Paper-based Synthetic Gene Networks

Science.gov (United States)

Pardee, Keith; Green, Alexander A.; Ferrante, Tom; Cameron, D. Ewen; DaleyKeyser, Ajay; Yin, Peng; Collins, James J.

2014-01-01

Synthetic gene networks have wide-ranging uses in reprogramming and rewiring organisms. To date, there has not been a way to harness the vast potential of these networks beyond the constraints of a laboratory or in vivo environment. Here, we present an in vitro paper-based platform that provides a new venue for synthetic biologists to operate, and a much-needed medium for the safe deployment of engineered gene circuits beyond the lab. Commercially available cell-free systems are freeze-dried onto paper, enabling the inexpensive, sterile and abiotic distribution of synthetic biology-based technologies for the clinic, global health, industry, research and education. For field use, we create circuits with colorimetric outputs for detection by eye, and fabricate a low-cost, electronic optical interface. We demonstrate this technology with small molecule and RNA actuation of genetic switches, rapid prototyping of complex gene circuits, and programmable in vitro diagnostics, including glucose sensors and strain-specific Ebola virus sensors. PMID:25417167

First study on gene expression of cement proteins and potential adhesion-related genes of a membranous-based barnacle as revealed from Next-Generation Sequencing technology

KAUST Repository

Lin, Hsiu Chin; Wong, Yue Him; Tsang, Ling Ming; Chu, Ka Hou; Qian, Pei Yuan; Chan, Benny K K

2013-01-01

This is the first study applying Next-Generation Sequencing (NGS) technology to survey the kinds, expression location, and pattern of adhesion-related genes in a membranous-based barnacle. A total of 77,528,326 and 59,244,468 raw sequence reads of total RNA were generated from the prosoma and the basis of Tetraclita japonica formosana, respectively. In addition, 55,441 and 67,774 genes were further assembled and analyzed. The combined sequence data from both body parts generates a total of 79,833 genes of which 47.7% were shared. Homologues of barnacle cement proteins - CP-19K, -52K, and -100K - were found and all were dominantly expressed at the basis where the cement gland complex is located. This is the main area where transcripts of cement proteins and other potential adhesion-related genes were detected. The absence of another common barnacle cement protein, CP-20K, in the adult transcriptome suggested a possible life-stage restricted gene function and/or a different mechanism in adhesion between membranous-based and calcareous-based barnacles. © 2013 © 2013 Taylor & Francis.

First study on gene expression of cement proteins and potential adhesion-related genes of a membranous-based barnacle as revealed from Next-Generation Sequencing technology

KAUST Repository

Lin, Hsiu Chin

2013-12-12

This is the first study applying Next-Generation Sequencing (NGS) technology to survey the kinds, expression location, and pattern of adhesion-related genes in a membranous-based barnacle. A total of 77,528,326 and 59,244,468 raw sequence reads of total RNA were generated from the prosoma and the basis of Tetraclita japonica formosana, respectively. In addition, 55,441 and 67,774 genes were further assembled and analyzed. The combined sequence data from both body parts generates a total of 79,833 genes of which 47.7% were shared. Homologues of barnacle cement proteins - CP-19K, -52K, and -100K - were found and all were dominantly expressed at the basis where the cement gland complex is located. This is the main area where transcripts of cement proteins and other potential adhesion-related genes were detected. The absence of another common barnacle cement protein, CP-20K, in the adult transcriptome suggested a possible life-stage restricted gene function and/or a different mechanism in adhesion between membranous-based and calcareous-based barnacles. © 2013 © 2013 Taylor & Francis.

Nano-scale gene delivery systems; current technology, obstacles, and future directions.

Science.gov (United States)

Garcia-Guerra, Antonio; Dunwell, Thomas L; Trigueros, Sonia

2018-01-07

Within the different applications of nanomedicine currently being developed, nano-gene delivery is appearing as an exciting new technique with the possibility to overcome recognised hurdles and fulfill several biological and medical needs. The central component of all delivery systems is the requirement for the delivery of genetic material into cells, and for them to eventually reside in the nucleus where their desired function will be exposed. However, genetic material does not passively enter cells; thus, a delivery system is necessary. The emerging field of nano-gene delivery exploits the use of new materials and the properties that arise at the nanometre-scale to produce delivery vectors that can effectively deliver genetic material into a variety of different types of cells. The novel physicochemical properties of the new delivery vectors can be used to address the current challenges existing in nucleic acid delivery in vitro and in vivo. While there is a growing interest in nanostructure-based gene delivery, the field is still in its infancy, and there is yet much to discover about nanostructures and their physicochemical properties in a biological context. We carry out an organized and focused search of bibliographic databases. Our results suggest that despite new breakthroughs in nanostructure synthesis and advanced characterization techniques, we still face many barriers in producing highly efficient and non-toxic delivery systems. In this review, we overview the types of systems currently used for clinical and biomedical research applications along with their advantages and disadvantages, as well as discussing barriers that arise from nano-scale interactions with biological material. In conclusion, we hope that by bringing the far reaching multidisciplinary nature of nano-gene delivery to light, new targeted nanotechnology-bases strategies are developed to overcome the major challenges covered in this review. Copyright© Bentham Science Publishers; For

A fisheye viewer for microarray-based gene expression data

Directory of Open Access Journals (Sweden)

Munson Ethan V

2006-10-01

Full Text Available Abstract Background Microarray has been widely used to measure the relative amounts of every mRNA transcript from the genome in a single scan. Biologists have been accustomed to reading their experimental data directly from tables. However, microarray data are quite large and are stored in a series of files in a machine-readable format, so direct reading of the full data set is not feasible. The challenge is to design a user interface that allows biologists to usefully view large tables of raw microarray-based gene expression data. This paper presents one such interface – an electronic table (E-table that uses fisheye distortion technology. Results The Fisheye Viewer for microarray-based gene expression data has been successfully developed to view MIAME data stored in the MAGE-ML format. The viewer can be downloaded from the project web site http://polaris.imt.uwm.edu:7777/fisheye/. The fisheye viewer was implemented in Java so that it could run on multiple platforms. We implemented the E-table by adapting JTable, a default table implementation in the Java Swing user interface library. Fisheye views use variable magnification to balance magnification for easy viewing and compression for maximizing the amount of data on the screen. Conclusion This Fisheye Viewer is a lightweight but useful tool for biologists to quickly overview the raw microarray-based gene expression data in an E-table.

Newer Gene Editing Technologies toward HIV Gene Therapy

Directory of Open Access Journals (Sweden)

Premlata Shankar

2013-11-01

Full Text Available Despite the great success of highly active antiretroviral therapy (HAART in ameliorating the course of HIV infection, alternative therapeutic approaches are being pursued because of practical problems associated with life-long therapy. The eradication of HIV in the so-called “Berlin patient” who received a bone marrow transplant from a CCR5-negative donor has rekindled interest in genome engineering strategies to achieve the same effect. Precise gene editing within the cells is now a realistic possibility with recent advances in understanding the DNA repair mechanisms, DNA interaction with transcription factors and bacterial defense mechanisms. Within the past few years, four novel technologies have emerged that can be engineered for recognition of specific DNA target sequences to enable site-specific gene editing: Homing Endonuclease, ZFN, TALEN, and CRISPR/Cas9 system. The most recent CRISPR/Cas9 system uses a short stretch of complementary RNA bound to Cas9 nuclease to recognize and cleave target DNA, as opposed to the previous technologies that use DNA binding motifs of either zinc finger proteins or transcription activator-like effector molecules fused to an endonuclease to mediate sequence-specific DNA cleavage. Unlike RNA interference, which requires the continued presence of effector moieties to maintain gene silencing, the newer technologies allow permanent disruption of the targeted gene after a single treatment. Here, we review the applications, limitations and future prospects of novel gene-editing strategies for use as HIV therapy.

Plant gene technology: social considerations

African Journals Online (AJOL)

Administrator

The genetic modification of plants by gene technology is of immense potential benefits, but there may be possible risks. ... As a new endeavour, however, people have a mixed ... reality by gene biotechnology (Watson, 1997). Industrial ...

Physical Mapping Technologies for the Identification and Characterization of Mutated Genes to Crop Quality

International Nuclear Information System (INIS)

2011-09-01

The improvement of quality traits in food and industrial crops is an important breeding objective for both developed and developing countries in order to add value to the crop and thereby increasing farmers' income. It has been well established that the application of mutagens can be a very important approach for manipulating many crop characteristics including quality. While mutation induction using nuclear techniques such as gamma irradiation is a power tool in generating new genotypes with favourable alleles for improving crop quality in plant breeding, a more thorough understanding of gene expression, gene interactions, and physical location will improve ability to manipulate and control genes, and directly lead to crop improvement. Physical mapping technologies, molecular markers and molecular cytogenetic techniques are tools available with the potential to enhance the ability to tag genes and gene complexes to facilitate the selection of desirable genotypes in breeding programmes, including those based on mutation breeding. This Coordinated Research Project (CRP) on 'Physical Mapping Technologies for the Identification and Characterization of Mutated Genes Contributing to Crop Quality' was conducted under the overall IAEA project objective of 'Identification, Characterization and Transfer of Mutated Genes'. The specific objectives of the CRP were to assist Member States in accelerating crop breeding programmes through the application of physical mapping and complementary genomic approaches, and the characterization and utilization of induced mutants for improvement of crop quality. The IAEA-TECDOC describes the success obtained in the application of molecular cytology, molecular markers, physical mapping and mutation technologies since the inception of the CRP in 2003. The CRP also resulted in two book chapters, 35 peer reviewed papers, 25 conference proceedings, one PhD thesis, and 22 published abstracts. In addition, thirteen sequences were submitted to the

Directed Vapor Deposition: Low Vacuum Materials Processing Technology

National Research Council Canada - National Science Library

Groves, J. F; Mattausch, G; Morgner, H; Hass, D. D; Wadley, H. N

2000-01-01

Directed vapor deposition (DVD) is a recently developed electron beam-based evaporation technology designed to enhance the creation of high performance thick and thin film coatings on small area surfaces...

Design and investigation of planar technology based ultra-wideband antenna with directional radiation patterns

Energy Technology Data Exchange (ETDEWEB)

Meena, M. L., E-mail: madan.meena.ece@gamil.com; Parmar, Girish, E-mail: girish-parmar2002@yahoo.com; Kumar, Mithilesh, E-mail: mith-kr@yahoo.com [Department of Electronics Engineering, Rajasthan Technical University, Kota (India)

2016-03-09

A novel design technique based on planar technology for ultra-wideband (UWB) antennas with different ground shape having directional radiation pattern is being presented here. Firstly, the L-shape corner reflector ground plane antenna is designed with microstrip feed line in order to achieve large bandwidth and directivity. Thereafter, for the further improvement in the directivity as well as for better impedance matching the parabolic-shape ground plane has been introduced. The coaxial feed line is given for the proposed directional antenna in order to achieve better impedance matching with 50 ohm transmission line. The simulation analysis of the antenna is done on CST Microwave Studio software using FR-4 substrate having thickness of 1.6 mm and dielectric constant of 4.4. The simulated result shows a good return loss (S11) with respect to -10 dB. The radiation pattern characteristic, angular width, directivity and bandwidth performance of the antenna have also been compared at different resonant frequencies. The designed antennas exhibit low cost, low reflection coefficient and better directivity in the UWB frequency band.

Why commercialization of gene therapy stalled; examining the life cycles of gene therapy technologies.

Science.gov (United States)

Ledley, F D; McNamee, L M; Uzdil, V; Morgan, I W

2014-02-01

This report examines the commercialization of gene therapy in the context of innovation theories that posit a relationship between the maturation of a technology through its life cycle and prospects for successful product development. We show that the field of gene therapy has matured steadily since the 1980s, with the congruent accumulation of >35 000 papers, >16 000 US patents, >1800 clinical trials and >$4.3 billion in capital investment in gene therapy companies. Gene therapy technologies comprise a series of dissimilar approaches for gene delivery, each of which has introduced a distinct product architecture. Using bibliometric methods, we quantify the maturation of each technology through a characteristic life cycle S-curve, from a Nascent stage, through a Growing stage of exponential advance, toward an Established stage and projected limit. Capital investment in gene therapy is shown to have occurred predominantly in Nascent stage technologies and to be negatively correlated with maturity. Gene therapy technologies are now achieving the level of maturity that innovation research and biotechnology experience suggest may be requisite for efficient product development. Asynchrony between the maturation of gene therapy technologies and capital investment in development-focused business models may have stalled the commercialization of gene therapy.

Gene doping detection: evaluation of approach for direct detection of gene transfer using erythropoietin as a model system.

Science.gov (United States)

Baoutina, A; Coldham, T; Bains, G S; Emslie, K R

2010-08-01

As clinical gene therapy has progressed toward realizing its potential, concern over misuse of the technology to enhance performance in athletes is growing. Although 'gene doping' is banned by the World Anti-Doping Agency, its detection remains a major challenge. In this study, we developed a methodology for direct detection of the transferred genetic material and evaluated its feasibility for gene doping detection in blood samples from athletes. Using erythropoietin (EPO) as a model gene and a simple in vitro system, we developed real-time PCR assays that target sequences within the transgene complementary DNA corresponding to exon/exon junctions. As these junctions are absent in the endogenous gene due to their interruption by introns, the approach allows detection of trace amounts of a transgene in a large background of the endogenous gene. Two developed assays and one commercial gene expression assay for EPO were validated. On the basis of ability of these assays to selectively amplify transgenic DNA and analysis of literature on testing of gene transfer in preclinical and clinical gene therapy, it is concluded that the developed approach would potentially be suitable to detect gene doping through gene transfer by analysis of small volumes of blood using regular out-of-competition testing.

Identification of rat genes by TWINSCAN gene prediction, RT-PCR, and direct sequencing

DEFF Research Database (Denmark)

Wu, Jia Qian; Shteynberg, David; Arumugam, Manimozhiyan

2004-01-01

an alternative approach: reverse transcription-polymerase chain reaction (RT-PCR) and direct sequencing based on dual-genome de novo predictions from TWINSCAN. We tested 444 TWINSCAN-predicted rat genes that showed significant homology to known human genes implicated in disease but that were partially...... in the single-intron experiment. Spliced sequences were amplified in 46 cases (34%). We conclude that this procedure for elucidating gene structures with native cDNA sequences is cost-effective and will become even more so as it is further optimized.......The publication of a draft sequence of a third mammalian genome--that of the rat--suggests a need to rethink genome annotation. New mammalian sequences will not receive the kind of labor-intensive annotation efforts that are currently being devoted to human. In this paper, we demonstrate...

Gene Directed Enzyme Prodrug Therapy Using Rabbit Cytochrome P450 4B1 in Murine Colon Adenocarcinoma

Energy Technology Data Exchange (ETDEWEB)

Kim, Sung Joo; Kang, Joo Hyun; Lee, Tae Sup; Kim, Kyeong Min; Woo, Kwang Sun; Chung, Wee Sup; Cheon, Gi Jeong; Choi, Chang Woon; Lim, Sang Moo [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

2007-07-01

The conventional cancer therapy is chemotherapy, surgical resection and/or radiotherapy. Chemotherapy using cytotoxic drug has some problems with lack of tumor selectivity resulting in toxicity to normal tissues. To enhance the tumor selectivity of cytotoxic drug, the application of suicidal gene therapy technology was designed. Suicidal gene therapy is based on the expression in tumor cells of a gene encoding an enzyme that converts a non-toxic prodrug into a cytotoxic product. Representative suicidal genes are Herpes simplex virus type 1 thymidine kinase (HSV1- tk) and cytosine deaminase (cd). Recently, a new prodrug-converting enzyme based on rabbit cytochrome P450 4B1 gene (cyp4B1) has been reported for therapy of experimental brain tumor. This enzyme activates the prodrugs such as 4-ipomeanol (4-IM) and 2- aminoanthracene (2-AA) to highly reactive furane epoxide and unsaturated dialdehyde intermediate, respectively. DNA alkylation seems to be the main mechanism of cytotoxicity of these activated drugs. In this study, we isolated cyp4B1 cDNA from rabbit lung, transduced cyp4B1 expression vector into murine colon cancer cell, and then analyzed the cytotoxic properties of cyp4b1-activated 2-AA in cyp4B1 transduced cells to verify the cyp4B1 enzyme system for gene directed enzyme prodrug therapy.

Gene Directed Enzyme Prodrug Therapy Using Rabbit Cytochrome P450 4B1 in Murine Colon Adenocarcinoma

International Nuclear Information System (INIS)

Kim, Sung Joo; Kang, Joo Hyun; Lee, Tae Sup; Kim, Kyeong Min; Woo, Kwang Sun; Chung, Wee Sup; Cheon, Gi Jeong; Choi, Chang Woon; Lim, Sang Moo

2007-01-01

The conventional cancer therapy is chemotherapy, surgical resection and/or radiotherapy. Chemotherapy using cytotoxic drug has some problems with lack of tumor selectivity resulting in toxicity to normal tissues. To enhance the tumor selectivity of cytotoxic drug, the application of suicidal gene therapy technology was designed. Suicidal gene therapy is based on the expression in tumor cells of a gene encoding an enzyme that converts a non-toxic prodrug into a cytotoxic product. Representative suicidal genes are Herpes simplex virus type 1 thymidine kinase (HSV1- tk) and cytosine deaminase (cd). Recently, a new prodrug-converting enzyme based on rabbit cytochrome P450 4B1 gene (cyp4B1) has been reported for therapy of experimental brain tumor. This enzyme activates the prodrugs such as 4-ipomeanol (4-IM) and 2- aminoanthracene (2-AA) to highly reactive furane epoxide and unsaturated dialdehyde intermediate, respectively. DNA alkylation seems to be the main mechanism of cytotoxicity of these activated drugs. In this study, we isolated cyp4B1 cDNA from rabbit lung, transduced cyp4B1 expression vector into murine colon cancer cell, and then analyzed the cytotoxic properties of cyp4b1-activated 2-AA in cyp4B1 transduced cells to verify the cyp4B1 enzyme system for gene directed enzyme prodrug therapy

A copula method for modeling directional dependence of genes

Directory of Open Access Journals (Sweden)

Park Changyi

2008-05-01

Full Text Available Abstract Background Genes interact with each other as basic building blocks of life, forming a complicated network. The relationship between groups of genes with different functions can be represented as gene networks. With the deposition of huge microarray data sets in public domains, study on gene networking is now possible. In recent years, there has been an increasing interest in the reconstruction of gene networks from gene expression data. Recent work includes linear models, Boolean network models, and Bayesian networks. Among them, Bayesian networks seem to be the most effective in constructing gene networks. A major problem with the Bayesian network approach is the excessive computational time. This problem is due to the interactive feature of the method that requires large search space. Since fitting a model by using the copulas does not require iterations, elicitation of the priors, and complicated calculations of posterior distributions, the need for reference to extensive search spaces can be eliminated leading to manageable computational affords. Bayesian network approach produces a discretely expression of conditional probabilities. Discreteness of the characteristics is not required in the copula approach which involves use of uniform representation of the continuous random variables. Our method is able to overcome the limitation of Bayesian network method for gene-gene interaction, i.e. information loss due to binary transformation. Results We analyzed the gene interactions for two gene data sets (one group is eight histone genes and the other group is 19 genes which include DNA polymerases, DNA helicase, type B cyclin genes, DNA primases, radiation sensitive genes, repaire related genes, replication protein A encoding gene, DNA replication initiation factor, securin gene, nucleosome assembly factor, and a subunit of the cohesin complex by adopting a measure of directional dependence based on a copula function. We have compared

Identification of direct regulatory targets of the transcription factor Sox10 based on function and conservation

Directory of Open Access Journals (Sweden)

Lee Sanghyuk

2008-09-01

Full Text Available Abstract Background Sox10, a member of the Sry-related HMG-Box gene family, is a critical transcription factor for several important cell lineages, most notably the neural crest stem cells and the derivative peripheral glial cells and melanocytes. Thus far, only a handful of direct target genes are known for this transcription factor limiting our understanding of the biological network it governs. Results We describe identification of multiple direct regulatory target genes of Sox10 through a procedure based on function and conservation. By combining RNA interference technique and DNA microarray technology, we have identified a set of genes that show significant down-regulation upon introduction of Sox10 specific siRNA into Schwannoma cells. Subsequent comparative genomics analyses led to potential binding sites for Sox10 protein conserved across several mammalian species within the genomic region proximal to these genes. Multiple sites belonging to 4 different genes (proteolipid protein, Sox10, extracellular superoxide dismutase, and pleiotrophin were shown to directly interact with Sox10 by chromatin immunoprecipitation assay. We further confirmed the direct regulation through the identified cis-element for one of the genes, extracellular superoxide dismutase, using electrophoretic mobility shift assay and reporter assay. Conclusion In sum, the process of combining differential expression profiling and comparative genomics successfully led to further defining the role of Sox10, a critical transcription factor for the development of peripheral glia. Our strategy utilizing relatively accessible techniques and tools should be applicable to studying the function of other transcription factors.

Establishing a novel single-copy primer-internal intron-spanning PCR (spiPCR) procedure for the direct detection of gene doping.

Science.gov (United States)

Beiter, Thomas; Zimmermann, Martina; Fragasso, Annunziata; Armeanu, Sorin; Lauer, Ulrich M; Bitzer, Michael; Su, Hua; Young, William L; Niess, Andreas M; Simon, Perikles

2008-01-01

So far, the abuse of gene transfer technology in sport, so-called gene doping, is undetectable. However, recent studies in somatic gene therapy indicate that long-term presence of transgenic DNA (tDNA) following various gene transfer protocols can be found in DNA isolated from whole blood using conventional PCR protocols. Application of these protocols for the direct detection of gene doping would require almost complete knowledge about the sequence of the genetic information that has been transferred. Here, we develop and describe the novel single-copy primer-internal intron-spanning PCR (spiPCR) procedure that overcomes this difficulty. Apart from the interesting perspectives that this spiPCR procedure offers in the fight against gene doping, this technology could also be of interest in biodistribution and biosafety studies for gene therapeutic applications.

DNA Array-Based Gene Profiling

Science.gov (United States)

Mocellin, Simone; Provenzano, Maurizio; Rossi, Carlo Riccardo; Pilati, Pierluigi; Nitti, Donato; Lise, Mario

2005-01-01

Cancer is a heterogeneous disease in most respects, including its cellularity, different genetic alterations, and diverse clinical behaviors. Traditional molecular analyses are reductionist, assessing only 1 or a few genes at a time, thus working with a biologic model too specific and limited to confront a process whose clinical outcome is likely to be governed by the combined influence of many genes. The potential of functional genomics is enormous, because for each experiment, thousands of relevant observations can be made simultaneously. Accordingly, DNA array, like other high-throughput technologies, might catalyze and ultimately accelerate the development of knowledge in tumor cell biology. Although in its infancy, the implementation of DNA array technology in cancer research has already provided investigators with novel data and intriguing new hypotheses on the molecular cascade leading to carcinogenesis, tumor aggressiveness, and sensitivity to antiblastic agents. Given the revolutionary implications that the use of this technology might have in the clinical management of patients with cancer, principles of DNA array-based tumor gene profiling need to be clearly understood for the data to be correctly interpreted and appreciated. In the present work, we discuss the technical features characterizing this powerful laboratory tool and review the applications so far described in the field of oncology. PMID:15621987

Detection of Gene Interactions Based on Syntactic Relations

Directory of Open Access Journals (Sweden)

Mi-Young Kim

2008-01-01

Full Text Available Interactions between proteins and genes are considered essential in the description of biomolecular phenomena, and networks of interactions are applied in a system's biology approach. Recently, many studies have sought to extract information from biomolecular text using natural language processing technology. Previous studies have asserted that linguistic information is useful for improving the detection of gene interactions. In particular, syntactic relations among linguistic information are good for detecting gene interactions. However, previous systems give a reasonably good precision but poor recall. To improve recall without sacrificing precision, this paper proposes a three-phase method for detecting gene interactions based on syntactic relations. In the first phase, we retrieve syntactic encapsulation categories for each candidate agent and target. In the second phase, we construct a verb list that indicates the nature of the interaction between pairs of genes. In the last phase, we determine direction rules to detect which of two genes is the agent or target. Even without biomolecular knowledge, our method performs reasonably well using a small training dataset. While the first phase contributes to improve recall, the second and third phases contribute to improve precision. In the experimental results using ICML 05 Workshop on Learning Language in Logic (LLL05 data, our proposed method gave an F-measure of 67.2% for the test data, significantly outperforming previous methods. We also describe the contribution of each phase to the performance.

Exploration of new perspectives and limitations in Agrobacterium mediated gene transfer technology. Progress report, [June 1, 1992-- May 31, 1994

Energy Technology Data Exchange (ETDEWEB)

Marton, L.

1994-12-31

This report describes progress aimed at constructing gene-transfer technology for Nicotiana plumbaginifolia. Most actual effort as described herein has so far been directed at exploring new perspectives and limitations in Agrobacterium mediated gene transfer. Accomplishments are described using a core homologous gene targeting vector.

Form gene clustering method about pan-ethnic-group products based on emotional semantic

Science.gov (United States)

Chen, Dengkai; Ding, Jingjing; Gao, Minzhuo; Ma, Danping; Liu, Donghui

2016-09-01

The use of pan-ethnic-group products form knowledge primarily depends on a designer's subjective experience without user participation. The majority of studies primarily focus on the detection of the perceptual demands of consumers from the target product category. A pan-ethnic-group products form gene clustering method based on emotional semantic is constructed. Consumers' perceptual images of the pan-ethnic-group products are obtained by means of product form gene extraction and coding and computer aided product form clustering technology. A case of form gene clustering about the typical pan-ethnic-group products is investigated which indicates that the method is feasible. This paper opens up a new direction for the future development of product form design which improves the agility of product design process in the era of Industry 4.0.

A high-throughput readout architecture based on PCI-Express Gen3 and DirectGMA technology

International Nuclear Information System (INIS)

Rota, L.; Vogelgesang, M.; Perez, L.E. Ardila; Caselle, M.; Chilingaryan, S.; Dritschler, T.; Zilio, N.; Kopmann, A.; Balzer, M.; Weber, M.

2016-01-01

Modern physics experiments produce multi-GB/s data rates. Fast data links and high performance computing stages are required for continuous data acquisition and processing. Because of their intrinsic parallelism and computational power, GPUs emerged as an ideal solution to process this data in high performance computing applications. In this paper we present a high-throughput platform based on direct FPGA-GPU communication. The architecture consists of a Direct Memory Access (DMA) engine compatible with the Xilinx PCI-Express core, a Linux driver for register access, and high- level software to manage direct memory transfers using AMD's DirectGMA technology. Measurements with a Gen3 x8 link show a throughput of 6.4 GB/s for transfers to GPU memory and 6.6 GB/s to system memory. We also assess the possibility of using the architecture in low latency systems: preliminary measurements show a round-trip latency as low as 1 μs for data transfers to system memory, while the additional latency introduced by OpenCL scheduling is the current limitation for GPU based systems. Our implementation is suitable for real-time DAQ system applications ranging from photon science and medical imaging to High Energy Physics (HEP) systems

Directed-energy process technology efforts

Science.gov (United States)

Alexander, P.

1985-01-01

A summary of directed-energy process technology for solar cells was presented. This technology is defined as directing energy or mass to specific areas on solar cells to produce a desired effect in contrast to exposing a cell to a thermal or mass flow environment. Some of these second generation processing techniques are: ion implantation; microwave-enhanced chemical vapor deposition; rapid thermal processing; and the use of lasers for cutting, assisting in metallization, assisting in deposition, and drive-in of liquid dopants. Advantages of directed energy techniques are: surface heating resulting in the bulk of the cell material being cooler and unchanged; better process control yields; better junction profiles, junction depths, and metal sintering; lower energy consumption during processing and smaller factory space requirements. These advantages should result in higher-efficiency cells at lower costs. The results of the numerous contracted efforts were presented as well as the application potentials of these new technologies.

Geothermal Technologies Program: Direct Use

Energy Technology Data Exchange (ETDEWEB)

2004-08-01

This general publication describes geothermal direct use systems, and how they have been effectively used throughout the country. It also describes the DOE program R&D efforts in this area, and summarizes several projects using direct use technology.

An enhanced topologically significant directed random walk in cancer classification using gene expression datasets

Directory of Open Access Journals (Sweden)

Choon Sen Seah

2017-12-01

Full Text Available Microarray technology has become one of the elementary tools for researchers to study the genome of organisms. As the complexity and heterogeneity of cancer is being increasingly appreciated through genomic analysis, cancerous classification is an emerging important trend. Significant directed random walk is proposed as one of the cancerous classification approach which have higher sensitivity of risk gene prediction and higher accuracy of cancer classification. In this paper, the methodology and material used for the experiment are presented. Tuning parameter selection method and weight as parameter are applied in proposed approach. Gene expression dataset is used as the input datasets while pathway dataset is used to build a directed graph, as reference datasets, to complete the bias process in random walk approach. In addition, we demonstrate that our approach can improve sensitive predictions with higher accuracy and biological meaningful classification result. Comparison result takes place between significant directed random walk and directed random walk to show the improvement in term of sensitivity of prediction and accuracy of cancer classification.

[Sequencing technology in gene diagnosis and its application].

Science.gov (United States)

Yibin, Guo

2014-11-01

The study of gene mutation is one of the hot topics in the field of life science nowadays, and the related detection methods and diagnostic technology have been developed rapidly. Sequencing technology plays an indispensable role in the definite diagnosis and classification of genetic diseases. In this review, we summarize the research progress in sequencing technology, evaluate the advantages and disadvantages of 1(st) ~3(rd) generation of sequencing technology, and describe its application in gene diagnosis. Also we made forecasts and prospects on its development trend.

[The progress and prospect of application of genetic testing technology-based gene detection technology in the diagnosis and treatment of hereditary cancer].

Science.gov (United States)

He, J X; Jiang, Y F

2017-08-06

Hereditary cancer is caused by specific pathogenic gene mutations. Early detection and early intervention are the most effective ways to prevent and control hereditary cancer. High-throughput sequencing based genetic testing technology (NGS) breaks through the restrictions of pedigree analysis, provide a convenient and efficient method to detect and diagnose hereditary cancer. Here, we introduce the mechanism of hereditary cancer, summarize, discuss and prospect the application of NGS and other genetic tests in the diagnosis of hereditary retinoblastoma, hereditary breast and ovarian cancer syndrome, hereditary colorectal cancer and other complex and rare hereditary tumors.

Technologies for direct production of flexible H2/CO synthesis gas

International Nuclear Information System (INIS)

Song Xueping; Guo Zhancheng

2006-01-01

The use of synthesis gas offers the opportunity to furnish a broad range of environmentally clean fuels and high value chemicals. However, synthesis gas manufacturing systems based on natural gas are capital intensive, and hence, there is great interest in technologies for cost effective synthesis gas production. Direct production of synthesis gas with flexible H 2 /CO ratio, which is in agreement with the stoichiometric ratios required by major synthesis gas based petrochemicals, can decrease the capital investment as well as the operating cost. Although CO 2 reforming and catalytic partial oxidation can directly produce desirable H 2 /CO synthesis gas, they are complicated and continued studies are necessary. In fact, direct production of flexible H 2 /CO synthesis gas can be obtained by optimizing the process schemes based on steam reforming and autothermal reforming as well as partial oxidation. This paper reviews the state of the art of the technologies

Nonviral Technologies for Gene Therapy in Cardiovascular Research

Directory of Open Access Journals (Sweden)

Cheng-Huang Su

2008-06-01

Full Text Available Gene therapy, which is still at an experimental stage, is a technique that attempts to correct or prevent a disease by delivering genes into an individual's cells and tissues. In gene delivery, a vector is a vehicle for transferring genetic material into cells and tissues. Synthetic vectors are considered to be prerequisites for gene delivery, because viral vectors have fundamental problems in relation to safety issues as well as large-scale production. Among the physical approaches, ultrasound with its associated bioeffects such as acoustic cavitation, especially inertial cavitation, can increase the permeability of cell membranes to macromolecules such as plasmid DNA. Microbubbles or ultrasound contrast agents lower the threshold for cavitation by ultrasound energy. Furthermore, ultrasound-enhanced gene delivery using polymers or other nonviral vectors may hold much promise for the future but is currently at the preclinical stage. We all know aging is cruel and inevitable. Currently, among the promising areas for gene therapy in acquired diseases, the incidences of cancer and ischemic cardiovascular diseases are strongly correlated with the aging process. As a result, gene therapy technology may play important roles in these diseases in the future. This brief review focuses on understanding the barriers to gene transfer as well as describing the useful nonviral vectors or tools that are applied to gene delivery and introducing feasible models in terms of ultrasound-based gene delivery.

Readout technologies for directional WIMP Dark Matter detection

International Nuclear Information System (INIS)

Battat, J.B.R.; Irastorza, I.G.; Aleksandrov, A.; Asada, T.; Baracchini, E.; Billard, J.; Bosson, G.; Bourrion, O.; Bouvier, J.; Buonaura, A.; Burdge, K.; Cebrián, S.

2016-01-01

The measurement of the direction of WIMP-induced nuclear recoils is a compelling but technologically challenging strategy to provide an unambiguous signature of the detection of Galactic dark matter. Most directional detectors aim to reconstruct the dark-matter-induced nuclear recoil tracks, either in gas or solid targets. The main challenge with directional detection is the need for high spatial resolution over large volumes, which puts strong requirements on the readout technologies. In this paper we review the various detector readout technologies used by directional detectors. In particular, we summarize the challenges, advantages and drawbacks of each approach, and discuss future prospects for these technologies.

Development of an ELA-DRA gene typing method based on pyrosequencing technology.

Science.gov (United States)

Díaz, S; Echeverría, M G; It, V; Posik, D M; Rogberg-Muñoz, A; Pena, N L; Peral-García, P; Vega-Pla, J L; Giovambattista, G

2008-11-01

The polymorphism of equine lymphocyte antigen (ELA) class II DRA gene had been detected by polymerase chain reaction-single-strand conformational polymorphism (PCR-SSCP) and reference strand-mediated conformation analysis. These methodologies allowed to identify 11 ELA-DRA exon 2 sequences, three of which are widely distributed among domestic horse breeds. Herein, we describe the development of a pyrosequencing-based method applicable to ELA-DRA typing, by screening samples from eight different horse breeds previously typed by PCR-SSCP. This sequence-based method would be useful in high-throughput genotyping of major histocompatibility complex genes in horses and other animal species, making this system interesting as a rapid screening method for animal genotyping of immune-related genes.

Gene transfer technology and genetic radioisotope targeting therapy

International Nuclear Information System (INIS)

Wang Jiaqiong; Wang Zizheng

2004-01-01

With deeper cognition about mechanisms of disease at the cellular and molecular level, gene therapy has become one of the most important research fields in medical molecular biology at present. Gene transfer technology plays an important role during the course of gene therapy, and further improvement should be made about vectors carrying target gene sequences. Also, gene survey is needed during gene therapy, and gene imaging is the most effective method. The combination of gene therapy and targeted radiotherapy, that is, 'Genetic Radioisotope Targeting Therapy', will be a novel approach to tumor gene therapy

Students' Perceptions of Self-Directed Learning and Collaborative Learning with and without Technology

Science.gov (United States)

Lee, K.; Tsai, P.-S.; Chai, C. S.; Koh, J. H. L.

2014-01-01

This study explored students' perceptions of self-directed learning (SDL) and collaborative learning (CL) with/without technology in an information and communications technology-supported classroom environment. The factors include SDL, CL, SDL supported by technology, and CL supported by technology. Based on the literature review, this study…

Scuba: scalable kernel-based gene prioritization.

Science.gov (United States)

Zampieri, Guido; Tran, Dinh Van; Donini, Michele; Navarin, Nicolò; Aiolli, Fabio; Sperduti, Alessandro; Valle, Giorgio

2018-01-25

The uncovering of genes linked to human diseases is a pressing challenge in molecular biology and precision medicine. This task is often hindered by the large number of candidate genes and by the heterogeneity of the available information. Computational methods for the prioritization of candidate genes can help to cope with these problems. In particular, kernel-based methods are a powerful resource for the integration of heterogeneous biological knowledge, however, their practical implementation is often precluded by their limited scalability. We propose Scuba, a scalable kernel-based method for gene prioritization. It implements a novel multiple kernel learning approach, based on a semi-supervised perspective and on the optimization of the margin distribution. Scuba is optimized to cope with strongly unbalanced settings where known disease genes are few and large scale predictions are required. Importantly, it is able to efficiently deal both with a large amount of candidate genes and with an arbitrary number of data sources. As a direct consequence of scalability, Scuba integrates also a new efficient strategy to select optimal kernel parameters for each data source. We performed cross-validation experiments and simulated a realistic usage setting, showing that Scuba outperforms a wide range of state-of-the-art methods. Scuba achieves state-of-the-art performance and has enhanced scalability compared to existing kernel-based approaches for genomic data. This method can be useful to prioritize candidate genes, particularly when their number is large or when input data is highly heterogeneous. The code is freely available at https://github.com/gzampieri/Scuba .

1997 Annual report. Technological Research Direction

International Nuclear Information System (INIS)

Instituto Nacional de Investigaciones Nucleares

1998-01-01

This document describes the results for one year of work. Here is presented the goals of the Technological Research Direction of the National Institute of Nuclear Research in Mexico, which is promoting and developing the production of high technologies in the nuclear sciences and related disciplines as well as to generate the technologies, products, quality insume for academic organizations, health, industrial and commercial that are required. (Author)

A relative variation-based method to unraveling gene regulatory networks.

Directory of Open Access Journals (Sweden)

Yali Wang

Full Text Available Gene regulatory network (GRN reconstruction is essential in understanding the functioning and pathology of a biological system. Extensive models and algorithms have been developed to unravel a GRN. The DREAM project aims to clarify both advantages and disadvantages of these methods from an application viewpoint. An interesting yet surprising observation is that compared with complicated methods like those based on nonlinear differential equations, etc., methods based on a simple statistics, such as the so-called Z-score, usually perform better. A fundamental problem with the Z-score, however, is that direct and indirect regulations can not be easily distinguished. To overcome this drawback, a relative expression level variation (RELV based GRN inference algorithm is suggested in this paper, which consists of three major steps. Firstly, on the basis of wild type and single gene knockout/knockdown experimental data, the magnitude of RELV of a gene is estimated. Secondly, probability for the existence of a direct regulation from a perturbed gene to a measured gene is estimated, which is further utilized to estimate whether a gene can be regulated by other genes. Finally, the normalized RELVs are modified to make genes with an estimated zero in-degree have smaller RELVs in magnitude than the other genes, which is used afterwards in queuing possibilities of the existence of direct regulations among genes and therefore leads to an estimate on the GRN topology. This method can in principle avoid the so-called cascade errors under certain situations. Computational results with the Size 100 sub-challenges of DREAM3 and DREAM4 show that, compared with the Z-score based method, prediction performances can be substantially improved, especially the AUPR specification. Moreover, it can even outperform the best team of both DREAM3 and DREAM4. Furthermore, the high precision of the obtained most reliable predictions shows that the suggested algorithm may be

Diamond bits for directional drilling of wells and technology of using them

Energy Technology Data Exchange (ETDEWEB)

Romanov, V P; Steblev, B Ye; Sumaneyev, N N

1979-01-01

Characteristics are presented for a diamond bit for directional drilling ADN-08. Technology of using it is described, as well as cutter bits for directional drilling. Based on specially developed technique, the economic effect of using the diamond bits is calculated. This indicates that the use of the diamond bits in rocks of the VIII category significantly improves the quality of directional drilling.

Bridging the Gap: Self-Directed Staff Technology Training

Directory of Open Access Journals (Sweden)

Kayla L. Quinney

2010-12-01

Full Text Available Undergraduates, as members of the Millennial Generation, are proficient in Web 2.0 technology and expect to apply these technologies to their coursework—including scholarly research. To remain relevant, academic libraries need to provide the technology that student patrons expect, and academic librarians need to learn and use these technologies themselves. Because leaders at the Harold B. Lee Library of Brigham Young University (HBLL perceived a gap in technology use between students and their staff and faculty, they developed and implemented the Technology Challenge, a self-directed technology training program that rewarded employees for exploring technology daily. The purpose of this paper is to examine the Technology Challenge through an analysis of results of surveys given to participants before and after the Technology Challenge was implemented. The program will also be evaluated in terms of the adult learning theories of andragogy and selfdirected learning. HBLL found that a self-directed approach fosters technology skills that librarians need to best serve students. In addition, it promotes lifelong learning habits to keep abreast of emerging technologies. This paper offers some insights and methods that could be applied in other libraries, the most valuable of which is the use of self-directed and andragogical training methods to help academic libraries better integrate modern technologies.

Challenges and opportunities for controlling and preventing animal diseases in developing countries through gene-based technologies

International Nuclear Information System (INIS)

Crowther, J.R.; Jeggo, M.H.

2005-01-01

Polymerase Chain Reaction (PCR) technology allows scientist to amplify, copy, identify, characterize and manipulate genes in a relatively simple way. Exploitation of the technology to devise new products and translate these to the commercial sector has been remarkable. Molecular technologies are not difficult to establish and use, and can appear to offer developing countries many opportunities. However, developing countries should look in a different way at the apparent advantages offered. Whilst molecular biological science appears to offer solutions to many problems, there are a number of drawbacks. This desire to adopt the latest technology often overrides any considerations of the use of more conventional technologies to address needs. The conventional, and often more practical, methods already provide many specific tools in the disease control area. Changing the technology can also deflect critical resources into the molecular field in terms of laboratory funding and training. This may cause redundancy of staff, limit further development in conventional techniques, and polarize scientists into the older (less glossy) and newer (molecular) camps. Animal disease diagnosis still primarily utilizes conventional techniques such as Enzyme Linked Immunosorbent Assay (ELISA). This will not change drastically in developing countries, but developments will combine such methods with more discriminatory molecular techniques, and a balanced and parallel development is needed. An understanding of the use and possible advantages of the various technologies is required by both scientists and policy-makers in developing nations. Vaccines based on molecular science could have a real impact in developing countries, but 'vaccinology' needs to examine both the animal (immunology of target species) and the disease agent itself. This is a research-based science and, as such, is expensive, with no surety of success. Developing countries should exploit links with developed countries

PCR-based detection of gene transfer vectors: application to gene doping surveillance.

Science.gov (United States)

Perez, Irene C; Le Guiner, Caroline; Ni, Weiyi; Lyles, Jennifer; Moullier, Philippe; Snyder, Richard O

2013-12-01

Athletes who illicitly use drugs to enhance their athletic performance are at risk of being banned from sports competitions. Consequently, some athletes may seek new doping methods that they expect to be capable of circumventing detection. With advances in gene transfer vector design and therapeutic gene transfer, and demonstrations of safety and therapeutic benefit in humans, there is an increased probability of the pursuit of gene doping by athletes. In anticipation of the potential for gene doping, assays have been established to directly detect complementary DNA of genes that are top candidates for use in doping, as well as vector control elements. The development of molecular assays that are capable of exposing gene doping in sports can serve as a deterrent and may also identify athletes who have illicitly used gene transfer for performance enhancement. PCR-based methods to detect foreign DNA with high reliability, sensitivity, and specificity include TaqMan real-time PCR, nested PCR, and internal threshold control PCR.

Space weather effects on ground based technology

Science.gov (United States)

Clark, T.

Space weather can affect a variety of forms of ground-based technology, usually as a result of either the direct effects of the varying geomagnetic field, or as a result of the induced electric field that accompanies such variations. Technologies affected directly by geomagnetic variations include magnetic measurements made d ringu geophysical surveys, and navigation relying on the geomagnetic field as a direction reference, a method that is particularly common in the surveying of well-bores in the oil industry. The most obvious technology affected by induced electric fields during magnetic storms is electric power transmission, where the example of the blackout in Quebec during the March 1989 magnetic storm is widely known. Additionally, space weather effects must be taken into account in the design of active cathodic protection systems on pipelines to protect them against corrosion. Long-distance telecommunication cables may also have to be designed to cope with space weather related effects. This paper reviews the effects of space weather in these different areas of ground-based technology, and provides examples of how mitigation against hazards may be achieved. (The paper does not include the effects of space weather on radio communication or satellite navigation systems).

Malaria Prevention by New Technology: Vectored Delivery of Antibody Genes

Science.gov (United States)

2017-10-01

AWARD NUMBER: W81XWH-15-1-0401 TITLE: Malaria Prevention by New Technology : Vectored Delivery of Antibody Genes PRINCIPAL INVESTIGATOR: Gary...CONTRACT NUMBER Malaria Prevention by New Technology : Vectored Delivery of Antibody Genes 5b. GRANT NUMBER W81XWH-15-1-0401 5c. PROGRAM ELEMENT...whole animals. Using a specific technology originally applied to expression of HIV antibodies, we demonstrated that mice can be protected from

CRISPR technologies for bacterial systems: Current achievements and future directions.

Science.gov (United States)

Choi, Kyeong Rok; Lee, Sang Yup

2016-11-15

Throughout the decades of its history, the advances in bacteria-based bio-industries have coincided with great leaps in strain engineering technologies. Recently unveiled clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated proteins (Cas) systems are now revolutionizing biotechnology as well as biology. Diverse technologies have been derived from CRISPR/Cas systems in bacteria, yet the applications unfortunately have not been actively employed in bacteria as extensively as in eukaryotic organisms. A recent trend of engineering less explored strains in industrial microbiology-metabolic engineering, synthetic biology, and other related disciplines-is demanding facile yet robust tools, and various CRISPR technologies have potential to cater to the demands. Here, we briefly review the science in CRISPR/Cas systems and the milestone inventions that enabled numerous CRISPR technologies. Next, we describe CRISPR/Cas-derived technologies for bacterial strain development, including genome editing and gene expression regulation applications. Then, other CRISPR technologies possessing great potential for industrial applications are described, including typing and tracking of bacterial strains, virome identification, vaccination of bacteria, and advanced antimicrobial approaches. For each application, we note our suggestions for additional improvements as well. In the same context, replication of CRISPR/Cas-based chromosome imaging technologies developed originally in eukaryotic systems is introduced with its potential impact on studying bacterial chromosomal dynamics. Also, the current patent status of CRISPR technologies is reviewed. Finally, we provide some insights to the future of CRISPR technologies for bacterial systems by proposing complementary techniques to be developed for the use of CRISPR technologies in even wider range of applications. Copyright © 2016. Published by Elsevier Inc.

Using FlyBase, a Database of Drosophila Genes and Genomes.

Science.gov (United States)

Marygold, Steven J; Crosby, Madeline A; Goodman, Joshua L

2016-01-01

For nearly 25 years, FlyBase (flybase.org) has provided a freely available online database of biological information about Drosophila species, focusing on the model organism D. melanogaster. The need for a centralized, integrated view of Drosophila research has never been greater as advances in genomic, proteomic, and high-throughput technologies add to the quantity and diversity of available data and resources.FlyBase has taken several approaches to respond to these changes in the research landscape. Novel report pages have been generated for new reagent types and physical interaction data; Drosophila models of human disease are now represented and showcased in dedicated Human Disease Model Reports; other integrated reports have been established that bring together related genes, datasets, or reagents; Gene Reports have been revised to improve access to new data types and to highlight functional data; links to external sites have been organized and expanded; and new tools have been developed to display and interrogate all these data, including improved batch processing and bulk file availability. In addition, several new community initiatives have served to enhance interactions between researchers and FlyBase, resulting in direct user contributions and improved feedback.This chapter provides an overview of the data content, organization, and available tools within FlyBase, focusing on recent improvements. We hope it serves as a guide for our diverse user base, enabling efficient and effective exploration of the database and thereby accelerating research discoveries.

Adaptation of the short intergenic spacers between co-directional genes to the Shine-Dalgarno motif among prokaryote genomes

DEFF Research Database (Denmark)

Caro, Albert Pallejà; García-Vallvé, Santiago; Romeu, Antoni

2009-01-01

ABSTRACT: BACKGROUND: In prokaryote genomes most of the co-directional genes are in close proximity. Even the coding sequence or the stop codon of a gene can overlap with the Shine-Dalgarno (SD) sequence of the downstream co-directional gene. In this paper we analyze how the presence of SD may...... influence the stop codon usage or the spacing lengths between co-directional genes. RESULTS: The SD sequences for 530 prokaryote genomes have been predicted using computer calculations of the base-pairing free energy between translation initiation regions and the 16S rRNA 3' tail. Genomes with a large...... to the discussion of which factors affect the intergenic lengths, which cannot be totally explained by the pressure to compact the prokaryote genomes....

