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Academic literature on the topic 'Synthetic pioneer factors'
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Journal articles on the topic "Synthetic pioneer factors"
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Sheikh, Abdul Haseeb Aamir, Muhammad Ikram, Rana Mamoon Ahmad, Hamza Qadeer, and Muhammad Nawaz. "Evaluation of key factors influencing process quality during construction projects in Pakistan." Grey Systems: Theory and Application 9, no. 3 (July 1, 2019): 321–35. http://dx.doi.org/10.1108/gs-01-2019-0002.
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Purpose The quality of construction projects is mainly dependent on the process quality during the construction phase than product quality. The key factors that influence the process quality of building projects in Pakistan during the construction phase of building life cycle are evaluated from literature. This paper aims to discuss these issues. Design/methodology/approach The factors were ranked using the traditional relative importance index (RII) and the second synthetic grey relational analysis method. The findings indicate that during the construction phase the selection of an appropriate contractor is the most important factor. The existence of feedback system and quality of shop drawings received from subcontractors are also very significant factors, according to the grey relational model. Findings Measures for the improvement of process quality in Pakistan are suggested. The results from both methods are not entirely comparable; however, if one considers uncertainty in data, then the second synthetic GRA-based ranking should be preferred over RII in decision making. Originality/value The study is pioneer in the evaluation of key factors influencing process quality during building construction projects in Pakistan using a set of traditional and novel methods. The results of this study are significant in improving the process quality during different phases of construction.
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Maleki, Masomeh, Reza Zarezadeh, Mohammad Nouri, Aydin Raei Sadigh, Farhad Pouremamali, Zatollah Asemi, Hossein Samadi Kafil, Forough Alemi, and Bahman Yousefi. "Graphene Oxide: A Promising Material for Regenerative Medicine and Tissue Engineering." Biomolecular Concepts 11, no. 1 (December 31, 2020): 182–200. http://dx.doi.org/10.1515/bmc-2020-0017.
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AbstractRegenerative medicine and tissue engineering have been considered pioneer fields in the life sciences, with an ultimate goal of restoring or switching lost or impaired body parts. Graphene oxide (GO) is the product of graphene oxidation and presents a great opportunity to make substantial progress in the field of regenerative medicine; for example, it supports the possibility of creating a cellular niche for stem cells on a nanoparticle surface. GO creates a fascinating structure for regulating stem cell behavior, as it can potentially applied to the noninvasive chase of stem cells in vivo, the liberation of active biological factors from stem cell-containing delivery systems, and the intracellular delivery of factors such as growth factors, DNA, or synthetic proteins in order to modulate stem cell differentiation and proliferation. Due to the interesting physicochemical properties of GO and its possible usage in tissue engineering approaches, the present review aims to elaborate on the ways in which GO can improve current regenerative strategies. In this respect, the applicability of GO to the repair and regeneration of various tissues and organs, including cardiac muscle, skeletal muscle, and nervous, bone, cartilage, adipose, and skin tissues, is discussed.
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Gui, Bin, Fu Gui, Tomoaki Takai, Chao Feng, Xiao Bai, Ladan Fazli, Xuesen Dong, et al. "Selective targeting of PARP-2 inhibits androgen receptor signaling and prostate cancer growth through disruption of FOXA1 function." Proceedings of the National Academy of Sciences 116, no. 29 (July 2, 2019): 14573–82. http://dx.doi.org/10.1073/pnas.1908547116.
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Androgen receptor (AR) is a ligand-activated transcription factor and a key driver of prostate cancer (PCa) growth and progression. Understanding the factors influencing AR-mediated gene expression provides new opportunities for therapeutic intervention. Poly(ADP-ribose) Polymerase (PARP) is a family of enzymes, which posttranslationally modify a range of proteins and regulate many different cellular processes. PARP-1 and PARP-2 are two well-characterized PARP members, whose catalytic activity is induced by DNA-strand breaks and responsible for multiple DNA damage repair pathways. PARP inhibitors are promising therapeutic agents that show synthetic lethality against many types of cancer (including PCa) with homologous recombination (HR) DNA-repair deficiency. Here, we show that, beyond DNA damage repair function, PARP-2, but not PARP-1, is a critical component in AR transcriptional machinery through interacting with the pioneer factor FOXA1 and facilitating AR recruitment to genome-wide prostate-specific enhancer regions. Analyses of PARP-2 expression at both mRNA and protein levels show significantly higher expression of PARP-2 in primary PCa tumors than in benign prostate tissues, and even more so in castration-resistant prostate cancer (CRPC) tumors. Selective targeting of PARP-2 by genetic or pharmacological means blocks interaction between PARP-2 and FOXA1, which in turn attenuates AR-mediated gene expression and inhibits AR-positive PCa growth. Next-generation antiandrogens act through inhibiting androgen synthesis (abiraterone) or blocking ligand binding (enzalutamide). Selective targeting of PARP-2, however, may provide an alternative therapeutic approach for AR inhibition by disruption of FOXA1 function, which may be beneficial to patients, irrespective of their DNA-repair deficiency status.
