The societal opportunities and challenges of genome editing.

PubMed

Carroll, Dana; Charo, R Alta

2015-11-05

The genome editing platforms currently in use have revolutionized the field of genetics. At an accelerating rate, these tools are entering areas with direct impact on human well being. Here, we discuss applications in agriculture and in medicine, and examine some associated societal issues.

Micro-UAV tracking framework for EO exploitation

NASA Astrophysics Data System (ADS)

Browning, David; Wilhelm, Joe; Van Hook, Richard; Gallagher, John

2012-06-01

Historically, the Air Force's research into aerial platforms for sensing systems has focused on low-, mid-, and highaltitude platforms. Though these systems are likely to comprise the majority of the Air Force's assets for the foreseeable future, they have limitations. Specifically, these platforms, their sensor packages, and their data exploitation software are unsuited for close-quarter surveillance, such as in alleys and inside of buildings. Micro-UAVs have been gaining in popularity, especially non-fixed-wing platforms such as quad-rotors. These platforms are much more appropriate for confined spaces. However, the types of video exploitation techniques that can effectively be used are different from the typical nadir-looking aerial platform. This paper discusses the creation of a framework for testing existing and new video exploitation algorithms, as well as describes a sample micro-UAV-based tracker.

CRISPR/Cas9 Platforms for Genome Editing in Plants: Developments and Applications.

PubMed

Ma, Xingliang; Zhu, Qinlong; Chen, Yuanling; Liu, Yao-Guang

2016-07-06

The clustered regularly interspaced short palindromic repeat (CRISPR)-associated protein9 (Cas9) genome editing system (CRISPR/Cas9) is adapted from the prokaryotic type II adaptive immunity system. The CRISPR/Cas9 tool surpasses other programmable nucleases, such as ZFNs and TALENs, for its simplicity and high efficiency. Various plant-specific CRISPR/Cas9 vector systems have been established for adaption of this technology to many plant species. In this review, we present an overview of current advances on applications of this technology in plants, emphasizing general considerations for establishment of CRISPR/Cas9 vector platforms, strategies for multiplex editing, methods for analyzing the induced mutations, factors affecting editing efficiency and specificity, and features of the induced mutations and applications of the CRISPR/Cas9 system in plants. In addition, we provide a perspective on the challenges of CRISPR/Cas9 technology and its significance for basic plant research and crop genetic improvement. Copyright © 2016 The Author. Published by Elsevier Inc. All rights reserved.

High-Content Analysis of CRISPR-Cas9 Gene-Edited Human Embryonic Stem Cells.

PubMed

Carlson-Stevermer, Jared; Goedland, Madelyn; Steyer, Benjamin; Movaghar, Arezoo; Lou, Meng; Kohlenberg, Lucille; Prestil, Ryan; Saha, Krishanu

2016-01-12

CRISPR-Cas9 gene editing of human cells and tissues holds much promise to advance medicine and biology, but standard editing methods require weeks to months of reagent preparation and selection where much or all of the initial edited samples are destroyed during analysis. ArrayEdit, a simple approach utilizing surface-modified multiwell plates containing one-pot transcribed single-guide RNAs, separates thousands of edited cell populations for automated, live, high-content imaging and analysis. The approach lowers the time and cost of gene editing and produces edited human embryonic stem cells at high efficiencies. Edited genes can be expressed in both pluripotent stem cells and differentiated cells. This preclinical platform adds important capabilities to observe editing and selection in situ within complex structures generated by human cells, ultimately enabling optical and other molecular perturbations in the editing workflow that could refine the specificity and versatility of gene editing. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Wafer-scale integrated micro-supercapacitors on an ultrathin and highly flexible biomedical platform.

PubMed

Maeng, Jimin; Meng, Chuizhou; Irazoqui, Pedro P

2015-02-01

We present wafer-scale integrated micro-supercapacitors on an ultrathin and highly flexible parylene platform, as progress toward sustainably powering biomedical microsystems suitable for implantable and wearable applications. All-solid-state, low-profile (<30 μm), and high-density (up to ~500 μF/mm(2)) micro-supercapacitors are formed on an ultrathin (~20 μm) freestanding parylene film by a wafer-scale parylene packaging process in combination with a polyaniline (PANI) nanowire growth technique assisted by surface plasma treatment. These micro-supercapacitors are highly flexible and shown to be resilient toward flexural stress. Further, direct integration of micro-supercapacitors into a radio frequency (RF) rectifying circuit is achieved on a single parylene platform, yielding a complete RF energy harvesting microsystem. The system discharging rate is shown to improve by ~17 times in the presence of the integrated micro-supercapacitors. This result suggests that the integrated micro-supercapacitor technology described herein is a promising strategy for sustainably powering biomedical microsystems dedicated to implantable and wearable applications.

Creating Math Videos: Comparing Platforms and Software

ERIC Educational Resources Information Center

Abbasian, Reza O.; Sieben, John T.

2016-01-01

In this paper we present a short tutorial on creating mini-videos using two platforms--PCs and tablets such as iPads--and software packages that work with these devices. Specifically, we describe the step-by-step process of creating and editing videos using a Wacom Intuos pen-tablet plus Camtasia software on a PC platform and using the software…

Optimal design and experimental analyses of a new micro-vibration control payload-platform

NASA Astrophysics Data System (ADS)

Sun, Xiaoqing; Yang, Bintang; Zhao, Long; Sun, Xiaofen

2016-07-01

This paper presents a new payload-platform, for precision devices, which possesses the capability of isolating the complex space micro-vibration in low frequency range below 5 Hz. The novel payload-platform equipped with smart material actuators is investigated and designed through optimization strategy based on the minimum energy loss rate, for the aim of achieving high drive efficiency and reducing the effect of the magnetic circuit nonlinearity. Then, the dynamic model of the driving element is established by using the Lagrange method and the performance of the designed payload-platform is further discussed through the combination of the controlled auto regressive moving average (CARMA) model with modified generalized prediction control (MGPC) algorithm. Finally, an experimental prototype is developed and tested. The experimental results demonstrate that the payload-platform has an impressive potential of micro-vibration isolation.

Applying Human ADAR1p110 and ADAR1p150 for Site-Directed RNA Editing-G/C Substitution Stabilizes GuideRNAs against Editing.

PubMed

Heep, Madeleine; Mach, Pia; Reautschnig, Philipp; Wettengel, Jacqueline; Stafforst, Thorsten

2017-01-14

Site-directed RNA editing is an approach to reprogram genetic information at the RNA level. We recently introduced a novel guideRNA that allows for the recruitment of human ADAR2 to manipulate genetic information. Here, we show that the current guideRNA design is already able to recruit another human deaminase, ADAR1, in both isoforms, p110 and p150. However, further optimization seems necessary as the current design is less efficient for ADAR1 isoforms. Furthermore, we describe hotspots at which the guideRNA itself is edited and show a way to circumvent this auto-editing without losing editing efficiency at the target. Both findings are important for the advancement of site-directed RNA editing as a tool in basic biology or as a platform for therapeutic editing.

Cell-type-specific genome editing with a microRNA-responsive CRISPR-Cas9 switch.

PubMed

Hirosawa, Moe; Fujita, Yoshihiko; Parr, Callum J C; Hayashi, Karin; Kashida, Shunnichi; Hotta, Akitsu; Woltjen, Knut; Saito, Hirohide

2017-07-27

The CRISPR-Cas9 system is a powerful genome-editing tool useful in a variety of biotechnology and biomedical applications. Here we developed a synthetic RNA-based, microRNA (miRNA)-responsive CRISPR-Cas9 system (miR-Cas9 switch) in which the genome editing activity of Cas9 can be modulated through endogenous miRNA signatures in mammalian cells. We created miR-Cas9 switches by using a miRNA-complementary sequence in the 5΄-UTR of mRNA encoding Streptococcus pyogenes Cas9. The miR-21-Cas9 or miR-302-Cas9 switches selectively and efficiently responded to miR-21-5p in HeLa cells or miR-302a-5p in human induced pluripotent stem cells, and post-transcriptionally attenuated the Cas9 activity only in the target cells. Moreover, the miR-Cas9 switches could differentially control the genome editing by sensing endogenous miRNA activities within a heterogeneous cell population. Our miR-Cas9 switch system provides a promising framework for cell-type selective genome editing and cell engineering based on intracellular miRNA information. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Gene Editing: Regulatory and Translation to Clinic.

PubMed

Ando, Dale; Meyer, Kathleen

2017-10-01

The clinical application and regulatory strategy of genome editing for ex vivo cell therapy is derived from the intersection of two fields of study: viral vector gene therapy trials; and clinical trials with ex vivo purification and engraftment of CD34 +  hematopoietic stem cells, T cells, and tumor cell vaccines. This article covers the regulatory and translational preclinical activities needed for a genome editing clinical trial modifying hematopoietic stem cells and the genesis of this current strategy based on previous clinical trials using genome-edited T cells. The SB-728 zinc finger nuclease platform is discussed because this is the most clinically advanced genome editing technology. Copyright © 2017 Elsevier Inc. All rights reserved.

Fabrication of a multifunctional nano-in-micro drug delivery platform by microfluidic templated encapsulation of porous silicon in polymer matrix.

PubMed

Zhang, Hongbo; Liu, Dongfei; Shahbazi, Mohammad-Ali; Mäkilä, Ermei; Herranz-Blanco, Bárbara; Salonen, Jarno; Hirvonen, Jouni; Santos, Hélder A

2014-07-09

A multifunctional nano-in-micro drug delivery platform is developed by conjugating the porous silicon nanoparticles with mucoadhesive polymers and subsequent encapsulation into a pH-responsive polymer using microfluidics. The multistage platform shows monodisperse size distribution and pH-responsive payload release, and the released nanoparticles are mucoadhesive. Moreover, this platform is capable of simultaneously loading and releasing multidrugs with distinct properties. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A-to-I editing of coding and non-coding RNAs by ADARs

PubMed Central

Nishikura, Kazuko

2016-01-01

Adenosine deaminases acting on RNA (ADARs) convert adenosine to inosine in double-stranded RNA. This A-to-I editing occurs not only in protein-coding regions of mRNAs, but also frequently in non-coding regions that contain inverted Alu repeats. Editing of coding sequences can result in the expression of functionally altered proteins that are not encoded in the genome, whereas the significance of Alu editing remains largely unknown. Certain microRNA (miRNA) precursors are also edited, leading to reduced expression or altered function of mature miRNAs. Conversely, recent studies indicate that ADAR1 forms a complex with Dicer to promote miRNA processing, revealing a new function of ADAR1 in the regulation of RNA interference. PMID:26648264

Quantifying Genome Editing Outcomes at Endogenous Loci using SMRT Sequencing

PubMed Central

Clark, Joseph; Punjya, Niraj; Sebastiano, Vittorio; Bao, Gang; Porteus, Matthew H

2014-01-01

SUMMARY Targeted genome editing with engineered nucleases has transformed the ability to introduce precise sequence modifications at almost any site within the genome. A major obstacle to probing the efficiency and consequences of genome editing is that no existing method enables the frequency of different editing events to be simultaneously measured across a cell population at any endogenous genomic locus. We have developed a novel method for quantifying individual genome editing outcomes at any site of interest using single molecule real time (SMRT) DNA sequencing. We show that this approach can be applied at various loci, using multiple engineered nuclease platforms including TALENs, RNA guided endonucleases (CRISPR/Cas9), and ZFNs, and in different cell lines to identify conditions and strategies in which the desired engineering outcome has occurred. This approach facilitates the evaluation of new gene editing technologies and permits sensitive quantification of editing outcomes in almost every experimental system used. PMID:24685129

Micro-algae come of age as a platform for recombinant protein production

PubMed Central

Specht, Elizabeth; Miyake-Stoner, Shigeki

2010-01-01

A complete set of genetic tools is still being developed for the micro-alga Chlamydomonas reinhardtii. Yet even with this incomplete set, this photosynthetic single-celled plant has demonstrated significant promise as a platform for recombinant protein expression. In recent years, techniques have been developed that allow for robust expression of genes from both the nuclear and plastid genome. With these advances, many research groups have examined the pliability of this and other micro-algae as biological machines capable of producing recombinant peptides and proteins. This review describes recent successes in recombinant protein production in Chlamydomonas, including production of complex mammalian therapeutic proteins and monoclonal antibodies at levels sufficient for production at economic parity with existing production platforms. These advances have also shed light on the details of algal protein production at the molecular level, and provide insight into the next steps for optimizing micro-algae as a useful platform for the production of therapeutic and industrially relevant recombinant proteins. PMID:20556634

Genome editing and the next generation of antiviral therapy

PubMed Central

Stone, Daniel; Niyonzima, Nixon

2016-01-01

Engineered endonucleases such as homing endonucleases (HEs), zinc finger nucleases (ZFNs), Tal-effector nucleases (TALENS) and the RNA-guided engineered nucleases (RGENs or CRISPR/Cas9) can target specific DNA sequences for cleavage, and are proving to be valuable tools for gene editing. Recently engineered endonucleases have shown great promise as therapeutics for the treatment of genetic disease and infectious pathogens. In this review, we discuss recent efforts to use the HE, ZFN, TALEN and CRISPR/Cas9 gene-editing platforms as antiviral therapeutics. We also discuss the obstacles facing gene-editing antiviral therapeutics as they are tested in animal models of disease and transition towards human application. PMID:27272125

Zinc Fingers, TALEs, and CRISPR Systems: A Comparison of Tools for Epigenome Editing.

PubMed

Waryah, Charlene Babra; Moses, Colette; Arooj, Mahira; Blancafort, Pilar

2018-01-01

The completion of genome, epigenome, and transcriptome mapping in multiple cell types has created a demand for precision biomolecular tools that allow researchers to functionally manipulate DNA, reconfigure chromatin structure, and ultimately reshape gene expression patterns. Epigenetic editing tools provide the ability to interrogate the relationship between epigenetic modifications and gene expression. Importantly, this information can be exploited to reprogram cell fate for both basic research and therapeutic applications. Three different molecular platforms for epigenetic editing have been developed: zinc finger proteins (ZFs), transcription activator-like effectors (TALEs), and the system of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and CRISPR-associated (Cas) proteins. These platforms serve as custom DNA-binding domains (DBDs), which are fused to epigenetic modifying domains to manipulate epigenetic marks at specific sites in the genome. The addition and/or removal of epigenetic modifications reconfigures local chromatin structure, with the potential to provoke long-lasting changes in gene transcription. Here we summarize the molecular structure and mechanism of action of ZF, TALE, and CRISPR platforms and describe their applications for the locus-specific manipulation of the epigenome. The advantages and disadvantages of each platform will be discussed with regard to genomic specificity, potency in regulating gene expression, and reprogramming cell phenotypes, as well as ease of design, construction, and delivery. Finally, we outline potential applications for these tools in molecular biology and biomedicine and identify possible barriers to their future clinical implementation.

Video Editing System

NASA Technical Reports Server (NTRS)

Schlecht, Leslie E.; Kutler, Paul (Technical Monitor)

1998-01-01

This is a proposal for a general use system based, on the SGI IRIS workstation platform, for recording computer animation to videotape. In addition, this system would provide features for simple editing and enhancement. Described here are a list of requirements for the system, and a proposed configuration including the SGI VideoLab Integrator, VideoMedia VLAN animation controller and the Pioneer rewritable laserdisc recorder.

In vivo genome editing of the albumin locus as a platform for protein replacement therapy

PubMed Central

Sharma, Rajiv; Anguela, Xavier M.; Doyon, Yannick; Wechsler, Thomas; DeKelver, Russell C.; Sproul, Scott; Paschon, David E.; Miller, Jeffrey C.; Davidson, Robert J.; Shivak, David; Zhou, Shangzhen; Rieders, Julianne; Gregory, Philip D.; Holmes, Michael C.; Rebar, Edward J.

2015-01-01

Site-specific genome editing provides a promising approach for achieving long-term, stable therapeutic gene expression. Genome editing has been successfully applied in a variety of preclinical models, generally focused on targeting the diseased locus itself; however, limited targeting efficiency or insufficient expression from the endogenous promoter may impede the translation of these approaches, particularly if the desired editing event does not confer a selective growth advantage. Here we report a general strategy for liver-directed protein replacement therapies that addresses these issues: zinc finger nuclease (ZFN) –mediated site-specific integration of therapeutic transgenes within the albumin gene. By using adeno-associated viral (AAV) vector delivery in vivo, we achieved long-term expression of human factors VIII and IX (hFVIII and hFIX) in mouse models of hemophilia A and B at therapeutic levels. By using the same targeting reagents in wild-type mice, lysosomal enzymes were expressed that are deficient in Fabry and Gaucher diseases and in Hurler and Hunter syndromes. The establishment of a universal nuclease-based platform for secreted protein production would represent a critical advance in the development of safe, permanent, and functional cures for diverse genetic and nongenetic diseases. PMID:26297739

RISC assembly: Coordination between small RNAs and Argonaute proteins.

PubMed

Kobayashi, Hotaka; Tomari, Yukihide

2016-01-01

Non-coding RNAs generally form ribonucleoprotein (RNP) complexes with their partner proteins to exert their functions. Small RNAs, including microRNAs, small interfering RNAs, and PIWI-interacting RNAs, assemble with Argonaute (Ago) family proteins into the effector complex called RNA-induced silencing complex (RISC), which mediates sequence-specific target gene silencing. RISC assembly is not a simple binding between a small RNA and Ago; rather, it follows an ordered multi-step pathway that requires specific accessory factors. Some steps of RISC assembly and RISC-mediated gene silencing are dependent on or facilitated by particular intracellular platforms, suggesting their spatial regulation. In this review, we summarize the currently known mechanisms for RISC assembly of each small RNA class and propose a revised model for the role of the chaperone machinery in the duplex-initiated RISC assembly pathway. This article is part of a Special Issue entitled: Clues to long noncoding RNA taxonomy1, edited by Dr. Tetsuro Hirose and Dr. Shinichi Nakagawa. Copyright © 2015 Elsevier B.V. All rights reserved.

Integrated micro-optofluidic platform for real-time detection of airborne microorganisms

NASA Astrophysics Data System (ADS)

Choi, Jeongan; Kang, Miran; Jung, Jae Hee

2015-11-01

We demonstrate an integrated micro-optofluidic platform for real-time, continuous detection and quantification of airborne microorganisms. Measurements of the fluorescence and light scattering from single particles in a microfluidic channel are used to determine the total particle number concentration and the microorganism number concentration in real-time. The system performance is examined by evaluating standard particle measurements with various sample flow rates and the ratios of fluorescent to non-fluorescent particles. To apply this method to real-time detection of airborne microorganisms, airborne Escherichia coli, Bacillus subtilis, and Staphylococcus epidermidis cells were introduced into the micro-optofluidic platform via bioaerosol generation, and a liquid-type particle collection setup was used. We demonstrate successful discrimination of SYTO82-dyed fluorescent bacterial cells from other residue particles in a continuous and real-time manner. In comparison with traditional microscopy cell counting and colony culture methods, this micro-optofluidic platform is not only more accurate in terms of the detection efficiency for airborne microorganisms but it also provides additional information on the total particle number concentration.

Integrated micro-optofluidic platform for real-time detection of airborne microorganisms

PubMed Central

Choi, Jeongan; Kang, Miran; Jung, Jae Hee

2015-01-01

We demonstrate an integrated micro-optofluidic platform for real-time, continuous detection and quantification of airborne microorganisms. Measurements of the fluorescence and light scattering from single particles in a microfluidic channel are used to determine the total particle number concentration and the microorganism number concentration in real-time. The system performance is examined by evaluating standard particle measurements with various sample flow rates and the ratios of fluorescent to non-fluorescent particles. To apply this method to real-time detection of airborne microorganisms, airborne Escherichia coli, Bacillus subtilis, and Staphylococcus epidermidis cells were introduced into the micro-optofluidic platform via bioaerosol generation, and a liquid-type particle collection setup was used. We demonstrate successful discrimination of SYTO82-dyed fluorescent bacterial cells from other residue particles in a continuous and real-time manner. In comparison with traditional microscopy cell counting and colony culture methods, this micro-optofluidic platform is not only more accurate in terms of the detection efficiency for airborne microorganisms but it also provides additional information on the total particle number concentration. PMID:26522006

Multidimensional Aptitude Battery-Second Edition Intelligence Testing of Remotely Piloted Aircraft Training Candidates Compared with Manned Airframe Training Candidates

DTIC Science & Technology

2015-03-01

assessing the general intelligence and neuropsychological aptitudes of USAF RPA pilot training candidates. Chappelle et al. obtained comprehensive...computer-based intelligence testing (Multidimensional Aptitude Battery-Second Edition [MAB-II]) and neuropsychological screening (MicroCog) on USAF MQ-1... schizophrenia , attention deficit hyperactivity disorder, and autism spectrum disorders) and not on very high functioning populations such as aviators

A micro-vibration generated method for testing the imaging quality on ground of space remote sensing

NASA Astrophysics Data System (ADS)

Gu, Yingying; Wang, Li; Wu, Qingwen

2018-03-01

In this paper, a novel method is proposed, which can simulate satellite platform micro-vibration and test the impact of satellite micro-vibration on imaging quality of space optical remote sensor on ground. The method can generate micro-vibration of satellite platform in orbit from vibrational degrees of freedom, spectrum, magnitude, and coupling path. Experiment results show that the relative error of acceleration control is within 7%, in frequencies from 7Hz to 40Hz. Utilizing this method, the system level test about the micro-vibration impact on imaging quality of space optical remote sensor can be realized. This method will have an important applications in testing micro-vibration tolerance margin of optical remote sensor, verifying vibration isolation and suppression performance of optical remote sensor, exploring the principle of micro-vibration impact on imaging quality of optical remote sensor.

Methods and Applications of CRISPR-Mediated Base Editing in Eukaryotic Genomes.

PubMed

Hess, Gaelen T; Tycko, Josh; Yao, David; Bassik, Michael C

2017-10-05

The past several years have seen an explosion in development of applications for the CRISPR-Cas9 system, from efficient genome editing, to high-throughput screening, to recruitment of a range of DNA and chromatin-modifying enzymes. While homology-directed repair (HDR) coupled with Cas9 nuclease cleavage has been used with great success to repair and re-write genomes, recently developed base-editing systems present a useful orthogonal strategy to engineer nucleotide substitutions. Base editing relies on recruitment of cytidine deaminases to introduce changes (rather than double-stranded breaks and donor templates) and offers potential improvements in efficiency while limiting damage and simplifying the delivery of editing machinery. At the same time, these systems enable novel mutagenesis strategies to introduce sequence diversity for engineering and discovery. Here, we review the different base-editing platforms, including their deaminase recruitment strategies and editing outcomes, and compare them to other CRISPR genome-editing technologies. Additionally, we discuss how these systems have been applied in therapeutic, engineering, and research settings. Lastly, we explore future directions of this emerging technology. Copyright © 2017 Elsevier Inc. All rights reserved.

ADAR2 induces reproducible changes in sequence and abundance of mature microRNAs in the mouse brain

PubMed Central

Vesely, Cornelia; Tauber, Stefanie; Sedlazeck, Fritz J.; Tajaddod, Mansoureh; von Haeseler, Arndt; Jantsch, Michael F.

2014-01-01

Adenosine deaminases that act on RNA (ADARs) deaminate adenosines to inosines in double-stranded RNAs including miRNA precursors. A to I editing is widespread and required for normal life. By comparing deep sequencing data of brain miRNAs from wild-type and ADAR2 deficient mouse strains, we detect editing sites and altered miRNA processing at high sensitivity. We detect 48 novel editing events in miRNAs. Some editing events reach frequencies of up to 80%. About half of all editing events depend on ADAR2 while some miRNAs are preferentially edited by ADAR1. Sixty-four percent of all editing events are located within the seed region of mature miRNAs. For the highly edited miR-3099, we experimentally prove retargeting of the edited miRNA to novel 3′ UTRs. We show further that an abundant editing event in miR-497 promotes processing by Drosha of the corresponding pri-miRNA. We also detect reproducible changes in the abundance of specific miRNAs in ADAR2-deficient mice that occur independent of adjacent A to I editing events. This indicates that ADAR2 binding but not editing of miRNA precursors may influence their processing. Correlating with changes in miRNA abundance we find misregulation of putative targets of these miRNAs in the presence or absence of ADAR2. PMID:25260591

Adenosine-to-inosine RNA editing by ADAR1 is essential for normal murine erythropoiesis

PubMed Central

Liddicoat, Brian J.; Hartner, Jochen C.; Piskol, Robert; Ramaswami, Gokul; Chalk, Alistair M.; Kingsley, Paul D.; Sankaran, Vijay G.; Wall, Meaghan; Purton, Louise E.; Seeburg, Peter H.; Palis, James; Orkin, Stuart H.; Lu, Jun; Li, Jin Billy; Walkley, Carl R.

2016-01-01

Adenosine deaminases that act on RNA (ADARs) convert adenosine residues to inosine in double-stranded RNA. In vivo, ADAR1 is essential for the maintenance of hematopoietic stem/progenitors. Whether other hematopoietic cell types also require ADAR1 has not been assessed. Using erythroid- and myeloid-restricted deletion of Adar1, we demonstrate that ADAR1 is dispensable for myelopoiesis but is essential for normal erythropoiesis. Adar1-deficient erythroid cells display a profound activation of innate immune signaling and high levels of cell death. No changes in microRNA levels were found in ADAR1-deficient erythroid cells. Using an editing-deficient allele, we demonstrate that RNA editing is the essential function of ADAR1 during erythropoiesis. Mapping of adenosine-to-inosine editing in purified erythroid cells identified clusters of hyperedited adenosines located in long 3’-untranslated regions of erythroid-specific transcripts and these are ADAR1-specific editing events. ADAR1-mediated RNA editing is essential for normal erythropoiesis. PMID:27373493

A novel technique based on in vitro oocyte injection to improve CRISPR/Cas9 gene editing in zebrafish

PubMed Central

Xie, Shao-Lin; Bian, Wan-Ping; Wang, Chao; Junaid, Muhammad; Zou, Ji-Xing; Pei, De-Sheng

2016-01-01

Contemporary improvements in the type II clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9) system offer a convenient way for genome editing in zebrafish. However, the low efficiencies of genome editing and germline transmission require a time-intensive and laborious screening work. Here, we reported a method based on in vitro oocyte storage by injecting oocytes in advance and incubating them in oocyte storage medium to significantly improve the efficiencies of genome editing and germline transmission by in vitro fertilization (IVF) in zebrafish. Compared to conventional methods, the prior micro-injection of zebrafish oocytes improved the efficiency of genome editing, especially for the sgRNAs with low targeting efficiency. Due to high throughputs, simplicity and flexible design, this novel strategy will provide an efficient alternative to increase the speed of generating heritable mutants in zebrafish by using CRISPR/Cas9 system. PMID:27680290

In vivo genome editing of the albumin locus as a platform for protein replacement therapy.

PubMed

Sharma, Rajiv; Anguela, Xavier M; Doyon, Yannick; Wechsler, Thomas; DeKelver, Russell C; Sproul, Scott; Paschon, David E; Miller, Jeffrey C; Davidson, Robert J; Shivak, David; Zhou, Shangzhen; Rieders, Julianne; Gregory, Philip D; Holmes, Michael C; Rebar, Edward J; High, Katherine A

2015-10-08

Site-specific genome editing provides a promising approach for achieving long-term, stable therapeutic gene expression. Genome editing has been successfully applied in a variety of preclinical models, generally focused on targeting the diseased locus itself; however, limited targeting efficiency or insufficient expression from the endogenous promoter may impede the translation of these approaches, particularly if the desired editing event does not confer a selective growth advantage. Here we report a general strategy for liver-directed protein replacement therapies that addresses these issues: zinc finger nuclease (ZFN) -mediated site-specific integration of therapeutic transgenes within the albumin gene. By using adeno-associated viral (AAV) vector delivery in vivo, we achieved long-term expression of human factors VIII and IX (hFVIII and hFIX) in mouse models of hemophilia A and B at therapeutic levels. By using the same targeting reagents in wild-type mice, lysosomal enzymes were expressed that are deficient in Fabry and Gaucher diseases and in Hurler and Hunter syndromes. The establishment of a universal nuclease-based platform for secreted protein production would represent a critical advance in the development of safe, permanent, and functional cures for diverse genetic and nongenetic diseases. © 2015 by The American Society of Hematology.

A Translational Pathway Toward a Clinical Trial Using the Second-Generation AAV Micro Dystrophin Vector

DTIC Science & Technology

2017-09-01

future experimental therapeutic studies in the canine model such as CRISPR -mediated gene editing, stem cell therapy, dystrophin-independent disease...There is no scientific/budget overlap with the current proposal.) CRISPR /Cas9-based gene editing for the correction of Duchenne muscular dystrophy...lab will perform in vivo gene delivery and functional outcome measurements in mice treated by AAV- CRISPR gene repair vectors and if needed will also

HIgh-Q Optical Micro-cavity Resonators as High Sensitive Bio-chemical and Ultrasonic Sensors

NASA Astrophysics Data System (ADS)

Ling, Tao

Optical micro-cavity resonators have quickly emerged in the past few years as a new sensing platform in a wide range of applications, such as bio-chemical molecular detection, environmental monitoring, acoustic and electromagnetic waves detection. In this thesis, we will mainly focus on developing high sensitivity silica micro-tube resonator bio-chemical sensors and high sensitivity polymer micro-ring resonator acoustic sensors. In high sensitivity silica micro-tube resonator bio-chemical sensors part: We first demonstrated a prism coupled silica micro-tube bio-chemical sensing platform to overcome the reliability problem in a fiber coupled thin wall silica micro-tube sensing platform. In refractive index sensing experiment, a unique resonance mode with sensitivity around 600nm/refractive index unit (RIU) has been observed. Surface sensing experiments also have been performed in this platform to detect lipid monolayer, lipid bilayer, electrostatic self assemble layer-by-layer as well as the interaction between the lipid bilayer and proteins. Then a theoretical study on various sensing properties on the silica micro-tube based sensing platform has been realized. Furthermore, we have proposed a coupled cavity system to further enhance the device's sensitivity above 1000nm/RIU. In high sensitivity polymer micro-ring resonator acoustic sensors part: We first presented a simplified fabrication process and realized a polymer microring with a Q factor around 6000. The fabricated device has been used to detect acoustic wave with noise equivalent pressure (NEP) around 230Pa over 1-75MHz frequency rang, which is comparable to state-of-art piezoelectric transducer and the device's frequency response also have been characterized to be up to 90MHz. A new fabrication process combined with resist reflow and thermal oxidation process has been used to improve the Q factor up to 10 5 and the device's NEP has been tested to be around 88Pa over 1-75MHz range. Further improving the device's Q factor has been realized by shifting the device's working wavelength to near-visible wavelength and further reducing the device's sidewall roughness. A record new high Q-˜x105 has been measured and the device's NEP as low as 21Pa has been measured. Furthermore, a smaller size polymer microring device has been developed and fabricated to realize larger angle beam forming applications.

RNA editing with CRISPR-Cas13.

PubMed

Cox, David B T; Gootenberg, Jonathan S; Abudayyeh, Omar O; Franklin, Brian; Kellner, Max J; Joung, Julia; Zhang, Feng

2017-11-24

Nucleic acid editing holds promise for treating genetic disease, particularly at the RNA level, where disease-relevant sequences can be rescued to yield functional protein products. Type VI CRISPR-Cas systems contain the programmable single-effector RNA-guided ribonuclease Cas13. We profiled type VI systems in order to engineer a Cas13 ortholog capable of robust knockdown and demonstrated RNA editing by using catalytically inactive Cas13 (dCas13) to direct adenosine-to-inosine deaminase activity by ADAR2 (adenosine deaminase acting on RNA type 2) to transcripts in mammalian cells. This system, referred to as RNA Editing for Programmable A to I Replacement (REPAIR), which has no strict sequence constraints, can be used to edit full-length transcripts containing pathogenic mutations. We further engineered this system to create a high-specificity variant and minimized the system to facilitate viral delivery. REPAIR presents a promising RNA-editing platform with broad applicability for research, therapeutics, and biotechnology. Copyright © 2017, American Association for the Advancement of Science.

RNA Editing with CRISPR-Cas13

PubMed Central

Cox, David B.T.; Gootenberg, Jonathan S.; Abudayyeh, Omar O.; Franklin, Brian; Kellner, Max J.; Joung, Julia; Zhang, Feng

2017-01-01

Nucleic acid editing holds promise for treating genetic disease, particularly at the RNA level, where disease-relevant sequences can be rescued to yield functional protein products. Type VI CRISPR-Cas systems contain the programmable single-effector RNA-guided RNases Cas13. Here, we profile Type VI systems to engineer a Cas13 ortholog capable of robust knockdown and demonstrate RNA editing by using catalytically-inactive Cas13 (dCas13) to direct adenosine to inosine deaminase activity by ADAR2 to transcripts in mammalian cells. This system, referred to as RNA Editing for Programmable A to I Replacement (REPAIR), has no strict sequence constraints, can be used to edit full-length transcripts containing pathogenic mutations. We further engineer this system to create a high specificity variant, REPAIRv2, that is 919 times more specific than REPAIRv1 as well as minimize the system to ease viral delivery. REPAIR presents a promising RNA editing platform with broad applicability for research, therapeutics, and biotechnology. PMID:29070703

Analysis of Macro-micro Simulation Models for Service-Oriented Public Platform: Coordination of Networked Services and Measurement of Public Values

NASA Astrophysics Data System (ADS)

Kinoshita, Yumiko

When service sectors are a major driver for the growth of the world economy, we are challenged to implement service-oriented infrastructure as e-Gov platform to achieve further growth and innovation for both developed and developing countries. According to recent trends in service industry, it is clarified that main factors for the growth of service sectors are investment into knowledge, trade, and the enhanced capacity of micro, small, and medium-sized enterprises (MSMEs). In addition, the design and deployment of public service platform require appropriate evaluation methodology. Reflecting these observations, this paper proposes macro-micro simulation approach to assess public values (PV) focusing on MSMEs. Linkage aggregate variables (LAVs) are defined to show connection between macro and micro impacts of public services. As a result, the relationship of demography, business environment, macro economy, and socio-economic impact are clarified and their values are quantified from the behavioral perspectives of citizens and firms.

Optical and electrical interfacing technologies for living cell bio-chips.

PubMed

Shacham-Diamand, Y; Belkin, S; Rishpon, J; Elad, T; Melamed, S; Biran, A; Yagur-Kroll, S; Almog, R; Daniel, R; Ben-Yoav, H; Rabner, A; Vernick, S; Elman, N; Popovtzer, R

2010-06-01

Whole-cell bio-chips for functional sensing integrate living cells on miniaturized platforms made by micro-system-technologies (MST). The cells are integrated, deposited or immersed in a media which is in contact with the chip. The cells behavior is monitored via electrical, electrochemical or optical methods. In this paper we describe such whole-cell biochips where the signal is generated due to the genetic response of the cells. The solid-state platform hosts the biological component, i.e. the living cells, and integrates all the required micro-system technologies, i.e. the micro-electronics, micro-electro optics, micro-electro or magneto mechanics and micro-fluidics. The genetic response of the cells expresses proteins that generate: a. light by photo-luminescence or bioluminescence, b. electrochemical signal by interaction with a substrate, or c. change in the cell impedance. The cell response is detected by a front end unit that converts it to current or voltage amplifies and filters it. The resultant signal is analyzed and stored for further processing. In this paper we describe three examples of whole-cell bio chips, photo-luminescent, bioluminescent and electrochemical, which are based on the genetic response of genetically modified E. coli microbes integrated on a micro-fluidics MEMS platform. We describe the chip outline as well as the basic modeling scheme of such sensors. We discuss the highlights and problems of such system, from the point of view of micro-system-technology.

Understanding Editing Behaviors in Multilingual Wikipedia.

PubMed

Kim, Suin; Park, Sungjoon; Hale, Scott A; Kim, Sooyoung; Byun, Jeongmin; Oh, Alice H

2016-01-01

Multilingualism is common offline, but we have a more limited understanding of the ways multilingualism is displayed online and the roles that multilinguals play in the spread of content between speakers of different languages. We take a computational approach to studying multilingualism using one of the largest user-generated content platforms, Wikipedia. We study multilingualism by collecting and analyzing a large dataset of the content written by multilingual editors of the English, German, and Spanish editions of Wikipedia. This dataset contains over two million paragraphs edited by over 15,000 multilingual users from July 8 to August 9, 2013. We analyze these multilingual editors in terms of their engagement, interests, and language proficiency in their primary and non-primary (secondary) languages and find that the English edition of Wikipedia displays different dynamics from the Spanish and German editions. Users primarily editing the Spanish and German editions make more complex edits than users who edit these editions as a second language. In contrast, users editing the English edition as a second language make edits that are just as complex as the edits by users who primarily edit the English edition. In this way, English serves a special role bringing together content written by multilinguals from many language editions. Nonetheless, language remains a formidable hurdle to the spread of content: we find evidence for a complexity barrier whereby editors are less likely to edit complex content in a second language. In addition, we find that multilinguals are less engaged and show lower levels of language proficiency in their second languages. We also examine the topical interests of multilingual editors and find that there is no significant difference between primary and non-primary editors in each language.

Understanding Editing Behaviors in Multilingual Wikipedia

PubMed Central

Hale, Scott A.; Kim, Sooyoung; Byun, Jeongmin; Oh, Alice H.

2016-01-01

Multilingualism is common offline, but we have a more limited understanding of the ways multilingualism is displayed online and the roles that multilinguals play in the spread of content between speakers of different languages. We take a computational approach to studying multilingualism using one of the largest user-generated content platforms, Wikipedia. We study multilingualism by collecting and analyzing a large dataset of the content written by multilingual editors of the English, German, and Spanish editions of Wikipedia. This dataset contains over two million paragraphs edited by over 15,000 multilingual users from July 8 to August 9, 2013. We analyze these multilingual editors in terms of their engagement, interests, and language proficiency in their primary and non-primary (secondary) languages and find that the English edition of Wikipedia displays different dynamics from the Spanish and German editions. Users primarily editing the Spanish and German editions make more complex edits than users who edit these editions as a second language. In contrast, users editing the English edition as a second language make edits that are just as complex as the edits by users who primarily edit the English edition. In this way, English serves a special role bringing together content written by multilinguals from many language editions. Nonetheless, language remains a formidable hurdle to the spread of content: we find evidence for a complexity barrier whereby editors are less likely to edit complex content in a second language. In addition, we find that multilinguals are less engaged and show lower levels of language proficiency in their second languages. We also examine the topical interests of multilingual editors and find that there is no significant difference between primary and non-primary editors in each language. PMID:27171158

[CRISPR/Cas system for genome editing in pluripotent stem cells].

PubMed

Vasil'eva, E A; Melino, D; Barlev, N A

2015-01-01

Genome editing systems based on site-specific nucleases became very popular for genome editing in modern bioengineering. Human pluripotent stem cells provide a unique platform for genes function study, disease modeling, and drugs testing. Consequently, technology for fast, accurate and well controlled genome manipulation is required. CRISPR/Cas (clustered regularly interspaced short palindromic repeat/CRISPR-associated) system could be employed for these purposes. This system is based on site-specific programmable nuclease Cas9. Numerous advantages of the CRISPR/Cas system and its successful application to human stem cells provide wide opportunities for genome therapy and regeneration medicine. In this publication, we describe and compare the main genome editing systems based on site-specific programmable nucleases and discuss opportunities and perspectives of the CRISPR/Cas system for application to pluripotent stem cells.

Latex Micro-balloon Pumping in Centrifugal Microfluidic Platforms

PubMed Central

Aeinehvand, Mohammad Mahdi; Ibrahim, Fatimah; Al-Faqheri, Wisam; Thio, Tzer Hwai Gilbert; Kazemzadeh, Amin; Wadi harun, Sulaiman; Madou, Marc

2014-01-01

Centrifugal microfluidic platforms have emerged as point-of-care diagnostic tools. However, the unidirectional nature of the centrifugal force limits the available space for multi-stepped processes on a single microfluidics disc. To overcome this limitation, a passive pneumatic pumping method actuated at high rotational speeds has been previously proposed to pump liquid against the centrifugal force. In this paper, a novel micro-balloon pumping method that relies on elastic energy stored in a latex membrane is introduced. It operates at low rotational speeds and pumps a larger volume of liquid towards the centre of the disc. Two different micro-balloon pumping designs have been developed to study the pump performance and capacity at a range of rotational frequencies from 0 to 1500 rpm. The behaviour of the micro-balloon pump on the centrifugal microfluidic platforms has been theoretically analysed and compared with the experimental data. The experimental data shows that, the developed pumping method dramatically decreases the required rotational speed to pump liquid compared to the previously developed pneumatic pumping methods. It also shows that within a range of rotational speed, desirable volume of liquid can be stored and pumped by adjusting the size of the micro-balloon. PMID:24441792

Functions of the RNA Editing Enzyme ADAR1 and Their Relevance to Human Diseases.

PubMed

Song, Chunzi; Sakurai, Masayuki; Shiromoto, Yusuke; Nishikura, Kazuko

2016-12-17

Adenosine deaminases acting on RNA (ADARs) convert adenosine to inosine in double-stranded RNA (dsRNA). Among the three types of mammalian ADARs, ADAR1 has long been recognized as an essential enzyme for normal development. The interferon-inducible ADAR1p150 is involved in immune responses to both exogenous and endogenous triggers, whereas the functions of the constitutively expressed ADAR1p110 are variable. Recent findings that ADAR1 is involved in the recognition of self versus non-self dsRNA provide potential explanations for its links to hematopoiesis, type I interferonopathies, and viral infections. Editing in both coding and noncoding sequences results in diseases ranging from cancers to neurological abnormalities. Furthermore, editing of noncoding sequences, like microRNAs, can regulate protein expression, while editing of Alu sequences can affect translational efficiency and editing of proximal sequences. Novel identifications of long noncoding RNA and retrotransposons as editing targets further expand the effects of A-to-I editing. Besides editing, ADAR1 also interacts with other dsRNA-binding proteins in editing-independent manners. Elucidating the disease-specific patterns of editing and/or ADAR1 expression may be useful in making diagnoses and prognoses. In this review, we relate the mechanisms of ADAR1's actions to its pathological implications, and suggest possible mechanisms for the unexplained associations between ADAR1 and human diseases.

Functions of the RNA Editing Enzyme ADAR1 and Their Relevance to Human Diseases

PubMed Central

Song, Chunzi; Sakurai, Masayuki; Shiromoto, Yusuke; Nishikura, Kazuko

2016-01-01

Adenosine deaminases acting on RNA (ADARs) convert adenosine to inosine in double-stranded RNA (dsRNA). Among the three types of mammalian ADARs, ADAR1 has long been recognized as an essential enzyme for normal development. The interferon-inducible ADAR1p150 is involved in immune responses to both exogenous and endogenous triggers, whereas the functions of the constitutively expressed ADAR1p110 are variable. Recent findings that ADAR1 is involved in the recognition of self versus non-self dsRNA provide potential explanations for its links to hematopoiesis, type I interferonopathies, and viral infections. Editing in both coding and noncoding sequences results in diseases ranging from cancers to neurological abnormalities. Furthermore, editing of noncoding sequences, like microRNAs, can regulate protein expression, while editing of Alu sequences can affect translational efficiency and editing of proximal sequences. Novel identifications of long noncoding RNA and retrotransposons as editing targets further expand the effects of A-to-I editing. Besides editing, ADAR1 also interacts with other dsRNA-binding proteins in editing-independent manners. Elucidating the disease-specific patterns of editing and/or ADAR1 expression may be useful in making diagnoses and prognoses. In this review, we relate the mechanisms of ADAR1′s actions to its pathological implications, and suggest possible mechanisms for the unexplained associations between ADAR1 and human diseases. PMID:27999332

Fly Ear Inspired Miniature Acoustic Sensors for Detection and Localization

DTIC Science & Technology

2011-07-31

Micro-Opto-Electro-Mechnical-System ( MOEMS ) sensor platform that is capable of integrating multiplexed Fabry-Perot (FP) interferometer based sensors. A...on a single MOEMS chip is shown in Figure 8. Light from a low coherence light source with a coherence length Lc is first sent to the reference...towards developing a low coherence interferometer based MOEMS detection system. An optical Micro-Electro-Mechanical-System (MEMS) sensor platform was

A standalone perfusion platform for drug testing and target validation in micro-vessel networks

PubMed Central

Zhang, Boyang; Peticone, Carlotta; Murthy, Shashi K.; Radisic, Milica

2013-01-01

Studying the effects of pharmacological agents on human endothelium includes the routine use of cell monolayers cultivated in multi-well plates. This configuration fails to recapitulate the complex architecture of vascular networks in vivo and does not capture the relationship between shear stress (i.e. flow) experienced by the cells and dose of the applied pharmacological agents. Microfluidic platforms have been applied extensively to create vascular systems in vitro; however, they rely on bulky external hardware to operate, which hinders the wide application of microfluidic chips by non-microfluidic experts. Here, we have developed a standalone perfusion platform where multiple devices were perfused at a time with a single miniaturized peristaltic pump. Using the platform, multiple micro-vessel networks, that contained three levels of branching structures, were created by culturing endothelial cells within circular micro-channel networks mimicking the geometrical configuration of natural blood vessels. To demonstrate the feasibility of our platform for drug testing and validation assays, a drug induced nitric oxide assay was performed on the engineered micro-vessel network using a panel of vaso-active drugs (acetylcholine, phenylephrine, atorvastatin, and sildenafil), showing both flow and drug dose dependent responses. The interactive effects between flow and drug dose for sildenafil could not be captured by a simple straight rectangular channel coated with endothelial cells, but it was captured in a more physiological branching circular network. A monocyte adhesion assay was also demonstrated with and without stimulation by an inflammatory cytokine, tumor necrosis factor-α. PMID:24404058

A Flexible Annular-Array Imaging Platform for Micro-Ultrasound

PubMed Central

Qiu, Weibao; Yu, Yanyan; Chabok, Hamid Reza; Liu, Cheng; Tsang, Fu Keung; Zhou, Qifa; Shung, K. Kirk; Zheng, Hairong; Sun, Lei

2013-01-01

Micro-ultrasound is an invaluable imaging tool for many clinical and preclinical applications requiring high resolution (approximately several tens of micrometers). Imaging systems for micro-ultrasound, including single-element imaging systems and linear-array imaging systems, have been developed extensively in recent years. Single-element systems are cheaper, but linear-array systems give much better image quality at a higher expense. Annular-array-based systems provide a third alternative, striking a balance between image quality and expense. This paper presents the development of a novel programmable and real-time annular-array imaging platform for micro-ultrasound. It supports multi-channel dynamic beamforming techniques for large-depth-of-field imaging. The major image processing algorithms were achieved by a novel field-programmable gate array technology for high speed and flexibility. Real-time imaging was achieved by fast processing algorithms and high-speed data transfer interface. The platform utilizes a printed circuit board scheme incorporating state-of-the-art electronics for compactness and cost effectiveness. Extensive tests including hardware, algorithms, wire phantom, and tissue mimicking phantom measurements were conducted to demonstrate good performance of the platform. The calculated contrast-to-noise ratio (CNR) of the tissue phantom measurements were higher than 1.2 in the range of 3.8 to 8.7 mm imaging depth. The platform supported more than 25 images per second for real-time image acquisition. The depth-of-field had about 2.5-fold improvement compared to single-element transducer imaging. PMID:23287923

Systematic characterization of A-to-I RNA editing hotspots in microRNAs across human cancers

PubMed Central

Wang, Yumeng; Xu, Xiaoyan; Yu, Shuangxing; Jeong, Kang Jin; Zhou, Zhicheng; Han, Leng; Tsang, Yiu Huen; Li, Jun; Chen, Hu; Mangala, Lingegowda S.; Yuan, Yuan; Eterovic, A. Karina; Lu, Yiling; Sood, Anil K.; Scott, Kenneth L.; Mills, Gordon B.; Liang, Han

2017-01-01

RNA editing, a widespread post-transcriptional mechanism, has emerged as a new player in cancer biology. Recent studies have reported key roles for individual miRNA editing events, but a comprehensive picture of miRNA editing in human cancers remains largely unexplored. Here, we systematically characterized the miRNA editing profiles of 8595 samples across 20 cancer types from miRNA sequencing data of The Cancer Genome Atlas and identified 19 adenosine-to-inosine (A-to-I) RNA editing hotspots. We independently validated 15 of them by perturbation experiments in several cancer cell lines. These miRNA editing events show extensive correlations with key clinical variables (e.g., tumor subtype, disease stage, and patient survival time) and other molecular drivers. Focusing on the RNA editing hotspot in miR-200b, a key tumor metastasis suppressor, we found that the miR-200b editing level correlates with patient prognosis opposite to the pattern observed for the wild-type miR-200b expression. We further experimentally showed that, in contrast to wild-type miRNA, the edited miR-200b can promote cell invasion and migration through its impaired ability to inhibit ZEB1/ZEB2 and acquired concomitant ability to repress new targets, including LIFR, a well-characterized metastasis suppressor. Our study highlights the importance of miRNA editing in gene regulation and suggests its potential as a biomarker for cancer prognosis and therapy. PMID:28411194

Trypanosome RNA Editing Mediator Complex proteins have distinct functions in gRNA utilization.

PubMed

Simpson, Rachel M; Bruno, Andrew E; Chen, Runpu; Lott, Kaylen; Tylec, Brianna L; Bard, Jonathan E; Sun, Yijun; Buck, Michael J; Read, Laurie K

2017-07-27

Uridine insertion/deletion RNA editing is an essential process in kinetoplastid parasites whereby mitochondrial mRNAs are modified through the specific insertion and deletion of uridines to generate functional open reading frames, many of which encode components of the mitochondrial respiratory chain. The roles of numerous non-enzymatic editing factors have remained opaque given the limitations of conventional methods to interrogate the order and mechanism by which editing progresses and thus roles of individual proteins. Here, we examined whole populations of partially edited sequences using high throughput sequencing and a novel bioinformatic platform, the Trypanosome RNA Editing Alignment Tool (TREAT), to elucidate the roles of three proteins in the RNA Editing Mediator Complex (REMC). We determined that the factors examined function in the progression of editing through a gRNA; however, they have distinct roles and REMC is likely heterogeneous in composition. We provide the first evidence that editing can proceed through numerous paths within a single gRNA and that non-linear modifications are essential, generating commonly observed junction regions. Our data support a model in which RNA editing is executed via multiple paths that necessitate successive re-modification of junction regions facilitated, in part, by the REMC variant containing TbRGG2 and MRB8180. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Micro-Editions of Unpublished Works

ERIC Educational Resources Information Center

Debregeas-Laurenie, Genevieve

1977-01-01

This article describes the micropublication program of Institut d'Ethnologie (Paris). The collection deals with ethnology, pre-history, and archeology. Material produced on microfiche includes notes from researchers' archives, rough field notes, and unique manuscripts. (Author/JAB)

A Cloud Based Real-Time Collaborative Platform for eHealth.

PubMed

Ionescu, Bogdan; Gadea, Cristian; Solomon, Bogdan; Ionescu, Dan; Stoicu-Tivadar, Vasile; Trifan, Mircea

2015-01-01

For more than a decade, the eHealth initiative has been a government concern of many countries. In an Electronic Health Record (EHR) System, there is a need for sharing the data with a group of specialists simultaneously. Collaborative platforms alone are just a part of a solution, while a collaborative platform with parallel editing capabilities and with synchronized data streaming are stringently needed. In this paper, the design and implementation of a collaborative platform used in healthcare is introduced by describing the high level architecture and its implementation. A series of eHealth services are identified and usage examples in a healthcare environment are given.

Modelling expertise at different levels of granularity using semantic similarity measures in the context of collaborative knowledge-curation platforms.

PubMed

Ziaimatin, Hasti; Groza, Tudor; Tudorache, Tania; Hunter, Jane

2016-12-01

Collaboration platforms provide a dynamic environment where the content is subject to ongoing evolution through expert contributions. The knowledge embedded in such platforms is not static as it evolves through incremental refinements - or micro-contributions. Such refinements provide vast resources of tacit knowledge and experience. In our previous work, we proposed and evaluated a Semantic and Time-dependent Expertise Profiling (STEP) approach for capturing expertise from micro-contributions. In this paper we extend our investigation to structured micro-contributions that emerge from an ontology engineering environment, such as the one built for developing the International Classification of Diseases (ICD) revision 11. We take advantage of the semantically related nature of these structured micro-contributions to showcase two major aspects: (i) a novel semantic similarity metric, in addition to an approach for creating bottom-up baseline expertise profiles using expertise centroids; and (ii) the application of STEP in this new environment combined with the use of the same semantic similarity measure to both compare STEP against baseline profiles, as well as to investigate the coverage of these baseline profiles by STEP.

Genome Editing of Erythroid Cell Culture Model Systems.

PubMed

Yik, Jinfen J; Crossley, Merlin; Quinlan, Kate G R

2018-01-01

Genome editing to introduce specific mutations or to knock out genes in model cell systems has become an efficient platform for research in the fields of molecular biology, genetics, and cell biology. With recent rapid improvements in genome editing techniques, bench-top manipulation of the genome in cell culture has become progressively easier. The application of this knowledge to erythroid cell culture systems now allows the rapid analysis of the downstream effects of virtually any engineered gene disruption or modification in cell systems. Here, we describe a CRISPR/Cas9-based approach to making genomic modifications in erythroid lineage cells which we have successfully used in both murine (MEL) and human (K562) erythroleukaemia immortalized cell lines.

The clinical applications of genome editing in HIV.

PubMed

Wang, Cathy X; Cannon, Paula M

2016-05-26

HIV/AIDS has long been at the forefront of the development of gene- and cell-based therapies. Although conventional gene therapy approaches typically involve the addition of anti-HIV genes to cells using semirandomly integrating viral vectors, newer genome editing technologies based on engineered nucleases are now allowing more precise genetic manipulations. The possible outcomes of genome editing include gene disruption, which has been most notably applied to the CCR5 coreceptor gene, or the introduction of small mutations or larger whole gene cassette insertions at a targeted locus. Disruption of CCR5 using zinc finger nucleases was the first-in-human application of genome editing and remains the most clinically advanced platform, with 7 completed or ongoing clinical trials in T cells and hematopoietic stem/progenitor cells (HSPCs). Here we review the laboratory and clinical findings of CCR5 editing in T cells and HSPCs for HIV therapy and summarize other promising genome editing approaches for future clinical development. In particular, recent advances in the delivery of genome editing reagents and the demonstration of highly efficient homology-directed editing in both T cells and HSPCs are expected to spur the development of even more sophisticated applications of this technology for HIV therapy. © 2016 by The American Society of Hematology.

Genome-editing Technologies for Gene and Cell Therapy.

PubMed

Maeder, Morgan L; Gersbach, Charles A

2016-03-01

Gene therapy has historically been defined as the addition of new genes to human cells. However, the recent advent of genome-editing technologies has enabled a new paradigm in which the sequence of the human genome can be precisely manipulated to achieve a therapeutic effect. This includes the correction of mutations that cause disease, the addition of therapeutic genes to specific sites in the genome, and the removal of deleterious genes or genome sequences. This review presents the mechanisms of different genome-editing strategies and describes each of the common nuclease-based platforms, including zinc finger nucleases, transcription activator-like effector nucleases (TALENs), meganucleases, and the CRISPR/Cas9 system. We then summarize the progress made in applying genome editing to various areas of gene and cell therapy, including antiviral strategies, immunotherapies, and the treatment of monogenic hereditary disorders. The current challenges and future prospects for genome editing as a transformative technology for gene and cell therapy are also discussed.

Genome-editing Technologies for Gene and Cell Therapy

PubMed Central

Maeder, Morgan L; Gersbach, Charles A

2016-01-01

Gene therapy has historically been defined as the addition of new genes to human cells. However, the recent advent of genome-editing technologies has enabled a new paradigm in which the sequence of the human genome can be precisely manipulated to achieve a therapeutic effect. This includes the correction of mutations that cause disease, the addition of therapeutic genes to specific sites in the genome, and the removal of deleterious genes or genome sequences. This review presents the mechanisms of different genome-editing strategies and describes each of the common nuclease-based platforms, including zinc finger nucleases, transcription activator-like effector nucleases (TALENs), meganucleases, and the CRISPR/Cas9 system. We then summarize the progress made in applying genome editing to various areas of gene and cell therapy, including antiviral strategies, immunotherapies, and the treatment of monogenic hereditary disorders. The current challenges and future prospects for genome editing as a transformative technology for gene and cell therapy are also discussed. PMID:26755333

Use of genome editing tools in human stem cell-based disease modeling and precision medicine.

PubMed

Wei, Yu-da; Li, Shuang; Liu, Gai-gai; Zhang, Yong-xian; Ding, Qiu-rong

2015-10-01

Precision medicine emerges as a new approach that takes into account individual variability. The successful conduct of precision medicine requires the use of precise disease models. Human pluripotent stem cells (hPSCs), as well as adult stem cells, can be differentiated into a variety of human somatic cell types that can be used for research and drug screening. The development of genome editing technology over the past few years, especially the CRISPR/Cas system, has made it feasible to precisely and efficiently edit the genetic background. Therefore, disease modeling by using a combination of human stem cells and genome editing technology has offered a new platform to generate " personalized " disease models, which allow the study of the contribution of individual genetic variabilities to disease progression and the development of precise treatments. In this review, recent advances in the use of genome editing in human stem cells and the generation of stem cell models for rare diseases and cancers are discussed.

Design and assessment of engineered CRISPR-Cpf1 and its use for genome editing.

PubMed

Li, Bin; Zeng, Chunxi; Dong, Yizhou

2018-05-01

Cpf1, a CRISPR endonuclease discovered in Prevotella and Francisella 1 bacteria, offers an alternative platform for CRISPR-based genome editing beyond the commonly used CRISPR-Cas9 system originally discovered in Streptococcus pyogenes. This protocol enables the design of engineered CRISPR-Cpf1 components, both CRISPR RNAs (crRNAs) to guide the endonuclease and Cpf1 mRNAs to express the endonuclease protein, and provides experimental procedures for effective genome editing using this system. We also describe quantification of genome-editing activity and off-target effects of the engineered CRISPR-Cpf1 in human cell lines using both T7 endonuclease I (T7E1) assay and targeted deep sequencing. This protocol enables rapid construction and identification of engineered crRNAs and Cpf1 mRNAs to enhance genome-editing efficiency using the CRISPR-Cpf1 system, as well as assessment of target specificity within 2 months. This protocol may also be appropriate for fine-tuning other types of CRISPR systems.

Highly sensitive dual mode electrochemical platform for microRNA detection

NASA Astrophysics Data System (ADS)

Jolly, Pawan; Batistuti, Marina R.; Miodek, Anna; Zhurauski, Pavel; Mulato, Marcelo; Lindsay, Mark A.; Estrela, Pedro

2016-11-01

MicroRNAs (miRNAs) play crucial regulatory roles in various human diseases including cancer, making them promising biomarkers. However, given the low levels of miRNAs present in blood, their use as cancer biomarkers requires the development of simple and effective analytical methods. Herein, we report the development of a highly sensitive dual mode electrochemical platform for the detection of microRNAs. The platform was developed using peptide nucleic acids as probes on gold electrode surfaces to capture target miRNAs. A simple amplification strategy using gold nanoparticles has been employed exploiting the inherent charges of the nucleic acids. Electrochemical impedance spectroscopy was used to monitor the changes in capacitance upon any binding event, without the need for any redox markers. By using thiolated ferrocene, a complementary detection mode on the same sensor was developed where the increasing peaks of ferrocene were recorded using square wave voltammetry with increasing miRNA concentration. This dual-mode approach allows detection of miRNA with a limit of detection of 0.37 fM and a wide dynamic range from 1 fM to 100 nM along with clear distinction from mismatched target miRNA sequences. The electrochemical platform developed can be easily expanded to other miRNA/DNA detection along with the development of microarray platforms.

A microfabricated platform to form three-dimensional toroidal multicellular aggregate.

PubMed

Masuda, Taisuke; Takei, Natsuki; Nakano, Takuma; Anada, Takahisa; Suzuki, Osamu; Arai, Fumihito

2012-12-01

Techniques that allow cells to self-assemble into three-dimensional (3D) spheroid microtissues provide powerful in vitro models that are becoming increasingly popular in fields such as stem cell research, tissue engineering, and cancer biology. Appropriate simulation of the 3D environment in which tissues normally develop and function is crucial for the engineering of in vitro models that can be used for the formation of complex tissues. We have developed a unique multicellular aggregate formation platform that utilizes a maskless gray-scale photolithography. The cellular aggregate formed using this platform has a toroidal-like geometry and includes a micro lumen that facilitates the supply of oxygen and growth factors and the expulsion of waste products. As a result, this platform was capable of rapidly producing hundreds of multicellular aggregates at a time, and of regulating the diameter of aggregates with complex design. These toroidal multicellular aggregates can grow as long-term culture. In addition, the micro lumen can be used as a continuous channel and for the insertion of a vascular system or a nerve system into the assembled tissue. These platform characteristics highlight its potential to be used in a wide variety of applications, e.g. as a bioactuator, as a micro-machine component or in drug screening and tissue engineering.

A Universal Platform for Identification of Novel Lung Cancer Biomarkers Based on Exosomes

DTIC Science & Technology

2017-10-01

yield ~4–1000-fold higher than that with UC, and EV-derived protein and microRNA levels are well- correlated between the two methods. Moreover, we...derived protein and microRNA levels are well- correlated between the two methods. Moreover, we demonstrated that ExoTIC is a modular platform that can...linear correlation between EV number and media volume. The TEM Figure 1. Schematic illustration of ExoTIC device for extracellular vesicle isolation

Accelerated Aging Experiments for Prognostics of Damage Growth in Composite Materials

DTIC Science & Technology

2011-09-01

possible resource to collect such data is an accelerated aging platform. To that end this paper describes a fatigue cycling experiment with the goal to...possible resource to collect such data is an accelerated aging platform. To that end this paper describes a fatigue cycling experiment with the goal to...suffer from two damage types: matrix micro-cracks and inter- laminar delamination. When subject to fatigue loading matrix micro-cracks develop in the

Systematic characterization of A-to-I RNA editing hotspots in microRNAs across human cancers.

PubMed

Wang, Yumeng; Xu, Xiaoyan; Yu, Shuangxing; Jeong, Kang Jin; Zhou, Zhicheng; Han, Leng; Tsang, Yiu Huen; Li, Jun; Chen, Hu; Mangala, Lingegowda S; Yuan, Yuan; Eterovic, A Karina; Lu, Yiling; Sood, Anil K; Scott, Kenneth L; Mills, Gordon B; Liang, Han

2017-07-01

RNA editing, a widespread post-transcriptional mechanism, has emerged as a new player in cancer biology. Recent studies have reported key roles for individual miRNA editing events, but a comprehensive picture of miRNA editing in human cancers remains largely unexplored. Here, we systematically characterized the miRNA editing profiles of 8595 samples across 20 cancer types from miRNA sequencing data of The Cancer Genome Atlas and identified 19 adenosine-to-inosine (A-to-I) RNA editing hotspots. We independently validated 15 of them by perturbation experiments in several cancer cell lines. These miRNA editing events show extensive correlations with key clinical variables (e.g., tumor subtype, disease stage, and patient survival time) and other molecular drivers. Focusing on the RNA editing hotspot in miR-200b, a key tumor metastasis suppressor, we found that the miR-200b editing level correlates with patient prognosis opposite to the pattern observed for the wild-type miR-200b expression. We further experimentally showed that, in contrast to wild-type miRNA, the edited miR-200b can promote cell invasion and migration through its impaired ability to inhibit ZEB1/ZEB2 and acquired concomitant ability to repress new targets, including LIFR , a well-characterized metastasis suppressor. Our study highlights the importance of miRNA editing in gene regulation and suggests its potential as a biomarker for cancer prognosis and therapy. © 2017 Wang et al.; Published by Cold Spring Harbor Laboratory Press.

Detection of canonical A-to-G editing events at 3′ UTRs and microRNA target sites in human lungs using next-generation sequencing

PubMed Central

Soundararajan, Ramani; Stearns, Timothy M.; Griswold, Anthony J.; Mehta, Arpit; Czachor, Alexander; Fukumoto, Jutaro; Lockey, Richard F.; King, Benjamin L.; Kolliputi, Narasaiah

2015-01-01

RNA editing is a post-transcriptional modification of RNA. The majority of these changes result from adenosine deaminase acting on RNA (ADARs) catalyzing the conversion of adenosine residues to inosine in double-stranded RNAs (dsRNAs). Massively parallel sequencing has enabled the identification of RNA editing sites in human transcriptomes. In this study, we sequenced DNA and RNA from human lungs and identified RNA editing sites with high confidence via a computational pipeline utilizing stringent analysis thresholds. We identified a total of 3,447 editing sites that overlapped in three human lung samples, and with 50% of these sites having canonical A-to-G base changes. Approximately 27% of the edited sites overlapped with Alu repeats, and showed A-to-G clustering (>3 clusters in 100 bp). The majority of edited sites mapped to either 3′ untranslated regions (UTRs) or introns close to splice sites; whereas, only few sites were in exons resulting in non-synonymous amino acid changes. Interestingly, we identified 652 A-to-G editing events in the 3′ UTR of 205 target genes that mapped to 932 potential miRNA target binding sites. Several of these miRNA edited sites were validated in silico. Additionally, we validated several A-to-G edited sites by Sanger sequencing. Altogether, our study suggests a role for RNA editing in miRNA-mediated gene regulation and splicing in human lungs. In this study, we have generated a RNA editome of human lung tissue that can be compared with other RNA editomes across different lung tissues to delineate a role for RNA editing in normal and diseased states. PMID:26486088

Detection of canonical A-to-G editing events at 3' UTRs and microRNA target sites in human lungs using next-generation sequencing.

PubMed

Soundararajan, Ramani; Stearns, Timothy M; Griswold, Anthony L; Mehta, Arpit; Czachor, Alexander; Fukumoto, Jutaro; Lockey, Richard F; King, Benjamin L; Kolliputi, Narasaiah

2015-11-03

RNA editing is a post-transcriptional modification of RNA. The majority of these changes result from adenosine deaminase acting on RNA (ADARs) catalyzing the conversion of adenosine residues to inosine in double-stranded RNAs (dsRNAs). Massively parallel sequencing has enabled the identification of RNA editing sites in human transcriptomes. In this study, we sequenced DNA and RNA from human lungs and identified RNA editing sites with high confidence via a computational pipeline utilizing stringent analysis thresholds. We identified a total of 3,447 editing sites that overlapped in three human lung samples, and with 50% of these sites having canonical A-to-G base changes. Approximately 27% of the edited sites overlapped with Alu repeats, and showed A-to-G clustering (>3 clusters in 100 bp). The majority of edited sites mapped to either 3' untranslated regions (UTRs) or introns close to splice sites; whereas, only few sites were in exons resulting in non-synonymous amino acid changes. Interestingly, we identified 652 A-to-G editing events in the 3' UTR of 205 target genes that mapped to 932 potential miRNA target binding sites. Several of these miRNA edited sites were validated in silico. Additionally, we validated several A-to-G edited sites by Sanger sequencing. Altogether, our study suggests a role for RNA editing in miRNA-mediated gene regulation and splicing in human lungs. In this study, we have generated a RNA editome of human lung tissue that can be compared with other RNA editomes across different lung tissues to delineate a role for RNA editing in normal and diseased states.

Concurrent Flow Lanes - Phase II

DOT National Transportation Integrated Search

2009-04-17

This report provides the findings from a research effort designed to ascertain whether or not a chosen simulation software platform, the VISSIM micro-simulation platform, provides a suitable environment for modeling and analyzing traffic operations, ...

PDB Editor: a user-friendly Java-based Protein Data Bank file editor with a GUI.

PubMed

Lee, Jonas; Kim, Sung Hou

2009-04-01

The Protein Data Bank file format is the format most widely used by protein crystallographers and biologists to disseminate and manipulate protein structures. Despite this, there are few user-friendly software packages available to efficiently edit and extract raw information from PDB files. This limitation often leads to many protein crystallographers wasting significant time manually editing PDB files. PDB Editor, written in Java Swing GUI, allows the user to selectively search, select, extract and edit information in parallel. Furthermore, the program is a stand-alone application written in Java which frees users from the hassles associated with platform/operating system-dependent installation and usage. PDB Editor can be downloaded from http://sourceforge.net/projects/pdbeditorjl/.

Black phosphorus nanosheets for rapid microRNA detection.

PubMed

Zhou, Jie; Li, Zhongjun; Ying, Ming; Liu, Maixian; Wang, Xiaomei; Wang, Xianyou; Cao, Liwei; Zhang, Han; Xu, Gaixia

2018-03-15

Herein, for the first time, a sensitive sensing platform for rapid detection of microRNA was developed by employing black phosphorus nanosheets as the fluorescence quenching material. The biosensor displayed a good linear response to microRNA ranging from 10 nM to 1000 nM. Moreover, the biosensor could distinguish triple nucleotide polymorphism.

Modelling expertise at different levels of granularity using semantic similarity measures in the context of collaborative knowledge-curation platforms

PubMed Central

Groza, Tudor; Tudorache, Tania; Hunter, Jane

2015-01-01

Collaboration platforms provide a dynamic environment where the content is subject to ongoing evolution through expert contributions. The knowledge embedded in such platforms is not static as it evolves through incremental refinements – or micro-contributions. Such refinements provide vast resources of tacit knowledge and experience. In our previous work, we proposed and evaluated a Semantic and Time-dependent Expertise Profiling (STEP) approach for capturing expertise from micro-contributions. In this paper we extend our investigation to structured micro-contributions that emerge from an ontology engineering environment, such as the one built for developing the International Classification of Diseases (ICD) revision 11. We take advantage of the semantically related nature of these structured micro-contributions to showcase two major aspects: (i) a novel semantic similarity metric, in addition to an approach for creating bottom-up baseline expertise profiles using expertise centroids; and (ii) the application of STEP in this new environment combined with the use of the same semantic similarity measure to both compare STEP against baseline profiles, as well as to investigate the coverage of these baseline profiles by STEP. PMID:28077914

Micro-array versus nano-array platforms: a comparative study for ODN detection based on SPR enhanced ellipsometry

NASA Astrophysics Data System (ADS)

Celen, Burcu; Demirel, Gökhan; Piskin, Erhan

2011-04-01

The rapid and sensitive detection of DNA has recently attracted worldwide attention for a variety of disease diagnoses and detection of harmful bacteria in food and drink. In this paper, we carried out a comparative study based on surface plasmon resonance enhanced ellipsometry (SPREE) for the detection of oligodeoxynucleotides (ODNs) using micro- and nano-array platforms. The micro-arrayed surfaces were fabricated by a photolithography approach using different types of mask having varying size and shape. Well-ordered arrays of high aspect ratio polymeric nanotubes were also obtained using high molecular weight polystyrene (PS) and anodic aluminum oxide (AAO) membranes having 200 nm pore diameters. The SPREE sensors were then prepared by direct coupling of thiolated probe-ODNs, which contain suitable spacer arms, on gold-coated micro- and nano-arrayed surfaces. We experimentally demonstrated that, for the first time, gold-coated free standing polymeric nano-arrayed platforms can easily be produced and lead to a significant sensor sensitivity gain compared to that of the conventional SPREE surfaces of about four times. We believe that such an enhancement in sensor response could be useful for next generation sensor systems.

Genome Editing: A New Approach to Human Therapeutics.