Enriching the gene set analysis of genome-wide data by incorporating directionality of gene expression and combining statistical hypotheses and methods

Science.gov (United States)

Väremo, Leif; Nielsen, Jens; Nookaew, Intawat

2013-01-01

Gene set analysis (GSA) is used to elucidate genome-wide data, in particular transcriptome data. A multitude of methods have been proposed for this step of the analysis, and many of them have been compared and evaluated. Unfortunately, there is no consolidated opinion regarding what methods should be preferred, and the variety of available GSA software and implementations pose a difficulty for the end-user who wants to try out different methods. To address this, we have developed the R package Piano that collects a range of GSA methods into the same system, for the benefit of the end-user. Further on we refine the GSA workflow by using modifications of the gene-level statistics. This enables us to divide the resulting gene set P-values into three classes, describing different aspects of gene expression directionality at gene set level. We use our fully implemented workflow to investigate the impact of the individual components of GSA by using microarray and RNA-seq data. The results show that the evaluated methods are globally similar and the major separation correlates well with our defined directionality classes. As a consequence of this, we suggest to use a consensus scoring approach, based on multiple GSA runs. In combination with the directionality classes, this constitutes a more thorough basis for an enriched biological interpretation. PMID:23444143

Technological change of the energy innovation system: From oil-based to bio-based energy

International Nuclear Information System (INIS)

Wonglimpiyarat, Jarunee

2010-01-01

This paper concerns the structural developments and the direction of technological change of the energy innovation system, based on the studies of Kuhn's model of scientific change and Schumpeter's model of technological change. The paper uses the case study of Thai government agencies for understanding the way governments can facilitate technological innovation. The analyses are based on a pre-foresight exercise to examine the potential of the bio-based energy and investigate a set of development policies necessary for the direction of energy system development. The results have shown that bio-based energy is seen as the next new wave for future businesses and one of the solutions to the problem of high oil prices to improve the world's economic security and sustainable development. (author)

Bi-directional gene set enrichment and canonical correlation analysis identify key diet-sensitive pathways and biomarkers of metabolic syndrome

Directory of Open Access Journals (Sweden)

Gaora Peadar Ó

2010-10-01

Full Text Available Abstract Background Currently, a number of bioinformatics methods are available to generate appropriate lists of genes from a microarray experiment. While these lists represent an accurate primary analysis of the data, fewer options exist to contextualise those lists. The development and validation of such methods is crucial to the wider application of microarray technology in the clinical setting. Two key challenges in clinical bioinformatics involve appropriate statistical modelling of dynamic transcriptomic changes, and extraction of clinically relevant meaning from very large datasets. Results Here, we apply an approach to gene set enrichment analysis that allows for detection of bi-directional enrichment within a gene set. Furthermore, we apply canonical correlation analysis and Fisher's exact test, using plasma marker data with known clinical relevance to aid identification of the most important gene and pathway changes in our transcriptomic dataset. After a 28-day dietary intervention with high-CLA beef, a range of plasma markers indicated a marked improvement in the metabolic health of genetically obese mice. Tissue transcriptomic profiles indicated that the effects were most dramatic in liver (1270 genes significantly changed; p Conclusion Bi-directional gene set enrichment analysis more accurately reflects dynamic regulatory behaviour in biochemical pathways, and as such highlighted biologically relevant changes that were not detected using a traditional approach. In such cases where transcriptomic response to treatment is exceptionally large, canonical correlation analysis in conjunction with Fisher's exact test highlights the subset of pathways showing strongest correlation with the clinical markers of interest. In this case, we have identified selenoamino acid metabolism and steroid biosynthesis as key pathways mediating the observed relationship between metabolic health and high-CLA beef. These results indicate that this type of

Suitable reference genes for the analysis of direct hyperplasia in mice

International Nuclear Information System (INIS)

Takagi, Soichi; Ohashi, Kazuo; Utoh, Rie; Tatsumi, Kohei; Shima, Midori; Okano, Teruo

2008-01-01

The liver is capable of undergoing a proliferative growth, known as direct hyperplasia, in which the naive liver increases in size due to stimulation with primary mitogens. To produce accurate gene expression data, housekeeping genes (HKGs) that are stably expressed need to be determined. In the present study, liver regeneration was promoted via the direct hyperplasia mode by inducing mice with 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene. Gene expression levels of nine commonly used HKGs were analyzed in the liver of different timing during the regeneration. The stability of gene expression was assessed using two different analysis programs, geNorm and NormFinder. Using these analyses, we identified that PPIA and RPL4 showed the most stable expression regardless of the status of the liver regeneration. In conclusion, the present study demonstrated that the use of PPIA and RPL4 were the most optimal in providing reliable normalization of gene expression when assessing liver regeneration attributed to direct hyperplasia.

Illuminating the gateway of gene silencing: perspective of RNA interference technology in clinical therapeutics.

Science.gov (United States)

Sindhu, Annu; Arora, Pooja; Chaudhury, Ashok

2012-07-01

A novel laboratory revolution for disease therapy, the RNA interference (RNAi) technology, has adopted a new era of molecular research as the next generation "Gene-targeted prophylaxis." In this review, we have focused on the chief technological challenges associated with the efforts to develop RNAi-based therapeutics that may guide the biomedical researchers. Many non-curable maladies, like neurodegenerative diseases and cancers have effectively been cured using this technology. Rapid advances are still in progress for the development of RNAi-based technologies that will be having a major impact on medical research. We have highlighted the recent discoveries associated with the phenomenon of RNAi, expression of silencing molecules in mammals along with the vector systems used for disease therapeutics.

Detection of EPO gene doping in blood.

Science.gov (United States)

Neuberger, Elmo W I; Jurkiewicz, Magdalena; Moser, Dirk A; Simon, Perikles

2012-11-01

Gene doping--or the abuse of gene therapy--will continue to threaten the sports world. History has shown that progress in medical research is likely to be abused in order to enhance human performance. In this review, we critically discuss the progress and the risks associated with the field of erythropoietin (EPO) gene therapy and its applicability to EPO gene doping. We present typical vector systems that are employed in ex vivo and in vivo gene therapy trials. Due to associated risks, gene doping is not a feasible alternative to conventional EPO or blood doping at this time. Nevertheless, it is well described that about half of the elite athlete population is in principle willing to risk its health to gain a competitive advantage. This includes the use of technologies that lack safety approval. Sophisticated detection approaches are a prerequisite for prevention of unapproved and uncontrolled use of gene therapy technology. In this review, we present current detection approaches for EPO gene doping, with a focus on blood-based direct and indirect approaches. Gene doping is detectable in principle, and recent DNA-based detection strategies enable long-term detection of transgenic DNA (tDNA) following in vivo gene transfer. Copyright © 2012 John Wiley & Sons, Ltd.

NATIONAL TECHNOLOGICAL INITIATIVE AS THE STRATEGIC DIRECTION OF THE TECHNOLOGICAL DEVELOPMENT OF RUSSIA

Directory of Open Access Journals (Sweden)

E. V. Sibirskaya

2018-01-01

Full Text Available Russia, having lost a significant part of a high-tech industrial complex during the reforms (1993–2000, sharply reducing the state support of scientific research and development, has turned into a power dependent on the conjuncture in the hydrocarbon energy market and from foreign sup-plies of technologies, consumption goods, including those necessary for life support, thus being on the "technological needle". The main factor of development was the resource-producing complex. This situation had a negative impact on the pace of the country's development, on its defense capability and created real prerequisites for the loss of technological, economic, and, in the long run, political sovereignty and disintegration of the state. Nevertheless, the availability of natural resources along with human capi-tal and geographic location is a global competitive advantage of theRussian Federation, and the task is to use this advantage maximally as one of the first echelon countries in the emerging world order. One of the most important tasks was the search for such a direction of technological devel-opment that allows, on the one hand, to preserve Russia's position in the world market of traditional products; on the other – to strengthen positions in the markets of products with a higher degree of processing of Russian raw materials (oil and gas complex and agro-industrial complex; and finally – to master new "growth points" (services, new markets, talents, technologies in the world market of high-tech products and services. The set tasks assume several solutions. First, scientific and technological development should be based on the strategy of scientific and technological development of theRussian Federationand the national technological initiative, as it sets both resource constraints and priorities in the needs of the economy in new products and new technological solutions. Secondly,Russiashould take into account existing and emerging trends in the

Applications of Gene Editing Technologies to Cellular Therapies.

Science.gov (United States)

Rein, Lindsay A M; Yang, Haeyoon; Chao, Nelson J

2018-03-27

Hematologic malignancies are characterized by genetic heterogeneity, making classic gene therapy with a goal of correcting 1 genetic defect ineffective in many of these diseases. Despite initial tribulations, gene therapy, as a field, has grown by leaps and bounds with the recent development of gene editing techniques including zinc finger nucleases, transcription activator-like effector nucleases, and clustered regularly interspaced short palindromic repeat (CRISPR) sequences and CRISPR-associated protein-9 (Cas9) nuclease or CRISPR/Cas9. These novel technologies have been applied to efficiently and specifically modify genetic information in target and effector cells. In particular, CRISPR/Cas9 technology has been applied to various hematologic malignancies and has also been used to modify and improve chimeric antigen receptor-modified T cells for the purpose of providing effective cellular therapies. Although gene editing is in its infancy in malignant hematologic diseases, there is much room for growth and application in the future. Copyright © 2018 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

GBOOST: a GPU-based tool for detecting gene-gene interactions in genome-wide case control studies.

Science.gov (United States)

Yung, Ling Sing; Yang, Can; Wan, Xiang; Yu, Weichuan

2011-05-01

Collecting millions of genetic variations is feasible with the advanced genotyping technology. With a huge amount of genetic variations data in hand, developing efficient algorithms to carry out the gene-gene interaction analysis in a timely manner has become one of the key problems in genome-wide association studies (GWAS). Boolean operation-based screening and testing (BOOST), a recent work in GWAS, completes gene-gene interaction analysis in 2.5 days on a desktop computer. Compared with central processing units (CPUs), graphic processing units (GPUs) are highly parallel hardware and provide massive computing resources. We are, therefore, motivated to use GPUs to further speed up the analysis of gene-gene interactions. We implement the BOOST method based on a GPU framework and name it GBOOST. GBOOST achieves a 40-fold speedup compared with BOOST. It completes the analysis of Wellcome Trust Case Control Consortium Type 2 Diabetes (WTCCC T2D) genome data within 1.34 h on a desktop computer equipped with Nvidia GeForce GTX 285 display card. GBOOST code is available at http://bioinformatics.ust.hk/BOOST.html#GBOOST.

Genotet: An Interactive Web-based Visual Exploration Framework to Support Validation of Gene Regulatory Networks.

Science.gov (United States)

Yu, Bowen; Doraiswamy, Harish; Chen, Xi; Miraldi, Emily; Arrieta-Ortiz, Mario Luis; Hafemeister, Christoph; Madar, Aviv; Bonneau, Richard; Silva, Cláudio T

2014-12-01

Elucidation of transcriptional regulatory networks (TRNs) is a fundamental goal in biology, and one of the most important components of TRNs are transcription factors (TFs), proteins that specifically bind to gene promoter and enhancer regions to alter target gene expression patterns. Advances in genomic technologies as well as advances in computational biology have led to multiple large regulatory network models (directed networks) each with a large corpus of supporting data and gene-annotation. There are multiple possible biological motivations for exploring large regulatory network models, including: validating TF-target gene relationships, figuring out co-regulation patterns, and exploring the coordination of cell processes in response to changes in cell state or environment. Here we focus on queries aimed at validating regulatory network models, and on coordinating visualization of primary data and directed weighted gene regulatory networks. The large size of both the network models and the primary data can make such coordinated queries cumbersome with existing tools and, in particular, inhibits the sharing of results between collaborators. In this work, we develop and demonstrate a web-based framework for coordinating visualization and exploration of expression data (RNA-seq, microarray), network models and gene-binding data (ChIP-seq). Using specialized data structures and multiple coordinated views, we design an efficient querying model to support interactive analysis of the data. Finally, we show the effectiveness of our framework through case studies for the mouse immune system (a dataset focused on a subset of key cellular functions) and a model bacteria (a small genome with high data-completeness).

NORMAL NASAL GENE EXPRESSION LEVELS USING CDNA ARRAY TECHNOLOGY

Science.gov (United States)

Normal Nasal Gene Expression Levels Using cDNA Array Technology. The nasal epithelium is a target site for chemically-induced toxicity and carcinogenicity. To detect and analyze genetic events which contribute to nasal tumor development, we first defined the gene expressi...

Novel Direct Steelmaking by Combining Microwave, Electric Arc, and Exothermal Heating Technologies

Energy Technology Data Exchange (ETDEWEB)

Dr. Xiaodi Huang; Dr. J. Y. Hwang

2005-03-28

Steel is a basic material broadly used by perhaps every industry and individual. It is critical to our nation's economy and national security. Unfortunately, the American steel industry is losing competitiveness in the world steel production field. There is an urgent need to develop the next generation of steelmaking technology for the American steel industry. Direct steelmaking through the combination of microwave, electric arc, and exothermal heating is a revolutionary change from current steelmaking technology. This technology can produce molten steel directly from a shippable agglomerate, consisting of iron oxide fines, powdered coal, and ground limestone. This technology is projected to eliminate many current intermediate steelmaking steps including coking, pellet sintering, blast furnace (BF) ironmaking, and basic oxygen furnace (BOF) steelmaking. This technology has the potential to (a) save up to 45% of the energy consumed by conventional steelmaking; (b) dramatically reduce the emission of CO{sub 2}, SO{sub 2}, NO{sub x}, VOCs, fine particulates, and air toxics; (c) substantially reduce waste and emission control costs; (d) greatly lower capital cost; and (e) considerably reduce steel production costs. This technology is based on the unique capability of microwaves to rapidly heat steelmaking raw materials to elevated temperature, then rapidly reduce iron oxides to metal by volumetric heating. Microwave heating, augmented with electric arc and exothermal reactions, is capable of producing molten steel. This technology has the components necessary to establish the ''future'' domestic steel industry as a technology leader with a strong economically competitive position in world markets. The project goals were to assess the utilization of a new steelmaking technology for its potential to achieve better overall energy efficiency, minimize pollutants and wastes, lower capital and operating costs, and increase the competitiveness of the

Direct digital conversion detector technology

Science.gov (United States)

Mandl, William J.; Fedors, Richard

1995-06-01

Future imaging sensors for the aerospace and commercial video markets will depend on low cost, high speed analog-to-digital (A/D) conversion to efficiently process optical detector signals. Current A/D methods place a heavy burden on system resources, increase noise, and limit the throughput. This paper describes a unique method for incorporating A/D conversion right on the focal plane array. This concept is based on Sigma-Delta sampling, and makes optimum use of the active detector real estate. Combined with modern digital signal processors, such devices will significantly increase data rates off the focal plane. Early conversion to digital format will also decrease the signal susceptibility to noise, lowering the communications bit error rate. Computer modeling of this concept is described, along with results from several simulation runs. A potential application for direct digital conversion is also reviewed. Future uses for this technology could range from scientific instruments to remote sensors, telecommunications gear, medical diagnostic tools, and consumer products.

PMS2 gene mutational analysis: direct cDNA sequencing to circumvent pseudogene interference.

Science.gov (United States)

Wimmer, Katharina; Wernstedt, Annekatrin

2014-01-01

The presence of highly homologous pseudocopies can compromise the mutation analysis of a gene of interest. In particular, when using PCR-based strategies, pseudogene co-amplification has to be effectively prevented. This is often achieved by using primers designed to be parental gene specific according to the reference sequence and by applying stringent PCR conditions. However, there are cases in which this approach is of limited utility. For example, it has been shown that the PMS2 gene exchanges sequences with one of its pseudogenes, named PMS2CL. This results in functional PMS2 alleles containing pseudogene-derived sequences at their 3'-end and in nonfunctional PMS2CL pseudogene alleles that contain gene-derived sequences. Hence, the paralogues cannot be distinguished according to the reference sequence. This shortcoming can be effectively circumvented by using direct cDNA sequencing. This approach is based on the selective amplification of PMS2 transcripts in two overlapping 1.6-kb RT-PCR products. In addition to avoiding pseudogene co-amplification and allele dropout, this method has also the advantage that it allows to effectively identify deletions, splice mutations, and de novo retrotransposon insertions that escape the detection of most DNA-based mutation analysis protocols.

Technology Transfer, Foreign Direct Investment and International Trade

OpenAIRE

Leonard K. Cheng

2000-01-01

By developing a Ricardian trade model that features technology transfer via foreign direct investment (FDI), we show that technology transfer via multinational enterprises (MNEs) increases world output and trade in goods and services. When there are many goods a continuous reduction in the cost of technology transfer will cause increasingly more technologically advanced goods to go through the product cycle, i.e., goods initially produced in the advanced North are later produced in the backwa...

Does Foreign Direct Investment Transfer Technology Across Borders? A Reexamination

OpenAIRE

Jürgen Bitzer; Monika Kerekes

2005-01-01

Reexamining foreign direct investment (FDI) as a potential channel for knowledge diffusion -- based on industry data from seventeen OECD countries during the period 1973-2000 -- we find that FDI-receiving countries benefit strongly from FDI-related knowledge spillovers. We do not find evidence for positive FDI-related technology sourcing effects. Instead, our results suggest that outward FDI might have negative effects on the output of the FDI-sending country.

Direct and long-term detection of gene doping in conventional blood samples.

Science.gov (United States)

Beiter, T; Zimmermann, M; Fragasso, A; Hudemann, J; Niess, A M; Bitzer, M; Lauer, U M; Simon, P

2011-03-01

The misuse of somatic gene therapy for the purpose of enhancing athletic performance is perceived as a coming threat to the world of sports and categorized as 'gene doping'. This article describes a direct detection approach for gene doping that gives a clear yes-or-no answer based on the presence or absence of transgenic DNA in peripheral blood samples. By exploiting a priming strategy to specifically amplify intronless DNA sequences, we developed PCR protocols allowing the detection of very small amounts of transgenic DNA in genomic DNA samples to screen for six prime candidate genes. Our detection strategy was verified in a mouse model, giving positive signals from minute amounts (20 μl) of blood samples for up to 56 days following intramuscular adeno-associated virus-mediated gene transfer, one of the most likely candidate vector systems to be misused for gene doping. To make our detection strategy amenable for routine testing, we implemented a robust sample preparation and processing protocol that allows cost-efficient analysis of small human blood volumes (200 μl) with high specificity and reproducibility. The practicability and reliability of our detection strategy was validated by a screening approach including 327 blood samples taken from professional and recreational athletes under field conditions.

A Framework for Developing Self-Directed Technology Use for Language Learning

Science.gov (United States)

Lai, Chun

2013-01-01

Critical to maximizing the potential of technology for learning is enhancing language learners' self-directed use of technology for learning purposes. This study aimed to enhance our understanding of the determinants of self-directed technology use through the construction of a structural equation modelling (SEM) framework of factors and…

New directions for veterinary technology.

Science.gov (United States)

Chadderdon, Linda M; Lloyd, James W; Pazak, Helene E

2014-01-01

Veterinary technology has generally established itself well in companion-animal and mixed-animal veterinary medical practice, but the career's growth trajectory is uncertain. Michigan State University (MSU) convened a national conference, "Creating the Future of Veterinary Technology-A National Dialogue," in November 2011 to explore ways to elevate the veterinary technician/technologist's role in the veterinary medical profession and to identify new directions in which the career could expand. Veterinary technicians/technologists might advance their place in private practice by not only improving their clinical skills, but by also focusing on areas such as practice management, leadership training, business training, conflict resolution, information technology, and marketing/communications. Some new employment settings for veterinary technicians/technologists include more participation within laboratory animal medicine and research, the rural farm industry, regulatory medicine, and shelter medicine. Achieving these ends would call for new training options beyond the current 2-year and 4-year degree programs. Participants suggested specialty training programs, hybrid programs of various types, online programs, veterinary technician residency programs of 12-18 months, and more integration of veterinary technician/technology students and veterinary medicine students at colleges of veterinary medicine.

Direct Metal Laser Sintering: A Digitised Metal Casting Technology

OpenAIRE

Venkatesh, K. Vijay; Nandini, V. Vidyashree

2013-01-01

Dental technology is undergoing advancements at a fast pace and technology is being imported from various other fields. One such imported technology is direct metal laser sintering technology for casting metal crowns. This article will discuss the process of laser sintering for making metal crowns and fixed partial dentures with a understanding of their pros and cons.

Direct metal laser sintering: a digitised metal casting technology.

Science.gov (United States)

Venkatesh, K Vijay; Nandini, V Vidyashree

2013-12-01

Dental technology is undergoing advancements at a fast pace and technology is being imported from various other fields. One such imported technology is direct metal laser sintering technology for casting metal crowns. This article will discuss the process of laser sintering for making metal crowns and fixed partial dentures with a understanding of their pros and cons.

Characteristics and Validation Techniques for PCA-Based Gene-Expression Signatures

Directory of Open Access Journals (Sweden)

Anders E. Berglund

2017-01-01

Full Text Available Background. Many gene-expression signatures exist for describing the biological state of profiled tumors. Principal Component Analysis (PCA can be used to summarize a gene signature into a single score. Our hypothesis is that gene signatures can be validated when applied to new datasets, using inherent properties of PCA. Results. This validation is based on four key concepts. Coherence: elements of a gene signature should be correlated beyond chance. Uniqueness: the general direction of the data being examined can drive most of the observed signal. Robustness: if a gene signature is designed to measure a single biological effect, then this signal should be sufficiently strong and distinct compared to other signals within the signature. Transferability: the derived PCA gene signature score should describe the same biology in the target dataset as it does in the training dataset. Conclusions. The proposed validation procedure ensures that PCA-based gene signatures perform as expected when applied to datasets other than those that the signatures were trained upon. Complex signatures, describing multiple independent biological components, are also easily identified.

Do GnRH analogues directly affect human endometrial epithelial cell gene expression?

KAUST Repository

Zhang, Xiaomei

2010-03-04

We examined whether Gonadotrophin-releasing hormone (GnRH) analogues [leuprolide acetate (LA) and ganirelix acetate (GA)] modulate gene expression in Ishikawa cells used as surrogate for human endometrial epithelial cells in vitro. The specific aims were: (i) to study the modulatory effect of GnRH analogues by RT-PCR [in the absence and presence of E2 and P4, and cyclic adenosine monophos-phate (cAMP)] on mRNA expression of genes modulated during the window of implantation in GnRH analogues/rFSH-treated assisted reproductive technology cycles including OPTINEURIN (OPTN), CHROMATIN MODIFYING PROTEIN (CHMP1A), PROSAPOSIN (PSAP), IGFBP-5 and SORTING NEXIN 7 (SNX7), and (ii) to analyze the 5\\'-flanking regions of such genes for the presence of putative steroid-response elements [estrogen-response elements (EREs) and P4-response element (PREs)]. Ishikawa cells were cytokeratin+/vimentin2 and expressed ERa,ERb, PR and GnRH-R proteins. At 6 and 24 h, neither LA nor GA alone had an effect on gene expression. GnRH analogues alone or following E2 and/or P4 co-incubation for 24 h also had no effect on gene expression, but P4 significantly increased expression of CHMP1A.E2 + P4 treatment for 4 days, alone or followed by GA, had no effect, but E2 + P4 treatment followed by LA significantly decreased IGFBP-5 expression. The addition of 8-Br cAMP did not modify gene expression, with the exception of IGFBP-5 that was significantly increased. The GnRH analogues did not modify intracellular cAMP levels. We identified conserved EREs for OPN, CHMP1A, SNX7 and PSAP and PREs for SNX7. We conclude that GnRH analogues appear not to have major direct effects on gene expression of human endo-metrial epithelial cells in vitro. © The Author 2010. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org.

Toxicogenomics-based identification of mechanisms for direct immunotoxicity.

Science.gov (United States)

Shao, Jia; Katika, Madhumohan R; Schmeits, Peter C J; Hendriksen, Peter J M; van Loveren, Henk; Peijnenburg, Ad A C M; Volger, Oscar L

2013-10-01

Compounds with direct immunotoxic properties, including metals, mycotoxins, agricultural pesticides, and industrial chemicals, form potential human health risks due to exposure through food, drinking water, and the environment. Insights into the mechanisms of action are currently lacking for the majority of these direct immunotoxicants. Therefore, the present work aimed to gain insights into the molecular mechanisms underlying direct immunotoxicity. To this end, we assessed in vitro the effects of 31 test compounds on the transcriptome of the human Jurkat T-cell line. These compounds included direct immunotoxicants, immunosuppressive drugs with different mode of actions, and nonimmunotoxic control chemicals. Pathway analysis of the microarray data allowed us to identify canonical pathways and Gene Ontology processes that were transcriptionally regulated in common by immunotoxicants (1) with structural similarities, such as tributyltin chloride and tributyltin oxide that activated the retinoic acid/X receptor signaling pathway and (2) without structural similarities, such as As2O3, dibutyltin chloride, diazinon, MeHg, ochratoxin A (OTA), S9-treated OTA, S9-treated cyclophosphamide, and S9-treated benzo[a]pyrene, which activated unfolded protein response, and FTY720, lindane, and propanil, which activated the cholesterol biosynthesis pathway. In addition, processes uniquely affected by individual immunotoxicants were identified, such as the induction of Notch receptor signaling and the downregulation of acute-phase response genes by OTA. These findings were validated by quantitative real-time PCR analysis of genes involved in these processes. Our study indicated that diverse modes of action are involved in direct immunotoxicity and that a set of pathways or genes, rather than one single gene, can be used to screen compounds for direct immunotoxicity.

Digital technology use in ELT classrooms and self-directed learning

Directory of Open Access Journals (Sweden)

Nehir Sert

2016-04-01

Full Text Available The digital era is a new challenge for teachers. While children get acquainted with digital technology before the age of six, teachers, who have encountered the digital world at a later time in their lives, struggle with it. Self-directed learning, which is crucial for lifelong learning, can be enhanced by the use of technology within and beyond classroom settings. The aim of this study was to examine the difference between the perceptions of students in low- and high-income groups about their use of technology in a general sense and their teachers’ use of technology in ELT classrooms. It also tested the correlation between the perceptions of their self-directed learning behaviours and their own/their teachers’ technology use. The population of the study consisted of 75 students from high- and 70 students from low-income groups. Causal comparative and correlational research methods were adopted in the study. The surveys to measure the students’ perceptions about technology use were developed by the researchers. A scale, established by Demirtas and Sert (2010, was used to identify the level of self-directed learning views of the students. The data were collected at the beginning of the first term of the 2015-2016 school year. The results indicated that there was no significant difference between perceptions of the low- and high-income students regarding their own technology use. Likewise, perceptions of the low- and high-income students did not differ regarding their teachers’ technology use. There was no correlation between the perceptions of the low-/high-income mixed group regarding their use of technology and their teachers’ use of technology. Lastly, self-directed learning perceptions of the low-/high-income mixed group did not correlate with their perceptions on any aspects of technology use. The educational implications of these results were discussed and suggestions were put forward in order to produce more effective learning

Driven to extinction? The ethics of eradicating mosquitoes with gene-drive technologies.

Science.gov (United States)

Pugh, Jonathan

2016-09-01

Mosquito-borne diseases represent a significant global disease burden, and recent outbreaks of such diseases have led to calls to reduce mosquito populations. Furthermore, advances in 'gene-drive' technology have raised the prospect of eradicating certain species of mosquito via genetic modification. This technology has attracted a great deal of media attention, and the idea of using gene-drive technology to eradicate mosquitoes has been met with criticism in the public domain. In this paper, I shall dispel two moral objections that have been raised in the public domain against the use of gene-drive technologies to eradicate mosquitoes. The first objection invokes the concept of the 'sanctity of life' in order to claim that we should not drive an animal to extinction. In response, I follow Peter Singer in raising doubts about general appeals to the sanctity of life, and argue that neither individual mosquitoes nor mosquitoes species considered holistically are appropriately described as bearing a significant degree of moral status. The second objection claims that seeking to eradicate mosquitoes amounts to displaying unacceptable degrees of hubris. Although I argue that this objection also fails, I conclude by claiming that it raises the important point that we need to acquire more empirical data about, inter alia, the likely effects of mosquito eradication on the ecosystem, and the likelihood of gene-drive technology successfully eradicating the intended mosquito species, in order to adequately inform our moral analysis of gene-drive technologies in this context. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Multi-label literature classification based on the Gene Ontology graph

Directory of Open Access Journals (Sweden)

Lu Xinghua

2008-12-01

Full Text Available Abstract Background The Gene Ontology is a controlled vocabulary for representing knowledge related to genes and proteins in a computable form. The current effort of manually annotating proteins with the Gene Ontology is outpaced by the rate of accumulation of biomedical knowledge in literature, which urges the development of text mining approaches to facilitate the process by automatically extracting the Gene Ontology annotation from literature. The task is usually cast as a text classification problem, and contemporary methods are confronted with unbalanced training data and the difficulties associated with multi-label classification. Results In this research, we investigated the methods of enhancing automatic multi-label classification of biomedical literature by utilizing the structure of the Gene Ontology graph. We have studied three graph-based multi-label classification algorithms, including a novel stochastic algorithm and two top-down hierarchical classification methods for multi-label literature classification. We systematically evaluated and compared these graph-based classification algorithms to a conventional flat multi-label algorithm. The results indicate that, through utilizing the information from the structure of the Gene Ontology graph, the graph-based multi-label classification methods can significantly improve predictions of the Gene Ontology terms implied by the analyzed text. Furthermore, the graph-based multi-label classifiers are capable of suggesting Gene Ontology annotations (to curators that are closely related to the true annotations even if they fail to predict the true ones directly. A software package implementing the studied algorithms is available for the research community. Conclusion Through utilizing the information from the structure of the Gene Ontology graph, the graph-based multi-label classification methods have better potential than the conventional flat multi-label classification approach to facilitate

Mode of foreign entry, technology transfer, and foreign direct investment policy

OpenAIRE

Mattoo, Aaditya; Olarreaga, Marcelo; Saggi, Kamal

2001-01-01

Foreign direct investment can take place through the direct entry of foreign firms or the acquisition of existing domestic firms. Mattoo, Olarreaga, and Saggi examine the preferences of a foreign firm and the host country government with respect to these two modes of foreign direct investment in the presence of costly technology transfer. The tradeoff between technology transfer and market...

Strategic Planning for Computer-Based Educational Technology.

Science.gov (United States)

Bozeman, William C.

1984-01-01

Offers educational practitioners direction for the development of a master plan for the implementation and application of computer-based educational technology by briefly examining computers in education, discussing organizational change from a theoretical perspective, and presenting an overview of the planning strategy known as the planning and…

Report on achievements in fiscal 1998. Development of useful substance production technology utilizing gene combination technology; 1998 nendo idenshi kumikae gijutsu wo riyoshita yuyo busshitsu seisan gijutsu kaihatsu seika hokokusho

Energy Technology Data Exchange (ETDEWEB)

NONE

2000-03-01

In developing a useful substance producing technology utilizing gene combination technology, plants are taken as a kind of useful substance producing arena, wherein useful protein genes of animals are introduced and manifested in the plants. Thereupon, technological development was carried out for the following items with regard to mass production of useful substances that can be utilized industrially, such as cytokine, by means of plant and cell cultivation: 1. Development of a useful substance producing technology utilizing gene combination technology, and 2. Comprehensive surveys and researches. For the technology to obtain and design useful substance producing genes originated from animals, development of a technology to search and acquire useful genes originated from animals, and a design and modification technology for useful genes. For the technology to introduce genes into gene combined plants, creation of plants combined with useful substance producing genes, and development of an introduction technology using plant virus vector. For the technology to produce high-function chemical substances in the gene combined plants, establishment of technologies for mass breeding and activity analysis of gene combined plants and cultivated cells, and for extraction and refinement of useful substances from the gene combined plants. In the comprehensive surveys and researches, technologies were surveyed and items of information were collected inside and outside the country. (NEDO)

Nanoscale Science, Engineering and Technology Research Directions

Energy Technology Data Exchange (ETDEWEB)

Lowndes, D. H.; Alivisatos, A. P.; Alper, M.; Averback, R. S.; Jacob Barhen, J.; Eastman, J. A.; Imre, D.; Lowndes, D. H.; McNulty, I.; Michalske, T. A.; Ho, K-M; Nozik, A. J.; Russell, T. P.; Valentin, R. A.; Welch, D. O.; Barhen, J.; Agnew, S. R.; Bellon, P.; Blair, J.; Boatner, L. A.; Braiman, Y.; Budai, J. D.; Crabtree, G. W.; Feldman, L. C.; Flynn, C. P.; Geohegan, D. B.; George, E. P.; Greenbaum, E.; Grigoropoulos, C.; Haynes, T. E.; Heberlein, J.; Hichman, J.; Holland, O. W.; Honda, S.; Horton, J. A.; Hu, M. Z.-C.; Jesson, D. E.; Joy, D. C.; Krauss, A.; Kwok, W.-K.; Larson, B. C.; Larson, D. J.; Likharev, K.; Liu, C. T.; Majumdar, A.; Maziasz, P. J.; Meldrum, A.; Miller, J. C.; Modine, F. A.; Pennycook, S. J.; Pharr, G. M.; Phillpot, S.; Price, D. L.; Protopopescu, V.; Poker, D. B.; Pui, D.; Ramsey, J. M.; Rao, N.; Reichl, L.; Roberto, J.; Saboungi, M-L; Simpson, M.; Strieffer, S.; Thundat, T.; Wambsganss, M.; Wendleken, J.; White, C. W.; Wilemski, G.; Withrow, S. P.; Wolf, D.; Zhu, J. H.; Zuhr, R. A.; Zunger, A.; Lowe, S.

1999-01-01

This report describes important future research directions in nanoscale science, engineering and technology. It was prepared in connection with an anticipated national research initiative on nanotechnology for the twenty-first century. The research directions described are not expected to be inclusive but illustrate the wide range of research opportunities and challenges that could be undertaken through the national laboratories and their major national scientific user facilities with the support of universities and industry.

Five disruptive technology directions for 5G

DEFF Research Database (Denmark)

Boccardi, Federico; W. Heath Jr., Robert; Lozano, Angel

2014-01-01

New research directions will lead to fundamental changes in the design of future fifth generation (5G) cellular networks. This article describes five technologies that could lead to both architectural and component disruptive design changes: device-centric architectures, millimeter wave, massive ...

Biased perception about gene technology: How perceived naturalness and affect distort benefit perception.

Science.gov (United States)

Siegrist, Michael; Hartmann, Christina; Sütterlin, Bernadette

2016-01-01

In two experiments, the participants showed biased responses when asked to evaluate the benefits of gene technology. They evaluated the importance of additional yields in corn fields due to a newly introduced variety, which would increase a farmer's revenues. In one condition, the newly introduced variety was described as a product of traditional breeding; in the other, it was identified as genetically modified (GM). The two experiments' findings showed that the same benefits were perceived as less important for a farmer when these were the result of GM crops compared with traditionally bred crops. Mediation analyses suggest that perceived naturalness and the affect associated with the technology per se influence the interpretation of the new information. The lack of perceived naturalness of gene technology seems to be the reason for the participants' perceived lower benefits of a new corn variety in the gene technology condition compared with the perceptions of the participants assigned to the traditional breeding condition. The strategy to increase the acceptance of gene technology by introducing plant varieties that better address consumer and producer needs may not work because people discount its associated benefits. Copyright © 2015 Elsevier Ltd. All rights reserved.

Proteome Profiling Outperforms Transcriptome Profiling for Coexpression Based Gene Function Prediction

Energy Technology Data Exchange (ETDEWEB)

Wang, Jing; Ma, Zihao; Carr, Steven A.; Mertins, Philipp; Zhang, Hui; Zhang, Zhen; Chan, Daniel W.; Ellis, Matthew J. C.; Townsend, R. Reid; Smith, Richard D.; McDermott, Jason E.; Chen, Xian; Paulovich, Amanda G.; Boja, Emily S.; Mesri, Mehdi; Kinsinger, Christopher R.; Rodriguez, Henry; Rodland, Karin D.; Liebler, Daniel C.; Zhang, Bing

2016-11-11

Coexpression of mRNAs under multiple conditions is commonly used to infer cofunctionality of their gene products despite well-known limitations of this “guilt-by-association” (GBA) approach. Recent advancements in mass spectrometry-based proteomic technologies have enabled global expression profiling at the protein level; however, whether proteome profiling data can outperform transcriptome profiling data for coexpression based gene function prediction has not been systematically investigated. Here, we address this question by constructing and analyzing mRNA and protein coexpression networks for three cancer types with matched mRNA and protein profiling data from The Cancer Genome Atlas (TCGA) and the Clinical Proteomic Tumor Analysis Consortium (CPTAC). Our analyses revealed a marked difference in wiring between the mRNA and protein coexpression networks. Whereas protein coexpression was driven primarily by functional similarity between coexpressed genes, mRNA coexpression was driven by both cofunction and chromosomal colocalization of the genes. Functionally coherent mRNA modules were more likely to have their edges preserved in corresponding protein networks than functionally incoherent mRNA modules. Proteomic data strengthened the link between gene expression and function for at least 75% of Gene Ontology (GO) biological processes and 90% of KEGG pathways. A web application Gene2Net (http://cptac.gene2net.org) developed based on the three protein coexpression networks revealed novel gene-function relationships, such as linking ERBB2 (HER2) to lipid biosynthetic process in breast cancer, identifying PLG as a new gene involved in complement activation, and identifying AEBP1 as a new epithelial-mesenchymal transition (EMT) marker. Our results demonstrate that proteome profiling outperforms transcriptome profiling for coexpression based gene function prediction. Proteomics should be integrated if not preferred in gene function and human disease studies

Gene-based testing of interactions in association studies of quantitative traits.

Directory of Open Access Journals (Sweden)

Li Ma

Full Text Available Various methods have been developed for identifying gene-gene interactions in genome-wide association studies (GWAS. However, most methods focus on individual markers as the testing unit, and the large number of such tests drastically erodes statistical power. In this study, we propose novel interaction tests of quantitative traits that are gene-based and that confer advantage in both statistical power and biological interpretation. The framework of gene-based gene-gene interaction (GGG tests combine marker-based interaction tests between all pairs of markers in two genes to produce a gene-level test for interaction between the two. The tests are based on an analytical formula we derive for the correlation between marker-based interaction tests due to linkage disequilibrium. We propose four GGG tests that extend the following P value combining methods: minimum P value, extended Simes procedure, truncated tail strength, and truncated P value product. Extensive simulations point to correct type I error rates of all tests and show that the two truncated tests are more powerful than the other tests in cases of markers involved in the underlying interaction not being directly genotyped and in cases of multiple underlying interactions. We applied our tests to pairs of genes that exhibit a protein-protein interaction to test for gene-level interactions underlying lipid levels using genotype data from the Atherosclerosis Risk in Communities study. We identified five novel interactions that are not evident from marker-based interaction testing and successfully replicated one of these interactions, between SMAD3 and NEDD9, in an independent sample from the Multi-Ethnic Study of Atherosclerosis. We conclude that our GGG tests show improved power to identify gene-level interactions in existing, as well as emerging, association studies.

Real-time positioning technology in horizontal directional drilling based on magnetic gradient tensor measurement

Science.gov (United States)

Deng, Guoqing; Yao, Aiguo

2017-04-01

Horizontal directional drilling (HDD) technology has been widely used in Civil Engineering. The dynamic position of the drill bit during construction is one of significant facts determining the accuracy of the trajectory of HDD. A new method now has been proposed to detecting the position of drill bit by measuring the magnetic gradient tensor of the ground solenoid magnetic beacon. Compared with traditional HDD positioning technologies, this new model is much easier to apply with lower request for construction sites and higher positioning efficiency. A direct current (DC) solenoid as a magnetic dipole is placed on ground near the drill bit, and related sensors array which contains four Micro-electromechanical Systems (MEMS ) tri-axial magnetometers, one MEMS tri-axial accelerometer and one MEMS tri-axial gyroscope is set up for measuring the magnetic gradient tensor of the magnetic dipole. The related HDD positioning model has been established and simulation experiments have been carried out to verify the feasibility and reliability of the proposed method. The experiments show that this method has good positioning accuracy in horizontal and vertical direction, and totally avoid the impact of the environmental magnetic field. It can be found that the posture of the magnetic beacon will impact the remote positioning precision within valid positioning range, and the positioning accuracy is higher with longer baseline for limited space in drilling tools. The results prove that the relative error can be limited in 2% by adjusting position of the magnetic beacon, the layers of the enameled coil, the sensitive of magnetometers and the baseline distance. Conclusion can be made that this new method can be applied in HDD positioning with better effect and wider application range than traditional method.

Telemetric Technologies for the Assay of Gene Expression

Science.gov (United States)

Paul, Anna-Lisa; Bamsey, Matthew; Berinstain, Alain; Neron, Philip; Graham, Thomas; Ferl, Robert

Telemetric data collection has been widely used in spaceflight applications where human participation is limited (orbital mission payloads) or unfeasible (planetary landers, satellites, and probes). The transmission of digital data from electronic sensors of typical environmental parameters, growth patterns and physical properties of materials is routine telemetry, and even the collection and transmission of deep space images is a standard tool of astrophysics. But telemetric imaging for current biological payloads has thus far been limited to the collection of standard white-light photography that is largely confined to reporting the surface characteristics of the specimens involved. Advances in imaging technologies that facilitate the collection of a variety of light wavelengths will expand the science return on biological payloads to include evaluations of the molecular genetic response of organisms to the spaceflight or extraterrestrial environment, with minimal or no human intervention. Advanced imaging technology in combination with biologically engineered sensor organisms can create a system that can report via telemetry on the patterns of gene expression required to adapt to a novel environment. The utilization of genetically engineered plants as biosensors has made elegant strides in the recent years, providing keen insights into the health of plants in general and particularly in the nature and cellular location of stress responses. Moreover, molecular responses to gravitational vectors have been elegantly analyzed with fluorescent tools. Green Fluorescence Protein (GFP) and other fluorophores have made it possible for analyses of gene expression and biological responses to occur telemetrically, with the information potentially delivered to the investigator over large distances as simple, preprocessed fluorescence images. Having previously deployed transgenic plant biosensors to evaluate responses to orbital spaceflight, we wish to develop both the plants

[Application of gene chip technology for acupuncture research over the past 15 years].

Science.gov (United States)

Jia, Wenrui; Zhang, Yue; Guo, Qiying; Sun, Qisheng; Guo, Qiulei; Ji, Zhi; Yang, Fangyuan; Zhan, He; Wang, He; Sui, Minghe; Hou, Zhongwei; Wang, Chaoyang; Liu, Qingguo

2017-12-12

To explore the application of gene chip technology in the acupuncture research so as to provide evidences for the mechanism of acupuncture for regulating bodies. The literature on the application of gene chip technology in the acupuncture field from 2001 to 2016 was collected in PubMed, Springer, CNKI and WANFANG databases, which was analyzed and summarized. There were some achievements of the technology for acupuncture research, focusing on the five aspects, including the study of the relationship between meridian-point and viscera, the influencing factors of acupuncture effect, the effect and mechanism of acupuncture analgesia, the mechanism of acupuncture anti-aging, the effect and mechanism of acupuncture for diseases of each system. Gene chip technology plays an important role in researching acupuncture mechanism. It is an important technology for genomics study of acupuncture. However, there are also some disadvantages such as high cost, deficient data mining, non-uniform observation objects, deficient professionals, etc. All those need further resolution so as to promote the application of this technology in the acupuncture researching field.

Prospects of power conversion technology of direct-cycle helium gas turbine for MHTGR

International Nuclear Information System (INIS)

Li Yong; Zhang Zuoyi

1999-01-01

The modular high temperature gas cooled reactor (MHTGR) is a modern passively safe reactor. The reactor and helium gas turbine may be combined for high efficiency's power conversion, because MHTGR has high outlet temperature up to 950 degree C. Two different schemes are planed separately by USA and South Africa. the helium gas turbine methodologies adopted by them are mainly based on the developed heavy duty industrial and aviation gas turbine technology. The author introduces the differences of two technologies and some design issues in the design and manufacture. Moreover, the author conclude that directly coupling a closed Brayton cycle gas turbine concept to the passively safe MHTGR is the developing direction of MHTGR due to its efficiency which is much higher than that of using steam turbine

Testing for direct genetic effects using a screening step in family-based association studies

Directory of Open Access Journals (Sweden)

Sharon M Lutz

2013-11-01

Full Text Available In genome wide association studies (GWAS, families based studies tend to have less power to detect genetic associations than population based studies, such as case-control studies. This can be an issue when testing if genes in a family based GWAS have a direct effect on the phenotype of interest or if the genes act indirectly through a secondary phenotype. When multiple SNPs are tested for a direct effect in the family based study, a screening step can be used to minimize the burden of multiple comparisons in the causal analysis. We propose a 2-stage screening step that can be incorporated into the family based association test (FBAT approach similar to the conditional mean model approach in the VanSteen-algorithm [1]. Simulations demonstrate that the type 1 error is preserved and this method is advantageous when multiple markers are tested. This method is illustrated by an application to the Framingham Heart Study.

Effects of Transcranial Direct Current Stimulation on Expression of Immediate Early Genes (IEG’s)

Science.gov (United States)

2015-12-01

TRANSCRANIAL DIRECT CURRENT STIMULATION OF EXPRESSION OF IMMEDIATE EARLY GENES (IEG’S) Jessica...AND SUBTITLE Effects of Transcranial Direct Current Stimulation on Expression of Immediate Early Genes (IEG’s) 5a. CONTRACT NUMBER In-House 5b...community in better understanding what is occurring biologically during tDCS. 15. SUBJECT TERMS Transcranial direct current stimulation

Membrane-based processes for wastewater nutrient recovery: Technology, challenges, and future direction.

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Xie, Ming; Shon, Ho Kyong; Gray, Stephen R; Elimelech, Menachem

2016-02-01

Wastewater nutrient recovery holds promise for more sustainable water and agricultural industries. We critically review three emerging membrane processes - forward osmosis (FO), membrane distillation (MD) and electrodialysis (ED) - that can advance wastewater nutrient recovery. Challenges associated with wastewater nutrient recovery were identified. The advantages and challenges of applying FO, MD, and ED technologies to wastewater nutrient recovery are discussed, and directions for future research and development are identified. Emphasis is given to exploration of the unique mass transfer properties of these membrane processes in the context of wastewater nutrient recovery. We highlight that hybridising these membrane processes with existing nutrient precipitation process will lead to better management of and more diverse pathways for near complete nutrient recovery in wastewater treatment facilities. Copyright © 2015 Elsevier Ltd. All rights reserved.

Graphene devices based on laser scribing technology

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Qiao, Yan-Cong; Wei, Yu-Hong; Pang, Yu; Li, Yu-Xing; Wang, Dan-Yang; Li, Yu-Tao; Deng, Ning-Qin; Wang, Xue-Feng; Zhang, Hai-Nan; Wang, Qian; Yang, Zhen; Tao, Lu-Qi; Tian, He; Yang, Yi; Ren, Tian-Ling

2018-04-01

Graphene with excellent electronic, thermal, optical, and mechanical properties has great potential applications. The current devices based on graphene grown by micromechanical exfoliation, chemical vapor deposition (CVD), and thermal decomposition of silicon carbide are still expensive and inefficient. Laser scribing technology, a low-cost and time-efficient method of fabricating graphene, is introduced in this review. The patterning of graphene can be directly performed on solid and flexible substrates. Therefore, many novel devices such as strain sensors, acoustic devices, memory devices based on laser scribing graphene are fabricated. The outlook and challenges of laser scribing technology have also been discussed. Laser scribing may be a potential way of fabricating wearable and integrated graphene systems in the future.

A New Direction for Technology-Based Economic Development: The Role of Innovation Intermediaries

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Bendis, Richard A.; Seline, Richard S.; Byler, Ethan J.

2008-01-01

Accelerating innovation to drive economic growth is the foremost goal for technology-based economic development organizations today. Realizing this goal through programmes is challenged by limited and outdated operating models. The authors outline their 21st Century Innovation Intermediary model, which pairs commercialization with regional…

Environmental Application of Reporter-Genes Based Biosensors for Chemical Contamination Screening

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Matejczyk Marzena

2014-12-01

Full Text Available The paper presents results of research concerning possibilities of applications of reporter-genes based microorganisms, including the selective presentation of defects and advantages of different new scientific achievements of methodical solutions in genetic system constructions of biosensing elements for environmental research. The most robust and popular genetic fusion and new trends in reporter genes technology – such as LacZ (β-galactosidase, xylE (catechol 2,3-dioxygenase, gfp (green fluorescent proteins and its mutated forms, lux (prokaryotic luciferase, luc (eukaryotic luciferase, phoA (alkaline phosphatase, gusA and gurA (β-glucuronidase, antibiotics and heavy metals resistance are described. Reporter-genes based biosensors with use of genetically modified bacteria and yeast successfully work for genotoxicity, bioavailability and oxidative stress assessment for detection and monitoring of toxic compounds in drinking water and different environmental samples, surface water, soil, sediments.

A Nonlinear Model for Gene-Based Gene-Environment Interaction

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Jian Sa

2016-06-01

Full Text Available A vast amount of literature has confirmed the role of gene-environment (G×E interaction in the etiology of complex human diseases. Traditional methods are predominantly focused on the analysis of interaction between a single nucleotide polymorphism (SNP and an environmental variable. Given that genes are the functional units, it is crucial to understand how gene effects (rather than single SNP effects are influenced by an environmental variable to affect disease risk. Motivated by the increasing awareness of the power of gene-based association analysis over single variant based approach, in this work, we proposed a sparse principle component regression (sPCR model to understand the gene-based G×E interaction effect on complex disease. We first extracted the sparse principal components for SNPs in a gene, then the effect of each principal component was modeled by a varying-coefficient (VC model. The model can jointly model variants in a gene in which their effects are nonlinearly influenced by an environmental variable. In addition, the varying-coefficient sPCR (VC-sPCR model has nice interpretation property since the sparsity on the principal component loadings can tell the relative importance of the corresponding SNPs in each component. We applied our method to a human birth weight dataset in Thai population. We analyzed 12,005 genes across 22 chromosomes and found one significant interaction effect using the Bonferroni correction method and one suggestive interaction. The model performance was further evaluated through simulation studies. Our model provides a system approach to evaluate gene-based G×E interaction.

Exploration Technology Program plans and directions

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Aldrich, A.; Rosen, R.; Craig, M.; Mankins, J. C.

During the first part of the next century, the United States will return to the Moon to create a permanent lunar base, and, before the year 2019, we will send a human mission to Mars. In addition to these human operations, the Space Exploration Initiative will integrally incorporate robotic lunar and Mars missions. In achieving these efforts to expand human presence and activity in space and also exerted and frontiers of human knowledge, the SEI will require an array of new technologies. Mission architecture definition is still underway, but previous studies indicate that the SEI will require developments in areas such as advanced engines for space transportation, in-space assembly and construction to support permanent basing of exploration systems in space, and advanced surface operations capabilities including adequate levels of power and surface roving vehicles, and technologies to support safely long-duration human operations in space. Plans are now being put into place to implement an Exploration Technology Program (ETP) which will develop the major technologies needed for SEI. In close coordination with other ongoing U.S. government research and development efforts, the ETP will provide in the near term clear demonstrations of potential exploration technologies, research results to support SEI architecture decisions, and a foundation of mature technology that is ready to be applied in the first round of SEI missions. In addition to the technology needed for the first round of SEI missions, the ETP will also put in place a foundation of research for longer-term technology needs—ultimately leading the human missions to Mars. The Space Exploration Initiative and the Exploration Technology Program will challenge the best and the brightest minds across government, industry and academia, inspiring students of all ages and making possible future terrestial applications of SEI technologies that may create whole new industries for the future.

Promoter library-based module combination (PLMC) technology for optimization of threonine biosynthesis in Corynebacterium glutamicum.

