacer-adjacent motifs (PAMs) for DNA target recognition. Here, we developed an in vivo, positive, and tunable screen termed PAM-SCANR (PAM screen achieved by NOT-gate repression) to elucidate functional PAMs as well as an interactive visualization scheme termed the PAM wheel to convey individual PAM sequences and their activities. PAM-SCANR and the PAM wheel identified known functional PAMs while revealing complex sequence-activity landscapes for the Bacillus halodurans I-C (Cascade), Escherichia coli I-E (Cascade), Streptococcus thermophilus II-A CRISPR1 (Cas9), and Francisella novicida V-A (Cpf1) systems. The PAM wheel was also readily applicable to existing high-throughput screens and garnered insights into SpyCas9 and SauCas9 PAM diversity. These tools offer powerful means of elucidating and visualizing functional PAMs toward accelerating our ability to understand and exploit the multitude of CRISPR-Cas systems in nature. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Worldwide Lineages of Clinical Pneumococci in a Japanese Teaching Hospital Identified by DiversiLab System.

    Science.gov (United States)

    Kashiwaya, Kiyoshi; Saga, Tomoo; Ishii, Yoshikazu; Sakata, Ryuji; Iwata, Morihiro; Yoshizawa, Sadako; Chang, Bin; Ohnishi, Makoto; Tateda, Kazuhiro

    2016-06-01

    Pneumococcal Molecular Epidemiology Network (PMEN) clones are representatives of worldwide-spreading pathogens. DiversiLab system, a repetitive PCR system, has been proposed as a less labor-and time-intensive genotyping platform alternative to conventional methods. However, the utility and analysis parameters of DiversiLab for identifying worldwide lineages was not established. To evaluate and optimize the performance of DiversiLab for identifying worldwide pneumococcal lineages, we examined 245 consecutive isolates of clinical Streptococcus pneumoniae from all age-group patients at a teaching hospital in Japan. The capsular swelling reaction of all isolates yielded 24 different serotypes. Intensive visual observation (VO) of DiversiLab band pattern difference divided all isolates into 73 clusters. Multilocus sequence typing (MLST) of representative 73 isolates from each VO cluster yielded 51 different STs. Among them, PMEN-related lineages accounted for 63% (46/73). Although the serotype of PMEN-related isolates was identical to that of the original PMEN clone in 70% (32/46), CC156-related PMEN lineages, namely Greece(6B)-22 and Colombia(23F)-26, harbored various capsular types discordant to the original PMEN clones. Regarding automated analysis, genotyping by extended Jaccard (XJ) with a 75% similarity index cutoff (SIC) showed the highest correlation with serotyping (adjusted Rand's coefficient, 0.528). Elevating the SIC for XJ to 85% increased the discriminatory power sufficient for distinguishing two major PMEN-related isolates of Taiwan(19F)-14 and Netherlands(3)-31. These results demonstrated a potential utility of DiversiLab for identifying worldwide lineage of pneumococcus. An optimized parameters of automated analysis should be useful especially for comparison for reference strains by "identification" function of DiversiLab. Copyright © 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd

  4. Application of 42K to Arabidopsis tissues using real-time radioisotope imaging system (RRIS)

    International Nuclear Information System (INIS)

    Aramaki, Toshinori; Sugita, Ryohei; Hirose, Atsushi; Kobayashi, Natsuko I.; Tanoi, Keitaro; Nakanishi, Tomoko M.

    2015-01-01

    We performed an imaging analysis of 42 K in Arabidopsis using real-time radioisotope imaging system (RRIS). First, we purified 42 K from an 42 Ar - 42 K generator. And then, we characterized RRIS performance by quantitatively determining 42 K using standard series. As a result, the dynamic range for 42 K was determined to be at least three orders of magnitude. Next, we evaluated the level of self-absorption in Arabidopsis organs by comparing the signal intensity detected using RRIS and the actual radioactivity detected by a gamma-counting method. There was no significant difference in detection efficiency between the thick bolt(stem) tissue and the thin leaf tissue. The reason for scarce self-absorption could be related to the relatively strong β ray emissions that have a maximum energy of 3525.4 keV. (author)

  5. Establishment of an in vitro system representing the chicken gut-associated lymphoid tissue.

    Science.gov (United States)

    Alitheen, Noorjahan Banu; McClure, Susan Jane; Yeap, Swee Keong; Kristeen-Teo, Ye Wen; Tan, Sheau Wei; McCullagh, Peter

    2012-01-01

    The bursa of Fabricius is critical for B cell development and differentiation in chick embryos. This study describes the production in vitro, from dissociated cell suspensions, of cellular agglomerates with functional similarities to the chicken bursa. Co-cultivation of epithelial and lymphoid cells obtained from embryos at the appropriate developmental stage regularly led to agglomerate formation within 48 hours. These agglomerates resembled bursal tissue in having lymphoid clusters overlaid by well organized epithelium. Whereas lymphocytes within agglomerates were predominantly Bu-1a(+), a majority of those emigrating onto the supporting membrane were Bu-1a(-) and IgM(+). Both agglomerates and emigrant cells expressed activation-induced deaminase with levels increasing after 24 hours. Emigrating cells were actively proliferating at a rate in excess of both the starting cell population and the population of cells remaining in agglomerates. The potential usefulness of this system for investigating the response of bursal tissue to avian Newcastle disease virus (strain AF2240) was examined.

  6. Tissue engineering

    CERN Document Server

    Fisher, John P; Bronzino, Joseph D

    2007-01-01

    Increasingly viewed as the future of medicine, the field of tissue engineering is still in its infancy. As evidenced in both the scientific and popular press, there exists considerable excitement surrounding the strategy of regenerative medicine. To achieve its highest potential, a series of technological advances must be made. Putting the numerous breakthroughs made in this field into a broad context, Tissue Engineering disseminates current thinking on the development of engineered tissues. Divided into three sections, the book covers the fundamentals of tissue engineering, enabling technologies, and tissue engineering applications. It examines the properties of stem cells, primary cells, growth factors, and extracellular matrix as well as their impact on the development of tissue engineered devices. Contributions focus on those strategies typically incorporated into tissue engineered devices or utilized in their development, including scaffolds, nanocomposites, bioreactors, drug delivery systems, and gene t...

  7. A molecular systems approach to modelling human skin pigmentation: identifying underlying pathways and critical components.

    Science.gov (United States)

    Raghunath, Arathi; Sambarey, Awanti; Sharma, Neha; Mahadevan, Usha; Chandra, Nagasuma

    2015-04-29

    Ultraviolet radiations (UV) serve as an environmental stress for human skin, and result in melanogenesis, with the pigment melanin having protective effects against UV induced damage. This involves a dynamic and complex regulation of various biological processes that results in the expression of melanin in the outer most layers of the epidermis, where it can exert its protective effect. A comprehensive understanding of the underlying cross talk among different signalling molecules and cell types is only possible through a systems perspective. Increasing incidences of both melanoma and non-melanoma skin cancers necessitate the need to better comprehend UV mediated effects on skin pigmentation at a systems level, so as to ultimately evolve knowledge-based strategies for efficient protection and prevention of skin diseases. A network model for UV-mediated skin pigmentation in the epidermis was constructed and subjected to shortest path analysis. Virtual knock-outs were carried out to identify essential signalling components. We describe a network model for UV-mediated skin pigmentation in the epidermis. The model consists of 265 components (nodes) and 429 directed interactions among them, capturing the manner in which one component influences the other and channels information. Through shortest path analysis, we identify novel signalling pathways relevant to pigmentation. Virtual knock-outs or perturbations of specific nodes in the network have led to the identification of alternate modes of signalling as well as enabled determining essential nodes in the process. The model presented provides a comprehensive picture of UV mediated signalling manifesting in human skin pigmentation. A systems perspective helps provide a holistic purview of interconnections and complexity in the processes leading to pigmentation. The model described here is extensive yet amenable to expansion as new data is gathered. Through this study, we provide a list of important proteins essential

  8. A Genome-Wide mQTL Analysis in Human Adipose Tissue Identifies Genetic Variants Associated with DNA Methylation, Gene Expression and Metabolic Traits

    DEFF Research Database (Denmark)

    Volkov, Petr; Olsson, Anders H; Gillberg, Linn

    2016-01-01

    Little is known about the extent to which interactions between genetics and epigenetics may affect the risk of complex metabolic diseases and/or their intermediary phenotypes. We performed a genome-wide DNA methylation quantitative trait locus (mQTL) analysis in human adipose tissue of 119 men, w...... and epigenetic variation in both cis and trans positions influencing gene expression in adipose tissue and in vivo (dys)metabolic traits associated with the development of obesity and diabetes.......Little is known about the extent to which interactions between genetics and epigenetics may affect the risk of complex metabolic diseases and/or their intermediary phenotypes. We performed a genome-wide DNA methylation quantitative trait locus (mQTL) analysis in human adipose tissue of 119 men......, where 592,794 single nucleotide polymorphisms (SNPs) were related to DNA methylation of 477,891 CpG sites, covering 99% of RefSeq genes. SNPs in significant mQTLs were further related to gene expression in adipose tissue and obesity related traits. We found 101,911 SNP-CpG pairs (mQTLs) in cis and 5...

  9. A Systems Genetic Approach to Identify Low Dose Radiation-Induced Lymphoma Susceptibility/DOE2013FinalReport

    Energy Technology Data Exchange (ETDEWEB)

    Balmain, Allan [University of California, San Francisco; Song, Ihn Young [University of California, San Francisco

    2013-05-15

    The ultimate goal of this project is to identify the combinations of genetic variants that confer an individual's susceptibility to the effects of low dose (0.1 Gy) gamma-radiation, in particular with regard to tumor development. In contrast to the known effects of high dose radiation in cancer induction, the responses to low dose radiation (defined as 0.1 Gy or less) are much less well understood, and have been proposed to involve a protective anti-tumor effect in some in vivo scientific models. These conflicting results confound attempts to develop predictive models of the risk of exposure to low dose radiation, particularly when combined with the strong effects of inherited genetic variants on both radiation effects and cancer susceptibility. We have used a Systems Genetics approach in mice that combines genetic background analysis with responses to low and high dose radiation, in order to develop insights that will allow us to reconcile these disparate observations. Using this comprehensive approach we have analyzed normal tissue gene expression (in this case the skin and thymus), together with the changes that take place in this gene expression architecture a) in response to low or high- dose radiation and b) during tumor development. Additionally, we have demonstrated that using our expression analysis approach in our genetically heterogeneous/defined radiation-induced tumor mouse models can uniquely identify genes and pathways relevant to human T-ALL, and uncover interactions between common genetic variants of genes which may lead to tumor susceptibility.

  10. Identifying three-dimensional nested groundwater flow systems in a Tóthian basin

    Science.gov (United States)

    Wang, Xu-Sheng; Wan, Li; Jiang, Xiao-Wei; Li, Hailong; Zhou, Yangxiao; Wang, Junzhi; Ji, Xiaohui

    2017-10-01

    Nested groundwater flow systems have been revealed in Tóth's theory as the structural property of basin-scale groundwater circulation but were only well known with two-dimensional (2D) profile models. The method of searching special streamlines across stagnation points for partitioning flow systems, which has been successfully applied in the 2D models, has never been implemented for three-dimensional (3D) Tóthian basins because of the difficulty in solving the dual stream functions. Alternatively, a new method is developed to investigate 3D nested groundwater flow systems without determination of stagnation points. Connective indices are defined to quantify the connection between individual recharge and discharge zones along streamlines. Groundwater circulation cells (GWCCs) are identified according to the distribution of the connective indices and then grouped into local, intermediate and regional flow systems. This method requires existing solution of the flow velocity vector and is implemented via particle tracking technique. It is applied in a hypothetical 3D Tóthian basin with an analytical solution of the flow field and in a real-world basin with a numerical modeling approach. Different spatial patterns of flow systems compared to 2D profile models are found. The outcrops boundaries of GWCCs on water table may significantly deviate from and are not parallel to the nearby water table divides. Topological network is proposed to represent the linked recharge-discharge zones through closed and open GWCCs. Sensitivity analysis indicates that the development of GWCCs depends on the basin geometry, hydraulic parameters and water table shape.

  11. Impact of the cardiovascular system-associated adipose tissue on atherosclerotic pathology.

    Science.gov (United States)

    Chistiakov, Dimitry A; Grechko, Andrey V; Myasoedova, Veronika A; Melnichenko, Alexandra A; Orekhov, Alexander N

    2017-08-01

    Cardiac obesity makes an important contribution to the pathogenesis of cardiovascular disease. One of the important pathways of this contribution is the inflammatory process that takes place in the adipose tissue. In this review, we consider the role of the cardiovascular system-associated fat in atherosclerotic cardiovascular pathology and a non-atherosclerotic cause of coronary artery disease, such as atrial fibrillation. Cardiovascular system-associated fat not only serves as the energy store, but also releases adipokines that control local and systemic metabolism, heart/vascular function and vessel tone, and a number of vasodilating and anti-inflammatory substances. Adipokine appears to play an important protective role in cardiovascular system. Under chronic inflammation conditions, the repertoire of signaling molecules secreted by cardiac fat can be altered, leading to a higher amount of pro-inflammatory messengers, vasoconstrictors, profibrotic modulators. This further aggravates cardiovascular inflammation and leads to hypertension, induction of the pathological tissue remodeling and cardiac fibrosis. Contemporary imaging techniques showed that epicardial fat thickness correlates with the visceral fat mass, which is an established risk factor and predictor of cardiovascular disease in obese subjects. However, this correlation is no longer present after adjustment for other covariates. Nevertheless, recent studies showed that pericardial fat volume and epicardial fat thickness can probably serve as a better indicator for atrial fibrillation. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. An All-Recombinant Protein-Based Culture System Specifically Identifies Hematopoietic Stem Cell Maintenance Factors

    Directory of Open Access Journals (Sweden)

    Aki Ieyasu

    2017-03-01

    Full Text Available Hematopoietic stem cells (HSCs are considered one of the most promising therapeutic targets for the treatment of various blood disorders. However, due to difficulties in establishing stable maintenance and expansion of HSCs in vitro, their insufficient supply is a major constraint to transplantation studies. To solve these problems we have developed a fully defined, all-recombinant protein-based culture system. Through this system, we have identified hemopexin (HPX and interleukin-1α as responsible for HSC maintenance in vitro. Subsequent molecular analysis revealed that HPX reduces intracellular reactive oxygen species levels within cultured HSCs. Furthermore, bone marrow immunostaining and 3D immunohistochemistry revealed that HPX is expressed in non-myelinating Schwann cells, known HSC niche constituents. These results highlight the utility of this fully defined all-recombinant protein-based culture system for reproducible in vitro HSC culture and its potential to contribute to the identification of factors responsible for in vitro maintenance, expansion, and differentiation of stem cell populations.

  13. Using an educational electronic documentation system to help nursing students accurately identify patient data.

    Science.gov (United States)

    Pobocik, Tamara

    2015-01-01

    This quantitative research study used a pretest/posttest design and reviewed how an educational electronic documentation system helped nursing students to identify the accurate "related to" statement of the nursing diagnosis for the patient in the case study. Students in the sample population were senior nursing students in a bachelor of science nursing program in the northeastern United States. Two distinct groups were used for a control and intervention group. The intervention group used the educational electronic documentation system for three class assignments. Both groups were given a pretest and posttest case study. The Accuracy Tool was used to score the students' responses to the related to statement of a nursing diagnosis given at the end of the case study. The scores of the Accuracy Tool were analyzed, and then the numeric scores were placed in SPSS, and the paired t test scores were analyzed for statistical significance. The intervention group's scores were statistically different from the pretest scores to posttest scores, while the control group's scores remained the same from pretest to posttest. The recommendation to nursing education is to use the educational electronic documentation system as a teaching pedagogy to help nursing students prepare for nursing practice. © 2014 NANDA International, Inc.

  14. Design modification and optimisation of the perfusion system of a tri-axial bioreactor for tissue engineering.

    Science.gov (United States)

    Hussein, Husnah; Williams, David J; Liu, Yang

    2015-07-01

    A systematic design of experiments (DOE) approach was used to optimize the perfusion process of a tri-axial bioreactor designed for translational tissue engineering exploiting mechanical stimuli and mechanotransduction. Four controllable design parameters affecting the perfusion process were identified in a cause-effect diagram as potential improvement opportunities. A screening process was used to separate out the factors that have the largest impact from the insignificant ones. DOE was employed to find the settings of the platen design, return tubing configuration and the elevation difference that minimise the load on the pump and variation in the perfusion process and improve the controllability of the perfusion pressures within the prescribed limits. DOE was very effective for gaining increased knowledge of the perfusion process and optimizing the process for improved functionality. It is hypothesized that the optimized perfusion system will result in improved biological performance and consistency.

  15. Identifying molecular effects of diet through systems biology: influence of herring diet on sterol metabolism and protein turnover in mice.

    Directory of Open Access Journals (Sweden)

    Intawat Nookaew

    Full Text Available BACKGROUND: Changes in lifestyle have resulted in an epidemic development of obesity-related diseases that challenge the healthcare systems worldwide. To develop strategies to tackle this problem the focus is on diet to prevent the development of obesity-associated diseases such as cardiovascular disease (CVD. This will require methods for linking nutrient intake with specific metabolic processes in different tissues. METHODOLOGY/PRINCIPAL FINDING: Low-density lipoprotein receptor-deficient (Ldlr -/- mice were fed a high fat/high sugar diet to mimic a westernized diet, being a major reason for development of obesity and atherosclerosis. The diets were supplemented with either beef or herring, and matched in macronutrient contents. Body composition, plasma lipids and aortic lesion areas were measured. Transcriptomes of metabolically important tissues, e.g. liver, muscle and adipose tissue were analyzed by an integrated approach with metabolic networks to directly map the metabolic effects of diet in these different tissues. Our analysis revealed a reduction in sterol metabolism and protein turnover at the transcriptional level in herring-fed mice. CONCLUSION: This study shows that an integrated analysis of transcriptome data using metabolic networks resulted in the identification of signature pathways. This could not have been achieved using standard clustering methods. In particular, this systems biology analysis could enrich the information content of biomedical or nutritional data where subtle changes in several tissues together affects body metabolism or disease progression. This could be applied to improve diets for subjects exposed to health risks associated with obesity.

  16. Reaction of the hemocoagulation system to tissue hypoxia in patients with chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Anna A. Bulanova

    2017-01-01

    Full Text Available Background. Nowadays little data related to the hemostatic system and fibrinolysis in patients with chronic obstructive pulmonary disease (COPD are available. This is due to the lack of standardized methods for studying the hemostasis system, as well as to the lack of a single functional test that allows the evaluation of the complete fibrinogenesis cycle in whole blood.Aim. The aim of our study was to develop a functional test capable of analyzing the blood gas composition in the “point-of-care test” method for the evaluation of the hemostatic potential in patients with COPD, based on a standardized test stimulus, which is tissue hypoxia. The current level of clinical and laboratory diagnostics requires personification and research of the hemo-coagulation system in real time (point-of-care test, which allows low-frequency piezotromboelastography(NVTEG to be performed.Materials and methods. NVTEG was chosen to estimate the state of the hemocoagulation system. Ten patients with COPD and 10 healthy volunteers were examined. Hypoxia was selected as a standardized test stimulus. Hypoxia conditions were caused by smoking one standard cigarette (composition: resin 10 mg/cig., nicotine 0,7 mg/cig., CO 10 mg/cig.. The degree of tissue hypoxia was assessed with the GASTAT-navi blood gas analyzer.Results. The study has shown that in response to the standard test stimulus, which is the tissue hypoxia caused by smoking of a standardized cigarette, two types of haemostatic potential reaction were detected both in patients with COPD and healthy volunteers. The first type of reaction – “hypercoagulation” – is characterized by the formation of chronometric and structural hypercoagulation at all stages of fibrinogenesis and increased coagulation activity by 25–30% compared with the response in healthy individuals. The second type of reaction – “hypocoagulation” – is characterized by the formation of chronometric and structural

  17. Development of a novel scoring system for identifying emerging chemical risks in the food chain.

    Science.gov (United States)

    Oltmanns, J; Licht, O; Bitsch, A; Bohlen, M-L; Escher, S E; Silano, V; MacLeod, M; Serafimova, R; Kass, G E N; Merten, C

    2018-02-21

    The European Food Safety Authority (EFSA) is responsible for risk assessment of all aspects of food safety, including the establishment of procedures aimed at the identification of emerging risks to food safety. Here, a scoring system was developed for identifying chemicals registered under the European REACH Regulation that could be of potential concern in the food chain using the following parameters: (i) environmental release based on maximum aggregated tonnages and environmental release categories; (ii) biodegradation in the environment; (iii) bioaccumulation and in vivo and in vitro toxicity. The screening approach was tested on 100 data-rich chemicals registered under the REACH Regulation at aggregated volumes of at least 1000 tonnes per annum. The results show that substance-specific data generated under the REACH Regulation can be used to identify potential emerging risks in the food chain. After application of the screening procedure, priority chemicals can be identified as potentially emerging risk chemicals through the integration of exposure, environmental fate and toxicity. The default approach is to generate a single total score for each substance using a predefined weighting scenario. However, it is also possible to use a pivot table approach to combine the individual scores in different ways that reflect user-defined priorities, which enables a very flexible, iterative definition of screening criteria. Possible applications of the approaches are discussed using illustrative examples. Either approach can then be followed by in-depth evaluation of priority substances to ensure the identification of substances that present a real emerging chemical risk in the food chain.

  18. Identifying (subsurface) anthropogenic heat sources that influence temperature in the drinking water distribution system

    Science.gov (United States)

    Agudelo-Vera, Claudia M.; Blokker, Mirjam; de Kater, Henk; Lafort, Rob

    2017-09-01

    The water temperature in the drinking water distribution system and at customers' taps approaches the surrounding soil temperature at a depth of 1 m. Water temperature is an important determinant of water quality. In the Netherlands drinking water is distributed without additional residual disinfectant and the temperature of drinking water at customers' taps is not allowed to exceed 25 °C. In recent decades, the urban (sub)surface has been getting more occupied by various types of infrastructures, and some of these can be heat sources. Only recently have the anthropogenic sources and their influence on the underground been studied on coarse spatial scales. Little is known about the urban shallow underground heat profile on small spatial scales, of the order of 10 m × 10 m. Routine water quality samples at the tap in urban areas have shown up locations - so-called hotspots - in the city, with relatively high soil temperatures - up to 7 °C warmer - compared to the soil temperatures in the surrounding rural areas. Yet the sources and the locations of these hotspots have not been identified. It is expected that with climate change during a warm summer the soil temperature in the hotspots can be above 25 °C. The objective of this paper is to find a method to identify heat sources and urban characteristics that locally influence the soil temperature. The proposed method combines mapping of urban anthropogenic heat sources, retrospective modelling of the soil temperature, analysis of water temperature measurements at the tap, and extensive soil temperature measurements. This approach provided insight into the typical range of the variation of the urban soil temperature, and it is a first step to identifying areas with potential underground heat stress towards thermal underground management in cities.

  19. Identifying bubble collapse in a hydrothermal system using hiddden Markov models

    Science.gov (United States)

    Dawson, Phillip B.; Benitez, M.C.; Lowenstern, Jacob B.; Chouet, Bernard A.

    2012-01-01

    Beginning in July 2003 and lasting through September 2003, the Norris Geyser Basin in Yellowstone National Park exhibited an unusual increase in ground temperature and hydrothermal activity. Using hidden Markov model theory, we identify over five million high-frequency (>15 Hz) seismic events observed at a temporary seismic station deployed in the basin in response to the increase in hydrothermal activity. The source of these seismic events is constrained to within ~100 m of the station, and produced ~3500–5500 events per hour with mean durations of ~0.35–0.45 s. The seismic event rate, air temperature, hydrologic temperatures, and surficial water flow of the geyser basin exhibited a marked diurnal pattern that was closely associated with solar thermal radiance. We interpret the source of the seismicity to be due to the collapse of small steam bubbles in the hydrothermal system, with the rate of collapse being controlled by surficial temperatures and daytime evaporation rates.