PubMed

Porteus, Matthew

2016-01-01

The ability to manipulate the genome with precise spatial and nucleotide resolution (genome editing) has been a powerful research tool. In the past decade, the tools and expertise for using genome editing in human somatic cells and pluripotent cells have increased to such an extent that the approach is now being developed widely as a strategy to treat human disease. The fundamental process depends on creating a site-specific DNA double-strand break (DSB) in the genome and then allowing the cell's endogenous DSB repair machinery to fix the break such that precise nucleotide changes are made to the DNA sequence. With the development and discovery of several different nuclease platforms and increasing knowledge of the parameters affecting different genome editing outcomes, genome editing frequencies now reach therapeutic relevance for a wide variety of diseases. Moreover, there is a series of complementary approaches to assessing the safety and toxicity of any genome editing process, irrespective of the underlying nuclease used. Finally, the development of genome editing has raised the issue of whether it should be used to engineer the human germline. Although such an approach could clearly prevent the birth of people with devastating and destructive genetic diseases, questions remain about whether human society is morally responsible enough to use this tool.

A coral-on-a-chip microfluidic platform enabling live-imaging microscopy of reef-building corals

PubMed Central

Shapiro, Orr H.; Kramarsky-Winter, Esti; Gavish, Assaf R.; Stocker, Roman; Vardi, Assaf

2016-01-01

Coral reefs, and the unique ecosystems they support, are facing severe threats by human activities and climate change. Our understanding of these threats is hampered by the lack of robust approaches for studying the micro-scale interactions between corals and their environment. Here we present an experimental platform, coral-on-a-chip, combining micropropagation and microfluidics to allow direct microscopic study of live coral polyps. The small and transparent coral micropropagates are ideally suited for live-imaging microscopy, while the microfluidic platform facilitates long-term visualization under controlled environmental conditions. We demonstrate the usefulness of this approach by imaging coral micropropagates at previously unattainable spatio-temporal resolutions, providing new insights into several micro-scale processes including coral calcification, coral–pathogen interaction and the loss of algal symbionts (coral bleaching). Coral-on-a-chip thus provides a powerful method for studying coral physiology in vivo at the micro-scale, opening new vistas in coral biology. PMID:26940983

A coral-on-a-chip microfluidic platform enabling live-imaging microscopy of reef-building corals.

PubMed

Shapiro, Orr H; Kramarsky-Winter, Esti; Gavish, Assaf R; Stocker, Roman; Vardi, Assaf

2016-03-04

Coral reefs, and the unique ecosystems they support, are facing severe threats by human activities and climate change. Our understanding of these threats is hampered by the lack of robust approaches for studying the micro-scale interactions between corals and their environment. Here we present an experimental platform, coral-on-a-chip, combining micropropagation and microfluidics to allow direct microscopic study of live coral polyps. The small and transparent coral micropropagates are ideally suited for live-imaging microscopy, while the microfluidic platform facilitates long-term visualization under controlled environmental conditions. We demonstrate the usefulness of this approach by imaging coral micropropagates at previously unattainable spatio-temporal resolutions, providing new insights into several micro-scale processes including coral calcification, coral-pathogen interaction and the loss of algal symbionts (coral bleaching). Coral-on-a-chip thus provides a powerful method for studying coral physiology in vivo at the micro-scale, opening new vistas in coral biology.

Multi-longitudinal-mode micro-laser model

NASA Astrophysics Data System (ADS)

Staliunas, Kestutis

2017-10-01

We derive a convenient model for broad aperture micro-lasers, such as microchip lasers, broad area semiconductor lasers, or VCSELs, taking into account several longitudinal mode families. We provide linear stability analysis, and show characteristic spatio-temporal dynamics in such multi-longitudinal mode laser models. Moreover, we derive the coupled mode model in the presence of intracavity refraction index modulation (intracavity photonic crystal). Contribution to the Topical Issue "Theory and Applications of the Lugiato-Lefever Equation", edited by Yanne K. Chembo, Damia Gomila, Mustapha Tlidi, Curtis R. Menyuk.

MicroShell Minimalist Shell for Xilinx Microprocessors

NASA Technical Reports Server (NTRS)

Werne, Thomas A.

2011-01-01

MicroShell is a lightweight shell environment for engineers and software developers working with embedded microprocessors in Xilinx FPGAs. (MicroShell has also been successfully ported to run on ARM Cortex-M1 microprocessors in Actel ProASIC3 FPGAs, but without project-integration support.) Micro Shell decreases the time spent performing initial tests of field-programmable gate array (FPGA) designs, simplifies running customizable one-time-only experiments, and provides a familiar-feeling command-line interface. The program comes with a collection of useful functions and enables the designer to add an unlimited number of custom commands, which are callable from the command-line. The commands are parameterizable (using the C-based command-line parameter idiom), so the designer can use one function to exercise hardware with different values. Also, since many hardware peripherals instantiated in FPGAs have reasonably simple register-mapped I/O interfaces, the engineer can edit and view hardware parameter settings at any time without stopping the processor. MicroShell comes with a set of support scripts that interface seamlessly with Xilinx's EDK tool. Adding an instance of MicroShell to a project is as simple as marking a check box in a library configuration dialog box and specifying a software project directory. The support scripts then examine the hardware design, build design-specific functions, conditionally include processor-specific functions, and complete the compilation process. For code-size constrained designs, most of the stock functionality can be excluded from the compiled library. When all of the configurable options are removed from the binary, MicroShell has an unoptimized memory footprint of about 4.8 kB and a size-optimized footprint of about 2.3 kB. Since MicroShell allows unfettered access to all processor-accessible memory locations, it is possible to perform live patching on a running system. This can be useful, for instance, if a bug is discovered in a routine but the system cannot be rebooted: Shell allows a skilled operator to directly edit the binary executable in memory. With some forethought, MicroShell code can be located in a different memory location from custom code, permitting the custom functionality to be overwritten at any time without stopping the controlling shell.

Emerging Role of CRISPR/Cas9 Technology for MicroRNAs Editing in Cancer Research.

PubMed

Aquino-Jarquin, Guillermo

2017-12-15

MicroRNAs (miRNA) are small, noncoding RNA molecules with a master role in the regulation of important tasks in different critical processes of cancer pathogenesis. Because there are different miRNAs implicated in all the stages of cancer, for example, functioning as oncogenes, this makes these small molecules suitable targets for cancer diagnosis and therapy. RNA-mediated interference has been one major approach for sequence-specific regulation of gene expression in eukaryotic organisms. Recently, the CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 system, first identified in bacteria and archaea as an adaptive immune response to invading genetic material, has been explored as a sequence-specific molecular tool for editing genomic sequences for basic research in life sciences and for therapeutic purposes. There is growing evidence that small noncoding RNAs, including miRNAs, can be targeted by the CRISPR/Cas9 system despite their lacking an open reading frame to evaluate functional loss. Thus, CRISPR/Cas9 technology represents a novel gene-editing strategy with compelling robustness, specificity, and stability for the modification of miRNA expression. Here, I summarize key features of current knowledge of genomic editing by CRISPR/Cas9 technology as a feasible strategy for globally interrogating miRNA gene function and miRNA-based therapeutic intervention. Alternative emerging strategies for nonviral delivery of CRISPR/Cas9 core components into human cells in a clinical context are also analyzed critically. Cancer Res; 77(24); 6812-7. ©2017 AACR . ©2017 American Association for Cancer Research.

Recent advance on genome editing for therapy of β-hemoglobinopathies.

PubMed

Liu, Jia-Wei; Hong, Tao; Qin, Xin; Liang, Ying-Min; Zhang, Ping

2018-02-20

β-hemoglobinopathies are one of six groups of common illnesses affecting human health. Although the genetic mechanisms have been elucidated for several decades, curable treatment options, other than allogeneic bone marrow transplantation, are still lacking. In recent years, rapid development in genome editing technologies and their clinical applications have opened up new directions for treatment of β-hemoglobinopathies. Genome editing technologies, as applied in autologous CD34 + hematopoietic stem and progenitor cells, represents a promising remedial means for the β-globin disorders. Hemoglobin gene mutations could be corrected with homologous recombination-mediated DNA repair pathway to repair the genetic defects, while the nonhomologous end-joining pathway may be used to silence the key repressor of fetal globin expression and reactivate fetal hemoglobin expression, thereby alleviating the clinical symptoms of β-hemoglobinopathies in patients. This review summarizes the recent advances on genome editing of β-hemoglobinopathies from the bench design to the establishment of clinical translational platforms, thereby providing critical insights and references on the application of genome editing technologies for the development of therapeutic strategies for β-hemoglobinopathies.

Integrated protein analysis platform based on column switch recycling size exclusion chromatography, microenzymatic reactor and microRPLC-ESI-MS/MS.

PubMed

Yuan, Huiming; Zhou, Yuan; Zhang, Lihua; Liang, Zhen; Zhang, Yukui

2009-10-30

An integrated platform with the combination of proteins and peptides separation was established via the unit of on-line proteins digestion, by which proteins were in sequence separated by column switch recycling size exclusion chromatography (csrSEC), on-line digested by an immobilized trypsin microreactor, trapped and desalted by two parallel C8 precolumns, separated by microRPLC with the linear gradient of organic modifier concentration, and identified by ESI-MS/MS. A 6-protein mixture, with Mr ranging from 10 kDa to 80 kDa, was used to evaluate the performance of the integrated platform, and all proteins were identified with sequence coverage over 5.67%. Our experimental results demonstrate that such an integrated platform is of advantages such as good time compatibility, high peak capacity, and facile automation, which might be a promising approach for proteome study.

Documentation of the ISA Micro Computed Tomography System

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brown, William D.; Smith, Jerel A.

2013-12-18

This document is intended to provide information on the ISA Micro Computed Tomography (MicroCT) system that will be installed in Yavne, Israel. X-ray source, detector, and motion control hardware are specified as well as specimen platforms, containers, and reference material types. Most of the details on the system are derived from Reference 1 and 2.

Consistency of two global MODIS aerosol products over ocean on Terra and Aqua CERES SSF datasets

NASA Astrophysics Data System (ADS)

Ignatov, Alexander; Minnis, Patrick; Wielicki, Bruce; Loeb, Norman G.; Remer, Lorraine A.; Kaufman, Yoram J.; Miller, Walter F.; Sun-Mack, Sunny; Laszlo, Istvan; Geier, Erika B.

2004-12-01

MODIS aerosol retrievals over ocean from Terra and Aqua platforms are available from the Clouds and the Earth's Radiant Energy System (CERES) Single Scanner Footprint (SSF) datasets generated at NASA Langley Research Center (LaRC). Two aerosol products are reported side by side. The primary M product is generated by subsetting and remapping the multi-spectral (0.44 - 2.1 μm) MOD04 aerosols onto CERES footprints. MOD04 processing uses cloud screening and aerosol algorithms developed by the MODIS science team. The secondary (AVHRR-like) A product is generated in only two MODIS bands: 1 and 6 on Terra, and ` and 7 on Aqua. The A processing uses NASA/LaRC cloud-screening and NOAA/NESDIS single channel aerosol algorthm. The M and A products have been documented elsewhere and preliminarily compared using two weeks of global Terra CERES SSF (Edition 1A) data in December 2000 and June 2001. In this study, the M and A aerosol optical depths (AOD) in MODIS band 1 and (0.64 μm), τ1M and τ1A, are further checked for cross-platform consistency using 9 days of global Terra CERES SSF (Edition 2A) and Aqua CERES SSF (Edition 1A) data from 13 - 21 October 2002.

RED: A Java-MySQL Software for Identifying and Visualizing RNA Editing Sites Using Rule-Based and Statistical Filters.

PubMed

Sun, Yongmei; Li, Xing; Wu, Di; Pan, Qi; Ji, Yuefeng; Ren, Hong; Ding, Keyue

2016-01-01

RNA editing is one of the post- or co-transcriptional processes that can lead to amino acid substitutions in protein sequences, alternative pre-mRNA splicing, and changes in gene expression levels. Although several methods have been suggested to identify RNA editing sites, there remains challenges to be addressed in distinguishing true RNA editing sites from its counterparts on genome and technical artifacts. In addition, there lacks a software framework to identify and visualize potential RNA editing sites. Here, we presented a software - 'RED' (RNA Editing sites Detector) - for the identification of RNA editing sites by integrating multiple rule-based and statistical filters. The potential RNA editing sites can be visualized at the genome and the site levels by graphical user interface (GUI). To improve performance, we used MySQL database management system (DBMS) for high-throughput data storage and query. We demonstrated the validity and utility of RED by identifying the presence and absence of C→U RNA-editing sites experimentally validated, in comparison with REDItools, a command line tool to perform high-throughput investigation of RNA editing. In an analysis of a sample data-set with 28 experimentally validated C→U RNA editing sites, RED had sensitivity and specificity of 0.64 and 0.5. In comparison, REDItools had a better sensitivity (0.75) but similar specificity (0.5). RED is an easy-to-use, platform-independent Java-based software, and can be applied to RNA-seq data without or with DNA sequencing data. The package is freely available under the GPLv3 license at http://github.com/REDetector/RED or https://sourceforge.net/projects/redetector.

RED: A Java-MySQL Software for Identifying and Visualizing RNA Editing Sites Using Rule-Based and Statistical Filters

PubMed Central

Sun, Yongmei; Li, Xing; Wu, Di; Pan, Qi; Ji, Yuefeng; Ren, Hong; Ding, Keyue

2016-01-01

RNA editing is one of the post- or co-transcriptional processes that can lead to amino acid substitutions in protein sequences, alternative pre-mRNA splicing, and changes in gene expression levels. Although several methods have been suggested to identify RNA editing sites, there remains challenges to be addressed in distinguishing true RNA editing sites from its counterparts on genome and technical artifacts. In addition, there lacks a software framework to identify and visualize potential RNA editing sites. Here, we presented a software − ‘RED’ (RNA Editing sites Detector) − for the identification of RNA editing sites by integrating multiple rule-based and statistical filters. The potential RNA editing sites can be visualized at the genome and the site levels by graphical user interface (GUI). To improve performance, we used MySQL database management system (DBMS) for high-throughput data storage and query. We demonstrated the validity and utility of RED by identifying the presence and absence of C→U RNA-editing sites experimentally validated, in comparison with REDItools, a command line tool to perform high-throughput investigation of RNA editing. In an analysis of a sample data-set with 28 experimentally validated C→U RNA editing sites, RED had sensitivity and specificity of 0.64 and 0.5. In comparison, REDItools had a better sensitivity (0.75) but similar specificity (0.5). RED is an easy-to-use, platform-independent Java-based software, and can be applied to RNA-seq data without or with DNA sequencing data. The package is freely available under the GPLv3 license at http://github.com/REDetector/RED or https://sourceforge.net/projects/redetector. PMID:26930599

Diving into marine genomics with CRISPR/Cas9 systems.

PubMed

Momose, Tsuyoshi; Concordet, Jean-Paul

2016-12-01

More and more genomes are sequenced and a great range of biological questions can be examined at the genomic level in a growing number of organisms. Testing the function of genome features, from gene networks, genome organization, conserved non-coding sequences to microRNAs, and, more generally, experimentally addressing the genotype-phenotype relationship is now possible owing to the clustered, regularly interspaced, short palindromic repeats (CRISPR)-Cas9 revolution of genome editing. In the present review, we give a brief overview of the CRISPR/Cas9 toolbox and different strategies for genome editing currently available. We list the first examples of applications to marine organisms and also draw from studies in more common laboratory models to suggest both guidelines for design of genome editing experiments as well as discuss challenges specific to marine organisms. In addition, we discuss future perspectives, including applications of CRISPR/Cas9 to base editing and targeted reprogramming of gene transcription. Copyright © 2016 Elsevier B.V. All rights reserved.

Concept for a Micro Autonomous Ultrasonic Instrument (MAUI)

NASA Technical Reports Server (NTRS)

Wilson, William C.; Atkinson, Gary M.

2002-01-01

We investigate a concept for the construction a mobile Micro Optical ElectroMechanical Systems (MOEMS) based laser ultrasonic instrument to serve as a Micro Autonomous Ultrasonic Instrument (MAUI). The system will consist of a laser ultrasonic instrument fabricated using Micro Electro-Mechanical Systems (MEMS) technology, and a MEMS based walking platform like those developed by Pister et al. at Berkeley. This small system will allow for automated remote Non-Destructive Evaluation (NDE) of aerospace vehicles.

The Audio-Visual Equipment Directory. Seventeenth Edition.

ERIC Educational Resources Information Center

Herickes, Sally, Ed.

The following types of audiovisual equipment are catalogued: 8 mm. and 16 mm. motion picture projectors, filmstrip and sound filmstrip projectors, slide projectors, random access projection equipment, opaque, overhead, and micro-projectors, record players, special purpose projection equipment, audio tape recorders and players, audio tape…

RNA editing produces glycine receptor alpha3(P185L), resulting in high agonist potency.

PubMed

Meier, Jochen C; Henneberger, Christian; Melnick, Igor; Racca, Claudia; Harvey, Robert J; Heinemann, Uwe; Schmieden, Volker; Grantyn, Rosemarie

2005-06-01

The function of supramedullary glycine receptors (GlyRs) is still unclear. Using Wistar rat collicular slices, we demonstrate GlyR-mediated inhibition of spike discharge elicited by low glycine (10 microM). Searching for the molecular basis of this phenomenon, we identified a new GlyR isoform. GlyR alpha3(P185L), a result of cytidine 554 deamination, confers high glycine sensitivity (EC50 approximately 5 microM) to neurons and thereby promotes the generation of sustained chloride conductances associated with tonic inhibition. The level of GlyR alpha3-C554U RNA editing is sensitive to experimentally induced brain lesion, inhibition of cytidine deamination by zebularine and inhibition of mRNA transcription by actinomycin D, but not to blockade of protein synthesis by cycloheximide. Conditional regulation of GlyR alpha3(P185L) is thus likely to be part of a post-transcriptional adaptive mechanism in neurons with enhanced excitability.

Engineering Delivery Vehicles for Genome Editing.

PubMed

Nelson, Christopher E; Gersbach, Charles A

2016-06-07

The field of genome engineering has created new possibilities for gene therapy, including improved animal models of disease, engineered cell therapies, and in vivo gene repair. The most significant challenge for the clinical translation of genome engineering is the development of safe and effective delivery vehicles. A large body of work has applied genome engineering to genetic modification in vitro, and clinical trials have begun using cells modified by genome editing. Now, promising preclinical work is beginning to apply these tools in vivo. This article summarizes the development of genome engineering platforms, including meganucleases, zinc finger nucleases, TALENs, and CRISPR/Cas9, and their flexibility for precise genetic modifications. The prospects for the development of safe and effective viral and nonviral delivery vehicles for genome editing are reviewed, and promising advances in particular therapeutic applications are discussed.

[Efficient genome editing in human pluripotent stem cells through CRISPR/Cas9].

PubMed

Liu, Gai-gai; Li, Shuang; Wei, Yu-da; Zhang, Yong-xian; Ding, Qiu-rong

2015-11-01

The RNA-guided CRISPR (clustered regularly interspaced short palindromic repeat)-associated Cas9 nuclease has offered a new platform for genome editing with high efficiency. Here, we report the use of CRISPR/Cas9 technology to target a specific genomic region in human pluripotent stem cells. We show that CRISPR/Cas9 can be used to disrupt a gene by introducing frameshift mutations to gene coding region; to knock in specific sequences (e.g. FLAG tag DNA sequence) to targeted genomic locus via homology directed repair; to induce large genomic deletion through dual-guide multiplex. Our results demonstrate the versatile application of CRISPR/Cas9 in stem cell genome editing, which can be widely utilized for functional studies of genes or genome loci in human pluripotent stem cells.

Combinatory RNA-Sequencing Analyses Reveal a Dual Mode of Gene Regulation by ADAR1 in Gastric Cancer.

PubMed

Cho, Charles J; Jung, Jaeeun; Jiang, Lushang; Lee, Eun Ji; Kim, Dae-Soo; Kim, Byung Sik; Kim, Hee Sung; Jung, Hwoon-Yong; Song, Ho-June; Hwang, Sung Wook; Park, Yangsoon; Jung, Min Kyo; Pack, Chan Gi; Myung, Seung-Jae; Chang, Suhwan

2018-04-25

Adenosine deaminase acting on RNA 1 (ADAR1) is known to mediate deamination of adenosine-to-inosine through binding to double-stranded RNA, the phenomenon known as RNA editing. Currently, the function of ADAR1 in gastric cancer is unclear. This study was aimed at investigating RNA editing-dependent and editing-independent functions of ADAR1 in gastric cancer, especially focusing on its influence on editing of 3' untranslated regions (UTRs) and subsequent changes in expression of messenger RNAs (mRNAs) as well as microRNAs (miRNAs). RNA-sequencing and small RNA-sequencing were performed on AGS and MKN-45 cells with a stable ADAR1 knockdown. Changed frequencies of editing and mRNA and miRNA expression were then identified by bioinformatic analyses. Targets of RNA editing were further validated in patients' samples. In the Alu region of both gastric cell lines, editing was most commonly of the A-to-I type in 3'-UTR or intron. mRNA and protein levels of PHACTR4 increased in ADAR1 knockdown cells, because of the loss of seed sequences in 3'-UTR of PHACTR4 mRNA that are required for miRNA-196a-3p binding. Immunohistochemical analyses of tumor and paired normal samples from 16 gastric cancer patients showed that ADAR1 expression was higher in tumors than in normal tissues and inversely correlated with PHACTR4 staining. On the other hand, decreased miRNA-148a-3p expression in ADAR1 knockdown cells led to increased mRNA and protein expression of NFYA, demonstrating ADAR1's editing-independent function. ADAR1 regulates post-transcriptional gene expression in gastric cancer through both RNA editing-dependent and editing-independent mechanisms.

Engineering Feasibility and Trade Studies for the NASA/VSGC MicroMaps Space Mission

NASA Technical Reports Server (NTRS)

Abdelkhalik, Ossama O.; Nairouz, Bassem; Weaver, Timothy; Newman, Brett

2003-01-01

Knowledge of airborne CO concentrations is critical for accurate scientific prediction of global scale atmospheric behavior. MicroMaps is an existing NASA owned gas filter radiometer instrument designed for space-based measurement of atmospheric CO vertical profiles. Due to programmatic changes, the instrument does not have access to the space environment and is in storage. MicroMaps hardware has significant potential for filling a critical scientific need, thus motivating concept studies for new and innovative scientific spaceflight missions that would leverage the MicroMaps heritage and investment, and contribute to new CO distribution data. This report describes engineering feasibility and trade studies for the NASA/VSGC MicroMaps Space Mission. Conceptual studies encompass: 1) overall mission analysis and synthesis methodology, 2) major subsystem studies and detailed requirements development for an orbital platform option consisting of a small, single purpose spacecraft, 3) assessment of orbital platform option consisting of the International Space Station, and 4) survey of potential launch opportunities for gaining assess to orbit. Investigations are of a preliminary first-order nature. Results and recommendations from these activities are envisioned to support future MicroMaps Mission design decisions regarding program down select options leading to more advanced and mature phases.

MicroRNAs and exosomes in depression: Potential diagnostic biomarkers.

PubMed

Tavakolizadeh, Jahanshir; Roshanaei, Kambiz; Salmaninejad, Arash; Yari, Reza; Nahand, Javid Sadri; Sarkarizi, Hoda Khoshdel; Mousavi, Seyed Mojtaba; Salarinia, Reza; Rahmati, Majid; Mousavi, Seyed Farshid; Mokhtari, Ryan; Mirzaei, Hamed

2018-05-01

Depression is known as one of important psychiatric disorders which could be associated with disability among various populations. Diagnostic and statistical manual of mental disorders, 4th edition (DSM-IV) and international statistical classification of diseases and related health problems (ICD-10) could be used as subjective diagnostic schemes for identification of mental disorders such as depression. Utilization of subjective diagnostic schemes are associated with limitations. Hence, it seems that employing of new diagnosis platforms is required. Multiple lines of evidence indicated that measurement of several biomarkers could be useful for detection patients with depression. Among of various types of biomarkers, microRNAs (miRNAs) have been emerged as powerful tools for diagnosis patients with depression. MiRNAs are small non-coding RNAs which act as epigenetic regulators. It has been showed that these molecules have critical roles in pathogenesis of many diseases such as depression. These molecules exert their effects via targeting a variety of cellular and molecular pathways involved in initiation and progression of depression. Hence, miRNAs could be used as diagnostic and therapeutic biomarkers in patients with depression. Besides miRNAs, exosomes as nano- carriers could have been emerged as diagnostic biomarkers in several diseases such as depression. These vesicles are able to carry several cargos such as DNAs, proteins, mRNAs, and miRNAs to recipient cells. Here, we summarized several miRNAs involved in pathogenesis and response to treatment of depression which could be used as diagnostic biomarkers. Moreover, we highlighted exosomes as new diagnostic biomarkers for patients with depression. © 2017 Wiley Periodicals, Inc.

Systematic quantification of HDR and NHEJ reveals effects of locus, nuclease, and cell type on genome-editing.

PubMed

Miyaoka, Yuichiro; Berman, Jennifer R; Cooper, Samantha B; Mayerl, Steven J; Chan, Amanda H; Zhang, Bin; Karlin-Neumann, George A; Conklin, Bruce R

2016-03-31

Precise genome-editing relies on the repair of sequence-specific nuclease-induced DNA nicking or double-strand breaks (DSBs) by homology-directed repair (HDR). However, nonhomologous end-joining (NHEJ), an error-prone repair, acts concurrently, reducing the rate of high-fidelity edits. The identification of genome-editing conditions that favor HDR over NHEJ has been hindered by the lack of a simple method to measure HDR and NHEJ directly and simultaneously at endogenous loci. To overcome this challenge, we developed a novel, rapid, digital PCR-based assay that can simultaneously detect one HDR or NHEJ event out of 1,000 copies of the genome. Using this assay, we systematically monitored genome-editing outcomes of CRISPR-associated protein 9 (Cas9), Cas9 nickases, catalytically dead Cas9 fused to FokI, and transcription activator-like effector nuclease at three disease-associated endogenous gene loci in HEK293T cells, HeLa cells, and human induced pluripotent stem cells. Although it is widely thought that NHEJ generally occurs more often than HDR, we found that more HDR than NHEJ was induced under multiple conditions. Surprisingly, the HDR/NHEJ ratios were highly dependent on gene locus, nuclease platform, and cell type. The new assay system, and our findings based on it, will enable mechanistic studies of genome-editing and help improve genome-editing technology.

Gene editing and clonal isolation of human induced pluripotent stem cells using CRISPR/Cas9.

PubMed

Yumlu, Saniye; Stumm, Jürgen; Bashir, Sanum; Dreyer, Anne-Kathrin; Lisowski, Pawel; Danner, Eric; Kühn, Ralf

2017-05-15

Human induced pluripotent stem cells (hiPSCs) represent an ideal in vitro platform to study human genetics and biology. The recent advent of programmable nucleases makes also the human genome amenable to experimental genetics through either the correction of mutations in patient-derived iPSC lines or the de novo introduction of mutations into otherwise healthy iPSCs. The production of specific and sometimes complex genotypes in multiple cell lines requires efficient and streamlined gene editing technologies. In this article we provide protocols for gene editing in hiPSCs. We presently achieve high rates of gene editing at up to three loci using a modified iCRISPR system. This system includes a doxycycline inducible Cas9 and sgRNA/reporter plasmids for the enrichment of transfected cells by fluorescence-activated cell sorting (FACS). Here we cover the selection of target sites, vector construction, transfection, and isolation and genotyping of modified hiPSC clones. Copyright © 2017 Elsevier Inc. All rights reserved.

Efficient delivery of genome-editing proteins using bioreducible lipid nanoparticles.

PubMed

Wang, Ming; Zuris, John A; Meng, Fantao; Rees, Holly; Sun, Shuo; Deng, Pu; Han, Yong; Gao, Xue; Pouli, Dimitra; Wu, Qi; Georgakoudi, Irene; Liu, David R; Xu, Qiaobing

2016-03-15

A central challenge to the development of protein-based therapeutics is the inefficiency of delivery of protein cargo across the mammalian cell membrane, including escape from endosomes. Here we report that combining bioreducible lipid nanoparticles with negatively supercharged Cre recombinase or anionic Cas9:single-guide (sg)RNA complexes drives the electrostatic assembly of nanoparticles that mediate potent protein delivery and genome editing. These bioreducible lipids efficiently deliver protein cargo into cells, facilitate the escape of protein from endosomes in response to the reductive intracellular environment, and direct protein to its intracellular target sites. The delivery of supercharged Cre protein and Cas9:sgRNA complexed with bioreducible lipids into cultured human cells enables gene recombination and genome editing with efficiencies greater than 70%. In addition, we demonstrate that these lipids are effective for functional protein delivery into mouse brain for gene recombination in vivo. Therefore, the integration of this bioreducible lipid platform with protein engineering has the potential to advance the therapeutic relevance of protein-based genome editing.

Microfluidic in-channel multi-electrode platform for neurotransmitter sensing

NASA Astrophysics Data System (ADS)

Kara, A.; Mathault, J.; Reitz, A.; Boisvert, M.; Tessier, F.; Greener, J.; Miled, A.

2016-03-01

In this project we present a microfluidic platform with in-channel micro-electrodes for in situ screening of bio/chemical samples through a lab-on-chip system. We used a novel method to incorporate electrochemical sensors array (16x20) connected to a PCB, which opens the way for imaging applications. A 200 μm height microfluidic channel was bonded to electrochemical sensors. The micro-channel contains 3 inlets used to introduce phosphate buffer saline (PBS), ferrocynide and neurotransmitters. The flow rate was controlled through automated micro-pumps. A multiplexer was used to scan electrodes and perform individual cyclic voltammograms by a custom potentiostat. The behavior of the system was linear in terms of variation of current versus concentration. It was used to detect the neurotransmitters serotonin, dopamine and glutamate.

High-Throughput Genome Editing and Phenotyping Facilitated by High Resolution Melting Curve Analysis

PubMed Central

Thomas, Holly R.; Percival, Stefanie M.; Yoder, Bradley K.; Parant, John M.

2014-01-01

With the goal to generate and characterize the phenotypes of null alleles in all genes within an organism and the recent advances in custom nucleases, genome editing limitations have moved from mutation generation to mutation detection. We previously demonstrated that High Resolution Melting (HRM) analysis is a rapid and efficient means of genotyping known zebrafish mutants. Here we establish optimized conditions for HRM based detection of novel mutant alleles. Using these conditions, we demonstrate that HRM is highly efficient at mutation detection across multiple genome editing platforms (ZFNs, TALENs, and CRISPRs); we observed nuclease generated HRM positive targeting in 1 of 6 (16%) open pool derived ZFNs, 14 of 23 (60%) TALENs, and 58 of 77 (75%) CRISPR nucleases. Successful targeting, based on HRM of G0 embryos correlates well with successful germline transmission (46 of 47 nucleases); yet, surprisingly mutations in the somatic tail DNA weakly correlate with mutations in the germline F1 progeny DNA. This suggests that analysis of G0 tail DNA is a good indicator of the efficiency of the nuclease, but not necessarily a good indicator of germline alleles that will be present in the F1s. However, we demonstrate that small amplicon HRM curve profiles of F1 progeny DNA can be used to differentiate between specific mutant alleles, facilitating rare allele identification and isolation; and that HRM is a powerful technique for screening possible off-target mutations that may be generated by the nucleases. Our data suggest that micro-homology based alternative NHEJ repair is primarily utilized in the generation of CRISPR mutant alleles and allows us to predict likelihood of generating a null allele. Lastly, we demonstrate that HRM can be used to quickly distinguish genotype-phenotype correlations within F1 embryos derived from G0 intercrosses. Together these data indicate that custom nucleases, in conjunction with the ease and speed of HRM, will facilitate future high-throughput mutation generation and analysis needed to establish mutants in all genes of an organism. PMID:25503746

Micro-Analyzer: automatic preprocessing of Affymetrix microarray data.

PubMed

Guzzi, Pietro Hiram; Cannataro, Mario

2013-08-01

A current trend in genomics is the investigation of the cell mechanism using different technologies, in order to explain the relationship among genes, molecular processes and diseases. For instance, the combined use of gene-expression arrays and genomic arrays has been demonstrated as an effective instrument in clinical practice. Consequently, in a single experiment different kind of microarrays may be used, resulting in the production of different types of binary data (images and textual raw data). The analysis of microarray data requires an initial preprocessing phase, that makes raw data suitable for use on existing analysis platforms, such as the TIGR M4 (TM4) Suite. An additional challenge to be faced by emerging data analysis platforms is the ability to treat in a combined way those different microarray formats coupled with clinical data. In fact, resulting integrated data may include both numerical and symbolic data (e.g. gene expression and SNPs regarding molecular data), as well as temporal data (e.g. the response to a drug, time to progression and survival rate), regarding clinical data. Raw data preprocessing is a crucial step in analysis but is often performed in a manual and error prone way using different software tools. Thus novel, platform independent, and possibly open source tools enabling the semi-automatic preprocessing and annotation of different microarray data are needed. The paper presents Micro-Analyzer (Microarray Analyzer), a cross-platform tool for the automatic normalization, summarization and annotation of Affymetrix gene expression and SNP binary data. It represents the evolution of the μ-CS tool, extending the preprocessing to SNP arrays that were not allowed in μ-CS. The Micro-Analyzer is provided as a Java standalone tool and enables users to read, preprocess and analyse binary microarray data (gene expression and SNPs) by invoking TM4 platform. It avoids: (i) the manual invocation of external tools (e.g. the Affymetrix Power Tools), (ii) the manual loading of preprocessing libraries, and (iii) the management of intermediate files, such as results and metadata. Micro-Analyzer users can directly manage Affymetrix binary data without worrying about locating and invoking the proper preprocessing tools and chip-specific libraries. Moreover, users of the Micro-Analyzer tool can load the preprocessed data directly into the well-known TM4 platform, extending in such a way also the TM4 capabilities. Consequently, Micro Analyzer offers the following advantages: (i) it reduces possible errors in the preprocessing and further analysis phases, e.g. due to the incorrect choice of parameters or due to the use of old libraries, (ii) it enables the combined and centralized pre-processing of different arrays, (iii) it may enhance the quality of further analysis by storing the workflow, i.e. information about the preprocessing steps, and (iv) finally Micro-Analzyer is freely available as a standalone application at the project web site http://sourceforge.net/projects/microanalyzer/. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Microprogramming Handbook. Second Edition.

ERIC Educational Resources Information Center

Microdata Corp., Santa Ana, CA.

Instead of instructions residing in the main memory as in a fixed instruction computer, a micro-programable computer has a separete read-only memory which is alterable so that the system can be efficiently adapted to the application at hand. Microprogramable computers are faster than fixed instruction computers for several reasons: instruction…

Maxi CAI with a Micro.

ERIC Educational Resources Information Center

Gerhold, George; And Others

This paper describes an effective microprocessor-based CAI system which has been repeatedly tested by a large number of students and edited accordingly. Tasks not suitable for microprocessor based systems (authoring, testing, and debugging) were handled on larger multi-terminal systems. This approach requires that the CAI language used on the…

The Role of the Army in Infrastructure and Capacity Building

DTIC Science & Technology

2010-02-01

Issues Volume I: Theory of War and Strategy 3rd edition, ed. J. Boone Bartholomees, Jr. (Carlisle: USAWC Strategic Studies Institute, 2009), 145...efforts. 34 Raj M. Desai and Homi Kharas, Do Philanthropic Citizens Behave Like Governments? Internet-Based Platforms and the Diffusion of International

Converged photonic data storage and switch platform for exascale disaggregated data centers

NASA Astrophysics Data System (ADS)

Pitwon, R.; Wang, K.; Worrall, A.

2017-02-01

We report on a converged optically enabled Ethernet storage, switch and compute platform, which could support future disaggregated data center architectures. The platform includes optically enabled Ethernet switch controllers, an advanced electro-optical midplane and optically interchangeable generic end node devices. We demonstrate system level performance using optically enabled Ethernet disk drives and micro-servers across optical links of varied lengths.

Bioelectronic platforms for optimal bio-anode of bio-electrochemical systems: From nano- to macro scopes.

PubMed

Kim, Bongkyu; An, Junyeong; Fapyane, Deby; Chang, In Seop

2015-11-01

The current trend of bio-electrochemical systems is to improve strategies related to their applicability and potential for scaling-up. To date, literature has suggested strategies, but the proposal of correlations between each research field remains insufficient. This review paper provides a correlation based on platform techniques, referred to as bio-electronics platforms (BEPs). These BEPs consist of three platforms divided by scope scale: nano-, micro-, and macro-BEPs. In the nano-BEP, several types of electron transfer mechanisms used by electrochemically active bacteria are discussed. In the micro-BEP, factors affecting the formation of conductive biofilms and transport of electrons in the conductive biofilm are investigated. In the macro-BEP, electrodes and separators in bio-anode are debated in terms of real applications, and a scale-up strategy is discussed. Overall, the challenges of each BEP are highlighted, and potential solutions are suggested. In addition, future research directions are provided and research ideas proposed to develop research interest. Copyright © 2015 Elsevier Ltd. All rights reserved.

Combining microfluidics, optogenetics and calcium imaging to study neuronal communication in vitro.

PubMed

Renault, Renaud; Sukenik, Nirit; Descroix, Stéphanie; Malaquin, Laurent; Viovy, Jean-Louis; Peyrin, Jean-Michel; Bottani, Samuel; Monceau, Pascal; Moses, Elisha; Vignes, Maéva

2015-01-01

In this paper we report the combination of microfluidics, optogenetics and calcium imaging as a cheap and convenient platform to study synaptic communication between neuronal populations in vitro. We first show that Calcium Orange indicator is compatible in vitro with a commonly used Channelrhodopsine-2 (ChR2) variant, as standard calcium imaging conditions did not alter significantly the activity of transduced cultures of rodent primary neurons. A fast, robust and scalable process for micro-chip fabrication was developed in parallel to build micro-compartmented cultures. Coupling optical fibers to each micro-compartment allowed for the independent control of ChR2 activation in the different populations without crosstalk. By analyzing the post-stimuli activity across the different populations, we finally show how this platform can be used to evaluate quantitatively the effective connectivity between connected neuronal populations.

Millstone: software for multiplex microbial genome analysis and engineering

DOE Office of Scientific and Technical Information (OSTI.GOV)

Goodman, Daniel B.; Kuznetsov, Gleb; Lajoie, Marc J.

Inexpensive DNA sequencing and advances in genome editing have made computational analysis a major rate-limiting step in adaptive laboratory evolution and microbial genome engineering. Here, we describe Millstone, a web-based platform that automates genotype comparison and visualization for projects with up to hundreds of genomic samples. To enable iterative genome engineering, Millstone allows users to design oligonucleotide libraries and create successive versions of reference genomes. Millstone is open source and easily deployable to a cloud platform, local cluster, or desktop, making it a scalable solution for any lab.

Millstone: software for multiplex microbial genome analysis and engineering.

PubMed

Goodman, Daniel B; Kuznetsov, Gleb; Lajoie, Marc J; Ahern, Brian W; Napolitano, Michael G; Chen, Kevin Y; Chen, Changping; Church, George M

2017-05-25

Inexpensive DNA sequencing and advances in genome editing have made computational analysis a major rate-limiting step in adaptive laboratory evolution and microbial genome engineering. We describe Millstone, a web-based platform that automates genotype comparison and visualization for projects with up to hundreds of genomic samples. To enable iterative genome engineering, Millstone allows users to design oligonucleotide libraries and create successive versions of reference genomes. Millstone is open source and easily deployable to a cloud platform, local cluster, or desktop, making it a scalable solution for any lab.

Millstone: software for multiplex microbial genome analysis and engineering

DOE PAGES

Goodman, Daniel B.; Kuznetsov, Gleb; Lajoie, Marc J.; ...

2017-05-25

Inexpensive DNA sequencing and advances in genome editing have made computational analysis a major rate-limiting step in adaptive laboratory evolution and microbial genome engineering. Here, we describe Millstone, a web-based platform that automates genotype comparison and visualization for projects with up to hundreds of genomic samples. To enable iterative genome engineering, Millstone allows users to design oligonucleotide libraries and create successive versions of reference genomes. Millstone is open source and easily deployable to a cloud platform, local cluster, or desktop, making it a scalable solution for any lab.

Smart-Phone Based Magnetic Levitation for Measuring Densities

PubMed Central

Knowlton, Stephanie; Yu, Chu Hsiang; Jain, Nupur

2015-01-01

Magnetic levitation, which uses a magnetic field to suspend objects in a fluid, is a powerful and versatile technology. We develop a compact magnetic levitation platform compatible with a smart-phone to separate micro-objects and estimate the density of the sample based on its levitation height. A 3D printed attachment is mechanically installed over the existing camera unit of a smart-phone. Micro-objects, which may be either spherical or irregular in shape, are suspended in a paramagnetic medium and loaded in a microcapillary tube which is then inserted between two permanent magnets. The micro-objects are levitated and confined in the microcapillary at an equilibrium height dependent on their volumetric mass densities (causing a buoyancy force toward the edge of the microcapillary) and magnetic susceptibilities (causing a magnetic force toward the center of the microcapillary) relative to the suspending medium. The smart-phone camera captures magnified images of the levitating micro-objects through an additional lens positioned between the sample and the camera lens cover. A custom-developed Android application then analyzes these images to determine the levitation height and estimate the density. Using this platform, we were able to separate microspheres with varying densities and calibrate their levitation heights to known densities to develop a technique for precise and accurate density estimation. We have also characterized the magnetic field, the optical imaging capabilities, and the thermal state over time of this platform. PMID:26308615

Tomato TILLING Technology: Development of a Reverse Genetics Tool for the Efficient Isolation of Mutants from Micro-Tom Mutant Libraries

PubMed Central

Okabe, Yoshihiro; Asamizu, Erika; Saito, Takeshi; Matsukura, Chiaki; Ariizumi, Tohru; Brès, Cécile; Rothan, Christophe; Mizoguchi, Tsuyoshi; Ezura, Hiroshi

2011-01-01

To accelerate functional genomic research in tomato, we developed a Micro-Tom TILLING (Targeting Induced Local Lesions In Genomes) platform. DNA pools were constructed from 3,052 ethyl methanesulfonate (EMS) mutant lines treated with 0.5 or 1.0% EMS. The mutation frequency was calculated by screening 10 genes. The 0.5% EMS population had a mild mutation frequency of one mutation per 1,710 kb, whereas the 1.0% EMS population had a frequency of one mutation per 737 kb, a frequency suitable for producing an allelic series of mutations in the target genes. The overall mutation frequency was one mutation per 1,237 kb, which affected an average of three alleles per kilobase screened. To assess whether a Micro-Tom TILLING platform could be used for efficient mutant isolation, six ethylene receptor genes in tomato (SlETR1–SlETR6) were screened. Two allelic mutants of SlETR1 (Sletr1-1 and Sletr1-2) that resulted in reduced ethylene responses were identified, indicating that our Micro-Tom TILLING platform provides a powerful tool for the rapid detection of mutations in an EMS mutant library. This work provides a practical and publicly accessible tool for the study of fruit biology and for obtaining novel genetic material that can be used to improve important agronomic traits in tomato. PMID:21965606

Smart-Phone Based Magnetic Levitation for Measuring Densities.

PubMed

Knowlton, Stephanie; Yu, Chu Hsiang; Jain, Nupur; Ghiran, Ionita Calin; Tasoglu, Savas

2015-01-01

Magnetic levitation, which uses a magnetic field to suspend objects in a fluid, is a powerful and versatile technology. We develop a compact magnetic levitation platform compatible with a smart-phone to separate micro-objects and estimate the density of the sample based on its levitation height. A 3D printed attachment is mechanically installed over the existing camera unit of a smart-phone. Micro-objects, which may be either spherical or irregular in shape, are suspended in a paramagnetic medium and loaded in a microcapillary tube which is then inserted between two permanent magnets. The micro-objects are levitated and confined in the microcapillary at an equilibrium height dependent on their volumetric mass densities (causing a buoyancy force toward the edge of the microcapillary) and magnetic susceptibilities (causing a magnetic force toward the center of the microcapillary) relative to the suspending medium. The smart-phone camera captures magnified images of the levitating micro-objects through an additional lens positioned between the sample and the camera lens cover. A custom-developed Android application then analyzes these images to determine the levitation height and estimate the density. Using this platform, we were able to separate microspheres with varying densities and calibrate their levitation heights to known densities to develop a technique for precise and accurate density estimation. We have also characterized the magnetic field, the optical imaging capabilities, and the thermal state over time of this platform.

Tomato TILLING technology: development of a reverse genetics tool for the efficient isolation of mutants from Micro-Tom mutant libraries.

PubMed

Okabe, Yoshihiro; Asamizu, Erika; Saito, Takeshi; Matsukura, Chiaki; Ariizumi, Tohru; Brès, Cécile; Rothan, Christophe; Mizoguchi, Tsuyoshi; Ezura, Hiroshi

2011-11-01

To accelerate functional genomic research in tomato, we developed a Micro-Tom TILLING (Targeting Induced Local Lesions In Genomes) platform. DNA pools were constructed from 3,052 ethyl methanesulfonate (EMS) mutant lines treated with 0.5 or 1.0% EMS. The mutation frequency was calculated by screening 10 genes. The 0.5% EMS population had a mild mutation frequency of one mutation per 1,710 kb, whereas the 1.0% EMS population had a frequency of one mutation per 737 kb, a frequency suitable for producing an allelic series of mutations in the target genes. The overall mutation frequency was one mutation per 1,237 kb, which affected an average of three alleles per kilobase screened. To assess whether a Micro-Tom TILLING platform could be used for efficient mutant isolation, six ethylene receptor genes in tomato (SlETR1-SlETR6) were screened. Two allelic mutants of SlETR1 (Sletr1-1 and Sletr1-2) that resulted in reduced ethylene responses were identified, indicating that our Micro-Tom TILLING platform provides a powerful tool for the rapid detection of mutations in an EMS mutant library. This work provides a practical and publicly accessible tool for the study of fruit biology and for obtaining novel genetic material that can be used to improve important agronomic traits in tomato.

Multi-angle lensless digital holography for depth resolved imaging on a chip.

PubMed

Su, Ting-Wei; Isikman, Serhan O; Bishara, Waheb; Tseng, Derek; Erlinger, Anthony; Ozcan, Aydogan

2010-04-26

A multi-angle lensfree holographic imaging platform that can accurately characterize both the axial and lateral positions of cells located within multi-layered micro-channels is introduced. In this platform, lensfree digital holograms of the micro-objects on the chip are recorded at different illumination angles using partially coherent illumination. These digital holograms start to shift laterally on the sensor plane as the illumination angle of the source is tilted. Since the exact amount of this lateral shift of each object hologram can be calculated with an accuracy that beats the diffraction limit of light, the height of each cell from the substrate can be determined over a large field of view without the use of any lenses. We demonstrate the proof of concept of this multi-angle lensless imaging platform by using light emitting diodes to characterize various sized microparticles located on a chip with sub-micron axial and lateral localization over approximately 60 mm(2) field of view. Furthermore, we successfully apply this lensless imaging approach to simultaneously characterize blood samples located at multi-layered micro-channels in terms of the counts, individual thicknesses and the volumes of the cells at each layer. Because this platform does not require any lenses, lasers or other bulky optical/mechanical components, it provides a compact and high-throughput alternative to conventional approaches for cytometry and diagnostics applications involving lab on a chip systems.

Collaborative Wikipedia Projects in the Virtual Classroom

ERIC Educational Resources Information Center

Kenny, A. J.; Wolt, J. D.; Hurd, H. S.

2013-01-01

Wikipedia is a web-based, free-content encyclopedia that is openly editable and, thus, provides a unique platform for collaborations. Wikipedia projects are increasingly being integrated into upper-level courses across the country to explore advanced concepts, communicate science, and provide high-quality information to the public. Here we outline…

CRISPR/Cas9-mediated noncoding RNA editing in human cancers.

PubMed

Yang, Jie; Meng, Xiaodan; Pan, Jinchang; Jiang, Nan; Zhou, Chengwei; Wu, Zhenhua; Gong, Zhaohui

2018-01-02

Cancer is characterized by multiple genetic and epigenetic alterations, including a higher prevalence of mutations of oncogenes and/or tumor suppressors. Mounting evidences have shown that noncoding RNAs (ncRNAs) are involved in the epigenetic regulation of cancer genes and their associated pathways. The clustered regularly interspaced short palindromic repeats (CRISPR)-associated nuclease 9 (CRISPR/Cas9) system, a revolutionary genome-editing technology, has shed light on ncRNA-based cancer therapy. Here, we briefly introduce the classifications and mechanisms of CRISPR/Cas9 system. Importantly, we mainly focused on the applications of CRISPR/Cas9 system as a molecular tool for ncRNA (microRNA, long noncoding RNA and circular RNA, etc.) editing in human cancers, and the novel techniques that are based on CRISPR/Cas9 system. Additionally, the off-target effects and the corresponding solutions as well as the challenges toward CRISPR/Cas9 were also evaluated and discussed. Long- and short-ncRNAs have been employed as targets in precision oncology, and CRISPR/Cas9-mediated ncRNA editing may provide an excellent way to cure cancer.

Contactless and non-invasive delivery of micro-particles lying on a non-customized rigid surface by using acoustic radiation force.

PubMed

Meng, Jianxin; Mei, Deqing; Jia, Kun; Fan, Zongwei; Yang, Keji

2014-07-01

In the existing acoustic micro-particle delivery methods, the micro-particles always lie and slide on the surface of platform in the whole delivery process. To avoid the damage and contamination of micro-particles caused by the sliding motion, this paper deals with a novel approach to trap micro-particles from non-customized rigid surfaces and freely manipulate them. The delivery process contains three procedures: detaching, transporting, and landing. Hence, the micro-particles no longer lie on the surface, but are levitated in the fluid, during the long range transporting procedure. It is very meaningful especially for the fragile and easily contaminated targets. To quantitatively analyze the delivery process, a theoretical model to calculate the acoustic radiation force exerting upon a micro-particle near the boundary in half space is built. An experimental device is also developed to validate the delivery method. A 100 μm diameter micro-silica bead adopted as the delivery target is detached from the upper surface of an aluminum platform and levitated in the fluid. Then, it is transported along the designated path with high precision in horizontal plane. The maximum deviation is only about 3.3 μm. During the horizontal transportation, the levitation of the micro-silica bead is stable, the maximum fluctuation is less than 1 μm. The proposed method may extend the application of acoustic radiation force and provide a promising tool for microstructure or cell manipulation. Copyright © 2014 Elsevier B.V. All rights reserved.

Small indels induced by CRISPR/Cas9 in the 5' region of microRNA lead to its depletion and Drosha processing retardance.

PubMed

Jiang, Qian; Meng, Xing; Meng, Lingwei; Chang, Nannan; Xiong, Jingwei; Cao, Huiqing; Liang, Zicai

2014-01-01

MicroRNA knockout by genome editing technologies is promising. In order to extend the application of the technology and to investigate the function of a specific miRNA, we used CRISPR/Cas9 to deplete human miR-93 from a cluster by targeting its 5' region in HeLa cells. Various small indels were induced in the targeted region containing the Drosha processing site and seed sequences. Interestingly, we found that even a single nucleotide deletion led to complete knockout of the target miRNA with high specificity. Functional knockout was confirmed by phenotype analysis. Furthermore, de novo microRNAs were not found by RNA-seq. Nevertheless, expression of the pri-microRNAs was increased. When combined with structural analysis, the data indicated that biogenesis was impaired. Altogether, we showed that small indels in the 5' region of a microRNA result in sequence depletion as well as Drosha processing retard.

Library Micro-Computing, Vol. 2. Reprints from the Best of "ONLINE" [and]"DATABASE."

ERIC Educational Resources Information Center

Online, Inc., Weston, CT.

Reprints of 19 articles pertaining to library microcomputing appear in this collection, the second of two volumes on this topic in a series of volumes of reprints from "ONLINE" and "DATABASE" magazines. Edited for information professionals who use electronically distributed databases, these articles address such topics as: (1)…

Micro-Scale Flapping Wings for the Advancement of Flying MEMS

DTIC Science & Technology

2009-03-01

section. As air strikes the airfoil, it is divided over and under the wing. The airfoil is curved in a manner such that the air passing over the wing moves...This table briefly describes the L-edit layout of Figure A.1. MUMPS Run 82 Micromirrors Mirrors fabricated to EENG 636 specifications Thermal

Proven and novel strategies for efficient editing of the human genome.

PubMed

Mussolino, Claudio; Mlambo, Tafadzwa; Cathomen, Toni

2015-10-01

Targeted gene editing with designer nucleases has become increasingly popular. The most commonly used designer nuclease platforms are engineered meganucleases, zinc-finger nucleases, transcription activator-like effector nucleases and the clustered regularly interspaced short palindromic repeat/Cas9 system. These powerful tools have greatly facilitated the generation of plant and animal models for basic research, and harbor an enormous potential for applications in biotechnology and gene therapy. This review recapitulates proven concepts of targeted genome engineering in primary human cells and elaborates on novel concepts that became possible with the dawn of RNA-guided nucleases and RNA-guided transcription factors. Copyright © 2015 Elsevier Ltd. All rights reserved.

High-Throughput Mechanobiology Screening Platform Using Micro- and Nanotopography.

PubMed

Hu, Junqiang; Gondarenko, Alexander A; Dang, Alex P; Bashour, Keenan T; O'Connor, Roddy S; Lee, Sunwoo; Liapis, Anastasia; Ghassemi, Saba; Milone, Michael C; Sheetz, Michael P; Dustin, Michael L; Kam, Lance C; Hone, James C

2016-04-13

We herein demonstrate the first 96-well plate platform to screen effects of micro- and nanotopographies on cell growth and proliferation. Existing high-throughput platforms test a limited number of factors and are not fully compatible with multiple types of testing and assays. This platform is compatible with high-throughput liquid handling, high-resolution imaging, and all multiwell plate-based instrumentation. We use the platform to screen for topographies and drug-topography combinations that have short- and long-term effects on T cell activation and proliferation. We coated nanofabricated "trench-grid" surfaces with anti-CD3 and anti-CD28 antibodies to activate T cells and assayed for interleukin 2 (IL-2) cytokine production. IL-2 secretion was enhanced at 200 nm trench width and >2.3 μm grating pitch; however, the secretion was suppressed at 100 nm width and <0.5 μm pitch. The enhancement on 200 nm grid trench was further amplified with the addition of blebbistatin to reduce contractility. The 200 nm grid pattern was found to triple the number of T cells in long-term expansion, a result with direct clinical applicability in adoptive immunotherapy.

CRISPR/Cas9 Based Genome Editing of Penicillium chrysogenum.

PubMed

Pohl, C; Kiel, J A K W; Driessen, A J M; Bovenberg, R A L; Nygård, Y

2016-07-15

CRISPR/Cas9 based systems have emerged as versatile platforms for precision genome editing in a wide range of organisms. Here we have developed powerful CRISPR/Cas9 tools for marker-based and marker-free genome modifications in Penicillium chrysogenum, a model filamentous fungus and industrially relevant cell factory. The developed CRISPR/Cas9 toolbox is highly flexible and allows editing of new targets with minimal cloning efforts. The Cas9 protein and the sgRNA can be either delivered during transformation, as preassembled CRISPR-Cas9 ribonucleoproteins (RNPs) or expressed from an AMA1 based plasmid within the cell. The direct delivery of the Cas9 protein with in vitro synthesized sgRNA to the cells allows for a transient method for genome engineering that may rapidly be applicable for other filamentous fungi. The expression of Cas9 from an AMA1 based vector was shown to be highly efficient for marker-free gene deletions.

The ontology life cycle: Integrated tools for editing, publishing, peer review, and evolution of ontologies

PubMed Central

Noy, Natalya; Tudorache, Tania; Nyulas, Csongor; Musen, Mark

2010-01-01

Ontologies have become a critical component of many applications in biomedical informatics. However, the landscape of the ontology tools today is largely fragmented, with independent tools for ontology editing, publishing, and peer review: users develop an ontology in an ontology editor, such as Protégé; and publish it on a Web server or in an ontology library, such as BioPortal, in order to share it with the community; they use the tools provided by the library or mailing lists and bug trackers to collect feedback from users. In this paper, we present a set of tools that bring the ontology editing and publishing closer together, in an integrated platform for the entire ontology lifecycle. This integration streamlines the workflow for collaborative development and increases integration between the ontologies themselves through the reuse of terms. PMID:21347039

Development and Potential Applications of CRISPR-Cas9 Genome Editing Technology in Sarcoma

PubMed Central

Liu, Tang; Shen, Jacson K.; Li, Zhihong; Choy, Edwin; Hornicek, Francis J.; Duan, Zhenfeng

2016-01-01

Sarcomas include some of the most aggressive tumors and typically respond poorly to chemotherapy. In recent years, specific gene fusion/mutations and gene over-expression/activation have been shown to drive sarcoma pathogenesis and development. These emerging genomic alterations may provide targets for novel therapeutic strategies and have the potential to transform sarcoma patient care. The RNA-guided nuclease CRISPR-Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-associated protein-9 nuclease) is a convenient and versatile platform for site-specific genome editing and epigenome targeted modulation. Given that sarcoma is believed to develop as a result of genetic alterations in mesenchymal progenitor/stem cells, CRISPR-Cas9 genome editing technologies hold extensive application potentials in sarcoma models and therapies. We review the development and mechanisms of the CRISPR-Cas9 system in genome editing and introduce its application in sarcoma research and potential therapy in clinic. Additionally, we propose future directions and discuss the challenges faced with these applications, providing concise and enlightening information for readers interested in this area. PMID:26806808

Development and potential applications of CRISPR-Cas9 genome editing technology in sarcoma.

PubMed

Liu, Tang; Shen, Jacson K; Li, Zhihong; Choy, Edwin; Hornicek, Francis J; Duan, Zhenfeng

2016-04-01

Sarcomas include some of the most aggressive tumors and typically respond poorly to chemotherapy. In recent years, specific gene fusion/mutations and gene over-expression/activation have been shown to drive sarcoma pathogenesis and development. These emerging genomic alterations may provide targets for novel therapeutic strategies and have the potential to transform sarcoma patient care. The RNA-guided nuclease CRISPR-Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-associated protein-9 nuclease) is a convenient and versatile platform for site-specific genome editing and epigenome targeted modulation. Given that sarcoma is believed to develop as a result of genetic alterations in mesenchymal progenitor/stem cells, CRISPR-Cas9 genome editing technologies hold extensive application potentials in sarcoma models and therapies. We review the development and mechanisms of the CRISPR-Cas9 system in genome editing and introduce its application in sarcoma research and potential therapy in clinic. Additionally, we propose future directions and discuss the challenges faced with these applications, providing concise and enlightening information for readers interested in this area. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

OpenStreetMap Collaborative Prototype, Phase 1

USGS Publications Warehouse

Wolf, Eric B.; Matthews, Greg D.; McNinch, Kevin; Poore, Barbara S.

2011-01-01

Phase One of the OpenStreetMap Collaborative Prototype (OSMCP) attempts to determine if the open source software developed for the OpenStreetMap (OSM, http://www.openstreetmap.org) can be used for data contributions and improvements that meet or exceed the requirements for integration into The National Map (http://www.nationalmap.gov). OpenStreetMap Collaborative Prototype Phase One focused on road data aggregated at the state level by the Kansas Data Access and Support Center (DASC). Road data from the DASC were loaded into a system hosted by the U.S. Geological Survey (USGS) National Geospatial Technical Operations Center (NGTOC) in Rolla, Missouri. U.S. Geological Survey editing specifications were developed by NGTOC personnel (J. Walters and G. Matthews, USGS, unpub. report, 2010). Interstate and U.S. Highways in the dataset were edited to the specifications by NGTOC personnel while State roads were edited by DASC personnel. Resulting data were successfully improved to meet standards for The National Map once the system and specifications were in place. The OSM software proved effective in providing a usable platform for collaborative data editing

Acceleration levels on board the Space Station and a tethered elevator for micro and variable-gravity applications

NASA Technical Reports Server (NTRS)

Lorenzini, E. C.; Cosmo, M.; Vetrella, S.; Moccia, A.

1988-01-01

This paper investigates the dynamics and acceleration levels of a new tethered system for micro and variable-gravity applications. The system consists of two platforms tethered on opposite sides to the Space Station. A fourth platform, the elevator, is placed in between the Space Station and the upper platform. Variable-g levels on board the elevator are obtained by moving this facility along the upper tether, while micro-g experiments are carried out on board the Space Station. By controlling the length of the lower tether the position of the system CM can be maintained on board the Space Station despite variations of the station's distribution of mass. The paper illustrates the mathematical model, the environmental perturbations and the control techniques which have been adopted for the simulation and control of the system dynamics. Two sets of results from two different simulation runs are shown. The first set shows the system dynamics and the acceleration spectra on board the Space Station and the elevator during station-keeping. The second set of results demonstrates the capability of the elevator to attain a preselected g-level.

A novel microRNA assay with optical detection and enzyme-free DNA circuits

NASA Astrophysics Data System (ADS)

Liao, Yuhui; Zhou, Xiaoming

2014-09-01

MicroRNAs (miRNAs) participate in the significant processes of life course, can be used as quantificational biomarkers for cellular level researches and related diseases. Conventional methods of miRNAs' quantitative detection are obsessed with low sensitivity, time and labour consuming. Otherwise, the emerging miRNAs detection approaches are mostly exposed to the expensive equipment demands and the professional operation, remains at the stage of laboratory and concept demonstration phase. Herein, we designed a novel miRNAs detection platform that based on enzyme-free DNA circuits and electrochemical luminescence (ECL). MicroRNA21 was chosen as the ideal analyte of this platform. The whole process consists of enzyme-free DNA circuits and ECL signal giving-out steps, achieves advantages of operating in constant temperature condition, without the participation of the enzyme, preferable sensitivity and specificity. Through this approach, the sensitivity achieved at 10pM. It is indicated that this miRNAs detection platform possesses potentials to be an innovation of miRNA detection technologies in routine tests. Benefits of the high penetration of ECL in well-equipped medical establishment, this approach could greatly lessen the obstacles in process of popularization and possess excellent prospects of practical application.

Detection of human microRNAs across miRNA Array and Next Generation DNA Sequencing Platforms

EPA Science Inventory

microRNA (miRNAs) are non-coding RNA molecules between 19 and 30 nucleotides in length that are believed to regulate approximately 30 per cent of all human genes. They act as negative regulators of their gene targets in many biological processes. Recent developments in microar...

Creating Micro-Videos to Demonstrate Technology Learning

ERIC Educational Resources Information Center

Frydenberg, Mark; Andone, Diana

2016-01-01

Short videos, also known as micro-videos, have emerged as a platform for sharing ideas, experiences, and life events on online social networks. This paper shares preliminary results of a study involving students from two universities who created six-second videos using the Vine mobile app to explain or illustrate technology concepts. An analysis…

CRISPR-Cas9 Targeting of PCSK9 in Human Hepatocytes In Vivo-Brief Report.

PubMed

Wang, Xiao; Raghavan, Avanthi; Chen, Tao; Qiao, Lyon; Zhang, Yongxian; Ding, Qiurong; Musunuru, Kiran

2016-05-01

Although early proof-of-concept studies of somatic in vivo genome editing of the mouse ortholog of proprotein convertase subtilisin/kexin type 9 (Pcsk9) in mice have established its therapeutic potential for the prevention of cardiovascular disease, the unique nature of genome-editing technology-permanent alteration of genomic DNA sequences-mandates that it be tested in vivo against human genes in normal human cells with human genomes to give reliable preclinical insights into the efficacy (on-target mutagenesis) and safety (lack of off-target mutagenesis) of genome-editing therapy before it can be used in patients. We used a clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated (Cas) 9 genome-editing system to target the human PCSK9 gene in chimeric liver-humanized mice bearing human hepatocytes. We demonstrated high on-target mutagenesis (approaching 50%), greatly reduced blood levels of human PCSK9 protein, and minimal off-target mutagenesis. This work yields important information on the efficacy and safety of CRISPR-Cas9 therapy targeting the human PCSK9 gene in human hepatocytes in vivo, and it establishes humanized mice as a useful platform for the preclinical assessment of applications of somatic in vivo genome editing. © 2016 American Heart Association, Inc.

CRISPR editing in biological and biomedical investigation.

PubMed

Huang, Jiaojiao; Wang, Yanfang; Zhao, Jianguo

2018-05-01

Recently, clustered regularly interspaced short palindromic repeats (CRISPR) based genomic editing technologies have armed researchers with powerful new tools to biological and biomedical investigations. To further improve and expand its functionality, natural, and engineered CRISPR associated nine proteins (Cas9s) have been investigated, various CRISPR delivery strategies have been tested and optimized, and multiple schemes have been developed to ensure precise mammalian genome editing. Benefiting from those in-depth understanding and further development of CRISPR, versatile CRISPR-based platforms for genome editing have been rapidly developed to advance investigations in biology and biomedicine. In biological research area, CRISPR has been widely adopted in both fundamental and applied research fields, such as accurate base editing, transcriptional regulation, and genome-wide screening. In biomedical research area, CRISPR has also shown its extensive applicability in the establishment of animal models for genetic disorders especially those large animals and non-human primates models, and gene therapy to combat virus infectious diseases, to correct monogenic disorders in vivo or in pluripotent cells. In this prospect article, after highlighting recent developments of CRISPR systems, we outline different applications and current limitations of CRISPR use in biological and biomedical investigation. Finally, we provide a perspective for future development and potential risks of this multifunctional technology. © 2017 Wiley Periodicals, Inc.

Fuel Testing for Sylvatex: Cooperative Research and Development Final Report, CRADA Number CRD-16-636

DOE Office of Scientific and Technical Information (OSTI.GOV)

Burton, Jonathan L.

Sylvatex is a green nano-chemistry company that has developed a platform technology utilizing renewable, non-toxic inputs to create a stable nanoparticle that can be used in multiple applications. Their mission is to increase the use of renewables globally, to empower a cleaner and healthier future. The main application is a fuel technology product - MicroX - that utilizes proprietary knowledge to scale low-cost, cleaner-burning renewable diesel fuel and additives by using a co-location commercial model. The aspects of this project will include testing of two Sylvatex MicroX fuels on an engine dynamometer platform. Industry standard ultra-low sulfur diesel (ULSD) B3more » fuel and a ULSD B20 will both be used for comparison of the Sylvatex fuels (U.S. standard diesel fuel at the pump contains an average of approximately 3% biodiesel; this is why B3 would be used as a baseline comparison). Sylvatex is currently using a prototype formulation (MicroX 1) that applies a high cost surfactant. An experimental formulation (MicroX 2) that uses lower cost materials is under development. The MicroX 1 will be blended at a 10% level into the B3 ULSD fuel and the MicroX 2 will be blended at a 10% level into both the B3 and the B20 ULSD fuels for study on the engine dynamometer test platform. All fuel blends will be tested over the FTP transient engine test cycle and a steady state ramped modal engine test cycle. Each test cycle will be performed a minimum of 3 times for each fuel. Tailpipe and/or engine out gaseous exhaust emissions (CO2, CO, NOx, THC, O2,), engine out PM emissions, and brake-specific fuel consumption rates will be evaluated for all test cycles.« less

Computer Aided Drafting Packages for Secondary Education. Edition 2. PC DOS Compatible Programs. A MicroSIFT Quarterly Report.

ERIC Educational Resources Information Center

Pollard, Jim

This report reviews eight IBM-compatible software packages that are available to secondary schools to teach computer-aided drafting (CAD). Software packages to be considered were selected following reviews of CAD periodicals, computers in education periodicals, advertisements, and recommendations of teachers. The packages were then rated by…

Computer Aided Drafting Packages for Secondary Education. Edition 1. Apple II and Macintosh. A MicroSIFT Quarterly Report.

ERIC Educational Resources Information Center

Pollard, Jim

This report reviews software packages for Apple Macintosh and Apple II computers available to secondary schools to teach computer-aided drafting (CAD). Products for the report were gathered through reviews of CAD periodicals, computers in education periodicals, advertisements, and teacher recommendations. The first section lists the primary…

Library Micro-Computing, Vol. 1. Reprints from the Best of "ONLINE" [and]"DATABASE."

ERIC Educational Resources Information Center

Online, Inc., Weston, CT.

Reprints of 18 articles pertaining to library microcomputing appear in this collection, the first of two volumes on this topic in a series of volumes of reprints from "ONLINE" and "DATABASE" magazines. Edited for information professionals who use electronically distributed databases, these articles address such topics as: (1) an integrated library…

CRISPR/Cas9-mediated genome editing of Epstein-Barr virus in human cells.

PubMed

Yuen, Kit-San; Chan, Chi-Ping; Wong, Nok-Hei Mickey; Ho, Chau-Ha; Ho, Ting-Hin; Lei, Ting; Deng, Wen; Tsao, Sai Wah; Chen, Honglin; Kok, Kin-Hang; Jin, Dong-Yan

2015-03-01

The CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 (CRISPR-associated 9) system is a highly efficient and powerful tool for RNA-guided editing of the cellular genome. Whether CRISPR/Cas9 can also cleave the genome of DNA viruses such as Epstein-Barr virus (EBV), which undergo episomal replication in human cells, remains to be established. Here, we reported on CRISPR/Cas9-mediated editing of the EBV genome in human cells. Two guide RNAs (gRNAs) were used to direct a targeted deletion of 558 bp in the promoter region of BART (BamHI A rightward transcript) which encodes viral microRNAs (miRNAs). Targeted editing was achieved in several human epithelial cell lines latently infected with EBV, including nasopharyngeal carcinoma C666-1 cells. CRISPR/Cas9-mediated editing of the EBV genome was efficient. A recombinant virus with the desired deletion was obtained after puromycin selection of cells expressing Cas9 and gRNAs. No off-target cleavage was found by deep sequencing. The loss of BART miRNA expression and activity was verified, supporting the BART promoter as the major promoter of BART RNA. Although CRISPR/Cas9-mediated editing of the multicopy episome of EBV in infected HEK293 cells was mostly incomplete, viruses could be recovered and introduced into other cells at low m.o.i. Recombinant viruses with an edited genome could be further isolated through single-cell sorting. Finally, a DsRed selectable marker was successfully introduced into the EBV genome during the course of CRISPR/Cas9-mediated editing. Taken together, our work provided not only the first genetic evidence that the BART promoter drives the expression of the BART transcript, but also a new and efficient method for targeted editing of EBV genome in human cells. © 2015 The Authors.

The silicon chip: A versatile micro-scale platform for micro- and nano-scale systems

NASA Astrophysics Data System (ADS)

Choi, Edward

Cutting-edge advances in micro- and nano-scale technology require instrumentation to interface with the external world. While technology feature sizes are continually being reduced, the size of experimentalists and their instrumentation do not mirror this trend. Hence there is a need for effective application-specific instrumentation to bridge the gap from the micro and nano-scale phenomena being studied to the comparative macro-scale of the human interfaces. This dissertation puts forward the idea that the silicon CMOS integrated circuit, or microchip in short, serves as an excellent platform to perform this functionality. The electronic interfaces designed for the semiconductor industry are particularly attractive as development platforms, and the reduction in feature sizes that has been a hallmark of the industry suggests that chip-scale instrumentation may be more closely coupled to the phenomena of interest, allowing finer control or improved measurement capabilities. Compatibility with commercial processes will further enable economies of scale through mass production, another welcome feature of this approach. Thus chip-scale instrumentation may replace the bulky, expensive, cumbersome-to-operate macro-scale prototypes currently in use for many of these applications. The dissertation examines four specific applications in which the chip may serve as the ideal instrumentation platform. These are nanorod manipulation, polypyrrole bilayer hinge microactuator control, organic transistor hybrid circuits, and contact fluorescence imaging. The thesis is structured around chapters devoted to each of these projects, in addition to a chapter on preliminary work on an RFID system that serves as a wireless interface model. Each of these chapters contains tools and techniques developed for chip-scale instrumentation, from custom scripts for automated layout and data collection to microfabrication processes. Implementation of these tools to develop systems for the applications above is evaluated. The viability of this approach is not limited to the examples listed in this work, and innovative new methodologies beyond those included here may be developed in the future for other systems which would benefit from the versatility of chip-scale platforms.