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Wei, Liang; Xu, Ning; Wang, Yiran; Zhou, Wei; Han, Guoqiang; Ma, Yanhe; Liu, Jun

2018-05-01

Due to the lack of efficient control elements and tools, the fine-tuning of gene expression in the multi-gene metabolic pathways is still a great challenge for engineering microbial cell factories, especially for the important industrial microorganism Corynebacterium glutamicum. In this study, the promoter library-based module combination (PLMC) technology was developed to efficiently optimize the expression of genes in C. glutamicum. A random promoter library was designed to contain the putative - 10 (NNTANANT) and - 35 (NNGNCN) consensus motifs, and refined through a three-step screening procedure to achieve numerous genetic control elements with different strength levels, including fluorescence-activated cell sorting (FACS) screening, agar plate screening, and 96-well plate screening. Multiple conventional strategies were employed for further precise characterizations of the promoter library, such as real-time quantitative PCR, sodium dodecyl sulfate polyacrylamide gel electrophoresis, FACS analysis, and the lacZ reporter system. These results suggested that the established promoter elements effectively regulated gene expression and showed varying strengths over a wide range. Subsequently, a multi-module combination technology was created based on the efficient promoter elements for combination and optimization of modules in the multi-gene pathways. Using this technology, the threonine biosynthesis pathway was reconstructed and optimized by predictable tuning expression of five modules in C. glutamicum. The threonine titer of the optimized strain was significantly improved to 12.8 g/L, an approximate 6.1-fold higher than that of the control strain. Overall, the PLMC technology presented in this study provides a rapid and effective method for combination and optimization of multi-gene pathways in C. glutamicum.

Monoclonal antibodies based on hybridoma technology.

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Yagami, Hisanori; Kato, Hiroshi; Tsumoto, Kanta; Tomita, Masahiro

2013-03-01

Based on the size and scope of the present global market for medicine, monoclonal antibodies (mAbs) have a very promising future, with applications for cancers through autoimmune ailments to infectious disease. Since mAbs recognize only their target antigens and not other unrelated proteins, pinpoint medical treatment is possible. Global demand is dramatically expanding. Hybridoma technology, which allows production of mAbs directed against antigens of interest is therefore privileged. However, there are some pivotal points for further development to generate therapeutic antibodies. One is selective generation of human mAbs. Employment of transgenic mice producing human antibodies would overcome this problem. Another focus is recognition sites and conformational epitopes in antigens may be just as important as linear epitopes, especially when membrane proteins such as receptors are targeted. Recognition of intact structures is of critical importance for medical purposes. In this review, we describe patent related information for therapeutic mAbs based on hybridoma technology and also discuss new advances in hybridoma technology that facilitate selective production of stereospecific mAbs.

Applying Sensor-Based Technology to Improve Construction Safety Management.

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Zhang, Mingyuan; Cao, Tianzhuo; Zhao, Xuefeng

2017-08-11

Construction sites are dynamic and complicated systems. The movement and interaction of people, goods and energy make construction safety management extremely difficult. Due to the ever-increasing amount of information, traditional construction safety management has operated under difficult circumstances. As an effective way to collect, identify and process information, sensor-based technology is deemed to provide new generation of methods for advancing construction safety management. It makes the real-time construction safety management with high efficiency and accuracy a reality and provides a solid foundation for facilitating its modernization, and informatization. Nowadays, various sensor-based technologies have been adopted for construction safety management, including locating sensor-based technology, vision-based sensing and wireless sensor networks. This paper provides a systematic and comprehensive review of previous studies in this field to acknowledge useful findings, identify the research gaps and point out future research directions.

RNA-seq based identification and mutant validation of gene targets related to ethanol resistance in cyanobacterial Synechocystis sp. PCC 6803

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Wang Jiangxin

2012-12-01

Full Text Available Abstract Background Fermentation production of biofuel ethanol consumes agricultural crops, which will compete directly with the food supply. As an alternative, photosynthetic cyanobacteria have been proposed as microbial factories to produce ethanol directly from solar energy and CO2. However, the ethanol productivity from photoautotrophic cyanobacteria is still very low, mostly due to the low tolerance of cyanobacterial systems to ethanol stress. Results To build a foundation necessary to engineer robust ethanol-producing cyanobacterial hosts, in this study we applied a quantitative transcriptomics approach with a next-generation sequencing technology, combined with quantitative reverse-transcript PCR (RT-PCR analysis, to reveal the global metabolic responses to ethanol in model cyanobacterial Synechocystis sp. PCC 6803. The results showed that ethanol exposure induced genes involved in common stress responses, transporting and cell envelope modification. In addition, the cells can also utilize enhanced polyhydroxyalkanoates (PHA accumulation and glyoxalase detoxication pathway as means against ethanol stress. The up-regulation of photosynthesis by ethanol was also further confirmed at transcriptional level. Finally, we used gene knockout strains to validate the potential target genes related to ethanol tolerance. Conclusion RNA-Seq based global transcriptomic analysis provided a comprehensive view of cellular response to ethanol exposure. The analysis provided a list of gene targets for engineering ethanol tolerance in cyanobacterium Synechocystis.

PRODUCTION OF PROTOTYPE PARTS USING DIRECT METAL LASER SINTERING TECHNOLOGY

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Josef Sedlak

2015-08-01

Full Text Available Unconventional methods of modern materials preparation include additive technologies which involve the sintering of powders of different chemical composition, granularity, physical, chemical and other utility properties. The technology called Rapid Prototyping, which uses different technological principles of producing components, belongs to this type of material preparation. The Rapid Prototyping technology facilities use photopolymers, thermoplastics, specially treated paper or metal powders. The advantage is the direct production of metal parts from input data and the fact that there is no need for the production of special tools (moulds, press tools, etc.. Unused powder from sintering technologies is re-used for production 98% of the time, which means that the process is economical, as well as ecological.The present paper discusses the technology of Direct Metal Laser Sintering (DMLS, which falls into the group of additive technologies of Rapid Prototyping (RP. The major objective is a detailed description of DMLS, pointing out the benefits it offers and its application in practice. The practical part describes the production and provides an economic comparison of several prototype parts that were designed for testing in the automotive industry.

Gene expression and gene therapy imaging

International Nuclear Information System (INIS)

Rome, Claire; Couillaud, Franck; Moonen, Chrit T.W.

2007-01-01

The fast growing field of molecular imaging has achieved major advances in imaging gene expression, an important element of gene therapy. Gene expression imaging is based on specific probes or contrast agents that allow either direct or indirect spatio-temporal evaluation of gene expression. Direct evaluation is possible with, for example, contrast agents that bind directly to a specific target (e.g., receptor). Indirect evaluation may be achieved by using specific substrate probes for a target enzyme. The use of marker genes, also called reporter genes, is an essential element of MI approaches for gene expression in gene therapy. The marker gene may not have a therapeutic role itself, but by coupling the marker gene to a therapeutic gene, expression of the marker gene reports on the expression of the therapeutic gene. Nuclear medicine and optical approaches are highly sensitive (detection of probes in the picomolar range), whereas MRI and ultrasound imaging are less sensitive and require amplification techniques and/or accumulation of contrast agents in enlarged contrast particles. Recently developed MI techniques are particularly relevant for gene therapy. Amongst these are the possibility to track gene therapy vectors such as stem cells, and the techniques that allow spatiotemporal control of gene expression by non-invasive heating (with MRI guided focused ultrasound) and the use of temperature sensitive promoters. (orig.)

Direct detection of hemophilia B F9 gene mutation using multiplex PCR and conformation sensitive gel electrophoresis

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Ki Young Yoo

2010-03-01

Full Text Available Purpose : The F9 gene is known to be the causative gene for hemophilia B, but unfortunately the detection rate for restriction fragment length polymorphism-based linkage analysis is only 55.6%. Direct DNA sequencing can detect 98% of mutations, but this alternative procedure is very costly. Here, we conducted multiplex polymerase chain reactions (PCRs and conformation sensitive gel electrophoresis (CSGE to perform a screened DNA sequencing for the F9 gene, and we compared the results with direct sequencing in terms of accuracy, cost, simplicity, and time consumption. Methods : A total of 27 unrelated hemophilia B patients were enrolled. Direct DNA sequencing was performed for 27 patients by a separate institute, and multiplex PCR-CSGE screened sequencing was done in our laboratory. Results of the direct DNA sequencing were used as a reference, to which the results of the multiplex PCR-CSGE screened sequencing were compared. For the patients whose mutation was not detected by the 2 methods, multiplex ligation-dependent probe amplification (MLPA was conducted. Results : With direct sequencing, the mutations could be identified from 26 patients (96.3%, whereas for multiplex PCR- CSGE screened sequencing, the mutations could be detected in 23 (85.2%. One patient’s mutation was identified by MLPA. A total of 21 different mutations were found among the 27 patients. Conclusion : Multiplex PCR-CSGE screened DNA sequencing detected 88.9% of mutations and reduced costs by 55.7% compared with direct DNA sequencing. However, it was more labor-intensive and time-consuming.

Site-Specific Integration of Exogenous Genes Using Genome Editing Technologies in Zebrafish

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Atsuo Kawahara

2016-05-01

Full Text Available The zebrafish (Danio rerio is an ideal vertebrate model to investigate the developmental molecular mechanism of organogenesis and regeneration. Recent innovation in genome editing technologies, such as zinc finger nucleases (ZFNs, transcription activator-like effector nucleases (TALENs and the clustered regularly interspaced short palindromic repeats (CRISPR/CRISPR associated protein 9 (Cas9 system, have allowed researchers to generate diverse genomic modifications in whole animals and in cultured cells. The CRISPR/Cas9 and TALEN techniques frequently induce DNA double-strand breaks (DSBs at the targeted gene, resulting in frameshift-mediated gene disruption. As a useful application of genome editing technology, several groups have recently reported efficient site-specific integration of exogenous genes into targeted genomic loci. In this review, we provide an overview of TALEN- and CRISPR/Cas9-mediated site-specific integration of exogenous genes in zebrafish.

Environmental Regulation, Foreign Direct Investment and Green Technological Progress—Evidence from Chinese Manufacturing Industries

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Hu, Jiangfeng; Wang, Zhao; Lian, Yuehan; Huang, Qinghua

2018-01-01

This study examines the spillover effects of foreign direct investment (FDI) on green technology progress rate (as measured by the green total factor productivity). The analysis utilizes two measures of FDI, labor-based FDI and capital-based FDI, and separately investigates four sets of industry classifications—high/low discharge regulation and high/low emission standard regulation. The results indicate that in the low discharge regulation and low emission standard regulation industry, labor-based FDI has a significant negative spillover effect, and capital-based FDI has a significant positive spillover effect. However, in the high-intensity environmental regulation industry, the negative influence of labor-based FDI is completely restrained, and capital-based FDI continues to play a significant positive green technological spillover effects. These findings have clear policy implications: the government should be gradually reducing the labor-based FDI inflow or increasing stringency of environmental regulation in order to reduce or eliminate the negative spillover effect of the labor-based FDI. PMID:29382112

Environmental Regulation, Foreign Direct Investment and Green Technological Progress—Evidence from Chinese Manufacturing Industries

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Jiangfeng Hu

2018-01-01

Full Text Available This study examines the spillover effects of foreign direct investment (FDI on green technology progress rate (as measured by the green total factor productivity. The analysis utilizes two measures of FDI, labor-based FDI and capital-based FDI, and separately investigates four sets of industry classifications—high/low discharge regulation and high/low emission standard regulation. The results indicate that in the low discharge regulation and low emission standard regulation industry, labor-based FDI has a significant negative spillover effect, and capital-based FDI has a significant positive spillover effect. However, in the high-intensity environmental regulation industry, the negative influence of labor-based FDI is completely restrained, and capital-based FDI continues to play a significant positive green technological spillover effects. These findings have clear policy implications: the government should be gradually reducing the labor-based FDI inflow or increasing stringency of environmental regulation in order to reduce or eliminate the negative spillover effect of the labor-based FDI.

Environmental Regulation, Foreign Direct Investment and Green Technological Progress-Evidence from Chinese Manufacturing Industries.

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Hu, Jiangfeng; Wang, Zhao; Lian, Yuehan; Huang, Qinghua

2018-01-29

This study examines the spillover effects of foreign direct investment (FDI) on green technology progress rate (as measured by the green total factor productivity). The analysis utilizes two measures of FDI, labor-based FDI and capital-based FDI, and separately investigates four sets of industry classifications-high/low discharge regulation and high/low emission standard regulation. The results indicate that in the low discharge regulation and low emission standard regulation industry, labor-based FDI has a significant negative spillover effect, and capital-based FDI has a significant positive spillover effect. However, in the high-intensity environmental regulation industry, the negative influence of labor-based FDI is completely restrained, and capital-based FDI continues to play a significant positive green technological spillover effects. These findings have clear policy implications: the government should be gradually reducing the labor-based FDI inflow or increasing stringency of environmental regulation in order to reduce or eliminate the negative spillover effect of the labor-based FDI.

Dual gene activation and knockout screen reveals directional dependencies in genetic networks. | Office of Cancer Genomics

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Understanding the direction of information flow is essential for characterizing how genetic networks affect phenotypes. However, methods to find genetic interactions largely fail to reveal directional dependencies. We combine two orthogonal Cas9 proteins from Streptococcus pyogenes and Staphylococcus aureus to carry out a dual screen in which one gene is activated while a second gene is deleted in the same cell. We analyze the quantitative effects of activation and knockout to calculate genetic interaction and directionality scores for each gene pair.

Directed natural product biosynthesis gene cluster capture and expression in the model bacterium Bacillus subtilis

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Li, Yongxin

2015-03-24

Bacilli are ubiquitous low G+C environmental Gram-positive bacteria that produce a wide assortment of specialized small molecules. Although their natural product biosynthetic potential is high, robust molecular tools to support the heterologous expression of large biosynthetic gene clusters in Bacillus hosts are rare. Herein we adapt transformation-associated recombination (TAR) in yeast to design a single genomic capture and expression vector for antibiotic production in Bacillus subtilis. After validating this direct cloning plug-and-playa approach with surfactin, we genetically interrogated amicoumacin biosynthetic gene cluster from the marine isolate Bacillus subtilis 1779. Its heterologous expression allowed us to explore an unusual maturation process involving the N-acyl-asparagine pro-drug intermediates preamicoumacins, which are hydrolyzed by the asparagine-specific peptidase into the active component amicoumacin A. This work represents the first direct cloning based heterologous expression of natural products in the model organism B. subtilis and paves the way to the development of future genome mining efforts in this genus.

Directed natural product biosynthesis gene cluster capture and expression in the model bacterium Bacillus subtilis

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Li, Yongxin; Li, Zhongrui; Yamanaka, Kazuya; Xu, Ying; Zhang, Weipeng; Vlamakis, Hera; Kolter, Roberto; Moore, Bradley S.; Qian, Pei-Yuan

2015-03-01

Bacilli are ubiquitous low G+C environmental Gram-positive bacteria that produce a wide assortment of specialized small molecules. Although their natural product biosynthetic potential is high, robust molecular tools to support the heterologous expression of large biosynthetic gene clusters in Bacillus hosts are rare. Herein we adapt transformation-associated recombination (TAR) in yeast to design a single genomic capture and expression vector for antibiotic production in Bacillus subtilis. After validating this direct cloning ``plug-and-play'' approach with surfactin, we genetically interrogated amicoumacin biosynthetic gene cluster from the marine isolate Bacillus subtilis 1779. Its heterologous expression allowed us to explore an unusual maturation process involving the N-acyl-asparagine pro-drug intermediates preamicoumacins, which are hydrolyzed by the asparagine-specific peptidase into the active component amicoumacin A. This work represents the first direct cloning based heterologous expression of natural products in the model organism B. subtilis and paves the way to the development of future genome mining efforts in this genus.

Positive-negative-selection-mediated gene targeting in rice

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Zenpei eShimatani

2015-01-01

Full Text Available Gene targeting (GT refers to the designed modification of genomic sequence(s through homologous recombination (HR. GT is a powerful tool both for the study of gene function and for molecular breeding. However, in transformation of higher plants, non-homologous end joining (NHEJ occurs overwhelmingly in somatic cells, masking HR-mediated GT. Positive-negative selection (PNS is an approach for finding HR-mediated GT events because it can eliminate NHEJ effectively by expression of a negative-selection marker gene. In rice—a major crop worldwide—reproducible PNS-mediated GT of endogenous genes has now been successfully achieved. The procedure is based on strong PNS using diphtheria toxin A-fragment as a negative marker, and has succeeded in the directed modification of several endogenous rice genes in various ways. In addition to gene knock-outs and knock-ins, a nucleotide substitution in a target gene was also achieved recently. This review presents a summary of the development of the rice PNS system, highlighting its advantages. Different types of gene modification and gene editing aimed at developing new plant breeding technology (NPBT based on PNS are discussed.

MicroArray Facility: a laboratory information management system with extended support for Nylon based technologies

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Beaudoing Emmanuel

2006-09-01

Full Text Available Abstract Background High throughput gene expression profiling (GEP is becoming a routine technique in life science laboratories. With experimental designs that repeatedly span thousands of genes and hundreds of samples, relying on a dedicated database infrastructure is no longer an option. GEP technology is a fast moving target, with new approaches constantly broadening the field diversity. This technology heterogeneity, compounded by the informatics complexity of GEP databases, means that software developments have so far focused on mainstream techniques, leaving less typical yet established techniques such as Nylon microarrays at best partially supported. Results MAF (MicroArray Facility is the laboratory database system we have developed for managing the design, production and hybridization of spotted microarrays. Although it can support the widely used glass microarrays and oligo-chips, MAF was designed with the specific idiosyncrasies of Nylon based microarrays in mind. Notably single channel radioactive probes, microarray stripping and reuse, vector control hybridizations and spike-in controls are all natively supported by the software suite. MicroArray Facility is MIAME supportive and dynamically provides feedback on missing annotations to help users estimate effective MIAME compliance. Genomic data such as clone identifiers and gene symbols are also directly annotated by MAF software using standard public resources. The MAGE-ML data format is implemented for full data export. Journalized database operations (audit tracking, data anonymization, material traceability and user/project level confidentiality policies are also managed by MAF. Conclusion MicroArray Facility is a complete data management system for microarray producers and end-users. Particular care has been devoted to adequately model Nylon based microarrays. The MAF system, developed and implemented in both private and academic environments, has proved a robust solution for

Strategies used for genetically modifying bacterial genome: ite-directed mutagenesis, gene inactivation, and gene over-expression*

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Xu, Jian-zhong; Zhang, Wei-guo

2016-01-01

With the availability of the whole genome sequence of Escherichia coli or Corynebacterium glutamicum, strategies for directed DNA manipulation have developed rapidly. DNA manipulation plays an important role in understanding the function of genes and in constructing novel engineering bacteria according to requirement. DNA manipulation involves modifying the autologous genes and expressing the heterogenous genes. Two alternative approaches, using electroporation linear DNA or recombinant suicide plasmid, allow a wide variety of DNA manipulation. However, the over-expression of the desired gene is generally executed via plasmid-mediation. The current review summarizes the common strategies used for genetically modifying E. coli and C. glutamicum genomes, and discusses the technical problem of multi-layered DNA manipulation. Strategies for gene over-expression via integrating into genome are proposed. This review is intended to be an accessible introduction to DNA manipulation within the bacterial genome for novices and a source of the latest experimental information for experienced investigators. PMID:26834010

A powerful score-based test statistic for detecting gene-gene co-association.

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Xu, Jing; Yuan, Zhongshang; Ji, Jiadong; Zhang, Xiaoshuai; Li, Hongkai; Wu, Xuesen; Xue, Fuzhong; Liu, Yanxun

2016-01-29

The genetic variants identified by Genome-wide association study (GWAS) can only account for a small proportion of the total heritability for complex disease. The existence of gene-gene joint effects which contains the main effects and their co-association is one of the possible explanations for the "missing heritability" problems. Gene-gene co-association refers to the extent to which the joint effects of two genes differ from the main effects, not only due to the traditional interaction under nearly independent condition but the correlation between genes. Generally, genes tend to work collaboratively within specific pathway or network contributing to the disease and the specific disease-associated locus will often be highly correlated (e.g. single nucleotide polymorphisms (SNPs) in linkage disequilibrium). Therefore, we proposed a novel score-based statistic (SBS) as a gene-based method for detecting gene-gene co-association. Various simulations illustrate that, under different sample sizes, marginal effects of causal SNPs and co-association levels, the proposed SBS has the better performance than other existed methods including single SNP-based and principle component analysis (PCA)-based logistic regression model, the statistics based on canonical correlations (CCU), kernel canonical correlation analysis (KCCU), partial least squares path modeling (PLSPM) and delta-square (δ (2)) statistic. The real data analysis of rheumatoid arthritis (RA) further confirmed its advantages in practice. SBS is a powerful and efficient gene-based method for detecting gene-gene co-association.

Heat-transfer-based detection of SNPs in the PAH gene of PKU patients

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Vanden Bon N

2014-03-01

Full Text Available Natalie Vanden Bon,1 Bart van Grinsven,2 Mohammed Sharif Murib,2 Weng Siang Yeap,2 Ken Haenen,2,3 Ward De Ceuninck,2,3 Patrick Wagner,2,3 Marcel Ameloot,1 Veronique Vermeeren,1 Luc Michiels11Biomedical Research Institute, Hasselt University, Diepenbeek, Belgium; 2Institute for Materials Research, Hasselt University, Diepenbeek, Belgium; 3IMOMEC, Diepenbeek, BelgiumAbstract: Conventional neonatal diagnosis of phenylketonuria is based on the presence of abnormal levels of phenylalanine in the blood. However, for carrier detection and prenatal diagnosis, direct detection of disease-correlated mutations is needed. To speed up and simplify mutation screening in genes, new technologies are developed. In this study, a heat-transfer method is evaluated as a mutation-detection technology in entire exons of the phenylalanine hydroxylase (PAH gene. This method is based on the change in heat-transfer resistance (Rth upon thermal denaturation of dsDNA (double-stranded DNA on nanocrystalline diamond. First, ssDNA (single-stranded DNA fragments that span the size range of the PAH exons were successfully immobilized on nanocrystalline diamond. Next, it was studied whether an Rth change could be observed during the thermal denaturation of these DNA fragments after hybridization to their complementary counterpart. A clear Rth shift during the denaturation of exon 5, exon 9, and exon 12 dsDNA was observed, corresponding to lengths of up to 123 bp. Finally, Rth was shown to detect prevalent single-nucleotide polymorphisms, c.473G>A (R158Q, c.932T>C (p.L311P, and c.1222C>T (R408W, correlated with phenylketonuria, displaying an effect related to the different melting temperatures of homoduplexes and heteroduplexes.Keywords: mutation detection, heat-transfer resistance, melting temperature, nanocrystalline diamond, persistence length

Evaluation of gene importance in microarray data based upon probability of selection

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Fu Li M

2005-03-01

Full Text Available Abstract Background Microarray devices permit a genome-scale evaluation of gene function. This technology has catalyzed biomedical research and development in recent years. As many important diseases can be traced down to the gene level, a long-standing research problem is to identify specific gene expression patterns linking to metabolic characteristics that contribute to disease development and progression. The microarray approach offers an expedited solution to this problem. However, it has posed a challenging issue to recognize disease-related genes expression patterns embedded in the microarray data. In selecting a small set of biologically significant genes for classifier design, the nature of high data dimensionality inherent in this problem creates substantial amount of uncertainty. Results Here we present a model for probability analysis of selected genes in order to determine their importance. Our contribution is that we show how to derive the P value of each selected gene in multiple gene selection trials based on different combinations of data samples and how to conduct a reliability analysis accordingly. The importance of a gene is indicated by its associated P value in that a smaller value implies higher information content from information theory. On the microarray data concerning the subtype classification of small round blue cell tumors, we demonstrate that the method is capable of finding the smallest set of genes (19 genes with optimal classification performance, compared with results reported in the literature. Conclusion In classifier design based on microarray data, the probability value derived from gene selection based on multiple combinations of data samples enables an effective mechanism for reducing the tendency of fitting local data particularities.

eSensor: an electrochemical detection-based DNA microarray technology enabling sample-to-answer molecular diagnostics

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Liu, Robin H.; Longiaru, Mathew

2009-05-01

DNA microarrays are becoming a widespread tool used in life science and drug screening due to its many benefits of miniaturization and integration. Microarrays permit a highly multiplexed DNA analysis. Recently, the development of new detection methods and simplified methodologies has rapidly expanded the use of microarray technologies from predominantly gene expression analysis into the arena of diagnostics. Osmetech's eSensor® is an electrochemical detection platform based on a low-to- medium density DNA hybridization array on a cost-effective printed circuit board substrate. eSensor® has been cleared by FDA for Warfarin sensitivity test and Cystic Fibrosis Carrier Detection. Other genetic-based diagnostic and infectious disease detection tests are under development. The eSensor® platform eliminates the need for an expensive laser-based optical system and fluorescent reagents. It allows one to perform hybridization and detection in a single and small instrument without any fluidic processing and handling. Furthermore, the eSensor® platform is readily adaptable to on-chip sample-to-answer genetic analyses using microfluidics technology. The eSensor® platform provides a cost-effective solution to direct sample-to-answer genetic analysis, and thus have a potential impact in the fields of point-of-care genetic analysis, environmental testing, and biological warfare agent detection.

Bystander or No Bystander for Gene Directed Enzyme Prodrug Therapy

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Adam V. Patterson

2009-11-01

Full Text Available Gene directed enzyme prodrug therapy (GDEPT of cancer aims to improve the selectivity of chemotherapy by gene transfer, thus enabling target cells to convert nontoxic prodrugs to cytotoxic drugs. A zone of cell kill around gene-modified cells due to transfer of toxic metabolites, known as the bystander effect, leads to tumour regression. Here we discuss the implications of either striving for a strong bystander effect to overcome poor gene transfer, or avoiding the bystander effect to reduce potential systemic effects, with the aid of three successful GDEPT systems. This review concentrates on bystander effects and drug development with regard to these enzyme prodrug combinations, namely herpes simplex virus thymidine kinase (HSV-TK with ganciclovir (GCV, cytosine deaminase (CD from bacteria or yeast with 5-fluorocytodine (5-FC, and bacterial nitroreductase (NfsB with 5-(azaridin-1-yl-2,4-dinitrobenzamide (CB1954, and their respective derivatives.

77 FR 46855 - Small Business Technology Transfer Program Policy Directive

Science.gov (United States)

2012-08-06

... SMALL BUSINESS ADMINISTRATION 13 CFR Chapter I RIN 3245-AF45 Small Business Technology Transfer Program Policy Directive AGENCY: Small Business Administration. ACTION: Final policy directive with request for comments. SUMMARY: The U.S. Small Business Administration (SBA) is amending its Small Business...

On promotion of base technologies of atomic energy

International Nuclear Information System (INIS)

1988-01-01

In the long term plan of atomic energy development and utilization decided in June, 1987 by the Atomic Energy Commission, it was recognized that hereafter, the opening-up of the new potential that atomic energy possesses should be aimed at, and the policy was shown so that the research and development hereafter place emphasis on the creative and innovative region which causes large technical innovation, by which the spreading effect to general science and technology can be expected, and the development of the base technologies that connect the basic research and project development is promoted. The trend of atomic energy development so far, the change of the situation surrounding atomic energy, the direction of technical development of atomic energy hereafter and the base technologies are discussed. The concept of the technical development of materilas, artificial intelligence, lasers, and the evaluation and reduction of radiation risks used for atomic energy is described. As the development plan of atomic energy base technologies, the subjects of technical development, the future image of technical development, the efficient promotion of the development and so on are shown. (Kato, I.)

Gene function prediction based on Gene Ontology Hierarchy Preserving Hashing.

Science.gov (United States)

Zhao, Yingwen; Fu, Guangyuan; Wang, Jun; Guo, Maozu; Yu, Guoxian

2018-02-23

Gene Ontology (GO) uses structured vocabularies (or terms) to describe the molecular functions, biological roles, and cellular locations of gene products in a hierarchical ontology. GO annotations associate genes with GO terms and indicate the given gene products carrying out the biological functions described by the relevant terms. However, predicting correct GO annotations for genes from a massive set of GO terms as defined by GO is a difficult challenge. To combat with this challenge, we introduce a Gene Ontology Hierarchy Preserving Hashing (HPHash) based semantic method for gene function prediction. HPHash firstly measures the taxonomic similarity between GO terms. It then uses a hierarchy preserving hashing technique to keep the hierarchical order between GO terms, and to optimize a series of hashing functions to encode massive GO terms via compact binary codes. After that, HPHash utilizes these hashing functions to project the gene-term association matrix into a low-dimensional one and performs semantic similarity based gene function prediction in the low-dimensional space. Experimental results on three model species (Homo sapiens, Mus musculus and Rattus norvegicus) for interspecies gene function prediction show that HPHash performs better than other related approaches and it is robust to the number of hash functions. In addition, we also take HPHash as a plugin for BLAST based gene function prediction. From the experimental results, HPHash again significantly improves the prediction performance. The codes of HPHash are available at: http://mlda.swu.edu.cn/codes.php?name=HPHash. Copyright © 2018 Elsevier Inc. All rights reserved.

Erythropoietin abuse and erythropoietin gene doping: detection strategies in the genomic era.

Science.gov (United States)

Diamanti-Kandarakis, Evanthia; Konstantinopoulos, Panagiotis A; Papailiou, Joanna; Kandarakis, Stylianos A; Andreopoulos, Anastasios; Sykiotis, Gerasimos P

2005-01-01

The administration of recombinant human erythropoietin (rhEPO) increases the maximum oxygen consumption capacity, and is therefore abused as a doping method in endurance sports. The detection of erythropoietin (EPO) abuse is based on direct pharmacological and indirect haematological approaches, both of which have several limitations. In addition, current detection methods cannot cope with the emerging doping strategies of EPO mimicry, analogues and gene doping, and thus novel detection strategies are urgently needed. Direct detection methods for EPO misuse can be either pharmacological approaches that identify exogenous substances based on their physicochemical properties, or molecular methods that recognise EPO transgenes or gene transfer vectors. Since direct detection with molecular methods requires invasive procedures, it is not appropriate for routine screening of large numbers of athletes. In contrast, novel indirect methods based on haematological and/or molecular profiling could be better suited as screening tools, and athletes who are suspect of doping would then be submitted to direct pharmacological and molecular tests. This article reviews the current state of the EPO doping field, discusses available detection methods and their shortcomings, outlines emerging pharmaceutical and genetic technologies in EPO misuse, and proposes potential directions for the development of novel detection strategies.

An Undergraduate Laboratory Class Using CRISPR/Cas9 Technology to Mutate Drosophila Genes

Science.gov (United States)

Adame, Vanesa; Chapapas, Holly; Cisneros, Marilyn; Deaton, Carol; Deichmann, Sophia; Gadek, Chauncey; Lovato, TyAnna L.; Chechenova, Maria B.; Guerin, Paul; Cripps, Richard M.

2016-01-01

CRISPR/Cas9 genome editing technology is used in the manipulation of genome sequences and gene expression. Because of the ease and rapidity with which genes can be mutated using CRISPR/Cas9, we sought to determine if a single-semester undergraduate class could be successfully taught, wherein students isolate mutants for specific genes using…

Inferring gene dependency network specific to phenotypic alteration based on gene expression data and clinical information of breast cancer.

Science.gov (United States)

Zhou, Xionghui; Liu, Juan

2014-01-01

Although many methods have been proposed to reconstruct gene regulatory network, most of them, when applied in the sample-based data, can not reveal the gene regulatory relations underlying the phenotypic change (e.g. normal versus cancer). In this paper, we adopt phenotype as a variable when constructing the gene regulatory network, while former researches either neglected it or only used it to select the differentially expressed genes as the inputs to construct the gene regulatory network. To be specific, we integrate phenotype information with gene expression data to identify the gene dependency pairs by using the method of conditional mutual information. A gene dependency pair (A,B) means that the influence of gene A on the phenotype depends on gene B. All identified gene dependency pairs constitute a directed network underlying the phenotype, namely gene dependency network. By this way, we have constructed gene dependency network of breast cancer from gene expression data along with two different phenotype states (metastasis and non-metastasis). Moreover, we have found the network scale free, indicating that its hub genes with high out-degrees may play critical roles in the network. After functional investigation, these hub genes are found to be biologically significant and specially related to breast cancer, which suggests that our gene dependency network is meaningful. The validity has also been justified by literature investigation. From the network, we have selected 43 discriminative hubs as signature to build the classification model for distinguishing the distant metastasis risks of breast cancer patients, and the result outperforms those classification models with published signatures. In conclusion, we have proposed a promising way to construct the gene regulatory network by using sample-based data, which has been shown to be effective and accurate in uncovering the hidden mechanism of the biological process and identifying the gene signature for

Cross-platform analysis of cancer microarray data improves gene expression based classification of phenotypes

Directory of Open Access Journals (Sweden)

Eils Roland

2005-11-01

Full Text Available Abstract Background The extensive use of DNA microarray technology in the characterization of the cell transcriptome is leading to an ever increasing amount of microarray data from cancer studies. Although similar questions for the same type of cancer are addressed in these different studies, a comparative analysis of their results is hampered by the use of heterogeneous microarray platforms and analysis methods. Results In contrast to a meta-analysis approach where results of different studies are combined on an interpretative level, we investigate here how to directly integrate raw microarray data from different studies for the purpose of supervised classification analysis. We use median rank scores and quantile discretization to derive numerically comparable measures of gene expression from different platforms. These transformed data are then used for training of classifiers based on support vector machines. We apply this approach to six publicly available cancer microarray gene expression data sets, which consist of three pairs of studies, each examining the same type of cancer, i.e. breast cancer, prostate cancer or acute myeloid leukemia. For each pair, one study was performed by means of cDNA microarrays and the other by means of oligonucleotide microarrays. In each pair, high classification accuracies (> 85% were achieved with training and testing on data instances randomly chosen from both data sets in a cross-validation analysis. To exemplify the potential of this cross-platform classification analysis, we use two leukemia microarray data sets to show that important genes with regard to the biology of leukemia are selected in an integrated analysis, which are missed in either single-set analysis. Conclusion Cross-platform classification of multiple cancer microarray data sets yields discriminative gene expression signatures that are found and validated on a large number of microarray samples, generated by different laboratories and

The expanding universe of transposon technologies for gene and cell engineering

Directory of Open Access Journals (Sweden)

Ivics Zoltán

2010-12-01

Full Text Available Abstract Transposable elements can be viewed as natural DNA transfer vehicles that, similar to integrating viruses, are capable of efficient genomic insertion. The mobility of class II transposable elements (DNA transposons can be controlled by conditionally providing the transposase component of the transposition reaction. Thus, a DNA of interest (be it a fluorescent marker, a small hairpin (shRNA expression cassette, a mutagenic gene trap or a therapeutic gene construct cloned between the inverted repeat sequences of a transposon-based vector can be used for stable genomic insertion in a regulated and highly efficient manner. This methodological paradigm opened up a number of avenues for genome manipulations in vertebrates, including transgenesis for the generation of transgenic cells in tissue culture, the production of germline transgenic animals for basic and applied research, forward genetic screens for functional gene annotation in model species, and therapy of genetic disorders in humans. Sleeping Beauty (SB was the first transposon shown to be capable of gene transfer in vertebrate cells, and recent results confirm that SB supports a full spectrum of genetic engineering including transgenesis, insertional mutagenesis, and therapeutic somatic gene transfer both ex vivo and in vivo. The first clinical application of the SB system will help to validate both the safety and efficacy of this approach. In this review, we describe the major transposon systems currently available (with special emphasis on SB, discuss the various parameters and considerations pertinent to their experimental use, and highlight the state of the art in transposon technology in diverse genetic applications.

The expanding universe of transposon technologies for gene and cell engineering.

Science.gov (United States)

Ivics, Zoltán; Izsvák, Zsuzsanna

2010-12-07

Transposable elements can be viewed as natural DNA transfer vehicles that, similar to integrating viruses, are capable of efficient genomic insertion. The mobility of class II transposable elements (DNA transposons) can be controlled by conditionally providing the transposase component of the transposition reaction. Thus, a DNA of interest (be it a fluorescent marker, a small hairpin (sh)RNA expression cassette, a mutagenic gene trap or a therapeutic gene construct) cloned between the inverted repeat sequences of a transposon-based vector can be used for stable genomic insertion in a regulated and highly efficient manner. This methodological paradigm opened up a number of avenues for genome manipulations in vertebrates, including transgenesis for the generation of transgenic cells in tissue culture, the production of germline transgenic animals for basic and applied research, forward genetic screens for functional gene annotation in model species, and therapy of genetic disorders in humans. Sleeping Beauty (SB) was the first transposon shown to be capable of gene transfer in vertebrate cells, and recent results confirm that SB supports a full spectrum of genetic engineering including transgenesis, insertional mutagenesis, and therapeutic somatic gene transfer both ex vivo and in vivo. The first clinical application of the SB system will help to validate both the safety and efficacy of this approach. In this review, we describe the major transposon systems currently available (with special emphasis on SB), discuss the various parameters and considerations pertinent to their experimental use, and highlight the state of the art in transposon technology in diverse genetic applications.

Effects of FVIII immunity on hepatocyte and hematopoietic stem cell–directed gene therapy of murine hemophilia A

Science.gov (United States)

Lytle, Allison M; Brown, Harrison C; Paik, Na Yoon; Knight, Kristopher A; Wright, J Fraser; Spencer, H Trent; Doering, Christopher B

2016-01-01

Immune responses to coagulation factors VIII (FVIII) and IX (FIX) represent primary obstacles to hemophilia treatment. Previously, we showed that hematopoietic stem cell (HSC) retroviral gene therapy induces immune nonresponsiveness to FVIII in both naive and preimmunized murine hemophilia A settings. Liver-directed adeno-associated viral (AAV)-FIX vector gene transfer achieved similar results in preclinical hemophilia B models. However, as clinical immune responses to FVIII and FIX differ, we investigated the ability of liver-directed AAV-FVIII gene therapy to affect FVIII immunity in hemophilia A mice. Both FVIII naive and preimmunized mice were administered recombinant AAV8 encoding a liver-directed bioengineered FVIII expression cassette. Naive animals receiving high or mid-doses subsequently achieved near normal FVIII activity levels. However, challenge with adjuvant-free recombinant FVIII induced loss of FVIII activity and anti-FVIII antibodies in mid-dose, but not high-dose AAV or HSC lentiviral (LV) vector gene therapy cohorts. Furthermore, unlike what was shown previously for FIX gene transfer, AAV-FVIII administration to hemophilia A inhibitor mice conferred no effect on anti-FVIII antibody or inhibitory titers. These data suggest that functional differences exist in the immune modulation achieved to FVIII or FIX in hemophilia mice by gene therapy approaches incorporating liver-directed AAV vectors or HSC-directed LV. PMID:26909355

A market-driven commercialization strategy for gasification-based technologies

International Nuclear Information System (INIS)

Klara, J.M.; Tomer, B.J.; Stiegel, G.J.

1998-01-01

In the wake of deregulation of power generation in the US, market-based competition is driving electricity generators to low-cost risk system. In such an environment, gasification-based technologies will not be competitive with low capital cost, efficient, and reliable natural gas-fired facilities for baseload power generation in the foreseeable future. The lack of a near-term market application poses a serious threat to the progress of gasification technology. With a reduction in direct federal funding of large-scale demonstration plants as the trend to reduce the size of government continues, an alternate approach to commercialize gasification-based technologies has been developed at DOE/FETC. This new strategy employs gasification in near-term markets where, due to its ability to coproduce a wide variety of commodity and premium products to meet market requirements, it is an attractive alternative. By obtaining operating experience in near-term coproduction applications, gasification system modules can be refined and improved leading to commercial guarantees and acceptance of gasification technology as a cost-effective technology for baseload power generation when this market begins to open domestically, sometime after 2005

Current and future technological advances in transdermal gene delivery.

Science.gov (United States)

Chen, Xianfeng

2017-12-19

Transdermal gene delivery holds significant advantages as it is able to minimize the problems of systemic administration such as enzymatic degradation, systemic toxicity, and poor delivery to target tissues. This technology has the potential to transform the treatment and prevention of a range of diseases. However, the skin poses a great barrier for gene delivery because of the "bricks-and-mortar" structure of the stratum corneum and the tight junctions between keratinocytes in the epidermis. This review systematically summarizes the typical physical and chemical approaches to overcome these barriers and facilitate gene delivery via skin for applications in vaccination, wound healing, skin cancers and skin diseases. Next, the advantages and disadvantages of different approaches are discussed and the insights for future development are provided. Copyright © 2017 Elsevier B.V. All rights reserved.

Evaluation of Gene-Based Family-Based Methods to Detect Novel Genes Associated With Familial Late Onset Alzheimer Disease

Directory of Open Access Journals (Sweden)

Maria V. Fernández

2018-04-01

Full Text Available Gene-based tests to study the combined effect of rare variants on a particular phenotype have been widely developed for case-control studies, but their evolution and adaptation for family-based studies, especially studies of complex incomplete families, has been slower. In this study, we have performed a practical examination of all the latest gene-based methods available for family-based study designs using both simulated and real datasets. We examined the performance of several collapsing, variance-component, and transmission disequilibrium tests across eight different software packages and 22 models utilizing a cohort of 285 families (N = 1,235 with late-onset Alzheimer disease (LOAD. After a thorough examination of each of these tests, we propose a methodological approach to identify, with high confidence, genes associated with the tested phenotype and we provide recommendations to select the best software and model for family-based gene-based analyses. Additionally, in our dataset, we identified PTK2B, a GWAS candidate gene for sporadic AD, along with six novel genes (CHRD, CLCN2, HDLBP, CPAMD8, NLRP9, and MAS1L as candidate genes for familial LOAD.

Developing a System for Directed Gene Introduction into Mammary Gland Via Targeted Infection of Retrovirus Receptor Transgenics

National Research Council Canada - National Science Library

Bates, Paul

1998-01-01

... (the Rous sarcoma virus receptor). Directed infection, and thus directed gene expression of cells expressing the viral receptor should provide a rapid and efficient method to test the mammary tumorigenic potential of genes in an animal model...

LCGbase: A Comprehensive Database for Lineage-Based Co-regulated Genes.

Science.gov (United States)

Wang, Dapeng; Zhang, Yubin; Fan, Zhonghua; Liu, Guiming; Yu, Jun

2012-01-01

Animal genes of different lineages, such as vertebrates and arthropods, are well-organized and blended into dynamic chromosomal structures that represent a primary regulatory mechanism for body development and cellular differentiation. The majority of genes in a genome are actually clustered, which are evolutionarily stable to different extents and biologically meaningful when evaluated among genomes within and across lineages. Until now, many questions concerning gene organization, such as what is the minimal number of genes in a cluster and what is the driving force leading to gene co-regulation, remain to be addressed. Here, we provide a user-friendly database-LCGbase (a comprehensive database for lineage-based co-regulated genes)-hosting information on evolutionary dynamics of gene clustering and ordering within animal kingdoms in two different lineages: vertebrates and arthropods. The database is constructed on a web-based Linux-Apache-MySQL-PHP framework and effective interactive user-inquiry service. Compared to other gene annotation databases with similar purposes, our database has three comprehensible advantages. First, our database is inclusive, including all high-quality genome assemblies of vertebrates and representative arthropod species. Second, it is human-centric since we map all gene clusters from other genomes in an order of lineage-ranks (such as primates, mammals, warm-blooded, and reptiles) onto human genome and start the database from well-defined gene pairs (a minimal cluster where the two adjacent genes are oriented as co-directional, convergent, and divergent pairs) to large gene clusters. Furthermore, users can search for any adjacent genes and their detailed annotations. Third, the database provides flexible parameter definitions, such as the distance of transcription start sites between two adjacent genes, which is extendable to genes that flanking the cluster across species. We also provide useful tools for sequence alignment, gene

Oxytocin receptor gene polymorphisms are associated with human directed social behavior in dogs (Canis familiaris.

Directory of Open Access Journals (Sweden)

Anna Kis

Full Text Available The oxytocin system has a crucial role in human sociality; several results prove that polymorphisms of the oxytocin receptor gene are related to complex social behaviors in humans. Dogs' parallel evolution with humans and their adaptation to the human environment has made them a useful species to model human social interactions. Previous research indicates that dogs are eligible models for behavioral genetic research, as well. Based on these previous findings, our research investigated associations between human directed social behaviors and two newly described (-212AG, 19131AG and one known (rs8679684 single nucleotide polymorphisms (SNPs in the regulatory regions (5' and 3' UTR of the oxytocin receptor gene in German Shepherd (N = 104 and Border Collie (N = 103 dogs. Dogs' behavior traits have been estimated in a newly developed test series consisting of five episodes: Greeting by a stranger, Separation from the owner, Problem solving, Threatening approach, Hiding of the owner. Buccal samples were collected and DNA was isolated using standard protocols. SNPs in the 3' and 5' UTR regions were analyzed by polymerase chain reaction based techniques followed by subsequent electrophoresis analysis. The gene-behavior association analysis suggests that oxytocin receptor gene polymorphisms have an impact in both breeds on (i proximity seeking towards an unfamiliar person, as well as their owner, and on (ii how friendly dogs behave towards strangers, although the mediating molecular regulatory mechanisms are yet unknown. Based on these results, we conclude that similarly to humans, the social behavior of dogs towards humans is influenced by the oxytocin system.

Oxytocin receptor gene polymorphisms are associated with human directed social behavior in dogs (Canis familiaris).

Science.gov (United States)

Kis, Anna; Bence, Melinda; Lakatos, Gabriella; Pergel, Enikő; Turcsán, Borbála; Pluijmakers, Jolanda; Vas, Judit; Elek, Zsuzsanna; Brúder, Ildikó; Földi, Levente; Sasvári-Székely, Mária; Miklósi, Adám; Rónai, Zsolt; Kubinyi, Enikő

2014-01-01

The oxytocin system has a crucial role in human sociality; several results prove that polymorphisms of the oxytocin receptor gene are related to complex social behaviors in humans. Dogs' parallel evolution with humans and their adaptation to the human environment has made them a useful species to model human social interactions. Previous research indicates that dogs are eligible models for behavioral genetic research, as well. Based on these previous findings, our research investigated associations between human directed social behaviors and two newly described (-212AG, 19131AG) and one known (rs8679684) single nucleotide polymorphisms (SNPs) in the regulatory regions (5' and 3' UTR) of the oxytocin receptor gene in German Shepherd (N = 104) and Border Collie (N = 103) dogs. Dogs' behavior traits have been estimated in a newly developed test series consisting of five episodes: Greeting by a stranger, Separation from the owner, Problem solving, Threatening approach, Hiding of the owner. Buccal samples were collected and DNA was isolated using standard protocols. SNPs in the 3' and 5' UTR regions were analyzed by polymerase chain reaction based techniques followed by subsequent electrophoresis analysis. The gene-behavior association analysis suggests that oxytocin receptor gene polymorphisms have an impact in both breeds on (i) proximity seeking towards an unfamiliar person, as well as their owner, and on (ii) how friendly dogs behave towards strangers, although the mediating molecular regulatory mechanisms are yet unknown. Based on these results, we conclude that similarly to humans, the social behavior of dogs towards humans is influenced by the oxytocin system.

Generation of Directly Converted Human Osteoblasts That Are Free of Exogenous Gene and Xenogenic Protein.

Science.gov (United States)

Yamamoto, Kenta; Sato, Yoshiki; Honjo, Kenichi; Ichioka, Hiroaki; Oseko, Fumishige; Sowa, Yoshihiro; Yamamoto, Toshiro; Kanamura, Narisato; Kishida, Tsunao; Mazda, Osam

2016-11-01

Generation of osteoblasts from human somatic cells may be applicable in an effective transplantation therapy against bone diseases. Recently we established a procedure to directly convert human fibroblasts into osteoblasts by transducing some transcription factor genes via retroviral vectors. However, retroviral vector-mediated transduction may potentially cause tumor formation from the infected cells, thus a non-viral gene transfection method may be more preferable for preparation of osteoblasts to be used for transplantation therapy. Here, we constructed a plasmid vector encoding Oct4, Osterix, and L-Myc that were an appropriate combination of transcription factors for this purpose. Osteoblast-like phenotypes including high alkaline phosphatase (ALP) activity, bone matrix production and osteoblast-specific gene expression were induced in normal human fibroblasts that were transfected with the plasmid followed by culturing in osteogenic medium. The plasmid-driven directly converted osteoblasts (p-dOBs) were obtained even in the absence of a xenogenic protein. The plasmid vector sequence had fallen out of the p-dOBs. The cells formed deposition of calcified bodies in situ after transplantation into mice. These results strongly suggest that p-dOBs can be put into practical use for a novel cell-based therapy against bone diseases. J. Cell. Biochem. 117: 2538-2545, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Effects of FVIII immunity on hepatocyte and hematopoietic stem cell–directed gene therapy of murine hemophilia A

Directory of Open Access Journals (Sweden)

Allison M Lytle

2016-01-01

Full Text Available Immune responses to coagulation factors VIII (FVIII and IX (FIX represent primary obstacles to hemophilia treatment. Previously, we showed that hematopoietic stem cell (HSC retroviral gene therapy induces immune nonresponsiveness to FVIII in both naive and preimmunized murine hemophilia A settings. Liver-directed adeno-associated viral (AAV-FIX vector gene transfer achieved similar results in preclinical hemophilia B models. However, as clinical immune responses to FVIII and FIX differ, we investigated the ability of liver-directed AAV-FVIII gene therapy to affect FVIII immunity in hemophilia A mice. Both FVIII naive and preimmunized mice were administered recombinant AAV8 encoding a liver-directed bioengineered FVIII expression cassette. Naive animals receiving high or mid-doses subsequently achieved near normal FVIII activity levels. However, challenge with adjuvant-free recombinant FVIII induced loss of FVIII activity and anti-FVIII antibodies in mid-dose, but not high-dose AAV or HSC lentiviral (LV vector gene therapy cohorts. Furthermore, unlike what was shown previously for FIX gene transfer, AAV-FVIII administration to hemophilia A inhibitor mice conferred no effect on anti-FVIII antibody or inhibitory titers. These data suggest that functional differences exist in the immune modulation achieved to FVIII or FIX in hemophilia mice by gene therapy approaches incorporating liver-directed AAV vectors or HSC-directed LV.

A novel safety device with metal counter meshing gears discriminator directly driven by axial flux permanent magnet micromotors based on MEMS technology

Science.gov (United States)

Zhang, Weiping; Chen, Wenyuan; Zhao, Xiaolin; Li, Shengyong; Jiang, Yong

2005-08-01

In a novel safety device based on MEMS technology for high consequence systems, the discriminator consists of two groups of metal counter meshing gears and two pawl/ratchet wheel mechanisms. Each group of counter meshing gears is onepiece and driven directly by an axial flux permanent magnet micromotor respectively. The energy-coupling element is an optical shutter with two collimators and a coupler wheel. The safety device's probability is less than 1/106. It is fabricated by combination of an LiGA-like process and precision mechanical engineering. The device has simple structure, few dynamic problems, high strength and strong reliability.

