Bridging the Gap: From 2D Cell Culture to 3D Microengineered Extracellular Matrices.

PubMed

Li, Yanfen; Kilian, Kristopher A

2015-12-30

Historically the culture of mammalian cells in the laboratory has been performed on planar substrates with media cocktails that are optimized to maintain phenotype. However, it is becoming increasingly clear that much of biology discerned from 2D studies does not translate well to the 3D microenvironment. Over the last several decades, 2D and 3D microengineering approaches have been developed that better recapitulate the complex architecture and properties of in vivo tissue. Inspired by the infrastructure of the microelectronics industry, lithographic patterning approaches have taken center stage because of the ease in which cell-sized features can be engineered on surfaces and within a broad range of biocompatible materials. Patterning and templating techniques enable precise control over extracellular matrix properties including: composition, mechanics, geometry, cell-cell contact, and diffusion. In this review article we explore how the field of engineered extracellular matrices has evolved with the development of new hydrogel chemistry and the maturation of micro- and nano- fabrication. Guided by the spatiotemporal regulation of cell state in developing tissues, techniques for micropatterning in 2D, pseudo-3D systems, and patterning within 3D hydrogels will be discussed in the context of translating the information gained from 2D systems to synthetic engineered 3D tissues. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Microfabricated microengine for use as a mechanical drive and power source in the microdomain and fabrication process

DOEpatents

Garcia, E.J.; Sniegowski, J.J.

1997-05-20

A microengine uses two synchronized linear actuators as a power source and converts oscillatory motion from the actuators into rotational motion via direct linkage connection to an output gear or wheel. The microengine provides output in the form of a continuously rotating output gear that is capable of delivering drive torque to a micromechanism. The microengine can be operated at varying speeds and its motion can be reversed. Linear actuators are synchronized in order to provide linear oscillatory motion to the linkage means in the X and Y directions according to a desired position, rotational direction and speed of said mechanical output means. The output gear has gear teeth on its outer perimeter for directly contacting a micromechanism requiring mechanical power. The gear is retained by a retaining means which allows said gear to rotate freely. The microengine is microfabricated of polysilicon on one wafer using surface micromachining batch fabrication. 30 figs.

Micro-engineered first wall tungsten armor for high average power laser fusion energy systems

NASA Astrophysics Data System (ADS)

Sharafat, Shahram; Ghoniem, Nasr M.; Anderson, Michael; Williams, Brian; Blanchard, Jake; Snead, Lance; HAPL Team

2005-12-01

The high average power laser program is developing an inertial fusion energy demonstration power reactor with a solid first wall chamber. The first wall (FW) will be subject to high energy density radiation and high doses of high energy helium implantation. Tungsten has been identified as the candidate material for a FW armor. The fundamental concern is long term thermo-mechanical survivability of the armor against the effects of high temperature pulsed operation and exfoliation due to the retention of implanted helium. Even if a solid tungsten armor coating would survive the high temperature cyclic operation with minimal failure, the high helium implantation and retention would result in unacceptable material loss rates. Micro-engineered materials, such as castellated structures, plasma sprayed nano-porous coatings and refractory foams are suggested as a first wall armor material to address these fundamental concerns. A micro-engineered FW armor would have to be designed with specific geometric features that tolerate high cyclic heating loads and recycle most of the implanted helium without any significant failure. Micro-engineered materials are briefly reviewed. In particular, plasma-sprayed nano-porous tungsten and tungsten foams are assessed for their potential to accommodate inertial fusion specific loads. Tests show that nano-porous plasma spray coatings can be manufactured with high permeability to helium gas, while retaining relatively high thermal conductivities. Tungsten foams where shown to be able to overcome thermo-mechanical loads by cell rotation and deformation. Helium implantation tests have shown, that pulsed implantation and heating releases significant levels of implanted helium. Helium implantation and release from tungsten was modeled using an expanded kinetic rate theory, to include the effects of pulsed implantations and thermal cycles. Although, significant challenges remain micro-engineered materials are shown to constitute potential candidate FW armor materials.

Microfabrication of human organs-on-chips.

PubMed

Huh, Dongeun; Kim, Hyun Jung; Fraser, Jacob P; Shea, Daniel E; Khan, Mohammed; Bahinski, Anthony; Hamilton, Geraldine A; Ingber, Donald E

2013-11-01

'Organs-on-chips' are microengineered biomimetic systems containing microfluidic channels lined by living human cells, which replicate key functional units of living organs to reconstitute integrated human organ-level pathophysiology in vitro. These microdevices can be used to test efficacy and toxicity of drugs and chemicals, and to create in vitro models of human disease. Thus, they potentially represent low-cost alternatives to conventional animal models for pharmaceutical, chemical and environmental applications. Here we describe a protocol for the fabrication, microengineering and operation of these microfluidic organ-on-chip systems. First, microengineering is used to fabricate a multilayered microfluidic device that contains two parallel elastomeric microchannels separated by a thin porous flexible membrane, along with two full-height, hollow vacuum chambers on either side; this requires ∼3.5 d to complete. To create a 'breathing' lung-on-a-chip that mimics the mechanically active alveolar-capillary interface of the living human lung, human alveolar epithelial cells and microvascular endothelial cells are cultured in the microdevice with physiological flow and cyclic suction applied to the side chambers to reproduce rhythmic breathing movements. We describe how this protocol can be easily adapted to develop other human organ chips, such as a gut-on-a-chip lined by human intestinal epithelial cells that experiences peristalsis-like motions and trickling fluid flow. Also, we discuss experimental techniques that can be used to analyze the cells in these organ-on-chip devices.

Optical fiber end-facet polymer suspended-mirror devices

NASA Astrophysics Data System (ADS)

Yao, Mian; Wu, Jushuai; Zhang, A. Ping; Tam, Hwa-Yaw; Wai, P. K. A.

2017-04-01

This paper presents a novel optical fiber device based on a polymer suspended mirror on the end facet of an optical fiber. With an own-developed optical 3D micro-printing technology, SU-8 suspended-mirror devices (SMDs) were successfully fabricated on the top of a standard single-mode optical fiber. Optical reflection spectra of the fabricated SU- 8 SMDs were measured and compared with theoretical analysis. The proposed technology paves a way towards 3D microengineering of the small end-facet of optical fibers to develop novel fiber-optic sensors.

Direct acceleration of electrons by a CO2 laser in a curved plasma waveguide

PubMed Central

Yi, Longqing; Pukhov, Alexander; Shen, Baifei

2016-01-01

Laser plasma interaction with micro-engineered targets at relativistic intensities has been greatly promoted by recent progress in the high contrast lasers and the manufacture of advanced micro- and nano-structures. This opens new possibilities for the physics of laser-matter interaction. Here we propose a novel approach that leverages the advantages of high-pressure CO2 laser, laser-waveguide interaction, as well as micro-engineered plasma structure to accelerate electrons to peak energy greater than 1 GeV with narrow slice energy spread (~1%) and high overall efficiency. The acceleration gradient is 26 GV/m for a 1.3 TW CO2 laser system. The micro-bunching of a long electron beam leads to the generation of a chain of ultrashort electron bunches with the duration roughly equal to half-laser-cycle. These results open a way for developing a compact and economic electron source for diverse applications. PMID:27320197

A wearable pressure sensor based on ultra-violet/ozone microstructured carbon nanotube/polydimethylsiloxane arrays for electronic skins.

PubMed

Yu, Guohui; Hu, Jingdong; Tan, Jianping; Gao, Yang; Lu, Yongfeng; Xuan, Fuzhen

2018-03-16

Pressure sensors with high performance (e.g., a broad pressure sensing range, high sensitivities, rapid response/relaxation speeds, temperature-stable sensing), as well as a cost-effective and highly efficient fabrication method are highly desired for electronic skins. In this research, a high-performance pressure sensor based on microstructured carbon nanotube/polydimethylsiloxane arrays was fabricated using an ultra-violet/ozone (UV/O 3 ) microengineering technique. The UV/O 3 microengineering technique is controllable, cost-effective, and highly efficient since it is conducted at room temperature in an ambient environment. The pressure sensor offers a broad pressure sensing range (7 Pa-50 kPa), a sensitivity of ∼ -0.101 ± 0.005 kPa -1 (<1 kPa), a fast response/relaxation speed of ∼10 ms, a small dependence on temperature variation, and a good cycling stability (>5000 cycles), which is attributed to the UV/O 3 engineered microstructures that amplify and transfer external applied forces and rapidly store/release the energy during the PDMS deformation. The sensors developed show the capability to detect external forces and monitor human health conditions, promising for the potential applications in electronic skin.

A wearable pressure sensor based on ultra-violet/ozone microstructured carbon nanotube/polydimethylsiloxane arrays for electronic skins

NASA Astrophysics Data System (ADS)

Yu, Guohui; Hu, Jingdong; Tan, Jianping; Gao, Yang; Lu, Yongfeng; Xuan, Fuzhen

2018-03-01

Pressure sensors with high performance (e.g., a broad pressure sensing range, high sensitivities, rapid response/relaxation speeds, temperature-stable sensing), as well as a cost-effective and highly efficient fabrication method are highly desired for electronic skins. In this research, a high-performance pressure sensor based on microstructured carbon nanotube/polydimethylsiloxane arrays was fabricated using an ultra-violet/ozone (UV/O3) microengineering technique. The UV/O3 microengineering technique is controllable, cost-effective, and highly efficient since it is conducted at room temperature in an ambient environment. The pressure sensor offers a broad pressure sensing range (7 Pa-50 kPa), a sensitivity of ˜ -0.101 ± 0.005 kPa-1 (<1 kPa), a fast response/relaxation speed of ˜10 ms, a small dependence on temperature variation, and a good cycling stability (>5000 cycles), which is attributed to the UV/O3 engineered microstructures that amplify and transfer external applied forces and rapidly store/release the energy during the PDMS deformation. The sensors developed show the capability to detect external forces and monitor human health conditions, promising for the potential applications in electronic skin.

Microengineered embryonic stem cells niche to induce neural differentiation.

PubMed

Joshi, Ramila; Tavana, Hossein

2015-08-01

A major challenge in therapeutic use of embryonic stem cells (ESCs) for treating neurodegenerative diseases is creating a niche in vitro for controlled neural-specific differentiation of ESCs. We employ a niche microengineering approach to derive neural cells from ESCs by mimicking embryonic development in terms of direct intercellular interactions. Using a polymeric aqueous two-phase system (ATPS) microprinting technology, murine ESCs (mESCs) are precisely localized over a monolayer of supporting stromal cells to allow formation of individual mESC colonies. Polyethylene glycol (PEG) and dextran (DEX) are dissolved in culture media to form two immiscible aqueous solutions. A robotic liquid handler is used to print a nanoliter-volume drop of the denser DEX phase solution containing mESCs onto a confluent layer of supporting PA6 stromal cells submerged in the aqueous PEG phase. mESCs proliferate into isolated colonies of uniform size. For the first time, a comprehensive protein expression analysis of individual mESC colonies is performed over a two-week culture period to track temporal progression of cells from a pluripotent stage to specific neural cells. Starting from day 4, the expression of nestin, neural cell adhesion molecule (NCAM), and beta-III tubulin shows a significant increase but then levels off after the first week of culture. The expression of specific neural cell markers glial fibrillary acidic protein (GFAP), 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNPase), and tyrosine hydroxylase (TH) is elevated during the second week of culture. This microengineering approach to control ESCs differentiation niche combined with the time-course protein expression analysis of individual differentiating colonies facilitates understanding of evolution of specific neural cells from ESCs and identifying underlying molecular markers.

The design, fabrication and characterization of fluidic membranes for micro-engines with the aim of frequency lowering

NASA Astrophysics Data System (ADS)

Chutani, R.; Formosa, F.; de Labachelerie, M.; Badel, A.; Lanzetta, F.

2016-12-01

This paper describes the design, microfabrication and linear dynamic characterization of low frequency thick membranes as a potential technological solution for resonant micro-engines, for which classical pistons cannot be used. The proposed structure is called a hybrid fluid-membrane and consists of two thin flexible membranes that encapsulate an incompressible fluid. Lower frequency structures, compared to geometrically equivalent single layer membranes, are thus obtained. Each flexible membrane is based on a composite structure which comprises a silicon planar logarithmic spiral spring embedded in a room temperature vulcanization silicone polymer. Thus, the stiffness and sealing features are dissociated for a better design control. The developed realization and assembly process is demonstrated at the wafer level. The process involves the anodic bonding of multiple stacks of silicon/glass structures, fluid filling and sealing. Various dimensions of hybrid fluid-membranes are successfully fabricated. Their dynamic characterization underlines the agreement between experimental and theoretical results. The results provide the opportunity for the design and fabrication of low frequency membranes to match the dynamics requirements of micro-engines.

Microengineering of Metals and Ceramics: Part I: Design, Tooling and Injection Molding; Volume 3: Advanced Micro & Nanosystems

NASA Astrophysics Data System (ADS)

Baltes, Henry; Brand, Oliver; Fedder, Gary K.; Hierold, Christofer; Korvink, Jan G.; Tabata, Osamu; Löhe, Detlef; Haußelt, Jürgen

2005-09-01

Microstructures, electronics, nanotechnology - these vast fields of research are growing together as the size gap narrows and many different materials are combined. Current research, engineering sucesses and newly commercialized products hint at the immense innovative potentials and future applications that open up once mankind controls shape and function from the atomic level right up to the visible world without any gaps. In this volume, authors from three major competence centres for microengineering illustrate step by step the process from designing and simulating microcomponents of metallic and ceramic materials to replicating micro-scale components by injection molding.

Downscaling of conventional laser cladding technique to microengineering

NASA Astrophysics Data System (ADS)

del Val, J.; Comesaña, R.; Lusquiños, F.; Riveiro, A.; Quintero, F.; Pou, J.

To get an adequate response to the high increase of micro-products demand, new techniques have been developed by different types of industries in the last years. One approach is to adapt the laser surface cladding technique to the scale of microengineering. A new experimental configuration has been developed based on a highly stable high power laser with a high beam quality and a micro-feeder adequate to supply submicron particles. This work collects our efforts to extend the operation range of the laser cladding to the laser micro-cladding in order to produce micro-coatings. The viability of this new technique has been demonstrated by depositing coatings with geometrical characteristics in the micrometer range (minimum values obtained: 32 μm of width and 12 μm of height).

Microengineered physiological biomimicry: organs-on-chips.

PubMed

Huh, Dongeun; Torisawa, Yu-suke; Hamilton, Geraldine A; Kim, Hyun Jung; Ingber, Donald E

2012-06-21

Microscale engineering technologies provide unprecedented opportunities to create cell culture microenvironments that go beyond current three-dimensional in vitro models by recapitulating the critical tissue-tissue interfaces, spatiotemporal chemical gradients, and dynamic mechanical microenvironments of living organs. Here we review recent advances in this field made over the past two years that are focused on the development of 'Organs-on-Chips' in which living cells are cultured within microfluidic devices that have been microengineered to reconstitute tissue arrangements observed in living organs in order to study physiology in an organ-specific context and to develop specialized in vitro disease models. We discuss the potential of organs-on-chips as alternatives to conventional cell culture models and animal testing for pharmaceutical and toxicology applications. We also explore challenges that lie ahead if this field is to fulfil its promise to transform the future of drug development and chemical safety testing.

A microengineered model of RBC transfusion-induced pulmonary vascular injury.

PubMed

Seo, Jeongyun; Conegliano, David; Farrell, Megan; Cho, Minseon; Ding, Xueting; Seykora, Thomas; Qing, Danielle; Mangalmurti, Nilam S; Huh, Dongeun

2017-06-13

Red blood cell (RBC) transfusion poses significant risks to critically ill patients by increasing their susceptibility to acute respiratory distress syndrome. While the underlying mechanisms of this life-threatening syndrome remain elusive, studies suggest that RBC-induced microvascular injury in the distal lung plays a central role in the development of lung injury following blood transfusion. Here we present a novel microengineering strategy to model and investigate this key disease process. Specifically, we created a microdevice for culturing primary human lung endothelial cells under physiological flow conditions to recapitulate the morphology and hemodynamic environment of the pulmonary microvascular endothelium in vivo. Perfusion of the microengineered vessel with human RBCs resulted in abnormal cytoskeletal rearrangement and release of intracellular molecules associated with regulated necrotic cell death, replicating the characteristics of acute endothelial injury in transfused lungs in vivo. Our data also revealed the significant effect of hemodynamic shear stress on RBC-induced microvascular injury. Furthermore, we integrated the microfluidic endothelium with a computer-controlled mechanical stretching system to show that breathing-induced physiological deformation of the pulmonary microvasculature may exacerbate vascular injury during RBC transfusion. Our biomimetic microsystem provides an enabling platform to mechanistically study transfusion-associated pulmonary vascular complications in susceptible patient populations.

Emerging microengineering tools for functional analysis and phenotyping of blood cells

PubMed Central

Li, Xiang; Chen, Weiqiang; Li, Zida; Li, Ling; Gu, Hongchen; Fu, Jianping

2014-01-01

The available techniques for assessing blood cell functions are limited considering the various types of blood cells and their diverse functions. In the past decade, rapid advancement in microengineering has enabled an array of blood cell functional measurements that are difficult or impossible to achieve using conventional bulk platforms. Such miniaturized blood cell assay platforms also provide attractive capabilities of reducing chemical consumption, cost, assay time, as well as exciting opportunities of device integration, automation, and assay standardization. This review summarizes these contemporary microengineering tools and discusses their promising potential for constructing accurate in vitro models and rapid clinical diagnosis using minimal amount of whole blood samples. PMID:25283971

Non-Destructive Damping Measurement for Wafer-Level Packaged Microelectromechanical System (MEMS) Acceleration Switches

DTIC Science & Technology

2014-09-01

Micromechanics and Microengineering . 2005;15:176–184. 10. Mohite SS, Kesari H, Sonti VR, Pratap R. Analytical solutions for the stiffness and damping...coefficients of squeeze films in MEMS devices with perforated back plates. Journal of Micromechanics and Microengineering . 2005;15:2083–2092. 11. Younis MI

Tissue cell assisted fabrication of tubular catalytic platinum microengines

NASA Astrophysics Data System (ADS)

Wang, Hong; Moo, James Guo Sheng; Pumera, Martin

2014-09-01

We report a facile platform for mass production of robust self-propelled tubular microengines. Tissue cells extracted from fruits of banana and apple, Musa acuminata and Malus domestica, are used as the support on which a thin platinum film is deposited by means of physical vapor deposition. Upon sonication of the cells/Pt-coated substrate in water, microscrolls of highly uniform sizes are spontaneously formed. Tubular microengines fabricated with the fruit cell assisted method exhibit a fast motion of ~100 bodylengths per s (~1 mm s-1). An extremely simple and affordable platform for mass production of the micromotors is crucial for the envisioned swarms of thousands and millions of autonomous micromotors performing biomedical and environmental remediation tasks.We report a facile platform for mass production of robust self-propelled tubular microengines. Tissue cells extracted from fruits of banana and apple, Musa acuminata and Malus domestica, are used as the support on which a thin platinum film is deposited by means of physical vapor deposition. Upon sonication of the cells/Pt-coated substrate in water, microscrolls of highly uniform sizes are spontaneously formed. Tubular microengines fabricated with the fruit cell assisted method exhibit a fast motion of ~100 bodylengths per s (~1 mm s-1). An extremely simple and affordable platform for mass production of the micromotors is crucial for the envisioned swarms of thousands and millions of autonomous micromotors performing biomedical and environmental remediation tasks. Electronic supplementary information (ESI) available: Related video. See DOI: 10.1039/c4nr03720k

Heterogeneous System-on-a-Chip Design for Self-Powered Wireless Sensor Networks in Non-Benign Environments

DTIC Science & Technology

2008-03-01

Paper CANEUS 2006-11045. [8] S. Janson, A . Huang, W. Hansen, L. Steffeney, and H . Helvajian , “Development of an Inspector Satellite Using...antenna will be required to achieve any meaningful range. Final Report for EOARD Grant FA8655-06-1-3053 53 Bibliography [1] Helvajian , H . and...International Astronautics Federation, Graz, Austria, Oct. 1993, Paper IAF-93-U.5.575 [3] H . Helvajian , Microengineering Aerospace Systems, Reston, VA

Emerging microengineered tools for functional analysis and phenotyping of blood cells.

PubMed

Li, Xiang; Chen, Weiqiang; Li, Zida; Li, Ling; Gu, Hongchen; Fu, Jianping

2014-11-01

The available techniques for assessing blood cell functions are limited considering the various types of blood cell and their diverse functions. In the past decade, rapid advances in microengineering have enabled an array of blood cell functional measurements that are difficult or impossible to achieve using conventional bulk platforms. Such miniaturized blood cell assay platforms also provide the attractive capabilities of reducing chemical consumption, cost, and assay time, as well as exciting opportunities for device integration, automation, and assay standardization. This review summarizes these contemporary microengineered tools and discusses their promising potential for constructing accurate in vitro models and rapid clinical diagnosis using minimal amounts of whole-blood samples. Copyright © 2014 Elsevier Ltd. All rights reserved.

Microfabrication of Cell-Laden Hydrogels for Engineering Mineralized and Load Bearing Tissues.

PubMed

Li, Chia-Cheng; Kharaziha, Mahshid; Min, Christine; Maas, Richard; Nikkhah, Mehdi

2015-01-01

Microengineering technologies and advanced biomaterials have extensive applications in the field of regenerative medicine. In this chapter, we review the integration of microfabrication techniques and hydrogel-based biomaterials in the field of dental, bone, and cartilage tissue engineering. We primarily discuss the major features that make hydrogels attractive candidates to mimic extracellular matrix (ECM), and we consider the benefits of three-dimensional (3D) culture systems for tissue engineering applications. We then focus on the fundamental principles of microfabrication techniques including photolithography, soft lithography and bioprinting approaches. Lastly, we summarize recent research on microengineering cell-laden hydrogel constructs for dental, bone and cartilage regeneration, and discuss future applications of microfabrication techniques for load-bearing tissue engineering.

Organ-on-a-Chip Systems: Microengineering to Biomimic Living Systems.

PubMed

Zheng, Fuyin; Fu, Fanfan; Cheng, Yao; Wang, Chunyan; Zhao, Yuanjin; Gu, Zhongze

2016-05-01

"Organ-on-a-chip" systems integrate microengineering, microfluidic technologies, and biomimetic principles to create key aspects of living organs faithfully, including critical microarchitecture, spatiotemporal cell-cell interactions, and extracellular microenvironments. This creative platform and its multiorgan integration recapitulating organ-level structures and functions can bring unprecedented benefits to a diversity of applications, such as developing human in vitro models for healthy or diseased organs, enabling the investigation of fundamental mechanisms in disease etiology and organogenesis, benefiting drug development in toxicity screening and target discovery, and potentially serving as replacements for animal testing. Recent advances in novel designs and examples for developing organ-on-a-chip platforms are reviewed. The potential for using this emerging technology in understanding human physiology including mechanical, chemical, and electrical signals with precise spatiotemporal controls are discussed. The current challenges and future directions that need to be pursued for these proof-of-concept studies are also be highlighted. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Advanced biomaterials and microengineering technologies to recapitulate the stepwise process of cancer metastasis.

PubMed

Peela, Nitish; Truong, Danh; Saini, Harpinder; Chu, Hunghao; Mashaghi, Samaneh; Ham, Stephanie L; Singh, Sunil; Tavana, Hossein; Mosadegh, Bobak; Nikkhah, Mehdi

2017-07-01

Cancer is one of the leading causes of death globally according to the World Health Organization. Although improved treatments and early diagnoses have reduced cancer related mortalities, metastatic disease remains a major clinical challenge. The local tumor microenvironment plays a significant role in cancer metastasis, where tumor cells respond and adapt to a plethora of biochemical and biophysical signals from stromal cells and extracellular matrix (ECM) proteins. Due to these complexities, there is a critical need to understand molecular mechanisms underlying cancer metastasis to facilitate the discovery of more effective therapies. In the past few years, the integration of advanced biomaterials and microengineering approaches has initiated the development of innovative platform technologies for cancer research. These technologies enable the creation of biomimetic in vitro models with physiologically relevant (i.e. in vivo-like) characteristics to conduct studies ranging from fundamental cancer biology to high-throughput drug screening. In this review article, we discuss the biological significance of each step of the metastatic cascade and provide a broad overview on recent progress to recapitulate these stages using advanced biomaterials and microengineered technologies. In each section, we will highlight the advantages and shortcomings of each approach and provide our perspectives on future directions. Copyright © 2017 Elsevier Ltd. All rights reserved.

Silicon microengineering for accelerometers

NASA Astrophysics Data System (ADS)

Satchell, D. W.

Silicon microengineering enables the excellent mechanical properties of silicon to be combined with electronic ones to produce accelerometers of good performance, small size and low cost. The design and fabrication of two types of analogue accelerometer, using this technique, are described. One employs implanted strain gauges to give a dc output, while the other has a strain-sensitive resonant structure which gives a varying frequency signal.

Microengineered open tubular columns for GC analysis

NASA Astrophysics Data System (ADS)

Wiranto, Goib; Haskard, Malcolm R.; Mulcahy, Dennis E.; Davey, David E.; Dawes, Ernest F.

1999-09-01

Microengineered open tubular (MOT) columns with semi rectangular cross-sections have been designed and fabricated using microengineering techniques. The creation of 100-micrometers wide, 20-micrometers deep, and 125-cm long columns employed isotropic etching on (100) silicon and anodic bonding with a Pyrex 7740 glass cover plate. Column geometry has been optimized to achieve maximum efficiency and allow extreme operating conditions. The walls of the microcolumns were coated with a non-polar liquid stationary phase. Performances of the MOT columns have been demonstrated by their ability to completely separate a series of hydrocarbon mixture in less than 1.25 min under isothermal condition of 150 degrees C. The achievable column efficiencies as measured in terms of theoretical plate height ranged from 0.57 to 1.45 mm, which agreed well with theoretical predictions.

Ultrasound-modulated bubble propulsion of chemically powered microengines.

PubMed

Xu, Tailin; Soto, Fernando; Gao, Wei; Garcia-Gradilla, Victor; Li, Jinxing; Zhang, Xueji; Wang, Joseph

2014-06-18

The use of an ultrasound (US) field for rapid and reversible control of the movement of bubble-propelled chemically powered PEDOT/Ni/Pt microengines is demonstrated. Such operation reflects the US-induced disruption of normal bubble evolution and ejection, essential for efficient propulsion of catalytic microtubular engines. It offers precise speed control, with sharp increases and decreases of the speed at low and high US powers, respectively. A wide range of speeds can thus be generated by tuning the US power. Extremely fast changes in the motor speed (<0.1 s) and reproducible "On/Off" activations are observed, indicating distinct advantages compared to motion control methods based on other external stimuli. Such effective control of the propulsion of chemically powered microengines, including remarkable "braking" ability, holds considerable promise for diverse applications.

Microengineered 3D cell-laden thermoresponsive hydrogels for mimicking cell morphology and orientation in cartilage tissue engineering.

PubMed

Mellati, Amir; Fan, Chia-Ming; Tamayol, Ali; Annabi, Nasim; Dai, Sheng; Bi, Jingxiu; Jin, Bo; Xian, Cory; Khademhosseini, Ali; Zhang, Hu

2017-01-01

Mimicking the zonal organization of native articular cartilage, which is essential for proper tissue functions, has remained a challenge. In this study, a thermoresponsive copolymer of chitosan-g-poly(N-isopropylacrylamide) (CS-g-PNIPAAm) was synthesized as a carrier of mesenchymal stem cells (MSCs) to provide a support for their proliferation and differentiation. Microengineered three-dimensional (3D) cell-laden CS-g-PNIPAAm hydrogels with different microstripe widths were fabricated to control cellular alignment and elongation in order to mimic the superficial zone of natural cartilage. Biochemical assays showed six- and sevenfold increment in secretion of glycosaminoglycans (GAGs) and total collagen from MSCs encapsulated within the synthesized hydrogel after 28 days incubation in chondrogenic medium. Chondrogenic differentiation was also verified qualitatively by histological and immunohistochemical assessments. It was found that 75 ± 6% of cells encapsulated within 50 μm wide microstripes were aligned with an aspect ratio of 2.07 ± 0.16 at day 5, which was more organized than those observed in unpatterned constructs (12 ± 7% alignment and a shape index of 1.20 ± 0.07). The microengineered constructs mimicked the cell shape and organization in the superficial zone of cartilage whiles the unpatterned one resembled the middle zone. Our results suggest that microfabrication of 3D cell-laden thermosensitive hydrogels is a promising platform for creating biomimetic structures leading to more successful multi-zonal cartilage tissue engineering. Biotechnol. Bioeng. 2017;114: 217-231. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Engineering three-dimensional cardiac microtissues for potential drug screening applications.

PubMed

Wang, L; Huang, G; Sha, B; Wang, S; Han, Y L; Wu, J; Li, Y; Du, Y; Lu, T J; Xu, F

2014-01-01

Heart disease is one of the major global health issues. Despite rapid advances in cardiac tissue engineering, limited successful strategies have been achieved to cure cardiovascular diseases. This situation is mainly due to poor understanding of the mechanism of diverse heart diseases and unavailability of effective in vitro heart tissue models for cardiovascular drug screening. With the development of microengineering technologies, three-dimensional (3D) cardiac microtissue (CMT) models, mimicking 3D architectural microenvironment of native heart tissues, have been developed. The engineered 3D CMT models hold greater potential to be used for assessing effective drugs candidates than traditional two-dimensional cardiomyocyte culture models. This review discusses the development of 3D CMT models and highlights their potential applications for high-throughput screening of cardiovascular drug candidates.

Demonstrating Optothermal Actuators for an Autonomous Mems Microrobot

DTIC Science & Technology

2004-03-01

of Toggled Microthermal Actuators,” Journal of Micromechanics and Microengineering, Vol. 14, pp 49-56, 2004. [10] S. Baglio, S. Castorina, L...127-132, 2000. [8] Y. Lai, J. McDonald, M. Kujath and T. Hubbard, “Force, Deflection and Power Measurements of Toggled Microthermal Actuators...Hubbard, "Force, Deflection and Power Measurements of Toggled Microthermal Actuators", Journal of Micromechanics and Microengineering, Vol. 14, pp 49

Microfluidic Organ/Body-on-a-Chip Devices at the Convergence of Biology and Microengineering.

PubMed

Perestrelo, Ana Rubina; Águas, Ana C P; Rainer, Alberto; Forte, Giancarlo

2015-12-10

Recent advances in biomedical technologies are mostly related to the convergence of biology with microengineering. For instance, microfluidic devices are now commonly found in most research centers, clinics and hospitals, contributing to more accurate studies and therapies as powerful tools for drug delivery, monitoring of specific analytes, and medical diagnostics. Most remarkably, integration of cellularized constructs within microengineered platforms has enabled the recapitulation of the physiological and pathological conditions of complex tissues and organs. The so-called "organ-on-a-chip" technology, which represents a new avenue in the field of advanced in vitro models, with the potential to revolutionize current approaches to drug screening and toxicology studies. This review aims to highlight recent advances of microfluidic-based devices towards a body-on-a-chip concept, exploring their technology and broad applications in the biomedical field.

Microfluidic Organ/Body-on-a-Chip Devices at the Convergence of Biology and Microengineering

PubMed Central

Perestrelo, Ana Rubina; Águas, Ana C. P.; Rainer, Alberto; Forte, Giancarlo

2015-01-01

Recent advances in biomedical technologies are mostly related to the convergence of biology with microengineering. For instance, microfluidic devices are now commonly found in most research centers, clinics and hospitals, contributing to more accurate studies and therapies as powerful tools for drug delivery, monitoring of specific analytes, and medical diagnostics. Most remarkably, integration of cellularized constructs within microengineered platforms has enabled the recapitulation of the physiological and pathological conditions of complex tissues and organs. The so-called “organ-on-a-chip” technology, which represents a new avenue in the field of advanced in vitro models, with the potential to revolutionize current approaches to drug screening and toxicology studies. This review aims to highlight recent advances of microfluidic-based devices towards a body-on-a-chip concept, exploring their technology and broad applications in the biomedical field. PMID:26690442

Electrical Microengineering of Redox Enzymes

DTIC Science & Technology

1994-03-31

coating applied to the electrode 41 to prevent lose of mediator graphite foil potassium -~0.02a 0.03  electrolyte wus dioxane with 15% 42...hexacyanoferrats(ll)d aqueous buffer carbon fiber’ none h 40-5000 biotin/avidin complex used to obtain a 43 surface layer of HRP Pt organic metal, potassium ...OFFICE OF NAVAL RESEARCH AD-A279 015 FINAL REPORT FOR CONTRACT NOOO 14-91 -J- 1656 R&T CODE 413h007---05 ELECTRICAL MICROENGINEERING OF REDOX ENZYMES

Microfluidics: Science and Engineering at the Edge of the Continuum

NASA Astrophysics Data System (ADS)

Breuer, Kenny

2002-11-01

The widespread growth of microengineering and the development of a new generation of micron- and nanometer scale diagnostic techniques has focussed much recent attention on the mechanics of fluids at the micron and sub-micron scale. Challenges with both scientific and engineering relevance have been raised by this activity, ranging from the prediction of viscous damping and lubrication effects in MEMS to the design of microengines to the understanding of bacterial propulsion. Identifying and addressing these challenges form the basis of this talk. >From a scientific perspective, a question that refuses to die is that of the applicability of the continuum hypothesis, and the possible existence of new physical phenomena only observable in small systems. To be brief, the reports of the demise of the Navier-Stokes equations are greatly exaggerated and to illustrate this we will review the more recent work on near-continuum fluid mechanics in micron and sub-micron scale devices with an emphasis on our own experiments on the breakdown of the continuum description in both gaseous and liquid flows. From an engineering perspective, the tight coupling between fluids, structures and manufacturing result in flows characterized by unfamiliar parameter regimes and unconventional geometries. We will look at several examples of such microfluidic engineering, drawn from MEMS (inertial instruments, microengines) and biology (bacterial propulsion) that illustrate the the unique design challenges that we encounter in microfluidic devices and the solutions (and lack of solutions) to these problems.

Applications of laser ablation to microengineering

NASA Astrophysics Data System (ADS)

Gower, Malcolm C.; Rizvi, Nadeem H.

2000-08-01

Applications of pulsed laser ablation to the manufacture of micro- electro-mechanical systems (MEMS) and micro-opto-electro-mechanical systems (MOEMS) devices are presented. Laser ablative processes used to manufacture a variety of microsystems technology (MST) components in the computer peripheral, sensing and biomedical industries are described together with a view of some future developments.

Microsystems in medicine.

PubMed

Wallrabe, U; Ruther, P; Schaller, T; Schomburg, W K

1998-03-01

The complexity of modern surgical and analytical methods requires the miniaturisation of many medical devices. The LIGA technique and also mechanical microengineering are well known for the batch fabrication of microsystems. Actuators and sensors are developed based on these techniques. The hydraulic actuation principle is advantageous for medical applications since the energy may be supplied by pressurised balanced salt solution. Some examples are turbines, pumps and valves. In addition, optical sensors and components are useful for analysis and inspection as represented by microspectrometers and spherical lenses. Finally, plastic containers with microporous bottoms allow a 3-dimensional growth of cell culture systems.

The influence of low-energy helium plasma on bubble formation in micro-engineered tungsten

NASA Astrophysics Data System (ADS)

Gao, Edward; Nadvornick, Warren; Doerner, Russ; Ghoniem, Nasr M.

2018-04-01

Four different types of micro-engineered tungsten surfaces were exposed to low energy helium plasma, with a planar surface as control. These samples include two surfaces covered with uniform W-coated rhenium micro-pillars; one with cylindrical pillars 1 μm in diameter and 25 μm in height, and one with dendritic conical pillars 4-10 μm in diameter and 20 μm in height. Additionally, two samples with reticulated open-cell foam geometry, one at 45 pores per inch (PPI), and the other at 80 PPI were fabricated with Chemical Vapor Deposition (CVD). The samples were exposed to helium plasma at 30-100 eV ion energy, 823-1123 K temperature, and 5 × 1025 - 2 × 1026 m-2 ion fluence. It is shown that the formation of nanometer-scale tendrils (fuzz) on micro-engineered W surfaces is greatly reduced as compared to planar surfaces. This is attributed to more significant ion backscattering and the increased effective surface area that intercept incident ions in micro-engineered W. A 20% decrease in the average ion incident angle on pillar type surfaces leads to ∼30% decrease in bubble size, down to 30 nm in diameter. W fuzz was found to be absent from pillar sides due to high ion backscattering rates from pillar sides. In foam samples, 28% higher PPI is observed to have 24.7%-36.7% taller fuzz, and 17.0%-25.0% larger subsurface bubbles. These are found to be an order of magnitude smaller than those found in planar surfaces of similar environment. The helium bubble density was found to increase with ion energy in pillars, roughly from 8.2% to 48.4%, and to increase with increasing PPI, from 36.4% to 116.2%, and with bubble concentrations up to 9.1 × 1021 m-3. Geometric shadowing effects in or near surface ligaments are observed in all foam samples, with near absence of helium bubbles or fuzz in deeper layers of the foam.

Design and optimization of the micro-engine turbine rotor manufacturing using the rapid prototyping technology

NASA Astrophysics Data System (ADS)

Vdovin, R. A.; Smelov, V. G.

2017-02-01

This work describes the experience in manufacturing the turbine rotor for the micro-engine. It demonstrates the design principles for the complex investment casting process combining the use of the ProCast software and the rapid prototyping techniques. At the virtual modelling stage, in addition to optimized process parameters, the casting structure was improved to obtain the defect-free section. The real production stage allowed demonstrating the performance and fitness of rapid prototyping techniques for the manufacture of geometrically-complex engine-building parts.

PUBLISHER'S ANNOUNCEMENT: A revised scope for Journal of Micromechanics and Microengineering A revised scope for Journal of Micromechanics and Microengineering

NASA Astrophysics Data System (ADS)

Forbes, Ian

2010-05-01

Journal of Micromechanics and Microengineering is well known for publishing excellent work in highly competitive timescales. The journal's coverage has consistently evolved to reflect the current state of the field, and from May 2010 it will revisit its scope once again. The aims of the journal remain unchanged, however: to be the first choice of authors and readers in MEMS and micro-scale research. The new scope continues to focus on highlighting the link between fabrication technologies and their capacity to create novel devices. This link will be considered paramount in the journal, and both prospective authors and readers should let it serve as an inspiration to them. The burgeoning fields of NEMS and nano-scale engineering are more explicitly supported in the new scope. Research which ten years ago would have been considered science fiction has, through the tireless efforts of the community, become reality. The Editorial Board feel it is important to reflect the growing significance of this work in the scope. The new scope, drafted by Editor-in-Chief Professor Mark Allen, and approved by the Editorial Board, is as follows: Journal of Micromechanics and Microengineering covers all aspects of microelectromechanical structures, devices, and systems, as well as micromechanics and micromechatronics. The journal focuses on original work in fabrication and integration technologies, on the micro- and nano-scale. The journal aims to highlight the link between new fabrication technologies and their capacity to create novel devices. Original work in microengineering and nanoengineering is also reported. Such work is defined as applications of these fabrication and integration technologies to structures in which key attributes of the devices or systems depend on specific micro- or nano-scale features. Such applications span the physical, chemical, electrical and biological realms. New fabrication and integration techniques for both silicon and non-silicon materials are reported. Relevant modelling papers in micro- and nanoengineering are reported where supported by experimental data. The journal also covers integration of interface electronics with micro- and nanoengineered systems, as well as vacuum microelectronics, microfabricated electrically passive elements, and other micro- or nanoengineering-enabled electrical devices.

Microengineering of magnetic bearings and actuators

NASA Astrophysics Data System (ADS)

Ghantasala, Muralihar K.; Qin, LiJiang; Sood, Dinesh K.; Zmood, Ronald B.

2000-06-01

Microengineering has evolved in the last decade as a subject of its own with the current research encompassing every possible area of devices from electromagnetic to optical and bio-micro electromechanical systems (MEMS). The primary advantage of the micro system technology is its small size, potential to produce high volume and low cost devices. However, the major impediments in the successful realization of many micro devices in practice are the reliability, packaging and integration with the existing microelectronics technology. Microengineering of actuators has recently grown tremendously due to its possible applicability to a wide range of devices of practical importance and the availability of a choice of materials. Selection of materials has been one of the important aspects of the design and fabrication of many micro system and actuators. This paper discusses the issues related to the selection of materials and subsequently their effect on the performance of the actuator. These will be discussed taking micro magnetic actuators and bearings, in particular, as examples. Fabrication and processing strategies and performance evaluation methods adopted will be described. Current status of the technology and projected futuristic applications in this area will be reviewed.

How Small Is Too Small? Technology into 2035

DTIC Science & Technology

2010-12-01

by Arrayed Polyimide Joint Actuators,” Journal of Micromechanics and Microengineering 10, no. 3 [2000]: 337–49.) 6 A more integrated microrobot is...application-specific in- tegrated circuit used for overall control; three piezoelectric legs used for forward, reverse, and z-axis rotation move- ments...a piezoelectric touch sensor; and power storage Figure 3. Captured video image of an integrated and autonomous micro- robot. (Reproduced from Seth

Where microbiology meets microengineering: design and applications of reporter bacteria.

PubMed

van der Meer, Jan Roelof; Belkin, Shimshon

2010-07-01

Bacteria have long been the targets for genetic manipulation, but more recently they have been synthetically designed to carry out specific tasks. Among the simplest of these tasks is chemical compound and toxicity detection coupled to the production of a quantifiable reporter signal. In this Review, we describe the current design of bacterial bioreporters and their use in a range of assays to measure the presence of harmful chemicals in water, air, soil, food or biological specimens. New trends for integrating synthetic biology and microengineering into the design of bacterial bioreporter platforms are also highlighted.

Microfabrication of hybrid fluid membrane for microengines

NASA Astrophysics Data System (ADS)

Chutani, R.; Formosa, F.; de Labachelerie, M.; Badel, A.; Lanzetta, F.

2015-12-01

This paper describes the microfabrication and dynamic characterization of thick membranes providing a technological solution for microengines. The studied membranes are called hybrid fluid-membrane (HFM) and consist of two thin membranes that encapsulate an incompressible fluid. This work details the microelectromechanical system (MEMS) scalable fabrication and characterization of HFMs. The membranes are composite structures based on Silicon spiral springs embedded in a polymer (RTV silicone). The anodic bonding of multiple stacks of Si/glass structures, the fluid filling and the sealing have been demonstrated. Various HFMs were successfully fabricated and their dynamic characterization demonstrates the agreement between experimental and theoretical results.

IR spectroscopic studies in microchannel structures

NASA Astrophysics Data System (ADS)

Guber, A. E.; Bier, W.

1998-06-01

By means of the various microengineering methods available, microreaction systems can be produced among others. These microreactors consist of microchannels, where chemical reactions take place under defined conditions. For optimum process control, continuous online analytics is envisaged in the microchannels. For this purpose, a special analytical module has been developed. It may be applied for IR spectroscopic studies at any point of the microchannel.

Satellite-On-A-Chip Feasibility for Distributed Space Missions

DTIC Science & Technology

2006-07-10

S.pdf Satellite Systems Conference and Exhibit, Monterey, [33] H . Helvajian and S. W. Janson, "The Fabrication of a CA, 2004, Paper AIAA-2004-3152. 100...pp. 12-15. 700. [52]0. Yadid-Pecht and R. Etienne-Cummings, CMOS [64]S. W. Janson, H . Helvajian , S. Amimoto, G. Smit, D. Imagers: From...Janson, H . Helvajian , and K. Breuer "MEMS, Hasler, "A 80 p W/frame 104x128 CMOS Imager Microengineering and Aerospace Systems," in Proc. Front End for

SAM-based Cell Transfer to Photopatterned Hydrogels for Microengineering Vascular-Like Structures

PubMed Central

Sadr, Nasser; Zhu, Mojun; Osaki, Tatsuya; Kakegawa, Takahiro; Yang, Yunzhi; Moretti, Matteo; Fukuda, Junji; Khademhosseini, Ali

2011-01-01

A major challenge in tissue engineering is to reproduce the native 3D microvascular architecture fundamental for in vivo functions. Current approaches still lack a network of perfusable vessels with native 3D structural organization. Here we present a new method combining self-assembled monolayer (SAM)-based cell transfer and gelatin methacrylate hydrogel photopatterning techniques for microengineering vascular structures. Human umbilical vein cell (HUVEC) transfer from oligopeptide SAM-coated surfaces to the hydrogel revealed two SAM desorption mechanisms: photoinduced and electrochemically triggered. The former, occurs concomitantly to hydrogel photocrosslinking, and resulted in efficient (>97%) monolayer transfer. The latter, prompted by additional potential application, preserved cell morphology and maintained high transfer efficiency of VE-cadherin positive monolayers over longer culture periods. This approach was also applied to transfer HUVECs to 3D geometrically defined vascular-like structures in hydrogels, which were then maintained in perfusion culture for 15 days. As a step toward more complex constructs, a cell-laden hydrogel layer was photopatterned around the endothelialized channel to mimic the vascular smooth muscle structure of distal arterioles. This study shows that the coupling of the SAM-based cell transfer and hydrogel photocrosslinking could potentially open up new avenues in engineering more complex, vascularized tissue constructs for regenerative medicine and tissue engineering applications. PMID:21802723

Measurements and analyses of principal dynamic parameters of building structures as a function of type of vibration excitation

NASA Astrophysics Data System (ADS)

Bartmański, Cezary; Bochenek, Wojciech; Passia, Henryk; Szade, Adam

2006-06-01

The methods of direct measurement and analysis of the dynamic response of a building structure through real-time recording of the amplitude of low-frequency vibration (tilt) have been presented. Subject to analyses was the reaction induced either by kinematic excitation (road traffic and mining-induced vibration) or controlled action of solid-fuel rocket micro-engines installed on the building. The forces were analysed by means of a set of transducers installed both in the ground and on the structure. After the action of excitation forces has been stopped, the system (structure) makes damped vibration around the static equilibrium position. It has been shown that the type of excitation affects the accuracy of evaluation of principal dynamic parameters of the structure. In the authors opinion these are the decrement of damping and natural vibration frequency. Positive results of tests with the use of excitation by means of short-action (0.6 second) rocket micro-engines give a chance to develop a reliable method for periodical assessment of acceptable loss of usability characteristics of building structures heavily influenced by environmental effects.

Mechanical characterization of bulk Sylgard 184 for microfluidics and microengineering

NASA Astrophysics Data System (ADS)

Johnston, I. D.; McCluskey, D. K.; Tan, C. K. L.; Tracey, M. C.

2014-03-01

Polydimethylsiloxane (PDMS) elastomers are extensively used for soft lithographic replication of microstructures in microfluidic and micro-engineering applications. Elastomeric microstructures are commonly required to fulfil an explicit mechanical role and accordingly their mechanical properties can critically affect device performance. The mechanical properties of elastomers are known to vary with both curing and operational temperatures. However, even for the elastomer most commonly employed in microfluidic applications, Sylgard 184, only a very limited range of data exists regarding the variation in mechanical properties of bulk PDMS with curing temperature. We report an investigation of the variation in the mechanical properties of bulk Sylgard 184 with curing temperature, over the range 25 °C to 200 °C. PDMS samples for tensile and compressive testing were fabricated according to ASTM standards. Data obtained indicates variation in mechanical properties due to curing temperature for Young's modulus of 1.32-2.97 MPa, ultimate tensile strength of 3.51-7.65 MPa, compressive modulus of 117.8-186.9 MPa and ultimate compressive strength of 28.4-51.7 GPa in a range up to 40% strain and hardness of 44-54 ShA.

Selective hydrophilic modification of Parylene C films: a new approach to cell micro-patterning for synthetic biology applications.

PubMed

Trantidou, T; Rao, C; Barrett, H; Camelliti, P; Pinto, K; Yacoub, M H; Athanasiou, T; Toumazou, C; Terracciano, C M; Prodromakis, T

2014-06-01

We demonstrate a simple, accurate and versatile method to manipulate Parylene C, a material widely known for its high biocompatibility, and transform it to a substrate that can effectively control the cellular microenvironment and consequently affect the morphology and function of the cells in vitro. The Parylene C scaffolds are fabricated by selectively increasing the material's surface water affinity through lithography and oxygen plasma treatment, providing free bonds for attachment of hydrophilic biomolecules. The micro-engineered constructs were tested as culture scaffolds for rat ventricular fibroblasts and neonatal myocytes (NRVM), toward modeling the unique anisotropic architecture of native cardiac tissue. The scaffolds induced the patterning of extracellular matrix compounds and therefore of the cells, which demonstrated substantial alignment compared to typical unstructured cultures. Ca(2+) cycling properties of the NRVM measured at rates of stimulation 0.5-2 Hz were significantly modified with a shorter time to peak and time to 90% decay, and a larger fluorescence amplitude (p < 0.001). The proposed technique is compatible with standard cell culturing protocols and exhibits long-term pattern durability. Moreover, it allows the integration of monitoring modalities into the micro-engineered substrates for a comprehensive interrogation of physiological parameters.

Microengineering as a tool to study substratum modulation and cell behaviour.

PubMed

Keatch, R P; Armoogum, K; Schor, S L; Pridham, M S; Banks, K; Khor, T Y; Matthew, C

2002-01-01

This research is an investigation of the means by which geometrical parameters (e.g. area and shape) and various surface attributes (materials and surface finish) of microengineered structures can modulate cellular response. This is based on biological observations indicating that: (i) the response of tissue cells to injury is determined by the net signal transduction response elicited by soluble regulatory molecules (e.g. cytokines), (ii) common matrix constituents (e.g. collagen) directly affect cell behaviour by the same signal transduction mechanisms mediating cytokine bioactivity, (iii) cellular response to cytokines is modulated by the precise nature of the extracellular matrix to which the target cells are adherent, including its biochemical composition and physical structure.