Military display market: third comprehensive edition

NASA Astrophysics Data System (ADS)

Desjardins, Daniel D.; Hopper, Darrel G.

2002-08-01

Defense displays comprise a niche market whose continually high performance requirements drive technology. The military displays market is being characterized to ascertain opportunities for synergy across platforms, and needs for new technology. All weapons systems are included. Some 382,585 displays are either now in use or planned in DoD weapon systems over the next 15 years, comprising displays designed into direct-view, projection-view, and virtual- image-view applications. This defense niche market is further fractured into 1163 micro-niche markets by the some 403 program offices who make decisions independently of one another. By comparison, a consumer electronics product has volumes of tens-of-millions of units for a single fixed design. Some 81% of defense displays are ruggedized versions of consumer-market driven designs. Some 19% of defense displays, especially in avionics cockpits and combat crewstations, are custom designs to gain the additional performance available in the technology base but not available in consumer-market-driven designs. Defense display sizes range from 13.6 to 4543 mm. More than half of defense displays are now based on some form of flat panel display technology, especially thin-film-transistor active matrix liquid crystal display (TFT AMLCD); the cathode ray tube (CRT) is still widely used but continuing to drop rapidly in defense market share.

Self-assembly micro optical filter

NASA Astrophysics Data System (ADS)

Zhang, Ping (Cerina); Le, Kevin; Malalur-Nagaraja-Rao, Smitha; Hsu, Lun-Chen; Chiao, J.-C.

2006-01-01

Optical communication and sensor industry face critical challenges in manufacturing for system integration. Due to the assembly complexity and integration platform variety, micro optical components require costly alignment and assembly procedures, in which many required manual efforts. Consequently, self-assembly device architectures have become a great interest and could provide major advantages over the conventional optical devices. In this paper, we discussed a self-assembly integration platform for micro optical components. To demonstrate the adaptability and flexibility of the proposed optical device architectures, we chose a commercially available MEMS fabrication foundry service - MUMPs (Multi-User MEMS Process). In this work, polysilicon layers of MUMPS are used as the 3-D structural material for construction of micro component framework and actuators. However, because the polysilicon has high absorption in the visible and near infrared wavelength ranges, it is not suitable for optical interaction. To demonstrate the required optical performance, hybrid integration of materials was proposed and implemented. Organic compound materials were applied on the silicon-based framework to form the required optical interfaces. Organic compounds provide good optical transparency, flexibility to form filters or lens and inexpensive manufacturing procedures. In this paper, we have demonstrated a micro optical filter integrated with self-assembly structures. We will discuss the self-assembly mechanism, optical filter designs, fabrication issues and results.

A LabVIEW Platform for Preclinical Imaging Using Digital Subtraction Angiography and Micro-CT.

PubMed

Badea, Cristian T; Hedlund, Laurence W; Johnson, G Allan

2013-01-01

CT and digital subtraction angiography (DSA) are ubiquitous in the clinic. Their preclinical equivalents are valuable imaging methods for studying disease models and treatment. We have developed a dual source/detector X-ray imaging system that we have used for both micro-CT and DSA studies in rodents. The control of such a complex imaging system requires substantial software development for which we use the graphical language LabVIEW (National Instruments, Austin, TX, USA). This paper focuses on a LabVIEW platform that we have developed to enable anatomical and functional imaging with micro-CT and DSA. Our LabVIEW applications integrate and control all the elements of our system including a dual source/detector X-ray system, a mechanical ventilator, a physiological monitor, and a power microinjector for the vascular delivery of X-ray contrast agents. Various applications allow cardiac- and respiratory-gated acquisitions for both DSA and micro-CT studies. Our results illustrate the application of DSA for cardiopulmonary studies and vascular imaging of the liver and coronary arteries. We also show how DSA can be used for functional imaging of the kidney. Finally, the power of 4D micro-CT imaging using both prospective and retrospective gating is shown for cardiac imaging.

A LabVIEW Platform for Preclinical Imaging Using Digital Subtraction Angiography and Micro-CT

PubMed Central

Badea, Cristian T.; Hedlund, Laurence W.; Johnson, G. Allan

2013-01-01

CT and digital subtraction angiography (DSA) are ubiquitous in the clinic. Their preclinical equivalents are valuable imaging methods for studying disease models and treatment. We have developed a dual source/detector X-ray imaging system that we have used for both micro-CT and DSA studies in rodents. The control of such a complex imaging system requires substantial software development for which we use the graphical language LabVIEW (National Instruments, Austin, TX, USA). This paper focuses on a LabVIEW platform that we have developed to enable anatomical and functional imaging with micro-CT and DSA. Our LabVIEW applications integrate and control all the elements of our system including a dual source/detector X-ray system, a mechanical ventilator, a physiological monitor, and a power microinjector for the vascular delivery of X-ray contrast agents. Various applications allow cardiac- and respiratory-gated acquisitions for both DSA and micro-CT studies. Our results illustrate the application of DSA for cardiopulmonary studies and vascular imaging of the liver and coronary arteries. We also show how DSA can be used for functional imaging of the kidney. Finally, the power of 4D micro-CT imaging using both prospective and retrospective gating is shown for cardiac imaging. PMID:27006920

Stem cell secretome-rich nanoclay hydrogel: a dual action therapy for cardiovascular regeneration

NASA Astrophysics Data System (ADS)

Waters, Renae; Pacelli, Settimio; Maloney, Ryan; Medhi, Indrani; Ahmed, Rafeeq P. H.; Paul, Arghya

2016-03-01

A nanocomposite hydrogel with photocrosslinkable micro-porous networks and a nanoclay component was successfully prepared to control the release of growth factor-rich stem cell secretome. The proven pro-angiogenic and cardioprotective potential of this new bioactive system provides a valuable therapeutic platform for cardiac tissue repair and regeneration.A nanocomposite hydrogel with photocrosslinkable micro-porous networks and a nanoclay component was successfully prepared to control the release of growth factor-rich stem cell secretome. The proven pro-angiogenic and cardioprotective potential of this new bioactive system provides a valuable therapeutic platform for cardiac tissue repair and regeneration. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr07806g

Murine pluripotent stem cells derived scaffold-free cartilage grafts from a micro-cavitary hydrogel platform.

PubMed

He, Pengfei; Fu, Jiayin; Wang, Dong-An

2016-04-15

By means of appropriate cell type and scaffold, tissue-engineering approaches aim to construct grafts for cartilage repair. Pluripotent stem cells especially induced pluripotent stem cells (iPSCs) are of promising cell candidates due to the pluripotent plasticity and abundant cell source. We explored three dimensional (3D) culture and chondrogenesis of murine iPSCs (miPSCs) on an alginate-based micro-cavity hydrogel (MCG) platform in pursuit of fabricating synthetic-scaffold-free cartilage grafts. Murine embryonic stem cells (mESCs) were employed in parallel as the control. Chondrogenesis was fulfilled using a consecutive protocol via mesoderm differentiation followed by chondrogenic differentiation; subsequently, miPSC and mESC-seeded constructs were further respectively cultured in chondrocyte culture (CC) medium. Alginate phase in the constructs was then removed to generate a graft only comprised of induced chondrocytic cells and cartilaginous extracellular matrix (ECMs). We found that from the mESC-seeded constructs, formation of intact grafts could be achieved in greater sizes with relatively fewer chondrocytic cells and abundant ECMs; from miPSC-seeded constructs, relatively smaller sized cartilaginous grafts could be formed by cells with chondrocytic phenotype wrapped by abundant and better assembled collagen type II. This study demonstrated successful creation of pluripotent stem cells-derived cartilage/chondroid graft from a 3D MCG interim platform. By the support of materials and methodologies established from this study, particularly given the autologous availability of iPSCs, engineered autologous cartilage engraftment may be potentially fulfilled without relying on the limited and invasive autologous chondrocytes acquisition. In this study, we explored chondrogenic differentiation of pluripotent stem cells on a 3D micro-cavitary hydrogel interim platform and creation of pluripotent stem cells-derived cartilage/chondroid graft via a consecutive procedure. Our results demonstrated chondrogenic differentiation could be realized on the platform via mesoderm differentiation. The mESCs/miPSCs derived chondrocytic cells were further cultured to finally generate a pluripotent stem cells-derived scaffold-free construct based on the micro-cavitary hydrogel platform, in which alginate hydrogel could be removed finally. Our results showed that miPSC-derived graft could be formed by cells with chondrocytic phenotype wrapped by abundant and assembled collagen type II. To our knowledge, this study is the first study that initials from pluripotent stem cell seeding on 3D scaffold environment and ends with a scaffold-free chondrogenic micro-tissue. By the support of materials and methodologies established from this study, engineered autologous iPSC-derived cartilage engraftment may be potentially developed instead of autologous chondrocytes grafts that have limited source. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Creating Micro-Videos to Demonstrate Technology Learning and Digital Literacy

ERIC Educational Resources Information Center

Frydenberg, Mark; Andone, Diana

2016-01-01

Purpose: Short videos, also known as micro-videos, have emerged as a platform for sharing ideas, experiences and life events via online social networks. This paper aims to share preliminary results of a study, involving students from two universities who created six-second videos using the Vine mobile app to explain or illustrate technological…

Gene Editing of Microalgae: Scientific Progress and Regulatory Challenges in Europe

PubMed Central

Spicer, Andrew

2018-01-01

It is abundantly clear that the development of gene editing technologies, represents a potentially powerful force for good with regard to human and animal health and addressing the challenges we continue to face in a growing global population. This now includes the development of approaches to modify microalgal strains for potential improvements in productivity, robustness, harvestability, processability, nutritional composition, and application. The rapid emergence and ongoing developments in this area demand a timely review and revision of the current definitions and regulations around genetically modified organisms (GMOs), particularly within Europe. Current practices within the EU provide exemptions from the GMO directives for organisms, including crop plants and micro-organisms that are produced through chemical or UV/radiation mutagenesis. However, organisms generated through gene editing, including microalgae, where only genetic changes in native genes are made, remain currently under the GMO umbrella; they are, as such, excluded from practical and commercial opportunities in the EU. In this review, we will review the advances that are being made in the area of gene editing in microalgae and the impact of regulation on commercial advances in this area with consideration to the current regulatory framework as it relates to GMOs including GM microalgae in Europe. PMID:29509719

Gene Editing of Microalgae: Scientific Progress and Regulatory Challenges in Europe.

PubMed

Spicer, Andrew; Molnar, Attila

2018-03-06

It is abundantly clear that the development of gene editing technologies, represents a potentially powerful force for good with regard to human and animal health and addressing the challenges we continue to face in a growing global population. This now includes the development of approaches to modify microalgal strains for potential improvements in productivity, robustness, harvestability, processability, nutritional composition, and application. The rapid emergence and ongoing developments in this area demand a timely review and revision of the current definitions and regulations around genetically modified organisms (GMOs), particularly within Europe. Current practices within the EU provide exemptions from the GMO directives for organisms, including crop plants and micro-organisms that are produced through chemical or UV/radiation mutagenesis. However, organisms generated through gene editing, including microalgae, where only genetic changes in native genes are made, remain currently under the GMO umbrella; they are, as such, excluded from practical and commercial opportunities in the EU. In this review, we will review the advances that are being made in the area of gene editing in microalgae and the impact of regulation on commercial advances in this area with consideration to the current regulatory framework as it relates to GMOs including GM microalgae in Europe.

Profiling Pre-MicroRNA and Mature MicroRNA Expressions Using a Single Microarray and Avoiding Separate Sample Preparation

PubMed Central

Gan, Lin; Denecke, Bernd

2013-01-01

Mature microRNA is a crucial component in the gene expression regulation network. At the same time, microRNA gene expression and procession is regulated in a precise and collaborated way. Pre-microRNAs mediate products during the microRNA transcription process, they can provide hints of microRNA gene expression regulation or can serve as alternative biomarkers. To date, little effort has been devoted to pre-microRNA expression profiling. In this study, three human and three mouse microRNA profile data sets, based on the Affymetrix miRNA 2.0 array, have been re-analyzed for both mature and pre-microRNA signals as a primary test of parallel mature/pre-microRNA expression profiling on a single platform. The results not only demonstrated a glimpse of pre-microRNA expression in human and mouse, but also the relationship of microRNA expressions between pre- and mature forms. The study also showed a possible application of currently available microRNA microarrays in profiling pre-microRNA expression in a time and cost effective manner. PMID:27605179

Micro/Nanoscale Parallel Patterning of Functional Biomolecules, Organic Fluorophores and Colloidal Nanocrystals

PubMed Central

2009-01-01

We describe the design and optimization of a reliable strategy that combines self-assembly and lithographic techniques, leading to very precise micro-/nanopositioning of biomolecules for the realization of micro- and nanoarrays of functional DNA and antibodies. Moreover, based on the covalent immobilization of stable and versatile SAMs of programmable chemical reactivity, this approach constitutes a general platform for the parallel site-specific deposition of a wide range of molecules such as organic fluorophores and water-soluble colloidal nanocrystals. PMID:20596482

E-Portfolio as a Corrective Platform towards EFL Students' Overall/Componential Writing Performance

ERIC Educational Resources Information Center

Saeedi, Zari; Meihami, Hussein

2015-01-01

This paper aims at accentuating and exploring the effect of using electronic portfolio (EP) platform in providing corrective feedback (CF) on EFL students' overall and micro-componential writing performance. Moreover, by conducting a semi-structured interview, the study seeks to obtain students' attitudes towards the use of EP in three aspects,…

Derepression of microRNA-mediated protein translation inhibition by apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3G (APOBEC3G) and its family members.

PubMed

Huang, Jialing; Liang, Zhihui; Yang, Bin; Tian, Heng; Ma, Jin; Zhang, Hui

2007-11-16

The apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3G (APOBEC3G or A3G) and its fellow cytidine deaminase family members are potent restrictive factors for human immunodeficiency virus type 1 (HIV-1) and many other retroviruses. A3G interacts with a vast spectrum of RNA-binding proteins and is located in processing bodies and stress granules. However, its cellular function remains to be further clarified. Using a luciferase reporter gene and green fluorescent protein reporter gene, we demonstrate that A3G and other APOBEC family members can counteract the inhibition of protein synthesis by various microRNAs (miRNAs) such as mir-10b, mir-16, mir-25, and let-7a. A3G could also enhance the expression level of miRNA-targeted mRNA. Further, A3G facilitated the association of microRNA-targeted mRNA with polysomes rather than with processing bodies. Intriguingly, experiments with a C288A/C291A A3G mutant indicated that this function of A3G is separable from its cytidine deaminase activity. Our findings suggest that the major cellular function of A3G, in addition to inhibiting the mobility of retrotransposons and replication of endogenous retroviruses, is most likely to prevent the decay of miRNA-targeted mRNA in processing bodies.

Let's Talk Politics. 1986 Indiana General Election Edition and Teacher Guide.

ERIC Educational Resources Information Center

Henn, Carl, Ed.

The candidates, important issues, party platforms, and the voting process of Indiana are presented. The term of office, salary, and duties are outlined for the following political offices: (1) United States Representative, (2) United States Senator, (3) secretary of state, (4) auditor of state, (5) treasurer of state, (6) clerk for the Supreme…

Wiki Use that Increases Communication and Collaboration Motivation

ERIC Educational Resources Information Center

Davidson, Robyn

2012-01-01

Communication and collaboration can be readily enabled by the use of many ICT tools. A wiki, which is an easily accessible and editable website, is one such platform that provides the opportunity for students to work on group projects without the barriers that arise from traditional group work. Whilst wiki use is becoming more common, its use in…

Teaching Earth Signals Analysis Using the Java-DSP Earth Systems Edition: Modern and Past Climate Change

ERIC Educational Resources Information Center

Ramamurthy, Karthikeyan Natesan; Hinnov, Linda A.; Spanias, Andreas S.

2014-01-01

Modern data collection in the Earth Sciences has propelled the need for understanding signal processing and time-series analysis techniques. However, there is an educational disconnect in the lack of instruction of time-series analysis techniques in many Earth Science academic departments. Furthermore, there are no platform-independent freeware…

Command and Control: US Army Staffs and the Operations Process

DTIC Science & Technology

2016-05-26

Architecture , 2nd ed. (New York: Elsevier, 2006). 2...Mainly technical experts in logistics and engineering, these proto-staff officers enabled both the Egyptian and Assyrian empires to conquer many of...Platform for Designing Business Architecture . New York: Elsevier, 2006, 2d edition. Gilbert, Felix. “Machiavelli: The Renaissance of the Art of War.” In

Virtual Reality as a Story Telling Platform for Geoscience Communication

NASA Astrophysics Data System (ADS)

Lazar, K.; Moysey, S. M.

2017-12-01

Capturing the attention of students and the public is a critical step for increasing societal interest and literacy in earth science issues. Virtual reality (VR) provides a means for geoscience engagement that is well suited to place-based learning through exciting and immersive experiences. One approach is to create fully-immersive virtual gaming environments where players interact with physical objects, such as rock samples and outcrops, to pursue geoscience learning goals. Developing an experience like this, however, can require substantial programming expertise and resources. At the other end of the development spectrum, it is possible for anyone to create immersive virtual experiences with 360-degree imagery, which can be made interactive using easy to use VR editing software to embed videos, audio, images, and other content within the 360-degree image. Accessible editing tools like these make the creation of VR experiences something that anyone can tackle. Using the VR editor ThingLink and imagery from Google Maps, for example, we were able to create an interactive tour of the Grand Canyon, complete with embedded assessments, in a matter of hours. The true power of such platforms, however, comes from the potential to engage students as content authors to create and share stories of place that explore geoscience issues from their personal perspective. For example, we have used combinations of 360-degree images with interactive mapping and web platforms to enable students with no programming experience to create complex web apps as highly engaging story telling platforms. We highlight here examples of how we have implemented such story telling approaches with students to assess learning in courses, to share geoscience research outcomes, and to communicate issues of societal importance.

Wafer integrated micro-scale concentrating photovoltaics

NASA Astrophysics Data System (ADS)

Gu, Tian; Li, Duanhui; Li, Lan; Jared, Bradley; Keeler, Gordon; Miller, Bill; Sweatt, William; Paap, Scott; Saavedra, Michael; Das, Ujjwal; Hegedus, Steve; Tauke-Pedretti, Anna; Hu, Juejun

2017-09-01

Recent development of a novel micro-scale PV/CPV technology is presented. The Wafer Integrated Micro-scale PV approach (WPV) seamlessly integrates multijunction micro-cells with a multi-functional silicon platform that provides optical micro-concentration, hybrid photovoltaic, and mechanical micro-assembly. The wafer-embedded micro-concentrating elements is shown to considerably improve the concentration-acceptance-angle product, potentially leading to dramatically reduced module materials and fabrication costs, sufficient angular tolerance for low-cost trackers, and an ultra-compact optical architecture, which makes the WPV module compatible with commercial flat panel infrastructures. The PV/CPV hybrid architecture further allows the collection of both direct and diffuse sunlight, thus extending the geographic and market domains for cost-effective PV system deployment. The WPV approach can potentially benefits from both the high performance of multijunction cells and the low cost of flat plate Si PV systems.

Optimized approach for Ion Proton RNA sequencing reveals details of RNA splicing and editing features of the transcriptome.

PubMed

Brown, Roger B; Madrid, Nathaniel J; Suzuki, Hideaki; Ness, Scott A

2017-01-01

RNA-sequencing (RNA-seq) has become the standard method for unbiased analysis of gene expression but also provides access to more complex transcriptome features, including alternative RNA splicing, RNA editing, and even detection of fusion transcripts formed through chromosomal translocations. However, differences in library methods can adversely affect the ability to recover these different types of transcriptome data. For example, some methods have bias for one end of transcripts or rely on low-efficiency steps that limit the complexity of the resulting library, making detection of rare transcripts less likely. We tested several commonly used methods of RNA-seq library preparation and found vast differences in the detection of advanced transcriptome features, such as alternatively spliced isoforms and RNA editing sites. By comparing several different protocols available for the Ion Proton sequencer and by utilizing detailed bioinformatics analysis tools, we were able to develop an optimized random primer based RNA-seq technique that is reliable at uncovering rare transcript isoforms and RNA editing features, as well as fusion reads from oncogenic chromosome rearrangements. The combination of optimized libraries and rapid Ion Proton sequencing provides a powerful platform for the transcriptome analysis of research and clinical samples.

CrisprGE: a central hub of CRISPR/Cas-based genome editing.

PubMed

Kaur, Karambir; Tandon, Himani; Gupta, Amit Kumar; Kumar, Manoj

2015-01-01

CRISPR system is a powerful defense mechanism in bacteria and archaea to provide immunity against viruses. Recently, this process found a new application in intended targeting of the genomes. CRISPR-mediated genome editing is performed by two main components namely single guide RNA and Cas9 protein. Despite the enormous data generated in this area, there is a dearth of high throughput resource. Therefore, we have developed CrisprGE, a central hub of CRISPR/Cas-based genome editing. Presently, this database holds a total of 4680 entries of 223 unique genes from 32 model and other organisms. It encompasses information about the organism, gene, target gene sequences, genetic modification, modifications length, genome editing efficiency, cell line, assay, etc. This depository is developed using the open source LAMP (Linux Apache MYSQL PHP) server. User-friendly browsing, searching facility is integrated for easy data retrieval. It also includes useful tools like BLAST CrisprGE, BLAST NTdb and CRISPR Mapper. Considering potential utilities of CRISPR in the vast area of biology and therapeutics, we foresee this platform as an assistance to accelerate research in the burgeoning field of genome engineering. © The Author(s) 2015. Published by Oxford University Press.

Consistency of Global Modis Aerosol Optical Depths over Ocean on Terra and Aqua Ceres SSF Datasets

NASA Technical Reports Server (NTRS)

Ignatov, Alexander; Minnis, Patrick; Miller, Walter F.; Wielicki, Bruce A.; Remer, Lorraine

2006-01-01

Aerosol retrievals over ocean from the Moderate Resolution Imaging Spectroradiometer (MODIS) onboard Terra and Aqua platforms are available from the Clouds and the Earth's Radiant Energy System (CERES) Single Scanner Footprint (SSF) datasets generated at NASA Langley Research Center (LaRC). Two aerosol products are reported side-by-side. The primary M product is generated by sub-setting and remapping the multi-spectral (0.47-2.1 micrometer) MODIS produced oceanic aerosol (MOD04/MYD04 for Terra/Aqua) onto CERES footprints. M*D04 processing uses cloud screening and aerosol algorithms developed by the MODIS science team. The secondary AVHRR-like A product is generated in only two MODIS bands 1 and 6 (on Aqua, bands 1 and 7). The A processing uses the CERES cloud screening algorithm, and NOAA/NESDIS glint identification, and single-channel aerosol retrieval algorithms. The M and A products have been documented elsewhere and preliminarily compared using 2 weeks of global Terra CERES SSF Edition 1A data in which the M product was based on MOD04 collection 3. In this study, the comparisons between the M and A aerosol optical depths (AOD) in MODIS band 1 (0.64 micrometers), tau(sub 1M) and tau(sub 1A) are re-examined using 9 days of global CERES SSF Terra Edition 2A and Aqua Edition 1B data from 13 - 21 October 2002, and extended to include cross-platform comparisons. The M and A products on the new CERES SSF release are generated using the same aerosol algorithms as before, but with different preprocessing and sampling procedures, lending themselves to a simple sensitivity check to non-aerosol factors. Both tau(sub 1M) and tau(sub 1A) generally compare well across platforms. However, the M product shows some differences, which increase with ambient cloud amount and towards the solar side of the orbit. Three types of comparisons conducted in this study - cross-platform, cross-product, and cross-release confirm the previously made observation that the major area for improvement in the current aerosol processing lies in a more formalized and standardized sampling (and most importantly, cloud screening) whereas optimization of the aerosol algorithm is deemed to be an important yet less critical element.

MPS Editor

NASA Technical Reports Server (NTRS)

Mathews, William S.; Liu, Ning; Francis, Laurie K.; OReilly, Taifun L.; Schrock, Mitchell; Page, Dennis N.; Morris, John R.; Joswig, Joseph C.; Crockett, Thomas M.; Shams, Khawaja S.

2011-01-01

Previously, it was time-consuming to hand-edit data and then set up simulation runs to find the effect and impact of the input data on a spacecraft. MPS Editor provides the user the capability to create/edit/update models and sequences, and immediately try them out using what appears to the user as one piece of software. MPS Editor provides an integrated sequencing environment for users. It provides them with software that can be utilized during development as well as actual operations. In addition, it provides them with a single, consistent, user friendly interface. MPS Editor uses the Eclipse Rich Client Platform to provide an environment that can be tailored to specific missions. It provides the capability to create and edit, and includes an Activity Dictionary to build the simulation spacecraft models, build and edit sequences of commands, and model the effects of those commands on the spacecraft. MPS Editor is written in Java using the Eclipse Rich Client Platform. It is currently built with four perspectives: the Activity Dictionary Perspective, the Project Adaptation Perspective, the Sequence Building Perspective, and the Sequence Modeling Perspective. Each perspective performs a given task. If a mission doesn't require that task, the unneeded perspective is not added to that project's delivery. In the Activity Dictionary Perspective, the user builds the project-specific activities, observations, calibrations, etc. Typically, this is used during the development phases of the mission, although it can be used later to make changes and updates to the Project Activity Dictionary. In the Adaptation Perspective, the user creates the spacecraft models such as power, data store, etc. Again, this is typically used during development, but will be used to update or add models of the spacecraft. The Sequence Building Perspective allows the user to create a sequence of activities or commands that go to the spacecraft. It provides a simulation of the activities and commands that have been created.

TALEN-Mediated Homologous Recombination Produces Site-Directed DNA Base Change and Herbicide-Resistant Rice.

PubMed

Li, Ting; Liu, Bo; Chen, Chih Ying; Yang, Bing

2016-05-20

Over the last decades, much endeavor has been made to advance genome editing technology due to its promising role in both basic and synthetic biology. The breakthrough has been made in recent years with the advent of sequence-specific endonucleases, especially zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs) and clustered regularly interspaced short palindromic repeats (CRISPRs) guided nucleases (e.g., Cas9). In higher eukaryotic organisms, site-directed mutagenesis usually can be achieved through non-homologous end-joining (NHEJ) repair to the DNA double-strand breaks (DSBs) caused by the exogenously applied nucleases. However, site-specific gene replacement or genuine genome editing through homologous recombination (HR) repair to DSBs remains a challenge. As a proof of concept gene replacement through TALEN-based HR in rice (Oryza sativa), we successfully produced double point mutations in rice acetolactate synthase gene (OsALS) and generated herbicide resistant rice lines by using TALENs and donor DNA carrying the desired mutations. After ballistic delivery into rice calli of TALEN construct and donor DNA, nine HR events with different genotypes of OsALS were obtained in T0 generation at the efficiency of 1.4%-6.3% from three experiments. The HR-mediated gene edits were heritable to the progeny of T1 generation. The edited T1 plants were as morphologically normal as the control plants while displayed strong herbicide resistance. The results demonstrate the feasibility of TALEN-mediated genome editing in rice and provide useful information for further genome editing by other nuclease-based genome editing platforms. Copyright © 2016 Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. Published by Elsevier Ltd. All rights reserved.

MicroScope in 2017: an expanding and evolving integrated resource for community expertise of microbial genomes

PubMed Central

Vallenet, David; Calteau, Alexandra; Cruveiller, Stéphane; Gachet, Mathieu; Lajus, Aurélie; Josso, Adrien; Mercier, Jonathan; Renaux, Alexandre; Rollin, Johan; Rouy, Zoe; Roche, David; Scarpelli, Claude; Médigue, Claudine

2017-01-01

The annotation of genomes from NGS platforms needs to be automated and fully integrated. However, maintaining consistency and accuracy in genome annotation is a challenging problem because millions of protein database entries are not assigned reliable functions. This shortcoming limits the knowledge that can be extracted from genomes and metabolic models. Launched in 2005, the MicroScope platform (http://www.genoscope.cns.fr/agc/microscope) is an integrative resource that supports systematic and efficient revision of microbial genome annotation, data management and comparative analysis. Effective comparative analysis requires a consistent and complete view of biological data, and therefore, support for reviewing the quality of functional annotation is critical. MicroScope allows users to analyze microbial (meta)genomes together with post-genomic experiment results if any (i.e. transcriptomics, re-sequencing of evolved strains, mutant collections, phenotype data). It combines tools and graphical interfaces to analyze genomes and to perform the expert curation of gene functions in a comparative context. Starting with a short overview of the MicroScope system, this paper focuses on some major improvements of the Web interface, mainly for the submission of genomic data and on original tools and pipelines that have been developed and integrated in the platform: computation of pan-genomes and prediction of biosynthetic gene clusters. Today the resource contains data for more than 6000 microbial genomes, and among the 2700 personal accounts (65% of which are now from foreign countries), 14% of the users are performing expert annotations, on at least a weekly basis, contributing to improve the quality of microbial genome annotations. PMID:27899624

Micro coring apparatus

NASA Technical Reports Server (NTRS)

Collins, David; Brooks, Marshall; Chen, Paul; Dwelle, Paul; Fischer, Ben

1989-01-01

A micro-coring apparatus for lunar exploration applications, that is compatible with the other components of the Walking Mobile Platform, was designed. The primary purpose of core sampling is to gain an understanding of the geological composition and properties of the prescribed environment. This procedure has been used extensively for Earth studies and in limited applications during lunar explorations. The corer is described and analyzed for effectiveness.

Integrated sample-to-detection chip for nucleic acid test assays.

PubMed

Prakash, R; Pabbaraju, K; Wong, S; Tellier, R; Kaler, K V I S

2016-06-01

Nucleic acid based diagnostic techniques are routinely used for the detection of infectious agents. Most of these assays rely on nucleic acid extraction platforms for the extraction and purification of nucleic acids and a separate real-time PCR platform for quantitative nucleic acid amplification tests (NATs). Several microfluidic lab on chip (LOC) technologies have been developed, where mechanical and chemical methods are used for the extraction and purification of nucleic acids. Microfluidic technologies have also been effectively utilized for chip based real-time PCR assays. However, there are few examples of microfluidic systems which have successfully integrated these two key processes. In this study, we have implemented an electro-actuation based LOC micro-device that leverages multi-frequency actuation of samples and reagents droplets for chip based nucleic acid extraction and real-time, reverse transcription (RT) PCR (qRT-PCR) amplification from clinical samples. Our prototype micro-device combines chemical lysis with electric field assisted isolation of nucleic acid in a four channel parallel processing scheme. Furthermore, a four channel parallel qRT-PCR amplification and detection assay is integrated to deliver the sample-to-detection NAT chip. The NAT chip combines dielectrophoresis and electrostatic/electrowetting actuation methods with resistive micro-heaters and temperature sensors to perform chip based integrated NATs. The two chip modules have been validated using different panels of clinical samples and their performance compared with standard platforms. This study has established that our integrated NAT chip system has a sensitivity and specificity comparable to that of the standard platforms while providing up to 10 fold reduction in sample/reagent volumes.

Mission demonstration concept for the long-duration storage and transfer of cryogenic propellants

NASA Astrophysics Data System (ADS)

McLean, C.; Deininger, W.; Ingram, K.; Schweickart, R.; Unruh, B.

This paper describes an experimental platform that will demonstrate the major technologies required for the handling and storage of cryogenic propellants in a low-to-zero-g environment. In order to develop a cost-effective, high value-added demonstration mission, a review of the complete mission concept of operations (CONOPS) was performed. The overall cost of such a mission is driven not only by the spacecraft platform and on-orbit experiments themselves, but also by the complexities of handling cryogenic propellants during ground-processing operations. On-orbit storage methodologies were looked at for both passive and active systems. Passive systems rely purely on isolation of the stored propellant from environmental thermal loads, while active cooling employs cryocooler technologies. The benefit trade between active and passive systems is mission-dependent due to the mass, power, and system-level penalties associated with active cooling systems. The experimental platform described in this paper is capable of demonstrating multiple advanced micro-g cryogenic propellant management technologies. In addition to the requirements of demonstrating these technologies, the methodology of propellant transfer must be evaluated. The handling of multiphase liquids in micro-g is discussed using flight-heritage micro-g propellant management device technologies as well as accelerated tank stratification for access to vapor-free or liquid-free propellants. The mission concept presented shows the extensibility of the experimental platform to demonstrate advanced cryogenic components and technologies, propellant transfer methodologies, as well as the validation of thermal and fluidic models, from subscale tankage to an operational architecture.

microMS: A Python Platform for Image-Guided Mass Spectrometry Profiling

NASA Astrophysics Data System (ADS)

Comi, Troy J.; Neumann, Elizabeth K.; Do, Thanh D.; Sweedler, Jonathan V.

2017-09-01

Image-guided mass spectrometry (MS) profiling provides a facile framework for analyzing samples ranging from single cells to tissue sections. The fundamental workflow utilizes a whole-slide microscopy image to select targets of interest, determine their spatial locations, and subsequently perform MS analysis at those locations. Improving upon prior reported methodology, a software package was developed for working with microscopy images. microMS, for microscopy-guided mass spectrometry, allows the user to select and profile diverse samples using a variety of target patterns and mass analyzers. Written in Python, the program provides an intuitive graphical user interface to simplify image-guided MS for novice users. The class hierarchy of instrument interactions permits integration of new MS systems while retaining the feature-rich image analysis framework. microMS is a versatile platform for performing targeted profiling experiments using a series of mass spectrometers. The flexibility in mass analyzers greatly simplifies serial analyses of the same targets by different instruments. The current capabilities of microMS are presented, and its application for off-line analysis of single cells on three distinct instruments is demonstrated. The software has been made freely available for research purposes. [Figure not available: see fulltext.

microMS: A Python Platform for Image-Guided Mass Spectrometry Profiling.

PubMed

Comi, Troy J; Neumann, Elizabeth K; Do, Thanh D; Sweedler, Jonathan V

2017-09-01

Image-guided mass spectrometry (MS) profiling provides a facile framework for analyzing samples ranging from single cells to tissue sections. The fundamental workflow utilizes a whole-slide microscopy image to select targets of interest, determine their spatial locations, and subsequently perform MS analysis at those locations. Improving upon prior reported methodology, a software package was developed for working with microscopy images. microMS, for microscopy-guided mass spectrometry, allows the user to select and profile diverse samples using a variety of target patterns and mass analyzers. Written in Python, the program provides an intuitive graphical user interface to simplify image-guided MS for novice users. The class hierarchy of instrument interactions permits integration of new MS systems while retaining the feature-rich image analysis framework. microMS is a versatile platform for performing targeted profiling experiments using a series of mass spectrometers. The flexibility in mass analyzers greatly simplifies serial analyses of the same targets by different instruments. The current capabilities of microMS are presented, and its application for off-line analysis of single cells on three distinct instruments is demonstrated. The software has been made freely available for research purposes. Graphical Abstract ᅟ.

Automatic and integrated micro-enzyme assay (AIμEA) platform for highly sensitive thrombin analysis via an engineered fluorescence protein-functionalized monolithic capillary column.

PubMed

Lin, Lihua; Liu, Shengquan; Nie, Zhou; Chen, Yingzhuang; Lei, Chunyang; Wang, Zhen; Yin, Chao; Hu, Huiping; Huang, Yan; Yao, Shouzhuo

2015-04-21

Nowadays, large-scale screening for enzyme discovery, engineering, and drug discovery processes require simple, fast, and sensitive enzyme activity assay platforms with high integration and potential for high-throughput detection. Herein, a novel automatic and integrated micro-enzyme assay (AIμEA) platform was proposed based on a unique microreaction system fabricated by a engineered green fluorescence protein (GFP)-functionalized monolithic capillary column, with thrombin as an example. The recombinant GFP probe was rationally engineered to possess a His-tag and a substrate sequence of thrombin, which enable it to be immobilized on the monolith via metal affinity binding, and to be released after thrombin digestion. Combined with capillary electrophoresis-laser-induced fluorescence (CE-LIF), all the procedures, including thrombin injection, online enzymatic digestion in the microreaction system, and label-free detection of the released GFP, were integrated in a single electrophoretic process. By taking advantage of the ultrahigh loading capacity of the AIμEA platform and the CE automatic programming setup, one microreaction column was sufficient for many times digestion without replacement. The novel microreaction system showed significantly enhanced catalytic efficiency, about 30 fold higher than that of the equivalent bulk reaction. Accordingly, the AIμEA platform was highly sensitive with a limit of detection down to 1 pM of thrombin. Moreover, the AIμEA platform was robust and reliable to detect thrombin in human serum samples and its inhibition by hirudin. Hence, this AIμEA platform exhibits great potential for high-throughput analysis in future biological application, disease diagnostics, and drug screening.

Cas9-based tools for targeted genome editing and transcriptional control.

PubMed

Xu, Tao; Li, Yongchao; Van Nostrand, Joy D; He, Zhili; Zhou, Jizhong

2014-03-01

Development of tools for targeted genome editing and regulation of gene expression has significantly expanded our ability to elucidate the mechanisms of interesting biological phenomena and to engineer desirable biological systems. Recent rapid progress in the study of a clustered, regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated (Cas) protein system in bacteria has facilitated the development of newly facile and programmable platforms for genome editing and transcriptional control in a sequence-specific manner. The core RNA-guided Cas9 endonuclease in the type II CRISPR system has been harnessed to realize gene mutation and DNA deletion and insertion, as well as transcriptional activation and repression, with multiplex targeting ability, just by customizing 20-nucleotide RNA components. Here we describe the molecular basis of the type II CRISPR/Cas system and summarize applications and factors affecting its utilization in model organisms. We also discuss the advantages and disadvantages of Cas9-based tools in comparison with widely used customizable tools, such as Zinc finger nucleases and transcription activator-like effector nucleases.

Synthetic CRISPR RNA-Cas9-guided genome editing in human cells.

PubMed

Rahdar, Meghdad; McMahon, Moira A; Prakash, Thazha P; Swayze, Eric E; Bennett, C Frank; Cleveland, Don W

2015-12-22

Genome editing with the clustered, regularly interspaced, short palindromic repeats (CRISPR)-Cas9 nuclease system is a powerful technology for manipulating genomes, including introduction of gene disruptions or corrections. Here we develop a chemically modified, 29-nucleotide synthetic CRISPR RNA (scrRNA), which in combination with unmodified transactivating crRNA (tracrRNA) is shown to functionally replace the natural guide RNA in the CRISPR-Cas9 nuclease system and to mediate efficient genome editing in human cells. Incorporation of rational chemical modifications known to protect against nuclease digestion and stabilize RNA-RNA interactions in the tracrRNA hybridization region of CRISPR RNA (crRNA) yields a scrRNA with enhanced activity compared with the unmodified crRNA and comparable gene disruption activity to the previously published single guide RNA. Taken together, these findings provide a platform for therapeutic applications, especially for nervous system disease, using successive application of cell-permeable, synthetic CRISPR RNAs to activate and then silence Cas9 nuclease activity.

Inertial focusing and passive micro-mixing techniques for rare cells capturing microfluidic platform

NASA Astrophysics Data System (ADS)

Phadke, Manisha; Shaner, Sebastian; Shah, Shreyas; Rodriguez, Ygnacio; Wibowo, Denni; Whulanza, Yudan; Teriete, Peter; Allen, Jeff; Kassegne, Sam

2018-02-01

Isolation and capture of rare cells continues to be a daunting task that is still looking for an innovative and efficient method. While a variety of approaches have been suggested over the past several years, immunocapturing in a microfluidic platform carries a substantial promise as shown by recent published works. In this paper, we introduced a combination of inertial focusing and passive micro-mixing through 3D chevron-type features in a microchannel to induce chaotic mixing within antibody-coated microchannels and, ultimately, promote rare cell capture. The device introduced in this work contains curved microchannels that consist of a series of staggered chevron grooves. The curved channels enable inertial focusing while the chevron grooves allow for chaotic mixing. The microfluidics platform microfabricated through soft lithography has a polydimethylsiloxane (PDMS) foundation and was thinly coated with an alginate hydrogel derivatized with streptavidin. We submitted that our qualitative and quantitative results demonstrated the potentials in advancements in rare cell isolation through this integration of two techniques.

Use of Parallel Micro-Platform for the Simulation the Space Exploration

NASA Astrophysics Data System (ADS)

Velasco Herrera, Victor Manuel; Velasco Herrera, Graciela; Rosano, Felipe Lara; Rodriguez Lozano, Salvador; Lucero Roldan Serrato, Karen

The purpose of this work is to create a parallel micro-platform, that simulates the virtual movements of a space exploration in 3D. One of the innovations presented in this design consists of the application of a lever mechanism for the transmission of the movement. The development of such a robot is a challenging task very different of the industrial manipulators due to a totally different target system of requirements. This work presents the study and simulation, aided by computer, of the movement of this parallel manipulator. The development of this model has been developed using the platform of computer aided design Unigraphics, in which it was done the geometric modeled of each one of the components and end assembly (CAD), the generation of files for the computer aided manufacture (CAM) of each one of the pieces and the kinematics simulation of the system evaluating different driving schemes. We used the toolbox (MATLAB) of aerospace and create an adaptive control module to simulate the system.

Embedded real-time operating system micro kernel design

NASA Astrophysics Data System (ADS)

Cheng, Xiao-hui; Li, Ming-qiang; Wang, Xin-zheng

2005-12-01

Embedded systems usually require a real-time character. Base on an 8051 microcontroller, an embedded real-time operating system micro kernel is proposed consisting of six parts, including a critical section process, task scheduling, interruption handle, semaphore and message mailbox communication, clock managent and memory managent. Distributed CPU and other resources are among tasks rationally according to the importance and urgency. The design proposed here provides the position, definition, function and principle of micro kernel. The kernel runs on the platform of an ATMEL AT89C51 microcontroller. Simulation results prove that the designed micro kernel is stable and reliable and has quick response while operating in an application system.

Design and analysis of photonic crystal micro-cavity based optical sensor platform

DOE Office of Scientific and Technical Information (OSTI.GOV)

Goyal, Amit Kumar, E-mail: amitgoyal.ceeri@gmail.com; Dutta, Hemant Sankar, E-mail: hemantdutta97@gmail.com; Pal, Suchandan, E-mail: spal@ceeri.ernet.in

2016-04-13

In this paper, the design of a two-dimensional photonic crystal micro-cavity based integrated-optic sensor platform is proposed. The behaviour of designed cavity is analyzed using two-dimensional Finite Difference Time Domain (FDTD) method. The structure is designed by deliberately inserting some defects in a photonic crystal waveguide structure. Proposed structure shows a quality factor (Q) of about 1e5 and the average sensitivity of 500nm/RIU in the wavelength range of 1450 – 1580 nm. Sensing technique is based on the detection of shift in upper-edge cut-off wavelength for a reference signal strength of –10 dB in accordance with the change in refractive index ofmore » analyte.« less

RNA Editing Modulates Human Hepatic Aryl Hydrocarbon Receptor Expression by Creating MicroRNA Recognition Sequence.

PubMed

Nakano, Masataka; Fukami, Tatsuki; Gotoh, Saki; Takamiya, Masataka; Aoki, Yasuhiro; Nakajima, Miki

2016-01-08

Adenosine to inosine (A-to-I) RNA editing is the most frequent type of post-transcriptional nucleotide conversion in humans, and it is catalyzed by adenosine deaminase acting on RNA (ADAR) enzymes. In this study we investigated the effect of RNA editing on human aryl hydrocarbon receptor (AhR) expression because the AhR transcript potentially forms double-stranded structures, which are targets of ADAR enzymes. In human hepatocellular carcinoma-derived Huh-7 cells, the ADAR1 knockdown reduced the RNA editing levels in the 3'-untranslated region (3'-UTR) of the AhR transcript and increased the AhR protein levels. The ADAR1 knockdown enhanced the ligand-mediated induction of CYP1A1, a gene downstream of AhR. We investigated the possibility that A-to-I RNA editing creates miRNA targeting sites in the AhR mRNA and found that the miR-378-dependent down-regulation of AhR was abolished by ADAR1 knockdown. These results indicated that the ADAR1-mediated down-regulation of AhR could be attributed to the creation of a miR-378 recognition site in the AhR 3'-UTR. The interindividual differences in the RNA editing levels within the AhR 3'-UTR in a panel of 32 human liver samples were relatively small, whereas the differences in ADAR1 expression were large (220-fold). In the human liver samples a significant inverse association was observed between the miR-378 and AhR protein levels, suggesting that the RNA-editing-dependent down-regulation of AhR by miR-378 contributes to the variability in the constitutive hepatic expression of AhR. In conclusion, this study uncovered for the first time that A-to-I RNA editing modulates the potency of xenobiotic metabolism in the human liver. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Integrated microfluidic platforms for investigating neuronal networks

NASA Astrophysics Data System (ADS)

Kim, Hyung Joon

This dissertation describes the development and application of integrated microfluidics-based assay platforms to study neuronal activities in the nervous system in-vitro. The assay platforms were fabricated using soft lithography and micro/nano fabrication including microfluidics, surface patterning, and nanomaterial synthesis. The use of integrated microfluidics-based assay platform allows culturing and manipulating many types of neuronal tissues in precisely controlled microenvironment. Furthermore, they provide organized multi-cellular in-vitro model, long-term monitoring with live cell imaging, and compatibility with molecular biology techniques and electrophysiology experiment. In this dissertation, the integrated microfluidics-based assay platforms are developed for investigation of neuronal activities such as local protein synthesis, impairment of axonal transport by chemical/physical variants, growth cone path finding under chemical/physical cues, and synaptic transmission in neuronal circuit. Chapter 1 describes the motivation, objectives, and scope for developing in-vitro platform to study various neuronal activities. Chapter 2 introduces microfluidic culture platform for biochemical assay with large-scale neuronal tissues that are utilized as model system in neuroscience research. Chapter 3 focuses on the investigation of impaired axonal transport by beta-Amyloid and oxidative stress. The platform allows to control neuronal processes and to quantify mitochondrial movement in various regions of axons away from applied drugs. Chapter 4 demonstrates the development of microfluidics-based growth cone turning assay to elucidate the mechanism underlying axon guidance under soluble factors and shear flow. Using this platform, the behaviors of growth cone of mammalian neurons are verified under the gradient of inhibitory molecules and also shear flow in well-controlled manner. In Chapter 5, I combine in-vitro multicellular model with microfabricated MEA (multielectrode array) or nanowire electrode array to study electrophysiology in neuronal network. Also, "diode-like" microgrooves to control the number of neuronal processes is embedded in this platform. Chapter 6 concludes with a possible future direction of this work. Interfacing micro/nanotechnology with primary neuron culture would open many doors in fundamental neuroscience research and also biomedical innovation.

U.S. Army Natick Soldier Research, Development & Engineering Center Testing Facilities And Equipment. Second Edition

DTIC Science & Technology

2011-04-01

30 Freeze Dryer ................................................. 30 High-Pressure Processing ............................... 30 Microwave Digestive...PP1 Power Platform Energy Analyzer ..... 41 Quintox Gas Combustion Analyzer .................... 41 FLIR Systems SC2000 Thermacam Handheld IR ...electronically directly to the contractor or printed on plotter paper , oak tag, or on CD. alloy steel, stainless steel, aluminum, copper and copper alloys

Managing the Platform: Higher Education and the Logic of Wikinomics

ERIC Educational Resources Information Center

Staley, David J.

2009-01-01

Wikipedia is an online free-content encyclopedia that anyone can edit and an efficient way to marshal the talents of many bright, capable people to produce knowledge. But the real significance of Wikipedia and similar Web 2.0 technologies is the way in which they organize people and activities, not simply the way in which they create and…

Micro-Inspector Spacecraft Testbed: Breadboard Subsystem Demonstrations

NASA Astrophysics Data System (ADS)

Mueller, Juergen; Goldberg, Hannah; Alkalai, Leon

2007-01-01

Micro-inspector is a 5-kg inspection platform designed to operate autonomously following operator up-linked command sequences around a host spacecraft to perform safety inspections, anomaly inspections, or imaging of large in-space assemblies as envisioned for future NASA exploration missions. Similarly, such an inspection platform may be adapted to military space missions. Micro-inspector relies on solar power and using celestial sensors for navigation, giving the system large flexibility in the missions and applications it may serve, including those beyond Earth orbit. Micro-Inspector, through its small size and low weight, poses minimal design impacts to the host. Its small size and weight also affords micro-inspector to be disposable, allowing multiple inspectors to be used by a single host for different inspection routines or as emergency back-up. Its low-pressure butane propulsion system combines safety and compactness through liquid propellant storage with an adequate performance of up to 30 m/s for inspection maneuvers around the host. Micro-inspector, since power limited through a body mounted solar array, thus avoiding the complexities of deployable structures, relies on many advanced, ultra-low power micro-technologies, such as a novel microvalve by VACCO Industries in its propulsion system, electrochromic surface modulating heat transfer from the spacecraft using no moving parts, low power dual processor and FPGA-based reconfigurable and SEU mitigating avionics, a low power RF telecom link based on the Mars Micro Transceiver, and micro attitude control sensors, such as commercial micro IMUs and a JPL developed micro sun sensor. Host safety is a key concern, and multiple safety features are employed by micro-inspector to prevent any accidental impact onto the host. Among these is an active, laser-based range-finding collision avoidance system, which constantly monitors the distance to the host and via the micro-inspector's control system maintains a safe distance. Micro-Inspector design, through funding from the NASA Explorations Systems Mission Directorate, has significantly advanced over the past year and is currently at PDR level and beyond. Special emphasis was placed on retiring risk in various subsystem areas through the use of advanced technologies. To this end, a micro-inspector test bed was set up to critically assess the readiness of component technologies and subsystems. Breadboard subsystem demonstrations and system integration were performed to place future design efforts on a solid basis.

MicroScope-an integrated resource for community expertise of gene functions and comparative analysis of microbial genomic and metabolic data.

PubMed

Médigue, Claudine; Calteau, Alexandra; Cruveiller, Stéphane; Gachet, Mathieu; Gautreau, Guillaume; Josso, Adrien; Lajus, Aurélie; Langlois, Jordan; Pereira, Hugo; Planel, Rémi; Roche, David; Rollin, Johan; Rouy, Zoe; Vallenet, David

2017-09-12

The overwhelming list of new bacterial genomes becoming available on a daily basis makes accurate genome annotation an essential step that ultimately determines the relevance of thousands of genomes stored in public databanks. The MicroScope platform (http://www.genoscope.cns.fr/agc/microscope) is an integrative resource that supports systematic and efficient revision of microbial genome annotation, data management and comparative analysis. Starting from the results of our syntactic, functional and relational annotation pipelines, MicroScope provides an integrated environment for the expert annotation and comparative analysis of prokaryotic genomes. It combines tools and graphical interfaces to analyze genomes and to perform the manual curation of gene function in a comparative genomics and metabolic context. In this article, we describe the free-of-charge MicroScope services for the annotation and analysis of microbial (meta)genomes, transcriptomic and re-sequencing data. Then, the functionalities of the platform are presented in a way providing practical guidance and help to the nonspecialists in bioinformatics. Newly integrated analysis tools (i.e. prediction of virulence and resistance genes in bacterial genomes) and original method recently developed (the pan-genome graph representation) are also described. Integrated environments such as MicroScope clearly contribute, through the user community, to help maintaining accurate resources. © The Author 2017. Published by Oxford University Press.

Design and Development of Micro-Power Generating Device for Biomedical Applications of Lab-on-a-Disc.

PubMed

Joseph, Karunan; Ibrahim, Fatimah; Cho, Jongman; Thio, Tzer Hwai Gilbert; Al-Faqheri, Wisam; Madou, Marc

2015-01-01

The development of micro-power generators for centrifugal microfluidic discs enhances the platform as a green point-of-care diagnostic system and eliminates the need for attaching external peripherals to the disc. In this work, we present micro-power generators that harvest energy from the disc's rotational movement to power biomedical applications on the disc. To implement these ideas, we developed two types of micro-power generators using piezoelectric films and an electromagnetic induction system. The piezoelectric-based generator takes advantage of the film's vibration during the disc's rotational motion, whereas the electromagnetic induction-based generator operates on the principle of current generation in stacks of coil exposed to varying magnetic flux. We have successfully demonstrated that at the spinning speed of 800 revolutions per minute (RPM) the piezoelectric film-based generator is able to produce up to 24 microwatts using 6 sets of films and the magnetic induction-based generator is capable of producing up to 125 milliwatts using 6 stacks of coil. As a proof of concept, a custom made localized heating system was constructed to test the capability of the magnetic induction-based generator. The heating system was able to achieve a temperature of 58.62 °C at 2200 RPM. This development of lab-on-a-disc micro power generators preserves the portability standards and enhances the future biomedical applications of centrifugal microfluidic platforms.

Planar-constructed spatial micro-stage

DOEpatents

Jokiel, Jr., Bernhard; Benavides, Gilbert L.; Bieg, Lothar F.; Allen, James J.

2004-01-13

A multiple degree of freedom platform assembly formed from a plurality of thin films on a substrate can, when activated, move out of the plane of the substrate without additional manufacturing steps. The platform is connected to the substrate by at least three linkages, each linkage being pivotally connected to the platform and the base. At least two of the base connections are to powered traveling devices that are manufactured at one end of a path and which may be moved to locations along the path to cause the platform to move to predetermined positions. The entire assembly, including hinges, is manufactured as planar structures; preferably by a thin film technology such as MEMS.

Predicting Active Users' Personality Based on Micro-Blogging Behaviors

PubMed Central

Hao, Bibo; Guan, Zengda; Zhu, Tingshao

2014-01-01

Because of its richness and availability, micro-blogging has become an ideal platform for conducting psychological research. In this paper, we proposed to predict active users' personality traits through micro-blogging behaviors. 547 Chinese active users of micro-blogging participated in this study. Their personality traits were measured by the Big Five Inventory, and digital records of micro-blogging behaviors were collected via web crawlers. After extracting 845 micro-blogging behavioral features, we first trained classification models utilizing Support Vector Machine (SVM), differentiating participants with high and low scores on each dimension of the Big Five Inventory. The classification accuracy ranged from 84% to 92%. We also built regression models utilizing PaceRegression methods, predicting participants' scores on each dimension of the Big Five Inventory. The Pearson correlation coefficients between predicted scores and actual scores ranged from 0.48 to 0.54. Results indicated that active users' personality traits could be predicted by micro-blogging behaviors. PMID:24465462

Genetic Constructor: An Online DNA Design Platform.

PubMed

Bates, Maxwell; Lachoff, Joe; Meech, Duncan; Zulkower, Valentin; Moisy, Anaïs; Luo, Yisha; Tekotte, Hille; Franziska Scheitz, Cornelia Johanna; Khilari, Rupal; Mazzoldi, Florencio; Chandran, Deepak; Groban, Eli

2017-12-15

Genetic Constructor is a cloud Computer Aided Design (CAD) application developed to support synthetic biologists from design intent through DNA fabrication and experiment iteration. The platform allows users to design, manage, and navigate complex DNA constructs and libraries, using a new visual language that focuses on functional parts abstracted from sequence. Features like combinatorial libraries and automated primer design allow the user to separate design from construction by focusing on functional intent, and design constraints aid iterative refinement of designs. A plugin architecture enables contributions from scientists and coders to leverage existing powerful software and connect to DNA foundries. The software is easily accessible and platform agnostic, free for academics, and available in an open-source community edition. Genetic Constructor seeks to democratize DNA design, manufacture, and access to tools and services from the synthetic biology community.

Flexible Wing Base Micro Aerial Vehicles: Micro Air Vehicles (MAVs) for Surveillance and Remote Sensor Delivery

NASA Technical Reports Server (NTRS)

Ifju, Peter

2002-01-01

Micro Air Vehicles (MAVs) will be developed for tracking individuals, locating terrorist threats, and delivering remote sensors, for surveillance and chemical/biological agent detection. The tasks are: (1) Develop robust MAV platform capable of carrying sensor payload. (2) Develop fully autonomous capabilities for delivery of sensors to remote and distant locations. The current capabilities and accomplishments are: (1) Operational electric (inaudible) 6-inch MAVs with novel flexible wing, providing superior aerodynamic efficiency and control. (2) Vision-based flight stability and control (from on-board cameras).

Enhanced guide-RNA design and targeting analysis for precise CRISPR genome editing of single and consortia of industrially relevant and non-model organisms.

PubMed

Mendoza, Brian J; Trinh, Cong T

2018-01-01

Genetic diversity of non-model organisms offers a repertoire of unique phenotypic features for exploration and cultivation for synthetic biology and metabolic engineering applications. To realize this enormous potential, it is critical to have an efficient genome editing tool for rapid strain engineering of these organisms to perform novel programmed functions. To accommodate the use of CRISPR/Cas systems for genome editing across organisms, we have developed a novel method, named CRISPR Associated Software for Pathway Engineering and Research (CASPER), for identifying on- and off-targets with enhanced predictability coupled with an analysis of non-unique (repeated) targets to assist in editing any organism with various endonucleases. Utilizing CASPER, we demonstrated a modest 2.4% and significant 30.2% improvement (F-test, P < 0.05) over the conventional methods for predicting on- and off-target activities, respectively. Further we used CASPER to develop novel applications in genome editing: multitargeting analysis (i.e. simultaneous multiple-site modification on a target genome with a sole guide-RNA requirement) and multispecies population analysis (i.e. guide-RNA design for genome editing across a consortium of organisms). Our analysis on a selection of industrially relevant organisms revealed a number of non-unique target sites associated with genes and transposable elements that can be used as potential sites for multitargeting. The analysis also identified shared and unshared targets that enable genome editing of single or multiple genomes in a consortium of interest. We envision CASPER as a useful platform to enhance the precise CRISPR genome editing for metabolic engineering and synthetic biology applications. https://github.com/TrinhLab/CASPER. ctrinh@utk.edu. Supplementary data are available at Bioinformatics online. © The Author (2017). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Benchmarking of TALE- and CRISPR/dCas9-Based Transcriptional Regulators in Mammalian Cells for the Construction of Synthetic Genetic Circuits.

PubMed

Lebar, Tina; Jerala, Roman

2016-10-21

Transcriptional activator-like effector (TALE)- and CRISPR/Cas9-based designable recognition domains represent a technological breakthrough not only for genome editing but also for building designed genetic circuits. Both platforms are able to target rarely occurring DNA segments, even within complex genomes. TALE and dCas9 domains, genetically fused to transcriptional regulatory domains, can be used for the construction of engineered logic circuits. Here we benchmarked the performance of the two platforms, targeting the same DNA sequences, to compare their advantages for the construction of designed circuits in mammalian cells. Optimal targeting strands for repression and activation of dCas9-based designed transcription factors were identified; both platforms exhibited good orthogonality and were used to construct functionally complete NOR gates. Although the CRISPR/dCas9 system is clearly easier to construct, TALE-based activators were significantly stronger, and the TALE-based platform performed better, especially for the construction of layered circuits.

miR-16-5p Is a Stably-Expressed Housekeeping MicroRNA in Breast Cancer Tissues from Primary Tumors and from Metastatic Sites

PubMed Central

Rinnerthaler, Gabriel; Hackl, Hubert; Gampenrieder, Simon Peter; Hamacher, Frank; Hufnagl, Clemens; Hauser-Kronberger, Cornelia; Zehentmayr, Franz; Fastner, Gerd; Sedlmayer, Felix; Mlineritsch, Brigitte; Greil, Richard

2016-01-01

For quantitative microRNA analyses in formalin-fixed paraffin-embedded (FFPE) tissue, expression levels have to be normalized to endogenous controls. To investigate the most stably-expressed microRNAs in breast cancer and its surrounding tissue, we used tumor samples from primary tumors and from metastatic sites. MiRNA profiling using TaqMan® Array Human MicroRNA Cards, enabling quantification of 754 unique human miRNAs, was performed in FFPE specimens from 58 patients with metastatic breast cancer. Forty-two (72%) samples were collected from primary tumors and 16 (28%) from metastases. In a cross-platform analysis of a validation cohort of 32 FFPE samples from patients with early breast cancer genome-wide microRNA expression analysis using SurePrintG3 miRNA (8 × 60 K)® microarrays from Agilent® was performed. Eleven microRNAs could be detected in all samples analyzed. Based on NormFinder and geNorm stability values and the high correlation (rho ≥ 0.8) with the median of all measured microRNAs, miR-16-5p, miR-29a-3p, miR-126-3p, and miR-222-3p are suitable single gene housekeeper candidates. In the cross-platform validation, 29 human microRNAs were strongly expressed (mean log2-intensity > 10) and 21 of these microRNAs including miR-16-5p and miR-29a-3p were also stably expressed (CV < 5%). Thus, miR-16-5p and miR-29a-3p are both strong housekeeper candidates. Their Normfinder stability values calculated across the primary tumor and metastases subgroup indicate that miR-29a-3p can be considered as the strongest housekeeper in a cohort with mainly samples from primary tumors, whereas miR-16-5p might perform better in a metastatic sample enriched cohort. PMID:26821018

miR-16-5p Is a Stably-Expressed Housekeeping MicroRNA in Breast Cancer Tissues from Primary Tumors and from Metastatic Sites.

PubMed

Rinnerthaler, Gabriel; Hackl, Hubert; Gampenrieder, Simon Peter; Hamacher, Frank; Hufnagl, Clemens; Hauser-Kronberger, Cornelia; Zehentmayr, Franz; Fastner, Gerd; Sedlmayer, Felix; Mlineritsch, Brigitte; Greil, Richard

2016-01-26

For quantitative microRNA analyses in formalin-fixed paraffin-embedded (FFPE) tissue, expression levels have to be normalized to endogenous controls. To investigate the most stably-expressed microRNAs in breast cancer and its surrounding tissue, we used tumor samples from primary tumors and from metastatic sites. MiRNA profiling using TaqMan(®) Array Human MicroRNA Cards, enabling quantification of 754 unique human miRNAs, was performed in FFPE specimens from 58 patients with metastatic breast cancer. Forty-two (72%) samples were collected from primary tumors and 16 (28%) from metastases. In a cross-platform analysis of a validation cohort of 32 FFPE samples from patients with early breast cancer genome-wide microRNA expression analysis using SurePrintG3 miRNA (8 × 60 K)(®) microarrays from Agilent(®) was performed. Eleven microRNAs could be detected in all samples analyzed. Based on NormFinder and geNorm stability values and the high correlation (rho ≥ 0.8) with the median of all measured microRNAs, miR-16-5p, miR-29a-3p, miR-126-3p, and miR-222-3p are suitable single gene housekeeper candidates. In the cross-platform validation, 29 human microRNAs were strongly expressed (mean log2-intensity > 10) and 21 of these microRNAs including miR-16-5p and miR-29a-3p were also stably expressed (CV < 5%). Thus, miR-16-5p and miR-29a-3p are both strong housekeeper candidates. Their Normfinder stability values calculated across the primary tumor and metastases subgroup indicate that miR-29a-3p can be considered as the strongest housekeeper in a cohort with mainly samples from primary tumors, whereas miR-16-5p might perform better in a metastatic sample enriched cohort.

MicroScope: a platform for microbial genome annotation and comparative genomics

PubMed Central

Vallenet, D.; Engelen, S.; Mornico, D.; Cruveiller, S.; Fleury, L.; Lajus, A.; Rouy, Z.; Roche, D.; Salvignol, G.; Scarpelli, C.; Médigue, C.

2009-01-01

The initial outcome of genome sequencing is the creation of long text strings written in a four letter alphabet. The role of in silico sequence analysis is to assist biologists in the act of associating biological knowledge with these sequences, allowing investigators to make inferences and predictions that can be tested experimentally. A wide variety of software is available to the scientific community, and can be used to identify genomic objects, before predicting their biological functions. However, only a limited number of biologically interesting features can be revealed from an isolated sequence. Comparative genomics tools, on the other hand, by bringing together the information contained in numerous genomes simultaneously, allow annotators to make inferences based on the idea that evolution and natural selection are central to the definition of all biological processes. We have developed the MicroScope platform in order to offer a web-based framework for the systematic and efficient revision of microbial genome annotation and comparative analysis (http://www.genoscope.cns.fr/agc/microscope). Starting with the description of the flow chart of the annotation processes implemented in the MicroScope pipeline, and the development of traditional and novel microbial annotation and comparative analysis tools, this article emphasizes the essential role of expert annotation as a complement of automatic annotation. Several examples illustrate the use of implemented tools for the review and curation of annotations of both new and publicly available microbial genomes within MicroScope’s rich integrated genome framework. The platform is used as a viewer in order to browse updated annotation information of available microbial genomes (more than 440 organisms to date), and in the context of new annotation projects (117 bacterial genomes). The human expertise gathered in the MicroScope database (about 280,000 independent annotations) contributes to improve the quality of microbial genome annotation, especially for genomes initially analyzed by automatic procedures alone. Database URLs: http://www.genoscope.cns.fr/agc/mage and http://www.genoscope.cns.fr/agc/microcyc PMID:20157493

MicroScope: a platform for microbial genome annotation and comparative genomics.

PubMed

Vallenet, D; Engelen, S; Mornico, D; Cruveiller, S; Fleury, L; Lajus, A; Rouy, Z; Roche, D; Salvignol, G; Scarpelli, C; Médigue, C

2009-01-01

The initial outcome of genome sequencing is the creation of long text strings written in a four letter alphabet. The role of in silico sequence analysis is to assist biologists in the act of associating biological knowledge with these sequences, allowing investigators to make inferences and predictions that can be tested experimentally. A wide variety of software is available to the scientific community, and can be used to identify genomic objects, before predicting their biological functions. However, only a limited number of biologically interesting features can be revealed from an isolated sequence. Comparative genomics tools, on the other hand, by bringing together the information contained in numerous genomes simultaneously, allow annotators to make inferences based on the idea that evolution and natural selection are central to the definition of all biological processes. We have developed the MicroScope platform in order to offer a web-based framework for the systematic and efficient revision of microbial genome annotation and comparative analysis (http://www.genoscope.cns.fr/agc/microscope). Starting with the description of the flow chart of the annotation processes implemented in the MicroScope pipeline, and the development of traditional and novel microbial annotation and comparative analysis tools, this article emphasizes the essential role of expert annotation as a complement of automatic annotation. Several examples illustrate the use of implemented tools for the review and curation of annotations of both new and publicly available microbial genomes within MicroScope's rich integrated genome framework. The platform is used as a viewer in order to browse updated annotation information of available microbial genomes (more than 440 organisms to date), and in the context of new annotation projects (117 bacterial genomes). The human expertise gathered in the MicroScope database (about 280,000 independent annotations) contributes to improve the quality of microbial genome annotation, especially for genomes initially analyzed by automatic procedures alone.Database URLs: http://www.genoscope.cns.fr/agc/mage and http://www.genoscope.cns.fr/agc/microcyc.

Load monitoring of aerospace structures utilizing micro-electro-mechanical systems for static and quasi-static loading conditions

NASA Astrophysics Data System (ADS)

Martinez, M.; Rocha, B.; Li, M.; Shi, G.; Beltempo, A.; Rutledge, R.; Yanishevsky, M.

2012-11-01

The National Research Council Canada (NRC) has worked on the development of structural health monitoring (SHM) test platforms for assessing the performance of sensor systems for load monitoring applications. The first SHM platform consists of a 5.5 m cantilever aluminum beam that provides an optimal scenario for evaluating the ability of a load monitoring system to measure bending, torsion and shear loads. The second SHM platform contains an added level of structural complexity, by consisting of aluminum skins with bonded/riveted stringers, typical of an aircraft lower wing structure. These two load monitoring platforms are well characterized and documented, providing loading conditions similar to those encountered during service. In this study, a micro-electro-mechanical system (MEMS) for acquiring data from triads of gyroscopes, accelerometers and magnetometers is described. The system was used to compute changes in angles at discrete stations along the platforms. The angles obtained from the MEMS were used to compute a second, third or fourth order degree polynomial surface from which displacements at every point could be computed. The use of a new Kalman filter was evaluated for angle estimation, from which displacements in the structure were computed. The outputs of the newly developed algorithms were then compared to the displacements obtained from the linear variable displacement transducers connected to the platforms. The displacement curves were subsequently post-processed either analytically, or with the help of a finite element model of the structure, to estimate strains and loads. The estimated strains were compared with baseline strain gauge instrumentation installed on the platforms. This new approach for load monitoring was able to provide accurate estimates of applied strains and shear loads.

MicroScope in 2017: an expanding and evolving integrated resource for community expertise of microbial genomes.

PubMed

Vallenet, David; Calteau, Alexandra; Cruveiller, Stéphane; Gachet, Mathieu; Lajus, Aurélie; Josso, Adrien; Mercier, Jonathan; Renaux, Alexandre; Rollin, Johan; Rouy, Zoe; Roche, David; Scarpelli, Claude; Médigue, Claudine

2017-01-04

The annotation of genomes from NGS platforms needs to be automated and fully integrated. However, maintaining consistency and accuracy in genome annotation is a challenging problem because millions of protein database entries are not assigned reliable functions. This shortcoming limits the knowledge that can be extracted from genomes and metabolic models. Launched in 2005, the MicroScope platform (http://www.genoscope.cns.fr/agc/microscope) is an integrative resource that supports systematic and efficient revision of microbial genome annotation, data management and comparative analysis. Effective comparative analysis requires a consistent and complete view of biological data, and therefore, support for reviewing the quality of functional annotation is critical. MicroScope allows users to analyze microbial (meta)genomes together with post-genomic experiment results if any (i.e. transcriptomics, re-sequencing of evolved strains, mutant collections, phenotype data). It combines tools and graphical interfaces to analyze genomes and to perform the expert curation of gene functions in a comparative context. Starting with a short overview of the MicroScope system, this paper focuses on some major improvements of the Web interface, mainly for the submission of genomic data and on original tools and pipelines that have been developed and integrated in the platform: computation of pan-genomes and prediction of biosynthetic gene clusters. Today the resource contains data for more than 6000 microbial genomes, and among the 2700 personal accounts (65% of which are now from foreign countries), 14% of the users are performing expert annotations, on at least a weekly basis, contributing to improve the quality of microbial genome annotations. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Bio-barcode gel assay for microRNA

NASA Astrophysics Data System (ADS)

Lee, Hyojin; Park, Jeong-Eun; Nam, Jwa-Min

2014-02-01

MicroRNA has been identified as a potential biomarker because expression level of microRNA is correlated with various cancers. Its detection at low concentrations would be highly beneficial for cancer diagnosis. Here, we develop a new type of a DNA-modified gold nanoparticle-based bio-barcode assay that uses a conventional gel electrophoresis platform and potassium cyanide chemistry and show this assay can detect microRNA at aM levels without enzymatic amplification. It is also shown that single-base-mismatched microRNA can be differentiated from perfectly matched microRNA and the multiplexed detection of various combinations of microRNA sequences is possible with this approach. Finally, differently expressed microRNA levels are selectively detected from cancer cells using the bio-barcode gel assay, and the results are compared with conventional polymerase chain reaction-based results. The method and results shown herein pave the way for practical use of a conventional gel electrophoresis for detecting biomolecules of interest even at aM level without polymerase chain reaction amplification.