Direction of Technology Development for Nuclear Power Plants at the O and M Phase

Energy Technology Data Exchange (ETDEWEB)

Jung, Insu; Park, Hwanpyo; Kim, Younghyun [Korea Institute of Construction Technology, Goyang (Korea, Republic of)

2014-05-15

Recently, Korea has attempted to advance overseas markets by securing competitive power in nuclear power technology. In order to develop and operate overall construction management systems with Korea's own brand equipped with sufficient applicability and competitive power in the market abroad and to ensure equal competitive power with other foreign advanced companies of nuclear power plants, Korea has launched a project called 'Data Centric Integration/Automation Technology for NP Project Management System' since July 2011. This project is divided into two phases: the first phase from 2012 to 2016 realizes EPCS stage, and the second phase from 2017 to 2020 extends to O and M stage. Appropriate technology development planning must be established if 'Data Centric Integration/Automation Technology for NP Project Management System' conducted at the first phase would extend to O and M stage at the second phase. Therefore, this study aimed at drawing out the direction of technology development based on present analysis of process at the operational phase of nuclear power plants in Korea conducted as previous study. This study analyzed current operation and maintenance systems first, analyzing the results of differences between the operation process of nuclear plants in Korea which was suggested at the previous study and the process of the Korea Hydro and Nuclear Power Co., Ltd. (hereafter referred to as 'KHNP') and drawing out the direction of technology development for nuclear power plants at the operational phase from the viewpoint of life cycle.

Direction of Technology Development for Nuclear Power Plants at the O and M Phase

International Nuclear Information System (INIS)

Jung, Insu; Park, Hwanpyo; Kim, Younghyun

2014-01-01

Recently, Korea has attempted to advance overseas markets by securing competitive power in nuclear power technology. In order to develop and operate overall construction management systems with Korea's own brand equipped with sufficient applicability and competitive power in the market abroad and to ensure equal competitive power with other foreign advanced companies of nuclear power plants, Korea has launched a project called 'Data Centric Integration/Automation Technology for NP Project Management System' since July 2011. This project is divided into two phases: the first phase from 2012 to 2016 realizes EPCS stage, and the second phase from 2017 to 2020 extends to O and M stage. Appropriate technology development planning must be established if 'Data Centric Integration/Automation Technology for NP Project Management System' conducted at the first phase would extend to O and M stage at the second phase. Therefore, this study aimed at drawing out the direction of technology development based on present analysis of process at the operational phase of nuclear power plants in Korea conducted as previous study. This study analyzed current operation and maintenance systems first, analyzing the results of differences between the operation process of nuclear plants in Korea which was suggested at the previous study and the process of the Korea Hydro and Nuclear Power Co., Ltd. (hereafter referred to as 'KHNP') and drawing out the direction of technology development for nuclear power plants at the operational phase from the viewpoint of life cycle

A Gene-Based Prognostic for Hepatocellular Carcinoma Patient Response to Adjuvant Transcatheter Arterial Chemoembolization | NCI Technology Transfer Center | TTC

Science.gov (United States)

The gold standard of care for hepatocellular carcinoma patients with intermediate- to locally advanced tumors is transcatheter arterial chemoembolization (TACE), a procedure whereby the tumor is targeted both with local chemotherapy and restriction of local blood supply. NCI scientists have identified a 14-gene signature predictive of response to TACE, and NCI seeks licensees or co-development partners to develop the technology toward commercialization.

KBERG: KnowledgeBase for Estrogen Responsive Genes

DEFF Research Database (Denmark)

Tang, Suisheng; Zhang, Zhuo; Tan, Sin Lam

2007-01-01

Estrogen has a profound impact on human physiology affecting transcription of numerous genes. To decipher functional characteristics of estrogen responsive genes, we developed KnowledgeBase for Estrogen Responsive Genes (KBERG). Genes in KBERG were derived from Estrogen Responsive Gene Database...... (ERGDB) and were analyzed from multiple aspects. We explored the possible transcription regulation mechanism by capturing highly conserved promoter motifs across orthologous genes, using promoter regions that cover the range of [-1200, +500] relative to the transcription start sites. The motif detection...... is based on ab initio discovery of common cis-elements from the orthologous gene cluster from human, mouse and rat, thus reflecting a degree of promoter sequence preservation during evolution. The identified motifs are linked to transcription factor binding sites based on the TRANSFAC database. In addition...

Characteristics of thin-film transistors based on silicon nitride passivation by excimer laser direct patterning

International Nuclear Information System (INIS)

Chen, Chao-Nan; Huang, Jung-Jie

2013-01-01

This study explored the removal of silicon nitride using KrF laser ablation technology with a high threshold fluence of 990 mJ/cm 2 . This technology was used for contact hole patterning to fabricate SiN x -passivation-based amorphous-silicon thin films in a transistor device. Compared to the photolithography process, laser direct patterning using KrF laser ablation technology can reduce the number of process steps by at least three. Experimental results showed that the mobility and threshold voltages of thin film transistors patterned using the laser process were 0.16 cm 2 /V-sec and 0.2 V, respectively. The device performance and the test results of gate voltage stress reliability demonstrated that laser direct patterning is a promising alternative to photolithography in the panel manufacturing of thin-film transistors for liquid crystal displays. - Highlights: ► KrF laser ablation technology is used to remove silicon nitride. ► A simple method for direct patterning contact-hole in thin-film-transistor device. ► Laser technology reduced processing by at least three steps

Recent Progress on PZT Based Piezoelectric Energy Harvesting Technologies

Directory of Open Access Journals (Sweden)

Min-Gyu Kang

2016-02-01

Full Text Available Energy harvesting is the most effective way to respond to the energy shortage and to produce sustainable power sources from the surrounding environment. The energy harvesting technology enables scavenging electrical energy from wasted energy sources, which always exist everywhere, such as in heat, fluids, vibrations, etc. In particular, piezoelectric energy harvesting, which uses a direct energy conversion from vibrations and mechanical deformation to the electrical energy, is a promising technique to supply power sources in unattended electronic devices, wireless sensor nodes, micro-electronic devices, etc., since it has higher energy conversion efficiency and a simple structure. Up to now, various technologies, such as advanced materials, micro- and macro-mechanics, and electric circuit design, have been investigated and emerged to improve performance and conversion efficiency of the piezoelectric energy harvesters. In this paper, we focus on recent progress of piezoelectric energy harvesting technologies based on PbZrxTi1-xO3 (PZT materials, which have the most outstanding piezoelectric properties. The advanced piezoelectric energy harvesting technologies included materials, fabrications, unique designs, and properties are introduced to understand current technical levels and suggest the future directions of piezoelectric energy harvesting.

FDA Regulation of Clinical Applications of CRISPR-CAS Gene-Editing Technology.

Science.gov (United States)

Grant, Evita V

Scientists have repurposed an adaptive immune system of single cell organisms to create a new type of gene-editing tool: CRISPR (clustered regularly interspaced short palindromic repeats)-Cas technology. Scientists in China have reported its use in the genome modification of non-viable human embryos. This has ignited a spirited debate about the moral, ethical, scientific, and social implications of human germline genome engineering. There have also been calls for regulations; however, FDA has yet to formally announce its oversight of clinical applications of CRISPR-Cas systems. This paper reviews FDA regulation of previously controversial biotechnology breakthroughs, recombinant DNA and human cloning. It then shows that FDA is well positioned to regulate CRISPR-Cas clinical applications, due to its legislative mandates, its existing regulatory frameworks for gene therapies and assisted reproductive technologies, and other considerations.

Amygdala-enriched genes identified by microarray technology are restricted to specific amygdaloid subnuclei

OpenAIRE

Zirlinger, M.; Kreiman, Gabriel; Anderson, D. J.

2001-01-01

Microarray technology represents a potentially powerful method for identifying cell type- and regionally restricted genes expressed in the brain. Here we have combined a microarray analysis of differential gene expression among five selected brain regions, including the amygdala, cerebellum, hippocampus, olfactory bulb, and periaqueductal gray, with in situ hybridization. On average, 0.3% of the 34,000 genes interrogated were highly enriched in each of the five regions...

Direct fabrication through electron beam melting technology of custom cranial implants designed in a PHANToM-based haptic environment

International Nuclear Information System (INIS)

Mazzoli, Alida; Germani, Michele; Raffaeli, Roberto

2009-01-01

Repairing critical human skull injuries requires the production and use of customized cranial implants and involves the integration of computer aided design and manufacturing (CAD and CAM). The main causes for large cranial defects are trauma, cranial tumors, infected craniotomy bone flaps and external neurosurgical decompression. The success of reconstructive cranial surgery depends upon: the preoperative evaluation of the defect, the design and manufacturing of the implant, and the skill of the operating surgeon. Cranial implant design is usually carried out manually using CAD although this process is very time-consuming and the quality of the end product depends wholly upon the skill of the operator. This paper presents an alternative automated method for the design of custom-made cranial plates in a PHANToM ® -based haptic environment, and their direct fabrication in biocompatible metal using electron beam melting (EBM) technology.

A New Two-Step Approach for Hands-On Teaching of Gene Technology: Effects on Students' Activities during Experimentation in an Outreach Gene Technology Lab

Science.gov (United States)

Scharfenberg, Franz-Josef; Bogner, Franz X.

2011-01-01

Emphasis on improving higher level biology education continues. A new two-step approach to the experimental phases within an outreach gene technology lab, derived from cognitive load theory, is presented. We compared our approach using a quasi-experimental design with the conventional one-step mode. The difference consisted of additional focused…

Ontology-based literature mining of E. coli vaccine-associated gene interaction networks.

Science.gov (United States)

Hur, Junguk; Özgür, Arzucan; He, Yongqun

2017-03-14

Pathogenic Escherichia coli infections cause various diseases in humans and many animal species. However, with extensive E. coli vaccine research, we are still unable to fully protect ourselves against E. coli infections. To more rational development of effective and safe E. coli vaccine, it is important to better understand E. coli vaccine-associated gene interaction networks. In this study, we first extended the Vaccine Ontology (VO) to semantically represent various E. coli vaccines and genes used in the vaccine development. We also normalized E. coli gene names compiled from the annotations of various E. coli strains using a pan-genome-based annotation strategy. The Interaction Network Ontology (INO) includes a hierarchy of various interaction-related keywords useful for literature mining. Using VO, INO, and normalized E. coli gene names, we applied an ontology-based SciMiner literature mining strategy to mine all PubMed abstracts and retrieve E. coli vaccine-associated E. coli gene interactions. Four centrality metrics (i.e., degree, eigenvector, closeness, and betweenness) were calculated for identifying highly ranked genes and interaction types. Using vaccine-related PubMed abstracts, our study identified 11,350 sentences that contain 88 unique INO interactions types and 1,781 unique E. coli genes. Each sentence contained at least one interaction type and two unique E. coli genes. An E. coli gene interaction network of genes and INO interaction types was created. From this big network, a sub-network consisting of 5 E. coli vaccine genes, including carA, carB, fimH, fepA, and vat, and 62 other E. coli genes, and 25 INO interaction types was identified. While many interaction types represent direct interactions between two indicated genes, our study has also shown that many of these retrieved interaction types are indirect in that the two genes participated in the specified interaction process in a required but indirect process. Our centrality analysis of

A single gene directs synthesis of a precursor protein with beta- and alpha-amylase activities in Bacillus polymyxa.

OpenAIRE

Uozumi, N; Sakurai, K; Sasaki, T; Takekawa, S; Yamagata, H; Tsukagoshi, N; Udaka, S

1989-01-01

The Bacillus polymyxa amylase gene comprises 3,588 nucleotides. The mature amylase comprises 1,161 amino acids with a molecular weight of 127,314. The gene appeared to be divided into two portions by the direct-repeat sequence located at almost the middle of the gene. The 5' region upstream of the direct-repeat sequence was shown to be responsible for the synthesis of beta-amylase. The 3' region downstream of the direct-repeat sequence contained four sequences homologous with those in other a...

A multiplex branched DNA assay for parallel quantitative gene expression profiling.

Science.gov (United States)

Flagella, Michael; Bui, Son; Zheng, Zhi; Nguyen, Cung Tuong; Zhang, Aiguo; Pastor, Larry; Ma, Yunqing; Yang, Wen; Crawford, Kimberly L; McMaster, Gary K; Witney, Frank; Luo, Yuling

2006-05-01

We describe a novel method to quantitatively measure messenger RNA (mRNA) expression of multiple genes directly from crude cell lysates and tissue homogenates without the need for RNA purification or target amplification. The multiplex branched DNA (bDNA) assay adapts the bDNA technology to the Luminex fluorescent bead-based platform through the use of cooperative hybridization, which ensures an exceptionally high degree of assay specificity. Using in vitro transcribed RNA as reference standards, we demonstrated that the assay is highly specific, with cross-reactivity less than 0.2%. We also determined that the assay detection sensitivity is 25,000 RNA transcripts with intra- and interplate coefficients of variance of less than 10% and less than 15%, respectively. Using three 10-gene panels designed to measure proinflammatory and apoptosis responses, we demonstrated sensitive and specific multiplex gene expression profiling directly from cell lysates. The gene expression change data demonstrate a high correlation coefficient (R(2)=0.94) compared with measurements obtained using the single-plex bDNA assay. Thus, the multiplex bDNA assay provides a powerful means to quantify the gene expression profile of a defined set of target genes in large sample populations.

NanoString, a novel digital color-coded barcode technology: current and future applications in molecular diagnostics.

Science.gov (United States)

Tsang, Hin-Fung; Xue, Vivian Weiwen; Koh, Su-Pin; Chiu, Ya-Ming; Ng, Lawrence Po-Wah; Wong, Sze-Chuen Cesar

2017-01-01

Formalin-fixed, paraffin-embedded (FFPE) tissue sample is a gold mine of resources for molecular diagnosis and retrospective clinical studies. Although molecular technologies have expanded the range of mutations identified in FFPE samples, the applications of existing technologies are limited by the low nucleic acids yield and poor extraction quality. As a result, the routine clinical applications of molecular diagnosis using FFPE samples has been associated with many practical challenges. NanoString technologies utilize a novel digital color-coded barcode technology based on direct multiplexed measurement of gene expression and offer high levels of precision and sensitivity. Each color-coded barcode is attached to a single target-specific probe corresponding to a single gene which can be individually counted without amplification. Therefore, NanoString is especially useful for measuring gene expression in degraded clinical specimens. Areas covered: This article describes the applications of NanoString technologies in molecular diagnostics and challenges associated with its applications and the future development. Expert commentary: Although NanoString technology is still in the early stages of clinical use, it is expected that NanoString-based cancer expression panels would play more important roles in the future in classifying cancer patients and in predicting the response to therapy for better personal therapeutic care.

State of technology of direct contact heat exchanging

Energy Technology Data Exchange (ETDEWEB)

Vallario, R.W.; DeBellis, D.E.

1984-05-01

Specific objectives of this study were to assess the state of technology development and to identify and evaluate the constraints to wider use of direct contact heat exchanger (DCHE) technology in the U.S. The scope of this study is relatively broad; it includes many types of generic systems and end-use applications, both current and future. Domestic and foreign experience with DCHE technology are compared, although the primary focus is on domestic experience. Twenty-two distinct applications of DCHE technology were identified in this study and are examined in this report. The general format is to describe each system, explore its potential applications, discuss current and past research activities and identify major implementation barriers. Finally, as a result of discussions with principal users of DCHE systems and with other knowledgeable sources, generic and specific R and D needs to overcome specific implementation barriers have been identified. The following list of DCHE systems/concepts has been classified into four major end-uses; there is also a category for specialized (other) applications.

The ethical introduction of genome-based information and technologies into public health.

Science.gov (United States)

Howard, H C; Swinnen, E; Douw, K; Vondeling, H; Cassiman, J-J; Cambon-Thomsen, A; Borry, P

2013-01-01

With the human genome project running from 1989 until its completion in 2003, and the incredible advances in sequencing technology and in bioinformatics during the last decade, there has been a shift towards an increase focus on studying common complex disorders which develop due to the interplay of many different genes as well as environmental factors. Although some susceptibility genes have been identified in some populations for disorders such as cancer, diabetes and cardiovascular diseases, the integration of this information into the health care system has proven to be much more problematic than for single gene disorders. Furthermore, with the 1000$ genome supposedly just around the corner, and whole genome sequencing gradually being integrated into research protocols as well as in the clinical context, there is a strong push for the uptake of additional genomic testing. Indeed, the advent of public health genomics, wherein genomics would be integrated in all aspects of health care and public health, should be taken seriously. Although laudable, these advances also bring with them a slew of ethical and social issues that challenge the normative frameworks used in clinical genetics until now. With this in mind, we highlight herein 5 principles that are used as a primer to discuss the ethical introduction of genome-based information and genome-based technologies into public health. Copyright © 2013 S. Karger AG, Basel.

Enhanced capillary electrophoretic screening of Alzheimer based on direct apolipoprotein E genotyping and one-step multiplex PCR.

Science.gov (United States)

Woo, Nain; Kim, Su-Kang; Sun, Yucheng; Kang, Seong Ho

2018-01-01

Human apolipoprotein E (ApoE) is associated with high cholesterol levels, coronary artery disease, and especially Alzheimer's disease. In this study, we developed an ApoE genotyping and one-step multiplex polymerase chain reaction (PCR) based-capillary electrophoresis (CE) method for the enhanced diagnosis of Alzheimer's. The primer mixture of ApoE genes enabled the performance of direct one-step multiplex PCR from whole blood without DNA purification. The combination of direct ApoE genotyping and one-step multiplex PCR minimized the risk of DNA loss or contamination due to the process of DNA purification. All amplified PCR products with different DNA lengths (112-, 253-, 308-, 444-, and 514-bp DNA) of the ApoE genes were analyzed within 2min by an extended voltage programming (VP)-based CE under the optimal conditions. The extended VP-based CE method was at least 120-180 times faster than conventional slab gel electrophoresis methods In particular, all amplified DNA fragments were detected in less than 10 PCR cycles using a laser-induced fluorescence detector. The detection limits of the ApoE genes were 6.4-62.0pM, which were approximately 100-100,000 times more sensitive than previous Alzheimer's diagnosis methods In addition, the combined one-step multiplex PCR and extended VP-based CE method was also successfully applied to the analysis of ApoE genotypes in Alzheimer's patients and normal samples and confirmed the distribution probability of allele frequencies. This combination of direct one-step multiplex PCR and an extended VP-based CE method should increase the diagnostic reliability of Alzheimer's with high sensitivity and short analysis time even with direct use of whole blood. Copyright © 2017 Elsevier B.V. All rights reserved.

Multiclass classification for skin cancer profiling based on the integration of heterogeneous gene expression series.

Science.gov (United States)

Gálvez, Juan Manuel; Castillo, Daniel; Herrera, Luis Javier; San Román, Belén; Valenzuela, Olga; Ortuño, Francisco Manuel; Rojas, Ignacio

2018-01-01

Most of the research studies developed applying microarray technology to the characterization of different pathological states of any disease may fail in reaching statistically significant results. This is largely due to the small repertoire of analysed samples, and to the limitation in the number of states or pathologies usually addressed. Moreover, the influence of potential deviations on the gene expression quantification is usually disregarded. In spite of the continuous changes in omic sciences, reflected for instance in the emergence of new Next-Generation Sequencing-related technologies, the existing availability of a vast amount of gene expression microarray datasets should be properly exploited. Therefore, this work proposes a novel methodological approach involving the integration of several heterogeneous skin cancer series, and a later multiclass classifier design. This approach is thus a way to provide the clinicians with an intelligent diagnosis support tool based on the use of a robust set of selected biomarkers, which simultaneously distinguishes among different cancer-related skin states. To achieve this, a multi-platform combination of microarray datasets from Affymetrix and Illumina manufacturers was carried out. This integration is expected to strengthen the statistical robustness of the study as well as the finding of highly-reliable skin cancer biomarkers. Specifically, the designed operation pipeline has allowed the identification of a small subset of 17 differentially expressed genes (DEGs) from which to distinguish among 7 involved skin states. These genes were obtained from the assessment of a number of potential batch effects on the gene expression data. The biological interpretation of these genes was inspected in the specific literature to understand their underlying information in relation to skin cancer. Finally, in order to assess their possible effectiveness in cancer diagnosis, a cross-validation Support Vector Machines (SVM)-based

Technological Change in a Small European Country: A Patent- Based Analysis for Greece

OpenAIRE

Maria Markatou

2012-01-01

The description of the development of the Greek technological change is the main aim of this paper. The analysis is based on the examination and elaboration of patent records and relies on the study of their technological content and their economic direction. Results show that technological change focuses on producing new technologies for the ‘agricultural sector’, ‘food’, ‘pharmaceuticals’, ‘metal shaping-separation’, ‘rubber-plastic products’, ‘building-housing’, ‘instruments’ and ‘electric...

Genome-wide specificity of DNA binding, gene regulation, and chromatin remodeling by TALE- and CRISPR/Cas9-based transcriptional activators.

Science.gov (United States)

Polstein, Lauren R; Perez-Pinera, Pablo; Kocak, D Dewran; Vockley, Christopher M; Bledsoe, Peggy; Song, Lingyun; Safi, Alexias; Crawford, Gregory E; Reddy, Timothy E; Gersbach, Charles A

2015-08-01

Genome engineering technologies based on the CRISPR/Cas9 and TALE systems are enabling new approaches in science and biotechnology. However, the specificity of these tools in complex genomes and the role of chromatin structure in determining DNA binding are not well understood. We analyzed the genome-wide effects of TALE- and CRISPR-based transcriptional activators in human cells using ChIP-seq to assess DNA-binding specificity and RNA-seq to measure the specificity of perturbing the transcriptome. Additionally, DNase-seq was used to assess genome-wide chromatin remodeling that occurs as a result of their action. Our results show that these transcription factors are highly specific in both DNA binding and gene regulation and are able to open targeted regions of closed chromatin independent of gene activation. Collectively, these results underscore the potential for these technologies to make precise changes to gene expression for gene and cell therapies or fundamental studies of gene function. © 2015 Polstein et al.; Published by Cold Spring Harbor Laboratory Press.

Experience with novel technologies for direct measurement of atmospheric NO2

Science.gov (United States)

Hueglin, Christoph; Hundt, Morten; Mueller, Michael; Schwarzenbach, Beat; Tuzson, Bela; Emmenegger, Lukas

2017-04-01

Nitrogen dioxide (NO2) is an air pollutant that has a large impact on human health and ecosystems, and it plays a key role in the formation of ozone and secondary particulate matter. Consequently, legal limit values for NO2 are set in the EU and elsewhere, and atmospheric observation networks typically include NO2 in their measurement programmes. Atmospheric NO2 is principally measured by chemiluminescence detection, an indirect measurement technique that requires conversion of NO2 into nitrogen monoxide (NO) and finally calculation of NO2 from the difference between total nitrogen oxides (NOx) and NO. Consequently, NO2 measurements with the chemiluminescence method have a relatively high measurement uncertainty and can be biased depending on the selectivity of the applied NO2 conversion method. In the past years, technologies for direct and selective measurement of NO2 have become available, e.g. cavity attenuated phase shift spectroscopy (CAPS), cavity enhanced laser absorption spectroscopy and quantum cascade laser absorption spectrometry (QCLAS). These technologies offer clear advantages over the indirect chemiluminescence method. We tested the above mentioned direct measurement techniques for NO2 over extended time periods at atmospheric measurement stations and report on our experience including comparisons with co-located chemiluminescence instruments equipped with molybdenum as well as photolytic NO2 converters. A still open issue related to the direct measurement of NO2 is instrument calibration. Accurate and traceable reference standards and NO2 calibration gases are needed. We present results from the application of different calibration strategies based on the use of static NO2 calibration gases as well as dynamic NO2 calibration gases produced by permeation and by gas-phase titration (GPT).

Rapid approach for cloning bacterial single-genes directly from soils ...

African Journals Online (AJOL)

Obtaining functional genes of bacteria from environmental samples usually depends on library-based approach which is not favored as its large amount of work with small possibility of positive clones. A kind of bacterial single-gene encoding glutamine synthetase (GS) was selected as example to detect the efficiency of ...

Gene-based vaccine development for improving animal production in developing countries. Possibilities and constraints

International Nuclear Information System (INIS)

Egerton, J.R.

2005-01-01

For vaccine production, recombinant antigens must be protective. Identifying protective antigens or candidate antigens is an essential precursor to vaccine development. Even when a protective antigen has been identified, cloning of its gene does not lead directly to vaccine development. The fimbrial protein of Dichelobacter nodosus, the agent of foot-rot in ruminants, was known to be protective. Recombinant vaccines against this infection are ineffective if expressed protein subunits are not assembled as mature fimbriae. Antigenic competition between different, but closely related, recombinant antigens limited the use of multivalent vaccines based on this technology. Recombinant antigens may need adjuvants to enhance response. DNA vaccines, potentiated with genes for different cytokines, may replace the need for aggressive adjuvants, and especially where cellular immunity is essential for protection. The expression of antigens from animal pathogens in plants and the demonstration of some immunity to a disease like rinderpest after ingestion of these, suggests an alternative approach to vaccination by injection. Research on disease pathogenesis and the identification of candidate antigens is specific to the disease agent. The definition of expression systems and the formulation of a vaccine for each disease must be followed by research to establish safety and efficacy. Where vaccines are based on unique gene sequences, the intellectual property is likely to be protected by patent. Organizations, licensed to produce recombinant vaccines, expect to recover their costs and to make a profit. The consequence is that genetically-derived vaccines are expensive. The capacity of vaccines to help animal owners of poorer countries depends not only on quality and cost but also on the veterinary infrastructure where they are used. Ensuring the existence of an effective animal health infrastructure in developing countries is as great a challenge for the developed world as

Characterization of Zur-dependent genes and direct Zur targets in Yersinia pestis

Directory of Open Access Journals (Sweden)

Wang Xiaoyi

2009-06-01

Full Text Available Abstract Background The zinc uptake regulator Zur is a Zn2+-sensing metalloregulatory protein involved in the maintenance of bacterial zinc homeostasis. Up to now, regulation of zinc homeostasis by Zur is poorly understood in Y. pestis. Results We constructed a zur null mutant of Y. pestis biovar microtus strain 201. Microarray expression analysis disclosed a set of 154 Zur-dependent genes of Y. pestis upon exposure to zinc rich condition. Real-time reverse transcription (RT-PCR was subsequently used to validate the microarray data. Based on the 154 Zur-dependent genes, predicted regulatory Zur motifs were used to screen for potential direct Zur targets including three putative operons znuA, znuCB and ykgM-RpmJ2. The LacZ reporter fusion analysis verified that Zur greatly repressed the promoter activity of the above three operons. The subsequent electrophoretic mobility shift assay (EMSA demonstrated that a purified Zur protein was able to bind to the promoter regions of the above three operons. The DNase I footprinting was used to identify the Zur binding sites for the above three operons, verifying the Zur box sequence as predicted previously in γ-Proteobacteria. The primer extension assay was further used to determine the transcription start sites for the above three operons and to localize the -10 and -35 elements. Zur binding sites overlapped the -10 sequence of its target promoters, which was consistent with the previous observation that Zur binding would block the entry of the RNA polymerase to repress the transcription of its target genes. Conclusion Zur as a repressor directly controls the transcription of znuA, znuCB and ykgM-RpmJ2 in Y. pestis by employing a conserved mechanism of Zur-promoter DNA association as observed in γ-Proteobacteria. Zur contributes to zinc homeostasis in Y. pestis likely through transcriptional repression of the high-affinity zinc uptake system ZnuACB and two alternative ribosomal proteins YkgM and RpmJ2.

Directional gene expression and antisense transcripts in sexual and asexual stages of Plasmodium falciparum

Directory of Open Access Journals (Sweden)

López-Barragán María J

2011-11-01

Full Text Available Abstract Background It has been shown that nearly a quarter of the initial predicted gene models in the Plasmodium falciparum genome contain errors. Although there have been efforts to obtain complete cDNA sequences to correct the errors, the coverage of cDNA sequences on the predicted genes is still incomplete, and many gene models for those expressed in sexual or mosquito stages have not been validated. Antisense transcripts have widely been reported in P. falciparum; however, the extent and pattern of antisense transcripts in different developmental stages remain largely unknown. Results We have sequenced seven bidirectional libraries from ring, early and late trophozoite, schizont, gametocyte II, gametocyte V, and ookinete, and four strand-specific libraries from late trophozoite, schizont, gametocyte II, and gametocyte V of the 3D7 parasites. Alignment of the cDNA sequences to the 3D7 reference genome revealed stage-specific antisense transcripts and novel intron-exon splicing junctions. Sequencing of strand-specific cDNA libraries suggested that more genes are expressed in one direction in gametocyte than in schizont. Alternatively spliced genes, antisense transcripts, and stage-specific expressed genes were also characterized. Conclusions It is necessary to continue to sequence cDNA from different developmental stages, particularly those of non-erythrocytic stages. The presence of antisense transcripts in some gametocyte and ookinete genes suggests that these antisense RNA may play an important role in gene expression regulation and parasite development. Future gene expression studies should make use of directional cDNA libraries. Antisense transcripts may partly explain the observed discrepancy between levels of mRNA and protein expression.

Direction of reprocessing technology development based on 30 years operation of Tokai reprocessing plant

International Nuclear Information System (INIS)

Nomura, S; Tanaka, T.; Ohshima, H.

2006-01-01

Full text: Full text: Recent global interest focuses the possibility of recycling of spent fuel with advanced fast reactor fuel cycle system. Goal of closed fuel cycle is to achieve the maximum use of uranium resources and minimum disposal of waste by multi recycle of TRU as a competitive nuclear energy system. The future reprocessing and fuel fabrication system should be synchronized completely with the advanced reactor system and waste treatment and disposal back-end system to complete closed fuel cycle. To realize such system, current reprocessing system should be changed to handle Pu-U-Minor Actinide with more reductions in the cost and less waste volume, as well as an inherent proliferation resistance. For the successful industrialization of advanced reprocessing technology, it is necessary to combine three key elements of R and D efforts, engineering base demonstration and experiences of plant operation. Tokai Reprocessing Facilities licensed a maximum capacity of 0.7tHM/day began a hot operation in 1977 and reprocessed l,100tHM U02 spent fuel and 20tHM ATR-MOX with a continuous technological improvements under IAEA full scope safeguards. With 30 years experience, candidate of key technologies proposed for realizing the next advanced reprocessing are as follows: 1) Simplified co-extraction process of Pu-Np-U by using multistage centrifugal extractors in stead of pulsed columns; 2) Corrosion free components in acid condition by using corrosion resistant refractory alloys and ceramics; 3) Co-conversion technology to MA containing MOX powder by micro-wave heating method for a short process for MA containing MOX pellets fabrication; 4) Advanced verification of high level radioactive liquid waste combining separation technology of TRU and LLFP elements; 5) Advanced chemical analysis and monitoring system for TRU elements in a plant. These advanced reprocessing technologies will be applied mainly to reprocess the LWR spent fuel accumulated past and future

Technology-based interventions in social work practice: a systematic review of mental health interventions.

Science.gov (United States)

Ramsey, Alex T; Montgomery, Katherine

2014-10-01

Despite concerns around the use of technology-based interventions, they are increasingly being employed by social workers as a direct practice methodology to address the mental health needs of vulnerable clients. Researchers have highlighted the importance of using innovative technologies within social work practice, yet little has been done to summarize the evidence and collectively assess findings. In this systematic review, we describe accounts of technology-based mental health interventions delivered by social workers over the past 10 years. Results highlight the impacts of these tools and summarize advantages and disadvantages to utilizing technologies as a method for delivering or facilitating interventions.

Interval-value Based Particle Swarm Optimization algorithm for cancer-type specific gene selection and sample classification

Directory of Open Access Journals (Sweden)

D. Ramyachitra

2015-09-01

Full Text Available Microarray technology allows simultaneous measurement of the expression levels of thousands of genes within a biological tissue sample. The fundamental power of microarrays lies within the ability to conduct parallel surveys of gene expression using microarray data. The classification of tissue samples based on gene expression data is an important problem in medical diagnosis of diseases such as cancer. In gene expression data, the number of genes is usually very high compared to the number of data samples. Thus the difficulty that lies with data are of high dimensionality and the sample size is small. This research work addresses the problem by classifying resultant dataset using the existing algorithms such as Support Vector Machine (SVM, K-nearest neighbor (KNN, Interval Valued Classification (IVC and the improvised Interval Value based Particle Swarm Optimization (IVPSO algorithm. Thus the results show that the IVPSO algorithm outperformed compared with other algorithms under several performance evaluation functions.

Interval-value Based Particle Swarm Optimization algorithm for cancer-type specific gene selection and sample classification.

Science.gov (United States)

Ramyachitra, D; Sofia, M; Manikandan, P

2015-09-01

Microarray technology allows simultaneous measurement of the expression levels of thousands of genes within a biological tissue sample. The fundamental power of microarrays lies within the ability to conduct parallel surveys of gene expression using microarray data. The classification of tissue samples based on gene expression data is an important problem in medical diagnosis of diseases such as cancer. In gene expression data, the number of genes is usually very high compared to the number of data samples. Thus the difficulty that lies with data are of high dimensionality and the sample size is small. This research work addresses the problem by classifying resultant dataset using the existing algorithms such as Support Vector Machine (SVM), K-nearest neighbor (KNN), Interval Valued Classification (IVC) and the improvised Interval Value based Particle Swarm Optimization (IVPSO) algorithm. Thus the results show that the IVPSO algorithm outperformed compared with other algorithms under several performance evaluation functions.

Beating Bias in the Directed Evolution of Proteins: Combining High-Fidelity on-Chip Solid-Phase Gene Synthesis with Efficient Gene Assembly for Combinatorial Library Construction.

Science.gov (United States)

Li, Aitao; Acevedo-Rocha, Carlos G; Sun, Zhoutong; Cox, Tony; Xu, Jia Lucy; Reetz, Manfred T

2018-02-02

Saturation mutagenesis (SM) constitutes a widely used technique in the directed evolution of selective enzymes as catalysts in organic chemistry and in the manipulation of metabolic paths and genomes, but the quality of the libraries is far from optimal due to the inherent amino acid bias. Herein, it is shown how this fundamental problem can be solved by applying high-fidelity solid-phase chemical gene synthesis on silicon chips followed by efficient gene assembly. Limonene epoxide hydrolase was chosen as the catalyst in the model desymmetrization of cyclohexene oxide with the stereoselective formation of (R,R)- and (S,S)-cyclohexane-1,2-diol. A traditional combinatorial PCR-based SM library, produced by simultaneous randomization at several residues by using a reduced amino acid alphabet, and the respective synthetic library were constructed and compared. Statistical analysis at the DNA level with massive sequencing demonstrates that, in the synthetic approach, 97 % of the theoretically possible DNA mutants are formed, whereas the traditional SM library contained only about 50 %. Screening at the protein level also showed the superiority of the synthetic library; many highly (R,R)- and (S,S)-selective variants being discovered are not found in the traditional SM library. With the prices of synthetic genes decreasing, this approach may point the way to future directed evolution. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Adenoviral delivery of pan-caspase inhibitor p35 enhances bystander killing by P450 gene-directed enzyme prodrug therapy using cyclophosphamide+

International Nuclear Information System (INIS)

Doloff, Joshua C; Su, Ting; Waxman, David J

2010-01-01

Cytochrome P450-based suicide gene therapy for cancer using prodrugs such as cyclophosphamide (CPA) increases anti-tumor activity, both directly and via a bystander killing mechanism. Bystander cell killing is essential for the clinical success of this treatment strategy, given the difficulty of achieving 100% efficient gene delivery in vivo using current technologies. Previous studies have shown that the pan-caspase inhibitor p35 significantly increases CPA-induced bystander killing by tumor cells that stably express P450 enzyme CYP2B6 (Schwartz et al, (2002) Cancer Res. 62: 6928-37). To further develop this approach, we constructed and characterized a replication-defective adenovirus, Adeno-2B6/p35, which expresses p35 in combination with CYP2B6 and its electron transfer partner, P450 reductase. The expression of p35 in Adeno-2B6/p35-infected tumor cells inhibited caspase activation, delaying the death of the CYP2B6 'factory' cells that produce active CPA metabolites, and increased bystander tumor cell killing compared to that achieved in the absence of p35. Tumor cells infected with Adeno-2B6/p35 were readily killed by cisplatin and doxorubicin, indicating that p35 expression is not associated with acquisition of general drug resistance. Finally, p35 did not inhibit viral release when the replication-competent adenovirus ONYX-017 was used as a helper virus to facilitate co-replication and spread of Adeno-2B6/p35 and further increase CPA-induced bystander cell killing. The introduction of p35 into gene therapeutic regimens constitutes an effective approach to increase bystander killing by cytochrome P450 gene therapy. This strategy may also be used to enhance other bystander cytotoxic therapies, including those involving the production of tumor cell toxic protein products

Designer Babies? Teacher Views on Gene Technology and Human Medicine.

Science.gov (United States)

Schibeci, Renato

1999-01-01

Summarizes the views of a sample of primary and high school teachers on the application of gene technology to human medicine. In general, high school teachers are more positive about these developments than primary teachers, and both groups of teachers are more positive than interested lay publics. Highlights ways in which this topic can be…

Actionable gene-based classification toward precision medicine in gastric cancer

Directory of Open Access Journals (Sweden)

Hiroshi Ichikawa

2017-10-01

Full Text Available Abstract Background Intertumoral heterogeneity represents a significant hurdle to identifying optimized targeted therapies in gastric cancer (GC. To realize precision medicine for GC patients, an actionable gene alteration-based molecular classification that directly associates GCs with targeted therapies is needed. Methods A total of 207 Japanese patients with GC were included in this study. Formalin-fixed, paraffin-embedded (FFPE tumor tissues were obtained from surgical or biopsy specimens and were subjected to DNA extraction. We generated comprehensive genomic profiling data using a 435-gene panel including 69 actionable genes paired with US Food and Drug Administration-approved targeted therapies, and the evaluation of Epstein-Barr virus (EBV infection and microsatellite instability (MSI status. Results Comprehensive genomic sequencing detected at least one alteration of 435 cancer-related genes in 194 GCs (93.7% and of 69 actionable genes in 141 GCs (68.1%. We classified the 207 GCs into four The Cancer Genome Atlas (TCGA subtypes using the genomic profiling data; EBV (N = 9, MSI (N = 17, chromosomal instability (N = 119, and genomically stable subtype (N = 62. Actionable gene alterations were not specific and were widely observed throughout all TCGA subtypes. To discover a novel classification which more precisely selects candidates for targeted therapies, 207 GCs were classified using hypermutated phenotype and the mutation profile of 69 actionable genes. We identified a hypermutated group (N = 32, while the others (N = 175 were sub-divided into six clusters including five with actionable gene alterations: ERBB2 (N = 25, CDKN2A, and CDKN2B (N = 10, KRAS (N = 10, BRCA2 (N = 9, and ATM cluster (N = 12. The clinical utility of this classification was demonstrated by a case of unresectable GC with a remarkable response to anti-HER2 therapy in the ERBB2 cluster. Conclusions This actionable gene-based

Directed partial correlation: inferring large-scale gene regulatory network through induced topology disruptions.

Directory of Open Access Journals (Sweden)

Yinyin Yuan

Full Text Available Inferring regulatory relationships among many genes based on their temporal variation in transcript abundance has been a popular research topic. Due to the nature of microarray experiments, classical tools for time series analysis lose power since the number of variables far exceeds the number of the samples. In this paper, we describe some of the existing multivariate inference techniques that are applicable to hundreds of variables and show the potential challenges for small-sample, large-scale data. We propose a directed partial correlation (DPC method as an efficient and effective solution to regulatory network inference using these data. Specifically for genomic data, the proposed method is designed to deal with large-scale datasets. It combines the efficiency of partial correlation for setting up network topology by testing conditional independence, and the concept of Granger causality to assess topology change with induced interruptions. The idea is that when a transcription factor is induced artificially within a gene network, the disruption of the network by the induction signifies a genes role in transcriptional regulation. The benchmarking results using GeneNetWeaver, the simulator for the DREAM challenges, provide strong evidence of the outstanding performance of the proposed DPC method. When applied to real biological data, the inferred starch metabolism network in Arabidopsis reveals many biologically meaningful network modules worthy of further investigation. These results collectively suggest DPC is a versatile tool for genomics research. The R package DPC is available for download (http://code.google.com/p/dpcnet/.

RNA-directed DNA methylation: Mechanisms and functions

KAUST Repository

Mahfouz, Magdy M.

2010-01-01

Epigenetic RNA based gene silencing mechanisms play a major role in genome stability and control of gene expression. Transcriptional gene silencing via RNA-directed DNA methylation (RdDM) guides the epigenetic regulation of the genome in response

The Technological Input-output Efficiency of High-technology Enterprises in China Based on the DEA method

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Lu Jing

2017-01-01

Full Text Available High-technology enterprises play the leader role in the regional economic progress, but nowadays technological resources have many problems such as division, separation and dispersing. It’s an urgent problem to be solved that how to evaluate input-output productivity of technological resources towards industries and regions scientifically and efficiently. Firstly the article analyzes the input-output efficiency status of technological resources at home and abroad. Then high-technology enterprises in 29 provinces, as the subject of evaluation, are analyzed for their operation efficiency by DEA. The article states the suggestions like balanced development among regions and reasonable structure of input and output by comparing the differences among regions. And the article estimates the technological resources configuration efficiency of 5 leader industries and explains the developmental characteristics and direction among industries. And on these bases the article conducts hypothesis testing for inner elements which might have an influence on the operational efficiency by Tobit model. Finally, the paper proposes many suggestions to the benefits of promoting the productivity of high-technology enterprise according to the comprehensive analysis.

Technology development for gene discovery and full-length sequencing

Energy Technology Data Exchange (ETDEWEB)

Marcelo Bento Soares

2004-07-19

In previous years, with support from the U.S. Department of Energy, we developed methods for construction of normalized and subtracted cDNA libraries, and constructed hundreds of high-quality libraries for production of Expressed Sequence Tags (ESTs). Our clones were made widely available to the scientific community through the IMAGE Consortium, and millions of ESTs were produced from our libraries either by collaborators or by our own sequencing laboratory at the University of Iowa. During this grant period, we focused on (1) the development of a method for preferential cloning of tissue-specific and/or rare transcripts, (2) its utilization to expedite EST-based gene discovery for the NIH Mouse Brain Molecular Anatomy Project, (3) further development and optimization of a method for construction of full-length-enriched cDNA libraries, and (4) modification of a plasmid vector to maximize efficiency of full-length cDNA sequencing by the transposon-mediated approach. It is noteworthy that the technology developed for preferential cloning of rare mRNAs enabled identification of over 2,000 mouse transcripts differentially expressed in the hippocampus. In addition, the method that we optimized for construction of full-length-enriched cDNA libraries was successfully utilized for the production of approximately fifty libraries from the developing mouse nervous system, from which over 2,500 full-ORF-containing cDNAs have been identified and accurately sequenced in their entirety either by our group or by the NIH-Mammalian Gene Collection Program Sequencing Team.

Gene Technology: Also a Gender Issue. Views of Dutch Informed Women on Genetic Screening and Gene Therapy.

Science.gov (United States)

van Berkel, Dymphie; Klinge, Ineke

1997-01-01

The views of Dutch women on the implications of the analysis of the human genome were studied by questionnaire and interview. Although a serious lack of knowledge about the topic was found, interviews produced a broad range of problematic issues. Attention to gender implications of gene technology is needed. (Author/EMK)

The Trojan Horse Liposome Technology for Nonviral Gene Transfer across the Blood-Brain Barrier

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Ruben J. Boado

2011-01-01

Full Text Available The application of blood-borne gene therapy protocols to the brain is limited by the presence of the blood-brain barrier (BBB. Viruses have been extensively used as gene delivery systems. However, their efficacy in brain is limited by the lack of transport across the BBB following intravenous (IV administration. Recent progress in the “Trojan Horse Liposome” (THL technology applied to transvascular non-viral gene therapy of the brain presents a promising solution to the trans-vascular brain gene delivery problem. THLs are comprised of immunoliposomes carrying nonviral gene expression plasmids. The tissue target specificity of the THL is provided by peptidomimetic monoclonal antibody (MAb component of the THL, which binds to specific endogenous receptors located on both the BBB and on brain cellular membranes, for example, insulin receptor and transferrin receptor. These MAbs mediate (a receptor-mediated transcytosis of the THL complex through the BBB, (b endocytosis into brain cells and (c transport to the brain cell nuclear compartment. The expression of the transgene in brain may be restricted using tissue/cell specific gene promoters. This manuscript presents an overview on the THL transport technology applied to brain disorders, including lysosomal storage disorders and Parkinson's disease.

Site-Directed Genome Knockout in Chicken Cell Line and Embryos Can Use CRISPR/Cas Gene Editing Technology

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Qisheng Zuo

2016-06-01

Full Text Available The present study established an efficient genome editing approach for the construction of stable transgenic cell lines of the domestic chicken (Gallus gallus domesticus. Our objectives were to facilitate the breeding of high-yield, high-quality chicken strains, and to investigate gene function in chicken stem cells. Three guide RNA (gRNAs were designed to knockout the C2EIP gene, and knockout efficiency was evaluated in DF-1 chicken fibroblasts and chicken ESCs using the luciferase single-strand annealing (SSA recombination assay, T7 endonuclease I (T7EI assay, and TA clone sequencing. In addition, the polyethylenimine-encapsulated Cas9/gRNA plasmid was injected into fresh fertilized eggs. At 4.5 d later, frozen sections of the embryos were prepared, and knockout efficiency was evaluated by the T7EI assay. SSA assay results showed that luciferase activity of the vector expressing gRNA-3 was double that of the control. Results of the T7EI assay and TA clone sequencing indicated that Cas9/gRNA vector-mediated gene knockdown efficiency was approximately 27% in both DF-1 cells and ESCs. The CRISPR/Cas9 vector was also expressed in chicken embryos, resulting in gene knockdown in three of the 20 embryos (gene knockdown efficiency 15%. Taken together, our results indicate that the CRISPR/Cas9 system can mediate stable gene knockdown at the cell and embryo levels in domestic chickens.

Aspergillus oryzae-based cell factory for direct kojic acid production from cellulose.

Science.gov (United States)

Yamada, Ryosuke; Yoshie, Toshihide; Wakai, Satoshi; Asai-Nakashima, Nanami; Okazaki, Fumiyoshi; Ogino, Chiaki; Hisada, Hiromoto; Tsutsumi, Hiroko; Hata, Yoji; Kondo, Akihiko

2014-05-18

Kojic acid (5-Hydroxy-2-(hydroxymethyl)-4-pyrone) is one of the major secondary metabolites in Aspergillus oryzae. It is widely used in food, pharmaceuticals, and cosmetics. The production cost, however, is too high for its use in many applications. Thus, an efficient and cost-effective kojic acid production process would be valuable. However, little is known about the complete set of genes for kojic acid production. Currently, kojic acid is produced from glucose. The efficient production of kojic acid using cellulose as an inexpensive substrate would help establish cost-effective kojic acid production. A kojic acid transcription factor gene over-expressing the A. oryzae strain was constructed. Three genes related to kojic acid production in this strain were transcribed in higher amounts than those found in the wild-type strain. This strain produced 26.4 g/L kojic acid from 80 g/L glucose. Furthermore, this strain was transformed with plasmid harboring 3 cellulase genes. The resultant A. oryzae strain successfully produced 0.18 g/L of kojic acid in 6 days of fermentation from the phosphoric acid swollen cellulose. Kojic acid was produced directly from cellulose material using genetically engineered A. oryzae. Because A. oryzae has efficient protein secretion ability and secondary metabolite productivity, an A. oryzae-based cell factory could be a platform for the production of various kinds of bio-based chemicals.

Digital technology use in ELT classrooms and self-directed learning

OpenAIRE

Nehir Sert; Ebru Boynueğri

2016-01-01

The digital era is a new challenge for teachers. While children get acquainted with digital technology before the age of six, teachers, who have encountered the digital world at a later time in their lives, struggle with it. Self-directed learning, which is crucial for lifelong learning, can be enhanced by the use of technology within and beyond classroom settings. The aim of this study was to examine the difference between the perceptions of students in low- and high-income groups about thei...

Directional output distance functions: endogenous directions based on exogenous normalization constraints

Science.gov (United States)

In this paper we develop a model for computing directional output distance functions with endogenously determined direction vectors. We show how this model is related to the slacks-based directional distance function introduced by Fare and Grosskopf and show how to use the slacks-based function to e...

The roles and functions of a lunar base Nuclear Technology Center

International Nuclear Information System (INIS)

Buden, D.; Angelo, J.A. Jr.

1991-01-01

This paper describes the roles and functions of a special Nuclear Technology Center which is developed as an integral part of a permanent lunar base. Numerous contemporary studies clearly point out that nuclear energy technology will play a major role in any successful lunar/Mars initiative program and in the overall establishment of humanity's solar system civilization. The key role of nuclear energy in the providing power has been recognized. A Nuclear Technology Center developed as part of of a permanent lunar base can also help bring about many other nuclear technology applications, such as producing radioisotopes for self-illumination, food preservation, waste sterilization, and medical treatment; providing thermal energy for mining, materials processing and agricultural; and as a source of emergency habitat power. Designing such a center will involve the deployment, operation, servicing and waste product management and disposal of megawatt class reactor power plants. This challenge must be met with a minimum of direct human support at the facility. Furthermore, to support the timely, efficient integration of this Nuclear Technology Center in the evolving lunar base infrastructure, an analog of such a facility will be needed here on Earth. 12 refs., 4 figs., 1 tab

Commentary on ``Future directions: Building technologies and design tools``

Energy Technology Data Exchange (ETDEWEB)

Quadrel, R.W.

1992-08-10

This paper presents a number of interesting and thought-provoking scenarios about the future use of advanced technology in the design and operation of commercial buildings. I will express my reactions in the following series of short paragraphs. These thoughts will, I hope, raise some new questions and offer fruitful directions for further exploration.

Terminator Operon Reporter: combining a transcription termination switch with reporter technology for improved gene synthesis and synthetic biology applications.