  20. An optical coherence tomography (OCT)-based air jet indentation system for measuring the mechanical properties of soft tissues

    International Nuclear Information System (INIS)

    Huang, Yan-Ping; Zheng, Yong-Ping; Wang, Shu-Zhe; Huang, Qing-Hua; Chen, Zhong-Ping; He, Yong-Hong

    2009-01-01

    A novel noncontact indentation system with the combination of an air jet and optical coherence tomography (OCT) was presented in this paper for the quantitative measurement of the mechanical properties of soft tissues. The key idea of this method is to use a pressure-controlled air jet as an indenter to compress the soft tissue in a noncontact way and utilize the OCT signals to extract the deformation induced. This indentation system provides measurement and mapping of tissue elasticity for small specimens with high scanning speed. Experiments were performed on 27 silicone tissue-mimicking phantoms with different Young's moduli, which were also measured by uniaxial compression tests. The regression coefficient of the indentation force to the indentation depth (N mm −1 ) was used as an indicator of the stiffness of tissue under air jet indentation. Results showed that the stiffness coefficients measured by the current system correlated well with the corresponding Young's moduli obtained by conventional mechanical testing (r = 0.89, p < 0.001). Preliminary in vivo tests also showed that the change of soft tissue stiffness with and without the contraction of the underlying muscles in the hand could be differentiated by the current measurement. This system may have broad applications in tissue assessment and characterization where alterations of mechanical properties are involved, in particular with the potential of noncontact micro-indentation for tissues

  1. Fates of identified pioneer cells in the developing antennal nervous system of the grasshopper Schistocerca gregaria.

    Science.gov (United States)

    Ehrhardt, Erica; Graf, Philip; Kleele, Tatjana; Liu, Yu; Boyan, George

    2016-01-01

    In the early embryonic grasshopper, two pairs of sibling cells near the apex of the antenna pioneer its dorsal and ventral nerve tracts to the brain. En route, the growth cones of these pioneers contact a so-called base pioneer associated with each tract and which acts as a guidepost cell. Both apical and basal pioneers express stereotypic molecular labels allowing them to be uniquely identified. Although their developmental origins are largely understood, the fates of the respective pioneers remain unclear. We therefore employed the established cell death markers acridine orange and TUNEL to determine whether the apical and basal pioneers undergo apoptosis during embryogenesis. Our data reveal that the apical pioneers maintain a consistent molecular profile from their birth up to mid-embryogenesis, at which point the initial antennal nerve tracts to the brain have been established. Shortly after this the apical pioneers undergo apoptosis. Death occurs at a developmental stage similar to that reported elsewhere for pioneers in a leg - an homologous appendage. Base pioneers, by contrast, progressively change their molecular profile and can no longer be unequivocally identified after mid-embryogenesis. At no stage up to then do they exhibit death labels. If they persist, the base pioneers must be assumed to adopt a new role in the developing antennal nervous system. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. A Ternary Nanofibrous Scaffold Potential for Central Nerve System Tissue Engineering.

    Science.gov (United States)

    Saadatkish, Niloufar; Nouri Khorasani, Saied; Morshed, Mohammad; Allafchian, Ali-Reza; Beigi, Mohammad-Hossein; Masoudi Rad, Maryam; Nasr-Esfahani, Mohammad Hossein; Esmaeely Neisiany, Rasoul

    2018-04-10

    In the present research, a ternary Polycaprolactone (PCL)/gelatin/fibrinogen nanofibrous scaffold for tissue engineering application was developed. Through this combination, PCL improved the scaffold mechanical properties; meanwhile, gelatin and fibrinogen provided more hydrophilicity and cell proliferation. Three types of nanofibrous scaffolds containing different fibrinogen contents were prepared and characterized. Morphological study of the nanofibers showed that the prepared nanofibers were smooth, uniform without any formation of beads with a significant reduction in nanofiber diameter after incorporation of fibrinogen. The chemical characterization of the scaffolds confirmed that no chemical reaction occurred between the scaffold components. The tensile test results of the scaffolds showed that increasing in fibrinogen content led to a decrease in mechanical properties. Furthermore, Adipose-derived stem cells (ADSCs) were employed to evaluate cell-scaffold interaction. Cell culture results indicated that higher cell proliferation occurred for the higher amount of fibrinogen. Statistical analysis was also carried out to evaluate the significant difference for the obtained results of water droplet contact angle and cell culture. Therefore, the results confirmed that PCL/Gel/Fibrinogen scaffold has a good potential for tissue engineering applications including Central Nerve System (CNS) tissue engineering. This article is protected by copyright. All rights reserved. © 2018 Wiley Periodicals, Inc.

  3. Visualizing feasible operating ranges within tissue engineering systems using a "windows of operation" approach: a perfusion-scaffold bioreactor case study.

    Science.gov (United States)

    McCoy, Ryan J; O'Brien, Fergal J

    2012-12-01

    Tissue engineering approaches to developing functional substitutes are often highly complex, multivariate systems where many aspects of the biomaterials, bio-regulatory factors or cell sources may be controlled in an effort to enhance tissue formation. Furthermore, success is based on multiple performance criteria reflecting both the quantity and quality of the tissue produced. Managing the trade-offs between different performance criteria is a challenge. A "windows of operation" tool that graphically represents feasible operating spaces to achieve user-defined levels of performance has previously been described by researchers in the bio-processing industry. This paper demonstrates the value of "windows of operation" to the tissue engineering field using a perfusion-scaffold bioreactor system as a case study. In our laboratory, perfusion bioreactor systems are utilized in the context of bone tissue engineering to enhance the osteogenic differentiation of cell-seeded scaffolds. A key challenge of such perfusion bioreactor systems is to maximize the induction of osteogenesis but minimize cell detachment from the scaffold. Two key operating variables that influence these performance criteria are the mean scaffold pore size and flow-rate. Using cyclooxygenase-2 and osteopontin gene expression levels as surrogate indicators of osteogenesis, we employed the "windows of operation" methodology to rapidly identify feasible operating ranges for the mean scaffold pore size and flow-rate that achieved user-defined levels of performance for cell detachment and differentiation. Incorporation of such tools into the tissue engineer's armory will hopefully yield a greater understanding of the highly complex systems used and help aid decision making in future translation of products from the bench top to the market place. Copyright © 2012 Wiley Periodicals, Inc.

  4. Identifying functional zones of denitrification in heterogeneous aquifer systems by numerical simulations - a case study

    Science.gov (United States)

    Jang, E.; Kalbacher, T.; He, W.; Shao, H.; Schueth, C.; Kolditz, O.

    2014-12-01

    Nitrate contamination in shallow groundwater is still one of the common problems in many countries. Because of its high solubility and anionic nature, nitrate can easily leach through soil and persist in groundwater for decades. High nitrate concentration has been suggested as a major cause of accelerated eutrophication, methemoglobinemia and gastric cancer. There are several factors influencing the fate of nitrate in groundwater system, which is e.g. distribution of N- sources to soil and groundwater, distribution and amount of reactive substances maintaining denitrification, rate of nitrate degradation and its kinetics, and geological characteristics of the aquifer. Nitrate transport and redox transformation processes are closely linked to complex and spatially distributed physical and chemical interaction, therefore it is difficult to predict and quantify in the field and laboratory experiment. Models can play a key role in elucidation of nitrate reduction pathway in groundwater system and in the design and evaluation of field tests to investigate in situ remediation technologies as well. The goal of the current study is to predict groundwater vulnerability to nitrate, to identify functional zones of denitrification in heterogeneous aquifer systems and to describe the uncertainty of the predictions due to scale effects. For this aim, we developed a kinetic model using multi-component mass transport code OpenGeoSys coupling with IPhreeqc module of the geochemical solver PHREEQC. The developed model included sequential aerobic and nitrate-based respiration, multi-Monod kinetics, multi-species biogeochemical reactions, and geological characteristics of the groundwater aquifer. Moreover water-rock interaction such as secondary mineral precipitation was also included in this model. In this presentation, we focused on the general modelling approach and present the simulation results of nitrate transport simulation in a hypothetical aquifer systems based on data from

  5. [Eye-associated lymphoid tissue (EALT) is continuously spread throughout the ocular surface from the lacrimal gland to the lacrimal drainage system].

    Science.gov (United States)

    Knop, E; Knop, N

    2003-11-01

    Components of the mucosal immune system (MALT) have been identified in the conjunctiva (as CALT) and the lacrimal drainage system (as LDALT). Their structural and functional relation with the established immune protection by the lacrimal gland is unclear. Macroscopically normal and complete tissues of the conjunctiva, lacrimal drainage system and lacrimal gland from human body donors were investigated by analysis of translucent whole mounts, and using histology, immunohistology as well as scanning and transmission electron microscopy. A typical diffuse lymphoid tissue, composed of effector cells of the immune system (T-lymphocytes and IgA producing plasma cells) under an epithelium that contains the IgA transporter SC, is not isolated in the conjunctiva and lacrimal drainage system. It is anatomically continuous from the lacrimal gland along its excretory ducts into the conjunctiva and from there via the lacrimal canaliculi into the lacrimal drainage system. Lymphoid follicles occur in a majority (about 60%) and with bilateral symmetry. The topography of CALT corresponds to the position of the cornea in the closed eye. These results show that the MALT of the lacrimal gland, conjunctiva and lacrimal drainage system constitute an anatomical and functional unit for immune protection of the ocular surface. Therefore it should be integrated as an "eye-associated lymphoid tissue" (EALT) into the MALT system of the body. EALT can detect ocular surface antigens by the lymphoid follicles and can supply other organs and the ocular surface including the lacrimal gland with specific effector cells via the regulated recirculation of lymphoid cells.

  6. Preservation of biomolecules in breast cancer tissue by a formalin-free histology system

    Directory of Open Access Journals (Sweden)

    Morales Azorides R

    2008-01-01

    Full Text Available Abstract Background The potential problems associated with the use of formalin in histology, such as health hazards, degradation of RNA and cross-linking of proteins are well recognized. We describe the utilization of a formalin-free fixation and processing system for tissue detection of two important biopredictors in breast cancer – estrogen receptor and HER2 – at the RNA and protein levels. Methods Parallel sections of 62 cases of breast cancer were fixed in an alcohol-based molecular fixative and in formalin. Molecular fixative samples were processed by a novel formalin-free microwave-assisted processing system that preserves DNA, RNA and proteins. Formalin-fixed samples were processed using the conventional method. Estrogen receptor was assessed by immunohistochemistry and real-time PCR. HER2 was assessed by immunohistochemistry, FISH, CISH and real-time PCR. Results The immunohistochemical reaction for estrogen receptor was similar in molecular- and formalin-fixed samples (Spearman Rank R = 0.83, p Conclusion The formalin-free tissue fixation and processing system is a practical platform for evaluation of biomolecular markers in breast cancer and it allows reliable DNA and RNA and protein studies.

  7. Implementing oxygen control in chip-based cell and tissue culture systems.

    Science.gov (United States)

    Oomen, Pieter E; Skolimowski, Maciej D; Verpoorte, Elisabeth

    2016-09-21

    Oxygen is essential in the energy metabolism of cells, as well as being an important regulatory parameter influencing cell differentiation and function. Interest in precise oxygen control for in vitro cultures of tissues and cells continues to grow, especially with the emergence of the organ-on-a-chip and the desire to emulate in vivo conditions. This was recently discussed in this journal in a Critical Review by Brennan et al. (Lab Chip (2014). DOI: ). Microfluidics can be used to introduce flow to facilitate nutrient supply to and waste removal from in vitro culture systems. Well-defined oxygen gradients can also be established. However, cells can quickly alter the oxygen balance in their vicinity. In this Tutorial Review, we expand on the Brennan paper to focus on the implementation of oxygen analysis in these systems to achieve continuous monitoring. Both electrochemical and optical approaches for the integration of oxygen monitoring in microfluidic tissue and cell culture systems will be discussed. Differences in oxygen requirements from one organ to the next are a challenging problem, as oxygen delivery is limited by its uptake into medium. Hence, we discuss the factors determining oxygen concentrations in solutions and consider the possible use of artificial oxygen carriers to increase dissolved oxygen concentrations. The selection of device material for applications requiring precise oxygen control is discussed in detail, focusing on oxygen permeability. Lastly, a variety of devices is presented, showing the diversity of approaches that can be employed to control and monitor oxygen concentrations in in vitro experiments.

  8. Immunohistochemical Analysis in the Rat Central Nervous System and Peripheral Lymph Node Tissue Sections.

    Science.gov (United States)

    Adzemovic, Milena Z; Zeitelhofer, Manuel; Leisser, Marianne; Köck, Ulricke; Kury, Angela; Olsson, Tomas

    2016-11-14

    Immunohistochemistry (IHC) provides highly specific, reliable and attractive protein visualization. Correct performance and interpretation of an IHC-based multicolor labeling is challenging, especially when utilized for assessing interrelations between target proteins in the tissue with a high fat content such as the central nervous system (CNS). Our protocol represents a refinement of the standard immunolabeling technique particularly adjusted for detection of both structural and soluble proteins in the rat CNS and peripheral lymph nodes (LN) affected by neuroinflammation. Nonetheless, with or without further modifications, our protocol could likely be used for detection of other related protein targets, even in other organs and species than here presented.

  9. Identifying Factors Influencing the Establishment of a Health System Reform Plan in Iran's Public Hospitals

    Directory of Open Access Journals (Sweden)

    Rasul Fani khiavi

    2016-09-01

    Full Text Available In today's world, health views have found a wider perspective in which non-medical expectations are particularly catered to. The health system reform plan seeks to improve society's health, decrease treatment costs, and increase patient satisfaction. This study investigated factors affecting the successful establishment of a health system reform plan. A mixed qualitative – quantitative approach was applied to conduct to explore influential factors associated with the establishment of a health system reform plan in Iran's public hospitals. The health systems and approaches to improving them in other countries have been studied. A Likert-based five-point questionnaire was the measurement instrument, and its content validity based on content validity ratio (CVR was 0.87. The construct validity, calculated using the factorial analysis and Kaiser Mayer Olkin (KMO techniques, was 0.964, which is a high level and suggests a correlation between the scale items. To complete the questionnaire, 185 experts, specialists, and executives of Iran’s health reform plan were selected using the Purposive Stratified Non Random Sampling and snowball methods. The data was then analyzed using exploratory factorial analysis and SPSS and LISREL software applications. The results of this research imply the existence of a pattern with a significant and direct relationship between the identified independent variables and the dependent variable of the establishment of a health system reform plan. The most important indices of establishing a health system reform plan, in the order of priority, were political support; suitable proportion and coverage of services presented in the society; management of resources; existence of necessary infrastructures; commitment of senior managers; constant planning, monitoring, and evaluation; and presentation of feedback to the plan's executives, intrasector/extrasector cooperation, and the plan’s guiding committee. Considering the

  10. Small RNA analysis in Petunia hybrida identifies unusual tissue-specific expression patterns of conserved miRNAs and of a 24mer RNA

    Science.gov (United States)

    Tedder, Philip; Zubko, Elena; Westhead, David R.; Meyer, Peter

    2009-01-01

    Two pools of small RNAs were cloned from inflorescences of Petunia hybrida using a 5′-ligation dependent and a 5′-ligation independent approach. The two libraries were integrated into a public website that allows the screening of individual sequences against 359,769 unique clones. The library contains 15 clones with 100% identity and 53 clones with one mismatch to miRNAs described for other plant species. For two conserved miRNAs, miR159 and miR390, we find clear differences in tissue-specific distribution, compared with other species. This shows that evolutionary conservation of miRNA sequences does not necessarily include a conservation of the miRNA expression profile. Almost 60% of all clones in the database are 24-nucleotide clones. In accordance with the role of 24mers in marking repetitive regions, we find them distributed across retroviral and transposable element sequences but other 24mers map to promoter regions and to different transcript regions. For one target region we observe tissue-specific variation of matching 24mers, which demonstrates that, as for 21mers, 24mer concentrations are not necessarily identical in different tissues. Asymmetric distribution of a putative novel miRNA in the two libraries suggests that the cloning method can be selective for the representation of certain small RNAs in a collection. PMID:19369427

  11. Three-dimensional hydrogel cell culture systems for modeling neural tissue

    Science.gov (United States)

    Frampton, John

    Two-dimensional (2-D) neural cell culture systems have served as physiological models for understanding the cellular and molecular events that underlie responses to physical and chemical stimuli, control sensory and motor function, and lead to the development of neurological diseases. However, the development of three-dimensional (3-D) cell culture systems will be essential for the advancement of experimental research in a variety of fields including tissue engineering, chemical transport and delivery, cell growth, and cell-cell communication. In 3-D cell culture, cells are provided with an environment similar to tissue, in which they are surrounded on all sides by other cells, structural molecules and adhesion ligands. Cells grown in 3-D culture systems display morphologies and functions more similar to those observed in vivo, and can be cultured in such a way as to recapitulate the structural organization and biological properties of tissue. This thesis describes a hydrogel-based culture system, capable of supporting the growth and function of several neural cell types in 3-D. Alginate hydrogels were characterized in terms of their biomechanical and biochemical properties and were functionalized by covalent attachment of whole proteins and peptide epitopes. Methods were developed for rapid cross-linking of alginate hydrogels, thus permitting the incorporation of cells into 3-D scaffolds without adversely affecting cell viability or function. A variety of neural cell types were tested including astrocytes, microglia, and neurons. Cells remained viable and functional for longer than two weeks in culture and displayed process outgrowth in 3-D. Cell constructs were created that varied in cell density, type and organization, providing experimental flexibility for studying cell interactions and behavior. In one set of experiments, 3-D glial-endothelial cell co-cultures were used to model blood-brain barrier (BBB) structure and function. This co-culture system was

  12. New scoring system identifies kidney outcome with radiation therapy in acute renal allograft rejection

    International Nuclear Information System (INIS)

    Chen, Luci M.; Godinez, Juan; Thisted, Ronald A.; Woodle, E. Steve; Thistlewaite, J. Richard; Powers, Claire; Haraf, Daniel

    2000-01-01

    concomitant immunosuppressive therapy. Independent factors examined by Cox regression modeling were: gender (p 0.005), creatinine levels (p = 0.000), HLA-DR (p = 0.05), PRA-Maximum >70% (p = 0.014). Each factor was scored using integral coefficients to generate four different groups. The Kaplan-Meier survival analyzed by group produces an interpretable separation of the risk factors for graft loss. Conclusions: The outcome in patients treated with radiation therapy for acute renal graft rejection can be predicted by a novel scoring system. Patients with scores of three or less are able to achieve 100% renal graft salvage, while patients who have scores of 12 or higher are not able to be salvaged with the current radiation therapy regimen. Future studies should be directed toward identifying more effective treatment for patients who have a high score based on our criteria. The scoring system should be utilized to identify patients at risk who could benefit from radiation therapy. Further study with a randomized trial utilizing this scoring system is needed to confirm the validity of the scoring system in predicting graft survival and the efficacy of radiation in patients who receive radiation therapy for acute graft rejection

  13. Adipose Tissue Dysfunction and Altered Systemic Amino Acid Metabolism Are Associated with Non-Alcoholic Fatty Liver Disease.

    Directory of Open Access Journals (Sweden)

    Sulin Cheng

    Full Text Available Fatty liver is a major cause of obesity-related morbidity and mortality. The aim of this study was to identify early metabolic alterations associated with liver fat accumulation in 50- to 55-year-old men (n = 49 and women (n = 52 with and without NAFLD.Hepatic fat content was measured using proton magnetic resonance spectroscopy (1H MRS. Serum samples were analyzed using a nuclear magnetic resonance (NMR metabolomics platform. Global gene expression profiles of adipose tissues and skeletal muscle were analyzed using Affymetrix microarrays and quantitative PCR. Muscle protein expression was analyzed by Western blot.Increased branched-chain amino acid (BCAA, aromatic amino acid (AAA and orosomucoid were associated with liver fat accumulation already in its early stage, independent of sex, obesity or insulin resistance (p<0.05 for all. Significant down-regulation of BCAA catabolism and fatty acid and energy metabolism was observed in the adipose tissue of the NAFLD group (p<0.001for all, whereas no aberrant gene expression in the skeletal muscle was found. Reduced BCAA catabolic activity was inversely associated with serum BCAA and liver fat content (p<0.05 for all.Liver fat accumulation, already in its early stage, is associated with increased serum branched-chain and aromatic amino acids. The observed associations of decreased BCAA catabolism activity, mitochondrial energy metabolism and serum BCAA concentration with liver fat content suggest that adipose tissue dysfunction may have a key role in the systemic nature of NAFLD pathogenesis.

  14. Comparative Proteomics Identifies Host Immune System Proteins Affected by Infection with Mycobacterium bovis.

    Directory of Open Access Journals (Sweden)

    Vladimir López

    2016-03-01

    Full Text Available Mycobacteria of the Mycobacterium tuberculosis complex (MTBC greatly impact human and animal health worldwide. The mycobacterial life cycle is complex, and the mechanisms resulting in pathogen infection and survival in host cells are not fully understood. Eurasian wild boar (Sus scrofa are natural reservoir hosts for MTBC and a model for mycobacterial infection and tuberculosis (TB. In the wild boar TB model, mycobacterial infection affects the expression of innate and adaptive immune response genes in mandibular lymph nodes and oropharyngeal tonsils, and biomarkers have been proposed as correlates with resistance to natural infection. However, the mechanisms used by mycobacteria to manipulate host immune response are not fully characterized. Our hypothesis is that the immune system proteins under-represented in infected animals, when compared to uninfected controls, are used by mycobacteria to guarantee pathogen infection and transmission. To address this hypothesis, a comparative proteomics approach was used to compare host response between uninfected (TB- and M. bovis-infected young (TB+ and adult animals with different infection status [TB lesions localized in the head (TB+ or affecting multiple organs (TB++]. The results identified host immune system proteins that play an important role in host response to mycobacteria. Calcium binding protein A9, Heme peroxidase, Lactotransferrin, Cathelicidin and Peptidoglycan-recognition protein were under-represented in TB+ animals when compared to uninfected TB- controls, but protein levels were higher as infection progressed in TB++ animals when compared to TB- and/or TB+ adult wild boar. MHCI was the only protein over-represented in TB+ adult wild boar when compared to uninfected TB- controls. The results reported here suggest that M. bovis manipulates host immune response by reducing the production of immune system proteins. However, as infection progresses, wild boar immune response recovers to

  15. Comparative Proteomics Identifies Host Immune System Proteins Affected by Infection with Mycobacterium bovis.

    Science.gov (United States)

    López, Vladimir; Villar, Margarita; Queirós, João; Vicente, Joaquín; Mateos-Hernández, Lourdes; Díez-Delgado, Iratxe; Contreras, Marinela; Alves, Paulo C; Alberdi, Pilar; Gortázar, Christian; de la Fuente, José

    2016-03-01

    Mycobacteria of the Mycobacterium tuberculosis complex (MTBC) greatly impact human and animal health worldwide. The mycobacterial life cycle is complex, and the mechanisms resulting in pathogen infection and survival in host cells are not fully understood. Eurasian wild boar (Sus scrofa) are natural reservoir hosts for MTBC and a model for mycobacterial infection and tuberculosis (TB). In the wild boar TB model, mycobacterial infection affects the expression of innate and adaptive immune response genes in mandibular lymph nodes and oropharyngeal tonsils, and biomarkers have been proposed as correlates with resistance to natural infection. However, the mechanisms used by mycobacteria to manipulate host immune response are not fully characterized. Our hypothesis is that the immune system proteins under-represented in infected animals, when compared to uninfected controls, are used by mycobacteria to guarantee pathogen infection and transmission. To address this hypothesis, a comparative proteomics approach was used to compare host response between uninfected (TB-) and M. bovis-infected young (TB+) and adult animals with different infection status [TB lesions localized in the head (TB+) or affecting multiple organs (TB++)]. The results identified host immune system proteins that play an important role in host response to mycobacteria. Calcium binding protein A9, Heme peroxidase, Lactotransferrin, Cathelicidin and Peptidoglycan-recognition protein were under-represented in TB+ animals when compared to uninfected TB- controls, but protein levels were higher as infection progressed in TB++ animals when compared to TB- and/or TB+ adult wild boar. MHCI was the only protein over-represented in TB+ adult wild boar when compared to uninfected TB- controls. The results reported here suggest that M. bovis manipulates host immune response by reducing the production of immune system proteins. However, as infection progresses, wild boar immune response recovers to limit pathogen

  16. Identifying Methane Sources with an Airborne Pulsed IPDA Lidar System Operating near 1.65 µm

    Science.gov (United States)

    Yerasi, A.; Bartholomew, J.; Tandy, W., Jr.; Emery, W. J.