Effect of roughened micro-threaded implant neck 
and platform switching on marginal bone loss: 
a multicenter retrospective study with 6-year follow-up.

PubMed

Di Stefano, Danilo Alessio; Giacometti, Edoardo; Greco, Gian Battista; Gastaldi, Giorgio; Gherlone, Enrico

2016-01-01

The aim of this retrospective study was to evaluate medium-term marginal peri-implant bone loss following placement of root-form implants featuring a micro-threaded rough-surfaced neck and a platform-switched implant-abutment connection. Records were identified of patients treated with such implants over a 3-year period at three Italian dental centers. Patient radiographs were digitized and subjected to computerized analysis of peri-implant bone resorption. Records of 112 patients who received 257 implants were analyzed. Although implant diameters and lengths varied, all had a 0.3-mm platform-switching width and a 2.5-mm high micro-threaded neck. All patients healed uneventfully, and no peri-implant infection, implant mobility, or radiolucency around the implant were detected at any follow-up control. At the 72-month control (average 71 ± 5 months) all implants were successful according to Albrektsson and Zarb's criteria. At implant level, average peri-implant bone resorption was 0.18 ± 0.12 mm at 6 months, 0.22 ± 0.15 mm at 12 months, 0.23 ± 0.16 mm at 24 months, 0.25 ± 0.17 mm at 36 months, 0.26 ± 0.15 mm at 48 months, and stable at subsequent controls, regardless of the implant diameter and length. At patient level, a similar trend was observed, with crestal bone loss stabilizing from 48 months onward. The surface, geometry, and platform-switching features of the implant under investigation allowed effective bone preservation on a medium-term basis.

PREFACE: MicroTherm' 2013 - Microtechnology and Thermal Problems in Electronics

NASA Astrophysics Data System (ADS)

Lisik, Zbigniew; Raj, Ewa

2014-04-01

MicroTherm is an International Conference on Microtechnology and Thermal Problems in Electronics organised as a cyclic event since 1996. The success of the first seminar, which was devoted mainly to thermal management aspects, and the successive conferences have led us to the tenth edition. Since the first meeting, the scope of the conference has expanded, following the progress of electronics. Now, it covers subjects connected with extreme temperature, electronics, sensors and measurement techniques, modelling, simulation, wide band-gap materials, packaging and reliability, renewable energy sources and photonics with special emphasis on microelectronic technologies. MicroTherm' 2013 was held in Lodz, Poland, on 25-28 June 2013. The programme consistied of invited talks and nine regular sessions in the form of planar discussions and poster presentations, including a Students' Session. The Students' session gave an opportunity for students and young researchers to present their first achievements in the field of science. The next MicroTherm Conference is going to be held on 22-25 June 2015, in Lodz — a beautiful, post-industrial city located in the centre of Poland. Please, feel invited to MicroTherm' 2015 (www.microtherm.dsod.pl). Ewa Raj and Zbigniew Lisik Editors

Micro- and nanodevices integrated with biomolecular probes

PubMed Central

Alapan, Yunus; Icoz, Kutay; Gurkan, Umut A.

2016-01-01

Understanding how biomolecules, proteins and cells interact with their surroundings and other biological entities has become the fundamental design criterion for most biomedical micro- and nanodevices. Advances in biology, medicine, and nanofabrication technologies complement each other and allow us to engineer new tools based on biomolecules utilized as probes. Engineered micro/nanosystems and biomolecules in nature have remarkably robust compatibility in terms of function, size, and physical properties. This article presents the state of the art in micro- and nanoscale devices designed and fabricated with biomolecular probes as their vital constituents. General design and fabrication concepts are presented and three major platform technologies are highlighted: microcantilevers, micro/nanopillars, and microfluidics. Overview of each technology, typical fabrication details, and application areas are presented by emphasizing significant achievements, current challenges, and future opportunities. PMID:26363089

Social Networks and the Building of Learning Communities: An Experimental Study of a Social MOOC

ERIC Educational Resources Information Center

de Lima, Mariana; Zorrilla, Marta

2017-01-01

This study aimed to analyze the student's behaviour in relation to their degree of commitment, participation, and contribution in a MOOC based on a social learning approach. Interaction data was collected on the learning platform and in social networks, both of which were used in the third edition of a social MOOC course. This data was then…

A Cas9 transgenic Plasmodium yoelii parasite for efficient gene editing.

PubMed

Qian, Pengge; Wang, Xu; Yang, Zhenke; Li, Zhenkui; Gao, Han; Su, Xin-Zhuan; Cui, Huiting; Yuan, Jing

2018-06-01

The RNA-guided endonuclease Cas9 has applied as an efficient gene-editing method in malaria parasite Plasmodium. However, the size (4.2 kb) of the commonly used Cas9 from Streptococcus pyogenes (SpCas9) limits its utility for genome editing in the parasites only introduced with cas9 plasmid. To establish the endogenous and constitutive expression of Cas9 protein in the rodent malaria parasite P. yoelii, we replaced the coding region of an endogenous gene sera1 with the intact SpCas9 coding sequence using the CRISPR/Cas9-mediated genome editing method, generating the cas9-knockin parasite (PyCas9ki) of the rodent malaria parasite P. yoelii. The resulted PyCas9ki parasite displays normal progression during the whole life cycle and possesses the Cas9 protein expression in asexual blood stage. By introducing the plasmid (pYCs) containing only sgRNA and homologous template elements, we successfully achieved both deletion and tagging modifications for different endogenous genes in the genome of PyCas9ki parasite. This cas9-knockin PyCas9ki parasite provides a new platform facilitating gene functions study in the rodent malaria parasite P. yoelii. Copyright © 2018 Elsevier B.V. All rights reserved.

CRISPR/Cas9-loxP-Mediated Gene Editing as a Novel Site-Specific Genetic Manipulation Tool.

PubMed

Yang, Fayu; Liu, Changbao; Chen, Ding; Tu, Mengjun; Xie, Haihua; Sun, Huihui; Ge, Xianglian; Tang, Lianchao; Li, Jin; Zheng, Jiayong; Song, Zongming; Qu, Jia; Gu, Feng

2017-06-16

Cre-loxP, as one of the site-specific genetic manipulation tools, offers a method to study the spatial and temporal regulation of gene expression/inactivation in order to decipher gene function. CRISPR/Cas9-mediated targeted genome engineering technologies are sparking a new revolution in biological research. Whether the traditional site-specific genetic manipulation tool and CRISPR/Cas9 could be combined to create a novel genetic tool for highly specific gene editing is not clear. Here, we successfully generated a CRISPR/Cas9-loxP system to perform gene editing in human cells, providing the proof of principle that these two technologies can be used together for the first time. We also showed that distinct non-homologous end-joining (NHEJ) patterns from CRISPR/Cas9-mediated gene editing of the targeting sequence locates at the level of plasmids (episomal) and chromosomes. Specially, the CRISPR/Cas9-mediated NHEJ pattern in the nuclear genome favors deletions (64%-68% at the human AAVS1 locus versus 4%-28% plasmid DNA). CRISPR/Cas9-loxP, a novel site-specific genetic manipulation tool, offers a platform for the dissection of gene function and molecular insights into DNA-repair pathways. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Improvements in algal lipid production: a systems biology and gene editing approach.

PubMed

Banerjee, Avik; Banerjee, Chiranjib; Negi, Sangeeta; Chang, Jo-Shu; Shukla, Pratyoosh

2018-05-01

In the wake of rising energy demands, microalgae have emerged as potential sources of sustainable and renewable carbon-neutral fuels, such as bio-hydrogen and bio-oil. For rational metabolic engineering, the elucidation of metabolic pathways in fine detail and their manipulation according to requirements is the key to exploiting the use of microalgae. Emergence of site-specific nucleases have revolutionized applied research leading to biotechnological gains. Genome engineering as well as modulation of the endogenous genome with high precision using CRISPR systems is being gradually employed in microalgal research. Further, to optimize and produce better algal platforms, use of systems biology network analysis and integration of omics data is required. This review discusses two important approaches: systems biology and gene editing strategies used on microalgal systems with a focus on biofuel production and sustainable solutions. It also emphasizes that the integration of such systems would contribute and compliment applied research on microalgae. Recent advances in microalgae are discussed, including systems biology, gene editing approaches in lipid bio-synthesis, and antenna engineering. Lastly, it has been attempted here to showcase how CRISPR/Cas systems are a better editing tool than existing techniques that can be utilized for gene modulation and engineering during biofuel production.

CRISPR/Cas9-mediated gene editing in human tripronuclear zygotes.

PubMed

Liang, Puping; Xu, Yanwen; Zhang, Xiya; Ding, Chenhui; Huang, Rui; Zhang, Zhen; Lv, Jie; Xie, Xiaowei; Chen, Yuxi; Li, Yujing; Sun, Ying; Bai, Yaofu; Songyang, Zhou; Ma, Wenbin; Zhou, Canquan; Huang, Junjiu

2015-05-01

Genome editing tools such as the clustered regularly interspaced short palindromic repeat (CRISPR)-associated system (Cas) have been widely used to modify genes in model systems including animal zygotes and human cells, and hold tremendous promise for both basic research and clinical applications. To date, a serious knowledge gap remains in our understanding of DNA repair mechanisms in human early embryos, and in the efficiency and potential off-target effects of using technologies such as CRISPR/Cas9 in human pre-implantation embryos. In this report, we used tripronuclear (3PN) zygotes to further investigate CRISPR/Cas9-mediated gene editing in human cells. We found that CRISPR/Cas9 could effectively cleave the endogenous β-globin gene (HBB). However, the efficiency of homologous recombination directed repair (HDR) of HBB was low and the edited embryos were mosaic. Off-target cleavage was also apparent in these 3PN zygotes as revealed by the T7E1 assay and whole-exome sequencing. Furthermore, the endogenous delta-globin gene (HBD), which is homologous to HBB, competed with exogenous donor oligos to act as the repair template, leading to untoward mutations. Our data also indicated that repair of the HBB locus in these embryos occurred preferentially through the non-crossover HDR pathway. Taken together, our work highlights the pressing need to further improve the fidelity and specificity of the CRISPR/Cas9 platform, a prerequisite for any clinical applications of CRSIPR/Cas9-mediated editing.

High-flux ionic diodes, ionic transistors and ionic amplifiers based on external ion concentration polarization by an ion exchange membrane: a new scalable ionic circuit platform.

PubMed

Sun, Gongchen; Senapati, Satyajyoti; Chang, Hsueh-Chia

2016-04-07

A microfluidic ion exchange membrane hybrid chip is fabricated using polymer-based, lithography-free methods to achieve ionic diode, transistor and amplifier functionalities with the same four-terminal design. The high ionic flux (>100 μA) feature of the chip can enable a scalable integrated ionic circuit platform for micro-total-analytical systems.

Dynamic photopatterning of cells in situ by Q-switched neodymium-doped yttrium ortho-vanadate laser.

PubMed

Deka, Gitanjal; Okano, Kazunori; Kao, Fu-Jen

2014-01-01

Cellular micropattering has been increasingly adopted in quantitative biological experiments. A Q-switched pulsed neodymium-doped yttrium ortho-vanadate (Nd∶YVO4) laser directed in-situ microfabrication technique for cell patterning is presented. A platform is designed uniquely to achieve laser ablation. The platform is comprised of thin gold coating over a glass surface that functions as a thermal transducer and is over-layered by a cell repellant polymer layer. Micropatterns are engraved on the platform, subsequently exposing specific cell adhesive micro-domains by ablating the gold-polymer coating photothermally. Experimental results indicate that the proposed approach is applicable under culture conditions, viable toward cells, and has a higher engraving speed. Possible uses in arraying isolated single cells on the platform are also shown. Additionally, based on those micro-patterns, dynamic cellular morphological changes and migrational speed in response to geometrical barriers are studied to demonstrate the potential applications of the proposed approach. Our results further demonstrate that cells in narrower geometry had elongated shapes and higher migrational speed than those in wider geometry. Importantly, the proposed approach will provide a valuable reference for efforts to study single cell dynamics and cellular migration related processes for areas such as cell division, wound healing, and cancer invasion.

Array Phase Shifters: Theory and Technology

NASA Technical Reports Server (NTRS)

Romanofsky, Robert R.

2007-01-01

While there are a myriad of applications for microwave phase shifters in instrumentation and metrology, power combining, amplifier linearization, and so on, the most prevalent use is in scanning phased-array antennas. And while this market continues to be dominated by military radar and tracking platforms, many commercial applications have emerged in the past decade or so. These new and potential applications span low-Earth-orbit (LEO) communications satellite constellations and collision warning radar, an aspect of the Intelligent Vehicle Highway System or Automated Highway System. In any case, the phase shifters represent a considerable portion of the overall antenna cost, with some estimates approaching 40 percent for receive arrays. Ferrite phase shifters continue to be the workhorse in military-phased arrays, and while there have been advances in thin film ferrite devices, the review of this device technology in the previous edition of this book is still highly relevant. This chapter will focus on three types of phase shifters that have matured in the past decade: GaAs MESFET monolithic microwave integrated circuit (MMIC), micro-electromechanical systems (MEMS), and thin film ferroelectric-based devices. A brief review of some novel devices including thin film ferrite phase shifters and superconducting switches for phase shifter applications will be provided. Finally, the effects of modulo 2 phase shift limitations, phase errors, and transient response on bit error rate degradation will be considered.

mirEX: a platform for comparative exploration of plant pri-miRNA expression data.

PubMed

Bielewicz, Dawid; Dolata, Jakub; Zielezinski, Andrzej; Alaba, Sylwia; Szarzynska, Bogna; Szczesniak, Michal W; Jarmolowski, Artur; Szweykowska-Kulinska, Zofia; Karlowski, Wojciech M

2012-01-01

mirEX is a comprehensive platform for comparative analysis of primary microRNA expression data. RT-qPCR-based gene expression profiles are stored in a universal and expandable database scheme and wrapped by an intuitive user-friendly interface. A new way of accessing gene expression data in mirEX includes a simple mouse operated querying system and dynamic graphs for data mining analyses. In contrast to other publicly available databases, the mirEX interface allows a simultaneous comparison of expression levels between various microRNA genes in diverse organs and developmental stages. Currently, mirEX integrates information about the expression profile of 190 Arabidopsis thaliana pri-miRNAs in seven different developmental stages: seeds, seedlings and various organs of mature plants. Additionally, by providing RNA structural models, publicly available deep sequencing results, experimental procedure details and careful selection of auxiliary data in the form of web links, mirEX can function as a one-stop solution for Arabidopsis microRNA information. A web-based mirEX interface can be accessed at http://bioinfo.amu.edu.pl/mirex.

Integrated microfluidic devices for combinatorial cell-based assays.

PubMed

Yu, Zeta Tak For; Kamei, Ken-ichiro; Takahashi, Hiroko; Shu, Chengyi Jenny; Wang, Xiaopu; He, George Wenfu; Silverman, Robert; Radu, Caius G; Witte, Owen N; Lee, Ki-Bum; Tseng, Hsian-Rong

2009-06-01

The development of miniaturized cell culture platforms for performing parallel cultures and combinatorial assays is important in cell biology from the single-cell level to the system level. In this paper we developed an integrated microfluidic cell-culture platform, Cell-microChip (Cell-microChip), for parallel analyses of the effects of microenvironmental cues (i.e., culture scaffolds) on different mammalian cells and their cellular responses to external stimuli. As a model study, we demonstrated the ability of culturing and assaying several mammalian cells, such as NIH 3T3 fibroblast, B16 melanoma and HeLa cell lines, in a parallel way. For functional assays, first we tested drug-induced apoptotic responses from different cell lines. As a second functional assay, we performed "on-chip" transfection of a reporter gene encoding an enhanced green fluorescent protein (EGFP) followed by live-cell imaging of transcriptional activation of cyclooxygenase 2 (Cox-2) expression. Collectively, our Cell-microChip approach demonstrated the capability to carry out parallel operations and the potential to further integrate advanced functions and applications in the broader space of combinatorial chemistry and biology.

Design and Development of Micro-Power Generating Device for Biomedical Applications of Lab-on-a-Disc

PubMed Central

Joseph, Karunan; Ibrahim, Fatimah; Cho, Jongman; Thio, Tzer Hwai Gilbert; Al-Faqheri, Wisam; Madou, Marc

2015-01-01

The development of micro-power generators for centrifugal microfluidic discs enhances the platform as a green point-of-care diagnostic system and eliminates the need for attaching external peripherals to the disc. In this work, we present micro-power generators that harvest energy from the disc’s rotational movement to power biomedical applications on the disc. To implement these ideas, we developed two types of micro-power generators using piezoelectric films and an electromagnetic induction system. The piezoelectric-based generator takes advantage of the film’s vibration during the disc’s rotational motion, whereas the electromagnetic induction-based generator operates on the principle of current generation in stacks of coil exposed to varying magnetic flux. We have successfully demonstrated that at the spinning speed of 800 revolutions per minute (RPM) the piezoelectric film-based generator is able to produce up to 24 microwatts using 6 sets of films and the magnetic induction-based generator is capable of producing up to 125 milliwatts using 6 stacks of coil. As a proof of concept, a custom made localized heating system was constructed to test the capability of the magnetic induction-based generator. The heating system was able to achieve a temperature of 58.62°C at 2200 RPM. This development of lab-on-a-disc micro power generators preserves the portability standards and enhances the future biomedical applications of centrifugal microfluidic platforms. PMID:26422249

An in-mold packaging process for plastic fluidic devices.

PubMed

Yoo, Y E; Lee, K H; Je, T J; Choi, D S; Kim, S K

2011-01-01

Micro or nanofluidic devices have many channel shapes to deliver chemical solutions, body fluids or any fluids. The channels in these devices should be covered to prevent the fluids from overflowing or leaking. A typical method to fabricate an enclosed channel is to bond or weld a cover plate to a channel plate. This solid-to-solid bonding process, however, takes a considerable amount of time for mass production. In this study, a new process for molding a cover layer that can enclose open micro or nanochannels without solid-to-solid bonding is proposed and its feasibility is estimated. First, based on the design of a model microchannel, a brass microchannel master core was machined and a plastic microchannel platform was injection-molded. Using this molded platform, a series of experiments was performed for four process or mold design parameters. Some feasible conditions were successfully found to enclosed channels without filling the microchannels for the injection molding of a cover layer over the plastic microchannel platform. In addition, the bond strength and seal performance were estimated in a comparison with those done by conventional bonding or welding processes.

Ras plasma membrane signalling platforms

PubMed Central

2005-01-01

The plasma membrane is a complex, dynamic structure that provides platforms for the assembly of many signal transduction pathways. These platforms have the capacity to impose an additional level of regulation on cell signalling networks. In this review, we will consider specifically how Ras proteins interact with the plasma membrane. The focus will be on recent studies that provide novel spatial and dynamic insights into the micro-environments that different Ras proteins utilize for signal transduction. We will correlate these recent studies suggesting Ras proteins might operate within a heterogeneous plasma membrane with earlier biochemical work on Ras signal transduction. PMID:15954863

A Hardware Platform for Tuning of MEMS Devices Using Closed-Loop Frequency Response

NASA Technical Reports Server (NTRS)

Ferguson, Michael I.; MacDonald, Eric; Foor, David

2005-01-01

We report on the development of a hardware platform for integrated tuning and closed-loop operation of MEMS gyroscopes. The platform was developed and tested for the second generation JPL/Boeing Post-Resonator MEMS gyroscope. The control of this device is implemented through a digital design on a Field Programmable Gate Array (FPGA). A software interface allows the user to configure, calibrate, and tune the bias voltages on the micro-gyro. The interface easily transitions to an embedded solution that allows for the miniaturization of the system to a single chip.

CRISPR/Cas9 in Genome Editing and Beyond.

PubMed

Wang, Haifeng; La Russa, Marie; Qi, Lei S

2016-06-02

The Cas9 protein (CRISPR-associated protein 9), derived from type II CRISPR (clustered regularly interspaced short palindromic repeats) bacterial immune systems, is emerging as a powerful tool for engineering the genome in diverse organisms. As an RNA-guided DNA endonuclease, Cas9 can be easily programmed to target new sites by altering its guide RNA sequence, and its development as a tool has made sequence-specific gene editing several magnitudes easier. The nuclease-deactivated form of Cas9 further provides a versatile RNA-guided DNA-targeting platform for regulating and imaging the genome, as well as for rewriting the epigenetic status, all in a sequence-specific manner. With all of these advances, we have just begun to explore the possible applications of Cas9 in biomedical research and therapeutics. In this review, we describe the current models of Cas9 function and the structural and biochemical studies that support it. We focus on the applications of Cas9 for genome editing, regulation, and imaging, discuss other possible applications and some technical considerations, and highlight the many advantages that CRISPR/Cas9 technology offers.

Gene Drive for Mosquito Control: Where Did It Come from and Where Are We Headed?

PubMed Central

Macias, Vanessa M.; Ohm, Johanna R.; Rasgon, Jason L.

2017-01-01

Mosquito-borne pathogens place an enormous burden on human health. The existing toolkit is insufficient to support ongoing vector-control efforts towards meeting disease elimination and eradication goals. The perspective that genetic approaches can potentially add a significant set of tools toward mosquito control is not new, but the recent improvements in site-specific gene editing with CRISPR/Cas9 systems have enhanced our ability to both study mosquito biology using reverse genetics and produce genetics-based tools. Cas9-mediated gene-editing is an efficient and adaptable platform for gene drive strategies, which have advantages over innundative release strategies for introgressing desirable suppression and pathogen-blocking genotypes into wild mosquito populations; until recently, an effective gene drive has been largely out of reach. Many considerations will inform the effective use of new genetic tools, including gene drives. Here we review the lengthy history of genetic advances in mosquito biology and discuss both the impact of efficient site-specific gene editing on vector biology and the resulting potential to deploy new genetic tools for the abatement of mosquito-borne disease. PMID:28869513

Automated 3D bioassembly of micro-tissues for biofabrication of hybrid tissue engineered constructs.

PubMed

Mekhileri, N V; Lim, K S; Brown, G C J; Mutreja, I; Schon, B S; Hooper, G J; Woodfield, T B F

2018-01-12

Bottom-up biofabrication approaches combining micro-tissue fabrication techniques with extrusion-based 3D printing of thermoplastic polymer scaffolds are emerging strategies in tissue engineering. These biofabrication strategies support native self-assembly mechanisms observed in developmental stages of tissue or organoid growth as well as promoting cell-cell interactions and cell differentiation capacity. Few technologies have been developed to automate the precise assembly of micro-tissues or tissue modules into structural scaffolds. We describe an automated 3D bioassembly platform capable of fabricating simple hybrid constructs via a two-step bottom-up bioassembly strategy, as well as complex hybrid hierarchical constructs via a multistep bottom-up bioassembly strategy. The bioassembly system consisted of a fluidic-based singularisation and injection module incorporated into a commercial 3D bioprinter. The singularisation module delivers individual micro-tissues to an injection module, for insertion into precise locations within a 3D plotted scaffold. To demonstrate applicability for cartilage tissue engineering, human chondrocytes were isolated and micro-tissues of 1 mm diameter were generated utilising a high throughput 96-well plate format. Micro-tissues were singularised with an efficiency of 96.0 ± 5.1%. There was no significant difference in size, shape or viability of micro-tissues before and after automated singularisation and injection. A layer-by-layer approach or aforementioned bottom-up bioassembly strategy was employed to fabricate a bilayered construct by alternatively 3D plotting a thermoplastic (PEGT/PBT) polymer scaffold and inserting pre-differentiated chondrogenic micro-tissues or cell-laden gelatin-based (GelMA) hydrogel micro-spheres, both formed via high-throughput fabrication techniques. No significant difference in viability between the construct assembled utilising the automated bioassembly system and manually assembled construct was observed. Bioassembly of pre-differentiated micro-tissues as well as chondrocyte-laden hydrogel micro-spheres demonstrated the flexibility of the platform while supporting tissue fusion, long-term cell viability, and deposition of cartilage-specific extracellular matrix proteins. This technology provides an automated and scalable pathway for bioassembly of both simple and complex 3D tissue constructs of clinically relevant shape and size, with demonstrated capability to facilitate direct spatial organisation and hierarchical 3D assembly of micro-tissue modules, ranging from biomaterial free cell pellets to cell-laden hydrogel formulations.

Developing cloud applications using the e-Science Central platform.

PubMed

Hiden, Hugo; Woodman, Simon; Watson, Paul; Cala, Jacek

2013-01-28

This paper describes the e-Science Central (e-SC) cloud data processing system and its application to a number of e-Science projects. e-SC provides both software as a service (SaaS) and platform as a service for scientific data management, analysis and collaboration. It is a portable system and can be deployed on both private (e.g. Eucalyptus) and public clouds (Amazon AWS and Microsoft Windows Azure). The SaaS application allows scientists to upload data, edit and run workflows and share results in the cloud, using only a Web browser. It is underpinned by a scalable cloud platform consisting of a set of components designed to support the needs of scientists. The platform is exposed to developers so that they can easily upload their own analysis services into the system and make these available to other users. A representational state transfer-based application programming interface (API) is also provided so that external applications can leverage the platform's functionality, making it easier to build scalable, secure cloud-based applications. This paper describes the design of e-SC, its API and its use in three different case studies: spectral data visualization, medical data capture and analysis, and chemical property prediction.

Developing cloud applications using the e-Science Central platform

PubMed Central

Hiden, Hugo; Woodman, Simon; Watson, Paul; Cala, Jacek

2013-01-01

This paper describes the e-Science Central (e-SC) cloud data processing system and its application to a number of e-Science projects. e-SC provides both software as a service (SaaS) and platform as a service for scientific data management, analysis and collaboration. It is a portable system and can be deployed on both private (e.g. Eucalyptus) and public clouds (Amazon AWS and Microsoft Windows Azure). The SaaS application allows scientists to upload data, edit and run workflows and share results in the cloud, using only a Web browser. It is underpinned by a scalable cloud platform consisting of a set of components designed to support the needs of scientists. The platform is exposed to developers so that they can easily upload their own analysis services into the system and make these available to other users. A representational state transfer-based application programming interface (API) is also provided so that external applications can leverage the platform's functionality, making it easier to build scalable, secure cloud-based applications. This paper describes the design of e-SC, its API and its use in three different case studies: spectral data visualization, medical data capture and analysis, and chemical property prediction. PMID:23230161

Micro- and nanodevices integrated with biomolecular probes.

PubMed

Alapan, Yunus; Icoz, Kutay; Gurkan, Umut A

2015-12-01

Understanding how biomolecules, proteins and cells interact with their surroundings and other biological entities has become the fundamental design criterion for most biomedical micro- and nanodevices. Advances in biology, medicine, and nanofabrication technologies complement each other and allow us to engineer new tools based on biomolecules utilized as probes. Engineered micro/nanosystems and biomolecules in nature have remarkably robust compatibility in terms of function, size, and physical properties. This article presents the state of the art in micro- and nanoscale devices designed and fabricated with biomolecular probes as their vital constituents. General design and fabrication concepts are presented and three major platform technologies are highlighted: microcantilevers, micro/nanopillars, and microfluidics. Overview of each technology, typical fabrication details, and application areas are presented by emphasizing significant achievements, current challenges, and future opportunities. Copyright © 2015 Elsevier Inc. All rights reserved.

Electroosmotic pumps and their applications in microfluidic systems

PubMed Central

Wang, Xiayan; Cheng, Chang; Wang, Shili; Liu, Shaorong

2009-01-01

Electroosmotic pumping is receiving increasing attention in recent years owing to the rapid development in micro total analytical systems. Compared with other micropumps, electroosmotic pumps (EOPs) offer a number of advantages such as creation of constant pulse-free flows and elimination of moving parts. The flow rates and pumping pressures of EOPs matches well with micro analysis systems. The common materials and fabrication technologies make it readily integrateable with lab-on-a-chip devices. This paper reviews the recent progress on EOP fabrications and applications in order to promote the awareness of EOPs to researchers interested in using micro- and nano-fluidic devices. The pros and cons of EOPs are also discussed, which helps these researchers in designing and constructing their micro platforms. PMID:20126306

Fuselet Authoring, Execution, and Management in Support of Global Strike Operations

DTIC Science & Technology

2008-07-01

can be implemented in a variety of languages such as Java , Extensible Stylesheet Language Transformations (XSLT), Groovy, and Jython. A primary...measurable and manageable. By creating transformations from reusable, parameterizable components rather than ad-hoc scripts , transformation logic is...deployable to any Java 2 Platform, Enterprise Edition (J2EE) server, but is tested regularly on the JBoss Application Server (AS) version 4.0.4.GA

76 FR 43263 - Application(s) for Duty-Free Entry of Scientific Instruments

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-20

.... Instrument: Nano test platform. Manufacturer: Micro Materials Ltd., UK. Intended Use: The instrument will be... will be used to study nano-scale domain formation associated with phase [[Page 43264

High resolution microphotonic needle for endoscopic imaging (Conference Presentation)

NASA Astrophysics Data System (ADS)

Tadayon, Mohammad Amin; Mohanty, Aseema; Roberts, Samantha P.; Barbosa, Felippe; Lipson, Michal

2017-02-01

GRIN (Graded index) lens have revolutionized micro endoscopy enabling deep tissue imaging with high resolution. The challenges of traditional GRIN lenses are their large size (when compared with the field of view) and their limited resolution. This is because of the relatively weak NA in standard graded index lenses. Here we introduce a novel micro-needle platform for endoscopy with much higher resolution than traditional GRIN lenses and a FOV that corresponds to the whole cross section of the needle. The platform is based on polymeric (SU-8) waveguide integrated with a microlens micro fabricated on a silicon substrate using a unique molding process. Due to the high index of refraction of the material the NA of the needle is much higher than traditional GRIN lenses. We tested the probe in a fluorescent dye solution (19.6 µM Alexa Flour 647 solution) and measured a numerical aperture of 0.25, focal length of about 175 µm and minimal spot size of about 1.6 µm. We show that the platform can image a sample with the field of view corresponding to the cross sectional area of the waveguide (80x100 µm2). The waveguide size can in principle be modified to vary size of the imaging field of view. This demonstration, combined with our previous work demonstrating our ability to implant the high NA needle in a live animal, shows that the proposed system can be used for deep tissue imaging with very high resolution and high field of view.

BioMEMS –Advancing the Frontiers of Medicine

PubMed Central

James, Teena; Mannoor, Manu Sebastian; Ivanov, Dentcho V.

2008-01-01

Biological and medical application of micro-electro-mechanical-systems (MEMS) is currently seen as an area of high potential impact. Integration of biology and microtechnology has resulted in the development of a number of platforms for improving biomedical and pharmaceutical technologies. This review provides a general overview of the applications and the opportunities presented by MEMS in medicine by classifying these platforms according to their applications in the medical field. PMID:27873858

Effects of Contributor Experience on the Quality of Health-Related Wikipedia Articles

PubMed Central

Fetahu, Besnik; Kimmerle, Joachim

2018-01-01

Background Consulting the Internet for health-related information is a common and widespread phenomenon, and Wikipedia is arguably one of the most important resources for health-related information. Therefore, it is relevant to identify factors that have an impact on the quality of health-related Wikipedia articles. Objective In our study we have hypothesized a positive effect of contributor experience on the quality of health-related Wikipedia articles. Methods We mined the edit history of all (as of February 2017) 18,805 articles that were listed in the categories on the portal health & fitness in the English language version of Wikipedia. We identified tags within the articles’ edit histories, which indicated potential issues with regard to the respective article’s quality or neutrality. Of all of the sampled articles, 99 (99/18,805, 0.53%) articles had at some point received at least one such tag. In our analysis we only considered those articles with a minimum of 10 edits (10,265 articles in total; 96 tagged articles, 0.94%). Additionally, to test our hypothesis, we constructed contributor profiles, where a profile consisted of all the articles edited by a contributor and the corresponding number of edits contributed. We did not differentiate between rollbacks and edits with novel content. Results Nonparametric Mann-Whitney U-tests indicated a higher number of previously edited articles for editors of the nontagged articles (mean rank tagged 2348.23, mean rank nontagged 5159.29; U=9.25, P<.001). However, we did not find a significant difference for the contributors’ total number of edits (mean rank tagged 4872.85, mean rank nontagged 5135.48; U=0.87, P=.39). Using logistic regression analysis with the respective article’s number of edits and number of editors as covariates, only the number of edited articles yielded a significant effect on the article’s status as tagged versus nontagged (dummy-coded; Nagelkerke R2 for the full model=.17; B [SE B]=-0.001 [0.00]; Wald c2 [1]=19.70; P<.001), whereas we again found no significant effect for the mere number of edits (Nagelkerke R2 for the full model=.15; B [SE B]=0.000 [0.01]; Wald c2 [1]=0.01; P=.94). Conclusions Our findings indicate an effect of contributor experience on the quality of health-related Wikipedia articles. However, only the number of previously edited articles was a predictor of the articles’ quality but not the mere volume of edits. More research is needed to disentangle the different aspects of contributor experience. We have discussed the implications of our findings with respect to ensuring the quality of health-related information in collaborative knowledge-building platforms. PMID:29748161

Near-field observation platform

NASA Astrophysics Data System (ADS)

Schlemmer, Harry; Baeurle, Constantin; Vogel, Holger

2008-04-01

A miniaturized near-field observation platform is presented comprising a sensitive daylight camera and an uncooled micro-bolometer thermal imager each equipped with a wide angle lens. Both cameras are optimised for a range between a few meters and 200 m. The platform features a stabilised line of sight and can therefore be used also on a vehicle when it is in motion. The line of sight either can be directed manually or the platform can be used in a panoramic mode. The video output is connected to a control panel where algorithms for moving target indication or tracking can be applied in order to support the observer. The near-field platform also can be netted with the vehicle system and the signals can be utilised, e.g. to designate a new target to the main periscope or the weapon sight.

Nonviral gene editing via CRISPR/Cas9 delivery by membrane-disruptive and endosomolytic helical polypeptide.

PubMed

Wang, Hong-Xia; Song, Ziyuan; Lao, Yeh-Hsing; Xu, Xin; Gong, Jing; Cheng, Du; Chakraborty, Syandan; Park, Ji Sun; Li, Mingqiang; Huang, Dantong; Yin, Lichen; Cheng, Jianjun; Leong, Kam W

2018-05-08

Effective and safe delivery of the CRISPR/Cas9 gene-editing elements remains a challenge. Here we report the development of PEGylated nanoparticles (named P-HNPs) based on the cationic α-helical polypeptide poly(γ-4-((2-(piperidin-1-yl)ethyl)aminomethyl)benzyl-l-glutamate) for the delivery of Cas9 expression plasmid and sgRNA to various cell types and gene-editing scenarios. The cell-penetrating α-helical polypeptide enhanced cellular uptake and promoted escape of pCas9 and/or sgRNA from the endosome and transport into the nucleus. The colloidally stable P-HNPs achieved a Cas9 transfection efficiency up to 60% and sgRNA uptake efficiency of 67.4%, representing an improvement over existing polycation-based gene delivery systems. After performing single or multiplex gene editing with an efficiency up to 47.3% in vitro, we demonstrated that P-HNPs delivering Cas9 plasmid/sgRNA targeting the polo-like kinase 1 (Plk1) gene achieved 35% gene deletion in HeLa tumor tissue to reduce the Plk1 protein level by 66.7%, thereby suppressing the tumor growth by >71% and prolonging the animal survival rate to 60% within 60 days. Capable of delivering Cas9 plasmids to various cell types to achieve multiplex gene knock-out, gene knock-in, and gene activation in vitro and in vivo, the P-HNP system offers a versatile gene-editing platform for biological research and therapeutic applications. Copyright © 2018 the Author(s). Published by PNAS.

Development of autonomous multirotor platform for exploration missions

NASA Astrophysics Data System (ADS)

Czyba, Roman; Janik, Marcin; Kurgan, Oliver; Niezabitowski, Michał; Nocoń, Marek

2016-06-01

This paper outlines development process of unmanned multirotor aerial vehicle HF-4X, which consists of design and manufacturing semi-autonomous UAV dedicated for indoor flight, which would be capable of stable and controllable mission flight. A micro air vehicle was designed to participate in the International Micro Air Vehicle Conference and Flight Competition. In this paper much attention was paid to the structure of flight control system, stabilization algorithms, analysis of IMU sensors, fusion algorithms.

Development of autonomous multirotor platform for exploration missions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Czyba, Roman; Janik, Marcin; Kurgan, Oliver

This paper outlines development process of unmanned multirotor aerial vehicle HF-4X, which consists of design and manufacturing semi-autonomous UAV dedicated for indoor flight, which would be capable of stable and controllable mission flight. A micro air vehicle was designed to participate in the International Micro Air Vehicle Conference and Flight Competition. In this paper much attention was paid to the structure of flight control system, stabilization algorithms, analysis of IMU sensors, fusion algorithms.

High Sensitivity Optomechanical Reference Accelerometer over 10 kHz

DTIC Science & Technology

2014-06-05

bandwidth of 10 kHz and is traceable. We have incorporated a Fabry-P erot fiber-optic micro-cavity that is currently capable of measuring the test-mass...10 kHz- bandwidth requires displacement detection sensitivities at levels of 10 16 m= Hz p . Optical detection schemes, such as Fabry-P erot ...based micro- mirror Fabry-P erot cavity19,20 was built to operate in reflec- tion as the optical sensor. The mechanical oscillator ground platform and

Delivery strategies of the CRISPR-Cas9 gene-editing system for therapeutic applications.

PubMed

Liu, Chang; Zhang, Li; Liu, Hao; Cheng, Kun

2017-11-28

The CRISPR-Cas9 genome-editing system is a part of the adaptive immune system in archaea and bacteria to defend against invasive nucleic acids from phages and plasmids. The single guide RNA (sgRNA) of the system recognizes its target sequence in the genome, and the Cas9 nuclease of the system acts as a pair of scissors to cleave the double strands of DNA. Since its discovery, CRISPR-Cas9 has become the most robust platform for genome engineering in eukaryotic cells. Recently, the CRISPR-Cas9 system has triggered enormous interest in therapeutic applications. CRISPR-Cas9 can be applied to correct disease-causing gene mutations or engineer T cells for cancer immunotherapy. The first clinical trial using the CRISPR-Cas9 technology was conducted in 2016. Despite the great promise of the CRISPR-Cas9 technology, several challenges remain to be tackled before its successful applications for human patients. The greatest challenge is the safe and efficient delivery of the CRISPR-Cas9 genome-editing system to target cells in human body. In this review, we will introduce the molecular mechanism and different strategies to edit genes using the CRISPR-Cas9 system. We will then highlight the current systems that have been developed to deliver CRISPR-Cas9 in vitro and in vivo for various therapeutic purposes. Copyright © 2017 Elsevier B.V. All rights reserved.

An integrated CRISPR Bombyx mori genome editing system with improved efficiency and expanded target sites.

PubMed

Ma, Sanyuan; Liu, Yue; Liu, Yuanyuan; Chang, Jiasong; Zhang, Tong; Wang, Xiaogang; Shi, Run; Lu, Wei; Xia, Xiaojuan; Zhao, Ping; Xia, Qingyou

2017-04-01

Genome editing enabled unprecedented new opportunities for targeted genomic engineering of a wide variety of organisms ranging from microbes, plants, animals and even human embryos. The serial establishing and rapid applications of genome editing tools significantly accelerated Bombyx mori (B. mori) research during the past years. However, the only CRISPR system in B. mori was the commonly used SpCas9, which only recognize target sites containing NGG PAM sequence. In the present study, we first improve the efficiency of our previous established SpCas9 system by 3.5 folds. The improved high efficiency was also observed at several loci in both BmNs cells and B. mori embryos. Then to expand the target sites, we showed that two newly discovered CRISPR system, SaCas9 and AsCpf1, could also induce highly efficient site-specific genome editing in BmNs cells, and constructed an integrated CRISPR system. Genome-wide analysis of targetable sites was further conducted and showed that the integrated system cover 69,144,399 sites in B. mori genome, and one site could be found in every 6.5 bp. The efficiency and resolution of this CRISPR platform will probably accelerate both fundamental researches and applicable studies in B. mori, and perhaps other insects. Copyright © 2017 Elsevier Ltd. All rights reserved.

Enabling functional genomics with genome engineering

PubMed Central

Hilton, Isaac B.; Gersbach, Charles A.

2015-01-01

Advances in genome engineering technologies have made the precise control over genome sequence and regulation possible across a variety of disciplines. These tools can expand our understanding of fundamental biological processes and create new opportunities for therapeutic designs. The rapid evolution of these methods has also catalyzed a new era of genomics that includes multiple approaches to functionally characterize and manipulate the regulation of genomic information. Here, we review the recent advances of the most widely adopted genome engineering platforms and their application to functional genomics. This includes engineered zinc finger proteins, TALEs/TALENs, and the CRISPR/Cas9 system as nucleases for genome editing, transcription factors for epigenome editing, and other emerging applications. We also present current and potential future applications of these tools, as well as their current limitations and areas for future advances. PMID:26430154

Adapting CRISPR/Cas9 for functional genomics screens.

PubMed

Malina, Abba; Katigbak, Alexandra; Cencic, Regina; Maïga, Rayelle Itoua; Robert, Francis; Miura, Hisashi; Pelletier, Jerry

2014-01-01

The use of CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated protein) for targeted genome editing has been widely adopted and is considered a "game changing" technology. The ease and rapidity by which this approach can be used to modify endogenous loci in a wide spectrum of cell types and organisms makes it a powerful tool for customizable genetic modifications as well as for large-scale functional genomics. The development of retrovirus-based expression platforms to simultaneously deliver the Cas9 nuclease and single guide (sg) RNAs provides unique opportunities by which to ensure stable and reproducible expression of the editing tools and a broad cell targeting spectrum, while remaining compatible with in vivo genetic screens. Here, we describe methods and highlight considerations for designing and generating sgRNA libraries in all-in-one retroviral vectors for such applications.

Nonlinear Silicon Photonics: Extending Platforms, Control, and Applications

NASA Astrophysics Data System (ADS)

Miller, Steven Andrew

Silicon photonics is a revolutionary technology that enables the control of light inside a silicon chip and holds promise to impact many applications from data center optical interconnects to optical sensing and even quantum optics. The tight confinement of light inside these chips greatly enhances light-matter interactions, making this an ideal platform for nonlinear photonics. Recently, microresonator-based Kerr frequency comb generation has become a prevalent emerging field, enabling the generation of a broadband optical pulse train by inputting a low-power continuous-wave laser into a low-loss chip-scale micro-cavity. These chip-scale combs have a wide variety of applications, including optical clocks, optical spectroscopy, and data communications. Several important applications in biological, chemical and atmospheric areas require combs generated in the visible and mid-infrared wavelength ranges, where there has been far less research and development compared with the near-infrared. Additionally, most platforms widely for combs are passive, limiting the ability to control and optimize the frequency combs. In this dissertation, we set out to address these shortcomings and introduce new tunability as well as wavelength flexibility in order to enable new applications for microresonator frequency combs. The silicon nitride platform for near-infrared combs is generally a passive platform with limited tuning capabilities. We overcome dispersion limitations in the visible range by leveraging the second-order nonlinearity of silicon nitride and demonstrate visible comb lines. We then further investigate the second-order nonlinearity of silicon nitride by measuring the linear electro-optic effect, a potential tuning mechanism. Finally, we introduce thermal tuning onto the silicon nitride platform and demonstrate tuning of the resonance extinction and dispersion of a micro-cavity using a coupled cavity design. We also address the silicon mid-infrared frequency comb platform. The transparency range of the traditional silicon platform prohibits operation beyond 4 mum wavelength. Here we show that a silicon photonics platform can be leveraged for broadband mid-infrared operation without introducing complexity in fabrication. Both an air-clad and fully suspended silicon platform can enable broadband, low-loss propagation and comb generation as high as 6 mum. We demonstrate a high quality factor resonator near 4 mum wavelength, more than an order of magnitude higher than the traditional platform. Finally, we discuss future avenues of research building on the work presented here.

Quality detection system and method of micro-accessory based on microscopic vision

NASA Astrophysics Data System (ADS)

Li, Dongjie; Wang, Shiwei; Fu, Yu

2017-10-01

Considering that the traditional manual detection of micro-accessory has some problems, such as heavy workload, low efficiency and large artificial error, a kind of quality inspection system of micro-accessory has been designed. Micro-vision technology has been used to inspect quality, which optimizes the structure of the detection system. The stepper motor is used to drive the rotating micro-platform to transfer quarantine device and the microscopic vision system is applied to get graphic information of micro-accessory. The methods of image processing and pattern matching, the variable scale Sobel differential edge detection algorithm and the improved Zernike moments sub-pixel edge detection algorithm are combined in the system in order to achieve a more detailed and accurate edge of the defect detection. The grade at the edge of the complex signal can be achieved accurately by extracting through the proposed system, and then it can distinguish the qualified products and unqualified products with high precision recognition.

Experimental investigation of evanescence-based infrared biodetection technique for micro-total-analysis systems.

PubMed

Chandrasekaran, Arvind; Packirisamy, Muthukumaran

2009-01-01

The advent of microoptoelectromechanical systems (MOEMS) and its integration with other technologies such as microfluidics, microthermal, immunoproteomics, etc. has led to the concept of an integrated micro-total-analysis systems (microTAS) or Lab-on-a-Chip for chemical and biological applications. Recently, research and development of microTAS have attained a significant growth rate over several biodetection sciences, in situ medical diagnoses, and point-of-care testing applications. However, it is essential to develop suitable biophysical label-free detection methods for the success, reliability, and ease of use of the microTAS. We proposed an infrared (IR)-based evanescence wave detection system on the silicon-on-insulator platform for biodetection with microTAS. The system operates on the principle of bio-optical interaction that occurs due to the evanescence of light from the waveguide device. The feasibility of biodetection has been experimentally investigated by the detection of horse radish peroxidase upon its reaction with hydrogen peroxide.

Micro-optics for microfluidic analytical applications.

PubMed

Yang, Hui; Gijs, Martin A M

2018-02-19

This critical review summarizes the developments in the integration of micro-optical elements with microfluidic platforms for facilitating detection and automation of bio-analytical applications. Micro-optical elements, made by a variety of microfabrication techniques, advantageously contribute to the performance of an analytical system, especially when the latter has microfluidic features. Indeed the easy integration of optical control and detection modules with microfluidic technology helps to bridge the gap between the macroscopic world and chip-based analysis, paving the way for automated and high-throughput applications. In our review, we start the discussion with an introduction of microfluidic systems and micro-optical components, as well as aspects of their integration. We continue with a detailed description of different microfluidic and micro-optics technologies and their applications, with an emphasis on the realization of optical waveguides and microlenses. The review continues with specific sections highlighting the advantages of integrated micro-optical components in microfluidic systems for tackling a variety of analytical problems, like cytometry, nucleic acid and protein detection, cell biology, and chemical analysis applications.

FRACOR-software toolbox for deterministic mapping of fracture corridors in oil fields on AutoCAD platform

NASA Astrophysics Data System (ADS)

Ozkaya, Sait I.

2018-03-01

Fracture corridors are interconnected large fractures in a narrow sub vertical tabular array, which usually traverse entire reservoir vertically and extended for several hundreds of meters laterally. Fracture corridors with their huge conductivities constitute an important element of many fractured reservoirs. Unlike small diffuse fractures, actual fracture corridors must be mapped deterministically for simulation or field development purposes. Fracture corridors can be identified and quantified definitely with borehole image logs and well testing. However, there are rarely sufficient image logs or well tests, and it is necessary to utilize various fracture corridor indicators with varying degrees of reliability. Integration of data from many different sources, in turn, requires a platform with powerful editing and layering capability. Available commercial reservoir characterization software packages, with layering and editing capabilities, can be cost intensive. CAD packages are far more affordable and may easily acquire the versatility and power of commercial software packages with addition of a small software toolbox. The objective of this communication is to present FRACOR, a software toolbox which enables deterministic 2D fracture corridor mapping and modeling on AutoCAD platform. The FRACOR toolbox is written in AutoLISPand contains several independent routines to import and integrate available fracture corridor data from an oil field, and export results as text files. The resulting fracture corridor maps consists mainly of fracture corridors with different confidence levels from combination of static and dynamic data and exclusion zones where no fracture corridor can exist. The exported text file of fracture corridors from FRACOR can be imported into an upscaling programs to generate fracture grid for dual porosity simulation or used for field development and well planning.

Fixed-Wing Micro Aerial Vehicle for Accurate Corridor Mapping

NASA Astrophysics Data System (ADS)

Rehak, M.; Skaloud, J.

2015-08-01

In this study we present a Micro Aerial Vehicle (MAV) equipped with precise position and attitude sensors that together with a pre-calibrated camera enables accurate corridor mapping. The design of the platform is based on widely available model components to which we integrate an open-source autopilot, customized mass-market camera and navigation sensors. We adapt the concepts of system calibration from larger mapping platforms to MAV and evaluate them practically for their achievable accuracy. We present case studies for accurate mapping without ground control points: first for a block configuration, later for a narrow corridor. We evaluate the mapping accuracy with respect to checkpoints and digital terrain model. We show that while it is possible to achieve pixel (3-5 cm) mapping accuracy in both cases, precise aerial position control is sufficient for block configuration, the precise position and attitude control is required for corridor mapping.

An integrated micro-manipulation and biosensing platform built in glass-based LTPS TFT technology

NASA Astrophysics Data System (ADS)

Chen, Lei-Guang; Wu, Dong-Yi; S-C Lu, Michael

2012-09-01

The glass-based low-temperature polycrystalline-silicon (LTPS) thin-film transistor (TFT) process, widely known for making liquid crystal displays, is utilized in this work to realize a fully integrated, microbead-based micro-manipulation and biosensing platform. The operation utilizes arrays of microelectrodes made of transparent iridium tin oxide (ITO) to move the immobilized polystyrene microbeads to the sensor surface by dielectrophoresis (DEP). Detection of remaining microbeads after a specific antigen/antibody reaction is accomplished by photo-detectors under the transparent electrodes. It was found that microbeads can be driven successfully by the 30 × 30 µm2 microelectrodes separated by 10 µm with no more than 6 Vp-p, which is compatible with the operating range of thin-film transistors. Microbeads immobilized with antimouse immunoglobulin (IgG) and prostate-specific antigen (PSA) antibody were successfully detected after specific binding, illustrating the potential of LTPS TFT microarrays for more versatile biosensing applications.

An application framework of three-dimensional reconstruction and measurement for endodontic research.

PubMed

Gao, Yuan; Peters, Ove A; Wu, Hongkun; Zhou, Xuedong

2009-02-01

The purpose of this study was to customize an application framework by using the MeVisLab image processing and visualization platform for three-dimensional reconstruction and assessment of tooth and root canal morphology. One maxillary first molar was scanned before and after preparation with ProTaper by using micro-computed tomography. With a customized application framework based on MeVisLab, internal and external anatomy was reconstructed. Furthermore, the dimensions of root canal and radicular dentin were quantified, and effects of canal preparation were assessed. Finally, a virtual preparation with risk analysis was performed to simulate the removal of a broken instrument. This application framework provided an economical platform and met current requirements of endodontic research. The broad-based use of high-quality free software and the resulting exchange of experience might help to improve the quality of endodontic research with micro-computed tomography.

Nano to micro delivery systems: targeting angiogenesis in brain tumors.

PubMed

Gilert, Ariel; Machluf, Marcelle

2010-10-08

Treating brain tumors using inhibitors of angiogenesis is extensively researched and tested in clinical trials. Although anti-angiogenic treatment holds a great potential for treating primary and secondary brain tumors, no clinical treatment is currently approved for brain tumor patients. One of the main hurdles in treating brain tumors is the blood brain barrier - a protective barrier of the brain, which prevents drugs from entering the brain parenchyma. As most therapeutics are excluded from the brain there is an urgent need to develop delivery platforms which will bypass such hurdles and enable the delivery of anti-angiogenic drugs into the tumor bed. Such delivery systems should be able to control release the drug or a combination of drugs at a therapeutic level for the desired time. In this mini-review we will discuss the latest improvements in nano and micro drug delivery platforms that were designed to deliver inhibitors of angiogenesis to the brain.

Nano to micro delivery systems: targeting angiogenesis in brain tumors

PubMed Central

2010-01-01

Treating brain tumors using inhibitors of angiogenesis is extensively researched and tested in clinical trials. Although anti-angiogenic treatment holds a great potential for treating primary and secondary brain tumors, no clinical treatment is currently approved for brain tumor patients. One of the main hurdles in treating brain tumors is the blood brain barrier - a protective barrier of the brain, which prevents drugs from entering the brain parenchyma. As most therapeutics are excluded from the brain there is an urgent need to develop delivery platforms which will bypass such hurdles and enable the delivery of anti-angiogenic drugs into the tumor bed. Such delivery systems should be able to control release the drug or a combination of drugs at a therapeutic level for the desired time. In this mini-review we will discuss the latest improvements in nano and micro drug delivery platforms that were designed to deliver inhibitors of angiogenesis to the brain. PMID:20932320

Optoelectronic tweezers integrated with lensfree holographic microscopy for wide-field interactive cell and particle manipulation on a chip.

PubMed

Huang, Kuo-Wei; Su, Ting-Wei; Ozcan, Aydogan; Chiou, Pei-Yu

2013-06-21

We demonstrate an optoelectronic tweezer (OET) coupled to a lensfree holographic microscope for real-time interactive manipulation of cells and micro-particles over a large field-of-view (FOV). This integrated platform can record the holographic images of cells and particles over the entire active area of a CCD sensor array, perform digital image reconstruction to identify target cells, dynamically track the positions of cells and particles, and project light beams to trigger light-induced dielectrophoretic forces to pattern and sort cells on a chip. OET technology has been previously shown to be capable of performing parallel single cell manipulation over a large area. However, its throughput has been bottlenecked by the number of cells that can be imaged within the limited FOV of a conventional microscope objective lens. Integrating lensfree holographic imaging with OET solves this fundamental FOV barrier, while also creating a compact on-chip cell/particle manipulation platform. Using this unique platform, we have successfully demonstrated real-time interactive manipulation of thousands of single cells and micro-particles over an ultra-large area of e.g., 240 mm(2) (i.e. 17.96 mm × 13.52 mm).

A lab-in-a-droplet bioassay strategy for centrifugal microfluidics with density difference pumping, power to disc and bidirectional flow control.

PubMed

Wang, Guanghui; Ho, Ho-Pui; Chen, Qiulan; Yang, Alice Kar-Lai; Kwok, Ho-Chin; Wu, Shu-Yuen; Kong, Siu-Kai; Kwan, Yiu-Wa; Zhang, Xuping

2013-09-21

In this paper, we present a lab-in-a-droplet bioassay strategy for a centrifugal microfluidics or lab-on-a-disc (LOAD) platform with three important advancements including density difference pumping, power to disc and bidirectional flow control. First, with the water based bioassay droplets trapped in a micro-channel filled with mineral oil, centrifugal force due to the density difference between the water and oil phases actuates droplet movement while the oil based medium remains stationary. Second, electricity is coupled to the rotating disc through a split-core transformer, thus enabling on-chip real-time heating in selected areas as desired and wireless programmable functionality. Third, an inertial mechanical structure is proposed to achieve bidirectional flow control within the spinning disc. The droplets can move back and forth between two heaters upon changing the rotational speed. Our platform is an essential and versatile solution for bioassays such as those involving DNA amplification, where localized temperature cycling is required. Finally, without the loss of generality, we demonstrate the functionality of our platform by performing real-time polymerase chain reaction (RT-PCR) in a linear microchannel made with PTFE (Teflon) micro-tubing.

Microengineered Conductive Elastomeric Electrodes for Long-Term Electrophysiological Measurements with Consistent Impedance under Stretch

PubMed Central

Hu, Dinglong; Cheng, Tin Kei; Xie, Kai; Lam, Raymond H. W.

2015-01-01

In this research, we develop a micro-engineered conductive elastomeric electrode for measurements of human bio-potentials with the absence of conductive pastes. Mixing the biocompatible polydimethylsiloxane (PDMS) silicone with other biocompatible conductive nano-particles further provides the material with an electrical conductivity. We apply micro-replica mold casting for the micro-structures, which are arrays of micro-pillars embedded between two bulk conductive-PDMS layers. These micro-structures can reduce the micro-structural deformations along the direction of signal transmission; therefore the corresponding electrical impedance under the physical stretch by the movement of the human body can be maintained. Additionally, we conduct experiments to compare the electrical properties between the bulk conductive-PDMS material and the microengineered electrodes under stretch. We also demonstrate the working performance of these micro-engineered electrodes in the acquisition of the 12-lead electrocardiographs (ECG) of a healthy subject. Together, the presented gel-less microengineered electrodes can provide a more convenient and stable bio-potential measurement platform, making tele-medical care more achievable with reduced technical barriers for instrument installation performed by patients/users themselves. PMID:26512662

Site-specific characterization of beetle horn shell with micromechanical bending test in focused ion beam system.

PubMed

Lee, Hyun-Taek; Kim, Ho-Jin; Kim, Chung-Soo; Gomi, Kenji; Taya, Minoru; Nomura, Shûhei; Ahn, Sung-Hoon

2017-07-15

Biological materials are the result of years of evolution and possess a number of efficient features and structures. Researchers have investigated the possibility of designing biomedical structures that take advantage of these structural features. Insect shells, such as beetle shells, are among the most promising types of biological material for biomimetic development. However, due to their intricate geometries and small sizes, it is challenging to measure the mechanical properties of these microscale structures. In this study, we developed an in-situ testing platform for site-specific experiments in a focused ion beam (FIB) system. Multi-axis nano-manipulators and a micro-force sensor were utilized in the testing platform to allow better results in the sample preparation and data acquisition. The entire test protocol, consisting of locating sample, ion beam milling and micro-mechanical bending tests, can be carried out without sample transfer or reattachment. We used our newly devised test platform to evaluate the micromechanical properties and structural features of each separated layer of the beetle horn shell. The Young's modulus of both the exocuticle and endocuticle layers was measured. We carried out a bending test to characterize the layers mechanically. The exocuticle layer bent in a brick-like manner, while the endocuticle layer exhibited a crack blunting effect. This paper proposed an in-situ manipulation/test method in focused ion beam for characterizing micromechanical properties of beetle horn shell. The challenge in precise and accurate fabrication for the samples with complex geometry was overcome by using nano-manipulators having multi-degree of freedom and a micro-gripper. With the aid of this specially designed test platform, bending tests were carried out on cantilever-shaped samples prepared by focused ion beam milling. Structural differences between exocuticle and endocuticle layers of beetle horn shell were explored and the results provided insight into the structural advantages of each biocomposite structure. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Fiber laser platform for highest flexibility and reliability in industrial femtosecond micromachining: TruMicro Series 2000

NASA Astrophysics Data System (ADS)

Jansen, Florian; Kanal, Florian; Kahmann, Max; Tan, Chuong; Diekamp, Holger; Scelle, Raphael; Budnicki, Aleksander; Sutter, Dirk

2018-02-01

In this work we present an ultrafast laser system distinguished by its industry-ready reliability and its outstanding flexibility that allows for real-time process-inherent parameter. The robust system design and linear amplifier architecture make the all-fiber series TruMicro 2000 ideally suited for passive coupling to hollow-core delivery fibers. In addition to details on the laser system itself, various application examples are shown, including welding of different glasses and ablation of silicon carbide and silicon.

10th Annual Systems Engineering Conference - Focusing on Improving Performance of Defense Systems Programs. Volume 1. Tuesday Presentations

DTIC Science & Technology

2007-10-25

Exchange Platforms Publishers Resellers iTunes Non-Profit/ Government/ Self- Managed Library of Congress Library Consortia Fed. Tech Transfer Sites Univ...Thompson Dialog – Thomson MicroPatent – Thomson Pharma – WIPO Digital Patent Library* (*nonprofit organization) • iTunes • IP Exchange Platforms...Elsevier SciDirect – Nat’l Acad. Press – Lexis, Westlaw – Newspaper web sites • iTunes • Resellers of Copyrighted Material – JSTOR – EBSCOHost

Technology Assessment for External Implementation of Artificial Gravity Utilizing the Deep Space Gateway Platform

NASA Astrophysics Data System (ADS)

Raychev, R.; Griko, Y. V.

2018-02-01

Scenario drafting for early technology assessment of the external space centrifuge with little mass and variable radius of rotation is proposed to counteract micro gravity-associated physiological alterations in all physiological systems.

A platform for rapid exploration of aging and diseases in a naturally short-lived vertebrate

PubMed Central

Harel, Itamar; Benayoun, Bérénice A.; Machado, Ben; Singh, Param Priya; Hu, Chi-Kuo; Pech, Matthew F.; Valenzano, Dario R.; Zhang, Elisa; Sharp, Sabrina C.; Artandi, Steven E.; Brunet, Anne

2015-01-01

Summary Aging is a complex process that affects multiple organs. Modeling aging and age-related diseases in the lab is challenging because classical vertebrate models have relatively long lifespans. Here we develop the first platform for rapid exploration of age-dependent traits and diseases in vertebrates, using the naturally short-lived African turquoise killifish. We provide an integrative genomic and genome-editing toolkit in this organism using our de novo-assembled genome and the CRISPR/Cas9 technology. We mutate many genes encompassing the hallmarks of aging, and for a subset, we produce stable lines within 2–3 months. As a proof-of-principle, we show that fish deficient for the protein subunit of telomerase exhibit the fastest onset of telomere-related pathologies among vertebrates. We further demonstrate the feasibility of creating specific genetic variants. This genome-to-phenotype platform represents a unique resource for studying vertebrate aging and disease in a high throughput manner and for investigating candidates arising from human genome-wide studies. PMID:25684364

Effects of Contributor Experience on the Quality of Health-Related Wikipedia Articles.

PubMed

Holtz, Peter; Fetahu, Besnik; Kimmerle, Joachim

2018-05-10

Consulting the Internet for health-related information is a common and widespread phenomenon, and Wikipedia is arguably one of the most important resources for health-related information. Therefore, it is relevant to identify factors that have an impact on the quality of health-related Wikipedia articles. In our study we have hypothesized a positive effect of contributor experience on the quality of health-related Wikipedia articles. We mined the edit history of all (as of February 2017) 18,805 articles that were listed in the categories on the portal health & fitness in the English language version of Wikipedia. We identified tags within the articles' edit histories, which indicated potential issues with regard to the respective article's quality or neutrality. Of all of the sampled articles, 99 (99/18,805, 0.53%) articles had at some point received at least one such tag. In our analysis we only considered those articles with a minimum of 10 edits (10,265 articles in total; 96 tagged articles, 0.94%). Additionally, to test our hypothesis, we constructed contributor profiles, where a profile consisted of all the articles edited by a contributor and the corresponding number of edits contributed. We did not differentiate between rollbacks and edits with novel content. Nonparametric Mann-Whitney U-tests indicated a higher number of previously edited articles for editors of the nontagged articles (mean rank tagged 2348.23, mean rank nontagged 5159.29; U=9.25, P<.001). However, we did not find a significant difference for the contributors' total number of edits (mean rank tagged 4872.85, mean rank nontagged 5135.48; U=0.87, P=.39). Using logistic regression analysis with the respective article's number of edits and number of editors as covariates, only the number of edited articles yielded a significant effect on the article's status as tagged versus nontagged (dummy-coded; Nagelkerke R 2 for the full model=.17; B [SE B]=-0.001 [0.00]; Wald c 2 [1]=19.70; P<.001), whereas we again found no significant effect for the mere number of edits (Nagelkerke R 2 for the full model=.15; B [SE B]=0.000 [0.01]; Wald c 2 [1]=0.01; P=.94). Our findings indicate an effect of contributor experience on the quality of health-related Wikipedia articles. However, only the number of previously edited articles was a predictor of the articles' quality but not the mere volume of edits. More research is needed to disentangle the different aspects of contributor experience. We have discussed the implications of our findings with respect to ensuring the quality of health-related information in collaborative knowledge-building platforms. ©Peter Holtz, Besnik Fetahu, Joachim Kimmerle. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 10.05.2018.

Elimination of HIV-1 Genomes from Human T-lymphoid Cells by CRISPR/Cas9 Gene Editing

PubMed Central

Kaminski, Rafal; Chen, Yilan; Fischer, Tracy; Tedaldi, Ellen; Napoli, Alessandro; Zhang, Yonggang; Karn, Jonathan; Hu, Wenhui; Khalili, Kamel

2016-01-01

We employed an RNA-guided CRISPR/Cas9 DNA editing system to precisely remove the entire HIV-1 genome spanning between 5′ and 3′ LTRs of integrated HIV-1 proviral DNA copies from latently infected human CD4+ T-cells. Comprehensive assessment of whole-genome sequencing of HIV-1 eradicated cells ruled out any off-target effects by our CRISPR/Cas9 technology that might compromise the integrity of the host genome and further showed no effect on several cell health indices including viability, cell cycle and apoptosis. Persistent co-expression of Cas9 and the specific targeting guide RNAs in HIV-1-eradicated T-cells protected them against new infection by HIV-1. Lentivirus-delivered CRISPR/Cas9 significantly diminished HIV-1 replication in infected primary CD4+ T-cell cultures and drastically reduced viral load in ex vivo culture of CD4+ T-cells obtained from HIV-1 infected patients. Thus, gene editing using CRISPR/Cas9 may provide a new therapeutic path for eliminating HIV-1 DNA from CD4+ T-cells and potentially serve as a novel and effective platform toward curing AIDS. PMID:26939770

Cellular Reprogramming, Genome Editing, and Alternative CRISPR Cas9 Technologies for Precise Gene Therapy of Duchenne Muscular Dystrophy

PubMed Central

Xu, Huaigeng

2017-01-01

In the past decade, the development of two innovative technologies, namely, induced pluripotent stem cells (iPSCs) and the CRISPR Cas9 system, has enabled researchers to model diseases derived from patient cells and precisely edit DNA sequences of interest, respectively. In particular, Duchenne muscular dystrophy (DMD) has been an exemplary monogenic disease model for combining these technologies to demonstrate that genome editing can correct genetic mutations in DMD patient-derived iPSCs. DMD is an X-linked genetic disorder caused by mutations that disrupt the open reading frame of the dystrophin gene, which plays a critical role in stabilizing muscle cells during contraction and relaxation. The CRISPR Cas9 system has been shown to be capable of targeting the dystrophin gene and rescuing its expression in in vitro patient-derived iPSCs and in vivo DMD mouse models. In this review, we highlight recent advances made using the CRISPR Cas9 system to correct genetic mutations and discuss how emerging CRISPR technologies and iPSCs in a combined platform can play a role in bringing a therapy for DMD closer to the clinic. PMID:28607562

Next stop for the CRISPR revolution: RNA-guided epigenetic regulators.

PubMed

Vora, Suhani; Tuttle, Marcelle; Cheng, Jenny; Church, George

2016-09-01

Clustered regularly interspaced short palindromic repeats (CRISPRs) and CRISPR-associated (Cas) proteins offer a breakthrough platform for cheap, programmable, and effective sequence-specific DNA targeting. The CRISPR-Cas system is naturally equipped for targeted DNA cutting through its native nuclease activity. As such, groups researching a broad spectrum of biological organisms have quickly adopted the technology with groundbreaking applications to genomic sequence editing in over 20 different species. However, the biological code of life is not only encoded in genetics but also in epigenetics as well. While genetic sequence editing is a powerful ability, we must also be able to edit and regulate transcriptional and epigenetic code. Taking inspiration from work on earlier sequence-specific targeting technologies such as zinc fingers (ZFs) and transcription activator-like effectors (TALEs), researchers quickly expanded the CRISPR-Cas toolbox to include transcriptional activation, repression, and epigenetic modification. In this review, we highlight advances that extend the CRISPR-Cas toolkit for transcriptional and epigenetic regulation, as well as best practice guidelines for these tools, and a perspective on future applications. © 2016 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.

Micro- and nanoengineering for stem cell biology: the promise with a caution.

PubMed

Kshitiz; Kim, Deok-Ho; Beebe, David J; Levchenko, Andre

2011-08-01

Current techniques used in stem cell research only crudely mimic the physiological complexity of the stem cell niches. Recent advances in the field of micro- and nanoengineering have brought an array of in vitro cell culture models that have enabled development of novel, highly precise and standardized tools that capture physiological details in a single platform, with greater control, consistency, and throughput. In this review, we describe the micro- and nanotechnology-driven modern toolkit for stem cell biologists to design novel experiments in more physiological microenvironments with increased precision and standardization, and caution them against potential challenges that the modern technologies might present. Copyright © 2011 Elsevier Ltd. All rights reserved.

Sediment-hosted micro-disseminated gold mineralization constrained by basin paleo-topographic highs in the Youjiang basin, South China

NASA Astrophysics Data System (ADS)

Liu, Jianming; Ye, Jie; Ying, Hanlong; Liu, Jiajun; Zheng, Minghua; Gu, Xuexiang

2002-06-01

The Youjiang basin is a Devonian-Triassic rift basin on the southern margin of the Yangtze Craton in South China. Strong syndepositional faulting defined the basin-and-range style paleo-topography that further developed into isolated carbonate platforms surrounded by siliciclastic filled depressions. Finally, thick Triassic siliciclastic deposits covered the platforms completely. In the Youjiang basin, numerous sediment-hosted, micro-disseminated gold (SMG) deposits occur mainly in Permian-Triassic chert and siliciclastic rocks. SMG ores are often auriferous sedimentary rocks with relatively low sulfide contents and moderate to weak alteration. Similar to Carlin-type gold ores in North America, SMG ores in the Youjiang basin are characterized by low-temperature mineral assemblages of pyrite, arsenopyrite, realgar, stibnite, cinnabar, marcasite, chalcedony and carbonate. Most of the SMG deposits are remarkably distributed around the carbonate platforms. Accordingly, there are platform-proximal and platform-distal SMG deposits. Platform-proximal SMG deposits often occur in the facies transition zone between the underlying platform carbonate rocks and the overlying siliciclastic rocks with an unconformity (often a paleo-karst surface) in between. In the ores and hostrocks there are abundant synsedimentary-syndiagenetic fabrics such as lamination, convolute bedding, slump texture, soft-sediment deformation etc. indicating submarine hydrothermal deposition and syndepositional faulting. Numerous fluid-escape and liquefaction fabrics imply strong fluid migration during sediment basin evolution. Such large-scale geological and fabric evidence implies that SMG ores were formed during basin evolution, probably in connection with basinal fluids. It is well known that basinal fluids (especially sediment-sourced fluids) will migrate generally (1) upwards, (2) towards basin margins or basin topographic highs, (3) and from thicker towards thinner deposits during basin evolution. The isolated carbonate platform (as a basin paleo-high) and related syndepositional fault system, together with the unconformity-related facies succession, may have controlled the migration pathway of ore-forming basinal fluids and subsequently determined the location of SMG deposits in the Youjiang basin. Unlike Carlin-type gold deposits, SMG mineralization in the Youjiang basin may represent an integral aspect of the dynamic evolution of extensional basins along divergent continental margins.

Desktop Genetics.