Three-dimensional microelectromechanical tilting platform operated by gear-driven racks

DOEpatents

Klody, Kelly A.; Habbit, Jr., Robert D.

2005-11-01

A microelectromechanical (MEM) tiltable-platform apparatus is disclosed which utilizes a light-reflective platform (i.e. a micromirror) which is supported above a substrate by flexures which can be bent upwards to tilt the platform in any direction over an angle of generally .+-.10 degrees using a gear-driven rack attached to each flexure. Each rack is driven by a rotary microengine (i.e. a micromotor); and an optional thermal actuator can be used in combination with each microengine for initially an initial uplifting of the platform away from the substrate. The MEM apparatus has applications for optical switching (e.g. between a pair of optical fibers) or for optical beam scanning.

Thin teflon-like films for MEMS: Film properties and reliability studies

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

Smith, B.K.; LaVigne, G.; Sniegowski, J.J.

1998-07-01

This work presents film properties and initial reliability studies for thin Teflon-like films applied to a unique test vehicle, the Sandia-designed and fabricated microengine. Results on microengines coated with the film show a factor of three improvement in their lifetime and an order of magnitude reduction in the coefficient of friction when compared to uncoated samples. Coefficients Of Friction (COF) of 0.07 for the Teflon-like film and 1.0 for uncoated samples are extracted from models which match the measured behavior of working microengines. These films, deposited form a plasma source, exhibit the ability to penetrate into very narrow, deep channelsmore » common to many MEMS devices. For as-deposited film, both the refractive index at 1.4 and the contact angle with water at 108{degree} show the film to be very similar to bulk Teflon PTFE. Film stability as a function of temperature has been examined using Fourier Transformation Infrared (FTIR) spectroscopy. The film structure as observed by the fluorine-carbon (F-C) peak is stable up to 200 C, but starts decomposing above 250 C. Film composition has been examined using X-ray photoelectron spectroscopy (XPS) and is quite different for directly exposed surfaces compared with deep, narrow channels where the deposition process is diffusion limited.« less

Space Station technology testbed: 2010 deep space transport

NASA Technical Reports Server (NTRS)

Holt, Alan C.

1993-01-01

A space station in a crew-tended or permanently crewed configuration will provide major R&D opportunities for innovative, technology and materials development and advanced space systems testing. A space station should be designed with the basic infrastructure elements required to grow into a major systems technology testbed. This space-based technology testbed can and should be used to support the development of technologies required to expand our utilization of near-Earth space, the Moon and the Earth-to-Jupiter region of the Solar System. Space station support of advanced technology and materials development will result in new techniques for high priority scientific research and the knowledge and R&D base needed for the development of major, new commercial product thrusts. To illustrate the technology testbed potential of a space station and to point the way to a bold, innovative approach to advanced space systems' development, a hypothetical deep space transport development and test plan is described. Key deep space transport R&D activities are described would lead to the readiness certification of an advanced, reusable interplanetary transport capable of supporting eight crewmembers or more. With the support of a focused and highly motivated, multi-agency ground R&D program, a deep space transport of this type could be assembled and tested by 2010. Key R&D activities on a space station would include: (1) experimental research investigating the microgravity assisted, restructuring of micro-engineered, materials (to develop and verify the in-space and in-situ 'tuning' of materials for use in debris and radiation shielding and other protective systems), (2) exposure of microengineered materials to the space environment for passive and operational performance tests (to develop in-situ maintenance and repair techniques and to support the development, enhancement, and implementation of protective systems, data and bio-processing systems, and virtual reality and telepresence/kinetic processes), (3) subsystem tests of advanced nuclear power, nuclear propulsion and communication systems (using boom extensions, remote station-keeping platforms and mobile EVA crew and robots), and (4) logistics support (crew and equipment) and command and control of deep space transport assembly, maintenance, and refueling (using a station-keeping platform).

SAM-based cell transfer to photopatterned hydrogels for microengineering vascular-like structures.

PubMed

Sadr, Nasser; Zhu, Mojun; Osaki, Tatsuya; Kakegawa, Takahiro; Yang, Yunzhi; Moretti, Matteo; Fukuda, Junji; Khademhosseini, Ali

2011-10-01

A major challenge in tissue engineering is to reproduce the native 3D microvascular architecture fundamental for in vivo functions. Current approaches still lack a network of perfusable vessels with native 3D structural organization. Here we present a new method combining self-assembled monolayer (SAM)-based cell transfer and gelatin methacrylate hydrogel photopatterning techniques for microengineering vascular structures. Human umbilical vein cell (HUVEC) transfer from oligopeptide SAM-coated surfaces to the hydrogel revealed two SAM desorption mechanisms: photoinduced and electrochemically triggered. The former, occurs concomitantly to hydrogel photocrosslinking, and resulted in efficient (>97%) monolayer transfer. The latter, prompted by additional potential application, preserved cell morphology and maintained high transfer efficiency of VE-cadherin positive monolayers over longer culture periods. This approach was also applied to transfer HUVECs to 3D geometrically defined vascular-like structures in hydrogels, which were then maintained in perfusion culture for 15 days. As a step toward more complex constructs, a cell-laden hydrogel layer was photopatterned around the endothelialized channel to mimic the vascular smooth muscle structure of distal arterioles. This study shows that the coupling of the SAM-based cell transfer and hydrogel photocrosslinking could potentially open up new avenues in engineering more complex, vascularized tissue constructs for regenerative medicine and tissue engineering applications. Copyright © 2011 Elsevier Ltd. All rights reserved.

Laser Material Processing for Microengineering Applications

NASA Technical Reports Server (NTRS)

Helvajian, H.

1995-01-01

The processing of materials via laser irradiation is presented in a brief survey. Various techniques currently used in laser processing are outlined and the significance to the development of space qualified microinstrumentation are identified. In general the laser processing technique permits the transferring of patterns (i.e. lithography), machining (i.e. with nanometer precision), material deposition (e.g., metals, dielectrics), the removal of contaminants/debris/passivation layers and the ability to provide process control through spectroscopy.

Microengineering of artificial capillaries

NASA Astrophysics Data System (ADS)

Moldovan, Nicanor I.

2002-11-01

Biocompatibility and functionality of implanted inorganic medical devices is limited by the local reaction of the organism, with a recently recognized contribution of nearby microvasculature. We explored the possibility to microengineer pre-embedded microvascular networks in the surface of inorganic devices. The implants would thus function as carriers of pre-assembled microvessels, ready to expand, and contribute to local angiogenesis. Based on our own studies on the role played by local microtopography in angiogenesis (the tunneling concept), we have shown the feasibility of endothelial cells cultivation in grooves created on the surface of the materials to be implanted, either polymeric or silicon. In order to develop this new technology, we devised an in situ approach to the study of the cellular behavior on micropatterned surfaces, by use of Laser Scanning Cytometry (LSC). In this report I will present our results regarding the LSC analysis of endothelial cells cultivated in grooves made on the surface of silicon wafers, and the consequences of this treatment on endothelial physiology. When comparing the growth of endothelial cells on line patterned and non-patterned areas, in terms of several morphological parameters of cell nuclei, our data support the conclusion that lateral confinement of endothelial cells induces a quiescent state, possibly by inhibiting their ability to proliferate.

Live single-cell laser tag.

PubMed

Binan, Loïc; Mazzaferri, Javier; Choquet, Karine; Lorenzo, Louis-Etienne; Wang, Yu Chang; Affar, El Bachir; De Koninck, Yves; Ragoussis, Jiannis; Kleinman, Claudia L; Costantino, Santiago

2016-05-20

The ability to conduct image-based, non-invasive cell tagging, independent of genetic engineering, is key to cell biology applications. Here we introduce cell labelling via photobleaching (CLaP), a method that enables instant, specific tagging of individual cells based on a wide array of criteria such as shape, behaviour or positional information. CLaP uses laser illumination to crosslink biotin onto the plasma membrane, coupled with streptavidin conjugates to label individual cells for genomic, cell-tracking, flow cytometry or ultra-microscopy applications. We show that the incorporated mark is stable, non-toxic, retained for several days, and transferred by cell division but not to adjacent cells in culture. To demonstrate the potential of CLaP for genomic applications, we combine CLaP with microfluidics-based single-cell capture followed by transcriptome-wide next-generation sequencing. Finally, we show that CLaP can also be exploited for inducing transient cell adhesion to substrates for microengineering cultures with spatially patterned cell types.

Cellular and multicellular form and function.

PubMed

Liu, Wendy F; Chen, Christopher S

2007-11-10

Engineering artificial tissue constructs requires the appropriate spatial arrangement of cells within scaffolds. The introduction of microengineering tools to the biological community has provided a valuable set of techniques to manipulate the cellular environment, and to examine how cell structure affects cellular function. Using micropatterning techniques, investigators have found that the geometric presentation of cell-matrix adhesions are important regulators of various cell behaviors including cell growth, proliferation, differentiation, polarity and migration. Furthermore, the presence of neighboring cells in multicellular aggregates has a significant impact on the proliferative and differentiated state of cells. Using microengineering tools, it will now be possible to manipulate the various environmental factors for practical applications such as engineering tissue constructs with greater control over the physical structure and spatial arrangement of cells within their surrounding microenvironment.

Microengineering of Metals and Ceramics: Part II: Special Replication Techniques, Automation and Properties; Volume 4: Advanced Micro & Nanosystems

NASA Astrophysics Data System (ADS)

Baltes, Henry; Brand, Oliver; Fedder, Gary K.; Hierold, Christofer; Korvink, Jan G.; Tabata, Osamu; Löhe, Detlef; Haußelt, Jürgen

2005-10-01

Microstructures, electronics, nanotechnology - these vast fields of research are growing together as the size gap narrows and many different materials are combined. Current research, engineering sucesses and newly commercialized products hint at the immense innovative potentials and future applications that open up once mankind controls shape and function from the atomic level right up to the visible world without any gaps. Continuing from the previous volume, authors from three major competence centres for microengineering here cover all aspects of specialized replication techniques and how to employ state-of-the-art technologies for testing and characterizing micro-scale components, and illustrate quality control aspects and strategies for automation of production procedures in view of future industrial production and commercialisation.

Directed 3D Cell Alignment and Elongation in Microengineered Hydrogels

DTIC Science & Technology

2010-01-01

Merok J, Vunjak- Novakovic G, Freed LE. Tissue engineering of functional cardiac muscle: molecular, structural, and electro- physiological studies. Am J...endothelial cells and smooth muscle cells. J Biomech 2004;37(4):531e9. [4] Vunjak- Novakovic G, Altman G, Horan R, Kaplan DL. Tissue engineering of...483e95. [9] Burdick JA, Vunjak- Novakovic G. Engineered microenvironments for controlled stem cell differentiation. Tissue Eng Part A 2009;15(2):205e19

3D Bioprinting for Tissue and Organ Fabrication

PubMed Central

Zhang, Yu Shrike; Yang, Jingzhou; Jia, Weitao; Dell’Erba, Valeria; Assawes, Pribpandao; Shin, Su Ryon; Dokmeci, Mehmet Remzi; Oklu, Rahmi; Khademhosseini, Ali

2016-01-01

The field of regenerative medicine has progressed tremendously over the past few decades in its ability to fabricate functional tissue substitutes. Conventional approaches based on scaffolding and microengineering are limited in their capacity of producing tissue constructs with precise biomimetic properties. Three-dimensional (3D) bioprinting technology, on the other hand, promises to bridge the divergence between artificially engineered tissue constructs and native tissues. In a sense, 3D bioprinting offers unprecedented versatility to co-deliver cells and biomaterials with precise control over their compositions, spatial distributions, and architectural accuracy, therefore achieving detailed or even personalized recapitulation of the fine shape, structure, and architecture of target tissues and organs. Here we briefly describe recent progresses of 3D bioprinting technology and associated bioinks suitable for the printing process. We then focus on the applications of this technology in fabrication of biomimetic constructs of several representative tissues and organs, including blood vessel, heart, liver, and cartilage. We finally conclude with future challenges in 3D bioprinting as well as potential solutions for further development. PMID:27126775

3D Bioprinting for Tissue and Organ Fabrication.

PubMed

Zhang, Yu Shrike; Yue, Kan; Aleman, Julio; Moghaddam, Kamyar Mollazadeh; Bakht, Syeda Mahwish; Yang, Jingzhou; Jia, Weitao; Dell'Erba, Valeria; Assawes, Pribpandao; Shin, Su Ryon; Dokmeci, Mehmet Remzi; Oklu, Rahmi; Khademhosseini, Ali

2017-01-01

The field of regenerative medicine has progressed tremendously over the past few decades in its ability to fabricate functional tissue substitutes. Conventional approaches based on scaffolding and microengineering are limited in their capacity of producing tissue constructs with precise biomimetic properties. Three-dimensional (3D) bioprinting technology, on the other hand, promises to bridge the divergence between artificially engineered tissue constructs and native tissues. In a sense, 3D bioprinting offers unprecedented versatility to co-deliver cells and biomaterials with precise control over their compositions, spatial distributions, and architectural accuracy, therefore achieving detailed or even personalized recapitulation of the fine shape, structure, and architecture of target tissues and organs. Here we briefly describe recent progresses of 3D bioprinting technology and associated bioinks suitable for the printing process. We then focus on the applications of this technology in fabrication of biomimetic constructs of several representative tissues and organs, including blood vessel, heart, liver, and cartilage. We finally conclude with future challenges in 3D bioprinting as well as potential solutions for further development.

An Embedded Fusion Processor

DTIC Science & Technology

2000-10-01

available from rooksj~,rl.af.mil [4] J. Lyke and G. Forman "Microengineering Aerospace Systems" H . Helvajian editor, The Aerospace Press 1999, Chapter 8...e h I O iinterface chip, and Synchronous Dynamic Random 1K-byte. The only consequence is that after the FIFO is Access Memory (SDRAM). Each interface...shown in figure 4a, that will be used for the 1/O interconnects in place of the perimeter bond pads used in the MCM3A. The 6’ h layer is used to

Small-scale heat detection using catalytic microengines irradiated by laser

NASA Astrophysics Data System (ADS)

Liu, Zhaoqian; Li, Jinxing; Wang, Jiao; Huang, Gaoshan; Liu, Ran; Mei, Yongfeng

2013-01-01

We demonstrate a novel approach to modulating the motion speed of catalytic microtubular engines via laser irradiation/heating with regard to small-scale heat detection. Laser irradiation on the engines leads to a thermal heating effect and thus enhances the engine speed. During a laser on/off period, the motion behaviour of a microengine can be repeatable and reversible, demonstrating a regulation of motion speeds triggered by laser illumination. Also, the engine velocity exhibits a linear dependence on laser power in various fuel concentrations, which implies an application potential as local heat sensors. Our work may hold great promise in applications such as lab on a chip, micro/nano factories, and environmental detection.We demonstrate a novel approach to modulating the motion speed of catalytic microtubular engines via laser irradiation/heating with regard to small-scale heat detection. Laser irradiation on the engines leads to a thermal heating effect and thus enhances the engine speed. During a laser on/off period, the motion behaviour of a microengine can be repeatable and reversible, demonstrating a regulation of motion speeds triggered by laser illumination. Also, the engine velocity exhibits a linear dependence on laser power in various fuel concentrations, which implies an application potential as local heat sensors. Our work may hold great promise in applications such as lab on a chip, micro/nano factories, and environmental detection. Electronic supplementary information (ESI) available. See DOI: 10.1039/c2nr32494f

Electrical stimulation of microengineered skeletal muscle tissue: Effect of stimulus parameters on myotube contractility and maturation.

PubMed

Banan Sadeghian, Ramin; Ebrahimi, Majid; Salehi, Sahar

2018-04-01

Skeletal muscle tissues engineered in vitro are aneural, are short in the number of fibres required to function properly and degenerate rapidly. Electrical stimulation has been widely used to compensate for such a lack of neural activity, yet the relationship between the stimulation parameters and the tissue response is subject to debate. Here we studied the effect of overnight electrical stimulation (training) on the contractility and maturity of aligned C2C12 myotubes developed on micropatterned gelatin methacryloyl (GelMA) substrates. Bipolar rectangular pulse (BRP) trains with frequency, half-duration and applied pulse train amplitudes of f = 1 Hz, t on  = 0.5 ms and V app  = {3 V, 4 V, 4.5 V}, respectively, were applied for 12 h to the myotubes formed on the microgrooved substrates. Aligned myotubes were contracting throughout the training period for V app  ≥ 4 V. Immediately after training, the samples were subjected to series of BRPs with 2 ≤ V app  ≤ 5 V and 0.2 ≤ t on  ≤ 0.9 ms, during which myotube contraction dynamics were recorded. Analysis of post-training contraction revealed that only the myotubes trained at V app  = 4 V displayed consistent and repeatable contraction profiles, showing the dynamics of myotube contractility as a function of triggering pulse voltage and current amplitudes, duration and imposed electrical energy. In addition, myotubes trained at V app  = 4 V displayed amplified expression levels of genes pertinent to sarcomere development correlated with myotube maturation. Our findings are imperative for a better understanding of the influence of electrical pulses on the maturation of microengineered myotubes. Copyright © 2017 John Wiley & Sons, Ltd.

Micromotor-based lab-on-chip immunoassays

NASA Astrophysics Data System (ADS)

García, Miguel; Orozco, Jahir; Guix, Maria; Gao, Wei; Sattayasamitsathit, Sirilak; Escarpa, Alberto; Merkoçi, Arben; Wang, Joseph

2013-01-01

Here we describe the first example of using self-propelled antibody-functionalized synthetic catalytic microengines for capturing and transporting target proteins between the different reservoirs of a lab-on-a-chip (LOC) device. A new catalytic polymer/Ni/Pt microtube engine, containing carboxy moieties on its mixed poly(3,4-ethylenedioxythiophene) (PEDOT)/COOH-PEDOT polymeric outermost layer, is further functionalized with the antibody receptor to selectively recognize and capture the target protein. The new motor-based microchip immunoassay operations are carried out without any bulk fluid flow, replacing the common washing steps in antibody-based protein bioassays with the active transport of the captured protein throughout the different reservoirs, where each step of the immunoassay takes place. A first microchip format involving an `on-the-fly' double-antibody sandwich assay (DASA) is used for demonstrating the selective capture of the target protein, in the presence of excess of non-target proteins. A secondary antibody tagged with a polymeric-sphere tracer allows the direct visualization of the binding events. In a second approach the immuno-nanomotor captures and transports the microsphere-tagged antigen through a microchannel network. An anti-protein-A modified microengine is finally used to demonstrate the selective capture, transport and convenient label-free optical detection of a Staphylococcus aureus target bacteria (containing proteinA in its cell wall) in the presence of a large excess of non-target (Saccharomyces cerevisiae) cells. The resulting nanomotor-based microchip immunoassay offers considerable potential for diverse applications in clinical diagnostics, environmental and security monitoring fields.Here we describe the first example of using self-propelled antibody-functionalized synthetic catalytic microengines for capturing and transporting target proteins between the different reservoirs of a lab-on-a-chip (LOC) device. A new catalytic polymer/Ni/Pt microtube engine, containing carboxy moieties on its mixed poly(3,4-ethylenedioxythiophene) (PEDOT)/COOH-PEDOT polymeric outermost layer, is further functionalized with the antibody receptor to selectively recognize and capture the target protein. The new motor-based microchip immunoassay operations are carried out without any bulk fluid flow, replacing the common washing steps in antibody-based protein bioassays with the active transport of the captured protein throughout the different reservoirs, where each step of the immunoassay takes place. A first microchip format involving an `on-the-fly' double-antibody sandwich assay (DASA) is used for demonstrating the selective capture of the target protein, in the presence of excess of non-target proteins. A secondary antibody tagged with a polymeric-sphere tracer allows the direct visualization of the binding events. In a second approach the immuno-nanomotor captures and transports the microsphere-tagged antigen through a microchannel network. An anti-protein-A modified microengine is finally used to demonstrate the selective capture, transport and convenient label-free optical detection of a Staphylococcus aureus target bacteria (containing proteinA in its cell wall) in the presence of a large excess of non-target (Saccharomyces cerevisiae) cells. The resulting nanomotor-based microchip immunoassay offers considerable potential for diverse applications in clinical diagnostics, environmental and security monitoring fields. Electronic supplementary information (ESI) available. See DOI: 10.1039/c2nr32400h

Carbonate-based Janus micromotors moving in ultra-light acidic environment generated by HeLa cells in situ

NASA Astrophysics Data System (ADS)

Guix, Maria; Meyer, Anne K.; Koch, Britta; Schmidt, Oliver G.

2016-02-01

Novel approaches to develop naturally-induced drug delivery in tumor environments in a deterministic and controlled manner have become of growing interest in recent years. Different polymeric-based microstructures and other biocompatible substances have been studied taking advantage of lactic acidosis phenomena in tumor cells, which decrease the tumor extracellular pH down to 6.8. Micromotors have recently demonstrated a high performance in living systems, revealing autonomous movement in the acidic environment of the stomach or moving inside living cells by using acoustic waves, opening the doors for implementation of such smart microengines into living entities. The need to develop biocompatible motors which are driven by natural fuel sources inherently created in biological systems has thus become of crucial importance. As a proof of principle, we here demonstrate calcium carbonate Janus particles moving in extremely light acidic environments (pH 6.5), whose motion is induced in conditioned acidic medium generated by HeLa cells in situ. Our system not only obviates the need for an external fuel, but also presents a selective activation of the micromotors which promotes their motion and consequent dissolution in presence of a quickly propagating cell source (i.e. tumor cells), therefore inspiring new micromotor configurations for potential drug delivery systems.

Carbonate-based Janus micromotors moving in ultra-light acidic environment generated by HeLa cells in situ

PubMed Central

Guix, Maria; Meyer, Anne K.; Koch, Britta; Schmidt, Oliver G.

2016-01-01

Novel approaches to develop naturally-induced drug delivery in tumor environments in a deterministic and controlled manner have become of growing interest in recent years. Different polymeric-based microstructures and other biocompatible substances have been studied taking advantage of lactic acidosis phenomena in tumor cells, which decrease the tumor extracellular pH down to 6.8. Micromotors have recently demonstrated a high performance in living systems, revealing autonomous movement in the acidic environment of the stomach or moving inside living cells by using acoustic waves, opening the doors for implementation of such smart microengines into living entities. The need to develop biocompatible motors which are driven by natural fuel sources inherently created in biological systems has thus become of crucial importance. As a proof of principle, we here demonstrate calcium carbonate Janus particles moving in extremely light acidic environments (pH 6.5), whose motion is induced in conditioned acidic medium generated by HeLa cells in situ. Our system not only obviates the need for an external fuel, but also presents a selective activation of the micromotors which promotes their motion and consequent dissolution in presence of a quickly propagating cell source (i.e. tumor cells), therefore inspiring new micromotor configurations for potential drug delivery systems. PMID:26905939

An improved design for AlGaN solar-blind avalanche photodiodes with enhanced avalanche ionization

NASA Astrophysics Data System (ADS)

Tang, Yin; Cai, Qing; Yang, Lian-Hong; Dong, Ke-Xiu; Chen, Dun-Jun; Lu, Hai; Zhang, Rong; Zheng, You-Dou

2017-03-01

Not Available Project supported by the State Key Project of Research and Development Plan, China (Grant No. 2016YFB0400903), the National Natural Science Foundation of China (Grant Nos. 61634002, 61274075, and 61474060), the Key Project of Jiangsu Province, China (Grant No. BE2016174), the Anhui University Natural Science Research Project, China (Grant No. KJ2015A153), the Open Fund (KFS) of State Key Lab of Optical Technologieson Nanofabrication and Microengineering, Institute of Optics and Electronics, Chinese Academy of Science.

Liver regenerative medicine: advances and challenges.

PubMed

Chistiakov, Dimitry A

2012-01-01

Liver transplantation is the standard care for many end-stage liver diseases. However, donor organs are scarce and some people succumb to liver failure before a donor is found. Liver regenerative medicine is a special interdisciplinary field of medicine focused on the development of new therapies incorporating stem cells, gene therapy and engineered tissues in order to repair or replace the damaged organ. In this review we consider the emerging progress achieved in the hepatic regenerative medicine within the last decade. The review starts with the characterization of liver organogenesis, fetal and adult stem/progenitor cells. Then, applications of primary hepatocytes, embryonic and adult (mesenchymal, hematopoietic and induced pluripotent) stem cells in cell therapy of liver diseases are considered. Current advances and challenges in producing mature hepatocytes from stem/progenitor cells are discussed. A section about hepatic tissue engineering includes consideration of synthetic and natural biomaterials in engineering scaffolds, strategies and achievements in the development of 3D bioactive matrices and 3D hepatocyte cultures, liver microengineering, generating bioartificial liver and prospects for fabrication of the bioengineered liver. Copyright © 2012 S. Karger AG, Basel.

Tuning group-velocity dispersion by optical force.

PubMed

Jiang, Wei C; Lin, Qiang

2013-07-15

We propose an optomechanical approach for dispersion dynamic tuning and microengineering by taking advantage of the optical force in nano-optomechanical structures. Simulations of a suspended coupled silicon waveguide show that the zero-dispersion wavelength can be tuned by 40 nm by an optical pump power of 3 mW. Our approach exhibits great potential for broad applications in dispersion-sensitive processes, which not only offers a new root toward versatile tunable nonlinear photonics but may also open up a great avenue toward a new regime of nonlinear dynamics coupling between nonlinear optical and optomechanical effects.

Non-Invasive Monitoring for Optimization of Therapeutic Drug Delivery by Biodegradable Fiber to Prostate Tumor

DTIC Science & Technology

2008-02-01

v ol um e (c m ^3 ) Injection Internal pump External Pump Treatment starts Rat’s condition before treatment 0 0.2 0.4 0.6 0.8 1 550 650...of polysilicon thermal flexure actuator,” J. of Micromechanics and Microengineering.9, 2005. [36] A. Grayson, et.al., “Electronic MEMS for...36. [59] Q-H. Huang and N. K. S. Lee, “Analysis and design of polysilicon thermal flexure actuator,” J. Micromech. Microeng. 9 (1) pp. 64–70 (1999

Designing 3-Dimensional In Vitro Oviduct Culture Systems to Study Mammalian Fertilization and Embryo Production.

PubMed

Ferraz, Marcia A M M; Henning, Heiko H W; Stout, Tom A E; Vos, Peter L A M; Gadella, Bart M

2017-07-01

The oviduct was long considered a largely passive conduit for gametes and embryos. However, an increasing number of studies into oviduct physiology have demonstrated that it specifically and significantly influences gamete interaction, fertilization and early embryo development. While oviduct epithelial cell (OEC) function has been examined during maintenance in conventional tissue culture dishes, cells seeded into these two-dimensional (2-D) conditions suffer a rapid loss of differentiated OEC characteristics, such as ciliation and secretory activity. Recently, three-dimensional (3-D) cell culture systems have been developed that make use of cell inserts to create basolateral and apical medium compartments with a confluent epithelial cell layer at the interface. Using such 3-D culture systems, OECs can be triggered to redevelop typical differentiated cell properties and levels of tissue organization can be developed that are not possible in a 2-D culture. 3-D culture systems can be further refined using new micro-engineering techniques (including microfluidics and 3-D printing) which can be used to produce 'organs-on-chips', i.e. live 3-D cultures that bio-mimic the oviduct. In this review, concepts for designing bio-mimic 3-D oviduct cultures are presented. The increased possibilities and concomitant challenges when trying to more closely investigate oviduct physiology, gamete activation, fertilization and embryo production are discussed.

Biomimetic three-dimensional tissue models for advanced high-throughput drug screening

PubMed Central

Nam, Ki-Hwan; Smith, Alec S.T.; Lone, Saifullah; Kwon, Sunghoon; Kim, Deok-Ho

2015-01-01

Most current drug screening assays used to identify new drug candidates are 2D cell-based systems, even though such in vitro assays do not adequately recreate the in vivo complexity of 3D tissues. Inadequate representation of the human tissue environment during a preclinical test can result in inaccurate predictions of compound effects on overall tissue functionality. Screening for compound efficacy by focusing on a single pathway or protein target, coupled with difficulties in maintaining long-term 2D monolayers, can serve to exacerbate these issues when utilizing such simplistic model systems for physiological drug screening applications. Numerous studies have shown that cell responses to drugs in 3D culture are improved from those in 2D, with respect to modeling in vivo tissue functionality, which highlights the advantages of using 3D-based models for preclinical drug screens. In this review, we discuss the development of microengineered 3D tissue models which accurately mimic the physiological properties of native tissue samples, and highlight the advantages of using such 3D micro-tissue models over conventional cell-based assays for future drug screening applications. We also discuss biomimetic 3D environments, based-on engineered tissues as potential preclinical models for the development of more predictive drug screening assays for specific disease models. PMID:25385716

Biological effect of microengineered grooved stents on strut healing: a randomised OCT-based comparative study in humans

PubMed Central

Vesga, Boris; Hernandez, Hector; Higuera, Sergio; Gasior, Pawel; Echeveri, Dario; Delgado, Juan A; Dager, Antonio; Arana, Camilo; Simonton, Charles; Maehara, Akiko; Palmaz, Julio; Granada, Juan F

2017-01-01

Objective To evaluate the biological effect of microengineered stent grooves (MSG) on early strut healing in humans by performing optical coherence tomography (OCT) analysis 3 weeks following the implantation. Background In the experimental setting, MSG accelerate endothelial cell migration and reduce neointimal proliferation compared with bare metal stent (BMS). Methods A total of 37 patients undergoing percutaneous coronary intervention with de novo coronary lesions were randomly assigned to either MSG (n=19) or an identical BMS controls (n=18). All patients underwent OCT imaging at 3 weeks. A total of 7959 struts were included in the final analysis. Results At 3 weeks following stent implantation, almost all struts analysed (~97%) had evidence of tissue coverage. The percentage of partially covered struts was comparable between both groups. However, the percentage of fully embedded struts was higher in the BMS group (81.22%, 49.75–95.52) compared with the MSG group (74.21%, 58.85–86.38). The stent-level analysis demonstrated reduction in neointimal formation (neointimal hyperplasia area and volume reduction of ~14% and ~19%, respectively) in the MSG versus the BMS group. In the strut-level analysis, an even greater reduction (~22% in neointimal thickness) was seen in the MSG group. Layered neointimal was present in ~6% of the OCT frames in the BMS group while it was not present in the MSG group. Conclusions MSG induced a more homogeneous and predictable pattern of surface healing in the early stages following stent implantation. The biological effect of MSG on stent healing has the potential to improve the safety profile of current generation drug-eluting stents. Classifications BMS, OCT, clinical trials. PMID:28674616

Biological effect of microengineered grooved stents on strut healing: a randomised OCT-based comparative study in humans.

PubMed

Vesga, Boris; Hernandez, Hector; Higuera, Sergio; Gasior, Pawel; Echeveri, Dario; Delgado, Juan A; Dager, Antonio; Arana, Camilo; Simonton, Charles; Maehara, Akiko; Palmaz, Julio; Granada, Juan F

2017-01-01

To evaluate the biological effect of microengineered stent grooves (MSG) on early strut healing in humans by performing optical coherence tomography (OCT) analysis 3 weeks following the implantation. In the experimental setting, MSG accelerate endothelial cell migration and reduce neointimal proliferation compared with bare metal stent (BMS). A total of 37 patients undergoing percutaneous coronary intervention with de novo coronary lesions were randomly assigned to either MSG (n=19) or an identical BMS controls (n=18). All patients underwent OCT imaging at 3 weeks. A total of 7959 struts were included in the final analysis. At 3 weeks following stent implantation, almost all struts analysed (~97%) had evidence of tissue coverage. The percentage of partially covered struts was comparable between both groups. However, the percentage of fully embedded struts was higher in the BMS group (81.22%, 49.75-95.52) compared with the MSG group (74.21%, 58.85-86.38). The stent-level analysis demonstrated reduction in neointimal formation (neointimal hyperplasia area and volume reduction of ~14% and ~19%, respectively) in the MSG versus the BMS group. In the strut-level analysis, an even greater reduction (~22% in neointimal thickness) was seen in the MSG group. Layered neointimal was present in ~6% of the OCT frames in the BMS group while it was not present in the MSG group. MSG induced a more homogeneous and predictable pattern of surface healing in the early stages following stent implantation. The biological effect of MSG on stent healing has the potential to improve the safety profile of current generation drug-eluting stents. BMS, OCT, clinical trials.

Hippo/YAP-mediated rigidity-dependent motor neuron differentiation of human pluripotent stem cells

NASA Astrophysics Data System (ADS)

Sun, Yubing; Yong, Koh Meng Aw; Villa-Diaz, Luis G.; Zhang, Xiaoli; Chen, Weiqiang; Philson, Renee; Weng, Shinuo; Xu, Haoxing; Krebsbach, Paul H.; Fu, Jianping

2014-06-01

Our understanding of the intrinsic mechanosensitive properties of human pluripotent stem cells (hPSCs), in particular the effects that the physical microenvironment has on their differentiation, remains elusive. Here, we show that neural induction and caudalization of hPSCs can be accelerated by using a synthetic microengineered substrate system consisting of poly(dimethylsiloxane) micropost arrays (PMAs) with tunable mechanical rigidities. The purity and yield of functional motor neurons derived from hPSCs within 23 days of culture using soft PMAs were improved more than fourfold and tenfold, respectively, compared with coverslips or rigid PMAs. Mechanistic studies revealed a multi-targeted mechanotransductive process involving Smad phosphorylation and nucleocytoplasmic shuttling, regulated by rigidity-dependent Hippo/YAP activities and actomyosin cytoskeleton integrity and contractility. Our findings suggest that substrate rigidity is an important biophysical cue influencing neural induction and subtype specification, and that microengineered substrates can thus serve as a promising platform for large-scale culture of hPSCs.

High Throughput and Mechano-Active Platforms to Promote Cartilage Regeneration and Repair

NASA Astrophysics Data System (ADS)

Mohanraj, Bhavana

Traumatic joint injuries initiate acute degenerative changes in articular cartilage that can lead to progressive loss of load-bearing function. As a result, patients often develop post-traumatic osteoarthritis (PTOA), a condition for which there currently exists no biologic interventions. To address this need, tissue engineering aims to mimic the structure and function of healthy, native counterparts. These constructs can be used to not only replace degenerated tissue, but also build in vitro, pre-clinical models of disease. Towards this latter goal, this thesis focuses on the design of a high throughput system to screen new therapeutics in a micro-engineered model of PTOA, and the development of a mechanically-responsive drug delivery system to augment tissue-engineered approaches for cartilage repair. High throughput screening is a powerful tool for drug discovery that can be adapted to include 3D tissue constructs. To facilitate this process for cartilage repair, we built a high throughput mechanical injury platform to create an engineered cartilage model of PTOA. Compressive injury of functionally mature constructs increased cell death and proteoglycan loss, two hallmarks of injury observed in vivo. Comparison of this response to that of native cartilage explants, and evaluation of putative therapeutics, validated this model for subsequent use in small molecule screens. A primary screen of 118 compounds identified a number of 'hits' and relevant pathways that may modulate pathologic signaling post-injury. To complement this process of therapeutic discovery, a stimuli-responsive delivery system was designed that used mechanical inputs as the 'trigger' mechanism for controlled release. The failure thresholds of these mechanically-activated microcapsules (MAMCs) were influenced by physical properties and composition, as well as matrix mechanical properties in 3D environments. TGF-beta released from the system upon mechano-activation stimulated stem cell chondrogenesis, demonstrating the potential of MAMCs to actively deliver therapeutics within demanding mechanical environments. Taken together, this work advances our capacity to identify and deliver new compounds of clinical relevance to modulate disease progression following traumatic injury using state-of-the-art micro-engineered screening tools and a novel mechanically-activated delivery system. These platforms advance strategies for cartilage repair and regeneration in PTOA and provide new options for the treatment of this debilitating condition.

Placenta-on-a-chip: a novel platform to study the biology of the human placenta.

PubMed

Lee, Ji Soo; Romero, Roberto; Han, Yu Mi; Kim, Hee Chan; Kim, Chong Jai; Hong, Joon-Seok; Huh, Dongeun

2016-01-01

Studying the biology of the human placenta represents a major experimental challenge. Although conventional cell culture techniques have been used to study different types of placenta-derived cells, current in vitro models have limitations in recapitulating organ-specific structure and key physiological functions of the placenta. Here we demonstrate that it is possible to leverage microfluidic and microfabrication technologies to develop a microengineered biomimetic model that replicates the architecture and function of the placenta. A "Placenta-on-a-Chip" microdevice was created by using a set of soft elastomer-based microfabrication techniques known as soft lithography. This microsystem consisted of two polydimethylsiloxane (PDMS) microfluidic channels separated by a thin extracellular matrix (ECM) membrane. To reproduce the placental barrier in this model, human trophoblasts (JEG-3) and human umbilical vein endothelial cells (HUVECs) were seeded onto the opposite sides of the ECM membrane and cultured under dynamic flow conditions to form confluent epithelial and endothelial layers in close apposition. We tested the physiological function of the microengineered placental barrier by measuring glucose transport across the trophoblast-endothelial interface over time. The permeability of the barrier study was analyzed and compared to that obtained from acellular devices and additional control groups that contained epithelial or endothelial layers alone. Our microfluidic cell culture system provided a tightly controlled fluidic environment conducive to the proliferation and maintenance of JEG-3 trophoblasts and HUVECs on the ECM scaffold. Prolonged culture in this model produced confluent cellular monolayers on the intervening membrane that together formed the placental barrier. This in vivo-like microarchitecture was also critical for creating a physiologically relevant effective barrier to glucose transport. Quantitative investigation of barrier function was conducted by calculating permeability coefficients and metabolic rates in varying conditions of barrier structure. The rates of glucose transport and metabolism were consistent with previously reported in vivo observations. The "Placenta-on-a-Chip" microdevice described herein provides new opportunities to simulate and analyze critical physiological responses of the placental barrier. This system may be used to address the major limitations of existing placenta model systems and serve to enable research platforms for reproductive biology and medicine.

Methodology of citrate-based biomaterial development and application

NASA Astrophysics Data System (ADS)

Tran, M. Richard

Biomaterials play central roles in modern strategies of regenerative medicine and tissue engineering. Attempts to find tissue-engineered solutions to cure various injuries or diseases have led to an enormous increase in the number of polymeric biomaterials over the past decade. The breadth of new materials arises from the multiplicity of anatomical locations, cell types, and mode of application, which all place application-specific requirements on the biomaterial. Unfortunately, many of the currently available biodegradable polymers are limited in their versatility to meet the wide range of requirements for tissue engineering. Therefore, a methodology of biomaterial development, which is able to address a broad spectrum of requirements, would be beneficial to the biomaterial field. This work presents a methodology of citrate-based biomaterial design and application to meet the multifaceted needs of tissue engineering. We hypothesize that (1) citric acid, a non-toxic metabolic product of the body (Krebs Cycle), can be exploited as a universal multifunctional monomer and reacted with various diols to produce a new class of soft biodegradable elastomers with the flexibility to tune the material properties of the resulting material to meet a wide range of requirements; (2) the newly developed citrate-based polymers can be used as platform biomaterials for the design of novel tissue engineering scaffolding; and (3) microengineering approaches in the form thin scaffold sheets, microchannels, and a new porogen design can be used to generate complex cell-cell and cell-microenvironment interactions to mimic tissue complexity and architecture. To test these hypotheses, we first developed a methodology of citrate-based biomaterial development through the synthesis and characterization of a family of in situ crosslinkable and urethane-doped elastomers, which are synthesized using simple, cost-effective strategies and offer a variety methods to tailor the material properties to meet the needs of a particular application. Next, we introduced a new porogen generation technique, and showed the potential application of the newly developed materials through the fabrication and characterization of scaffold sheets, multiphasic small diameter vascular grafts, and multichanneled nerve guides. Finally, the in vivo applications of citrate-based materials are exemplified through the evaluation of peripheral nerve regeneration using multichanneled guides and the ability to assist in injection-based endoscopic mucosal resection therapy. The results presented in this work show that citric acid can be utilized as a cornerstone in the development of novel biodegradable materials, and combined with microengineering approaches to produce the next generation of tissue engineering scaffolding. These enabling new biomaterials and scaffolding strategies should address many of the existing challenges in tissue engineering and advance the field as a whole.

Selected papers from the 7th International Conference on Microtechnologies in Medicine and Biology (MMB 2013)

NASA Astrophysics Data System (ADS)

Meng, Ellis; Takayama, Shuichi

2014-03-01

In this special section of Journal of Micromechanics and Microengineering are a collection of the best microengineering papers presented at the 7th International Conference on Microtechnologies in Medicine and Biology (MMB 2013) which took place in the seaside town of Marina del Rey, California, USA on 10-12 April, 2013. During the 3-day conference, participants enjoyed talks from 6 invited keynote speakers and 125 flash oral/poster presentations. The MMB conference is a biennial meeting with the primary purpose of fostering interactions between biologists and medical researchers, clinicians, chemists, physicists and engineers to enhance and strengthen the potential microtechnologies that will revolutionize the fields of medicine and biological sciences. The conference possesses a unique format where all poster presenters provide a brief 60 s oral presentation highlighting their research. This format was devised to provide training and exposure for young researchers, especially PhD students and postdocs, in the field and stimulate interdisciplinary exchanges. Therefore, MMB provides an intimate intellectual venue the facilitate discussions and collaborations to advance new research tools and technologies for medicine and biological sciences. The MMB conference series was co-founded by Professor David Beebe (University of Wisconsin—Madison) and Professor André Dittmar (University of Lyon) and was the first international meeting to provide a forum focusing on emerging applications of microtechnologies to unmet needs in medicine and biology. The series was held for the first time in 2000, in Lyon, France and followed by Madison, USA (2002), Oahu Island in Hawaii, USA (2005), Okinawa, Japan (2006), Québec City, Canada (2009), Lucerne, Switzerland (2011), and Marina del Rey, USA (2013). The next conference will be held in Seoul, Korea in 2015. This collection of articles highlights recent progress in microtechnologies with medical and biological applications. We are grateful to the many authors who contributed their research achievements to this exciting issue and to the anonymous reviewers for their invaluable insights and suggestions. We would also like to express our thanks to our colleagues on the international steering committee for their dedicated review of the selected presentations that appears at the conference. Finally, we appreciate the support of the editorial staff of Journal of Micromechanics and Microengineering for this inaugural MMB special issue. We look forward to continued collaboration in future MMB conferences.

Micromotor-based lab-on-chip immunoassays.

PubMed

García, Miguel; Orozco, Jahir; Guix, Maria; Gao, Wei; Sattayasamitsathit, Sirilak; Escarpa, Alberto; Merkoçi, Arben; Wang, Joseph

2013-02-21

Here we describe the first example of using self-propelled antibody-functionalized synthetic catalytic microengines for capturing and transporting target proteins between the different reservoirs of a lab-on-a-chip (LOC) device. A new catalytic polymer/Ni/Pt microtube engine, containing carboxy moieties on its mixed poly(3,4-ethylenedioxythiophene) (PEDOT)/COOH-PEDOT polymeric outermost layer, is further functionalized with the antibody receptor to selectively recognize and capture the target protein. The new motor-based microchip immunoassay operations are carried out without any bulk fluid flow, replacing the common washing steps in antibody-based protein bioassays with the active transport of the captured protein throughout the different reservoirs, where each step of the immunoassay takes place. A first microchip format involving an 'on-the-fly' double-antibody sandwich assay (DASA) is used for demonstrating the selective capture of the target protein, in the presence of excess of non-target proteins. A secondary antibody tagged with a polymeric-sphere tracer allows the direct visualization of the binding events. In a second approach the immuno-nanomotor captures and transports the microsphere-tagged antigen through a microchannel network. An anti-protein-A modified microengine is finally used to demonstrate the selective capture, transport and convenient label-free optical detection of a Staphylococcus aureus target bacteria (containing proteinA in its cell wall) in the presence of a large excess of non-target (Saccharomyces cerevisiae) cells. The resulting nanomotor-based microchip immunoassay offers considerable potential for diverse applications in clinical diagnostics, environmental and security monitoring fields.

Microfluidic hydrogels for tissue engineering.

PubMed

Huang, Guo You; Zhou, Li Hong; Zhang, Qian Cheng; Chen, Yong Mei; Sun, Wei; Xu, Feng; Lu, Tian Jian

2011-03-01

With advanced properties similar to the native extracellular matrix, hydrogels have found widespread applications in tissue engineering. Hydrogel-based cellular constructs have been successfully developed to engineer different tissues such as skin, cartilage and bladder. Whilst significant advances have been made, it is still challenging to fabricate large and complex functional tissues due mainly to the limited diffusion capability of hydrogels. The integration of microfluidic networks and hydrogels can greatly enhance mass transport in hydrogels and spatiotemporally control the chemical microenvironment of cells, mimicking the function of native microvessels. In this review, we present and discuss recent advances in the fabrication of microfluidic hydrogels from the viewpoint of tissue engineering. Further development of new hydrogels and microengineering technologies will have a great impact on tissue engineering.

Laser Embossing of Micro-and Submicrometer Surface Structures in Copper

NASA Astrophysics Data System (ADS)

Ehrhardt, Martin; Lorenz, Pierre; Frost, Frank; Zimmer, Klaus

Micro- and submicrometer structures have been transferred from nickel foils into solid copper surfaces by laser microembossing. The developed arrangement for laser microembossing allows a large-area replication using multi- pulse laser scanning scheme, guaranties a low contamination of the embossed surface and enables the utilization of thick workpieces. In the micrometer range the replicated patterns feature a high accuracy regarding the shape. A significant difference between the master and the replication pattern could be observed for the laser embossing of submicrometer patterns. In conclusion, the results show that the proposed laser embossing process is a promising method with a number of applications in microengineering.

Near-infrared light-triggered "on/off" motion of polymer multilayer rockets.

PubMed

Wu, Zhiguang; Lin, Xiankun; Wu, Yingjie; Si, Tieyan; Sun, Jianmin; He, Qiang

2014-06-24

We describe an approach to modulating the on-demand motion of catalytic polymer-based microengines via near-infrared (NIR) laser irradiation. The polymer multilayer motor was fabricated by the template-assisted layer-by-layer assembly and subsequently deposition of platinum nanoparticles inside and a thin gold shell outside. Then a mixed monolayer of a tumor-targeted peptide and an antifouling poly(ethylene glycol) was functionalized on the gold shell. The microengines remain motionless at the critical peroxide concentration (0.1%, v/v); however, NIR illumination on the engines leads to a photothermal effect and thus rapidly triggers the motion of the catalytic engines. Computational modeling explains the photothermal effect and gives the temperature profile accordingly. Also, the photothermal effect can alone activate the motion of the engines in the absence of the peroxide fuel, implying that it may eliminate the use of toxic fuel in the future. The targeted recognition ability and subsequently killing of cancer cells by the photothermal effect under the higher power of a NIR laser were illustrated. Our results pave the way to apply self-propelled synthetic engines in biomedical fields.

EDITORIAL: 16th European Workshop on Micromechanics (MME 2005)

NASA Astrophysics Data System (ADS)

Enoksson, Professor Peter

2006-06-01

This special issue of Journal of Micromechanics and Microengineering is devoted to the 16th European Workshop on Micromechanics (MME 2005), which was held in Göteborg, Sweden, at the Chalmers Conference Centre on the premises of Chalmers University of Technology, 4-6 September 2005. Göteborg is the second largest city in Sweden and is situated on the beautiful south-west coast. With its relaxed and friendly atmosphere Göteborg proudly lives up to its reputation of having the charm of a small town with all the opportunities of a big city. The MME workshop is a well recognized and established European event for creating microsensors and microactuators in the field of micromachining, microengineering and technology. The very first workshop was held at Twente University, The Netherlands, in 1989. Scientists and people from industry who are interested in the field gather annually for this event. The goals are stimulation and improvement of know-how in the field, as well as establishing cooperation and friendship between delegates. Thus MME is arranged so that people can meet in a friendly and informal atmosphere. That is why the accent is on mutual discussions around poster presentations rather than on formal oral presentations. The contributions, which came from 21 countries, were presented in four sessions and five keynote presentations. I am proud to present 24 high-quality papers from MME 2005 selected for their novelty and relevance to Journal of Micromechanics and Microengineering. Each paper passed a rigorous peer review process. May I take this opportunity to thank those authors who contributed their research to this special issue, which I hope gives an excellent overview of topics discussed at the workshop. I would also like to express my gratitude to Professor Robert Puers for advising on the selection of papers and to Dr Anke Sanz-Velasco for helping to coordinate the special issue with the Institute of Physics Publishing office at the start. I hope you enjoy reading this selection of papers.

Editorial

NASA Astrophysics Data System (ADS)

Puers, R.

2007-01-01

As we enter the 2007 volume of Journal of Micromechanics and Microengineering, the journal's seventeenth, I would like to take the opportunity to reflect on the achievements of the past year. The considerable increase in submissions to the journal, as you all may have noticed by the steadily increasing volume, is the most visible change. A total of 3272 pages were published in 2006, an increase of 12% on 2005. More exciting, and maybe less noticeable, is that the journal's ISI® impact factor saw a significant increase to 2.499. This is an achievement we can all be proud of. If the journal and its impact factor are growing, it is only because more of you are choosing to submit your high-quality work to the journal, and because more of you are choosing to refer to recent papers published within the journal! I would like to take this opportunity to thank each of you, readers, authors and referees alike. The large amount of submitted articles has naturally had a considerable impact on the number of referees. In 2006 around 750 experts agreed to our requests to review. We have requested, and received, reports from at least 36 different countries. We would like to express our thanks to all of our referees for their careful and well constructed reports which are of great assistance in maintaining the rigorous quality standards of Journal of Micromechanics and Microengineering. All this would not of course be possible without the constant influx of magnificent papers dealing with the many fascinating aspects of microengineering and micromachining. I believe we have achieved a clear and distinct profile in the broad spectrum of journals in this field, and it is my sincerest hope that we can even enhance this profile. This is of course unthinkable without the efforts of each individual researcher in our community. I therefore wish each of you a prosperous and adventurous 2007 in your quest to expand the frontiers in micromachining. Let's continue the path we have chosen.