Science.gov (United States)

Zampini, Massimiliano; Mur, Luis A J; Rees Stevens, Pauline; Pachebat, Justin A; Newbold, C James; Hayes, Finbarr; Kingston-Smith, Alison

2016-05-25

Synthetic biology is characterized by the development of novel and powerful DNA fabrication methods and by the application of engineering principles to biology. The current study describes Terminator Operon Reporter (TOR), a new gene assembly technology based on the conditional activation of a reporter gene in response to sequence errors occurring at the assembly stage of the synthetic element. These errors are monitored by a transcription terminator that is placed between the synthetic gene and reporter gene. Switching of this terminator between active and inactive states dictates the transcription status of the downstream reporter gene to provide a rapid and facile readout of the accuracy of synthetic assembly. Designed specifically and uniquely for the synthesis of protein coding genes in bacteria, TOR allows the rapid and cost-effective fabrication of synthetic constructs by employing oligonucleotides at the most basic purification level (desalted) and without the need for costly and time-consuming post-synthesis correction methods. Thus, TOR streamlines gene assembly approaches, which are central to the future development of synthetic biology.

Direct disposal of spent nuclear fuel. The current status of technology January 1987

International Nuclear Information System (INIS)

Wheelton, I.S.; Kelly, B.R.; Wood, E.

1987-02-01

The Study assesses the degree and status of research and development worldwide on Direct Disposal of Spent Nuclear Fuel. It is limited to technological, radiological and waste management aspects appertaining to Light Water and AGR Reactor Systems and reviews the 'State of the Art' in terms of applicability to the United Kingdom. The report concludes that much technology exists both at National and International level which the UK can apply to the subject of Direct Disposal. (author)

Technology Spillover from Foreign Direct Investment in Turkey

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Özcan Karahan

2016-12-01

quarterly data for the period of 2002 and 2015 in Turkey. Thus we try to examine whether technological diffusion generated by FDI inflows to Turkey enhances the innovative capability of the country or not. Design/methodology/approach – The variables Foreign Direct Investment (FDI and Gross Domestic Product (GDP are sourced from Electronic Data Delivery System (EDDS in Central Bank of the Republic of Turkey. FDI series consist of values called "Net Incurrence of Liabilities" in Balance of Payments Analytical Presentation while GDP series gather from the expenditure based GDP data in EDDS. Both Johansen Cointegration Test and Granger Causality Test are applied to examine between Foreign Direct Investment flows and economic growth in Turkey. Findings – Results reveal that there is not any significant link among the FDI and economic growth during the studied time period in Turkey. It seems that FDI inflows to Turkey is not complementary to economic growth, which shows that positive spillover effect sourced from FDI inflows to Turkey does not exist. Research limitations/implications – Policymakers should recognize that technology spillover effects of FDI do not occur without greater absorptive capacity. Attracting FDI is only one part of the story and thus not yield the desired benefits itself. Positive effects of FDI depends on the overall incentive and capacity structure of the host country. Then the key policy implication here is that policymakers should give same weight of policies aimed at attracting FDI versus those that seek to improve local economic conditions. Originality/value – This study insight the spillover effects of FDI based on Turkish experience that benefits from FDI do not occur automatically and effortlessly in developing countries.

Immunologic applications of conditional gene modification technology in the mouse.

Science.gov (United States)

Sharma, Suveena; Zhu, Jinfang

2014-04-02

Since the success of homologous recombination in altering mouse genome and the discovery of Cre-loxP system, the combination of these two breakthroughs has created important applications for studying the immune system in the mouse. Here, we briefly summarize the general principles of this technology and its applications in studying immune cell development and responses; such implications include conditional gene knockout and inducible and/or tissue-specific gene over-expression, as well as lineage fate mapping. We then discuss the pros and cons of a few commonly used Cre-expressing mouse lines for studying lymphocyte development and functions. We also raise several general issues, such as efficiency of gene deletion, leaky activity of Cre, and Cre toxicity, all of which may have profound impacts on data interpretation. Finally, we selectively list some useful links to the Web sites as valuable mouse resources. Copyright © 2014 John Wiley & Sons, Inc.

Development of a rapid method for direct detection of tet(M) genes in soil from Danish farmland

DEFF Research Database (Denmark)

Agersø, Yvonne; Sengeløv, Gitte; Jensen, Lars Bogø

2004-01-01

. The tet(M) gene was directly detected in 10-80% of the samples from the various farmland soils and could be detected in all samples tested after selective enrichment. To validate the obtained results, the method was applied to garden soil samples where lower prevalence of resistance was found. Result......A method for direct detection of antibiotic resistance genes in soil samples has been developed. The tetracycline resistance gene, tet(M), was used as a model. The method was validated on Danish farmland soil that had repeatedly been treated with pig manure slurry containing resistant bacteria......: A detection limit of 10(2)-10(3) copies of the tet(M) gene per gram of soil (in a Bacillus cereus group bacterium) was achieved. tet(M) gene was detected in soil samples with the highest prevalence on farmland treated with pig manure slurry....

A locked nucleic acid (LNA-based real-time PCR assay for the rapid detection of multiple bacterial antibiotic resistance genes directly from positive blood culture.

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Lingxiang Zhu

Full Text Available Bacterial strains resistant to various antibiotic drugs are frequently encountered in clinical infections, and the rapid identification of drug-resistant strains is highly essential for clinical treatment. We developed a locked nucleic acid (LNA-based quantitative real-time PCR (LNA-qPCR method for the rapid detection of 13 antibiotic resistance genes and successfully used it to distinguish drug-resistant bacterial strains from positive blood culture samples. A sequence-specific primer-probe set was designed, and the specificity of the assays was assessed using 27 ATCC bacterial strains and 77 negative blood culture samples. No cross-reaction was identified among bacterial strains and in negative samples, indicating 100% specificity. The sensitivity of the assays was determined by spiking each bacterial strain into negative blood samples, and the detection limit was 1-10 colony forming units (CFU per reaction. The LNA-qPCR assays were first applied to 72 clinical bacterial isolates for the identification of known drug resistance genes, and the results were verified by the direct sequencing of PCR products. Finally, the LNA-qPCR assays were used for the detection in 47 positive blood culture samples, 19 of which (40.4% were positive for antibiotic resistance genes, showing 91.5% consistency with phenotypic susceptibility results. In conclusion, LNA-qPCR is a reliable method for the rapid detection of bacterial antibiotic resistance genes and can be used as a supplement to phenotypic susceptibility testing for the early detection of antimicrobial resistance to allow the selection of appropriate antimicrobial treatment and to prevent the spread of resistant isolates.

Direct chemical oxidation: a non-thermal technology for the destruction of organic wastes

Energy Technology Data Exchange (ETDEWEB)

Balazs, G.B.; Cooper, J. F.; Lewis, P. R.; Adamson, M. G.

1998-02-01

Direct Chemical Oxidation (DCO) is a non-thermal, ambient pressure, aqueous-based technology for the oxidative destruction of the organic components of hazardous or mixed waste streams. The process has been developed for applications in waste treatment and chemical demilitarization and decontamination at LLNL since 1992, and is applicable to the destruction of virtually all solid or liquid organics, including: chlorosolvents, oils and greases, detergents, organic-contaminated soils or sludges, explosives, chemical and biological warfare agents, and PCB's. [1-15] The process normally operates at 80-100 C, a heating requirement which increases the difficulty of surface decontamination of large objects or, for example, treatment of a wide area contaminated soil site. The driver for DCO work in FY98 was thus to investigate the use of catalysts to demonstrate the effectiveness of the technology for organics destruction at temperatures closer to ambient. In addition, DCO is at a sufficiently mature stage of development that technology transfer to a commercial entity was a logical next step, and was thus included in FY98 tasks.

Mass spectrometry-based proteomics: basic principles and emerging technologies and directions.

Science.gov (United States)

Van Riper, Susan K; de Jong, Ebbing P; Carlis, John V; Griffin, Timothy J

2013-01-01

As the main catalytic and structural molecules within living systems, proteins are the most likely biomolecules to be affected by radiation exposure. Proteomics, the comprehensive characterization of proteins within complex biological samples, is therefore a research approach ideally suited to assess the effects of radiation exposure on cells and tissues. For comprehensive characterization of proteomes, an analytical platform capable of quantifying protein abundance, identifying post-translation modifications and revealing members of protein complexes on a system-wide level is necessary. Mass spectrometry (MS), coupled with technologies for sample fractionation and automated data analysis, provides such a versatile and powerful platform. In this chapter we offer a view on the current state of MS-proteomics, and focus on emerging technologies within three areas: (1) New instrumental methods; (2) New computational methods for peptide identification; and (3) Label-free quantification. These emerging technologies should be valuable for researchers seeking to better understand biological effects of radiation on living systems.

A novel BDNF gene promoter directs expression to skeletal muscle

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Heinrich Gerhard

2003-06-01

Full Text Available Abstract Background Cell-specific expression of the gene that encodes brain-derived neurotrophic factor (BDNF is required for the normal development of peripheral sensory neurons and efficient synaptic transmission in the mature central and peripheral nervous system. The control of BDNF gene expression involves multiple tissue and cell-specific promoters that are differentially regulated. The molecular mechanisms that are responsible for tissue and cell-specific expression of these promoters are still incompletely understood. Results The cloning and analysis of three additional zebrafish (Danio rerio BDNF gene exons and two associated promoters, is reported. Among them are two exons that generate a novel tripartite mature transcript. The exons were located on the transcription unit, whose overall organization was determined by cloning, Southern blot hybridization and sequence analysis, and compared with the pufferfish (Fugu rubripes and mammalian BDNF loci, revealing a conserved but more compact organization. Structural and functional analysis of the exons, their adjacent promoters and 5' flanks, showed that they are expressed cell-specifically. The promoter associated with the 5' exon of the tripartite transcript is GC-rich, TATA-less and the 5' flank adjacent to it contains multiple Sp1, Mef2, and AP1 elements. A fusion gene containing the promoter and 1.5 KB of 5' flank is directed exclusively to skeletal muscle of transiently transfected embryos. The second promoter, whose associated 5' exon contains a 25-nucleotide segment of identity with a mammalian BDNF gene exon, was transiently expressed in yolk of the early embryo. RT-PCR analysis of total RNA from whole juvenile fish and adult female skeletal muscle revealed tissue-specific expression of the 5' exons but the novel exon could not be detected even after two rounds of nested PCR. Conclusion The zebrafish BDNF gene is as complex as the mammalian gene yet much more compact. Its exons are

Technology based Education System

DEFF Research Database (Denmark)

Kant Hiran, Kamal; Doshi, Ruchi; Henten, Anders

2016-01-01

Abstract - Education plays a very important role for the development of the country. Education has multiple dimensions from schooling to higher education and research. In all these domains, there is invariably a need for technology based teaching and learning tools are highly demanded in the acad......Abstract - Education plays a very important role for the development of the country. Education has multiple dimensions from schooling to higher education and research. In all these domains, there is invariably a need for technology based teaching and learning tools are highly demanded...... in the academic institutions. Thus, there is a need of comprehensive technology support system to cater the demands of all educational actors. Cloud Computing is one such comprehensive and user-friendly technology support environment that is the need of an hour. Cloud computing is the emerging technology that has...

Clustering gene expression data based on predicted differential effects of GV interaction.

Science.gov (United States)

Pan, Hai-Yan; Zhu, Jun; Han, Dan-Fu

2005-02-01

Microarray has become a popular biotechnology in biological and medical research. However, systematic and stochastic variabilities in microarray data are expected and unavoidable, resulting in the problem that the raw measurements have inherent "noise" within microarray experiments. Currently, logarithmic ratios are usually analyzed by various clustering methods directly, which may introduce bias interpretation in identifying groups of genes or samples. In this paper, a statistical method based on mixed model approaches was proposed for microarray data cluster analysis. The underlying rationale of this method is to partition the observed total gene expression level into various variations caused by different factors using an ANOVA model, and to predict the differential effects of GV (gene by variety) interaction using the adjusted unbiased prediction (AUP) method. The predicted GV interaction effects can then be used as the inputs of cluster analysis. We illustrated the application of our method with a gene expression dataset and elucidated the utility of our approach using an external validation.

The Integrative Method Based on the Module-Network for Identifying Driver Genes in Cancer Subtypes

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Xinguo Lu

2018-01-01

Full Text Available With advances in next-generation sequencing(NGS technologies, a large number of multiple types of high-throughput genomics data are available. A great challenge in exploring cancer progression is to identify the driver genes from the variant genes by analyzing and integrating multi-types genomics data. Breast cancer is known as a heterogeneous disease. The identification of subtype-specific driver genes is critical to guide the diagnosis, assessment of prognosis and treatment of breast cancer. We developed an integrated frame based on gene expression profiles and copy number variation (CNV data to identify breast cancer subtype-specific driver genes. In this frame, we employed statistical machine-learning method to select gene subsets and utilized an module-network analysis method to identify potential candidate driver genes. The final subtype-specific driver genes were acquired by paired-wise comparison in subtypes. To validate specificity of the driver genes, the gene expression data of these genes were applied to classify the patient samples with 10-fold cross validation and the enrichment analysis were also conducted on the identified driver genes. The experimental results show that the proposed integrative method can identify the potential driver genes and the classifier with these genes acquired better performance than with genes identified by other methods.

A comparative study of mutation screening of sarcomeric genes (MYBPC3, MYH7, TNNT2 using single gene approach versus targeted gene panel next generation sequencing in a cohort of HCM patients in Egypt

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Heba Sh. Kassem

2017-10-01

Full Text Available Background: NGS enables simultaneous sequencing of large numbers of associated genes in genetic heterogeneous disorders, in a more rapid and cost-effective manner than traditional technologies. However there have been limited direct comparisons between NGS and more established technologies to assess the sensitivity and false negative rates of this new approach. The scope of the present manuscript is to compare variants detected in MYBPC3, MYH7 and TNNT2 genes using the stepwise dHPLC/Sanger versus targeted NGS. Methods: In this study, we have analysed a group of 150 samples of patients from the Bibliotheca Alexandrina-Aswan Heart Centre National HCM program. The genetic testing was simultaneously undertaken by high throughput denaturing high-performance liquid chromatography (dHPLC followed by Sanger based sequencing and targeted next generation deep sequencing using panel of inherited cardiac genes (ICC. The panel included over 100 genes including the 3 sarcomeric genes. Analysis of the sequencing data of the 3 genes was undertaken in a double blinded strategy. Results: NGS analysis detected all pathogenic and likely pathogenic variants identified by dHPLC (50 in total, some samples had double hits. There was a 0% false negative rate for NGS based analysis. Nineteen variants were missed by dHPLC and detected by NGS, thus increasing the diagnostic yield in this co- analysed cohort from 22.0% (33/150 to 31.3% (47/150.Of interest to note that the mutation spectrum in this Egyptian HCM population revealed a high rate of homozygosity in MYBPC3 and MYH7 genes in comparison to other population studies (6/150, 4%. None of the homozygous samples were detected by dHPLC analysis. Conclusion: NGS provides a useful and rapid tool to allow panoramic screening of several genes simultaneously with a high sensitivity rate amongst genes of known etiologic role allowing high throughput analysis of HCM patients and relevant control series in a less characterised

Integration of Technology-based Behavioral Health Interventions in Substance Abuse and Addiction Services.

Science.gov (United States)

Ramsey, Alex

2015-08-01

The past decade has witnessed revolutionary changes to the delivery of health services, ushered in to a great extent by the introduction of electronic health record systems. More recently, a new class of technological advancements-technology-based behavioral health interventions, which involve the delivery of evidence-informed practices via computers, web-based applications, mobile phones, wearable sensors, or other technological platforms-has emerged and is primed to once again radically shift current models for behavioral healthcare. Despite the promise and potential of these new therapeutic approaches, a greater understanding of the impact of technology-based interventions on cornerstone issues of mental health and addiction services-namely access, quality, and cost -is needed. The current review highlights 1) relevant conceptual frameworks that guide this area of research, 2) key studies that inform the relevance of technology-based interventions for behavioral healthcare access, quality, and cost, 3) pressing methodological issues that require attention, 4) unresolved questions that warrant further investigation, and 5) practical implications that underscore important new directions for this emerging area of research.

Tensor decomposition-based unsupervised feature extraction identifies candidate genes that induce post-traumatic stress disorder-mediated heart diseases.

Science.gov (United States)

Taguchi, Y-H

2017-12-21

Although post-traumatic stress disorder (PTSD) is primarily a mental disorder, it can cause additional symptoms that do not seem to be directly related to the central nervous system, which PTSD is assumed to directly affect. PTSD-mediated heart diseases are some of such secondary disorders. In spite of the significant correlations between PTSD and heart diseases, spatial separation between the heart and brain (where PTSD is primarily active) prevents researchers from elucidating the mechanisms that bridge the two disorders. Our purpose was to identify genes linking PTSD and heart diseases. In this study, gene expression profiles of various murine tissues observed under various types of stress or without stress were analyzed in an integrated manner using tensor decomposition (TD). Based upon the obtained features, ∼ 400 genes were identified as candidate genes that may mediate heart diseases associated with PTSD. Various gene enrichment analyses supported biological reliability of the identified genes. Ten genes encoding protein-, DNA-, or mRNA-interacting proteins-ILF2, ILF3, ESR1, ESR2, RAD21, HTT, ATF2, NR3C1, TP53, and TP63-were found to be likely to regulate expression of most of these ∼ 400 genes and therefore are candidate primary genes that cause PTSD-mediated heart diseases. Approximately 400 genes in the heart were also found to be strongly affected by various drugs whose known adverse effects are related to heart diseases and/or fear memory conditioning; these data support the reliability of our findings. TD-based unsupervised feature extraction turned out to be a useful method for gene selection and successfully identified possible genes causing PTSD-mediated heart diseases.

Link-based quantitative methods to identify differentially coexpressed genes and gene Pairs

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Ye Zhi-Qiang

2011-08-01

Full Text Available Abstract Background Differential coexpression analysis (DCEA is increasingly used for investigating the global transcriptional mechanisms underlying phenotypic changes. Current DCEA methods mostly adopt a gene connectivity-based strategy to estimate differential coexpression, which is characterized by comparing the numbers of gene neighbors in different coexpression networks. Although it simplifies the calculation, this strategy mixes up the identities of different coexpression neighbors of a gene, and fails to differentiate significant differential coexpression changes from those trivial ones. Especially, the correlation-reversal is easily missed although it probably indicates remarkable biological significance. Results We developed two link-based quantitative methods, DCp and DCe, to identify differentially coexpressed genes and gene pairs (links. Bearing the uniqueness of exploiting the quantitative coexpression change of each gene pair in the coexpression networks, both methods proved to be superior to currently popular methods in simulation studies. Re-mining of a publicly available type 2 diabetes (T2D expression dataset from the perspective of differential coexpression analysis led to additional discoveries than those from differential expression analysis. Conclusions This work pointed out the critical weakness of current popular DCEA methods, and proposed two link-based DCEA algorithms that will make contribution to the development of DCEA and help extend it to a broader spectrum.

A Morpholino-based screen to identify novel genes involved in craniofacial morphogenesis

Science.gov (United States)

Melvin, Vida Senkus; Feng, Weiguo; Hernandez-Lagunas, Laura; Artinger, Kristin Bruk; Williams, Trevor

2014-01-01

BACKGROUND The regulatory mechanisms underpinning facial development are conserved between diverse species. Therefore, results from model systems provide insight into the genetic causes of human craniofacial defects. Previously, we generated a comprehensive dataset examining gene expression during development and fusion of the mouse facial prominences. Here, we used this resource to identify genes that have dynamic expression patterns in the facial prominences, but for which only limited information exists concerning developmental function. RESULTS This set of ~80 genes was used for a high throughput functional analysis in the zebrafish system using Morpholino gene knockdown technology. This screen revealed three classes of cranial cartilage phenotypes depending upon whether knockdown of the gene affected the neurocranium, viscerocranium, or both. The targeted genes that produced consistent phenotypes encoded proteins linked to transcription (meis1, meis2a, tshz2, vgll4l), signaling (pkdcc, vlk, macc1, wu:fb16h09), and extracellular matrix function (smoc2). The majority of these phenotypes were not altered by reduction of p53 levels, demonstrating that both p53 dependent and independent mechanisms were involved in the craniofacial abnormalities. CONCLUSIONS This Morpholino-based screen highlights new genes involved in development of the zebrafish craniofacial skeleton with wider relevance to formation of the face in other species, particularly mouse and human. PMID:23559552

Area–Oriented Technology Mapping for LUT–Based Logic Blocks

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Kubica Marcin

2017-03-01

Full Text Available One of the main aspects of logic synthesis dedicated to FPGA is the problem of technology mapping, which is directly associated with the logic decomposition technique. This paper focuses on using configurable properties of CLBs in the process of logic decomposition and technology mapping. A novel theory and a set of efficient techniques for logic decomposition based on a BDD are proposed. The paper shows that logic optimization can be efficiently carried out by using multiple decomposition. The essence of the proposed synthesis method is multiple cutting of a BDD. A new diagram form called an SMTBDD is proposed. Moreover, techniques that allow finding the best technology mapping oriented to configurability of CLBs are presented. In the experimental section, the presented method (MultiDec is compared with academic and commercial tools. The experimental results show that the proposed technology mapping strategy leads to good results in terms of the number of CLBs.

Disease Control in Animals Using Molecular Technology by Inactivation of ASO, RNAi and ss-siRNA Genes

Directory of Open Access Journals (Sweden)

Muhamad Ali

2014-03-01

Full Text Available Globalization causes high mobility of human and livestock, hence increase the transmission of infectious diseases, including avian influenza, severe acute respiratory syndrome (SARS, and swine influenza. Therefore, prevention of those diseases is required. Vaccines are effective to prevent infectious diseases; however, their development takes a long time and they cannot provide immediate protection in pandemic cases. This paper describes several gene silencing technologies including antisense oligonucleotide (ASO, RNA interference (RNAi and single strand-small interfering RNA (ss-siRNA for controlling diseases. The primary mechanism of these technologies is inhibition of gene expression, typically by causing the destruction of specific RNA molecule of the pathogen. The use of gene silencing technologies is expected to give new alternative that is more effective in eradication of infectious diseases in animals before threaten human being.

LEGO: a novel method for gene set over-representation analysis by incorporating network-based gene weights.

Science.gov (United States)

Dong, Xinran; Hao, Yun; Wang, Xiao; Tian, Weidong

2016-01-11

Pathway or gene set over-representation analysis (ORA) has become a routine task in functional genomics studies. However, currently widely used ORA tools employ statistical methods such as Fisher's exact test that reduce a pathway into a list of genes, ignoring the constitutive functional non-equivalent roles of genes and the complex gene-gene interactions. Here, we develop a novel method named LEGO (functional Link Enrichment of Gene Ontology or gene sets) that takes into consideration these two types of information by incorporating network-based gene weights in ORA analysis. In three benchmarks, LEGO achieves better performance than Fisher and three other network-based methods. To further evaluate LEGO's usefulness, we compare LEGO with five gene expression-based and three pathway topology-based methods using a benchmark of 34 disease gene expression datasets compiled by a recent publication, and show that LEGO is among the top-ranked methods in terms of both sensitivity and prioritization for detecting target KEGG pathways. In addition, we develop a cluster-and-filter approach to reduce the redundancy among the enriched gene sets, making the results more interpretable to biologists. Finally, we apply LEGO to two lists of autism genes, and identify relevant gene sets to autism that could not be found by Fisher.

GeneRank: Using search engine technology for the analysis of microarray experiments

Directory of Open Access Journals (Sweden)

Breitling Rainer

2005-09-01

Full Text Available Abstract Background Interpretation of simple microarray experiments is usually based on the fold-change of gene expression between a reference and a "treated" sample where the treatment can be of many types from drug exposure to genetic variation. Interpretation of the results usually combines lists of differentially expressed genes with previous knowledge about their biological function. Here we evaluate a method – based on the PageRank algorithm employed by the popular search engine Google – that tries to automate some of this procedure to generate prioritized gene lists by exploiting biological background information. Results GeneRank is an intuitive modification of PageRank that maintains many of its mathematical properties. It combines gene expression information with a network structure derived from gene annotations (gene ontologies or expression profile correlations. Using both simulated and real data we find that the algorithm offers an improved ranking of genes compared to pure expression change rankings. Conclusion Our modification of the PageRank algorithm provides an alternative method of evaluating microarray experimental results which combines prior knowledge about the underlying network. GeneRank offers an improvement compared to assessing the importance of a gene based on its experimentally observed fold-change alone and may be used as a basis for further analytical developments.

GeneRank: using search engine technology for the analysis of microarray experiments.

Science.gov (United States)

Morrison, Julie L; Breitling, Rainer; Higham, Desmond J; Gilbert, David R

2005-09-21

Interpretation of simple microarray experiments is usually based on the fold-change of gene expression between a reference and a "treated" sample where the treatment can be of many types from drug exposure to genetic variation. Interpretation of the results usually combines lists of differentially expressed genes with previous knowledge about their biological function. Here we evaluate a method--based on the PageRank algorithm employed by the popular search engine Google--that tries to automate some of this procedure to generate prioritized gene lists by exploiting biological background information. GeneRank is an intuitive modification of PageRank that maintains many of its mathematical properties. It combines gene expression information with a network structure derived from gene annotations (gene ontologies) or expression profile correlations. Using both simulated and real data we find that the algorithm offers an improved ranking of genes compared to pure expression change rankings. Our modification of the PageRank algorithm provides an alternative method of evaluating microarray experimental results which combines prior knowledge about the underlying network. GeneRank offers an improvement compared to assessing the importance of a gene based on its experimentally observed fold-change alone and may be used as a basis for further analytical developments.

Probe-based recording technology

International Nuclear Information System (INIS)

Naberhuis, Steve

2002-01-01

The invention of the scanning tunneling microscope (STM) prompted researchers to contemplate whether such technology could be used as the basis for the storage and retrieval of information. With magnetic data storage technology facing limits in storage density due to the thermal instability of magnetic bits, the super-paramagnetic limit, the heir-apparent for information storage at higher densities appeared to be variants of the STM or similar probe-based storage techniques such as atomic force microscopy (AFM). Among these other techniques that could provide replacement technology for magnetic storage, near-field optical scanning optical microscopy (NSOM or SNOM) has also been investigated. Another alternative probe-based storage technology called atomic resolution storage (ARS) is also currently under development. An overview of these various technologies is herein presented, with an analysis of the advantages and disadvantages inherent in each particularly with respect to reduced device dimensions. The role of micro electro mechanical systems (MEMS) is emphasized

1997 Annual report. Technological Research Direction; Informe Anual 1997. Direccion de Investigacion Tecnologica

Energy Technology Data Exchange (ETDEWEB)

NONE

1998-12-01

This document describes the results for one year of work. Here is presented the goals of the Technological Research Direction of the National Institute of Nuclear Research in Mexico, which is promoting and developing the production of high technologies in the nuclear sciences and related disciplines as well as to generate the technologies, products, quality insume for academic organizations, health, industrial and commercial that are required. (Author)

DIRECTIONS OF PREPARATION OF FUTURE TEACHERS TO THE USE OF DISTANCE LEARNING TECHNOLOGIES IN PROFESSIONAL ACTIVITY (PRAXIOLOGICAL ASPECT OF THE ACTIVITY APPROACH

Directory of Open Access Journals (Sweden)

Tatyana A. Boronenko

2015-01-01

Full Text Available The aim of the article is to demonstrate the need of preparing future teachers to use distance learning technologies in the professional activities. Introduction in educational process of distance learning technologies contributes to improving the quality of education. Methods. The authors’ technique of preparation of students of pedagogical specialities to work in the information-educational environment is designed on the basis of the analysis and generalisation of numerous scientific publications. Results. The system of training to implementation of the distance learning technologies in the teaching activity is developed and described, consisting of the following directions: realisation within the program of the principal educational program of specialised training courses in variable-based curriculum parts; the organisation of educational and research activity of students with the use of distance learning technologies; classroom-based and extracurricular independent work of students directed to designing of teaching and learning aids and materials on the basis of distance learning technologies; application of elements of distance learning technologies for students’ teaching; attraction of students to formation of corpus of multimedia educational resources of university. The purposes, the content and expected results of each direction are specified. Scientific novelty. The authors point out that concrete scientifically wellfounded methodical recommendations for the future teachers on implementation of distance learning technologies haven’t been presented in the Russian literature till now; despite an abundance of scientifically-information sources of distance learning technologies and sufficiently high-leveled degree knowledge of the issues of its efficiency in educational activity, conditions of introduction of such technologies in high school, construction of models of distance training. Authors of article have tried to close this

Environmental Measurement-While-Drilling System and Horizontal Directional Drilling Technology Demonstration, Hanford Site

International Nuclear Information System (INIS)

Williams, C.V.; Lockwood, G.J.; Normann, R.A.; Myers, D.A.; Gardner, M.G.; Williamson, T.; Huffman, J.

1999-01-01

The Environmental Measurement-While-Drilling (EMWD) system and Horizontal Directional Drilling (HDD) were successfully demonstrated at the Mock Tank Leak Simulation Site and the Drilling Technology Test Site, Hanford, Washington. The use of directional drilling offers an alternative to vertical drilling site characterization. Directional drilling can develop a borehole under a structure, such as a waste tank, from an angled entry and leveling off to horizontal at the desired depth. The EMWD system represents an innovative blend of new and existing technology that provides the capability of producing real-time environmental and drill bit data during drilling operations. The technology demonstration consisted of the development of one borehole under a mock waste tank at a depth of approximately minus8 m (minus27 ft.), following a predetermined drill path, tracking the drill path to within a radius of approximately1.5 m (5 ft.), and monitoring for zones of radiological activity using the EMWD system. The purpose of the second borehole was to demonstrate the capability of drilling to a depth of ∼ -21 m (-70 ft.), the depth needed to obtain access under the Hanford waste tanks, and continue drilling horizontally. This report presents information on the HDD and EMWD technologies, demonstration design, results of the demonstrations, and lessons learned

Search Engine for Antimicrobial Resistance: A Cloud Compatible Pipeline and Web Interface for Rapidly Detecting Antimicrobial Resistance Genes Directly from Sequence Data.

Science.gov (United States)

Rowe, Will; Baker, Kate S; Verner-Jeffreys, David; Baker-Austin, Craig; Ryan, Jim J; Maskell, Duncan; Pearce, Gareth

2015-01-01

Antimicrobial resistance remains a growing and significant concern in human and veterinary medicine. Current laboratory methods for the detection and surveillance of antimicrobial resistant bacteria are limited in their effectiveness and scope. With the rapidly developing field of whole genome sequencing beginning to be utilised in clinical practice, the ability to interrogate sequencing data quickly and easily for the presence of antimicrobial resistance genes will become increasingly important and useful for informing clinical decisions. Additionally, use of such tools will provide insight into the dynamics of antimicrobial resistance genes in metagenomic samples such as those used in environmental monitoring. Here we present the Search Engine for Antimicrobial Resistance (SEAR), a pipeline and web interface for detection of horizontally acquired antimicrobial resistance genes in raw sequencing data. The pipeline provides gene information, abundance estimation and the reconstructed sequence of antimicrobial resistance genes; it also provides web links to additional information on each gene. The pipeline utilises clustering and read mapping to annotate full-length genes relative to a user-defined database. It also uses local alignment of annotated genes to a range of online databases to provide additional information. We demonstrate SEAR's application in the detection and abundance estimation of antimicrobial resistance genes in two novel environmental metagenomes, 32 human faecal microbiome datasets and 126 clinical isolates of Shigella sonnei. We have developed a pipeline that contributes to the improved capacity for antimicrobial resistance detection afforded by next generation sequencing technologies, allowing for rapid detection of antimicrobial resistance genes directly from sequencing data. SEAR uses raw sequencing data via an intuitive interface so can be run rapidly without requiring advanced bioinformatic skills or resources. Finally, we show that SEAR

Identification of Human HK Genes and Gene Expression Regulation Study in Cancer from Transcriptomics Data Analysis

Science.gov (United States)

Zhang, Zhang; Liu, Jingxing; Wu, Jiayan; Yu, Jun

2013-01-01

The regulation of gene expression is essential for eukaryotes, as it drives the processes of cellular differentiation and morphogenesis, leading to the creation of different cell types in multicellular organisms. RNA-Sequencing (RNA-Seq) provides researchers with a powerful toolbox for characterization and quantification of transcriptome. Many different human tissue/cell transcriptome datasets coming from RNA-Seq technology are available on public data resource. The fundamental issue here is how to develop an effective analysis method to estimate expression pattern similarities between different tumor tissues and their corresponding normal tissues. We define the gene expression pattern from three directions: 1) expression breadth, which reflects gene expression on/off status, and mainly concerns ubiquitously expressed genes; 2) low/high or constant/variable expression genes, based on gene expression level and variation; and 3) the regulation of gene expression at the gene structure level. The cluster analysis indicates that gene expression pattern is higher related to physiological condition rather than tissue spatial distance. Two sets of human housekeeping (HK) genes are defined according to cell/tissue types, respectively. To characterize the gene expression pattern in gene expression level and variation, we firstly apply improved K-means algorithm and a gene expression variance model. We find that cancer-associated HK genes (a HK gene is specific in cancer group, while not in normal group) are expressed higher and more variable in cancer condition than in normal condition. Cancer-associated HK genes prefer to AT-rich genes, and they are enriched in cell cycle regulation related functions and constitute some cancer signatures. The expression of large genes is also avoided in cancer group. These studies will help us understand which cell type-specific patterns of gene expression differ among different cell types, and particularly for cancer. PMID:23382867

Network for development of electroporation-based technologies and treatments: COST TD1104.

Science.gov (United States)

Miklavčič, Damijan

2012-10-01

Exposure of biological cells to a sufficiently strong external electric field results in increased permeability of cell membranes, referred to as "electroporation." Since all types of cells (animal, plant and microorganism) can be effectively electroporated, electroporation is considered to be a universal method and a platform technology. Electroporation has become a widely used technology applicable to, e.g., cancer treatment, gene transfection, food and biomass processing and microbial inactivation. However, despite significant progress in electroporation-based applications, there is a lack of coordination and interdisciplinary exchange of knowledge between researchers from different scientific domains. Thus, critical mass for new major breakthroughs is missing. This is why we decided to establish cooperation between research groups working in different fields of electroporation. Cooperation in Science and Technology (COST), which funds networking and capacity-building activities, presents a perfect framework for such scientific cooperation. This COST action aims at (1) providing necessary steps toward EU cooperation of science and technology to foster basic understanding of electroporation; (2) improving communication between research groups, resulting in streamlining European research and development activities; and (3) enabling development of new and further development of existing electroporation-based applications by integrating multidisciplinary research teams, as well as providing comprehensive training for early-stage researchers. Results of this COST action will provide multiple societal, scientific and technological benefits from improving existing electroporation-based applications to adding new ones in the fields of medicine, biotechnology and environmental preservation.

Study on the generation technology of Li brocade pattern mutant genes based on the AI and Java technology

Science.gov (United States)

Zhou, Yuping; Zhang, Qi

2018-04-01

In the information environment, digital and information processing to Li brocade patterns reveals an important means of Li ethnic style and inheriting the national culture. Adobe Illustrator CS3 and Java language were used in the paper to make "variation" processing to Li brocade patterns, and generate "Li brocade pattern mutant genes". The generation of pattern mutant genes includes color mutation, shape mutation, adding and missing transform, and twisted transform, etc. Research shows that Li brocade pattern mutant genes can be generated by using the Adobe Illustrator CS3 and the image processing tools of Java language edit, etc.

Activation of Fetal γ-globin Gene Expression via Direct Protein Delivery of Synthetic Zinc-finger DNA-Binding Domains

Directory of Open Access Journals (Sweden)

Mir A Hossain

2016-01-01

Full Text Available Reactivation of γ-globin expression has been shown to ameliorate disease phenotypes associated with mutations in the adult β-globin gene, including sickle cell disease. Specific mutations in the promoter of the γ-globin genes are known to prevent repression of the genes in the adult and thus lead to hereditary persistence of fetal hemoglobin. One such hereditary persistence of fetal hemoglobin is associated with a sequence located 567 bp upstream of the Gγ-globin gene which assembles a GATA-containing repressor complex. We generated two synthetic zinc-finger DNA-binding domains (ZF-DBDs targeting this sequence. The -567Gγ ZF-DBDs associated with high affinity and specificity with the target site in the γ-globin gene promoter. We delivered the -567Gγ ZF-DBDs directly to primary erythroid cells. Exposure of these cells to the recombinant -567Gγ ZF-DBDs led to increased expression of the γ-globin gene. Direct protein delivery of ZF-DBDs that compete with transcription regulatory proteins will have broad implications for modulating gene expression in analytical or therapeutic settings.

Contradictory directionalities of digital learning technology and its implications for the scope of imaginable possibilities for collaborating

DEFF Research Database (Denmark)

Chimirri, Niklas Alexander

Contradictory learning directionalities are immanent to digital learning technology: Any technology suggests a limited multiplicity of situated uses in a learning practice, of understandings of how to learn and of what learning should be about. Herewith any technology offers a scope of imaginable...... possibilities for acting through it. Sociomaterially maintained learning directionalities – among others through the intended uses of learning technology in educational arrangements – afford the enactment of a delimited ensemble of experiential modes, sensualities, epistemologies, knowledges, and future hopes....... Next to offering opportunities to expand the learners’ scope of possibilities for transforming these learning directionalities together, digital learning technology thus also promotes the taken for grantedness of particular understandings of (most often instrumental) learning. They may consequently...

Assessment of Direct-to-Consumer Genetic Testing Policy in Korea Based on Consumer Preference.

Science.gov (United States)

Jeong, Gicheol

2017-01-01

In June 2016, Korea permitted direct-to-consumer genetic testing (DTC-GT) on 42 genes. However, both the market and industry have not yet been fully activated. Considering the aforementioned context, this study provides important insights. The Korean DTC-GT policy assessment is based on consumer preference analysis using a discrete choice experiment. In August 2016, a web-based survey was conducted to collect data from 1,200 respondents. The estimation results show that consumers prefer a DTC-GT product that is cheap, tests various items or genes, offers accurate test results, and guarantees the confidentiality of all information. However, consumers are not entirely satisfied by current DTC-GT products due to the existence of insufficient and/or inadequate policies. First, the permitted testing of 42 genes is insufficient to satisfy consumers' curiosity regarding their genes. Second, the accuracy of the DTC-GT products has not been fully verified, assessed, and communicated to consumers. Finally, regulatory loopholes that allow information leaks in the DTC-GT process can occur. These findings imply that DTC-GT requires an improvement in government policy-making criteria and the implementation of practical measures to guarantee test accuracy and genetic information. © 2017 S. Karger AG, Basel.

Data Integration for Microarrays: Enhanced Inference for Gene Regulatory Networks

Directory of Open Access Journals (Sweden)

Alina Sîrbu

2015-05-01

Full Text Available Microarray technologies have been the basis of numerous important findings regarding gene expression in the few last decades. Studies have generated large amounts of data describing various processes, which, due to the existence of public databases, are widely available for further analysis. Given their lower cost and higher maturity compared to newer sequencing technologies, these data continue to be produced, even though data quality has been the subject of some debate. However, given the large volume of data generated, integration can help overcome some issues related, e.g., to noise or reduced time resolution, while providing additional insight on features not directly addressed by sequencing methods. Here, we present an integration test case based on public Drosophila melanogaster datasets (gene expression, binding site affinities, known interactions. Using an evolutionary computation framework, we show how integration can enhance the ability to recover transcriptional gene regulatory networks from these data, as well as indicating which data types are more important for quantitative and qualitative network inference. Our results show a clear improvement in performance when multiple datasets are integrated, indicating that microarray data will remain a valuable and viable resource for some time to come.

Data Integration for Microarrays: Enhanced Inference for Gene Regulatory Networks.

Science.gov (United States)

Sîrbu, Alina; Crane, Martin; Ruskin, Heather J

2015-05-14

Microarray technologies have been the basis of numerous important findings regarding gene expression in the few last decades. Studies have generated large amounts of data describing various processes, which, due to the existence of public databases, are widely available for further analysis. Given their lower cost and higher maturity compared to newer sequencing technologies, these data continue to be produced, even though data quality has been the subject of some debate. However, given the large volume of data generated, integration can help overcome some issues related, e.g., to noise or reduced time resolution, while providing additional insight on features not directly addressed by sequencing methods. Here, we present an integration test case based on public Drosophila melanogaster datasets (gene expression, binding site affinities, known interactions). Using an evolutionary computation framework, we show how integration can enhance the ability to recover transcriptional gene regulatory networks from these data, as well as indicating which data types are more important for quantitative and qualitative network inference. Our results show a clear improvement in performance when multiple datasets are integrated, indicating that microarray data will remain a valuable and viable resource for some time to come.

On promotion of base technologies of atomic energy. Aiming at breakthrough in atomic energy technologies in 21st century

Energy Technology Data Exchange (ETDEWEB)

1988-09-01

In the long term plan of atomic energy development and utilization decided in June, 1987 by the Atomic Energy Commission, it was recognized that hereafter, the opening-up of the new potential that atomic energy possesses should be aimed at, and the policy was shown so that the research and development hereafter place emphasis on the creative and innovative region which causes large technical innovation, by which the spreading effect to general science and technology can be expected, and the development of the base technologies that connect the basic research and project development is promoted. The trend of atomic energy development so far, the change of the situation surrounding atomic energy, the direction of technical development of atomic energy hereafter and the base technologies are discussed. The concept of the technical development of materilas, artificial intelligence, lasers, and the evaluation and reduction of radiation risks used for atomic energy is described. As the development plan of atomic energy base technologies, the subjects of technical development, the future image of technical development, the efficient promotion of the development and so on are shown. (Kato, I.).

Gene Editing With CRISPR/Cas9 RNA-Directed Nuclease.

Science.gov (United States)

Doetschman, Thomas; Georgieva, Teodora

2017-03-03

Genetic engineering of model organisms and cultured cells has for decades provided important insights into the mechanisms underlying cardiovascular development and disease. In the past few years the development of several nuclease systems has broadened the range of model/cell systems that can be engineered. Of these, the CRISPR (clustered regularly interspersed short palindromic repeats)/Cas9 (CRISPR-associated protein 9) system has become the favorite for its ease of application. Here we will review this RNA-guided nuclease system for gene editing with respect to its usefulness for cardiovascular studies and with an eye toward potential therapy. Studies on its off-target activity, along with approaches to minimize this activity will be given. The advantages of gene editing versus gene targeting in embryonic stem cells, including the breadth of species and cell types to which it is applicable, will be discussed. We will also cover its use in iPSC for research and possible therapeutic purposes; and we will review its use in muscular dystrophy studies where considerable progress has been made toward dystrophin correction in mice. The CRISPR/Ca9s system is also being used for high-throughput screening of genes, gene regulatory regions, and long noncoding RNAs. In addition, the CRISPR system is being used for nongene-editing purposes such as activation and inhibition of gene expression, as well as for fluorescence tagging of chromosomal regions and individual mRNAs to track their cellular location. Finally, an approach to circumvent the inability of post-mitotic cells to support homologous recombination-based gene editing will be presented. In conclusion, applications of the CRISPR/Cas system are expanding at a breath-taking pace and are revolutionizing approaches to gain a better understanding of human diseases. © 2017 American Heart Association, Inc.

Is gene technology in agriculture able to prevent hunger in the world?

NARCIS (Netherlands)

Goewie, E.A.

2002-01-01

The worldpopulation grows rapidly: the number of mouths to feed increases. Is ar agriculture without gene technology able to produce sufficiently in order to prevent hunger? Research indicates that hunger is not the result of short comings in agricultural outputs. It is however the result of

Ethical issues of CRISPR technology and gene editing through the lens of solidarity.

Science.gov (United States)

Mulvihill, John J; Capps, Benjamin; Joly, Yann; Lysaght, Tamra; Zwart, Hub A E; Chadwick, Ruth

2017-06-01

The avalanche of commentaries on CRISPR-Cas9 technology, a bacterial immune system modified to recognize any short DNA sequence, cut it out, and insert a new one, has rekindled hopes for gene therapy and other applications and raised criticisms of engineering genes in future generations. This discussion draws on articles that emphasize ethics, identified partly through PubMed and Google, 2014-2016. CRISPR-Cas9 has taken the pace and prospects for genetic discovery and applications to a high level, stoking anticipation for somatic gene engineering to help patients. We support a moratorium on germ line manipulation. We place increased emphasis on the principle of solidarity and the public good. The genetic bases of some diseases are not thoroughly addressable with CRISPR-Cas9. We see no new ethical issues, compared with gene therapy and genetic engineering in general, apart from the explosive rate of findings. Other controversies include eugenics, patentability and unrealistic expectations of professionals and the public. Biggest issues are the void of research on human germ cell biology, the appropriate routes for oversight and transparency, and the scientific and ethical areas of reproductive medicine. The principle of genomic solidarity and priority on public good should be a lens for bringing clarity to CRISPR debates. The valid claim of genetic exceptionalism supports restraint on experimentation in human germ cells, given the trans-generational dangers and the knowledge gap in germ cell biology. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

DNA base sequence changes induced by ultraviolet light mutagenesis of a gene on a chromosome in Chinese hamster ovary cells

Energy Technology Data Exchange (ETDEWEB)

Romac, S; Leong, P; Sockett, H; Hutchinson, F [Yale Univ., New Haven, CT (USA). Dept. of Molecular Biophysics and Biochemistry

1989-09-20

The DNA base sequence changes induced by mutagenesis with ultraviolet light have been determined in a gene on a chromosome of cultured Chinese hamster ovary (CHO) cells. The gene was the Excherichia coli gpt gene, of which a single copy was stably incorporated and expressed in the CHO cell genome. The cells were irradiated with ultraviolet light and gpt{sup -} colonies were selected by resistance to 6-thioguanine. The gpt gene was amplified from chromosomal DNA by use of the polymerase chain reaction (PCR) and the amplified DNA sequenced directly by the dideoxy method. Of the 58 sequenced mutants of independent origin 53 were base change mutations. Forty-one base substitutions were single base changes, ten had two adjacent (or tandem) base changes, and one had two base changes separated by a single base-pair. Only one mutant had a multiple base change mutation with two or more well separated base changes. In contrast much higher levels of such mutations were reported in ultraviolet mutagenesis of genes on a shuttle vector in primate cells. Two deletions of a single base-pair were observed and three deletions ranging from 6 to 37 base-pairs. The mutation spectrum in the gpt gene had similarities to the ultraviolet mutation spectra for several genes in prokaryotes, which suggests similarities in mutational mechanisms in prokaryotes and eukaryotes. (author).

Producer firms, technology diffusion and spillovers to local suppliers : Examining the effects of Foreign Direct Investment and the technology gap

NARCIS (Netherlands)

Jordaan, J.A.

2017-01-01

In this paper, we conduct a detailed examination of the effects of Foreign Direct Investment (FDI) and the technology gap on local technology dissemination and spillovers. Using unique firm level data from surveys among FDI firms and domestic producer firms and a random sample of their suppliers in

Direct effect of ownership and technology import: Firm level evidence from large and medium-enterprises in Shanghai

Institute of Scientific and Technical Information of China (English)

ZHU Pingfang; LI Lei

2007-01-01

This paper explores the direct effect of ownership and technology imports under the fiamework of neoclassical economic theory.The econometric analysis is based on panel data from a random sample of large and mediumenterprises in Shanghai,during the period of 1998 to 2003.The results show that Sino-foreign joint ventures,Sino-foralgn cooperative enterprises and foreignfunded enterprises (SANZI) enjoy higher labor productivity and total factor productlvity (TFP) than domestic enterprises.Intra-firm diffusion of non-codified technology,proxied by ovwnership,is the main source of their better performance,whereas internally transferred codified technology makes little contribution to TFP.For state-owned enterprises,codified technology imports have significantly raised both labor productivity and TFP,but such positive effect is significantly dependent on the S&T human resource.In contrast,no evidence supports that introduction of foreign technology has enhanced the productivity in domestic nonstate-owned enterprises.The empirical results indicate that SANZI do not have a distinct advantage in their codified technology.In addition,inadequate investment in assimilation process and research and development together with inefficient management of science and technology activities,may impede the use of imported technology.

Hypoxia-response element (HRE)-directed transcriptional regulation of the rat lysyl oxidase gene in response to cobalt and cadmium.

Science.gov (United States)

Gao, Song; Zhou, Jing; Zhao, Yinzhi; Toselli, Paul; Li, Wande

2013-04-01

Lysyl oxidase (LO) catalyzes crosslink of collagen, elastin, and histone H1, stabilizing the extracellular matrix and cell nucleus. This enzyme displays dual functions for tumorigenesis, i.e., as a tumor suppressor inactivating the ras oncogene and as a tumor promoter enhancing malignant cell metastasis. To elucidate LO transcriptional regulation, we have cloned the 804 base pair region upstream of the translation start site (ATG) of the rat LO gene with the maximal promoter activity. Computer analysis indicated that at least four hypoxia-response element (HRE) consensuses (5'-ACGTG-3') exist in the cloned LO promoter. Treatment of rat lung fibroblasts (RFL6) with CoCl2 (Co, 10-100 μM), a chemical hypoxia reagent, enhanced LO mRNA expression and promoter activities. Overexpression of LO was associated with upregulation of hypoxia-inducible factor (HIF)-1α at mRNA levels in cobalt (Co)-treated cells. Thus, LO is a hypoxia-responsive gene. Dominant negative-HIF-1α inhibited LO promoter activities stimulated by Co. Electrophoretic mobility shift, oligonucleotide competition, and in vitro translated HIF-1α binding assays indicated that only one HRE mapped at -387/-383 relative to ATG was functionally active among four consensuses. Site-directed mutation of this HRE significantly diminished the Co-induced and LO promoter-directed expression of the reporter gene. Cadmium (Cd), an inducer of reactive oxygen species, inhibited HIF-1α mRNA expression and HIF-1α binding to the LO gene in Co-treated cells as revealed by RT-PCR and ChIP assays, respectively. Thus, modulation of the HRE activity by Co and Cd plays a critical role in LO gene transactivation.