PubMed

Hough, Soren H; Ajetunmobi, Ayokunmi; Brody, Leigh; Humphryes-Kirilov, Neil; Perello, Edward

2016-11-01

Desktop Genetics is a bioinformatics company building a gene-editing platform for personalized medicine. The company works with scientists around the world to design and execute state-of-the-art clustered regularly interspaced short palindromic repeats (CRISPR) experiments. Desktop Genetics feeds the lessons learned about experimental intent, single-guide RNA design and data from international genomics projects into a novel CRISPR artificial intelligence system. We believe that machine learning techniques can transform this information into a cognitive therapeutic development tool that will revolutionize medicine.

CoMetaR: A Collaborative Metadata Repository for Biomedical Research Networks.

PubMed

Stöhr, Mark R; Helm, Gudrun; Majeed, Raphael W; Günther, Andreas

2017-01-01

The German Center for Lung Research (DZL) is a research network with the aim of researching respiratory diseases. To perform consortium-wide queries through one single interface, it requires a uniform conceptual structure. No single terminology covers all our concepts. To achieve a broadly accepted and complete ontology, we developed a platform for collaborative metadata management "CoMetaR". Anyone can browse and discuss the ontology while editing can be performed by authenticated users.

Publishing and Editing of Semantically-Enabled Scientific Metadata Across Multiple Web Platforms: Challenges and Experiences

NASA Astrophysics Data System (ADS)

Patton, E. W.; West, P.; Greer, R.; Jin, B.

2011-12-01

Following on work presented at the 2010 AGU Fall Meeting, we present a number of real-world collections of semantically-enabled scientific metadata ingested into the Tetherless World RDF2HTML system as structured data and presented and edited using that system. Two separate datasets from two different domains (oceanography and solar sciences) are made available using existing web standards and services, e.g. encoded using ontologies represented with the Web Ontology Language (OWL) and stored in a SPARQL endpoint for querying. These datasets are deployed for use in three different web environments, i.e. Drupal, MediaWiki, and a custom web portal written in Java, to highlight the cross-platform nature of the data presentation. Stylesheets used to transform concepts in each domain as well as shared terms into HTML will be presented to show the power of using common ontologies to publish data and support reuse of existing terminologies. In addition, a single domain dataset is shared between two separate portal instances to demonstrate the ability for this system to offer distributed access and modification of content across the Internet. Lastly, we will highlight challenges that arose in the software engineering process, outline the design choices we made in solving those issues, and discuss how future improvements to this and other systems will enable the evolution of distributed, decentralized collaborations for scientific data sharing across multiple research groups.

Bridge-Scour Data Management System user's manual

USGS Publications Warehouse

Landers, Mark N.; Mueller, David S.; Martin, Gary R.

1996-01-01

The Bridge-Scour Data Management System (BSDMS) supports preparation, compilation, and analysis of bridge-scour data. The BSDMS provides interactive storage, retrieval, selection, editing, and display of bridge-scour data sets. Bridge-scour data sets include more than 200 site and measurement attributes of the channel geometry, flow hydraulics, hydrology, sediment, geomorphic-setting, location, and bridge specifications. This user's manual provides a general overview of the structure and organization of BSDMS data sets and detailed instructions to operate the program. Attributes stored by the BSDMS are described along with an illustration of the input screen where the attribute can be entered or edited. Measured scour depths can be compared with scour depths predicted by selected published equations using the BSDMS. The selected published equations available in the computational portion of the BSDMS are described. This manual is written for BSDMS, version 2.0. The data base will facilitate: (1) developing improved estimators of scour for specific regions or conditions; (2) describing scour processes; and (3) reducing risk from scour at bridges. BSDMS is available in DOS and UNIX versions. The program was written to be portable and, therefore, can be used on multiple computer platforms. Installation procedures depend on the computer platform, and specific installation instructions are distributed with the software. Sample data files and data sets of 384 pier-scour measurements from 56 bridges in 14 States are also distributed with the software.

CRISPR-Cas9D10A Nickase-Assisted Genome Editing in Lactobacillus casei

PubMed Central

Song, Xin; Huang, He; Xiong, Zhiqiang

2017-01-01

ABSTRACT Lactobacillus casei has drawn increasing attention as a health-promoting probiotic, while effective genetic manipulation tools are often not available, e.g., the single-gene knockout in L. casei still depends on the classic homologous recombination-dependent double-crossover strategy, which is quite labor-intensive and time-consuming. In the present study, a rapid and precise genome editing plasmid, pLCNICK, was established for L. casei genome engineering based on CRISPR-Cas9D10A. In addition to the P23-Cas9D10A and Pldh-sgRNA (single guide RNA) expression cassettes, pLCNICK includes the homologous arms of the target gene as repair templates. The ability and efficiency of chromosomal engineering using pLCNICK were evaluated by in-frame deletions of four independent genes and chromosomal insertion of an enhanced green fluorescent protein (eGFP) expression cassette at the LC2W_1628 locus. The efficiencies associated with in-frame deletions and chromosomal insertion is 25 to 62%. pLCNICK has been proved to be an effective, rapid, and precise tool for genome editing in L. casei, and its potential application in other lactic acid bacteria (LAB) is also discussed in this study. IMPORTANCE The lack of efficient genetic tools has limited the investigation and biotechnological application of many LAB. The CRISPR-Cas9D10A nickase-based genome editing in Lactobacillus casei, an important food industrial microorganism, was demonstrated in this study. This genetic tool allows efficient single-gene deletion and insertion to be accomplished by one-step transformation, and the cycle time is reduced to 9 days. It facilitates a rapid and precise chromosomal manipulation in L. casei and overcomes some limitations of previous methods. This editing system can serve as a basic technological platform and offers the possibility to start a comprehensive investigation on L. casei. As a broad-host-range plasmid, pLCNICK has the potential to be adapted to other Lactobacillus species for genome editing. PMID:28864652

CRISPR-Cas in Medicinal Chemistry: Applications and Regulatory Concerns.

PubMed

Duardo-Sanchez, Aliuska

2017-01-01

A rapid search in scientific publication's databases shows how the use of CRISPR-Cas genome editions' technique has considerably expanded, and its growing importance, in modern molecular biology. Just in pub-med platform, the search of the term gives more than 3000 results. Specifically, in Drug Discovery, Medicinal Chemistry and Chemical Biology in general CRISPR method may have multiple applications. Some of these applications are: resistance-selection studies of antimalarial lead organic compounds; investigation of druggability; development of animal models for chemical compounds testing, etc. In this paper, we offer a review of the most relevant scientific literature illustrated with specific examples of application of CRISPR technique to medicinal chemistry and chemical biology. We also present a general overview of the main legal and ethical trends regarding this method of genome editing. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Cornerstones of CRISPR-Cas in drug development and therapy

PubMed Central

Fellmann, Christof; Gowen, Benjamin G.; Lin, Pei-Chun; Doudna, Jennifer A.; Corn, Jacob E.

2017-01-01

The recent development of CRISPR-Cas systems as easily accessible and programmable tools for genome editing and regulation is spurring a revolution in biology. Paired with the rapid expansion of personalized and reference genomic sequence information, technologies based on CRISPR-Cas are enabling nearly unlimited genetic manipulation even in previously difficult contexts, including human cells. Although much attention has focused on the potential of CRISPR-Cas to cure Mendelian diseases, the technology also holds promise to transform the development of therapies to treat complex heritable and somatic disorders. Here we discuss how CRISPR-Cas can impact the next generation of drugs through accelerating the identification and validation of high-value targets, uncovering high confidence biomarkers and developing differentiated breakthrough therapies. We focus on the promises, pitfalls and hurdles of this revolutionary gene editing technology, and also discuss key aspects of different CRISPR-Cas screening platforms and offer our perspectives on the best practices in genome engineering. PMID:28008168

Enabling functional genomics with genome engineering.

PubMed

Hilton, Isaac B; Gersbach, Charles A

2015-10-01

Advances in genome engineering technologies have made the precise control over genome sequence and regulation possible across a variety of disciplines. These tools can expand our understanding of fundamental biological processes and create new opportunities for therapeutic designs. The rapid evolution of these methods has also catalyzed a new era of genomics that includes multiple approaches to functionally characterize and manipulate the regulation of genomic information. Here, we review the recent advances of the most widely adopted genome engineering platforms and their application to functional genomics. This includes engineered zinc finger proteins, TALEs/TALENs, and the CRISPR/Cas9 system as nucleases for genome editing, transcription factors for epigenome editing, and other emerging applications. We also present current and potential future applications of these tools, as well as their current limitations and areas for future advances. © 2015 Hilton and Gersbach; Published by Cold Spring Harbor Laboratory Press.

Project MAGNET High-level Vector Survey Data Reduction

NASA Technical Reports Server (NTRS)

Coleman, Rachel J.

1992-01-01

Since 1951, the U.S. Navy, under its Project MAGNET program, has been continuously collecting vector aeromagnetic survey data to support the U.S. Defense Mapping Agency's world magnetic and charting program. During this forty-year period, a variety of survey platforms and instrumentation configurations have been used. The current Project MAGNET survey platform is a Navy Orion RP-3D aircraft which has been specially modified and specially equipped with a redundant suite of navigational positioning, attitude, and magnetic sensors. A review of the survey data collection procedures and calibration and editing techniques applied to the data generated by this suite of instrumentation will be presented. Among the topics covered will be the determination of its parameters from the low-level calibration maneuvers flown over geomagnetic observatories.

Transcriptome complexity in cardiac development and diseases--an expanding universe between genome and phenome.

PubMed

Gao, Chen; Wang, Yibin

2014-01-01

With the advancement of transcriptome profiling by micro-arrays and high-throughput RNA-sequencing, transcriptome complexity and its dynamics are revealed at different levels in cardiovascular development and diseases. In this review, we will highlight the recent progress in our knowledge of cardiovascular transcriptome complexity contributed by RNA splicing, RNA editing and noncoding RNAs. The emerging importance of many of these previously under-explored aspects of gene regulation in cardiovascular development and pathology will be discussed.

Integrated Kerr comb-based reconfigurable transversal differentiator for microwave photonic signal processing

NASA Astrophysics Data System (ADS)

Xu, Xingyuan; Wu, Jiayang; Shoeiby, Mehrdad; Nguyen, Thach G.; Chu, Sai T.; Little, Brent E.; Morandotti, Roberto; Mitchell, Arnan; Moss, David J.

2018-01-01

An arbitrary-order intensity differentiator for high-order microwave signal differentiation is proposed and experimentally demonstrated on a versatile transversal microwave photonic signal processing platform based on integrated Kerr combs. With a CMOS-compatible nonlinear micro-ring resonator, high quality Kerr combs with broad bandwidth and large frequency spacings are generated, enabling a larger number of taps and an increased Nyquist zone. By programming and shaping individual comb lines' power, calculated tap weights are realized, thus achieving a versatile microwave photonic signal processing platform. Arbitrary-order intensity differentiation is demonstrated on the platform. The RF responses are experimentally characterized, and systems demonstrations for Gaussian input signals are also performed.

NASA NDE Applications for Mobile MEMS Devices and Sensors

NASA Technical Reports Server (NTRS)

Wilson, William C.; Atkinson, Gary M.; Barclay, R. O.

2008-01-01

NASA would like new devices and sensors for performing nondestructive evaluation (NDE) of aerospace vehicles. These devices must be small in size/volume, mass, and power consumption. The devices must be autonomous and mobile so they can access the internal structures of aircraft and spacecraft and adequately monitor the structural health of these craft. The platforms must be mobile in order to transport NDE sensors for evaluating structural integrity and determining whether further investigations will be required. Microelectromechanical systems (MEMS) technology is crucial to the development of the mobile platforms and sensor systems. This paper presents NASA s needs for micro mobile platforms and MEMS sensors that will enable NDE to be performed on aerospace vehicles.

Development of a Micro-UAV Hyperspectral Imaging Platform for Assessing Hydrogeological Hazards

NASA Astrophysics Data System (ADS)

Chen, Z.; Alabsi, M.

2015-12-01

The exacerbating global weather changes have cast significant impacts upon the proportion of water supplied to agriculture. Therefore, one of the 21stCentury Grant Challenges faced by global population is securing water for food. However, the soil-water behavior in an agricultural environment is complex; among others, one of the key properties we recognize is water repellence or hydrophobicity, which affects many hydrogeological and hazardous conditions such as excessive water infiltration, runoff, and soil erosion. Under a US-Israel research program funded by USDA and BARD at Israel, we have proposed the development of a novel micro-unmanned aerial vehicle (micro-UAV or drone) based hyperspectral imaging platform for identifying and assessing soil repellence at low altitudes with enhanced flexibility, much reduced cost, and ultimately easy use. This aerial imaging system consists of a generic micro-UAV, hyperspectral sensor aided by GPS/IMU, on-board computing units, and a ground station. The target benefits of this system include: (1) programmable waypoint navigation and robotic control for multi-view imaging; (2) ability of two- or three-dimensional scene reconstruction for complex terrains; and (3) fusion with other sensors to realize real-time diagnosis (e.g., humidity and solar irradiation that may affect soil-water sensing). In this talk we present our methodology and processes in integration of hyperspectral imaging, on-board sensing and computing, hyperspectral data modeling, and preliminary field demonstration and verification of the developed prototype.

Fully Self-Contained Vision-Aided Navigation and Landing of a Micro Air Vehicle Independent from External Sensor Inputs

NASA Technical Reports Server (NTRS)

Brockers, Roland; Susca, Sara; Zhu, David; Matthies, Larry

2012-01-01

Direct-lift micro air vehicles have important applications in reconnaissance. In order to conduct persistent surveillance in urban environments, it is essential that these systems can perform autonomous landing maneuvers on elevated surfaces that provide high vantage points without the help of any external sensor and with a fully contained on-board software solution. In this paper, we present a micro air vehicle that uses vision feedback from a single down looking camera to navigate autonomously and detect an elevated landing platform as a surrogate for a roof top. Our method requires no special preparation (labels or markers) of the landing location. Rather, leveraging the planar character of urban structure, the landing platform detection system uses a planar homography decomposition to detect landing targets and produce approach waypoints for autonomous landing. The vehicle control algorithm uses a Kalman filter based approach for pose estimation to fuse visual SLAM (PTAM) position estimates with IMU data to correct for high latency SLAM inputs and to increase the position estimate update rate in order to improve control stability. Scale recovery is achieved using inputs from a sonar altimeter. In experimental runs, we demonstrate a real-time implementation running on-board a micro aerial vehicle that is fully self-contained and independent from any external sensor information. With this method, the vehicle is able to search autonomously for a landing location and perform precision landing maneuvers on the detected targets.

WebProtégé: a collaborative Web-based platform for editing biomedical ontologies.

PubMed

Horridge, Matthew; Tudorache, Tania; Nuylas, Csongor; Vendetti, Jennifer; Noy, Natalya F; Musen, Mark A

2014-08-15

WebProtégé is an open-source Web application for editing OWL 2 ontologies. It contains several features to aid collaboration, including support for the discussion of issues, change notification and revision-based change tracking. WebProtégé also features a simple user interface, which is geared towards editing the kinds of class descriptions and annotations that are prevalent throughout biomedical ontologies. Moreover, it is possible to configure the user interface using views that are optimized for editing Open Biomedical Ontology (OBO) class descriptions and metadata. Some of these views are shown in the Supplementary Material and can be seen in WebProtégé itself by configuring the project as an OBO project. WebProtégé is freely available for use on the Web at http://webprotege.stanford.edu. It is implemented in Java and JavaScript using the OWL API and the Google Web Toolkit. All major browsers are supported. For users who do not wish to host their ontologies on the Stanford servers, WebProtégé is available as a Web app that can be run locally using a Servlet container such as Tomcat. Binaries, source code and documentation are available under an open-source license at http://protegewiki.stanford.edu/wiki/WebProtege. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Wolf Testing: Open Source Testing Software

NASA Astrophysics Data System (ADS)

Braasch, P.; Gay, P. L.

2004-12-01

Wolf Testing is software for easily creating and editing exams. Wolf Testing allows the user to create an exam from a database of questions, view it on screen, and easily print it along with the corresponding answer guide. The questions can be multiple choice, short answer, long answer, or true and false varieties. This software can be accessed securely from any location, allowing the user to easily create exams from home. New questions, which can include associated pictures, can be added through a web-interface. After adding in questions, they can be edited, deleted, or duplicated into multiple versions. Long-term test creation is simplified, as you are able to quickly see what questions you have asked in the past and insert them, with or without editing, into future tests. All tests are archived in the database. Written in PHP and MySQL, this software can be installed on any UNIX / Linux platform, including Macintosh OS X. The secure interface keeps students out, and allows you to decide who can create tests and who can edit information already in the database. Tests can be output as either html with pictures or rich text without pictures, and there are plans to add PDF and MS Word formats as well. We would like to thank Dr. Wolfgang Rueckner and the Harvard University Science Center for providing incentive to start this project, computers and resources to complete this project, and inspiration for the project's name. We would also like to thank Dr. Ronald Newburgh for his assistance in beta testing.

Angular dependant micro-ESR characterization of a locally doped Gd3+:Al2O3 hybrid system for quantum applications

NASA Astrophysics Data System (ADS)

Wisby, I. S.; de Graaf, S. E.; Gwilliam, R.; Adamyan, A.; Kubatkin, S. E.; Meeson, P. J.; Tzalenchuk, A. Ya.; Lindstrom, T.

Rare-earth doped crystals interfaced with superconducting quantum circuitry are an attractive platform for quantum memory and transducer applications. Here we present a detailed characterization of a locally implanted Gd3+ in Al2O3 system coupled to a superconducting micro-resonator, by performing angular dependent micro-electron-spin-resonance (micro-ESR) measurements at mK temperatures. The device is fabricated using a hard Si3N4 mask to facilitate a local ion-implantation technique for precision control of the dopant location. The technique is found not to degrade the internal quality factor of the resonators which remains above 105 (1). We find the measured angular dependence of the micro-ESR spectra to be in excellent agreement with the modelled Hamiltonian, supporting the conclusion that the dopant ions are successfully integrated into their relevant lattice sites whilst maintaining crystalline symmetries. Furthermore, we observe clear contributions from individual microwave field components of our micro-resonator, emphasising the need for controllable local implantation. 1 Wisby et al. Appl. Phys. Lett. 105, 102601 (2014)

Recent Advances in Micro-/Nanostructured Metal-Organic Frameworks towards Photonic and Electronic Applications.

PubMed

Yang, Xiaogang; Lin, Xianqing; Zhao, Yong Sheng; Yan, Dongpeng

2018-05-02

Micro- and nanometer-sized metal-organic frameworks (MOFs) materials have attracted great attention due to their unique properties and various potential applications in photonics, electronics, high-density storage, chemo-, and biosensors. The study of these materials supplies insight into how the crystal structure, molecular components, and micro-/nanoscale effects can influence the performance of inorganic-organic hybrid materials. In this Minireview article, we introduce recent breakthroughs in the controlled synthesis of MOF micro-/nanomaterials with specific structures and compositions, the tunable photonic and electronic properties of which would provide a novel platform for multifunctional applications. Firstly, the design strategies for MOFs based on self-assembly and crystal engineering principles are introduced. Attention is then focused on the methods of fabrication of low-dimensional MOF micro-/nanostructures. Their new applications including two-photon excited fluorescence, multi-photon pumped lasing, optical waveguides, nonlinear optical (NLO), and field-effect transistors are also outlined. Finally, we briefly discuss perspectives on the further development of these hybrid crystalline micro-/nanomaterials. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Light-focusing human micro-lenses generated from pluripotent stem cells model lens development and drug-induced cataract in vitro

PubMed Central

Murphy, Patricia; Kabir, Md Humayun; Srivastava, Tarini; Mason, Michele E.; Dewi, Chitra U.; Lim, Seakcheng; Yang, Andrian; Djordjevic, Djordje; Killingsworth, Murray C.; Ho, Joshua W. K.; Harman, David G.

2018-01-01

ABSTRACT Cataracts cause vision loss and blindness by impairing the ability of the ocular lens to focus light onto the retina. Various cataract risk factors have been identified, including drug treatments, age, smoking and diabetes. However, the molecular events responsible for these different forms of cataract are ill-defined, and the advent of modern cataract surgery in the 1960s virtually eliminated access to human lenses for research. Here, we demonstrate large-scale production of light-focusing human micro-lenses from spheroidal masses of human lens epithelial cells purified from differentiating pluripotent stem cells. The purified lens cells and micro-lenses display similar morphology, cellular arrangement, mRNA expression and protein expression to human lens cells and lenses. Exposing the micro-lenses to the emergent cystic fibrosis drug Vx-770 reduces micro-lens transparency and focusing ability. These human micro-lenses provide a powerful and large-scale platform for defining molecular disease mechanisms caused by cataract risk factors, for anti-cataract drug screening and for clinically relevant toxicity assays. PMID:29217756

Light-focusing human micro-lenses generated from pluripotent stem cells model lens development and drug-induced cataract in vitro.

PubMed

Murphy, Patricia; Kabir, Md Humayun; Srivastava, Tarini; Mason, Michele E; Dewi, Chitra U; Lim, Seakcheng; Yang, Andrian; Djordjevic, Djordje; Killingsworth, Murray C; Ho, Joshua W K; Harman, David G; O'Connor, Michael D

2018-01-09

Cataracts cause vision loss and blindness by impairing the ability of the ocular lens to focus light onto the retina. Various cataract risk factors have been identified, including drug treatments, age, smoking and diabetes. However, the molecular events responsible for these different forms of cataract are ill-defined, and the advent of modern cataract surgery in the 1960s virtually eliminated access to human lenses for research. Here, we demonstrate large-scale production of light-focusing human micro-lenses from spheroidal masses of human lens epithelial cells purified from differentiating pluripotent stem cells. The purified lens cells and micro-lenses display similar morphology, cellular arrangement, mRNA expression and protein expression to human lens cells and lenses. Exposing the micro-lenses to the emergent cystic fibrosis drug Vx-770 reduces micro-lens transparency and focusing ability. These human micro-lenses provide a powerful and large-scale platform for defining molecular disease mechanisms caused by cataract risk factors, for anti-cataract drug screening and for clinically relevant toxicity assays. © 2018. Published by The Company of Biologists Ltd.

Superhydrophobic surface prepared by micro-milling and WEDM on aluminum alloy

NASA Astrophysics Data System (ADS)

Yanling, Wan; Jian, Yang; Huadong, Yu

2018-06-01

To simulate the hydrophobic microstructure of rice leaf surface, high-speed precision micro-milling machine was used to fabricate micro groove array structure on the surface of aluminum alloy. The micro-and nanostructure was constructed on the surface of the grooved convex platform by Wire Cut Electrical Discharge Machining (WEDM). The surface morphology and hydrophobic properties of the aluminum alloy microstructures fabricated by two processing methods were observed respectively, and the hydrophobic mechanism was analyzed. The results show that the contact angle was effectively improved from 49° up to 158.4° in the vertical direction, and 146.7° in the parallel direction. The change of surface wettability from hydrophilic to hydrophobic was realized. By comparison, the micro-and nanostructure fabricated by WEDM had improved the hydrophobic stability of the aluminum alloy surface while enlarging the contact Angle, and the micro-milling groove structure further amplified the contact angle and greatly reduced the contact area of the water droplet, it was also observed that the drop took longer to completely spread on the sample after WEDM.

INTEGRATING MESO-AND MICRO-SIMULATION MODELS TO EVALUATE TRAFFIC MANAGEMENT STRATEGIES, YEAR 2

DOT National Transportation Integrated Search

2017-07-04

In the Year 1 Report, the Arizona State University (ASU) Project Team described the development of a hierarchical multi-resolution simulation platform to test proactive traffic management strategies. The scope was to integrate an easily available mic...

Micro-CTvlab: A web based virtual gallery of biological specimens using X-ray microtomography (micro-CT)

PubMed Central

Faulwetter, Sarah; Chatzinikolaou, Eva; Michalakis, Nikitas; Filiopoulou, Irene; Minadakis, Nikos; Panteri, Emmanouela; Perantinos, George; Gougousis, Alexandros; Arvanitidis, Christos

2016-01-01

Abstract Background During recent years, X-ray microtomography (micro-CT) has seen an increasing use in biological research areas, such as functional morphology, taxonomy, evolutionary biology and developmental research. Micro-CT is a technology which uses X-rays to create sub-micron resolution images of external and internal features of specimens. These images can then be rendered in a three-dimensional space and used for qualitative and quantitative 3D analyses. However, the online exploration and dissemination of micro-CT datasets are rarely made available to the public due to their large size and a lack of dedicated online platforms for the interactive manipulation of 3D data. Here, the development of a virtual micro-CT laboratory (Micro-CTvlab) is described, which can be used by everyone who is interested in digitisation methods and biological collections and aims at making the micro-CT data exploration of natural history specimens freely available over the internet. New information The Micro-CTvlab offers to the user virtual image galleries of various taxa which can be displayed and downloaded through a web application. With a few clicks, accurate, detailed and three-dimensional models of species can be studied and virtually dissected without destroying the actual specimen. The data and functions of the Micro-CTvlab can be accessed either on a normal computer or through a dedicated version for mobile devices. PMID:27956848

Micro-CTvlab: A web based virtual gallery of biological specimens using X-ray microtomography (micro-CT).

PubMed

Keklikoglou, Kleoniki; Faulwetter, Sarah; Chatzinikolaou, Eva; Michalakis, Nikitas; Filiopoulou, Irene; Minadakis, Nikos; Panteri, Emmanouela; Perantinos, George; Gougousis, Alexandros; Arvanitidis, Christos

2016-01-01

During recent years, X-ray microtomography (micro-CT) has seen an increasing use in biological research areas, such as functional morphology, taxonomy, evolutionary biology and developmental research. Micro-CT is a technology which uses X-rays to create sub-micron resolution images of external and internal features of specimens. These images can then be rendered in a three-dimensional space and used for qualitative and quantitative 3D analyses. However, the online exploration and dissemination of micro-CT datasets are rarely made available to the public due to their large size and a lack of dedicated online platforms for the interactive manipulation of 3D data. Here, the development of a virtual micro-CT laboratory (Micro-CT vlab ) is described, which can be used by everyone who is interested in digitisation methods and biological collections and aims at making the micro-CT data exploration of natural history specimens freely available over the internet. The Micro-CT vlab offers to the user virtual image galleries of various taxa which can be displayed and downloaded through a web application. With a few clicks, accurate, detailed and three-dimensional models of species can be studied and virtually dissected without destroying the actual specimen. The data and functions of the Micro-CT vlab can be accessed either on a normal computer or through a dedicated version for mobile devices.

T-Check in Technologies for Interoperability: Web Services and Security--Single Sign-On

DTIC Science & Technology

2007-12-01

following tools: • Apache Tomcat 6.0—a Java Servlet container to host the Web services and a simple Web client application [Apache 2007a] • Apache Axis...Eclipse. Eclipse – an open development platform. http://www.eclipse.org/ (2007) [Hunter 2001] Hunter, Jason. Java Servlet Programming, 2nd Edition...Citation SAML 1.1 Java Toolkit SAML Ping Identity’s SAML-1.1 implementation [SourceID 2006] OpenSAML SAML An open source implementation of SAML 1.1

Virus-Mimetic Fusogenic Exosomes for Direct Delivery of Integral Membrane Proteins to Target Cell Membranes.

PubMed

Yang, Yoosoo; Hong, Yeonsun; Nam, Gi-Hoon; Chung, Jin Hwa; Koh, Eunee; Kim, In-San

2017-04-01

An efficient system for direct delivery of integral membrane proteins is successfully developed using a new biocompatible exosome-based platform. Fusogenic exosomes harboring viral fusogen, vascular stomatitis virus (VSV)-G protein, can fuse with and modify plasma membranes in a process called "membrane editing." This can facilitate the transfer of biologically active membrane proteins into the target cell membranes both in vitro and in vivo. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Space micro-guidance and control - Applications and architectures

NASA Technical Reports Server (NTRS)

Mettler, Edward; Hadaegh, Fred Y.

1992-01-01

The features and the components of a new microscale guidance, navigation, and control (GN&C) system for future space systems are discussed. An approach is described for the utilization of new microengineering technologies for achieving major reductions in the GN&C system's mass, size, power, and costs. The micro-GN&C system and the component concepts include microactuated adaptive optics, micromachined inertial sensors, fiberoptic data nets with light-power transmission, and VLSI microcomputers. The GN&C system will be applied in microspacecraft, microlanders, microrovers, remote sensing platforms, interferometers, and deployable reflectors.

Space micro-guidance and control - Applications and architectures

NASA Astrophysics Data System (ADS)

Mettler, Edward; Hadaegh, Fred Y.

1992-07-01

The features and the components of a new microscale guidance, navigation, and control (GN&C) system for future space systems are discussed. An approach is described for the utilization of new microengineering technologies for achieving major reductions in the GN&C system's mass, size, power, and costs. The micro-GN&C system and the component concepts include microactuated adaptive optics, micromachined inertial sensors, fiberoptic data nets with light-power transmission, and VLSI microcomputers. The GN&C system will be applied in microspacecraft, microlanders, microrovers, remote sensing platforms, interferometers, and deployable reflectors.

DynaMiTES - A dynamic cell culture platform for in vitro drug testing PART 1 - Engineering of microfluidic system and technical simulations.

PubMed

Mattern, Kai; Beißner, Nicole; Reichl, Stephan; Dietzel, Andreas

2018-05-01

Conventional safety and efficacy test models, such as animal experiments or static in vitro cell culture models, can often not reliably predict the most promising drug candidates. Therefore, a novel microfluidic cell culture platform, called Dynamic Micro Tissue Engineering System (DynaMiTES), was designed to allow online analysis of drugs permeating through barrier forming tissues under dynamic conditions combined with monitoring of the transepithelial electrical resistance (TEER) by electrodes optimized for homogeneous current distribution. A variety of pre-cultivated cell culture inserts can be integrated and exposed to well controlled dynamic micro flow conditions, resulting in a tightly regulated exposure of the cells to tested drugs, drug formulations and shear forces. With these qualities, the new system can provide more relevant information compared to static measurements. As a first in vitro model, a three-dimensional hemicornea construct consisting of human keratocytes (HCK-Ca) and epithelial cells (HCE-T) was successfully tested in the DynaMiTES. Thereby, we were able to demonstrate the functionality and cell compatibility of this new organ on chip test platform. The modular design of the DynaMiTES allows fast adaptation suitable for the investigation of drug permeation through other important cellular barriers. Copyright © 2017. Published by Elsevier B.V.

Future robotic platforms in urologic surgery: Recent Developments

PubMed Central

Herrell, S. Duke; Webster, Robert; Simaan, Nabil

2014-01-01

Purpose of review To review recent developments at Vanderbilt University of new robotic technologies and platforms designed for minimally invasive urologic surgery and their design rationale and potential roles in advancing current urologic surgical practice. Recent findings Emerging robotic platforms are being developed to improve performance of a wider variety of urologic interventions beyond the standard minimally invasive robotic urologic surgeries conducted presently with the da Vinci platform. These newer platforms are designed to incorporate significant advantages of robotics to improve the safety and outcomes of transurethral bladder surgery and surveillance, further decrease the invasiveness of interventions by advancing LESS surgery, and allow for previously impossible needle access and ablation delivery. Summary Three new robotic surgical technologies that have been developed at Vanderbilt University are reviewed, including a robotic transurethral system to enhance bladder surveillance and TURBT, a purpose-specific robotic system for LESS, and a needle sized robot that can be used as either a steerable needle or small surgeon-controlled micro-laparoscopic manipulator. PMID:24253803

Wirelessly powered micro-tracer enabled by miniaturized antenna and microfluidic channel

NASA Astrophysics Data System (ADS)

Duan, G.; Zhao, X.; Seren, H. R.; Chen, C.; Zhang, X.

2015-12-01

A miniaturized antenna, 380μm by 380μm in size, was fabricated and integrated with a commercialized passive RFID chip to form a micro-tracer, whose size was 2mm by 1mm in total. The micro-tracer was wirelessly powered and interrogated by a single layer spiral reader antenna through near field coupling. To maximize the working distance, the resonant frequency of micro-tracer and reader antenna were matched at 840MHz. Due to the ultra small size of the tracer antenna, power transfer efficiency decreased dramatically as the distance between tracer antenna and reader antenna increased, thus the working distance of the microtracer was limited within 1mm. To achieve massive operation of the micro-tracer, a microfluidic platform was fabricated with in channel focusing and separation. Acrylic sheets were laser cut to define the channel and cover structure, then bonded together layer by layer with a glass substrate, on which reader antenna was integrated. Pump oil was used as the fluidic media carrying the micro-tracer flowing inside the microfluidic channel. The wireless power transfer and real-time communication was demonstrated with the micro-tracer flowing above the reader antenna, as the ID of the micro-tracer was retrieved and displayed on a computer screen.

Design considerations for quasi-phase-matching in doubly resonant lithium niobate hexagonal micro-resonators

NASA Astrophysics Data System (ADS)

Sono, Tleyane J.; Riziotis, Christos; Mailis, Sakellaris; Eason, Robert W.

2017-09-01

Fabrication capabilities of high optical quality hexagonal superstructures by chemical etching of inverted ferroelectric domains in lithium niobate platform suggests a route for efficient implementation of compact hexagonal microcavities. Such nonlinear optical hexagonal micro-resonators are proposed as a platform for second harmonic generation (SHG) by the combined mechanisms of total internal reflection (TIR) and quasi-phase-matching (QPM). The proposed scheme for SHG via TIR-QPM in a hexagonal microcavity can improve the efficiency and also the compactness of SHG devices compared to traditional linear-type based devices. A simple theoretical model based on six-bounce trajectory and phase matching conditions was capable for obtaining the optimal cavity size. Furthermore numerical simulation results based on finite difference time domain beam propagation method analysis confirmed the solutions obtained by demonstrating resonant operation of the microcavity for the second harmonic wave produced by TIR-QPM. Design aspects, optimization issues and characteristics of the proposed nonlinear device are presented.

Hybrid integration of III-V semiconductor lasers on silicon waveguides using optofluidic microbubble manipulation

PubMed Central

Jung, Youngho; Shim, Jaeho; Kwon, Kyungmook; You, Jong-Bum; Choi, Kyunghan; Yu, Kyoungsik

2016-01-01

Optofluidic manipulation mechanisms have been successfully applied to micro/nano-scale assembly and handling applications in biophysics, electronics, and photonics. Here, we extend the laser-based optofluidic microbubble manipulation technique to achieve hybrid integration of compound semiconductor microdisk lasers on the silicon photonic circuit platform. The microscale compound semiconductor block trapped on the microbubble surface can be precisely assembled on a desired position using photothermocapillary convective flows induced by focused laser beam illumination. Strong light absorption within the micro-scale compound semiconductor object allows real-time and on-demand microbubble generation. After the assembly process, we verify that electromagnetic radiation from the optically-pumped InGaAsP microdisk laser can be efficiently coupled to the single-mode silicon waveguide through vertical evanescent coupling. Our simple and accurate microbubble-based manipulation technique may provide a new pathway for realizing high precision fluidic assembly schemes for heterogeneously integrated photonic/electronic platforms as well as microelectromechanical systems. PMID:27431769

A non-resonant fiber scanner based on an electrothermally-actuated MEMS stage

PubMed Central

Zhang, Xiaoyang; Duan, Can; Liu, Lin; Li, Xingde; Xie, Huikai

2015-01-01

Scanning fiber tips provides the most convenient way for forward-viewing fiber-optic microendoscopy. In this paper, a distal fiber scanning method based on a large-displacement MEMS actuator is presented. A single-mode fiber is glued on the micro-platform of an electrothermal MEMS stage to realize large range non-resonantscanning. The micro-platform has a large piston scan range of up to 800 µm at only 6V. The tip deflection of the fiber can be further amplified by placing the MEMS stage at a proper location along the fiber. A quasi-static model of the fiber-MEMS assembly has been developed and validated experimentally. The frequency response has also been studied and measured. A fiber tip deflection of up to 1650 µm for the 45 mm-long movable fiber portion has been achieved when the MEMS electrothermal stage was placed 25 mm away from the free end. The electrothermally-actuated MEMS stage shows a great potential for forward viewing fiber scanning and optical applications. PMID:26347583

The MicroArray Quality Control (MAQC) project shows inter- and intraplatform reproducibility of gene expression measurements

PubMed Central

2012-01-01

Over the last decade, the introduction of microarray technology has had a profound impact on gene expression research. The publication of studies with dissimilar or altogether contradictory results, obtained using different microarray platforms to analyze identical RNA samples, has raised concerns about the reliability of this technology. The MicroArray Quality Control (MAQC) project was initiated to address these concerns, as well as other performance and data analysis issues. Expression data on four titration pools from two distinct reference RNA samples were generated at multiple test sites using a variety of microarray-based and alternative technology platforms. Here we describe the experimental design and probe mapping efforts behind the MAQC project. We show intraplatform consistency across test sites as well as a high level of interplatform concordance in terms of genes identified as differentially expressed. This study provides a resource that represents an important first step toward establishing a framework for the use of microarrays in clinical and regulatory settings. PMID:16964229

High-throughput platform assay technology for the discovery of pre-microrna-selective small molecule probes.

PubMed

Lorenz, Daniel A; Song, James M; Garner, Amanda L

2015-01-21

MicroRNAs (miRNA) play critical roles in human development and disease. As such, the targeting of miRNAs is considered attractive as a novel therapeutic strategy. A major bottleneck toward this goal, however, has been the identification of small molecule probes that are specific for select RNAs and methods that will facilitate such discovery efforts. Using pre-microRNAs as proof-of-concept, herein we report a conceptually new and innovative approach for assaying RNA-small molecule interactions. Through this platform assay technology, which we term catalytic enzyme-linked click chemistry assay or cat-ELCCA, we have designed a method that can be implemented in high throughput, is virtually free of false readouts, and is general for all nucleic acids. Through cat-ELCCA, we envision the discovery of selective small molecule ligands for disease-relevant miRNAs to promote the field of RNA-targeted drug discovery and further our understanding of the role of miRNAs in cellular biology.

Fabrication of microlens array with controllable high NA and tailored optical characteristics using confined ink-jetting

NASA Astrophysics Data System (ADS)

Wang, Li; Luo, Yu; Liu, ZengZeng; Feng, Xueming; Lu, Bingheng

2018-06-01

This work presents an economic and controllable fabricating method of high numerical aperture (NA) polymer microlens array (MLA) based on ink-jetting technology. The MLAs are ink-jetted to align on micro platforms patterned flexible PDMS substrate. The shape of a sole lens is constructed by the ink-jetted pre-cured polymer volume confined on a micro platform. In this way, MLAs with targeted geometries-as well as tailored optical characteristics-can be printed, leading to freely designed optical properties. High NA from 0.446 to 0.885 and focal lengths between 99.26 μm and 39.45 μm are demonstrated, confirming theoretical predictions. Particularly, both the simulations and experimental measurements in optical properties are carried out, demonstrating that microlenses with shapes beyond a hemisphere (CA > 90°) exhibits higher light utilization efficiency and wider viewing angle. Meanwhile, the MLAs are fabricated on flexible PDMS substrates and can be attached to other curved surfaces for wider field of view imaging and higher sensitivity.

A microfluidic biochip platform for electrical quantification of proteins.

PubMed

Valera, Enrique; Berger, Jacob; Hassan, Umer; Ghonge, Tanmay; Liu, Julia; Rappleye, Michael; Winter, Jackson; Abboud, Daniel; Haidry, Zeeshan; Healey, Ryan; Hung, Na-Teng; Leung, Nathaniel; Mansury, Naif; Hasnain, Alexander; Lannon, Christine; Price, Zachary; White, Karen; Bashir, Rashid

2018-05-15

Sepsis, an adverse auto-immune response to an infection often causing life-threatening complications, results in the highest mortality and treatment cost of any illness in US hospitals. Several immune biomarker levels, including Interleukin 6 (IL-6), have shown a high correlation to the onset and progression of sepsis. Currently, no technology diagnoses and stratifies sepsis progression using biomarker levels. This paper reports a microfluidic biochip platform to detect proteins in undiluted human plasma samples. The device uses a differential enumeration platform that integrates Coulter counting principles, antigen specific capture chambers, and micro size bead based immunodetection to quantify cytokines. This microfluidic biochip was validated as a potential point of care technology by quantifying IL-6 from plasma samples (n = 29) with good correlation (R2 = 0.81) and agreement (Bland-Altman) compared to controls. In combination with previous applications, this point of care platform can potentially detect cell and protein biomarkers simultaneously for sepsis stratification.

Novel Uses of Video to Accelerate the Surgical Learning Curve.

PubMed

Ibrahim, Andrew M; Varban, Oliver A; Dimick, Justin B

2016-04-01

Surgeons are under enormous pressure to continually improve and learn new surgical skills. Novel uses of surgical video in the preoperative, intraoperative, and postoperative setting are emerging to accelerate the learning curve of surgical skill and minimize harm to patients. In the preoperative setting, social media outlets provide a valuable platform for surgeons to collaborate and plan for difficult operative cases. Live streaming of video has allowed for intraoperative telementoring. Finally, postoperative use of video has provided structure for peer coaching to evaluate and improve surgical skill. Applying these approaches into practice is becoming easier as most of our surgical platforms (e.g., laparoscopic, and endoscopy) now have video recording technology built in and video editing software has become more user friendly. Future applications of video technology are being developed, including possible integration into accreditation and board certification.

Micro-Etched Platforms for Thermal Inactivation of Bacillus Anthracis and Bacillus Thuringiensis Spores

DTIC Science & Technology

2008-03-01

slips was first coated with a detergent wash. Commercially available Ivory soap shavings were diluted with sterile Millipore® water in a...environments. This removed controllable variability between the Bacillus species and increased the confidence in continued use of such surrogacy

The MicroArray Quality Control (MAQC) project shows inter- and intraplatform reproducibility of gene expression measurements

EPA Science Inventory

Over the last decade, the introduction of microarray technology has had a profound impact on gene expression research. The publication of studies with dissimilar or altogether contradictory results, obtained using different microarray platforms to analyze identical RNA samples, ...

Test Waveform Applications for JPL STRS Operating Environment

NASA Technical Reports Server (NTRS)

Lux, James P.; Peters, Kenneth J.; Taylor, Gregory H.; Lang, Minh; Stern, Ryan A.; Duncan, Courtney B.

2013-01-01

This software demonstrates use of the JPL Space Telecommunications Radio System (STRS) Operating Environment (OE), tests APIs (application programming interfaces) presented by JPL STRS OE, and allows for basic testing of the underlying hardware platform. This software uses the JPL STRS Operating Environment ["JPL Space Tele com - munications Rad io System Operating Environment,"(NPO-4776) NASA Tech Briefs, commercial edition, Vol. 37, No. 1 (January 2013), p. 47] to interact with the JPL-SDR Software Defined Radio developed for the CoNNeCT (COmmunications, Navigation, and Networking rEconfigurable Testbed) Project as part of the SCaN Testbed installed on the International Space Station (ISS). These are the first applications that are compliant with the new NASA STRS Architecture Standard. Several example waveform applications are provided to demonstrate use of the JPL STRS OE for the JPL-SDR platform used for the CoNNeCT Project. The waveforms provide a simple digitizer and playback capability for the SBand RF slice, and a simple digitizer for the GPS slice [CoNNeCT Global Positioning System RF Module, (NPO-47764) NASA Tech Briefs, commercial edition, Vol. 36, No. 3 (March 2012), p. 36]. These waveforms may be used for hardware test, as well as for on-orbit or laboratory checkout. Additional example waveforms implement SpaceWire and timer modules, which can be used for time transfer and demonstration of communication between the two Xilinx FPGAs in the JPLSDR. The waveforms are also compatible with ground-based use of the JPL STRS OE on radio breadboards and Linux.

Universal lab-on-a-chip platform for complex, perfused 3D cell cultures

NASA Astrophysics Data System (ADS)

Sonntag, F.; Schmieder, F.; Ströbel, J.; Grünzner, S.; Busek, M.; Günther, K.; Steege, T.; Polk, C.; Klotzbach, U.

2016-03-01

The miniaturization, rapid prototyping and automation of lab-on-a-chip technology play nowadays a very important role. Lab-on-a-chip technology is successfully implemented not only for environmental analysis and medical diagnostics, but also as replacement of animals used for the testing of substances in the pharmaceutical and cosmetics industries. For that purpose the Fraunhofer IWS and partners developed a lab-on-a-chip platform for perfused cell-based assays in the last years, which includes different micropumps, valves, channels, reservoirs and customized cell culture modules. This technology is already implemented for the characterization of different human cell cultures and organoids, like skin, liver, endothelium, hair follicle and nephron. The advanced universal lab-on-a-chip platform for complex, perfused 3D cell cultures is divided into a multilayer basic chip with integrated micropump and application-specific 3D printed cell culture modules. Moreover a technology for surface modification of the printed cell culture modules by laser micro structuring and a complex and flexibly programmable controlling device based on an embedded Linux system was developed. A universal lab-on-a-chip platform with an optional oxygenator and a cell culture module for cubic scaffolds as well as first cell culture experiments within the cell culture device will be presented. The module is designed for direct interaction with robotic dispenser systems. This offers the opportunity to combine direct organ printing of cells and scaffolds with the microfluidic cell culture module. The characterization of the developed system was done by means of Micro-Particle Image Velocimetry (μPIV) and an optical oxygen measuring system.

Systematic and Open Identification of Researchers and Authors: Focus on Open Researcher and Contributor ID

PubMed Central

Akazhanov, Nurbek A.; Voronov, Alexander A.; Kitas, George D.

2014-01-01

Unique identifiers of researchers and authors can help all stakeholders of scientific communications improve their workflows. There have been several attempts to establish professional networks of scholars and list their scholarly achievements on digital platforms. Some of these platforms such as Google Scholar, Web of Knowledge and PubMed are searched to pick relevant peer reviewers, assess authors' publication history or choose suitable candidates for research and academic projects. However, each of these hubs has its specific applications, limiting the universal use for permanent tagging of researcher profiles. The Open Researcher and Contributor ID (ORCID) initiative, launched in 2012, is aimed at registering scholarly contributors and averting the persistent ambiguity of recorded author names. The ORCID registry is growing fast and integrating with other ID-generating platforms, thereby increasing the functionality of the integrated systems. ORCID identifiers are increasingly used for selecting peer reviewers and acknowledging various scholarly contributions (e.g., published articles, reviewer comments, conference presentations). The initiative offers unique opportunities for transparent disclosures of author contributions and competing interests and improving ethical standards of research, editing, and publishing. PMID:25408574

Systematic and open identification of researchers and authors: focus on open researcher and contributor ID.

PubMed

Gasparyan, Armen Yuri; Akazhanov, Nurbek A; Voronov, Alexander A; Kitas, George D

2014-11-01

Unique identifiers of researchers and authors can help all stakeholders of scientific communications improve their workflows. There have been several attempts to establish professional networks of scholars and list their scholarly achievements on digital platforms. Some of these platforms such as Google Scholar, Web of Knowledge and PubMed are searched to pick relevant peer reviewers, assess authors' publication history or choose suitable candidates for research and academic projects. However, each of these hubs has its specific applications, limiting the universal use for permanent tagging of researcher profiles. The Open Researcher and Contributor ID (ORCID) initiative, launched in 2012, is aimed at registering scholarly contributors and averting the persistent ambiguity of recorded author names. The ORCID registry is growing fast and integrating with other ID-generating platforms, thereby increasing the functionality of the integrated systems. ORCID identifiers are increasingly used for selecting peer reviewers and acknowledging various scholarly contributions (e.g., published articles, reviewer comments, conference presentations). The initiative offers unique opportunities for transparent disclosures of author contributions and competing interests and improving ethical standards of research, editing, and publishing.

Study on application of dynamic monitoring of land use based on mobile GIS technology

NASA Astrophysics Data System (ADS)

Tian, Jingyi; Chu, Jian; Guo, Jianxing; Wang, Lixin

2006-10-01

The land use dynamic monitoring is an important mean to maintain the real-time update of the land use data. Mobile GIS technology integrates GIS, GPS and Internet. It can update the historic al data in real time with site-collected data and realize the data update in large scale with high precision. The Monitoring methods on the land use change data with the mobile GIS technology were discussed. Mobile terminal of mobile GIS has self-developed for this study with GPS-25 OEM and notebook computer. The RTD (real-time difference) operation mode is selected. Mobile GIS system of dynamic monitoring of land use have developed with Visual C++ as operation platform, MapObjects control as graphic platform and MSCmm control as communication platform, which realizes organic integration of GPS, GPRS and GIS. This system has such following basic functions as data processing, graphic display, graphic editing, attribute query and navigation. Qinhuangdao city was selected as the experiential area. Shown by the study result, the mobile GIS integration system of dynamic monitoring of land use developed by this study has practical application value.

In Situ Gene Therapy via AAV-CRISPR-Cas9-Mediated Targeted Gene Regulation.

PubMed

Moreno, Ana M; Fu, Xin; Zhu, Jie; Katrekar, Dhruva; Shih, Yu-Ru V; Marlett, John; Cabotaje, Jessica; Tat, Jasmine; Naughton, John; Lisowski, Leszek; Varghese, Shyni; Zhang, Kang; Mali, Prashant

2018-04-25

Development of efficacious in vivo delivery platforms for CRISPR-Cas9-based epigenome engineering will be critical to enable the ability to target human diseases without permanent modification of the genome. Toward this, we utilized split-Cas9 systems to develop a modular adeno-associated viral (AAV) vector platform for CRISPR-Cas9 delivery to enable the full spectrum of targeted in situ gene regulation functionalities, demonstrating robust transcriptional repression (up to 80%) and activation (up to 6-fold) of target genes in cell culture and mice. We also applied our platform for targeted in vivo gene-repression-mediated gene therapy for retinitis pigmentosa. Specifically, we engineered targeted repression of Nrl, a master regulator of rod photoreceptor determination, and demonstrated Nrl knockdown mediates in situ reprogramming of rod cells into cone-like cells that are resistant to retinitis pigmentosa-specific mutations, with concomitant prevention of secondary cone loss. Furthermore, we benchmarked our results from Nrl knockdown with those from in vivo Nrl knockout via gene editing. Taken together, our AAV-CRISPR-Cas9 platform for in vivo epigenome engineering enables a robust approach to target disease in a genomically scarless and potentially reversible manner. Copyright © 2018 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

Fabrication of 3D electro-thermal micro actuators in silica glass by femtosecond laser wet etch and microsolidics

NASA Astrophysics Data System (ADS)

Li, Qichao; Shan, Chao; Yang, Qing; Chen, Feng; Bian, Hao; Hou, Xun

2017-02-01

This paper demonstrates a novel electro-thermal micro actuator's design, fabrication and device tests which combine microfluidic technology and microsolidics process. A three-dimensional solenoid microchannel with high aspect ratio is fabricated inside the silica glass by an improved femtosecond laser wet etch (FLWE) technology, and the diameter of the spiral coil is only 200 μm. Molten alloy (Bi/In/Sn/Pb) with high melting point is injected into the three-dimensional solenoid microchannel inside the silica glass , then it solidifys and forms an electro-thermal micro actuator. The device is capable of achieving precise temperature control and quick response, and can also be easily integrated into MEMS, sensors and `lab on a chip' (LOC) platform inside the fused silica substrate.

Flow optimization study of a batch microfluidics PET tracer synthesizing device

PubMed Central

Elizarov, Arkadij M.; Meinhart, Carl; van Dam, R. Michael; Huang, Jiang; Daridon, Antoine; Heath, James R.; Kolb, Hartmuth C.

2010-01-01

We present numerical modeling and experimental studies of flow optimization inside a batch microfluidic micro-reactor used for synthesis of human-scale doses of Positron Emission Tomography (PET) tracers. Novel techniques are used for mixing within, and eluting liquid out of, the coin-shaped reaction chamber. Numerical solutions of the general incompressible Navier Stokes equations along with time-dependent elution scalar field equation for the three dimensional coin-shaped geometry were obtained and validated using fluorescence imaging analysis techniques. Utilizing the approach presented in this work, we were able to identify optimized geometrical and operational conditions for the micro-reactor in the absence of radioactive material commonly used in PET related tracer production platforms as well as evaluate the designed and fabricated micro-reactor using numerical and experimental validations. PMID:21072595

Widely tunable 11 GHz femtosecond fiber laser based on a nonmode-locked source [Widely tunable 11 GHz femtosecond fiber laser based on a non-modelocked source

DOE PAGES

Prantil, Matthew A.; Cormier, Eric; Dawson, Jay W.; ...

2013-08-19

An 11 GHz fiber laser built on a modulated CW platform is described and characterized. This compact, vibrationinsensitive, fiber based system can be operated at wavelengths compatible with high energy fiber technology, is driven by an RF signal directly, and is tunable over a wide range of drive frequencies. The demonstration system when operated at 1040 nm is capable of 50 ns bursts of 575 micro-pulses produced at a macro-pulse rate of 83 kHz where the macro-pulse and micro-pulse energies are 1.8 μJ and 3.2 nJ respectively. Micro-pulse durations of 850 fs are demonstrated. Finally, we discuss extensions to shortermore » duration.« less

Teaching practice of Internet information technology in College English Course

NASA Astrophysics Data System (ADS)

Zhao, Dandan

2018-03-01

The rapid development of “Internet+ Education” enables College English teachers to use the vast network platform with modern educational technology in teaching. The article put forward the practical mode of Micro-lecture in College English Teaching in this context to present a feasible approach to College English course.

ADAR1 regulates ARHGAP26 gene expression through RNA editing by disrupting miR-30b-3p and miR-573 binding.

PubMed

Wang, Qiong; Hui, Haipeng; Guo, Zhendong; Zhang, Weina; Hu, Yaou; He, Tao; Tai, Yanhong; Peng, Peng; Wang, Li

2013-11-01

Rho GTPase activating protein 26 (ARHGAP26) is a negative regulator of the Rho family that converts the small G proteins RhoA and Cdc42 to their inactive GDP-bound forms. It is essential for the CLIC/GEEC endocytic pathway, cell spreading, and muscle development. The present study shows that ARHGAP26 mRNA undergoes extensive A-to-I RNA editing in the 3' UTR that is specifically catalyzed by ADAR1. Furthermore, the mRNA and protein levels of ARHGAP26 were decreased in cells in which ADAR1 was knocked down. Conversely, ADAR1 overexpression increased the abundance of ARHGAP26 mRNA and protein. In addition, we found that both miR-30b-3p and miR-573 target the ARHGAP26 gene and that RNA editing of ARHGAP26 mediated by ADAR1 abolished the repression of its expression by miR-30b-3p or miR-573. When ADAR1 was overexpressed, the reduced abundance of ARHGAP26 protein mediated by miR-30b-3p or miR-573 was rescued. Importantly, we also found that knocking down ADAR1 elevated RhoA activity, which was consistent with the reduced level of ARHGAP26. Conversely, when ADAR1 was overexpressed, the amount of RhoA-GTP decreased. The similar expression patterns of ARHGAP26 and ADAR1 in human tissue samples further confirmed our findings. Taken together, our results suggest that ADAR1 regulates the expression of ARHGAP26 through A-to-I RNA editing by disrupting the binding of miR-30b-3p and miR-573 within the 3' UTR of ARHGAP26. This study provides a novel insight into the mechanism by which ADAR1 and its RNA editing function regulate microRNA-mediated modulation of target genes.

Micro-Nanostructures of Cellulose-Collagen for Critical Sized Bone Defect Healing.

PubMed

Aravamudhan, Aja; Ramos, Daisy M; Nip, Jonathan; Kalajzic, Ivo; Kumbar, Sangamesh G

2018-02-01

Bone tissue engineering strategies utilize biodegradable polymeric matrices alone or in combination with cells and factors to provide mechanical support to bone, while promoting cell proliferation, differentiation, and tissue ingrowth. The performance of mechanically competent, micro-nanostructured polymeric matrices, in combination with bone marrow stromal cells (BMSCs), is evaluated in a critical sized bone defect. Cellulose acetate (CA) is used to fabricate a porous microstructured matrix. Type I collagen is then allowed to self-assemble on these microstructures to create a natural polymer-based, micro-nanostructured matrix (CAc). Poly (lactic-co-glycolic acid) matrices with identical microstructures serve as controls. Significantly higher number of implanted host cells are distributed in the natural polymer based micro-nanostructures with greater bone density and more uniform cell distribution. Additionally, a twofold increase in collagen content is observed with natural polymer based scaffolds. This study establishes the benefits of natural polymer derived micro-nanostructures in combination with donor derived BMSCs to repair and regenerate critical sized bone defects. Natural polymer based materials with mechanically competent micro-nanostructures may serve as an alternative material platform for bone regeneration. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

PLGA nano/micro particles encapsulated with pertussis toxoid (PTd) enhances Th1/Th17 immune response in a murine model.

PubMed

Li, Pan; Asokanathan, Catpagavalli; Liu, Fang; Khaing, Kyi Kyi; Kmiec, Dorota; Wei, Xiaoqing; Song, Bing; Xing, Dorothy; Kong, Deling

2016-11-20

Poly(lactic-co-glycolic acid) (PLGA) based nano/micro particles were investigated as a potential vaccine platform for pertussis antigen. Presentation of pertussis toxoid as nano/micro particles (NP/MP) gave similar antigen-specific IgG responses in mice compared to soluble antigen. Notably, in cell line based assays, it was found that PLGA based nano/micro particles enhanced the phagocytosis of fluorescent antigen-nano/micro particles by J774.2 murine monocyte/macrophage cells compared to soluble antigen. More importantly, when mice were immunised with the antigen-nano/micro particles they significantly increased antigen-specific Th1 cytokines INF-γ and IL-17 secretion in splenocytes after in vitro re-stimulation with heat killed Bordetalla pertussis, indicating the induction of a Th1/Th17 response. Also, presentation of pertussis antigen in a NP/MP formulation is able to provide protection against respiratory infection in a murine model. Thus, the NP/MP formulation may provide an alternative to conventional acellular vaccines to achieve a more balanced Th1/Th2 immune response. Copyright © 2016 Elsevier B.V. All rights reserved.

Implementing and Quantifying the Shape-Memory Effect of Single Polymeric Micro/Nanowires with an Atomic Force Microscope.

PubMed

Fang, Liang; Gould, Oliver E C; Lysyakova, Liudmila; Jiang, Yi; Sauter, Tilman; Frank, Oliver; Becker, Tino; Schossig, Michael; Kratz, Karl; Lendlein, Andreas

2018-04-23

The implementation of shape-memory effects (SME) in polymeric micro- or nano-objects currently relies on the application of indirect macroscopic manipulation techniques, for example, stretchable molds or phantoms, to ensembles of small objects. Here, we introduce a method capable of the controlled manipulation and SME quantification of individual micro- and nano-objects in analogy to macroscopic thermomechanical test procedures. An atomic force microscope was utilized to address individual electro-spun poly(ether urethane) (PEU) micro- or nanowires freely suspended between two micropillars on a micro-structured silicon substrate. In this way, programming strains of 10±1% or 21±1% were realized, which could be successfully fixed. An almost complete restoration of the original free-suspended shape during heating confirmed the excellent shape-memory performance of the PEU wires. Apparent recovery stresses of σ max,app =1.2±0.1 and 33.3±0.1 MPa were obtained for a single microwire and nanowire, respectively. The universal AFM test platform described here enables the implementation and quantification of a thermomechanically induced function for individual polymeric micro- and nanosystems. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Magnetic alginate microfibers as scaffolding elements for the fabrication of microvascular-like structures.

PubMed

Sun, Tao; Shi, Qing; Huang, Qiang; Wang, Huaping; Xiong, Xiaolu; Hu, Chengzhi; Fukuda, Toshio

2018-01-15

Traditional cell-encapsulating scaffolds may elicit adverse host responses and inhomogeneity in cellular distribution. Thus, fabrication techniques for cellular self-assembly with micro-scaffold incorporation have been used recently to generate toroidal cellular modules for the bottom-up construction of vascular-like structures. The micro-scaffolds show advantage in promoting tissue formation. However, owing to the lack of annular cell micro-scaffolds, it remains a challenge to engineer micro-scale toroidal cellular modules (micro-TCMs) to fabricate microvascular-like structures. Here, magnetic alginate microfibers (MAMs) are used as scaffolding elements, where a winding strategy enables them to be formed into micro-rings as annular cell micro-scaffolds. These micro-rings were investigated for NIH/3T3 fibroblast growth as a function of surface chemistry and MAM size. Afterwards, micro-TCMs were successfully fabricated with the formation of NIH/3T3 fibroblasts and extracellular matrix layers on the three-dimensional micro-ring surfaces. Simple non-contact magnetic assembly was used to stack the micro-TCMs along a micro-pillar, after which cell fusion rapidly connected the assembled micro-TCMs into a microvascular-like structure. Endothelial cells or drugs encapsulated in the MAMs could be included in the microvascular-like structures as in vitro cellular models for vascular tissue engineering, or as miniaturization platforms for pharmaceutical drug testing in the future. Magnetic alginate microfibers functioned as scaffolding elements for guiding cell growth in micro-scale toroidal cellular modules (micro-TCMs) and provided a magnetic functionality to the micro-TCMs for non-contact 3D assembly in external magnetic fields. By using the liquid/air interface, the non-contact spatial manipulation of the micro-TCMs in the liquid environment was performed with a cost-effective motorized electromagnetic needle. A new biofabrication paradigm of construct of microvascular-like structure. The micro-tubal-shaped structures allowed direct cell-to-cell contact that solved problems of cell-encapsulating scaffolds. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Exploiting endogenous CRISPR-Cas system for multiplex genome editing in Clostridium tyrobutyricum and engineer the strain for high-level butanol production.

PubMed

Zhang, Jie; Zong, Wenming; Hong, Wei; Zhang, Zhong-Tian; Wang, Yi

2018-03-09

Although CRISPR-Cas9/Cpf1 have been employed as powerful genome engineering tools, heterologous CRISPR-Cas9/Cpf1 are often difficult to introduce into bacteria and archaea due to their severe toxicity. Since most prokaryotes harbor native CRISPR-Cas systems, genome engineering can be achieved by harnessing these endogenous immune systems. Here, we report the exploitation of Type I-B CRISPR-Cas of Clostridium tyrobutyricum for genome engineering. In silico CRISPR array analysis and plasmid interference assay revealed that TCA or TCG at the 5'-end of the protospacer was the functional protospacer adjacent motif (PAM) for CRISPR targeting. With a lactose inducible promoter for CRISPR array expression, we significantly decreased the toxicity of CRISPR-Cas and enhanced the transformation efficiency, and successfully deleted spo0A with an editing efficiency of 100%. We further evaluated effects of the spacer length on genome editing efficiency. Interestingly, spacers ≤ 20 nt led to unsuccessful transformation consistently, likely due to severe off-target effects; while a spacer of 30-38 nt is most appropriate to ensure successful transformation and high genome editing efficiency. Moreover, multiplex genome editing for the deletion of spo0A and pyrF was achieved in a single transformation, with an editing efficiency of up to 100%. Finally, with the integration of the alcohol dehydrogenase gene (adhE1 or adhE2) to replace cat1 (the key gene responsible for butyrate production and previously could not be deleted), two mutants were created for n-butanol production, with the butanol titer reached historically record high of 26.2 g/L in a batch fermentation. Altogether, our results demonstrated the easy programmability and high efficiency of endogenous CRISPR-Cas. The developed protocol herein has a broader applicability to other prokaryotes containing endogenous CRISPR-Cas systems. C. tyrobutyricum could be employed as an excellent platform to be engineered for biofuel and biochemical production using the CRISPR-Cas based genome engineering toolkit. Copyright © 2018 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

Fanconi anemia gene editing by the CRISPR/Cas9 system.

PubMed

Osborn, Mark J; Gabriel, Richard; Webber, Beau R; DeFeo, Anthony P; McElroy, Amber N; Jarjour, Jordan; Starker, Colby G; Wagner, John E; Joung, J Keith; Voytas, Daniel F; von Kalle, Christof; Schmidt, Manfred; Blazar, Bruce R; Tolar, Jakub

2015-02-01

Genome engineering with designer nucleases is a rapidly progressing field, and the ability to correct human gene mutations in situ is highly desirable. We employed fibroblasts derived from a patient with Fanconi anemia as a model to test the ability of the clustered regularly interspaced short palindromic repeats/Cas9 nuclease system to mediate gene correction. We show that the Cas9 nuclease and nickase each resulted in gene correction, but the nickase, because of its ability to preferentially mediate homology-directed repair, resulted in a higher frequency of corrected clonal isolates. To assess the off-target effects, we used both a predictive software platform to identify intragenic sequences of homology as well as a genome-wide screen utilizing linear amplification-mediated PCR. We observed no off-target activity and show RNA-guided endonuclease candidate sites that do not possess low sequence complexity function in a highly specific manner. Collectively, we provide proof of principle for precision genome editing in Fanconi anemia, a DNA repair-deficient human disorder.

DNATagger, colors for codons.

PubMed

Scherer, N M; Basso, D M

2008-09-16

DNATagger is a web-based tool for coloring and editing DNA, RNA and protein sequences and alignments. It is dedicated to the visualization of protein coding sequences and also protein sequence alignments to facilitate the comprehension of evolutionary processes in sequence analysis. The distinctive feature of DNATagger is the use of codons as informative units for coloring DNA and RNA sequences. The codons are colored according to their corresponding amino acids. It is the first program that colors codons in DNA sequences without being affected by "out-of-frame" gaps of alignments. It can handle single gaps and gaps inside the triplets. The program also provides the possibility to edit the alignments and change color patterns and translation tables. DNATagger is a JavaScript application, following the W3C guidelines, designed to work on standards-compliant web browsers. It therefore requires no installation and is platform independent. The web-based DNATagger is available as free and open source software at http://www.inf.ufrgs.br/~dmbasso/dnatagger/.

Inheritable Silencing of Endogenous Genes by Hit-and-Run Targeted Epigenetic Editing.

PubMed

Amabile, Angelo; Migliara, Alessandro; Capasso, Paola; Biffi, Mauro; Cittaro, Davide; Naldini, Luigi; Lombardo, Angelo

2016-09-22

Gene silencing is instrumental to interrogate gene function and holds promise for therapeutic applications. Here, we repurpose the endogenous retroviruses' silencing machinery of embryonic stem cells to stably silence three highly expressed genes in somatic cells by epigenetics. This was achieved by transiently expressing combinations of engineered transcriptional repressors that bind to and synergize at the target locus to instruct repressive histone marks and de novo DNA methylation, thus ensuring long-term memory of the repressive epigenetic state. Silencing was highly specific, as shown by genome-wide analyses, sharply confined to the targeted locus without spreading to nearby genes, resistant to activation induced by cytokine stimulation, and relieved only by targeted DNA demethylation. We demonstrate the portability of this technology by multiplex gene silencing, adopting different DNA binding platforms and interrogating thousands of genomic loci in different cell types, including primary T lymphocytes. Targeted epigenome editing might have broad application in research and medicine. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Interspecies Chimerism with Mammalian Pluripotent Stem Cells.

PubMed

Wu, Jun; Platero-Luengo, Aida; Sakurai, Masahiro; Sugawara, Atsushi; Gil, Maria Antonia; Yamauchi, Takayoshi; Suzuki, Keiichiro; Bogliotti, Yanina Soledad; Cuello, Cristina; Morales Valencia, Mariana; Okumura, Daiji; Luo, Jingping; Vilariño, Marcela; Parrilla, Inmaculada; Soto, Delia Alba; Martinez, Cristina A; Hishida, Tomoaki; Sánchez-Bautista, Sonia; Martinez-Martinez, M Llanos; Wang, Huili; Nohalez, Alicia; Aizawa, Emi; Martinez-Redondo, Paloma; Ocampo, Alejandro; Reddy, Pradeep; Roca, Jordi; Maga, Elizabeth A; Esteban, Concepcion Rodriguez; Berggren, W Travis; Nuñez Delicado, Estrella; Lajara, Jeronimo; Guillen, Isabel; Guillen, Pedro; Campistol, Josep M; Martinez, Emilio A; Ross, Pablo Juan; Izpisua Belmonte, Juan Carlos

2017-01-26

Interspecies blastocyst complementation enables organ-specific enrichment of xenogenic pluripotent stem cell (PSC) derivatives. Here, we establish a versatile blastocyst complementation platform based on CRISPR-Cas9-mediated zygote genome editing and show enrichment of rat PSC-derivatives in several tissues of gene-edited organogenesis-disabled mice. Besides gaining insights into species evolution, embryogenesis, and human disease, interspecies blastocyst complementation might allow human organ generation in animals whose organ size, anatomy, and physiology are closer to humans. To date, however, whether human PSCs (hPSCs) can contribute to chimera formation in non-rodent species remains unknown. We systematically evaluate the chimeric competency of several types of hPSCs using a more diversified clade of mammals, the ungulates. We find that naïve hPSCs robustly engraft in both pig and cattle pre-implantation blastocysts but show limited contribution to post-implantation pig embryos. Instead, an intermediate hPSC type exhibits higher degree of chimerism and is able to generate differentiated progenies in post-implantation pig embryos. Copyright © 2017 Elsevier Inc. All rights reserved.

FIREDOC users manual, 3rd edition

NASA Astrophysics Data System (ADS)

Jason, Nora H.

1993-12-01

FIREDOC is the on-line bibliographic database which reflects the holdings (published reports, journal articles, conference proceedings, books, and audiovisual items) of the Fire Research Information Services (FRIS) at the Building and Fire Research Laboratory (BFRL), National Institute of Standards and Technology (NIST). This manual provides step-by-step procedures for entering and exiting the database via telecommunication lines, as well as a number of techniques for searching the database and processing the results of the searches. This Third Edition is necessitated by the change to a UNIX platform. The new computer allows for faster response time if searching via a modem and, in addition, offers internet accessibility. FIREDOC may be used with personal computers, using DOS or Windows, or with Macintosh computers and workstations. A new section on how to access Internet is included, and one on how to obtain the references of interest to you. Appendix F: Quick Guide to Getting Started will be useful to both modem and Internet users.

High-throughput microfluidic single-cell digital polymerase chain reaction.

PubMed

White, A K; Heyries, K A; Doolin, C; Vaninsberghe, M; Hansen, C L

2013-08-06

Here we present an integrated microfluidic device for the high-throughput digital polymerase chain reaction (dPCR) analysis of single cells. This device allows for the parallel processing of single cells and executes all steps of analysis, including cell capture, washing, lysis, reverse transcription, and dPCR analysis. The cDNA from each single cell is distributed into a dedicated dPCR array consisting of 1020 chambers, each having a volume of 25 pL, using surface-tension-based sample partitioning. The high density of this dPCR format (118,900 chambers/cm(2)) allows the analysis of 200 single cells per run, for a total of 204,000 PCR reactions using a device footprint of 10 cm(2). Experiments using RNA dilutions show this device achieves shot-noise-limited performance in quantifying single molecules, with a dynamic range of 10(4). We performed over 1200 single-cell measurements, demonstrating the use of this platform in the absolute quantification of both high- and low-abundance mRNA transcripts, as well as micro-RNAs that are not easily measured using alternative hybridization methods. We further apply the specificity and sensitivity of single-cell dPCR to performing measurements of RNA editing events in single cells. High-throughput dPCR provides a new tool in the arsenal of single-cell analysis methods, with a unique combination of speed, precision, sensitivity, and specificity. We anticipate this approach will enable new studies where high-performance single-cell measurements are essential, including the analysis of transcriptional noise, allelic imbalance, and RNA processing.

Digital microfabrication of user-defined 3D microstructures in cell-laden hydrogels.