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Hashino, Eri, Marlene Shero, Dirk Junghans, Hermann Rohrer, Jeffrey Milbrandt, and Eugene M. Johnson. "GDNF and neurturin are target-derived factors essential for cranial parasympathetic neuron development." Development 128, no. 19 (October 1, 2001): 3773–82. http://dx.doi.org/10.1242/dev.128.19.3773.
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During development, parasympathetic ciliary ganglion neurons arise from the neural crest and establish synaptic contacts on smooth and striate muscle in the eye. The factors that promote the ciliary ganglion pioneer axons to grow toward their targets have yet to be determined. Here, we show that glial cell line-derived neurotrophic factor (GDNF) and neurturin (NRTN) constitute target-derived factors for developing ciliary ganglion neurons. Both GDNF and NRTN are secreted from eye muscle located in the target and trajectory pathway of ciliary ganglion pioneer axons during the period of target innervation. After this period, however, the synthesis of GDNF declines markedly, while that of NRTN is maintained throughout the cell death period. Furthermore, both in vitro and in vivo function-blocking of GDNF at early embryonic ages almost entirely suppresses ciliary axon outgrowth. These results demonstrate that target-derived GDNF is necessary for ciliary ganglion neurons to innervate ciliary muscle in the eye. Since the down-regulation of GDNF in the eye is accompanied by down-regulation of GFRα1 and Ret, but not of GFRα2, in innervating ciliary ganglion neurons, the results also suggest that target-derived GDNF regulates the expression of its high-affinity coreceptors.
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Frater, R. H., W. M. Goss, and H. W. Wendt. "Bernard Yarnton Mills 1920–2011." Historical Records of Australian Science 24, no. 2 (2013): 294. http://dx.doi.org/10.1071/hr13002.
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Bernie Mills is remembered globally as an influential pioneer in the evolving field of radio astronomy. His contributions with the ‘Mills Cross' at the CSIRO Division of Radiophysics and later at the University of Sydney's School of Physics and the development of the Molonglo Observatory Synthesis Telescope (MOST) were widely recognized as astronomy evolved in the years 1948–85 and radio astronomy changed the viewpoint of the astronomer as a host of new objects were discovered.
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Schaeffner, Marisa, Paulina Mrozek-Gorska, Alexander Buschle, Anne Woellmer, Takanobu Tagawa, Filippo M. Cernilogar, Gunnar Schotta, et al. "BZLF1 interacts with chromatin remodelers promoting escape from latent infections with EBV." Life Science Alliance 2, no. 2 (March 29, 2019): e201800108. http://dx.doi.org/10.26508/lsa.201800108.
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A hallmark of EBV infections is its latent phase, when all viral lytic genes are repressed. Repression results from a high nucleosome occupancy and epigenetic silencing by cellular factors such as the Polycomb repressive complex 2 (PRC2) and DNA methyltransferases that, respectively, introduce repressive histone marks and DNA methylation. The viral transcription factor BZLF1 acts as a molecular switch to induce transition from the latent to the lytic or productive phase of EBV’s life cycle. It is unknown how BZLF1 can bind to the epigenetically silenced viral DNA and whether it directly reactivates the viral genome through chromatin remodeling. We addressed these fundamental questions and found that BZLF1 binds to nucleosomal DNA motifs both in vivo and in vitro. BZLF1 co-precipitates with cellular chromatin remodeler ATPases, and the knock-down of one of them, INO80, impaired lytic reactivation and virus synthesis. In Assay for Transposase-Accessible Chromatin-seq experiments, non-accessible chromatin opens up locally when BZLF1 binds to its cognate sequence motifs in viral DNA. We conclude that BZLF1 reactivates the EBV genome by directly binding to silenced chromatin and recruiting cellular chromatin-remodeling enzymes, which implement a permissive state for lytic viral transcription. BZLF1 shares this mode of action with a limited number of cellular pioneer factors, which are instrumental in transcriptional activation, differentiation, and reprogramming in all eukaryotic cells.
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Tan, Yi, Jia Li, Linglei Zhang, Min Chen, Yaowen Zhang, and Ruidong An. "Mechanism Underlying Flow Velocity and Its Corresponding Influence on the Growth of Euglena gracilis, a Dominant Bloom Species in Reservoirs." International Journal of Environmental Research and Public Health 16, no. 23 (November 22, 2019): 4641. http://dx.doi.org/10.3390/ijerph16234641.