Effects of Assisted Reproduction Technology on Placental Imprinted Gene Expression

Science.gov (United States)

Katagiri, Yukiko; Aoki, Chizu; Tamaki-Ishihara, Yuko; Fukuda, Yusuke; Kitamura, Mamoru; Matsue, Yoichi; So, Akiko; Morita, Mineto

2010-01-01

We used placental tissue to compare the imprinted gene expression of IGF2, H19, KCNQ1OT1, and CDKN1C of singletons conceived via assisted reproduction technology (ART) with that of spontaneously conceived (SC) singletons. Of 989 singletons examined (ART n = 65; SC n = 924), neonatal weight was significantly lower (P < .001) in the ART group than in the SC group, but placental weight showed no significant difference. Gene expression analyzed by real-time PCR was similar for both groups with appropriate-for-date (AFD) birth weight. H19 expression was suppressed in fetal growth retardation (FGR) cases in the ART and SC groups compared with AFD cases (P < .02 and P < .05, resp.). In contrast, CDKN1C expression was suppressed in FGR cases in the ART group (P < .01), while KCNQ1OT1 expression was hyperexpressed in FGR cases in the SC group (P < .05). As imprinted gene expression patterns differed between the ART and SC groups, we speculate that ART modifies epigenetic status even though the possibilities always exist. PMID:20706653

Self-Directed Learning: College Students' Technology Preparedness Change in the Last 10 Years

Science.gov (United States)

Caravello, Michael J.; Jiménez, Joel R.; Kahl, Lois J.; Brachio, Brian; Morote, Elsa-Sofia

2015-01-01

This study compares a sample of approximately 44 first year college students in 2005 and 2015 on Long Island, New York, in their technology preparedness and self-directed instruction. The researchers used a survey instrument including demographic information focused upon students' preparation for classroom technology in high school and college.…

Novel enabling technologies of gene isolation and plant transformation for improved crop protection

Energy Technology Data Exchange (ETDEWEB)

Torok, Tamas

2013-02-04

Meeting the needs of agricultural producers requires the continued development of improved transgenic crop protection products. The completed project focused on developing novel enabling technologies of gene discovery and plant transformation to facilitate the generation of such products.

Gene therapy prospects--intranasal delivery of therapeutic genes.

Science.gov (United States)

Podolska, Karolina; Stachurska, Anna; Hajdukiewicz, Karolina; Małecki, Maciej

2012-01-01

Gene therapy is recognized to be a novel method for the treatment of various disorders. Gene therapy strategies involve gene manipulation on broad biological processes responsible for the spreading of diseases. Cancer, monogenic diseases, vascular and infectious diseases are the main targets of gene therapy. In order to obtain valuable experimental and clinical results, sufficient gene transfer methods are required. Therapeutic genes can be administered into target tissues via gene carriers commonly defined as vectors. The retroviral, adenoviral and adeno-associated virus based vectors are most frequently used in the clinic. So far, gene preparations may be administered directly into target organs or by intravenous, intramuscular, intratumor or intranasal injections. It is common knowledge that the number of gene therapy clinical trials has rapidly increased. However, some limitations such as transfection efficiency and stable and long-term gene expression are still not resolved. Consequently, great effort is focused on the evaluation of new strategies of gene delivery. There are many expectations associated with intranasal delivery of gene preparations for the treatment of diseases. Intranasal delivery of therapeutic genes is regarded as one of the most promising forms of pulmonary gene therapy research. Gene therapy based on inhalation of gene preparations offers an alternative way for the treatment of patients suffering from such lung diseases as cystic fibrosis, alpha-1-antitrypsin defect, or cancer. Experimental and first clinical trials based on plasmid vectors or recombinant viruses have revealed that gene preparations can effectively deliver therapeutic or marker genes to the cells of the respiratory tract. The noninvasive intranasal delivery of gene preparations or conventional drugs seems to be very encouraging, although basic scientific research still has to continue.

Identification of a gene expression profile that discriminates indirect-acting genotoxins from direct-acting genotoxins

Energy Technology Data Exchange (ETDEWEB)

Hu Ting; Gibson, David P.; Carr, Gregory J.; Torontali, Suzanne M.; Tiesman, Jay P.; Chaney, Joel G.; Aardema, Marilyn J

2004-05-18

During the safety evaluation process of new drugs and chemicals, a battery of genotoxicity tests is conducted starting with in vitro genotoxicity assays. Obtaining positive results in in vitro genotoxicity tests is not uncommon. Follow-up studies to determine the biological relevance of positive genotoxicity results are costly, time consuming, and utilize animals. More efficient methods, especially for identifying a putative mode of action like an indirect mechanism of genotoxicity (where DNA molecules are not the initial primary targets), would greatly improve the risk assessment for genotoxins. To this end, we are participating in an International Life Sciences Institute (ILSI) project involving studies of gene expression changes caused by model genotoxins. The purpose of the work is to evaluate gene expression tools in general, and specifically for discriminating genotoxins that are direct-acting from indirect-acting. Our lab has evaluated gene expression changes as well as micronuclei (MN) in L5178Y TK{sup +/-} mouse lymphoma cells treated with six compounds. Direct-acting genotoxins (where DNA is the initial primary target) that were evaluated included the DNA crosslinking agents, mitomycin C (MMC) and cisplatin (CIS), and an alkylating agent, methyl methanesulfonate (MMS). Indirect-acting genotoxins included hydroxyurea (HU), a ribonucleotide reductase inhibitor, taxol (TXL), a microtubule inhibitor, and etoposide (ETOP), a DNA topoisomerase II inhibitor. Microarray gene expression analysis was conducted using Affymetrix mouse oligonucleotide arrays on RNA samples derived from cells which were harvested immediately after the 4 h chemical treatment, and 20 h after the 4 h chemical treatment. The evaluation of these experimental results yields evidence of differentially regulated genes at both 4 and 24 h time points that appear to have discriminating power for direct versus indirect genotoxins, and therefore may serve as a fingerprint for classifying chemicals

A Simplified Method for Gene Knockout and Direct Screening of Recombinant Clones for Application in Paenibacillus polymyxa.

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Seong-Bin Kim

Full Text Available Paenibacillus polymyxa is a bacterium widely used in agriculture, industry, and environmental remediation because it has multiple functions including nitrogen fixation and produces various biologically active compounds. Among these compounds are the antibiotics polymyxins, and the bacterium is currently being reassessed for medical application. However, a lack of genetic tools for manipulation of P. polymyxa has limited our understanding of the biosynthesis of these compounds.To facilitate an understanding of the genetic determinants of the bacterium, we have developed a system for marker exchange mutagenesis directly on competent cells of P. polymyxa under conditions where homologous recombination is enhanced by denaturation of the suicide plasmid DNA. To test this system, we targeted P. polymyxa α-and β-amylase genes for disruption. Chloramphenicol or erythromycin resistance genes were inserted into the suicide plasmid pGEM7Z-f+ (Promega. To mediate homologous recombination and replacement of the targeted genes with the antibiotic resistance genes nucleotide sequences of the α-and β-amylase genes were cloned into the plasmid flanking the antibiotic resistance genes.We have created a simple system for targeted gene deletion in P. polymyxa E681. We propose that P. polymyxa isogenic mutants could be developed using this system of marker exchange mutagenesis. α-and β-amylase genes provide a useful tool for direct recombinant screening in P. polymyxa.

Semantic Disease Gene Embeddings (SmuDGE): phenotype-based disease gene prioritization without phenotypes

KAUST Repository

AlShahrani, Mona; Hoehndorf, Robert

2018-01-01

In the past years, several methods have been developed to incorporate information about phenotypes into computational disease gene prioritization methods. These methods commonly compute the similarity between a disease's (or patient's) phenotypes and a database of gene-to-phenotype associations to find the phenotypically most similar match. A key limitation of these methods is their reliance on knowledge about phenotypes associated with particular genes which is highly incomplete in humans as well as in many model organisms such as the mouse. Results: We developed SmuDGE, a method that uses feature learning to generate vector-based representations of phenotypes associated with an entity. SmuDGE can be used as a trainable semantic similarity measure to compare two sets of phenotypes (such as between a disease and gene, or a disease and patient). More importantly, SmuDGE can generate phenotype representations for entities that are only indirectly associated with phenotypes through an interaction network; for this purpose, SmuDGE exploits background knowledge in interaction networks comprising of multiple types of interactions. We demonstrate that SmuDGE can match or outperform semantic similarity in phenotype-based disease gene prioritization, and furthermore significantly extends the coverage of phenotype-based methods to all genes in a connected interaction network.

Semantic Disease Gene Embeddings (SmuDGE): phenotype-based disease gene prioritization without phenotypes

KAUST Repository

Alshahrani, Mona

2018-04-30

In the past years, several methods have been developed to incorporate information about phenotypes into computational disease gene prioritization methods. These methods commonly compute the similarity between a disease\\'s (or patient\\'s) phenotypes and a database of gene-to-phenotype associations to find the phenotypically most similar match. A key limitation of these methods is their reliance on knowledge about phenotypes associated with particular genes which is highly incomplete in humans as well as in many model organisms such as the mouse. Results: We developed SmuDGE, a method that uses feature learning to generate vector-based representations of phenotypes associated with an entity. SmuDGE can be used as a trainable semantic similarity measure to compare two sets of phenotypes (such as between a disease and gene, or a disease and patient). More importantly, SmuDGE can generate phenotype representations for entities that are only indirectly associated with phenotypes through an interaction network; for this purpose, SmuDGE exploits background knowledge in interaction networks comprising of multiple types of interactions. We demonstrate that SmuDGE can match or outperform semantic similarity in phenotype-based disease gene prioritization, and furthermore significantly extends the coverage of phenotype-based methods to all genes in a connected interaction network.

Developing strategies for detection of gene doping.

Science.gov (United States)

Baoutina, Anna; Alexander, Ian E; Rasko, John E J; Emslie, Kerry R

2008-01-01

It is feared that the use of gene transfer technology to enhance athletic performance, the practice that has received the term 'gene doping', may soon become a real threat to the world of sport. As recognised by the anti-doping community, gene doping, like doping in any form, undermines principles of fair play in sport and most importantly, involves major health risks to athletes who partake in gene doping. One attraction of gene doping for such athletes and their entourage lies in the apparent difficulty of detecting its use. Since the realisation of the threat of gene doping to sport in 2001, the anti-doping community and scientists from different disciplines concerned with potential misuse of gene therapy technologies for performance enhancement have focused extensive efforts on developing robust methods for gene doping detection which could be used by the World Anti-Doping Agency to monitor athletes and would meet the requirements of a legally defensible test. Here we review the approaches and technologies which are being evaluated for the detection of gene doping, as well as for monitoring the efficacy of legitimate gene therapy, in relation to the detection target, the type of sample required for analysis and detection methods. We examine the accumulated knowledge on responses of the body, at both cellular and systemic levels, to gene transfer and evaluate strategies for gene doping detection based on current knowledge of gene technology, immunology, transcriptomics, proteomics, biochemistry and physiology. (c) 2008 John Wiley & Sons, Ltd.

Gene-set analysis based on the pharmacological profiles of drugs to identify repurposing opportunities in schizophrenia.

Science.gov (United States)

de Jong, Simone; Vidler, Lewis R; Mokrab, Younes; Collier, David A; Breen, Gerome

2016-08-01

Genome-wide association studies (GWAS) have identified thousands of novel genetic associations for complex genetic disorders, leading to the identification of potential pharmacological targets for novel drug development. In schizophrenia, 108 conservatively defined loci that meet genome-wide significance have been identified and hundreds of additional sub-threshold associations harbour information on the genetic aetiology of the disorder. In the present study, we used gene-set analysis based on the known binding targets of chemical compounds to identify the 'drug pathways' most strongly associated with schizophrenia-associated genes, with the aim of identifying potential drug repositioning opportunities and clues for novel treatment paradigms, especially in multi-target drug development. We compiled 9389 gene sets (2496 with unique gene content) and interrogated gene-based p-values from the PGC2-SCZ analysis. Although no single drug exceeded experiment wide significance (corrected pneratinib. This is a proof of principle analysis showing the potential utility of GWAS data of schizophrenia for the direct identification of candidate drugs and molecules that show polypharmacy. © The Author(s) 2016.

Educational technology in medical education.

Science.gov (United States)

Han, Heeyoung; Resch, David S; Kovach, Regina A

2013-01-01

This article aims to review the past practices of educational technology and envision future directions for medical education. The discussion starts with a historical review of definitions and perspectives of educational technology, in which the authors propose that educators adopt a broader process-oriented understanding of educational technology. Future directions of e-learning, simulation, and health information technology are discussed based on a systems view of the technological process. As new technologies continue to arise, this process-oriented understanding and outcome-based expectations of educational technology should be embraced. With this view, educational technology should be valued in terms of how well the technological process informs and facilitates learning, and the acquisition and maintenance of clinical expertise.

Inference of time-delayed gene regulatory networks based on dynamic Bayesian network hybrid learning method.

Science.gov (United States)

Yu, Bin; Xu, Jia-Meng; Li, Shan; Chen, Cheng; Chen, Rui-Xin; Wang, Lei; Zhang, Yan; Wang, Ming-Hui

2017-10-06

Gene regulatory networks (GRNs) research reveals complex life phenomena from the perspective of gene interaction, which is an important research field in systems biology. Traditional Bayesian networks have a high computational complexity, and the network structure scoring model has a single feature. Information-based approaches cannot identify the direction of regulation. In order to make up for the shortcomings of the above methods, this paper presents a novel hybrid learning method (DBNCS) based on dynamic Bayesian network (DBN) to construct the multiple time-delayed GRNs for the first time, combining the comprehensive score (CS) with the DBN model. DBNCS algorithm first uses CMI2NI (conditional mutual inclusive information-based network inference) algorithm for network structure profiles learning, namely the construction of search space. Then the redundant regulations are removed by using the recursive optimization algorithm (RO), thereby reduce the false positive rate. Secondly, the network structure profiles are decomposed into a set of cliques without loss, which can significantly reduce the computational complexity. Finally, DBN model is used to identify the direction of gene regulation within the cliques and search for the optimal network structure. The performance of DBNCS algorithm is evaluated by the benchmark GRN datasets from DREAM challenge as well as the SOS DNA repair network in Escherichia coli , and compared with other state-of-the-art methods. The experimental results show the rationality of the algorithm design and the outstanding performance of the GRNs.

Subgenomic Diversity Patterns Caused by Directional Selection in Bread Wheat Gene Pools

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Kai Voss-Fels

2015-07-01

Full Text Available Genetic diversity represents the fundamental key to breeding success, providing the basis for breeders to select varieties with constantly improving yield performance. On the other hand, strong selection during domestication and breeding have eliminated considerable genetic diversity in the breeding pools of major crops, causing erosion of genetic potential for adaptation to emerging challenges like climate change. High-throughput genomic technologies can address this dilemma by providing detailed knowledge to characterize and replenish genetic diversity in breeding programs. In hexaploid bread wheat ( L., the staple food for 35% of the world’s population, bottlenecks during allopolyploidisation followed by strong artificial selection have considerably narrowed diversity to the extent that yields in many regions appear to be unexpectedly stagnating. In this study, we used a 90,000 single nucleotide polymorphism (SNP wheat genotyping array to assay high-frequency, polymorphic SNP markers in 460 accessions representing different phenological diversity groups from Asian, Australian, European, and North American bread wheat breeding materials. Detailed analysis of subgroup diversity at the chromosome and subgenome scale revealed highly distinct patterns of conserved linkage disequilibrium between different gene pools. The data enable identification of genome regions in most need of rejuvenation with novel diversity and provide a high-resolution molecular basis for genomic-assisted introgression of new variation into chromosome segments surrounding directionally selected metaloci conferring important adaptation and quality traits.

Youth, Technology and HIV: Recent Advances and Future Directions

Science.gov (United States)

Hightow-Weidman, Lisa B.; Muessig, Kathryn E.; Bauermeister, Jose; Zhang, Chen; LeGrand, Sara

2015-01-01

Technology, including mobile technologies and social media, offers powerful tools to reach, engage, and retain youth and young adults in HIV prevention and care interventions both in the United States and globally. In this report we focus on HIV, technology, and youth, presenting a synthesis of recently published (Jan 2014-May 2015) observational and experimental studies relevant for understanding and intervening on HIV risk, prevention and care. We present findings from a selection of the 66 relevant citations identified, highlighting studies that demonstrate a novel approach to technology interventions among youth in regard to content, delivery, target population or public health impact. We discuss current trends globally and in the US in how youth are using technology, as well as emergent research issues in this field – including the need for new theories for developing technology-based HIV interventions and new metrics of engagement, exposure, and evaluation. PMID:26385582

Dual CRISPR-Cas9 Cleavage Mediated Gene Excision and Targeted Integration in Yarrowia lipolytica.

Science.gov (United States)

Gao, Difeng; Smith, Spencer; Spagnuolo, Michael; Rodriguez, Gabriel; Blenner, Mark

2018-05-29

CRISPR-Cas9 technology has been successfully applied in Yarrowia lipolytica for targeted genomic editing including gene disruption and integration; however, disruptions by existing methods typically result from small frameshift mutations caused by indels within the coding region, which usually resulted in unnatural protein. In this study, a dual cleavage strategy directed by paired sgRNAs is developed for gene knockout. This method allows fast and robust gene excision, demonstrated on six genes of interest. The targeted regions for excision vary in length from 0.3 kb up to 3.5 kb and contain both non-coding and coding regions. The majority of the gene excisions are repaired by perfect nonhomologous end-joining without indel. Based on this dual cleavage system, two targeted markerless integration methods are developed by providing repair templates. While both strategies are effective, homology mediated end joining (HMEJ) based method are twice as efficient as homology recombination (HR) based method. In both cases, dual cleavage leads to similar or improved gene integration efficiencies compared to gene excision without integration. This dual cleavage strategy will be useful for not only generating more predictable and robust gene knockout, but also for efficient targeted markerless integration, and simultaneous knockout and integration in Y. lipolytica. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Characterization of Genes for Beef Marbling Based on Applying Gene Coexpression Network

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Dajeong Lim

2014-01-01

Full Text Available Marbling is an important trait in characterization beef quality and a major factor for determining the price of beef in the Korean beef market. In particular, marbling is a complex trait and needs a system-level approach for identifying candidate genes related to the trait. To find the candidate gene associated with marbling, we used a weighted gene coexpression network analysis from the expression value of bovine genes. Hub genes were identified; they were topologically centered with large degree and BC values in the global network. We performed gene expression analysis to detect candidate genes in M. longissimus with divergent marbling phenotype (marbling scores 2 to 7 using qRT-PCR. The results demonstrate that transmembrane protein 60 (TMEM60 and dihydropyrimidine dehydrogenase (DPYD are associated with increasing marbling fat. We suggest that the network-based approach in livestock may be an important method for analyzing the complex effects of candidate genes associated with complex traits like marbling or tenderness.

A Model-Based Joint Identification of Differentially Expressed Genes and Phenotype-Associated Genes

Science.gov (United States)

Seo, Minseok; Shin, Su-kyung; Kwon, Eun-Young; Kim, Sung-Eun; Bae, Yun-Jung; Lee, Seungyeoun; Sung, Mi-Kyung; Choi, Myung-Sook; Park, Taesung

2016-01-01

Over the last decade, many analytical methods and tools have been developed for microarray data. The detection of differentially expressed genes (DEGs) among different treatment groups is often a primary purpose of microarray data analysis. In addition, association studies investigating the relationship between genes and a phenotype of interest such as survival time are also popular in microarray data analysis. Phenotype association analysis provides a list of phenotype-associated genes (PAGs). However, it is sometimes necessary to identify genes that are both DEGs and PAGs. We consider the joint identification of DEGs and PAGs in microarray data analyses. The first approach we used was a naïve approach that detects DEGs and PAGs separately and then identifies the genes in an intersection of the list of PAGs and DEGs. The second approach we considered was a hierarchical approach that detects DEGs first and then chooses PAGs from among the DEGs or vice versa. In this study, we propose a new model-based approach for the joint identification of DEGs and PAGs. Unlike the previous two-step approaches, the proposed method identifies genes simultaneously that are DEGs and PAGs. This method uses standard regression models but adopts different null hypothesis from ordinary regression models, which allows us to perform joint identification in one-step. The proposed model-based methods were evaluated using experimental data and simulation studies. The proposed methods were used to analyze a microarray experiment in which the main interest lies in detecting genes that are both DEGs and PAGs, where DEGs are identified between two diet groups and PAGs are associated with four phenotypes reflecting the expression of leptin, adiponectin, insulin-like growth factor 1, and insulin. Model-based approaches provided a larger number of genes, which are both DEGs and PAGs, than other methods. Simulation studies showed that they have more power than other methods. Through analysis of

A Model-Based Joint Identification of Differentially Expressed Genes and Phenotype-Associated Genes.

Directory of Open Access Journals (Sweden)

Samuel Sunghwan Cho

Full Text Available Over the last decade, many analytical methods and tools have been developed for microarray data. The detection of differentially expressed genes (DEGs among different treatment groups is often a primary purpose of microarray data analysis. In addition, association studies investigating the relationship between genes and a phenotype of interest such as survival time are also popular in microarray data analysis. Phenotype association analysis provides a list of phenotype-associated genes (PAGs. However, it is sometimes necessary to identify genes that are both DEGs and PAGs. We consider the joint identification of DEGs and PAGs in microarray data analyses. The first approach we used was a naïve approach that detects DEGs and PAGs separately and then identifies the genes in an intersection of the list of PAGs and DEGs. The second approach we considered was a hierarchical approach that detects DEGs first and then chooses PAGs from among the DEGs or vice versa. In this study, we propose a new model-based approach for the joint identification of DEGs and PAGs. Unlike the previous two-step approaches, the proposed method identifies genes simultaneously that are DEGs and PAGs. This method uses standard regression models but adopts different null hypothesis from ordinary regression models, which allows us to perform joint identification in one-step. The proposed model-based methods were evaluated using experimental data and simulation studies. The proposed methods were used to analyze a microarray experiment in which the main interest lies in detecting genes that are both DEGs and PAGs, where DEGs are identified between two diet groups and PAGs are associated with four phenotypes reflecting the expression of leptin, adiponectin, insulin-like growth factor 1, and insulin. Model-based approaches provided a larger number of genes, which are both DEGs and PAGs, than other methods. Simulation studies showed that they have more power than other methods

Rapid direct identification of Cryptococcus neoformans from pigeon droppings by nested PCR using CNLAC1 gene.

Science.gov (United States)

Chae, H S; Park, G N; Kim, S H; Jo, H J; Kim, J T; Jeoung, H Y; An, D J; Kim, N H; Shin, B W; Kang, Y I; Chang, K S

2012-08-01

Isolation and identification of Cryptococcus neoformans and pathogenic yeast-like fungi from pigeon droppings has been taken for a long time and requires various nutrients for its growth. In this study, we attempted to establish a rapid direct identification method of Cr. neoformans from pigeon dropping samples by nested-PCR using internal transcribed spacer (ITS) CAP64 and CNLAC1 genes, polysaccharide capsule gene and laccase-associated gene to produce melanin pigment, respectively, which are common genes of yeasts. The ITS and CAP64 genes were amplified in all pathogenic yeasts, but CNLAC1 was amplified only in Cr. neoformans. The ITS gene was useful for yeast genotyping depending on nucleotide sequence. Homology of CAP64 genes among the yeasts were very high. The specificity of PCR using CNLAC1 was demonstrated in Cr. neoformans environmental strains but not in other yeast-like fungi. The CNLAC1 gene was detected in 5 serotypes of Cr. neoformans. The nested-PCR amplified up to 10(-11) μg of the genomic DNA and showed high sensitivity. All pigeon droppings among 31 Cr. neoformans-positive samples were positive and all pigeon droppings among 348 Cr. neoformans-negative samples were negative by the direct nested-PCR. In addition, after primary enrichment of pigeon droppings in Sabouraud dextrose broth, all Cr. neoformans-negative samples were negative by the nested-PCR, which showed high specificity. The nested-PCR showed high sensitivity without culture of pigeon droppings. Nested-PCR using CNLAC1 provides a rapid and reliable molecular diagnostic method to overcome weak points such as long culture time of many conventional methods.

Predicting Essential Genes and Proteins Based on Machine Learning and Network Topological Features: A Comprehensive Review

Science.gov (United States)

Zhang, Xue; Acencio, Marcio Luis; Lemke, Ney

2016-01-01

Essential proteins/genes are indispensable to the survival or reproduction of an organism, and the deletion of such essential proteins will result in lethality or infertility. The identification of essential genes is very important not only for understanding the minimal requirements for survival of an organism, but also for finding human disease genes and new drug targets. Experimental methods for identifying essential genes are costly, time-consuming, and laborious. With the accumulation of sequenced genomes data and high-throughput experimental data, many computational methods for identifying essential proteins are proposed, which are useful complements to experimental methods. In this review, we show the state-of-the-art methods for identifying essential genes and proteins based on machine learning and network topological features, point out the progress and limitations of current methods, and discuss the challenges and directions for further research. PMID:27014079

Directed evolution induces tributyrin hydrolysis in a virulence factor of Xylella fastidiosa using a duplicated gene as a template.

Science.gov (United States)

Gouran, Hossein; Chakraborty, Sandeep; Rao, Basuthkar J; Asgeirsson, Bjarni; Dandekar, Abhaya

2014-01-01

Duplication of genes is one of the preferred ways for natural selection to add advantageous functionality to the genome without having to reinvent the wheel with respect to catalytic efficiency and protein stability. The duplicated secretory virulence factors of Xylella fastidiosa (LesA, LesB and LesC), implicated in Pierce's disease of grape and citrus variegated chlorosis of citrus species, epitomizes the positive selection pressures exerted on advantageous genes in such pathogens. A deeper insight into the evolution of these lipases/esterases is essential to develop resistance mechanisms in transgenic plants. Directed evolution, an attempt to accelerate the evolutionary steps in the laboratory, is inherently simple when targeted for loss of function. A bigger challenge is to specify mutations that endow a new function, such as a lost functionality in a duplicated gene. Previously, we have proposed a method for enumerating candidates for mutations intended to transfer the functionality of one protein into another related protein based on the spatial and electrostatic properties of the active site residues (DECAAF). In the current work, we present in vivo validation of DECAAF by inducing tributyrin hydrolysis in LesB based on the active site similarity to LesA. The structures of these proteins have been modeled using RaptorX based on the closely related LipA protein from Xanthomonas oryzae. These mutations replicate the spatial and electrostatic conformation of LesA in the modeled structure of the mutant LesB as well, providing in silico validation before proceeding to the laborious in vivo work. Such focused mutations allows one to dissect the relevance of the duplicated genes in finer detail as compared to gene knockouts, since they do not interfere with other moonlighting functions, protein expression levels or protein-protein interaction.

Acute TNF-induced repression of cell identity genes is mediated by NFκB-directed redistribution of cofactors from super-enhancers

DEFF Research Database (Denmark)

Schmidt, Søren Fisker; Larsen, Bjørk Ditlev; Loft, Anne

2015-01-01

The proinflammatory cytokine tumor necrosis factor (TNF) plays a central role in low-grade adipose tissue inflammation and development of insulin resistance during obesity. In this context, nuclear factor κ-light-chain-enhancer of activated B cells (NFκB) is directly involved and required for the...... specifically repressing super-enhancer-associated cell identity genes....... binding to the associated enhancers but rather loss of cofactors and enhancer RNA (eRNA) selectively from high-occupancy sites within super-enhancers. Based on these data, we have developed models that, with high accuracy, predict which enhancers and genes are repressed by TNF in adipocytes. We show...... that these models are applicable to other cell types where TNF represses genes associated with super-enhancers in a highly cell-type-specific manner. Our results propose a novel paradigm for NFκB-mediated repression, whereby NFκB selectively redistributes cofactors from high-occupancy enhancers, thereby...

Development of gene diagnosis for diabetes and cholecystis based on gene analysis of CCK-A receptor

International Nuclear Information System (INIS)

Kono, Akira

1998-01-01

The gene structures of CCK, A type receptor in human, the rat and the mouse were investigated aiming to clarify that the aberration of the gene is involved in the incidences of diabetes and cholecystis. In this fiscal year, 1997, the normal structure of the gene and the accurate base sequence were analyzed using DNA fragments bound to 32 P-labelled cDNA of human CCKAR originated from the gene library of leucocyte. This gene contained about 2.2 x 10 5 base pairs and the base sequence was completely determined and registered to Japan DNA data bank (D85606). In addition, the genome structures and base sequences of mouse and rat CCKAR were analyzed and registered (D 85605 and D 50608, respectively). The differences in the base sequence of CCKAR among the species were found in the promotor region and the intron regions, suggesting that there might be differences in splicing among species. (M.N.)

From Flavr Savr Tomatoes to STEM Cell Therapy: Young People's Understandings of Gene Technology, 15 Years On

Science.gov (United States)

Lewis, Jenny

2014-01-01

This paper explores knowledge and understanding of basic genetics and gene technologies in school students who have been taught to a "science for all" National Curriculum and compares 482 students in 1995 (gene technology was a new and rapidly developing area of science with potential to impact on everyday life; the first cohort of…

Gene ontology based transfer learning for protein subcellular localization

Directory of Open Access Journals (Sweden)

Zhou Shuigeng

2011-02-01

protein subcellular localization. We evaluate GO-TLM performance against three baseline models: MultiLoc, MultiLoc-GO and Euk-mPLoc on the benchmark datasets the baseline models adopted. 5-fold cross validation experiments show that GO-TLM achieves substantial accuracy improvement against the baseline models: 80.38% against model Euk-mPLoc 67.40% with 12.98% substantial increase; 96.65% and 96.27% against model MultiLoc-GO 89.60% and 89.60%, with 7.05% and 6.67% accuracy increase on dataset MultiLoc plant and dataset MultiLoc animal, respectively; 97.14%, 95.90% and 96.85% against model MultiLoc-GO 83.70%, 90.10% and 85.70%, with accuracy increase 13.44%, 5.8% and 11.15% on dataset BaCelLoc plant, dataset BaCelLoc fungi and dataset BaCelLoc animal respectively. For BaCelLoc independent sets, GO-TLM achieves 81.25%, 80.45% and 79.46% on dataset BaCelLoc plant holdout, dataset BaCelLoc plant holdout and dataset BaCelLoc animal holdout, respectively, as compared against baseline model MultiLoc-GO 76%, 60.00% and 73.00%, with accuracy increase 5.25%, 20.45% and 6.46%, respectively. Conclusions Since direct homology-based GO term transfer may be prone to introducing noise and outliers to the target protein, we design an explicitly weighted kernel learning system (called Gene Ontology Based Transfer Learning Model, GO-TLM to transfer to the target protein the known knowledge about related homologous proteins, which can reduce the risk of outliers and share knowledge between homologous proteins, and thus achieve better predictive performance for protein subcellular localization. Cross validation and independent test experimental results show that the homology-based GO term transfer and explicitly weighing the GO kernels substantially improve the prediction performance.

Proceedings of the advanced research and technology development direct utilization, instrumentation and diagnostics contractors' review meeting

Energy Technology Data Exchange (ETDEWEB)

Geiling, D.W. (USDOE Morgantown Energy Technology Center, WV (USA)); Goldberg, P.M. (eds.) (USDOE Pittsburgh Energy Technology Center, PA (USA))

1990-01-01

The 1990 Advanced Research and Technology Development (AR TD) Direct Utilization, and Instrumentation and Diagnostics Contractors Review Meeting was held September 16--18, 1990, at the Hyatt at Chatham Center in Pittsburgh, PA. The meeting was sponsored by the US Department of Energy (DOE), Office of Fossil Energy, and the Pittsburgh and Morgantown Energy Technology Centers. Each year the meeting provides a forum for the exchange of information among the DOE AR TD contractors and interested parties. This year's meeting was hosted by the Pittsburgh Energy Technology Center and was attended by 120 individuals from industry, academia, national laboratories, and other governmental agencies. Papers were presented on research addressing coal surface, science, devolatilization and combustion, ash behavior, emission controls for gases particulates, fluid bed combustion and utilization in diesels and turbines. Individual reports are processed separately for the data bases.

Encryption Technology based on Human Biometrics

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Wei Yang

2017-08-01

Full Text Available The research progress of encryption technologies based on human biometrics is reviewed in this paper.The technologies that utilize human biometrics to make information encryption and identity authentication,and the technologies which combine biometrics encryption with optical encryption methods are introduced in detail.The advantages and disadvantages of these encryption systems are discussed,and the obstacles in practical applications are pointed out.Finally,the prospect of the new encryption technologies that are based on human biometrics are predicted.

Comparison of a PCR-Based Method with Culture and Direct Examination for Diagnosis of Acanthamoeba keratitis

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S Farnia

2009-05-01

Full Text Available "nBackground: The aim was to compare three different methods (direct examination, culture and PCR meth­ods for the diagnosis of Acanthamoeba keratitis (AK in corneal scrapes."nMethods: Twenty eight corneal scrapes and contact lenses were collected from keratitis patients and re­ferred to the De­partment of Medical Parasitology and Mycology, School of Public Health, Tehran Univer­sity of Medical Sci­ences. Corneal scrapes were divided in three parts for direct examination, culture on non-nutrient agar and PCR analysis. PCR analysis was also performed using a 18S rRNA gene primer pair (DF3 region. DF3 (Diagnostic frag­ment 3 is a region of the nuclear small subunit ribosomal RNA gene which is specific for detecting Acan­thamoeba strains."nResults:  Acanthamoeba was the causative agent of keratitis in 50% of the patients. Direct smear of all pre­pared corneal scrapes in AK patients was negative and culture was positive in only 14.3% of the isolates. PCR analysis was positive in 71.4% of AK patients. These three methods were negative in corneal scrapes of non-AK patients. The sensitivity and specificity of PCR technique for the detection of Acanthamoeba sp. were calculated as 71.4% and 100%, respectively."nConclusion: According to high sensitivity and specificity of PCR-based method, this study confirmed that PCR using 18S rRNA gene primers (DF3 region is more useful for detecting AK cases compare to culture and direct microscopy methods.

The development of genes associated with radiosensitivity of cervical cancer

International Nuclear Information System (INIS)

Li Hongyan; Chen Zhihua; He Guifang

2007-01-01

It has a good application prospect to predict effects of radiotherapy by examining radiosensitivity of patients with cervical cancers before their radiotherapy. Prediction of tumor cell radiosensitivity according to their level of gene expression and gene therapy to reverse radio-resistance prior to radiation on cervical cancers are heated researches on tumor therapy. The expression of some proliferation-related genes, apoptosis-related genes and hypoxia-related genes can inerease the radiosensitivity of cervical cancer. Microarray technology may have more direct applications to the study of biological pathway contributing to radiation resistance and may lead to development of alternative treatment modalities. (authors)

A Possible Technology Development Path to Direct Imaging of Exo-Earths from Space

Science.gov (United States)

Siegler, Nicholas

2018-01-01

We describe a possible roadmap to achieving the technological capability to search for biosignatures on an Earth-like exoplanet from a future space telescope. The detection of Earth-like exoplanets in the habitable zone of their stars, and their spectroscopic characterization in a search for biosignatures, requires starlight suppression that exceeds the current best ground-based performance by orders of magnitude. The required planet/star brightness ratio of order 1e-10 at visible wavelengths can be obtained by blocking stellar photons with an occulter, either externally (a starshade) or internally (a coronagraph) to the telescope system, and managing diffracted starlight, so as to directly image the exoplanet in reflected starlight. Coronagraph instruments require advancement in telescope aperture (either monolithic or segmented), aperture obscurations (obscured by secondary mirror and its support struts), and wavefront error sensitivity (e.g. line-of-sight jitter, telescope vibration, polarization). The starshade, which has never been used in a science application, benefits a mission by being decoupled from the telescope, allowing a loosening of telescope stability requirements. In doing so, it transfers the difficult technology from the telescope system to a large deployable structure (tens of meters to greater than ~ 100 m in diameter) that must be positioned precisely at a distance of tens of thousands of kilometers from the telescope. Two ongoing mission concept studies, HabEx and LUVOIR, include the direct imaging of Earth-sized habitable exoplanets as a central science theme.

Compact four-channel terahertz demultiplexer based on directional coupling photonic crystal

Science.gov (United States)

Jiu-Sheng, Li; Han, Liu; Le, Zhang

2015-09-01

Electromagnetic polarization conveys valuable information for signal processing. Manipulation of terahertz wavelength demultiplexer exhibits tremendous potential in developing application of terahertz science and technology. We propose an approach to separate efficiently four frequencies terahertz waves based on three cascaded directional coupling two-dimensional photonic crystal waveguides. Both plane wave expansion method and finite-difference time-domain method are used to calculate and analyze the characteristics of the proposed device. The simulation results show that the designed terahertz wavelength demultiplexer can split four different wavelengths of terahertz wave into different propagation directions with high transmittance and low crosstalk. The present device is very compact and the total size is 6.8×10.6 mm2. This enables the terahertz wavelength demultiplexer to be used in terahertz wave system and terahertz wave integrated circuit fields.

State of the Art of Fuzzy Methods for Gene Regulatory Networks Inference

Directory of Open Access Journals (Sweden)

Tuqyah Abdullah Al Qazlan

2015-01-01

Full Text Available To address one of the most challenging issues at the cellular level, this paper surveys the fuzzy methods used in gene regulatory networks (GRNs inference. GRNs represent causal relationships between genes that have a direct influence, trough protein production, on the life and the development of living organisms and provide a useful contribution to the understanding of the cellular functions as well as the mechanisms of diseases. Fuzzy systems are based on handling imprecise knowledge, such as biological information. They provide viable computational tools for inferring GRNs from gene expression data, thus contributing to the discovery of gene interactions responsible for specific diseases and/or ad hoc correcting therapies. Increasing computational power and high throughput technologies have provided powerful means to manage these challenging digital ecosystems at different levels from cell to society globally. The main aim of this paper is to report, present, and discuss the main contributions of this multidisciplinary field in a coherent and structured framework.

Directed natural product biosynthesis gene cluster capture and expression in the model bacterium Bacillus subtilis

KAUST Repository

Li, Yongxin; Li, Zhongrui; Yamanaka, Kazuya; Xu, Ying; Zhang, Weipeng; Vlamakis, Hera; Kolter, Roberto; Moore, Bradley S.; Qian, Pei-Yuan

2015-01-01

validating this direct cloning plug-and-playa approach with surfactin, we genetically interrogated amicoumacin biosynthetic gene cluster from the marine isolate Bacillus subtilis 1779. Its heterologous expression allowed us to explore an unusual maturation

Service quality and perceived value of technology-based service encounters: evaluation of clinical staff satisfaction in Taiwan.

Science.gov (United States)

Hung, Chung-Jye; Chang, Hsin Hsin; Eng, Cheng Joo; Wong, Kit Hong

Previous research has evaluated technology-based service encounters (TBSEs) in the delivery of health care by assessing patient satisfaction. This study examined service quality and perceived value of TBSEs used in health organisations from the perspective of clinical staff, with staff technology readiness as a moderator. A quantitative survey was conducted in Taiwan, across private and public healthcare organisations. Results showed that TBSEs had a direct effect on service quality and perceived value, which in turn had a direct effect on staff satisfaction in using TBSEs. However, service quality had no effect on perceived value when moderated by technology readiness. Theoretical and managerial implications of these findings are discussed.

Keep in touch (KIT): perspectives on introducing internet-based communication and information technologies in palliative care.

Science.gov (United States)

Guo, Qiaohong; Cann, Beverley; McClement, Susan; Thompson, Genevieve; Chochinov, Harvey Max

2016-08-02

Hospitalized palliative patients need to keep in touch with their loved ones. Regular social contact may be especially difficult for individuals on palliative care in-patient units due to the isolating nature of hospital settings. Technology can help mitigate isolation by facilitating social connection. This study aimed to explore the acceptability of introducing internet-based communication and information technologies for patients on a palliative care in-patient unit. In the first phase of the Keep in Touch (KIT) project, a diverse group of key informants were consulted regarding their perspectives on web-based communication on in-patient palliative care units. Participants included palliative patients, family members, direct care providers, communication and information technology experts, and institutional administrators. Data was collected through focus groups, interviews and drop-in consultations, and was analyzed for themes, consensus, and major differences across participant groups. Hospitalized palliative patients and their family members described the challenges of keeping in touch with family and friends. Participants identified numerous examples of ways that communication and information technologies could benefit patients' quality of life and care. Patients and family members saw few drawbacks associated with the use of such technology. While generally supportive, direct care providers were concerned that patient requests for assistance in using the technology would place increased demands on their time. Administrators and IT experts recognized issues such as privacy and costs related to offering these technologies throughout an organization and in the larger health care system. This study affirmed the acceptability of offering internet-based communication and information technologies on palliative care in-patient units. It provides the foundation for trialing these technologies on a palliative in-patient unit. Further study is needed to confirm the

Residual DNA analysis in biologics development: review of measurement and quantitation technologies and future directions.

Science.gov (United States)

Wang, Xing; Morgan, Donna M; Wang, Gan; Mozier, Ned M

2012-02-01

Residual DNA (rDNA) is comprised of deoxyribonucleic acid (DNA) fragments and longer length molecules originating from the host organism that may be present in samples from recombinant biological processes. Although similar in basic structural base pair units, rDNA may exist in different sizes and physical forms. Interest in measuring rDNA in recombinant products is based primarily on demonstration of effective purification during manufacturing, but also on some hypothetical concerns that, in rare cases, depending on the host expression system, some DNA sequences may be potentially infectious or oncogenic (e.g., HIV virus and the Ras oncogene, respectively). Recent studies suggest that a sequence known as long interspersed nucleotide element-1 (LINE-1), widely distributed in the mammalian genome, is active as a retrotransposon that can be transcribed to RNA, reverse-transcribed into DNA and inserts into a new site in genome. This integration process could potentially disrupt critical gene functions or induce tumorigenesis in mammals. Genomic DNA from microbial sources, on the other hand, could add to risk of immunogenicity to the target recombinant protein being expressed, due to the high CpG content and unmethylated DNA sequence. For these and other reasons, it is necessary for manufacturers to show clearance of DNA throughout production processes and to confirm low levels in the final drug substance using an appropriately specific and quantitative analytical method. The heterogeneity of potential rDNA sequences that might be makes the testing of all potential analytes challenging. The most common methodology for rDNA quantitation used currently is real-time polymerase chain reaction (RT-PCR), a robust and proven technology. Like most rDNA quantitation methods, the specificity of RT-PCR is limited by the sequences to which the primers are directed. To address this, primase-based whole genome amplification is introduced herein. This paper will review the recent

Identification of hookworm DAF-16/FOXO response elements and direct gene targets.

Directory of Open Access Journals (Sweden)

Xin Gao

2010-08-01

Full Text Available The infective stage of the parasitic nematode hookworm is developmentally arrested in the environment and needs to infect a specific host to complete its life cycle. The canine hookworm (Ancylostoma caninum is an excellent model for investigating human hookworm infections. The transcription factor of A. caninum, Ac-DAF-16, which has a characteristic fork head or "winged helix" DNA binding domain (DBD, has been implicated in the resumption of hookworm development in the host. However, the precise roles of Ac-DAF-16 in hookworm parasitism and its downstream targets are unknown. In the present study, we combined molecular techniques and bioinformatics to identify a group of Ac-DAF-16 binding sites and target genes.The DNA binding domain of Ac-DAF-16 was used to select genomic fragments by in vitro genomic selection. Twenty four bound genomic fragments were analyzed for the presence of the DAF-16 family binding element (DBE and possible alternative Ac-DAF-16 bind motifs. The 22 genes linked to these genomic fragments were identified using bioinformatics tools and defined as candidate direct gene targets of Ac-DAF-16. Their developmental stage-specific expression patterns were examined. Also, a new putative DAF-16 binding element was identified.Our results show that Ac-DAF-16 is involved in diverse biological processes throughout hookworm development. Further investigation of these target genes will provide insights into the molecular basis by which Ac-DAF-16 regulates its downstream gene network in hookworm infection.

Development of gene diagnosis for diabetes and cholecystitis based on gene analysis of CCK-A receptor

International Nuclear Information System (INIS)

Kono, Akira

1999-01-01

Base sequence analysis of CCKAR gene (a gene of A-type receptor for cholecystokinin) from OLETF rat, a model rat for insulin-independent diabetes was made based on the base sequence of wild CCKAR gene, which had been clarified in the previous year. From the pancreas of OLETF rat, DNA was extracted and transduced into λphage after fragmentation to construct the gene library of OLETF. Then, λphage DNA clone bound with labelled cDNA of CCKAR gene was analyzed and the gene structure was compared with that of the wild gene. It was demonstrated that CCKAR gene of OLETF had a deletion (6800 b.p.) ranging from the promoter region to the Exon 2, suggesting that CCKAR gene is not functional in OLETF rat. The whole sequence of this mutant gene was registered into Japan DNA Bank (D 50610). Then, F 2 offspring rats were obtained through crossing OLETF (female) and F344 (male) and the time course-changes in the blood glucose level after glucose loading were compared among them. The blood glucose level after glucose loading was significantly higher in the homo-mutant F 2 (CCKAR,-/-) as well as the parent OLETF rat than hetero-mutant F 2 (CCKARm-/+) or the wild rat (CCKAR,+/+). This suggests that CCKAR gene might be involved in the control of blood glucose level and an alteration of the expression level or the functions of CCKAR gene might affect the blood glucose level. (M.N.)

Gene Overexpression Resources in Cereals for Functional Genomics and Discovery of Useful Genes

Directory of Open Access Journals (Sweden)

Kiyomi Abe

2016-09-01

Full Text Available Identification and elucidation of functions of plant genes is valuable for both basic and applied research. In addition to natural variation in model plants, numerous loss-of-function resources have been produced by mutagenesis with chemicals, irradiation, or insertions of transposable elements or T-DNA. However, we may be unable to observe loss-of-function phenotypes for genes with functionally redundant homologs, and for those essential for growth and development. To offset such disadvantages, gain-of-function transgenic resources have been exploited. Activation-tagged lines have been generated using obligatory overexpression of endogenous genes by random insertion of an enhancer. Recent progress in DNA sequencing technology and bioinformatics has enabled the preparation of genomewide collections of full-length cDNAs (fl-cDNAs in some model species. Using the fl-cDNA clones, a novel gain-of-function strategy, Fl-cDNA OvereXpressor gene (FOX-hunting system, has been developed. A mutant phenotype in a FOX line can be directly attributed to the overexpressed fl-cDNA. Investigating a large population of FOX lines could reveal important genes conferring favorable phenotypes for crop breeding. Alternatively, a unique loss-of-function approach Chimeric REpressor gene Silencing Technology (CRES-T has been developed. In CRES-T, overexpression of a chimeric repressor, composed of the coding sequence of a transcription factor (TF and short peptide designated as the repression domain, could interfere with the action of endogenous TF in plants. Although plant TFs usually consist of gene families, CRES-T is effective, in principle, even for the TFs with functional redundancy. In this review, we focus on the current status of the gene-overexpression strategies and resources for identifying and elucidating novel functions of cereal genes. We discuss the potential of these research tools for identifying useful genes and phenotypes for application in crop

Holding the Edge: Maintaining the Defense Technology Base

Science.gov (United States)

1989-04-01

psychological , with the shedding of isolationist technology that is close or equal to that of the United attitudes and inhibitions. Reaction by European States...are directed toward aleveling could work against what should be a good common set of enabling technologies, with applica- leeida carld work aanst

Advanced location-based technologies and services

CERN Document Server

Karimi, Hassan A

2013-01-01

Due to the rapid increase in the number of mobile device users worldwide, location-based services (LBSs) have become pervasive, and the demand for them will continue to grow. Exploring recent changes in the technology and its uses, Advanced Location-Based Technologies and Services takes an in-depth look at new and existing technologies, techniques, applications, and opportunities. Under the editorial guidance of Hassan Karimi, with contributions from experts in the field, the book examines the breadth and depth of advanced LBS technologies and techniques. The book provides up-to-date informati

NetGen: a novel network-based probabilistic generative model for gene set functional enrichment analysis.

Science.gov (United States)

Sun, Duanchen; Liu, Yinliang; Zhang, Xiang-Sun; Wu, Ling-Yun

2017-09-21

High-throughput experimental techniques have been dramatically improved and widely applied in the past decades. However, biological interpretation of the high-throughput experimental results, such as differential expression gene sets derived from microarray or RNA-seq experiments, is still a challenging task. Gene Ontology (GO) is commonly used in the functional enrichment studies. The GO terms identified via current functional enrichment analysis tools often contain direct parent or descendant terms in the GO hierarchical structure. Highly redundant terms make users difficult to analyze the underlying biological processes. In this paper, a novel network-based probabilistic generative model, NetGen, was proposed to perform the functional enrichment analysis. An additional protein-protein interaction (PPI) network was explicitly used to assist the identification of significantly enriched GO terms. NetGen achieved a superior performance than the existing methods in the simulation studies. The effectiveness of NetGen was explored further on four real datasets. Notably, several GO terms which were not directly linked with the active gene list for each disease were identified. These terms were closely related to the corresponding diseases when accessed to the curated literatures. NetGen has been implemented in the R package CopTea publicly available at GitHub ( http://github.com/wulingyun/CopTea/ ). Our procedure leads to a more reasonable and interpretable result of the functional enrichment analysis. As a novel term combination-based functional enrichment analysis method, NetGen is complementary to current individual term-based methods, and can help to explore the underlying pathogenesis of complex diseases.

CRISPR technologies for bacterial systems: Current achievements and future directions

DEFF Research Database (Denmark)

Choi, Kyeong Rok; Lee, Sang Yup

2016-01-01

Throughout the decades of its history, the advances in bacteria-based bio-industries have coincided with great leaps in strain engineering technologies. Recently unveiled clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated proteins (Cas) systems are now revolution......Throughout the decades of its history, the advances in bacteria-based bio-industries have coincided with great leaps in strain engineering technologies. Recently unveiled clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated proteins (Cas) systems are now...... revolutionizing biotechnology as well as biology. Diverse technologies have been derived from CRISPR/Cas systems in bacteria, yet the applications unfortunately have not been actively employed in bacteria as extensively as in eukaryotic organisms. A recent trend of engineering less explored strains in industrial...... microbiology-metabolic engineering, synthetic biology, and other related disciplines-is demanding facile yet robust tools, and various CRISPR technologies have potential to cater to the demands. Here, we briefly review the science in CRISPR/Cas systems and the milestone inventions that enabled numerous CRISPR...

Direct Repression of Evening Genes by CIRCADIAN CLOCK-ASSOCIATED1 in the Arabidopsis Circadian Clock.

Science.gov (United States)

Kamioka, Mari; Takao, Saori; Suzuki, Takamasa; Taki, Kyomi; Higashiyama, Tetsuya; Kinoshita, Toshinori; Nakamichi, Norihito

2016-03-01

The circadian clock is a biological timekeeping system that provides organisms with the ability to adapt to day-night cycles. Timing of the expression of four members of the Arabidopsis thaliana PSEUDO-RESPONSE REGULATOR(PRR) family is crucial for proper clock function, and transcriptional control of PRRs remains incompletely defined. Here, we demonstrate that direct regulation of PRR5 by CIRCADIAN CLOCK-ASSOCIATED1 (CCA1) determines the repression state of PRR5 in the morning. Chromatin immunoprecipitation followed by deep sequencing (ChIP-seq) analyses indicated that CCA1 associates with three separate regions upstream of PRR5 CCA1 and its homolog LATE ELONGATED HYPOCOTYL (LHY) suppressed PRR5 promoter activity in a transient assay. The regions bound by CCA1 in the PRR5 promoter gave rhythmic patterns with troughs in the morning, when CCA1 and LHY are at high levels. Furthermore,ChIP-seq revealed that CCA1 associates with at least 449 loci with 863 adjacent genes. Importantly, this gene set contains genes that are repressed but upregulated incca1 lhy double mutants in the morning. This study shows that direct binding by CCA1 in the morning provides strong repression of PRR5, and repression by CCA1 also temporally regulates an evening-expressed gene set that includes PRR5. © 2016 American Society of Plant Biologists. All rights reserved.