PubMed

Soman, Pranav; Chung, Peter H; Zhang, A Ping; Chen, Shaochen

2013-11-01

Complex 3D interfacial arrangements of cells are found in several in vivo biosystems such as blood vasculature, renal glomeruli, and intestinal villi. Current tissue engineering techniques fail to develop suitable 3D microenvironments to evaluate the concurrent effects of complex topography and cell encapsulation. There is a need to develop new fabrication approaches that control cell density and distribution within complex 3D features. In this work, we present a dynamic projection printing process that allows rapid construction of complex 3D structures using custom-defined computer-aided-design (CAD) files. Gelatin-methacrylate (GelMA) constructs featuring user-defined spiral, pyramid, flower, and dome micro-geometries were fabricated with and without encapsulated cells. Encapsulated cells demonstrate good cell viability across all geometries both on the scaffold surface and internal to the structures. Cells respond to geometric cues individually as well as collectively throughout the larger-scale patterns. Time-lapse observations also reveal the dynamic nature of mechanical interactions between cells and micro-geometry. When compared to conventional cell-seeding, cell encapsulation within complex 3D patterned scaffolds provides long-term control over proliferation, cell morphology, and geometric guidance. Overall, this biofabrication technique offers a flexible platform to evaluate cell interactions with complex 3D micro-features, with the ability to scale-up towards high-throughput screening platforms. © 2013 Wiley Periodicals, Inc.

Giga-pixel fluorescent imaging over an ultra-large field-of-view using a flatbed scanner.

PubMed

Göröcs, Zoltán; Ling, Yuye; Yu, Meng Dai; Karahalios, Dimitri; Mogharabi, Kian; Lu, Kenny; Wei, Qingshan; Ozcan, Aydogan

2013-11-21

We demonstrate a new fluorescent imaging technique that can screen for fluorescent micro-objects over an ultra-wide field-of-view (FOV) of ~532 cm(2), i.e., 19 cm × 28 cm, reaching a space-bandwidth product of more than 2 billion. For achieving such a large FOV, we modified the hardware and software of a commercially available flatbed scanner, and added a custom-designed absorbing fluorescent filter, a two-dimensional array of external light sources for computer-controlled and high-angle fluorescent excitation. We also re-programmed the driver of the scanner to take full control of the scanner hardware and achieve the highest possible exposure time, gain and sensitivity for detection of fluorescent micro-objects through the gradient index self-focusing lens array that is positioned in front of the scanner sensor chip. For example, this large FOV of our imaging platform allows us to screen more than 2.2 mL of undiluted whole blood for detection of fluorescent micro-objects within <5 minutes. This high-throughput fluorescent imaging platform could be useful for rare cell research and cytometry applications by enabling rapid screening of large volumes of optically dense media. Our results constitute the first time that a flatbed scanner has been converted to a fluorescent imaging system, achieving a record large FOV.

Poly(dimethylsiloxane) microchip-based immunoassay with multiple reaction zones: Toward on-chip multiplex detection platform

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shao, Guocheng; Wang, Jun; Li, Zhaohui

2011-09-20

In this work, a poly(dimethylsiloxane) (PDMS) microchip-based immuno-sensing platform with integrated pneumatic micro valves is described. The microchip was fabricated with multiple layer soft lithography technology. By controlling the activation status of corresponding valves, reagent flows in the microchannel network can be well manipulated so that immuno-reactions only take place at designated reaction zones (DRZs). Four DRZs are included in the prototype microchip. Since these DRZs are all isolated from each other by micro valves, cross contamination is prevented. Using the inner surface of the all-PDMS microchannel as immunoassay substrate, on-chip sandwich format solid phase immunoassay was performed to demonstratemore » the feasibility of this immuno-sensing platform. Mouse IgG and fluorescein isothiocyanate (FITC) were used as the model analyte and the signal reporter respectively. Only 10 ul sample is needed for the assay and low detection limit of 5 ng/ml (≈33 pM) was achieved though low-cost polyclonal antibodies were used in our experiment for feasibility study only. The encouraging results from mouse IgG immunoassay proved the feasibility of our microchip design. With slight modification of the assay protocol, the same chip design can be used for multi-target detection and can provide a simple, cost-effective and integrated microchip solution for multiplex immunoassay applications.« less

Simple and Sensitive Quantification of MicroRNAs via PS@Au Microspheres-Based DNA Probes and DSN-Assisted Signal Amplification Platform.

PubMed

Zhao, Qian; Piao, Jiafang; Peng, Weipan; Wang, Yang; Zhang, Bo; Gong, Xiaoqun; Chang, Jin

2018-01-31

Identifying the microRNA (miRNA) expression level can provide critical information for early diagnosis of cancers or monitoring the cancer therapeutic efficacy. This paper focused on a kind of gold-nanoparticle-coated polystyrene microbeads (PS@Au microspheres)-based DNA probe as miRNA capture and duplex-specific nuclease (DSN) signal amplification platform based on an RGB value readout for detection of miRNAs. In virtue of the outstanding selectivity and simple experimental operation, 5'-fluorochrome-labeled molecular beacons (MBs) were immobilized on PS@Au microspheres via their 3'-thiol, in the wake of the fluorescence quenching by nanoparticle surface energy transfer (NSET). Target miRNAs were captured by the PS@Au microspheres-based DNA probe through DNA/RNA hybridization. DSN enzyme subsequently selectively cleaved the DNA to recycle the target miRNA and release of fluorophores, thereby triggering the signal amplification with more free fluorophores. The RGB value measurement enabled a detection limit of 50 fM, almost 4 orders of magnitude lower than PS@Au microspheres-based DNA probe detection without DSN. Meanwhile, by different encoding of dyes, miRNA-21 and miRNA-10b were simultaneously detected in the same sample. Considering the ability for quantitation, high sensitivity, and convenient merits, the PS@Au microspheres-based DNA probe and DSN signal amplification platform supplied valuable information for early diagnosis of cancers.

Automation Framework for Flight Dynamics Products Generation

NASA Technical Reports Server (NTRS)

Wiegand, Robert E.; Esposito, Timothy C.; Watson, John S.; Jun, Linda; Shoan, Wendy; Matusow, Carla

2010-01-01

XFDS provides an easily adaptable automation platform. To date it has been used to support flight dynamics operations. It coordinates the execution of other applications such as Satellite TookKit, FreeFlyer, MATLAB, and Perl code. It provides a mechanism for passing messages among a collection of XFDS processes, and allows sending and receiving of GMSEC messages. A unified and consistent graphical user interface (GUI) is used for the various tools. Its automation configuration is stored in text files, and can be edited either directly or using the GUI.

[Medical cooperation on the internet].

PubMed

Meier, N; Lenzen, H; Renger, B C

1998-01-01

Post-1999, the economically united EEC will pose new challenges to European business, industry and citizen. It is a key objective that in the domain of European "infostructure" these problems are challenged and overcome, and that "advanced communications technologies and services" (ACTS) become the cement which binds the Community together. Within ACTS, 130 different projects are building new services. The consortium Emerald develops a telemedicine platform, setting up teleworking with teleconference, computer supported co-operative work (cscw, joint editing), demonstration and teleteaching for radiology, cardiology, nuclear medicine and radio surgery working environments.

A Sub-Orbital Platform for Flight Tests of Small Space Capsules

NASA Astrophysics Data System (ADS)

Pereira, P. Moraes A. L., Jr.; Silva, C. R.; Villas Bôas, D. J.; Corrêa, F., Jr.; Miyoshi, J. H.; Loures da Costa, L. E.

2002-01-01

In the development of a small recoverable space capsule, flight tests using sub-orbital rockets are considered. For this test series, a platform for aerodynamic and thermal measurements as also for qualification tests of onboard sub-systems and equipment was specified and is actually under development. This platform, known as SARA Suborbital, is specified to withstand a sub-orbital flight with the high performance sounding rocket VS40 and to be recovered at the sea. To perform the testing program, a flight trajectory with adequate aeroballistic parameters, as for instance high velocities in dense atmosphere and average re-entry velocity, is considered. The testing program includes measurements of aerodynamic pressures and thermal characteristics, three- axis acceleration, acoustic pressure level inside the platform and vibration environment. Beside this, tests to characterise the performance of the data acquisition and transmission system, the micro-gravity environment and to qualify the recovery system will be carried out. During the return flight, the dynamics of parachutes deployment and platform water impact, as also rescue procedures will also be observed. The present article shows the concept of the platform, describes in detail the experiments, and concludes with a discussion on the flight trajectory and recovery procedure.

Development and calibration of an air-floating six-axis force measurement platform using self-calibration

NASA Astrophysics Data System (ADS)

Huang, Bin; Wang, Xiaomeng; Li, Chengwei; Yi, Jiajing; Lu, Rongsheng; Tao, Jiayue

2016-09-01

This paper describes the design, working principle, as well as calibration of an air-floating six-axis force measurement platform, where the floating plate and nozzles were connected without contact, preventing inter-dimensional coupling and increasing precision significantly. The measurement repeatability error of the force size in the platform is less than 0.2% full scale (FS), which is significantly better than the precision of 1% FS in the six-axis force sensors on the current market. We overcame the difficulties of weight loading device in high-precision calibration by proposing a self-calibration method based on the floating plate gravity and met the calibration precision requirement of 0.02% FS. This study has general implications for the development and calibration of high-precision multi-axis force sensors. In particular, the air-floating six-axis force measurement platform could be applied to the calibration of some special sensors such as flexible tactile sensors and may be used as a micro-nano mechanical assembly platform for real-time assembly force testing.

A Mobile-Based Community Health Management Information System for Community Health Workers and Their Supervisors in 2 Districts of Zambia

PubMed Central

Biemba, Godfrey; Chiluba, Boniface; Yeboah-Antwi, Kojo; Silavwe, Vichaels; Lunze, Karsten; Mwale, Rodgers K; Russpatrick, Scott; Hamer, Davidson H

2017-01-01

ABSTRACT Introduction: Effective community health management information systems (C-HMIS) are important in low-resource countries that rely heavily on community-based health care providers. Zambia currently lacks a functioning C-HMIS to provide real-time, community-based health information from community health workers (CHWs) to health center staff and higher levels of the health system. Program Description: We developed a C-HMIS mobile platform for use by CHWs providing integrated community case management (iCCM) services and their supervisors to address challenges of frequent stock-outs and inadequate supportive supervision of iCCM-trained CHWs. The platform used simple feature mobile phones on which were loaded the District Health Information System version 2 (DHIS2) software and Java 2 platform micro edition (J2ME) aggregation and tracker applications. This project was implemented in Chipata and Chadiza districts, which supported previous mHealth programs and had cellular coverage from all 3 major network carriers in Zambia. A total of 40 CHWs and 20 CHW supervisors received mobile phones with data bundles and training in the mobile application, after which they implemented the program over a period of 5.5 months, from February to mid-July 2016. CHWs used the mobile phones to submit data on iCCM cases seen, managed, and referred, as well as iCCM medical and diagnostic supplies received and dispensed. Using their mobile phones, the supervisors tracked CHWs' reported cases with medicine consumption, sent CHWs feedback on their referrals, and received SMS reminders to set up mentorship sessions. Observations: CHWs were able to use the mobile application to send weekly reports to health center supervisors on disease caseloads and medical commodities consumed, to make drug and supply requisitions, and to send pre-referral notices to health centers. Health center staff used the mobile system to provide feedback to CHWs on the case outcomes of referred patients and to receive automated monthly SMS reminders to invite CHWs to the facility for mentorship. District- and central-level staff were able to access community-level health data in real time using passwords. Lessons Learned: C-HMIS, using simple feature phones, was feasible and viable for the provision of real-time community-based health information to all levels of the health care system in Zambia, but smartphones, laptops, or desktop computers are needed to perform data analysis and visualization. Ongoing technical support is needed to address the hardware and software challenges CHWs face in their day-to-day interaction with the application on their mobile phones. PMID:28855233

A Mobile-Based Community Health Management Information System for Community Health Workers and Their Supervisors in 2 Districts of Zambia.

PubMed

Biemba, Godfrey; Chiluba, Boniface; Yeboah-Antwi, Kojo; Silavwe, Vichaels; Lunze, Karsten; Mwale, Rodgers K; Russpatrick, Scott; Hamer, Davidson H

2017-09-27

Effective community health management information systems (C-HMIS) are important in low-resource countries that rely heavily on community-based health care providers. Zambia currently lacks a functioning C-HMIS to provide real-time, community-based health information from community health workers (CHWs) to health center staff and higher levels of the health system. We developed a C-HMIS mobile platform for use by CHWs providing integrated community case management (iCCM) services and their supervisors to address challenges of frequent stock-outs and inadequate supportive supervision of iCCM-trained CHWs. The platform used simple feature mobile phones on which were loaded the District Health Information System version 2 (DHIS2) software and Java 2 platform micro edition (J2ME) aggregation and tracker applications. This project was implemented in Chipata and Chadiza districts, which supported previous mHealth programs and had cellular coverage from all 3 major network carriers in Zambia. A total of 40 CHWs and 20 CHW supervisors received mobile phones with data bundles and training in the mobile application, after which they implemented the program over a period of 5.5 months, from February to mid-July 2016. CHWs used the mobile phones to submit data on iCCM cases seen, managed, and referred, as well as iCCM medical and diagnostic supplies received and dispensed. Using their mobile phones, the supervisors tracked CHWs' reported cases with medicine consumption, sent CHWs feedback on their referrals, and received SMS reminders to set up mentorship sessions. CHWs were able to use the mobile application to send weekly reports to health center supervisors on disease caseloads and medical commodities consumed, to make drug and supply requisitions, and to send pre-referral notices to health centers. Health center staff used the mobile system to provide feedback to CHWs on the case outcomes of referred patients and to receive automated monthly SMS reminders to invite CHWs to the facility for mentorship. District- and central-level staff were able to access community-level health data in real time using passwords. C-HMIS, using simple feature phones, was feasible and viable for the provision of real-time community-based health information to all levels of the health care system in Zambia, but smartphones, laptops, or desktop computers are needed to perform data analysis and visualization. Ongoing technical support is needed to address the hardware and software challenges CHWs face in their day-to-day interaction with the application on their mobile phones. © Biemba et al.

The Promise of Macromolecular Crystallization in Micro-fluidic Chips

NASA Technical Reports Server (NTRS)

vanderWoerd, Mark; Ferree, Darren; Pusey, Marc

2003-01-01

Micro-fluidics, or lab on a chip technology, is proving to be a powerful, rapid, and efficient approach to a wide variety of bio-analytical and microscale bio-preparative needs. The low materials consumption, combined with the potential for packing a large number of experiments in a few cubic centimeters, makes it an attractive technique for both initial screening and subsequent optimization of macromolecular crystallization conditions. Screening operations, which require equilibrating macromolecule solution with a standard set of premixed solutions, are relatively straightforward and have been successfully demonstrated in a micro-fluidics platform. More complex optimization methods, where crystallization solutions are independently formulated from a range of stock solutions, are considerably more complex and have yet to be demonstrated. To be competitive with either approach, a micro-fluidics system must offer ease of operation, be able to maintain a sealed environment over several weeks to months, and give ready access for the observation of crystals as they are grown.

Evaluation of microRNA alignment techniques

PubMed Central

Kaspi, Antony; El-Osta, Assam

2016-01-01

Genomic alignment of small RNA (smRNA) sequences such as microRNAs poses considerable challenges due to their short length (∼21 nucleotides [nt]) as well as the large size and complexity of plant and animal genomes. While several tools have been developed for high-throughput mapping of longer mRNA-seq reads (>30 nt), there are few that are specifically designed for mapping of smRNA reads including microRNAs. The accuracy of these mappers has not been systematically determined in the case of smRNA-seq. In addition, it is unknown whether these aligners accurately map smRNA reads containing sequence errors and polymorphisms. By using simulated read sets, we determine the alignment sensitivity and accuracy of 16 short-read mappers and quantify their robustness to mismatches, indels, and nontemplated nucleotide additions. These were explored in the context of a plant genome (Oryza sativa, ∼500 Mbp) and a mammalian genome (Homo sapiens, ∼3.1 Gbp). Analysis of simulated and real smRNA-seq data demonstrates that mapper selection impacts differential expression results and interpretation. These results will inform on best practice for smRNA mapping and enable more accurate smRNA detection and quantification of expression and RNA editing. PMID:27284164

Evaluation of trabecular bone patterns on dental radiographic images: influence of cortical bone

NASA Astrophysics Data System (ADS)

Amouriq, Yves; Evenou, Pierre; Arlicot, Aurore; Normand, Nicolas; Layrolle, Pierre; Weiss, Pierre; Guédon, Jean-Pierre

2010-03-01

For some authors trabecular bone is highly visible in intraoral radiographs. For other authors, the observed intrabony trabecular pattern is a representation of only the endosteal surface of cortical bone, not of intermedullary striae. The purpose of this preliminary study was to investigate the true anatomical structures that are visible in routine dental radiographs and classically denoted trabecular bone. This is a major point for bone texture analysis on radiographs. Computed radiography (CR) images of dog mandible section in molar region were compared with simulations calculated from high-resolution micro-CT volumes. Calculated simulations were obtained using the Mojette Transform. By digitally editing the CT volume, the simulations were separated into trabecular and cortical components into a region of interest. Different images were compared and correlated, some bone micro-architecture parameters calculated. A high correlation was found between computed radiographs and calculated simulations from micro-CT. The Mojette transform was successful to obtain high quality images. Cortical bone did not contribute to change in a major way simulated images. These first results imply that intrabony trabecular pattern observed on radiographs can not only be a representation of the cortical bone endosteal surface and that trabecular bone is highly visible in intraoral radiographs.

Preliminary profiling of microRNA in the normal and regenerating liver of Chiloscyllium plagiosum.

PubMed

Cheng, Dandan; Chen, Yanna; Lu, Conger; Qian, Yuezhong; Lv, Zhengbing

2017-12-01

Liver is a vital organ present in animals for detoxification, protein synthesis, digestion and other functions and its powerful regenerative capacity is well known. C. plagiosum is an abundant fish that is representative of the cartilaginous class in the southeast coastal region of China and its liver accounts for >70% of the fish's visceral weight and contains many bioactive substances. MicroRNAs (microRNAs) play important roles in a wide range of biological processes in eukaryotes, including cell proliferation, differentiation, apoptosis. However, microRNAs in response to liver regeneration has not been well studied. This study aimed to identify the microRNAs that participate in liver regeneration and other liver-related diseases and to improve our understanding of the mechanisms of liver regeneration in sharks. To this end, normal and regenerating liver tissues from C. plagiosum were harvested 0, 3, 6, 12 and 24h after partial hepatectomy (pH) and were sequenced using the Illumina/Solexa platform. In total, 309 known microRNAs and 590 novel microRNAs were identified in C. plagiosum. There were many microRNAs differentially expressed in the normal and regenerating livers between time points. Using target prediction and GO analysis, most of the differentially expressed microRNAs were assigned to functional categories that may be involved in regulating liver regeneration, such as cell proliferation, differentiation and apoptosis. The microRNA expression profile of liver regeneration will pave the way for the development of effective strategies to fight against liver disease and other related disease. Copyright © 2017 Elsevier Inc. All rights reserved.

Design of a Microlecture Mobile Learning System Based on Smartphone and Web Platforms

ERIC Educational Resources Information Center

Wen, Chuanxue; Zhang, Junfei

2015-01-01

This paper first analyzes the concept and features of microlecture, mobile learning, and ubiquitous learning, then presents the combination of microlecture and mobile learning, to propose a novel way of micro-learning through mobile terminals. Details are presented of a microlecture mobile learning system (MMLS) that can support multiplatforms,…

Electronic desalting for controlling the ionic environment in droplet-based biosensing platforms

DOE Office of Scientific and Technical Information (OSTI.GOV)

Swaminathan, Vikhram Vilasur; Dak, Piyush; Alam, Muhammad A., E-mail: rbashir@illinois.edu, E-mail: alam@purdue.edu

2015-02-02

The ability to control the ionic environment in saline waters and aqueous electrolytes is useful for desalination as well as electronic biosensing. We demonstrate a method of electronic desalting at micro-scale through on-chip micro electrodes. We show that, while desalting is limited in bulk solutions with unlimited availability of salts, significant desalting of ≥1 mM solutions can be achieved in sub-nanoliter volume droplets with diameters of ∼250 μm. Within these droplets, by using platinum-black microelectrodes and electrochemical surface treatments, we can enhance the electrode surface area to achieve >99% and 41% salt removal in 1 mM and 10 mM salt concentrations, respectively. Through self-consistentmore » simulations and experimental measurements, we demonstrate that conventional double-layer theory over-predicts the desalting capacity and, hence, cannot be used to model systems that are mass limited or undergoing significant salt removal from the bulk. Our results will provide a better understanding of capacitive desalination, as well as a method for salt manipulation in high-throughput droplet-based microfluidic sensing platforms.« less

Micro-fluidic (Lab-on the- Chip) PCR Array Cartridge for Biological Screening in a Hand Held Device: FInal Report for CRADA no 264. PNNL-T2-258-RU with CombiMatrix Corp

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rainina, Evguenia I.

2010-10-31

The worldwide emergence of both new and old diseases resulting from human expansion and also human and materials mobility has and will continue to place stress on both medical and clinical diagnostics. The classical approach to bioagents detection involves the use of differential metabolic assays to determine species type in the case of most bacteria, or the use of cell culture and electron microscopy to diagnose viruses and some bacteria that are intracellular parasites. The long-term goal in bioagent detection is to develop a hand-held instrument featuring disposable cartridges which contain all the necessary reagents, reaction chambers, waste chambers, andmore » micro-fluidics to extract, concentrate, amplify, and analyze nucleic acids. This GIPP project began development of a sensory platform using nucleic-acid based probes. Although research was not completed, initial findings indicated that an advanced sensing device could theoretically be built on a DNA/RNA-based technology platform.« less

Optimal Control Design Using an H2 Method for the Glovebox Integrated Microgravity Isolation Technology (g-LIMIT)

NASA Technical Reports Server (NTRS)

Calhoun, Phillip C.; Hampton, R. David; Whorton, Mark S.

2001-01-01

The acceleration environment on the International Space Station (ISS) will likely exceed the requirements of many micro-gravity experiments. The Glovebox Integrated Microgravity Isolation Technology (g-LIMIT) is being built by the NASA Marshall Space Flight Center to attenuate the nominal acceleration environment and provide some isolation for micro-gravity science experiments. G-LIMIT uses Lorentz (voice-coil) magnetic actuators to isolate a platform for mounting science payloads from the nominal acceleration environment. The system utilizes payload acceleration, relative position, and relative orientation measurements in a feedback controller to accomplish the vibration isolation task. The controller provides current command to six magnetic actuators, producing the required experiment isolation from the ISS acceleration environment. This paper presents the development of a candidate control law to meet the acceleration attenuation requirements for the g-LIMIT experiment platform. The controller design is developed using linear optimal control techniques for both frequency-weighted H(sub 2) and H(sub infinity) norms. Comparison of the performance and robustness to plant uncertainty for these two optimal control design approaches are included in the discussion.

Electronic desalting for controlling the ionic environment in droplet-based biosensing platforms

NASA Astrophysics Data System (ADS)

Swaminathan, Vikhram Vilasur; Dak, Piyush; Reddy, Bobby; Salm, Eric; Duarte-Guevara, Carlos; Zhong, Yu; Fischer, Andrew; Liu, Yi-Shao; Alam, Muhammad A.; Bashir, Rashid

2015-02-01

The ability to control the ionic environment in saline waters and aqueous electrolytes is useful for desalination as well as electronic biosensing. We demonstrate a method of electronic desalting at micro-scale through on-chip micro electrodes. We show that, while desalting is limited in bulk solutions with unlimited availability of salts, significant desalting of ≥1 mM solutions can be achieved in sub-nanoliter volume droplets with diameters of ˜250 μm. Within these droplets, by using platinum-black microelectrodes and electrochemical surface treatments, we can enhance the electrode surface area to achieve >99% and 41% salt removal in 1 mM and 10 mM salt concentrations, respectively. Through self-consistent simulations and experimental measurements, we demonstrate that conventional double-layer theory over-predicts the desalting capacity and, hence, cannot be used to model systems that are mass limited or undergoing significant salt removal from the bulk. Our results will provide a better understanding of capacitive desalination, as well as a method for salt manipulation in high-throughput droplet-based microfluidic sensing platforms.

Driving platform for OLED lighting investigations

NASA Astrophysics Data System (ADS)

Vogel, Uwe; Elgner, Andreas; Kreye, Daniel; Amelung, Jörg; Scholles, Michael

2006-08-01

OLED technology may be excellently suitable for lighting applications by combining high efficiency, cost effective manufacturing and the use of low cost materials. Certain issues remain to be solved so far, including OLED brightness, color, lifetime, large area uniformity and encapsulation. Another aspect, that might be capable in addressing some of the mentioned issues, is OLED lighting electrical driving. We report on the design of a driving platform for OLED lighting test panels or substrates. It is intended for being a test environment for lighting substrates as well as demonstration/presentation environment. It is based on a 128-channel passive-matrix driver/controller ASIC OC2. Its key component is an MSP430-compatible 16-bit micro-controller core including embedded Flash memory (program), EEPROM (parameter), and RAM (data memory). A significant feature of the device is an electronic approach for improving the lifetime/uniformity behavior of connected OLED. The embedded micro-controller is the key to the high versatility of OC2, since by firmware modification it can be adapted to various applications and conditions. Here its application for an OLED lighting driving platform is presented. Major features of this platform are PC-control mode (via USB interface), stand-alone mode (no external control necessary, just power supply), on-board OLED panel parameter storage, flat geometry of OLED lighting panel carrier (board), AC and DC driving regimes, adjustable reverse voltage, dedicated user SW (PC/Windows-based), sub-tile patterning and single sub-tile control, combination of multiple channels for increasing driving current. This publication contains results of the project "High Brightness OLEDs for ICT & Next Generation Lighting Applications" (OLLA), funded by the European Commission.

Clinimetrics and clinical psychometrics: macro- and micro-analysis.

PubMed

Tomba, Elena; Bech, Per

2012-01-01

Clinimetrics was introduced three decades ago to specify the domain of clinical markers in clinical medicine (indexes or rating scales). In this perspective, clinical validity is the platform for selecting the various indexes or rating scales (macro-analysis). Psychometric validation of these indexes or rating scales is the measuring aspect (micro-analysis). Clinical judgment analysis by experienced psychiatrists is included in the macro-analysis and the item response theory models are especially preferred in the micro-analysis when using the total score as a sufficient statistic. Clinical assessment tools covering severity of illness scales, prognostic measures, issues of co-morbidity, longitudinal assessments, recovery, stressors, lifestyle, psychological well-being, and illness behavior have been identified. The constructive dialogue in clinimetrics between clinical judgment and psychometric validation procedures is outlined for generating developments of clinical practice in psychiatry. Copyright © 2012 S. Karger AG, Basel.

Porous silicon and diatoms micro-shells: an example of inverse biomimetic

NASA Astrophysics Data System (ADS)

De Tommasi, Edoardo; Rea, Ilaria; Rendina, Ivo; De Stefano, Luca

2011-05-01

Porous silicon (PSi) is by far a very useful technological platform for optical monitoring of chemical and biological substances and due to its peculiar physical and morphological properties it is worldwide used in sensing experiments. On the other hand, we have discovered a natural material, the micro-shells of marine diatoms, ubiquitous unicellular algae, which are made of hydrated amorphous silica, but, most of all, show geometrical structures made of complex patterns of pores which are surprisingly similar to those of porous silicon. Moreover, under laser irradiation, this material is photoluminescent and the photoluminescence is very sensitive to the surrounding atmosphere, which means that the material can act as a transducer. Starting from our experience on PSi devices, we explore the optical and photonic properties of marine diatoms micro-shells in a sort of inverse biomimicry.

Non-viral delivery systems for CRISPR/Cas9-based genome editing: Challenges and opportunities.

PubMed

Li, Ling; Hu, Shuo; Chen, Xiaoyuan

2018-07-01

In recent years, CRISPR (clustered regularly interspaced short palindromic repeat)/Cas (CRISPR-associated) genome editing systems have become one of the most robust platforms in basic biomedical research and therapeutic applications. To date, efficient in vivo delivery of the CRISPR/Cas9 system to the targeted cells remains a challenge. Although viral vectors have been widely used in the delivery of the CRISPR/Cas9 system in vitro and in vivo, their fundamental shortcomings, such as the risk of carcinogenesis, limited insertion size, immune responses and difficulty in large-scale production, severely limit their further applications. Alternative non-viral delivery systems for CRISPR/Cas9 are urgently needed. With the rapid development of non-viral vectors, lipid- or polymer-based nanocarriers have shown great potential for CRISPR/Cas9 delivery. In this review, we analyze the pros and cons of delivering CRISPR/Cas9 systems in the form of plasmid, mRNA, or protein and then discuss the limitations and challenges of CRISPR/Cas9-based genome editing. Furthermore, current non-viral vectors that have been applied for CRISPR/Cas9 delivery in vitro and in vivo are outlined in details. Finally, critical obstacles for non-viral delivery of CRISPR/Cas9 system are highlighted and promising strategies to overcome these barriers are proposed. Published by Elsevier Ltd.

The Integrity bare-metal stent made by continuous sinusoid technology.

PubMed

Turco, Mark A

2011-05-01

The Integrity Coronary Stent System (Medtronic Vascular, CA, USA) is a low-profile, open-cell, cobalt-chromium-alloy advanced bare-metal iteration of the well-known Driver/Micro-Driver Coronary Stent System (Medtronic Vascular). The Integrity stent is made with a process called continuous sinusoid technology. This process allows stent construction via wrapping a single thin strand of wire around a mandrel in a sinusoid configuration, with laser fusion of adjacent crowns. The wire-forming process and fusion pattern provide the stent with a continuous preferential bending plane, intended to allow easier access to, and smoother tracking within, distal and tortuous vessels while radial strength is maintained. Continuous sinusoid technology represents innovation in the design of stent platforms and will provide a future stent platform for newer technology, including drug-eluting stent platforms, drug-filled stents and core wire stents.

Unmanned Aerial Vehicles for Environmental Monitoring with Special Reference to Heat Loss

NASA Astrophysics Data System (ADS)

Anweiler, Stanisław; Piwowarski, Dawid; Ulbrich, Roman

2017-10-01

This paper presents the design and implementation of device for remote and automatic monitoring of temperature field of large objects. The project aimed to create a quadcopter flying platform equipped with a thermal imaging camera. The object of the research was district heating installations above ground and underground. The results of the work on the implementation of low-cost (below 750 EUR) and efficient heat loss monitoring system. The system consists of a small (<2kg) multirotor platform. To perform thermal images micro camera FlirOne with microcomputer Raspberry Pi3 was used. Exploitation of UAVs in temperature field monitoring reveals only a fraction of their capabilities. The fast-growing multirotor platform market continues to deliver new solutions and improvements. Their use in monitoring the environment is limited only by the imagination of the user.

Optoelectrofluidic platforms for chemistry and biology.

PubMed

Hwang, Hyundoo; Park, Je-Kyun

2011-01-07

Extraordinary advances in lab on a chip systems have been made on the basis of the development of micro/nanofluidics and its fusion with other technologies based on electrokinetics and optics. Optoelectrofluidic technology, which has been recently introduced as a new manipulation scheme, allows programmable manipulation of particles or fluids in microenvironments based on optically induced electrokinetics. Herein, the behaviour of particles or fluids can be controlled by inducing or perturbing electric fields on demand in an optical manner, which includes photochemical, photoconductive, and photothermal effects. This elegant scheme of the optoelectrofluidic platform has attracted attention in various fields of science and engineering. A lot of research on optoelectrofluidic manipulation technologies has been reported and the field has advanced rapidly, although some technical hurdles still remain. This review describes recent developments and future perspectives of optoelectrofluidic platforms for chemical and biological applications.

Emergent behavior of cells on microfabricated soft polymeric substrates

NASA Astrophysics Data System (ADS)

Anand, Sandeep Venkit

In recent years, cell based bio-actuators like cardiomyocytes and skeletal muscle cells have emerged as popular choices for powering biological machines consisting of soft polymeric scaffolds at the micro and macro scales. This is owing to their unique ability to generate spontaneous, synchronous contractions either autonomously or under externally applied fields. Most of the biological machine designs reported in literature use single cells or cell clusters conjugated with biocompatible soft polymers like polydimethylsiloxane (PDMS) and hydrogels to produce some form of locomotion by converting chemical energy of the cells to mechanical energy. The mode of locomotion may vary, but the fundamental mechanism that these biological machines exploit to achieve locomotion stems from cell substrate interactions leading to large deformations of the substrates (relative to the cell size). However, the effect of such large scale, dynamic deformation of the substrates on the cellular and cluster level organization of the cells remains elusive. This dissertation tries to explore the emergent behavior of cells on different types of micro-scale deformable, soft polymeric substrates. In the first part of the dissertation, contractile dynamics of primary cardiomyocyte clusters is studied by culturing them on deformable thin polymeric films. The cell clusters beat and generate sufficient forces to deform the substrates out of plane. Over time, the clusters reorient their force dipoles along the direction of maximum compliance. This suggests that the cells are capable of sensing substrate deformations through a mechanosensitive feedback mechanism and dynamically reorganizing themselves. Results are further validated through finite element analysis. The development, characterization and quantification of a novel 1D/2D like polymeric platform for cell culture is presented in the second part. The platform consists of a 2D surface anchoring a long (few millimeters) narrow filament (1D) with a single cell scale (micro scale) cross section. We plate C2C12 cells on the platform and characterize their migration, proliferation, and differentiation patterns in contrast to 2D culture. We find that the cells land on the 2D surface, and then migrate to the filament only when the 2D surface has become nearly confluent. Individual and isolated cells randomly approaching the filament always retract away towards the 2D surface. Once on the filament, their differentiation to myotubes is expedited compared to that on 2D substrate. The myotubes generate periodic twitching forces that deform the filament producing more than 17 um displacement at the tip. Such flagellar motion can be used to develop autonomous micro scale bio-bots. Finally, the design and fabrication of a polymeric micro-pillar based force sensor capable of measuring cellular focal-adhesion forces under externally applied stretch is discussed. The force sensor consists of arrays of uniformly spaced PDMS micro-pillars of 1-2 um diameter and 2-3 um spacing on a macroscale PDMS substrate. The tips of the micro-pillars are selectively patterned with fluorescently labeled ECM proteins using micro-contact printing to promote cell adhesion while simultaneously acting as markers for strain measurements. Cells adhere and spread on top of the pillars causing them to deform. When stretched, the cells reorganize their internal structure and modulate their traction forces in response to the applied stretch. The dynamically varying cellular forces in response to the stretch are computed by measuring the cell induced displacements estimated by isolating the displacements caused by the applied stretch from the net displacements of the tips.

Micro-tensile testing system

DOEpatents

Wenski, Edward G [Lenexa, KS

2007-08-21

A micro-tensile testing system providing a stand-alone test platform for testing and reporting physical or engineering properties of test samples of materials having thicknesses of approximately between 0.002 inch and 0.030 inch, including, for example, LiGA engineered materials. The testing system is able to perform a variety of static, dynamic, and cyclic tests. The testing system includes a rigid frame and adjustable gripping supports to minimize measurement errors due to deflection or bending under load; serrated grips for securing the extremely small test sample; high-speed laser scan micrometers for obtaining accurate results; and test software for controlling the testing procedure and reporting results.

Micro-tensile testing system

DOEpatents

Wenski, Edward G.

2006-01-10

A micro-tensile testing system providing a stand-alone test platform for testing and reporting physical or engineering properties of test samples of materials having thicknesses of approximately between 0.002 inch and 0.030 inch, including, for example, LiGA engineered materials. The testing system is able to perform a variety of static, dynamic, and cyclic tests. The testing system includes a rigid frame and adjustable gripping supports to minimize measurement errors due to deflection or bending under load; serrated grips for securing the extremely small test sample; high-speed laser scan micrometers for obtaining accurate results; and test software for controlling the testing procedure and reporting results.

Micro-tensile testing system

DOEpatents

Wenski, Edward G [Lenexa, KS

2007-07-17

A micro-tensile testing system providing a stand-alone test platform for testing and reporting physical or engineering properties of test samples of materials having thicknesses of approximately between 0.002 inch and 0.030 inch, including, for example, LiGA engineered materials. The testing system is able to perform a variety of static, dynamic, and cyclic tests. The testing system includes a rigid frame and adjustable gripping supports to minimize measurement errors due to deflection or bending under load; serrated grips for securing the extremely small test sample; high-speed laser scan micrometers for obtaining accurate results; and test software for controlling the testing procedure and reporting results.

Control of integrated micro-resonator wavelength via balanced homodyne locking.

PubMed

Cox, Jonathan A; Lentine, Anthony L; Trotter, Douglas C; Starbuck, Andrew L

2014-05-05

We describe and experimentally demonstrate a method for active control of resonant modulators and filters in an integrated photonics platform. Variations in resonance frequency due to manufacturing processes and thermal fluctuations are corrected by way of balanced homodyne locking. The method is compact, insensitive to intensity fluctuations, minimally disturbs the micro-resonator, and does not require an arbitrary reference to lock. We demonstrate long-term stable locking of an integrated filter to a laser swept over 1.25 THz. In addition, we show locking of a modulator with low bit error rate while the chip temperature is varied from 5 to 60° C.

Design and prototyping of a chip-based multi-micro-organoid culture system for substance testing, predictive to human (substance) exposure.

PubMed

Sonntag, Frank; Schilling, Niels; Mader, Katja; Gruchow, Mathias; Klotzbach, Udo; Lindner, Gerd; Horland, Reyk; Wagner, Ilka; Lauster, Roland; Howitz, Steffen; Hoffmann, Silke; Marx, Uwe

2010-07-01

Dynamic miniaturized human multi-micro-organ bioreactor systems are envisaged as a possible solution for the embarrassing gap of predictive substance testing prior to human exposure. A rational approach was applied to simulate and design dynamic long-term cultures of the smallest possible functional human organ units, human "micro-organoids", on a chip the shape of a microscope slide. Each chip contains six identical dynamic micro-bioreactors with three different micro-organoid culture segments each, a feed supply and waste reservoirs. A liver, a brain cortex and a bone marrow micro-organoid segment were designed into each bioreactor. This design was translated into a multi-layer chip prototype and a routine manufacturing procedure was established. The first series of microscopable, chemically resistant and sterilizable chip prototypes was tested for matrix compatibility and primary cell culture suitability. Sterility and long-term human cell survival could be shown. Optimizing the applied design approach and prototyping tools resulted in a time period of only 3 months for a single design and prototyping cycle. This rapid prototyping scheme now allows for fast adjustment or redesign of inaccurate architectures. The designed chip platform is thus ready to be evaluated for the establishment and maintenance of the human liver, brain cortex and bone marrow micro-organoids in a systemic microenvironment. Copyright (c) 2010 Elsevier B.V. All rights reserved.

Micro-Ring Structures Stabilize Microdroplets to Enable Long Term Spheroid Culture in 384 Hanging Drop Array Plates

PubMed Central

Hsiao, Amy Y.; Tung, Yi-Chung; Kuo, Chuan-Hsien; Mosadegh, Bobak; Bedenis, Rachel; Pienta, Kenneth J.; Takayama, Shuichi

2012-01-01

Using stereolithography, 20 different structural variations comprised of millimeter diameter holes surrounded by trenches, plateaus, or micro-ring structures were prepared and tested for their ability to stably hold arrays of microliter sized droplets within the structures over an extended period of time. The micro-ring structures were the most effective in stabilizing droplets against mechanical and chemical perturbations. After confirming the importance of micro-ring structures using rapid prototyping, we developed an injection molding tool for mass production of polystyrene 3D cell culture plates with an array of 384 such micro-ring surrounded through-hole structures. These newly designed and injection molded polystyrene 384 hanging drop array plates with micro-rings were stable and robust against mechanical perturbations as well as surface fouling-facilitated droplet spreading making them capable of long term cell spheroid culture of up to 22 days within the droplet array. This is a significant improvement over previously reported 384 hanging drop array plates which are susceptible to small mechanical shocks and could not reliably maintain hanging drops for longer than a few days. With enhanced droplet stability, the hanging drop array plates with micro-ring structures provide better platforms and open up new opportunities for high-throughput preparation of microscale 3D cell constructs for drug screening and cell analysis. PMID:22057945

Micro-ring structures stabilize microdroplets to enable long term spheroid culture in 384 hanging drop array plates.

PubMed

Hsiao, Amy Y; Tung, Yi-Chung; Kuo, Chuan-Hsien; Mosadegh, Bobak; Bedenis, Rachel; Pienta, Kenneth J; Takayama, Shuichi

2012-04-01

Using stereolithography, 20 different structural variations comprised of millimeter diameter holes surrounded by trenches, plateaus, or micro-ring structures were prepared and tested for their ability to stably hold arrays of microliter sized droplets within the structures over an extended period of time. The micro-ring structures were the most effective in stabilizing droplets against mechanical and chemical perturbations. After confirming the importance of micro-ring structures using rapid prototyping, we developed an injection molding tool for mass production of polystyrene 3D cell culture plates with an array of 384 such micro-ring surrounded through-hole structures. These newly designed and injection molded polystyrene 384 hanging drop array plates with micro-rings were stable and robust against mechanical perturbations as well as surface fouling-facilitated droplet spreading making them capable of long term cell spheroid culture of up to 22 days within the droplet array. This is a significant improvement over previously reported 384 hanging drop array plates which are susceptible to small mechanical shocks and could not reliably maintain hanging drops for longer than a few days. With enhanced droplet stability, the hanging drop array plates with micro-ring structures provide better platforms and open up new opportunities for high-throughput preparation of microscale 3D cell constructs for drug screening and cell analysis.

[An implantable micro-device using wireless power transmission for measuring aortic aneurysm sac pressure].

PubMed

Guo, Xudong; Ge, Bin; Wang, Wenxing

2013-08-01

In order to detect endoleaks after endovascular aneurysm repair (EVAR), we developed an implantable micro-device based on wireless power transmission to measure aortic aneurysm sac pressure. The implantable micro-device is composed of a miniature wireless pressure sensor, an energy transmitting coil, a data recorder and a data processing platform. Power transmission without interconnecting wires is performed by a transmitting coil and a receiving coil. The coupling efficiency of wireless power transmission depends on the coupling coefficient between the transmitting coil and the receiving coil. With theoretical analysis and experimental study, we optimized the geometry of the receiving coil to increase the coupling coefficient. In order to keep efficiency balance and satisfy the maximizing conditions, we designed a closed loop power transmission circuit, including a receiving voltage feedback module based on wireless communication. The closed loop improved the stability and reliability of transmission energy. The prototype of the micro-device has been developed and the experiment has been performed. The experiments showed that the micro-device was feasible and valid. For normal operation, the distance between the transmitting coil and the receiving coil is smaller than 8cm. Besides, the distance between the micro-device and the data recorder is within 50cm.

Nanotechnologies in Cuba: Popularization and Training

NASA Astrophysics Data System (ADS)

Rodríguez Castellanos, Carlos

In Cuba, as in other countries, activities in the field of nanotechnology emerged from the converging development of research in materials physics and chemistry, microelectronics, supramolecular physics, microbiology and molecular biology. During the 1990s, theoretical and experimental work on semiconductor nanostructures gained in importance. Cuban physicists organized the Red CYTED (Network CYTED) to "study fabrication and characterization of semiconductor nanostructures for micro and optoelectronics" which functioned between 1998 and 2003 with the participation of eight Spanish-American countries. The network organized various courses and scientific meetings, edited a book and supported the scientific collaboration among the participant institutions.

A Conceptual Design for a Small Deployer Satellite

NASA Astrophysics Data System (ADS)

Zumbo, S.

2002-01-01

In the last few years, the space scientific and industrial communities have demonstrated a renewed interest for small missions based on new categories of space platforms: micro &nano satellites. The cost reduction w.r.t. larger satellite missions, the shorter time from concept to launch, the risk distribution and the possibility to use this kind of bus both for stand-alone projects and as complementary to larger programs, are key factors that make this new kind of technology suitable for a wide range of space related activities. In particular it is now possible to conceive new mission philosophy implying the realisation of micro satellite constellations, with S/C flying in close formation to form a network of distributed sensors either for near-real time telecommunication or Earth remote sensing and disaster monitoring systems or physics and astronomical researches for Earth-Sun dynamics and high energy radiation studies. At the same time micro satellite are becoming important test- beds for new technologies that will eventually be used on larger missions, with relevant spin-offs potentialities towards other industrial fields. The foreseen social and economical direct benefits, the reduced mission costs and the possibility even for a small skilled team to manage all the project, represent very attractive arguments for universities and research institutes to invest funds and human resources to get first order technical and theoretical skills in the field of micro satellite design, with important influences on the training programs of motivated students that are directly involved in all the project's phases. In consideration of these space market important new trends and of the academic benefits that could be guaranteed by undertaking a micro satellite mission project, basing on its long space activities heritage, University of Rome "La Sapienza" - Aerospace and Astronautics Department, with the support of the Italian Space Agency, Alenia Spazio and of important industrial partners, has started the development of a space mission, named DeSat, focused on a new highly innovative micro satellite bus for LEO, entirely designed by an integrated team of students and researchers. The first mission is scheduled to fly at the end of 2003 on a converted Russian ICBM. The paper is intended to present the main features of DeSat mission, its goals and the activities that have been done by students and researchers to achieve the micro satellite platform design. The principal payload of the entire system is represented by a recirculating ball screw boom whose mass reaches one third of the total mass budget. The goal of the mission is to demonstrate the validity of its design also for space applications, which may range from precise off platform positioning of devices and instruments to GPS interferometry, sensor measurements and robotics. The satellite geometry, when the boom is in deployed configuration, is so stretched that the name "deployable satellite" has come out naturally. The large deployment mechanism, compared to the small bus, has influenced the design of every satellite subsystem leading to innovative solutions in terms of design, materials, equipment and instruments.

Signal-on fluorescence biosensor for microRNA-21 detection based on DNA strand displacement reaction and Mg2+-dependent DNAzyme cleavage.

PubMed

Yin, Huan-Shun; Li, Bing-Chen; Zhou, Yun-Lei; Wang, Hai-Yan; Wang, Ming-Hui; Ai, Shi-Yun

2017-10-15

MicroRNAs have been involved into many biological processes and are regarded as disease biomarkers. Simple, rapid, sensitive and selective method for microRNA detection is crucial for early diagnosis and therapy of diseases. In this work, sensitive fluorescence assay was developed for microRNA-21 detection based on DNA polymerase induced strand displacement amplification reaction, Mg 2+ -dependent DNAzyme catalysis reaction, and magnetic separation. In the presence of target microRNA-21, amounts of trigger DNA could be produced with DNA polymerase induced strand displacement amplification reaction, and the trigger DNA could be further hybridized with signal DNA, which was labeled with biotin and AMCA dye. After introduction of Mg 2+ , trigger DNA could form DNAzyme to cleave signal DNA. After magnetic separation, the DNA fragment with AMCA dye could give fluorescence signal, which was related to microRNA-21 concentration. Based on the two efficient signal amplifications, the developed method showed high detection sensitivity with low detection limit of 0.27fM (3σ). In addition, this fluorescence strategy also possessed excellent detection specificity, and could be applied to analyze microRNA-21 expression level in serum of cancer patient. According to the obtained results, the developed fluorescence method might be a promising detection platform for microRNA-21 quantitative analysis in biomedical research and clinical diagnosis. Copyright © 2017 Elsevier B.V. All rights reserved.

Free-floating epithelial micro-tissue arrays: a low cost and versatile technique.

PubMed

Flood, P; Alvarez, L; Reynaud, E G

2016-10-11

Three-dimensional (3D) tissue models are invaluable tools that can closely reflect the in vivo physiological environment. However, they are usually difficult to develop, have a low throughput and are often costly; limiting their utility to most laboratories. The recent availability of inexpensive additive manufacturing printers and open source 3D design software offers us the possibility to easily create affordable 3D cell culture platforms. To demonstrate this, we established a simple, inexpensive and robust method for producing arrays of free-floating epithelial micro-tissues. Using a combination of 3D computer aided design and 3D printing, hydrogel micro-moulding and collagen cell encapsulation we engineered microenvironments that consistently direct the growth of micro-tissue arrays. We described the adaptability of this technique by testing several immortalised epithelial cell lines (MDCK, A549, Caco-2) and by generating branching morphology and micron to millimetre scaled micro-tissues. We established by fluorescence and electron microscopy that micro-tissues are polarised, have cell type specific differentiated phenotypes and regain native in vivo tissue qualities. Finally, using Salmonella typhimurium we show micro-tissues display a more physiologically relevant infection response compared to epithelial monolayers grown on permeable filter supports. In summary, we have developed a robust and adaptable technique for producing arrays of epithelial micro-tissues. This in vitro model has the potential to be a valuable tool for studying epithelial cell and tissue function/architecture in a physiologically relevant context.

Theoretical calculations and experimental verification for the pumping effect caused by the dynamic micro-tapered angle

NASA Astrophysics Data System (ADS)

Cai, Yufei; Zhang, Jianhui; Zhu, Chunling; Huang, Jun; Jiang, Feng

2016-05-01

The atomizer with micro cone apertures has advantages of ultra-fine atomized droplets, low power consumption and low temperature rise. The current research of this kind of atomizer mainly focuses on the performance and its application while there is less research of the principle of the atomization. Under the analysis of the dispenser and its micro-tapered aperture's deformation, the volume changes during the deformation and vibration of the micro-tapered aperture on the dispenser are calculated by coordinate transformation. Based on the characters of the flow resistance in a cone aperture, it is found that the dynamic cone angle results from periodical changes of the volume of the micro-tapered aperture of the atomizer and this change drives one-way flows. Besides, an experimental atomization platform is established to measure the atomization rates with different resonance frequencies of the cone aperture atomizer. The atomization performances of cone aperture and straight aperture atomizers are also measured. The experimental results show the existence of the pumping effect of the dynamic tapered angle. This effect is usually observed in industries that require low dispersion and micro- and nanoscale grain sizes, such as during production of high-pressure nozzles and inhalation therapy. Strategies to minimize the pumping effect of the dynamic cone angle or improve future designs are important concerns. This research proposes that dynamic micro-tapered angle is an important cause of atomization of the atomizer with micro cone apertures.

Propagation of THz pulses in rectangular subwavelength dielectric waveguides

NASA Astrophysics Data System (ADS)

Lu, Yao; Wu, Qiang; Zhang, Qi; Wang, Ride; Zhao, Wenjuan; Zhang, Deng; Pan, Chongpei; Qi, Jiwei; Xu, Jingjun

2018-06-01

Rectangular subwavelength waveguides are necessary for the development of micro/nanophotonic devices and on-chip platforms. Using a time-resolved imaging system, we studied the transient properties and the propagation modes of THz pulses in rectangular subwavelength dielectric waveguides. The dynamic process of THz pulses was systematically recorded to a movie. In addition, an anomalous group velocity dispersion was demonstrated in rectangular subwavelength waveguides. By using the effective index method, we theoretically calculated the modes in rectangular subwavelength waveguides, which agree well with the experiments and simulations. This work provides the opportunity to improve the analysis and design of the integrated platforms and photonic devices.

Stranded Whole Transcriptome RNA-Seq for All RNA Types

PubMed Central

Yan, Pearlly X.; Fang, Fang; Buechlein, Aaron; Ford, James B.; Tang, Haixu; Huang, Tim H.; Burow, Matthew E.; Liu, Yunlong; Rusch, Douglas B.

2015-01-01

Stranded whole transcriptome RNA-Seq described in this unit captures quantitative expression data for all types of RNA including, but not limited to miRNA (microRNA), piRNA (Piwi-interacting RNA), snoRNA (small nucleolar RNA), lincRNA (large non-coding intergenic RNA), SRP RNA (signal recognition particle RNA), tRNA (transfer RNA), mtRNA (mitochondrial RNA) and mRNA (messenger RNA). The size and nature of these types of RNA are irrelevant to the approach described here. Barcoded libraries for multiplexing on the Illumina platform are generated with this approach but it can be applied to other platforms with a few modifications. PMID:25599667

Computational Systems Biology Approach Predicts Regulators and Targets of microRNAs and Their Genomic Hotspots in Apoptosis Process.

PubMed

Alanazi, Ibrahim O; Ebrahimie, Esmaeil

2016-07-01

Novel computational systems biology tools such as common targets analysis, common regulators analysis, pathway discovery, and transcriptomic-based hotspot discovery provide new opportunities in understanding of apoptosis molecular mechanisms. In this study, after measuring the global contribution of microRNAs in the course of apoptosis by Affymetrix platform, systems biology tools were utilized to obtain a comprehensive view on the role of microRNAs in apoptosis process. Network analysis and pathway discovery highlighted the crosstalk between transcription factors and microRNAs in apoptosis. Within the transcription factors, PRDM1 showed the highest upregulation during the course of apoptosis, with more than 9-fold expression increase compared to non-apoptotic condition. Within the microRNAs, MIR1208 showed the highest expression in non-apoptotic condition and downregulated by more than 6 fold during apoptosis. Common regulators algorithm showed that TNF receptor is the key upstream regulator with a high number of regulatory interactions with the differentially expressed microRNAs. BCL2 and AKT1 were the key downstream targets of differentially expressed microRNAs. Enrichment analysis of the genomic locations of differentially expressed microRNAs led us to the discovery of chromosome bands which were highly enriched (p < 0.01) with the apoptosis-related microRNAs, such as 13q31.3, 19p13.13, and Xq27.3 This study opens a new avenue in understanding regulatory mechanisms and downstream functions in the course of apoptosis as well as distinguishing genomic-enriched hotspots for apoptosis process.

Magnetic bead droplet immunoassay of oligomer amyloid β for the diagnosis of Alzheimer's disease using micro-pillars to enhance the stability of the oil-water interface.

PubMed

Kim, Jeong Ah; Kim, Moojong; Kang, Sung Min; Lim, Kun Taek; Kim, Tae Song; Kang, Ji Yoon

2015-05-15

Despite scientific progress in the study of Alzheimer's disease (AD), it is still challenging to develop a robust and sensitive methodology for the early diagnosis of AD due to the lack of a decisive biomarker in blood. Recent reports on the oligomer amyloid β (Aβ) as a biomarker demonstrated its possibility for identifying early onset of AD in patients, but its low concentration in blood requires highly reliable detection techniques. To overcome the low reliability and labor-intensive procedures of conventional enzyme-linked immunosorbent assay (ELISA), we present a magnetic bead-droplet immunoassay platform for simple and highly sensitive detection of oligomer Aβ for the diagnosis of AD. This microchip consists of chambers that contain water-based reagents or oil for consecutive assay procedures, and there are arrays of micro-pillars fabricated between the two adjacent chambers to form robust water-oil interfaces. With the aid of these micro-pillars, magnetic beads can stably pass through each chamber by linearly actuating a magnet along the microchip. The robust water-oil interface and simple procedures of the assay make it possible to obtain reliable results from this microchip. The intensity of the fluorescence at the read-out chamber increased quantitatively and linearly, depending on the amount of serially-diluted standard Aβ solution. The results of the assay indicated that the limit of detection was about 10 pg/mL even though it was done with manual manipulation of the magnet. This platform simplified the complicated ELISA procedure and achieved high sensitivity that was no lower than that of the conventional magnetic bead immunoassay. The magnetic bead-droplet platform reduced the assay time to 45 min, and it also reduced the amount of antibody usage in a single diagnosis significantly (10-30 ng of antibody per single assay). Consequently, this microfluidic chip has strong potential as a feasible system for use in the diagnosis of AD with a fast and easy immunoassay process, since the suggested platform can be automated with ease for point-of-care testing as well as high-throughput diagnostic equipment. Copyright © 2014 Elsevier B.V. All rights reserved.

Microstructures as IR-sensors with Staphylococcus aureus bacteria

NASA Astrophysics Data System (ADS)

Baikova, T. V.; Danilov, P. A.; Gonchukov, S. A.; Yermachenko, V. M.; Ionin, A. A.; Khmelnitskii, R. A.; Kudryashov, S. I.; Nguyen, T. T. H.; Rudenko, A. A.; Saraeva, I. N.; Svistunova, T. S.; Zayarny, D. A.

2017-09-01

Using a micro-hole grating in a supported silver film as a laser-fabricated novel optical platform for surface-enhanced IR absoprtion/reflection spectroscopy, characteristic absorption bands of Staphylococcus aureus, especially - its buried carotenoid fragments - were detected in FT-IR spectra with 10-fold analytical enhancement, paving the way to spectral express-identification of the pathogenic microorganisms.

BEAMing LAMP: single-molecule capture and on-bead isothermal amplification for digital detection of hepatitis C virus in plasma.

PubMed

Chen, Jiyun; Xu, Xiaomin; Huang, Zhimei; Luo, Yuan; Tang, Lijuan; Jiang, Jian-Hui

2018-01-02

A novel dNAD platform (BEAMing LAMP) by combining emulsion micro-reactors, single-molecule magnetic capture and on-bead loop-mediated isothermal amplification has been developed for DNA detection, which enables absolute and high-precision quantification of a target with a detection limit of 300 copies.

Comprehensive Study of the Flow Control Strategy in a Wirelessly Charged Centrifugal Microfluidic Platform with Two Rotation Axes.

PubMed

Zhu, Yunzeng; Chen, Yiqi; Meng, Xiangrui; Wang, Jing; Lu, Ying; Xu, Youchun; Cheng, Jing

2017-09-05

Centrifugal microfluidics has been widely applied in the sample-in-answer-out systems for the analyses of nucleic acids, proteins, and small molecules. However, the inherent characteristic of unidirectional fluid propulsion limits the flexibility of these fluidic chips. Providing an extra degree of freedom to allow the unconstrained and reversible pumping of liquid is an effective strategy to address this limitation. In this study, a wirelessly charged centrifugal microfluidic platform with two rotation axes has been constructed and the flow control strategy in such platform with two degrees of freedom was comprehensively studied for the first time. Inductively coupled coils are installed on the platform to achieve wireless power transfer to the spinning stage. A micro servo motor is mounted on both sides of the stage to alter the orientation of the device around a secondary rotation axis on demand during stage rotation. The basic liquid operations on this platform, including directional transport of liquid, valving, metering, and mixing, are comprehensively studied and realized. Finally, a chip for the simultaneous determination of hexavalent chromium [Cr(VI)] and methanal in water samples is designed and tested based on the strategy presented in this paper, demonstrating the potential use of this platform for on-site environmental monitoring, food safety testing, and other life science applications.

Investigation on active vibration isolation of a Stewart platform with piezoelectric actuators

NASA Astrophysics Data System (ADS)

Wang, Chaoxin; Xie, Xiling; Chen, Yanhao; Zhang, Zhiyi

2016-11-01

A Stewart platform with piezoelectric actuators is presented for micro-vibration isolation. The Jacobi matrix of the Stewart platform, which reveals the relationship between the position/pointing of the payload and the extensions of the six struts, is derived by kinematic analysis. The dynamic model of the Stewart platform is established by the FRF (frequency response function) synthesis method. In the active control loop, the direct feedback of integrated forces is combined with the FxLMS based adaptive feedback to dampen vibration of inherent modes and suppress transmission of periodic vibrations. Numerical simulations were conducted to prove vibration isolation performance of the Stewart platform under random and periodical disturbances, respectively. In the experiment, the output consistencies of the six piezoelectric actuators were measured at first and the theoretical Jacobi matrix as well as the feedback gain of each piezoelectric actuator was subsequently modified according to the measured consistencies. The direct feedback loop was adjusted to achieve sufficient active damping and the FxLMS based adaptive feedback control was adopted to suppress vibration transmission in the six struts. Experimental results have demonstrated that the Stewart platform can achieve 30 dB attenuation of periodical disturbances and 10-20 dB attenuation of random disturbances in the frequency range of 5-200 Hz.

Optical MEMS platform for low-cost on-chip integration of planar light circuits and optical switching

NASA Astrophysics Data System (ADS)

German, Kristine A.; Kubby, Joel; Chen, Jingkuang; Diehl, James; Feinberg, Kathleen; Gulvin, Peter; Herko, Larry; Jia, Nancy; Lin, Pinyen; Liu, Xueyuan; Ma, Jun; Meyers, John; Nystrom, Peter; Wang, Yao Rong

2004-07-01

Xerox Corporation has developed a technology platform for on-chip integration of latching MEMS optical waveguide switches and Planar Light Circuit (PLC) components using a Silicon On Insulator (SOI) based process. To illustrate the current state of this new technology platform, working prototypes of a Reconfigurable Optical Add/Drop Multiplexer (ROADM) and a l-router will be presented along with details of the integrated latching MEMS optical switches. On-chip integration of optical switches and PLCs can greatly reduce the size, manufacturing cost and operating cost of multi-component optical equipment. It is anticipated that low-cost, low-overhead optical network products will accelerate the migration of functions and services from high-cost long-haul markets to price sensitive markets, including networks for metropolitan areas and fiber to the home. Compared to the more common silica-on-silicon PLC technology, the high index of refraction of silicon waveguides created in the SOI device layer enables miniaturization of optical components, thereby increasing yield and decreasing cost projections. The latching SOI MEMS switches feature moving waveguides, and are advantaged across multiple attributes relative to alternative switching technologies, such as thermal optical switches and polymer switches. The SOI process employed was jointly developed under the auspice of the NIST APT program in partnership with Coventor, Corning IntelliSense Corp., and MicroScan Systems to enable fabrication of a broad range of free space and guided wave MicroOptoElectroMechanical Systems (MOEMS).

Micro- and nanofluidic systems in devices for biological, medical and environmental research

NASA Astrophysics Data System (ADS)

Evstrapov, A. A.

2017-11-01

The use of micro- and nanofluidic systems in modern analytical instruments allow you to implement a number of unique opportunities and achieve ultra-high measurement sensitivity. The possibility of manipulation of the individual biological objects (cells, bacteria, viruses, proteins, nucleic acids) in a liquid medium caused the development of devices on microchip platform for methods: chromatographic and electrophoretic analyzes; polymerase chain reaction; sequencing of nucleic acids; immunoassay; cytometric studies. Development of micro and nano fabrication technologies, materials science, surface chemistry, analytical chemistry, cell engineering have led to the creation of a unique systems such as “lab-on-a-chip”, “human-on-a-chip” and other. This article discusses common in microfluidics materials and methods of making functional structures. Examples of integration of nanoscale structures in microfluidic devices for the implementation of new features and improve the technical characteristics of devices and systems are shown.

The MITy micro-rover: Sensing, control, and operation

NASA Technical Reports Server (NTRS)

Malafeew, Eric; Kaliardos, William

1994-01-01

The sensory, control, and operation systems of the 'MITy' Mars micro-rover are discussed. It is shown that the customized sun tracker and laser rangefinder provide internal, autonomous dead reckoning and hazard detection in unstructured environments. The micro-rover consists of three articulated platforms with sensing, processing and payload subsystems connected by a dual spring suspension system. A reactive obstacle avoidance routine makes intelligent use of robot-centered laser information to maneuver through cluttered environments. The hazard sensors include a rangefinder, inclinometers, proximity sensors and collision sensors. A 486/66 laptop computer runs the graphical user interface and programming environment. A graphical window displays robot telemetry in real time and a small TV/VCR is used for real time supervisory control. Guidance, navigation, and control routines work in conjunction with the mapping and obstacle avoidance functions to provide heading and speed commands that maneuver the robot around obstacles and towards the target.

Sub-wavelength InAs quantum dot micro-disk lasers epitaxially grown on exact Si (001) substrates

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wan, Yating; Li, Qiang; Lau, Kei May, E-mail: eekmlau@ust.hk

Subwavelength micro-disk lasers (MDLs) as small as 1 μm in diameter on exact (001) silicon were fabricated using colloidal lithography. The micro-cavity gain medium incorporating five-stacked InAs quantum dot layers was grown on a high crystalline quality GaAs-on-V-grooved-Si template with no absorptive intermediate buffers. Under continuous-wave optical pumping, the MDLs on silicon exhibit lasing in the 1.2-μm wavelength range with low thresholds down to 35 μW at 10 K. The MDLs compare favorably with devices fabricated on native GaAs substrates and state-of-the-art work reported elsewhere. Feasibility of device miniaturization can be projected by size-dependent lasing characteristics. The results show a promising path towardsmore » dense integration of photonic components on the mainstream complementary metal–oxide–semiconductor platform.« less

Optical test course teaching practice on WeChat public platform

NASA Astrophysics Data System (ADS)

Fu, Yuegang; Liu, Zhiying

2017-08-01

With the development of information technological progress, M-Learning and Micro-learning is becoming more and more popular among learners as a new micro-learning resources. Micro-curriculum is playing a more and more important role in daily learning. The students can create a new way of optical course learning through "WeChat". Under the mutual interaction of two or more parties, the use of "WeChat" can fully arouse the students' interest in learning, make the subjective initiative of students, and achieve the ultimate goal of improving the level of students. In this paper, through the analysis of the current situation of college students using the "WeChat", a new teaching model suitable for "optics" teaching is summarized, and the use of "WeChat" has been infiltrated into the teaching process, using science and technology to assist teaching. Students' interest in autonomous learning.

Web Apollo: a web-based genomic annotation editing platform.

PubMed

Lee, Eduardo; Helt, Gregg A; Reese, Justin T; Munoz-Torres, Monica C; Childers, Chris P; Buels, Robert M; Stein, Lincoln; Holmes, Ian H; Elsik, Christine G; Lewis, Suzanna E

2013-08-30

Web Apollo is the first instantaneous, collaborative genomic annotation editor available on the web. One of the natural consequences following from current advances in sequencing technology is that there are more and more researchers sequencing new genomes. These researchers require tools to describe the functional features of their newly sequenced genomes. With Web Apollo researchers can use any of the common browsers (for example, Chrome or Firefox) to jointly analyze and precisely describe the features of a genome in real time, whether they are in the same room or working from opposite sides of the world.

CRISPR/Cas9 for Human Genome Engineering and Disease Research.

PubMed

Xiong, Xin; Chen, Meng; Lim, Wendell A; Zhao, Dehua; Qi, Lei S

2016-08-31

The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) system, a versatile RNA-guided DNA targeting platform, has been revolutionizing our ability to modify, manipulate, and visualize the human genome, which greatly advances both biological research and therapeutics development. Here, we review the current development of CRISPR/Cas9 technologies for gene editing, transcription regulation, genome imaging, and epigenetic modification. We discuss the broad application of this system to the study of functional genomics, especially genome-wide genetic screening, and to therapeutics development, including establishing disease models, correcting defective genetic mutations, and treating diseases.

Building technology services that address student needs.

PubMed

Le Ber, Jeanne M; Lombardo, Nancy T; Wimmer, Erin

2015-01-01

A 16-question technology use survey was conducted to assess incoming health sciences students' knowledge of and interest in current technologies, and to identify student device and tool preferences. Survey questions were developed by colleagues at a peer institution and then edited to match this library's student population. Two years of student responses have been compiled, compared, and reviewed as a means for informing library decisions related to technology and resource purchases. Instruction and event programming have been revised to meet student preferences. Based on the number of students using Apple products, librarians are addressing the need to become more proficient with this platform.

A Roadmap for using Agile Development in a Traditional System

NASA Technical Reports Server (NTRS)

Streiffert, Barbara; Starbird, Thomas

2006-01-01

I. Ensemble Development Group: a) Produces activity planning software for in spacecraft; b) Built on Eclipse Rich Client Platform (open source development and runtime software); c) Funded by multiple sources including the Mars Technology Program; d) Incorporated the use of Agile Development. II. Next Generation Uplink Planning System: a) Researches the Activity Planning and Sequencing Subsystem for Mars Science Laboratory (APSS); b) APSS includes Ensemble, Activity Modeling, Constraint Checking, Command Editing and Sequencing tools plus other uplink generation utilities; c) Funded by the Mars Technology Program; d) Integrates all of the tools for APSS.

Web Apollo: a web-based genomic annotation editing platform

PubMed Central

2013-01-01

Web Apollo is the first instantaneous, collaborative genomic annotation editor available on the web. One of the natural consequences following from current advances in sequencing technology is that there are more and more researchers sequencing new genomes. These researchers require tools to describe the functional features of their newly sequenced genomes. With Web Apollo researchers can use any of the common browsers (for example, Chrome or Firefox) to jointly analyze and precisely describe the features of a genome in real time, whether they are in the same room or working from opposite sides of the world. PMID:24000942

[Relationship of job stress with job burnout and quality of work life in workers for offshore oil platforms].

PubMed

Zhang, Y; Liu, X L; Wei, T D; Lan, Y J

2017-03-20

Objective: To evaluate the current status of job burnout and qual ity of work life (QWL) in workers for offshore oil platforms, and to analyze the relationship of job stress with job burnout and QWL and the direct and indirect effects of job stress on QWL. Methods: Cluster random sampling was used to select 382 work-ers for 8 oil platforms of China National Offshore Oil Corporation in October 2015. A self - designed questionnaire was used to collect the individual characteristics of subjects. The Quality of Work Life Scale (QWL7 - 32) , Occupa-tional Stress Inventory - Revised Edition (OSI - R) , and Maslach Burnout Inventory - General Survey (MBI - GS) were used to investigate the QWL, job stress, and job burnout of subjects. Results: Among all the workers for offshore oil platforms, 87.2% had mild job burnout. The total QWL score was 116.01 ± 16.73; 8.3% of the workers had poor QWL, and 68.5% had moderate QWL. QWL was reduced with heavier task, vaguer task, and increasing mental stress and physical stress ( P <0.05) , and increased with more social support ( P <0.05) . Job stress had di-rect and indirect effects on QWL; stress reaction had the most effect on QWL (total effect size - 0.509) , followed by social support (total effect size 0.444) . Conclusion: Most workers for offshore oil platforms have mild job burn-out and moderate QWL. Job stress is associated with job burnout and QWL, and stress reaction and social support have relatively high influence on QWL.

The iCRISPR platform for rapid genome editing in human pluripotent stem cells.

PubMed

Zhu, Zengrong; González, Federico; Huangfu, Danwei

2014-01-01

Human pluripotent stem cells (hPSCs) have the potential to generate all adult cell types, including rare or inaccessible human cell populations, thus providing a unique platform for disease studies. To realize this promise, it is essential to develop methods for efficient genetic manipulations in hPSCs. Established using TALEN (transcription activator-like effector nuclease) and CRISPR (clustered regularly interspaced short palindromic repeats)/Cas (CRISPR-associated) systems, the iCRISPR platform supports a variety of genome-engineering approaches with high efficiencies. Here, we first describe the establishment of the iCRISPR platform through TALEN-mediated targeting of inducible Cas9 expression cassettes into the AAVS1 locus. Next, we provide a series of technical procedures for using iCRISPR to achieve one-step knockout of one or multiple gene(s), "scarless" introduction of precise nucleotide alterations, as well as inducible knockout during hPSC differentiation. We present an optimized workflow, as well as guidelines for the selection of CRISPR targeting sequences and the design of single-stranded DNA (ssDNA) homology-directed DNA repair templates for the introduction of specific nucleotide alterations. We have successfully used these protocols in four different hPSC lines, including human embryonic stem cells and induced pluripotent stem cells. Once the iCRISPR platform is established, clonal lines with desired genetic modifications can be established in as little as 1 month. The methods described here enable a wide range of genome-engineering applications in hPSCs, thus providing a valuable resource for the creation of diverse hPSC-based disease models with superior speed and ease.

Tudor staphylococcal nuclease is a structure-specific ribonuclease that degrades RNA at unstructured regions during microRNA decay.