A microengineered collagen scaffold for generating a polarized crypt-villus architecture of human small intestinal epithelium.

PubMed

Wang, Yuli; Gunasekara, Dulan B; Reed, Mark I; DiSalvo, Matthew; Bultman, Scott J; Sims, Christopher E; Magness, Scott T; Allbritton, Nancy L

2017-06-01

The human small intestinal epithelium possesses a distinct crypt-villus architecture and tissue polarity in which proliferative cells reside inside crypts while differentiated cells are localized to the villi. Indirect evidence has shown that the processes of differentiation and migration are driven in part by biochemical gradients of factors that specify the polarity of these cellular compartments; however, direct evidence for gradient-driven patterning of this in vivo architecture has been hampered by limitations of the in vitro systems available. Enteroid cultures are a powerful in vitro system; nevertheless, these spheroidal structures fail to replicate the architecture and lineage compartmentalization found in vivo, and are not easily subjected to gradients of growth factors. In the current work, we report the development of a micropatterned collagen scaffold with suitable extracellular matrix and stiffness to generate an in vitro self-renewing human small intestinal epithelium that replicates key features of the in vivo small intestine: a crypt-villus architecture with appropriate cell-lineage compartmentalization and an open and accessible luminal surface. Chemical gradients applied to the crypt-villus axis promoted the creation of a stem/progenitor-cell zone and supported cell migration along the crypt-villus axis. This new approach combining microengineered scaffolds, biophysical cues and chemical gradients to control the intestinal epithelium ex vivo can serve as a physiologically relevant mimic of the human small intestinal epithelium, and is broadly applicable to model other tissues that rely on gradients for physiological function. Copyright © 2017 Elsevier Ltd. All rights reserved.

Minimally invasive surgery. Future developments.

PubMed Central

Wickham, J. E.

1994-01-01

The rapid development of minimally invasive surgery means that there will be fundamental changes in interventional treatment. Technological advances will allow new minimally invasive procedures to be developed. Application of robotics will allow some procedures to be done automatically, and coupling of slave robotic instruments with virtual reality images will allow surgeons to perform operations by remote control. Miniature motors and instruments designed by microengineering could be introduced into body cavities to perform operations that are currently impossible. New materials will allow changes in instrument construction, such as use of memory metals to make heat activated scissors or forceps. With the reduced trauma associated with minimally invasive surgery, fewer operations will require long hospital stays. Traditional surgical wards will become largely redundant, and hospitals will need to cope with increased through-put of patients. Operating theatres will have to be equipped with complex high technology equipment, and hospital staff will need to be trained to manage it. Conventional nursing care will be carried out more in the community. Many traditional specialties will be merged, and surgical training will need fundamental revision to ensure that surgeons are competent to carry out the new procedures. Images Fig 1 Fig 2 Fig 3 Fig 4 Fig 5 PMID:8312776

Fabrication of plastic microparts on wafer level

NASA Astrophysics Data System (ADS)

Weber, Lutz; Ehrfeld, Wolfgang; Begemann, Marc; Berg, Udo; Michel, Frank

1999-08-01

In the recent years micromolding has become one of the most important key technologies of microengineering. At the current state of art, the mass fabrication of plastic microparts for a wide range of applications like telecommunications, sensors, medical technology and biochemistry is feasible. Here a micro motor, plastic optical waveguides, a micro pump, and nanotiterplates are presented.

Microstructural heterogeneity directs micromechanics and mechanobiology in native and engineered fibrocartilage

NASA Astrophysics Data System (ADS)

Han, Woojin M.; Heo, Su-Jin; Driscoll, Tristan P.; Delucca, John F.; McLeod, Claire M.; Smith, Lachlan J.; Duncan, Randall L.; Mauck, Robert L.; Elliott, Dawn M.

2016-04-01

Treatment strategies to address pathologies of fibrocartilaginous tissue are in part limited by an incomplete understanding of structure-function relationships in these load-bearing tissues. There is therefore a pressing need to develop micro-engineered tissue platforms that can recreate the highly inhomogeneous tissue microstructures that are known to influence mechanotransductive processes in normal and diseased tissue. Here, we report the quantification of proteoglycan-rich microdomains in developing, ageing and diseased fibrocartilaginous tissues, and the impact of these microdomains on endogenous cell responses to physiologic deformation within a native-tissue context. We also developed a method to generate heterogeneous tissue-engineered constructs (hetTECs) with non-fibrous proteoglycan-rich microdomains engineered into the fibrous structure, and show that these hetTECs match the microstructural, micromechanical and mechanobiological benchmarks of native tissue. Our tissue-engineered platform should facilitate the study of the mechanobiology of developing, homeostatic, degenerating and regenerating fibrous tissues.

Microstructural heterogeneity directs micromechanics and mechanobiology in native and engineered fibrocartilage.

PubMed

Han, Woojin M; Heo, Su-Jin; Driscoll, Tristan P; Delucca, John F; McLeod, Claire M; Smith, Lachlan J; Duncan, Randall L; Mauck, Robert L; Elliott, Dawn M

2016-04-01

Treatment strategies to address pathologies of fibrocartilaginous tissue are in part limited by an incomplete understanding of structure-function relationships in these load-bearing tissues. There is therefore a pressing need to develop micro-engineered tissue platforms that can recreate the highly inhomogeneous tissue microstructures that are known to influence mechanotransductive processes in normal and diseased tissue. Here, we report the quantification of proteoglycan-rich microdomains in developing, ageing and diseased fibrocartilaginous tissues, and the impact of these microdomains on endogenous cell responses to physiologic deformation within a native-tissue context. We also developed a method to generate heterogeneous tissue-engineered constructs (hetTECs) with non-fibrous proteoglycan-rich microdomains engineered into the fibrous structure, and show that these hetTECs match the microstructural, micromechanical and mechanobiological benchmarks of native tissue. Our tissue-engineered platform should facilitate the study of the mechanobiology of developing, homeostatic, degenerating and regenerating fibrous tissues.

Microstructural Heterogeneity in Native and Engineered Fibrocartilage Directs Micromechanics and Mechanobiology

PubMed Central

Han, Woojin M; Heo, Su-Jin; Driscoll, Tristan P; Delucca, John F; McLeod, Claire M; Smith, Lachlan J; Duncan, Randall L; Mauck, Robert L; Elliott, Dawn M

2015-01-01

Treatment strategies to address pathologies of fibrocartilaginous tissue are in part limited by an incomplete understanding of structure-function relationships in these load-bearing tissues. There is therefore a pressing need to develop microengineered tissue platforms that can recreate the highly inhomogeneous tissue microstructures that are known to influence mechanotransductive processes in normal and diseased tissue. Here, we report the quantification of proteoglycan-rich microdomains in developing, aging, and diseased fibrocartilaginous tissues, and the impact of these microdomains on endogenous cell responses to physiologic deformation within a native-tissue context. We also developed a method to generate heterogeneous tissue engineered constructs (hetTECs) with microscale non-fibrous proteoglycan-rich microdomains engineered into the fibrous structure, and show that these hetTECs match the microstructural, micromechanical, and mechanobiological benchmarks of native tissue. Our tissue engineered platform should facilitate the study of the mechanobiology of developing, homeostatic, degenerating, and regenerating fibrous tissues. PMID:26726994

Organs-on-a-chip: a focus on compartmentalized microdevices.

PubMed

Moraes, Christopher; Mehta, Geeta; Lesher-Perez, Sasha Cai; Takayama, Shuichi

2012-06-01

Advances in microengineering technologies have enabled a variety of insights into biomedical sciences that would not have been possible with conventional techniques. Engineering microenvironments that simulate in vivo organ systems may provide critical insight into the cellular basis for pathophysiologies, development, and homeostasis in various organs, while curtailing the high experimental costs and complexities associated with in vivo studies. In this article, we aim to survey recent attempts to extend tissue-engineered platforms toward simulating organ structure and function, and discuss the various approaches and technologies utilized in these systems. We specifically focus on microtechnologies that exploit phenomena associated with compartmentalization to create model culture systems that better represent the in vivo organ microenvironment.

Capture and 3D culture of colonic crypts and colonoids in a microarray platform.

PubMed

Wang, Yuli; Ahmad, Asad A; Shah, Pavak K; Sims, Christopher E; Magness, Scott T; Allbritton, Nancy L

2013-12-07

Crypts are the basic structural and functional units of colonic epithelium and can be isolated from the colon and cultured in vitro into multi-cell spheroids termed "colonoids". Both crypts and colonoids are ideal building blocks for construction of an in vitro tissue model of the colon. Here we proposed and tested a microengineered platform for capture and in vitro 3D culture of colonic crypts and colonoids. An integrated platform was fabricated from polydimethylsiloxane which contained two fluidic layers separated by an array of cylindrical microwells (150 μm diameter, 150 μm depth) with perforated bottoms (30 μm opening, 10 μm depth) termed "microstrainers". As fluid moved through the array, crypts or colonoids were retained in the microstrainers with a >90% array-filling efficiency. Matrigel as an extracellular matrix was then applied to the microstrainers to generate isolated Matrigel pockets encapsulating the crypts or colonoids. After supplying the essential growth factors, epidermal growth factor, Wnt-3A, R-spondin 2 and noggin, 63 ± 13% of the crypts and 77 ± 8% of the colonoids cultured in the microstrainers over a 48-72 h period formed viable 3D colonoids. Thus colonoid growth on the array was similar to that under standard culture conditions (78 ± 5%). Additionally the colonoids displayed the same morphology and similar numbers of stem and progenitor cells as those under standard culture conditions. Immunofluorescence staining confirmed that the differentiated cell-types of the colon, goblet cells, enteroendocrine cells and absorptive enterocytes, formed on the array. To demonstrating the utility of the array in tracking the colonoid fate, quantitative fluorescence analysis was performed on the arrayed colonoids exposed to reagents such as Wnt-3A and the γ-secretase inhibitor LY-411575. The successful formation of viable, multi-cell type colonic tissue on the microengineered platform represents a first step in the building of a "colon-on-a-chip" with the goal of producing the physiologic structure and organ-level function of the colon for controlled experiments.

Microengineering neocartilage scaffolds.

PubMed

Petersen, Erik F; Spencer, Richard G S; McFarland, Eric W

2002-06-30

Advances in micropatterning methodologies have made it possible to create structures with precise architecture on the surface of cell culture substrata. We applied these techniques to fabricate microfeatures (15-65 microm wide; 40 microm deep) on the surface of a flexible, biocompatible polysaccharide gel. The micropatterned polymer gels were subsequently applied as scaffolds for chondrocyte culture and proved effective in maintaining key aspects of the chondrogenic phenotype. These were rounded cell morphology and a positive and statistically significant (p < 0.0001) immunofluorescence assay for the production of type II collagen throughout the maximum culture time of 10 days after cell seeding. Further, cells housed within individual surface features were observed to proliferate, while serial application of chondrocytes resulted in the formation of cellular aggregates. These methods represent a novel approach to the problem of engineering reparative cartilage in vitro. Copyright 2002 Wiley Periodicals, Inc.

Comparison of ion coupling strategies for a microengineered quadrupole mass filter.

PubMed

Wright, Steven; Syms, Richard R A; O'Prey, Shane; Hong, Guodong; Holmes, Andrew S

2009-01-01

The limitations of conventional machining and assembly techniques require that designs for quadrupole mass analyzers with rod diameters less than a millimeter are not merely scale versions of larger instruments. We show how silicon planar processing techniques and microelectromechanical systems (MEMS) design concepts can be used to incorporate complex features into the construction of a miniature quadrupole mass filter chip that could not easily be achieved using other microengineering approaches. Three designs for the entrance and exit to the filter consistent with the chosen materials and techniques have been evaluated. The differences between these seemingly similar structures have a significant effect on the performance. Although one of the designs results in severe attenuation of transmission with increasing mass, the other two can be scanned to m/z = 400 without any corruption of the mass spectrum. At m/z = 219, the variation in the transmission of the three designs was found to be approximately four orders of magnitude. A maximum resolution of M/DeltaM = 87 at 10% peak height has been achieved at m/z = 219 with a filter operated at 6 MHz and constructed using rods measuring (508 +/- 5) microm in diameter.

EDITORIAL: 15th European Workshop on Micromechanics (MME)

NASA Astrophysics Data System (ADS)

Puers, Bob

2005-07-01

This special issue of Journal of Micromechanics and Microengineering is entirely devoted to the fifteenth European Workshop on Micromechanics (MME), which was held in Leuven, at the Faculty Club, 5-7 September 2004. In this issue you will find a selection of papers presented at this workshop. The MME Workshop is organized every year to gather mostly European scientists and people from industry to discuss topics related to micromachining and microengineering in an informal manner. The first workshop was held at Twente University, the Netherlands, in 1989. The success of that event inaugurated a series of workshops traveling all over Europe. Looking back on the fifteen years of micromachining it is evident that the field has become more mature. More application driven research is now replacing the basic pure technology driven research we once got so excited about. Yet, half of the contributions still cover problems related to fabrication, production and reliability. Traditionally, the workshop aims to bring together young scientists in the field, with emphasis on discussions and communications in a friendly and informal atmosphere. The goal is to stimulate and to improve knowledge in the field, as well as to promote friendships between researchers. This edition of the workshop was no different. More than 70 papers were contributed, and it was decided to widen the scope with contributions also covering non-silicon technologies. This trend had already been informally introduced some years ago. After the third edition, it was decided to open up a selection of the contributed papers to a broader public by publishing them in a special issue of Journal of Micromechanics and Microengineering, and this has continued to the present day. Since the purpose of the workshop clearly is to stimulate younger scientists to enter the field, even immature research is presented there. The selection in this issue, however, aims to bring to you the more advanced level research work. Even so, without doubt, such a selection was not an easy task to perform. A careful choice was made by the Programme Committee of the MME Workshop at first, followed by the regular reviewing procedure at the heart of IOP Publishing. I am proud to be able to present to you this collection of 23 papers. We decided also to include papers dealing with non-lithography based manufacturing techniques in this special issue, in an attempt to widen the scope. With this special issue we hope to give you a good overview of the topics dealt with in this workshop. It goes without saying that all the above was not possible without the individual contributions of all the authors. I owe them much gratitude. Gathered here are contributions of an excellent scientific quality, reflecting a clear up-to-date image of what is going on in Europe in this field. I also wish to extend my thanks to the editorial staff of Journal of Micromechanics and Microengineering. Collaboration with them turns work into pleasure. I wish you a pleasant reading.

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.

Activation and control of microlens liquid arrays on functionalized polar electric crystal substrates by electro-wetting effect and temperature

NASA Astrophysics Data System (ADS)

Ferraro, Pietro; Grilli, Simonetta; Miccio, Lisa; Vespini, Veronica; Finizio, Sergio DeNicola Andrea

2008-11-01

In recent years a variety of liquid bases optical elements have been conceived, designed and fabricated even for commercial products like digital cameras o cellular phone cameras. The impressive development of microfluidic systems in conjunction with optics has led to the creation of a completely new Science field of investigation named optofludics. Optofludics, among others topics, deals with investigation and methods for realizing liquid micro-lenses. A variety of liquid micro-lenses have been designed and realized by using different configurations. We demonstrate that a lensing effect can be obtained in an open microfluidic system by using a thin layer of liquid on a polar electric crystal such as Lithium Niobate (LiNbO3). Electrowetting patterning on LiNbO3 surface is obtained by pyroelectric effect consisting in a simple but reliable electrodes-less and circuit-less configuration. The electrodes are intrinsically embedded into the substrate. The material is functionalised by means of a micro-engineering electric filed poling process. Lens array with variable focus has been demonstrated with a large number of lens elements (10x10) on micrometric scale (aperture of single lens 100 microns).

Near infrared-modulated propulsion of catalytic Janus polymer multilayer capsule motors.

PubMed

Wu, Yingjie; Si, Tieyan; Lin, Xiankun; He, Qiang

2015-01-11

The use of a near-infrared (NIR) laser for reversible modulation of a bubble-driven Janus polymer capsule motor is demonstrated. This process was mediated through illumination of the metal face of the Janus capsule motor at the critical concentration of peroxide fuel. Such an effective control of the propulsion of chemically powered microengines holds a considerable promise for diverse applications.

Mechanical Computing in Microelectromechanical Systems (MEMS)

DTIC Science & Technology

2003-03-01

New York: John Wiley and Sons, Inc., 1968. 25. Helvajian , H . and S. Janson, Microengineering Aerospace Systems, ch. Micro- engineering Space Systems...sacrificial layer. (g)Strip remaining resist. ( h ) Deposit a structural layer(conformal deposition is shown). (i) Deposit resist. (j) Expose resist...layer is then deposited, and assuming a conformal process, the structural layer will follow the topography of the sacrificial layer (Figure 2.9( h

EDITORIAL: The 19th MicroMechanics Europe Workshop (MME 2008) The 19th MicroMechanics Europe Workshop (MME 2008)

NASA Astrophysics Data System (ADS)

Schnakenberg, Uwe

2009-07-01

This special issue of Journal of Micromechanics and Microengineering is devoted to the 19th MicroMechanics Europe Workshop (MME 08), which took place at the RWTH Aachen University, Aachen, Germany, from 28-30 September, 2008. The workshop is a well recognized and established European event in the field of micro system technology using thin-film technologies for creating micro components, micro sensors, micro actuators, and micro systems. The first MME Workshop was held 1989 in Enschede (The Netherlands) and continued 1990 in Berlin (Germany), 1992 in Leuven (Belgium), and then was held annually in Neuchâtel (Switzerland), Pisa (Italy), Copenhagen (Denmark), Barcelona (Spain), Southampton (UK), Ulvik in Hardanger (Norway), Gif-sur-Yvette (France), Uppsala (Sweden), Cork (Ireland), Sinaia (Romania), Delft (The Netherlands), Leuven (Belgium), Göteborg (Sweden), Southampton (UK), and in Guimarães (Portugal). The two day workshop was attended by 180 delegates from 26 countries all over Europe and from Armenia, Austria, Bulgaria, Canada, China, Cuba, Iran, Japan, Korea, Malaysia, Taiwan, Turkey, and the United States of America. A total of 97 papers were accepted for presentation and there were a further five keynote presentations. I am proud to present 22 high-quality papers from MME 2008 selected for their novelty and relevance to Journal of Micromechanics and Microengineering. All the papers went through the regular reviewing procedure of IOP Publishing. I am eternally grateful to all the referees for their excellent work. I would also like to extend my thanks to the members of the Programme Committee of MME 2008, Dr Reinoud Wolffenbuttel, Professor José Higino Correia, and Dr Patrick Pons for pre-selection of the papers as well as to Professor Robert Puers for advice on the final selection of papers. My thanks also go to Dr Ian Forbes of IOP Publishing for managing the entire process and to the editorial staff of Journal of Micromechanics and Microengineering. I trust that this special issue will provide new trends of the emerging field of micro system technology and I hope you enjoy reading it.

Organs-on-chips at the frontiers of drug discovery

PubMed Central

Esch, Eric W.; Bahinski, Anthony; Huh, Dongeun

2016-01-01

Improving the effectiveness of preclinical predictions of human drug responses is critical to reducing costly failures in clinical trials. Recent advances in cell biology, microfabrication and microfluidics have enabled the development of microengineered models of the functional units of human organs — known as organs-on-chips — that could provide the basis for preclinical assays with greater predictive power. Here, we examine the new opportunities for the application of organ-on-chip technologies in a range of areas in preclinical drug discovery, such as target identification and validation, target-based screening, and phenotypic screening. We also discuss emerging drug discovery opportunities enabled by organs-on-chips, as well as important challenges in realizing the full potential of this technology. PMID:25792263

Micro-engineered remote palpation device for assessing tissue compliance.

PubMed

Hien, M; Yang, T H J; Leung, S K W; Reuben, R L; Habib, F K; McNeill, S A; Schneider, A; McBride, G; Stevens, R; Else, R W

2008-01-01

This paper concerns the operation of the actuator for a prototype micro-engineered mechanical palpation device for deployment via a cystoscope to measure the dynamic mechanical properties of the prostate gland in vivo. The subassembly consists of a 400x200 microm silicon (Si) piston manufactured using deep reactive ion etching (DRIE) housed within an anodically bonded glass-Si-glass sandwiched housing. The micro-channel on the Si layer was formed by powder blasting and contains the micro-piston with one end pointing to the side of the housing and the other facing a via hole leading to a capillary tube. The opening on the side of the housing was sealed by a 5 microm thick silicone membrane which acts to retain the micro-piston and act as a return spring. A 320 microm diameter capillary forms the connection between the micro-channel and a micro-syringe which is operated by a programmable syringe pump to produce a reciprocating action. A pressure sensor is connected along the capillary tube to measure the dynamic pressure within the system. The micro-piston has already been used, separately actuated to measure the dynamic mechanical properties of known viscoelastic materials and prostate tissue. The purpose of the present work is to assess the functionality of the actuator assembly.

Investigation on vascular cytotoxicity and extravascular transport of cationic polymer nanoparticles using perfusable 3D microvessel model.

PubMed

Ahn, Jungho; Cho, Chong-Su; Cho, Seong Woo; Kang, Joo H; Kim, Sung-Yon; Min, Dal-Hee; Song, Joon Myong; Park, Tae-Eun; Jeon, Noo Li

2018-05-25

Vascular networks are the first sites exposed to cationic polymer nanoparticles (NPs) administered intravenously, and thus function as a barrier for NPs reaching the target organ. While cationic polymer NPs have been intensively studied as non-viral delivery systems, their biological effects in human microvessels have been poorly investigated due to a lack of appropriate in vitro systems. Here, we employed a three-dimensional microvessel on a chip, which accurately models in vivo conditions. An open and perfused microvessel surrounded by pericytes was shown to reproduce the important features of living vasculature, including barrier function and biomarkers. Using this microvessel chip, we observed contraction of the microvascular lumen induced by perfused polyethylenimine (PEI)/DNA NPs. We demonstrated that the oxidative stress present when microvessels were exposed to PEI NPs led to rearrangement of microtubules resulting in microvessel contraction. Furthermore, the transcytotic behavior of PEI NPs was analyzed in the microvessel by monitoring the escape of PEI NPs from the microvascular lumen into the perivascular region, which was not possible in two-dimensional culture systems. With our new understanding of the different behaviors of cationic polymer NPs depending on their transcytotic route, we suggest that caveolae-mediated transcytosis is a powerful route for efficient extravascular transport. Microvascular networks are not only biological system constituting largest surface area in the body and but also first site exposed to nanoparticle in vivo. While cationic polymer NPs have been intensively studied as non-viral delivery systems, its biological effects in human microvessel have been poorly investigated due to lack of appropriate in vitro systems. Here, we microengineered an open and perfused 3D pericyte incorporated microvessel model which possesses same morphological characteristic of in vivo. Using the microengineered model, this study represents the first report of transcytotic behavior of NPs in 3D microvessel, and its effect on extravasation efficiency. Our study lays the groundwork for the integration of innovative technologies to examine blood vessel-nanoparticle interaction, which a critical but ill-defined phenomenon. Copyright © 2018. Published by Elsevier Ltd.

Organs-on-a-chip for drug discovery.

PubMed

Selimović, Seila; Dokmeci, Mehmet R; Khademhosseini, Ali

2013-10-01

The current drug discovery process is arduous and costly, and a majority of the drug candidates entering clinical trials fail to make it to the marketplace. The standard static well culture approaches, although useful, do not fully capture the intricate in vivo environment. By merging the advances in microfluidics with microfabrication technologies, novel platforms are being introduced that lead to the creation of organ functions on a single chip. Within these platforms, microengineering enables precise control over the cellular microenvironment, whereas microfluidics provides an ability to perfuse the constructs on a chip and to connect individual sections with each other. This approach results in microsystems that may better represent the in vivo environment. These organ-on-a-chip platforms can be utilized for developing disease models as well as for conducting drug testing studies. In this article, we highlight several key developments in these microscale platforms for drug discovery applications. Copyright © 2013 Elsevier Ltd. All rights reserved.

Microengineering in cardiovascular research: new developments and translational applications.

PubMed

Chan, Juliana M; Wong, Keith H K; Richards, Arthur Mark; Drum, Chester L

2015-04-01

Microfluidic, cellular co-cultures that approximate macro-scale biology are important tools for refining the in vitro study of organ-level function and disease. In recent years, advances in technical fabrication and biological integration have provided new insights into biological phenomena, improved diagnostic measurements, and made major steps towards de novo tissue creation. Here we review applications of these technologies specific to the cardiovascular field, emphasizing three general categories of use: reductionist vascular models, tissue-engineered vascular models, and point-of-care diagnostics. With continued progress in the ability to purposefully control microscale environments, the detailed study of both primary and cultured cells may find new relevance in the general cardiovascular research community. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Cardiology.

On the radiation tolerance of SU-8, a new material for gaseous microstructure radiation detector fabrication

NASA Astrophysics Data System (ADS)

Key, M. J.; Cindro, V.; Lozano, M.

2004-12-01

SU-8 photosensitive epoxy resin was developed for the fabrication of high-aspect ratio microstructures in MEMS and microengineering applications, and has potential for use in the construction of novel gaseous micropattern radiation detectors. However, little is known of the behaviour of the cured material under irradiation. Mechanical properties of SU-8 film have been measured as a function of neutron exposure and compared with Kapton ® polyimide and Mylar ® PET polyester films, materials routinely used in gaseous radiation detectors, to asses the suitability of SU-8 based microstructures for gaseous detector applications. After exposure to a reactor core neutron fluence of 7.5×10 18 n cm -2, the new material showed a high level of resistance to radiation damage, comparable to Kapton film.

New integrated silicon-PDMS process for compliant micro-mechanisms

NASA Astrophysics Data System (ADS)

Haouas, Wissem; Dahmouche, Redwan; Agnus, Joël; Le Fort-Piat, Nadine; Laurent, Guillaume J.

2017-12-01

Polydimethylsiloxane (PDMS) elastomers are used for many applications, such as microfluidics and micro-engineering. This paper presents a new process of integrating soft elastomers into a silicon structure without any assembly steps. The novelty of this process is the use of only one deep reactive ion etch (DRIE) instead of two or more as developed in previous works. Thus, this fabrication process allows the use of elastomers that are usually not compatible with some fabrication processes. Compliant flexures with different interference shapes have been designed, simulated, fabricated, and characterized for generic use and notably for micro-robot joints and compliant micro-systems. The experimental results show that the 400 μm  ×  400 μm cross-sectional area samples can be bended more than 60\\circ without delamination.

Functional differentiation of human pluripotent stem cells on a chip.

PubMed

Giobbe, Giovanni G; Michielin, Federica; Luni, Camilla; Giulitti, Stefano; Martewicz, Sebastian; Dupont, Sirio; Floreani, Annarosa; Elvassore, Nicola

2015-07-01

Microengineering human "organs-on-chips" remains an open challenge. Here, we describe a robust microfluidics-based approach for the differentiation of human pluripotent stem cells directly on a chip. Extrinsic signal modulation, achieved through optimal frequency of medium delivery, can be used as a parameter for improved germ layer specification and cell differentiation. Human cardiomyocytes and hepatocytes derived on chips showed functional phenotypes and responses to temporally defined drug treatments.

Recent advances in microparticle continuous separation.

PubMed

Kersaudy-Kerhoas, M; Dhariwal, R; Desmulliez, M P Y

2008-03-01

Recent advances in microparticle separation in continuous flow are presented. It is intended for scientists in the field of separation science in biology, chemistry and microsystems engineering. Recent techniques of micron-sized particle separation within microsystems are described with emphasis on five different categories: optical, magnetic, fluidic-only, electrical and minor separation methods. Examples from the growing literature are explained with insights on separation efficiency and microengineering challenges. Current applications of the techniques are discussed.

Thermoelctric Properties of Bi and Bismuth Telluride Composites

NASA Astrophysics Data System (ADS)

Huber, Tito E.; Calcao, Ricky

1998-03-01

It has been suggested that microengineering traditional thermoelectric materials into composites may leadto asignificant improvement in their thermoelectric performance. One approach for the fabrication of nanostructured materials is the utilization of nanochannel insulators as a matrix for the synthesis of dense composites using high pressure injection of the melt. We will discuss the synthesis and structural properties of oriented Bi and Bismuth Telluride wire arrays prepared with this technique. Funded by the Army Research Office.

Enzymatic Fuel Cells: Towards Self-Powered Implantable and Wearable Diagnostics.

PubMed

Gonzalez-Solino, Carla; Lorenzo, Mirella Di

2018-01-29

With the rapid progress in nanotechnology and microengineering, point-of-care and personalised healthcare, based on wearable and implantable diagnostics, is becoming a reality. Enzymatic fuel cells (EFCs) hold great potential as a sustainable means to power such devices by using physiological fluids as the fuel. This review summarises the fundamental operation of EFCs and discusses the most recent advances for their use as implantable and wearable self-powered sensors.

Creation and Optimization of Novel Solar Cell Power via Bimaterial Piezoelectric MEMS Device

DTIC Science & Technology

2011-12-01

piezoelectric mechanical vibration energy harvesters ,” Integrated Ferroelectrics, vol. 71, pp. 121–160, 2005. [32] Y. C. Shu, I. C. Lien, “Efficiency of...energy conversion for a piezoelectric power harvesting system.” Journal of Micromechanics and Microengineering, vol. 16, pp. 2429–2438, 2006. [33] C. D...maximum efficiency for piezoelectric vibrations occurs at the natural, or resonant, frequency for the referenced material. If the alternative

Enzymatic Fuel Cells: Towards Self-Powered Implantable and Wearable Diagnostics

PubMed Central

Gonzalez-Solino, Carla; Lorenzo, Mirella Di

2018-01-01

With the rapid progress in nanotechnology and microengineering, point-of-care and personalised healthcare, based on wearable and implantable diagnostics, is becoming a reality. Enzymatic fuel cells (EFCs) hold great potential as a sustainable means to power such devices by using physiological fluids as the fuel. This review summarises the fundamental operation of EFCs and discusses the most recent advances for their use as implantable and wearable self-powered sensors. PMID:29382147

Progress of the Swedish-Australian research collaboration on uncooled smart IR sensors

NASA Astrophysics Data System (ADS)

Liddiard, Kevin C.; Ringh, Ulf; Jansson, Christer; Reinhold, Olaf

1998-10-01

Progress is reported on the development of uncooled microbolometer IR focal plane detector arrays (IRFPDA) under a research collaboration between the Swedish Defence Research Establishment (FOA), and the Defence Science and Technology Organization (DSTO), Australia. The paper describes current focal plane detector arrays designed by Electro-optic Sensor Design (EOSD) for readout circuits developed by FOA. The readouts are fabricated in 0.8 micrometer CMOS, and have a novel signal conditioning and 16 bit parallel ADC design. The arrays are post-processed at DSTO on wafers supplied by FOA. During the past year array processing has been carried out at a new microengineering facility at DSTO, Salisbury, South Australia. A number of small format 16 X 16 arrays have been delivered to FOA for evaluation, and imaging has been demonstrated with these arrays. A 320 X 240 readout with 320 parallel 16 bit ADCs has been developed and IRFPDAs for this readout have been fabricated and are currently being evaluated.

EDITORIAL: Welcome to the 2008 volume

NASA Astrophysics Data System (ADS)

Puers, R.

2008-01-01

It is my pleasure to address these few lines to you all on the occasion of the start of the 2008 volume of Journal of Micromechanics and Microengineering, the journal's eighteenth year, and my eleventh year of service as Editor-in-Chief. As in previous years, I would like to take the opportunity to reflect on the achievements of the past year. The number of submissions to the journal continues to grow, to almost 800 in 2007. Importantly, the journal's ISI® impact factor remains at a solid 2.321. This is an achievement we can all be proud of. In 2007, an incredible 350 000 papers were downloaded, which clearly reflects the visibility and appreciation of our research work. These excellent results are entirely due to the fact that more of you are choosing to submit your high-quality work to the journal, and because more of you are also choosing to cite recent papers published within the journal. I would like to take this opportunity to thank each one of you: readers, authors and referees alike. To cope with the steadily increasing number of incoming papers, the review process had to be expanded. In 2007, more than 700 experts selected from 35 countries agreed to our requests to referee. In the name of the entire team, I would like to express my thanks to all our referees for their careful and well constructed reports, which are of paramount importance in maintaining the quality standards of Journal of Micromechanics and Microengineering. The average time to produce an individual report is a mere 19 days, contributing towards a very favourable overall processing time which is an attractive feature of the journal. Of course all this would not be possible without the constant hard work of the publishing, production and marketing staff in Bristol. In the name of the Editorial Board, contributing authors and readers, I wish to thank them for their support. Finally, I believe we have established a clear and distinct profile in the broad spectrum of journals in our field, and I hope we can expand this profile even further. This is not possible without the efforts of every individual researcher in our community. I therefore wish each of you a prosperous and adventurous 2008 in your quest to shift the frontiers in micromachining and microengineering. May health and prosperity be yours as you work to achieve these goals!

Performance Testing of a Microfabricated Propulsion System for Nanosatellite Applications (POSTPRINT)

DTIC Science & Technology

2005-04-22

References [1] Janson S, Helvajian H and Robinson E 1993 The concept of nanosatellite for revolutionary, low-cost space systems 44th International...technologies J. Micromech. Microeng. 8 54–6 [4] Helvajian H 1997 Microengineering Technology for Space Systems (Reston, VA: AIAA) [5] Ketsdever A D 2000 System...nanosatellite applications (POSTPRINT) 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Andrew D. Ketsdever (AFRL/PRSA); Riki H . Lee and

Artificial enzyme-powered microfish for water-quality testing.

PubMed

Orozco, Jahir; García-Gradilla, Victor; D'Agostino, Mattia; Gao, Wei; Cortés, Allan; Wang, Joseph

2013-01-22

We present a novel micromotor-based strategy for water-quality testing based on changes in the propulsion behavior of artificial biocatalytic microswimmers in the presence of aquatic pollutants. The new micromotor toxicity testing concept mimics live-fish water testing and relies on the toxin-induced inhibition of the enzyme catalase, responsible for the biocatalytic bubble propulsion of tubular microengines. The locomotion and survival of the artificial microfish are thus impaired by exposure to a broad range of contaminants, that lead to distinct time-dependent irreversible losses in the catalase activity, and hence of the propulsion behavior. Such use of enzyme-powered biocompatible polymeric (PEDOT)/Au-catalase tubular microengine offers highly sensitive direct optical visualization of changes in the swimming behavior in the presence of common contaminants and hence to a direct real-time assessment of the water quality. Quantitative data on the adverse effects of the various toxins upon the swimming behavior of the enzyme-powered artificial swimmer are obtained by estimating common ecotoxicological parameters, including the EC(50) (exposure concentration causing 50% attenuation of the microfish locomotion) and the swimmer survival time (lifetime expectancy). Such novel use of artificial microfish addresses major standardization and reproducibility problems as well as ethical concerns associated with live-fish toxicity assays and hence offers an attractive alternative to the common use of aquatic organisms for water-quality testing.

Hybrid Filter Membrane

NASA Technical Reports Server (NTRS)

Laicer, Castro; Rasimick, Brian; Green, Zachary

2012-01-01

Cabin environmental control is an important issue for a successful Moon mission. Due to the unique environment of the Moon, lunar dust control is one of the main problems that significantly diminishes the air quality inside spacecraft cabins. Therefore, this innovation was motivated by NASA s need to minimize the negative health impact that air-suspended lunar dust particles have on astronauts in spacecraft cabins. It is based on fabrication of a hybrid filter comprising nanofiber nonwoven layers coated on porous polymer membranes with uniform cylindrical pores. This design results in a high-efficiency gas particulate filter with low pressure drop and the ability to be easily regenerated to restore filtration performance. A hybrid filter was developed consisting of a porous membrane with uniform, micron-sized, cylindrical pore channels coated with a thin nanofiber layer. Compared to conventional filter media such as a high-efficiency particulate air (HEPA) filter, this filter is designed to provide high particle efficiency, low pressure drop, and the ability to be regenerated. These membranes have well-defined micron-sized pores and can be used independently as air filters with discreet particle size cut-off, or coated with nanofiber layers for filtration of ultrafine nanoscale particles. The filter consists of a thin design intended to facilitate filter regeneration by localized air pulsing. The two main features of this invention are the concept of combining a micro-engineered straight-pore membrane with nanofibers. The micro-engineered straight pore membrane can be prepared with extremely high precision. Because the resulting membrane pores are straight and not tortuous like those found in conventional filters, the pressure drop across the filter is significantly reduced. The nanofiber layer is applied as a very thin coating to enhance filtration efficiency for fine nanoscale particles. Additionally, the thin nanofiber coating is designed to promote capture of dust particles on the filter surface and to facilitate dust removal with pulse or back airflow.

EDITORIAL: Selected papers from the 11th International Workshop on Micro and Nanotechnology for Power Generation and Energy Conversion Applications (PowerMEMS 2011) Selected papers from the 11th International Workshop on Micro and Nanotechnology for Power Generation and Energy Conversion Applications (PowerMEMS 2011)

NASA Astrophysics Data System (ADS)

Cho, Young-Ho

2012-09-01

This special section of Journal of Micromechanics and Microengineering features papers selected from the 11th International Workshop on Micro and Nanotechnology for Power Generation and Energy Conversion Applications (PowerMEMS 2011), held at Sejong Hotel in Seoul, Korea during 15-18 November 2011. Since the first PowerMEMS workshop held in Sendai, Japan in 2000, the workshop has developed as the premier forum for reporting research results in micro and nanotechnology for power generation, energy conversion, harvesting and processing applications, including in-depth technical issues on nanostructures and materials for small-scale high-density energy and thermal management. Potential PowerMEMS applications cover not only portable power devices for consumer electronics and remote sensors, but also micro engines, impulsive thrusters and fuel cells for systems ranging from the nanometer to the millimeter scale. The 2011 technical program consists of 1 plenary talk, 4 invited talks and 118 contributed presentations. The 48 oral and 70 poster presentations, selected by 27 Technical Program Committee Members from 131 submitted abstracts, have stimulated lively discussion maximizing the interaction between participants. Among them, this special section includes 9 papers covering micro-scale power generators, energy converters, harvesters, thrusters and thermal coolers. Finally, we are grateful to the members of the International Steering Committee, the Technical Program Committee, and the Local Organizing Committee for their efforts and contributions to PowerMEMS 2011. We also thank the two companies Samsung Electro-Mechanics and LG Elite for technical tour arrangements. Special thanks go to Dr Ian Forbes, the editorial staff of the Journal of Micromechanics and Microengineering, as well as to the staff of IOP Publishing for making this special section possible.

Enhancing the reliability and throughput of neurosphere culture on hydrogel microwell arrays.

PubMed

Cordey, Myriam; Limacher, Monika; Kobel, Stefan; Taylor, Verdon; Lutolf, Matthias P

2008-10-01

The neurosphere assay is the standard retrospective assay to test the self-renewal capability and multipotency of neural stem cells (NSCs) in vitro. However, it has recently become clear that not all neurospheres are derived from a NSC and that on conventional cell culture substrates, neurosphere motility may cause frequent neurosphere "merging" [Nat Methods 2006;3:801-806; Stem Cells 2007;25:871-874]. Combining biomimetic hydrogel matrix technology with microengineering, we developed a microwell array platform on which NSC fate and neurosphere formation can be unequivocally attributed to a single founding cell. Using time-lapse microscopy and retrospective immunostaining, the fate of several hundred single NSCs was quantified. Compared with conventional neurosphere culture methods on plastic dishes, we detected a more than 100% increase in single NSC viability on soft hydrogels. Effective confinement of single proliferating cells to microwells led to neurosphere formation of vastly different sizes, a high percentage of which showed stem cell phenotypes after one week in culture. The reliability and increased throughput of this platform should help to better elucidate the function of sphere-forming stem/progenitor cells independent of their proliferation dynamics. Disclosure of potential conflicts of interest is found at the end of this article.

A Review of 3D Printing Techniques and the Future in Biofabrication of Bioprinted Tissue.

PubMed

Patra, Satyajit; Young, Vanesa

2016-06-01

3D printing has been around in the art, micro-engineering, and manufacturing worlds for decades. Similarly, research for traditionally engineered skin tissue has been in the works since the 1990s. As of recent years, the medical field also began to take advantage of the untapped potential of 3D printing for the biofabrication of tissue. To do so, researchers created a set of goals for fabricated tissues based on the characteristics of natural human tissues and organs. Fabricated tissue was then measured against this set of standards. Researchers were interested in not only creating tissue that functioned like natural tissues but in creating techniques for 3D printing that would print tissues quickly, efficiently, and ultimately result in the ability to mass produce fabricated tissues. Three promising methods of 3D printing emerged from their research: thermal inkjet printing with bioink, direct-write bioprinting, and organ printing using tissue spheroids. This review will discuss all three printing techniques, as well as their advantages, disadvantages, and the possibility of future advancements in the field of tissue fabrication.

Visible light induced electropolymerization of suspended hydrogel bioscaffolds in a microfluidic chip.

PubMed

Li, Pan; Yu, Haibo; Liu, Na; Wang, Feifei; Lee, Gwo-Bin; Wang, Yuechao; Liu, Lianqing; Li, Wen Jung

2018-05-23

The development of microengineered hydrogels co-cultured with cells in vitro could advance in vivo bio-systems in both structural complexity and functional hierarchy, which holds great promise for applications in regenerative tissues or organs, drug discovery and screening, and bio-sensors or bio-actuators. Traditional hydrogel microfabrication technologies such as ultraviolet (UV) laser or multiphoton laser stereolithography and three-dimensional (3D) printing systems have advanced the development of 3D hydrogel micro-structures but need either expensive and complex equipment, or harsh material selection with limited photoinitiators. Herein, we propose a simple and flexible hydrogel microfabrication method based on a ubiquitous visible-light projection system combined with a custom-designed photosensitive microfluidic chip, to rapidly (typically several to tens of seconds) fabricate various two-dimensional (2D) hydrogel patterns and 3D hydrogel constructs. A theoretical layer-by-layer model that involves continuous polymerizing-delaminating-polymerizing cycles is presented to explain the polymerization and structural formation mechanism of hydrogels. A large area of hydrogel patterns was efficiently fabricated without the usage of costly laser systems or photoinitiators, i.e., a stereoscopic mesh-like hydrogel network with intersecting hydrogel micro-belts was fabricated via a series of dynamic-changing digital light projections. The pores and gaps of the hydrogel network are tunable, which facilitates the supply of nutrients and discharge of waste in the construction of 3D thick bio-models. Cell co-culture experiments showed the effective regulation of cell spreading by hydrogel scaffolds fabricated by the new method presented here. This visible light enabled hydrogel microfabrication method may provide new prospects for designing cell-based units for advanced biomedical studies, e.g., for 3D bio-models or bio-actuators in the future.

Modeling the lung: Design and development of tissue engineered macro- and micro-physiologic lung models for research use.

PubMed

Nichols, Joan E; Niles, Jean A; Vega, Stephanie P; Argueta, Lissenya B; Eastaway, Adriene; Cortiella, Joaquin

2014-09-01

Respiratory tract specific cell populations, or tissue engineered in vitro grown human lung, have the potential to be used as research tools to mimic physiology, toxicology, pathology, as well as infectious diseases responses of cells or tissues. Studies related to respiratory tract pathogenesis or drug toxicity testing in the past made use of basic systems where single cell populations were exposed to test agents followed by evaluations of simple cellular responses. Although these simple single-cell-type systems provided good basic information related to cellular responses, much more can be learned from cells grown in fabricated microenvironments which mimic in vivo conditions in specialized microfabricated chambers or by human tissue engineered three-dimensional (3D) models which allow for more natural interactions between cells. Recent advances in microengineering technology, microfluidics, and tissue engineering have provided a new approach to the development of 2D and 3D cell culture models which enable production of more robust human in vitro respiratory tract models. Complex models containing multiple cell phenotypes also provide a more reasonable approximation of what occurs in vivo without the confounding elements in the dynamic in vivo environment. The goal of engineering good 3D human models is the formation of physiologically functional respiratory tissue surrogates which can be used as pathogenesis models or in the case of 2D screening systems for drug therapy evaluation as well as human toxicity testing. We hope that this manuscript will serve as a guide for development of future respiratory tract model systems as well as a review of conventional models. © 2014 by the Society for Experimental Biology and Medicine.

Self-powered microthermionic converter

DOEpatents

Marshall, Albert C.; King, Donald B.; Zavadil, Kevin R.; Kravitz, Stanley H.; Tigges, Chris P.; Vawter, Gregory A.

2004-08-10

A self-powered microthermionic converter having an internal thermal power source integrated into the microthermionic converter. These converters can have high energy-conversion efficiencies over a range of operating temperatures. Microengineering techniques are used to manufacture the converter. The utilization of an internal thermal power source increases potential for mobility and incorporation into small devices. High energy efficiency is obtained by utilization of micron-scale interelectrode gap spacing. Alpha-particle emitting radioisotopes can be used for the internal thermal power source, such as curium and polonium isotopes.

Polysilicon for everything?

NASA Astrophysics Data System (ADS)

Ward, M. C. L.; McNie, Mark E.; Bunyan, Robert J.; King, David O.; Carline, Roger T.; Wilson, Rebecca; Gillham, J. P.

1998-09-01

We review some of the attractive attributes of microengineering and relate them to features of the highly successful silicon microelectronics industry. We highlight the need for cost effective functionality rather than ultimate performance as a driver for success and review key examples of polysilicon devices from this point of view. The effective exploitation of the data generated by the cost effective polysilicon sensors is also considered and we conclude that `non traditional' data analysis will need to be exploited if full use is to be made of polysilicon devices.

Microengineering Laser Plasma Interactions at Relativistic Intensities.

PubMed

Jiang, S; Ji, L L; Audesirk, H; George, K M; Snyder, J; Krygier, A; Poole, P; Willis, C; Daskalova, R; Chowdhury, E; Lewis, N S; Schumacher, D W; Pukhov, A; Freeman, R R; Akli, K U

2016-02-26

We report on the first successful proof-of-principle experiment to manipulate laser-matter interactions on microscales using highly ordered Si microwire arrays. The interaction of a high-contrast short-pulse laser with a flat target via periodic Si microwires yields a substantial enhancement in both the total and cutoff energies of the produced electron beam. The self-generated electric and magnetic fields behave as an electromagnetic lens that confines and guides electrons between the microwires as they acquire relativistic energies via direct laser acceleration.

Exact analysis of two kinds of piezoelectric actuator

NASA Astrophysics Data System (ADS)

Rong, Han; Zhifei, Shi

2008-02-01

Two kinds of piezoelectric hollow cylinder actuator are studied in this paper. One is the expansion actuator and the other is the contraction actuator. Using the Airy stress function method, the analytical solutions of these two kinds of actuators are obtained based on the theory of piezo-elasticity. The solutions are compared with numerical results and good agreement is found. Inherent properties of these two kinds of piezoelectric cylinder actuator are presented and discussed. Findings have applications in the field of micromechanics and microengineering.

Microengineering Laser Plasma Interactions at Relativistic Intensities

NASA Astrophysics Data System (ADS)

Jiang, S.; Ji, L. L.; Audesirk, H.; George, K. M.; Snyder, J.; Krygier, A.; Poole, P.; Willis, C.; Daskalova, R.; Chowdhury, E.; Lewis, N. S.; Schumacher, D. W.; Pukhov, A.; Freeman, R. R.; Akli, K. U.

2016-02-01

We report on the first successful proof-of-principle experiment to manipulate laser-matter interactions on microscales using highly ordered Si microwire arrays. The interaction of a high-contrast short-pulse laser with a flat target via periodic Si microwires yields a substantial enhancement in both the total and cutoff energies of the produced electron beam. The self-generated electric and magnetic fields behave as an electromagnetic lens that confines and guides electrons between the microwires as they acquire relativistic energies via direct laser acceleration.

A Low-Cost Femtosatellite to Enable Distributed Space Missions

DTIC Science & Technology

2006-09-20

pdfs/CyroBroSS.pdf Concept in Distributed Space-based Sensing," in Proc. AIAA [36] H . Helvajian and S. W. Janson, "The Fabrication of a 100 gm Defense...press/pressOl.php [21] F. A. Herrero, M. DiJoseph, T. E. Moore, J. A. Slavin, and R. [38] S. W. Janson, H . Helvajian , S. Amimoto, G. Smit, D. Mayer...Congress," [39] H . Helvajian , Microengineering Aerospace Systems, Reston, Subcommittee on Space and Aeronautics, Committee on VA, AIAA Press, 1999

Characteristics of photonic nanojets from two-layer dielectric hemisphere

NASA Astrophysics Data System (ADS)

Liu, Yunyue; Liu, Xianchao; Li, Ling; Chen, Weidong; Chen, Yan; Huang, Yuerong; Xie, Zhengwei

2017-10-01

Not Available Project supported by State Key Laboratory of Optical Technologies on Nano-Fabrication and Micro-Engineering, Institute of Optics and Electronics, Chinese Academy of Sciences; Sichuan Provincial Department of Education, China (Grant No. 16ZA0047); the State Key Laboratory of Metastable Materials Science and Technology, Yansan University, China (Grant No. 201509); and the Large Precision Instruments Open Project Foundation of Sichuan Normal University, China (Grant Nos. DJ2015-57, DJ2015-58, DJ2015-60, DJ2016-58, and DJ2016-59).