Sendai viroplexes for epidermal growth factor receptor-directed delivery of interleukin-12 and salmosin genes to cancer cells.

Science.gov (United States)

Kim, Jung Seok; Kim, Min Woo; Jeong, Hwa Yeon; Kang, Seong Jae; Park, Sang Il; Lee, Yeon Kyung; Kim, Hong Sung; Kim, Keun Sik; Park, Yong Serk

2016-07-01

The effective delivery of therapeutic genes to target cells has been a fundamental goal in cancer gene therapy because of its advantages with respect to both safety and transfection efficiency. In the present, study we describe a tumor-directed gene delivery system that demonstrates remarkable efficacy in gene delivery and minimizes the off-target effects of gene transfection. The system consists of a well-verified cationic O,O'-dimyristyl-N-lysyl glutamate (DMKE), Sendai virus fusion (F) protein and hemagglutinin-neuraminidase (HN) protein, referred to as cationic Sendai F/HN virosomes. To achieve tumor-specific recognition, anti-epidermal growth factor (EGF) receptor antibody was coupled to the surface of the virosomes containing interleukin-12 (IL-12) and/or salmosin genes that have potent anti-angiogenetic functions. Among the virosomal formulations, the anti-EGF receptor (EGFR) viroplexes, prepared via complexation of plasmid DNA (pDNA) with cationic DMKE lipid, exhibited more efficient gene transfection to tumor cells over-expressing EGF receptors compared to the neutrally-charged anti-EGFR virosomes encapsulating pDNA. In addition, the anti-EGFR viroplexes with IL-12 and salmosin genes exhibited the most effective therapeutic efficacy in a mouse tumor model. Especially when combined with doxorubicin, transfection of the two genes via the anti-EGFR viroplexes exhibited an enhanced inhibitory effect on tumor growth and metastasis in lungs. The results of the present study suggest that anti-EGFR viroplexes can be utilized as an effective strategy for tumor-directed gene delivery. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Field demonstration and transition of SCAPS direct push VOC in-situ sensing technologies

International Nuclear Information System (INIS)

Davis, William M.

1999-01-01

This project demonstrated two in-situ volatile organic compound (VOC) samplers in combination with the direct sampling ion trap mass spectrometer (DSITMS). The technologies chosen were the Vadose Sparge and the Membrane Interface Probe (MIP) sensing systems. Tests at two demonstration sites showed the newer VOC technologies capable of providing in situ contaminant measurements at two to four times the rate of the previously demonstrated Hydrosparge sensor. The results of this project provide initial results supporting the utility of these new technologies to provide rapid site characterization of VOC contaminants in the subsurface

Foreign direct investment and technology spillovers in Mexico: 20 years of NAFTA

OpenAIRE

Armas, Enrique; Rodríguez, José Carlos

2017-01-01

This article analyses the development of technology capabilities in the manufacturing sector of Mexico during the last two decades. It has been argued that the inclusion of Mexico in the North America Free Trade Agreement (NAFTA) in 1994 would be enough to catch up with Canada and the United States. In this regard, trade liberalisation and foreign direct investment (FDI) would have been two strategic tools to close the technology gap between Mexico and its commercial partners in North America...

Review of Magneto cardiography Technology based on SQUID

Energy Technology Data Exchange (ETDEWEB)

Lee, Y. H.; Kwon, H.; Kim, J. M.; Kim, K.; Yu, K. K.; Park, Y. K. [Brain and Cognition Measurement Lab, Korea Research Institute of Standards and Science, Daejeon (Korea, Republic of)

2012-04-15

Electric activity of cardiac muscles generates magnetic fields. Magnetocardiography (or MCG) technology, measuring these magnetic signals, can provide useful information for the diagnosis of heart diseases. It is already about 40 years ago that the first measurement of MCG signals was done by D. Cohen using SQUID (superconducting quantum interference device) sensor inside a magnetically shielded room. In the early period of MCG history, bulky point-contact RF-SQUID was used as the magnetic sensor. Thanks to the development of Nb-based Josephson junction technology in mid 1980s and new design of tightly-coupled DC-SQUID, low-noise SQUID sensors could be developed in late 1980s. In around 1990, several groups developed multi-channel MCG systems and started clinical study. However, it is quite recent years that the true usefulness of MCG was verified in clinical practice, for example, in the diagnosis of coronary artery disease. For the practical MCG system, technical elements of MCG system should be optimized in terms of performance, fabrication cost and operation cost. In this review, development history, technical issue, and future development direction of MCG technology are described.

TwinFocus, a concentrated photovoltaic module based on mature technologies

Directory of Open Access Journals (Sweden)

Antonini Piergiorgio

2014-01-01

Full Text Available Among solar power generation, concentrated photovoltaics (CPV based on multijunction (MJ solar cells, is one of the most promising technology for hot climates. The fact that multijunction solar cells based on direct band gap semiconductors demonstrate lower dependence on temperature than silicon solar cells boosted their use in concentrated photovoltaics modules. Departing from the mainstream design of Fresnel lenses, the CPV module based on TwinFocus design with off-axis quasi parabolic mirrors differentiates itself for its compactness and the possibility of easy integration also in roof-top applications. A detailed description of the module and of the systems will be given together with measured performances, and expectations for the next release.

Efficient Placement of Directional Antennas

Energy Technology Data Exchange (ETDEWEB)

Pan, Feng [Los Alamos National Laboratory; Kasiviswanathan, Shiva [Los Alamos National Laboratory

2010-09-20

Directional antenna is an technology for the proliferation of wireless networks. In centralized wireless network, wireless devices communicate through base stations. Directed antennas are placed on base stations and form a backbone of communication. The communication between base stations and wireless devices can be interfered due to a large number of wireless device. Methodically positioning and orienting directed antennas can help to reduce the interference while saving energy. An integer linear programming is developed for siting and directing antennas on multiple base stations, and this formulation can be extended to model non-overlapping channels. Through the integer programming formulation, optimal antenna positions can be used to analyze the performance of directed antennas with different parameters like the number base stations and the number of non-overlapping channels.

CRISPR-Cas9 technology and its application in haematological disorders

Science.gov (United States)

Zhang, Han; McCarty, Nami

2018-01-01

Summary The recent advent of the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-CRISPR associated protein 9 (Cas9) system for precise genome editing has revolutionized methodologies in haematology and oncology studies. CRISPR-Cas9 technology can be used to remove and correct genes or mutations, and to introduce site-specific therapeutic genes in human cells. Inherited haematological disorders represent ideal targets for CRISPR-Cas9-mediated gene therapy. Correcting disease-causing mutations could alleviate disease-related symptoms in the near future. The CRISPR-Cas9 system is also a useful tool for delineating molecular mechanisms involving haematological malignancies. Prior to the use of CRISPR-Cas9-mediated gene correction in humans, appropriate delivery systems with higher efficiency and specificity must be identified, and ethical guidelines for applying the technology with controllable safety must be established. Here, the latest applications of CRISPR-Cas9 technology in haematological disorders, current challenges and future directions are reviewed and discussed. PMID:27619566

Design and specificity of long ssDNA donors for CRISPR-based knock-in

OpenAIRE

Leonetti, Manuel; Li, Han; Beckman, Kyle; Pessino, Veronica; Huang, Bo; Weissman, Jonathan

2017-01-01

CRISPR/Cas technologies have transformed our ability to manipulate genomes for research and gene-based therapy. In particular, homology-directed repair after genomic cleavage allows for precise modification of genes using exogenous donor sequences as templates. While both single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA) forms of donors have been used as repair templates, a systematic comparison of the performance and specificity of repair using ssDNA versus dsDNA donors is still la...

High Technology Service Value Maximization through an MCDM-Based Innovative e-Business Model

Science.gov (United States)

Huang, Chi-Yo; Tzeng, Gwo-Hshiung; Ho, Wen-Rong; Chuang, Hsiu-Tyan; Lue, Yeou-Feng

The emergence of the Internet has changed the high technology marketing channels thoroughly in the past decade while E-commerce has already become one of the most efficient channels which high technology firms may skip the intermediaries and reach end customers directly. However, defining appropriate e-business models for commercializing new high technology products or services through Internet are not that easy. To overcome the above mentioned problems, a novel analytic framework based on the concept of high technology customers’ competence set expansion by leveraging high technology service firms’ capabilities and resources as well as novel multiple criteria decision making (MCDM) techniques, will be proposed in order to define an appropriate e-business model. An empirical example study of a silicon intellectual property (SIP) commercialization e-business model based on MCDM techniques will be provided for verifying the effectiveness of this novel analytic framework. The analysis successful assisted a Taiwanese IC design service firm to define an e-business model for maximizing its customer’s SIP transactions. In the future, the novel MCDM framework can be applied successful to novel business model definitions in the high technology industry.

[Characterization of Black and Dichothrix Cyanobacteria Based on the 16S Ribosomal RNA Gene Sequence

Science.gov (United States)

Ortega, Maya

2010-01-01

My project focuses on characterizing different cyanobacteria in thrombolitic mats found on the island of Highborn Cay, Bahamas. Thrombolites are interesting ecosystems because of the ability of bacteria in these mats to remove carbon dioxide from the atmosphere and mineralize it as calcium carbonate. In the future they may be used as models to develop carbon sequestration technologies, which could be used as part of regenerative life systems in space. These thrombolitic communities are also significant because of their similarities to early communities of life on Earth. I targeted two cyanobacteria in my research, Dichothrix spp. and whatever black is, since they are believed to be important to carbon sequestration in these thrombolitic mats. The goal of my summer research project was to molecularly identify these two cyanobacteria. DNA was isolated from each organism through mat dissections and DNA extractions. I ran Polymerase Chain Reactions (PCR) to amplify the 16S ribosomal RNA (rRNA) gene in each cyanobacteria. This specific gene is found in almost all bacteria and is highly conserved, meaning any changes in the sequence are most likely due to evolution. As a result, the 16S rRNA gene can be used for bacterial identification of different species based on the sequence of their 16S rRNA gene. Since the exact sequence of the Dichothrix gene was unknown, I designed different primers that flanked the gene based on the known sequences from other taxonomically similar cyanobacteria. Once the 16S rRNA gene was amplified, I cloned the gene into specialized Escherichia coli cells and sent the gene products for sequencing. Once the sequence is obtained, it will be added to a genetic database for future reference to and classification of other Dichothrix sp.

A PLSPM-Based Test Statistic for Detecting Gene-Gene Co-Association in Genome-Wide Association Study with Case-Control Design

Science.gov (United States)

Zhang, Xiaoshuai; Yang, Xiaowei; Yuan, Zhongshang; Liu, Yanxun; Li, Fangyu; Peng, Bin; Zhu, Dianwen; Zhao, Jinghua; Xue, Fuzhong

2013-01-01

For genome-wide association data analysis, two genes in any pathway, two SNPs in the two linked gene regions respectively or in the two linked exons respectively within one gene are often correlated with each other. We therefore proposed the concept of gene-gene co-association, which refers to the effects not only due to the traditional interaction under nearly independent condition but the correlation between two genes. Furthermore, we constructed a novel statistic for detecting gene-gene co-association based on Partial Least Squares Path Modeling (PLSPM). Through simulation, the relationship between traditional interaction and co-association was highlighted under three different types of co-association. Both simulation and real data analysis demonstrated that the proposed PLSPM-based statistic has better performance than single SNP-based logistic model, PCA-based logistic model, and other gene-based methods. PMID:23620809

Plant-based food and feed protein structure changes induced by gene-transformation, heating and bio-ethanol processing: a synchrotron-based molecular structure and nutrition research program.

Science.gov (United States)

Yu, Peiqiang

2010-11-01

Unlike traditional "wet" analytical methods which during processing for analysis often result in destruction or alteration of the intrinsic protein structures, advanced synchrotron radiation-based Fourier transform infrared microspectroscopy has been developed as a rapid and nondestructive and bioanalytical technique. This cutting-edge synchrotron-based bioanalytical technology, taking advantages of synchrotron light brightness (million times brighter than sun), is capable of exploring the molecular chemistry or structure of a biological tissue without destruction inherent structures at ultra-spatial resolutions. In this article, a novel approach is introduced to show the potential of the advanced synchrotron-based analytical technology, which can be used to study plant-based food or feed protein molecular structure in relation to nutrient utilization and availability. Recent progress was reported on using synchrotron-based bioanalytical technique synchrotron radiation-based Fourier transform infrared microspectroscopy and diffused reflectance infrared Fourier transform spectroscopy to detect the effects of gene-transformation (Application 1), autoclaving (Application 2), and bio-ethanol processing (Application 3) on plant-based food and feed protein structure changes on a molecular basis. The synchrotron-based technology provides a new approach for plant-based protein structure research at ultra-spatial resolutions at cellular and molecular levels.

Manipulation of cell cycle progression can counteract the apparent loss of correction frequency following oligonucleotide-directed gene repair

Directory of Open Access Journals (Sweden)

Kmiec Eric B

2007-02-01

Full Text Available Abstract Background Single-stranded oligonucleotides (ssODN are used routinely to direct specific base alterations within mammalian genomes that result in the restoration of a functional gene. Despite success with the technique, recent studies have revealed that following repair events, correction frequencies decrease as a function of time, possibly due to a sustained activation of damage response signals in corrected cells that lead to a selective stalling. In this study, we use thymidine to slow down the replication rate to enhance repair frequency and to maintain substantial levels of correction over time. Results First, we utilized thymidine to arrest cells in G1 and released the cells into S phase, at which point specific ssODNs direct the highest level of correction. Next, we devised a protocol in which cells are maintained in thymidine following the repair reaction, in which the replication is slowed in both corrected and non-corrected cells and the initial correction frequency is retained. We also present evidence that cells enter a senescence state upon prolonged treatment with thymidine but this passage can be avoided by removing thymidine at 48 hours. Conclusion Taken together, we believe that thymidine may be used in a therapeutic fashion to enable the maintenance of high levels of treated cells bearing repaired genes.

Exploring the role of peptides in polymer-based gene delivery.

Science.gov (United States)

Sun, Yanping; Yang, Zhen; Wang, Chunxi; Yang, Tianzhi; Cai, Cuifang; Zhao, Xiaoyun; Yang, Li; Ding, Pingtian

2017-09-15

Polymers are widely studied as non-viral gene vectors because of their strong DNA binding ability, capacity to carry large payload, flexibility of chemical modifications, low immunogenicity, and facile processes for manufacturing. However, high cytotoxicity and low transfection efficiency substantially restrict their application in clinical trials. Incorporating functional peptides is a promising approach to address these issues. Peptides demonstrate various functions in polymer-based gene delivery systems, such as targeting to specific cells, breaching membrane barriers, facilitating DNA condensation and release, and lowering cytotoxicity. In this review, we systematically summarize the role of peptides in polymer-based gene delivery, and elaborate how to rationally design polymer-peptide based gene delivery vectors. Polymers are widely studied as non-viral gene vectors, but suffer from high cytotoxicity and low transfection efficiency. Incorporating short, bioactive peptides into polymer-based gene delivery systems can address this issue. Peptides demonstrate various functions in polymer-based gene delivery systems, such as targeting to specific cells, breaching membrane barriers, facilitating DNA condensation and release, and lowering cytotoxicity. In this review, we highlight the peptides' roles in polymer-based gene delivery, and elaborate how to utilize various functional peptides to enhance the transfection efficiency of polymers. The optimized peptide-polymer vectors should be able to alter their structures and functions according to biological microenvironments and utilize inherent intracellular pathways of cells, and consequently overcome the barriers during gene delivery to enhance transfection efficiency. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

SUSTAINABILITY LOGISTICS BASING SCIENCE AND TECHNOLOGY OBJECTIVE DEMONSTRATION; SELECTED TECHNOLOGY ASSESSMENT

Science.gov (United States)

2018-03-22

BASING SCIENCE AND TECHNOLOGY OBJECTIVE – DEMONSTRATION; SELECTED TECHNOLOGY ASSESSMENT by Gregg J. Gildea Paul D. Carpenter Benjamin J...Campbell William F. Harris* Michael A. McCluskey** and José A. Miletti*** *General Dynamics Information Technology Fairfax, VA 22030 **Maneuver...SCIENCE AND TECHNOLOGY OBJECTIVE – DEMONSTRATION; SELECTED TECHNOLOGY ASSESSMENT 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT

Cytoplasmic-genetic male sterility gene provides direct evidence for some hybrid rice recently evolving into weedy rice

Science.gov (United States)

Zhang, Jingxu; Lu, Zuomei; Dai, Weimin; Song, Xiaoling; Peng, Yufa; Valverde, Bernal E.; Qiang, Sheng

2015-01-01

Weedy rice infests paddy fields worldwide at an alarmingly increasing rate. There is substantial evidence indicating that many weedy rice forms originated from or are closely related to cultivated rice. There is suspicion that the outbreak of weedy rice in China may be related to widely grown hybrid rice due to its heterosis and the diversity of its progeny, but this notion remains unsupported by direct evidence. We screened weedy rice accessions by both genetic and molecular marker tests for the cytoplasmic male sterility (CMS) genes (Wild abortive, WA, and Boro type, BT) most widely used in the production of indica and japonica three-line hybrid rice as a diagnostic trait of direct parenthood. Sixteen weedy rice accessions of the 358 tested (4.5%) contained the CMS-WA gene; none contained the CMS-BT gene. These 16 accessions represent weedy rices recently evolved from maternal hybrid rice derivatives, given the primarily maternal inheritance of this trait. Our results provide key direct evidence that hybrid rice can be involved in the evolution of some weedy rice accessions, but is not a primary factor in the recent outbreak of weedy rice in China. PMID:26012494

Cytoplasmic-genetic male sterility gene provides direct evidence for some hybrid rice recently evolving into weedy rice.

Science.gov (United States)

Zhang, Jingxu; Lu, Zuomei; Dai, Weimin; Song, Xiaoling; Peng, Yufa; Valverde, Bernal E; Qiang, Sheng

2015-05-27

Weedy rice infests paddy fields worldwide at an alarmingly increasing rate. There is substantial evidence indicating that many weedy rice forms originated from or are closely related to cultivated rice. There is suspicion that the outbreak of weedy rice in China may be related to widely grown hybrid rice due to its heterosis and the diversity of its progeny, but this notion remains unsupported by direct evidence. We screened weedy rice accessions by both genetic and molecular marker tests for the cytoplasmic male sterility (CMS) genes (Wild abortive, WA, and Boro type, BT) most widely used in the production of indica and japonica three-line hybrid rice as a diagnostic trait of direct parenthood. Sixteen weedy rice accessions of the 358 tested (4.5%) contained the CMS-WA gene; none contained the CMS-BT gene. These 16 accessions represent weedy rices recently evolved from maternal hybrid rice derivatives, given the primarily maternal inheritance of this trait. Our results provide key direct evidence that hybrid rice can be involved in the evolution of some weedy rice accessions, but is not a primary factor in the recent outbreak of weedy rice in China.

Mediated Effects of Technology Competencies and Experiences on Relations among Attitudes Towards Technology Use, Technology Ownership, and Self Efficacy about Technological Pedagogical Content Knowledge

Science.gov (United States)

Yerdelen-Damar, Sevda; Boz, Yezdan; Aydın-Günbatar, Sevgi

2017-08-01

This study examined the relations of preservice science teachers' attitudes towards technology use, technology ownership, technology competencies, and experiences to their self-efficacy beliefs about technological pedagogical content knowledge (TPACK). The present study also investigated interrelations among preservice teachers' attitudes towards technology use, technology ownership, technology competencies, and experiences. The participants of study were 665 elementary preservice science teachers (467 females, 198 males) from 7 colleges in Turkey. The proposed model based on educational technology literature was tested using structural equation modeling. The model testing results revealed that preservice teachers' technology competencies and experiences mediated the relation of technology ownership to their TPACK self efficacy beliefs. The direct relation of their possession of technology to their TPACK self efficacy beliefs was insignificant while the indirect relation through their technology competencies and experiences was significant. The results also indicated there were significant direct effects of preservice teachers' attitudes towards technology use, technology competencies, and experiences on their TPACK self efficacy beliefs.

A postprocessing method in the HMC framework for predicting gene function based on biological instrumental data

Science.gov (United States)

Feng, Shou; Fu, Ping; Zheng, Wenbin

2018-03-01

Predicting gene function based on biological instrumental data is a complicated and challenging hierarchical multi-label classification (HMC) problem. When using local approach methods to solve this problem, a preliminary results processing method is usually needed. This paper proposed a novel preliminary results processing method called the nodes interaction method. The nodes interaction method revises the preliminary results and guarantees that the predictions are consistent with the hierarchy constraint. This method exploits the label dependency and considers the hierarchical interaction between nodes when making decisions based on the Bayesian network in its first phase. In the second phase, this method further adjusts the results according to the hierarchy constraint. Implementing the nodes interaction method in the HMC framework also enhances the HMC performance for solving the gene function prediction problem based on the Gene Ontology (GO), the hierarchy of which is a directed acyclic graph that is more difficult to tackle. The experimental results validate the promising performance of the proposed method compared to state-of-the-art methods on eight benchmark yeast data sets annotated by the GO.

Commentary on Future directions: Building technologies and design tools''

Energy Technology Data Exchange (ETDEWEB)

Quadrel, R.W.

1992-08-10

This paper presents a number of interesting and thought-provoking scenarios about the future use of advanced technology in the design and operation of commercial buildings. I will express my reactions in the following series of short paragraphs. These thoughts will, I hope, raise some new questions and offer fruitful directions for further exploration.

Speeding disease gene discovery by sequence based candidate prioritization

Directory of Open Access Journals (Sweden)

Porteous David J

2005-03-01

Full Text Available Abstract Background Regions of interest identified through genetic linkage studies regularly exceed 30 centimorgans in size and can contain hundreds of genes. Traditionally this number is reduced by matching functional annotation to knowledge of the disease or phenotype in question. However, here we show that disease genes share patterns of sequence-based features that can provide a good basis for automatic prioritization of candidates by machine learning. Results We examined a variety of sequence-based features and found that for many of them there are significant differences between the sets of genes known to be involved in human hereditary disease and those not known to be involved in disease. We have created an automatic classifier called PROSPECTR based on those features using the alternating decision tree algorithm which ranks genes in the order of likelihood of involvement in disease. On average, PROSPECTR enriches lists for disease genes two-fold 77% of the time, five-fold 37% of the time and twenty-fold 11% of the time. Conclusion PROSPECTR is a simple and effective way to identify genes involved in Mendelian and oligogenic disorders. It performs markedly better than the single existing sequence-based classifier on novel data. PROSPECTR could save investigators looking at large regions of interest time and effort by prioritizing positional candidate genes for mutation detection and case-control association studies.

Gene and Cell Doping: The New Frontier - Beyond Myth or Reality.

Science.gov (United States)

Neuberger, Elmo W I; Simon, Perikles

2017-01-01

The advent of gene transfer technologies in clinical studies aroused concerns that these technologies will be misused for performance-enhancing purposes in sports. However, during the last 2 decades, the field of gene therapy has taken a long and winding road with just a few gene therapeutic drugs demonstrating clinical benefits in humans. The current state of gene therapy is that viral vector-mediated gene transfer shows the now long-awaited initial success for safe, and in some cases efficient, gene transfer in clinical trials. Additionally, the use of small interfering RNA promises an efficient therapy through gene silencing, even though a number of safety concerns remain. More recently, the development of the molecular biological CRISPR/Cas9 system opened new possibilities for efficient and highly targeted genome editing. This chapter aims to define and consequently demystify the term "gene doping" and discuss the current reality concerning gene- and cell-based physical enhancement strategies. The technological progress in the field of gene therapy will be illustrated, and the recent clinical progress as well as technological difficulties will be highlighted. Comparing the attractiveness of these technologies with conventional doping practices reveals that current gene therapy technologies remain unattractive for doping purposes and unlikely to outperform conventional doping. However, future technological advances may raise the attractiveness of gene doping, thus making it easier to develop detection strategies. Currently available detection strategies are introduced in this chapter showing that many forms of genetic manipulation can already be detected in principle. © 2017 S. Karger AG, Basel.

Virtual maintenance technology for reactor system based on PPR technology

International Nuclear Information System (INIS)

Wu Yaxiang; Ma Baiyong

2009-01-01

Based on the Product, Process and Resources (PPR) technology, the establishing technology of virtual maintenance environment for the reactor system and the process structure tree for virtual maintenance is studied, and the flow for the maintainability design and simulation for reactor system is put forward. Based on the subsection simulation of maintenance process and layered design of maintenance actions, the leveled structure of the reactor system virtual maintenance task is studied. The relation for the data of product, process and resource is described by Plan Evaluation and Review Technology (PERT) diagram to define the maintenance operation. (authors)

Inferring Gene Regulatory Networks Using Conditional Regulation Pattern to Guide Candidate Genes.

Directory of Open Access Journals (Sweden)

Fei Xiao

Full Text Available Combining path consistency (PC algorithms with conditional mutual information (CMI are widely used in reconstruction of gene regulatory networks. CMI has many advantages over Pearson correlation coefficient in measuring non-linear dependence to infer gene regulatory networks. It can also discriminate the direct regulations from indirect ones. However, it is still a challenge to select the conditional genes in an optimal way, which affects the performance and computation complexity of the PC algorithm. In this study, we develop a novel conditional mutual information-based algorithm, namely RPNI (Regulation Pattern based Network Inference, to infer gene regulatory networks. For conditional gene selection, we define the co-regulation pattern, indirect-regulation pattern and mixture-regulation pattern as three candidate patterns to guide the selection of candidate genes. To demonstrate the potential of our algorithm, we apply it to gene expression data from DREAM challenge. Experimental results show that RPNI outperforms existing conditional mutual information-based methods in both accuracy and time complexity for different sizes of gene samples. Furthermore, the robustness of our algorithm is demonstrated by noisy interference analysis using different types of noise.

The emergence of new technology-based industries: the case of fuel cells and its technological relatedness to regional knowledge bases

DEFF Research Database (Denmark)

Tanner, Anne Nygaard

2016-01-01

to emerging radical technologies that create the foundation for new industries. The article develops a new measure for technological relatedness between the knowledge base of a region and that of a radical technology based on patent classes. It demonstrates that emerging fuel cell technology develops where...... the regional knowledge base is technologically related to that of fuel cells and consequently confirms the evolutionary thesis.......Evolutionary economic geographers propose that regional diversification is a path-dependent process whereby industries grow out of pre-existing industrial structures through technologically related localised knowledge spillovers and learning. This article examines whether this also applies...

Horizontal Directional Drilling-Length Detection Technology While Drilling Based on Bi-Electro-Magnetic Sensing

Directory of Open Access Journals (Sweden)

Yudan Wang

2017-04-01

Full Text Available The drilling length is an important parameter in the process of horizontal directional drilling (HDD exploration and recovery, but there has been a lack of accurate, automatically obtained statistics regarding this parameter. Herein, a technique for real-time HDD length detection and a management system based on the electromagnetic detection method with a microprocessor and two magnetoresistive sensors employing the software LabVIEW are proposed. The basic principle is to detect the change in the magnetic-field strength near a current coil while the drill stem and drill-stem joint successively pass through the current coil forward or backward. The detection system consists of a hardware subsystem and a software subsystem. The hardware subsystem employs a single-chip microprocessor as the main controller. A current coil is installed in front of the clamping unit, and two magneto resistive sensors are installed on the sides of the coil symmetrically and perpendicular to the direction of movement of the drill pipe. Their responses are used to judge whether the drill-stem joint is passing through the clamping unit; then, the order of their responses is used to judge the movement direction. The software subsystem is composed of a visual software running on the host computer and a software running in the slave microprocessor. The host-computer software processes, displays, and saves the drilling-length data, whereas the slave microprocessor software operates the hardware system. A combined test demonstrated the feasibility of the entire drilling-length detection system.

Hypoxia-Response Element (HRE)–Directed Transcriptional Regulation of the Rat Lysyl Oxidase Gene in Response to Cobalt and Cadmium

Science.gov (United States)

Li, Wande

2013-01-01

Lysyl oxidase (LO) catalyzes crosslink of collagen, elastin, and histone H1, stabilizing the extracellular matrix and cell nucleus. This enzyme displays dual functions for tumorigenesis, i.e., as a tumor suppressor inactivating the ras oncogene and as a tumor promoter enhancing malignant cell metastasis. To elucidate LO transcriptional regulation, we have cloned the 804 base pair region upstream of the translation start site (ATG) of the rat LO gene with the maximal promoter activity. Computer analysis indicated that at least four hypoxia-response element (HRE) consensuses (5′-ACGTG-3′) exist in the cloned LO promoter. Treatment of rat lung fibroblasts (RFL6) with CoCl2 (Co, 10–100 μM), a chemical hypoxia reagent, enhanced LO mRNA expression and promoter activities. Overexpression of LO was associated with upregulation of hypoxia-inducible factor (HIF)-1α at mRNA levels in cobalt (Co)–treated cells. Thus, LO is a hypoxia-responsive gene. Dominant negative-HIF-1α inhibited LO promoter activities stimulated by Co. Electrophoretic mobility shift, oligonucleotide competition, and in vitro translated HIF-1α binding assays indicated that only one HRE mapped at −387/−383 relative to ATG was functionally active among four consensuses. Site-directed mutation of this HRE significantly diminished the Co-induced and LO promoter-directed expression of the reporter gene. Cadmium (Cd), an inducer of reactive oxygen species, inhibited HIF-1α mRNA expression and HIF-1α binding to the LO gene in Co-treated cells as revealed by RT-PCR and ChIP assays, respectively. Thus, modulation of the HRE activity by Co and Cd plays a critical role in LO gene transactivation. PMID:23161664

The gene-editing of super-ego.

Science.gov (United States)

Hofmann, Bjørn

2018-04-17

New emerging biotechnologies, such as gene editing, vastly extend our ability to alter the human being. This comes together with strong aspirations to improve humans not only physically, but also mentally, morally, and socially. These conjoined ambitions aggregate to what can be labelled "the gene editing of super-ego." This article investigates a general way used to argue for new biotechnologies, such as gene-editing: if it is safe and efficacious to implement technology X for the purpose of a common good Y, why should we not do so? This is a rhetorical question with a conditional, and may be dismissed as such. Moreover, investigating the question transformed into a formal argument reveals that the argument does not hold either. Nonetheless, the compelling force of the question calls for closer scrutiny, revealing that this way of arguing for biotechnology is based on five assumptions. Analysis of these assumptions shows their significant axiological, empirical, and philosophical challenges. This makes it reasonable to claim that these kinds of question based promotions of specific biotechnologies fail. Hence, the aspirations to make a super-man with a super-ego appear fundamentally flawed. As these types of moral bioenhancement arguments become more prevalent, a revealing hype test is suggested: What is special with this technology (e.g., gene editing), compared to existing methods, that makes it successful in improving human social characteristics in order to make the world a better place for all? Valid answers to this question will provide good reasons to pursue such technologies. Hence, the aim is not to bar the development of modern biotechnology, but rather to ensure good developments and applications of highly potent technologies. So far, we still have a long way to go to make persons with goodness gene(s).

Horizontal directional drilling: a green and sustainable technology for site remediation.

Science.gov (United States)

Lubrecht, Michael D

2012-03-06

Sustainability has become an important factor in the selection of remedies to clean up contaminated sites. Horizontal directional drilling (HDD) is a relatively new drilling technology that has been successfully adapted to site remediation. In addition to the benefits that HDD provides for the logistics of site cleanup, it also delivers sustainability advantages, compared to alternative construction methods.

A Bayesian variable selection procedure for ranking overlapping gene sets

DEFF Research Database (Denmark)

Skarman, Axel; Mahdi Shariati, Mohammad; Janss, Luc

2012-01-01

Background Genome-wide expression profiling using microarrays or sequence-based technologies allows us to identify genes and genetic pathways whose expression patterns influence complex traits. Different methods to prioritize gene sets, such as the genes in a given molecular pathway, have been de...

Specific Destruction of HIV Proviral p17 Gene in T Lymphoid Cells Achieved by the Genome Editing Technology.

Science.gov (United States)

Kishida, Tsunao; Ejima, Akika; Mazda, Osam

2016-01-01

Recent development in genome editing technologies has enabled site-directed deprivation of a nucleotide sequence in the chromosome in mammalian cells. Human immunodeficiency (HIV) infection causes integration of proviral DNA into the chromosome, which potentially leads to re-emergence of the virus, but conventional treatment cannot delete the proviral DNA sequence from the cells infected with HIV. In the present study, the transcription activator-like effector nucleases (TALENs) specific for the HIV p17 gene were constructed, and their activities to destroy the target sequence were evaluated. SSA assay showed a high activity of a pair of p17-specific TALENs. A human T lymphoid cell line, Jurkat, was infected with a lentivirus vector followed by transfection with the TALEN-HIV by electroporation. The target sequence was destructed in approximately 10-95% of the p17 polymerase chain reaction clones, and the efficiencies depended on the Jurkat-HIV clones. Because p17 plays essential roles for assembly and budding of HIV, and this gene has relatively low nucleotide sequence diversity, genome editing procedures targeting p17 may provide a therapeutic benefit for HIV infection.

The main directions of technologic modernization in the field of subsurface resources management

Directory of Open Access Journals (Sweden)

Vyacheslav Petrovich Pakhomov

2011-09-01

Full Text Available One of the priorities of Russia's transition to post-industrial development is the upgrade of mineral resources sector as a major system-building industry which includes exploration, extraction, refining, transportation and processing of minerals. The main directions of modernization in the subsoil resources management are improvement of methods and technologies under exploration, automation and computerization of work and equipment at the stages of production and transportation of mineral resources, improvement of equipment and technology with the use of nanotechnology in the stages of enrichment and processing of mineral raw materials. Actual direction of modernization in the ore mining industry today is creation and improvement of techniques and technologies to work in the northern climate according to the Program of subsoil resources development of the North and the Arctic shelf. Due to the exhaustion of large raw mineral deposits and geological complexity of the conditions of mining, there is a need for new types of mining and extraction equipment in the industry and development of processes to extract minerals from the non-traditional raw materials.

Network Diffusion-Based Prioritization of Autism Risk Genes Identifies Significantly Connected Gene Modules

Directory of Open Access Journals (Sweden)

Ettore Mosca

2017-09-01

Full Text Available Autism spectrum disorder (ASD is marked by a strong genetic heterogeneity, which is underlined by the low overlap between ASD risk gene lists proposed in different studies. In this context, molecular networks can be used to analyze the results of several genome-wide studies in order to underline those network regions harboring genetic variations associated with ASD, the so-called “disease modules.” In this work, we used a recent network diffusion-based approach to jointly analyze multiple ASD risk gene lists. We defined genome-scale prioritizations of human genes in relation to ASD genes from multiple studies, found significantly connected gene modules associated with ASD and predicted genes functionally related to ASD risk genes. Most of them play a role in synapsis and neuronal development and function; many are related to syndromes that can be in comorbidity with ASD and the remaining are involved in epigenetics, cell cycle, cell adhesion and cancer.

iSyTE 2.0: a database for expression-based gene discovery in the eye

Science.gov (United States)

Kakrana, Atul; Yang, Andrian; Anand, Deepti; Djordjevic, Djordje; Ramachandruni, Deepti; Singh, Abhyudai; Huang, Hongzhan

2018-01-01

Abstract Although successful in identifying new cataract-linked genes, the previous version of the database iSyTE (integrated Systems Tool for Eye gene discovery) was based on expression information on just three mouse lens stages and was functionally limited to visualization by only UCSC-Genome Browser tracks. To increase its efficacy, here we provide an enhanced iSyTE version 2.0 (URL: http://research.bioinformatics.udel.edu/iSyTE) based on well-curated, comprehensive genome-level lens expression data as a one-stop portal for the effective visualization and analysis of candidate genes in lens development and disease. iSyTE 2.0 includes all publicly available lens Affymetrix and Illumina microarray datasets representing a broad range of embryonic and postnatal stages from wild-type and specific gene-perturbation mouse mutants with eye defects. Further, we developed a new user-friendly web interface for direct access and cogent visualization of the curated expression data, which supports convenient searches and a range of downstream analyses. The utility of these new iSyTE 2.0 features is illustrated through examples of established genes associated with lens development and pathobiology, which serve as tutorials for its application by the end-user. iSyTE 2.0 will facilitate the prioritization of eye development and disease-linked candidate genes in studies involving transcriptomics or next-generation sequencing data, linkage analysis and GWAS approaches. PMID:29036527

Directed evolution combined with synthetic biology strategies expedite semi-rational engineering of genes and genomes.

Science.gov (United States)

Kang, Zhen; Zhang, Junli; Jin, Peng; Yang, Sen

2015-01-01

Owing to our limited understanding of the relationship between sequence and function and the interaction between intracellular pathways and regulatory systems, the rational design of enzyme-coding genes and de novo assembly of a brand-new artificial genome for a desired functionality or phenotype are difficult to achieve. As an alternative approach, directed evolution has been widely used to engineer genomes and enzyme-coding genes. In particular, significant developments toward DNA synthesis, DNA assembly (in vitro or in vivo), recombination-mediated genetic engineering, and high-throughput screening techniques in the field of synthetic biology have been matured and widely adopted, enabling rapid semi-rational genome engineering to generate variants with desired properties. In this commentary, these novel tools and their corresponding applications in the directed evolution of genomes and enzymes are discussed. Moreover, the strategies for genome engineering and rapid in vitro enzyme evolution are also proposed.

HTGR technology development: status and direction

International Nuclear Information System (INIS)

Kasten, P.R.

1982-01-01

During the last two years there has been an extensive and comprehensive effort expended primarily by General Atomic (GA) in generating a revised technology development plan. Oak Ridge National Laboratory (ORNL) has assisted in this effort, primarily through its interactions over the past years in working together with GA in technology development, but also through detailed review of the initial versions of the technology development plan as prepared by GA. The plan covers Fuel Technology, Materials Technology (including metals, graphite, and ceramics), Plant Technology (including methods, safety, structures, systems, heat exchangers, control and electrical, and mechanical), and Component Design Verification and Support areas

Direct convertor based upon space charge effects

International Nuclear Information System (INIS)

Gitomer, S.J.

1977-01-01

A device capable of converting directly the kinetic energy of charged particles into electrical energy is considered. The device differs from earlier ones (such as Post's periodic focus electrostatic direct convertor) in that it makes use of the space charge repulsion in a high density charged particle beam. The beam is directed into a monotonic decelerating electrostatic field of a several-stage planar-finned structure. The collector fins coincide with vacuum equipotential surfaces. Space charge blowup of the beam directs particles onto various collector fins. The energy efficiency of a 4-stage device has been determined using a numberical simulation approach. We find that efficiencies approaching 75 percent are possible. An approximate scaling law is derived for the space charge based direct converter and a comparison is made to the periodic focus direct convertor. We find the space charge based direct convertor to be superior to a number of ways

Novel PVA-DNA nanoparticles prepared by ultra high pressure technology for gene delivery

International Nuclear Information System (INIS)

Kimura, Tsuyoshi; Okuno, Akira; Miyazaki, Kozo; Furuzono, Tsutomu; Ohya, Yuichi; Ouchi, Tatsuro; Mutsuo, Shingo; Yoshizawa, Hidekazu; Kitamura, Yoshiro; Fujisato, Toshiyta; Kishida, Akio

2004-01-01

Polyvinyl alcohol (PVA)-DNA nanoparticles have been developed by ultra high pressure (UHP) technology. Mixture solutions of DNA and PVA having various molecular weights (Mw) and degree of saponifications (DS) were treated under 10,000 atmospheres (981 MPa) condition at 40 deg. C for 10 min. Agarose gel electrophoresis and scanning electron microscope observation revealed that the PVA-DNA nanoparticles with average diameter of about 200 nm were formed. Using PVA of higher Mw and degree of saponifications, the amount of nanoparticles formed increased. The driving force of nanoparticle formation was the hydrogen bonding between DNA and PVA. In order to apply the PVA-DNA nanoparticles for gene delivery, the cytotoxicity and the cellular uptake of them were investigated using Raw264 cell lines. The cell viability was not influenced whether the presence of the PVA-DNA nanoparticles. Further, the nanoparticles internalized into cells were observed by fluorescent microscope. These results indicates that the PVA-DNA nanoparticles prepared by UHP technology showed be useful as drug carrier, especially for gene delivery

Regulation of gene expression by manipulating transcriptional repressor activity using a novel CoSRI technology.

Science.gov (United States)

Xu, Yue; Li, Song Feng; Parish, Roger W

2017-07-01

Targeted gene manipulation is a central strategy for studying gene function and identifying related biological processes. However, a methodology for manipulating the regulatory motifs of transcription factors is lacking as these factors commonly possess multiple motifs (e.g. repression and activation motifs) which collaborate with each other to regulate multiple biological processes. We describe a novel approach designated conserved sequence-guided repressor inhibition (CoSRI) that can specifically reduce or abolish the repressive activities of transcription factors in vivo. The technology was evaluated using the chimeric MYB80-EAR transcription factor and subsequently the endogenous WUS transcription factor. The technology was employed to develop a reversible male sterility system applicable to hybrid seed production. In order to determine the capacity of the technology to regulate the activity of endogenous transcription factors, the WUS repressor was chosen. The WUS repression motif could be inhibited in vivo and the transformed plants exhibited the wus-1 phenotype. Consequently, the technology can be used to manipulate the activities of transcriptional repressor motifs regulating beneficial traits in crop plants and other eukaryotic organisms. © 2016 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

Gene doping: gene delivery for olympic victory.

Science.gov (United States)

Gould, David

2013-08-01

With one recently recommended gene therapy in Europe and a number of other gene therapy treatments now proving effective in clinical trials it is feasible that the same technologies will soon be adopted in the world of sport by unscrupulous athletes and their trainers in so called 'gene doping'. In this article an overview of the successful gene therapy clinical trials is provided and the potential targets for gene doping are highlighted. Depending on whether a doping gene product is secreted from the engineered cells or is retained locally to, or inside engineered cells will, to some extent, determine the likelihood of detection. It is clear that effective gene delivery technologies now exist and it is important that detection and prevention plans are in place. © 2012 The Author. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.

Environmental life cycle assessment of methanol and electricity co-production system based on coal gasification technology.

Science.gov (United States)

Śliwińska, Anna; Burchart-Korol, Dorota; Smoliński, Adam

2017-01-01

This paper presents a life cycle assessment (LCA) of greenhouse gas emissions generated through methanol and electricity co-production system based on coal gasification technology. The analysis focuses on polygeneration technologies from which two products are produced, and thus, issues related to an allocation procedure for LCA are addressed in this paper. In the LCA, two methods were used: a 'system expansion' method based on two approaches, the 'avoided burdens approach' and 'direct system enlargement' methods and an 'allocation' method involving proportional partitioning based on physical relationships in a technological process. Cause-effect relationships in the analysed production process were identified, allowing for the identification of allocation factors. The 'system expansion' method involved expanding the analysis to include five additional variants of electricity production technologies in Poland (alternative technologies). This method revealed environmental consequences of implementation for the analysed technologies. It was found that the LCA of polygeneration technologies based on the 'system expansion' method generated a more complete source of information on environmental consequences than the 'allocation' method. The analysis shows that alternative technologies chosen for generating LCA results are crucial. Life cycle assessment was performed for the analysed, reference and variant alternative technologies. Comparative analysis was performed between the analysed technologies of methanol and electricity co-production from coal gasification as well as a reference technology of methanol production from the natural gas reforming process. Copyright © 2016 Elsevier B.V. All rights reserved.

Fast gene ontology based clustering for microarray experiments.

Science.gov (United States)

Ovaska, Kristian; Laakso, Marko; Hautaniemi, Sampsa

2008-11-21

Analysis of a microarray experiment often results in a list of hundreds of disease-associated genes. In order to suggest common biological processes and functions for these genes, Gene Ontology annotations with statistical testing are widely used. However, these analyses can produce a very large number of significantly altered biological processes. Thus, it is often challenging to interpret GO results and identify novel testable biological hypotheses. We present fast software for advanced gene annotation using semantic similarity for Gene Ontology terms combined with clustering and heat map visualisation. The methodology allows rapid identification of genes sharing the same Gene Ontology cluster. Our R based semantic similarity open-source package has a speed advantage of over 2000-fold compared to existing implementations. From the resulting hierarchical clustering dendrogram genes sharing a GO term can be identified, and their differences in the gene expression patterns can be seen from the heat map. These methods facilitate advanced annotation of genes resulting from data analysis.

Evolutionary dynamics of DNA-binding sites and direct target genes of a floral master regulatory transcription factor [RNA-Seq

NARCIS (Netherlands)

Muiño, J.M.; Bruijn, de S.A.; Vingron, Martin; Angenent, G.C.; Kaufmann, Kerstin

2015-01-01

Plant development is controlled by transcription factors (TFs) which form complex gene-regulatory networks. Genome-wide TF DNA-binding studies revealed that these TFs have several thousands of binding sites in the Arabidopsis genome, and may regulate the expression of many genes directly. Given the

Apoptosis Gene Information System--AGIS.

Science.gov (United States)

Sakharkar, Kishore R; Clement, Marie V; Chow, Vincent T K; Pervaiz, Shazib

2006-05-01

Genes implicated in apoptosis have great relevance to biology, medicine and oncology. Here, we describe a unique resource, Apoptosis Gene Information System (AGIS) that provides data for over 2400 genes involved directly or indirectly, in apoptotic pathways of more than 350 different organisms. The organization of this information system is based on the principle of one-gene, one record. AGIS will be updated on a six monthly basis as new information becomes available. AGIS can be accessed at: http://www.cellfate.org/AGIS/.

Cre/lox-based multiple markerless gene disruption in the genome of the extreme thermophile Thermus thermophilus.

Science.gov (United States)

Togawa, Yoichiro; Nunoshiba, Tatsuo; Hiratsu, Keiichiro

2018-02-01

Markerless gene-disruption technology is particularly useful for effective genetic analyses of Thermus thermophilus (T. thermophilus), which have a limited number of selectable markers. In an attempt to develop a novel system for the markerless disruption of genes in T. thermophilus, we applied a Cre/lox system to construct a triple gene disruptant. To achieve this, we constructed two genetic tools, a loxP-htk-loxP cassette and cre-expressing plasmid, pSH-Cre, for gene disruption and removal of the selectable marker by Cre-mediated recombination. We found that the Cre/lox system was compatible with the proliferation of the T. thermophilus HB27 strain at the lowest growth temperature (50 °C), and thus succeeded in establishing a triple gene disruptant, the (∆TTC1454::loxP, ∆TTC1535KpnI::loxP, ∆TTC1576::loxP) strain, without leaving behind a selectable marker. During the process of the sequential disruption of multiple genes, we observed the undesired deletion and inversion of the chromosomal region between multiple loxP sites that were induced by Cre-mediated recombination. Therefore, we examined the effects of a lox66-htk-lox71 cassette by exploiting the mutant lox sites, lox66 and lox71, instead of native loxP sites. We successfully constructed a (∆TTC1535::lox72, ∆TTC1537::lox72) double gene disruptant without inducing the undesired deletion of the 0.7-kbp region between the two directly oriented lox72 sites created by the Cre-mediated recombination of the lox66-htk-lox71 cassette. This is the first demonstration of a Cre/lox system being applicable to extreme thermophiles in a genetic manipulation. Our results indicate that this system is a powerful tool for multiple markerless gene disruption in T. thermophilus.

Comparative analysis of methods for gene transcription profiling data derived from different microarray technologies in rat and mouse models of diabetes

Directory of Open Access Journals (Sweden)

Bihoreau Marie-Thérèse

2009-02-01

Full Text Available Abstract Background Microarray technologies are widely used to quantify the abundance of transcripts corresponding to thousands of genes. To maximise the robustness of transcriptome results, we have tested the performance and reproducibility of rat and mouse gene expression data obtained with Affymetrix, Illumina and Operon platforms. Results We present a thorough analysis of the degree of reproducibility provided by analysing the transcriptomic profile of the same animals of several experimental groups under different popular microarray technologies in different tissues. Concordant results from inter- and intra-platform comparisons were maximised by testing many popular computational methods for generating fold changes and significances and by only considering oligonucleotides giving high expression levels. The choice of Affymetrix signal extraction technique was shown to have the greatest effect on the concordance across platforms. In both species, when choosing optimal methods, the agreement between data generated on the Affymetrix and Illumina was excellent; this was verified using qRT-PCR on a selection of genes present on all platforms. Conclusion This study provides an extensive assessment of analytical methods best suited for processing data from different microarray technologies and can assist integration of technologically different gene expression datasets in biological systems.

Hypoxia-inducible factor directs POMC gene to mediate hypothalamic glucose sensing and energy balance regulation.

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Hai Zhang

2011-07-01

Full Text Available Hypoxia-inducible factor (HIF is a nuclear transcription factor that responds to environmental and pathological hypoxia to induce metabolic adaptation, vascular growth, and cell survival. Here we found that HIF subunits and HIF2α in particular were normally expressed in the mediobasal hypothalamus of mice. Hypothalamic HIF was up-regulated by glucose to mediate the feeding control of hypothalamic glucose sensing. Two underlying molecular pathways were identified, including suppression of PHDs by glucose metabolites to prevent HIF2α degradation and the recruitment of AMPK and mTOR/S6K to regulate HIF2α protein synthesis. HIF activation was found to directly control the transcription of POMC gene. Genetic approach was then employed to develop conditional knockout mice with HIF inhibition in POMC neurons, revealing that HIF loss-of-function in POMC neurons impaired hypothalamic glucose sensing and caused energy imbalance to promote obesity development. The metabolic effects of HIF in hypothalamic POMC neurons were independent of leptin signaling or pituitary ACTH pathway. Hypothalamic gene delivery of HIF counteracted overeating and obesity under conditions of nutritional excess. In conclusion, HIF controls hypothalamic POMC gene to direct the central nutrient sensing in regulation of energy and body weight balance.