    2016-12-01

    Methane is a powerful greenhouse gas that is predicted to play an important role in future global climate trends. It would therefore be beneficial to locate areas that produce methane in significant amounts so that these trends can be better understood. In this investigation, some initial performance test results of a lidar system called the Advanced Leak Detector Lidar - Natural Gas (ALDL-NG) are discussed. The feasibility of applying its fundamental principle of operation to methane source identification is also explored. The ALDL-NG was originally created by the Ball Aerospace & Technologies Corp. to reveal leaks emanating from pipelines that transport natural gas, which is primarily composed of methane. It operates in a pulsed integrated path differential absorption (IPDA) configuration and it is carried by a piloted, single-engine aircraft. In order to detect the presence of natural gas leaks, the laser wavelengths of its online and offline channels operate in the 1.65 µm region. The functionality of the ALDL-NG was tested during a recent field campaign in Colorado. It was determined that the ambient concentration of methane in the troposphere ( 1.8 ppm) could indeed be retrieved from ALDL-NG data with a lower-than-expected uncertainty ( 0.2 ppm). Furthermore, when the ALDL-NG scanned over areas that were presumed to be methane sources (feedlots, landfills, etc.), significantly higher concentrations of methane were retrieved. These results are intriguing because the ALDL-NG was not specifically designed to observe anything beyond natural gas pipelines. Nevertheless, they strongly indicate that utilizing an airborne pulsed IPDA lidar system operating near 1.65 µm may very well be a viable technique for identifying methane sources. Perhaps future lidar systems could build upon the heritage of the ALDL-NG and measure methane concentration with even better precision for a variety of scientific applications.

  17. Characterization of novel tumor stroma markers identified by gene expression profiling of human cancer tissues and 3D co-culture models

    International Nuclear Information System (INIS)

    Rupp, C.

    2010-01-01

    The tumor stroma plays an important role in tumorigenesis. During cancer progression it undergoes changes in architecture, gene expression and secretion of proteolytic enzymes that are essential for the invasive and metastatic phenotype of malignant tumors. Cancer associated fibroblasts (Cafes) represent the major cellular component of the stroma and recent studies demonstrated the prognostic and therapeutic significance of CaF-related molecular signatures. The identification and characterization of genes and signaling pathways involved in the molecular interactions between tumor and stromal cells has been the focus of this study. For that purpose we have used two complementary approaches: the identification of novel tumor stroma targets in human colon cancer samples using whole genome Affymetrix GeneChip analysis and the validation of theses targets in a newly established of 3D co-culture model that mimics the cellular and molecular heterogeneity of human cancers. We have demonstrated increased expression of gene sets related to hypoxia, epithelial-to-mesenchymal transition (EMT) and TGFβ pathway activation in CAFs vs their normal counterparts in both systems. The putative TGFβ target IGFBP7 (insulin-like growth factor binding protein 7) was identified as a tumor stroma marker of epithelial cancers and as a tumor antigen in mesenchyme-derived sarcomas. IGFPB7 was shown to promote anchorage-independent growth in malignant mesenchymal cells and malignant epithelial cells with an EMT-phenotype, whereas a tumor suppressor function was observed in tumor epithelial cells. In summary, we have demonstrated that a number of important signaling pathways involved in cancer progression and metastasis are specifically dysregulated in the tumor stroma both in our in vivo screen and in the in vitro 3D model, illustrating the value of these approaches for the identification and characterization of novel stromal markers. (author) [de

  18. An automated robot arm system for small animal tissue biopsy under dual-image modality

    International Nuclear Information System (INIS)

    Huang, Y.H.; Wu, T.H.; Lin, M.H.; Yang, C.C.; Guo, W.Y.; Wang, Z.J.; Chen, C.L.; Lee, J.S.

    2006-01-01

    The ability to non-invasively monitor cell biology in vivo is one of the most important goals of molecular imaging. Imaging procedures could be inter-subject performed repeatedly at different investigating stages; thereby need not sacrifice small animals during the entire study period. Thus, the ultimate goal of this study was to design a stereotactic image-guided system for small animals and integrated it with an automatic robot arm for in vivo tissue biopsy analysis. The system was composed of three main parts, including one small animal stereotactic frame, one imaging-fusion software and an automatic robot arm system. The system has been thoroughly evaluated with three components; the robot position accuracy was 0.05±0.02 mm, the image registration accuracy was 0.37±0.18 mm and the system integration was satisfactorily within 1.20±0.39 mm of error. From these results, the system demonstrated sufficient accuracy to guide the micro-injector from the planned delivery routes into practice. The entire system accuracy was limited by the image fusion and orientation procedures, due to its nature of the blurred PET imaging obtained from the small objects. The primary improvement is to acquire as higher resolution as possible the fused imaging for localizing the targets in the future

  19. A comparison of neural tube defects identified by two independent routine recording systems for congenital malformations in Northern Ireland.

    Science.gov (United States)

    Nevin, N C; McDonald, J R; Walby, A L

    1978-12-01

    The efficiency of two systems for recording congenital malformations has been compared; one system, the Registrar General's Congenital Malformation Notification, is based on registering all malformed infants, and the other, the Child Health System, records all births. In Northern Ireland for three years [1974--1976], using multiple sources of ascertainment, a total of 686 infants with neural tube defects was identified among 79 783 live and stillbirths. The incidence for all neural tube defects in 8 60 per 1 000 births. The Registrar General's Congenital Malformation Notification System identified 83.6% whereas the Child Health System identified only 63.3% of all neural tube defects. Both systems together identified 86.2% of all neural tube defects. The two systems are suitable for monitoring of malformations and the addition of information from the Genetic Counselling Clinics would enhance the data for epidemiological studies.

  20. A System for Continual Quality Improvement of Normal Tissue Delineation for Radiation Therapy Treatment Planning

    Energy Technology Data Exchange (ETDEWEB)

    Breunig, Jennifer; Hernandez, Sophy; Lin, Jeffrey; Alsager, Stacy; Dumstorf, Christine; Price, Jennifer; Steber, Jennifer; Garza, Richard; Nagda, Suneel; Melian, Edward; Emami, Bahman [Department of Radiation Oncology, Loyola University Medical Center, Maywood, Illinois (United States); Roeske, John C., E-mail: jroeske@lumc.edu [Department of Radiation Oncology, Loyola University Medical Center, Maywood, Illinois (United States)

    2012-08-01

    Purpose: To implement the 'plan-do-check-act' (PDCA) cycle for the continual quality improvement of normal tissue contours used for radiation therapy treatment planning. Methods and Materials: The CT scans of patients treated for tumors of the brain, head and neck, thorax, pancreas and prostate were selected for this study. For each scan, a radiation oncologist and a diagnostic radiologist, outlined the normal tissues ('gold' contours) using Radiation Therapy Oncology Group (RTOG) guidelines. A total of 30 organs were delineated. Independently, 5 board-certified dosimetrists and 1 trainee then outlined the same organs. Metrics used to compare the agreement between the dosimetrists' contours and the gold contours included the Dice Similarity Coefficient (DSC), and a penalty function using distance to agreement. Based on these scores, dosimetrists were re-trained on those organs in which they did not receive a passing score, and they were subsequently re-tested. Results: Passing scores were achieved on 19 of 30 organs evaluated. These scores were correlated to organ volume. For organ volumes <8 cc, the average DSC was 0.61 vs organ volumes {>=}8 cc, for which the average DSC was 0.91 (P=.005). Normal tissues that had the lowest scores included the lenses, optic nerves, chiasm, cochlea, and esophagus. Of the 11 organs that were considered for re-testing, 10 showed improvement in the average score, and statistically significant improvement was noted in more than half of these organs after education and re-assessment. Conclusions: The results of this study indicate the feasibility of applying the PDCA cycle to assess competence in the delineation of individual organs, and to identify areas for improvement. With testing, guidance, and re-evaluation, contouring consistency can be obtained across multiple dosimetrists. Our expectation is that continual quality improvement using the PDCA approach will ensure more accurate treatments and dose

  1. A System for Continual Quality Improvement of Normal Tissue Delineation for Radiation Therapy Treatment Planning

    International Nuclear Information System (INIS)

    Breunig, Jennifer; Hernandez, Sophy; Lin, Jeffrey; Alsager, Stacy; Dumstorf, Christine; Price, Jennifer; Steber, Jennifer; Garza, Richard; Nagda, Suneel; Melian, Edward; Emami, Bahman; Roeske, John C.

    2012-01-01

    Purpose: To implement the “plan-do-check-act” (PDCA) cycle for the continual quality improvement of normal tissue contours used for radiation therapy treatment planning. Methods and Materials: The CT scans of patients treated for tumors of the brain, head and neck, thorax, pancreas and prostate were selected for this study. For each scan, a radiation oncologist and a diagnostic radiologist, outlined the normal tissues (“gold” contours) using Radiation Therapy Oncology Group (RTOG) guidelines. A total of 30 organs were delineated. Independently, 5 board-certified dosimetrists and 1 trainee then outlined the same organs. Metrics used to compare the agreement between the dosimetrists' contours and the gold contours included the Dice Similarity Coefficient (DSC), and a penalty function using distance to agreement. Based on these scores, dosimetrists were re-trained on those organs in which they did not receive a passing score, and they were subsequently re-tested. Results: Passing scores were achieved on 19 of 30 organs evaluated. These scores were correlated to organ volume. For organ volumes <8 cc, the average DSC was 0.61 vs organ volumes ≥8 cc, for which the average DSC was 0.91 (P=.005). Normal tissues that had the lowest scores included the lenses, optic nerves, chiasm, cochlea, and esophagus. Of the 11 organs that were considered for re-testing, 10 showed improvement in the average score, and statistically significant improvement was noted in more than half of these organs after education and re-assessment. Conclusions: The results of this study indicate the feasibility of applying the PDCA cycle to assess competence in the delineation of individual organs, and to identify areas for improvement. With testing, guidance, and re-evaluation, contouring consistency can be obtained across multiple dosimetrists. Our expectation is that continual quality improvement using the PDCA approach will ensure more accurate treatments and dose assessment in

  2. Systems biology of adipose tissue metabolism: regulation of growth, signaling and inflammation.

    Science.gov (United States)

    Manteiga, Sara; Choi, Kyungoh; Jayaraman, Arul; Lee, Kyongbum

    2013-01-01

    Adipose tissue (AT) depots actively regulate whole body energy homeostasis by orchestrating complex communications with other physiological systems as well as within the tissue. Adipocytes readily respond to hormonal and nutritional inputs to store excess nutrients as intracellular lipids or mobilize the stored fat for utilization. Co-ordinated regulation of metabolic pathways balancing uptake, esterification, and hydrolysis of lipids is accomplished through positive and negative feedback interactions of regulatory hubs comprising several pleiotropic protein kinases and nuclear receptors. Metabolic regulation in adipocytes encompasses biogenesis and remodeling of uniquely large lipid droplets (LDs). The regulatory hubs also function as energy and nutrient sensors, and integrate metabolic regulation with intercellular signaling. Over-nutrition causes hypertrophic expansion of adipocytes, which, through incompletely understood mechanisms, initiates a cascade of metabolic and signaling events leading to tissue remodeling and immune cell recruitment. Macrophage activation and polarization toward a pro-inflammatory phenotype drives a self-reinforcing cycle of pro-inflammatory signals in the AT, establishing an inflammatory state. Sustained inflammation accelerates lipolysis and elevates free fatty acids in circulation, which robustly correlates with development of obesity-related diseases. The adipose regulatory network coupling metabolism, growth, and signaling of multiple cell types is exceedingly complex. While components of the regulatory network have been individually studied in exquisite detail, systems approaches have rarely been utilized to comprehensively assess the relative engagements of the components. Thus, need and opportunity exist to develop quantitative models of metabolic and signaling networks to achieve a more complete understanding of AT biology in both health and disease. Copyright © 2013 Wiley Periodicals, Inc.

  3. An Optimized Small Tissue Handling System for Immunohistochemistry and In Situ Hybridization.

    Directory of Open Access Journals (Sweden)

    Giovanni Anthony

    Full Text Available Recent development in 3D printing technology has opened an exciting possibility for manufacturing 3D devices on one's desktop. We used 3D modeling programs to design 3D models of a tissue-handling system and these models were "printed" in a stereolithography (SLA 3D printer to create precision histology devices that are particularly useful to handle multiple samples with small dimensions in parallel. Our system has been successfully tested for in situ hybridization of zebrafish embryos. Some of the notable features include: (1 A conveniently transferrable chamber with 6 mesh-bottomed wells, each of which can hold dozens of zebrafish embryos. This design allows up to 6 different samples to be treated per chamber. (2 Each chamber sits in a well of a standard 6-well tissue culture plate. Thus, up to 36 different samples can be processed in tandem using a single 6 well plate. (3 Precisely fitting lids prevent solution evaporation and condensation, even at high temperatures for an extended period of time: i.e., overnight riboprobe hybridization. (4 Flat bottom mesh maximizes the consistent treatment of individual tissue samples. (5 A magnet-based lifter was created to handle up to 6 chambers (= 36 samples in unison. (6 The largely transparent resin aids in convenient visual inspection both with eyes and using a stereomicroscope. (7 Surface engraved labeling enables an accurate tracking of different samples. (8 The dimension of wells and chambers minimizes the required amount of precious reagents. (9 Flexible parametric modeling enables an easy redesign of the 3D models to handle larger or more numerous samples. Precise dimensions of 3D models and demonstration of how we use our devices in whole mount in situ hybridization are presented. We also provide detailed information on the modeling software, 3D printing tips, as well as 3D files that can be used with any 3D printer.

  4. Bioprinting of a mechanically enhanced three-dimensional dual cell-laden construct for osteochondral tissue engineering using a multi-head tissue/organ building system

    International Nuclear Information System (INIS)

    Shim, Jin-Hyung; Lee, Jung-Seob; Cho, Dong-Woo; Kim, Jong Young

    2012-01-01

    The aim of this study was to build a mechanically enhanced three-dimensional (3D) bioprinted construct containing two different cell types for osteochondral tissue regeneration. Recently, the production of 3D cell-laden structures using various scaffold-free cell printing technologies has opened up new possibilities. However, ideal 3D complex tissues or organs have not yet been printed because gel-state hydrogels have been used as the principal material and are unable to maintain the desired 3D structure due to their poor mechanical strength. In this study, thermoplastic biomaterial polycaprolactone (PCL), which shows relatively high mechanical properties as compared with hydrogel, was used as a framework for enhancing the mechanical stability of the bioprinted construct. Two different alginate solutions were then infused into the previously prepared framework consisting of PCL to create the 3D construct for osteochondral printing. For this work, a multi-head tissue/organ building system (MtoBS), which was particularly designed to dispense thermoplastic biomaterial and hydrogel having completely different rheology properties, was newly developed and used to bioprint osteochondral tissue. It was confirmed that the line width, position and volume control of PCL and alginate solutions were adjustable in the MtoBS. Most importantly, dual cell-laden 3D constructs consisting of osteoblasts and chondrocytes were successfully fabricated. Further, the separately dispensed osteoblasts and chondrocytes not only retained their initial position and viability, but also proliferated up to 7 days after being dispensed. (paper)

  5. Bioprinting of a mechanically enhanced three-dimensional dual cell-laden construct for osteochondral tissue engineering using a multi-head tissue/organ building system

    Science.gov (United States)

    Shim, Jin-Hyung; Lee, Jung-Seob; Kim, Jong Young; Cho, Dong-Woo

    2012-08-01

    The aim of this study was to build a mechanically enhanced three-dimensional (3D) bioprinted construct containing two different cell types for osteochondral tissue regeneration. Recently, the production of 3D cell-laden structures using various scaffold-free cell printing technologies has opened up new possibilities. However, ideal 3D complex tissues or organs have not yet been printed because gel-state hydrogels have been used as the principal material and are unable to maintain the desired 3D structure due to their poor mechanical strength. In this study, thermoplastic biomaterial polycaprolactone (PCL), which shows relatively high mechanical properties as compared with hydrogel, was used as a framework for enhancing the mechanical stability of the bioprinted construct. Two different alginate solutions were then infused into the previously prepared framework consisting of PCL to create the 3D construct for osteochondral printing. For this work, a multi-head tissue/organ building system (MtoBS), which was particularly designed to dispense thermoplastic biomaterial and hydrogel having completely different rheology properties, was newly developed and used to bioprint osteochondral tissue. It was confirmed that the line width, position and volume control of PCL and alginate solutions were adjustable in the MtoBS. Most importantly, dual cell-laden 3D constructs consisting of osteoblasts and chondrocytes were successfully fabricated. Further, the separately dispensed osteoblasts and chondrocytes not only retained their initial position and viability, but also proliferated up to 7 days after being dispensed.

  6. Using geographic information systems to identify prospective marketing areas for a special library.

    Science.gov (United States)

    McConnaughy, Rozalynd P; Wilson, Steven P

    2006-05-04

    The Center for Disability Resources (CDR) Library is the largest collection of its kind in the Southeastern United States, consisting of over 5,200 books, videos/DVDs, brochures, and audiotapes covering a variety of disability-related topics, from autism to transition resources. The purpose of the library is to support the information needs of families, faculty, students, staff, and other professionals in South Carolina working with individuals with disabilities. The CDR Library is funded on a yearly basis; therefore, maintaining high usage is crucial. A variety of promotional efforts have been used to attract new patrons to the library. Anyone in South Carolina can check out materials from the library, and most of the patrons use the library remotely by requesting materials, which are then mailed to them. The goal of this project was to identify areas of low geographic usage as a means of identifying locations for future library marketing efforts. Nearly four years worth of library statistics were compiled in a spreadsheet that provided information per county on the number of checkouts, the number of renewals, and the population. Five maps were created using ArcView GIS software to create visual representations of patron checkout and renewal behavior per county. Out of the 46 counties in South Carolina, eight counties never checked out materials from the library. As expected urban areas and counties near the library's physical location have high usage totals. The visual representation of the data made identification of low usage regions easier than using a standalone database with no visual-spatial component. The low usage counties will be the focus of future Center for Disability Resources Library marketing efforts. Due to the impressive visual-spatial representations created with Geographic Information Systems, which more efficiently communicate information than stand-alone database information can, librarians may benefit from the software's use as a

  7. Verification of an interaction model of an ultrasonic oscillatory system with periodontal tissues

    Directory of Open Access Journals (Sweden)

    V. A. Karpuhin

    2014-01-01

    Full Text Available Verification of an interaction model of an ultrasonic oscillatory system with biological tissues which was developed in COMSOL Multiphysics was carried out. It was shown that calculation results in COMSOL Multiphysics obtained using the “Finer” grid (the ratio of the grid step to a minimum transversal section area of the model ≤ 0.3 mm-1 best of all qualitatively and quantitatively corresponded to practical results. The average relative error of the obtained results in comparison with the experimental ones did not exceed 4.0%. Influence of geometrical parameters (thickness of load on electrical admittance of the ultrasonic oscillatory system interacting with biological tissues was investigated. It was shown that increase in thickness of load within the range from 0 to 95 mm led to decrease in calculated values of natural resonance frequency of longitudinal fluctuations and electrical admittance from 26,58 to 26,35 kHz and from 0,86 to 0,44 mS.

  8. The commissioning and acceptance of a commercially manufactured radiotherapy beam tissue compensating filter system

    International Nuclear Information System (INIS)

    Sorell, M.J.; Sorell, G.C.; Nicholls, R.L.

    1990-01-01

    The principles of tissue compensation in radiotherapy and the methods for their implementation on the GE RT/Plan computer are briefly described. The HEK Medizintechnik GmbH Medical Systems Tissue Compensator cutting device is also described, along with the tesing procedure adopted for its commissioning and quality assurance testing of the total system. The HEK machine hardware proved to be well engineered, but there were many deficiencies in the software supplied to interface it to the planning computer. Most errors were fatal to the program producing a compensator but a number of errors allowed the cutter to manufacture shapes which on close inspection turned out to be incorrect. These faults were traced to incorrect algorithms and/or incorrect software implementation. It is stressed that the software errors were entirely the responsibility of HEK and that the GE equipment and software were not deficient in any way. However, the experiences of the Adelaide group suggest that caution should be exercised when purchasing two pieces of interacting equipment from separate suppliers. 2 refs., 1 tab., 4 figs

  9. Identifying Stream/Aquifer Exchange by Temperature Gradient in a Guarani Aquifer System Outcrop Zone

    Science.gov (United States)

    Wendland, E.; Rosa, D. M. S.; Anache, J. A. A.; Lowry, C.; Lin, Y. F. F.

    2017-12-01

    Recharge of the Guarani Aquifer System (GAS) in South America is supposed to occur mainly in the outcrop zones, where the GAS appears as an unconfined aquifer (10% of the 1.2 Million km2 aquifer extension). Previous evaluations of recharge are based essentially on water balance estimates for the whole aquifer area or water table fluctuations in monitoring wells. To gain a more detailed understanding of the recharge mechanisms the present work aimed to study the stream aquifer interaction in a watershed (Ribeirão da Onça) at an outcrop zone. Two Parshall flumes were installed 1.3 km apart for discharge measurement in the stream. Along this distance an optic fiber cable was deployed to identify stretches with gaining and losing behavior. In order to estimate groundwater discharge in specific locations, 8 temperature sticks were set up along the stream reach to measure continuously the vertical temperature gradient. A temperature probe with 4 thermistors was also used to map the shallow streambed temperature gradient manually along the whole distance. The obtained results show a discharge difference of 250 m3/h between both flumes. Since the last significant rainfall (15 mm) in the watershed occurred 3 months ago, this value can be interpreted as the base flow contribution to the stream during the dry season. Given the temperature difference between groundwater ( 24oC) and surface water ( 17oC) the fiber-optic distributed temperature sensing (FO-DTS) allowed the identification of stretches with gaining behavior. Temperature gradients observed at the streambed varied between 0.67 and 14.33 oC/m. The study demonstrated that heat may be used as natural tracer even in tropical conditions, where the groundwater temperature is higher than the surface water temperature during the winter. The obtained results show that the discharge difference between both flumes can not be extrapolated without detailed analysis. Gaining and loosing stretches have to be identified on order

  10. Novel bio-synthetic hybrid materials and coculture systems for musculoskeletal tissue engineering

    Science.gov (United States)

    Lee, Hyeseung Janice

    Tissue Engineering is a truly exciting field of this age, trying to regenerate and repair impaired tissues. Unlike the old artificial implants, tissue engineering aims at making a long-term functional biological replacement. One strategy for such tissue engineering requires the following three components: cells, scaffolds, and soluble factors. Cells are cultured in a three-dimensional (3D) scaffold with medium containing various soluble factors. Once a tissue is developed in vitro, then it is implanted in vivo. The overall goal of this thesis was to develop novel bio-synthetic hybrid scaffolds and coculture system for musculoskeletal tissue engineering. The most abundant cartilage extracellular matrix (ECM) components are collagen and glycosaminoglycan (GAG), which are the natural scaffold for chondrocytes. As two different peptides, collagen mimetic peptide (CMP) and hyaluronic acid binding peptide (HABPep) were previously shown to bind to collagen and hyaluronic acid (HA) of GAG, respectively, it was hypothesized that immobilizing CMP and HABP on 3D scaffold would results in an interaction between ECM components and synthetic scaffolds via peptide-ECM bindings. CMP or HABPep-conjugated photopolymerizable poly(ethylene oxide) diacrylate (PEODA) hydrogels were synthesized and shown to retain encapsulated collagen or HA, respectively. This result supported that conjugated CMP and HABPep can interact with collagen and HA, respectively, and can serve as biological linkers in 3D synthetic hydrogels. When chondrocytes or mesenchymal stem cells (MSCs) were seeded, cells in CMP-conjugated scaffolds produced significantly more amount of type II collagen and GAG, compared to those in control scaffolds. Moreover, MSCs cultured in CMP-conjugated scaffolds exhibited lower level of hypertrophic markers, cbfa-1 and type X collagen. These results demonstrated that enhanced interaction between collagen and scaffold via CMP improves chondrogenesis of chondrocytes and MSCs and

  11. Testing the potential of geochemical techniques for identifying hydrological systems within landslides in partly weathered marls

    Science.gov (United States)

    Bogaard, T. A.; Buma, J. T.; Klawer, C. J. M.