Engineering Approaches Toward Deconstructing and Controlling the Stem Cell Environment

PubMed Central

Edalat, Faramarz; Bae, Hojae; Manoucheri, Sam; Cha, Jae Min; Khademhosseini, Ali

2012-01-01

Stem cell-based therapeutics have become a vital component in tissue engineering and regenerative medicine. The microenvironment within which stem cells reside, i.e. the niche, plays a crucial role in regulating stem cell self-renewal and differentiation. However, current biological techniques lack the means to recapitulate the complexity of this microenvironment. Nano- and microengineered materials offer innovative methods to: (1) deconstruct the stem cell niche to understand the effects of individual elements; (2) construct complex tissue-like structures resembling the niche to better predict and control cellular processes; and (3) transplant stem cells or activate endogenous stem cell populations for regeneration of aged or diseased tissues. Here, we highlight some of the latest advances in this field and discuss future applications and directions of the use of nano- and microtechnologies for stem cell engineering. PMID:22101755

Towards manipulating relativistic laser pulses with micro-tube plasma lenses

PubMed Central

Ji, L. L.; Snyder, J.; Pukhov, A.; Freeman, R. R.; Akli, K. U.

2016-01-01

Efficient coupling of intense laser pulses to solid-density matter is critical to many applications including ion acceleration for cancer therapy. At relativistic intensities, the focus has been mainly on investigating various laser beams irradiating initially overdense flat interfaces with little or no control over the interaction. Here, we propose a novel approach that leverages recent advancements in 3D direct laser writing (DLW) of materials and high contrast lasers to manipulate the laser-matter interactions on the micro-scales. We demonstrate, via simulations, that usable intensities ≥1023 Wcm−2 could be achieved with current tabletop lasers coupled to micro-engineered plasma lenses. We show that these plasma optical elements act as a lens to focus laser light. These results open new paths to engineering light-matter interactions at ultra-relativistic intensities. PMID:26979657

Engineering approaches toward deconstructing and controlling the stem cell environment.

PubMed

Edalat, Faramarz; Bae, Hojae; Manoucheri, Sam; Cha, Jae Min; Khademhosseini, Ali

2012-06-01

Stem cell-based therapeutics have become a vital component in tissue engineering and regenerative medicine. The microenvironment within which stem cells reside, i.e., the niche, plays a crucial role in regulating stem cell self-renewal and differentiation. However, current biological techniques lack the means to recapitulate the complexity of this microenvironment. Nano- and microengineered materials offer innovative methods to (1) deconstruct the stem cell niche to understand the effects of individual elements; (2) construct complex tissue-like structures resembling the niche to better predict and control cellular processes; and (3) transplant stem cells or activate endogenous stem cell populations for regeneration of aged or diseased tissues. In this article, we highlight some of the latest advances in this field and discuss future applications and directions of the use of nano- and microtechnologies for stem cell engineering.

Liver of the "visible man".

PubMed

Fasel, J H; Gingins, P; Kalra, P; Magnenat-Thalmann, N; Baur, C; Cuttat, J F; Muster, M; Gailloud, P

1997-01-01

Endoscopic surgery, also called minimally invasive surgery, is presumed drastically to reduce postoperative morbidity and thus to offer both human and economic benefits. For the surgeon, however, this approach leads to a number of gestural challenges that require extensive training to be mastered. In order to replace experimentation on animals and patients, we developed a simulator for endoscopic surgery. To achieve this goal, a first step was to develop a working prototype, a "standard patient," on which the informatic and microengineering tools could be validated. We used the visible man dataset for this purpose. The external shape of the visible man's liver, his biliary passages, and his extrahepatic portal system turned out to be fully within the standard pattern of normal anatomy. Anatomic variations were observed in the intrahepatic right portal vein, the hepatic veins, and the arterial blood supply to the liver. Thus, the visible man dataset reveals itself to be well suited for the simulation of minimally invasive surgical operation such as endoscopic cholecystectomy.

Screen-Printed Electrodes Modified with “Green” Metals for Electrochemical Stripping Analysis of Toxic Elements

PubMed Central

Economou, Anastasios

2018-01-01

This work reviews the field of screen-printed electrodes (SPEs) modified with “green” metals for electrochemical stripping analysis of toxic elements. Electrochemical stripping analysis has been established as a useful trace analysis technique offering many advantages compared to competing optical techniques. Although mercury has been the preferred electrode material for stripping analysis, the toxicity of mercury and the associated legal requirements in its use and disposal have prompted research towards the development of “green” metals as alternative electrode materials. When combined with the screen-printing technology, such environment-friendly metals can lead to disposable sensors for trace metal analysis with excellent operational characteristics. This review focuses on SPEs modified with Au, Bi, Sb, and Sn for stripping analysis of toxic elements. Different modification approaches (electroplating, bulk modification, use of metal precursors, microengineering techniques) are considered and representative applications are described. A developing related field, namely biosensing based on stripping analysis of metallic nanoprobe labels, is also briefly mentioned. PMID:29596391

Screen-Printed Electrodes Modified with "Green" Metals for Electrochemical Stripping Analysis of Toxic Elements.

PubMed

Economou, Anastasios

2018-03-29

This work reviews the field of screen-printed electrodes (SPEs) modified with "green" metals for electrochemical stripping analysis of toxic elements. Electrochemical stripping analysis has been established as a useful trace analysis technique offering many advantages compared to competing optical techniques. Although mercury has been the preferred electrode material for stripping analysis, the toxicity of mercury and the associated legal requirements in its use and disposal have prompted research towards the development of "green" metals as alternative electrode materials. When combined with the screen-printing technology, such environment-friendly metals can lead to disposable sensors for trace metal analysis with excellent operational characteristics. This review focuses on SPEs modified with Au, Bi, Sb, and Sn for stripping analysis of toxic elements. Different modification approaches (electroplating, bulk modification, use of metal precursors, microengineering techniques) are considered and representative applications are described. A developing related field, namely biosensing based on stripping analysis of metallic nanoprobe labels, is also briefly mentioned.

Three-dimensional microarchitected materials and devices using nanoparticle assembly by pointwise spatial printing.

PubMed

Saleh, Mohammad Sadeq; Hu, Chunshan; Panat, Rahul

2017-03-01

Three-dimensional (3D) hierarchical materials are important to a wide range of emerging technological applications. We report a method to synthesize complex 3D microengineered materials, such as microlattices, with nearly fully dense truss elements with a minimum diameter of approximately 20 μm and having high aspect ratios (up to 20:1) without using any templating or supporting materials. By varying the postprocessing conditions, we have also introduced an additional control over the internal porosity of the truss elements to demonstrate a hierarchical porous structure with an overall void size and feature size control of over five orders of magnitudes in length scale. The method uses direct printing of nanoparticle dispersions using the Aerosol Jet technology in 3D space without templating or supporting materials followed by binder removal and sintering. In addition to 3D microlattices, we have also demonstrated directly printed stretchable interconnects, spirals, and pillars. This assembly method could be implemented by a variety of microdroplet generation methods for fast and large-scale fabrication of the hierarchical materials for applications in tissue engineering, ultralight or multifunctional materials, microfluidics, and micro-optoelectronics.

In vitro spatially organizing the differentiation in individual multicellular stem cell aggregates.

PubMed

Qi, Hao; Huang, Guoyou; Han, Yu Long; Lin, Wang; Li, Xiujun; Wang, Shuqi; Lu, Tian Jian; Xu, Feng

2016-01-01

With significant potential as a robust source to produce specific somatic cells for regenerative medicine, stem cells have attracted increasing attention from both academia and government. In vivo, stem cell differentiation is a process under complicated regulations to precisely build tissue with unique spatial structures. Since multicellular spheroidal aggregates of stem cells, commonly called as embryoid bodies (EBs), are considered to be capable of recapitulating the events in early stage of embryonic development, a variety of methods have been developed to form EBs in vitro for studying differentiation of embryonic stem cells. The regulation of stem cell differentiation is crucial in directing stem cells to build tissue with the correct spatial architecture for specific functions. However, stem cells within the three-dimensional multicellular aggregates undergo differentiation in a less unpredictable and spatially controlled manner in vitro than in vivo. Recently, various microengineering technologies have been developed to manipulate stem cells in vitro in a spatially controlled manner. Herein, we take the spotlight on these technologies and researches that bring us the new potential for manipulation of stem cells for specific purposes.

Minimally invasive surgery. Future developments.

PubMed

Wickham, J E

1994-01-15

The rapid development of minimally invasive surgery means that there will be fundamental changes in interventional treatment. Technological advances will allow new minimally invasive procedures to be developed. Application of robotics will allow some procedures to be done automatically, and coupling of slave robotic instruments with virtual reality images will allow surgeons to perform operations by remote control. Miniature motors and instruments designed by microengineering could be introduced into body cavities to perform operations that are currently impossible. New materials will allow changes in instrument construction, such as use of memory metals to make heat activated scissors or forceps. With the reduced trauma associated with minimally invasive surgery, fewer operations will require long hospital stays. Traditional surgical wards will become largely redundant, and hospitals will need to cope with increased through-put of patients. Operating theatres will have to be equipped with complex high technology equipment, and hospital staff will need to be trained to manage it. Conventional nursing care will be carried out more in the community. Many traditional specialties will be merged, and surgical training will need fundamental revision to ensure that surgeons are competent to carry out the new procedures.

Neutron scattering as a probe of liquid crystal polymer-reinforced composite materials

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

Hjelm, R.P.; Douglas, E.P.; Benicewicz, B.C.

1995-12-31

This is the final report of a three-year Laboratory-Directed Research and Development (LDRD) project at the Los Alamos National Laboratory (LANL). This research project sought to obtain nanoscale and molecular level information on the mechanism of reinforcement in liquid crystal polymer (LCP)-reinforced composites, to realize molecular-reinforced LCP composites, and to test the validity of the concept of molecular reinforcement. Small-angle neutron scattering was used to study the structures in the ternary phase diagram of LCP with liquid crystal thermosets and solvent on length scales ranging from 1-100 nm. The goal of the scattering measurements is to understand the phase morphologymore » and degree of segregation of the reinforcing and matrix components. This information helps elucidate the physics of self assembly in these systems. This work provides an experimental basis for a microengineering approach to composites of vastly improved properties.« less

Micromolding of polymer waveguides

NASA Astrophysics Data System (ADS)

Hanemann, Thomas; Ulrich, Hermann; Ruprecht, Robert; Hausselt, Juergen H.

1999-10-01

In microsystem technology the fabrication of either passive or active micro optical components made from polymers becomes more and more evident with respect to the intense expanding application possibilities e.g. in telecommunication. Actually, the LIGA process developed at the FZK, Germany allows the direct fabrication of microcomponents with lateral dimensions in the micrometer range, structural details in the submicrometer range, high aspect ratios of up to several hundreds and a final average surface roughness of less than 50 nm in small up to large scales. The molding of polymer components for microoptical applications, especially in the singlemode range, is determined by the achievable maximum accuracy of the molding technique itself and of the acceptable tolerances for low damping and coupling losses. Following the LIGA and related technique e.g. mechanical microengineering we want to present in this work the fabrication of polymer singlemode waveguides using a combination of micromolding and light- curing steps.

A Microelectromechanical High-Density Energy Storage/Rapid Release System

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

Rodgers, M. Steven; Allen, Jim J.; Meeks, Kent D.

1999-07-21

One highly desirable characteristic of electrostatically driven microelectromechanical systems (MEMS) is that they consume very little power. The corresponding drawback is that the force they produce may be inadequate for many applications. It has previously been demonstrated that gear reduction units or microtransmissions can substantially increase the torque generated by microengines. Operating speed, however, is also reduced by the transmission gear ratio. Some applications require both high speed and high force. If this output is only required for a limited period of time, then energy could be stored in a mechanical system and rapidly released upon demand. We have designed,more » fabricated, and demonstrated a high-density energy storage/rapid release system that accomplishes this task. Built using a 5-level surface micromachining technology, the assembly closely resembles a medieval crossbow. Energy releases on the order of tens of nanojoules have already been demonstrated, and significantly higher energy systems are under development.« less

Microelectromechanical high-density energy storage/rapid release system

NASA Astrophysics Data System (ADS)

Rodgers, M. Steven; Allen, James J.; Meeks, Kent D.; Jensen, Brian D.; Miller, Samuel L.

1999-08-01

One highly desirable characteristic of electrostatically driven microelectromechanical systems (MEMS) is that they consume very little power. The corresponding drawback is that the force they produce may be inadequate for many applications. It has previously been demonstrated that gear reduction units or microtransmissions can substantially increase the torque generated by microengines. Operating speed, however, is also reduced by the transmission gear ratio. Some applications require both high speed and high force. If this output is only required for a limited period of time, then energy could be stored in a mechanical system and rapidly released upon demand. We have designed, fabricated, and demonstrated a high-density energy storage/rapid release system that accomplishes this task. Built using a 5-level surface micromachining technology, the assembly closely resembles a medieval crossbow. Energy releases on the order of tens of nanojoules have already been demonstrated, and significantly higher energy systems are under development.

New type of microengine using internal combustion of hydrogen and oxygen

NASA Astrophysics Data System (ADS)

Svetovoy, Vitaly B.; Sanders, Remco G. P.; Ma, Kechun; Elwenspoek, Miko C.

2014-03-01

Microsystems become part of everyday life but their application is restricted by lack of strong and fast motors (actuators) converting energy into motion. For example, widespread internal combustion engines cannot be scaled down because combustion reactions are quenched in a small space. Here we present an actuator with the dimensions 100 × 100 × 5 μm3 that is using internal combustion of hydrogen and oxygen as part of its working cycle. Water electrolysis driven by short voltage pulses creates an extra pressure of 0.5-4 bar for a time of 100-400 μs in a chamber closed by a flexible membrane. When the pulses are switched off this pressure is released even faster allowing production of mechanical work in short cycles. We provide arguments that this unexpectedly fast pressure decrease is due to spontaneous combustion of the gases in the chamber. This actuator is the first step to truly microscopic combustion engines.

Smart membranes for nitrate removal, water purification, and selective ion transportation

DOEpatents

Wilson, William D [Pleasanton, CA; Schaldach, Charlene M [Pleasanton, CA; Bourcier, William L [Livermore, CA; Paul, Phillip H [Livermore, CA

2009-12-15

A computer designed nanoengineered membrane for separation of dissolved species. One embodiment provides an apparatus for treatment of a fluid that includes ions comprising a microengineered porous membrane, a system for producing an electrical charge across the membrane, and a series of nanopores extending through the membrane. The nanopores have a pore size such that when the fluid contacts the membrane, the nanopores will be in a condition of double layer overlap and allow passage only of ions opposite to the electrical charge across the membrane.

Building vascular networks.

PubMed

Bae, Hojae; Puranik, Amey S; Gauvin, Robert; Edalat, Faramarz; Carrillo-Conde, Brenda; Peppas, Nicholas A; Khademhosseini, Ali

2012-11-14

Only a few engineered tissues-skin, cartilage, bladder-have achieved clinical success, and biomaterials designed to replace more complex organs are still far from commercial availability. This gap exists in part because biomaterials lack a vascular network to transfer the oxygen and nutrients necessary for survival and integration after transplantation. Thus, generation of a functional vasculature is essential to the clinical success of engineered tissue constructs and remains a key challenge for regenerative medicine. In this Perspective, we discuss recent advances in vascularization of biomaterials through the use of biochemical modification, exogenous cells, or microengineering technology.

Microengineering of cellular interactions.

PubMed

Folch, A; Toner, M

2000-01-01

Tissue function is modulated by an intricate architecture of cells and biomolecules on a micrometer scale. Until now, in vitro cellular interactions were mainly studied by random seeding over homogeneous substrates. Although this strategy has led to important discoveries, it is clearly a nonoptimal analog of the in vivo scenario. With the incorporation--and adaptation--of microfabrication technology into biology, it is now possible to design surfaces that reproduce some of the aspects of that architecture. This article reviews past research on the engineering of cell-substrate, cell-cell, and cell-medium interactions on the micrometer scale.

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.

Building Vascular Networks

PubMed Central

Bae, Hojae; Puranik, Amey S.; Gauvin, Robert; Edalat, Faramarz; Carrillo-Conde, Brenda; Peppas, Nicholas A.; Khademhosseini, Ali

2013-01-01

Only a few engineered tissues—skin, cartilage, bladder—have achieved clinical success, and biomaterials designed to replace more complex organs are still far from commercial availability. This gap exists in part because biomaterials lack a vascular network to transfer the oxygen and nutrients necessary for survival and integration after transplantation. Thus, generation of a functional vasculature is essential to the clinical success of engineered tissue constructs and remains a key challenge for regenerative medicine. In this Perspective, we discuss recent advances in vascularization of biomaterials through the use of biochemical modification, exogenous cells, or microengineering technology. PMID:23152325

A novel instrument for studying the flow behaviour of erythrocytes through microchannels simulating human blood capillaries.

PubMed

Sutton, N; Tracey, M C; Johnston, I D; Greenaway, R S; Rampling, M W

1997-05-01

A novel instrument has been developed to study the microrheology of erythrocytes as they flow through channels of dimensions similar to human blood capillaries. The channels are produced in silicon substrates using microengineering technology. Accurately defined, physiological driving pressures and temperatures are employed whilst precise, real-time image processing allows individual cells to be monitored continuously during their transit. The instrument characterises each cell in a sample of ca. 1000 in terms of its volume and flow velocity profile during its transit through a channel. The unique representation of the data in volume/velocity space provides new insight into the microrheological behaviour of blood. The image processing and subsequent data analysis enable the system to reject anomalous events such as multiple cell transits, thereby ensuring integrity of the resulting data. By employing an array of microfluidic flow channels we can integrate a number of different but precise and highly reproducible channel sizes and geometries within one array, thereby allowing multiple, concurrent isobaric measurements on one sample. As an illustration of the performance of the system, volume/velocity data sets recorded in a microfluidic device incorporating multiple channels of 100 microns length and individual widths ranging between 3.0 and 4.0 microns are presented.

Research highlights: Microtechnologies for engineering the cellular environment.

PubMed

Tseng, Peter; Kunze, Anja; Kittur, Harsha; Di Carlo, Dino

2014-04-07

In this issue we highlight recent microtechnology-enabled approaches to control the physical and biomolecular environment around cells: (1) developing micropatterned surfaces to quantify cell affinity choices between two adhesive patterns, (2) controlling topographical cues to align cells and improve reprogramming to a pluripotent state, and (3) controlling gradients of biomolecules to maintain pluripotency in embryonic stem cells. Quantitative readouts of cell-surface affinity in environments with several cues should open up avenues in tissue engineering where self-assembly of complex multi-cellular structures is possible by precisely engineering relative adhesive cues in three dimensional constructs. Methods of simple and local epigenetic modification of chromatin structure with microtopography and biomolecular gradients should also be of use in regenerative medicine, as well as in high-throughput quantitative analysis of external signals that impact and can be used to control cells. Overall, approaches to engineer the cellular environment will continue to be an area of further growth in the microfluidic and lab on a chip community, as the scale of the technologies seamlessly matches that of biological systems. However, because of regulations and other complexities with tissue engineered therapies, these micro-engineering approaches will likely first impact organ-on-a-chip technologies that are poised to improve drug discovery pipelines.

Perfectly monodisperse micro-bubble production by novel mechanical means. Scaling laws.

NASA Astrophysics Data System (ADS)

Ganan-Calvo, Alfonso M.; Gordillo, Jose M.; Ouarti, Nawel; Prevost, Thomas; Sampedro, Jose L.

2000-11-01

A continuous stream of controllable, perfectly homogeneous size micro-bubbles (of the order of some microns and larger) can be produced by a novel, extremely simple mechanical means that we call "Flow Focusing" (e.g. see Ganan-Calvo 1998, Phys. Rev. Lett. vol. 80, 285). Using this technique, a capillary gas micro-jet is formed ("focused") by a co-flowing stream of liquid forced through a sub-millimetric orifice. This gas micro-jet undergoes a rapid capillary breakup (e.g. Chandrasekhar 1961 "Hydrodynamic and Hydromagnetic Stability", p. 541) with a strong frequency "self-locking" effect. In this work we present a theoretical model which predicts the micro-bubble size as a function of the physical and geometrical parameters of the system. A complete experimental study is also provided, and the raw data are collapsed into a universal scaling law given by our theoretical model. This novel micro-fluidics phenomenon may have a wide variety of applications ranging from bio-medicine, pharmaceutical specialities, food industry, and even for the mesoscale micro-templating of micro-engineered materials (i.e. photonic crystals, smart materials, etc.).

Tissue Quality Assessment Using a Novel Direct Elasticity Assessment Device (The E-Finger): A Cadaveric Study of Prostatectomy Dissection

PubMed Central

Good, Daniel W.; Khan, Ashfaq; Hammer, Steven; Scanlan, Paul; Shu, Wenmiao; Phipps, Simon; Parson, Simon H.; Stewart, Grant D.; Reuben, Robert; McNeill, S. Alan

2014-01-01

Introduction Minimally invasive radical prostatectomy (RP) (robotic and laparoscopic), have brought improvements in the outcomes of RP due to improved views and increased degrees of freedom of surgical devices. Robotic and laparoscopic surgeries do not incorporate haptic feedback, which may result in complications secondary to inadequate tissue dissection (causing positive surgical margins, rhabdosphincter damage, etc). We developed a micro-engineered device (6 mm2 sized) [E-finger]) capable of quantitative elasticity assessment, with amplitude ratio, mean ratio and phase lag representing this. The aim was to assess the utility of the device in differentiating peri-prostatic tissue types in order to guide prostate dissection. Material and Methods Two embalmed and 2 fresh frozen cadavers were used in the study. Baseline elasticity values were assessed in bladder, prostate and rhabdosphincter of pre-dissected embalmed cadavers using the micro-engineered device. A measurement grid was created to span from the bladder, across the prostate and onto the rhabdosphincter of fresh frozen cadavers to enable a systematic quantitative elasticity assessment of the entire area by 2 independent assessors. Tissue was sectioned along each row of elasticity measurement points, and stained with haematoxylin and eosin (H&E). Image analysis was performed with Image Pro Premier to determine the histology at each measurement point. Results Statistically significant differences in elasticity were identified between bladder, prostate and sphincter in both embalmed and fresh frozen cadavers (p = <0.001). Intra-class correlation (ICC) reliability tests showed good reliability (average ICC = 0.851). Sensitivity and specificity for tissue identification was 77% and 70% respectively to a resolution of 6 mm2. Conclusions This cadaveric study has evaluated the ability of our elasticity assessment device to differentiate bladder, prostate and rhabdosphincter to a resolution of 6 mm2. The results provide useful data for which to continue to examine the use of elasticity assessment devices for tissue quality assessment with the aim of giving haptic feedback to surgeons performing complex surgery. PMID:25384014

Multistep synthesis on SU-8: combining microfabrication and solid-phase chemistry on a single material.

PubMed

Cavalli, Gabriel; Banu, Shahanara; Ranasinghe, Rohan T; Broder, Graham R; Martins, Hugo F P; Neylon, Cameron; Morgan, Hywel; Bradley, Mark; Roach, Peter L

2007-01-01

SU-8 is an epoxy-novolac resin and a well-established negative photoresist for microfabrication and microengineering. The photopolymerized resist is an extremely highly crosslinked polymer showing outstanding chemical and physical robustness with residual surface epoxy groups amenable for chemical functionalization. In this paper we describe, for the first time, the preparation and surface modification of SU-8 particles shaped as microbars, the attachment of appropriate linkers, and the successful application of these particles to multistep solid-phase synthesis leading to oligonucleotides and peptides attached in an unambiguous manner to the support surface.

Modeling and optimization of the hot embossing process for micro- and nanocomponent fabrication

NASA Astrophysics Data System (ADS)

Worgull, M.; Heckele, Mathias P.; Hétu, J. F.; Kabanemi, K. K.

2006-01-01

Hot embossing and injection molding belong to the established plastic molding processes in microengineering. Based on experimental findings, a variety of microstructures have been replicated using these processes. However, with increasing requirements regarding the embossing surface, and the simultaneous decrease of the structure size down into the nanorange, increasing know-how is needed to adapt hot embossing to industrial standards. To reach this objective, a German-Canadian cooperation project has been launched to study hot embossing theoretically by process simulation and experimentally. The present publication reports on the proceeding and present first results.

Automotive sensors: past, present and future

NASA Astrophysics Data System (ADS)

Prosser, S. J.

2007-07-01

This paper will provide a review of past, present and future automotive sensors. Today's vehicles have become highly complex sophisticated electronic control systems and the majority of innovations have been solely achieved through electronics and the use of advanced sensors. A range of technologies have been used over the past twenty years including silicon microengineering, thick film, capacitive, variable reluctance, optical and radar. The automotive sensor market continues to grow with respect to vehicle production level in recognition of the transition to electronically controlled electrically actuated systems. The environment for these sensors continues to be increasingly challenging with respect to robustness, reliability, quality and cost.

AIAA spacecraft GN&C interface standards initiative: Overview

NASA Technical Reports Server (NTRS)

Challoner, A. Dorian

1995-01-01

The American Institute of Aeronautics and Astronautics (AIAA) has undertaken an important standards initiative in the area of spacecraft guidance, navigation, and control (GN&C) subsystem interfaces. The objective of this effort is to establish standards that will promote interchangeability of major GN&C components, thus enabling substantially lower spacecraft development costs. Although initiated by developers of conventional spacecraft GN&C, it is anticipated that interface standards will also be of value in reducing the development costs of micro-engineered spacecraft. The standardization targets are specifically limited to interfaces only, including information (i.e. data and signal), power, mechanical, thermal, and environmental interfaces between various GN&C components and between GN&C subsystems and other subsystems. The current emphasis is on information interfaces between various hardware elements (e.g., between star trackers and flight computers). The poster presentation will briefly describe the program, including the mechanics and schedule, and will publicize the technical products as they exist at the time of the conference. In particular, the rationale for the adoption of the AS1773 fiber-optic serial data bus and the status of data interface standards at the application layer will be presented.

Characterization of N-doped polycrystalline diamond films deposited on microgrinding tools

NASA Astrophysics Data System (ADS)

Jackson, M. J.; Ahmed, W.

2005-10-01

Chemical vapor deposited diamond films have many industrial applications but are assuming increasing importance in the area of microengineering, most notably in the development of diamond coated microgrinding tools. For these applications the control of structure and morphology is of critical importance. The crystallite size, orientation, surface roughness, and the degree of sp 3 character have a profound effect on the tribological properties of the films deposited. In this article, we present experimental results on the effects of nitrogen doping on the surface morphology, crystallite size, and wear of microgrinding tools. The sp 3 character optimizes at 200 ppm nitrogen, and above this value the surface becomes much smoother and crystal sizes decrease considerably. Fracture-induced wear of the diamond grain is the most important mechanism of material removal from a microgrinding tool during the grinding process. Fracture occurs as a consequence of tensile stresses induced into diamond grains by grinding forces to which they are subjected. The relationship between the wear of diamond coated grinding tools, component grinding forces, and induced stresses in the model diamond grains is described in detail. A significant correlation was found between the maximum value of tensile stress induced in the diamond grain and the appropriate wheel-wear parameter (grinding ratio). It was concluded that the magnitude of tensile stresses induced in the diamond grain by grinding forces at the rake face is the best indicator of tool wear during the grinding process.

Exploring novel structures for manipulating relativistic laser-plasma interaction

NASA Astrophysics Data System (ADS)

Ji, Liangliang

2016-10-01

The prospect of realizing compact particle accelerators and x-ray sources based on high power lasers has gained numerous attention. Utilization of all the proposed schemes in the field requires the laser-matter-interaction process to be repeatable or moreover, controllable. This has been very challenging at ultra-high light intensities due to the pre-pulse issue and the limitation on target manufacturing. With recent development on pulse cleaning technique, such as XPW and the use of plasma mirror, we now propose a novel approach that leverages recent advancements in 3D nano-printing of materials and high contrast lasers to manipulate the laser-matter interactions on the micro-scales. The current 3D direct laser-writing (DLW) technique can produce repeatable structures with at a resolution as high as 100 nm. Based on 3D PIC simulations, we explored two typical structures, the micro-cylinder and micro-tube targets. The former serves to enhance and control laser-electron acceleration and the latter is dedicated to manipulate relativistic light intensity. First principle-of-proof experiments were carried out in the SCARLET laser facility and confirmed some of our predictions on enhancing direct laser acceleration of electrons and ion acceleration. We believe that the use of the micro-structured elements provides another degree of freedom in LPI and these new results will open new paths towards micro-engineering interaction process that will benefit high field science, laser-based proton therapy, near-QED physics, and relativistic nonlinear optics. This work is supported by the AFOSR Basic Research Initiative (FA9550-14-1-0085).

Microfluidic Fabrication of Cell Adhesive Chitosan Microtubes

PubMed Central

Oh, Jonghyun; Kim, Keekyoung; Won, Sung Wook; Cha, Chaenyung; Gaharwar, Akhilesh; Selimović, Šeila; Bae, Hojae; Lee, Kwang Ho; Lee, Dong Hwan; Lee, Sang-Hoon; Khademhosseini, Ali

2013-01-01

Chitosan has been used as a scaffolding material in tissue engineering due to its mechanical properties and biocompatibility. With increased appreciation of the effect of micro- and nanoscale environments on cellular behavior, there is increased emphasis on generating microfabricated chitosan structures. Here we employed a microfluidic coaxial flow-focusing system to generate cell adhesive chitosan microtubes of controlled sizes by modifying the flow rates of a chitosan pre-polymer solution and phosphate buffered saline (PBS). The microtubes were extruded from a glass capillary with a 300 μm inner diameter. After ionic crosslinking with sodium tripolyphosphate (TPP), fabricated microtubes had inner and outer diameter ranges of 70-150 μm and 120-185 μm. Computational simulation validated the controlled size of microtubes and cell attachment. To enhance cell adhesiveness on the microtubes, we mixed gelatin with the chitosan pre-polymer solution and adjusted the pH values of the chitosan pre-polymer solution with gelatin and TPP. During the fabrication of microtubes, fibroblasts suspended in core PBS flow adhered to the inner surface of chitosan-gelatin microtubes. To achieve physiological pH values, we adjusted pH values of chiotsan pre-polymer solution and TPP. In particular, we were able to improve cell viability to 92% with pH values of 5.8 and 7.4 for chitosan and TPP solution respectively. Cell culturing for three days showed that the addition of the gelatin enhanced cell spreading and proliferation inside the chitosan-gelatin microtubes. The microfluidic fabrication method for ionically crosslinked chitosan microtubes at physiological pH can be compatible with a variety of cells and used as a versatile platform for microengineered tissue engineering. PMID:23355068

International Conference on the Mechanical Technology of Inertial Devices, University of Newcastle-upon-Tyne, England, Apr. 7-9, 1987, Proceedings

NASA Astrophysics Data System (ADS)

Various papers on the mechanical technology of inertial devices are presented. The topics addressed include: development of a directional gyroscope for remotely piloted vehicles and similar applications; a two-degree-of-freedom gyroscope with frictionless inner and outer gimbal pickoffs; oscillogyro design, manufacture, and performance; development of miniature two-axis rate gyroscope; mechanical design aspects of the electrostatically suspended gyroscope; role of gas-lubricated bearings in current and future sensors; development of a new microporous retainer material for precision ball bearings; design study for a high-stability, large-centrifuge test bed; evaluation of a two-axis rate gyro; operating principles of a two-axis angular rate transducer; and nutation frequency analysis. Also considered are: triaxial laser gyro; mechanical design considerations for a ring laser gyro dither mechanism; environmental considerations in the design of fiberoptic gyroscopes; manufacturing aspects of some critical high-precision mechanical components of inertial devices; dynamics and control of a gyroscopic force measurement system; high precision and high performance motion systems; use of multiple acceleration references to obtain high precision centrifuge data at low cost; gyro testing and evaluation at the Communications Research Centre; review of the mechanical design and development of a high-performance accelerometer; and silicon microengineering for accelerometers.

Directing stem cell fate on hydrogel substrates by controlling cell geometry, matrix mechanics and adhesion ligand composition.

PubMed

Lee, Junmin; Abdeen, Amr A; Zhang, Douglas; Kilian, Kristopher A

2013-11-01

There is a dynamic relationship between physical and biochemical signals presented in the stem cell microenvironment to guide cell fate determination. Model systems that modulate cell geometry, substrate stiffness or matrix composition have proved useful in exploring how these signals influence stem cell fate. However, the interplay between these physical and biochemical cues during differentiation remains unclear. Here, we demonstrate a microengineering strategy to vary single cell geometry and the composition of adhesion ligands - on substrates that approximate the mechanical properties of soft tissues - to study adipogenesis and neurogenesis in adherent mesenchymal stem cells. Cells cultured in small circular islands show elevated expression of adipogenesis markers while cells that spread in anisotropic geometries tend to express elevated neurogenic markers. Arraying different combinations of matrix protein in a myriad of 2D and pseudo-3D geometries reveals optimal microenvironments for controlling the differentiation of stem cells to these "soft" lineages without the use of media supplements. © 2013 Elsevier Ltd. All rights reserved.

Reynolds numbers influence the directionality of self-propelled microjet engines in the 10(-4) regime.

PubMed

Zhao, Guanjia; Nguyen, Nam-Trung; Pumera, Martin

2013-08-21

The motion directionality of self-propelled bubble-jet microengines is influenced by their velocities and/or viscosity of the media in which they move. The influence of the fuel concentration from 1 to 3 wt% of H2O2 in 0.5% steps and of the glycerol fraction from 0 to 64% in aqueous solution on the directionality of the microjets motions is examined systematically. We show that with decreasing Reynolds numbers of the system (that is, with increasing viscosity or decreasing velocity of the microjets), the directionality of the motion shifts from circular to linear motion. This translates to a shorter travel time towards a designated target for the microjets despite moving at a slower speed, since the movements are linear instead of circular. We show that such dependence of trajectories of microjets on Re is a general issue. This observation has a strong implication for the real-world applications of microjets.

Compliant displacement-multiplying apparatus for microelectromechanical systems

DOEpatents

Kota, Sridhar; Rodgers, M. Steven; Hetrick, Joel A.

2001-01-01

A pivotless compliant structure is disclosed that can be used to increase the geometric advantage or mechanical advantage of a microelectromechanical (MEM) actuator such as an electrostatic comb actuator, a capacitive-plate electrostatic actuator, or a thermal actuator. The compliant structure, based on a combination of interconnected flexible beams and cross-beams formed of one or more layers of polysilicon or silicon nitride, can provide a geometric advantage of from about 5:1 to about 60:1 to multiply a 0.25-3 .mu.m displacement provided by a short-stroke actuator so that such an actuator can be used to generate a displacement stroke of about 10-34 .mu.m to operate a ratchet-driven MEM device or a microengine. The compliant structure has less play than conventional displacement-multiplying devices based on lever arms and pivoting joints, and is expected to be more reliable than such devices. The compliant structure and an associated electrostatic or thermal actuator can be formed on a common substrate (e.g. silicon) using surface micromachining.

A three dimensional micropatterned tumor model for breast cancer cell migration studies.

PubMed

Peela, Nitish; Sam, Feba S; Christenson, Wayne; Truong, Danh; Watson, Adam W; Mouneimne, Ghassan; Ros, Robert; Nikkhah, Mehdi

2016-03-01

Breast cancer cell invasion is a highly orchestrated process driven by a myriad of complex microenvironmental stimuli, making it difficult to isolate and assess the effects of biochemical or biophysical cues (i.e. tumor architecture, matrix stiffness) on disease progression. In this regard, physiologically relevant tumor models are becoming instrumental to perform studies of cancer cell invasion within well-controlled conditions. Herein, we explored the use of photocrosslinkable hydrogels and a novel, two-step photolithography technique to microengineer a 3D breast tumor model. The microfabrication process enabled precise localization of cell-encapsulated circular constructs adjacent to a low stiffness matrix. To validate the model, breast cancer cell lines (MDA-MB-231, MCF7) and non-tumorigenic mammary epithelial cells (MCF10A) were embedded separately within the tumor model, all of which maintained high viability throughout the experiments. MDA-MB-231 cells exhibited extensive migratory behavior and invaded the surrounding matrix, whereas MCF7 or MCF10A cells formed clusters that stayed confined within the circular tumor regions. Additionally, real-time cell tracking indicated that the speed and persistence of MDA-MB-231 cells were substantially higher within the surrounding matrix compared to the circular constructs. Z-stack imaging of F-actin/α-tubulin cytoskeletal organization revealed unique 3D protrusions in MDA-MB-231 cells and an abundance of 3D clusters formed by MCF7 and MCF10A cells. Our results indicate that gelatin methacrylate (GelMA) hydrogel, integrated with the two-step photolithography technique, has great promise in the development of 3D tumor models with well-defined architecture and tunable stiffness. Copyright © 2015 Elsevier Ltd. All rights reserved.

Thermo-rheological behaviour of polymer melts in microinjection moulding

NASA Astrophysics Data System (ADS)

Vasco, J. C.; Maia, J. M.; Pouzada, A. S.

2009-10-01

Microinjection has proven to be one of the most efficient replication methods for microcomponents and microsystems in various domains of microengineering. The use of available commercial microinjection equipment to evaluate the polymeric flow in microchannels would surely contribute to enhancing knowledge on polymeric flow at the microscale under industrial conditions. This approach is appropriate since rheological phenomena such as wall slip, surface tension, melt pressure drop and polymer flow length can be studied. These aspects are not fully dealt with in current commercial simulation software packages. In this study a micromould was designed to assess and characterize the flow in microchannels under realistic industrial conditions.

A novel photochemical machining process for magnesium aerospace and biomedical microengineering applications

NASA Astrophysics Data System (ADS)

Allen, D. M.; Simpkins, M.; Almond, H.

2010-10-01

Research was carried out to evaluate the feasibility of fabricating perforated (filigree) magnesium microcomponents with metal wire widths of the order of the metal thickness using a photochemical machining (PCM) process. Experimentally, it has been demonstrated for the first time that metal wire widths of 0.15 mm can be achieved within a 2D, 0.25 mm thick magnesium foil to fabricate microcomponents for use as micro air vehicle (MAV) wings or stents through a bespoke PCM process. This etching process differs significantly from the industrial etching process used currently to manufacture magnesium letterpress printing plates and embossing dies.

Manufacturing of three-dimensionally microstructured nanocomposites through microfluidic infiltration.

PubMed

Dermanaki-Farahani, Rouhollah; Lebel, Louis Laberge; Therriault, Daniel

2014-03-12

Microstructured composite beams reinforced with complex three-dimensionally (3D) patterned nanocomposite microfilaments are fabricated via nanocomposite infiltration of 3D interconnected microfluidic networks. The manufacturing of the reinforced beams begins with the fabrication of microfluidic networks, which involves layer-by-layer deposition of fugitive ink filaments using a dispensing robot, filling the empty space between filaments using a low viscosity resin, curing the resin and finally removing the ink. Self-supported 3D structures with other geometries and many layers (e.g. a few hundreds layers) could be built using this method. The resulting tubular microfluidic networks are then infiltrated with thermosetting nanocomposite suspensions containing nanofillers (e.g. single-walled carbon nanotubes), and subsequently cured. The infiltration is done by applying a pressure gradient between two ends of the empty network (either by applying a vacuum or vacuum-assisted microinjection). Prior to the infiltration, the nanocomposite suspensions are prepared by dispersing nanofillers into polymer matrices using ultrasonication and three-roll mixing methods. The nanocomposites (i.e. materials infiltrated) are then solidified under UV exposure/heat cure, resulting in a 3D-reinforced composite structure. The technique presented here enables the design of functional nanocomposite macroscopic products for microengineering applications such as actuators and sensors.

Manufacturing of Three-dimensionally Microstructured Nanocomposites through Microfluidic Infiltration

PubMed Central

Dermanaki-Farahani, Rouhollah; Lebel, Louis Laberge; Therriault, Daniel

2014-01-01

Microstructured composite beams reinforced with complex three-dimensionally (3D) patterned nanocomposite microfilaments are fabricated via nanocomposite infiltration of 3D interconnected microfluidic networks. The manufacturing of the reinforced beams begins with the fabrication of microfluidic networks, which involves layer-by-layer deposition of fugitive ink filaments using a dispensing robot, filling the empty space between filaments using a low viscosity resin, curing the resin and finally removing the ink. Self-supported 3D structures with other geometries and many layers (e.g. a few hundreds layers) could be built using this method. The resulting tubular microfluidic networks are then infiltrated with thermosetting nanocomposite suspensions containing nanofillers (e.g. single-walled carbon nanotubes), and subsequently cured. The infiltration is done by applying a pressure gradient between two ends of the empty network (either by applying a vacuum or vacuum-assisted microinjection). Prior to the infiltration, the nanocomposite suspensions are prepared by dispersing nanofillers into polymer matrices using ultrasonication and three-roll mixing methods. The nanocomposites (i.e. materials infiltrated) are then solidified under UV exposure/heat cure, resulting in a 3D-reinforced composite structure. The technique presented here enables the design of functional nanocomposite macroscopic products for microengineering applications such as actuators and sensors. PMID:24686754

EDITORIAL: Selected papers from the 22nd MicroMechanics and Microsystems Europe Workshop (MME 2011) Selected papers from the 22nd MicroMechanics and Microsystems Europe Workshop (MME 2011)

NASA Astrophysics Data System (ADS)

Ohlckers, Per

2012-07-01

This special section of Journal of Micromechanics and Microengineering is a selection of 13 of the best papers presented at the 22nd Micromechanics and Microsystems Europe Workshop, which was arranged in Toensberg, Norway, 19-22 June, 2011. 110 participants attended the 3 day workshop that had 5 invited keynote speakers and 80 submitted poster presentations. The MME Workshop is organized every year to gather mostly European scientists and people from industry to discuss topics related to research in micromechanics and microsystems in an informal manner. A distinct feature of this specialized workshop is to be an excellent venue for young scientists in the field, such as PhD students, to present their latest work. This workshop series was inaugurated in Enschede, the Netherlands in 1989, followed by: Berlin, Germany (1990), Leuven, Belgium (1992), Neuchatel, Switzerland (1993), Pisa, Italy (1994), Copenhagen, Denmark (1995), Barcelona, Spain (1996) [1], Southampton, UK (1997) [2], Ulvik, Norway (1998) [3], Gif-sur-Yvette, France (1999) [4], Uppsala, Sweden (2000), Cork, Ireland (2001) [5], Sinaia, Romania (2002) [6], Delft, The Netherlands (2003) [7], Leuven, Belgium (2004) [8], Goteborg, Sweden (2005) [9], Southampton, UK (2006) [10], Guimaraes, Portugal (2007) [11], Aachen, Germany (2008) [12], Toulouse, France (2009) [13] and Enschede, the Netherlands (2010) [14]. The workshop series has remained remarkably true to its original concept such as still having micromechanics as a priority topic while, at the same time, adapting to recent research topics such as microsystems integration. It is nice to observe that an earlier fragmented and mostly academic research field now has matured into a very strong industrial field being one of the fastest growing industries in the world, with successful applications on all levels from high end to low end, from space to consumer applications, with the inclusion of microsystems in smartphones such as three-axis accelerometers and three-axis gyroscopes as the most recent 'killer' application. Regardless of application, low cost, high performance and high reliability seem to give us the winning hand leaving competing technology platforms in the dust, for instance in automotive applications. First, I would like to thank the authors of the selected papers for each of their individual excellent contributions. My gratitude also goes to my fellow members in the programme committee (Leon Abelmann, Marin Hill and Martin Hoffmann) for their devotion in the selection of invited speakers and submitted papers, as well as the anonymous JMM reviewers for their careful selection of the final 13 papers included here. Last, but not least, it has been an honour and pleasure for me to collaborate with the editorial staff of Journal of Micromechanics and Microengineering, with the selected best papers presented at MME 2011 included in this special section. This collaboration will continue also for MME 2012, and hopefully also for many future MME workshops. References [1] Morante J R 1997 Preface J. Micromech. Microeng. 7 [2] Evans A G R 1998 Preface J. Micromech. Microeng. 8 [3] Ohlckers P 1999 Introduction J. Micromech. Microeng. 9 [4] Bosseboeuf A 2000 Editorial J. Micromech. Microeng. 10 [5] Hill M 2002 Preface J. Micromech. Microeng. 12 [6] Dascalu D and Muller A 2003 Preface J. Micromech. Microeng. 13 [7] Wolffenbuttel R F 2004 14th Micromechanics Europe Workshop (MME 2003) J. Micromech. Microeng. 14 [8] Puers R 2005 15th European Workshop on Micromechanics (MME 2004) J. Micromech. Microeng. 15 [9] Enoksson P 2006 16th European Workshop on Micromechanics (MME 2005) J. Micromech. Microeng. 16 [10] Morgan H 2007 The 17th European Workshop on Micromechanics (MME 2006) J. Micromech. Microeng. 17 [11] Correia J H 2008 The 18th European Workshop on Micromechanics (MME 2007) J. Micromech. Microeng. 18 060201 [12] Schnakenberg U 2009 The 19th MicroMechanics Europe Workshop (MME 2008) J. Micromech. Microeng. 19 070201 [13] Pons P 2010 Selected papers from the 20th Micromechanics Europe Workshop (MME 2009) (Toulouse, France, 20-22 September, 2009) J. Micromech. Microeng. 20 060201 [14] Abelmann L 2011 Selected papers from the 21th Micromechanics Europe Workshop (MME 2010) (Enschede, the Netherlands, 26-29 September, 2010) J. Micromech. Microeng. 21 070201

Electrically Driven Microengineered Bioinspired Soft Robots.

PubMed

Shin, Su Ryon; Migliori, Bianca; Miccoli, Beatrice; Li, Yi-Chen; Mostafalu, Pooria; Seo, Jungmok; Mandla, Serena; Enrico, Alessandro; Antona, Silvia; Sabarish, Ram; Zheng, Ting; Pirrami, Lorenzo; Zhang, Kaizhen; Zhang, Yu Shrike; Wan, Kai-Tak; Demarchi, Danilo; Dokmeci, Mehmet R; Khademhosseini, Ali

2018-03-01

To create life-like movements, living muscle actuator technologies have borrowed inspiration from biomimetic concepts in developing bioinspired robots. Here, the development of a bioinspired soft robotics system, with integrated self-actuating cardiac muscles on a hierarchically structured scaffold with flexible gold microelectrodes is reported. Inspired by the movement of living organisms, a batoid-fish-shaped substrate is designed and reported, which is composed of two micropatterned hydrogel layers. The first layer is a poly(ethylene glycol) hydrogel substrate, which provides a mechanically stable structure for the robot, followed by a layer of gelatin methacryloyl embedded with carbon nanotubes, which serves as a cell culture substrate, to create the actuation component for the soft body robot. In addition, flexible Au microelectrodes are embedded into the biomimetic scaffold, which not only enhance the mechanical integrity of the device, but also increase its electrical conductivity. After culturing and maturation of cardiomyocytes on the biomimetic scaffold, they show excellent myofiber organization and provide self-actuating motions aligned with the direction of the contractile force of the cells. The Au microelectrodes placed below the cell layer further provide localized electrical stimulation and control of the beating behavior of the bioinspired soft robot. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Faster and exact implementation of the continuous cellular automaton for anisotropic etching simulations

NASA Astrophysics Data System (ADS)

Ferrando, N.; Gosálvez, M. A.; Cerdá, J.; Gadea, R.; Sato, K.

2011-02-01

The current success of the continuous cellular automata for the simulation of anisotropic wet chemical etching of silicon in microengineering applications is based on a relatively fast, approximate, constant time stepping implementation (CTS), whose accuracy against the exact algorithm—a computationally slow, variable time stepping implementation (VTS)—has not been previously analyzed in detail. In this study we show that the CTS implementation can generate moderately wrong etch rates and overall etching fronts, thus justifying the presentation of a novel, exact reformulation of the VTS implementation based on a new state variable, referred to as the predicted removal time (PRT), and the use of a self-balanced binary search tree that enables storage and efficient access to the PRT values in each time step in order to quickly remove the corresponding surface atom/s. The proposed PRT method reduces the simulation cost of the exact implementation from {O}(N^{5/3}) to {O}(N^{3/2} log N) without introducing any model simplifications. This enables more precise simulations (only limited by numerical precision errors) with affordable computational times that are similar to the less precise CTS implementation and even faster for low reactivity systems.

Magnetic assembly and annealing of colloidal lattices and superlattices.

PubMed

Tierno, Pietro

2014-07-08

The ability to assemble mesoscopic colloidal lattices above a surface is important for fundamental studies related with nucleation and crystallization but also for a variety of technological applications in photonics and microengineering. Current techniques based on particle sedimentation above a lithographic template are limited by a slow deposition process and by the use of static templates, which make difficult to implement fast annealing procedures. Here it is demonstrated a method to realize and anneal a series of colloidal lattices displaying triangular, honeycomb, or kagome-like symmetry above a structure magnetic substrate. By using a binary mixture of particles, superlattices can be realized increasing further the variety and complexity of the colloidal patterns which can be produced.