Hypoxia-Inducible Factor Directs POMC Gene to Mediate Hypothalamic Glucose Sensing and Energy Balance Regulation

Science.gov (United States)

Zhang, Hai; Zhang, Guo; Gonzalez, Frank J.; Park, Sung-min; Cai, Dongsheng

2011-01-01

Hypoxia-inducible factor (HIF) is a nuclear transcription factor that responds to environmental and pathological hypoxia to induce metabolic adaptation, vascular growth, and cell survival. Here we found that HIF subunits and HIF2α in particular were normally expressed in the mediobasal hypothalamus of mice. Hypothalamic HIF was up-regulated by glucose to mediate the feeding control of hypothalamic glucose sensing. Two underlying molecular pathways were identified, including suppression of PHDs by glucose metabolites to prevent HIF2α degradation and the recruitment of AMPK and mTOR/S6K to regulate HIF2α protein synthesis. HIF activation was found to directly control the transcription of POMC gene. Genetic approach was then employed to develop conditional knockout mice with HIF inhibition in POMC neurons, revealing that HIF loss-of-function in POMC neurons impaired hypothalamic glucose sensing and caused energy imbalance to promote obesity development. The metabolic effects of HIF in hypothalamic POMC neurons were independent of leptin signaling or pituitary ACTH pathway. Hypothalamic gene delivery of HIF counteracted overeating and obesity under conditions of nutritional excess. In conclusion, HIF controls hypothalamic POMC gene to direct the central nutrient sensing in regulation of energy and body weight balance. PMID:21814490

Machine learning approaches to supporting the identification of photoreceptor-enriched genes based on expression data

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Simpson David

2006-03-01

Full Text Available Abstract Background Retinal photoreceptors are highly specialised cells, which detect light and are central to mammalian vision. Many retinal diseases occur as a result of inherited dysfunction of the rod and cone photoreceptor cells. Development and maintenance of photoreceptors requires appropriate regulation of the many genes specifically or highly expressed in these cells. Over the last decades, different experimental approaches have been developed to identify photoreceptor enriched genes. Recent progress in RNA analysis technology has generated large amounts of gene expression data relevant to retinal development. This paper assesses a machine learning methodology for supporting the identification of photoreceptor enriched genes based on expression data. Results Based on the analysis of publicly-available gene expression data from the developing mouse retina generated by serial analysis of gene expression (SAGE, this paper presents a predictive methodology comprising several in silico models for detecting key complex features and relationships encoded in the data, which may be useful to distinguish genes in terms of their functional roles. In order to understand temporal patterns of photoreceptor gene expression during retinal development, a two-way cluster analysis was firstly performed. By clustering SAGE libraries, a hierarchical tree reflecting relationships between developmental stages was obtained. By clustering SAGE tags, a more comprehensive expression profile for photoreceptor cells was revealed. To demonstrate the usefulness of machine learning-based models in predicting functional associations from the SAGE data, three supervised classification models were compared. The results indicated that a relatively simple instance-based model (KStar model performed significantly better than relatively more complex algorithms, e.g. neural networks. To deal with the problem of functional class imbalance occurring in the dataset, two data re

Future Directions for Building Services Technologies in Denmark

DEFF Research Database (Denmark)

Marsh, Rob

2008-01-01

strategies for the effective integration of building services, and by developing new industrialised solutions for building services. The paper is based on the current Danish situation, and is based on linking research on building services, user needs, building design and new industrial processes.  ......  The hypothesis of this paper is that industrial transformation in the Danish construction sector needs in the future to focus on integrating building services technologies into the buildings. This can be illustrated by analysing historical developments in building services usage, exploring design...

Direct detection of the AR-E211 G > A gene polymorphism from blood and tissue samples without DNA isolation.

Science.gov (United States)

Reptova, Silvie; Trtkova, Katerina Smesny; Kolar, Zdenek

2014-04-01

The pathogenesis of prostate cancer (CaP) involves alterations in a gene structure of the androgen receptor (AR). The single nucleotide polymorphism AR-E211 G > A localized in exon 1 of the AR gene (G1733A) was detected using direct polymerase chain reaction and restriction digestion (PCR-RFLP) method on blood and tissue samples without prior DNA isolation. We used blood samples of patients with a diagnosis of benign prostatic hyperplasia (BPH) or CaP. From monitored group of CaP patients were selected specimen in formalin-fixed paraffin-embedded tissue blocks with morphology of BPH and CaP. The main objective of our study was to develop a method based the direct PCR-RFLP analysis from blood and tissue without prior DNA isolation for faster genotyping analysis of a large number of samples. We found no statistically significant differences in allelic % of the AR-E211 G > A polymorphism between BPH and CaP patients (p ≤ 0.8462). Genotyping of the AR-E211 G > A variant in blood was not identical with tumor tissue genotyping analysis. Significant agreement between blood and tissue AR-E211 G > A polymorphism only in non-tumor tissue focus was confirmed. Although we analyzed a limited number of the tissue samples, we suppose that a presence of the minor allele A may be associated with cancer transformation-induced changes of the modified AR gene.

Efficacy of computer technology-based HIV prevention interventions: a meta-analysis.

Science.gov (United States)

Noar, Seth M; Black, Hulda G; Pierce, Larson B

2009-01-02

To conduct a meta-analysis of computer technology-based HIV prevention behavioral interventions aimed at increasing condom use among a variety of at-risk populations. Systematic review and meta-analysis of existing published and unpublished studies testing computer-based interventions. Meta-analytic techniques were used to compute and aggregate effect sizes for 12 randomized controlled trials that met inclusion criteria. Variables that had the potential to moderate intervention efficacy were also tested. The overall mean weighted effect size for condom use was d = 0.259 (95% confidence interval = 0.201, 0.317; Z = 8.74, P partners, and incident sexually transmitted diseases. In addition, interventions were significantly more efficacious when they were directed at men or women (versus mixed sex groups), utilized individualized tailoring, used a Stages of Change model, and had more intervention sessions. Computer technology-based HIV prevention interventions have similar efficacy to more traditional human-delivered interventions. Given their low cost to deliver, ability to customize intervention content, and flexible dissemination channels, they hold much promise for the future of HIV prevention.

Launching technological innovations

DEFF Research Database (Denmark)

Talke, Katrin; Salomo, Søren

2009-01-01

have received less attention. This study considers the interdependencies between strategic, internally and externally, directed tactical launch activities and investigates both direct and indirect performance effects. The analysis is based upon data from 113 technological innovations launched...

A New Two-Step Approach for Hands-On Teaching of Gene Technology: Effects on Students' Activities During Experimentation in an Outreach Gene Technology Lab

Science.gov (United States)

Scharfenberg, Franz-Josef; Bogner, Franz X.

2011-08-01

Emphasis on improving higher level biology education continues. A new two-step approach to the experimental phases within an outreach gene technology lab, derived from cognitive load theory, is presented. We compared our approach using a quasi-experimental design with the conventional one-step mode. The difference consisted of additional focused discussions combined with students writing down their ideas (step one) prior to starting any experimental procedure (step two). We monitored students' activities during the experimental phases by continuously videotaping 20 work groups within each approach ( N = 131). Subsequent classification of students' activities yielded 10 categories (with well-fitting intra- and inter-observer scores with respect to reliability). Based on the students' individual time budgets, we evaluated students' roles during experimentation from their prevalent activities (by independently using two cluster analysis methods). Independently of the approach, two common clusters emerged, which we labeled as `all-rounders' and as `passive students', and two clusters specific to each approach: `observers' as well as `high-experimenters' were identified only within the one-step approach whereas under the two-step conditions `managers' and `scribes' were identified. Potential changes in group-leadership style during experimentation are discussed, and conclusions for optimizing science teaching are drawn.

Attending to others: how digital technologies direct young people's nightlife

Directory of Open Access Journals (Sweden)

J. Truong

2018-05-01

Full Text Available It is a growing phenomenon that young people use mobile information and communication technologies during their nightlife. This article offers an empirical examination of how young people's nightlife is shaped by engagement with the mobile phone application WhatsApp. Drawing on Sara Ahmed's phenomenological concept of orientation, I examine how WhatsApp extends young people's nightlife and how young people become orientated therein. On the one hand, I show that nightlife acquires new boundaries and fixities that encourage young people to direct their attention towards missing social relations and absent nightlife places. On the other hand, I find that young people create new perceptions of how to inhabit and spend leisure time and space. I argue that digital technologies reorientate young people, which I suggest offers novel means of addressing young people's contemporary nightlife practices, places, spaces, and social relations.

Sex-based differences in gene expression in hippocampus following postnatal lead exposure

International Nuclear Information System (INIS)

Schneider, J.S.; Anderson, D.W.; Sonnenahalli, H.; Vadigepalli, R.

2011-01-01

The influence of sex as an effect modifier of childhood lead poisoning has received little systematic attention. Considering the paucity of information available concerning the interactive effects of lead and sex on the brain, the current study examined the interactive effects of lead and sex on gene expression patterns in the hippocampus, a structure involved in learning and memory. Male or female rats were fed either 1500 ppm lead-containing chow or control chow for 30 days beginning at weaning.Blood lead levels were 26.7 ± 2.1 μg/dl and 27.1 ± 1.7 μg/dl for females and males, respectively. The expression of 175 unique genes was differentially regulated between control male and female rats. A total of 167 unique genes were differentially expressed in response to lead in either males or females. Lead exposure had a significant effect without a significant difference between male and female responses in 77 of these genes. In another set of 71 genes, there were significant differences in male vs. female response. A third set of 30 genes was differentially expressed in opposite directions in males vs. females, with the majority of genes expressed at a lower level in females than in males. Highly differentially expressed genes in males and females following lead exposure were associated with diverse biological pathways and functions. These results show that a brief exposure to lead produced significant changes in expression of a variety of genes in the hippocampus and that the response of the brain to a given lead exposure may vary depending on sex. - Highlights: → Postnatal lead exposure has a significant effect on hippocampal gene expression patterns. → At least one set of genes was affected in opposite directions in males and females. → Differentially expressed genes were associated with diverse biological pathways.

How does the extracellular matrix direct gene expression

Energy Technology Data Exchange (ETDEWEB)

Bissell, M J; Hall, H G; Parry, G

1982-01-01

Based on the existing literature, a model is presented that postulates a ''dynamic reciprocity'' between the extracellular matrix (ECM) on the one hand and the cytoskeleton and the nuclear matrix on the other hand. The ECM is postulated to exert physical and chemical influences on the geometry and the biochemistry of the cell via transmembrane receptors so as to alter the pattern of gene expression by changing the association of the cytoskeleton with mRNA and the interaction of the chromatin with the nuclear matrix. This, in turn, would affect the ECM, which would affect the cell.

Sequence based polymorphic (SBP marker technology for targeted genomic regions: its application in generating a molecular map of the Arabidopsis thaliana genome

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Sahu Binod B

2012-01-01

Full Text Available Abstract Background Molecular markers facilitate both genotype identification, essential for modern animal and plant breeding, and the isolation of genes based on their map positions. Advancements in sequencing technology have made possible the identification of single nucleotide polymorphisms (SNPs for any genomic regions. Here a sequence based polymorphic (SBP marker technology for generating molecular markers for targeted genomic regions in Arabidopsis is described. Results A ~3X genome coverage sequence of the Arabidopsis thaliana ecotype, Niederzenz (Nd-0 was obtained by applying Illumina's sequencing by synthesis (Solexa technology. Comparison of the Nd-0 genome sequence with the assembled Columbia-0 (Col-0 genome sequence identified putative single nucleotide polymorphisms (SNPs throughout the entire genome. Multiple 75 base pair Nd-0 sequence reads containing SNPs and originating from individual genomic DNA molecules were the basis for developing co-dominant SBP markers. SNPs containing Col-0 sequences, supported by transcript sequences or sequences from multiple BAC clones, were compared to the respective Nd-0 sequences to identify possible restriction endonuclease enzyme site variations. Small amplicons, PCR amplified from both ecotypes, were digested with suitable restriction enzymes and resolved on a gel to reveal the sequence based polymorphisms. By applying this technology, 21 SBP markers for the marker poor regions of the Arabidopsis map representing polymorphisms between Col-0 and Nd-0 ecotypes were generated. Conclusions The SBP marker technology described here allowed the development of molecular markers for targeted genomic regions of Arabidopsis. It should facilitate isolation of co-dominant molecular markers for targeted genomic regions of any animal or plant species, whose genomic sequences have been assembled. This technology will particularly facilitate the development of high density molecular marker maps, essential for

Optical Fiber Sensors Based on Fiber Ring Laser Demodulation Technology.

Science.gov (United States)

Xie, Wen-Ge; Zhang, Ya-Nan; Wang, Peng-Zhao; Wang, Jian-Zhang

2018-02-08

A review for optical fiber sensors based on fiber ring laser (FRL) demodulation technology is presented. The review focuses on the principles, main structures, and the sensing performances of different kinds of optical fiber sensors based on FRLs. First of all, the theory background of the sensors has been discussed. Secondly, four different types of sensors are described and compared, which includes Mach-Zehnder interferometer (MZI) typed sensors, Fabry-Perot interferometer (FPI) typed sensors, Sagnac typed sensors, and fiber Bragg grating (FBG) typed sensors. Typical studies and main properties of each type of sensors are presented. Thirdly, a comparison of different types of sensors are made. Finally, the existing problems and future research directions are pointed out and analyzed.

Fast Gene Ontology based clustering for microarray experiments

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Ovaska Kristian

2008-11-01

Full Text Available Abstract Background Analysis of a microarray experiment often results in a list of hundreds of disease-associated genes. In order to suggest common biological processes and functions for these genes, Gene Ontology annotations with statistical testing are widely used. However, these analyses can produce a very large number of significantly altered biological processes. Thus, it is often challenging to interpret GO results and identify novel testable biological hypotheses. Results We present fast software for advanced gene annotation using semantic similarity for Gene Ontology terms combined with clustering and heat map visualisation. The methodology allows rapid identification of genes sharing the same Gene Ontology cluster. Conclusion Our R based semantic similarity open-source package has a speed advantage of over 2000-fold compared to existing implementations. From the resulting hierarchical clustering dendrogram genes sharing a GO term can be identified, and their differences in the gene expression patterns can be seen from the heat map. These methods facilitate advanced annotation of genes resulting from data analysis.

Reporter gene imaging: potential impact on therapy

International Nuclear Information System (INIS)

Serganova, Inna; Blasberg, Ronald

2005-01-01

Positron emission tomography (PET)-based molecular-genetic imaging in living organisms has enjoyed exceptional growth over the past 5 years; this is particularly striking since it has been identified as a new discipline only within the past decade. Positron emission tomography is one of three imaging technologies (nuclear, magnetic resonance and optical) that has begun to incorporate methods that are established in molecular and cell biology research. The convergence of these disciplines and the wider application of multi-modality imaging are at the heart of this success story. Most current molecular-genetic imaging strategies are 'indirect,' coupling a 'reporter gene' with a complimentary 'reporter probe.' Reporter gene constructs can be driven by constitutive promoter elements and used to monitor gene therapy vectors and the efficacy of trans gene targeting and transduction, as well as to monitor adoptive cell-based therapies. Inducible promoters can be used as 'sensors' to regulate the magnitude of reporter gene expression and can be used to provide information about endogenous cell processes. Reporter systems can also be constructed to monitor mRNA stabilization and specific protein-protein interactions. Promoters can be cell specific and restrict transgene expression to certain tissue and organs. The translation of reporter gene imaging to specific clinical applications is discussed. Several examples that have potential for patient imaging studies in the near future include monitoring adenoviral-based gene therapy, oncolytic herpes virus therapy, adoptive cell-based therapies and Salmonella-based tumor-targeted cancer therapy and imaging. The primary translational applications of noninvasive in vivo reporter gene imaging are likely to be (a) quantitative monitoring of the gene therapy vector and the efficacy of transduction in clinical protocols, by imaging the location, extent and duration of transgene expression; (b) monitoring cell trafficking, targeting

FY 1998 report on the results of the development of the utilization technology of biological resources such as bioconsortia. Development of the consortium based analysis technology; 1998 nendo fukugo seibutsukei nado seibutsu shigen riyo gijutsu kaihatsu seika hokokusho. Fukugo seibutsukei kaiseki gijutsu no kaihatsu

Energy Technology Data Exchange (ETDEWEB)

NONE

1999-03-01

For the purpose of establishing the analysis technology and industrial utilization technology required for the establishment of the utilization technology of consortia's high functions which are already used in the fermentation technology field over the limit of the conventional bio-technology using functions of single biological species, study was made to look for the consortium based analysis technology by which the consortium base can be analyzed as it is using the molecular biological method. Studies were made in the following four fields: 1) new identification technology of eucaryote using II DNA topoisomerase genes (PCR amplification method of II DNA topoisomerase genes); 2) method to detect new recognition peptide activated microorganism (adjustment of cortical antigen); 3) technology to elucidate detection/response mechanism of the specific environment and adaptation/resistance mechanism of the specific environment; 4) incubation method inside 3D matrices. In 3), studies were made of the analysis of inhibition mechanism of korormicin and separation of solvent-resistant oil degradable bacteria. In 4), for the settlement and dynamic analysis of microorganism consortium by studying incubation conditions, conducted was the molecular system analysis of bacteria and eumycetes inhabiting in sponge. (NEDO)

Gene array analysis of neural crest cells identifies transcription factors necessary for direct conversion of embryonic fibroblasts into neural crest cells

Directory of Open Access Journals (Sweden)

Tsutomu Motohashi

2016-03-01

Full Text Available Neural crest cells (NC cells are multipotent cells that emerge from the edge of the neural folds and migrate throughout the developing embryo. Although the gene regulatory network for generation of NC cells has been elucidated in detail, it has not been revealed which of the factors in the network are pivotal to directing NC identity. In this study we analyzed the gene expression profile of a pure NC subpopulation isolated from Sox10-IRES-Venus mice and investigated whether these genes played a key role in the direct conversion of Sox10-IRES-Venus mouse embryonic fibroblasts (MEFs into NC cells. The comparative molecular profiles of NC cells and neural tube cells in 9.5-day embryos revealed genes including transcription factors selectively expressed in developing trunk NC cells. Among 25 NC cell-specific transcription factor genes tested, SOX10 and SOX9 were capable of converting MEFs into SOX10-positive (SOX10+ cells. The SOX10+ cells were then shown to differentiate into neurons, glial cells, smooth muscle cells, adipocytes and osteoblasts. These SOX10+ cells also showed limited self-renewal ability, suggesting that SOX10 and SOX9 directly converted MEFs into NC cells. Conversely, the remaining transcription factors, including well-known NC cell specifiers, were unable to convert MEFs into SOX10+ NC cells. These results suggest that SOX10 and SOX9 are the key factors necessary for the direct conversion of MEFs into NC cells.

Advances and Research Directions in Data-Warehousing Technology

Directory of Open Access Journals (Sweden)

Mukesh Mohania

1999-11-01

Full Text Available Information is one of the most valuable assets of an organisation and when used properly can assist in intelligent decision making that can significantly improve the functioning of an organisation. Data Warehousing is a recent technology that allows information to be easily and efficiently accessed for decision-making activities by collecting data from many operational, legacy and possibly heterogeneous data sources. On-Line Analytical Processing (OLAP tools are well-suited for complex data analysis, such as multi-dimensional data analysis, and to assist in decision support activities while data mining tools take the process one step further and actively search the data for patterns and hidden knowledge in the data held in the warehouse. Many organisations are building, or are planning to develop, a data warehouse for their operational and decision support needs. In this paper, we present an overview of data warehousing, multi-dimensional databases, OLAP and data mining technology and discuss the directions of current research in the area. We also discuss recent developments in data warehouse modelling, view selection and maintenance, indexing schemes, parallel query processing and data mining issues. A number of technical issues for exploratory research are presented and possible solutions are also discussed.

Status of radiation-based measurement technology

International Nuclear Information System (INIS)

Moon, B. S.; Lee, J. W.; Chung, C. E.; Hong, S. B.; Kim, J. T.; Park, W. M.; Kim, J. Y.

1999-03-01

This report describes the status of measurement equipment using radiation source and new technologies in this field. This report includes the development status in Korea together with a brief description of the technology development and application status in ten countries including France, America, and Japan. Also this report describes technical factors related to radiation-based measurement and trends of new technologies. Measurement principles are also described for the equipment that is widely used among radiation-based measurement, such as level measurement, density measurement, basis weight measurement, moisture measurement, and thickness measurement. (author). 7 refs., 2 tabs., 21 figs

Performance-Based Technology Selection Filter description report

International Nuclear Information System (INIS)

O'Brien, M.C.; Morrison, J.L.; Morneau, R.A.; Rudin, M.J.; Richardson, J.G.

1992-05-01

A formal methodology has been developed for identifying technology gaps and assessing innovative or postulated technologies for inclusion in proposed Buried Waste Integrated Demonstration (BWID) remediation systems. Called the Performance-Based Technology Selection Filter, the methodology provides a formalized selection process where technologies and systems are rated and assessments made based on performance measures, and regulatory and technical requirements. The results are auditable, and can be validated with field data. This analysis methodology will be applied to the remedial action of transuranic contaminated waste pits and trenches buried at the Idaho National Engineering Laboratory (INEL)

Performance-Based Technology Selection Filter description report

Energy Technology Data Exchange (ETDEWEB)

O' Brien, M.C.; Morrison, J.L.; Morneau, R.A.; Rudin, M.J.; Richardson, J.G.

1992-05-01

A formal methodology has been developed for identifying technology gaps and assessing innovative or postulated technologies for inclusion in proposed Buried Waste Integrated Demonstration (BWID) remediation systems. Called the Performance-Based Technology Selection Filter, the methodology provides a formalized selection process where technologies and systems are rated and assessments made based on performance measures, and regulatory and technical requirements. The results are auditable, and can be validated with field data. This analysis methodology will be applied to the remedial action of transuranic contaminated waste pits and trenches buried at the Idaho National Engineering Laboratory (INEL).

Clinical and molecular characterization of a cohort of patients with novel nucleotide alterations of the Dystrophin gene detected by direct sequencing

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Corti Stefania

2011-03-01

Full Text Available Abstract Background Duchenne and Becker Muscular dystrophies (DMD/BMD are allelic disorders caused by mutations in the dystrophin gene, which encodes a sarcolemmal protein responsible for muscle integrity. Deletions and duplications account for approximately 75% of mutations in DMD and 85% in BMD. The implementation of techniques allowing complete gene sequencing has focused attention on small point mutations and other mechanisms underlying complex rearrangements. Methods We selected 47 patients (41 families; 35 DMD, 6 BMD without deletions and duplications in DMD gene (excluded by multiplex ligation-dependent probe amplification and multiplex polymerase chain reaction analysis. This cohort was investigated by systematic direct sequence analysis to study sequence variation. We focused our attention on rare mutational events which were further studied through transcript analysis. Results We identified 40 different nucleotide alterations in DMD gene and their clinical correlates; altogether, 16 mutations were novel. DMD probands carried 9 microinsertions/microdeletions, 19 nonsense mutations, and 7 splice-site mutations. BMD patients carried 2 nonsense mutations, 2 splice-site mutations, 1 missense substitution, and 1 single base insertion. The most frequent stop codon was TGA (n = 10 patients, followed by TAG (n = 7 and TAA (n = 4. We also analyzed the molecular mechanisms of five rare mutational events. They are two frame-shifting mutations in the DMD gene 3'end in BMD and three novel splicing defects: IVS42: c.6118-3C>A, which causes a leaky splice-site; c.9560A>G, which determines a cryptic splice-site activation and c.9564-426 T>G, which creates pseudoexon retention within IVS65. Conclusion The analysis of our patients' sample, carrying point mutations or complex rearrangements in DMD gene, contributes to the knowledge on phenotypic correlations in dystrophinopatic patients and can provide a better understanding of pre-mRNA maturation defects

In Vivo Gene Therapy of Hemophilia B: Sustained Partial Correction in Factor IX-Deficient Dogs

Science.gov (United States)

Kay, Mark A.; Rothenberg, Steven; Landen, Charles N.; Bellinger, Dwight A.; Leland, Frances; Toman, Carol; Finegold, Milton; Thompson, Arthur R.; Read, M. S.; Brinkhous, Kenneth M.; Woo, Savio L. C.

1993-10-01

The liver represents a model organ for gene therapy. A method has been developed for hepatic gene transfer in vivo by the direct infusion of recombinant retroviral vectors into the portal vasculature, which results in the persistent expression of exogenous genes. To determine if these technologies are applicable for the treatment of hemophilia B patients, preclinical efficacy studies were done in a hemophilia B dog model. When the canine factor IX complementary DNA was transduced directly into the hepatocytes of affected dogs in vivo, the animals constitutively expressed low levels of canine factor IX for more than 5 months. Persistent expression of the clotting. factor resulted in reductions of whole blood clotting and partial thromboplastin times of the treated animals. Thus, long-term treatment of hemophilia B patients may be feasible by direct hepatic gene therapy in vivo.

Two-Way Gene Interaction From Microarray Data Based on Correlation Methods.

Science.gov (United States)

Alavi Majd, Hamid; Talebi, Atefeh; Gilany, Kambiz; Khayyer, Nasibeh

2016-06-01

Gene networks have generated a massive explosion in the development of high-throughput techniques for monitoring various aspects of gene activity. Networks offer a natural way to model interactions between genes, and extracting gene network information from high-throughput genomic data is an important and difficult task. The purpose of this study is to construct a two-way gene network based on parametric and nonparametric correlation coefficients. The first step in constructing a Gene Co-expression Network is to score all pairs of gene vectors. The second step is to select a score threshold and connect all gene pairs whose scores exceed this value. In the foundation-application study, we constructed two-way gene networks using nonparametric methods, such as Spearman's rank correlation coefficient and Blomqvist's measure, and compared them with Pearson's correlation coefficient. We surveyed six genes of venous thrombosis disease, made a matrix entry representing the score for the corresponding gene pair, and obtained two-way interactions using Pearson's correlation, Spearman's rank correlation, and Blomqvist's coefficient. Finally, these methods were compared with Cytoscape, based on BIND, and Gene Ontology, based on molecular function visual methods; R software version 3.2 and Bioconductor were used to perform these methods. Based on the Pearson and Spearman correlations, the results were the same and were confirmed by Cytoscape and GO visual methods; however, Blomqvist's coefficient was not confirmed by visual methods. Some results of the correlation coefficients are not the same with visualization. The reason may be due to the small number of data.

An ultra-high-speed direct digital frequency synthesizer implemented in GaAs HBT technology

International Nuclear Information System (INIS)

Chen Gaopeng; Wu Danyu; Jin Zhi; Liu Xinyu

2010-01-01

This paper presents a 10-GHz 8-bit direct digital synthesizer (DDS) microwave monolithic integrated circuit implemented in 1 μm GaAs HBT technology. The DDS takes a double-edge-trigger (DET) 8-stage pipeline accumulator with sine-weighted DAC-based ROM-less architecture, which can maximize the utilization ratio of the GaAs HBT's high-speed potential. With an output frequency up to 5 GHz, the DDS gives an average spurious free dynamic range of 23.24 dBc through the first Nyquist band, and consumes 2.4 W of DC power from a single -4.6 V DC supply. Using 1651 GaAs HBT transistors, the total area of the DDS chip is 2.4 x 2.0 mm 2 . (semiconductor integrated circuits)

Recent Trends of Polymer Mediated Liposomal Gene Delivery System

Directory of Open Access Journals (Sweden)

Shyamal Kumar Kundu

2014-01-01

Full Text Available Advancement in the gene delivery system have resulted in clinical successes in gene therapy for patients with several genetic diseases, such as immunodeficiency diseases, X-linked adrenoleukodystrophy (X-ALD blindness, thalassemia, and many more. Among various delivery systems, liposomal mediated gene delivery route is offering great promises for gene therapy. This review is an attempt to depict a portrait about the polymer based liposomal gene delivery systems and their future applications. Herein, we have discussed in detail the characteristics of liposome, importance of polymer for liposome formulation, gene delivery, and future direction of liposome based gene delivery as a whole.

Activating human genes with zinc finger proteins, transcription activator-like effectors and CRISPR/Cas9 for gene therapy and regenerative medicine.

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Gersbach, Charles A; Perez-Pinera, Pablo

2014-08-01

New technologies have recently been developed to control the expression of human genes in their native genomic context by engineering synthetic transcription factors that can be targeted to any DNA sequence. The ability to precisely regulate any gene as it occurs naturally in the genome provides a means to address a variety of diseases and disorders. This approach also circumvents some of the traditional challenges of gene therapy. In this editorial, we review the technologies that have enabled targeted human gene activation, including the engineering of transcription factors based on zinc finger proteins, transcription activator-like effectors and the CRISPR/Cas9 system. Additionally, we highlight examples in which these methods have been developed for therapeutic applications and discuss challenges and opportunities.

Network-based differential gene expression analysis suggests cell cycle related genes regulated by E2F1 underlie the molecular difference between smoker and non-smoker lung adenocarcinoma

Science.gov (United States)

2013-01-01

Background Differential gene expression (DGE) analysis is commonly used to reveal the deregulated molecular mechanisms of complex diseases. However, traditional DGE analysis (e.g., the t test or the rank sum test) tests each gene independently without considering interactions between them. Top-ranked differentially regulated genes prioritized by the analysis may not directly relate to the coherent molecular changes underlying complex diseases. Joint analyses of co-expression and DGE have been applied to reveal the deregulated molecular modules underlying complex diseases. Most of these methods consist of separate steps: first to identify gene-gene relationships under the studied phenotype then to integrate them with gene expression changes for prioritizing signature genes, or vice versa. It is warrant a method that can simultaneously consider gene-gene co-expression strength and corresponding expression level changes so that both types of information can be leveraged optimally. Results In this paper, we develop a gene module based method for differential gene expression analysis, named network-based differential gene expression (nDGE) analysis, a one-step integrative process for prioritizing deregulated genes and grouping them into gene modules. We demonstrate that nDGE outperforms existing methods in prioritizing deregulated genes and discovering deregulated gene modules using simulated data sets. When tested on a series of smoker and non-smoker lung adenocarcinoma data sets, we show that top differentially regulated genes identified by the rank sum test in different sets are not consistent while top ranked genes defined by nDGE in different data sets significantly overlap. nDGE results suggest that a differentially regulated gene module, which is enriched for cell cycle related genes and E2F1 targeted genes, plays a role in the molecular differences between smoker and non-smoker lung adenocarcinoma. Conclusions In this paper, we develop nDGE to prioritize

Gene Disruption Technologies Have the Potential to Transform Stored Product Insect Pest Control.

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Perkin, Lindsey C; Adrianos, Sherry L; Oppert, Brenda

2016-09-19

Stored product insects feed on grains and processed commodities manufactured from grain post-harvest, reducing the nutritional value and contaminating food. Currently, the main defense against stored product insect pests is the pesticide fumigant phosphine. Phosphine is highly toxic to all animals, but is the most effective and economical control method, and thus is used extensively worldwide. However, many insect populations have become resistant to phosphine, in some cases to very high levels. New, environmentally benign and more effective control strategies are needed for stored product pests. RNA interference (RNAi) may overcome pesticide resistance by targeting the expression of genes that contribute to resistance in insects. Most data on RNAi in stored product insects is from the coleopteran genetic model, Tribolium castaneum, since it has a strong RNAi response via injection of double stranded RNA (dsRNA) in any life stage. Additionally, Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) technology has been suggested as a potential resource for new pest control strategies. In this review we discuss background information on both gene disruption technologies and summarize the advances made in terms of molecular pest management in stored product insects, mainly T. castaneum, as well as complications and future needs.

Shrinkage covariance matrix approach based on robust trimmed mean in gene sets detection

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Karjanto, Suryaefiza; Ramli, Norazan Mohamed; Ghani, Nor Azura Md; Aripin, Rasimah; Yusop, Noorezatty Mohd

2015-02-01

Microarray involves of placing an orderly arrangement of thousands of gene sequences in a grid on a suitable surface. The technology has made a novelty discovery since its development and obtained an increasing attention among researchers. The widespread of microarray technology is largely due to its ability to perform simultaneous analysis of thousands of genes in a massively parallel manner in one experiment. Hence, it provides valuable knowledge on gene interaction and function. The microarray data set typically consists of tens of thousands of genes (variables) from just dozens of samples due to various constraints. Therefore, the sample covariance matrix in Hotelling's T2 statistic is not positive definite and become singular, thus it cannot be inverted. In this research, the Hotelling's T2 statistic is combined with a shrinkage approach as an alternative estimation to estimate the covariance matrix to detect significant gene sets. The use of shrinkage covariance matrix overcomes the singularity problem by converting an unbiased to an improved biased estimator of covariance matrix. Robust trimmed mean is integrated into the shrinkage matrix to reduce the influence of outliers and consequently increases its efficiency. The performance of the proposed method is measured using several simulation designs. The results are expected to outperform existing techniques in many tested conditions.

[From gene cloning to expressional analysis--practice and experience from educational reform of experimental gene engineering].

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Wu, Yan-Hua; Guo, Bin; Lou, Hui-Ling; Cui, Yu-Liang; Gu, Hui-Juan; Qiao, Shou-Yi

2012-02-01

Experimental gene engineering is a laboratory course focusing on the molecular structure, expression pattern and biological function of genes. Providing our students with a solid knowledge base and correct ways to conduct research is very important for high-quality education of genetic engineering. Inspired by recent progresses in this field, we improved the experimental gene engineering course by adding more updated knowledge and technologies and emphasizing on the combination of teaching and research, with the aim of offering our students a good start in their scientific careers.

Foreign direct investment and technology spillovers in Mexico: 20 years of NAFTA

Directory of Open Access Journals (Sweden)

Enrique Armas

2017-10-01

Full Text Available This article analyses the development of technology capabilities in the manufacturing sector of Mexico during the last two decades. It has been argued that the inclusion of Mexico in the North America Free Trade Agreement (NAFTA in 1994 would be enough to catch up with Canada and the United States. In this regard, trade liberalisation and foreign direct investment (FDI would have been two strategic tools to close the technology gap between Mexico and its commercial partners in North America. Yet, after twenty years of NAFTA, it has been demonstrated that many indigenous firms in Mexico must develop an absorptive capacity to benefit from FDI. This paper suggests that the debate on the Asian miracle in the 1990s could be an adequate theoretical framework to discuss technology development and industrialisation in the case of emerging economies. In fact, this debate reveals two alternative approaches to explain the development of technology capabilities: (i the accumulation view of growth, and (ii the assimilation view of growth. Therefore, the Asian miracle exemplifies how entrepreneurship, learning and a supporting innovation policy could be an adequate strategy to benefit from FDI and technology spillovers in the case of emerging economies.

Evolutionary dynamics of DNA-binding sites and direct target genes of a floral master regulatory transcription factor [ChIP-Seq

NARCIS (Netherlands)

Muiño, J.M.; Bruijn, de S.A.; Vingron, Martin; Angenent, G.C.; Kaufmann, K.

2015-01-01

Plant development is controlled by transcription factors (TFs) which form complex gene-regulatory networks. Genome-wide TF DNA-binding studies revealed that these TFs have several thousands of binding sites in the Arabidopsis genome, and may regulate the expression of many genes directly. Given the

Development of a direct push based in-situ thermal conductivity measurement system

Science.gov (United States)

Chirla, Marian Andrei; Vienken, Thomas; Dietrich, Peter; Bumberger, Jan

2016-04-01

push based approaches, called Thermal Conductivity Profiler (TCP), that operates based on the principles of a hollow cylindrical geometry heat source. To determinate thermal conductivity in situ, the transient temperature at the middle of the probe and electrical power dissipation is measured. At the same time, this work presents laboratory results obtained when this novel hollow cylindrical probe system was tested on different materials for calibration. By using the hollow cylindrical probe, the thermal conductivity results have an error of less than 2.5% error for solid samples (Teflon, Agar jelly, and Nylatron). These findings are useful to achieve a proper thermal energy balance in the shallow subsurface by using direct push technology and TCP. By providing information of layers with high thermal conductivity, suitable for thermal storage capability, can be used determine borehole heat exchanger design and, therefore, determine geothermal heat pump architecture.

Antibiotic resistance genes fate and removal by a technological treatment solution for water reuse in agriculture.

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Luprano, Maria Laura; De Sanctis, Marco; Del Moro, Guido; Di Iaconi, Claudio; Lopez, Antonio; Levantesi, Caterina

2016-11-15

In order to mitigate the potential effects on the human health which are associated to the use of treated wastewater in agriculture, antibiotic resistance genes (ARGs) are required to be carefully monitored in wastewater reuse processes and their spread should be prevented by the development of efficient treatment technologies. Objective of this study was the assessment of ARGs reduction efficiencies of a novel technological treatment solution for agricultural reuse of municipal wastewaters. The proposed solution comprises an advanced biological treatment (Sequencing Batch Biofilter Granular Reactor, SBBGR), analysed both al laboratory and pilot scale, followed by sand filtration and two different disinfection final stages: ultraviolet light (UV) radiation and peracetic acid (PAA) treatments. By Polymerase Chain Reaction (PCR), the presence of 9 ARGs (ampC, mecA, ermB, sul1, sul2, tetA, tetO, tetW, vanA) were analysed and by quantitative PCR (qPCR) their removal was determined. The obtained results were compared to the reduction of total bacteria (16S rDNA gene) and of a faecal contamination indicator (Escherichia coli uidA gene). Only four of the analysed genes (ermB, sul1, sul2, tetA) were detected in raw wastewater and their abundance was estimated to be 3.4±0.7 x10(4) - 9.6±0.5 x10(9) and 1.0±0.3 x10(3) to 3.0±0.1 x10(7) gene copies/mL in raw and treated wastewaters, respectively. The results show that SBBGR technology is promising for the reduction of ARGs, achieving stable removal performance ranging from 1.0±0.4 to 2.8±0.7 log units, which is comparable to or higher than that reported for conventional activated sludge treatments. No reduction of the ARGs amount normalized to the total bacteria content (16S rDNA), was instead obtained, indicating that these genes are removed together with total bacteria and not specifically eliminated. Enhanced ARGs removal was obtained by sand filtration, while no reduction was achieved by both UV and PAA disinfection

What drives technology-based distractions? A structural equation model on social-psychological factors of technology-based driver distraction engagement.

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Chen, Huei-Yen Winnie; Donmez, Birsen

2016-06-01

With the proliferation of new mobile and in-vehicle technologies, understanding the motivations behind a driver's voluntary engagement with such technologies is crucial from a safety perspective, yet is complex. Previous literature either surveyed a large number of distractions that may be diverse, or too focuses on one particular activity, such as cell phone use. Further, earlier studies about social-psychological factors underlying driver distraction tend to focus on one or two factors in-depth, and those that examine a more comprehensive set of factors are often limited in their analyses methods. The present work considers a wide array of social-psychological factors within a structural equation model to predict their influence on a focused set of technology-based distractions. A better understanding of these facilitators can enhance the design of distraction mitigation strategies. We analysed survey responses about three technology-based driver distractions: holding phone conversations, manually interacting with cell phones, and adjusting the settings of in-vehicle technology, as well as responses on five social-psychological factors: attitude, descriptive norm, injunctive norm, technology inclination, and a risk/sensation seeking personality. Using data collected from 525 drivers (ages: 18-80), a structural equation model was built to analyse these social-psychological factors as latent variables influencing self-reported engagement in these three technology-based distractions. Self-reported engagement in technology-based distractions was found to be largely influenced by attitudes about the distractions. Personality and social norms also played a significant role, but technology inclination did not. A closer look at two age groups (18-30 and 30+) showed that the effect of social norms, especially of injunctive norm (i.e., perceived approvals), was less prominent in the 30+ age group, while personality remained a significant predictor for the 30+ age group but

Development of germline manipulation technologies in livestock

International Nuclear Information System (INIS)

Whitelaw, C.B.A.

2005-01-01

Genetic improvement by conventional breeding is restricted to those genetic loci present in the parental breeding individuals. Gene addition through transgenic technology offers a route to overcome this restriction. The transgene can be introduced into the germ cells or the fertilized zygote, using viral vectors, by simple co-culture or direct micro-injection. Alternatively, the transgene can be incorporated into a somatic cell, which is then incorporated into a developing embryo. This latter approach allows gene-targeting strategies to be employed. Using pronuclear injection methods, transgenic livestock have been generated with the aim of enhancing breeding traits of agricultural importance, or for biomedical applications. Neither has been taken beyond the development phase. Before they are, in addition to issues of commercial development, basic technological issues addressing inefficiency and complexity of the methodology need to be overcome, and appropriate gene targets identified. At the moment, perhaps the most encouraging development involves the use of viral vectors that offer increased simplicity and efficiency. By combining this new technology with transgenes that evoke the powerful intracellular machinery involved in RNA interference, pioneering applications to generate animals that are less susceptible to infectious disease may be possible. (author)

Direct gene transfer in the Gottingen minipig CNS using stereotaxic lentiviral microinjections

DEFF Research Database (Denmark)

GLUD, AN; Hedegaard, Claus; Nielsen, Mette Slot

2010-01-01

We aim to induce direct viral mediated gene transfer in the substantia nigra (SN) of the Gottingen minipig using MRI guided stereotaxic injections of lentiviral vectors encoding enhanced green fluorescent protein (EGFP). Nine female Gottingen minipigs were injected unilaterally into the SN with 6...... per 2.5 microliters lentivirus capable of transducing cells and mediating expression of recombinant EGFP. The animals were euthanized after four (n=3) or twenty weeks (n=6). Fresh brain tissue from three animals was used for PCR. The remaining six brains were cryo- or paraffin...

Profiling microbial lignocellulose degradation and utilization by emergent omics technologies.

Science.gov (United States)

Rosnow, Joshua J; Anderson, Lindsey N; Nair, Reji N; Baker, Erin S; Wright, Aaron T

2017-08-01

The use of plant materials to generate renewable biofuels and other high-value chemicals is the sustainable and preferable option, but will require considerable improvements to increase the rate and efficiency of lignocellulose depolymerization. This review highlights novel and emerging technologies that are being developed and deployed to characterize the process of lignocellulose degradation. The review will also illustrate how microbial communities deconstruct and metabolize lignocellulose by identifying the necessary genes and enzyme activities along with the reaction products. These technologies include multi-omic measurements, cell sorting and isolation, nuclear magnetic resonance spectroscopy (NMR), activity-based protein profiling, and direct measurement of enzyme activity. The recalcitrant nature of lignocellulose necessitates the need to characterize the methods microbes employ to deconstruct lignocellulose to inform new strategies on how to greatly improve biofuel conversion processes. New technologies are yielding important insights into microbial functions and strategies employed to degrade lignocellulose, providing a mechanistic blueprint in order to advance biofuel production.

Developing technology-enhanced active learning for medical education: challenges, solutions, and future directions.

Science.gov (United States)

McCoy, Lise; Pettit, Robin K; Lewis, Joy H; Bennett, Thomas; Carrasco, Noel; Brysacz, Stanley; Makin, Inder Raj S; Hutman, Ryan; Schwartz, Frederic N

2015-04-01

Growing up in an era of video games and Web-based applications has primed current medical students to expect rapid, interactive feedback. To address this need, the A.T. Still University-School of Osteopathic Medicine in Arizona (Mesa) has developed and integrated a variety of approaches using technology-enhanced active learning for medical education (TEAL-MEd) into its curriculum. Over the course of 3 years (2010-2013), the authors facilitated more than 80 implementations of games and virtual patient simulations into the education of 550 osteopathic medical students. The authors report on 4 key aspects of the TEAL-MEd initiative, including purpose, portfolio of tools, progress to date regarding challenges and solutions, and future directions. Lessons learned may be of benefit to medical educators at academic and clinical training sites who wish to implement TEAL-MEd activities.

Density based pruning for identification of differentially expressed genes from microarray data

Directory of Open Access Journals (Sweden)

Xu Jia

2010-11-01

Full Text Available Abstract Motivation Identification of differentially expressed genes from microarray datasets is one of the most important analyses for microarray data mining. Popular algorithms such as statistical t-test rank genes based on a single statistics. The false positive rate of these methods can be improved by considering other features of differentially expressed genes. Results We proposed a pattern recognition strategy for identifying differentially expressed genes. Genes are mapped to a two dimension feature space composed of average difference of gene expression and average expression levels. A density based pruning algorithm (DB Pruning is developed to screen out potential differentially expressed genes usually located in the sparse boundary region. Biases of popular algorithms for identifying differentially expressed genes are visually characterized. Experiments on 17 datasets from Gene Omnibus Database (GEO with experimentally verified differentially expressed genes showed that DB pruning can significantly improve the prediction accuracy of popular identification algorithms such as t-test, rank product, and fold change. Conclusions Density based pruning of non-differentially expressed genes is an effective method for enhancing statistical testing based algorithms for identifying differentially expressed genes. It improves t-test, rank product, and fold change by 11% to 50% in the numbers of identified true differentially expressed genes. The source code of DB pruning is freely available on our website http://mleg.cse.sc.edu/degprune

Progresses towards safe and efficient gene therapy vectors.

Science.gov (United States)

Chira, Sergiu; Jackson, Carlo S; Oprea, Iulian; Ozturk, Ferhat; Pepper, Michael S; Diaconu, Iulia; Braicu, Cornelia; Raduly, Lajos-Zsolt; Calin, George A; Berindan-Neagoe, Ioana

2015-10-13

The emergence of genetic engineering at the beginning of the 1970's opened the era of biomedical technologies, which aims to improve human health using genetic manipulation techniques in a clinical context. Gene therapy represents an innovating and appealing strategy for treatment of human diseases, which utilizes vehicles or vectors for delivering therapeutic genes into the patients' body. However, a few past unsuccessful events that negatively marked the beginning of gene therapy resulted in the need for further studies regarding the design and biology of gene therapy vectors, so that this innovating treatment approach can successfully move from bench to bedside. In this paper, we review the major gene delivery vectors and recent improvements made in their design meant to overcome the issues that commonly arise with the use of gene therapy vectors. At the end of the manuscript, we summarized the main advantages and disadvantages of common gene therapy vectors and we discuss possible future directions for potential therapeutic vectors.

Gas Sensors Based on Molecular Imprinting Technology.

Science.gov (United States)

Zhang, Yumin; Zhang, Jin; Liu, Qingju

2017-07-04

Molecular imprinting technology (MIT); often described as a method of designing a material to remember a target molecular structure (template); is a technique for the creation of molecularly imprinted polymers (MIPs) with custom-made binding sites complementary to the target molecules in shape; size and functional groups. MIT has been successfully applied to analyze; separate and detect macromolecular organic compounds. Furthermore; it has been increasingly applied in assays of biological macromolecules. Owing to its unique features of structure specificity; predictability; recognition and universal application; there has been exploration of the possible application of MIPs in the field of highly selective gas sensors. In this present study; we outline the recent advances in gas sensors based on MIT; classify and introduce the existing molecularly imprinted gas sensors; summarize their advantages and disadvantages; and analyze further research directions.

Results-Based Organization Design for Technology Entrepreneurs

Directory of Open Access Journals (Sweden)

Chris McPhee

2012-05-01

Full Text Available Faced with considerable uncertainty, entrepreneurs would benefit from clearly defined objectives, a plan to achieve these objectives (including a reasonable expectation that this plan will work, as well as a means to measure progress and make requisite course corrections. In this article, the author combines the benefits of results-based management with the benefits of organization design to describe a practical approach that technology entrepreneurs can use to design their organizations so that they deliver desired outcomes. This approach links insights from theory and practice, builds logical connections between entrepreneurial activities and desired outcomes, and measures progress toward those outcomes. This approach also provides a mechanism for entrepreneurs to make continual adjustments and improvements to their design and direction in response to data, customer and stakeholder feedback, and changes in their business environment.

The application of gene-based technologies in the study of Newcastle disease virus isolates from Uganda

International Nuclear Information System (INIS)

Otim, M.O.; Bisgaard, M.; Christensen, H.; Jorgensen, P.; Handberg, K.

2005-01-01

Molecular techniques were used to characterize 16 Newcastle disease (ND) Virus (NDV) isolates from ND outbreaks in chickens in eastern Uganda in 2001, and evaluate ND epidemiology, with emphasis on molecular aspects. F and HN genes, which are the major determinants of virulence, were studied. Strain pathogenicity was derived from genetic analysis of the F gene sequence and intracerebral pathogenicity index (ICPI). Comparative genetic and phylogenetic tree analyses were performed on the HN genes of the isolates and some strains selected from GenBank. ClustalX 1.81 and Phylip were used for gene alignment analysis and the final phylogeny was produced by the neighbour-joining method. F gene cleavage site sequence analysis, phylogenetic analysis and biological characterization showed that the strains were very virulent and closely related, being of common ancestry. All the Ugandan NDV isolates formed separate clades from the currently known genotypes, suggesting that they are a novel genotype, unrelated to those that have caused previous pandemics. (author)

Comparative study on gene set and pathway topology-based enrichment methods.

Science.gov (United States)

Bayerlová, Michaela; Jung, Klaus; Kramer, Frank; Klemm, Florian; Bleckmann, Annalen; Beißbarth, Tim

2015-10-22

Enrichment analysis is a popular approach to identify pathways or sets of genes which are significantly enriched in the context of differentially expressed genes. The traditional gene set enrichment approach considers a pathway as a simple gene list disregarding any knowledge of gene or protein interactions. In contrast, the new group of so called pathway topology-based methods integrates the topological structure of a pathway into the analysis. We comparatively investigated gene set and pathway topology-based enrichment approaches, considering three gene set and four topological methods. These methods were compared in two extensive simulation studies and on a benchmark of 36 real datasets, providing the same pathway input data for all methods. In the benchmark data analysis both types of methods showed a comparable ability to detect enriched pathways. The first simulation study was conducted with KEGG pathways, which showed considerable gene overlaps between each other. In this study with original KEGG pathways, none of the topology-based methods outperformed the gene set approach. Therefore, a second simulation study was performed on non-overlapping pathways created by unique gene IDs. Here, methods accounting for pathway topology reached higher accuracy than the gene set methods, however their sensitivity was lower. We conducted one of the first comprehensive comparative works on evaluating gene set against pathway topology-based enrichment methods. The topological methods showed better performance in the simulation scenarios with non-overlapping pathways, however, they were not conclusively better in the other scenarios. This suggests that simple gene set approach might be sufficient to detect an enriched pathway under realistic circumstances. Nevertheless, more extensive studies and further benchmark data are needed to systematically evaluate these methods and to assess what gain and cost pathway topology information introduces into enrichment analysis. Both

A sight on the current nanoparticle-based gene delivery vectors