    2004-03-01

    This paper's objective is to determine how useful geochemistry can be in landslide investigations. More specifically, what additional information can be gained by analysing the cation exchange capacity (CEC) and cation composition in respect to the hydrological system of a landslide area in clayey material. Two cores from the Boulc-Mondorès landslide (France) and one core from the Alvera landslide (Italy) were analysed. The NH 4Ac and NaCl laboratory techniques are tested. The geochemical results are compared with the core descriptions and interpreted with respect to their usefulness. Both analysis techniques give identical results for CEC, and are plausible on the basis of the available clay content information. The determination of the exchangeable cations was more difficult, since part of the marls dissolved. With the ammonium-acetate method more of the marls are dissolved than with the sodium-chloride method. The NaCl method is preferred for the determination of the cation fractions at the complex, be it that this method has the disadvantage that the sodium fraction cannot be determined. To overcome this problem, it is recommended to try other displacement fluids. In the Boulc-Mondorès example, the subsurface information that can be extracted from CEC analyses was presented. In the Boulc-Mondorès cores deviant intervals of CEC could be identified. These are interpreted as weathered layers (and preferential flow paths) that may develop or have already developed into slip surfaces. The major problem of the CEC analyses was to explain the origin of the differences found in the core samples. Both Alvera and Boulc-Mondorès examples show transitions in cation composition with depth. It was shown that the exchangeable caution fractions can be useful in locating boundaries between water types, especially the boundary between the superficial, rain-fed hydrological system and the lower, regional groundwater system. This information may be important for landslide

  12. A Bewildering and Dynamic Picture of Exoplanetary Systems Identified by the Kepler Mission (Invited)

    Science.gov (United States)

    Jenkins, J. M.

    2013-12-01

    notion of the habitable zone for single stars and static planetary system configurations. This talk will provide an overview of the science results from the Kepler Mission and the work ahead to derive the frequency of Earth-size planets in the habitable zone of solar-like stars from the treasure trove of Kepler data. NASA's quest for exoplanets continues with the Transiting Exoplanet Survey Satellite (TESS) mission, slated for launch in May 2017 by NASA's Explorer Program. TESS will conduct an all- sky transit survey to identify the 1000 best small exoplanets in the solar neighborhood for follow up observations and characterization. TESS's targets will include all F, G, K dwarfs from +4 to +12 magnitude and all M dwarfs known within ~200 light-years. 500,000 target stars will be observed over two years with ~500 square degrees observed continuously for a year in each hemisphere in the James Webb Space Telescopes continuously viewable zones. Since the typical TESS target star is 5 magnitudes brighter than that of Kepler and 10 times closer, TESS discoveries will afford significant opportunities to measure the masses of the exoplanets and to characterize their atmospheres with JWST, ELTs and other exoplanet explorers. TESS' discoveries will raise new questions regarding habitability that will be open to investigation through active efforts to characterize their atmospheres and search for biomarkers. Funding for this mission is provided by NASA's Science Mission Directorate.

  13. Identifying novel glioma associated pathways based on systems biology level meta-analysis.

    Science.gov (United States)

    Hu, Yangfan; Li, Jinquan; Yan, Wenying; Chen, Jiajia; Li, Yin; Hu, Guang; Shen, Bairong

    2013-01-01

    With recent advances in microarray technology, including genomics, proteomics, and metabolomics, it brings a great challenge for integrating this "-omics" data to analysis complex disease. Glioma is an extremely aggressive and lethal form of brain tumor, and thus the study of the molecule mechanism underlying glioma remains very important. To date, most studies focus on detecting the differentially expressed genes in glioma. However, the meta-analysis for pathway analysis based on multiple microarray datasets has not been systematically pursued. In this study, we therefore developed a systems biology based approach by integrating three types of omics data to identify common pathways in glioma. Firstly, the meta-analysis has been performed to study the overlapping of signatures at different levels based on the microarray gene expression data of glioma. Among these gene expression datasets, 12 pathways were found in GeneGO database that shared by four stages. Then, microRNA expression profiles and ChIP-seq data were integrated for the further pathway enrichment analysis. As a result, we suggest 5 of these pathways could be served as putative pathways in glioma. Among them, the pathway of TGF-beta-dependent induction of EMT via SMAD is of particular importance. Our results demonstrate that the meta-analysis based on systems biology level provide a more useful approach to study the molecule mechanism of complex disease. The integration of different types of omics data, including gene expression microarrays, microRNA and ChIP-seq data, suggest some common pathways correlated with glioma. These findings will offer useful potential candidates for targeted therapeutic intervention of glioma.

  14. Seeing through Musculoskeletal Tissues: Improving In Situ Imaging of Bone and the Lacunar Canalicular System through Optical Clearing

    Science.gov (United States)

    Berke, Ian M.; Miola, Joseph P.; David, Michael A.; Smith, Melanie K.; Price, Christopher

    2016-01-01

    In situ, cells of the musculoskeletal system reside within complex and often interconnected 3-D environments. Key to better understanding how 3-D tissue and cellular environments regulate musculoskeletal physiology, homeostasis, and health is the use of robust methodologies for directly visualizing cell-cell and cell-matrix architecture in situ. However, the use of standard optical imaging techniques is often of limited utility in deep imaging of intact musculoskeletal tissues due to the highly scattering nature of biological tissues. Drawing inspiration from recent developments in the deep-tissue imaging field, we describe the application of immersion based optical clearing techniques, which utilize the principle of refractive index (RI) matching between the clearing/mounting media and tissue under observation, to improve the deep, in situ imaging of musculoskeletal tissues. To date, few optical clearing techniques have been applied specifically to musculoskeletal tissues, and a systematic comparison of the clearing ability of optical clearing agents in musculoskeletal tissues has yet to be fully demonstrated. In this study we tested the ability of eight different aqueous and non-aqueous clearing agents, with RIs ranging from 1.45 to 1.56, to optically clear murine knee joints and cortical bone. We demonstrated and quantified the ability of these optical clearing agents to clear musculoskeletal tissues and improve both macro- and micro-scale imaging of musculoskeletal tissue across several imaging modalities (stereomicroscopy, spectroscopy, and one-, and two-photon confocal microscopy) and investigational techniques (dynamic bone labeling and en bloc tissue staining). Based upon these findings we believe that optical clearing, in combination with advanced imaging techniques, has the potential to complement classical musculoskeletal analysis techniques; opening the door for improved in situ investigation and quantification of musculoskeletal tissues. PMID:26930293

  15. Seeing through Musculoskeletal Tissues: Improving In Situ Imaging of Bone and the Lacunar Canalicular System through Optical Clearing.

    Directory of Open Access Journals (Sweden)

    Ian M Berke

    Full Text Available In situ, cells of the musculoskeletal system reside within complex and often interconnected 3-D environments. Key to better understanding how 3-D tissue and cellular environments regulate musculoskeletal physiology, homeostasis, and health is the use of robust methodologies for directly visualizing cell-cell and cell-matrix architecture in situ. However, the use of standard optical imaging techniques is often of limited utility in deep imaging of intact musculoskeletal tissues due to the highly scattering nature of biological tissues. Drawing inspiration from recent developments in the deep-tissue imaging field, we describe the application of immersion based optical clearing techniques, which utilize the principle of refractive index (RI matching between the clearing/mounting media and tissue under observation, to improve the deep, in situ imaging of musculoskeletal tissues. To date, few optical clearing techniques have been applied specifically to musculoskeletal tissues, and a systematic comparison of the clearing ability of optical clearing agents in musculoskeletal tissues has yet to be fully demonstrated. In this study we tested the ability of eight different aqueous and non-aqueous clearing agents, with RIs ranging from 1.45 to 1.56, to optically clear murine knee joints and cortical bone. We demonstrated and quantified the ability of these optical clearing agents to clear musculoskeletal tissues and improve both macro- and micro-scale imaging of musculoskeletal tissue across several imaging modalities (stereomicroscopy, spectroscopy, and one-, and two-photon confocal microscopy and investigational techniques (dynamic bone labeling and en bloc tissue staining. Based upon these findings we believe that optical clearing, in combination with advanced imaging techniques, has the potential to complement classical musculoskeletal analysis techniques; opening the door for improved in situ investigation and quantification of musculoskeletal

  16. Computerized Adaptive Test vs. decision trees: Development of a support decision system to identify suicidal behavior.

    Science.gov (United States)

    Delgado-Gomez, D; Baca-Garcia, E; Aguado, D; Courtet, P; Lopez-Castroman, J

    2016-12-01

    Several Computerized Adaptive Tests (CATs) have been proposed to facilitate assessments in mental health. These tests are built in a standard way, disregarding useful and usually available information not included in the assessment scales that could increase the precision and utility of CATs, such as the history of suicide attempts. Using the items of a previously developed scale for suicidal risk, we compared the performance of a standard CAT and a decision tree in a support decision system to identify suicidal behavior. We included the history of past suicide attempts as a class for the separation of patients in the decision tree. The decision tree needed an average of four items to achieve a similar accuracy than a standard CAT with nine items. The accuracy of the decision tree, obtained after 25 cross-validations, was 81.4%. A shortened test adapted for the separation of suicidal and non-suicidal patients was developed. CATs can be very useful tools for the assessment of suicidal risk. However, standard CATs do not use all the information that is available. A decision tree can improve the precision of the assessment since they are constructed using a priori information. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Identifying bubble collapse in a hydrothermal system using hidden Markov models

    Science.gov (United States)

    Dawson, P.B.; Benitez, M.C.; Lowenstern, J. B.; Chouet, B.A.

    2012-01-01

    Beginning in July 2003 and lasting through September 2003, the Norris Geyser Basin in Yellowstone National Park exhibited an unusual increase in ground temperature and hydrothermal activity. Using hidden Markov model theory, we identify over five million high-frequency (>15Hz) seismic events observed at a temporary seismic station deployed in the basin in response to the increase in hydrothermal activity. The source of these seismic events is constrained to within ???100 m of the station, and produced ???3500-5500 events per hour with mean durations of ???0.35-0.45s. The seismic event rate, air temperature, hydrologic temperatures, and surficial water flow of the geyser basin exhibited a marked diurnal pattern that was closely associated with solar thermal radiance. We interpret the source of the seismicity to be due to the collapse of small steam bubbles in the hydrothermal system, with the rate of collapse being controlled by surficial temperatures and daytime evaporation rates. copyright 2012 by the American Geophysical Union.

  18. Structural magnetic resonance imaging can identify trigeminal system abnormalities in classical trigeminal neuralgia

    Directory of Open Access Journals (Sweden)

    Danielle DeSouza

    2016-10-01

    Full Text Available Classical trigeminal neuralgia (TN is a chronic pain disorder that has been described as one ofthe most severe pains one can suffer. The most prevalent theory of TN etiology is that the trigeminal nerve is compressed at the root entry zone (REZ by blood vessels. However, there is significant evidence showing a lack of neurovascular compression (NVC for many cases of classical TN. Furthermore, a considerable number of patients who are asymptomatic have MR evidence of NVC. Since there is no validated animal model that reproduces the clinical features of TN, our understanding of TN pathology mainly comes from biopsy studies that have limitations. Sophisticated structural MRI techniques including diffusion tensor imaging provide new opportunities to assess the trigeminal nerves and CNS to provide insight into TN etiology and pathogenesis. Specifically, studies have used high-resolution structural MRI methods to visualize patterns of trigeminal nerve-vessel relationships and to detect subtle pathological features at the trigeminal REZ. Structural MRI has also identified CNS abnormalities in cortical and subcortical gray matter and white matter and demonstrated that effective neurosurgical treatment for TN is associated with a reversal of specific nerve and brain abnormalities. In conclusion, this review highlights the advanced structural neuroimaging methods that are valuable tools to assess the trigeminal system in TN and may inform our current understanding of TN pathology. These methods may in the future have clinical utility for the development of neuroimaging-based biomarkers of TN.

  19. Identifying N fertilizer regime and vegetable production system in tropical Brazil using (15) N natural abundance.

    Science.gov (United States)

    Inácio, Caio T; Urquiaga, Segundo; Chalk, Phillip M; Mata, Maria Gabriela F; Souza, Paulo O

    2015-12-01

    This study was conducted in areas of vegetable production in tropical Brazil, with the objectives of (i) measuring the variation in δ(15)  N in soils, organic N fertilizer sources and lettuce (Lactuca sativa L.) from different farming systems, (ii) measuring whether plant δ(15)  N can differentiate organic versus conventional lettuce and (iii) identifying the factors affecting lettuce δ(15)  N. Samples of soil, lettuce and organic inputs were taken from two organic, one conventional and one hydroponic farm. The two organic farms had different N-sources with δ(15)  N values ranging from 0.0 to +14.9‰ (e.g. leguminous green manure and animal manure compost, respectively), and differed significantly (P hydroponic lettuce δ(15)  N (+4.5 ± 0.2‰) due to manure inputs. The N from leguminous green manure made a small contribution to the N nutrition of lettuce in the multi-N-source organic farm. To differentiate organic versus conventional farms using δ(15)  N the several subsets of mode of fertilization should be considered. Comparisons of δ(15)  N of soil, organic inputs and lettuce allowed a qualitative analysis of the relative importance of different N inputs. © 2015 Society of Chemical Industry.

  20. A systems approach identifies networks and genes linking sleep and stress: implications for neuropsychiatric disorders.

    Science.gov (United States)

    Jiang, Peng; Scarpa, Joseph R; Fitzpatrick, Karrie; Losic, Bojan; Gao, Vance D; Hao, Ke; Summa, Keith C; Yang, He S; Zhang, Bin; Allada, Ravi; Vitaterna, Martha H; Turek, Fred W; Kasarskis, Andrew

    2015-05-05

    Sleep dysfunction and stress susceptibility are comorbid complex traits that often precede and predispose patients to a variety of neuropsychiatric diseases. Here, we demonstrate multilevel organizations of genetic landscape, candidate genes, and molecular networks associated with 328 stress and sleep traits in a chronically stressed population of 338 (C57BL/6J × A/J) F2 mice. We constructed striatal gene co-expression networks, revealing functionally and cell-type-specific gene co-regulations important for stress and sleep. Using a composite ranking system, we identified network modules most relevant for 15 independent phenotypic categories, highlighting a mitochondria/synaptic module that links sleep and stress. The key network regulators of this module are overrepresented with genes implicated in neuropsychiatric diseases. Our work suggests that the interplay among sleep, stress, and neuropathology emerges from genetic influences on gene expression and their collective organization through complex molecular networks, providing a framework for interrogating the mechanisms underlying sleep, stress susceptibility, and related neuropsychiatric disorders. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  1. Identifying Opportunities for Exploiting Cross-Layer Interactions in Adaptive Wireless Systems

    Directory of Open Access Journals (Sweden)

    Troy Weingart

    2007-01-01

    Full Text Available The flexibility of cognitive and software-defined radio heralds an opportunity for researchers to reexamine how network protocol layers operate with respect to providing quality of service aware transmission among wireless nodes. This opportunity is enhanced by the continued development of spectrally responsive devices—ones that can detect and respond to changes in the radio frequency environment. Present wireless network protocols define reliability and other performance-related tasks narrowly within layers. For example, the frame size employed on 802.11 can substantially influence the throughput, delay, and jitter experienced by an application, but there is no simple way to adapt this parameter. Furthermore, while the data link layer of 802.11 provides error detection capabilities across a link, it does not specify additional features, such as forward error correction schemes, nor does it provide a means for throttling retransmissions at the transport layer (currently, the data link and transport layer can function counterproductively with respect to reliability. This paper presents an analysis of the interaction of physical, data link, and network layer parameters with respect to throughput, bit error rate, delay, and jitter. The goal of this analysis is to identify opportunities where system designers might exploit cross-layer interactions to improve the performance of Voice over IP (VoIP, instant messaging (IM, and file transfer applications.

  2. Portable fluorescence lifetime spectroscopy system for in-situ interrogation of biological tissues

    Science.gov (United States)

    Saito Nogueira, Marcelo; Cosci, Alessandro; Teixeira Rosa, Ramon Gabriel; Salvio, Ana Gabriela; Pratavieira, Sebastião; Kurachi, Cristina

    2017-12-01

    Fluorescence spectroscopy and lifetime techniques are potential methods for optical diagnosis and characterization of biological tissues with an in-situ, fast, and noninvasive interrogation. Several diseases may be diagnosed due to differences in the fluorescence spectra of targeted fluorophores, when, these spectra are similar, considering steady-state fluorescence, others may be detected by monitoring their fluorescence lifetime. Despite this complementarity, most of the current fluorescence lifetime systems are not robust and portable, and not being feasible for clinical applications. We describe the assembly of a fluorescence lifetime spectroscopy system in a suitcase, its characterization, and validation with clinical measurements of skin lesions. The assembled system is all encased and robust, maintaining its mechanical, electrical, and optical stability during transportation, and is feasible for clinical measurements. The instrument response function measured was about 300 ps, and the system is properly calibrated. At the clinical study, the system showed to be reliable, and the achieved spectroscopy results support its potential use as an auxiliary tool for skin diagnostics.

  3. A Bioactive Hydrogel and 3D Printed Polycaprolactone System for Bone Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Ivan Hernandez

    2017-07-01

    Full Text Available In this study, a hybrid system consisting of 3D printed polycaprolactone (PCL filled with hydrogel was developed as an application for reconstruction of long bone defects, which are innately difficult to repair due to large missing segments of bone. A 3D printed gyroid scaffold of PCL allowed a larger amount of hydrogel to be loaded within the scaffolds as compared to 3D printed mesh and honeycomb scaffolds of similar volumes and strut thicknesses. The hydrogel was a mixture of alginate, gelatin, and nano-hydroxyapatite, infiltrated with human mesenchymal stem cells (hMSC to enhance the osteoconductivity and biocompatibility of the system. Adhesion and viability of hMSC in the PCL/hydrogel system confirmed its cytocompatibility. Biomineralization tests in simulated body fluid (SBF showed the nucleation and growth of apatite crystals, which confirmed the bioactivity of the PCL/hydrogel system. Moreover, dissolution studies, in SBF revealed a sustained dissolution of the hydrogel with time. Overall, the present study provides a new approach in bone tissue engineering to repair bone defects with a bioactive hybrid system consisting of a polymeric scaffold, hydrogel, and hMSC.

  4. A Bioactive Hydrogel and 3D Printed Polycaprolactone System for Bone Tissue Engineering.

    Science.gov (United States)

    Hernandez, Ivan; Kumar, Alok; Joddar, Binata

    2017-09-01

    In this study, a hybrid system consisting of 3D printed polycaprolactone (PCL) filled with hydrogel was developed as an application for reconstruction of long bone defects, which are innately difficult to repair due to large missing segments of bone. A 3D printed gyroid scaffold of PCL allowed a larger amount of hydrogel to be loaded within the scaffolds as compared to 3D printed mesh and honeycomb scaffolds of similar volumes and strut thicknesses. The hydrogel was a mixture of alginate, gelatin, and nano-hydroxyapatite, infiltrated with human mesenchymal stem cells (hMSC) to enhance the osteoconductivity and biocompatibility of the system. Adhesion and viability of hMSC in the PCL/hydrogel system confirmed its cytocompatibility. Biomineralization tests in simulated body fluid (SBF) showed the nucleation and growth of apatite crystals, which confirmed the bioactivity of the PCL/hydrogel system. Moreover, dissolution studies, in SBF revealed a sustained dissolution of the hydrogel with time. Overall, the present study provides a new approach in bone tissue engineering to repair bone defects with a bioactive hybrid system consisting of a polymeric scaffold, hydrogel, and hMSC.

  5. Portable fluorescence lifetime spectroscopy system for in-situ interrogation of biological tissues.

    Science.gov (United States)

    Saito Nogueira, Marcelo; Cosci, Alessandro; Teixeira Rosa, Ramon Gabriel; Salvio, Ana Gabriela; Pratavieira, Sebastião; Kurachi, Cristina

    2017-10-01

    Fluorescence spectroscopy and lifetime techniques are potential methods for optical diagnosis and characterization of biological tissues with an in-situ, fast, and noninvasive interrogation. Several diseases may be diagnosed due to differences in the fluorescence spectra of targeted fluorophores, when, these spectra are similar, considering steady-state fluorescence, others may be detected by monitoring their fluorescence lifetime. Despite this complementarity, most of the current fluorescence lifetime systems are not robust and portable, and not being feasible for clinical applications. We describe the assembly of a fluorescence lifetime spectroscopy system in a suitcase, its characterization, and validation with clinical measurements of skin lesions. The assembled system is all encased and robust, maintaining its mechanical, electrical, and optical stability during transportation, and is feasible for clinical measurements. The instrument response function measured was about 300 ps, and the system is properly calibrated. At the clinical study, the system showed to be reliable, and the achieved spectroscopy results support its potential use as an auxiliary tool for skin diagnostics. (2017) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE).

  6. Bioreactor systems for tissue engineering II. Strategies for the expansion and directed differentiation of stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Kasper, Cornelia [Hannover Univ. (Germany). Inst. fuer Technische Chemie; Griensven, Martijn van [Ludwig Boltzmann Institut fuer Klinische und Experimentelle Traumatologie, Wien (Austria); Poertner, Ralf (eds.) [Technische Univ. Hamburg-Harburg (Germany). Inst. Biotechnologie und Verfahrenstechnik

    2010-07-01

    Alternative Sources of Adult Stem Cells: Human Amniotic Membrane, by S. Wolbank, M. van Griensven, R. Grillari-Voglauer, and A. Peterbauer-Scherb; - Mesenchymal Stromal Cells Derived from Human Umbilical Cord Tissues: Primitive Cells with Potential for Clinical and Tissue Engineering Applications, by P. Moretti, T. Hatlapatka, D. Marten, A. Lavrentieva, I. Majore, R. Hass and C. Kasper; - Isolation, Characterization, Differentiation, and Application of Adipose-Derived Stem Cells, by J. W. Kuhbier, B. Weyand, C. Radtke, P. M. Vogt, C. Kasper and K. Reimers; - Induced Pluripotent Stem Cells: Characteristics and Perspectives, by T. Cantz and U. Martin; - Induced Pluripotent Stem Cell Technology in Regenerative Medicine and Biology, by D. Pei, J. Xu, Q. Zhuang, H.-F. Tse and M. A. Esteban; - Production Process for Stem Cell Based Therapeutic Implants: Expansion of the Production Cell Line and Cultivation of Encapsulated Cells, by C. Weber, S. Pohl, R. Poertner, P. Pino-Grace, D. Freimark, C. Wallrapp, P. Geigle and P. Czermak; - Cartilage Engineering from Mesenchymal Stem Cells, by C. Goepfert, A. Slobodianski, A.F. Schilling, P. Adamietz and R. Poertner; - Outgrowth Endothelial Cells: Sources, Characteristics and Potential Applications in Tissue Engineering and Regenerative Medicine, by S. Fuchs, E. Dohle, M. Kolbe, C. J. Kirkpatrick; - Basic Science and Clinical Application of Stem Cells in Veterinary Medicine, by I. Ribitsch, J. Burk, U. Delling, C. Geissler, C. Gittel, H. Juelke, W. Brehm; - Bone Marrow Stem Cells in Clinical Application: Harnessing Paracrine Roles and Niche Mechanisms, by R. M. El Backly, R. Cancedda; - Clinical Application of Stem Cells in the Cardiovascular System, C. Stamm, K. Klose, Y.-H. Choi. (orig.)