Sensing interactions in the microworld with optical tweezers

NASA Astrophysics Data System (ADS)

Pacoret, Cécile; Bowman, Richard; Gibson, Graham; Sinan, Haliyo D.; Bergander, Arvid; Carberry, David; Régnier, Stéphane; Padgett, Miles

2009-08-01

Optical Tweezers have become a widespread tool in Cell Biology, microengineering and other fields requiring delicate micromanipulation. But for those sensitive tasks, it remains difficult to handle objects without damaging them. As the precision in position and force measurement increase, the richness of information cannot be fully exploited with simple interfaces such as a mouse or a common joystick. For this reason, we propose a haptic force-feedback optical tweezer command and a force-feedback system controlled by one hand. The system combines accurate force measurement using a fast camera and the coupling of these measured forces with a human operator. The overall transparency allows even the feeling of the Brownian motion.

EDITORIAL: The 18th European Workshop on Micromechanics (MME 07)

NASA Astrophysics Data System (ADS)

Correia, J. H.

2008-06-01

This special issue of Journal of Micromechanics and Microengineering is devoted to the 18th European Workshop on Micromechanics (MME 07), which took place at the University of Minho, Guimarães, Portugal from 16-18 September 2007. Since the first workshop at the University of Twente in 1989 the field of micromechanics has grown substantially and new fields have been added: optics, RF, biomedical, chemistry, and in recent years the emergence of nanotechnology. This year an extensive programme was scheduled with contributions from new materials research to new manufacturing techniques. In addition, the invited speakers presented a review of the state-of-the-art in several main trends in current research, with the focus on micro/nanosystems in the ICT Work Programme in EC FP7. As ever, the two day workshop was attended by delegates from all over Europe, the USA, Brazil, Egypt, Japan and Canada. A total of 96 papers were accepted for presentation and there were a further five keynote presentations. The workshop provides a forum for young researchers to learn about new experimental methods and to enhance their knowledge of the field. This special issue presents a selection of 17 of the best papers from the workshop. The papers highlight fluidic and optical devices, energy scavenging microsystems, neural probe arrays and microtechnology fabrication techniques. All the papers went through the regular reviewing procedure of IOP Publishing, and I am grateful to all the referees for their excellent work. I would also like to extend my thanks to Professor Robert Puers for advice on the final selection of papers and to Ian Forbes of IOP Publishing for managing the entire process. My thanks also go to the editorial staff of Journal of Micromechanics and Microengineering. I believe that this special issue will provide a good overview of the topics presented at the workshop and I hope you enjoy reading it.

EDITORIAL: Selected papers from the 20th Micromechanics Europe Workshop (MME 09) (Toulouse, France, 20-22 September 2009) Selected papers from the 20th Micromechanics Europe Workshop (MME 09) (Toulouse, France, 20-22 September 2009)

NASA Astrophysics Data System (ADS)

Pons, Patrick

2010-06-01

This special section of the Journal of Micromechanics and Microengineering is devoted to the 20th European Workshop on Micromechanics (MME 2009), which was held in Toulouse, France, 20-22 September 2009. The MME workshop series started in 1989 in Twente and was the first European event created in the field of micro machining technology for developing micro components, micro sensors, micro actuators, and micro systems. Over the last two decades the MEMS community has grown considerably, and the MME workshops have sustained this progress through annual meetings all around Europe: Twente (The Netherlands, 1989), Berlin (Germany, 1990), Leuven (Belgium, 1992), Neuchatel (Switzerland, 1993), Pisa (Italy, 1994), Copenhagen (Denmark, 1995), Barcelona (Spain, 1996), Southampton (United Kingdom, 1997), Ulvik (Norway, 1998), Gif-sur-Yvette (France, 1999), Uppsala (Sweden, 2000), Cork (Ireland, 2001), Sinaia (Romania, 2002), Delft (The Netherlands, 2003), Leuven (Belgium, 2004), Goteborg (Sweden, 2005), Southampton (United Kingdom, 2006), Guimaraes (Portugal, 2007) and Aachen (Germany, 2008). For twenty years, MME conferences have provided an excellent opportunity to bring together many, predominantly European, scientists and engineers to present and discuss the latest developments in this field. For the 20th anniversary of the MicroMechanics Europe Workshop, 115 papers from 23 countries were submitted. Selected contributions were presented during four poster sessions, including short oral presentations. A very interesting feature of the MME workshops is their ability to promote young researchers. Six invited speakers from research centres and industry also gave an overview on advanced technological, characterization and simulation tools. The two day workshop was attended by 185 delegates from 22 countries all over Europe, and from Japan, Taiwan, USA and Mexico. On behalf of the MME 2009 Program Committee, I would like to express my sincere gratitude to all authors of submitted papers. Their high levels of quality and considerable quantity serve as the foundation of this workshop's success. I'm also grateful to all the Program Committee members (Professor Miko Elwenspoek, Dr Martin Hill and Dr Uwe Schnakenberg) who gave their valuable time to review these numerous papers. I am proud to present 20 high-quality papers from MME 2009, selected through the regular review procedure of IOP Publishing, for their novelty and relevance to Journal of Micromechanics and Microengineering. These papers give a good overview of the topics presented during the workshop (microtechnology, characterization, sensors and actuators). I would also like to express my gratitude to Professor Robert Puers for advising on paper selection and to Dr Ian Forbes for coordinating this special section with the IOP Publishing office. I hope you enjoy reading this selection of papers.

Microengineered cell and tissue systems for drug screening and toxicology applications: Evolution of in-vitro liver technologies

PubMed Central

Usta, O. B.; McCarty, W. J.; Bale, S.; Hegde, M.; Jindal, R.; Bhushan, A.; Golberg, I.; Yarmush, M. L.

2015-01-01

The liver performs many key functions, the most prominent of which is serving as the metabolic hub of the body. For this reason, the liver is the focal point of many investigations aimed at understanding an organism’s toxicological response to endogenous and exogenous challenges. Because so many drug failures have involved direct liver toxicity or other organ toxicity from liver generated metabolites, the pharmaceutical industry has constantly sought superior, predictive in-vitro models that can more quickly and efficiently identify problematic drug candidates before they incur major development costs, and certainly before they are released to the public. In this broad review, we present a survey and critical comparison of in-vitro liver technologies along a broad spectrum, but focus on the current renewed push to develop “organs-on-a-chip”. One prominent set of conclusions from this review is that while a large body of recent work has steered the field towards an ever more comprehensive understanding of what is needed, the field remains in great need of several key advances, including establishment of standard characterization methods, enhanced technologies that mimic the in-vivo cellular environment, and better computational approaches to bridge the gap between the in-vitro and in-vivo results. PMID:26167518

Surface-micromachined chain for use in microelectromechanical structures

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

Vernon, Sr., George E.

2001-01-01

A surface-micromachined chain and a microelectromechanical (MEM) structure incorporating such a chain are disclosed. The surface-micromachined chain can be fabricated in place on a substrate (e.g. a silicon substrate) by depositing and patterning a plurality of alternating layers of a chain-forming material (e.g. polycrystalline silicon) and a sacrificial material (e.g. silicon dioxide or a silicate glass). The sacrificial material is then removed by etching to release the chain for movement. The chain has applications for forming various types of MEM devices which include a microengine (e.g. an electrostatic motor) connected to rotate a drive sprocket, with the surface-micromachined chain beingmore » connected between the drive sprocket and one or more driven sprockets.« less

Microfabrication of individual 200 microm diameter transdermal microconduits using high voltage pulsing in salicylic acid and benzoic acid.

PubMed

Ilic, L; Gowrishankar, T R; Vaughan, T E; Herndon, T O; Weaver, J C

2001-01-01

We describe an extension of semiconductor fabrication methods that creates individual approximately 200 microm diameter aqueous pathways through human stratum corneum at predetermined sites. Our hypothesis is that spatially localized electroporation of the multilamellar lipid bilayer membranes provides rapid delivery of salicylic acid to the keratin within corneocytes, leading to localized keratin disruption and then to a microconduit. A microconduit penetrating the isolated stratum corneum supports a volumetric flow of order 0.01 ml per s with a pressure difference of only 0.01 atm (about 10(2) Pa). This study provides a method for rapidly microengineering a pathway in the skin to interface future devices for transdermal drug delivery and sampling of biologically relevant fluids.

Review: nanoparticles in delivery of cardiovascular drugs.

PubMed

Arayne, M Saeed; Sultana, Najma; Qureshi, Faiza

2007-10-01

Everything in nature is built upward from the atomic level to define limits and structures to everything. Nanomedicines marked the field of medicine from nanobiotechnology, biological micro-electromechanical systems, microfluidics, biosensors, drug delivery, microarrays to tissue microengineering. Since then nanoparticles has overcome many challenges from blood brain barrier to targeting tumors. Where solid biodegradable nanoparticles were a step up liposome, targeting nanoparticles opened a whole new field for drug delivery. In this article, we attempt to discuss how the pioneered technique is serving in the drug delivery to cardiovascular system and how with the manipulation of their properties, nanoparticles can be made to fulfill desired function. Also how nanocarriers are improving molecular imaging to help improve diagnosis and treatment of cardiovascular disease is focused in this article.

Microengineering of soft functional materials by controlling the fiber network formation.

PubMed

Li, Jing-Liang; Liu, Xiang-Yang

2009-11-26

The engineering of soft functional materials based on the construction of three-dimensional interconnecting self-organized nanofiber networks is reported. The system under investigation is an organogel formed by N-lauroyl-L-glutamic acid di-n-butylamide (GP-1) in propylene glycol. The engineering of soft functional materials is implemented by controlling primary nucleation kinetics of GP-1, which can be achieved by both reducing thermodynamic driving force and/or introducing a tiny amount of specific copolymers (i.e., poly(methyl methacrylate comethacrylic acid)). The primary nucleation rate of GP-1 is correlated to the number density of GP-1 spherulites, which determines the overall rheological properties of soft functional materials. The results show that the presence of a tiny amount of the polymer (0.01-0.06%) can effectively inhibit the nucleation of GP-1 spherulites, which leads to the formation of integrated fiber networks. It follows that with the additive approach, the viscoelasticity of the soft functional material is significantly enhanced (i.e., more than 1.5 times at 40 degrees C). A combination of the thermal and additive approach led to an improvement of 3.5 times in the viscosity of the gel.

Optical detection system for MEMS-type pressure sensor

NASA Astrophysics Data System (ADS)

Sareło, K.; Górecka-Drzazga, A.; Dziuban, J. A.

2015-07-01

In this paper a special optical detection system designed for a MEMS-type (micro-electro-mechanical system) silicon pressure sensor is presented. The main part of the optical system—a detection unit with a perforated membrane—is bonded to the silicon sensor, and placed in a measuring system. An external light source illuminates the membrane of the pressure sensor. Owing to the light reflected from the deflected membrane sensor, the optical pattern consisting of light points is visible, and pressure can be estimated. The optical detection unit (20   ×   20   ×   20.4 mm3) is fabricated using microengineering techniques. Its dimensions are adjusted to the dimensions of the pressure sensor (5   ×   5 mm2 silicon membrane). Preliminary tests of the optical detection unit integrated with the silicon pressure sensor are carried out. For the membrane sensor from 15 to 60 µm thick, a repeatable detection of the differential pressure in the range of 0 to 280 kPa is achieved. The presented optical microsystem is especially suitable for the pressure measurements in a high radiation environment.

Tungsten coating for improved wear resistance and reliability of microelectromechanical devices

DOEpatents

Fleming, James G.; Mani, Seethambal S.; Sniegowski, Jeffry J.; Blewer, Robert S.

2001-01-01

A process is disclosed whereby a 5-50-nanometer-thick conformal tungsten coating can be formed over exposed semiconductor surfaces (e.g. silicon, germanium or silicon carbide) within a microelectromechanical (MEM) device for improved wear resistance and reliability. The tungsten coating is formed after cleaning the semiconductor surfaces to remove any organic material and oxide film from the surface. A final in situ cleaning step is performed by heating a substrate containing the MEM device to a temperature in the range of 200-600 .degree. C. in the presence of gaseous nitrogen trifluoride (NF.sub.3). The tungsten coating can then be formed by a chemical reaction between the semiconductor surfaces and tungsten hexafluoride (WF.sub.6) at an elevated temperature, preferably about 450.degree. C. The tungsten deposition process is self-limiting and covers all exposed semiconductor surfaces including surfaces in close contact. The present invention can be applied to many different types of MEM devices including microrelays, micromirrors and microengines. Additionally, the tungsten wear-resistant coating of the present invention can be used to enhance the hardness, wear resistance, electrical conductivity, optical reflectivity and chemical inertness of one or more semiconductor surfaces within a MEM device.

Brownian Carnot engine

PubMed Central

Dinis, L.; Petrov, D.; Parrondo, J. M. R.; Rica, R. A.

2016-01-01

The Carnot cycle imposes a fundamental upper limit to the efficiency of a macroscopic motor operating between two thermal baths1. However, this bound needs to be reinterpreted at microscopic scales, where molecular bio-motors2 and some artificial micro-engines3–5 operate. As described by stochastic thermodynamics6,7, energy transfers in microscopic systems are random and thermal fluctuations induce transient decreases of entropy, allowing for possible violations of the Carnot limit8. Here we report an experimental realization of a Carnot engine with a single optically trapped Brownian particle as the working substance. We present an exhaustive study of the energetics of the engine and analyse the fluctuations of the finite-time efficiency, showing that the Carnot bound can be surpassed for a small number of non-equilibrium cycles. As its macroscopic counterpart, the energetics of our Carnot device exhibits basic properties that one would expect to observe in any microscopic energy transducer operating with baths at different temperatures9–11. Our results characterize the sources of irreversibility in the engine and the statistical properties of the efficiency—an insight that could inspire new strategies in the design of efficient nano-motors. PMID:27330541

A microfluidic in-line ELISA for measuring secreted protein under perfusion.

PubMed

Luan, Qiyue; Cahoon, Stacey; Wu, Agnes; Bale, Shyam Sundhar; Yarmush, Martin; Bhushan, Abhinav

2017-11-11

Recent progress in the development of microfluidic microphysiological systems such as 'organs-on-chips' and microfabricated cell culture is geared to simulate organ-level physiology. These tissue models leverage microengineering technologies that provide capabilities of presenting cultured cells with input signals in a more physiologically relevant context such as perfused flow. Proteins that are secreted from cells have important information about the health of the cells. Techniques to quantify cellular proteins include mass spectrometry to ELISA (enzyme-linked immunosorbent assay). Although our capability to perturb the cells in the microphysiological systems with varying inputs is well established, we lack the tools to monitor in-line the cellular responses. User intervention for sample collection and off-site is cumbersome, causes delays in obtaining results, and is especially expensive because of collection, storage, and offline processing of the samples, and in many case, technically impractical to carry out because of limitated sample volumes. To address these shortcomings, we report the development of an ELISA that is carried out in-line under perfusion within a microfluidic device. Using this assay, we measured the albumin secreted from perfused hepatocytes without and under stimulation by IL-6. Since the method is based on a sandwich ELISA, we envision broad application of this technology to not just organs-on-chips but also to characterizing the temporal release and measurement of soluble factors and response to drugs.

EDITORIAL: Selected papers from the 9th International Workshop on Micro and Nanotechnology for Power Generation and Energy Conversion Applications (PowerMEMS 2009) Selected papers from the 9th International Workshop on Micro and Nanotechnology for Power Generation and Energy Conversion Applications (PowerMEMS 2009)

NASA Astrophysics Data System (ADS)

Ghodssi, Reza; Livermore, Carol; Arnold, David

2010-10-01

This special section of the Journal of Micromechanics and Microengineering presents papers selected from the 9th International Workshop on Micro and Nanotechnology for Power Generation and Energy Conversion Applications (PowerMEMS 2009), which was held in Washington DC, USA from 1-4 December 2009. Since it was first held in Sendai, Japan in 2000, the PowerMEMS workshop has focused on small-scale systems that process, convert, or generate macroscopically significant amounts of power, typically with high power density or high energy density. In the workshop's early years, much of the research presented was on small-scale fueled systems, such as micro heat engines and micro fuel cells. The past nine years have seen a dramatic expansion in the range of technologies that are brought to bear on the challenge of high-power, small-scale systems, as well as an increase in the applications for such technologies. At this year's workshop, 158 contributed papers were presented, along with invited and plenary presentations. The papers focused on applications from micro heat engines and fuel cells, to energy harvesting and its enabling electronics, to thermal management and propulsion. Also presented were the technologies that enable these applications, such as the structuring of microscale, nanoscale and biological systems for power applications, as well as combustion and catalysis at small scales. This special section includes a selection of 12 expanded papers representing energy harvesting, chemical and fueled systems, and elastic energy storage at small scales. We would like to express our appreciation to the members of the International Steering Committee, the Technical Program Committee, the Local Organizing Committee, and to the workshop's financial supporters. We are grateful to the referees for their contributions to the review process. Finally, we would like to thank Dr Ian Forbes, the editorial staff of the Journal of Micromechanics and Microengineering, and the staff of IOP Publishing for making this special section possible.

Localized, stepwise template growth of functional nanowires from an amino acid-supported framework in a microfluidic chip.

PubMed

Puigmartí-Luis, Josep; Rubio-Martínez, Marta; Imaz, Inhar; Cvetković, Benjamin Z; Abad, Llibertat; Pérez Del Pino, Angel; Maspoch, Daniel; Amabilino, David B

2014-01-28

A spatially controlled synthesis of nanowire bundles of the functional crystalline coordination polymer (CP) Ag(I)TCNQ (tetracyanoquinodimethane) from previously fabricated and trapped monovalent silver CP (Ag(I)Cys (cysteine)) using a room-temperature microfluidic-assisted templated growth method is demonstrated. The incorporation of microengineered pneumatic clamps in a two-layer polydimethylsiloxane-based (PDMS) microfluidic platform was used. Apart from guiding the formation of the Ag(I)Cys coordination polymer, this microfluidic approach enables a local trapping of the in situ synthesized structures with a simple pneumatic clamp actuation. This method not only enables continuous and multiple chemical events to be conducted upon the trapped structures, but the excellent fluid handling ensures a precise chemical activation of the amino acid-supported framework in a position controlled by interface and clamp location that leads to a site-specific growth of Ag(I)TCNQ nanowire bundles. The synthesis is conducted stepwise starting with Ag(I)Cys CPs, going through silver metal, and back to a functional CP (Ag(I)TCNQ); that is, a novel microfluidic controlled ligand exchange (CP → NP → CP) is presented. Additionally, the pneumatic clamps can be employed further to integrate the conductive Ag(I)TCNQ nanowire bundles onto electrode arrays located on a surface, hence facilitating the construction of the final functional interfaced systems from solution specifically with no need for postassembly manipulation. This localized self-supported growth of functional matter from an amino acid-based CP shows how sequential localized chemistry in a fluid cell can be used to integrate molecular systems onto device platforms using a chip incorporating microengineered pneumatic tools. The control of clamp pressure and in parallel the variation of relative flow rates of source solutions permit deposition of materials at different locations on a chip that could be useful for device array preparation. The in situ reaction and washing procedures make this approach a powerful one for the fabrication of multicomponent complex nanomaterials using a soft bottom-up approach.

Thermal relaxation and critical instability of near-critical fluid microchannel flow.

PubMed

Chen, Lin; Zhang, Xin-Rong; Okajima, Junnosuke; Maruyama, Shigenao

2013-04-01

We present two-dimensional numerical investigations of the temperature and velocity evolution of a pure near-critical fluid confined in microchannels. The fluid is subjected to two sides heating after it reached isothermal steady state. We focus on the abnormal behaviors of the near-critical fluid in response to the sudden imposed heat flux. New thermal-mechanical effects dominated by fluid instability originating from the boundary and local equilibrium process are reported. Near the microchannel boundaries, the instability grows very quickly and an unexpected vortex formation mode is identified when near-critical thermal-mechanical effect is interacting with the microchannel shear flow. The mechanism of the new kind of Kelvin-Helmholtz instability induced by boundary expansion and density stratification processes is also discussed in detail. This mechanism may bring about innovations in the field of microengineering.

Thermal relaxation and critical instability of near-critical fluid microchannel flow

NASA Astrophysics Data System (ADS)

Chen, Lin; Zhang, Xin-Rong; Okajima, Junnosuke; Maruyama, Shigenao

2013-04-01

We present two-dimensional numerical investigations of the temperature and velocity evolution of a pure near-critical fluid confined in microchannels. The fluid is subjected to two sides heating after it reached isothermal steady state. We focus on the abnormal behaviors of the near-critical fluid in response to the sudden imposed heat flux. New thermal-mechanical effects dominated by fluid instability originating from the boundary and local equilibrium process are reported. Near the microchannel boundaries, the instability grows very quickly and an unexpected vortex formation mode is identified when near-critical thermal-mechanical effect is interacting with the microchannel shear flow. The mechanism of the new kind of Kelvin-Helmholtz instability induced by boundary expansion and density stratification processes is also discussed in detail. This mechanism may bring about innovations in the field of microengineering.

Recent lab-on-chip developments for novel drug discovery.

PubMed

Khalid, Nauman; Kobayashi, Isao; Nakajima, Mitsutoshi

2017-07-01

Microelectromechanical systems (MEMS) and micro total analysis systems (μTAS) revolutionized the biochemical and electronic industries, and this miniaturization process became a key driver for many markets. Now, it is a driving force for innovations in life sciences, diagnostics, analytical sciences, and chemistry, which are called 'lab-on-a-chip, (LOC)' devices. The use of these devices allows the development of fast, portable, and easy-to-use systems with a high level of functional integration for applications such as point-of-care diagnostics, forensics, the analysis of biomolecules, environmental or food analysis, and drug development. In this review, we report on the latest developments in fabrication methods and production methodologies to tailor LOC devices. A brief overview of scale-up strategies is also presented together with their potential applications in drug delivery and discovery. The impact of LOC devices on drug development and discovery has been extensively reviewed in the past. The current research focuses on fast and accurate detection of genomics, cell mutations and analysis, drug delivery, and discovery. The current research also differentiates the LOC devices into new terminology of microengineering, like organ-on-a-chip, stem cells-on-a-chip, human-on-a-chip, and body-on-a-chip. Key challenges will be the transfer of fabricated LOC devices from lab-scale to industrial large-scale production. Moreover, extensive toxicological studies are needed to justify the use of microfabricated drug delivery vehicles in biological systems. It will also be challenging to transfer the in vitro findings to suitable and promising in vivo models. WIREs Syst Biol Med 2017, 9:e1381. doi: 10.1002/wsbm.1381 For further resources related to this article, please visit the WIREs website. © 2017 Wiley Periodicals, Inc.

Mechanical Characterization of Microengineered Epithelial Cysts by Using Atomic Force Microscopy.

PubMed

Shen, Yusheng; Guan, Dongshi; Serien, Daniela; Takeuchi, Shoji; Tong, Penger; Yobas, Levent; Huang, Pingbo

2017-01-24

Most organs contain interconnected tubular tissues that are one-cell-thick, polarized epithelial monolayers enclosing a fluid-filled lumen. Such tissue organization plays crucial roles in developmental and normal physiology, and the proper functioning of these tissues depends on their regulation by complex biochemical perturbations and equally important, but poorly understood, mechanical perturbations. In this study, by combining micropatterning techniques and atomic force microscopy, we developed a simple in vitro experimental platform for characterizing the mechanical properties of the MDCK II cyst, the simplest model of lumen-enclosing epithelial monolayers. By using this platform, we estimated the elasticity of the cyst monolayer and showed that the presence of a luminal space influences cyst mechanics substantially, which could be attributed to polarization and tissue-level coordination. More interestingly, the results from force-relaxation experiments showed that the cysts also displayed tissue-level poroelastic characteristics that differed slightly from those of single cells. Our study provides the first quantitative findings, to our knowledge, on the tissue-level mechanics of well-polarized epithelial cysts and offers new insights into the interplay between cyst mechanics and cyst physiology. Moreover, our simple platform is a potentially useful tool for enhancing the current understanding of cyst mechanics in health and disease. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Physically Triggered Morphology Changes in a Novel Acremonium Isolate Cultivated in Precisely Engineered Microfabricated Environments

PubMed Central

Catón, Laura; Yurkov, Andrey; Giesbers, Marcel; Dijksterhuis, Jan; Ingham, Colin J.

2017-01-01

Fungi are strongly affected by their physical environment. Microfabrication offers the possibility of creating new culture environments and ecosystems with defined characteristics. Here, we report the isolation of a novel member of the fungal genus Acremonium using a microengineered cultivation chip. This isolate was unusual in that it organizes into macroscopic structures when initially cultivated within microwells with a porous aluminum oxide (PAO) base. These “templated mycelial bundles” (TMB) were formed from masses of parallel hyphae with side branching suppressed. TMB were highly hydrated, facilitating the passive movement of solutes along the bundle. By using a range of culture chips, it was deduced that the critical factors in triggering the TMB were growth in microwells from 50 to 300 μm in diameter with a PAO base. Cultivation experiments, using spores and pigments as tracking agents, indicate that bulk growth of the TMB occurs at the base. TMB morphology is highly coherent and is maintained after growing out of the microwells. TMB can explore their environment by developing unbundled lateral hyphae; TMB only followed if nutrients were available. Because of the ease of fabricating numerous microstructures, we suggest this is a productive approach for exploring morphology and growth in multicellular microorganisms and microbial communities. PMID:28769882

The influence of physical characteristics on ablation effects in UV laser assisted micro-engineering

NASA Astrophysics Data System (ADS)

Ostendorf, Andreas; Kulik, Christian J.; Temme, Thorsten; Otte, Frank; Samm, Katja

2004-10-01

The development of the recent years led to an increased importance of frequency-converted diode-pumped solid-state lasers (DPSSL) for industrial drilling, cutting and structuring applications. The UV laser systems show favorable beam absorption in a broad range of MEMS and MOEMS relevant materials like ceramics, metals and polymers. Their short pulses in the range of tH = 20 nanoseconds and the excellent beam quality offer the possibility of manufacturing with a minimum heat affected zone (HAZ) in the surrounding material and thereby a decreasing of initial fusing and debris. To obtain the reachable ablation quality, especially on metals, in this paper copper, tungsten, tantalum, molybdenum, nickel, iron, aluminum and titanium were machined under identical conditions. Material properties like heat conductivity, optical and thermal penetration depth, are decisive for the magnitude of the mentioned side-effects. The correlation of these physical values of different metals to those effects is the subject of this paper. Results of systematically accomplished experiences using a frequency tripled DPSSL with a wavelength of λ = 355 nm in order to investigate this correlation are presented. Due to thermal effects, the ablation quality of metals differ from each other extremely. These information enable a prediction of the reachable quality of the desired structure.

Screening applications in drug discovery based on microfluidic technology

PubMed Central

Eribol, P.; Uguz, A. K.; Ulgen, K. O.

2016-01-01

Microfluidics has been the focus of interest for the last two decades for all the advantages such as low chemical consumption, reduced analysis time, high throughput, better control of mass and heat transfer, downsizing a bench-top laboratory to a chip, i.e., lab-on-a-chip, and many others it has offered. Microfluidic technology quickly found applications in the pharmaceutical industry, which demands working with leading edge scientific and technological breakthroughs, as drug screening and commercialization are very long and expensive processes and require many tests due to unpredictable results. This review paper is on drug candidate screening methods with microfluidic technology and focuses specifically on fabrication techniques and materials for the microchip, types of flow such as continuous or discrete and their advantages, determination of kinetic parameters and their comparison with conventional systems, assessment of toxicities and cytotoxicities, concentration generations for high throughput, and the computational methods that were employed. An important conclusion of this review is that even though microfluidic technology has been in this field for around 20 years there is still room for research and development, as this cutting edge technology requires ingenuity to design and find solutions for each individual case. Recent extensions of these microsystems are microengineered organs-on-chips and organ arrays. PMID:26865904

Screening applications in drug discovery based on microfluidic technology.

PubMed

Eribol, P; Uguz, A K; Ulgen, K O

2016-01-01

Microfluidics has been the focus of interest for the last two decades for all the advantages such as low chemical consumption, reduced analysis time, high throughput, better control of mass and heat transfer, downsizing a bench-top laboratory to a chip, i.e., lab-on-a-chip, and many others it has offered. Microfluidic technology quickly found applications in the pharmaceutical industry, which demands working with leading edge scientific and technological breakthroughs, as drug screening and commercialization are very long and expensive processes and require many tests due to unpredictable results. This review paper is on drug candidate screening methods with microfluidic technology and focuses specifically on fabrication techniques and materials for the microchip, types of flow such as continuous or discrete and their advantages, determination of kinetic parameters and their comparison with conventional systems, assessment of toxicities and cytotoxicities, concentration generations for high throughput, and the computational methods that were employed. An important conclusion of this review is that even though microfluidic technology has been in this field for around 20 years there is still room for research and development, as this cutting edge technology requires ingenuity to design and find solutions for each individual case. Recent extensions of these microsystems are microengineered organs-on-chips and organ arrays.

Cell-microenvironment interactions and architectures in microvascular systems

PubMed Central

Bersini, Simone; Yazdi, Iman K.; Talò, Giuseppe; Shin, Su Ryon; Moretti, Matteo; Khademhosseini, Ali

2016-01-01

In the past decade, significant advances have been made in the design and optimization of novel biomaterials and microfabrication techniques to generate vascularized tissues. Novel microfluidic systems have facilitated the development and optimization of in vitro models for exploring the complex pathophysiological phenomena that occur inside a microvascular environment. To date, most of these models have focused on engineering of increasingly complex systems, rather than analyzing the molecular and cellular mechanisms that drive microvascular network morphogenesis and remodeling. In fact, mutual interactions among endothelial cells (ECs), supporting mural cells and organ-specific cells, as well as between ECs and the extracellular matrix, are key driving forces for vascularization. This review focuses on the integration of materials science, microengineering and vascular biology for the development of in vitro microvascular systems. Various approaches currently being applied to study cell-cell/cell-matrix interactions, as well as biochemical/biophysical cues promoting vascularization and their impact on microvascular network formation, will be identified and discussed. Finally, this review will explore in vitro applications of microvascular systems, in vivo integration of transplanted vascularized tissues, and the important challenges for vascularization and controlling the microcirculatory system within the engineered tissues, especially for microfabrication approaches. It is likely that existing models and more complex models will further our understanding of the key elements of vascular network growth, stabilization and remodeling to translate basic research principles into functional, vascularized tissue constructs for regenerative medicine applications, drug screening and disease models. PMID:27417066

Cell-microenvironment interactions and architectures in microvascular systems.

PubMed

Bersini, Simone; Yazdi, Iman K; Talò, Giuseppe; Shin, Su Ryon; Moretti, Matteo; Khademhosseini, Ali

2016-11-01

In the past decade, significant advances have been made in the design and optimization of novel biomaterials and microfabrication techniques to generate vascularized tissues. Novel microfluidic systems have facilitated the development and optimization of in vitro models for exploring the complex pathophysiological phenomena that occur inside a microvascular environment. To date, most of these models have focused on engineering of increasingly complex systems, rather than analyzing the molecular and cellular mechanisms that drive microvascular network morphogenesis and remodeling. In fact, mutual interactions among endothelial cells (ECs), supporting mural cells and organ-specific cells, as well as between ECs and the extracellular matrix, are key driving forces for vascularization. This review focuses on the integration of materials science, microengineering and vascular biology for the development of in vitro microvascular systems. Various approaches currently being applied to study cell-cell/cell-matrix interactions, as well as biochemical/biophysical cues promoting vascularization and their impact on microvascular network formation, will be identified and discussed. Finally, this review will explore in vitro applications of microvascular systems, in vivo integration of transplanted vascularized tissues, and the important challenges for vascularization and controlling the microcirculatory system within the engineered tissues, especially for microfabrication approaches. It is likely that existing models and more complex models will further our understanding of the key elements of vascular network growth, stabilization and remodeling to translate basic research principles into functional, vascularized tissue constructs for regenerative medicine applications, drug screening and disease models. Copyright © 2016 Elsevier Inc. All rights reserved.

Microscopy and microanalysis 1996

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

Bailey, G.W.; Corbett, J.M.; Dimlich, R.V.W.

1996-12-31

The Proceedings of this Annual Meeting contain paper of members from the three societies. These proceedings emphasizes the common research interests and attempts to eliminate some unwanted overlap. Topics covered are: microscopic analysis of animals with altered gene expression and in-situ gene and antibody localizations, high-resolution elemental mapping of nucleoprofein interactions, plant biology and pathology, quantitative HREM analysis of perfect and defected materials, computational methods for TEM image analysis, high-resolution FESM in materials research, frontiers in polymer microscopy and microanalysis, oxidation and corrosion, micro XRD and XRF, molecular microspectroscopy and spectral imaging, advances in confocal and multidimensional light microscopy, analyticalmore » electron microscopy in biology, correlative microscopy in biological sciences, grain-boundary microengineering, surfaces and interfaces, telepresence microscopy in education and research, MSA educational outreach, quantitative electron probe microanalysis, frontiers of analytical electron microscopy, critical issues in ceramic microstructures, dynamic organization of the cell, pathology, microbiology, high-resolution biological and cryo SEM, and scanning-probe microscopy.« less

Capturing extracellular matrix properties in vitro: Microengineering materials to decipher cell and tissue level processes.

PubMed

Abdeen, Amr A; Lee, Junmin; Kilian, Kristopher A

2016-05-01

Rapid advances in biology have led to the establishment of new fields with tremendous translational potential including regenerative medicine and immunoengineering. One commonality to these fields is the need to extract cells for manipulation in vitro; however, results obtained in laboratory cell culture will often differ widely from observations made in vivo. To more closely emulate native cell biology in the laboratory, designer engineered environments have proved a successful methodology to decipher the properties of the extracellular matrix that govern cellular decision making. Here, we present an overview of matrix properties that affect cell behavior, strategies for recapitulating important parameters in vitro, and examples of how these properties can affect cell and tissue level processes, with emphasis on leveraging these tools for immunoengineering. © 2016 by the Society for Experimental Biology and Medicine.

Electrowetting in a water droplet with a movable floating substrate

NASA Astrophysics Data System (ADS)

Shahzad, Amir; Masud, A. R.; Song, Jang-Kun

2016-05-01

Electrowetting (EW) enables facile manipulation of a liquid droplet on a hydrophobic surface. In this study, manipulation of an electrolyte droplet having a small floating object on it was investigated on a solid hydrophobic substrate under the EW process. Herein, the floating object exhibited a vertical motion under an applied electric field owing to the spreading and contraction of the droplet on its connecting substrates. The field-induced height variation of the floating object was significantly influenced by the thicknesses of the dielectric and hydrophobic materials. A small mass was also placed on the top floating object and its effect on the spreading of the droplet was observed. In this system, the height of the top floating object is precisely controllable under the application of an electric voltage. The proposed system is expected to be highly useful in the design of nano- and micro-oscillatory systems for microengineering.

Smart electronics and microengineering: the Australian focus

NASA Astrophysics Data System (ADS)

Hariz, Alex

1998-04-01

Integrated MEMS together with signal-conditioning electronics on the same chip appears to be the ultimate solution to realizing smart computer devices integratable into larger systems. This in principle will lead to systems with decentralized intelligence leading to applications in numerous fields. It is conceived that such devices would be the product of merging two mature technologies, that of microsensors and that of IC manufacture which is enjoying a well established success. Using common and suitable materials it is reasonable to expect a high degree of compatibility with little modification to standard processes. The various aspects of this co-integration will be analyzed and factors critical to the viability of the process, that go beyond mere technical feasibility will be highlighted. Australian research in this area is strong and continues to grow. We will pinpoint opportunities and constraints to the promising prospect of smart electronics and MEMS.

Electrowetting in a water droplet with a movable floating substrate.

PubMed

Shahzad, Amir; Masud, A R; Song, Jang-Kun

2016-05-01

Electrowetting (EW) enables facile manipulation of a liquid droplet on a hydrophobic surface. In this study, manipulation of an electrolyte droplet having a small floating object on it was investigated on a solid hydrophobic substrate under the EW process. Herein, the floating object exhibited a vertical motion under an applied electric field owing to the spreading and contraction of the droplet on its connecting substrates. The field-induced height variation of the floating object was significantly influenced by the thicknesses of the dielectric and hydrophobic materials. A small mass was also placed on the top floating object and its effect on the spreading of the droplet was observed. In this system, the height of the top floating object is precisely controllable under the application of an electric voltage. The proposed system is expected to be highly useful in the design of nano- and micro-oscillatory systems for microengineering.

Dielectric Optical-Controllable Magnifying Lens by Nonlinear Negative Refraction

PubMed Central

Cao, Jianjun; Shang, Ce; Zheng, Yuanlin; Feng, Yaming; Chen, Xianfeng; Liang, Xiaogan; Wan, Wenjie

2015-01-01

A simple optical lens plays an important role for exploring the microscopic world in science and technology by refracting light with tailored spatially varying refractive indices. Recent advancements in nanotechnology enable novel lenses, such as, superlens and hyperlens, with sub-wavelength resolution capabilities by specially designed materials’ refractive indices with meta-materials and transformation optics. However, these artificially nano- or micro-engineered lenses usually suffer high losses from metals and are highly demanding in fabrication. Here, we experimentally demonstrate, for the first time, a nonlinear dielectric magnifying lens using negative refraction by degenerate four-wave mixing in a plano-concave glass slide, obtaining magnified images. Moreover, we transform a nonlinear flat lens into a magnifying lens by introducing transformation optics into the nonlinear regime, achieving an all-optical controllable lensing effect through nonlinear wave mixing, which may have many potential applications in microscopy and imaging science. PMID:26149952

Deep Reactive Ion Etching (DRIE) of High Aspect Ratio SiC Microstructures using a Time-Multiplexed Etch-Passivate Process

NASA Technical Reports Server (NTRS)

Evans, Laura J.; Beheim, Glenn M.

2006-01-01

High aspect ratio silicon carbide (SiC) microstructures are needed for microengines and other harsh environment micro-electro-mechanical systems (MEMS). Previously, deep reactive ion etching (DRIE) of low aspect ratio (AR less than or = 1) deep (greater than 100 micron) trenches in SiC has been reported. However, existing DRIE processes for SiC are not well-suited for definition of high aspect ratio features because such simple etch-only processes provide insufficient control over sidewall roughness and slope. Therefore, we have investigated the use of a time-multiplexed etch-passivate (TMEP) process, which alternates etching with polymer passivation of the etch sidewalls. An optimized TMEP process was used to etch high aspect ratio (AR greater than 5) deep (less than 100 micron) trenches in 6H-SiC. Power MEMS structures (micro turbine blades) in 6H-SiC were also fabricated.

Superhydrophobicity enhancement through substrate flexibility.

PubMed

Vasileiou, Thomas; Gerber, Julia; Prautzsch, Jana; Schutzius, Thomas M; Poulikakos, Dimos

2016-11-22

Inspired by manifestations in nature, microengineering and nanoengineering of synthetic materials to achieve superhydrophobicity has been the focus of much work. Generally, hydrophobicity is enhanced through the combined effects of surface texturing and chemistry; being durable, rigid materials are the norm. However, many natural and technical surfaces are flexible, and the resulting effect on hydrophobicity has been largely ignored. Here, we show that the rational tuning of flexibility can work synergistically with the surface microtexture or nanotexture to enhance liquid repellency performance, characterized by impalement and breakup resistance, contact time reduction, and restitution coefficient increase. Reduction in substrate areal density and stiffness imparts immediate acceleration and intrinsic responsiveness to impacting droplets (∼350 × g), mitigating the collision and lowering the impalement probability by ∼60% without the need for active actuation. Furthermore, we exemplify the above discoveries with materials ranging from man-made (thin steel or polymer sheets) to nature-made (butterfly wings).

Computer Generated Diffraction Patterns Of Rough Surfaces

NASA Astrophysics Data System (ADS)

Rakels, Jan H.

1989-03-01

It is generally accepted, that optical methods are the most promising for the in-process measurement of surface finish. These methods have the advantages of being non-contacting and fast data acquisition. In the Micro-Engineering Centre at the University of Warwick, an optical sensor has been devised which can measure the rms roughness, slope and wavelength of turned and precision ground surfaces. The operation of this device is based upon the Kirchhoff-Fresnel diffraction integral. Application of this theory to ideal turned surfaces is straightforward, and indeed the theoretically calculated diffraction patterns are in close agreement with patterns produced by an actual optical instrument. Since it is mathematically difficult to introduce real surface profiles into the diffraction integral, a computer program has been devised, which simulates the operation of the optical sensor. The program produces a diffraction pattern as a graphical output. Comparison between computer generated and actual diffraction patterns of the same surfaces show a high correlation.

Inductively guided circuits for ultracold dressed atoms

PubMed Central

Sinuco-León, German A.; Burrows, Kathryn A.; Arnold, Aidan S.; Garraway, Barry M.

2014-01-01

Recent progress in optics, atomic physics and material science has paved the way to study quantum effects in ultracold atomic alkali gases confined to non-trivial geometries. Multiply connected traps for cold atoms can be prepared by combining inhomogeneous distributions of DC and radio-frequency electromagnetic fields with optical fields that require complex systems for frequency control and stabilization. Here we propose a flexible and robust scheme that creates closed quasi-one-dimensional guides for ultracold atoms through the ‘dressing’ of hyperfine sublevels of the atomic ground state, where the dressing field is spatially modulated by inductive effects over a micro-engineered conducting loop. Remarkably, for commonly used atomic species (for example, 7Li and 87Rb), the guide operation relies entirely on controlling static and low-frequency fields in the regimes of radio-frequency and microwave frequencies. This novel trapping scheme can be implemented with current technology for micro-fabrication and electronic control. PMID:25348163

Skeletal Muscle Differentiation on a Chip Shows Human Donor Mesoangioblasts' Efficiency in Restoring Dystrophin in a Duchenne Muscular Dystrophy Model.

PubMed

Serena, Elena; Zatti, Susi; Zoso, Alice; Lo Verso, Francesca; Tedesco, F Saverio; Cossu, Giulio; Elvassore, Nicola

2016-12-01

: Restoration of the protein dystrophin on muscle membrane is the goal of many research lines aimed at curing Duchenne muscular dystrophy (DMD). Results of ongoing preclinical and clinical trials suggest that partial restoration of dystrophin might be sufficient to significantly reduce muscle damage. Different myogenic progenitors are candidates for cell therapy of muscular dystrophies, but only satellite cells and pericytes have already entered clinical experimentation. This study aimed to provide in vitro quantitative evidence of the ability of mesoangioblasts to restore dystrophin, in terms of protein accumulation and distribution, within myotubes derived from DMD patients, using a microengineered model. We designed an ad hoc experimental strategy to miniaturize on a chip the standard process of muscle regeneration independent of variables such as inflammation and fibrosis. It is based on the coculture, at different ratios, of human dystrophin-positive myogenic progenitors and dystrophin-negative myoblasts in a substrate with muscle-like physiological stiffness and cell micropatterns. Results showed that both healthy myoblasts and mesoangioblasts restored dystrophin expression in DMD myotubes. However, mesoangioblasts showed unexpected efficiency with respect to myoblasts in dystrophin production in terms of the amount of protein produced (40% vs. 15%) and length of the dystrophin membrane domain (210-240 µm vs. 40-70 µm). These results show that our microscaled in vitro model of human DMD skeletal muscle validated previous in vivo preclinical work and may be used to predict efficacy of new methods aimed at enhancing dystrophin accumulation and distribution before they are tested in vivo, reducing time, costs, and variability of clinical experimentation. This study aimed to provide in vitro quantitative evidence of the ability of human mesoangioblasts to restore dystrophin, in terms of protein accumulation and distribution, within myotubes derived from patients with Duchenne muscular dystrophy (DMD), using a microengineered model. An ad hoc experimental strategy was designed to miniaturize on a chip the standard process of muscle regeneration independent of variables such as inflammation and fibrosis. This microscaled in vitro model, which validated previous in vivo preclinical work, revealed that mesoangioblasts showed unexpected efficiency as compared with myoblasts in dystrophin production. Consequently, this model may be used to predict efficacy of new drugs or therapies aimed at enhancing dystrophin accumulation and distribution before they are tested in vivo. ©AlphaMed Press.

Self-Cleaning Synthetic Adhesive Surfaces Mimicking Tokay Geckos.

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

Branson, Eric D.; Singh, Seema; Burckel, David Bruce

2006-11-01

A gecko's extraordinary ability to suspend itself from walls and ceilings of varied surface roughness has interested humans for hundreds of years. Many theories and possible explanations describing this phenomenon have been proposed including sticky secretions, microsuckers, and electrostatic forces; however, today it is widely accepted that van der Waals forces play the most important role in this type of dry adhesion. Inarguably, the vital feature that allows a gecko's suspension is the presence of billions 3 of tiny hairs on the pad of its foot called spatula. These features are small enough to reach within van der Waals distancesmore » of any surface (spatula radius %7E100 nm); thus, the combined effect of billions of van der Waals interactions is more than sufficient to hold a gecko's weight to surfaces such as smooth ceilings or wet glass. Two lithographic approaches were used to make hierarchal structures with dimensions similar to the gecko foot dimensions noted above. One approach combined photo-lithography with soft lithography (micro-molding). In this fabrication scheme the fiber feature size, defined by the alumina micromold was 0.2 um in diameter and 60 um in height. The second approach followed more conventional photolithography-based patterning. Patterned features with dimensions %7E0.3 mm in diameter by 0.5 mm tall were produced. We used interfacial force microscopy employing a parabolic diamond tip with a diameter of 200 nm to measure the surface adhesion of these structures. The measured adhesive forces ranged from 0.3 uN - 0.6 uN, yielding an average bonding stress between 50 N/cm2 to 100 N/cm2. By comparison the reported literature value for the average stress of a Tokay gecko foot is 10 N/cm2. Acknowledgements This work was funded by Sandia National Laboratory's Laboratory Directed Research & Development program (LDRD). All coating processes were conducted in the cleanroom facility located at the University of New Mexico's Center for High Technology Materials (CHTM). SEM images were performed at UNM's Center for Micro-Engineering on equipment funded by a NSF New Mexico EPSCoR grant. 4« less

Computer Simulation Of An In-Process Surface Finish Sensor.

NASA Astrophysics Data System (ADS)

Rakels, Jan H.

1987-01-01

It is generally accepted, that optical methods are the most promising for the in-process measurement of surface finish. These methods have the advantages of being non-contacting and fast data acquisition. Furthermore, these optical instruments can be easily retrofitted on existing machine-tools. In the Micro-Engineering Centre at the University of Warwick, an optical sensor has been developed which can measure the rms roughness, slope and wavelength of turned and precision ground surfaces during machining. The operation of this device is based upon the Kirchhoff-Fresnel diffraction integral. Application of this theory to ideal turned and ground surfaces is straightforward, and indeed the calculated diffraction patterns are in close agreement with patterns produced by an actual optical instrument. Since it is mathematically difficult to introduce real machine-tool behaviour into the diffraction integral, a computer program has been devised, which simulates the operation of the optical sensor. The program produces a diffraction pattern as a graphical output. Comparison between computer generated and actual diffraction patterns of the same surfaces show a high correlation. The main aim of this program is to construct an atlas, which maps known machine-tool errors versus optical diffraction patterns. This atlas can then be used for machine-tool condition diagnostics. It has been found that optical monitoring is very sensitive to minor defects. Therefore machine-tool detoriation can be detected before it is detrimental.

The micro-Petri dish, a million-well growth chip for the culture and high-throughput screening of microorganisms.

PubMed

Ingham, Colin J; Sprenkels, Ad; Bomer, Johan; Molenaar, Douwe; van den Berg, Albert; van Hylckama Vlieg, Johan E T; de Vos, Willem M

2007-11-13

A miniaturized, disposable microbial culture chip has been fabricated by microengineering a highly porous ceramic sheet with up to one million growth compartments. This versatile culture format, with discrete compartments as small as 7 x 7 mum, allowed the growth of segregated microbial samples at an unprecedented density. The chip has been used for four complementary applications in microbiology. (i) As a fast viable counting system that showed a dynamic range of over 10,000, a low degree of bias, and a high culturing efficiency. (ii) In high-throughput screening, with the recovery of 1 fluorescent microcolony in 10,000. (iii) In screening for an enzyme-based, nondominant phenotype by the targeted recovery of Escherichia coli transformed with the plasmid pUC18, based on expression of the lacZ reporter gene without antibiotic-resistance selection. The ease of rapid, successive changes in the environment of the organisms on the chip, needed for detection of beta-galactosidase activity, highlights an advantageous feature that was also used to screen a metagenomic library for the same activity. (iv) In high-throughput screening of >200,000 isolates from Rhine water based on metabolism of a fluorogenic organophosphate compound, resulting in the recovery of 22 microcolonies with the desired phenotype. These isolates were predicted, on the basis of rRNA sequence, to include six new species. These four applications suggest that the potential for such simple, readily manufactured chips to impact microbial culture is extensive and may facilitate the full automation and multiplexing of microbial culturing, screening, counting, and selection.

Forces and thin water film drainage in deformable asymmetric nanoscale contacts.

PubMed

Schönherr, Holger

2015-01-27

Gas-liquid interfaces are omnipresent in daily life, and processes involving these interfaces are the basis for a broad range of applications that span from established industrial processes to modern microengineering, technology, and medical applications for diagnosis and treatment. Despite the rapid progress in understanding intermolecular forces at such interfaces from a theoretical point of view and, in particular, from an experimental point of view down to sub-nanometer length scales, the quantitative description of all relevant forces, particularly the hydrophobic interaction and the dynamic behavior of nanometer-scale confined water films, was until now unsatisfactory. This situation is particularly the case for the elusive description and understanding of the origins of the so-called hydrophobic interaction. For soft, deformable interfaces, such as those found in asymmetric contacts between gas bubbles and a solid, a complete picture has begun to emerge that has direct consequences for interfacial water at (bio)interfaces, functionalized gas microbubbles, surface nanobubbles, and beyond.

Low Friction Droplet Transportation on a Substrate with a Selective Leidenfrost Effect.