PubMed

Li, Chia-Lung; Yang, Wei-Zen; Shi, Zhonghao; Yuan, Hanna S

2018-05-01

Tudor staphylococcal nuclease (TSN) is an evolutionarily conserved ribonuclease in eukaryotes that is composed of five staphylococcal nuclease-like domains (SN1-SN5) and a Tudor domain. TSN degrades hyper-edited double-stranded RNA, including primary miRNA precursors containing multiple I•U and U•I pairs, and mature miRNA during miRNA decay. However, how TSN binds and degrades its RNA substrates remains unclear. Here, we show that the C. elegans TSN (cTSN) is a monomeric Ca 2+ -dependent ribonuclease, cleaving RNA chains at the 5'-side of the phosphodiester linkage to produce degraded fragments with 5'-hydroxyl and 3'-phosphate ends. cTSN degrades single-stranded RNA and double-stranded RNA containing mismatched base pairs, but is not restricted to those containing multiple I•U and U•I pairs. cTSN has at least two catalytic active sites located in the SN1 and SN3 domains, since mutations of the putative Ca 2+ -binding residues in these two domains strongly impaired its ribonuclease activity. We further show by small-angle X-ray scattering that rice osTSN has a flexible two-lobed structure with open to closed conformations, indicating that TSN may change its conformation upon RNA binding. We conclude that TSN is a structure-specific ribonuclease targeting not only single-stranded RNA, but also unstructured regions of double-stranded RNA. This study provides the molecular basis for how TSN cooperates with RNA editing to eliminate duplex RNA in cell defense, and how TSN selects and degrades RNA during microRNA decay. © 2018 Li et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

A Reward-Based Behavioral Platform to Measure Neural Activity during Head-Fixed Behavior.

PubMed

Micallef, Andrew H; Takahashi, Naoya; Larkum, Matthew E; Palmer, Lucy M

2017-01-01

Understanding the neural computations that contribute to behavior requires recording from neurons while an animal is behaving. This is not an easy task as most subcellular recording techniques require absolute head stability. The Go/No-Go sensory task is a powerful decision-driven task that enables an animal to report a binary decision during head-fixation. Here we discuss how to set up an Ardunio and Python based platform system to control a Go/No-Go sensory behavior paradigm. Using an Arduino micro-controller and Python-based custom written program, a reward can be delivered to the animal depending on the decision reported. We discuss the various components required to build the behavioral apparatus that can control and report such a sensory stimulus paradigm. This system enables the end user to control the behavioral testing in real-time and therefore it provides a strong custom-made platform for probing the neural basis of behavior.

Time and Space Partitioning the EagleEye Reference Misson

NASA Astrophysics Data System (ADS)

Bos, Victor; Mendham, Peter; Kauppinen, Panu; Holsti, Niklas; Crespo, Alfons; Masmano, Miguel; de la Puente, Juan A.; Zamorano, Juan

2013-08-01

We discuss experiences gained by porting a Software Validation Facility (SVF) and a satellite Central Software (CSW) to a platform with support for Time and Space Partitioning (TSP). The SVF and CSW are part of the EagleEye Reference mission of the European Space Agency (ESA). As a reference mission, EagleEye is a perfect candidate to evaluate practical aspects of developing satellite CSW for and on TSP platforms. The specific TSP platform we used consists of a simulated LEON3 CPU controlled by the XtratuM separation micro-kernel. On top of this, we run five separate partitions. Each partition runs its own real-time operating system or Ada run-time kernel, which in turn are running the application software of the CSW. We describe issues related to partitioning; inter-partition communication; scheduling; I/O; and fault-detection, isolation, and recovery (FDIR).

Opportunities of CMOS-MEMS integration through LSI foundry and open facility

NASA Astrophysics Data System (ADS)

Mita, Yoshio; Lebrasseur, Eric; Okamoto, Yuki; Marty, Frédéfic; Setoguchi, Ryota; Yamada, Kentaro; Mori, Isao; Morishita, Satoshi; Imai, Yoshiaki; Hosaka, Kota; Hirakawa, Atsushi; Inoue, Shu; Kubota, Masanori; Denoual, Matthieu

2017-06-01

Since the 2000s, several countries have established micro- and nanofabrication platforms for the research and education community as national projects. By combining such platforms with VLSI multichip foundry services, various integrated devices, referred to as “CMOS-MEMS”, can be realized without constructing an entire cleanroom. In this paper, we summarize MEMS-last postprocess schemes for CMOS devices on a bulk silicon wafer as well as on a silicon-on-insulator (SOI) wafer using an open-access cleanroom of the Nanotechnology Platform of MEXT Japan. The integration devices presented in this article are free-standing structures and postprocess isolated LSI devices. Postprocess issues are identified with their solutions, such as the reactive ion etching (RIE) lag for dry release and the impact of the deep RIE (DRIE) postprocess on transistor characteristics. Integration with nonsilicon materials is proposed as one of the future directions.

Photonic elements in smart systems for use in aerospace platforms

NASA Astrophysics Data System (ADS)

Adamovsky, Grigory; Baumbick, Robert J.; Tabib-Azar, Massood

1998-07-01

To compete globally in the next millennium, designers of new transportation vehicles will have to be innovative. Keen competition will reward innovative concepts that are developed and proven first. In order to improve reliability of aerospace platforms and reduce operating cots, new technologies must be exploited to produce autonomous systems, based on highly distributed, smart systems, which can be treated as line replaceable units. These technologies include photonics, which provide sensing and information transfer functions, and micro electro mechanical systems that will produce the actuation and, in some cases, may even provide a computing capability that resembles the hydro- mechanical control system used in older aircraft systems. The combination of these technologies will provide unique systems that will enable achieving the reliability and cost goals dictated by global market. In the article we review some of these issues and discuss a role of photonics in smart system for aerospace platforms.

Optical and acoustical UAV detection

NASA Astrophysics Data System (ADS)

Christnacher, Frank; Hengy, Sébastien; Laurenzis, Martin; Matwyschuk, Alexis; Naz, Pierre; Schertzer, Stéphane; Schmitt, Gwenael

2016-10-01

Recent world events have highlighted that the proliferation of UAVs is bringing with it a new and rapidly increasing threat for national defense and security agencies. Whilst many of the reported UAV incidents seem to indicate that there was no terrorist intent behind them, it is not unreasonable to assume that it may not be long before UAV platforms are regularly employed by terrorists or other criminal organizations. The flight characteristics of many of these mini- and micro-platforms present challenges for current systems which have been optimized over time to defend against the traditional air-breathing airborne platforms. A lot of programs to identify cost-effective measures for the detection, classification, tracking and neutralization have begun in the recent past. In this paper, lSL shows how the performance of a UAV detection and tracking concept based on acousto-optical technology can be powerfully increased through active imaging.

Diy Geospatial Web Service Chains: Geochaining Make it Easy

NASA Astrophysics Data System (ADS)

Wu, H.; You, L.; Gui, Z.

2011-08-01

It is a great challenge for beginners to create, deploy and utilize a Geospatial Web Service Chain (GWSC). People in Computer Science are usually not familiar with geospatial domain knowledge. Geospatial practitioners may lack the knowledge about web services and service chains. The end users may lack both. However, integrated visual editing interfaces, validation tools, and oneclick deployment wizards may help to lower the learning curve and improve modelling skills so beginners will have a better experience. GeoChaining is a GWSC modelling tool designed and developed based on these ideas. GeoChaining integrates visual editing, validation, deployment, execution etc. into a unified platform. By employing a Virtual Globe, users can intuitively visualize raw data and results produced by GeoChaining. All of these features allow users to easily start using GWSC, regardless of their professional background and computer skills. Further, GeoChaining supports GWSC model reuse, meaning that an entire GWSC model created or even a specific part can be directly reused in a new model. This greatly improves the efficiency of creating a new GWSC, and also contributes to the sharing and interoperability of GWSC.

Integrated Micro/nanoengineered Functional Biomaterials for Cell Mechanics and Mechanobiology: A Materials Perspective

PubMed Central

Shao, Yue

2014-01-01

The rapid development of micro/nanoengineered functional biomaterials in the last two decades has empowered materials scientists and bioengineers to precisely control different aspects of the in vitro cell microenvironment. Following a philosophy of reductionism, many studies using synthetic functional biomaterials have revealed instructive roles of individual extracellular biophysical and biochemical cues in regulating cellular behaviors. Development of integrated micro/nanoengineered functional biomaterials to study complex and emergent biological phenomena has also thrived rapidly in recent years, revealing adaptive and integrated cellular behaviors closely relevant to human physiological and pathological conditions. Working at the interface between materials science and engineering, biology, and medicine, we are now at the beginning of a great exploration using micro/nanoengineered functional biomaterials for both fundamental biology study and clinical and biomedical applications such as regenerative medicine and drug screening. In this review, we present an overview of state of the art micro/nanoengineered functional biomaterials that can control precisely individual aspects of cell-microenvironment interactions and highlight them as well-controlled platforms for mechanistic studies of mechano-sensitive and -responsive cellular behaviors and integrative biology research. We also discuss the recent exciting trend where micro/nanoengineered biomaterials are integrated into miniaturized biological and biomimetic systems for dynamic multiparametric microenvironmental control of emergent and integrated cellular behaviors. The impact of integrated micro/nanoengineered functional biomaterials for future in vitro studies of regenerative medicine, cell biology, as well as human development and disease models are discussed. PMID:24339188

On micro-electrokinetic scalar turbulence in microfluidics at a low Reynolds number.

PubMed

Wang, Guiren; Yang, Fang; Zhao, Wei; Chen, Chien-Pin

2016-03-21

We recently demonstrated the direct observation of micro-electrokinetic turbulence in a microchannel at a low Reynolds number (Re) when a pressure-driven flow was forced electrokinetically. Here, we characterize the corresponding scalar turbulence and surprisingly find that the corresponding turbulent mixing has some typical and important features of scalar turbulence, such as the Obukhov-Corrsin (O-C) -5/3 spectrum of concentration fluctuation, which can commonly be realized only at high Re in macroflows. This discovery could provide a new perspective of scalar turbulence and an avenue for control of transport phenomena in lab-on-a-chip platforms. This will deepen our fundamental understanding of transport phenomena in microfluidics.

Price Based Local Power Distribution Management System (Local Power Distribution Manager) v1.0

DOE Office of Scientific and Technical Information (OSTI.GOV)

BROWN, RICHARD E.; CZARNECKI, STEPHEN; SPEARS, MICHAEL

2016-11-28

A trans-active energy micro-grid controller is implemented in the VOLTTRON distributed control platform. The system uses the price of electricity as the mechanism for conducting transactions that are used to manage energy use and to balance supply and demand. In order to allow testing and analysis of the control system, the implementation is designed to run completely as a software simulation, while allowing the inclusion of selected hardware that physically manages power. Equipment to be integrated with the micro-grid controller must have an IP (Internet Protocol)-based network connection and a software "driver" must exist to translate data communications between themore » device and the controller.« less

Ultrasound-driven Megahertz Faraday Waves for Generation of Monodisperse Micro Droplets and Applications

NASA Astrophysics Data System (ADS)

Tsai, Chen S.; Mao, Rong W.; Lin, Shih K.; Tsai, Shirley C.; Boss, Gerry; Brenner, Matt; Smaldone, Gerry; Mahon, Sari; Shahverdi, Kaveh; Zhu, Yun

Our theoretical findings on instability of Faraday waves at megahertz (MHz) drive frequency and realization of silicon-based MHz multiple-Fourier horn ultrasonic nozzles (MFHUNs) together have enabled generation of mono-disperse droplets of controllable diameter (2.5-6.0 μm) at very low electrical drive power (<0.5 Watt). The resulting battery-run clogging-free droplet generator has imminent application to pulmonary (inhalation) drug delivery and other potential applications. Here an update of advances on analysis and design of the MHz MFHUNs and the underlying physical mechanism for generation of mono-disperse micro droplets, and the nebulizer platform for application to detoxification of cyanide poisoning are presented.

A low cost micro-station to monitor soil water potential for irrigation management

NASA Astrophysics Data System (ADS)

Vannutelli, Edoardo; Masseroni, Daniele; Facchi, Arianna; Gandolfi, Claudio; Renga, Filippo

2014-05-01

The RISPArMiA project (which stands for "reduction of water wastage through the continuous monitoring of agri-environmental parameters") won in 2013 the contest called "LINFAS - The New Ideas Make Sustainable Agriculture" and sponsored by two Italian Foundations (Fondazione Italiana Accenture and Fondazione Collegio Università Milanesi). The objective of the RISPArMiA project is to improve the irrigation efficiency at the farm scale, by providing the farmer with a valuable decision support system for the management of irrigation through the use of low-cost sensors and technologies that can easily be interfaced with Mobile devices. Through the installation of tensiometric sensors within the cropped field, the soil water potential can be continuously monitored. Using open hardware electronic platforms, a data-logger for storing the measured data will be built. Data will be then processed through a software that will allow the conversion of the monitored information into an irrigation advice. This will be notified to the farmer if the measured soil water potential exceed literature crop-specific tensiometric thresholds. Through an extrapolation conducted on the most recent monitored data, it will be also possible to obtain a simple soil water potential prevision in absence of rain events. All the information will be sent directly to a virtual server and successively on the farmer Mobile devices. Each micro-station is completely autonomous from the energy point of view, since it is powered by batteries recharged by a solar panel. The transmission modulus consists of a GSM apparatus with a SIM card. The use of free platforms (Arduino) and low cost sensors (Watermark 200SS tensiometers and soil thermocouples) will significantly reduce the costs of construction of the micro-station which are expected to be considerably lower than those required for similar instruments on the market today . Six prototype micro-stations are actually under construction. Their field testing will be conducted on maize and peach orchard fields in the 2014 agricultural season, and the results will be published at the end of the year. In this work the micro-station prototype will be described in all its components, and the experimental field activities will be illustrated.

Occupational exposure to electric and magnetic fields during work tasks at 110 kV substations in the Tampere region.

PubMed

Korpinen, Leena H; Pääkkönen, Rauno J

2010-04-01

The occupational exposure to electric and magnetic fields during various work tasks at seven 110 kV substations in Finland's Tampere region was studied. The aim was to investigate if the action values (10 kV/m for the E-field and 500 microT for the B-field) of the EU Directive 2004/40/EC were exceeded. Electric and magnetic fields were measured during the following work tasks: (1) walking or operating devices on the ground; (2) working from a service platform; (3) working around the power transformer on the ground or using a ladder; and (4) changing a bulb from a man hoist. In work task 2 "working from a service platform" the measured electric field (maximum value 16.6 kV/m) exceeded 10 kV/m in three cases. In the future it is important to study if the limit value (10 mA/m(2)) of Directive 2004/40/EC is exceeded at 110 kV substations. The occupational 500 microT action value of the magnetic flux density field (B-field) was not exceeded in any working situation.

A multilevel Lab on chip platform for DNA analysis.

PubMed

Marasso, Simone Luigi; Giuri, Eros; Canavese, Giancarlo; Castagna, Riccardo; Quaglio, Marzia; Ferrante, Ivan; Perrone, Denis; Cocuzza, Matteo

2011-02-01

Lab-on-chips (LOCs) are critical systems that have been introduced to speed up and reduce the cost of traditional, laborious and extensive analyses in biological and biomedical fields. These ambitious and challenging issues ask for multi-disciplinary competences that range from engineering to biology. Starting from the aim to integrate microarray technology and microfluidic devices, a complex multilevel analysis platform has been designed, fabricated and tested (All rights reserved-IT Patent number TO2009A000915). This LOC successfully manages to interface microfluidic channels with standard DNA microarray glass slides, in order to implement a complete biological protocol. Typical Micro Electro Mechanical Systems (MEMS) materials and process technologies were employed. A silicon/glass microfluidic chip and a Polydimethylsiloxane (PDMS) reaction chamber were fabricated and interfaced with a standard microarray glass slide. In order to have a high disposable system all micro-elements were passive and an external apparatus provided fluidic driving and thermal control. The major microfluidic and handling problems were investigated and innovative solutions were found. Finally, an entirely automated DNA hybridization protocol was successfully tested with a significant reduction in analysis time and reagent consumption with respect to a conventional protocol.

Estimate of the effect of micro-vibration on the performance of the Algerian satellite (Alsat-1B) imager

NASA Astrophysics Data System (ADS)

Serief, Chahira

2017-11-01

Alsat-1B, launched into a 670 km sun-synchronous orbit on board the PSLV launch vehicle from the Sriharikota launch site in India on 26 September 2016, is a medium resolution Earth Observation satellite with a mass of 100 kg. Alsat-1B will be used for agricultural and resource monitoring, disaster management, land use mapping and urban planning. It is based on the SSTL-100 platform, and flies a 24 m multispectral imager and a 12 m panchromatic imager delivering images with a swath width of 140 km. One of the main factors affecting the performance of satellite-borne optical imaging systems is micro-vibration. Micro-vibration is a low level mechanical disturbance inevitably generated from moving parts on a satellite and exceptionally difficult to be controlled by the attitude and orbital control system (AOCS) of a spacecraft. Micro-vibration usually causes problems for optical imaging systems onboard Earth Observation satellites. The major effect of micro-vibration is the excitation of the support structures for the optical elements during imaging operations which can result in severe degradation of image quality by smearing and distortion. Quantitative characterization of image degradation caused by micro-vibration is thus quite useful and important as part of system level analysis which can help preventing micro-vibration influence by proper design and restoring the degraded image. The aim of this work is to provide quantitative estimates of the effect of micro-vibration on the performance of Alsat-1B imager, which may be experienced operationally, in terms of the modulation transfer function (MTF) and based on ground micro-vibration tests results.

Dynamic and programmable self-assembly of micro-rafts at the air-water interface

PubMed Central

Wang, Wendong; Giltinan, Joshua; Zakharchenko, Svetlana; Sitti, Metin

2017-01-01

Dynamic self-assembled material systems constantly consume energy to maintain their spatiotemporal structures and functions. Programmable self-assembly translates information from individual parts to the collective whole. Combining dynamic and programmable self-assembly in a single platform opens up the possibilities to investigate both types of self-assembly simultaneously and to explore their synergy. This task is challenging because of the difficulty in finding suitable interactions that are both dissipative and programmable. We present a dynamic and programmable self-assembling material system consisting of spinning at the air-water interface circular magnetic micro-rafts of radius 50 μm and with cosinusoidal edge-height profiles. The cosinusoidal edge-height profiles not only create a net dissipative capillary repulsion that is sustained by continuous torque input but also enable directional assembly of micro-rafts. We uncover the layered arrangement of micro-rafts in the patterns formed by dynamic self-assembly and offer mechanistic insights through a physical model and geometric analysis. Furthermore, we demonstrate programmable self-assembly and show that a 4-fold rotational symmetry encoded in individual micro-rafts translates into 90° bending angles and square-based tiling in the assembled structures of micro-rafts. We anticipate that our dynamic and programmable material system will serve as a model system for studying nonequilibrium dynamics and statistical mechanics in the future. PMID:28560332

Dynamic and programmable self-assembly of micro-rafts at the air-water interface.

PubMed

Wang, Wendong; Giltinan, Joshua; Zakharchenko, Svetlana; Sitti, Metin

2017-05-01

Dynamic self-assembled material systems constantly consume energy to maintain their spatiotemporal structures and functions. Programmable self-assembly translates information from individual parts to the collective whole. Combining dynamic and programmable self-assembly in a single platform opens up the possibilities to investigate both types of self-assembly simultaneously and to explore their synergy. This task is challenging because of the difficulty in finding suitable interactions that are both dissipative and programmable. We present a dynamic and programmable self-assembling material system consisting of spinning at the air-water interface circular magnetic micro-rafts of radius 50 μm and with cosinusoidal edge-height profiles. The cosinusoidal edge-height profiles not only create a net dissipative capillary repulsion that is sustained by continuous torque input but also enable directional assembly of micro-rafts. We uncover the layered arrangement of micro-rafts in the patterns formed by dynamic self-assembly and offer mechanistic insights through a physical model and geometric analysis. Furthermore, we demonstrate programmable self-assembly and show that a 4-fold rotational symmetry encoded in individual micro-rafts translates into 90° bending angles and square-based tiling in the assembled structures of micro-rafts. We anticipate that our dynamic and programmable material system will serve as a model system for studying nonequilibrium dynamics and statistical mechanics in the future.

Micro-grid platform based on NODE.JS architecture, implemented in electrical network instrumentation

NASA Astrophysics Data System (ADS)

Duque, M.; Cando, E.; Aguinaga, A.; Llulluna, F.; Jara, N.; Moreno, T.

2016-05-01

In this document, I propose a theory about the impact of systems based on microgrids in non-industrialized countries that have the goal to improve energy exploitation through alternatives methods of a clean and renewable energy generation and the creation of the app to manage the behavior of the micro-grids based on the NodeJS, Django and IOJS technologies. The micro-grids allow the optimal way to manage energy flow by electric injection directly in electric network small urban's cells in a low cost and available way. In difference from conventional systems, micro-grids can communicate between them to carry energy to places that have higher demand in accurate moments. This system does not require energy storage, so, costs are lower than conventional systems like fuel cells, solar panels or else; even though micro-grids are independent systems, they are not isolated. The impact that this analysis will generate, is the improvement of the electrical network without having greater control than an intelligent network (SMART-GRID); this leads to move to a 20% increase in energy use in a specified network; that suggest there are others sources of energy generation; but for today's needs, we need to standardize methods and remain in place to support all future technologies and the best option are the Smart Grids and Micro-Grids.

Microcomputer-based artificial vision support system for real-time image processing for camera-driven visual prostheses.

PubMed

Fink, Wolfgang; You, Cindy X; Tarbell, Mark A

2010-01-01

It is difficult to predict exactly what blind subjects with camera-driven visual prostheses (e.g., retinal implants) can perceive. Thus, it is prudent to offer them a wide variety of image processing filters and the capability to engage these filters repeatedly in any user-defined order to enhance their visual perception. To attain true portability, we employ a commercial off-the-shelf battery-powered general purpose Linux microprocessor platform to create the microcomputer-based artificial vision support system (microAVS(2)) for real-time image processing. Truly standalone, microAVS(2) is smaller than a deck of playing cards, lightweight, fast, and equipped with USB, RS-232 and Ethernet interfaces. Image processing filters on microAVS(2) operate in a user-defined linear sequential-loop fashion, resulting in vastly reduced memory and CPU requirements during execution. MiccroAVS(2) imports raw video frames from a USB or IP camera, performs image processing, and issues the processed data over an outbound Internet TCP/IP or RS-232 connection to the visual prosthesis system. Hence, microAVS(2) affords users of current and future visual prostheses independent mobility and the capability to customize the visual perception generated. Additionally, microAVS(2) can easily be reconfigured for other prosthetic systems. Testing of microAVS(2) with actual retinal implant carriers is envisioned in the near future.

Efficient CRISPR/Cas9 Genome Editing of Phytoene desaturase in Cassava.

PubMed

Odipio, John; Alicai, Titus; Ingelbrecht, Ivan; Nusinow, Dmitri A; Bart, Rebecca; Taylor, Nigel J

2017-01-01

CRISPR/Cas9 has become a powerful genome-editing tool for introducing genetic changes into crop species. In order to develop capacity for CRISPR/Cas9 technology in the tropical staple cassava ( Manihot esculenta ), the Phytoene desaturase ( MePDS ) gene was targeted in two cultivars using constructs carrying gRNAs targeting two sequences within MePDS exon 13. After Agrobacterium -mediated delivery of CRISPR/Cas9 reagents into cassava cells, both constructs induced visible albino phenotypes within cotyledon-stage somatic embryos regenerating on selection medium and the plants regenerated therefrom. A total of 58 (cv. 60444) and 25 (cv. TME 204) plant lines were recovered, of which 38 plant lines (19 from each cultivar) were analyzed for mutagenesis. The frequency of plant lines showing albino phenotype was high, ranging from 90 to 100% in cv. TME 204. Observed albino phenotypes were comprised of full albinos devoid of green tissue and chimeras containing a mixture of white and green tissues. Sequence analysis revealed that 38/38 (100%) of the plant lines examined carried mutations at the targeted MePDS site, with insertions, deletions, and substitutions recorded. One putatively mono-allelic homozygous line (1/19) was found from cv. 60444, while 1 (1/19) and 4 (4/19) putatively bi-allelic homozygous lines were found in 60444 and TME204, respectively. The remaining plant lines, comprised mostly of the chimeras, were found to be putatively heterozygous. We observed minor (1 bp) nucleotide substitutions and or deletions upstream of the 5' and or downstream of the 3' targeted MePDS region. The data reported demonstrates that CRISPR/Cas9-mediated genome editing of cassava is highly efficient and relatively simple, generating multi-allelic mutations in both cultivars studied. Modification of MePDS described here generates visually detectable mutated events in a relatively short time frame of 6-8 weeks, and does not require sequencing to confirm editing at the target. It therefore provides a valuable platform to facilitate rapid assessment and optimization of CRISPR/Cas9 and other genome-editing technologies in cassava.

Automated system for the calibration of magnetometers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Petrucha, Vojtech; Kaspar, Petr; Ripka, Pavel

2009-04-01

A completely nonmagnetic calibration platform has been developed and constructed at DTU Space (Technical University of Denmark). It is intended for on-site scalar calibration of high-precise fluxgate magnetometers. An enhanced version of the same platform is being built at the Czech Technical University. There are three axes of rotation in this design (compared to two axes in the previous version). The addition of the third axis allows us to calibrate more complex devices. An electronic compass based on a vector fluxgate magnetometer and micro electro mechanical systems (MEMS) accelerometer is one example. The new platform can also be used tomore » evaluate the parameters of the compass in all possible variations in azimuth, pitch, and roll. The system is based on piezoelectric motors, which are placed on a platform made of aluminum, brass, plastic, and glass. Position sensing is accomplished through custom-made optical incremental sensors. The system is controlled by a microcontroller, which executes commands from a computer. The properties of the system as well as calibration and measurement results will be presented.« less

On-chip photonic particle sensor

NASA Astrophysics Data System (ADS)

Singh, Robin; Ma, Danhao; Agarwal, Anu; Anthony, Brian

2018-02-01

We propose an on-chip photonic particle sensor design that can perform particle sizing and counting for various environmental applications. The sensor is based on micro photonic ring resonators that are able to detect the presence of the free space particles through the interaction with their evanescent electric field tail. The sensor can characterize a wide range of the particle size ranging from a few nano meters to micron ( 1 micron). The photonic platform offers high sensitivity, compactness, fast response of the device. Further, FDTD simulations are performed to analyze different particle-light interactions. Such a compact and portable platform, packaged with integrated photonic circuit provides a useful sensing modality in space shuttle and environmental applications.

A System for Supporting Development and Update of the International Classification of Health Interventions (ICHI).

PubMed

Donada, Marc; Della Mea, Vincenzo; Cumerlato, Megan; Rankin, Nicole; Madden, Richard

2018-01-01

The International Classification of Health Interventions (ICHI) is a member of the WHO Family of International Classifications, being developed to provide a common tool for reporting and analysing health interventions for statistical purposes. A web-based platform for classification development and update has been specifically developed to support the initial development step and then, after final approval, the continuous revision and update of the classification. The platform provides features for classification editing, versioning, comment management and URI identifiers. During the last 12 months it has been used for developing the ICHI Beta version, replacing the previous process based on the exchange of Excel files. At November 2017, 90 users have provided input to the development of the classification, which has resulted in 2913 comments and 2971 changes in the classification, since June 2017. Further work includes the development of an URI API for machine to machine communication, following the model established for ICD-11.

Speech to Text Translation for Malay Language

NASA Astrophysics Data System (ADS)

Al-khulaidi, Rami Ali; Akmeliawati, Rini

2017-11-01

The speech recognition system is a front end and a back-end process that receives an audio signal uttered by a speaker and converts it into a text transcription. The speech system can be used in several fields including: therapeutic technology, education, social robotics and computer entertainments. In most cases in control tasks, which is the purpose of proposing our system, wherein the speed of performance and response concern as the system should integrate with other controlling platforms such as in voiced controlled robots. Therefore, the need for flexible platforms, that can be easily edited to jibe with functionality of the surroundings, came to the scene; unlike other software programs that require recording audios and multiple training for every entry such as MATLAB and Phoenix. In this paper, a speech recognition system for Malay language is implemented using Microsoft Visual Studio C#. 90 (ninety) Malay phrases were tested by 10 (ten) speakers from both genders in different contexts. The result shows that the overall accuracy (calculated from Confusion Matrix) is satisfactory as it is 92.69%.

An u-Service Model Based on a Smart Phone for Urban Computing Environments

NASA Astrophysics Data System (ADS)

Cho, Yongyun; Yoe, Hyun

In urban computing environments, all of services should be based on the interaction between humans and environments around them, which frequently and ordinarily in home and office. This paper propose an u-service model based on a smart phone for urban computing environments. The suggested service model includes a context-aware and personalized service scenario development environment that can instantly describe user's u-service demand or situation information with smart devices. To do this, the architecture of the suggested service model consists of a graphical service editing environment for smart devices, an u-service platform, and an infrastructure with sensors and WSN/USN. The graphic editor expresses contexts as execution conditions of a new service through a context model based on ontology. The service platform deals with the service scenario according to contexts. With the suggested service model, an user in urban computing environments can quickly and easily make u-service or new service using smart devices.

From abstract to publication: the fate of research presented at an annual forensic meeting.

PubMed

Tambuscio, Silvia; Boghossian, Elie; Sauvageau, Anny

2010-11-01

In forensic sciences, the fate of abstracts presented at international meetings has not yet been assessed. The purpose of this study is to estimate publication ratio and evaluate possible predictors of publication after the 58th edition of the 2006 American Academy of Forensic Sciences annual meeting. Section of the meeting, type of presentation (oral platform or poster), number of authors per abstract and per paper, time span to publication, countries involved, and journal of publication were tabulated. A total of 623 abstracts were presented, from which 102 were subsequently published as a full paper. The overall publication rate was 16.4%, ranging from 3.4% (jurisprudence) to 28.8% (toxicology). The type of presentation (oral platform or poster) did not significantly affect the outcome of the abstract. However, a higher number of authors, foreign authors, and international collaboration were found to be good predictive factors of publication. © 2010 American Academy of Forensic Sciences.

Empower multiplex cell and tissue-specific CRISPR-mediated gene manipulation with self-cleaving ribozymes and tRNA.

PubMed

Xu, Li; Zhao, Lixia; Gao, Yandi; Xu, Jing; Han, Renzhi

2017-03-17

Clustered regularly interspaced short palindromic repeat/Cas9 (CRISPR/Cas9) system has emerged in recent years as a highly efficient RNA-guided gene manipulation platform. Simultaneous editing or transcriptional activation/suppression of different genes becomes feasible with the co-delivery of multiple guide RNAs (gRNAs). Here, we report that multiple gRNAs linked with self-cleaving ribozymes and/or tRNA could be simultaneously expressed from a single U6 promoter to exert genome editing of dystrophin and myosin binding protein C3 in human and mouse cells. Moreover, this strategy allows the expression of multiple gRNAs for synergistic transcription activation of follistatin when used with catalytically inactive dCas9-VP64 or dCas9-p300core fusions. Finally, the gRNAs linked by the self-cleaving ribozymes and tRNA could be expressed from RNA polymerase type II (pol II) promoters such as generic CMV and muscle/heart-specific MHCK7. This is particularly useful for in vivo applications when the packaging capacity of recombinant adeno-associated virus is limited while tissue-specific delivery of gRNAs and Cas9 is desired. Taken together, this study provides a novel strategy to enable tissue-specific expression of more than one gRNAs for multiplex gene editing from a single pol II promoter. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Heterologous and endogenous U6 snRNA promoters enable CRISPR/Cas9 mediated genome editing in Aspergillus niger.

PubMed

Zheng, Xiaomei; Zheng, Ping; Sun, Jibin; Kun, Zhang; Ma, Yanhe

2018-01-01

U6 promoters have been used for single guide RNA (sgRNA) transcription in the clustered regularly interspaced short palindromic repeats/CRISPR-associated protein (CRISPR/Cas9) genome editing system. However, no available U6 promoters have been identified in Aspergillus niger, which is an important industrial platform for organic acid and protein production. Two CRISPR/Cas9 systems established in A. niger have recourse to the RNA polymerase II promoter or in vitro transcription for sgRNA synthesis, but these approaches generally increase cloning efforts and genetic manipulation. The validation of functional RNA polymerase II promoters is therefore an urgent need for A. niger . Here, we developed a novel CRISPR/Cas9 system in A. niger for sgRNA expression, based on one endogenous U6 promoter and two heterologous U6 promoters. The three tested U6 promoters enabled sgRNA transcription and the disruption of the polyketide synthase albA gene in A. niger . Furthermore, this system enabled highly efficient gene insertion at the targeted genome loci in A. niger using donor DNAs with homologous arms as short as 40-bp. This study demonstrated that both heterologous and endogenous U6 promoters were functional for sgRNA expression in A. niger . Based on this result, a novel and simple CRISPR/Cas9 toolbox was established in A. niger, that will benefit future gene functional analysis and genome editing.

Bioclipse: an open source workbench for chemo- and bioinformatics.

PubMed

Spjuth, Ola; Helmus, Tobias; Willighagen, Egon L; Kuhn, Stefan; Eklund, Martin; Wagener, Johannes; Murray-Rust, Peter; Steinbeck, Christoph; Wikberg, Jarl E S

2007-02-22

There is a need for software applications that provide users with a complete and extensible toolkit for chemo- and bioinformatics accessible from a single workbench. Commercial packages are expensive and closed source, hence they do not allow end users to modify algorithms and add custom functionality. Existing open source projects are more focused on providing a framework for integrating existing, separately installed bioinformatics packages, rather than providing user-friendly interfaces. No open source chemoinformatics workbench has previously been published, and no successful attempts have been made to integrate chemo- and bioinformatics into a single framework. Bioclipse is an advanced workbench for resources in chemo- and bioinformatics, such as molecules, proteins, sequences, spectra, and scripts. It provides 2D-editing, 3D-visualization, file format conversion, calculation of chemical properties, and much more; all fully integrated into a user-friendly desktop application. Editing supports standard functions such as cut and paste, drag and drop, and undo/redo. Bioclipse is written in Java and based on the Eclipse Rich Client Platform with a state-of-the-art plugin architecture. This gives Bioclipse an advantage over other systems as it can easily be extended with functionality in any desired direction. Bioclipse is a powerful workbench for bio- and chemoinformatics as well as an advanced integration platform. The rich functionality, intuitive user interface, and powerful plugin architecture make Bioclipse the most advanced and user-friendly open source workbench for chemo- and bioinformatics. Bioclipse is released under Eclipse Public License (EPL), an open source license which sets no constraints on external plugin licensing; it is totally open for both open source plugins as well as commercial ones. Bioclipse is freely available at http://www.bioclipse.net.

CRISPR-Cas9 systems: versatile cancer modelling platforms and promising therapeutic strategies.

PubMed

Wen, Wan-Shun; Yuan, Zhi-Min; Ma, Shi-Jie; Xu, Jiang; Yuan, Dong-Tang

2016-03-15

The RNA-guided nuclease CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats-CRISPR associated nuclease 9) and its variants such as nickase Cas9, dead Cas9, guide RNA scaffolds and RNA-targeting Cas9 are convenient and versatile platforms for site-specific genome editing and epigenome modulation. They are easy-to-use, simple-to-design and capable of targeting multiple loci simultaneously. Given that cancer develops from cumulative genetic and epigenetic alterations, CRISPR-Cas9 and its variants (hereafter referred to as CRISPR-Cas9 systems) hold extensive application potentials in cancer modeling and therapy. To date, they have already been applied to model oncogenic mutations in cell lines (e.g., Choi and Meyerson, Nat Commun 2014;5:3728) and in adult animals (e.g., Xue et al., Nature 2014;514:380-4), as well as to combat cancer by disabling oncogenic viruses (e.g., Hu et al., Biomed Res Int 2014;2014:612823) or by manipulating cancer genome (e.g., Liu et al., Nat Commun 2014;5:5393). Given the importance of epigenome and transcriptome in tumourigenesis, manipulation of cancer epigenome and transcriptome for cancer modeling and therapy is a promising area in the future. Whereas (epi)genetic modifications of cancer microenvironment with CRISPR-Cas9 systems for therapeutic purposes represent another promising area in cancer research. Herein, we introduce the functions and mechanisms of CRISPR-Cas9 systems in genome editing and epigenome modulation, retrospect their applications in cancer modelling and therapy, discuss limitations and possible solutions and propose future directions, in hope of providing concise and enlightening information for readers interested in this area. © 2015 UICC.

Space Technology 5: Enabling Future Micro-Sat Constellation Science Missions

NASA Technical Reports Server (NTRS)

Carlisle, Candace C.; Webb, Evan H.

2004-01-01

The Space Technology 5 (ST-5) Project is part of NASA s New Millennium Program. ST-5 will consist of a constellation of three micro-satellites, each approximately 25 kg in mass. The mission goals are to demonstrate the research-quality science capability of the ST-5 spacecraft; to operate the three spacecraft as a constellation; and to design, develop and flight-validate three capable micro-satellites with new technologies. ST-5 is designed to measurably raise the utility of small satellites by providing high functionality in a low mass, low power, and low volume package. The whole of ST-5 is greater than the sum of its parts: the collection of components into the ST-5 spacecraft allows it to perform the functionality of a larger scientific spacecraft on a micro-satellite platform. The ST-5 mission was originally designed to be launched as a secondary payload into a Geosynchronous Transfer Orbit (GTO). Recently, the mission has been replanned for a Pegasus XL dedicated launch into an elliptical polar orbit. A three-month flight demonstration phase, beginning in March 2006, will validate the ability to perform science measurements, as well as the technologies and constellation operations. ST- 5 s technologies and concepts will then be transferred to future micro-sat science missions.

Real-time monitoring of lactate extrusion and glucose consumption of cultured cells using a lab-on-valve system.

PubMed

Schulz, Craig M; Scampavia, Louis; Ruzicka, Jaromir

2002-12-01

Microsequential injection (microST) provides microfluidic operations that are ideally suited for cellular function studies and as a means of validating targets for drug discovery. MicroSI carried out within the lab-on-valve (LOV) manifold, is an ideal platform for spectroscopic studies on living cells that are grown on microcarrier beads and kept thermostated while their metabolism is probed in real-time. In this paper a microbioreactor is integrated into the LOV manifold allowing measurement of cellular lactate extrusion and glucose consumption rates of a cell culture that is automatically renewed prior to each measurement. Glucose consumption and lactate extrusion are monitored using NAD-linked enzymatic assays. The microSI-LOV setup has demonstrated a linear analysis range of 0.05-1.00 mM for lactate and 0.1-5.6 mM for glucose. These assays were conducted in a serial fashion requiring 3 microL of cellular perfusate and 10 s for glucose determination and 30 s for the lactate assay. Overall waste generated per lactate/glucose assay is < 200 microL. This work was performed using two different transfected hepatocyte cell lines, which adhere to Cytopore microcarrier beads. This novel approach to metabolic screening allows for the rapid evaluation of the effects of dosing cells with chemical agents.

Real-time dynamics of high-velocity micro-particle impact

NASA Astrophysics Data System (ADS)

Veysset, David; Hsieh, Alex; Kooi, Steve; Maznev, Alex A.; Tang, Shengchang; Olsen, Bradley D.; Nelson, Keith A.

High-velocity micro-particle impact is important for many areas of science and technology, from space exploration to the development of novel drug delivery platforms. We present real-time observations of supersonic micro-particle impacts using multi-frame imaging. In an all optical laser-induced projectile impact test, a monolayer of micro-particles is placed on a transparent substrate coated with a laser absorbing polymer layer. Ablation of a laser-irradiated polymer region accelerates the micro-particles into free space with speeds up to 1.0 km/s. The particles are monitored during the impact on the target with an ultrahigh-speed multi-frame camera that can record up to 16 images with time resolution as short as 3 ns. In particular, we investigated the high-velocity impact deformation response of poly(urethane urea) (PUU) elastomers to further the fundamental understanding of the molecular influence on dynamical behaviors of PUUs. We show the dynamic-stiffening response of the PUUs and demonstrate the significance of segmental dynamics in the response. We also present movies capturing individual particle impact and penetration in gels, and discuss the observed dynamics. The results will provide an impetus for modeling high-velocity microscale impact responses and high strain rate deformation in polymers, gels, and other materials.

Space Technology 5: Enabling Future Micro-Sat Constellation Science Missions

NASA Technical Reports Server (NTRS)

Carlisle, Candace C.; Webb, Evan H.; Slavin, James A.

2004-01-01

The Space Technology 5 (ST-5) Project is part of NASA s New Millennium Program. ST-5 will consist of a constellation of three micro-satellites, each approximately 25 kg in mass. The mission goals are to demonstrate the research-quality science capability of the ST-5 spacecraft, to operate the three spacecraft as a constellation; and to design, develop and flight-validate three capable micro-satellites with new technologies. ST-5 is designed to measurably raise the utility of small satellites by providing high functionality in a low mass, low power, and low volume package. The whole of ST-5 is greater than the sum of its parts: the collection of components into the ST-5 spacecraft allows it to perform the functionality of a larger scientific spacecraft on a micro-satellite platform. The ST-5 mission was originally designed to be launched as a secondary payload into a Geosynchronous Transfer Orbit (GTO). Recently, the mission has been replanned for a Pegasus XL dedicated launch into an elliptical polar orbit. A three-month flight demonstration phase, beginning in March 2006, will validate the ability to perform science measurements, as well as the technologies and constellation operations. ST- 5 s technologies and concepts will then be transferred to future micro-sat science missions.

A customizable system for real-time image processing using the Blackfin DSProcessor and the MicroC/OS-II real-time kernel

NASA Astrophysics Data System (ADS)

Coffey, Stephen; Connell, Joseph

2005-06-01

This paper presents a development platform for real-time image processing based on the ADSP-BF533 Blackfin processor and the MicroC/OS-II real-time operating system (RTOS). MicroC/OS-II is a completely portable, ROMable, pre-emptive, real-time kernel. The Blackfin Digital Signal Processors (DSPs), incorporating the Analog Devices/Intel Micro Signal Architecture (MSA), are a broad family of 16-bit fixed-point products with a dual Multiply Accumulate (MAC) core. In addition, they have a rich instruction set with variable instruction length and both DSP and MCU functionality thus making them ideal for media based applications. Using the MicroC/OS-II for task scheduling and management, the proposed system can capture and process raw RGB data from any standard 8-bit greyscale image sensor in soft real-time and then display the processed result using a simple PC graphical user interface (GUI). Additionally, the GUI allows configuration of the image capture rate and the system and core DSP clock rates thereby allowing connectivity to a selection of image sensors and memory devices. The GUI also allows selection from a set of image processing algorithms based in the embedded operating system.

[Relationship between occupational stress and mental health in offshore oil platform workers].

PubMed

Wu, Hongtao; Xiao, Taiqin; Zou, Jianfang; Shan, Yongle; Li, Zijian

2014-02-01

To investigate the relationship between occupational stress and mental health in offshore oil platform workers and to provide a scientific basis for protection of their mental health. A total of 768 workers on offshore oil platform were surveyed with the Occupational Stress Inventory Revised Edition and Symptom Check List-90 (SCL-90). The total score of Occupational Role Questionnaire (ORQ) for the workers (160.27±24.63) was significantly lower than the national norm (166.52±27.01) (P < 0.01); the total score of Personal Strain Questionnaire (PSQ) (101.96±19.8) was significantly higher than the national norm (92.45±17.33) (P < 0.01). The total score of Personal Resource Questionnaire (PRQ) for the workers was not significantly different from the national norm (P > 0.05), but the items of recreation, social support, and rational/cognitive found significant difference (P < 0.05). The total score of SCL-90 was positively correlated with all items of ORQ and PSQ (P < 0.01) and negatively correlated with all items of PRQ (P < 0.01). The multiple stepwise regression analysis showed that current work seniority, education background, drinking, role overload, role insufficiency, role ambiguity, responsibility, physical environment, and rational/cognitive conduct impacted the score of SCL-90 (P < 0.05). The mental health of workers on offshore oil platform is related to occupational stress, and role overload, role ambiguity, physical environment, and rational/cognitive conduct, etc, are closely associated with the workers' mental health.

Engineered CRISPR Systems for Next Generation Gene Therapies.

PubMed

Pineda, Michael; Moghadam, Farzaneh; Ebrahimkhani, Mo R; Kiani, Samira

2017-09-15

An ideal in vivo gene therapy platform provides safe, reprogrammable, and precise strategies which modulate cell and tissue gene regulatory networks with a high temporal and spatial resolution. Clustered regularly interspaced short palindromic repeats (CRISPR), a bacterial adoptive immune system, and its CRISPR-associated protein 9 (Cas9), have gained attention for the ability to target and modify DNA sequences on demand with unprecedented flexibility and precision. The precision and programmability of Cas9 is derived from its complexation with a guide-RNA (gRNA) that is complementary to a desired genomic sequence. CRISPR systems open-up widespread applications including genetic disease modeling, functional screens, and synthetic gene regulation. The plausibility of in vivo genetic engineering using CRISPR has garnered significant traction as a next generation in vivo therapeutic. However, there are hurdles that need to be addressed before CRISPR-based strategies are fully implemented. Some key issues center on the controllability of the CRISPR platform, including minimizing genomic-off target effects and maximizing in vivo gene editing efficiency, in vivo cellular delivery, and spatial-temporal regulation. The modifiable components of CRISPR systems: Cas9 protein, gRNA, delivery platform, and the form of CRISPR system delivered (DNA, RNA, or ribonucleoprotein) have recently been engineered independently to design a better genome engineering toolbox. This review focuses on evaluating CRISPR potential as a next generation in vivo gene therapy platform and discusses bioengineering advancements that can address challenges associated with clinical translation of this emerging technology.

Ultra-short pulse delivery at high average power with low-loss hollow core fibers coupled to TRUMPF's TruMicro laser platforms for industrial applications

NASA Astrophysics Data System (ADS)

Baumbach, S.; Pricking, S.; Overbuschmann, J.; Nutsch, S.; Kleinbauer, J.; Gebs, R.; Tan, C.; Scelle, R.; Kahmann, M.; Budnicki, A.; Sutter, D. H.; Killi, A.

2017-02-01

Multi-megawatt ultrafast laser systems at micrometer wavelength are commonly used for material processing applications, including ablation, cutting and drilling of various materials or cleaving of display glass with excellent quality. There is a need for flexible and efficient beam guidance, avoiding free space propagation of light between the laser head and the processing unit. Solid core step index fibers are only feasible for delivering laser pulses with peak powers in the kW-regime due to the optical damage threshold in bulk silica. In contrast, hollow core fibers are capable of guiding ultra-short laser pulses with orders of magnitude higher peak powers. This is possible since a micro-structured cladding confines the light within the hollow core and therefore minimizes the spatial overlap between silica and the electro-magnetic field. We report on recent results of single-mode ultra-short pulse delivery over several meters in a lowloss hollow core fiber packaged with industrial connectors. TRUMPF's ultrafast TruMicro laser platforms equipped with advanced temperature control and precisely engineered opto-mechanical components provide excellent position and pointing stability. They are thus perfectly suited for passive coupling of ultra-short laser pulses into hollow core fibers. Neither active beam launching components nor beam trackers are necessary for a reliable beam delivery in a space and cost saving packaging. Long term tests with weeks of stable operation, excellent beam quality and an overall transmission efficiency of above 85 percent even at high average power confirm the reliability for industrial applications.

Capturing Micro-topography of an Arctic Tundra Landscape through Digital Elevation Models (DEMs) Acquired from Various Remote Sensing Platforms

NASA Astrophysics Data System (ADS)

Vargas, S. A., Jr.; Tweedie, C. E.; Oberbauer, S. F.

2013-12-01

The need to improve the spatial and temporal scaling and extrapolation of plot level measurements of ecosystem structure and function to the landscape level has been identified as a persistent research challenge in the arctic terrestrial sciences. Although there has been a range of advances in remote sensing capabilities on satellite, fixed wing, helicopter and unmanned aerial vehicle platforms over the past decade, these present costly, logistically challenging (especially in the Arctic), technically demanding solutions for applications in an arctic environment. Here, we present a relatively low cost alternative to these platforms that uses kite aerial photography (KAP). Specifically, we demonstrate how digital elevation models (DEMs) were derived from this system for a coastal arctic landscape near Barrow, Alaska. DEMs of this area acquired from other remote sensing platforms such as Terrestrial Laser Scanning (TLS), Airborne Laser Scanning, and satellite imagery were also used in this study to determine accuracy and validity of results. DEMs interpolated using the KAP system were comparable to DEMs derived from the other platforms. For remotely sensing acre to kilometer square areas of interest, KAP has proven to be a low cost solution from which derived products that interface ground and satellite platforms can be developed by users with access to low-tech solutions and a limited knowledge of remote sensing.

A systematic exploration of the micro-blog feature space for teens stress detection.

PubMed

Zhao, Liang; Li, Qi; Xue, Yuanyuan; Jia, Jia; Feng, Ling

2016-01-01

In the modern stressful society, growing teenagers experience severe stress from different aspects from school to friends, from self-cognition to inter-personal relationship, which negatively influences their smooth and healthy development. Being timely and accurately aware of teenagers psychological stress and providing effective measures to help immature teenagers to cope with stress are highly valuable to both teenagers and human society. Previous work demonstrates the feasibility to sense teenagers' stress from their tweeting contents and context on the open social media platform-micro-blog. However, a tweet is still too short for teens to express their stressful status in a comprehensive way. Considering the topic continuity from the tweeting content to the follow-up comments and responses between the teenager and his/her friends, we combine the content of comments and responses under the tweet to supplement the tweet content. Also, such friends' caring comments like "what happened?", "Don't worry!", "Cheer up!", etc. provide hints to teenager's stressful status. Hence, in this paper, we propose to systematically explore the micro-blog feature space, comprised of four kinds of features [tweeting content features (FW), posting features (FP), interaction features (FI), and comment-response features (FC) between teenagers and friends] for teenager' stress category and stress level detection. We extract and analyze these feature values and their impacts on teens stress detection. We evaluate the framework through a real user study of 36 high school students aged 17. Different classifiers are employed to detect potential stress categories and corresponding stress levels. Experimental results show that all the features in the feature space positively affect stress detection, and linguistic negative emotion, proportion of negative sentences, friends' caring comments and teen's reply rate play more significant roles than the rest features. Micro-blog platform provides easy and effective channel to detect teenagers' psychological stress. Involving comments and responses under the tweet supplement the detection and improves the detection accuracy of 16.8 %.

Use of micro-optical coherence tomography to analyze barrier integrity of intestinal epithelial cells (Conference Presentation)

NASA Astrophysics Data System (ADS)

Som, Avira; Leung, Hui Min; Chu, Kengyeh; Eaton, Alex D.; Hurley, Bryan P.; Tearney, Guillermo J.

2017-02-01

The intestinal epithelial barrier provides protection from external threats that enter the digestive system and persist beyond passage through the stomach. The effects of toxic agents on the intestinal epithelial cell monolayer have not been fully characterized at a cellular level as live imaging of this dynamic interplay at sufficient resolution to interpret cellular responses presents technological challenges. Using a high-resolution native contrast modality called Micro-Optical Coherence Tomography (μOCT), we generated real-time 3D images depicting the impact of the chemical agent EDTA on polarized intestinal epithelial monolayers. Within minutes following application of EDTA, we observed a change in the uniformity of epithelial surface thickness and loss of the edge brightness associated with the apical surface. These observations were measured by generating computer algorithms which quantify imaged-based events changing over time, thus providing parallel graphed data to pair with video. The imaging platform was designed to monitor epithelial monolayers prior to and following application of chemical agents in order to provide a comprehensive account of monolayer behavior at baseline conditions and immediately following exposure. Furthermore, the platform was designed to simultaneously measure continuous trans-epithelial electric resistance (TEER) in order to define the progressive loss of barrier integrity of the cell monolayer following exposure to toxic agents and correlate these findings to image-based metrics. This technological image-based experimental platform provides a novel means to characterize mechanisms that impact the intestinal barrier and, in future efforts, can be applied to study the impact of disease relevant agents such as enteric pathogens and enterotoxins.

3D MOEMS-based optical micro-bench platform for the miniaturization of sensing devices

NASA Astrophysics Data System (ADS)

Garcia-Blanco, Sonia; Caron, Jean-Sol; Leclair, Sébastien; Topart, Patrice A.; Jerominek, Hubert

2008-02-01

As we enter into the 21st century, the need for miniaturized portable diagnostic devices is increasing continuously. Portable devices find important applications for point-of-care diagnostics, patient self-monitoring and in remote areas, such as unpopulated regions where the cost of large laboratory facilities is not justifiable, underdeveloped countries and other remote locations such as space missions. The advantage of miniaturized sensing optical systems includes not only the reduced weight and size but also reduced cost, decreased time to results and robustness (e.g. no need for frequent re-alignments). Recent advances in micro-fabrication and assembly technologies have enabled important developments in the field of miniaturized sensing systems. INO has developed a technology platform for the three dimensional integration of MOEMS on an optical microbench. Building blocks of the platform include microlenses, micromirrors, dichroic beamsplitters, filters and optical fibers, which can be positioned using passive alignment structures to build the desired miniaturised system. The technology involves standard microfabrication, thick resist UV-lithography, thick metal electroplating, soldering, replication in sol-gel materials and flip-chip bonding processes. The technology is compatible with wafer-to-wafer bonding. A placement accuracy of +/- 5 μm has been demonstrated thanks to the integration of alignment marks co registered with other optical elements fabricated on different wafers. In this paper, the building blocks of the technology will be detailed. The design and fabrication of a 5x5 channels light processing unit including optical fibers, mirrors and collimating microlenses will be described. Application of the technology to various kinds of sensing devices will be discussed.

Micro-engineering a platform to reconstruct physiology and functionality of the human brain microvasculature in vitro

NASA Astrophysics Data System (ADS)

Daghighi, Yasaman; Heidari, Hossein; Taylor, Hayden

2018-02-01

A predominant unsolved challenge in tissue engineering is the need of a robust technique for producing vascular networks, particularly when modeling human brain tissue. The availability of reliable in vitro human brain microvasculature models would advance our understanding of its function and would provide a platform for highthroughput drug screening. Current strategies for modeling vascularized brain tissue suffer from limitations such as (1) culturing non-human cell lines, (2) limited multi-cell co-culture, and (3) the effects of neighboring physiologically unrealistic rigid polymeric surfaces, such as solid membranes. We demonstrate a new micro-engineered platform that can address these shortcomings. Specifically, we have designed and prototyped a molding system to enable the precise casting of 100μm-diameter coaxial hydrogel structures laden with the requisite cells to mimic a vascular lumen. Here we demonstrate that a fine wire with diameter 130 μm or a needle with outer diameter 300 μm can be used as a temporary mold insert, and agarose-collagen composite matrix can be cast around these inserts and thermally gelled. When the wire or needle is retracted under the precise positional control afforded by our system, a microchannel is formed which is then seeded with human microvascular endothelial cells. After seven days of culture these cells produce an apparently confluent monolayer on the channel walls. In principle, this platform could be used to create multilayered cellular structures. By arranging a fine wire and a hollow needle coaxially, three distinct zones could be defined in the model: first, the bulk gel surrounding the needle; then, after needle retraction, a cylindrical shell of matrix; and finally, after retraction of the wire, a lumen. Each zone could be independently cell-seeded. To this end, we have also successfully 3D cultured human astrocytes and SY5Y glial cells in our agarose-collagen matrix. Our approach ultimately promises scalable and repeatable production of vascular structures with physiologically realistic mechanical properties.

Drive to miniaturization: integrated optical networks on mobile platforms

NASA Astrophysics Data System (ADS)

Salour, Michael M.; Batayneh, Marwan; Figueroa, Luis

2011-11-01

With rapid growth of the Internet, bandwidth demand for data traffic is continuing to explode. In addition, emerging and future applications are becoming more and more network centric. With the proliferation of data communication platforms and data-intensive applications (e.g. cloud computing), high-bandwidth materials such as video clips dominating the Internet, and social networking tools, a networking technology is very desirable which can scale the Internet's capability (particularly its bandwidth) by two to three orders of magnitude. As the limits of Moore's law are approached, optical mesh networks based on wavelength-division multiplexing (WDM) have the ability to satisfy the large- and scalable-bandwidth requirements of our future backbone telecommunication networks. In addition, this trend is also affecting other special-purpose systems in applications such as mobile platforms, automobiles, aircraft, ships, tanks, and micro unmanned air vehicles (UAVs) which are becoming independent systems roaming the sky while sensing data, processing, making decisions, and even communicating and networking with other heterogeneous systems. Recently, WDM optical technologies have seen advances in its transmission speeds, switching technologies, routing protocols, and control systems. Such advances have made WDM optical technology an appealing choice for the design of future Internet architectures. Along these lines, scientists across the entire spectrum of the network architectures from physical layer to applications have been working on developing devices and communication protocols which can take full advantage of the rapid advances in WDM technology. Nevertheless, the focus has always been on large-scale telecommunication networks that span hundreds and even thousands of miles. Given these advances, we investigate the vision and applicability of integrating the traditionally large-scale WDM optical networks into miniaturized mobile platforms such as UAVs. We explain the benefits of WDM optical technology for these applications. We also describe some of the limitations of WDM optical networks as the size of a vehicle gets smaller, such as in micro-UAVs, and study the miniaturization and communication system limitations in such environments.

Mapping Depositional Facies on Great Bahama Bank: An Integration of Groundtruthing and Remote Sensing Methods

NASA Astrophysics Data System (ADS)

Hariss, M.; Purkis, S.; Ellis, J. M.; Swart, P. K.; Reijmer, J.

2013-12-01

Great Bahama Bank (GBB) has been used in many models to illustrate depositional facies variation across flat-topped, isolated carbonate platforms. Such models have served as subsurface analogs at a variety of scales. In this presentation we have integrated Landsat TM imagery, a refined bathymetric digital elevation model, and seafloor sample data compiled into ArcGIS and analyzed with eCognition to develop a depositional facies map that is more robust than previous versions. For the portion of the GBB lying to the west of Andros Island, the facies map was generated by pairing an extensive set of GPS-constrained field observations and samples (n=275) (Reijmer et al., 2009, IAS Spec Pub 41) with computer and manual interpretation of the Landsat imagery. For the remainder of the platform, which lacked such rigorous ground-control, the Landsat imagery was segmented into lithotopes - interpreted to be distinct bodies of uniform sediment - using a combination of edge detection, spectral and textural analysis, and manual editing. A map was then developed by assigning lithotopes to facies classes on the basis of lessons derived from the portion of the platform for which we had rigorous conditioning. The new analysis reveals that GBB is essentially a very grainy platform with muddier accumulations only in the lee of substantial island barriers; in this regard Andros Island, which is the largest island on GBB, exerts a direct control over the muddiest portion of GBB. Mudstones, wackestones, and mud-rich packstones cover 7%, 6%, and 15%, respectively, of the GBB platform top. By contrast, mud-poor packstones, grainstones, and rudstones account for 19%, 44%, and 3%, respectively. Of the 44% of the platform-top classified as grainstone, only 4% is composed of 'high-energy' deposits characterized by the development of sandbar complexes. The diversity and size of facies bodies is broadly the same on the eastern and western limb of the GBB platform, though the narrower eastern limb, the New Providence Platform, hosts a higher prevalence of high energy grainstones. The most abrupt lateral facies changes are observed leeward of islands, areas which also hold the highest diversity in facies type.

Nanoscale platforms for messenger RNA delivery.

PubMed

Li, Bin; Zhang, Xinfu; Dong, Yizhou

2018-05-04

Messenger RNA (mRNA) has become a promising class of drugs for diverse therapeutic applications in the past few years. A series of clinical trials are ongoing or will be initiated in the near future for the treatment of a variety of diseases. Currently, mRNA-based therapeutics mainly focuses on ex vivo transfection and local administration in clinical studies. Efficient and safe delivery of therapeutically relevant mRNAs remains one of the major challenges for their broad applications in humans. Thus, effective delivery systems are urgently needed to overcome this limitation. In recent years, numerous nanoscale biomaterials have been constructed for mRNA delivery in order to protect mRNA from extracellular degradation and facilitate endosomal escape after cellular uptake. Nanoscale platforms have expanded the feasibility of mRNA-based therapeutics, and enabled its potential applications to protein replacement therapy, cancer immunotherapy, therapeutic vaccines, regenerative medicine, and genome editing. This review focuses on recent advances, challenges, and future directions in nanoscale platforms designed for mRNA delivery, including lipid and lipid-derived nanoparticles, polymer-based nanoparticles, protein derivatives mRNA complexes, and other types of nanomaterials. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Biology-Inspired Nanomaterials > Lipid-Based Structures Biology-Inspired Nanomaterials > Nucleic Acid-Based Structures. © 2018 Wiley Periodicals, Inc.

What Can OpenEI Do For You?

ScienceCinema

None

2018-02-06

Open Energy Information (OpenEI) is an open source web platform—similar to the one used by Wikipedia—developed by the US Department of Energy (DOE) and the National Renewable Energy Laboratory (NREL) to make the large amounts of energy-related data and information more easily searched, accessed, and used both by people and automated machine processes. Built utilizing the standards and practices of the Linked Open Data community, the OpenEI platform is much more robust and powerful than typical web sites and databases. As an open platform, all users can search, edit, add, and access data in OpenEI for free. The user community contributes the content and ensures its accuracy and relevance; as the community expands, so does the content's comprehensiveness and quality. The data are structured and tagged with descriptors to enable cross-linking among related data sets, advanced search functionality, and consistent, usable formatting. Data input protocols and quality standards help ensure the content is structured and described properly and derived from a credible source. Although DOE/NREL is developing OpenEI and seeding it with initial data, it is designed to become a true community model with millions of users, a large core of active contributors, and numerous sponsors.

An open source web interface for linking models to infrastructure system databases

NASA Astrophysics Data System (ADS)

Knox, S.; Mohamed, K.; Harou, J. J.; Rheinheimer, D. E.; Medellin-Azuara, J.; Meier, P.; Tilmant, A.; Rosenberg, D. E.

2016-12-01

Models of networked engineered resource systems such as water or energy systems are often built collaboratively with developers from different domains working at different locations. These models can be linked to large scale real world databases, and they are constantly being improved and extended. As the development and application of these models becomes more sophisticated, and the computing power required for simulations and/or optimisations increases, so has the need for online services and tools which enable the efficient development and deployment of these models. Hydra Platform is an open source, web-based data management system, which allows modellers of network-based models to remotely store network topology and associated data in a generalised manner, allowing it to serve multiple disciplines. Hydra Platform uses a web API using JSON to allow external programs (referred to as `Apps') to interact with its stored networks and perform actions such as importing data, running models, or exporting the networks to different formats. Hydra Platform supports multiple users accessing the same network and has a suite of functions for managing users and data. We present ongoing development in Hydra Platform, the Hydra Web User Interface, through which users can collaboratively manage network data and models in a web browser. The web interface allows multiple users to graphically access, edit and share their networks, run apps and view results. Through apps, which are located on the server, the web interface can give users access to external data sources and models without the need to install or configure any software. This also ensures model results can be reproduced by removing platform or version dependence. Managing data and deploying models via the web interface provides a way for multiple modellers to collaboratively manage data, deploy and monitor model runs and analyse results.

UPC BarcelonaTech Platform. Innovative aerobatic parabolic flights for life sciences experiments.

NASA Astrophysics Data System (ADS)

Perez-Poch, Antoni; Gonzalez, Daniel

We present an innovative method of performing parabolic flights with aerobatic single-engine planes. A parabolic platform has been established in Sabadell Airport (Barcelona, Spain) to provide an infraestructure ready to allow Life Sciences reduced gravity experiments to be conducted in parabolic flights. Test flights have demonstrated that up to 8 seconds of reduced gravity can be achieved by using a two-seat CAP10B aircraft, with a gravity range between 0.1 and 0.01g in the three axis. A parabolic flight campaign may be implemented with a significant reduction in budget compared to conventional parabolic flight campaigns, and with a very short time-to-access to the platform. Operational skills and proficiency of the pilot controling the aircraft during the maneuvre, sensitivity to wind gusts, and aircraft balance are the key issues that make a parabola successful. Efforts are focused on improving the total “zero-g” time and the quality of reduced gravity achieved, as well as providing more space for experiments. We report results of test flights that have been conducted in order to optimize the quality and total microgravity time. A computer sofware has been developed and implemented to help the pilot optimize his or her performance. Finally, we summarize the life science experiments that have been conducted in this platform. Specific focus is given to the very successful 'Barcelona ZeroG Challenge', this year in its third edition. This educational contest gives undergraduate and graduate students worldwide the opportunity to design their research within our platform and test it on flight, thus becoming real researchers. We conclude that aerobatic parabolic flights have proven to be a safe, unexpensive and reliable way to conduct life sciences reduced gravity experiments.

Design of smart composite platforms for adaptive trust vector control and adaptive laser telescope for satellite applications

NASA Astrophysics Data System (ADS)

Ghasemi-Nejhad, Mehrdad N.

2013-04-01

This paper presents design of smart composite platforms for adaptive trust vector control (TVC) and adaptive laser telescope for satellite applications. To eliminate disturbances, the proposed adaptive TVC and telescope systems will be mounted on two analogous smart composite platform with simultaneous precision positioning (pointing) and vibration suppression (stabilizing), SPPVS, with micro-radian pointing resolution, and then mounted on a satellite in two different locations. The adaptive TVC system provides SPPVS with large tip-tilt to potentially eliminate the gimbals systems. The smart composite telescope will be mounted on a smart composite platform with SPPVS and then mounted on a satellite. The laser communication is intended for the Geosynchronous orbit. The high degree of directionality increases the security of the laser communication signal (as opposed to a diffused RF signal), but also requires sophisticated subsystems for transmission and acquisition. The shorter wavelength of the optical spectrum increases the data transmission rates, but laser systems require large amounts of power, which increases the mass and complexity of the supporting systems. In addition, the laser communication on the Geosynchronous orbit requires an accurate platform with SPPVS capabilities. Therefore, this work also addresses the design of an active composite platform to be used to simultaneously point and stabilize an intersatellite laser communication telescope with micro-radian pointing resolution. The telescope is a Cassegrain receiver that employs two mirrors, one convex (primary) and the other concave (secondary). The distance, as well as the horizontal and axial alignment of the mirrors, must be precisely maintained or else the optical properties of the system will be severely degraded. The alignment will also have to be maintained during thruster firings, which will require vibration suppression capabilities of the system as well. The innovative platform has been designed to have tip-tilt pointing and simultaneous multi-degree-of-freedom vibration isolation capability for pointing stabilization. Analytical approaches have been employed for determining the loads in the components as well as optimizing the design of the system. The different critical components such as telescope tube struts, flexure joints, and the secondary mirror mount have been designed and analyzed using finite element technique. The Simultaneous Precision Positioning and Vibration Suppression (SPPVS) smart composites platforms for the adaptive TVC and adaptive composite telescope are analogous (e.g., see work by Ghasemi-Nejhad and co-workers [1, 2]), where innovative concepts and control strategies are introduced, and experimental verifications of simultaneous thrust vector control and vibration isolation of satellites were performed. The smart composite platforms function as an active structural interface between the main thruster of a satellite and the satellite structure for the adaptive TVC application and as an active structural interface between the main smart composite telescope and the satellite structure for the adaptive laser communication application. The cascaded multiple feedback loops compensate the hysteresis (for piezoelectric stacks inside the three linear actuators that individually have simultaneous precision positioning and vibration suppression), dead-zone, back-lash, and friction nonlinearities very well, and provide precision and quick smart platform control and satisfactory thrust vector control capability. In addition, for example for the adaptive TVC, the experimental results show that the smart composite platform satisfactorily provided precision and fast smart platform control as well as the satisfactory thrust vector control capability. The vibration controller isolated 97% of the vibration energy due to the thruster firing.

A coordinated set of ecosystem research platforms open to international research in ecotoxicology, AnaEE-France.

PubMed

Mougin, Christian; Azam, Didier; Caquet, Thierry; Cheviron, Nathalie; Dequiedt, Samuel; Le Galliard, Jean-François; Guillaume, Olivier; Houot, Sabine; Lacroix, Gérard; Lafolie, François; Maron, Pierre-Alain; Michniewicz, Radika; Pichot, Christian; Ranjard, Lionel; Roy, Jacques; Zeller, Bernd; Clobert, Jean; Chanzy, André

2015-10-01

The infrastructure for Analysis and Experimentation on Ecosystems (AnaEE-France) is an integrated network of the major French experimental, analytical, and modeling platforms dedicated to the biological study of continental ecosystems (aquatic and terrestrial). This infrastructure aims at understanding and predicting ecosystem dynamics under global change. AnaEE-France comprises complementary nodes offering access to the best experimental facilities and associated biological resources and data: Ecotrons, seminatural experimental platforms to manipulate terrestrial and aquatic ecosystems, in natura sites equipped for large-scale and long-term experiments. AnaEE-France also provides shared instruments and analytical platforms dedicated to environmental (micro) biology. Finally, AnaEE-France provides users with data bases and modeling tools designed to represent ecosystem dynamics and to go further in coupling ecological, agronomical, and evolutionary approaches. In particular, AnaEE-France offers adequate services to tackle the new challenges of research in ecotoxicology, positioning its various types of platforms in an ecologically advanced ecotoxicology approach. AnaEE-France is a leading international infrastructure, and it is pioneering the construction of AnaEE (Europe) infrastructure in the field of ecosystem research. AnaEE-France infrastructure is already open to the international community of scientists in the field of continental ecotoxicology.

An Attenuated CRISPR-Cas System in Enterococcus faecalis Permits DNA Acquisition.

PubMed

Hullahalli, Karthik; Rodrigues, Marinelle; Nguyen, Uyen Thy; Palmer, Kelli

2018-05-01

Antibiotic-resistant bacteria are critical public health concerns. Among the prime causative factors for the spread of antibiotic resistance is horizontal gene transfer (HGT). A useful model organism for investigating the relationship between HGT and antibiotic resistance is the opportunistic pathogen Enterococcus faecalis , since the species possesses highly conjugative plasmids that readily disseminate antibiotic resistance genes and virulence factors in nature. Unlike many commensal E. faecalis strains, the genomes of multidrug-resistant (MDR) E. faecalis clinical isolates are enriched for mobile genetic elements (MGEs) and lack c lustered r egularly i nterspaced s hort p alindromic r epeats (CRISPR) and C RISPR- as sociated protein (Cas) genome defense systems. CRISPR-Cas systems cleave foreign DNA in a programmable, sequence-specific manner and are disadvantageous for MGE-derived genome expansion. An unexplored facet of CRISPR biology in E. faecalis is that MGEs that are targeted by native CRISPR-Cas systems can be maintained transiently. Here, we investigate the basis for this "CRISPR tolerance." We observe that E. faecalis can maintain self-targeting constructs that direct Cas9 to cleave the chromosome, but at a fitness cost. Interestingly, DNA repair genes were not upregulated during self-targeting, but integrated prophages were strongly induced. We determined that low cas9 expression contributes to this transient nonlethality and used this knowledge to develop a robust CRISPR-assisted genome-editing scheme. Our results suggest that E. faecalis has maximized the potential for DNA acquisition by attenuating its CRISPR machinery, thereby facilitating the acquisition of potentially beneficial MGEs that may otherwise be restricted by genome defense. IMPORTANCE CRISPR-Cas has provided a powerful toolkit to manipulate bacteria, resulting in improved genetic manipulations and novel antimicrobials. These powerful applications rely on the premise that CRISPR-Cas chromosome targeting, which leads to double-stranded DNA breaks, is lethal. In this study, we show that chromosomal CRISPR targeting in Enterococcus faecalis is transiently nonlethal. We uncover novel phenotypes associated with this "CRISPR tolerance" and, after determining its genetic basis, develop a genome-editing platform in E. faecalis with negligible off-target effects. Our findings reveal a novel strategy exploited by a bacterial pathogen to cope with CRISPR-induced conflicts to more readily accept DNA, and our robust CRISPR editing platform will help simplify genetic modifications in this organism. Copyright © 2018 Hullahalli et al.