  7. A review of decellularized stem cell matrix: a novel cell expansion system for cartilage tissue engineering

    Directory of Open Access Journals (Sweden)

    M Pei

    2011-11-01

    Full Text Available Cell-based therapy is a promising biological approach for the treatment of cartilage defects. Due to the small size of autologous cartilage samples available for cell transplantation in patients, cells need to be expanded to yield a sufficient cell number for cartilage repair. However, chondrocytes and adult stem cells tend to become replicatively senescent once they are expanded on conventional plastic flasks. Many studies demonstrate that the loss of cell properties is concomitant with the decreased cell proliferation capacity. This is a significant challenge for cartilage tissue engineering and regeneration. Despite much progress having been made in cell expansion, there are still concerns over expanded cell size and quality for cell transplantation applications. Recently, in vivo investigations in stem cell niches have suggested the importance of developing an in vitro stem cell microenvironment for cell expansion and tissue-specific differentiation. Our and other investigators’ work indicates that a decellularized stem cell matrix (DSCM may provide such an expansion system to yield large-quantity and high-quality cells for cartilage tissue engineering and regeneration. This review briefly introduces key parameters in an in vivo stem cell niche and focuses on our recent work on DSCM for its rejuvenating or reprograming effect on various adult stem cells and chondrocytes. Since research in DSCM is still in its infancy, we are only able to discuss some potential mechanisms of DSCM on cell proliferation and chondrogenic potential. Further investigations of the underlying mechanism and in vivo regeneration capacity will allow this approach to be used in clinics.

  8. Creating Interactions between Tissue-Engineered Skeletal Muscle and the Peripheral Nervous System.

    Science.gov (United States)

    Smith, Alec S T; Passey, Samantha L; Martin, Neil R W; Player, Darren J; Mudera, Vivek; Greensmith, Linda; Lewis, Mark P

    2016-01-01

    Effective models of mammalian tissues must allow and encourage physiologically (mimetic) correct interactions between co-cultured cell types in order to produce culture microenvironments as similar as possible to those that would normally occur in vivo. In the case of skeletal muscle, the development of such a culture model, integrating multiple relevant cell types within a biomimetic scaffold, would be of significant benefit for investigations into the development, functional performance, and pathophysiology of skeletal muscle tissue. Although some work has been published regarding the behaviour of in vitro muscle models co-cultured with organotypic slices of CNS tissue or with stem cell-derived neurospheres, little investigation has so far been made regarding the potential to maintain isolated motor neurons within a 3D biomimetic skeletal muscle culture platform. Here, we review the current state of the art for engineering neuromuscular contacts in vitro and provide original data detailing the development of a 3D collagen-based model for the co-culture of primary muscle cells and motor neurons. The devised culture system promotes increased myoblast differentiation, forming arrays of parallel, aligned myotubes on which areas of nerve-muscle contact can be detected by immunostaining for pre- and post-synaptic proteins. Quantitative RT-PCR results indicate that motor neuron presence has a positive effect on myotube maturation, suggesting neural incorporation influences muscle development and maturation in vitro. The importance of this work is discussed in relation to other published neuromuscular co-culture platforms along with possible future directions for the field. © 2016 S. Karger AG, Basel.

  9. A novel bioprinting method and system for forming hybrid tissue engineering constructs.

    Science.gov (United States)

    Shanjani, Y; Pan, C C; Elomaa, L; Yang, Y

    2015-12-18

    Three dimensional (3D) bioprinting is a promising approach to form tissue engineering constructs (TECs) via positioning biomaterials, growth factors, and cells with controlled spatial distribution due to its layer-by-layer manufacturing nature. Hybrid TECs composed of relatively rigid porous scaffolds for structural and mechanical integrity and soft hydrogels for cell- and growth factor-loading have a tremendous potential to tissue regeneration under mechanical loading. However, despite excessive progress in the field, the current 3D bioprinting techniques and systems fall short in integration of such soft and rigid multifunctional components. Here we present a novel 3D hybrid bioprinting technology (Hybprinter) and its capability enabling integration of soft and rigid components for TECs. Hybprinter employs digital light processing-based stereolithography (DLP-SLA) and molten material extrusion techniques for soft and rigid materials, respectively. In this study, poly-ethylene glycol diacrylate (PEGDA) and poly-(ε-caprolactone) (PCL) were used as a model material for soft hydrogel and rigid scaffold, respectively. It was shown that geometrical accuracy, swelling ratio and mechanical properties of the hydrogel component can be tailored by DLP-SLA module. We have demonstrated the printability of variety of complex hybrid construct designs using Hybprinter technology and characterized the mechanical properties and functionality of such constructs. The compressive mechanical stiffness of a hybrid construct (90% hydrogel) was significantly higher than hydrogel itself (∼6 MPa versus 100 kPa). In addition, viability of cells incorporated within the bioprinted hybrid constructs was determined approximately 90%. Furthermore, a functionality of a hybrid construct composed of porous scaffold with an embedded hydrogel conduit was characterized for vascularized tissue engineering applications. High material diffusion and high cell viability in about 2.5 mm distance

  10. Fluorescence excitation analysis by two-photon confocal laser scanning microscopy: a new method to identify fluorescent nanoparticles on histological tissue sections

    Directory of Open Access Journals (Sweden)

    Kahn E

    2012-10-01

    Full Text Available Edmond Kahn,1 Nicolas Tissot,3 Perrine Frere,3 Aurélien Dauphin,3 Mohamed Boumhras,2,4 Claude-Marie Bachelet,3 Frédérique Frouin,1 Gérard Lizard21Institut National de la Santé et de la Recherche Médicale (INSERM U678/UMR-S UPMC, CHU Pitié-Salpêtrière, Paris, France; 2Equipe Biochimie du Peroxysome, Inflammation et Métabolisme Lipidique EA7270, Faculté des Sciences Gabriel, Université de Bourgogne-INSERM Dijon, France; 3Plateforme d'Imagerie cellulaire, UPMC, Paris, France; 4Laboratory of Biochemistry and Neuroscience, Applied Toxicology Group, Faculty of Science and Technology, Settat, MoroccoAbstract: In the present study, we make use of the ability of two-photon confocal laser scanning microscopes (CLSMs equipped with tunable lasers to produce spectral excitation image sequences. Furthermore, unmixing, which is usually performed on emission image sequences, is performed on these excitation image sequences. We use factor analysis of medical image sequences (FAMIS, which produces factor images, to unmix spectral image sequences of stained structures in tissue sections to provide images of characterized stained cellular structures. This new approach is applied to histological tissue sections of mouse aorta containing labeled iron nanoparticles stained with Texas Red and counterstained with SYTO13, to obtain visual information about the accumulation of these nanoparticles in the arterial wall. The possible presence of Texas Red is determined using a two-photon CLSM associated with FAMIS via the excitation spectra. Texas Red and SYTO13 are thus differentiated, and corresponding factor images specify their possible presence and cellular localization. In conclusion, the designed protocol shows that sequences of images obtained by excitation in a two-photon CLSM enables characterization of Texas Red-stained nanoparticles and other markers. This methodology offers an alternative and complementary solution to the conventional use of emission

  11. Identifying problems and generating recommendations for enhancing complex systems: applying the abstraction hierarchy framework as an analytical tool.

    Science.gov (United States)

    Xu, Wei

    2007-12-01

    This study adopts J. Rasmussen's (1985) abstraction hierarchy (AH) framework as an analytical tool to identify problems and pinpoint opportunities to enhance complex systems. The process of identifying problems and generating recommendations for complex systems using conventional methods is usually conducted based on incompletely defined work requirements. As the complexity of systems rises, the sheer mass of data generated from these methods becomes unwieldy to manage in a coherent, systematic form for analysis. There is little known work on adopting a broader perspective to fill these gaps. AH was used to analyze an aircraft-automation system in order to further identify breakdowns in pilot-automation interactions. Four steps follow: developing an AH model for the system, mapping the data generated by various methods onto the AH, identifying problems based on the mapped data, and presenting recommendations. The breakdowns lay primarily with automation operations that were more goal directed. Identified root causes include incomplete knowledge content and ineffective knowledge structure in pilots' mental models, lack of effective higher-order functional domain information displayed in the interface, and lack of sufficient automation procedures for pilots to effectively cope with unfamiliar situations. The AH is a valuable analytical tool to systematically identify problems and suggest opportunities for enhancing complex systems. It helps further examine the automation awareness problems and identify improvement areas from a work domain perspective. Applications include the identification of problems and generation of recommendations for complex systems as well as specific recommendations regarding pilot training, flight deck interfaces, and automation procedures.

  12. Experimental concepts for toxicity prevention and tissue restoration after central nervous system irradiation

    Directory of Open Access Journals (Sweden)

    Astner Sabrina T

    2007-06-01

    Full Text Available Abstract Several experimental strategies of radiation-induced central nervous system toxicity prevention have recently resulted in encouraging data. The present review summarizes the background for this research and the treatment results. It extends to the perspectives of tissue regeneration strategies, based for example on stem and progenitor cells. Preliminary data suggest a scenario with individually tailored strategies where patients with certain types of comorbidity, resulting in impaired regeneration reserve capacity, might be considered for toxicity prevention, while others might be "salvaged" by delayed interventions that circumvent the problem of normal tissue specificity. Given the complexity of radiation-induced changes, single target interventions might not suffice. Future interventions might vary with patient age, elapsed time from radiotherapy and toxicity type. Potential components include several drugs that interact with neurodegeneration, cell transplantation (into the CNS itself, the blood stream, or both and creation of reparative signals and a permissive microenvironment, e.g., for cell homing. Without manipulation of the stem cell niche either by cell transfection or addition of appropriate chemokines and growth factors and by providing normal perfusion of the affected region, durable success of such cell-based approaches is hard to imagine.

  13. Bioreactor perfusion system for the long-term maintenance of tissue-engineered skeletal muscle organoids

    Science.gov (United States)

    Chromiak, J. A.; Shansky, J.; Perrone, C.; Vandenburgh, H. H.

    1998-01-01

    Three-dimensional skeletal muscle organ-like structures (organoids) formed in tissue culture by fusion of proliferating myoblasts into parallel networks of long, unbranched myofibers provide an in vivo-like model for examining the effects of growth factors, tension, and space flight on muscle cell growth and metabolism. To determine the feasibility of maintaining either avian or mammalian muscle organoids in a commercial perfusion bioreactor system, we measured metabolism, protein turnover. and autocrine/paracrine growth factor release rates. Medium glucose was metabolized at a constant rate in both low-serum- and serum-free media for up to 30 d. Total organoid noncollagenous protein and DNA content decreased approximately 22-28% (P skeletal muscle growth factors prostaglandin F2alpha (PGF2alpha) and insulin-like growth factor-1 (IGF-1) could be measured accurately in collected media fractions, even after storage at 37 degrees C for up to 10 d. In contrast, creatine kinase activity (a marker of cell damage) in collected media fractions was unreliable. These results provide initial benchmarks for long-term ex vivo studies of tissue-engineered skeletal muscle.

  14. Establishment of an In Vitro System Representing the Chicken Gut-Associated Lymphoid Tissue

    Science.gov (United States)

    Alitheen, Noorjahan Banu; McClure, Susan Jane; Yeap, Swee Keong; Kristeen-Teo, Ye Wen; Tan, Sheau Wei; McCullagh, Peter

    2012-01-01

    The bursa of Fabricius is critical for B cell development and differentiation in chick embryos. This study describes the production in vitro, from dissociated cell suspensions, of cellular agglomerates with functional similarities to the chicken bursa. Co-cultivation of epithelial and lymphoid cells obtained from embryos at the appropriate developmental stage regularly led to agglomerate formation within 48 hours. These agglomerates resembled bursal tissue in having lymphoid clusters overlaid by well organized epithelium. Whereas lymphocytes within agglomerates were predominantly Bu-1a+, a majority of those emigrating onto the supporting membrane were Bu-1a− and IgM+. Both agglomerates and emigrant cells expressed activation-induced deaminase with levels increasing after 24 hours. Emigrating cells were actively proliferating at a rate in excess of both the starting cell population and the population of cells remaining in agglomerates. The potential usefulness of this system for investigating the response of bursal tissue to avian Newcastle disease virus (strain AF2240) was examined. PMID:23185307

  15. Establishment of an in vitro system representing the chicken gut-associated lymphoid tissue.

    Directory of Open Access Journals (Sweden)

    Noorjahan Banu Alitheen

    Full Text Available The bursa of Fabricius is critical for B cell development and differentiation in chick embryos. This study describes the production in vitro, from dissociated cell suspensions, of cellular agglomerates with functional similarities to the chicken bursa. Co-cultivation of epithelial and lymphoid cells obtained from embryos at the appropriate developmental stage regularly led to agglomerate formation within 48 hours. These agglomerates resembled bursal tissue in having lymphoid clusters overlaid by well organized epithelium. Whereas lymphocytes within agglomerates were predominantly Bu-1a(+, a majority of those emigrating onto the supporting membrane were Bu-1a(- and IgM(+. Both agglomerates and emigrant cells expressed activation-induced deaminase with levels increasing after 24 hours. Emigrating cells were actively proliferating at a rate in excess of both the starting cell population and the population of cells remaining in agglomerates. The potential usefulness of this system for investigating the response of bursal tissue to avian Newcastle disease virus (strain AF2240 was examined.

  16. Choice of Illumination System & Fluorophore for Multiplex Immunofluorescence on FFPE Tissue Sections.

    Directory of Open Access Journals (Sweden)

    Sandrine Prost

    Full Text Available The recent availability of novel dyes and alternative light sources to facilitate complex tissue immunofluorescence studies such as multiplex labelling has not been matched by reports critically evaluating the considerations and relative benefits of these new tools, particularly in combination. Product information is often limited to wavelengths used for older fluorophores (FITC, TRITC & corresponding Alexa dyes family. Consequently, novel agents such as Quantum dots are not widely appreciated or used, despite highly favourable properties including extremely bright emission, stability and potentially reduced tissue autofluorescence at the excitation wavelength. Using spectral analysis, we report here a detailed critical appraisal and comparative evaluation of different light sources and fluorophores in multiplex immunofluorescence of clinical biopsy sections. The comparison includes mercury light, metal halide and 3 different LED-based systems, using 7 Qdots (525, 565, 585, 605, 625, 705, Cy3 and Cy5. We discuss the considerations relevant to achieving the best combination of light source and fluorophore for accurate multiplex fluorescence quantitation. We highlight practical limitations and confounders to quantitation with filter-based approaches.

  17. Tissue-mimicking bladder wall phantoms for evaluating acoustic radiation force-optical coherence elastography systems.

    Science.gov (United States)

    Ejofodomi, O'tega A; Zderic, Vesna; Zara, Jason M

    2010-04-01

    Acoustic radiation force-optical coherence elastography (ARF-OCE) systems are novel imaging systems that have the potential to simultaneously quantify and characterize the optical and mechanical properties of in vivo tissues. This article presents the construction of bladder wall phantoms for use in ARF-OCE systems. Mechanical, acoustic, and optical properties are reported and compared to published values for the urinary bladder. The phantom consisted of 0.2000 +/- 0.0089 and 6.0000 +/- 0.2830 microm polystyrene microspheres (Polysciences Inc., Warrington, PA, Catalog Nos. 07304 and 07312), 7.5 +/- 1.5 microm copolymer microspheres composed of acrylonitrile and vinylidene chloride, (Expancel, Duluth, GA, Catalog No. 461 DU 20), and bovine serum albumin within a gelatin matrix. Young's modulus was measured by successive compression of the phantom and obtaining the slope of the resulting force-displacement data. Acoustic measurements were performed using the transmission method. The phantoms were submerged in a water bath and placed between transmitting and receiving 13 mm diameter unfocused transducers operating at a frequency of 3.5 MHz. A MATLAB algorithm to extract the optical scattering coefficient from optical coherence tomography (OCT) images of the phantom was used. The phantoms possess a Young's modulus of 17.12 +/- 2.72 kPa, a mass density of 1.05 +/- 0.02 g/cm3, an acoustic attenuation coefficient of 0.66 +/- 0.08 dB/cm/MHz, a speed of sound of 1591 +/- 8.76 m/s, and an optical scattering coefficient of 1.80 +/- 0.23 mm(-1). Ultrasound and OCT images of the bladder wall phantom are presented. A material that mimics the mechanical, optical, and acoustic properties of healthy bladder wall has been developed. This tissue-mimicking bladder wall phantom was developed as a control tool to investigate the feasibility of using ARF-OCE to detect the mechanical and optical changes that may be indicative of the onset or development of cancer in the urinary bladder

  18. Persistent identifiers for CMIP6 data in the Earth System Grid Federation

    Science.gov (United States)

    Buurman, Merret; Weigel, Tobias; Juckes, Martin; Lautenschlager, Michael; Kindermann, Stephan

    2016-04-01

    The Earth System Grid Federation (ESGF) is a distributed data infrastructure that will provide access to the CMIP6 experiment data. The data consist of thousands of datasets composed of millions of files. Over the course of the CMIP6 operational phase, datasets may be retracted and replaced by newer versions that consist of completely or partly new files. Each dataset is hosted at a single data centre, but can have one or several backups (replicas) at other data centres. To keep track of the different data entities and relationships between them, to ensure their consistency and improve exchange of information about them, Persistent Identifiers (PIDs) are used. These are unique identifiers that are registered at a globally accessible server, along with some metadata (the PID record). While usually providing access to the data object they refer to, as long as it exists, the metadata record will remain available even beyond the object's lifetime. Besides providing access to data and metadata, PIDs will allow scientists to communicate effectively and on a fine granularity about CMIP6 data. The initiative to introduce PIDs in the ESGF infrastructure has been described and agreed upon through a series of white papers governed by the WGCM Infrastructure Panel (WIP). In CMIP6, each dataset and each file is assigned a PID that keeps track of the data object's physical copies throughout the object lifetime. In addition to this, its relationship with other data objects is stored in the PID recordA human-readable version of this information is available on an information page also linked in the PID record. A possible application that exploits the information available from the PID records is a smart information tool, which a scientific user can call to find out if his/her version was replaced by a new one, to view and browse the related datasets and files, and to get access to the various copies or to additional metadata on a dedicated website. The PID registration process is

  19. Testing the potential of geochemical techniques in identifying hydrological systems within landslides in partly weathered marls

    Science.gov (United States)

    Bogaard, T. A.

    2003-04-01

    This paper’s objectives are twofold: to test the potential of cation exchange capacity (CEC) analysis for refinement of the knowledge of the hydrological system in landslide areas; and to examine two laboratory CEC analysis techniques on their applicability to partly weathered marls. The NH4Ac and NaCl laboratory techniques are tested. The geochemical results are compared with the core descriptions and interpreted with respect to their usefulness. Both analysis techniques give identical results for CEC, and are plausible on the basis of the available clay content information. The determination of the exchangeable cations was more difficult, since part of the marls dissolved. With the ammonium-acetate method more of the marls are dissolved than with the sodium-chloride method. This negatively affects the results of the exchangeable cations. Therefore, the NaCl method is to be preferred for the determination of the cation fractions at the complex, be it that this method has the disadvantage that the sodium fraction cannot be determined. To overcome this problem it is recommended to try and use another salt e.g. SrCl2 as displacement fluid. Both Alvera and Boulc-Mondorès examples show transitions in cation composition with depth. It was shown that the exchangeable cation fractions can be useful in locating boundaries between water types, especially the boundary between the superficial, rain fed hydrological system and the lower, regional ground water system. This information may be important for landslide interventions since the hydrological system and the origin of the water need to be known in detail. It is also plausible that long-term predictions of slope stability may be improved by knowledge of the hydrogeochemical evolution of clayey landslides. In the Boulc-Mondorès example the subsurface information that can be extracted from CEC analyses was presented. In the Boulc-Mondorès cores deviant intervals of CEC could be identified. These are interpreted as

  20. A New Approach for Identifying Ionospheric Gradients in the Context of the Gagan System

    Science.gov (United States)

    Kudala, Ravi Chandra

    The Indian Space Research Organization and the Airports Authority of India are jointly implementing the Global Positioning System (GPS) aided GEO Augmented Navigation (GAGAN) system in order to meet the following required navigation performance (RNP) parameters: integrity, continuity, accuracy, and availability (for aircraft operations). Such a system provides the user with orbit, clock, and ionospheric corrections in addition to ranging signals via the geostationary earth orbit satellite (GEOSAT). The equatorial ionization anomaly (EIA), due to rapid non-uniform electron-ion recombination that persists on the Indian subcontinent, causes ionospheric gradients. Ionospheric gradients represent the most severe threat to high-integrity differential GNSS systems such as GAGAN. In order to ensure integrity under conditions of an ionospheric storm, the following three objectives must be met: careful monitoring, error bounding, and sophisticated storm-front modeling. The first objective is met by continuously tracking data due to storms, and, on quiet days, determining precise estimates of the threat parameters from reference monitoring stations. The second objective is met by quantifying the above estimates of threat parameters due to storms through maximum and minimum typical thresholds. In the context GAGAN, this work proposes a new method for identifying ionospheric gradients, in addition to determining an appropriate upper bound, in order to sufficiently understand error during storm days. Initially, carrier phase data of the GAGAN network from Indian TEC stations for both storm and quiet days was used for estimating ionospheric spatial and temporal gradients (the vertical ionospheric gradient (σVIG) and the rate of the TEC index (ROTI), respectively) in multiple viewing directions. Along similar lines, using the carrier to noise ratio (C/N0) for the same data, the carrier to noise ratio index (σCNRI) was derived. Subsequently, the one-toone relationship between

  1. caTIES: a grid based system for coding and retrieval of surgical pathology reports and tissue specimens in support of translational research.

    Science.gov (United States)

    Crowley, Rebecca S; Castine, Melissa; Mitchell, Kevin; Chavan, Girish; McSherry, Tara; Feldman, Michael

    2010-01-01

    The authors report on the development of the Cancer Tissue Information Extraction System (caTIES)--an application that supports collaborative tissue banking and text mining by leveraging existing natural language processing methods and algorithms, grid communication and security frameworks, and query visualization methods. The system fills an important need for text-derived clinical data in translational research such as tissue-banking and clinical trials. The design of caTIES addresses three critical issues for informatics support of translational research: (1) federation of research data sources derived from clinical systems; (2) expressive graphical interfaces for concept-based text mining; and (3) regulatory and security model for supporting multi-center collaborative research. Implementation of the system at several Cancer Centers across the country is creating a potential network of caTIES repositories that could provide millions of de-identified clinical reports to users. The system provides an end-to-end application of medical natural language processing to support multi-institutional translational research programs.

  2. [Oral rehabilitation with metalloceramic restorations in patients with non-differentiated systemic connective tissue dysplasia].

    Science.gov (United States)

    Stafeev, А А

    2015-01-01

    False formation of connective tissues have a great influence on structure and function of organs and tissues of the human body. In prosthodontics, the changes in connective tissues greatly occur during clinical stages of preparing metal ceramic dentures. The algorithm of treatment patients with connective tissue dysplasia during metal ceramic dentures was developed and introduced into practical dentistry based on studying the morphology and functionality of dentition and clinical experience.

  3. Development of a GAL4-VP16/UAS trans-activation system for tissue specific expression in Medicago truncatula.

    Directory of Open Access Journals (Sweden)

    Amélie Sevin-Pujol

    Full Text Available Promoters with tissue-specific activity are very useful to address cell-autonomous and non cell autonomous functions of candidate genes. Although this strategy is widely used in Arabidopsis thaliana, its use to study tissue-specific regulation of root symbiotic interactions in legumes has only started recently. Moreover, using tissue specific promoter activity to drive a GAL4-VP16 chimeric transcription factor that can bind short upstream activation sequences (UAS is an efficient way to target and enhance the expression of any gene of interest. Here, we developed a collection of promoters with different root cell layers specific activities in Medicago truncatula and tested their abilities to drive the expression of a chimeric GAL4-VP16 transcription factor in a trans-activation UAS: β-Glucuronidase (GUS reporter gene system. By developing a binary vector devoted to modular Golden Gate cloning together with a collection of adapted tissue specific promoters and coding sequences we could test the activity of four of these promoters in trans-activation GAL4/UAS systems and compare them to "classical" promoter GUS fusions. Roots showing high levels of tissue specific expression of the GUS activity could be obtained with this trans-activation system. We therefore provide the legume community with new tools for efficient modular Golden Gate cloning, tissue specific expression and a trans-activation system. This study provides the ground work for future development of stable transgenic lines in Medicago truncatula.