PubMed

Dodd, Linzi E; Wood, David; Geraldi, Nicasio R; Wells, Gary G; McHale, Glen; Xu, Ben B; Stuart-Cole, Simone; Martin, James; Newton, Michael I

2016-08-31

An energy saving Leidenfrost levitation method is introduced to transport microdroplets with virtually frictionless contact between the liquid and solid substrate. Through microengineering of the heating units, selective areas of the whole substrate can be electrothermally activated. A droplet can be levitated as a result of the Leidenfrost effect and further transported when the substrate is tilted slightly. Selective electroheating produces a uniform temperature distribution on the heating units within 1 s in response to a triggering voltage. Alongside these experimental observations, finite element simulations were conducted to understand the role of substrate thermal conductivity on the temperature profile of the selectively heated substrate. We also generated phase diagrams to verify the Leidenfrost regime for different substrate materials. Finally, we demonstrated the possibility of controlling low friction high speed droplet transportation (∼65 mm/s) when the substrate is tilted (∼7°) by structurally designing the substrate. This work establishes the basis for an entirely new approach to droplet microfluidics.

Sprinkler head revisited: momentum, forces, and flows in Machian propulsion

NASA Astrophysics Data System (ADS)

Jenkins, Alejandro

2011-09-01

Many experimenters, starting with Ernst Mach in 1883, have reported that if a device alternately sucks in and then expels a surrounding fluid, it moves in the same direction as if it only expelled fluid. This surprising phenomenon, which we call Machian propulsion, is explained by conservation of momentum: the outflow efficiently transfers momentum away from the device and into the surrounding medium, while the inflow can do so only by viscous diffusion. However, many previous theoretical discussions have focused instead on the difference in the shapes of the outflow and the inflow. Whereas the argument based on conservation is straightforward and complete, the analysis of the shapes of the flows is more subtle and requires conservation in the first place. Our discussion covers three devices that have usually been treated separately: the reverse sprinkler (also called the inverse, or Feynman sprinkler), the putt-putt boat, and the aspirating cantilever. We then briefly mention some applications of Machian propulsion, ranging from microengineering to astrophysics.

Local induction of acetylcholine receptor clustering in myotube cultures using microfluidic application of agrin.

PubMed

Tourovskaia, Anna; Kosar, T Fettah; Folch, Albert

2006-03-15

During neuromuscular synaptogenesis, the exchange of spatially localized signals between nerve and muscle initiates the coordinated focal accumulation of the acetylcholine (ACh) release machinery and the ACh receptors (AChRs). One of the key first steps is the release of the proteoglycan agrin focalized at the axon tip, which induces the clustering of AChRs on the postsynaptic membrane at the neuromuscular junction. The lack of a suitable method for focal application of agrin in myotube cultures has limited the majority of in vitro studies to the application of agrin baths. We used a microfluidic device and surface microengineering to focally stimulate muscle cells with agrin at a small portion of their membrane and at a time and position chosen by the user. The device is used to verify the hypothesis that focal application of agrin to the muscle cell membrane induces local aggregation of AChRs in differentiated C2C12 myotubes.

Practical, microfabrication-free device for single-cell isolation.

PubMed

Lin, Liang-I; Chao, Shih-Hui; Meldrum, Deirdre R

2009-08-21

Microfabricated devices have great potential in cell-level studies, but are not easily accessible for the broad biology community. This paper introduces the Microscale Oil-Covered Cell Array (MOCCA) as a low-cost device for high throughput single-cell analysis that can be easily produced by researchers without microengineering knowledge. Instead of using microfabricated structures to capture cells, MOCCA isolates cells in discrete aqueous droplets that are separated by oil on patterned hydrophilic areas across a relatively more hydrophobic substrate. The number of randomly seeded Escherichia coli bacteria in each discrete droplet approaches single-cell levels. The cell distribution on MOCCA is well-fit with Poisson distribution. In this pioneer study, we created an array of 900-picoliter droplets. The total time needed to seed cells in approximately 3000 droplets was less than 10 minutes. Compared to traditional microfabrication techniques, MOCCA dramatically lowers the cost of microscale cell arrays, yet enhances the fabrication and operational efficiency for single-cell analysis.

Elastomer actuators: systematic improvement in properties by use of composite materials

NASA Astrophysics Data System (ADS)

Molberg, Martin; Leterrier, Yves; Plummer, Christopher J. G.; Löwe, Christiane; Opris, Dorina M.; Clemens, Frank; Månson, Jan-Anders E.

2010-04-01

Dielectric elastomer actuators (DEAs) have attracted increasing attention over the last few years owing to their outstanding properties, e.g. their large actuation strains, high energy density, and pliability, which have opened up a wide spectrum of potential applications in fields ranging from microengineering to medical prosthetics. There is consequently a huge demand for new elastomer materials with improved properties to enhance the performance of DEAs and to overcome the limitations associated with currently available materials, such as the need for high activation voltages and the poor long-term stability. The electrostatic pressure that activates dielectric elastomers can be increased by higher permittivity of the elastomer and thus may lead to lower activation voltages. This has led us to consider composite elastomeric dielectrics based on thermoplastic elastomers or PDMS, and conductive polyaniline or ceramic (soft doped PZT) powder fillers. The potential of such materials and strategies to counter the adverse effects of increased conductivity and elastic modulus are discussed.

Novel silicon microchannels device for use in red blood cell deformability studies

NASA Astrophysics Data System (ADS)

Zheng, Xiao-Lin; Liao, Yan-Jian; Zhang, Wen-Xian

2001-10-01

Currently, a number of techniques are used to access cell deformability. We study a novel silicon microchannels device for use in red blood cell deformability. The channels are produced in silicon substrate using microengineering technology. The microgrooves formed in the surface of a single-crystal silicon substrate. They were converted to channels by tightly covering them with an optical flat glass plate. An array of flow channels (number 950 in parallel) have typical dimensions of 5 micrometers width X 5.5 Xm depth, and 30 micrometers length. There the RBC's are forced to pass through channels. Thus, the microchannels are used to simulate human blood capillaries. It provides a specific measurement of individual cell in terms of both flow velocity profile and an index of cell volume while the cell flow through the channels. It dominates the complex cellular flow behavior, such as, the viscosity of whole blood is a nonlinear function of shear rate, index of filtration, etc.

Vibration measurement by atomic force microscopy with laser readout

NASA Astrophysics Data System (ADS)

Snitka, Valentinas J.; Mizariene, Vida; Kalinauskas, Margiris; Lucinskas, Paulius

1998-06-01

Micromachined cantilever beams are widely used for different microengineering and nanotechnology actuators and sensors applications. The micromechanical cantilever tip-based data storage devices with reading real data at the rates exceeding 1Mbit/s have been demonstrated. The vibrational noise spectrum of a cantilever limits the data storage resolution. Therefore the possibility to measure the microvibrations and acoustic fields in different micromachined devices are of great interest. We describe a method to study a micromechanical cantilever and surface vibrations based on laser beam deflection measurements. The influence of piezoelectric plate vibrations and the tip- surface contact condition on the cantilever vibrations were investigated in the frequency range of 1-200 kHz. The experiments were performed using the measurement results. The V-shaped cantilevers exited by the normal vibrations due to the non-linearity at the tip-surface contact vibrates with a complex motion and has a lateral vibration mode coupled with normal vibration mode. The possibility to use laser deflection technique for the vibration measurements in micromachined structures with nano resolution is shown.

Nanotechnology in Glycomics: Applications in Diagnostics, Therapy, Imaging, and Separation Processes

PubMed Central

Dosekova, Erika; Filip, Jaroslav; Bertok, Tomas; Both, Peter; Kasak, Peter; Tkac, Jan

2017-01-01

This review comprehensively covers the most recent achievements (from 2013) in the successful integration of nanomaterials in the field of glycomics. The first part of the paper addresses the beneficial properties of nanomaterials for the construction of biosensors, bioanalytical devices, and protocols for the detection of various analytes, including viruses and whole cells, together with their key characteristics. The second part of the review focuses on the application of nanomaterials integrated with glycans for various biomedical applications, that is, vaccines against viral and bacterial infections and cancer cells, as therapeutic agents, for in vivo imaging and nuclear magnetic resonance imaging, and for selective drug delivery. The final part of the review describes various ways in which glycan enrichment can be effectively done using nanomaterials, molecularly imprinted polymers with polymer thickness controlled at the nanoscale, with a subsequent analysis of glycans by mass spectrometry. A short section describing an active glycoprofiling by microengines (microrockets) is covered as well. PMID:27859448

Nanotechnology in Glycomics: Applications in Diagnostics, Therapy, Imaging, and Separation Processes.

PubMed

Dosekova, Erika; Filip, Jaroslav; Bertok, Tomas; Both, Peter; Kasak, Peter; Tkac, Jan

2017-05-01

This review comprehensively covers the most recent achievements (from 2013) in the successful integration of nanomaterials in the field of glycomics. The first part of the paper addresses the beneficial properties of nanomaterials for the construction of biosensors, bioanalytical devices, and protocols for the detection of various analytes, including viruses and whole cells, together with their key characteristics. The second part of the review focuses on the application of nanomaterials integrated with glycans for various biomedical applications, that is, vaccines against viral and bacterial infections and cancer cells, as therapeutic agents, for in vivo imaging and nuclear magnetic resonance imaging, and for selective drug delivery. The final part of the review describes various ways in which glycan enrichment can be effectively done using nanomaterials, molecularly imprinted polymers with polymer thickness controlled at the nanoscale, with a subsequent analysis of glycans by mass spectrometry. A short section describing an active glycoprofiling by microengines (microrockets) is covered as well. © 2016 Wiley Periodicals, Inc.

Superhydrophobic Surface Coatings for Microfluidics and MEMs.

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

Branson, Eric D.; Singh, Seema; Houston, Jack E.

2006-11-01

Low solid interfacial energy and fractally rough surface topography confer to Lotus plants superhydrophobic (SH) properties like high contact angles, rolling and bouncing of liquid droplets, and self-cleaning of particle contaminants. This project exploits the porous fractal structure of a novel, synthetic SH surface for aerosol collection, its self-cleaning properties for particle concentration, and its slippery nature 3 to enhance the performance of fluidic and MEMS devices. We propose to understand fundamentally the conditions needed to cause liquid droplets to roll rather than flow/slide on a surface and how this %22rolling transition%22 influences the boundary condition describing fluid flow inmore » a pipe or micro-channel. Rolling of droplets is important for aerosol collection strategies because it allows trapped particles to be concentrated and transported in liquid droplets with no need for a pre-defined/micromachined fluidic architecture. The fluid/solid boundary condition is important because it governs flow resistance and rheology and establishes the fluid velocity profile. Although many research groups are exploring SH surfaces, our team is the first to unambiguously determine their effects on fluid flow and rheology. SH surfaces could impact all future SNL designs of collectors, fluidic devices, MEMS, and NEMS. Interfaced with inertial focusing aerosol collectors, SH surfaces would allow size-specific particle populations to be collected, concentrated, and transported to a fluidic interface without loss. In microfluidic systems, we expect to reduce the energy/power required to pump fluids and actuate MEMS. Plug-like (rather than parabolic) velocity profiles can greatly improve resolution of chip-based separations and enable unprecedented control of concentration profiles and residence times in fluidic-based micro-reactors. Patterned SH/hydrophilic channels could induce mixing in microchannels and enable development of microflow control elements. Acknowledgements This work was funded by Sandia National Laboratory's Laboratory Directed Research & Development program (LDRD). Some coating processes were conducted in the cleanroom facility located at the University of New Mexico's Center for High Technology Materials (CHTM). SEM images were performed at UNM's Center for Micro-Engineering on equipment funded by a NSF New Mexico EPSCoR grant. 4« less

A density functional study of silicon fullerene endohedral X@Si20F20 and exohedral X-Si20F20 (X=O2-, S2-, Se2-) complexes

NASA Astrophysics Data System (ADS)

Behzadi, Hadi; Esrafili, Mehdi D.; Manzetti, Sergio; Roonasi, Payman

2014-02-01

This study reports the structure and electronic properties of three stable endohedral X@Si20F20 and exohedral X-Si20F20 (X=O2-, S2-, Se2-) complexes. The study revealed that the endohedral complexes with S2- and Se2- result as energy minimum structures, with the guest anion located in the cage center. In the case of endohedral O2--complexes, the pattern is quite different whereas the O2- complexes dramatically deviated from the architecture of S2- and Se2-, by having O2- located toward one of silicon atoms in the cage. With respect to the exohedral form, the energy minimized structure is obtained by positioning the anion between two silicon atoms and forming two Si-X bonds. For both cases, the strength of the interactions is calculated to increase accordingly to the pattern: Se2-@Si20F20 (Se2--Si20F20)

In vitro models and systems for evaluating the dynamics of drug delivery to the healthy and diseased brain.

PubMed

Modarres, Hassan Pezeshgi; Janmaleki, Mohsen; Novin, Mana; Saliba, John; El-Hajj, Fatima; RezayatiCharan, Mahdi; Seyfoori, Amir; Sadabadi, Hamid; Vandal, Milène; Nguyen, Minh Dang; Hasan, Anwarul; Sanati-Nezhad, Amir

2018-03-10

The blood-brain barrier (BBB) plays a crucial role in maintaining brain homeostasis and transport of drugs to the brain. The conventional animal and Transwell BBB models along with emerging microfluidic-based BBB-on-chip systems have provided fundamental functionalities of the BBB and facilitated the testing of drug delivery to the brain tissue. However, developing biomimetic and predictive BBB models capable of reasonably mimicking essential characteristics of the BBB functions is still a challenge. In addition, detailed analysis of the dynamics of drug delivery to the healthy or diseased brain requires not only biomimetic BBB tissue models but also new systems capable of monitoring the BBB microenvironment and dynamics of barrier function and delivery mechanisms. This review provides a comprehensive overview of recent advances in microengineering of BBB models with different functional complexity and mimicking capability of healthy and diseased states. It also discusses new technologies that can make the next generation of biomimetic human BBBs containing integrated biosensors for real-time monitoring the tissue microenvironment and barrier function and correlating it with the dynamics of drug delivery. Such integrated system addresses important brain drug delivery questions related to the treatment of brain diseases. We further discuss how the combination of in vitro BBB systems, computational models and nanotechnology supports for characterization of the dynamics of drug delivery to the brain. Copyright © 2018 Elsevier B.V. All rights reserved.

Wide band laser-plasma soft X-ray source using a gas puff target for direct photo-etching of polymers

NASA Astrophysics Data System (ADS)

Bartnik, Andrzej; Fiedorowicz, Henryk; Jarocki, Roman; Kostecki, Jerzy; Rakowski, Rafał; Szczurek, Mirosław

2005-09-01

Organic polymers (PMMA, PTFE, PET, and PI) are considered as the important materials in microengineering, especially for biological and medical applications. Micromachining of such materials is possible with the use of different techniques that involve electromagnetic radiation or charged particle beams. Another possibility of high aspect ratio micromachining of PTFE is direct photo-etching using synchrotron radiation. X-ray and ultraviolet radiation from other sources, for micromachining of materials by direct photo-etching can be also applied. In this paper we present the results of investigation of a wide band soft X-ray source and its application for direct photo-etching of organic polymers. X-ray radiation in the wavelength range from about 3 nm to 20 nm was produced as a result of irradiation of a double-stream gas puff target with laser pulses of energy 0.8 J and time duration of about 3 ns. The spectra, plasma size and absolute energies of soft X-ray pulses for different gas puff targets were measured. Photo-etching process of polymers irradiated with the use of the soft X-ray radiation was analyzed and investigated. Samples of organic polymers were placed inside a vacuum chamber of the x-ray source, close to the gas puff target at the distance of about 2 cm from plasmas created by focused laser pulses. A fine metal grid placed in front of the samples was used as a mask to form structures by x-ray ablation. The results of photo-etching process for several minutes exposition with l0Hz repetition rate were presented. High ablation efficiency was obtained with the use of the gas puff target containing xenon surrounded by helium.

Optical, electrical and elastic properties of ferroelectric domain walls in lithium niobate and lithium titanate

NASA Astrophysics Data System (ADS)

Kim, Sungwon

Ferroelectric LiNbO3 and LiTaO3 crystals have developed, over the last 50 years as key materials for integrated and nonlinear optics due to their large electro-optic and nonlinear optical coefficients and a broad transparency range from 0.4 mum-4.5 mum wavelengths. Applications include high speed optical modulation and switching in 40GHz range, second harmonic generation, optical parametric amplification, pulse compression and so on. Ferroelectric domain microengineering has led to electro-optic scanners, dynamic focusing lenses, total internal reflection switches, and quasi-phase matched (QPM) frequency doublers. Most of these applications have so far been on non-stoichiometric compositions of these crystals. Recent breakthroughs in crystal growth have however opened up an entirely new window of opportunity from both scientific and technological viewpoint. The growth of stoichiometric composition crystals has led to the discovery of many fascinating effects arising from the presence or absence of atomic defects, such as an order of magnitude changes in coercive fields, internal fields, domain backswitching and stabilization phenomenon. On the nanoscale, unexpected features such as the presence of wide regions of optical contrast and strain have been discovered at 180° domain walls. Such strong influence of small amounts of nonstoichiometric defects on material properties has led to new device applications, particularly those involving domain patterning and shaping such as QPM devices in thick bulk crystals and improved photorefractive damage compositions. The central focus of this dissertation is to explore the role of nonstoichiometry and its precise influence on macroscale and nanoscale properties in lithium niobate and tantalate. Macroscale properties are studied using a combination of in-situ and high-speed electro-optic imaging microscopy and electrical switching experiments. Local static and dynamic strain properties at individual domain walls is studied using X-ray synchrotron imaging with and without in-situ electric fields. Nanoscale optical properties are studied using Near Field Scanning Optical Microscopy(NSOM). Finite Difference Time Domain(FDTD) codes, Beam Propagation Method(BPM) codes and X-ray tracing codes have been developed to successfully simulate NSOM images and X-ray topography images to extract the local optical and strain properties, respectively. A 3-D ferroelectric domain simulation code based on Time Dependent Ginzburg Landau(TDGL) theory and group theory has been developed to understand the nature of these local wall strains and the preferred wall orientations. By combining these experimental and numerical tools, We have also proposed a defect-dipole model and a mechanism by which the defect interacts with the domain walls. This thesis has thus built a more comprehensive picture of the influence of defects on domain walls on nanoscale and macroscale, and raises new scientific questions about the exact nature of domain walls-defect interactions. Besides the specific problem of ferroelectrics, the experimental and simulation tools, developed in this thesis will have wider application in the area of materials science.

Thermomagnetic coolers based on Bi and Bi-Sb nanocomposites

NASA Astrophysics Data System (ADS)

Huber, Tito E.; Constant, Pierre

2001-02-01

Bulk Bi, a semimetal, and Bi-Sb, have the highest thermoelectric figure of merit Z at 100 K. The thermoelectric properties of these materials are strongly anisotropic. The best thermoelectric performance is observed when the electrical current flows along the trigonal axis. However, Bi single crystals are easily cleaved along the trigonal planes. This lack of strength has largely prevented the use of these materials in practical thermoelectric coolers. Composite technology offers the opportunity to increase the toughness of Bi and Bi-Sb. Also, microengineering Bi into composites may lead to a significant improvement in their thermoelectric performance, because of the reduction of phonon conductivity from phonon scattering at the grain boundaries and interfaces. It has been shown theoretically that quantum-wire structures have the potential to significantly improve Z over the bulk value. We have synthesized microwire composites and present measurements of its electrical conductivity and Seebeck coefficient that are very encouraging. The role that a tough thermoelectric cooler could have in extending the lifetime of a space system such as Space InfraRed Telescope Facility (SIRTF) is briefly discussed. .

Reliability Modeling of Microelectromechanical Systems Using Neural Networks

NASA Technical Reports Server (NTRS)

Perera. J. Sebastian

2000-01-01

Microelectromechanical systems (MEMS) are a broad and rapidly expanding field that is currently receiving a great deal of attention because of the potential to significantly improve the ability to sense, analyze, and control a variety of processes, such as heating and ventilation systems, automobiles, medicine, aeronautical flight, military surveillance, weather forecasting, and space exploration. MEMS are very small and are a blend of electrical and mechanical components, with electrical and mechanical systems on one chip. This research establishes reliability estimation and prediction for MEMS devices at the conceptual design phase using neural networks. At the conceptual design phase, before devices are built and tested, traditional methods of quantifying reliability are inadequate because the device is not in existence and cannot be tested to establish the reliability distributions. A novel approach using neural networks is created to predict the overall reliability of a MEMS device based on its components and each component's attributes. The methodology begins with collecting attribute data (fabrication process, physical specifications, operating environment, property characteristics, packaging, etc.) and reliability data for many types of microengines. The data are partitioned into training data (the majority) and validation data (the remainder). A neural network is applied to the training data (both attribute and reliability); the attributes become the system inputs and reliability data (cycles to failure), the system output. After the neural network is trained with sufficient data. the validation data are used to verify the neural networks provided accurate reliability estimates. Now, the reliability of a new proposed MEMS device can be estimated by using the appropriate trained neural networks developed in this work.

Electronic Transport Properties of Bismuth Microwire Arrays

NASA Astrophysics Data System (ADS)

Solomon, S.; Huber, T. E.; Bouffard, M.; Graf, M. J.

2002-03-01

Bulk Bi, a semimetal, and Bi-Sb, have the highest thermoelectric figure of merit Z at 100 K. The thermoelectric properties of these materials are strongly anisotropic. The best thermoelectric performance is observed when the electrical current flows along the trigonal axis. However, Bi single crystals are easily cleaved along the trigonal planes. This lack of strength has largely prevented the use of these materials in practical thermoelectric coolers. Composite technology offers the opportunity to increase the toughness of Bi and Bi-Sb. Also, microengineering Bi into composites may lead to a significant improvement in their thermoelectric performance, because of the reduction of phonon conductivity from phonon scattering at the grain boundaries and interfaces. X-ray diffraction studies show that the microwires in the array are highly oriented along the crystal direction normal to the (003) lattice plane of the rombohedral crystal structure of Bi . Measurements of the resistance of arrays of 3 mm and 10 mm diameter wires have been carried out over a wide range of temperatures (1.8 K 300 K) and magnetic fields (0-8 T), and orientations of the sample with respect to the magnetic field (0-90o) which includes the magnetic and transverse orientation. The zero field resistivity was studied and it was found that, at low temperatures, the wire boundary scattering is the dominant process. The longitudinal magnetoresistance is negative, in contrast to the longitudinal magnetoresistance of bulk crystals oriented in direction perpendicular to the trigonal plane of the rhombohedral crystal lattice who exhibit negligible magnetoresistance. This results are interpreted in terms of a size effect. Research supported by NASA and NSF.

Evolutionary transition of dental formula in Late Cretaceous eutherian mammals.

PubMed

Averianov, Alexander O; Archibald, J David

2015-10-01

Kulbeckia kulbecke, stem placental mammal from the Late Cretaceous of Uzbekistan, shows a transitional stage of evolution in the dental formula from five to four premolars. A non-replaced dP3/dp3 may occur as individual variation. In other specimens, the lower premolars are crowded with no space for development of dp3. As is evident from the CT scanning of one juvenile specimen, the development of dp3 started in a late ontogenetic stage and was confined to the pulp cavity of the developing p2. This dp3 would have been resorbed in a later ontogenetic stage, as the roots of p2 formed. The initial stage of reduction of the third premolar can be traced to stem therians (Juramaia and Eomaia), which have both dP3 and P3 present in the adult dentition. Further delay in the development of dP3/dp3 led to the loss of the permanent P3/p3 (a possible synapomorphy for Eutheria). The dP3/dp3 was present during most of the adult stages in the Late Cretaceous stem placentals Zhelestidae and Gypsonictops. This tooth is totally absent in basal taxa of Placentalia, which normally have at most four premolars.

Effects of Process Parameters on Ultrasonic Micro-Hole Drilling in Glass and Ruby

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

Schorderet, Alain; Deghilage, Emmanuel; Agbeviade, Kossi

2011-05-04

Brittle materials such as ceramics, glasses and oxide single crystals find increasing applications in advanced micro-engineering products. Machining small features in such materials represents a manufacturing challenge. Ultrasonic drilling constitutes a promising technique for realizing simple micro-holes of high diameter-to-depth ratio. The process involves impacting abrasive particles in suspension in a liquid slurry between tool and work piece. Among the process performance criteria, the drilling time (productivity) is one of the most important quantities to evaluate the suitability of the process for industrial applications.This paper summarizes recent results pertaining to the ultrasonic micro-drilling process obtained with a semi-industrial 3-axis machine.more » The workpiece is vibrated at 40 kHz frequency with an amplitude of several micrometers. A voice-coil actuator and a control loop based on the drilling force impose the tool feed. In addition, the tool is rotated at a prescribed speed to improve the drilling speed as well as the hole geometry. Typically, a WC wire serves as tool to bore 200 {mu}m diameter micro-holes of 300 to 1,000 {mu}m depth in glass and ruby. The abrasive slurry contains B4C particles of 1 {mu}m to 5 {mu}m diameter in various concentrations.This paper discusses, on the basis of the experimental results, the influence of several parameters on the drilling time. First, the results show that the control strategy based on the drilling force allows to reach higher feed rates (avoiding tool breakage). Typically, a 8 um/s feed rate is achieved with glass and 0.9 {mu}m/s with ruby. Tool rotation, even for values as low as 50 rpm, increases productivity and improves holes geometry. Drilling with 1 {mu}m and 5 {mu}m B4C particles yields similar productivity results. Our future research will focus on using the presented results to develop a model that can serve to optimize the process for different applications.« less

Hepatitis B virus X protein shifts human hepatic transforming growth factor (TGF)-beta signaling from tumor suppression to oncogenesis in early chronic hepatitis B.

PubMed

Murata, Miki; Matsuzaki, Koichi; Yoshida, Katsunori; Sekimoto, Go; Tahashi, Yoshiya; Mori, Shigeo; Uemura, Yoshiko; Sakaida, Noriko; Fujisawa, Junichi; Seki, Toshihito; Kobayashi, Kazuki; Yokote, Koutaro; Koike, Kazuhiko; Okazaki, Kazuichi

2009-04-01

Hepatitis B virus X (HBx) protein is suspected to participate in oncogenesis during chronic hepatitis B progression. Transforming growth factor beta (TGF-beta) signaling involves both tumor suppression and oncogenesis. TGF-beta activates TGF-beta type I receptor (TbetaRI) and c-Jun N-terminal kinase (JNK), which differentially phosphorylate the mediator Smad3 to become C-terminally phosphorylated Smad3 (pSmad3C) and linker-phosphorylated Smad3 (pSmad3L). Reversible shifting of Smad3-mediated signaling between tumor suppression and oncogenesis in HBx-expressing hepatocytes indicated that TbetaRI-dependent pSmad3C transmitted a tumor-suppressive TGF-beta signal, while JNK-dependent pSmad3L promoted cell growth. We used immunostaining, immunoblotting, and in vitro kinase assay to compare pSmad3L- and pSmad3C-mediated signaling in biopsy specimens representing chronic hepatitis, cirrhosis, or hepatocellular carcinoma (HCC) from 90 patients chronically infected with hepatitis B virus (HBV) with signaling in liver specimens from HBx transgenic mice. In proportion to plasma HBV DNA levels, early chronic hepatitis B specimens showed prominence of pSmad3L in hepatocytic nuclei. HBx-activated JNK/pSmad3L/c-Myc oncogenic pathway was enhanced, while the TbetaRI/pSmad3C/p21(WAF1) tumor-suppressive pathway was impaired as human and mouse HBx-associated hepatocarcinogenesis progressed. Of 28 patients with chronic hepatitis B who showed strong oncogenic pSmad3L signaling, six developed HCC within 12 years; only one of 32 patients showing little pSmad3L developed HCC. In contrast, seven of 30 patients with little Smad3C phosphorylation developed HCC, while no patient who retained hepatocytic tumor-suppressive pSmad3C developed HCC within 12 years. HBx shifts hepatocytic TGF-beta signaling from the tumor-suppressive pSmad3C pathway to the oncogenic pSmad3L pathway in early carcinogenic process. Hepatocytic pSmad3L and pSmad3C assessment in HBV-infected liver specimens should prove clinically useful for predicting risk of HCC.

The effects of simultaneous dual focus lenses on refractive development in infant monkeys.

PubMed

Arumugam, Baskar; Hung, Li-Fang; To, Chi-Ho; Holden, Brien; Smith, Earl L

2014-10-16

We investigated the effects of two simultaneously imposed, competing focal planes on refractive development in monkeys. Starting at 3 weeks of age and continuing until 150 ± 4 days of age, rhesus monkeys were reared with binocular dual-focus spectacle lenses. The treatment lenses had central 2-mm zones of zero power and concentric annular zones with alternating powers of +3.0 diopter [D] and plano (pL or 0 D) (n = 7; +3D/pL) or -3.0 D and plano (n = 7; -3D/pL). Retinoscopy, keratometry, and A-scan ultrasonography were performed every 2 weeks throughout the treatment period. For comparison purposes data were obtained from monkeys reared with full field (FF) +3.0 (n = 4) or -3.0 D (n = 5) lenses over both eyes and 33 control animals reared with unrestricted vision. The +3 D/pL lenses slowed eye growth resulting in hyperopic refractive errors that were similar to those produced by FF+3 D lenses (+3 D/pL = +5.25 D, FF +3 D = +4.63 D; P = 0.32), but significantly more hyperopic than those observed in control monkeys (+2.50 D, P = 0.0001). One -3 D/pL monkey developed compensating axial myopia; however, in the other -3 D/pL monkeys refractive development was dominated by the zero-powered portions of the treatment lenses. The refractive errors for the -3 D/pL monkeys were more hyperopic than those in the FF -3 D monkeys (-3 D/pL = +3.13 D, FF -3D = -1.69 D; P = 0.01), but similar to those in control animals (P = 0.15). In the monkeys treated with dual-focus lenses, refractive development was dominated by the more anterior (i.e., relatively myopic) image plane. The results indicate that imposing relative myopic defocus over a large proportion of the retina is an effective means for slowing ocular growth. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

The Effects of Simultaneous Dual Focus Lenses on Refractive Development in Infant Monkeys

PubMed Central

Arumugam, Baskar; Hung, Li-Fang; To, Chi-ho; Holden, Brien; Smith, Earl L.

2014-01-01

Purpose. We investigated the effects of two simultaneously imposed, competing focal planes on refractive development in monkeys. Methods. Starting at 3 weeks of age and continuing until 150 ± 4 days of age, rhesus monkeys were reared with binocular dual-focus spectacle lenses. The treatment lenses had central 2-mm zones of zero power and concentric annular zones with alternating powers of +3.0 diopter [D] and plano (pL or 0 D) (n = 7; +3D/pL) or −3.0 D and plano (n = 7; −3D/pL). Retinoscopy, keratometry, and A-scan ultrasonography were performed every 2 weeks throughout the treatment period. For comparison purposes data were obtained from monkeys reared with full field (FF) +3.0 (n = 4) or −3.0 D (n = 5) lenses over both eyes and 33 control animals reared with unrestricted vision. Results. The +3 D/pL lenses slowed eye growth resulting in hyperopic refractive errors that were similar to those produced by FF+3 D lenses (+3 D/pL = +5.25 D, FF +3 D = +4.63 D; P = 0.32), but significantly more hyperopic than those observed in control monkeys (+2.50 D, P = 0.0001). One −3 D/pL monkey developed compensating axial myopia; however, in the other −3 D/pL monkeys refractive development was dominated by the zero-powered portions of the treatment lenses. The refractive errors for the −3 D/pL monkeys were more hyperopic than those in the FF −3 D monkeys (−3 D/pL = +3.13 D, FF −3D = −1.69 D; P = 0.01), but similar to those in control animals (P = 0.15). Conclusions. In the monkeys treated with dual-focus lenses, refractive development was dominated by the more anterior (i.e., relatively myopic) image plane. The results indicate that imposing relative myopic defocus over a large proportion of the retina is an effective means for slowing ocular growth. PMID:25324283

Analysis of single mammalian cells on-chip.

PubMed

Sims, Christopher E; Allbritton, Nancy L

2007-04-01

A goal of modern biology is to understand the molecular mechanisms underlying cellular function. The ability to manipulate and analyze single cells is crucial for this task. The advent of microengineering is providing biologists with unprecedented opportunities for cell handling and investigation on a cell-by-cell basis. For this reason, lab-on-a-chip (LOC) technologies are emerging as the next revolution in tools for biological discovery. In the current discussion, we seek to summarize the state of the art for conventional technologies in use by biologists for the analysis of single, mammalian cells, and then compare LOC devices engineered for these same single-cell studies. While a review of the technical progress is included, a major goal is to present the view point of the practicing biologist and the advances that might increase adoption by these individuals. The LOC field is expanding rapidly, and we have focused on areas of broad interest to the biology community where the technology is sufficiently far advanced to contemplate near-term application in biological experimentation. Focus areas to be covered include flow cytometry, electrophoretic analysis of cell contents, fluorescent-indicator-based analyses, cells as small volume reactors, control of the cellular microenvironment, and single-cell PCR.

Developing Learning Model P3E to Improve Students’ Critical Thinking Skills of Islamic Senior High School

NASA Astrophysics Data System (ADS)

Bahtiar; Rahayu, Y. S.; Wasis

2018-01-01

This research aims to produce P3E learning model to improve students’ critical thinking skills. The developed model is named P3E, consisting of 4 (four) stages namely; organization, inquiry, presentation, and evaluation. This development research refers to the development stage by Kemp. The design of the wide scale try-out used pretest-posttest group design. The wide scale try-out was conducted in grade X of 2016/2017 academic year. The analysis of the results of this development research inludes three aspects, namely: validity, practicality, and effectiveness of the model developed. The research results showed; (1) the P3E learning model was valid, according to experts with an average value of 3.7; (2) The completion of the syntax of the learning model developed obtained 98.09% and 94.39% for two schools based on the assessment of the observers. This shows that the developed model is practical to be implemented; (3) the developed model is effective for improving students’ critical thinking skills, although the n-gain of the students’ critical thinking skills was 0.54 with moderate category. Based on the results of the research above, it can be concluded that the developed P3E learning model is suitable to be used to improve students’ critical thinking skills.

MicroRNA-141-3p/200a-3p target and may be involved in post-transcriptional repression of RNA decapping enzyme Dcp2 during renal development.

PubMed

Zhang, Ming-Nan; Tang, Qun-Ye; Li, Rui-Min; Song, Man-Gen

2018-06-18

The RNA decapping enzyme Dcp2 is a crucial enzyme involved in the process of RNA turnover, which can post-transcriptionally regulate gene expression. Dcp2 has been found to be highly expressed in embryonic, but not adult, kidneys. Here we showed that Dcp2 mRNA was expressed, but Dcp2 proteins were absent, in mouse kidneys after postnatal day 10 (P10). In kidneys of adult Dcp2-IRES-EGFP knock-in mice, Dcp2 was undetectable but EGFP was expressed, indicating that Dcp2 mRNA was not completely silenced in adult kidneys. Using luciferase reporter assays, we found that miR-141-3p/200a-3p directly targeted the 3' UTR of Dcp2 mRNA. Overexpression of miR-141-3p and miR-200a-3p downregulated endogenous Dcp2 protein expression. Furthermore, miR-141-3p and miR-200a-3p expression was low in embryonic kidneys but increased dramatically after P10 and was negatively correlated with Dcp2 protein expression during renal development. These results suggest miR-141-3p/200a-3p may be involved in post-transcriptional repression of Dcp2 expression during renal development. IRES: internal ribosome entry site; EGFP: enhanced green fluorescent protein; UTR: untranslated region.

Interplay between singing and cortical processing of music: a longitudinal study in children with cochlear implants.

PubMed

Torppa, Ritva; Huotilainen, Minna; Leminen, Miika; Lipsanen, Jari; Tervaniemi, Mari

2014-01-01

Informal music activities such as singing may lead to augmented auditory perception and attention. In order to study the accuracy and development of music-related sound change detection in children with cochlear implants (CIs) and normal hearing (NH) aged 4-13 years, we recorded their auditory event-related potentials twice (at T1 and T2, 14-17 months apart). We compared their MMN (preattentive discrimination) and P3a (attention toward salient sounds) to changes in piano tone pitch, timbre, duration, and gaps. Of particular interest was to determine whether singing can facilitate auditory perception and attention of CI children. It was found that, compared to the NH group, the CI group had smaller and later timbre P3a and later pitch P3a, implying degraded discrimination and attention shift. Duration MMN became larger from T1 to T2 only in the NH group. The development of response patterns for duration and gap changes were not similar in the CI and NH groups. Importantly, CI singers had enhanced or rapidly developing P3a or P3a-like responses over all change types. In contrast, CI non-singers had rapidly enlarging pitch MMN without enlargement of P3a, and their timbre P3a became smaller and later over time. These novel results show interplay between MMN, P3a, brain development, cochlear implantation, and singing. They imply an augmented development of neural networks for attention and more accurate neural discrimination associated with singing. In future studies, differential development of P3a between CI and NH children should be taken into account in comparisons of these groups. Moreover, further studies are needed to assess whether singing enhances auditory perception and attention of children with CIs.

Glucose Sensing with Phenylboronic Acid Functionalized Hydrogel-Based Optical Diffusers

PubMed Central

2018-01-01

Phenylboronic acids have emerged as synthetic receptors that can reversibly bind to cis-diols of glucose molecules. The incorporation of phenylboronic acids in hydrogels offers exclusive attributes; for example, the binding process with glucose induces Donnan osmotic pressure resulting in volumetric changes in the matrix. However, their practical applications are hindered because of complex readout approaches and their time-consuming fabrication processes. Here, we demonstrate a microimprinting method to fabricate densely packed concavities in phenylboronic acid functionalized hydrogel films. A microengineered optical diffuser structure was imprinted on a phenylboronic acid based cis-diol recognizing motif prepositioned in a hydrogel film. The diffuser structure engineered on the hydrogel was based on laser-inscribed arrays of imperfect microlenses that focused the incoming light at different focal lengths and direction resulting in a diffused profile of light in transmission and reflection readout modes. The signature of the dimensional modulation was detected in terms of changing focal lengths of the microlenses due to the volumetric expansion of the hydrogel that altered the diffusion spectra and transmitted beam profile. The transmitted optical light spread and intensity through the sensor was measured to determine variation in glucose concentrations at physiological conditions. The sensor was integrated in a contact lens and placed over an artificial eye. Artificial stimulation of variation in glucose concentration allowed quantitative measurements using a smartphone’s photodiode. A smartphone app was utilized to convert the received light intensity to quantitative glucose concentration values. The developed sensing platform offers low cost, rapid fabrication, and easy detection scheme as compared to other optical sensing counterparts. The presented detection scheme may have applications in wearable real-time biomarker monitoring devices at point-of-care settings. PMID:29529366

The potential of ocean acidification on suppressing larval development in the Pacific oyster Crassostrea gigas and blood cockle Arca inflata Reeve

NASA Astrophysics Data System (ADS)

Li, Jiaqi; Jiang, Zengjie; Zhang, Jihong; Mao, Yuze; Bian, Dapeng; Fang, Jianguang

2014-11-01

We evaluated the effect of pH on larval development in larval Pacific oyster ( Crassostrea gigas) and blood cockle ( Arca inflata Reeve). The larvae were reared at pH 8.2 (control), 7.9, 7.6, or 7.3 beginning 30 min or 24 h post fertilization. Exposure to lower pH during early embryonic development inhibited larval shell formation in both species. Compared with the control, larvae took longer to reach the D-veliger stage when reared under pH 7.6 and 7.3. Exposure to lower pH immediately after fertilization resulted in significantly delayed shell formation in the Pacific oyster larvae at pH 7.3 and blood cockle larvae at pH 7.6 and 7.3. However, when exposure was delayed until 24 h post fertilization, shell formation was only inhibited in blood cockle larvae reared at pH 7.3. Thus, the early embryonic stages were more sensitive to acidified conditions. Our results suggest that ocean acidification will have an adverse effect on embryonic development in bivalves. Although the effects appear subtle, they may accumulate and lead to subsequent issues during later larval development.

Welcome to the 2014 volume of Journal of Micromechanics and Microengineering

NASA Astrophysics Data System (ADS)

Fang, Weileun

2014-01-01

It is my great honor to serve as the Editor-in-Chief of Journal of Micromechanics and Microengineering (JMM) starting from 2014, the 24th year of the journal. I would also like to take this opportunity to convey my sincere appreciation to (i) the past editors for their vision to bring this journal to be such a significant publication and research platform in MEMS and microsystems technology; (ii) the reviewers for their precious time and valuable comments that enhance the publication quality of this journal; and (iii) the authors for their choice to publish their best work in this journal and their contribution to our community; (iv) the readers who extend the journal's impact not only to their research fields but to industry and all human society; and finally (v) the publication team at IOP Publishing. As the sixth Editor-in-Chief, I will aim to continue my predecessors' leadership and guidance, and further extend the distinguished reputation of JMM. In the past year, the number of submissions to this journal neared 900, an increase on last year, with the acceptance number of 401 (an acceptance rate lower than 50%). I would also like to point out the articles published in 2013 has jumped up to 383, showing a healthy growth compared to 365 in year 2012. To achieve this progress, the average times of the receipt-first decision and the receipt-accept confirmations are 39 days and 104 days, respectively. Furthermore, the average time of the accept-web publication is within 26 days, which is a considerable improvement in this journal. All abovementioned numbers together become a very attractive feature of this journal. To deal with the rapid expansion of the incoming papers and associated reviewing process we have tremendous help from the members of the journal's Editorial Board and referees worldwide, whom I would like to acknowledge since their well-constructed evaluation is of great importance to continuously enhancing the quality of the journal. Of course it would not be possible without the support from the publishing, production and marketing staff in Bristol, through whom the publication process of this journal is greatly expedited, which is an important feature of this journal. Last but not least, we have established a distinct and renowned profile in our Editorial Board, with a diversified spectrum in our research fields. I wish the profile can be further extended to cover not only the existing research topics, but the new trends and emerging fields relevant to MEMS and microsystems. Again, this is not possible without the efforts and contributions from our community. I also wish each of you can bring young blood and new researchers to our community, thus creating a prosperous era for the next ten years of this journal. I therefore wish all of you a healthy and prosperous 2014!

Impact of cumulative gain in expertise on the efficiency of handmade cloning in cattle.

PubMed

Gerger, R P C; Rossetto, Rafael; Ribeiro, E S; Ortigari, Ivens; Zago, Fabiano Carminatti; Aguiar, L H; Costa, U M; Lopes, Rui Fernando Félix; Ambrósio, Carlos Eduardo; Miglino, Maria Angélica; Rodrigues, José Luiz; Forell, Fabiana; Bertolini, Luciana Relly; Bertolini, Marcelo

2017-06-01

The aim of this study was to determine the effects of the cumulative gain in expertise in carrying out handmade cloning (HMC) procedures on embryo yield and pregnancy outcome in cattle. Results from in vitro and in vivo embryo development after HMC during three periods of 7 months, separated by 3-month intervals, were compiled and designated as P1, P2 and P3. Blastocyst yield, morphological quality and stage of development, and pregnancy per embryo transfer (ET) on Day 30 of gestation were compared. Zona-intact oocytes were activated chemically in each experiment replicate, and development of parthenogenetic blastocysts was used as a control measurement of oocyte quality and in vitro culture conditions. A total of 21,231 cumulus-oocyte complexes (COCs) were in vitro-matured, with 5,432, 10,721 and 5078 COCs used in 16, 18 and 10 replicates for P1, P2 and P3, respectively. Cloned blastocyst yields on Day 7 increased from 15.5% (124/798) in P1 to 21.6% (309/1428) and 36.6% (280/764) in P2 and P3, respectively. No differences were observed in blastocyst development of parthenogenetic embryos, which average 30.0, 37.6, and 36.4% in P1, P2, and P3, respectively. A 10-fold higher probability of obtaining cloned blastocysts at more advanced stages of development and of higher morphological grade was seen during P3 compared with P1. Pregnancy per ET on Day 30 also increased with gain in expertise, being 6.7% (2/30), 20.8% (10/48) and 40.0% (24/60) for P1, P2 and P3, respectively. The relative efficiency for the establishment of pregnancies (per total COC) increased from 0.04% (1:2716) in P1 to 0.22% (1:460) in P2, reaching 0.47% (1:212) in P3. Results demonstrated a gradual improvement in in vitro and in vivo embryo development over time after establishment of HMC procedures in the laboratory, highlighting the importance of gaining experience and technical skills on the overall cloning efficiency. Copyright © 2017 Elsevier Inc. All rights reserved.

Ratiometric photoluminescence sensing based on Ti3C2 MXene quantum dots as an intracellular pH sensor.

PubMed

Chen, Xu; Sun, Xueke; Xu, Wen; Pan, Gencai; Zhou, Donglei; Zhu, Jinyang; Wang, He; Bai, Xue; Dong, Biao; Song, Hongwei

2018-01-18

Intracellular pH sensing is of importance and can be used as an indicator for monitoring the evolution of various diseases and the health of cells. Here, we developed a new class of surface-functionalized MXene quantum dots (QDs), Ti 3 C 2 , by the sonication cutting and hydrothermal approach and further explored their intracellular pH sensing. The functionalized Ti 3 C 2 QDs exhibit bright excitation-dependent blue photoluminescence (PL) originating from the size effect and surface defects. Meanwhile, Ti 3 C 2 QDs demonstrate a high PL response induced by the deprotonation of the surface defects. Furthermore, combining the highly pH sensitive Ti 3 C 2 QDs with the pH insensitive [Ru(dpp) 3 ]Cl 2 , we developed a ratiometric pH sensor to quantitatively monitor the intracellular pH values. These novel MXene quantum dots can serve as a promising platform for developing practical fluorescent nanosensors.

Internal Tandem Duplication in FLT3 Attenuates Proliferation and Regulates Resistance to the FLT3 Inhibitor AC220 by Modulating p21Cdkn1a and Pbx1 in Hematopoietic Cells

PubMed Central

Abe, Mariko; Pelus, Louis M.; Singh, Pratibha; Hirade, Tomohiro; Onishi, Chie; Purevsuren, Jamiyan; Taketani, Takeshi; Yamaguchi, Seiji; Fukuda, Seiji

2016-01-01

Internal tandem duplication (ITD) mutations in the Fms-related tyrosine kinase 3 (FLT3) gene (FLT3-ITD) are associated with poor prognosis in patients with acute myeloid leukemia (AML). Due to the development of drug resistance, few FLT3-ITD inhibitors are effective against FLT3-ITD+ AML. In this study, we show that FLT3-ITD activates a novel pathway involving p21Cdkn1a (p21) and pre-B cell leukemia transcription factor 1 (Pbx1) that attenuates FLT3-ITD cell proliferation and is involved in the development of drug resistance. FLT3-ITD up-regulated p21 expression in both mouse bone marrow c-kit+-Sca-1+-Lin- (KSL) cells and Ba/F3 cells. The loss of p21 expression enhanced growth factor-independent proliferation and sensitivity to cytarabine as a consequence of concomitantly enriching the S+G2/M phase population and significantly increasing the expression of Pbx1, but not Evi-1, in FLT3-ITD+ cells. This enhanced cell proliferation following the loss of p21 was partially abrogated when Pbx1 expression was silenced in FLT3-ITD+ primary bone marrow colony-forming cells and Ba/F3 cells. When FLT3-ITD was antagonized with AC220, a selective inhibitor of FLT3-ITD, p21 expression was decreased coincident with Pbx1 mRNA up-regulation and a rapid decline in the number of viable FLT3-ITD+ Ba/F3 cells; however, the cells eventually became refractory to AC220. Overexpressing p21 in FLT3-ITD+ Ba/F3 cells delayed the emergence of cells that were refractory to AC220, whereas p21 silencing accelerated their development. These data indicate that FLT3-ITD is capable of inhibiting FLT3-ITD+ cell proliferation through the p21/Pbx1 axis and that treatments that antagonize FLT3-ITD contribute to the subsequent development of cells that are refractory to a FLT3-ITD inhibitor by disrupting p21 expression. PMID:27387666

Inhibition of c-Jun NH2-terminal kinase switches Smad3 signaling from oncogenesis to tumor- suppression in rat hepatocellular carcinoma.

PubMed

Nagata, Hiromitsu; Hatano, Etsuro; Tada, Masaharu; Murata, Miki; Kitamura, Koji; Asechi, Hiroyuki; Narita, Masato; Yanagida, Atsuko; Tamaki, Nobuyuki; Yagi, Shintaro; Ikai, Iwao; Matsuzaki, Koichi; Uemoto, Shinji

2009-06-01

Transforming growth factor beta (TGF-beta) signaling involves both tumor-suppression and oncogenesis. TGF-beta activates the TGF-beta type I receptor (TbetaRI) and c-Jun N-terminal kinase (JNK), which differentially phosphorylate the mediator Smad3 to become COOH-terminally phosphorylated Smad3 (pSmad3C) and linker-phosphorylated Smad3 (pSmad3L). TbetaRI-dependent pSmad3C transmits a tumor-suppressive TGF-beta signal, while JNK-dependent pSmad3L promotes carcinogenesis in human chronic liver disorders. The aim of this study is to elucidate how SP600125, a JNK inhibitor, affected rat hepatocellular carcinoma (HCC) development, while focusing on the domain-specific phosphorylation of Smad3. The rats received subcutaneous injections of either SP600125 or vehicle 11 times weekly together with 100 ppm N-diethylnitrosamine (DEN) administration for 56 days and were sacrificed in order to evaluate HCC development 28 days after the last DEN administration. The number of tumor nodules greater than 3 mm in diameter and the liver weight/body weight ratio were significantly lower in the SP600125-treated rats than those in the vehicle-treated rats (7.9 +/- 0.8 versus 17.7 +/- 0.9: P < 0.001; 6.3 +/- 1.2 versus 7.1 +/- 0.2%: P < 0.05). SP600125 significantly prolonged the median survival time in rats with DEN-induced HCC (113 versus 97 days: log-rank P = 0.0018). JNK/pSmad3L/c-Myc was enhanced in the rat hepatocytes exposed to DEN. However, TbetaRI/pSmad3C/p21(WAF1) was impaired as DEN-induced HCC developed and progressed. The specific inhibition of JNK activity by SP600125 suppressed pSmad3L/c-Myc in the damaged hepatocytes and enhanced pSmad3C/p21(WAF1), acting as a tumor suppressor in normal hepatocytes. Administration of SP600125 to DEN-treated rats shifted hepatocytic Smad3-mediated signal from oncogenesis to tumor suppression, thus suggesting that JNK could be a therapeutic target of human HCC development and progression.