The effects of gamma irradiation on micro-hotplates with integrated temperature sensing diodes

NASA Astrophysics Data System (ADS)

Francis, Laurent A.; André, Nicolas; Boufouss, El Hafed; Gérard, Pierre; Ali, Zeeshan; Udrea, Florin; Flandre, Denis

2014-06-01

Micro-hotplates are MEMS structures of interest for low-power gas sensing, lab-on-chips and space applications, such as micro-thrusters. Micro-hotplates usually consist in a Joule heater suspended on a thin-film membrane while thermopiles or thermodiodes are added as temperature sensors and for feedback control. The implementation of micro-hotplates using a Silicon-On-Insulator technology makes them suited for co-integration with analog integrated circuits and operation at elevated environmental temperatures in a range from 200 to 300 °C, while the heater allows thermal cycling in the kHz regime up to 700 °C, e.g. necessary for the activation of gas sensitive metal-oxide on top of the membrane, with mWrange electrical power. The demonstrated resistance of micro-hotplates to gamma radiations can extend their use in nuclear plants, biomedical sterilization and space applications. In this work, we present results from electrical tests on micro-hotplates during their irradiation by Cobalt-60 gamma rays with total doses up to 18.90 kGy. The micro-hotplates are fabricated using a commercial 1.0 μm Silicon-On-Insulator technology with a tungsten Joule heater, which allows power-controlled operation above 600 °C with less than 60 mW, and temperature sensing silicon diodes located on the membrane and on the bulk. We show the immunity of the sensing platform to the harsh radiation environment. Beside the good tolerance of the thermodiodes and the membrane materials to the total radiation dose, the thermodiode located on the heating membrane is constantly annealed during irradiation and keeps a constant sensitivity while post-irradiation annealing can restore the thermodiode.

Modelling and control synthesis of a micro-combined heat and power interface for a concentrating solar power system in off-grid rural power applications

NASA Astrophysics Data System (ADS)

Prinsloo, Gerro; Dobson, Robert; Brent, Alan; Mammoli, Andrea

2016-05-01

Concentrating solar power co-generation systems have been identified as potential stand-alone solar energy supply solutions in remote rural energy applications. This study describes the modelling and synthesis of a combined heat and power Stirling CSP system in order to evaluate its potential performance in small off-grid rural village applications in Africa. This Stirling micro-Combined Heat and Power (micro-CHP) system has a 1 kW electric capacity, with 3 kW of thermal generation capacity which is produced as waste heat recovered from the solar power generation process. As part of the development of an intelligent microgrid control and distribution solution, the Trinum micro-CHP system and other co-generation systems are systematically being modelled on the TRNSYS simulation platform. This paper describes the modelling and simulation of the Trinum micro-CHP configuration on TRNSYS as part of the process to develop the control automation solution for the smart rural microgrid in which the Trinum will serve as a solar powerpack. The results present simulated performance outputs for the Trinum micro-CHP system for a number of remote rural locations in Africa computed from real-time TRNSYS solar irradiation and weather data (yearly, monthly, daily) for the relevant locations. The focus of this paper is on the parametric modelling of the Trinum Stirling micro-CHP system, with specific reference to this system as a TRNSYS functional block in the microgrid simulation. The model is used to forecast the solar energy harvesting potential of the Trinum micro-CHP unit at a number of remote rural sites in Africa.

Integrated micro/nanoengineered functional biomaterials for cell mechanics and mechanobiology: a materials perspective.

PubMed

Shao, Yue; Fu, Jianping

2014-03-12

The rapid development of micro/nanoengineered functional biomaterials in the last two decades has empowered materials scientists and bioengineers to precisely control different aspects of the in vitro cell microenvironment. Following a philosophy of reductionism, many studies using synthetic functional biomaterials have revealed instructive roles of individual extracellular biophysical and biochemical cues in regulating cellular behaviors. Development of integrated micro/nanoengineered functional biomaterials to study complex and emergent biological phenomena has also thrived rapidly in recent years, revealing adaptive and integrated cellular behaviors closely relevant to human physiological and pathological conditions. Working at the interface between materials science and engineering, biology, and medicine, we are now at the beginning of a great exploration using micro/nanoengineered functional biomaterials for both fundamental biology study and clinical and biomedical applications such as regenerative medicine and drug screening. In this review, an overview of state of the art micro/nanoengineered functional biomaterials that can control precisely individual aspects of cell-microenvironment interactions is presented and they are highlighted them as well-controlled platforms for mechanistic studies of mechano-sensitive and -responsive cellular behaviors and integrative biology research. The recent exciting trend where micro/nanoengineered biomaterials are integrated into miniaturized biological and biomimetic systems for dynamic multiparametric microenvironmental control of emergent and integrated cellular behaviors is also discussed. The impact of integrated micro/nanoengineered functional biomaterials for future in vitro studies of regenerative medicine, cell biology, as well as human development and disease models are discussed. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Design and Functional Validation of a Mechanism for Dual-Spinning CubeSats

NASA Technical Reports Server (NTRS)

Peters, Eric; Dave, Pratik; Kingsbury, Ryan; Marinan, Anne; Wise, Evan; Pong, Chris; Prinkey, Meghan; Cahoy, Kerri; Miller, David W.; Sklair, Devon

2014-01-01

The mission of the Micro-sized Microwave Atmospheric Satellite (MicroMAS) is to collect useful atmospheric images using a miniature passive microwave radiometer payload hosted on a low-cost CubeSat platform. In order to collect this data, the microwave radiometer payload must rotate to scan the ground-track perpendicular to the satellite's direction of travel. A custom motor assembly was developed to facilitate the rotation of the payload while allowing the spacecraft bus to remained fixed in the local-vertical, local-horizontal (LVLH) frame for increased pointing accuracy. This paper describes the mechanism used to enable this dual-spinning operation for CubeSats, and the lessons learned during the design, fabrication, integration, and testing phases of the mechanism's development lifecycle.

Flotation Immunoassay: Masking the Signal from Free Reporters in Sandwich Immunoassays

PubMed Central

Chen, Hui; Hagström, Anna E. V.; Kim, Jinsu; Garvey, Gavin; Paterson, Andrew; Ruiz-Ruiz, Federico; Raja, Balakrishnan; Strych, Ulrich; Rito-Palomares, Marco; Kourentzi, Katerina; Conrad, Jacinta C.; Atmar, Robert L.; Willson, Richard C.

2016-01-01

In this work, we demonstrate that signal-masking reagents together with appropriate capture antibody carriers can eliminate the washing steps in sandwich immunoassays. A flotation immunoassay (FI) platform was developed with horseradish peroxidase chemiluminescence as the reporter system, the dye Brilliant Blue FCF as the signal-masking reagent, and buoyant silica micro-bubbles as the capture antibody carriers. Only reporters captured on micro-bubbles float above the dye and become visible in an analyte-dependent manner. These FIs are capable of detecting proteins down to attomole levels and as few as 106 virus particles. This signal-masking strategy represents a novel approach to simple, sensitive and quantitative immunoassays in both laboratory and point-of-care settings. PMID:27075635

Investigation of optical information for a single micro grating device combined with MATA by SMart process

NASA Astrophysics Data System (ADS)

Tsai, Chien-Chung; Huang, Yi-Chao; Yang, Tsa-Hsien; Chen, Jen-Chieh

2006-01-01

The concentric circles type and saw-tooth type of micro grating device based upon the diffraction theory are proposed in this study. The geometry dimension of micro optical device is 200 × 200 μm2, the interval of grating is 4 μm, and the depth is 0.75 μm. The Micro Array Thermal Actuator, MATA, is applied to drive the micro grating device, and the pre-elevating structure is designed to lift the micro grating device by the residual stress of polysilicon combined with metal. The micro grating device is fabricated by Surface Micromachining for applications and research technology platform, SMart, common process. The incident ray of He-Ne laser focused by a lens which focal length is 250 mm is applied to be the light source for the experiment, and then analyzes the optical information of the outgoing ray. From the experimental results, the basic optical features are examined based upon the concentric circles type and saw-tooth type of micro grating device, respectively. The outgoing ray angle of central spot is 60° in theory. The measurements are 59.475° for the concentric circles type and 59.88° for the saw-tooth type. The outgoing ray angle of the first stripe is 46.9° in theory, and 46.81° for the concentric circles type and 46.67° for the saw-tooth type are measured from the experiment. The variation of outgoing ray angle is smaller than 1% compared the measurement results with theory of diffraction on the central spot and first stripe characteristics. The work successfully demonstrates the micro grating device with highly accurate performance by the verification of optical information. All of the efforts will be contributed to Controlled Blazed Diffraction micro grating device, CBDMG, and that will be the main device of Integrate Opto-Electronics applied on display to develop in the future.

Micro Cantilever Movement Detection with an Amorphous Silicon Array of Position Sensitive Detectors

PubMed Central

Contreras, Javier; Costa, Daniel; Pereira, Sonia; Fortunato, Elvira; Martins, Rodrigo; Wierzbicki, Rafal; Heerlein, Holger; Ferreira, Isabel

2010-01-01

The movement of a micro cantilever was detected via a self constructed portable data acquisition prototype system which integrates a linear array of 32 1D amorphous silicon position sensitive detectors (PSD). The system was mounted on a microscope using a metal structure platform and the movement of the 30 μm wide by 400 μm long cantilever was tracked by analyzing the signals acquired by the 32 sensor array electronic readout system and the relevant data algorithm. The obtained results show a linear behavior of the photocurrent relating X and Y movement, with a non-linearity of about 3%, a spatial resolution of less than 2 μm along the lateral dimension of the sensor as well as of less than 3 μm along the perpendicular dimension of the sensor, when detecting just the micro-cantilever, and a spatial resolution of less than 1 μm when detecting the holding structure. PMID:22163648

In vivo carbon-edited detection with proton echo-planar spectroscopic imaging (ICED PEPSI): [3,4-(13)CH(2)]glutamate/glutamine tomography in rat brain.

PubMed

Hyder, F; Renken, R; Rothman, D L

1999-12-01

A method for in vivo carbon-edited detection with proton echo-planar spectroscopic imaging (ICED PEPSI) is described. This method is composed of an echo-planar based acquisition implemented with (13)C-(1)H J editing spectroscopy and is intended for high temporal and spatial resolution in vivo spectroscopic imaging of (13)C turnover, from D-[1,6-(13)C]glucose to glutamate and glutamine, in the brain. At a static magnetic field strength of 7 T, both in vitro and in vivo chemical shift imaging data are presented with a spatial resolution of 8 microL (i.e., 1.25 x 1.25 x 5.00 mm(3)) and a maximum spectral bandwidth of 5.2 ppm in (1)H. Chemical shift imaging data acquired every 11 minutes allowed detection of regional [4-(13)CH(2)]glutamate turnover in rat brain. The [4-(13)CH(2)]glutamate turnover curves, which can be converted to tricarboxylic acid cycle fluxes, showed that the tricarboxylic acid cycle flux (V(TCA)) in pure gray and white matter can range from 1.2 +/- 0.2 to 0.5 +/- 0.1 micromol/g/min, respectively, for morphine-anesthetized rats. The mean cortical V(TCA) from 32 voxels of 1.0 +/- 0.3 micromol/g/min (N = 3) is in excellent agreement with previous localized measurements that have demonstrated that V(TCA) can range from 0.9-1.1 micromol/g/min under identical anesthetized conditions. Magn Reson Med 42:997-1003, 1999. Copyright 1999 Wiley-Liss, Inc.

Path from schizophrenia genomics to biology: gene regulation and perturbation in neurons derived from induced pluripotent stem cells and genome editing.

PubMed

Duan, Jubao

2015-02-01

Schizophrenia (SZ) is a devastating mental disorder afflicting 1% of the population. Recent genome-wide association studies (GWASs) of SZ have identified >100 risk loci. However, the causal variants/genes and the causal mechanisms remain largely unknown, which hinders the translation of GWAS findings into disease biology and drug targets. Most risk variants are noncoding, thus likely regulate gene expression. A major mechanism of transcriptional regulation is chromatin remodeling, and open chromatin is a versatile predictor of regulatory sequences. MicroRNA-mediated post-transcriptional regulation plays an important role in SZ pathogenesis. Neurons differentiated from patient-specific induced pluripotent stem cells (iPSCs) provide an experimental model to characterize the genetic perturbation of regulatory variants that are often specific to cell type and/or developmental stage. The emerging genome-editing technology enables the creation of isogenic iPSCs and neurons to efficiently characterize the effects of SZ-associated regulatory variants on SZ-relevant molecular and cellular phenotypes involving dopaminergic, glutamatergic, and GABAergic neurotransmissions. SZ GWAS findings equipped with the emerging functional genomics approaches provide an unprecedented opportunity for understanding new disease biology and identifying novel drug targets.

Highly Tunable Complementary Micro/Submicro-Nanopatterned Surfaces Combining Block Copolymer Self-Assembly and Colloidal Lithography.

PubMed

Chang, Tongxin; Du, Binyang; Huang, Haiying; He, Tianbai

2016-08-31

Two kinds of large-area ordered and highly tunable micro/submicro-nanopatterned surfaces in a complementary manner were successfully fabricated by elaborately combining block copolymer self-assembly and colloidal lithography. Employing a monolayer of polystyrene (PS) colloidal spheres assembled on top as etching mask, polystyrene-block-poly(2-vinylpyridine) (PS-b-P2VP) or polystyrene-block-poly(4-vinylpyridine) (PS-b-P4VP) micelle films were patterned into micro/submicro patches by plasma etching, which could be further transferred into micropatterned metal nanoarrays by subsequent metal precursor loading and a second plasma etching. On the other hand, micro/submicro-nanopatterns in a complementary manner were generated via preloading a metal precursor in initial micelle films before the assembly of PS colloidal spheres on top. Both kinds of micro/submicro-nanopatterns showed good fidelity at the micro/submicroscale and nanoscale; meanwhile, they could be flexibly tuned by the sample and processing parameters. Significantly, when the PS colloidal sphere size was reduced to 250 nm, a high-resolution submicro-nanostructured surface with 3-5 metal nanoparticles in each patch or a single-nanoparticle interconnected honeycomb network was achieved. Moreover, by applying gold (Au) nanoparticles as anchoring points, micronanopatterned Au arrays can serve as a flexible template to pattern bovine serum albumin (BSA) molecules. This facile and cost-effective approach may provide a novel platform for fabrication of micropatterned nanoarrays with high tunability and controllability, which are promising in the applications of biological and microelectronic fields.

Coalescence of liquid droplets in micro fluidic device

NASA Astrophysics Data System (ADS)

Wu, Mingming; Cubaud, Thomas; Ho, Chih-Ming; Chiou, Peiyu; Wu, Ming C.

2003-11-01

We study experimentally the initial dynamic process when two droplets (diameter range 100μm -1000μm) merge in micro fluidic device. It is known that passive mixing in micro fluidic device relies mostly on a time consuming process - diffusion. In digital fluidic platform,(S.K. Cho, H. Moon, and C.J. Kim, J. of Microelectromechanical Systems, Vol 12, No 1, 70(2003).) we find that the surface-tension-driven flow at the initial stage of the merging can be used to enhance mixing. In our experiments, the droplets are manipulated by two different methods, and results are compared. In one method, the droplet is manipulated by pressure driven flow in micro channels, and in the other, the droplet is moved using an optical electro-wetting device. The droplet is seeded with 4 μm diameter latex particles for visualizing the mixing process. The outlines of the droplets as well as the flow patterns marked by the latex particles inside the droplets are recorded using a high speed imaging system. This work is supported by the National Science Foundation (CTS-0121340), Institute for CMISE (a NASA URETI), DARPA MPG program, and DARPA Optoelectronics Center Program (CHIPS).

A Reward-Based Behavioral Platform to Measure Neural Activity during Head-Fixed Behavior

PubMed Central

Micallef, Andrew H.; Takahashi, Naoya; Larkum, Matthew E.; Palmer, Lucy M.

2017-01-01

Understanding the neural computations that contribute to behavior requires recording from neurons while an animal is behaving. This is not an easy task as most subcellular recording techniques require absolute head stability. The Go/No-Go sensory task is a powerful decision-driven task that enables an animal to report a binary decision during head-fixation. Here we discuss how to set up an Ardunio and Python based platform system to control a Go/No-Go sensory behavior paradigm. Using an Arduino micro-controller and Python-based custom written program, a reward can be delivered to the animal depending on the decision reported. We discuss the various components required to build the behavioral apparatus that can control and report such a sensory stimulus paradigm. This system enables the end user to control the behavioral testing in real-time and therefore it provides a strong custom-made platform for probing the neural basis of behavior. PMID:28620282

A Platform to Monitor Tumor Cellular and Vascular Response to Radiation Therapy by Optical Coherence Tomography and Fluorescence Microscopy in vivo

NASA Astrophysics Data System (ADS)

Leung, Michael Ka Kit

Radiotherapy plays a significant role in cancer treatment, and is thought to be curative by mainly killing tumor cells through damage to their genetic material. However, recent findings indicate that the tumor's vascular blood supply is also a major determinant of radiation response. The goals of this thesis are to: (1) develop an experimental platform for small animals to deliver ionizing radiation and perform high-resolution optical imaging to treatment targets, and (2) use this toolkit to longitudinally monitor the response of tumors and the associated vasculature. The thesis has achieved: (1) customization of a novel micro-irradiator for mice, (2) technical development of an improved optical coherence tomography imaging system, (3) comprehensive experimental protocol and imaging optimization for optical microscopy in a specialized animal model, and (4) completion of a feasibility study to demonstrate the capabilities of the experimental platform in monitoring the response of tumor and vasculature to radiotherapy.

[Construction of 2-dimensional tumor microvascular architecture phenotype in non-small cell lung cancer].

PubMed

Liu, Jin-kang; Wang, Xiao-yi; Xiong, Zeng; Zhou, Hui; Zhou, Jian-hua; Fu, Chun-yan; Li, Bo

2008-08-01

To construct a technological platform of 2-dimensional tumor microvascular architecture phenotype (2D-TAMP) expression. Thirty samples of non-small cell lung cancer (NSCLC) were collected after surgery. The corresponding sections of tumor tissue specimens to the slice of CT perfusion imaging were selected. Immunohistochemical staining,Gomori methenamine silver stain, and electron microscope observation were performed to build a technological platform of 2D-TMAP expression by detecting the morphology and the integrity of basement membrane of microvasculature, microvascular density, various microvascular subtype, the degree of the maturity and lumenization of microvasculature, and the characteristics of immunogenetics of microvasculature. The technological platform of 2D-TMAP expression was constructed successfully. There was heterogeneity in 2D-TMAP expression of non-small cell lung cancer. The microvascular of NSCLC had certain characteristics. 2D-TMAP is a key technology that can be used to observe the overall state of micro-environment in tumor growth.

An image processing and analysis tool for identifying and analysing complex plant root systems in 3D soil using non-destructive analysis: Root1.

PubMed

Flavel, Richard J; Guppy, Chris N; Rabbi, Sheikh M R; Young, Iain M

2017-01-01

The objective of this study was to develop a flexible and free image processing and analysis solution, based on the Public Domain ImageJ platform, for the segmentation and analysis of complex biological plant root systems in soil from x-ray tomography 3D images. Contrasting root architectures from wheat, barley and chickpea root systems were grown in soil and scanned using a high resolution micro-tomography system. A macro (Root1) was developed that reliably identified with good to high accuracy complex root systems (10% overestimation for chickpea, 1% underestimation for wheat, 8% underestimation for barley) and provided analysis of root length and angle. In-built flexibility allowed the user interaction to (a) amend any aspect of the macro to account for specific user preferences, and (b) take account of computational limitations of the platform. The platform is free, flexible and accurate in analysing root system metrics.

Metre-scale cyclicity in Middle Eocene platform carbonates in northern Egypt: Implications for facies development and sequence stratigraphy

NASA Astrophysics Data System (ADS)

Tawfik, Mohamed; El-Sorogy, Abdelbaset; Moussa, Mahmoud

2016-07-01

The shallow-water carbonates of the Middle Eocene in northern Egypt represent a Tethyan reef-rimmed carbonate platform with bedded inner-platform facies. Based on extensive micro- and biofacies documentation, five lithofacies associations were defined and their respective depositional environments were interpreted. Investigated sections were subdivided into three third-order sequences, named S1, S2 and S3. Sequence S1 is interpreted to correspond to the Lutetian, S2 corresponds to the Late Lutetian and Early Bartonian, and S3 represents the Late Bartonian. Each of the three sequences was further subdivided into fourth-order cycle sets and fifth-order cycles. The complete hierarchy of cycles can be correlated along 190 km across the study area, and highlighting a general "layer-cake" stratigraphic architecture. The documentation of the studied outcrops may contribute to the better regional understanding of the Middle Eocene formations in northern Egypt and to Tethyan pericratonic carbonate models in general.

CRISPR Editing in Biological and Biomedical Investigation.

PubMed

Ju, Xing-Da; Xu, Jing; Sun, Zhong Sheng

2018-01-01

The CRISPR (clustered regularly interspaced short palindromic repeat)-Cas (CRISPR-associated protein) system, a prokaryotic RNA-based adaptive immune system against viral infection, is emerging as a powerful genome editing tool in broad research areas. To further improve and expand its functionality, various CRISPR delivery strategies have been tested and optimized, and key CRISPR system components such as Cas protein have been engineered with different purposes. Benefiting from more in-depth understanding and further development of CRISPR, versatile CRISPR-based platforms for genome editing have been rapidly developed to advance investigations in biology and biomedicine. In biological research area, CRISPR has been widely adopted in both fundamental and applied research fields, such as genomic and epigenomic modification, genome-wide screening, cell and animal research, agriculture transforming, livestock breeding, food manufacture, industrial biotechnology, and gene drives in disease agents control. In biomedical research area, CRISPR has also shown its extensive applicability in the establishment of animal models for genetic disorders, generation of tissue donors, implementation of antimicrobial and antiviral studies, identification and assessment of new drugs, and even treatment for clinical diseases. However, there are still several problems to consider, and the biggest concerns are the off-target effects and ethical issues of this technology. In this prospect article, after highlighting recent development of CRISPR systems, we outline different applications and current limitations of CRISPR in biological and biomedical investigation. Finally, we provide a perspective on future development and potential risks of this multifunctional technology. J. Cell. Biochem. 119: 52-61, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Polar Motions Measurement Study.

DTIC Science & Technology

1984-09-01

tiltmeters and a single GG1389 RLG. The sensors and their electronics are fixed to a platform that is mounted on a computer-driven ULIRADEX precision...gyroscopes ; and accelerometers and/or tiltmeters . It is marginally feasible, using laser gyros equivalent to the Honeywell GG1389, either...using one CLIC- enhanced GG1389 ring laser gyro, two state-of-the-art tiltmeters , an Ultradex indexer, and a Hewlett-Packard micro-computer..--.~ ’k

The Instrumented Frisbee(Registered TradeMark) as a Prototype for Planetary Entry Probes

NASA Technical Reports Server (NTRS)

Lorenz, Ralph D.

2005-01-01

A Frisbee has been equipped with sensors, batteries and micro-controllers for data acquisition to record its translational accelerations and attitude motion. The experiments explore the capabilities and limitations of sensors on a rapidly-rotating platform moving in air, and illustrate several of the complex gyrodynamic aspects of frisbee flight. The experiments constitute an instructive exercise in aerospace vehicle systems integration and in attitude reconstruction.

[A novel serial port auto trigger system for MOSFET dose acquisition].

PubMed

Luo, Guangwen; Qi, Zhenyu

2013-01-01

To synchronize the radiation of microSelectron-HDR (Nucletron afterloading machine) and measurement of MOSFET dose system, a trigger system based on interface circuit was designed and corresponding monitor and trigger program were developed on Qt platform. This interface and control system was tested and showed stable operate and reliable work. This adopted serial port detect technique may expand to trigger application of other medical devices.

Electrodeposition and Screening of Photoelectrochemical Activity in Conjugated Polymers Using Scanning Electrochemical Cell Microscopy.

PubMed

Aaronson, Barak D B; Garoz-Ruiz, Jesus; Byers, Joshua C; Colina, Alvaro; Unwin, Patrick R

2015-11-24

A number of renewable energy systems require an understanding and correlation of material properties and photoelectrochemical activity on the micro to nanoscale. Among these, conducting polymer electrodes continue to be important materials. In this contribution, an ultrasensitive scanning electrochemical cell microscopy (SECCM) platform is used to electrodeposit microscale thin films of poly(3-hexylthiophene) (P3HT) on an optically transparent gold electrode and to correlate the morphology (film thickness and structural order) with photoactivity. The electrochemical growth of P3HT begins with a thin ordered film up to 10 nm thick, after which a second more disordered film is deposited, as revealed by micro-Raman spectroscopy. A decrease in photoactivity for the thicker films, measured in situ immediately following film deposition, is attributed to an increase in bulk film disorder that limits charge transport. Higher resolution ex situ SECCM phototransient measurements, using a smaller diameter probe, show local variations in photoactivity within a given deposit. Even after aging, thinner, more ordered regions within a deposit exhibit sustained enhanced photocurrent densities compared to areas where the film is thicker and more disordered. The platform opens up new possibilities for high-throughput combinatorial correlation studies, by allowing materials fabrication and high spatial resolution probing of processes in photoelectrochemical materials.

Development of a standardized differential-reflective bioassay for microbial pathogens

NASA Astrophysics Data System (ADS)

Wilhelm, Jay; Auld, J. R. X.; Smith, James E.

2008-04-01

This research examines standardizing a method for the rapid/semi-automated identification of microbial contaminates. It introduces a method suited to test for food/water contamination, serology, urinalysis and saliva testing for any >1 micron sized molecule that can be effectively bound to an identifying marker with exclusivity. This optical biosensor method seeks to integrate the semi-manual distribution of a collected sample onto a "transparent" substrate array of binding sites that will then be applied to a standard optical data disk and run for analysis. The detection of most microbe species is possible in this platform because the relative scale is greater than the resolution of the standard-scale digital information on a standard CD or DVD. This paper explains the critical first stage in the advance of this detection concept. This work has concentrated on developing the necessary software component needed to perform highly sensitive small-scale recognition using the standard optical disk as a detection platform. Physical testing has made significant progress in demonstrating the ability to utilize a standard optical drive for the purposes of micro-scale detection through the exploitation of CIRC error correction. Testing has also shown a definable trend in the optimum scale and geometry of micro-arrayed attachment sites for the technology's concept to reach achievement.

Engineering an in vitro organotypic model for studying cardiac hypertrophy.

PubMed

Jain, Aditi; Hasan, Jafar; Desingu, Perumal Arumugam; Sundaresan, Nagalingam R; Chatterjee, Kaushik

2018-05-01

Neonatal cardiomyocytes cultured on flat surfaces are commonly used as a model to study cardiac failure of diverse origin. A major drawback of such a system is that the cardiomyocytes do not exhibit alignment, organization and calcium transients, similar to the native heart. Therefore, there is a need to develop in vitro platforms that recapitulate the cellular microenvironment of the murine heart as organotypic models to study cardiovascular diseases. In this study, we report an engineered platform that mimics cardiac cell organization and function of the heart. For this purpose, microscale ridges were fabricated on silicon using ultraviolet lithography and reactive ion etching techniques. Physical characterization of the microstructures was done using scanning electron microscopy and atomic force microscopy. Cardiomyocytes grown on these micro-ridges showed global parallel alignment and elliptical nuclear morphology as observed in the heart. Interestingly, calcium currents traversed the engineered cardiomyocytes in a coordinated and directional manner. Moreover, the cardiomyocytes on the engineered substrates were found to be responsive to hypertrophic stimuli, as observed by the expression of a fetal gene, atrial natriuretic peptide and increase in calcium transients upon agonist treatment. Taken together, our work demonstrates that micro-ridges can be used to obtain cardiomyocyte response in vitro, which closely resembles mammalian heart. Copyright © 2018 Elsevier B.V. All rights reserved.

Human COL7A1-corrected induced pluripotent stem cells for the treatment of recessive dystrophic epidermolysis bullosa

PubMed Central

Sebastiano, Vittorio; Zhen, Hanson Hui; Haddad, Bahareh; Bashkirova, Elizaveta; Melo, Sandra P.; Wang, Pei; Leung, Thomas L.; Siprashvili, Zurab; Tichy, Andrea; Li, Jiang; Ameen, Mohammed; Hawkins, John; Lee, Susie; Li, Lingjie; Schwertschkow, Aaron; Bauer, Gerhard; Lisowski, Leszek; Kay, Mark A.; Kim, Seung K.; Lane, Alfred T.; Wernig, Marius; Oro, Anthony E.

2015-01-01

Patients with recessive dystrophic epidermolysis bullosa (RDEB) lack functional type VII collagen owing to mutations in the gene COL7A1 and suffer severe blistering and chronic wounds that ultimately lead to infection and development of lethal squamous cell carcinoma. The discovery of induced pluripotent stem cells (iPSCs) and the ability to edit the genome bring the possibility to provide definitive genetic therapy through corrected autologous tissues. We generated patient-derived COL7A1-corrected epithelial keratinocyte sheets for autologous grafting. We demonstrate the utility of sequential reprogramming and adenovirus-associated viral genome editing to generate corrected iPSC banks. iPSC-derived keratinocytes were produced with minimal heterogeneity, and these cells secreted wild-type type VII collagen, resulting in stratified epidermis in vitro in organotypic cultures and in vivo in mice. Sequencing of corrected cell lines before tissue formation revealed heterogeneity of cancer-predisposing mutations, allowing us to select COL7A1-corrected banks with minimal mutational burden for downstream epidermis production. Our results provide a clinical platform to use iPSCs in the treatment of debilitating genodermatoses, such as RDEB. PMID:25429056

Artificial Virus Delivers CRISPR-Cas9 System for Genome Editing of Cells in Mice.

PubMed

Li, Ling; Song, Linjiang; Liu, Xiaowei; Yang, Xi; Li, Xia; He, Tao; Wang, Ning; Yang, Suleixin; Yu, Chuan; Yin, Tao; Wen, Yanzhu; He, Zhiyao; Wei, Xiawei; Su, Weijun; Wu, Qinjie; Yao, Shaohua; Gong, Changyang; Wei, Yuquan

2017-01-24

CRISPR-Cas9 has emerged as a versatile genome-editing platform. However, due to the large size of the commonly used CRISPR-Cas9 system, its effective delivery has been a challenge and limits its utility for basic research and therapeutic applications. Herein, a multifunctional nucleus-targeting "core-shell" artificial virus (RRPHC) was constructed for the delivery of CRISPR-Cas9 system. The artificial virus could efficiently load with the CRISPR-Cas9 system, accelerate the endosomal escape, and promote the penetration into the nucleus without additional nuclear-localization signal, thus enabling targeted gene disruption. Notably, the artificial virus is more efficient than SuperFect, Lipofectamine 2000, and Lipofectamine 3000. When loaded with a CRISPR-Cas9 plasmid, it induced higher targeted gene disruption efficacy than that of Lipofectamine 3000. Furthermore, the artificial virus effectively targets the ovarian cancer via dual-receptor-mediated endocytosis and had minimum side effects. When loaded with the Cas9-hMTH1 system targeting MTH1 gene, RRPHC showed effective disruption of MTH1 in vivo. This strategy could be adapted for delivering CRISPR-Cas9 plasmid or other functional nucleic acids in vivo.

Advancing chimeric antigen receptor T cell therapy with CRISPR/Cas9.

PubMed

Ren, Jiangtao; Zhao, Yangbing

2017-09-01

The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (CRISPR/Cas9) system, an RNA-guided DNA targeting technology, is triggering a revolution in the field of biology. CRISPR/Cas9 has demonstrated great potential for genetic manipulation. In this review, we discuss the current development of CRISPR/Cas9 technologies for therapeutic applications, especially chimeric antigen receptor (CAR) T cell-based adoptive immunotherapy. Different methods used to facilitate efficient CRISPR delivery and gene editing in T cells are compared. The potential of genetic manipulation using CRISPR/Cas9 system to generate universal CAR T cells and potent T cells that are resistant to exhaustion and inhibition is explored. We also address the safety concerns associated with the use of CRISPR/Cas9 gene editing and provide potential solutions and future directions of CRISPR application in the field of CAR T cell immunotherapy. As an integration-free gene insertion method, CRISPR/Cas9 holds great promise as an efficient gene knock-in platform. Given the tremendous progress that has been made in the past few years, we believe that the CRISPR/Cas9 technology holds immense promise for advancing immunotherapy.

The use of CRISPR/Cas associated technologies for cell transplant applications.

PubMed

Cowan, Peter J

2016-10-01

In this review, I will summarize recent developments in the use of the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) genome editing system for cell transplant applications, ranging from transplantation of corrected autologous patient stem cells to treat inherited diseases, to the tailoring of donor pigs for cell xenotransplantation. Rational engineering of the Cas9 nuclease to improve its specificity will also be discussed. Over the past year, CRISPR/Cas9 has been used in preclinical studies to correct mutations in a rapidly increasing spectrum of diseases including hematological, neuromuscular, and respiratory disorders. The growing popularity of CRISPR/Cas9 over earlier genome editing platforms is partly due to its ease of use and flexibility, which is evident from the success of complex manipulations such as specific deletion of up to 725 kb in patient-derived stem cells, and simultaneous disruption of up to 62 endogenous retrovirus loci in pig cells. In addition, high-fidelity variants of Cas9 with greatly increased specificity are now available. CRISPR/Cas9 is a fast-evolving technology that is likely to have a significant impact on autologous, allogeneic, and xenogeneic cell transplantation.

Epitranscriptomics: A New Regulatory Mechanism of Brain Development and Function

PubMed Central

Noack, Florian; Calegari, Federico

2018-01-01

Epigenetic modifications of DNA and chromatin are long known to control stem cell differentiation and organ function but the role of similar modifications at the level or regulatory RNAs is just beginning to emerge. Over 160 RNA modifications have been identified but their abundance, distribution and functional significance are not known. The few available maps of RNA modifications indicated their dynamic regulation during somatic stem cell differentiation, brain development and function in adulthood suggesting a hitherto unsuspected layer of regulation both at the level of RNA metabolism and post-transcriptional control of gene expression. The advent of programmable, RNA-specific CRISPR-Cas editing platforms together with the identification of RNA modifying enzymes now offers the opportunity to investigate the functional role of these elusive epitranscriptome changes. Here, we discuss recent insights in studying the most abundant modifications in functional mRNAs and lncRNAs, N6-methyladenosine and 5-(hydroxy-)methylcytosine, and their role in regulating somatic stem cell differentiation with particular attention to neural stem cells during mammalian corticogenesis. An outlook on novel CRISPR-Cas based systems that allow stem cell reprogramming by epitranscriptome-editing will also be discussed. PMID:29515357

Inhibition of HSV-1 Replication by Gene Editing Strategy

PubMed Central

Roehm, Pamela C.; Shekarabi, Masoud; Wollebo, Hassen S.; Bellizzi, Anna; He, Lifan; Salkind, Julian; Khalili, Kamel

2016-01-01

HSV-1 induced illness affects greater than 85% of adults worldwide with no permanent curative therapy. We used RNA-guided CRISPR/Cas9 gene editing to specifically target for deletion of DNA sequences of the HSV-1 genome that span the region directing expression of ICP0, a key viral protein that stimulates HSV-1 gene expression and replication. We found that CRISPR/Cas9 introduced InDel mutations into exon 2 of the ICP0 gene profoundly reduced HSV-1 infectivity in permissive human cell culture models and protected permissive cells against HSV-1 infection. CRISPR/Cas9 mediated targeting ICP0 prevented HSV-1-induced disintegration of promonocytic leukemia (PML) nuclear bodies, an intracellular event critical to productive HSV-1 infection that is initiated by interaction of the ICP0 N-terminus with PML. Combined treatment of cells with CRISPR targeting ICP0 plus the immediate early viral proteins, ICP4 or ICP27, completely abrogated HSV-1 infection. We conclude that RNA-guided CRISPR/Cas9 can be used to develop a novel, specific and efficacious therapeutic and prophylactic platform for targeted viral genomic ablation to treat HSV-1 diseases. PMID:27064617

CRISPR/Cas9 genome editing in human pluripotent stem cells: Harnessing human genetics in a dish.

PubMed

González, Federico

2016-07-01

Because of their extraordinary differentiation potential, human pluripotent stem cells (hPSCs) can differentiate into virtually any cell type of the human body, providing a powerful platform not only for generating relevant cell types useful for cell replacement therapies, but also for modeling human development and disease. Expanding this potential, structures resembling human organs, termed organoids, have been recently obtained from hPSCs through tissue engineering. Organoids exhibit multiple cell types self-organizing into structures recapitulating in part the physiology and the cellular interactions observed in the organ in vivo, offering unprecedented opportunities for human disease modeling. To fulfill this promise, tissue engineering in hPSCs needs to be supported by robust and scalable genome editing technologies. With the advent of the CRISPR/Cas9 technology, manipulating the genome of hPSCs has now become an easy task, allowing modifying their genome with superior precision, speed, and throughput. Here we review current and potential applications of the CRISPR/Cas9 technology in hPSCs and how they contribute to establish hPSCs as a model of choice for studying human genetics. Developmental Dynamics 245:788-806, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

An Overview of CRISPR-Based Tools and Their Improvements: New Opportunities in Understanding Plant–Pathogen Interactions for Better Crop Protection

PubMed Central

Barakate, Abdellah; Stephens, Jennifer

2016-01-01

Modern omics platforms have made the determination of susceptible/resistance genes feasible in any species generating huge numbers of potential targets for crop protection. However, the efforts to validate these targets have been hampered by the lack of a fast, precise, and efficient gene targeting system in plants. Now, the repurposing of clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system has solved this problem. CRISPR/Cas9 is the latest synthetic endonuclease that has revolutionized basic research by allowing facile genome editing in prokaryotes and eukaryotes. Gene knockout is now feasible at an unprecedented efficiency with the possibility of multiplexing several targets and even genome-wide mutagenesis screening. In a short time, this powerful tool has been engineered for an array of applications beyond gene editing. Here, we briefly describe the CRISPR/Cas9 system, its recent improvements and applications in gene manipulation and single DNA/RNA molecule analysis. We summarize a few recent tests targeting plant pathogens and discuss further potential applications in pest control and plant–pathogen interactions that will inform plant breeding for crop protection. PMID:27313592

Personalized therapeutic strategies for patients with retinitis pigmentosa.

PubMed

Zheng, Andrew; Li, Yao; Tsang, Stephen H

2015-03-01

Retinitis pigmentosa (RP) encompasses many different hereditary retinal degenerations that are caused by a vast array of different gene mutations and have highly variable disease presentations and severities. This heterogeneity poses a significant therapeutic challenge, although an answer may eventually be found through two recent innovations: induced pluripotent stem cells (iPSCs) and clustered regularly interspaced short palindromic repeats (CRISPR)/Cas genome editing. This review discusses the wide-ranging applications of iPSCs and CRISPR-including disease modelling, diagnostics and therapeutics - with an ultimate view towards understanding how these two technologies can come together to address disease heterogeneity and orphan genes in a novel personalized medicine platform. An extensive literature search was conducted in PubMed and Google Scholar, with a particular focus on high-impact research published within the last 1 - 2 years and centered broadly on the subjects of retinal gene therapy, iPSC-derived outer retina cells, stem cell transplantation and CRISPR/Cas gene editing. For the retinal pigment epithelium, autologous transplantation of gene-corrected grafts derived from iPSCs may well be technically feasible in the near future. Photoreceptor transplantation faces more significant unresolved technical challenges but remains an achievable, if more distant, goal given the rapid pace of advancements in the field.

Strategies for cloning and manipulating natural and synthetic chromosomes.

PubMed

Karas, Bogumil J; Suzuki, Yo; Weyman, Philip D

2015-02-01

Advances in synthetic biology methods to assemble and edit DNA are enabling genome engineering at a previously impracticable scale and scope. The synthesis of the Mycoplasma mycoides genome followed by its transplantation to convert a related cell into M. mycoides has transformed strain engineering. This approach exemplifies the combination of newly emerging chromosome-scale genome editing strategies that can be defined in three main steps: (1) chromosome acquisition into a microbial engineering platform, (2) alteration and improvement of the acquired chromosome, and (3) installation of the modified chromosome into the original or alternative organism. In this review, we outline recent progress in methods for acquiring chromosomes and chromosome-scale DNA molecules in the workhorse organisms Bacillus subtilis, Escherichia coli, and Saccharomyces cerevisiae. We present overviews of important genetic strategies and tools for each of the three organisms, point out their respective strengths and weaknesses, and highlight how the host systems can be used in combination to facilitate chromosome assembly or engineering. Finally, we highlight efforts for the installation of the cloned/altered chromosomes or fragments into the target organism and present remaining challenges in expanding this powerful experimental approach to a wider range of target organisms.

Repurposing CRISPR/Cas9 for in situ functional assays.

PubMed

Malina, Abba; Mills, John R; Cencic, Regina; Yan, Yifei; Fraser, James; Schippers, Laura M; Paquet, Marilène; Dostie, Josée; Pelletier, Jerry

2013-12-01

RNAi combined with next-generation sequencing has proven to be a powerful and cost-effective genetic screening platform in mammalian cells. Still, this technology has its limitations and is incompatible with in situ mutagenesis screens on a genome-wide scale. Using p53 as a proof-of-principle target, we readapted the CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 (CRISPR associated 9) genome-editing system to demonstrate the feasibility of this methodology for targeted gene disruption positive selection assays. By using novel "all-in-one" lentiviral and retroviral delivery vectors heterologously expressing both a codon-optimized Cas9 and its synthetic guide RNA (sgRNA), we show robust selection for the CRISPR-modified Trp53 locus following drug treatment. Furthermore, by linking Cas9 expression to GFP fluorescence, we use an "all-in-one" system to track disrupted Trp53 in chemoresistant lymphomas in the Eμ-myc mouse model. Deep sequencing analysis of the tumor-derived endogenous Cas9-modified Trp53 locus revealed a wide spectrum of mutants that were enriched with seemingly limited off-target effects. Taken together, these results establish Cas9 genome editing as a powerful and practical approach for positive in situ genetic screens.

Repurposing CRISPR/Cas9 for in situ functional assays

PubMed Central

Malina, Abba; Mills, John R.; Cencic, Regina; Yan, Yifei; Fraser, James; Schippers, Laura M.; Paquet, Marilène; Dostie, Josée; Pelletier, Jerry

2013-01-01

RNAi combined with next-generation sequencing has proven to be a powerful and cost-effective genetic screening platform in mammalian cells. Still, this technology has its limitations and is incompatible with in situ mutagenesis screens on a genome-wide scale. Using p53 as a proof-of-principle target, we readapted the CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 (CRISPR associated 9) genome-editing system to demonstrate the feasibility of this methodology for targeted gene disruption positive selection assays. By using novel “all-in-one” lentiviral and retroviral delivery vectors heterologously expressing both a codon-optimized Cas9 and its synthetic guide RNA (sgRNA), we show robust selection for the CRISPR-modified Trp53 locus following drug treatment. Furthermore, by linking Cas9 expression to GFP fluorescence, we use an “all-in-one” system to track disrupted Trp53 in chemoresistant lymphomas in the Eμ-myc mouse model. Deep sequencing analysis of the tumor-derived endogenous Cas9-modified Trp53 locus revealed a wide spectrum of mutants that were enriched with seemingly limited off-target effects. Taken together, these results establish Cas9 genome editing as a powerful and practical approach for positive in situ genetic screens. PMID:24298059

Accelerator/Experiment Operations - FY 2016

DOE Office of Scientific and Technical Information (OSTI.GOV)

Blake, A.; Convery, M.; Geer, S.

2016-10-01

This Technical Memorandum summarizes the Fermilab accelerator and experiment operations for FY 2016. It is one of a series of annual publications intended to gather information in one place. In this case, the information concerns the FY 2016 NOvA, MINOS+ and MINERvA experiments using the Main Injector Neutrino Beam (NuMI), the MicroBooNE experiment and the activities in the SciBooNE Hall using the Booster Neutrino Beam (BNB), and the SeaQuest experiment, LArIAT experiment and Meson Test Beam activities in the 120 GeV external switchyard beam (SY120). Each section was prepared by the relevant authors, and was then edited for inclusion inmore » this summary.« less

An impedimetric micro-immunosensing assay to detect Alzheimer's disease biomarker: Aβ40.

PubMed

Zakaria, Norazreen; Ramli, Muhammad Zaki; Ramasamy, Kalavathy; Meng, Lim Siong; Yean, Chan Yean; Banga Singh, Kirnpal Kaur; Zain, Zainiharyati Mohd; Low, Kim-Fatt

2018-06-04

A miniaturized biosensing platform, based on monoclonal amyloid-beta antibodies (mAβ ab ) that were immobilized on a disc-shaped platinum/iridium (Pt/Ir) microelectrode surface coupled with an impedimetric signal transducer, was developed for the label-free and sensitive detection of amyloid-beta peptide fragment 1-40 (Aβ40); a reliable biomarker for early diagnosis of Alzheimer's disease (AD). A Pt/Ir microelectrode was electropolymerized with poly (ortho-phenylenediamine), a conducting free amine-containing aromatic polymer; followed by crosslinking with glutaraldehyde for subsequent coupling of mAβ ab on the microelectrode surface. This modification strategy efficiently improved the impedimetric detection performance of Aβ40 in terms of charge transfer resistance (∼400-fold difference) and normalized impedance magnitude percentage change (∼40% increase) compared with a passive adsorption-based immobilization method. The sensitivity of the micro-immunosensing assay was found to be 1056 kΩ/(pg/mL)/cm 2 and the limit of detection was found to be 4.81 pg/mL with a dynamic range of 1-10 4  pg/mL (R 2  = 0.9932). The overall precision of the assay, as measured by relative standard deviation, ranged from 0.84 to 5.15%, demonstrating its reliability and accuracy; while in respect to assay durability and stability, the immobilized mAβ ab were able to maintain 80% of their binding activity to Aβ40 after incubation for 48 h at ambient temperature (25 °C). To validate the practical applicability, the assay was tested using brain tissue lysates prepared from AD-induced rats. Results indicate that the proposed impedimetric micro-immunosensing platform is highly versatile and adaptable for the quantitative detection of other disease-related biomarkers. Copyright © 2018 Elsevier Inc. All rights reserved.

Vibration of mechanically-assembled 3D microstructures formed by compressive buckling

NASA Astrophysics Data System (ADS)

Wang, Heling; Ning, Xin; Li, Haibo; Luan, Haiwen; Xue, Yeguang; Yu, Xinge; Fan, Zhichao; Li, Luming; Rogers, John A.; Zhang, Yihui; Huang, Yonggang

2018-03-01

Micro-electromechanical systems (MEMS) that rely on structural vibrations have many important applications, ranging from oscillators and actuators, to energy harvesters and vehicles for measurement of mechanical properties. Conventional MEMS, however, mostly utilize two-dimensional (2D) vibrational modes, thereby imposing certain limitations that are not present in 3D designs (e.g., multi-directional energy harvesting). 3D vibrational micro-platforms assembled through the techniques of controlled compressive buckling are promising because of their complex 3D architectures and the ability to tune their vibrational behavior (e.g., natural frequencies and modes) by reversibly changing their dimensions by deforming their soft, elastomeric substrates. A clear understanding of such strain-dependent vibration behavior is essential for their practical applications. Here, we present a study on the linear and nonlinear vibration of such 3D mesostructures through analytical modeling, finite element analysis (FEA) and experiment. An analytical solution is obtained for the vibration mode and linear natural frequency of a buckled ribbon, indicating a mode change as the static deflection amplitude increases. The model also yields a scaling law for linear natural frequency that can be extended to general, complex 3D geometries, as validated by FEA and experiment. In the regime of nonlinear vibration, FEA suggests that an increase of amplitude of external loading represents an effective means to enhance the bandwidth. The results also uncover a reduced nonlinearity of vibration as the static deflection amplitude of the 3D structures increases. The developed analytical model can be used in the development of new 3D vibrational micro-platforms, for example, to enable simultaneous measurement of diverse mechanical properties (density, modulus, viscosity etc.) of thin films and biomaterials.

Mask-less deposition of Au-SnO2 nanocomposites on CMOS MEMS platform for ethanol detection.

PubMed

Santra, S; Sinha, A K; De Luca, A; Ali, S Z; Udrea, F; Guha, P K; Ray, S K; Gardner, J W

2016-03-29

Here we report on the mask-less deposition of Au-SnO2 nanocomposites with a silicon-on-insulator (SOI) complementary metal oxide semiconductor (CMOS) micro electro mechanical system (MEMS) platform through the use of dip pen nanolithography (DPN) to create a low-cost ethanol sensor. MEMS technology is used in order to achieve low power consumption, by the employment of a membrane structure formed using deep reactive ion etching technique. The device consists of an embedded tungsten micro-heater with gold interdigitated electrodes on top of the SOI membrane. The tungsten micro-heater is used to raise the membrane temperature up to its operating temperature and the electrodes are used to measure the resistance of the nanocomposite sensing layer. The CMOS MEMS devices have high electro-thermal efficiency, with 8.2 °C temperature increase per mW power of consumption. The sensing material (Au-SnO2 nanocomposite) was synthesised starting from SnO nanoplates, then Au nanoparticles were attached chemically to the surface of SnO nanoplates, finally the mixture was heated at 700 °C in an oven in air for 4 h. This composite material was sonicated for 2 h in terpineol to make a viscous homogeneous slurry and then 'written' directly across the electrode area using the DPN technique without any mask. The devices were characterised by exposure to ethanol vapour in humid air in the concentration range of 100-1000 ppm. The sensitivity varied from 1.2 to 0.27 ppm(-1) for 100-1000 ppm of ethanol at 10% relative humid air. Selectivity measurements showed that the sensors were selective towards ethanol when they were exposed to acetone and toluene.

Mask-less deposition of Au-SnO2 nanocomposites on CMOS MEMS platform for ethanol detection

NASA Astrophysics Data System (ADS)

Santra, S.; Sinha, A. K.; De Luca, A.; Ali, S. Z.; Udrea, F.; Guha, P. K.; Ray, S. K.; Gardner, J. W.

2016-03-01

Here we report on the mask-less deposition of Au-SnO2 nanocomposites with a silicon-on-insulator (SOI) complementary metal oxide semiconductor (CMOS) micro electro mechanical system (MEMS) platform through the use of dip pen nanolithography (DPN) to create a low-cost ethanol sensor. MEMS technology is used in order to achieve low power consumption, by the employment of a membrane structure formed using deep reactive ion etching technique. The device consists of an embedded tungsten micro-heater with gold interdigitated electrodes on top of the SOI membrane. The tungsten micro-heater is used to raise the membrane temperature up to its operating temperature and the electrodes are used to measure the resistance of the nanocomposite sensing layer. The CMOS MEMS devices have high electro-thermal efficiency, with 8.2 °C temperature increase per mW power of consumption. The sensing material (Au-SnO2 nanocomposite) was synthesised starting from SnO nanoplates, then Au nanoparticles were attached chemically to the surface of SnO nanoplates, finally the mixture was heated at 700 °C in an oven in air for 4 h. This composite material was sonicated for 2 h in terpineol to make a viscous homogeneous slurry and then ‘written’ directly across the electrode area using the DPN technique without any mask. The devices were characterised by exposure to ethanol vapour in humid air in the concentration range of 100-1000 ppm. The sensitivity varied from 1.2 to 0.27 ppm-1 for 100-1000 ppm of ethanol at 10% relative humid air. Selectivity measurements showed that the sensors were selective towards ethanol when they were exposed to acetone and toluene.

Historic Shipwrecks as Ecosystem Monitoring Platforms in the Wake of Deepwater Horizon? Results of the Gulf of Mexico Shipwreck Corrosion, Hydrocarbon Exposure, Microbiology, and Archaeology (GOM-SCHEMA) Project

NASA Astrophysics Data System (ADS)

Damour, M.; Hamdan, L. J.; Salerno, J. L.; McGown, C.; Blackwell, C. A.; Church, R.; Warren, D.; Horrell, C.; Jordan, B.; Moore, J.

2016-02-01

Historic shipwrecks and other archaeological sites are protected by a well-established body of historic preservation laws intended to preserve these sensitive, non-renewable resources. While the cultural, historical, and archaeological value of historic shipwrecks is unequivocal, their function and value as ecosystem monitoring platforms following a major environmental disaster is becoming apparent. Shipwrecks have been found in previous studies to serve as artificial reefs and hotspots of biodiversity, essentially providing the basis for an intact ecosystem. This is especially true in the deepwater marine environment where natural hard-bottom is sparse. Micro- and macro-infaunal diversity on shipwrecks and their sensitivity to environmental change demonstrates the suitability of these platforms for monitoring ecosystem impact and recovery. After the 2010 Deepwater Horizon oil spill, the Bureau of Ocean Energy Management (BOEM) and partners initiated a multidisciplinary study to examine spill effects on shipwrecks and their associated microbial communities. To assess these impacts and to perform comparative analyses, the team collected microbiological, geochemical, and archaeological data at wooden- and metal-hulled shipwrecks within and outside of the subsurface spill-impacted area. Microbial community biodiversity informs us of micro-scale changes while 3D laser and sonar data reveal macro-scale changes. A multidisciplinary approach informs us of the roles microorganisms have in shipwreck degradation and corrosion as well as their response to ecosystem impacts. Results of the study identified multiple lines of evidence that sites were impacted by exposure to spill-related contaminants. Future multidisciplinary studies at these sites, as part of a long-term monitoring program, should inform on ecosystem recovery.

Micro-nano-bio acoustic system for the detection of foodborne pathogens in real samples.

PubMed

Papadakis, George; Murasova, Pavla; Hamiot, Audrey; Tsougeni, Katerina; Kaprou, Georgia; Eck, Michael; Rabus, David; Bilkova, Zuzana; Dupuy, Bruno; Jobst, Gerhard; Tserepi, Angeliki; Gogolides, Evangelos; Gizeli, Electra

2018-07-15

The fast and efficient detection of foodborne pathogens is a societal priority, given the large number of food-poisoning outbreaks, and a scientific and technological challenge, given the need to detect as little as 1 viable cell in 25 gr of food. Here, we present the first approach that achieves the above goal, thanks to the use of a micro/nano-technology and the detection capability of acoustic wave sensors. Starting from 1 Salmonella cell in 25 ml of milk, we employ immuno-magnetic beads to capture cells after only 3 h of pre-enrichment and subsequently demonstrate efficient DNA amplification using the Loop Mediated Isothermal Amplification method (LAMP) and acoustic detection in an integrated platform, within an additional ½ h. The demonstrated 4 h sample-to-analysis time comes as a huge improvement to the current need of few days to obtain the same result. In addition, the work presents the first reported Lab-on-Chip platform that comprises an acoustic device as the sensing element, exhibiting impressive analytical features, namely, an acoustic limit of detection of 2 cells/μl or 3 aM of the DNA target and ability to detect in a label-free manner dsDNA amplicons in impure samples. The use of food samples together with the incorporation of the necessary pre-enrichment step and ability for multiple analysis with an internal control, make the proposed methodology highly relevant to real-world applications. Moreover, the work suggests that acoustic wave devices can be used as an attractive alternative to electrochemical sensors in integrated platforms for applications in food safety and the point-of-care diagnostics. Copyright © 2018. Published by Elsevier B.V.

Evaluation of a micro/nanofluidic chip platform for the high-throughput detection of bacteria and their antibiotic resistance genes in post-neurosurgical meningitis.

PubMed

Zhang, Guojun; Zheng, Guanghui; Zhang, Yan; Ma, Ruimin; Kang, Xixiong

2018-05-01

Post-neurosurgical meningitis (PNM) is one of the most severe hospital-acquired infections worldwide, and a large number of pathogens, especially those possessing multi-resistance genes, are related to these infections. Existing methods for detecting bacteria and measuring their response to antibiotics lack sensitivity and stability, and laboratory-based detection methods are inconvenient, requiring at least 24h to complete. Rapid identification of bacteria and the determination of their susceptibility to antibiotics are urgently needed, in order to combat the emergence of multi-resistant bacterial strains. This study evaluated a novel, fast, and easy-to-use micro/nanofluidic chip platform (MNCP), which overcomes the difficulties of diagnosing bacterial infections in neurosurgery. This platform can identify 10 genus or species targets and 13 genetic resistance determinants within 1h, and it is very simple to operate. A total of 108 bacterium-containing cerebrospinal fluid (CSF) cultures were tested using the MNCP for the identification of bacteria and determinants of genetic resistance. The results were compared to those obtained with conventional identification and antimicrobial susceptibility testing methods. For the 108 CSF cultures, the concordance rate between the MNCP and the conventional identification method was 94.44%; six species attained 100% consistency. For the production of carbapenemase- and extended-spectrum beta-lactamase (ESBL)-related antibiotic resistance genes, both the sensitivity and specificity of the MNCP tests were high (>90.0%) and could fully meet the requirements of clinical diagnosis. The MNCP is fast, accurate, and easy to use, and has great clinical potential in the treatment of post-neurosurgical meningitis. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Radiological and micro-computed tomography analysis of the bone at dental implants inserted 2, 3 and 4 mm apart in a minipig model with platform switching incorporated.

PubMed

Elian, Nicolas; Bloom, Mitchell; Dard, Michel; Cho, Sang-Choon; Trushkowsky, Richard D; Tarnow, Dennis

2014-02-01

The purpose of this study was to assess the effect of inter-implant distance on interproximal bone utilizing platform switching. Analysis of interproximal bone usually depends on traditional two-dimensional radiographic assessment. Although there has been increased reliability of current techniques, there has been an inability to track bone level changes over time and in three dimensions. Micro-CT has provided three-dimensional imaging that can be used in conjunction with traditional two-dimensional radiographic techniques. This study was performed on 24 female minipigs. Twelve animals received three implants with an inter-implant distance of 3 mm on one side of the mandible and another three implants on the contra-lateral side, where the implants were placed 2 mm apart creating a split mouth design. Twelve other animals received three implants with an inter-implant distance of 3 mm on one side of the mandible and another three implants on the contra-lateral side, where the implants were placed 4 mm apart creating a split mouth design too. The quantitative evaluation was performed comparatively on radiographs taken at t 0 (immediately after implantation) and at t 8 weeks (after termination). The samples were scanned by micro-computed tomography (μCT) to quantify the first bone to implant contact (fBIC) and bone volume/total volume (BV/TV). Mixed model regressions using the nonparametric Brunner-Langer method were used to determine the effect of inter-implant distance on the measured outcomes. The change in bone level was determined using radiography and its mean was 0.05 mm for an inter-implant distance of 3 and 0.00 mm for a 2 mm distance (P = 0.7268). The mean of this outcome was 0.18 mm for the 3 mm and for 4 mm inter-implant distance (P = 0.9500). Micro-computed tomography showed that the fBIC was always located above the reference, 0.27 and 0.20 mm for the comparison of 2-3 mm (P = 0.4622) and 0.49 and 0.34 mm for the inter-implant distance of 3 and 4 mm (P = 0.1699). BV/TV inside the defined parallelepipedic masks reached 82.38% for the 2 mm inter-implant distance and 85.00% for 3 mm, P = 0.8432. For the comparison of the 3-4 mm inter-implant distance, the means were 84.69% and 84.38%, respectively, P = 0.8401. Non-inferiority tests for the smaller inter-implant distances for both comparisons showed similar differences and similar tolerance ranges. The effect of a smaller interproximal distances between implants on bone level, fBIC and BV/TV assessed by two convergent investigation methods, radiology and μCT, was similar to that of larger distances. Implants can potentially be placed 2 mm apart instead of 3 mm and 3 mm apart instead of 4 mm when platform switching is utilized. Further research with a conventional platform is warranted. © 2012 John Wiley & Sons A/S.

An Indirect Method to Measure Abutment Screw Preload: A Pilot Study Based on Micro-CT Scanning.

PubMed

Rezende, Carlos Eduardo E; Griggs, Jason Alan; Duan, Yuanyuan; Mushashe, Amanda M; Nolasco, Gisele Maria Correr; Borges, Ana Flávia Sanches; Rubo, José Henrique

2015-01-01

This study aimed to measure the preload in different implant platform geometries based on micro-CT images. External hexagon (EH) implants and Morse Tapered (MT) implants (n=5) were used for the preload measurement. The abutment screws were scanned in micro-CT to obtain their virtual models, which were used to record their initial length. The abutments were screwed on the implant with a 20 Ncm torque and the set composed by implant, abutment screw and abutment were taken to the micro-CT scanner to obtain virtual slices of the specimens. These slices allowed the measurement of screw lengths after torque application and based on the screw elongation. Preload values were calculated using the Hooke's Law. The preloads of both groups were compared by independent t-test. Removal torque of each specimen was recorded. To evaluate the accuracy of the micro-CT technique, three rods with known lengths were scanned and the length of their virtual model was measured and compared with the original length. One rod was scanned four times to evaluate the measuring method variation. There was no difference between groups for preload (EH = 461.6 N and MT = 477.4 N), but the EH group showed higher removal torque values (13.8 ± 4.7 against 8.2 ± 3.6 N cm for MT group). The micro-CT technique showed a variability of 0.053% and repeatability showed an error of 0.23 to 0.28%. Within the limitations of this study, there was no difference between external hexagon and Morse taper for preload. The method using micro-CT may be considered for preload calculation.

Angle-Dependent Microresonator ESR Characterization of Locally Doped Gd3 + :Al2O3

NASA Astrophysics Data System (ADS)

Wisby, I. S.; de Graaf, S. E.; Gwilliam, R.; Adamyan, A.; Kubatkin, S. E.; Meeson, P. J.; Tzalenchuk, A. Ya.; Lindström, T.

2016-08-01

Interfacing rare-earth-doped crystals with superconducting circuit architectures provides an attractive platform for quantum memory and transducer devices. Here, we present the detailed characterization of such a hybrid system: a locally implanted rare-earth Gd3 + in Al2O3 spin system coupled to a superconducting microresonator. We investigate the properties of the implanted spin system through angular-dependent microresonator electron spin resonance (micro-ESR) spectroscopy. We find, despite the high-energy near-surface implantation, the resulting micro-ESR spectra to be in excellent agreement with the modeled Hamiltonian, supporting the integration of dopant ions into their relevant lattice sites while maintaining crystalline symmetries. Furthermore, we observe clear contributions from individual microwave field components of our microresonator, emphasizing the need for controllable local implantation.

Magnetic Particles Coupled to Disposable Screen Printed Transducers for Electrochemical Biosensing

PubMed Central

Yáñez-Sedeño, Paloma; Campuzano, Susana; Pingarrón, José M.

2016-01-01

Ultrasensitive biosensing is currently a growing demand that has led to the development of numerous strategies for signal amplification. In this context, the unique properties of magnetic particles; both of nano- and micro-size dimensions; have proved to be promising materials to be coupled with disposable electrodes for the design of cost-effective electrochemical affinity biosensing platforms. This review addresses, through discussion of selected examples, the way that nano- and micro-magnetic particles (MNPs and MMPs; respectively) have contributed significantly to the development of electrochemical affinity biosensors, including immuno-, DNA, aptamer and other affinity modes. Different aspects such as type of magnetic particles, assay formats, detection techniques, sensitivity, applicability and other relevant characteristics are discussed. Research opportunities and future development trends in this field are also considered. PMID:27681733

High-Volume Production of Lightweight Multijunction Solar Cells

NASA Technical Reports Server (NTRS)

Youtsey, Christopher

2015-01-01

MicroLink Devices, Inc., has transitioned its 6-inch epitaxial lift-off (ELO) solar cell fabrication process into a manufacturing platform capable of sustaining large-volume production. This Phase II project improves the ELO process by reducing cycle time and increasing the yield of large-area devices. In addition, all critical device fabrication processes have transitioned to 6-inch production tool sets designed for volume production. An emphasis on automated cassette-to-cassette and batch processes minimizes operator dependence and cell performance variability. MicroLink Devices established a pilot production line capable of at least 1,500 6-inch wafers per month at greater than 80 percent yield. The company also increased the yield and manufacturability of the 6-inch reclaim process, which is crucial to reducing the cost of the cells.

High-Throughput Screening Enhances Kidney Organoid Differentiation from Human Pluripotent Stem Cells and Enables Automated Multidimensional Phenotyping.

PubMed

Czerniecki, Stefan M; Cruz, Nelly M; Harder, Jennifer L; Menon, Rajasree; Annis, James; Otto, Edgar A; Gulieva, Ramila E; Islas, Laura V; Kim, Yong Kyun; Tran, Linh M; Martins, Timothy J; Pippin, Jeffrey W; Fu, Hongxia; Kretzler, Matthias; Shankland, Stuart J; Himmelfarb, Jonathan; Moon, Randall T; Paragas, Neal; Freedman, Benjamin S

2018-05-15

Organoids derived from human pluripotent stem cells are a potentially powerful tool for high-throughput screening (HTS), but the complexity of organoid cultures poses a significant challenge for miniaturization and automation. Here, we present a fully automated, HTS-compatible platform for enhanced differentiation and phenotyping of human kidney organoids. The entire 21-day protocol, from plating to differentiation to analysis, can be performed automatically by liquid-handling robots, or alternatively by manual pipetting. High-content imaging analysis reveals both dose-dependent and threshold effects during organoid differentiation. Immunofluorescence and single-cell RNA sequencing identify previously undetected parietal, interstitial, and partially differentiated compartments within organoids and define conditions that greatly expand the vascular endothelium. Chemical modulation of toxicity and disease phenotypes can be quantified for safety and efficacy prediction. Screening in gene-edited organoids in this system reveals an unexpected role for myosin in polycystic kidney disease. Organoids in HTS formats thus establish an attractive platform for multidimensional phenotypic screening. Copyright © 2018 Elsevier Inc. All rights reserved.

ICW eHealth Framework.

PubMed

Klein, Karsten; Wolff, Astrid C; Ziebold, Oliver; Liebscher, Thomas

2008-01-01

The ICW eHealth Framework (eHF) is a powerful infrastructure and platform for the development of service-oriented solutions in the health care business. It is the culmination of many years of experience of ICW in the development and use of in-house health care solutions and represents the foundation of ICW product developments based on the Java Enterprise Edition (Java EE). The ICW eHealth Framework has been leveraged to allow development by external partners - enabling adopters a straightforward integration into ICW solutions. The ICW eHealth Framework consists of reusable software components, development tools, architectural guidelines and conventions defining a full software-development and product lifecycle. From the perspective of a partner, the framework provides services and infrastructure capabilities for integrating applications within an eHF-based solution. This article introduces the ICW eHealth Framework's basic architectural concepts and technologies. It provides an overview of its module and component model, describes the development platform that supports the complete software development lifecycle of health care applications and outlines technological aspects, mainly focusing on application development frameworks and open standards.

Biomedical research platforms and their influence on article submissions and journal rankings: An update.

PubMed Central

Lippi, Giuseppe; Favaloro, Emmanuel J; Simundic, Ana-Maria

2012-01-01

After being indexed in 2006 in EMBASE/Excerpta Medica and Scopus, and later in Science Citation Index Expanded and Journal Citation Reports/Science Edition citation databases, Biochemia Medica launched a new web page and online manuscript submission system in 2010, and celebrated its first Impact Factor in the same year. Now, starting from the end of the 2011, the journal will also be indexed in PubMed/Medline, and this will contribute to increase the journal’s exposure and accessibility worldwide. This is an important breakthrough, which is expected to further increase the popularity of the journal, as well as the submission rate and citations. Although several tools are currently available as Web resources to retrieve scientific articles, whose functioning and basic criteria are thought to be rather similar, the functionality, coverage, notoriety and prominence may differ widely. The recent indexing of Biochemia Medica in PubMed/Medline has thereby given us the opportunity to provide a timely update on biomedical research platforms, their relationship with article submissions and journal rankings. PMID:22384515

A Web Browsing System by Eye-gaze Input

NASA Astrophysics Data System (ADS)

Abe, Kiyohiko; Owada, Kosuke; Ohi, Shoichi; Ohyama, Minoru

We have developed an eye-gaze input system for people with severe physical disabilities, such as amyotrophic lateral sclerosis (ALS) patients. This system utilizes a personal computer and a home video camera to detect eye-gaze under natural light. The system detects both vertical and horizontal eye-gaze by simple image analysis, and does not require special image processing units or sensors. We also developed the platform for eye-gaze input based on our system. In this paper, we propose a new web browsing system for physically disabled computer users as an application of the platform for eye-gaze input. The proposed web browsing system uses a method of direct indicator selection. The method categorizes indicators by their function. These indicators are hierarchized relations; users can select the felicitous function by switching indicators group. This system also analyzes the location of selectable object on web page, such as hyperlink, radio button, edit box, etc. This system stores the locations of these objects, in other words, the mouse cursor skips to the object of candidate input. Therefore it enables web browsing at a faster pace.

Automation of diagnostic genetic testing: mutation detection by cyclic minisequencing.

PubMed

Alagrund, Katariina; Orpana, Arto K

2014-01-01

The rising role of nucleic acid testing in clinical decision making is creating a need for efficient and automated diagnostic nucleic acid test platforms. Clinical use of nucleic acid testing sets demands for shorter turnaround times (TATs), lower production costs and robust, reliable methods that can easily adopt new test panels and is able to run rare tests in random access principle. Here we present a novel home-brew laboratory automation platform for diagnostic mutation testing. This platform is based on the cyclic minisequecing (cMS) and two color near-infrared (NIR) detection. Pipetting is automated using Tecan Freedom EVO pipetting robots and all assays are performed in 384-well micro plate format. The automation platform includes a data processing system, controlling all procedures, and automated patient result reporting to the hospital information system. We have found automated cMS a reliable, inexpensive and robust method for nucleic acid testing for a wide variety of diagnostic tests. The platform is currently in clinical use for over 80 mutations or polymorphisms. Additionally to tests performed from blood samples, the system performs also epigenetic test for the methylation of the MGMT gene promoter, and companion diagnostic tests for analysis of KRAS and BRAF gene mutations from formalin fixed and paraffin embedded tumor samples. Automation of genetic test reporting is found reliable and efficient decreasing the work load of academic personnel.

A JAVA-based multimedia tool for clinical practice guidelines.

PubMed

Maojo, V; Herrero, C; Valenzuela, F; Crespo, J; Lazaro, P; Pazos, A

1997-01-01

We have developed a specific language for the representation of Clinical Practice Guidelines (CPGs) and Windows C++ and platform independent JAVA applications for multimedia presentation and edition of electronically stored CPGs. This approach facilitates translation of guidelines and protocols from paper to computer-based flowchart representations. Users can navigate through the algorithm with a friendly user interface and access related multimedia information within the context of each clinical problem. CPGs can be stored in a computer server and distributed over the World Wide Web, facilitating dissemination, local adaptation, and use as a reference element in medical care. We have chosen the Agency for Health Care and Policy Research's heart failure guideline to demonstrate the capabilities of our tool.