  4. A systems genetics approach identifies genes and pathways for type 2 diabetes in human islets

    DEFF Research Database (Denmark)

    Taneera, Jalal; Lang, Stefan; Sharma, Amitabh

    2012-01-01

    Close to 50 genetic loci have been associated with type 2 diabetes (T2D), but they explain only 15% of the heritability. In an attempt to identify additional T2D genes, we analyzed global gene expression in human islets from 63 donors. Using 48 genes located near T2D risk variants, we identified ...

  5. Plasma luminescence feedback control system for precise ultrashort pulse laser tissue ablation

    Science.gov (United States)

    Kim, Beop-Min; Feit, Michael D.; Rubenchik, Alexander M.; Gold, David M.; Darrow, Christopher B.; Marion, John E., II; Da Silva, Luiz B.

    1998-05-01

    Plasma luminescence spectroscopy was used for precise ablation of bone tissue without damaging nearby soft tissue using an ultrashort pulse laser. Strong contrast of the luminescence spectra between bone marrow and spinal cord provided the real time feedback control so bone tissue is selectively ablated while preserving the spinal cord.

  6. Mesenchymal stem cells for the treatment of systemic lupus erythematosus: is the cure for connective tissue diseases within connective tissue?

    Science.gov (United States)

    Carrion, Flavio A; Figueroa, Fernando E

    2011-05-11

    Mesenchymal stem cells (MSCs) are now known to display not only adult stem cell multipotency but also robust anti-inflammatory and regenerative properties. After widespread in vitro and in vivo preclinical testing in several autoimmune disease models, allogenic MSCs have been successfully applied in patients with severe treatment-refractory systemic lupus erythematosus. The impressive results of these uncontrolled phase I and II trials - mostly in patients with non-responding renal disease - point to the need to perform controlled multicentric trials. In addition, they suggest that there is much to be learned from the basic and clinical science of MSCs in order to reap the full potential of these multifaceted progenitor cells in the treatment of autoimmune diseases.

  7. Telerobotic system concept for real-time soft-tissue imaging during radiotherapy beam delivery.

    Science.gov (United States)

    Schlosser, Jeffrey; Salisbury, Kenneth; Hristov, Dimitre

    2010-12-01

    The curative potential of external beam radiation therapy is critically dependent on having the ability to accurately aim radiation beams at intended targets while avoiding surrounding healthy tissues. However, existing technologies are incapable of real-time, volumetric, soft-tissue imaging during radiation beam delivery, when accurate target tracking is most critical. The authors address this challenge in the development and evaluation of a novel, minimally interfering, telerobotic ultrasound (U.S.) imaging system that can be integrated with existing medical linear accelerators (LINACs) for therapy guidance. A customized human-safe robotic manipulator was designed and built to control the pressure and pitch of an abdominal U.S. transducer while avoiding LINAC gantry collisions. A haptic device was integrated to remotely control the robotic manipulator motion and U.S. image acquisition outside the LINAC room. The ability of the system to continuously maintain high quality prostate images was evaluated in volunteers over extended time periods. Treatment feasibility was assessed by comparing a clinically deployed prostate treatment plan to an alternative plan in which beam directions were restricted to sectors that did not interfere with the transabdominal U.S. transducer. To demonstrate imaging capability concurrent with delivery, robot performance and U.S. target tracking in a phantom were tested with a 15 MV radiation beam active. Remote image acquisition and maintenance of image quality with the haptic interface was successfully demonstrated over 10 min periods in representative treatment setups of volunteers. Furthermore, the robot's ability to maintain a constant probe force and desired pitch angle was unaffected by the LINAC beam. For a representative prostate patient, the dose-volume histogram (DVH) for a plan with restricted sectors remained virtually identical to the DVH of a clinically deployed plan. With reduced margins, as would be enabled by real

  8. Telerobotic system concept for real-time soft-tissue imaging during radiotherapy beam delivery

    International Nuclear Information System (INIS)

    Schlosser, Jeffrey; Salisbury, Kenneth; Hristov, Dimitre

    2010-01-01

    Purpose: The curative potential of external beam radiation therapy is critically dependent on having the ability to accurately aim radiation beams at intended targets while avoiding surrounding healthy tissues. However, existing technologies are incapable of real-time, volumetric, soft-tissue imaging during radiation beam delivery, when accurate target tracking is most critical. The authors address this challenge in the development and evaluation of a novel, minimally interfering, telerobotic ultrasound (U.S.) imaging system that can be integrated with existing medical linear accelerators (LINACs) for therapy guidance. Methods: A customized human-safe robotic manipulator was designed and built to control the pressure and pitch of an abdominal U.S. transducer while avoiding LINAC gantry collisions. A haptic device was integrated to remotely control the robotic manipulator motion and U.S. image acquisition outside the LINAC room. The ability of the system to continuously maintain high quality prostate images was evaluated in volunteers over extended time periods. Treatment feasibility was assessed by comparing a clinically deployed prostate treatment plan to an alternative plan in which beam directions were restricted to sectors that did not interfere with the transabdominal U.S. transducer. To demonstrate imaging capability concurrent with delivery, robot performance and U.S. target tracking in a phantom were tested with a 15 MV radiation beam active. Results: Remote image acquisition and maintenance of image quality with the haptic interface was successfully demonstrated over 10 min periods in representative treatment setups of volunteers. Furthermore, the robot's ability to maintain a constant probe force and desired pitch angle was unaffected by the LINAC beam. For a representative prostate patient, the dose-volume histogram (DVH) for a plan with restricted sectors remained virtually identical to the DVH of a clinically deployed plan. With reduced margins, as

  9. GROWTH AND ROOTING SYSTEM OF ACACIA MANGIUM OBTAINED BY TISSUE CULTURE

    Directory of Open Access Journals (Sweden)

    SUPRIYANTO

    1991-01-01

    Full Text Available Since 1980/1981, the government of Indonesia through the Ministry of Forestry has started to reforest logged-over, alang-alang, unproductive areas and to convert them to Forest Industry Plantation. The target is 300 000 ha per year. It means, 750 million seedlings should be provided per year (planting distance 2 m x 2 m. The tree species to be planted in forest industry plantation should have shorter life cycle (8 - 10 years, good stem-form, good rooting system, and should be fast growing. Acacia mangium has been selected as one of the important tree species for forest industry plantation due to its growth, quality of fiber wood (pulp and paper industry and rooting system (produce a lot of secondary root and nitrogen fixater (Soebardjo 1986. The reforestation of logged-over Dipterocarp forests in Malaysia with A. mangium has also been considered (Appanah and Weinland 1989. Generally, reforestation with A. mangium is done with seedlings obtained by seed germination. A. mangium produce a lot of seeds but its production is still limited by the season, while the conventional method of vegetative propagation through cuttings gave very low percentage of rooted-cuttings (1% (Umboh and Syamsul Yani 1989. The micropropagation of A. mangium through tissue culture is a promising method. The production of A. mangium plantlets through that method has been done at the Forest Genetic Laboratory, Tropical Forest Biology, SEAMEO BIOTROP (Situmorang 1988, Umboh 1988, Umboh et al. 1989, 1990. These rooted-plantlets (plantlings were first put in the green house (acclimatization before planting in the field. Field tests of some agricultural plants have been done but information on forest trees species is still lacking because the production of plantlings through tissue culture is still limited as there are still problems of their rooting. In fact, the progress of reproducing woody plants by tissue culture has been much slower than with herbaceous plants. The major

  10. Deep sequencing of small RNAs identifies canonical and non-canonical miRNA and endogenous siRNAs in mammalian somatic tissues.

    Science.gov (United States)

    Castellano, Leandro; Stebbing, Justin

    2013-03-01

    MicroRNAs (miRNAs) are small RNA molecules that regulate gene expression. They are characterized by specific maturation processes defined by canonical and non-canonical biogenic pathways. Analysis of ∼0.5 billion sequences from mouse data sets derived from different tissues, developmental stages and cell types, partly characterized by either ablation or mutation of the main proteins belonging to miRNA processor complexes, reveals 66 high-confidence new genomic loci coding for miRNAs that could be processed in a canonical or non-canonical manner. A proportion of the newly discovered miRNAs comprises mirtrons, for which we define a new sub-class. Notably, some of these newly discovered miRNAs are generated from untranslated and open reading frames of coding genes, and we experimentally validate these. We also show that many annotated miRNAs do not present miRNA-like features, as they are neither processed by known processing complexes nor loaded on AGO2; this indicates that the current miRNA miRBase database list should be refined and re-defined. Accordingly, a group of them map on ribosomal RNA molecules, whereas others cannot undergo genuine miRNA biogenesis. Notably, a group of annotated miRNAs are Dgcr8 independent and DICER dependent endogenous small interfering RNAs that derive from a unique hairpin formed from a short interspersed nuclear element.

  11. A Novel microCT Method for Bone and Marrow Adipose Tissue Alignment Identifies Key Differences Between Mandible and Tibia in Rats.

    Science.gov (United States)

    Coutel, Xavier; Olejnik, Cécile; Marchandise, Pierre; Delattre, Jérôme; Béhal, Hélène; Kerckhofs, Greet; Penel, Guillaume

    2018-01-30

    Bone homeostasis is influenced by the bone marrow adipose tissue (BMAT). BMAT distribution varies from one anatomical location in the skeleton to another. We developed an advanced microfocus computed tomography imaging and analysis protocol that allows accurate alignment of both the BMAT distribution and bone micro-architecture as well as calculation of the distance of the BMAT adipocytes from the bone surface. Using this protocol, we detected a different spatial BMAT distribution between the rat tibia and mandible: in the proximal metaphysis of the tibia a large amount of BMAT (~ 20% of the total BMAT) was located close to the bone surface (BMAT was located between 40 and 60 µm from the bone surface. In the alveolar ridge of rats, the trabecular bone volume was 48.3% higher compared to the proximal metaphysis of the tibia (p BMAT content with almost no contact with the bone surface. These findings are of great interest because of the importance of the fat-bone interaction and its potential relevance to several resorptive bone diseases.

  12. Galectin-3 and Beclin1/Atg6 genes in human cancers: using cDNA tissue panel, qRT-PCR, and logistic regression model to identify cancer cell biomarkers.

    Directory of Open Access Journals (Sweden)

    Halliday A Idikio

    Full Text Available Cancer biomarkers are sought to support cancer diagnosis, predict cancer patient response to treatment and survival. Identifying reliable biomarkers for predicting cancer treatment response needs understanding of all aspects of cancer cell death and survival. Galectin-3 and Beclin1 are involved in two coordinated pathways of programmed cell death, apoptosis and autophagy and are linked to necroptosis/necrosis. The aim of the study was to quantify galectin-3 and Beclin1 mRNA in human cancer tissue cDNA panels and determine their utility as biomarkers of cancer cell survival.A panel of 96 cDNAs from eight (8 different normal and cancer tissue types were used for quantitative real-time polymerase chain reaction (qRT-PCR using ABI7900HT. Miner2.0, a web-based 4- and 3-parameter logistic regression software was used to derive individual well polymerase chain reaction efficiencies (E and cycle threshold (Ct values. Miner software derived formula was used to calculate mRNA levels and then fold changes. The ratios of cancer to normal tissue levels of galectin-3 and Beclin1 were calculated (using the mean for each tissue type. Relative mRNA expressions for galectin-3 were higher than for Beclin1 in all tissue (normal and cancer types. In cancer tissues, breast, kidney, thyroid and prostate had the highest galectin-3 mRNA levels compared to normal tissues. High levels of Beclin1 mRNA levels were in liver and prostate cancers when compared to normal tissues. Breast, kidney and thyroid cancers had high galectin-3 levels and low Beclin1 levels.Galectin-3 expression patterns in normal and cancer tissues support its reported roles in human cancer. Beclin1 expression pattern supports its roles in cancer cell survival and in treatment response. qRT-PCR analysis method used may enable high throughput studies to generate molecular biomarker sets for diagnosis and predicting cancer treatment response.

  13. A deep-learning classifier identifies patients with clinical heart failure using whole-slide images of H&E tissue.

    Directory of Open Access Journals (Sweden)

    Jeffrey J Nirschl

    Full Text Available Over 26 million people worldwide suffer from heart failure annually. When the cause of heart failure cannot be identified, endomyocardial biopsy (EMB represents the gold-standard for the evaluation of disease. However, manual EMB interpretation has high inter-rater variability. Deep convolutional neural networks (CNNs have been successfully applied to detect cancer, diabetic retinopathy, and dermatologic lesions from images. In this study, we develop a CNN classifier to detect clinical heart failure from H&E stained whole-slide images from a total of 209 patients, 104 patients were used for training and the remaining 105 patients for independent testing. The CNN was able to identify patients with heart failure or severe pathology with a 99% sensitivity and 94% specificity on the test set, outperforming conventional feature-engineering approaches. Importantly, the CNN outperformed two expert pathologists by nearly 20%. Our results suggest that deep learning analytics of EMB can be used to predict cardiac outcome.

  14. Undifferentiated Connective Tissue Disease

    Science.gov (United States)

    ... Home Conditions Undifferentiated Connective Tissue Disease (UCTD) Undifferentiated Connective Tissue Disease (UCTD) Make an Appointment Find a Doctor ... by Barbara Goldstein, MD (February 01, 2016) Undifferentiated connective tissue disease (UCTD) is a systemic autoimmune disease. This ...

  15. Potential of stem cell based therapy and tissue engineering in the regeneration of the central nervous system

    International Nuclear Information System (INIS)

    An Yihua; Tsang, Kent K S; Zhang Han

    2006-01-01

    The insufficiency of self-repair and regeneration of the central nervous system (CNS) leads to difficulty of rehabilitation of the injured brain. In the past few decades, the significant progress in cell therapy and tissue engineering has contributed to the functional recovery of the CNS to a great extent. The present review focuses on the potential role of stem cell based therapy and tissue engineering in the regeneration of the CNS. (topical review)

  16. Studies of Bystander Effects in 3-D Tissue Systems Using a Low-LET Microbeam

    International Nuclear Information System (INIS)

    Brenner, David J.

    2009-01-01

    frequency was also observed. When cells were cultured in medium donated from cells exposed to 5 Gy X-rays, a significant bystander effect was observed for clonogenic survival. When cells were cultured for 5 h with supernatant from donor cells exposed to 2 cGy and were then irradiated with 4 Gy X-rays, they failed to show an increase in survival compared with cells directly irradiated with 4 Gy. However, a twofold reduction in the oncogenic transformation frequency was seen. An adaptive dose of X-rays cancelled out the majority of the bystander effect produced by alpha-particles. For oncogenic transformation, but not cell survival, radioadaption can occur in unirradiated cells via a transmissible factor(s). A pilot study was undertaken to observe the bystander effect in a realistic multicellular three-dimensional morphology. We found bystander responses in a three-dimensional, normal human-tissue system. Endpoints were induction of micronucleated and apoptotic cells. A charged-particle microbeam was used, allowing irradiation of cells in defined locations in the tissue yet guaranteeing that no cells located more than a few micrometers away receive any radiation exposure. Unirradiated cells up to 1 mm distant from irradiated cells showed a significant enhancement in effect over background, with an average increase in effect of 1.7-fold for micronuclei and 2.8-fold for apoptosis. The surprisingly long range of bystander signals in human tissue suggests that bystander responses may be important in extrapolating radiation risk estimates from epidemiologically accessible doses down to very low doses where nonhit bystander cells will predominate. Finally, it would be of great benefit to develop a reproducible tissue system suitable for critical radiobiological assays. We have developed a reliable protocol to harvest cells from tissue samples and to investigate the damage induced on a single cell basis. In order to result in a valid tool for bystander experiments, the method

  17. IDENTIFYING OPERATIONAL REQUIREMENTS TO SELECT SUITABLE DECISION MODELS FOR A PUBLIC SECTOR EPROCUREMENT DECISION SUPPORT SYSTEM

    Directory of Open Access Journals (Sweden)

    Mohamed Adil

    2014-10-01

    Full Text Available Public sector procurement should be a transparent and fair process. Strict legal requirements are enforced on public sector procurement to make it a standardised process. To make fair decisions on selecting suppliers, a practical method which adheres to legal requirements is important. The research that is the base for this paper aimed at identifying a suitable Multi-Criteria Decision Analysis (MCDA method for the specific legal and functional needs of the Maldivian Public Sector. To identify such operational requirements, a set of focus group interviews were conducted in the Maldives with public officials responsible for procurement decision making. Based on the operational requirements identified through focus groups, criteria-based evaluation is done on published MCDA methods to identify the suitable methods for e-procurement decision making. This paper describes the identification of the operational requirements and the results of the evaluation to select suitable decision models for the Maldivian context.

  18. Thermogelling chitosan–collagen–bioactive glass nanoparticle hybrids as potential injectable systems for tissue engineering

    Energy Technology Data Exchange (ETDEWEB)

    Moreira, Cheisy D.F.; Carvalho, Sandhra M.; Mansur, Herman S., E-mail: hmansur@demet.ufmg.br; Pereira, Marivalda M., E-mail: mpereira@demet.ufmg.br

    2016-01-01

    Recently, stimuli-responsive nanocomposite-derived hydrogels have gained prominence in tissue engineering because they can be applied as injectable scaffolds in bone and cartilage repair. Due to the great potential of these systems, this study aimed to synthesize and characterize novel thermosensitive chitosan-based composites, chemically modified with collagen and reinforced by bioactive glass nanoparticles (BG) on the development of injectable nanohybrids for regenerative medicine applications. Thus, the composite hydrogels were extensively characterized by structural, morphological, rheological, and biological testing. The composites showed thermosensitive response with the gelation temperature at approximately 37 °C, which is compatible with the human body temperature. In addition, scanning electron microscopy (SEM) analysis indicated that the chitosan hydrogels exhibited 3D-porous structures, and the incorporation of collagen in the system caused increase on the average pore size. Fourier transform infrared spectroscopy (FTIR) analysis indicated the main functional groups of each component of the composite system and their chemical interactions forming the scaffold. Moreover, rheological measurements were employed to assess the viscoelastic behavior of the hydrogels as a function of the temperature. The results demonstrated that the addition of collagen and bioactive glass increases the mechanical properties after the gelation process. The addition of 2 wt.% of BG nanoparticles caused an increase of approximately 39% on stiffness compared to pure chitosan and the addition of 30 wt.% collagen caused a further increase on the stiffness by 95%. The cytotoxicity and cell viability of the hydrogels were assessed by MTT and LIVE/DEAD® assays, where the results demonstrated no toxic effect of the composites on the human osteosarcoma cell culture (SAOS) and kidney cells line of human embryo (HEK 293T). Hence, it can be stated that innovative composites were

  19. Identifying and confirming information and system quality requirements for multi-agency disaster management

    NARCIS (Netherlands)

    Bharosa, N.; Appelman, J.A.; Van Zanten, B.; Zuurmond, A.

    2009-01-01

    This paper investigates the relevance and assurance of information and system quality as requirements for information systems success during disaster management. Despite the many examples of poor information quality and poor system quality, research on the relevance and assurance of these

  20. Diagnostic accuracy of subcutaneous abdominal fat tissue aspiration for detecting systemic amyloidosis and its utility in clinical practice

    NARCIS (Netherlands)

    van Gameren, Ingrid I.; Hazenberg, BPC; Bijzet, J.; van Rijswijk, M.H.

    Objective. Aspiration of subcutaneous abdominal fat is a simple and fast method for detecting systemic amyloidosis; however, the sensitivity of this approach remains undetermined. The aim of this study was to assess the accuracy of fat tissue aspiration for detecting systemic amyloidosis and the

  1. Expression of insulin-like growth factor system components in colorectal tissue and its relation with serum IGF levels

    NARCIS (Netherlands)

    Vrieling, A.; Voskuil, D.W.; Bosma, A.; Majoor, D.M.; Doorn, van J.; Cats, A.; Depla, A.; Timmer, R.; Witteman, B.J.M.; Wesseling, J.; Kampman, E.; van't Veer, L.J.

    2009-01-01

    Context: The insulin-like growth factor (IGF)-system has been implicated in colorectal tumor carcinogenesis. Although both tumor expression levels and serum concentrations of IGF-system components are related to colorectal cancer risk, it is unknown whether IGF levels in tissue and serum are

  2. Expression of insulin-like growth factor system components in colorectal tissue and its relation with serum IGF levels.

    NARCIS (Netherlands)

    Vrieling, A.; Voskuil, D.W.; Bosma, A.; Majoor, D.M.; Doorn, J. van; Cats, A.; Depla, A.C.; Timmer, R.; Witteman, B.J.; Wesseling, J.; Kampman, E.; Veer, L.J. van 't

    2009-01-01

    CONTEXT: The insulin-like growth factor (IGF)-system has been implicated in colorectal tumor carcinogenesis. Although both tumor expression levels and serum concentrations of IGF-system components are related to colorectal cancer risk, it is unknown whether IGF levels in tissue and serum are

  3. Development of a fluorescence endoscopic system for pH mapping of gastric tissue

    Science.gov (United States)

    Rochon, Philippe; Mordon, Serge; Buys, Bruno; Dhelin, Guy; Lesage, Jean C.; Chopin, Claude

    2003-10-01

    Measurement of gastro intestinal intramucosal pH (pHim) has been recognized as an important factor in the detection of hypoxia induced dysfonctions. However, current pH measurements techniques are limited in terms of time and spatial resolutions. A major advance in accurate pH measurement was the development of the ratiometric fluorescent indicator dye, 2',7'-bis(carboxyethyl)-5,6-carboxyfluorescein (BCECF). BCECF which pKa is in the physiological pH range is suitable for pH tissue measurements in vivo. This study aimed to develop and evaluate an endoscopic imaging system for real time pH measurements in the stomach in order to provide to ICU a new tool for gastro intestinal intramucosal pH (pHim) measurements. This fluorescence imaging technique should allow the temporal exploration of sequential events, particularly in ICU where the pHim provides a predictive information of the patient' status. The experimental evaluations of this new and innovative endoscopic fluorescence system confirms the accuracy of pH measurement using BCECF.

  4. The interplay between adipose tissue and the cardiovascular system: is fat always bad?

    Science.gov (United States)

    Akoumianakis, Ioannis; Antoniades, Charalambos

    2017-07-01

    Obesity is a risk factor for cardiovascular disease (CVD). However, clinical research has revealed a paradoxically protective role for obesity in patients with chronic diseases including CVD, suggesting that the biological 'quality' of adipose tissue (AT) may be more important than overall AT mass or body weight. Importantly, AT is recognised as a dynamic organ secreting a wide range of biologically active adipokines, microRNAs, gaseous messengers, and other metabolites that affect the cardiovascular system in both endocrine and paracrine ways. Despite being able to mediate normal cardiovascular function under physiological conditions, AT undergoes a phenotypic shift characterised by acquisition of pro-oxidant and pro-inflammatory properties in cases of CVD. Crucially, recent evidence suggests that AT depots such as perivascular AT and epicardial AT are able to modify their phenotype in response to local signals of vascular and myocardial origin, respectively. Utilisation of this unique property of certain AT depots to dynamically track cardiovascular biology may reveal novel diagnostic and prognostic tools against CVD. Better understanding of the mechanisms controlling the 'quality' of AT secretome, as well as the communication links between AT and the cardiovascular system, is required for the efficient management of CVD. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For Permissions, please email: journals.permissions@oup.com.