P2X3 and P2X2/3 Receptors Play a Crucial Role in Articular Hyperalgesia Development Through Inflammatory Mechanisms in the Knee Joint Experimental Synovitis.

PubMed

Teixeira, Juliana Maia; Bobinski, Franciane; Parada, Carlos Amílcar; Sluka, Kathleen A; Tambeli, Cláudia Herrera

2017-10-01

Osteoarthritis (OA) is a degenerative and progressive disease characterized by cartilage breakdown and by synovial membrane inflammation, which results in disability, joint swelling, and pain. The purinergic P2X3 and P2X2/3 receptors contribute to development of inflammatory hyperalgesia, participate in arthritis processes in the knee joint, and are expressed in chondrocytes and nociceptive afferent fibers innervating the knee joint. In this study, we hypothesized that P2X3 and P2X2/3 receptors activation by endogenous ATP (adenosine 5'-triphosphate) induces articular hyperalgesia in the knee joint of male and female rats through an indirect sensitization of primary afferent nociceptors dependent on the previous release of pro-inflammatory cytokines and/or on neutrophil migration. We found that the blockade of articular P2X3 and P2X2/3 receptors significantly attenuated carrageenan-induced hyperalgesia in the knee joint of male and estrus female rats in a similar manner. The carrageenan-induced knee joint inflammation increased the expression of P2X3 receptors in chondrocytes of articular cartilage. Further, the blockade of articular P2X3 and P2X2/3 receptors significantly reduced the increased concentration of TNF-α, IL-6, and CINC-1 and the neutrophil migration induced by carrageenan. These findings indicate that P2X3 and P2X2/3 receptors activation by endogenous ATP is essential to hyperalgesia development in the knee joint through an indirect sensitization of primary afferent nociceptors dependent on the previous release of pro-inflammatory cytokines and/or on neutrophil migration.

Interplay between singing and cortical processing of music: a longitudinal study in children with cochlear implants

PubMed Central

Torppa, Ritva; Huotilainen, Minna; Leminen, Miika; Lipsanen, Jari; Tervaniemi, Mari

2014-01-01

Informal music activities such as singing may lead to augmented auditory perception and attention. In order to study the accuracy and development of music-related sound change detection in children with cochlear implants (CIs) and normal hearing (NH) aged 4–13 years, we recorded their auditory event-related potentials twice (at T1 and T2, 14–17 months apart). We compared their MMN (preattentive discrimination) and P3a (attention toward salient sounds) to changes in piano tone pitch, timbre, duration, and gaps. Of particular interest was to determine whether singing can facilitate auditory perception and attention of CI children. It was found that, compared to the NH group, the CI group had smaller and later timbre P3a and later pitch P3a, implying degraded discrimination and attention shift. Duration MMN became larger from T1 to T2 only in the NH group. The development of response patterns for duration and gap changes were not similar in the CI and NH groups. Importantly, CI singers had enhanced or rapidly developing P3a or P3a-like responses over all change types. In contrast, CI non-singers had rapidly enlarging pitch MMN without enlargement of P3a, and their timbre P3a became smaller and later over time. These novel results show interplay between MMN, P3a, brain development, cochlear implantation, and singing. They imply an augmented development of neural networks for attention and more accurate neural discrimination associated with singing. In future studies, differential development of P3a between CI and NH children should be taken into account in comparisons of these groups. Moreover, further studies are needed to assess whether singing enhances auditory perception and attention of children with CIs. PMID:25540628

Creating and facilitating change for Person-Centred Coordinated Care (P3C): The development of the Organisational Change Tool (P3C-OCT).

PubMed

Horrell, Jane; Lloyd, Helen; Sugavanam, Thavapriya; Close, James; Byng, Richard

2018-04-01

Person Centred Coordinated Care (P3C) is a UK priority for patients, carers, professionals, commissioners and policy makers. Services are developing a range of approaches to deliver this care with a lack of tools to guide implementation. A scoping review and critical examination of current policy, key literature and NHS guidelines, together with stakeholder involvement led to the identification of domains, subdomains and component activities (processes and behaviours) required to deliver P3C. These were validated through codesign with stakeholders via a series of workshops and cognitive interviews. Six core domains of P3C were identified as follows: (i) my goals, (ii) care planning, (iii) transitions, (iv) decision making (v), information and communication and (vi) organizational support activities. These were populated by 29 core subdomains (question items). A number of response codes (components) to each question provide examples of the processes and activities that can be actioned to achieve each core subdomain of P3C. The P3C-OCT provides a coherent approach to monitoring progress and supporting practice development towards P3C. It can be used to generate a shared understanding of the core domains of P3C at a service delivery level, and support reorganization of care for those with complex needs. The tool can reliably detect change over time, as demonstrated in a sample of 40 UK general practices. It is currently being used in four UK evaluations of new models of care and being further developed as a training tool for the delivery of P3C. © 2017 The Authors Health Expectations Published by John Wiley & Sons Ltd.

Controlled Pd(0)/t Bu3P Catalyzed Suzuki Cross-Coupling Polymerization of AB-Type Monomers with ArPd(t Bu3P)X or Pd2(dba)3/t Bu3P/ArX as the Initiator

DOE PAGES

Zhang, Honghai; Xing, Chun-Hui; Hu, Qiao-Sheng; ...

2015-02-05

The synthesis of well-defined and functionalized conjugated polymers, which are essential in the development of efficient organic electronics, through Suzuki cross-coupling polymerizations has been a challenging task. We developed controlled Pd(0)/t-Bu3P-catalyzed Suzuki cross-coupling polymerizations of AB-type monomers via the chain-growth mechanism with a series of in situ generated ArPd(t-Bu3P)X (X = I, Br, Cl) complexes as initiators. Among them, the combinations of Pd2(dba)3/t-Bu3P/p-BrC6H4I, Pd2(dba)3/t-Bu3P/p-BrC6H4CH2OH and Pd2(dba)3/t-Bu3P/p-PhCOC6H4Br were identified as highly robust initiator systems, resulting in polymers with predictable molecular weight and narrow polydispersity (PDI~1.13-1.20). In addition, Pd2(dba)3/t-Bu3P/p-BrC6H4CH2OH and Pd2(dba)3/t-Bu3P/p-PhCOC6H4Br initiator systems afforded functional polymers with >95% fidelity. Our results pavedmore » the road to access well-defined conjugated polymers, including conjugated polymers with complex polymer architectures such as block copolymers and branch copolymers.« less

Osteoclastic miR-214 targets TRAF3 to contribute to osteolytic bone metastasis of breast cancer

PubMed Central

Liu, Jin; Li, Defang; Dang, Lei; Liang, Chao; Guo, Baosheng; Lu, Cheng; He, Xiaojuan; Cheung, Hilda Y. S.; He, Bing; Liu, Biao; Li, Fangfei; Lu, Jun; Wang, Luyao; Shaikh, Atik Badshah; Jiang, Feng; Lu, Changwei; Peng, Songlin; Zhang, Zongkang; Zhang, Bao-Ting; Pan, Xiaohua; Xiao, Lianbo; Lu, Aiping; Zhang, Ge

2017-01-01

The role of osteoclastic miRNAs in regulating osteolytic bone metastasis (OBM) of breast cancer is still underexplored. Here, we examined the expression profiles of osteoclastogenic miRNAs in human bone specimens and identified that miR-214-3p was significantly upregulated in breast cancer patients with OBM. Consistently, we found increased miR-214-3p within osteoclasts, which was associated with the elevated bone resorption, during the development of OBM in human breast cancer xenografted nude mice (BCX). Furthermore, genetic ablation of osteoclastic miR-214-3p in nude mice prevent the development of OBM. Conditioned medium from MDA-MB-231 cells dramatically stimulated miR-214-3p expression to promote osteoclast differentiation. Mechanistically, a series of in vitro study showed that miR-214-3p directly targeted Traf3 to promote osteoclast activity and bone-resorbing activity. In addition, osteoclast-specific miR-214-3p knock-in mice showed remarkably increased bone resorption when compared to the littermate controls, which was attenuated after osteoclast-targeted treatment with Traf3 3′UTR-containing plasmid. In BCX nude mice, osteoclast-targeted antagomir-214-3p delivery could recover the TRAF3 protein expression and attenuate the development of OBM, respectively. Collectively, inhibition of osteoclastic miR-214-3p may be a potential therapeutic strategy for breast cancer patients with OBM. Meanwhile, the intraosseous TRAF3 could be a promising biomarker for evaluation of the treatment response of antagomir-214-3p. PMID:28071724

Smad2/3 Linker Phosphorylation Is a Possible Marker of Pancreatic Stem/Progenitor Cells in the Regenerative Phase of Acute Pancreatitis.

PubMed

Sakao, Masayuki; Sakaguchi, Yutaku; Suzuki, Ryo; Takahashi, Yu; Kishimoto, Masanobu; Fukui, Toshiro; Uchida, Kazushige; Nishio, Akiyoshi; Matsuzaki, Koichi; Okazaki, Kazuichi

The aims of this study are to characterize cell proliferation and differentiation during regeneration after pancreatitis and pancreatic buds during development to evaluate the role of Smad2/3, phosphorylated at the specific linker threonine residues (pSmad2/3L-Thr) in positive cells. Male C57BL/6 mice received hourly intraperitoneal injections of cerulein and were analyzed after induced pancreatitis. Pancreatitis-affected tissue sections and pancreatic buds were immunostained for pSmad2/3L-Thr, with other markers thought to be stem/progenitor markers of the pancreas. pSmad2/3L-Thr immunostaining-positive cells increased as the pancreatitis progressed. The expression of pSmad2/3L-Thr was seen in acinar cells and ductlike tubular complexes. These results suggest that pSmad2/3L-Thr is expressed during acinar-ductal metaplasia. Immunohistochemical colocalization of pSmad2/3L-Thr with Ki67 was never observed. pSmad2/3L-Thr-positive cells may remain in an undifferentiated state. During the pancreatic development process, pSmad2/3L-Thr was expressed as other markers. pSmad2/3L-Thr develops in duct structure of the undifferentiated cell population in the last part of viviparity that acinar structure is formed clearly. pSmad2/3L-Thr expression occurs during acinar-ductal metaplasia after pancreatitis and may represent the contribution of stem cells and/or progenitor cells to the differentiation of the pancreas.

Chronic inflammation associated with hepatitis C virus infection perturbs hepatic transforming growth factor beta signaling, promoting cirrhosis and hepatocellular carcinoma.

PubMed

Matsuzaki, Koichi; Murata, Miki; Yoshida, Katsunori; Sekimoto, Go; Uemura, Yoshiko; Sakaida, Noriko; Kaibori, Masaki; Kamiyama, Yasuo; Nishizawa, Mikio; Fujisawa, Junichi; Okazaki, Kazuichi; Seki, Toshihito

2007-07-01

Many patients with chronic hepatitis caused by hepatitis C virus (HCV) infection develop liver fibrosis with high risk for hepatocellular carcinoma (HCC), but the mechanism underling this process is unclear. Conversely, transforming growth factor beta (TGF-beta) activates not only TGF-beta type I receptor (TbetaRI) but also c-Jun N-terminal kinase (JNK), which convert the mediator Smad3 into two distinctive phosphoisoforms: C-terminally phosphorylated Smad3 (pSmad3C) and linker-phosphorylated Smad3 (pSmad3L). Whereas the TbetaRI/pSmad3C pathway suppresses epithelial cell growth by upregulating p21(WAF1) transcription, JNK/pSmad3L-mediated signaling promotes extracellular matrix deposition, partly, by upregulating plasminogen activator inhibitor 1 (PAI-1). We studied the domain-specific Smad3 phosphorylation in biopsy specimens representing chronic hepatitis, cirrhosis, or HCC from 100 patients chronically infected with HCV, and correlated Smad3 phosphorylation with clinical course. As HCV-infected livers progressed from chronic hepatitis through cirrhosis to HCC, hepatocytic pSmad3L/PAI-1 increased with fibrotic stage and necroinflammatory grade, and pSmad3C/p21(WAF1) decreased. Of 14 patients with chronic hepatitis C with strong hepatocytic pSmad3L positivity, 8 developed HCC within 12 years; only 1 of 12 showing little pSmad3L positivity developed HCC. We further sought molecular mechanisms in vitro. JNK activation by the pro-inflammatory cytokine interleukin-1beta stimulated the pSmad3L/PAI-1 pathway in facilitating hepatocytic invasion, in the meantime reducing TGF-beta-dependent tumor-suppressive activity by the pSmad3C/p21(WAF1) pathway. These results indicate that chronic inflammation associated with HCV infection shifts hepatocytic TGF-beta signaling from tumor-suppression to fibrogenesis, accelerating liver fibrosis and increasing risk for HCC.

Aqueous two-phase printing of cell-containing contractile collagen microgels.

PubMed

Moraes, Christopher; Simon, Arlyne B; Putnam, Andrew J; Takayama, Shuichi

2013-12-01

This work describes the use of aqueous two-phase systems to print cell-containing contractile collagen microdroplets. The fully aqueous conditions enable convenient formation of sub-microliter 'microgels' that are much smaller than otherwise possible to fabricate while maintaining high cell viability. The produced microgels contract over several days, mimicking the behavior of macroscale contraction assays, which have been valued as an important biological readout for over three decades. Use of microgels not only reduces reagent consumption and increases throughput of the assay, but also improves transport of molecules into and out of the collagen matrix, thereby enabling efficient and more precise studies of timed stimulation profiles. Utility of the technology is demonstrated by analyzing the effects of TGF-β1 on gel contraction, and we demonstrate that brief 'burst' stimulation profiles in microgels prompt contraction of the matrix, a feature not observed in the conventional macroscale assay. The fully aqueous process also enables the integration of contractile collagen microgels within existing cell culture systems, and we demonstrate proof-of-principle experiments in which a contractile collagen droplet is fabricated in situ on an existing epithelial monolayer. The simplicity, versatility and ability to robustly produce collagen microgels should allow effective translation of this microengineering technology into a variety of research environments. Copyright © 2013 Elsevier Ltd. All rights reserved.

Validation of bending tests by nanoindentation for micro-contact analysis of MEMS switches

NASA Astrophysics Data System (ADS)

Broue, Adrien; Fourcade, Thibaut; Dhennin, Jérémie; Courtade, Frédéric; Charvet, Pierre–Louis; Pons, Patrick; Lafontan, Xavier; Plana, Robert

2010-08-01

Research on contact characterization for microelectromechanical system (MEMS) switches has been driven by the necessity to reach a high-reliability level for micro-switch applications. One of the main failures observed during cycling of the devices is the increase of the electrical contact resistance. The key issue is the electromechanical behaviour of the materials used at the contact interface where the current flows through. Metal contact switches have a large and complex set of failure mechanisms according to the current level. This paper demonstrates the validity of a new methodology using a commercial nanoindenter coupled with electrical measurements on test vehicles specially designed to investigate the micro-scale contact physics. Dedicated validation tests and modelling are performed to assess the introduced methodology by analyzing the gold contact interface with 5 µm2 square bumps at various current levels. Contact temperature rise is measured, which affects the mechanical properties of the contact materials and modifies the contact topology. In addition, the data provide a better understanding of micro-contact behaviour related to the impact of current at low- to medium-power levels. This article was originally submitted for the special section 'Selected papers from the 20th Micromechanics Europe Workshop (MME 09) (Toulouse, France, 20-22 September 2009)', Journal of Micromechanics and Microengineering, volume 20, issue 6.

A two-axis micromachined silicon actuator with micrometer range electrostatic actuation and picometer sensitive capacitive detection

NASA Astrophysics Data System (ADS)

Ayela, F.; Bret, J. L.; Chaussy, J.; Fournier, T.; Ménégaz, E.

2000-05-01

This article presents an innovative micromachined silicon actuator. A 50-μm-thick silicon foil is anodically bonded onto a broached Pyrex substrate. A free standing membrane and four coplanar electrodes in close proximity are then lithographied and etched. The use of phosphorus doped silicon with low electrical resistivity allows the application of an electrostatic force between one electrode and the moving diaphragm. This plane displacement and the induced interelectrode variation are capacitively detected. Due to the very low electrical resistivity of the doped silicon, there is no need to metallize the vertical trenches of the device. No piezoelectric transducer takes place so that the mechanical device is free from any hysteretic or temperature dependance. The range of the possible actuation along the x and y axis is around 5 μm. The actual sensitivity is xn=0.54 Å/Hz1/2 and yn=0.14 Å/Hz1/2. The microengineering steps and the electronic setup devoted to design the actuator and to perform relative capacitive measurements ΔC/C=10-6 from an initial value C≈10-13 F are described. The elaborated tests and performances of the device are presented. As a conclusion, some experimental projects using this subnanometric sensitive device are mentioned.

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

MANI,SEETHAMBAL S.; FLEMING,JAMES G.; WALRAVEN,JEREMY A.

Two major problems associated with Si-based MEMS (MicroElectroMechanical Systems) devices are stiction and wear. Surface modifications are needed to reduce both adhesion and friction in micromechanical structures to solve these problems. In this paper, the authors present a CVD (Chemical Vapor Deposition) process that selectively coats MEMS devices with tungsten and significantly enhances device durability. Tungsten CVD is used in the integrated-circuit industry, which makes this approach manufacturable. This selective deposition process results in a very conformal coating and can potentially address both stiction and wear problems confronting MEMS processing. The selective deposition of tungsten is accomplished through the siliconmore » reduction of WF{sub 6}. The self-limiting nature of the process ensures consistent process control. The tungsten is deposited after the removal of the sacrificial oxides to minimize stress and process integration problems. The tungsten coating adheres well and is hard and conducting, which enhances performance for numerous devices. Furthermore, since the deposited tungsten infiltrates under adhered silicon parts and the volume of W deposited is less than the amount of Si consumed, it appears to be possible to release adhered parts that are contacted over small areas such as dimples. The wear resistance of tungsten coated parts has been shown to be significantly improved by microengine test structures.« less

Two coupled, driven Ising spin systems working as an engine.

PubMed

Basu, Debarshi; Nandi, Joydip; Jayannavar, A M; Marathe, Rahul

2017-05-01

Miniaturized heat engines constitute a fascinating field of current research. Many theoretical and experimental studies are being conducted that involve colloidal particles in harmonic traps as well as bacterial baths acting like thermal baths. These systems are micron-sized and are subjected to large thermal fluctuations. Hence, for these systems average thermodynamic quantities, such as work done, heat exchanged, and efficiency, lose meaning unless otherwise supported by their full probability distributions. Earlier studies on microengines are concerned with applying Carnot or Stirling engine protocols to miniaturized systems, where system undergoes typical two isothermal and two adiabatic changes. Unlike these models we study a prototype system of two classical Ising spins driven by time-dependent, phase-different, external magnetic fields. These spins are simultaneously in contact with two heat reservoirs at different temperatures for the full duration of the driving protocol. Performance of the model as an engine or a refrigerator depends only on a single parameter, namely the phase between two external drivings. We study this system in terms of fluctuations in efficiency and coefficient of performance (COP). We find full distributions of these quantities numerically and study the tails of these distributions. We also study reliability of the engine. We find the fluctuations dominate mean values of efficiency and COP, and their probability distributions are broad with power law tails.

Digital holographic characterization of liquid microlenses array fabricated in electrode-less configuration

NASA Astrophysics Data System (ADS)

Miccio, L.; Vespini, V.; Grilli, S.; Paturzo, M.; Finizio, A.; De Nicola, S.; Ferraro, P.

2009-06-01

We show how thin liquid film on polar dielectric substrate can form an array of liquid micro-lenses. The effect is driven by the pyroelectric effect leading to a new concept in electro-wetting (EW). EW is a viable method for actuation of liquids in microfluidic systems and requires the design and fabrication of complex electrodes for suitable actuation of liquids. When compared to conventional electrowetting devices, the pyroelectric effect allowed to have an electrode-less and circuitless configuration. In our case the surface electric charge induced by the thermal stimulus is able to pattern selectively the surface wettability according to geometry of the ferroelectric domains micro-engineered into the lithium niobate crystal. We show that different geometries of liquid microlenses can be obtained showing also a tuneability of the focal lenses down to 1.6 mm. Thousand of liquid microlenses, each with 100 μm diameter, can be formed and actuated. Also different geometries such as hemi-cylindrical and toroidal liquid structures can be easily obtained. By means of a digital holography method, an accurate characterization of the micro-lenses curvature is performed and presented. The preliminary results concerning the imaging capability of the micro-lens array are also reported. Microlens array can find application in medical stereo-endoscopy, imaging, telecommunication and optical data storage too.

Mechanical Coupling of Smooth Muscle Cells Using Microengineered Substrates and Local Stimulation

NASA Astrophysics Data System (ADS)

Copeland, Craig; Hunter, David; Tung, Leslie; Chen, Christopher; Reich, Daniel

2013-03-01

Mechanical stresses directly affect many cellular processes, including signal transduction, growth, differentiation, and survival. Cells can themselves generate such stresses by activating myosin to contract the actin cytoskeleton, which in turn can regulate both cell-substrate and cell-cell interactions. We are studying mechanical forces at cell-cell and cell-substrate interactions using arrays of selectively patterned flexible PDMS microposts combined with the ability to apply local chemical stimulation. Micropipette ``spritzing'', a laminar flow technique, uses glass micropipettes mounted on a microscope stage to deliver drugs to controlled regions within a cellular construct while cell traction forces are recorded via the micropost array. The pipettes are controlled by micromanipulators allowing for rapid and precise movement across the array and the ability to treat multiple constructs within a sample. This technique allows for observing the propagation of a chemically induced mechanical stimulus through cell-cell and cell-substrate interactions. We have used this system to administer the acto-myosin inhibitors Blebbistatin and Y-27632 to single cells and observed the subsequent decrease in cell traction forces. Experiments using trypsin-EDTA have shown this system to be capable of single cell manipulation through removal of one cell within a pair configuration while leaving the other cell unaffected. This project is supported in part by NIH grant HL090747

Two coupled, driven Ising spin systems working as an engine

NASA Astrophysics Data System (ADS)

Basu, Debarshi; Nandi, Joydip; Jayannavar, A. M.; Marathe, Rahul

2017-05-01

Miniaturized heat engines constitute a fascinating field of current research. Many theoretical and experimental studies are being conducted that involve colloidal particles in harmonic traps as well as bacterial baths acting like thermal baths. These systems are micron-sized and are subjected to large thermal fluctuations. Hence, for these systems average thermodynamic quantities, such as work done, heat exchanged, and efficiency, lose meaning unless otherwise supported by their full probability distributions. Earlier studies on microengines are concerned with applying Carnot or Stirling engine protocols to miniaturized systems, where system undergoes typical two isothermal and two adiabatic changes. Unlike these models we study a prototype system of two classical Ising spins driven by time-dependent, phase-different, external magnetic fields. These spins are simultaneously in contact with two heat reservoirs at different temperatures for the full duration of the driving protocol. Performance of the model as an engine or a refrigerator depends only on a single parameter, namely the phase between two external drivings. We study this system in terms of fluctuations in efficiency and coefficient of performance (COP). We find full distributions of these quantities numerically and study the tails of these distributions. We also study reliability of the engine. We find the fluctuations dominate mean values of efficiency and COP, and their probability distributions are broad with power law tails.

Label-free isolation and deposition of single bacterial cells from heterogeneous samples for clonal culturing

NASA Astrophysics Data System (ADS)

Riba, J.; Gleichmann, T.; Zimmermann, S.; Zengerle, R.; Koltay, P.

2016-09-01

The isolation and analysis of single prokaryotic cells down to 1 μm and less in size poses a special challenge and requires micro-engineered devices to handle volumes in the picoliter to nanoliter range. Here, an advanced Single-Cell Printer (SCP) was applied for automated and label-free isolation and deposition of bacterial cells encapsulated in 35 pl droplets by inkjet-like printing. To achieve this, dispenser chips to generate micro droplets have been fabricated with nozzles 20 μm in size. Further, the magnification of the optical system used for cell detection was increased. Redesign of the optical path allows for collision-free addressing of any flat substrate since no compartment protrudes below the nozzle of the dispenser chip anymore. The improved system allows for deterministic isolation of individual bacterial cells. A single-cell printing efficiency of 93% was obtained as shown by printing fluorescent labeled E. coli. A 96-well plate filled with growth medium is inoculated with single bacteria cells on average within about 8 min. Finally, individual bacterial cells from a heterogeneous sample of E. coli and E. faecalis were isolated for clonal culturing directly on agar plates in user-defined array geometry.

Unraveling shock-induced chemistry using ultrafast lasers

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

Moore, David Steven

The exquisite time synchronicity between shock and diagnostics needed to unravel chemical events occurring in picoseconds has been achieved using a shaped ultrafast laser pulse to both drive the shocks and interrogate the sample via a multiplicity of optical diagnostics. The shaped laser drive pulse can produce well-controlled shock states of sub-ns duration with sub-10 ps risetimes, sufficient for investigation offast reactions or phase transformations in a thin layer with picosecond time resolution. The shock state is characterized using ultrafast dynamic ellipsometry (UDE) in either planar or Gaussian spatial geometries, the latter allowing measurements of the equation of state ofmore » materials at a range of stresses in a single laser pulse. Time-resolved processes in materials are being interrogated using UDE, ultrafast infrared absorption, ultrafast UV/visible absorption, and femtosecond stimulated Raman spectroscopy. Using these tools we showed that chemistry in an energetic thin film starts only after an induction time of a few tens of ps, an observation that allows differentiation between proposed shock-induced reaction mechanisms. These tools are presently being applied to a variety of energetic and reactive sample systems, from nitromethane and carbon disulfide, to microengineered interfaces in tunable energetic mixtures. Recent results will be presented, and future trends outlined.« less

Electrophoretic deposition of thermites onto micro-engineered electrodes prepared by direct-ink writing.

PubMed

Sullivan, K T; Zhu, C; Tanaka, D J; Kuntz, J D; Duoss, E B; Gash, A E

2013-02-14

This work combines electrophoretic deposition (EPD) with direct-ink writing (DIW) to prepare thin films of Al/CuO thermites onto patterned two- and three-dimensional silver electrodes. DIW was used to write the electrodes using a silver nanoparticle ink, and EPD was performed in a subsequent step to deposit the thermite onto the conductive electrodes. Unlike conventional lithographic techniques, DIW is a low-cost and versatile alternative to print fine-featured electrodes, and adds the benefit of printing self-supported three-dimensional structures. EPD provides a method for depositing the composite thermite only onto the conductive electrodes, and with controlled thicknesses, which provides fine spatial and mass control, respectively. EPD has previously been shown to produce well-mixed thermite composites which can pack to reasonably high densities without the need for any postprocessing. Homogeneous mixing is particularly important in reactive composities, where good mixing can enhance the reaction kinetics by decreasing the transport distance between the components. Several two- and three-dimensional designs were investigated to highlight the versatility of using DIW and EPD together. In addition to energetic applications, we anticipate that this combination of techniques will have a variety of other applications, which would benefit from the controlled placement of a thin film of one material onto a conductive architecture of a second material.

Role of phosphoinositide 3-kinase regulatory isoforms in development and actin rearrangement.

PubMed

Brachmann, Saskia M; Yballe, Claudine M; Innocenti, Metello; Deane, Jonathan A; Fruman, David A; Thomas, Sheila M; Cantley, Lewis C

2005-04-01

Class Ia phosphoinositide 3-kinases (PI3Ks) are heterodimers of p110 catalytic and p85 regulatory subunits that mediate a variety of cellular responses to growth and differentiation factors. Although embryonic development is not impaired in mice lacking all isoforms of the p85alpha gene (p85alpha-/- p55alpha-/- p50alpha-/-) or in mice lacking the p85beta gene (p85beta-/-) (D. A. Fruman, F. Mauvais-Jarvis, D. A. Pollard, C. M. Yballe, D. Brazil, R. T. Bronson, C. R. Kahn, and L. C. Cantley, Nat Genet. 26:379-382, 2000; K. Ueki, C. M. Yballe, S. M. Brachmann, D. Vicent, J. M. Watt, C. R. Kahn, and L. C. Cantley, Proc. Natl. Acad. Sci. USA 99:419-424, 2002), we show here that loss of both genes results in lethality at embryonic day 12.5 (E12.5). The phenotypes of these embryos, including subepidermal blebs flanking the neural tube at E8 and bleeding into the blebs during the turning process, are similar to defects observed in platelet-derived growth factor receptor alpha null (PDGFRalpha-/-) mice (P. Soriano, Development 124:2691-2700, 1997), suggesting that PI3K is an essential mediator of PDGFRalpha signaling at this developmental stage. p85alpha-/- p55alpha+/+ p50alpha+/+ p85beta-/- mice had similar but less severe defects, indicating that p85alpha and p85beta have a critical and redundant function in development. Mouse embryo fibroblasts deficient in all p85alpha and p85beta gene products (p85alpha-/- p55alpha-/- p50alpha-/- p85beta-/-) are defective in PDGF-induced membrane ruffling. Overexpression of the Rac-specific GDP-GTP exchange factor Vav2 or reintroduction of p85alpha or p85beta rescues the membrane ruffling defect. Surprisingly, reintroduction of p50alpha also restored PDGF-dependent membrane ruffling. These results indicate that class Ia PI3K is critical for PDGF-dependent actin rearrangement but that the SH3 domain and the Rho/Rac/Cdc42-interacting domain of p85, which lacks p50alpha, are not required for this response.

Characterization of rtSH3p13 gene encoding a development protein involved in vesicular traffic in spermiogenesis.

PubMed

Qiao, Yuan; Yang, Ju Xiang; Zhang, Xiao Dong L; Liu, Yu; Zhang, Jian Chao; Zong, Shu Dong; Miao, Shi Ying; Wang, Lin Fang; Koide, Samuel S

2004-06-01

A cDNA, designated as rtSH3p13, was isolated from a rat testis cDNA library. It consists of 1463 bp nuclear acids, which encodes a protein of 312 amino acids and was assigned the GenBank accession number AF227439. The deduced rtSH3p13 protein is a truncated isoform of SH3p13 as a result of mRNA alternative splicing. It is mainly expressed in the rat testis, detected in spermatids at the steps 8-19 of spermiogenesis, and found around the acrosome. During postnatal development, rtSH3p13 appears on day 18 and reaches maximum on day 60. Further experimental results suggested that rtSH3p13 forms a complex with activated epidermal growth factor receptor (EGFR) and interacts with synaptojanin I. Surprisingly, similar to SH3 domain, the V region of rtSH3p13 also inhibits endocytosis in CHO cells. Our results reveal a link between an rtSH3p13-synaptojanin-clathrin complex-mediated formation of pits and the process of spermiogenesis.

Development of Temporomandibular Disorders is associated with greater bodily pain experience

PubMed Central

Lim, Pei Feng; Smith, Shad; Bhalang, Kanokporn; Slade, Gary D.; Maixner, William

2009-01-01

Objectives The aim of this study is to examine the difference in the report of bodily pain experienced by subjects who develop temporomandibular disorders (TMD) and by those who do not develop TMD over a 3 year observation period. Methods This is a 3 year prospective study of 266 females aged 18–34 years initially free of TMD pain. All subjects completed the Symptom Report Questionnaire (SRQ) at baseline and yearly intervals, and at the time they developed TMD (if applicable). The SRQ is a self-report instrument evaluating the extent and location of pain experienced in the prior 6 months. Statistical analysis was carried out using repeated measures ANOVA. Results Over the 3 year period, 16 subjects developed TMD based on the Research Diagnostic Criteria for TMD. Subjects who developed TMD reported more headaches (P=0.0089), muscle soreness or pain (P=0.005), joint soreness or pain (P=0.0012), back pain (P=0.0001), chest pain (P=0.0004), abdominal pain (P=0.0021), and menstrual pain (P=0.0036) than subjects who did not develop TMD at both the baseline and final visits. Subjects who developed TMD also reported significantly more headache (P=0.0006), muscle soreness or pain (P=0.0059), and other pains (P=0.0188) when they were diagnosed with TMD compared to the baseline visit. Discussion The development of TMD was accompanied by increases in headaches, muscle soreness or pain, and other pains that were not observed in the subjects who did not develop TMD. Subjects who developed TMD also report higher experience of joint, back, chest and menstrual pain at baseline. PMID:20090437

Longitudinal anterior-to-posterior shift of collateral channels in patients with moyamoya disease: an implication for its hemorrhagic onset.

PubMed

Yamamoto, Shusuke; Hori, Satoshi; Kashiwazaki, Daina; Akioka, Naoki; Kuwayama, Naoya; Kuroda, Satoshi

2018-03-23

OBJECTIVE This study aimed to assess longitudinal changes in the collateral channels originating from the lenticulostriate artery (LSA), posterior communicating artery (PCoA), and anterior and posterior choroidal arteries (AChA and PChA, respectively) during disease progression and/or aging. The impact of collateral channels on onset type was also examined. METHODS This study included 71 involved hemispheres in 41 patients with moyamoya disease. The disease was categorized into 6 stages according to Suzuki's angiographic staging system. The degree of development of each moyamoya vessel was categorized into 3 grades. RESULTS The LSA started to dilate in stage 2, showed the most prominent development in stage 3, and decreased in more advanced stages (p < 0.001). The AChA most notably developed in stage 3 and gradually shrank (p = 0.04). The PCoA started to dilate in stage 3 and showed the most prominent development in stage 4 (p = 0.03). The PChA started to dilate in stage 3 and showed the most prominent development in stages 4 to 5 (p < 0.001). Patient age was negatively related to LSA development (p = 0.01, R = 0.30) and was positively associated with the abnormal dilation and extension of the PCoA (p = 0.02, R = 0.28) and PChA (p < 0.001, R = 0.45). The PCoA, AChA, and PChA more distinctly developed in hemispheres with intracerebral or intraventricular hemorrhage than in hemispheres with ischemic stroke or transient ischemic attack (p < 0.001, p = 0.03, and p = 0.03, respectively). CONCLUSIONS This study suggests that the collateral channels through moyamoya vessels longitudinally shift from the anterior to posterior component during disease progression and aging, which may be closely related to the onset of hemorrhagic stroke in adult moyamoya disease.

MicroRNA-187-3p mitigates non-small cell lung cancer (NSCLC) development through down-regulation of BCL6

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

Sun, Chengcao; Li, Shujun; Wuhan Hospital for the Prevention and Treatment of Occupational Diseases, 430071 Wuhan

2016-02-26

Hsa-microRNA-187-3p (miR-187-3p) has recently been discovered having anticancer efficacy in different organs. However, the role of miR-187-3p on non-small cell lung cancer (NSCLC) is still ambiguous. In this study, we investigated the role of miR-187-3p on the development of NSCLC. The results indicated that miR-187-3p was significantly down-regulated in primary tumor tissues and very low levels were found in NSCLC cell lines. Ectopic expression of miR-187-3p in NSCLC cell lines significantly suppressed cell growth as evidenced by cell viability assay and colony formation assay, through inhibition of BCL6. In addition, miR-187-3p induced apoptosis, as indicated by concomitantly with up-regulation ofmore » the activities of caspase-3 and caspase-7, and inhibited cellular migration and invasiveness through inhibition of BCL6. Further, oncogene BCL6 was revealed to be a putative target of miR-187-3p, which was inversely correlated with miR-187-3p expression in NSCLC. Taken together, our results demonstrated that miR-187-3p played a pivotal role on NSCLC through inhibiting cell proliferation, migration, invasion, and promoting apoptosis by targeting oncogenic BCL6.« less

Hybrid Pluggable Processing Pipeline (HyP3): Programmatic Access to Cloud-Based Processing of SAR Data

NASA Astrophysics Data System (ADS)

Weeden, R.; Horn, W. B.; Dimarchi, H.; Arko, S. A.; Hogenson, K.

2017-12-01

A problem often faced by Earth science researchers is the question of how to scale algorithms that were developed against few datasets and take them to regional or global scales. This problem only gets worse as we look to a future with larger and larger datasets becoming available. One significant hurdle can be having the processing and storage resources available for such a task, not to mention the administration of those resources. As a processing environment, the cloud offers nearly unlimited potential for compute and storage, with limited administration required. The goal of the Hybrid Pluggable Processing Pipeline (HyP3) project was to demonstrate the utility of the Amazon cloud to process large amounts of data quickly and cost effectively. Principally built by three undergraduate students at the ASF DAAC, the HyP3 system relies on core Amazon cloud services such as Lambda, Relational Database Service (RDS), Elastic Compute Cloud (EC2), Simple Storage Service (S3), and Elastic Beanstalk. HyP3 provides an Application Programming Interface (API) through which users can programmatically interface with the HyP3 system; allowing them to monitor and control processing jobs running in HyP3, and retrieve the generated HyP3 products when completed. This presentation will focus on the development techniques and enabling technologies that were used in developing the HyP3 system. Data and process flow, from new subscription through to order completion will be shown, highlighting the benefits of the cloud for each step. Because the HyP3 system can be accessed directly from a user's Python scripts, powerful applications leveraging SAR products can be put together fairly easily. This is the true power of HyP3; allowing people to programmatically leverage the power of the cloud.

Design and Development of a High Altitude Protective Assembly.

DTIC Science & Technology

CWU-3/P ANTIGRAVITY SUITS, CWU-12/P ANTIEXPOSURE SUITS, HAPA(HIGH ALTITUDE PROTECTIVE ASSEMBLIES), *HIGH ALTITUDE PROTECTIVE ASSEMBLIES, LPU-3/P LIFE PRESERVERS, MA-3 VENTILATION GARMENTS, PARACHUTE HARNESSES, PARTIAL PRESSURE SUITS.

PNPLA3 and RNF7 Gene Variants are Associated with the Risk of Developing Liver Fibrosis and Cirrhosis in an Eastern European Population.

PubMed

Kupcinskas, Juozas; Valantiene, Irena; Varkalaitė, Greta; Steponaitiene, Ruta; Skieceviciene, Jurgita; Sumskiene, Jolanta; Petrenkiene, Vitalija; Kondrackiene, Jurate; Kiudelis, Gediminas; Lammert, Frank; Kupcinskas, Limas

2017-03-01

Genome-wide association studies have revealed an association between the risk of developing liver fibrosis or cirrhosis and the single nucleotide polymorphisms (SNPs) of the PNPLA3, RNF7, MERTK and PCSK7 genes. We aimed to validate these results in an Eastern European population. We evaluated the associations between the PNPLA3 (rs738409), RNF7 (rs16851720), MERTK (rs4374383) and PCSK7 (rs236918) variants and liver fibrosis and cirrhosis in a series of consecutive patients recruited at the Department of Gastroenterology, Lithuanian University of Health Sciences Hospital, during the period 2012-2015. The study included 317 individuals with liver cirrhosis, 154 individuals with liver fibrosis, and 498 controls. The studied SNPs were determined using RT-PCR TaqMan assays. MERTK and PCSK7 SNPs were not associated with liver fibrosis or cirrhosis. The PNPLA3 SNP rs738409 was associated with a higher risk of developing liver fibrosis (aOR: 1.65, P=0.001) and cirrhosis (aOR: 1.92, P=5.57*10-7). PNPLA3 genotypes were also associated with higher risk of developing liver fibrosis and cirrhosis in dominant (aOR: 1.98, P=2.20*10-5; aOR: 1.67, P=0.008, respectively) and recessive (aOR: 3.94, P=5.16*10-5; aOR: 3.02, P=0.003, respectively) models. RNF7 rs16851720 was associated with liver cirrhosis comparing CC vs. AA + CA genotypes (aOR: 0.26, P=0.020). Our study showed that PNPLA3 rs738409 and RNF7 rs16851720 confer an increased risk of developing liver fibrosis and cirrhosis in this Eastern European population, while the MERTK and PCSK7 SNPs are not associated with these conditions.

Progress on the Multiphysics Capabilities of the Parallel Electromagnetic ACE3P Simulation Suite

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

Kononenko, Oleksiy

2015-03-26

ACE3P is a 3D parallel simulation suite that is being developed at SLAC National Accelerator Laboratory. Effectively utilizing supercomputer resources, ACE3P has become a key tool for the coupled electromagnetic, thermal and mechanical research and design of particle accelerators. Based on the existing finite-element infrastructure, a massively parallel eigensolver is developed for modal analysis of mechanical structures. It complements a set of the multiphysics tools in ACE3P and, in particular, can be used for the comprehensive study of microphonics in accelerating cavities ensuring the operational reliability of a particle accelerator.

Kinetics of PTEN-mediated PI(3,4,5)P3 hydrolysis on solid supported membranes

PubMed Central

Liu, Chun; Deb, Sanghamitra; Ferreira, Vinicius S.; Xu, Eric; Baumgart, Tobias

2018-01-01

Phosphatidylinositides play important roles in cellular signaling and migration. Phosphatidylinositol-3,4,5-trisphosphate (PI(3,4,5)P3) is an important phosphatidylinositide because it acts as a secondary messenger to trigger cell movement and proliferation. A high level of PI(3,4,5)P3 at the plasma membrane is known to contribute to tumorigenesis. One key enzyme that regulates PI(3,4,5)P3 levels at the plasma membrane is phosphatase and tensin homologue deleted on chromosome 10 (PTEN), which dephosphorylates PI(3,4,5)P3 through hydrolysis to form phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2). It has been reported that PI(4,5)P2 is involved in positive feedback in the PI(3,4,5)P3 hydrolysis by PTEN. However, how PI(3,4,5)P3 dephosphorylation by PTEN is regulated, is still under debate. How other PI(3,4,5)P3-binding proteins affect the dephosphorylation kinetics catalyzed by PTEN also remains unclear. Here, we develop a fluorescent-protein biosensor approach to study how PI(3,4,5)P3 dephosphorylation is regulated by PTEN as well as its membrane-mediated feedback mechanisms. Our observation of sigmoidal kinetics of the PI(3,4,5)P3 hydrolysis reaction supports the notion of autocatalysis in PTEN function. We developed a kinetic model to describe the observed reaction kinetics, which allowed us to i) distinguish between membrane-recruitment and allosteric activation of PTEN by PI(4,5)P2, ii) account for the influence of the biosensor on the observed reaction kinetics, and iii) demonstrate that all of these mechanisms contribute to the kinetics of PTEN-mediated catalysis. PMID:29447222

Kinetics of PTEN-mediated PI(3,4,5)P3 hydrolysis on solid supported membranes.

PubMed

Liu, Chun; Deb, Sanghamitra; Ferreira, Vinicius S; Xu, Eric; Baumgart, Tobias

2018-01-01

Phosphatidylinositides play important roles in cellular signaling and migration. Phosphatidylinositol-3,4,5-trisphosphate (PI(3,4,5)P3) is an important phosphatidylinositide because it acts as a secondary messenger to trigger cell movement and proliferation. A high level of PI(3,4,5)P3 at the plasma membrane is known to contribute to tumorigenesis. One key enzyme that regulates PI(3,4,5)P3 levels at the plasma membrane is phosphatase and tensin homologue deleted on chromosome 10 (PTEN), which dephosphorylates PI(3,4,5)P3 through hydrolysis to form phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2). It has been reported that PI(4,5)P2 is involved in positive feedback in the PI(3,4,5)P3 hydrolysis by PTEN. However, how PI(3,4,5)P3 dephosphorylation by PTEN is regulated, is still under debate. How other PI(3,4,5)P3-binding proteins affect the dephosphorylation kinetics catalyzed by PTEN also remains unclear. Here, we develop a fluorescent-protein biosensor approach to study how PI(3,4,5)P3 dephosphorylation is regulated by PTEN as well as its membrane-mediated feedback mechanisms. Our observation of sigmoidal kinetics of the PI(3,4,5)P3 hydrolysis reaction supports the notion of autocatalysis in PTEN function. We developed a kinetic model to describe the observed reaction kinetics, which allowed us to i) distinguish between membrane-recruitment and allosteric activation of PTEN by PI(4,5)P2, ii) account for the influence of the biosensor on the observed reaction kinetics, and iii) demonstrate that all of these mechanisms contribute to the kinetics of PTEN-mediated catalysis.

Alteration of development and gene expression induced by in ovo-nanoinjection of 3-hydroxybenzo[c]phenanthrene into Japanese medaka (Oryzias latipes) embryos.

PubMed

Chen, Kun; Tsutsumi, Yuki; Yoshitake, Shuhei; Qiu, Xuchun; Xu, Hai; Hashiguchi, Yasuyuki; Honda, Masato; Tashiro, Kosuke; Nakayama, Kei; Hano, Takeshi; Suzuki, Nobuo; Hayakawa, Kazuichi; Shimasaki, Yohei; Oshima, Yuji

2017-01-01

Benzo[c]phenanthrene (BcP) is a highly toxic polycyclic aromatic hydrocarbon (PAHs) found throughout the environment. In fish, it is metabolized to 3-hydroxybenzo[c]phenanthrene (3-OHBcP). In the present study, we observed the effects of 1nM 3-OHBcP on the development and gene expression of Japanese medaka (Oryzias latipes) embryos. Embryos were nanoinjected with the chemical after fertilization. Survival, developmental stage, and heart rate of the embryos were observed, and gene expression differences were quantified by messenger RNA sequencing (mRNA-Seq). The exposure to 1nM 3-OHBcP accelerated the development of medaka embryos on the 1st, 4th, and 6th days post fertilization (dpf), and increased heart rates significantly on the 5th dpf. Physical development differences of exposed medaka embryos were consistent with the gene expression profiles of the mRNA-Seq results for the 3rd dpf, which show that the expression of 780 genes differed significantly between the solvent control and 1nM 3-OHBcP exposure groups. The obvious expression changes in the exposure group were found for genes involved in organ formation (eye, muscle, heart), energy supply (ATPase and ATP synthase), and stress-response (heat shock protein genes). The acceleration of development and increased heart rate, which were consistent with the changes in mRNA expression, suggested that 3-OHBcP affects the development of medaka embryos. The observation on the developmental stages and heart beat, in ovo-nanoinjection and mRNA-Seq may be efficient tools to evaluate the effects of chemicals on embryos. Copyright © 2016 Elsevier B.V. All rights reserved.

Number of Bacteria and Time of Coincubation With Bacteria Required for the Development of Acanthamoeba Keratitis.

PubMed

Nakagawa, Hayate; Hattori, Takaaki; Koike, Naohito; Ehara, Tomoko; Narimatsu, Akitomo; Kumakura, Shigeto; Matsumoto, Tetsuya; Goto, Hiroshi

2017-03-01

We hypothesized that bacteria may be a factor contributing to the development of Acanthamoeba keratitis (AK). We investigated interactions between Acanthamoeba and Pseudomonas aeruginosa for the development of keratitis in rabbit corneas. Acanthamoeba castellanii (ATCC50492) and P. aeruginosa (PAO-1) were used. Two densities of P. aeruginosa (high, 1 × 10/mL; low, 3 × 10/mL) and 2 durations of coincubation (long, 6 h; short, 2 h) of Acanthamoeba with 1 × 10/mL of P. aeruginosa were tested. Acanthamoeba alone or Acanthamoeba coincubated with P. aeruginosa was inoculated into rabbit corneas. After inoculation, levofloxacin (LVFX) eye drops were administered. The clinical score of the cornea was evaluated after inoculation. Acanthamoeba alone did not produce keratitis during a 5-day observation period. Rabbit corneas inoculated with Acanthamoeba coincubated with low-density P. aeruginosa followed by topical LVFX were clear with few infiltrates. Corneas inoculated with Acanthamoeba coincubated with high-density P. aeruginosa followed by LVFX treatment developed severe keratitis, and clinical scores were significantly higher compared with high-density P. aeruginosa alone followed by LVFX treatment (scores 7, 9.6, 8.5 vs. 3, 3.5, 3.25 on days 1-3, all P < 0.01). The long (6 h) coincubation time of Acanthamoeba with high-density P. aeruginosa resulted in more severe keratitis compared with short (2 h) coincubation (scores, 9.7, 12.7, 12.1, 9.8, 8.7 vs. 7, 9.6, 8.5, 6.9, 5.6 on days 1-5, all P < 0.01). These results suggest that the presence of bacteria is essential and a critical number of bacteria is required for the development of AK. The time of coexistence with bacteria may be an important determinant of the severity of AK.

Intracranial pressure changes during mouse development.