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The effects of hydrodynamics on algae growth have received considerable attention, and flow velocity is one of the most frequently discussed factors. For Euglena gracilis, which aggregates resources and is highly resistant to environmental changes, the mechanism underlying the impact of flow velocity on its growth is poorly understood. Experiments were conducted to examine the response of algae growth to different velocities, and several enzymes were tested to determine their physiological mechanisms. Significant differences in the growth of E. gracilis were found at different flow velocities, and this phenomenon is unique compared to the growth of other algal species. With increasing flow velocity and time, the growth of E. gracilis is gradually inhibited. In particular, we found that the pioneer enzyme is peroxidase (POD) and that the main antioxidant enzyme is catalase (CAT) when E. gracilis experiences flow velocity stress. Hysteresis between total phosphorus (TP) consumption and alkaline phosphatase (AKP) synthesis was observed. Under experimental control conditions, the results indicate that flow velocities above 0.1 m/s may inhibit growth and that E. gracilis prefers a relatively slow or even static flow velocity, and this finding could be beneficial for the control of E. gracilis blooms.
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Kerkhof, Stefanie van de. "Regionale Industrialisierung revisited – Die niederrheinische Textilregion von der Protoindustrialisierung bis zum 20. Jahrhundert als Fallbeispiel." Jahrbuch für Wirtschaftsgeschichte / Economic History Yearbook 61, no. 2 (November 25, 2020): 319–50. http://dx.doi.org/10.1515/jbwg-2020-0014.
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AbstractThe concept of Regional Industrialization developed by Rainer Fremdling, Toni Pierenkemper and Richard Tilly is based on a small-scale research approach and composes regions according to criteria of homogeneity. This paper argues that the concept is fruitful in regard to textile regions and their analysis in a long-term perspective from proto-industrialization to the 20th century. It examines relevant factors such as capital, labour, raw materials, transfer of capital, technology and knowledge in order to analyse the specific regional path of growth. Especially the role of migrant pioneer entrepreneurs and the institutional-cultural setting, i.e. the state monopolies of the regional silk and velvet producers are addressed. Mechanisation and the factory system were introduced relatively late in comparison to other regions in the wool and cotton branch of textile industry. But innovations in weaving and energy technology diffused rather rapidly in Krefeld, Mönchengladbach and the rural surroundings. The paper shows how the growing textile industry of the left lower Rhine region diversified during the Great Depression of the 1870s-90s and induced forward and backward linkages to the machinery, tool and chemical industries. In all segments of the textile industry in the region (silk, velvet, cotton, wool, synthetics) path dependencies evolved which still have an effect on research institutions and industrial culture today.
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Lee, W. S., J. C. Lee, and Y. S. Hwang. "197 Effect of STC-4771, An Intermediate of ABA Synthesis, on the Anthocyanin Accumulation in Grapes." HortScience 35, no. 3 (June 2000): 425A—425. http://dx.doi.org/10.21273/hortsci.35.3.425a.
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The coloration of grape berries depends on the anthocyanin synthesis during maturation. The quality of berries is often decreased due to the poor color development when berries are grown under unfavorable environments and/or inadequate internal factors are involved. It has been well-known that the level of ABA at ripening is closely associated with anthocyanin synthesis; thus, the external application of ABA results in the increase of anthocyanin content even in berries grown under favorable conditions. However, the agricultural use of natural ABA is not possible because of high prices. This experiment was conducted to study the potential of STC-4771 as a substitute for ABA. The effect of STC-4771 was studied in `Kyoho', `Pione', and `Delaware' grapes. Chemicals were applied when ≈10% of berries in a cluster were colored. In `Kyoho', anthocyanin synthesis was enhanced at a concentration of 100 mg/L and there was a trend in color enhancement in `Pione', regardless of treatment concentration, between 10 to 40 mg/L. However, no clear effect was found in `Delaware' at 50 to 100 mg/L. In an in vitro experiment, anthocyanin was only increased when an adequate amount of sucrose (0.6 m) was added in the incubation medium under light. Natural ABA effectively increased the anthocyanin content of berry segments even under shading condition through four bagging materials, but no effect was confirmed in STC treatment.
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Stojkovic, N., B. Vukotic, and M. M. Cirkovic. "Habitability of galaxies and the application of merger trees in astrobiology." Serbian Astronomical Journal, no. 198 (2019): 25–43. http://dx.doi.org/10.2298/saj1998025s.