  5. Identify Web-page Content meaning using Knowledge based System for Dual Meaning Words

    OpenAIRE

    Sinha, Sukanta; Dattagupta, Rana; Mukhopadhyay, Debajyoti

    2012-01-01

    Meaning of Web-page content plays a big role while produced a search result from a search engine. Most of the cases Web-page meaning stored in title or meta-tag area but those meanings do not always match with Web-page content. To overcome this situation we need to go through the Web-page content to identify the Web-page meaning. In such cases, where Webpage content holds dual meaning words that time it is really difficult to identify the meaning of the Web-page. In this paper, we are introdu...

  6. How many proteins can be identified in a 2DE gel spot within an analysis of a complex human cancer tissue proteome?

    Science.gov (United States)

    Zhan, Xianquan; Yang, Haiyan; Peng, Fang; Li, Jianglin; Mu, Yun; Long, Ying; Cheng, Tingting; Huang, Yuda; Li, Zhao; Lu, Miaolong; Li, Na; Li, Maoyu; Liu, Jianping; Jungblut, Peter R

    2018-04-01

    Two-dimensional gel electrophoresis (2DE) in proteomics is traditionally assumed to contain only one or two proteins in each 2DE spot. However, 2DE resolution is being complemented by the rapid development of high sensitivity mass spectrometers. Here we compared MALDI-MS, LC-Q-TOF MS and LC-Orbitrap Velos MS for the identification of proteins within one spot. With LC-Orbitrap Velos MS each Coomassie Blue-stained 2DE spot contained an average of at least 42 and 63 proteins/spot in an analysis of a human glioblastoma proteome and a human pituitary adenoma proteome, respectively, if a single gel spot was analyzed. If a pool of three matched gel spots was analyzed this number further increased up to an average of 230 and 118 proteins/spot for glioblastoma and pituitary adenoma proteome, respectively. Multiple proteins per spot confirm the necessity of isotopic labeling in large-scale quantification of different protein species in a proteome. Furthermore, a protein abundance analysis revealed that most of the identified proteins in each analyzed 2DE spot were low-abundance proteins. Many proteins were present in several of the analyzed spots showing the ability of 2DE-MS to separate at the protein species level. Therefore, 2DE coupled with high-sensitivity LC-MS has a clearly higher sensitivity as expected until now to detect, identify and quantify low abundance proteins in a complex human proteome with an estimated resolution of about 500 000 protein species. This clearly exceeds the resolution power of bottom-up LC-MS investigations. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Colloquium: Modeling the dynamics of multicellular systems: Application to tissue engineering

    Science.gov (United States)

    Kosztin, Ioan; Vunjak-Novakovic, Gordana; Forgacs, Gabor

    2012-10-01

    Tissue engineering is a rapidly evolving discipline that aims at building functional tissues to improve or replace damaged ones. To be successful in such an endeavor, ideally, the engineering of tissues should be based on the principles of developmental biology. Recent progress in developmental biology suggests that the formation of tissues from the composing cells is often guided by physical laws. Here a comprehensive computational-theoretical formalism is presented that is based on experimental input and incorporates biomechanical principles of developmental biology. The formalism is described and it is shown that it correctly reproduces and predicts the quantitative characteristics of the fundamental early developmental process of tissue fusion. Based on this finding, the formalism is then used toward the optimization of the fabrication of tubular multicellular constructs, such as a vascular graft, by bioprinting, a novel tissue engineering technology.

  8. Altered gut microbiota and endocannabinoid system tone in obese and diabetic leptin-resistant mice: impact on apelin regulation in adipose tissue

    Directory of Open Access Journals (Sweden)

    Lucie eGeurts

    2011-07-01

    Full Text Available Growing evidence supports the role of gut microbiota in the development of obesity, type 2 diabetes and low-grade inflammation. The endocrine activity of adipose tissue has been found to contribute to the regulation of glucose homeostasis and low-grade inflammation. Among the key hormones produced by this tissue, apelin has been shown to regulate glucose homeostasis. Recently, it has been proposed that gut microbiota participate in adipose tissue metabolism via the endocannabinoid system and gut microbiota-derived compounds, namely lipopolysaccharide (LPS. We have investigated gut microbiota composition in obese and diabetic leptin-resistant mice (db/db by combining pyrosequencing and phylogenetic microarray analysis of 16S ribosomal RNA gene sequences. We observed a significant higher abundance of Firmicutes, Proteobacteria and Fibrobacteres phyla in db/db mice compared to lean mice. The abundance of 10 genera was significantly affected by the genotype. We identified the roles of the endocannabinoid system and LPS in the regulation of apelinergic system tone (apelin and APJ mRNA expression in genetic obese and diabetic mice. By using in vivo and in vitro models, we have demonstrated that both the endocannabinoid system and low-grade inflammation differentially regulate apelin and APJ mRNA expression in adipose tissue. Finally, deep-gut microbiota profiling revealed that the gut microbial community of type 2 diabetic mice is significantly different from that of their lean counterparts. This indicates specific relationships between the gut microbiota and the regulation of the apelinergic system. However, the exact roles of specific bacteria in shaping the phenotype of db/db mice remain to be determined.

  9. A systems biology approach identified different regulatory networks targeted by KSHV miR-K12-11 in B cells and endothelial cells.

    Science.gov (United States)

    Yang, Yajie; Boss, Isaac W; McIntyre, Lauren M; Renne, Rolf

    2014-08-08

    Kaposi's sarcoma associated herpes virus (KSHV) is associated with tumors of endothelial and lymphoid origin. During latent infection, KSHV expresses miR-K12-11, an ortholog of the human tumor gene hsa-miR-155. Both gene products are microRNAs (miRNAs), which are important post-transcriptional regulators that contribute to tissue specific gene expression. Advances in target identification technologies and molecular interaction databases have allowed a systems biology approach to unravel the gene regulatory networks (GRNs) triggered by miR-K12-11 in endothelial and lymphoid cells. Understanding the tissue specific function of miR-K12-11 will help to elucidate underlying mechanisms of KSHV pathogenesis. Ectopic expression of miR-K12-11 differentially affected gene expression in BJAB cells of lymphoid origin and TIVE cells of endothelial origin. Direct miRNA targeting accounted for a small fraction of the observed transcriptome changes: only 29 genes were identified as putative direct targets of miR-K12-11 in both cell types. However, a number of commonly affected biological pathways, such as carbohydrate metabolism and interferon response related signaling, were revealed by gene ontology analysis. Integration of transcriptome profiling, bioinformatic algorithms, and databases of protein-protein interactome from the ENCODE project identified different nodes of GRNs utilized by miR-K12-11 in a tissue-specific fashion. These effector genes, including cancer associated transcription factors and signaling proteins, amplified the regulatory potential of a single miRNA, from a small set of putative direct targets to a larger set of genes. This is the first comparative analysis of miRNA-K12-11's effects in endothelial and B cells, from tissues infected with KSHV in vivo. MiR-K12-11 was able to broadly modulate gene expression in both cell types. Using a systems biology approach, we inferred that miR-K12-11 establishes its GRN by both repressing master TFs and influencing

  10. Methodical aspects of radionuclide study of locomotor system in patients with systemic diseases of connective tissue with single photon emission computed tomography

    International Nuclear Information System (INIS)

    Potsibyina, V.V.; Oderyij, Je.A.

    1998-01-01

    The original technique was used to examine 427 patients aged 18-64 with systemic diseases of locomotor system connective tissue and 65 controls. In addition to clinical studies, radionuclide signs of locomotor system lesions was investigated with NUCLETRON APEX SP-6 CT unit using labeled with Tc-99m and osteotropic radiopharmaceuticals

  11. GISMOWA: Geospatial Risk-Based Analysis Identifying Water Quality Monitoring Sites in Distribution Systems

    DEFF Research Database (Denmark)

    Larsen, Sille Lyster; Christensen, Sarah Christine Boesgaard; Albrechtsen, Hans-Jørgen

    2017-01-01

    distribution systems as a transparent and simple-to-use tool facilitating a complete overview of the distribution system, including sensitive consumers and consumers in general, thus fulfilling a precondition for a HACCP-based monitoring strategy of drinking water. (C) 2017 American Society of Civil Engineers....

  12. Identifying Characteristics of a "Good School" in the British and Saudi Arabian Education Systems

    Science.gov (United States)

    Alzahrani, Saeed Musaid H.; Hammersley-Fletcher, Linda; Bright, Geoff

    2016-01-01

    This study aims at establishing whether primary schools in the Saudi education system conform to the characteristics of what are referred to as "good schools" in the British education system. The findings established through this study show that only 43.75% of primary schools in Saudi conform to the characteristics of what are referred…

  13. Identifying parameters in active magnetic bearing system using LFT formulation and Youla factorization

    DEFF Research Database (Denmark)

    Lauridsen, Jonas; Sekunda, André Krabdrup; Santos, Ilmar

    2015-01-01

    the LFT matrices represent the mapping of the uncertainties in and out of the full and reduced FE system matrices. Scaling the LFT matrices easily leads to the amplitudes of the uncertainty parameters., Youla Parametrization method is applied to transform the identification problem into an open...... for model-based control design and fast identification., The paper elucidates how nodal parametric uncertainties, which are easily represented in the full FE coordinate system, can be represented in the new coordinate system of the reduced model. The uncertainty is described as a single column vector...... of the system matrix A of the full FE model while it is represented as several elements spread over multiple rows and columns of the system matrix of the reduced model. The parametric uncertainty, for both the full and reduced FE model, is represented using Linear Fractional Transformation (LFT). In this way...

  14. A data analysis method for identifying deterministic components of stable and unstable time-delayed systems with colored noise

    Energy Technology Data Exchange (ETDEWEB)

    Patanarapeelert, K. [Faculty of Science, Department of Mathematics, Mahidol University, Rama VI Road, Bangkok 10400 (Thailand); Frank, T.D. [Institute for Theoretical Physics, University of Muenster, Wilhelm-Klemm-Str. 9, 48149 Muenster (Germany)]. E-mail: tdfrank@uni-muenster.de; Friedrich, R. [Institute for Theoretical Physics, University of Muenster, Wilhelm-Klemm-Str. 9, 48149 Muenster (Germany); Beek, P.J. [Faculty of Human Movement Sciences and Institute for Fundamental and Clinical Human Movement Sciences, Vrije Universiteit, Van der Boechorststraat 9, 1081 BT Amsterdam (Netherlands); Tang, I.M. [Faculty of Science, Department of Physics, Mahidol University, Rama VI Road, Bangkok 10400 (Thailand)

    2006-12-18

    A method is proposed to identify deterministic components of stable and unstable time-delayed systems subjected to noise sources with finite correlation times (colored noise). Both neutral and retarded delay systems are considered. For vanishing correlation times it is shown how to determine their noise amplitudes by minimizing appropriately defined Kullback measures. The method is illustrated by applying it to simulated data from stochastic time-delayed systems representing delay-induced bifurcations, postural sway and ship rolling.

  15. An in vivo cis-regulatory screen at the type 2 diabetes associated TCF7L2 locus identifies multiple tissue-specific enhancers.

    Directory of Open Access Journals (Sweden)

    Daniel Savic

    Full Text Available Genome-wide association studies (GWAS have repeatedly shown an association between non-coding variants in the TCF7L2 locus and risk for type 2 diabetes (T2D, implicating a role for cis-regulatory variation within this locus in disease etiology. Supporting this hypothesis, we previously localized complex regulatory activity to the TCF7L2 T2D-associated interval using an in vivo bacterial artificial chromosome (BAC enhancer-trapping reporter strategy. To follow-up on this broad initial survey of the TCF7L2 regulatory landscape, we performed a fine-mapping enhancer scan using in vivo mouse transgenic reporter assays. We functionally interrogated approximately 50% of the sequences within the T2D-associated interval, utilizing sequence conservation within this 92-kb interval to determine the regulatory potential of all evolutionary conserved sequences that exhibited conservation to the non-eutherian mammal opossum. Included in this study was a detailed functional interrogation of sequences spanning both protective and risk alleles of single nucleotide polymorphism (SNP rs7903146, which has exhibited allele-specific enhancer function in pancreatic beta cells. Using these assays, we identified nine segments regulating various aspects of the TCF7L2 expression profile and that constitute nearly 70% of the sequences tested. These results highlight the regulatory complexity of this interval and support the notion that a TCF7L2 cis-regulatory disruption leads to T2D predisposition.

  16. Identifying a cooperative control mechanism between an applied field and the environment of open quantum systems

    Science.gov (United States)

    Gao, Fang; Rey-de-Castro, Roberto; Wang, Yaoxiong; Rabitz, Herschel; Shuang, Feng

    2016-05-01

    Many systems under control with an applied field also interact with the surrounding environment. Understanding the control mechanisms has remained a challenge, especially the role played by the interaction between the field and the environment. In order to address this need, here we expand the scope of the Hamiltonian-encoding and observable-decoding (HE-OD) technique. HE-OD was originally introduced as a theoretical and experimental tool for revealing the mechanism induced by control fields in closed quantum systems. The results of open-system HE-OD analysis presented here provide quantitative mechanistic insights into the roles played by a Markovian environment. Two model open quantum systems are considered for illustration. In these systems, transitions are induced by either an applied field linked to a dipole operator or Lindblad operators coupled to the system. For modest control yields, the HE-OD results clearly show distinct cooperation between the dynamics induced by the optimal field and the environment. Although the HE-OD methodology introduced here is considered in simulations, it has an analogous direct experimental formulation, which we suggest may be applied to open systems in the laboratory to reveal mechanistic insights.

  17. Identifying and eliminating inefficiencies in information system usage: A lean perspective

    NARCIS (Netherlands)

    Blijleven, Vincent; Koelemeijer, Kitty; Jaspers, Monique

    2017-01-01

    Objectives: Mismatches frequently occur between information system (IS) dictated workflows and actual workflows of IS users. The resulting impeded workflows negatively influence the efficiency with which goods or services are produced and delivered to customers. Within a healthcare context, impeded

  18. Systems Genetics Reveals the Functional Context of PCOS Loci and Identifies Genetic and Molecular Mechanisms of Disease Heterogeneity

    Science.gov (United States)

    Xu, Ning; Cui, Jinrui; Mengesha, Emebet; Chen, Yii-Der I.; Taylor, Kent D.; Azziz, Ricardo; Goodarzi, Mark O.

    2015-01-01

    Genome wide association studies (GWAS) have revealed 11 independent risk loci for polycystic ovary syndrome (PCOS), a common disorder in young women characterized by androgen excess and oligomenorrhea. To put these risk loci and the single nucleotide polymorphisms (SNPs) therein into functional context, we measured DNA methylation and gene expression in subcutaneous adipose tissue biopsies to identify PCOS-specific alterations. Two genes from the LHCGR region, STON1-GTF2A1L and LHCGR, were overexpressed in PCOS. In analysis stratified by obesity, LHCGR was overexpressed only in non-obese PCOS women. Although not differentially expressed in the entire PCOS group, INSR was underexpressed in obese PCOS subjects only. Alterations in gene expression in the LHCGR, RAB5B and INSR regions suggest that SNPs in these loci may be functional and could affect gene expression directly or indirectly via epigenetic alterations. We identified reduced methylation in the LHCGR locus and increased methylation in the INSR locus, changes that are concordant with the altered gene expression profiles. Complex patterns of meQTL and eQTL were identified in these loci, suggesting that local genetic variation plays an important role in gene regulation. We propose that non-obese PCOS women possess significant alterations in LH receptor expression, which drives excess androgen secretion from the ovary. Alternatively, obese women with PCOS possess alterations in insulin receptor expression, with underexpression in metabolic tissues and overexpression in the ovary, resulting in peripheral insulin resistance and excess ovarian androgen production. These studies provide a genetic and molecular basis for the reported clinical heterogeneity of PCOS. PMID:26305227

  19. Systems Genetics Reveals the Functional Context of PCOS Loci and Identifies Genetic and Molecular Mechanisms of Disease Heterogeneity.

    Directory of Open Access Journals (Sweden)

    Michelle R Jones

    2015-08-01

    Full Text Available Genome wide association studies (GWAS have revealed 11 independent risk loci for polycystic ovary syndrome (PCOS, a common disorder in young women characterized by androgen excess and oligomenorrhea. To put these risk loci and the single nucleotide polymorphisms (SNPs therein into functional context, we measured DNA methylation and gene expression in subcutaneous adipose tissue biopsies to identify PCOS-specific alterations. Two genes from the LHCGR region, STON1-GTF2A1L and LHCGR, were overexpressed in PCOS. In analysis stratified by obesity, LHCGR was overexpressed only in non-obese PCOS women. Although not differentially expressed in the entire PCOS group, INSR was underexpressed in obese PCOS subjects only. Alterations in gene expression in the LHCGR, RAB5B and INSR regions suggest that SNPs in these loci may be functional and could affect gene expression directly or indirectly via epigenetic alterations. We identified reduced methylation in the LHCGR locus and increased methylation in the INSR locus, changes that are concordant with the altered gene expression profiles. Complex patterns of meQTL and eQTL were identified in these loci, suggesting that local genetic variation plays an important role in gene regulation. We propose that non-obese PCOS women possess significant alterations in LH receptor expression, which drives excess androgen secretion from the ovary. Alternatively, obese women with PCOS possess alterations in insulin receptor expression, with underexpression in metabolic tissues and overexpression in the ovary, resulting in peripheral insulin resistance and excess ovarian androgen production. These studies provide a genetic and molecular basis for the reported clinical heterogeneity of PCOS.

  20. Systems Genetics Reveals the Functional Context of PCOS Loci and Identifies Genetic and Molecular Mechanisms of Disease Heterogeneity.

    Science.gov (United States)

    Jones, Michelle R; Brower, Meredith A; Xu, Ning; Cui, Jinrui; Mengesha, Emebet; Chen, Yii-Der I; Taylor, Kent D; Azziz, Ricardo; Goodarzi, Mark O

    2015-08-01

    Genome wide association studies (GWAS) have revealed 11 independent risk loci for polycystic ovary syndrome (PCOS), a common disorder in young women characterized by androgen excess and oligomenorrhea. To put these risk loci and the single nucleotide polymorphisms (SNPs) therein into functional context, we measured DNA methylation and gene expression in subcutaneous adipose tissue biopsies to identify PCOS-specific alterations. Two genes from the LHCGR region, STON1-GTF2A1L and LHCGR, were overexpressed in PCOS. In analysis stratified by obesity, LHCGR was overexpressed only in non-obese PCOS women. Although not differentially expressed in the entire PCOS group, INSR was underexpressed in obese PCOS subjects only. Alterations in gene expression in the LHCGR, RAB5B and INSR regions suggest that SNPs in these loci may be functional and could affect gene expression directly or indirectly via epigenetic alterations. We identified reduced methylation in the LHCGR locus and increased methylation in the INSR locus, changes that are concordant with the altered gene expression profiles. Complex patterns of meQTL and eQTL were identified in these loci, suggesting that local genetic variation plays an important role in gene regulation. We propose that non-obese PCOS women possess significant alterations in LH receptor expression, which drives excess androgen secretion from the ovary. Alternatively, obese women with PCOS possess alterations in insulin receptor expression, with underexpression in metabolic tissues and overexpression in the ovary, resulting in peripheral insulin resistance and excess ovarian androgen production. These studies provide a genetic and molecular basis for the reported clinical heterogeneity of PCOS.

  1. Transcription factor expression uniquely identifies most postembryonic neuronal lineages in the Drosophila thoracic central nervous system.

    Science.gov (United States)

    Lacin, Haluk; Zhu, Yi; Wilson, Beth A; Skeath, James B

    2014-03-01

    Most neurons of the adult Drosophila ventral nerve cord arise from a burst of neurogenesis during the third larval instar stage. Most of this growth occurs in thoracic neuromeres, which contain 25 individually identifiable postembryonic neuronal lineages. Initially, each lineage consists of two hemilineages--'A' (Notch(On)) and 'B' (Notch(Off))--that exhibit distinct axonal trajectories or fates. No reliable method presently exists to identify these lineages or hemilineages unambiguously other than labor-intensive lineage-tracing methods. By combining mosaic analysis with a repressible cell marker (MARCM) analysis with gene expression studies, we constructed a gene expression map that enables the rapid, unambiguous identification of 23 of the 25 postembryonic lineages based on the expression of 15 transcription factors. Pilot genetic studies reveal that these transcription factors regulate the specification and differentiation of postembryonic neurons: for example, Nkx6 is necessary and sufficient to direct axonal pathway selection in lineage 3. The gene expression map thus provides a descriptive foundation for the genetic and molecular dissection of adult-specific neurogenesis and identifies many transcription factors that are likely to regulate the development and differentiation of discrete subsets of postembryonic neurons.

  2. Computer Vision System For Locating And Identifying Defects In Hardwood Lumber

    Science.gov (United States)

    Conners, Richard W.; Ng, Chong T.; Cho, Tai-Hoon; McMillin, Charles W.

    1989-03-01

    This paper describes research aimed at developing an automatic cutup system for use in the rough mills of the hardwood furniture and fixture industry. In particular, this paper describes attempts to create the vision system that will power this automatic cutup system. There are a number of factors that make the development of such a vision system a challenge. First there is the innate variability of the wood material itself. No two species look exactly the same, in fact, they can have a significant visual difference in appearance among species. Yet a truly robust vision system must be able to handle a variety of such species, preferably with no operator intervention required when changing from one species to another. Secondly, there is a good deal of variability in the definition of what constitutes a removable defect. The hardwood furniture and fixture industry is diverse in the nature of the products that it makes. The products range from hardwood flooring to fancy hardwood furniture, from simple mill work to kitchen cabinets. Thus depending on the manufacturer, the product, and the quality of the product the nature of what constitutes a removable defect can and does vary. The vision system must be such that it can be tailored to meet each of these unique needs, preferably without any additional program modifications. This paper will describe the vision system that has been developed. It will assess the current system capabilities, and it will discuss the directions for future research. It will be argued that artificial intelligence methods provide a natural mechanism for attacking this computer vision application.

  3. Previously Identified Deficiencies Not Corrected in the General Fund Enterprise Business System Program

    Science.gov (United States)

    2011-06-15

    Army AAA Report No. A-2009-0226- FFM , “Examination of Federal Financial Management Improvement Act Compliance - Test Validation General Fund Enterprise...Business System Release 1.2,” September 30, 2009 AAA Report No. A-2009-0231- FFM , “General Fund Enterprise Business System - Federal Financial...Management Improvement Act Compliance Examination of Release 1.3 Functionality,” September 30, 2009 AAA Report No. A-2009-0232- FFM , “General Fund

  4. A Simple, Visually Oriented Communication System to Improve Postoperative Care Following Microvascular Free Tissue Transfer: Development, Results, and Implications.

    Science.gov (United States)

    Henderson, Peter W; Landford, Wilmina; Gardenier, Jason; Otterburn, David M; Rohde, Christine H; Spector, Jason A

    2016-07-01

    Background Communication, particularly transmission of information between the surgical and nursing teams, has been identified as one of the most crucial determinants of patient outcomes. Nonetheless, transfer of information among and between the physician and nursing teams in the immediate postoperative period is often informal, verbal, and inconsistent. Methods An iterative process of multidisciplinary information gathering was undertaken to create a novel postoperative communication system (the "Pop-form"). Once developed, nurses were surveyed on multiple measures regarding the perceived likelihood that it would improve their ability to provide directed patient care. Data were quantified using a Likert scale (0-10), and statistically analyzed. Results The Pop-form records and transfers operative details, specific anatomic monitoring parameters, and senior physician contact information. Sixty-eight nurses completed surveys. The perceived usefulness of different components of the Pop-form system was as follows: 8.9 for the description of the procedure; 9.3 for the operative diagram; 9.4 for the monitoring details and parameters; and 9.4 for the direct contact information for the appropriate surgical team member. All respondents were in favor of widespread adoption of the Pop-form. Conclusion This uniform, visual communication system requires less than 1 minute to compose, yet formalizes and standardizes inter-team communication, and therefore shows promise for improving outcomes following microvascular free tissue transfer. We believe that this simple, innovative communication tool has the potential to be more broadly applied to many other health care settings. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  5. Identifying compensatory movement patterns in the upper extremity using a wearable sensor system.

    Science.gov (United States)

    Ranganathan, Rajiv; Wang, Rui; Dong, Bo; Biswas, Subir

    2017-11-30

    Movement impairments such as those due to stroke often result in the nervous system adopting atypical movements to compensate for movement deficits. Monitoring these compensatory patterns is critical for improving functional outcomes during rehabilitation. The purpose of this study was to test the feasibility and validity of a wearable sensor system for detecting compensatory trunk kinematics during activities of daily living. Participants with no history of neurological impairments performed reaching and manipulation tasks with their upper extremity, and their movements were recorded by a wearable sensor system and validated using a motion capture system. Compensatory movements of the trunk were induced using a brace that limited range of motion at the elbow. Our results showed that the elbow brace elicited compensatory movements of the trunk during reaching tasks but not manipulation tasks, and that a wearable sensor system with two sensors could reliably classify compensatory movements (~90% accuracy). These results show the potential of the wearable system to assess and monitor compensatory movements outside of a lab setting.

  6. In vitro systems toxicology approach to investigate the effects of repeated cigarette smoke exposure on human buccal and gingival organotypic epithelial tissue cultures.

    Science.gov (United States)

    Schlage, Walter K; Iskandar, Anita R; Kostadinova, Radina; Xiang, Yang; Sewer, Alain; Majeed, Shoaib; Kuehn, Diana; Frentzel, Stefan; Talikka, Marja; Geertz, Marcel; Mathis, Carole; Ivanov, Nikolai; Hoeng, Julia; Peitsch, Manuel C

    2014-10-01

    Smoking has been associated with diseases of the lung, pulmonary airways and oral cavity. Cytologic, genomic and transcriptomic changes in oral mucosa correlate with oral pre-neoplasia, cancer and inflammation (e.g. periodontitis). Alteration of smoking-related gene expression changes in oral epithelial cells is similar to that in bronchial and nasal epithelial cells. Using a systems toxicology approach, we have previously assessed the impact of cigarette smoke (CS) seen as perturbations of biological processes in human nasal and bronchial organotypic epithelial culture models. Here, we report our further assessment using in vitro human oral organotypic epithelium models. We exposed the buccal and gingival organotypic epithelial tissue cultures to CS at the air-liquid interface. CS exposure was associated with increased secretion of inflammatory mediators, induction of cytochrome P450s activity and overall weak toxicity in both tissues. Using microarray technology, gene-set analysis and a novel computational modeling approach leveraging causal biological network models, we identified CS impact on xenobiotic metabolism-related pathways accompanied by a more subtle alteration in inflammatory processes. Gene-set analysis further indicated that the CS-induced pathways in the in vitro buccal tissue models resembled those in the in vivo buccal biopsies of smokers from a published dataset. These findings support the translatability of systems responses from in vitro to in vivo and demonstrate the applicability of oral organotypical tissue models for an impact assessment of CS on various tissues exposed during smoking, as well as for impact assessment of reduced-risk products.

  7. A new laser reflectance system capable of measuring changing cross-sectional area of soft tissues during tensile testing.

    Science.gov (United States)

    Pokhai, Gabriel G; Oliver, Michele L; Gordon, Karen D

    2009-09-01

    Determination of the biomechanical properties of soft tissues such as tendons and ligaments is dependent on the accurate measurement of their cross-sectional area (CSA). Measurement methods, which involve contact with the specimen, are problematic because soft tissues are easily deformed. Noncontact measurement methods are preferable in this regard, but may experience difficulty in dealing with the complex cross-sectional shapes and glistening surfaces seen in soft tissues. Additionally, existing CSA measurement systems are separated from the materials testing machine, resulting in the inability to measure CSA during testing. Furthermore, CSA measurements are usually made in a different orientation, and with a different preload, prior to testing. To overcome these problems, a noncontact laser reflectance system (LRS) was developed. Designed to fit in an Instron 8872 servohydraulic test machine, the system measures CSA by orbiting a laser transducer in a circular path around a soft tissue specimen held by tissue clamps. CSA measurements can be conducted before and during tensile testing. The system was validated using machined metallic specimens of various shapes and sizes, as well as different sizes of bovine tendons. The metallic specimens could be measured to within 4% accuracy, and the tendons to within an average error of 4.3%. Statistical analyses showed no significant differences between the measurements of the LRS and those of the casting method, an established measurement technique. The LRS was successfully used to measure the changing CSA of bovine tendons during uniaxial tensile testing. The LRS developed in this work represents a simple, quick, and accurate way of reconstructing complex cross-sectional profiles and calculating cross-sectional areas. In addition, the LRS represents the first system capable of automatically measuring changing CSA of soft tissues during tensile testing, facilitating the calculation of more accurate biomechanical properties.

  8. A 3D bioprinting system to produce human-scale tissue constructs with structural integrity.

    Science.gov (United States)

    Kang, Hyun-Wook; Lee, Sang Jin; Ko, In Kap; Kengla, Carlos; Yoo, James J; Atala, Anthony

    2016-03-01

    A challenge for tissue engineering is producing three-dimensional (3D), vascularized cellular constructs of clinically relevant size, shape and structural integrity. We present an integrated tissue-organ printer (ITOP) that can fabricate stable, human-scale tissue constructs of any shape. Mechanical stability is achieved by printing cell-laden hydrogels together with biodegradable polymers in integrated patterns and anchored on sacrificial hydrogels. The correct shape of the tissue construct is achieved by representing clinical imaging data as a computer model of the anatomical defect and translating the model into a program that controls the motions of the printer nozzles, which dispense cells to discrete locations. The incorporation of microchannels into the tissue constructs facilitates diffusion of nutrients to printed cells, thereby overcoming the diffusion limit of 100-200 μm for cell survival in engineered tissues. We demonstrate capabilities of the ITOP by fabricating mandible and calvarial bone, cartilage and skeletal muscle. Future development of the ITOP is being directed to the production of tissues for human applications and to the building of more complex tissues and solid organs.

  9. Shape memory alloy fixator system for suturing tissue in minimal access surgery.

    Science.gov (United States)

    Xu, W; Frank, T G; Stockham, G; Cuschieri, A

    1999-01-01

    A new technique for suturing human tissue is described in which tissue closure is achieved by means of small fixators made from shape memory alloy. The aim of the development is to provide an alternative to thread suturing in minimal access surgery, which is quicker and requires less skill to achieve the required suturing quality. The design of the fixators is described in terms of the thermal shape recovery of shape memory alloy and a novel form of finite element analysis, which uses a nonlinear elastic element for the material property. Thermal analysis of the fixators and surrounding tissue is used to predict the temperature distribution during and after the application of electric current heating. This was checked in an in vitro experiment, which confirmed that deployment caused no detectable collateral damage to surrounding tissue. In vivo animal studies on the use of the shape memory alloy fixator for suturing tissue are ongoing to establish safety and healing effects.

  10. Identifying and Modeling Dynamic Preference Evolution in Multipurpose Water Resources Systems

    Science.gov (United States)

    Mason, E.; Giuliani, M.; Castelletti, A.; Amigoni, F.

    2018-04-01

    Multipurpose water systems are usually operated on a tradeoff of conflicting operating objectives. Under steady state climatic and socioeconomic conditions, such tradeoff is supposed to represent a fair and/or efficient preference. Extreme variability in external forcing might affect water operators' risk aversion and force a change in her/his preference. Properly accounting for these shifts is key to any rigorous retrospective assessment of the operator's behaviors, and to build descriptive models for projecting the future system evolution. In this study, we explore how the selection of different preferences is linked to variations in the external forcing. We argue that preference selection evolves according to recent, extreme variations in system performance: underperforming in one of the objectives pushes the preference toward the harmed objective. To test this assumption, we developed a rational procedure to simulate the operator's preference selection. We map this selection onto a multilateral negotiation, where multiple virtual agents independently optimize different objectives. The agents periodically negotiate a compromise policy for the operation of the system. Agents' attitudes in each negotiation step are determined by the recent system performance measured by the specific objective they maximize. We then propose a numerical model of preference dynamics that implements a concept from cognitive psychology, the availability bias. We test our modeling framework on a synthetic lake operated for flood control and water supply. Results show that our model successfully captures the operator's preference selection and dynamic evolution driven by extreme wet and dry situations.

  11. Neutron activation analysis of the central nervous system tissues in neurological diseases

    Energy Technology Data Exchange (ETDEWEB)

    Yasui, Masayuki; Ota, Kiichiro [Wakayama Medical Coll. (Japan); Sasajima, Kazuhisa

    1994-07-01

    As the diseases due to excessive metals in living bodies and the metals of their causes, Minamata disease due to Hg, itai-itai disease due to Cd, dialysis brain disease due to Al, hemochromatosis due to Fe, Wilson disease due to Cu and so on have been known. Also as the neural diseases, in which the possibility that metals take part in them is presumed, there are amyotrophic lateral sclerosis, Alzheimer disease, Parkinson disease, Parkinsonism dementia and so on. In order to know the causes of the diseases due to excessive metals in living bodies and neurological diseases, the authors have measured Cu, Ca, Al, Mn, Zn and Fe in central nervous system tissues by activation analysis nondestructive method. The cases investigated were 4 cases of hepatocerebral diseases, 6 cases of ALS, 4 cases of Parkinson disease, 4 cases of Parkinsonism dementia, 4 cases of multiple sclerosis and 5 cases without CNS disease for the control. The method of measurement is described. The results for respective diseases are reported. Cu and Fe are in the relation of mirror images, and Cu formed Cu-superoxide dismutase (SOD) similarly to Zn and Mn as SOD carrier metals, and protects living bodies and CNS from oxidative stress. (K.I.).

  12. A virtual tissue bank for primary central nervous system lymphomas in immunocompetent individuals.

    Science.gov (United States)

    Ponzoni, Maurilio; Kwee, Ivo; Mazzucchelli, Luca; Ferreri, Andrés J M; Zucca, Emanuele; Doglioni, Claudio; Cavalli, Franco; Bertoni, Francesco

    2007-01-01

    Primary central nervous system lymphoma (PCNSL) is a rare form of extranodal non-Hodgkin's lymphoma with continuously increasing incidence in both immunosuppressed and immunocompetent individuals. PCNSL is a very aggressive tumor with a poor outcome, and its clinical outcome is much worse than for nodal lymphomas. Differently from lymphomas arising in lymph nodes or in other extranodal sites, the treatment of PCNSL remains very unsatisfactory. Current biologic knowledge of PCNSL is still limited and several fundamental questions remain to be answered. This is mainly due to the paucity of PCNSL material for adequate translational research. With the aim of providing biologic material to investigators interested in PCNSL, we have implemented a virtual tissue bank (VTB) for PCNSL in immunocompetent patients. After registration, the VTB is accessible via any web browser at www.ielsg.org. Only anonymous data are centralized at the website of the International Extranodal Lymphoma Study Group, whilst the pathologic material is maintained at the local pathology institutes. (c) 2007 S. Karger AG, Basel.

  13. Application of synchrotron radiation for elemental microanalysis of human central nervous system tissue

    Energy Technology Data Exchange (ETDEWEB)

    Szczerbowska-Boruchowska, M.; Lankosz, M.; Ostachowicz, J. [Mining University, Dept. of Radipmetry, Faculty of Physics and Nuclear Techniques, Krakow (Poland); Adamek, D.; Krygowska-Wajs, A.; Tomik, B.; Szczudlik, A. [Jagiellonian University, Institute of Neurology, Collegium Medicum, Krakow (Poland); Simionovici, A.; Bohic, S. [European Synchrotron Radiation Facility ESRF, 38 - Grenoble (France)

    2002-08-01

    The pathogenesis of two neuro-degenerative diseases i.e, Parkinson's Disease (PD) and amyotrophic lateral sclerosis (ALS) are still not known. It is supposed that disturbance of metal ions homeostasis may promote degeneration and atrophy of neurons. As a preliminary study, the quantitative and topographic elemental analysis of selected parts of human brain and spinal cord was performed using synchrotron microbeam-X ray fluorescence ({mu}-SXRF) technique. The samples were taken during the autopsy from patients with PD, ALS and from patients died due to non-neurological conditions events. X-ray fluorescence imaging showed that increased concentration of selected elements are observed in neurons perikaryal parts in compare with surrounding area. Moreover, comparable analysis showed significant differences in accumulation of selected elements between the pathological and control case. The investigations indicate that micro-beam of synchrotron radiation can be satisfactory applied for analysis of central nervous system tissue providing useful information about distribution and contents of elements at the single cell level. (authors)

  14. Human engineered heart tissue as a model system for drug testing.

    Science.gov (United States)

    Eder, Alexandra; Vollert, Ingra; Hansen, Arne; Eschenhagen, Thomas

    2016-01-15

    Drug development is time- and cost-intensive and, despite extensive efforts, still hampered by the limited value of current preclinical test systems to predict side effects, including proarrhythmic and cardiotoxic effects in clinical practice. Part of the problem may be related to species-dependent differences in cardiomyocyte biology. Therefore, the event of readily available human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (CM) has raised hopes that this human test bed could improve preclinical safety pharmacology as well as drug discovery approaches. However, hiPSC-CM are immature and exhibit peculiarities in terms of ion channel function, gene expression, structural organization and functional responses to drugs that limit their present usefulness. Current efforts are thus directed towards improving hiPSC-CM maturity and high-content readouts. Culturing hiPSC-CM as 3-dimensional engineered heart tissue (EHT) improves CM maturity and anisotropy and, in a 24-well format using silicone racks, enables automated, multiplexed high content readout of contractile function. This review summarizes the principal technology and focuses on advantages and disadvantages of this technology and its potential for preclinical drug screening. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Identifying the closeness of eigenstates in quantum many-body systems

    International Nuclear Information System (INIS)

    Li Hai-bin; Yang Yang; Wang Pei; Wang Xiao-guang

    2017-01-01

    We propose a quantity called modulus fidelity to measure the closeness of two quantum pure states. We use it to investigate the closeness of eigenstates in one-dimensional hard-core bosons. When the system is integrable, eigenstates close to their neighbor or not, which leads to a large fluctuation in the distribution of modulus fidelity. When the system becomes chaos, the fluctuation is reduced dramatically, which indicates all eigenstates become close to each other. It is also found that two kind of closeness, i.e., closeness of eigenstates and closeness of eigenvalues, are not correlated at integrability but correlated at chaos. We also propose that the closeness of eigenstates is the underlying mechanism of eigenstate thermalization hypothesis (ETH) which explains the thermalization in quantum many-body systems. (paper)

  16. Identifying Causal Gateways and Mediators in Complex Spatio-Temporal Systems

    Czech Academy of Sciences Publication Activity Database

    Runge, J.; Petoukhov, V.; Donges, J.F.; Hlinka, Jaroslav; Jajcay, Nikola; Vejmelka, Martin; Hartman, David; Marwan, N.; Paluš, Milan; Kurths, J.

    2015-01-01

    Roč. 6, 7 October (2015), Article 8502 ISSN 2041-1723 R&D Projects: GA ČR(CZ) GA14-02634S; GA ČR GA13-23940S; GA MZd(CZ) NV15-29835A Grant - others:GA MŠk(CZ) LL1201; AV ČR + DAAD(CZ-DE) DAAD-15-30 Program:Bilaterální spolupráce Institutional support: RVO:67985807 Keywords : causality * climate * complex systems * dimension reduction * atmospheric dynamics * networks * dynamical systems Subject RIV: DG - Athmosphere Sciences, Meteorology Impact factor: 11.329, year: 2015

  17. Nanoparticle enabled transdermal drug delivery systems for enhanced dose control and tissue targeting

    Science.gov (United States)

    Palmer, Brian C.; DeLouise, Lisa A.

    2017-01-01

    Transdermal drug delivery systems have been around for decades, and current technologies (e.g. patches, ointments, and creams) enhance the skin permeation of low molecular weight, lipophilic drugs that are efficacious at low doses. The objective of current transdermal drug delivery research is to discover ways to enhance skin penetration of larger, hydrophilic drugs and macromolecules for disease treatment and vaccination. Nanocarriers made of lipids, metals, or polymers have been successfully used to increase penetration of drugs or vaccines, control drug release, and target drugs to specific areas of skin in vivo. While more research is needed to identify the safety of nanocarriers, this technology has the potential to expand the use of transdermal routes of administration to a wide array of therapeutics. Here, we review the current state of nanoparticle skin delivery systems with special emphasis on targeting skin diseases. PMID:27983701

  18. Nanoparticle-Enabled Transdermal Drug Delivery Systems for Enhanced Dose Control and Tissue Targeting.

    Science.gov (United States)

    Palmer, Brian C; DeLouise, Lisa A

    2016-12-15

    Transdermal drug delivery systems have been around for decades, and current technologies (e.g., patches, ointments, and creams) enhance the skin permeation of low molecular weight, lipophilic drugs that are efficacious at low doses. The objective of current transdermal drug delivery research is to discover ways to enhance skin penetration of larger, hydrophilic drugs and macromolecules for disease treatment and vaccination. Nanocarriers made of lipids, metals, or polymers have been successfully used to increase penetration of drugs or vaccines, control drug release, and target drugs to specific areas of skin in vivo. While more research is needed to identify the safety of nanocarriers, this technology has the potential to expand the use of transdermal routes of administration to a wide array of therapeutics. Here, we review the current state of nanoparticle skin delivery systems with special emphasis on targeting skin diseases.

  19. Nanoparticle-Enabled Transdermal Drug Delivery Systems for Enhanced Dose Control and Tissue Targeting

    Directory of Open Access Journals (Sweden)

    Brian C. Palmer

    2016-12-01

    Full Text Available Transdermal drug delivery systems have been around for decades, and current technologies (e.g., patches, ointments, and creams enhance the skin permeation of low molecular weight, lipophilic drugs that are efficacious at low doses. The objective of current transdermal drug delivery research is to discover ways to enhance skin penetration of larger, hydrophilic drugs and macromolecules for disease treatment and vaccination. Nanocarriers made of lipids, metals, or polymers have been successfully used to increase penetration of drugs or vaccines, control drug release, and target drugs to specific areas of skin in vivo. While more research is needed to identify the safety of nanocarriers, this technology has the potential to expand the use of transdermal routes of administration to a wide array of therapeutics. Here, we review the current state of nanoparticle skin delivery systems with special emphasis on targeting skin diseases.

  20. Monte Carlo and discrete-ordinate simulations of spectral radiances in a coupled air-tissue system.

    Science.gov (United States)

    Hestenes, Kjersti; Nielsen, Kristian P; Zhao, Lu; Stamnes, Jakob J; Stamnes, Knut

    2007-04-20

    We perform a detailed comparison study of Monte Carlo (MC) simulations and discrete-ordinate radiative-transfer (DISORT) calculations of spectral radiances in a 1D coupled air-tissue (CAT) system consisting of horizontal plane-parallel layers. The MC and DISORT models have the same physical basis, including coupling between the air and the tissue, and we use the same air and tissue input parameters for both codes. We find excellent agreement between radiances obtained with the two codes, both above and in the tissue. Our tests cover typical optical properties of skin tissue at the 280, 540, and 650 nm wavelengths. The normalized volume scattering function for internal structures in the skin is represented by the one-parameter Henyey-Greenstein function for large particles and the Rayleigh scattering function for small particles. The CAT-DISORT code is found to be approximately 1000 times faster than the CAT-MC code. We also show that the spectral radiance field is strongly dependent on the inherent optical properties of the skin tissue.

  1. Towards 3D ultrasound image based soft tissue tracking: a transrectal ultrasound prostate image alignment system.

    Science.gov (United States)

    Baumann, Michael; Mozer, Pierre; Daanen, Vincent; Troccaz, Jocelyne

    2007-01-01

    The emergence of real-time 3D ultrasound (US) makes it possible to consider image-based tracking of subcutaneous soft tissue targets for computer guided diagnosis and therapy. We propose a 3D transrectal US based tracking system for precise prostate biopsy sample localisation. The aim is to improve sample distribution, to enable targeting of unsampled regions for repeated biopsies, and to make post-interventional quality controls possible. Since the patient is not immobilized, since the prostate is mobile and due to the fact that probe movements are only constrained by the rectum during biopsy acquisition, the tracking system must be able to estimate rigid transformations that are beyond the capture range of common image similarity measures. We propose a fast and robust multi-resolution attribute-vector registration approach that combines global and local optimization methods to solve this problem. Global optimization is performed on a probe movement model that reduces the dimensionality of the search space and thus renders optimization efficient. The method was tested on 237 prostate volumes acquired from 14 different patients for 3D to 3D and 3D to orthogonal 2D slices registration. The 3D-3D version of the algorithm converged correctly in 96.7% of all cases in 6.5s with an accuracy of 1.41mm (r.m.s.) and 3.84mm (max). The 3D to slices method yielded a success rate of 88.9% in 2.3s with an accuracy of 1.37mm (r.m.s.) and 4.3mm (max).

  2. Immunofluorescence in multiple tissues utilizing serum from a patient affected by systemic lupus erythematosus

    Directory of Open Access Journals (Sweden)

    Piotr Brzezinski

    2012-01-01

    Full Text Available Introduction: Lupus erythematosus is a chronic, inflammatory autoimmune disease that can affect multiple organs. Lupus can affect many parts of the body, especially in systemic lupus erythematosus (SLE; affected tissues may include the joints, skin, kidneys, heart, lungs, blood vessels, and brain. Case report: A 46-year-old female presented with pruritus, photosensitivity and edema of the cheeks of about 2 years duration, and was evaluated by a dermatologist. On examination, multiple telangiectasias were present on the cheeks, with erythema, edema and a malar rash observed. A review of systems documented breathing difficulty and pleuitic pain, joint pain and joint edema, photosensitivity, cardiac dysrhythmia, and periodic pain in the back close to the kidneys. Methods: Skin biopsies for hematoxylin and eosin testing, as well for direct and indirect immunofluorescence were performed, in addition to multiple diagnostic blood tests, chest radiography and directed immunologic testing. Results: The blood testing showed elevated C-reactive protein. Direct and indirect immunofluorescence testing utilizing monkey esophagus, mouse and pig heart and kidney, normal human eyelid skin and veal brain demonstrated strong reactivity to several components of smooth muscle, nerves, blood vessels, skin basement membrane zone and sweat gland ducts and skin meibomian glands. Anti-endomysium antibodies were detected as well as others, especially using FITC conjugated Complement/C1q, FITC conjugated anti-human immunoglobulin IgG and FITC conjugated anti-human fibrinogen. Conclusions: We conclude that both direct and indirect immunofluorescence using several substrates can unveil previously undocumented autoantibodies in multiple organs in lupus erythematosus, and that these findings could be utilized to complement existing diagnostic testing for this disorder.

  3. Can surveillance systems identify and avert adverse drug events? A prospective evaluation of a commercial application.

    Science.gov (United States)

    Jha, Ashish K; Laguette, Julia; Seger, Andrew; Bates, David W

    2008-01-01

    Computerized monitors can effectively detect and potentially prevent adverse drug events (ADEs). Most monitors have been developed in large academic hospitals and are not readily usable in other settings. We assessed the ability of a commercial program to identify and prevent ADEs in a community hospital. and Measurement We prospectively evaluated the commercial application in a community-based hospital. We examined the frequency and types of alerts produced, how often they were associated with ADEs and potential ADEs, and the potential financial impact of monitoring for ADEs. Among 2,407 patients screened, the application generated 516 high priority alerts. We were able to review 266 alerts at the time they were generated and among these, 30 (11.3%) were considered substantially important to warrant contacting the physician caring for the patient. These 30 alerts were associated with 4 ADEs and 11 potential ADEs. In all 15 cases, the responsible physician was unaware of the event, leading to a change in clinical care in 14 cases. Overall, 23% of high priority alerts were associated with an ADE (95% confidence interval [CI] 12% to 34%) and another 15% were associated with a potential ADE (95% CI 6% to 24%). Active surveillance used approximately 1.5 hours of pharmacist time daily. A commercially available, computer-based ADE detection tool was effective at identifying ADEs. When used as part of an active surveillance program, it can have an impact on preventing or ameliorating ADEs.

  4. Serotonin 5-HT4 receptors and forebrain cholinergic system: receptor expression in identified cell populations.

    Science.gov (United States)

    Peñas-Cazorla, Ra