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Galaxies represent the main form of organization of matter in our universe. Therefore, they are of obvious interest for the new multidisciplinary field of astrobiology. In particular, to study habitability of galaxies represents one of the main emerging challenges of theoretical and numerical astrobiology. Its theoretical underpinnings are, however, often confused and vague. Here we present a systematic attempt to list and categorize major causal factors playing a role in emergent habitability of galaxies. Furthermore, we argue that the methodology of cosmological merger trees is particularly useful in delineating what are systematic and lawful astrobiological properties of galaxies at present epoch vs. those which are product of historical contingency and, in particular, interaction with wider extragalactic environment. Employing merger trees extracted from cosmological N-body simulations as a new and promising research method for astrobiology has been pioneered by Stanway et al. (2018). We analyse the general issue of applicability of merger trees and present preliminary results on a set of trees extracted from the Illustris Project. In a sense, this approach is directly complementary to using large-scale cosmological simulations to study habitable zones of individual galaxies with high mass/spatial resolution; taken together, they usher a new era of synergy and synthesis between cosmology and astrobiology.
Dissertations / Theses on the topic "Synthetic pioneer factors"
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"Opening Chromatin and Improving CRISPR / Cas9 Editing." Master's thesis, 2019. http://hdl.handle.net/2286/R.I.53846.
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abstract: The research question explored in this thesis is how CRISPR mediated editing is influenced by artificially opened chromatin in cells. Closed chromatin poses a barrier to Cas9 binding and editing at target genes. Synthetic pioneer factors (PFs) are a promising new approach to artificially open condensed heterochromatin allowing greater access of target DNA to Cas9. The Haynes lab has constructed fusions of enzymatic chromatin-modifying domains designed to remodel chromatin and increase Cas9 editing efficiency. With a library of PFs available, this research focuses on analyzing the behavior of Cas9 in chromatin that has been artificially opened by PFs. The types and frequency of INDELs (insertions & deletions) were determined after non-homologous end joining (NHEJ) in PF and Cas9-treated cells using quantitative Sanger sequencing and Synthego’s ICE software. Furthermore, NOME-seq analysis was carried out to map nucleosome position in PF and Cas9 treated cells. Although this experiment was unsuccessful, the heat map generated with data obtained from Synthego ICE predicts a possible presence of nucleosome in the vicinity suggesting that perhaps a fully open chromatin state was not achieved. Linear Regression analysis with certain assumptions confirms that with the increase in distance downstream of cut-site, the editing frequency decreases exponentially. Nevertheless, further experimental work should be carried out to investigate this hypothesis.Dissertation/Thesis
Masters Thesis Biomedical Engineering 2019
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"Engineering Open Chromatin with Synthetic Pioneer Factors: Enhancing Mammalian Transgene Expression and Improving Cas9-Mediated Genome Editing in Closed Chromatin." Doctoral diss., 2019. http://hdl.handle.net/2286/R.I.53692.
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abstract: Chromatin is the dynamic structure of proteins and nucleic acids into which eukaryotic genomes are organized. For those looking to engineer mammalian genomes, chromatin is both an opportunity and an obstacle. While chromatin provides another tool with which to control gene expression, regional density can lead to variability in genome editing efficiency by CRISPR/Cas9 systems. Many groups have attempted to de-silence chromatin to regulate genes and enhance DNA's accessibility to nucleases, but inconsistent results leave outstanding questions. Here, I test different types of activators, to analyze changes in chromatin features that result for chromatin opening, and to identify the critical biochemical features that support artificially generated open, transcriptionally active chromatin.
I designed, built, and tested a panel of synthetic pioneer factors (SPiFs) to open condensed, repressive chromatin with the aims of 1) activating repressed transgenes in mammalian cells and 2) reversing the inhibitory effects of closed chromatin on Cas9-endonuclease activity. Pioneer factors are unique in their ability to bind DNA in closed chromatin. In order to repurpose this natural function, I designed SPiFs from a Gal4 DNA binding domain, which has inherent pioneer functionality, fused with chromatin-modifying peptides with distinct functions.
SPiFs with transcriptional activation as their primary mechanism were able to reverse this repression and induced a stably active state. My work also revealed the active site from proto-oncogene MYB as a novel transgene activator. To determine if MYB could be used generally to restore transgene expression, I fused it to a deactivated Cas9 and targeted a silenced transgene in native heterochromatin. The resulting activator was able to reverse silencing and can be chemically controlled with a small molecule drug.
Other SPiFs in my panel did not increase gene expression. However, pretreatment with several of these expression-neutral SPiFs increased Cas9-mediated editing in closed chromatin, suggesting a crucial difference between chromatin that is accessible and that which contains genes being actively transcribed. Understanding this distinction will be vital to the engineering of stable transgenic cell lines for product production and disease modeling, as well as therapeutic applications such as restoring epigenetic order to misregulated disease cells.Dissertation/Thesis
Doctoral Dissertation Biological Design 2019