PubMed

Moazen, Mehran; Alazmani, Ali; Rafferty, Katherine; Liu, Zi-Jun; Gustafson, Jennifer; Cunningham, Michael L; Fagan, Michael J; Herring, Susan W

2016-01-04

During early stages of postnatal development, pressure from the growing brain as well as cerebrospinal fluid, i.e. intracranial pressure (ICP), load the calvarial bones. It is likely that such loading contributes to the peripheral bone formation at the sutural edges of calvarial bones, especially shortly after birth when the brain is growing rapidly. The aim of this study was to quantify ICP during mouse development. A custom pressure monitoring system was developed and calibrated. It was then used to measure ICP in a total of seventy three wild type mice at postnatal (P) day 3, 10, 20, 31 and 70. Retrospectively, the sample in each age group with the closest ICP to the average value was scanned using micro-computed tomography to estimate cranial growth. ICP increased from 1.33±0.87mmHg at P3 to 1.92±0.78mmHg at P10 and 3.60±1.08mmHg at P20. In older animals, ICP plateaued at about 4mmHg. There were statistically significant differences between the ICP at the P3 vs. P20, and P10 vs. P20. In the samples that were scanned, intracranial volume and skull length followed a similar pattern of increase up to P20 and then plateaued at older ages. These data are consistent with the possibility of ICP being a contributing factor to bone formation at the sutures during early stages of development. The data can be further used for development and validation of computational models of skull growth. Copyright © 2015 Elsevier Ltd. All rights reserved.

Differences in cortical development assessed by fetal MRI in late-onset intrauterine growth restriction.

PubMed

Egaña-Ugrinovic, Gabriela; Sanz-Cortes, Magdalena; Figueras, Francesc; Bargalló, Nuria; Gratacós, Eduard

2013-08-01

The objective of the study was to evaluate cortical development parameters by magnetic resonance imaging (MRI) in late-onset intrauterine growth-restricted (IUGR) fetuses and normally grown fetuses. A total of 52 IUGR and 50 control fetuses were imaged using a 3T MRI scanner at 37 weeks of gestational age. T2 half-Fourier acquisition single-shot turbo spin-echo anatomical acquisitions were obtained in 3 planes. Cortical sulcation (fissures depth corrected by biparietal diameter), brain volumetry, and asymmetry indices were assessed by means of manual delineation and compared between cases and controls. Late-onset IUGR fetuses had significantly deeper measurements in the left insula (late-onset IUGR: 0.293 vs control: 0.267; P = .02) and right insula (0.379 vs 0.318; P < .01) and the left cingulate fissure (0.096 vs 0.087; P = .03) and significantly lower intracranial (441.25 cm(3) vs 515.82 cm(3); P < .01), brain (276.47 cm(3) vs 312.07 cm(3); P < .01), and left opercular volumes (2.52 cm(3) vs 3.02 cm(3); P < .01). IUGR fetuses showed significantly higher right insular asymmetry indices. Late-onset IUGR fetuses had a different pattern of cortical development assessed by MRI, supporting the existence of in utero brain reorganization. Cortical development could be useful to define fetal brain imaging-phenotypes characteristic of IUGR. Copyright © 2013 Mosby, Inc. All rights reserved.

Effects of elevated seawater pCO2 on early development of scallop Argopecten irradias (Lamarck, 1819)

NASA Astrophysics Data System (ADS)

Wang, Weimin; Liu, Guangxing; Zhang, Tianwen; Chen, Hongju; Tang, Liao; Mao, Xuewei

2016-12-01

To investigate the effects of elevated seawater pCO2 on the early developmental stages of marine benthic calcifying organisms, we exposed the eggs and larvae of Argopecten irradias, an important bivalve species in Chinese aquaculture, in seawater equilibrated with CO2-enriched (1000 ppm) gas mixtures. We demonstrated that elevated seawater pCO2 significantly interfered with fertilization and larval development and resulted in an increased aberration rate. Fertilization in the treatment (pH 7.6) was 74.3% ± 3.8%, which was 9.7% lower than that in the control (pH 8.3) (84.0% ±3.0%). Hatching success decreased by 23.7%, and aberration rate increased by 30.3% under acidic condition. Larvae in acidified seawater still developed a shell during the post-embryonic phase. However, the shell length and height in the treatment were smaller than those in the control. The development of embryos differed significantly at 12 h after fertilization between the two experimental groups. Embryos developed slower in acidified seawater. Nearly half of the embryos in the control developed into D-shaped larvae at 48 h after fertilization, which were considerably more than those in the treatment (11.7%). Results suggest that future ocean acidification (OA) would cause detrimental effects on the early development of A. irradias.

Measurement of OH, H2SO4, MSA, and HNO3 Aboard the P-3B Aircraft

NASA Technical Reports Server (NTRS)

Eisele, F. L.

2003-01-01

This paper addresses the measurement of OH, H2SO4, MSA, and HNO3 aboard the P-3B aircraft under the following headings: 1) Performance Report; 2) Highlights of OH, H2SO4, and MSA Measurements Made Aboard the NASA P-3B During TRACE-P; 3) Development and characteristics of an airborne-based instrument used to measure nitric acid during the NASA TRACE-P field experiment.

Involvement of neurotrophin-3 (NT-3) in the functional elimination of synaptic contacts during neuromuscular development.

PubMed

Garcia, Neus; Santafé, Manel M; Tomàs, Marta; Lanuza, Maria A; Besalduch, Nuria; Tomàs, Josep

2010-04-05

Confocal immunohistochemistry shows that neurotrophin-3 (NT-3) and its receptor tropomyosin-related tyrosin kinase C (trkC) are present in both neonatal (P6) and adult (P45) mouse motor nerve terminals in neuromuscular junctions (NMJ) colocalized with several synaptic proteins. NT-3 incubation (1-3h, in the range 10-200ng/ml) does not change the size of the evoked and spontaneous endplate potentials at P45. However, NT-3 (1h, 100ng/ml) strongly potentiates evoked ACh release from the weak (70%) and the strong (50%) axonal inputs on dually innervated postnatal endplates (P6) but not in the most developed postnatal singly innervated synapses at P6. The present results indicate that NT-3 has a role in the developmental mechanism that eliminates redundant synapses though it cannot modulate synaptic transmission locally as the NMJ matures.

Photopic visual input is necessary for emmetropization in mice

PubMed Central

Tkatchenko, Tatiana V.; Shen, Yimin; Braun, Rod D.; Bawa, Gurinder; Kumar, Pradeep; Avrutsky, Ivan; Tkatchenko, Andrei V.

2013-01-01

It was recently demonstrated that refractive errors in mice stabilize around emmetropic values during early postnatal development, and that they develop experimental myopia in response to both visual form deprivation and imposed optical defocus similar to other vertebrate species. Animal studies also suggest that photopic vision plays critical role in emmetropization in diurnal species; however, it is unknown whether refractive eye development is guided by photopic vision in the mouse, which is a nocturnal species. We used an infrared mouse photorefractor and a high-resolution MRI to clarify the role of photopic visual input in refractive eye development in the mouse. Refractive eye development and form-deprivation myopia in P21-P89 C57BL/6J mice were analyzed under 12:12 h light-dark cycle, constant light and constant darkness regimens. Animals in all experimental groups were myopic at P21 (-13.2 ± 1.6 D, light-dark cycle; -12.5 ± 0.9 D, constant light; -12.5 ± 2.0 D, constant dark). The mean refractive error in the light-dark-cycle-reared animals was -0.5 ± 1.3 D at P32 and, and did not change significantly until P40 (+0.3 ± 0.6 D, P40). Animals in this group became progressively hyperopic between P40 and P89 (+2.2 ± 0.6, P67; +3.7 ± 2.0, P89). The mean refractive error in the constant-light-reared mice was -1.0 ± 0.7 D at P32 and remained stable until P89 (+0.1 ± 0.6, P40; +0.3 ± 0.6, P67; 0.0 ± 0.4, P89). Dark-reared animals exhibited highly hyperopic refractive errors at P32 (+5.2 ± 1.8) and became progressively more hyperopic with age (+8.7 ± 1.9, P40; +11.2 ± 1.4, P67). MRI analysis revealed that emmetropization in the P40-P89 constant-light-reared animals was associated with larger eyes, a longer axial length and a larger vitreous chamber compared to the light-dark-cycle-reared mice. Constant-light-reared mice also developed 4 times higher degrees of form-deprivation myopia on average compared to light-dark-cycle-reared animals (-12.0 ± 1.4, constant light; -2.7 ± 0.7, light-dark cycle). Dark-rearing completely prevented the development of form-deprivation myopia (-0.3 ± 0.5). Thus, photopic vision plays important role in normal refractive eye development and ocular response to visual form deprivation in the mouse. PMID:23838522

Involvement of Smad3 phosphoisoform-mediated signaling in the development of colonic cancer in IL-10-deficient mice.

PubMed

Hachimine, Daisaku; Uchida, Kazushige; Asada, Masanori; Nishio, Akiyoshi; Kawamata, Seiji; Sekimoto, Go; Murata, Miki; Yamagata, Hideo; Yoshida, Katsunori; Mori, Shigeo; Tahashi, Yoshiya; Matsuzaki, Koichi; Okazaki, Kazuichi

2008-06-01

Chronic inflammation predisposes to cancer. Transforming growth factor (TGF)-beta, a multifunctional protein, suppresses the growth of normal colonic epithelial cells, whereas it stimulates the proliferation of cancer cells. Interleukin (IL)-10-deficient mice, which develop colitis and colorectal cancer, show an increased level of plasma TGF-beta. Although TGF-beta may be a key molecule in the development of colon cancer arising from chronic colitis in IL-10-deficient mice, the role of TGF-beta still remains unclear. TGF-beta activates not only TGF-beta type I receptor (TbetaRI) but also c-Jun N-terminal kinase (JNK), which converts the mediator Smad3 into two distinctive phosphoisoforms: C-terminally phosphorylated Smad3 (pSmad3C) and linker-phosphorylated Smad3 (pSmad3L). We studied C57BL/6-IL-10-deficient mice (n=18) at 4 to 32 weeks of age. We investigated histology, and pSmad2/3L, pSmad2/3C, and p53 by immunohistochemistry. pSmad3L staining was detected in the cancer cells in all 10 mice with colonic cancer and in the epithelial cells in 7 of 12 mice with colonic dysplasia, but not in the normal or colitic mice. pSmad3c was detected without any significant difference between stages. p53 was weakly stained in a few cancer cells in 5 out of 10 mice. Smad3L signaling plays an important role in the carcinogenesis of chronic colitis in IL-10-deficient mice.

Permanent first molar extraction in adolescents and young adults and its effect on the development of third molar.

PubMed

Halicioglu, Koray; Toptas, Orcun; Akkas, Ismail; Celikoglu, Mevlut

2014-01-01

The aim of the present study was to determine the prevalence of permanent first molar (P1M) extraction among Turkish adolescents and young adult subpopulation, and to investigate the effects of P1M extraction on development of the third molars (3Ms) in the same quadrant. A retrospective study including 2,925 panoramic radiographs (PRs) taken from patients (aged 13-20 years) who were examined to identify cases of had at least one maxillary or mandibular P1Ms extracted was performed. Additionally, 294 PRs with the maxillary or mandibular unilateral loss of a P1M were used to assess the developmental grades of the 3Ms. Statistical analyses were performed by means of parametric tests after performing a Shapiro-Wilks normality test to the data. A total of 945 patients (32.3 %) presented with at least one P1M extraction with no gender difference (P = 0.297). There were more cases of mandibular P1Ms extracted (784 patients, 1,066 teeth) than maxillary P1Ms extracted (441 patients, 549 teeth) (P < 0.001). The development of the 3Ms on the extraction side, in the both maxilla and mandible, was significantly accelerated when compared with the contralateral teeth (P = 0.000, P = 0.000, respectively). No statistically significant differences were found in the differences in the developmental of the 3Ms between the maxilla and mandible (P = 0.718). High prevalence of P1Ms extraction among Turkish adolescents and young adults shows a need for targeted dental actions, including prevention and treatment. The development of the 3Ms on the extraction side, in the both maxilla and mandible, was significantly accelerated. To date, no information about prevalence of P1Ms extraction among Turkish adolescents and young adults is documented. In addition, the present study has a larger population and complementary information about 3Ms development than previous studies.

Differential deletions in 3p are associated with the development of head and neck squamous cell carcinoma in Indian patients.

PubMed

Chakraborty, Suman Bhusan; Dasgupta, Santanu; Roy, Anup; Sengupta, Arunava; Ray, Bidyut; Roychoudhury, Susanta; Panda, Chinmay Kumar

2003-10-15

In this study we performed detailed deletion mapping of two broad regions in the short arm (p) of chromosome 3 (i.e., 3p21.2 approximately p22 and 3p12 approximately p13), which were shown to have a high rate of deletions in head and neck lesions in our previous study. Using 18 highly polymorphic microsatellite markers, the deletion mapping was done in 35 dysplastic lesions and 46 primary head and neck squamous cell carcinoma (HNSCC) samples from Indian patients. Within the 21.6-megabase (Mb) region of 3p21.1 approximately p21.33, we have identified four areas (D1, 3p21.33; D2, 3p21.32; D3, 3p21.31; D4, 3p21.1) that showed a high frequency (46%-69%) of deletions in our samples. In the 3p12 approximately p13 region, we narrowed down the deletion within the 0.7-Mb region (D5, 3p12.1). Among these five regions (D1-D5), deletion in D3 is suggested to be necessary for the development of early dysplastic lesions, whereas the deletion in D2 may be necessary for dysplastic lesions and tumor progression. On the other hand, the deletion in D5 is significantly associated with progression of the lesions from mild/moderate to severe dysplasia. The deletions in D1 and D4, however, are required for tumor progression. As in our previous study, microsatellite size alterations (MA) were observed to be high in and around the highly deleted regions and gradually increased during the progression of the tumor. Loss of normal copy/interstitial alterations of chromosome 3 in the late stages of the tumor as well as rare biallelic alterations around the highly deleted regions also were seen in our samples. Human papilloma virus infection has been found to be associated with the deletion in the D5 region and MA in the D1 region, whereas nodal involvement of the tumor correlated only with the MA in D1 and D5. Thus, this study indicates that multiple tumor suppressor genes whose differential deletions are associated with the development of HNSCC may be present in 3p.

MicroRNA-142-3p Induces Atherosclerosis-Associated Endothelial Cell Apoptosis by Directly Targeting Rictor.

PubMed

Qin, Bing; Shu, Yaqing; Long, Ling; Li, Haiyan; Men, Xuejiao; Feng, Li; Yang, Huan; Lu, Zhengqi

2018-06-27

Atherosclerosis, a multifactorial chronic disease, is the main cause of death and impairment in the world. Endothelial cells (ECs) apoptosis plays a crucial role in the onset and development of atherosclerosis, whereas the underlying molecular mechanisms are unclear. MicroRNA-142-3p (miR-142-3p) is a well-defined tumor suppressor in several types of cancer, while the role of miR-142-3p in ECs apoptosis and the development of atherosclerosis has yet to be elucidated. Therefore, the present study aimed to investigate the role of miR-142-3p in ECs apoptosis during atherosclerosis and the underlying mechanism. Human aortic endothelial cells (HAECs) were treated with oxidized low-density lipoprotein (ox-LDL). The expression level of miR-142-3p was detected using qRT-PCR. Apoptosis was determined via flow cytometry and Caspase-3 activity assay. Prediction of the binding between miR-142-3p and 3'-UTR of Rictor mRNA was performed by bioinformatics analyses and confirmed by a dual luciferase reporter assay. The effects of miR-142-3p on endothelial apoptosis and atherosclerosis were further analyzed in an in vivo model using ApoE-/- mice fed with high-fat diet (HFD). MiR-142-3p expression was substantially up-regulated during the ox-LDL-elicited apoptosis in HAECs. Forced expression of miR-142-3p exacerbated apoptosis in ECs whereas inhibition of miR-142-3p could partly alleviate apoptotic cell death mediated by ox-LDL. Further analysis identified Rictor as a direct target of miR-142-3p, and Rictor knockdown abolished the anti-apoptotic effect of miR-142-3p inhibitor. Moreover, the Akt/endothelial nitric oxide synthase (eNOS) signaling pathway was found to mediate the beneficial effect of miR-142-3p inhibitor on endothelial apoptosis. Finally, systemic treatment with miR-142-3p antagomir attenuated endothelial apoptosis and retarded the progression of atherosclerosis in the aorta of ApoE-/- mice. Down-regulation of miR-142-3p inhibited ECs apoptosis and atherosclerotic development by up-regulating the expression of Rictor and activating the Akt/eNOS signaling pathway. This indicates that miR-142-3p may be a potential target for the prevention and treatment of atherosclerosis. © 2018 The Author(s). Published by S. Karger AG, Basel.

Acidic intracellular pH shift during Caenorhabditis elegans larval development

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

Wadsworth, W.G.; Riddle, D.L.

1988-11-01

During recovery from the developmentally arrested, nonfeeding dauer stage of the nemotode Caenorhabditis elegans, metabolic activation is accompanied by a decrease in intracellular pH (pH{sub i}). Phosphorus-31 nuclear magnetic resonance ({sup 31}P NMR) analyses of perchloric acid extracts show that inorganic phosphate predominates in dauer larvae, whereas ATP and other high-energy metabolites are abundant within 6 hr after dauer larvae have been placed in food to initiate development. Although metabolic activation has been associated with an alkaline pH{sub i} shift in other organisms, in vivo {sup 31}P NMR analysis of recovering dauer larvae shows a pH{sub i} decrease from {approx}more » 7.3 to {approx} 6.3 within 3 hr after the animals encounter food. This shift occurs before feeding begins, and it coincides with, or soon follows, the developmental commitment to recover from the dauer stage, suggesting that control of pH{sub i} may be important in the regulation of larval development in nematodes.« less

Analysis of alterative cleavage and polyadenylation by 3′ region extraction and deep sequencing

PubMed Central

Hoque, Mainul; Ji, Zhe; Zheng, Dinghai; Luo, Wenting; Li, Wencheng; You, Bei; Park, Ji Yeon; Yehia, Ghassan; Tian, Bin

2012-01-01

Alternative cleavage and polyadenylation (APA) leads to mRNA isoforms with different coding sequences (CDS) and/or 3′ untranslated regions (3′UTRs). Using 3′ Region Extraction And Deep Sequencing (3′READS), a method which addresses the internal priming and oligo(A) tail issues that commonly plague polyA site (pA) identification, we comprehensively mapped pAs in the mouse genome, thoroughly annotating 3′ ends of genes and revealing over five thousand pAs (~8% of total) flanked by A-rich sequences, which have hitherto been overlooked. About 79% of mRNA genes and 66% of long non-coding RNA (lncRNA) genes have APA; but these two gene types have distinct usage patterns for pAs in introns and upstream exons. Promoter-distal pAs become relatively more abundant during embryonic development and cell differentiation, a trend affecting pAs in both 3′-most exons and upstream regions. Upregulated isoforms generally have stronger pAs, suggesting global modulation of the 3′ end processing activity in development and differentiation. PMID:23241633

Neuropsychology and neuropharmacology of P3a and P3b.

PubMed

Polich, John; Criado, José R

2006-05-01

Perspectives on the P300 event-related brain potential (ERP) are reviewed by outlining the distinction between the P3a and P3b subcomponents. The critical factor for eliciting P3a is how target/standard discrimination difficulty rather than novelty modulates task processing. The neural loci of P3a and P3b generation are sketched and a theoretical model is developed. P3a originates from stimulus-driven disruption of frontal attention engagement during task processing. P3b originates when temporal-parietal mechanisms process the stimulus information for memory storage. The neuropharmacological implications of this view are then outlined by evaluating how acute and chronic use of ethanol, marijuana, and nicotine affect P3a and P3b. The findings suggest that the circuit underlying ERP generation is influenced in a different ways for acute intake and varies between chronic use levels across drugs. Theoretical implications are assessed.

Mild achondroplasia/hypochondroplasia with acanthosis nigricans, normal development, and a p.Ser348Cys FGFR3 mutation.

PubMed

Couser, Natario L; Pande, Chetna K; Turcott, Christie M; Spector, Elaine B; Aylsworth, Arthur S; Powell, Cynthia M

2017-04-01

Pathogenic allelic variants in the fibroblast growth factor receptor 3 (FGFR3) gene have been associated with a number of phenotypes including achondroplasia, hypochondroplasia, thanatophoric dysplasia, Crouzon syndrome with acanthosis nigricans (Crouzonodermoskeletal syndrome), and SADDAN (severe achondroplasia with developmental delay and acanthosis nigricans). Crouzon syndrome with acanthosis nigricans is caused by the pathogenic variant c.1172C>A (p.Ala391Glu) in the FGFR3 gene. The p.Lys650Thr pathogenic variant in FGFR3 has been linked to acanthosis nigricans without significant craniofacial or skeletal abnormalities. Recently, an infant with achondroplasia and a novel p.Ser348Cys FGFR3 mutation was reported. We describe the clinical history of an 8-year-old child with a skeletal dysplasia in the achondroplasia-hypochondroplasia spectrum, acanthosis nigricans, typical development, and the recently described p.Ser348Cys FGFR3 mutation. © 2017 Wiley Periodicals, Inc.

Medicinal chemistry of P2X receptors: allosteric modulators.

PubMed

Müller, Christa E

2015-01-01

P2X receptors are trimeric ligand-gated ion channels whose potential as novel drug targets for a number of diseases has been recognized. They are mainly involved in inflammatory processes, including neuroinflammation, and pain sensation. The orthosteric binding site is lined by basic amino acid residues that bind the negatively charged agonist ATP. Therefore it is not easy to develop orthosteric ligands that possess drug-like properties for such a highly polar binding site. However, ligand-gated ion channels offer multiple additional binding sites for allosteric ligands, positive or negative allosteric modulators enhancing or blocking receptor function. So far, the P2X3 (and P2X2/3), as well as the P2X7 receptor subtype have been the main focus of drug development efforts. A number of potent and selective allosteric antagonists have been developed to block these receptors. We start to see the development of novel allosteric ligands also for the other P2X receptor subtypes, P2X1, P2X2 and especially P2X4. The times when only poor, non-selective, non-drug-like tools for studying P2X receptor function were available have been overcome. The first clinical studies with allosteric P2X3 and P2X7 antagonists suggest that P2X therapeutics may soon become a reality.

EDITORIAL: The Fourth International Workshop on Microfactories (IWMF'04)

NASA Astrophysics Data System (ADS)

Chu, Jiaru; Maeda, Ryutaro

2005-10-01

This special section of Journal of Micromechanics and Microengineering is devoted to the fourth International Workshop on Microfactories. After the first three successful Workshops, which took place in Tsukuba, Japan in 1998, Fribourg, Switzerland in 2000 and Minneapolis, USA in 2002, the fourth (IWMF'04) was held in Shanghai, China on 15-17 October 2004. The concept of the `microfactory' and miniaturized production systems was first proposed by the Mechanical Engineering Laboratory in Japan who demonstrated the feasibility of downsizing energy-saving, distributed and eventually environmentally conscious manufacturing systems. There is incredible potential in reducing the physical scale of numerous processes related to the manufacture of many forms of future dense `mechatronic' products and in the manipulation of microscopic and nanoscopic objects and materials for the benefit of mankind. Small systems capable of these operations can be referred to as `microfactories'. A worldwide effort is currently underway to bring such microfactories to fruition. MEMS, MST and micromachines are regarded as synonyms, but they do not necessarily have the same meaning. In particular, differences can be found in their technological approaches. Roughly speaking, research and development in the USA is based primarily on surface or bulk silicon micromachining processes, and the ideal realization of MEMS seems to be the monolithic device. The European approach also focuses on integration between electronics and mechanics but, especially in connection with the development of `µTAS', it also demands the integration of non-mechanical components into the system. In Japan the approaches for MST are said to be rather less focused. Besides the above-mentioned `classical' microsystem technologies, down-scaling of conventional manufacturing methods, or non-silicon based device processing within this field, completely new technological methods are also considered as `microsystem technologies'. Out of more than 150 submitted abstracts, 138 papers were accepted for presentation at the workshop. Of these, a selection of seven high-quality papers have been chosen for presentation in this special section. We would like to express our appreciation of the outstanding efforts made by all involved in the workshop, especially the local committee for all the detailed planning required to make it an interesting meeting.

A Novel Microdeletion in 1(p34.2p34.3), Involving the "SLC2A1" ("GLUT1") Gene, and Severe Delayed Development

ERIC Educational Resources Information Center

Vermeer, Sascha; Koolen, David A; Visser, Gepke; Brackel, Hein J. L.; van der Burgt, Ineke; de Leeuw, Nicole; Willemsen, Michel A. A. P.; Sistermans, Erik A.; Pfundt, Rolph; de Vries, Bert B. A.

2007-01-01

A "de novo" 4.1-megabase microdeletion of chromosome 1p34.2p34.3 has been identified by array-based comparative genomic hybridization in a young male with severely delayed development, microcephaly, pronounced hypotonia, and facial dysmorphism. The deleted region encompasses 48 genes, among them the glucose transporter 1 ("SLC2A1" or "GLUT1")…

Characterization of lipids and antioxidant capacity of novel nutraceutical egg products developed with omega-3-rich oils.

PubMed

Kassis, Nissan M; Gigliotti, Joseph C; Beamer, Sarah K; Tou, Janet C; Jaczynski, Jacek

2012-01-15

Cardiovascular disease has had an unquestioned status of the number one cause of death in the US since 1921. Omega-3 polyunsaturated fatty acids (ω-3 PUFAs) have cardio-protective benefits. However, egg is typically a poor source of ω-3 PUFAs and, in general, the American diet is low in these cardio-protective fatty acids. Novel, nutritionally enhanced egg products were developed by substituting yolk with ω-3 PUFA-rich flaxseed, menhaden, algae, or krill oil. Experimental egg products matched composition of hen egg (whole egg). The experimental egg products, mixed whole egg, and a liquid egg product (Egg Beaters) were microwave-cooked and compared. Although fat, protein, and moisture contents of experimental egg products matched (P > 0.05) mixed whole egg, experimental egg products had more (P < 0.05) ω-3 PUFAs, lower (P < 0.05) ω-6/ω-3 ratio, and depending on oil added, a higher (P < 0.05) unsaturated/saturated fatty acids ratio compared to mixed whole egg. Triglycerides were the main lipid class in all experimental egg products except those developed with krill oil, which had even more phospholipids than mixed whole egg. Analysis of thiobarbituric acid reactive substances showed that lipid oxidation of experimental egg products was lower (P < 0.05) or similar (P > 0.05) to mixed whole egg, except for experimental egg products with krill oil. However, peroxide value showed that all egg samples had minimal oxidation. Experimental egg products developed with menhaden or flaxseed oil had the highest (P < 0.05) concentration of the antioxidant, ethyoxquin compared to all other egg samples. However, experimental egg products with krill oil likely contained a natural antioxidant, astaxanthin. This study demonstrated an alternative approach to developing novel, nutraceutical egg products. Instead of dietary modification of chicken feed, yolk substitution with ω-3 PUFAs oils resulted in enhancement of ω-3 PUFAs beyond levels possible to achieve by modifying chicken feed. Copyright © 2011 Society of Chemical Industry.

Exploring the role of pain as an early predictor of category 2 pressure ulcers: a prospective cohort study.

PubMed

Smith, Isabelle L; Brown, Sarah; McGinnis, Elizabeth; Briggs, Michelle; Coleman, Susanne; Dealey, Carol; Muir, Delia; Nelson, E Andrea; Stevenson, Rebecca; Stubbs, Nikki; Wilson, Lyn; Brown, Julia M; Nixon, Jane

2017-01-20

To explore pressure area related pain as a predictor of category ≥2 pressure ulcer (PU) development. Multicentre prospective cohort study. UK hospital and community settings. Consenting acutely ill patients aged ≥18 years, defined as high risk (Braden bedfast/chairfast AND completely immobile/very limited mobility; pressure area related pain or; category 1 PU). Patients too unwell, unable to report pain, 2 or more category ≥2 PUs. Twice weekly for 30 days. Development and time to development of one or more category ≥2 PUs. Of 3819 screened, 1266 were eligible, 634 patients were recruited, 32 lost to follow-up, providing a 602 analysis population. 152 (25.2%) developed one or more category ≥2 PUs. 464 (77.1%) patients reported pressure area related pain on a healthy, altered or category 1 skin site of whom 130 (28.0%) developed a category ≥2 PU compared with 22 (15.9%) of those without pain. Full stepwise variable selection was used throughout the analyses. (1) Multivariable logistic regression model to assess 9 a priori factors: presence of category 1 PU (OR=3.25, 95% CI (2.17 to 4.86), p<0.0001), alterations to intact skin (OR=1.98, 95% CI (1.30 to 3.00), p=0.0014), pressure area related pain (OR=1.56, 95% CI (0.93 to 2.63), p=0.0931). (2) Multivariable logistic regression model to account for overdispersion: presence of category 1 PU (OR=3.20, 95% CI (2.11 to 4.85), p<0.0001), alterations to intact skin (OR=1.90, 95% CI (1.24 to 2.91), p=0.0032), pressure area related pain (OR=1.85, 95% CI (1.07 to 3.20), p=0.0271), pre-existing category 2 PU (OR=2.09, 95% CI (1.35 to 3.23), p=0.0009), presence of chronic wound (OR=1.66, 95% CI (1.06 to 2.62), p=0.0277), Braden activity (p=0.0476). (3) Accelerated failure time model: presence of category 1 PU (AF=2.32, 95% CI (1.73 to 3.12), p<0.0001), pressure area related pain (AF=2.28, 95% CI (1.59 to 3.27), p<0.0001). (4) 2-level random-intercept logistic regression model: skin status which comprised 2 levels (versus healthy skin); alterations to intact skin (OR=4.65, 95% CI (3.01 to 7.18), p<0.0001), presence of category 1 PU (OR=17.30, 95% CI (11.09 to 27.00), p<0.0001) and pressure area related pain (OR=2.25, 95% CI (1.53 to 3.29), p<0.0001). This is the first study to assess pain as a predictor of category ≥2 PU development. In all 4 models, pain emerged as a risk factor associated with an increased probability of category ≥2 PU development. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Prevalence, Timing, Causes, and Outcomes of Hyponatremia in Hospitalized Orthopaedic Surgery Patients.

PubMed

Hennrikus, Eileen; Ou, George; Kinney, Bradley; Lehman, Erik; Grunfeld, Robert; Wieler, Jane; Damluji, Abdulla; Davis, Charles; Mets, Berend

2015-11-18

Hyponatremia is common among orthopaedic patients and is associated with adverse clinical outcomes. We examined the prevalence, timing, causes, and outcomes of hyponatremia in adult hospitalized orthopaedic surgery patients. We evaluated the medical records of 1067 consecutive orthopaedic surgery patients admitted to a tertiary academic institution. The medical records were reviewed to investigate hyponatremia (serum sodium <135 mEq/L) that (1) had been present on hospital admission or (2) had developed postoperatively. The primary outcomes were the prevalence and timing of, and risk factors for, presentation with or development of hyponatremia. Secondary outcomes were hospital length of stay, total hospital cost, and discharge disposition. Multivariable logistic regression models were used to assess the variables associated with hyponatremia and the effects of hyponatremia on clinical outcomes. Of the 1067 patients, seventy-one (7%) had preoperative hyponatremia and 319 (30%) developed hyponatremia postoperatively. Of the latter, 298 (93%) developed hyponatremia within forty-eight hours postoperatively. Compared with patients with normonatremia, those who presented with hyponatremia, on the average, were older (67.2 versus 60.5 years, p < 0.001), had longer hospital stays (4.6 versus 3.3 days, p < 0.001), incurred higher hospital costs ($19,200 versus $17,000, p = 0.006), and were more likely to be discharged to an extended-care facility (odds ratio [OR] = 2.87, p < 0.001). Developing hyponatremia postoperatively resulted, on average, in a longer hospital stay (3.7 versus 3.3 days, p = 0.002) and greater hospital cost ($18,800 versus $17,000, p < 0.001). Age (OR = 1.13 per decade, p = 0.012), spine surgery (OR = 2.76 versus knee, p < 0.001), hip surgery (OR = 1.76 versus knee, p < 0.001), and the amount of lactated Ringer solution used (OR = 1.16, p = 0.002) increased the risk of developing hyponatremia. Hyponatremia in orthopaedic patients is associated with longer, costlier hospitalizations. The factors that significantly increased the risk of developing postoperative hyponatremia were an older age, spine fusion, hip arthroplasty, and the amount of lactated Ringer solution used. Copyright © 2015 by The Journal of Bone and Joint Surgery, Incorporated.

ArI/ArII laser induced fluorescence system for measurement of neutral and ion dynamics in a large scale helicon plasma.

PubMed

Kelly, R F; Meaney, K D; Gilmore, M; Desjardins, T R; Zhang, Y

2016-11-01

In order to investigate the role of both neutral and ion dynamics in large-scale helicon discharges, a laser induced fluorescence (LIF) system capable of measuring both ArI and ArII fluorescence using a single tunable laser is being developed. The system is based on a >250 mW solid state laser. For ArI measurements, the laser pumps the metastable ( 2 P 0 3/2 )4s level to the ( 2 P 0 1/2 )4p level using 696.7352 nm light, and fluorescence radiation from decay to the ( 2 P 0 1/2 )4s level at 772.6333 nm is observed. For ArII, currently in development, the metastable ( 3 P)3d 4 F 7/2 level will be pumped to the ( 3 P)4p 4 D 0 7/2 level using 688.8511 nm, and decay fluorescence to the ( 3 P)4s 4 P 5/2 level at 434.9285 nm measured. Here all wavelengths are in a vacuum.

Development of Personalized Fitting Device With 3-Dimensional Solution for Prevention of NIV Oronasal Mask-Related Pressure Ulcers.

PubMed

Shikama, Maiko; Nakagami, Gojiro; Noguchi, Hiroshi; Mori, Taketoshi; Sanada, Hiromi

2018-05-22

Pressure ulcers related to oronasal masks used with noninvasive ventilation (NIV), along with patient discomfort, occur due to improper fit of the mask. We developed a personalized fitting device using a 3-dimensional (3D) scanning solution to prevent the formation of NIV mask-related pressure ulcers. This study aimed to evaluate the effectiveness of the proposed personalized fitting device. We conducted a randomized crossover experimental study of 20 healthy participants to study the use of this personalized fitting device between the face and an NIV mask designed with 3D solutions. The fitting device was not used under the NIV mask for the control. The outcome measures were the presence of blanchable erythema, standardized redness intensity, discomfort level, and contact pressure. The incidence of blanchable erythema and standardized redness intensity values were significantly lower for subjects who used the fitting device when worn for 30 min ( P < .001). The discomfort levels at the forehead, nasal bridge, and both cheeks, as well as leakage, were significantly reduced as well ( P = .008, P < .001, P = .001, P = .002, P = .001, P = .02, P < .001, P < .001, P < .001). Contact pressure at the nasal bridge, where pressure ulcers most frequently develop, was significantly decreased with the fitting device ( P < .001). Personalized fitting devices that incorporate 3D scanning solutions may contribute to the prevention of NIV mask-related pressure ulcers and the reduction of discomfort. Copyright © 2018 by Daedalus Enterprises.

Sinus hypoplasia in the cystic fibrosis rat resolves in the absence of chronic infection.

PubMed

Grayson, Jessica; Tipirneni, Kiranya E; Skinner, Daniel F; Fort, Matthew; Cho, Do-Yeon; Zhang, Shaoyan; Prince, Andrew C; Lim, Dong-Jin; Mackey, Calvin; Woodworth, Bradford A

2017-09-01

Sinus hypoplasia is a hallmark characteristic in cystic fibrosis (CF). Chronic rhinosinusitis (CRS) is nearly universal from a young age, impaired sinus development could be secondary to loss of the cystic fibrosis transmembrane conductance regulator (CFTR) or consequences of chronic infection during maturation. The objective of this study was to assess sinus development relative to overall growth in a novel CF animal model. Sinus development was evaluated in CFTR -/- and CFTR +/+ rats at 3 stages of development: newborn; 3 weeks; and 16 weeks. Microcomputed tomography (microCT) scanning, cultures, and histology were performed. Three-dimensional sinus and skull volumes were quantified. At birth, sinus volumes were decreased in CFTR -/- rats compared with wild-type rats (mean ± SEM: 11.3 ± 0.85 mm 3 vs 14.5 ± 0.73 mm 3 ; p < 0.05), despite similar weights (8.4 ± 0.46 gm vs 8.3 ± 0.51 gm; p = 0.86). CF rat weights declined by 16 weeks (378.4 ± 10.6 gm vs 447.4 ± 15.9 gm; p < 0.05), sinus volume increased similar to wild-type rats (201.1 ± 3.77 gm vs 203.4 ± 7.13 gm; p = 0.8). The ratio of sinus volume to body weight indicates hypoplasia present at birth (1.37 ± 0.12 vs 1.78 ± 0.11; p < 0.05) and showed an increase compared with CFTR +/+ animals by 16 weeks (0.53 ± 0.02 vs 0.46 ± 0.02; p < 0.05). Rats did not develop histologic evidence of chronic infection. CF rat sinuses are smaller at birth, but develop volumes similar to wild-type rats with maturation. This suggests that loss of CFTR may confer sinus hypoplasia at birth, but normal development ensues without chronic sinus infection. © 2017 ARS-AAOA, LLC.

Update: the role of FoxP3 in allergic disease.

PubMed

Paik, Young; Dahl, Matthew; Fang, Deyu; Calhoun, Karen

2008-06-01

T-regulatory cells play a key role in allergic and asthmatic inflammatory airway diseases. This review discusses the importance of a critical gene associated with T-regulatory cells. Forkhead box P3 is a forkhead-winged helix transcription factor gene involved in immune function in allergy and asthma. Recently, many functions of forkhead box P3 and its influence on the immune system have been elucidated. T-regulatory cells that are CD4+CD25+ and express forkhead box P3, influence the development and expression of atopy and allergic response. The exact mechanisms are not yet delineated, but multiple recent studies provide greater understanding of the mechanism of forkhead box P3 and its influence on these T-regulatory cells. Greater understanding of the molecular and immunological mechanisms underlying the T-regulatory cells and forkhead box P3 will permit the development of targeted treatment modalities to influence disease processes such as allergic rhinitis and bronchial asthma.

Evaluation of protective effect of multiantigenic DNA vaccine encoding MIC3 and ROP18 antigen segments of Toxoplasma gondii in mice.

PubMed

Qu, Daofeng; Han, Jianzhong; Du, Aifang

2013-07-01

The high incidence and severe damage caused by Toxoplasma gondii infection clearly indicates the need for the development of a vaccine. In this study, we evaluated the immune responses and protection against toxoplasmosis by immunizing ICR mice with a multiantigenic DNA vaccine. To develop the multiantigenic vaccine, two T. gondii antigens, MIC3 and ROP18, selected on the basis of previous studies were chosen. ICR mice were immunized subcutaneously with PBS, empty pcDNA3.1 vector, pMIC3, pROP18, and pROP18-MIC3, respectively. The results of lymphocyte proliferation assay, cytokine, and antibody determinations showed that mice immunized with pROP18-MIC3 elicited stronger humoral and Th1-type cellular immune responses than those immunized with single-gene plasmids, empty plasmid, or phosphate-buffered saline. After a lethal challenge with the highly virulent T. gondii RH strain, a prolonged survival time in pROP18-MIC3-immunized mice was observed in comparison to control groups. Our study indicates that the introduction of multiantigenic DNA vaccine is more powerful and efficient than single-gene vaccine, and deserves further evaluation and development.

p62 as a therapeutic target for inhibition of autophagy in prostate cancer.

PubMed

Wang, Lei; Kim, Donghern; Wise, James T F; Shi, Xianglin; Zhang, Zhuo; DiPaola, Robert S

2018-04-01

To test the hypothesis that p62 is an optimal target for autophagy inhibition and Verteporfin, a clinically available drug approved by FDA to treat macular degeneration that inhibits autophagy by targeting p62 protein, can be developed clinically to improve therapy for advanced prostate cancer. Forced expression of p62 in PC-3 cells and normal prostate epithelial cells, RWPE-1 and PZ-HPV7, were carried out by transfection of these cells with pcDNA3.1/p62 or p62 shRNA plasmid. Autophagosomes and autophagic flux were measured by transfection of tandem fluorescence protein mCherry-GFP-LC3 construct. Apoptosis was measured by Annexin V/PI staining. Tumorigenesis was measured by a xenograft tumor growth model. Verteporfin inhibited cell growth and colony formation in PC-3 cells. Verteporfin generated crosslinked p62 oligomers, resulting in inhibition of autophagy and constitutive activation of Nrf2 as well as its target genes, Bcl-2 and TNF-α. In normal prostate epithelial cells, forced expression of p62 caused constitutive Nrf2 activation, development of apoptosis resistance, and Verteporfin treatment exhibited inhibitory effects. Verteporfin treatment also inhibited starvation-induced autophagic flux of these cells. Verteporfin inhibited tumorigenesis of both normal prostate epithelial cells with p62 expression and prostate cancer cells and decreased p62, constitutive Nrf2, and Bcl-xL in xenograft tumor tissues, indicating that p62 can be developed as a drug target against prostate cancer. p62 has a high potential to be developed as a therapeutic target. Verteporfin represents a prototypical agent with therapeutic potential against prostate cancer through inhibition of autophagy by a novel mechanism of p62 inhibition. © 2018 Wiley Periodicals, Inc.

p38 mitogen-activated protein kinase (MAPK) first regulates filamentous actin at the 8-16-cell stage during preimplantation development.

PubMed

Paliga, Andrew J M; Natale, David R; Watson, Andrew J

2005-08-01

The MAPK (mitogen-activated protein kinase) superfamily of proteins consists of four separate signalling cascades: the c-Jun N-terminal kinase or stress-activated protein kinases (JNK/SAPK); the ERKs (extracellular-signal-regulated kinases); the ERK5 or big MAPK1; and the p38 MAPK group of protein kinases, all of which are highly conserved. To date, our studies have focused on defining the role of the p38 MAPK pathway during preimplantation development. p38 MAPK regulates actin filament formation through the downstream kinases MAPKAPK2/3 (MAPK-activated protein kinase 2/3) or MAPKAPK5 [PRAK (p38 regulated/activated kinase)] and subsequently through HSP25/27 (heat-shock protein 25/27). We recently reported that 2-cell-stage murine embryos treated with cytokine-suppressive anti-inflammatory drugs (CSAIDtrade mark; SB203580 and SB220025) display a reversible blockade of development at the 8-16-cell stage, indicating that p38 (MAPK) activity is required to complete murine preimplantation development. In the present study, we have investigated the stage-specific action and role of p38 MAPK in regulating filamentous actin during murine preimplantation development. Treatment of 8-cell-stage embryos with SB203580 and SB220025 (CSAIDtrade mark) resulted in a blockade of preimplantation development, loss of rhodamine phalloidin fluorescence, MK-p (phosphorylated MAPKAPK2/3), HSP-p (phosphorylated HSP25/27) and a redistribution of alpha-catenin immunofluorescence by 12 h of treatment. In contrast, treatment of 2- and 4-cell-stage embryos with CSAIDtrade mark drugs resulted in a loss of MK-p and HSP-p, but did not result in a loss of rhodamine phalloidin fluorescence. All these effects of p38 MAPK inhibition were reversed upon removal of the inhibitor, and development resumed in a delayed but normal manner to the blastocyst stage. Treatment of 8-cell embryos with PD098059 (ERK pathway inhibitor) did not affect development or fluorescence of MK-p, HSP-p or rhodamine phalloidin. Murine preimplantation development becomes dependent on p38 MAPK at the 8-16-cell stage, which corresponds to the stage when p38 MAPK first regulates filamentous actin during early development.

High serum uric acid level and low urine pH as predictors of metabolic syndrome: a retrospective cohort study in a Japanese urban population.

PubMed

Hara, Shigeko; Tsuji, Hiroshi; Ohmoto, Yuki; Amakawa, Kazuhisa; Hsieh, Shiun Dong; Arase, Yasuji; Nakajima, Hiromu

2012-02-01

The objective of this study was to evaluate whether hyperuricemia, acidic urine, or their combination predicts metabolic syndrome (MetS). In study 1, 69,094 subjects who received a general health checkup between 1985 and 2005 were included in a cross-sectional study of serum uric acid (SUA) and urine pH in relation to MetS. In study 2, the association of SUA and urine pH with MetS development over a 5-year period was evaluated in 5617 subjects with body mass index less than 25 kg/m(2) at the first examination. In study 1, higher SUA and lower urine pH were both positively correlated to MetS status (P < .001). The combination of high SUA and low urine pH was significantly associated with higher MetS prevalence compared with the combination of low SUA and high urine pH (odds ratio, 3.383; 95% confidence interval [CI], 3.034-3.784 in men; odds ratio, 4.000; 95% CI, 2.992-5.452 in women). In study 2, the top quartile of SUA levels was associated with higher MetS development compared with the bottom quartile during the 5-year period in men (hazard ratio [HR], 1.793; 95% CI, 1.084-2.966; P = .023). In women, the HR was 3.732 (95% CI, 0.391-35.62; P = .252) for the upper vs the lower half of SUA levels. For urine pH, the HR was 1.955 (95% CI, 1.089-3.509; P = .025) for the bottom vs the top quartile in men. A likelihood ratio test confirmed that high SUA and low urine pH act synergistically in the development of MetS. High SUA, low urine pH, and their combination are predictive risk factors for MetS development. Copyright © 2012 Elsevier Inc. All rights reserved.

EDITORIAL: Special issue for papers selected from The 8th International Workshop on Micro and Nanotechnology for Power Generation and Energy Conversion Applications (PowerMEMS 2008) Special issue for papers selected from The 8th International Workshop on Micro and Nanotechnology for Power Generation and Energy Conversion Applications (PowerMEMS 2008)

NASA Astrophysics Data System (ADS)

Tanaka, Shuji

2009-09-01

This special issue of the Journal of Micromechanics and Microengineering features papers selected from The 8th International Workshop on Micro and Nanotechnology for Power Generation and Energy Conversion Applications (PowerMEMS 2008) with the 2nd Symposium on Micro Environmental Machine Systems (μMEMS 2008). The workshop was held in Sendai, Japan on 9-12 November 2008 by Tohoku University. This is the second time that the PowerMEMS workshop has been held in Sendai, following the first workshop in 2000. Power MEMS is one of the newest categories of MEMS, which encompasses microdevices and microsystems for power generation, energy conversion and propulsion. The first concept of Power MEMS was born in the late 1990's from a MEMS-based gas turbine project at Massachusetts Institute of Technology. After that, the research and development of Power MEMS have been promoted by the strong need for compact power sources with high energy and/or power density. Since its inception, Power MEMS has expanded to include not only various MEMS-based power generators but also small energy machines and microdevices for macro power generators. Previously, the main topics of the PowerMEMS workshop were miniaturized gas turbines and micro fuel cells, but recently, energy harvesting has been the hottest topic. In 2008, energy harvesting had a 41% share in the 118 accepted regular papers. This special issue includes 19 papers on various topics. Finally, I would like to express my sincere appreciation to the members of the International Steering Committee, the Technical Program Committee, the Local Organizing Committee and financial supporters. This special issue was edited in collaboration with the staff of IOP Publishing.

77 FR 8236 - National Assessment Governing Board; Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-14

... Education, National Assessment Governing Board. ACTION: Notice of open and closed meeting sessions. SUMMARY...: Committee Meeting: Assessment Development Committee (ADC): Closed Session: 9 a.m.-3 p.m. Open Session: 3 p.m.-5 p.m. March 1 Committee Meetings Ad Hoc Committee: Open Session 2:30 p.m.-4 p.m. Executive...

Investigations of the structure and electromagnetic interactions of few body systems

NASA Astrophysics Data System (ADS)

Harper, E. P.; Lehman, D. R.; Prats, F.

The structure and electromagnetic interactions of few-body systems were investigated. The structural properties of the very light nuclei are examined by developing theoretical models that begin from the basic interactions between the constituents and that are solved exactly (numerically), i.e., full three- or four-body dynamics. Such models are then used in an attempt to understand the details of the strong and electromagnetic interactions of the few-nucleon nuclei after the basic underlying reaction mechanisms are understood with simpler models. Topics included: (1) set up the equations for the low-energy photodisintegration of (3)He and (3)H including final-state interactions and the E1 plus E2 operators; (2) develop a unified picture of the p + d (YIELDS) (3)He + (GAMMA), p + d (YIELDS) (3)He + (PI) (0), p + d (YIELDS) (3)H + (PI) (+) reactions at intermediate energies; (3) calculate the elastic and inelastic (1(+) (YIELDS) 0 (+)) form factors for (6)Li with three-body ((ALPHA)NN) wave functions; (4) calculate static properties (RMS radius, magnetic moment, and quadrupole moment) of (6)Li with three-body wave functions; and (5) develop the theory for the coincidence reactions (6)Li(p,2p)n(ALPHA), (6)Li(e,e'p)n(ALPHA), and (6)Li(e,e'd)(ALPHA).

Selective amplification and sequencing of cyclic phosphate-containing RNAs by the cP-RNA-seq method.

PubMed

Honda, Shozo; Morichika, Keisuke; Kirino, Yohei

2016-03-01

RNA digestions catalyzed by many ribonucleases generate RNA fragments that contain a 2',3'-cyclic phosphate (cP) at their 3' termini. However, standard RNA-seq methods are unable to accurately capture cP-containing RNAs because the cP inhibits the adapter ligation reaction. We recently developed a method named cP-RNA-seq that is able to selectively amplify and sequence cP-containing RNAs. Here we describe the cP-RNA-seq protocol in which the 3' termini of all RNAs, except those containing a cP, are cleaved through a periodate treatment after phosphatase treatment; hence, subsequent adapter ligation and cDNA amplification steps are exclusively applied to cP-containing RNAs. cP-RNA-seq takes ∼6 d, excluding the time required for sequencing and bioinformatics analyses, which are not covered in detail in this protocol. Biochemical validation of the existence of cP in the identified RNAs takes ∼3 d. Even though the cP-RNA-seq method was developed to identify angiogenin-generating 5'-tRNA halves as a proof of principle, the method should be applicable to global identification of cP-containing RNA repertoires in various transcriptomes.

Twisting microfluidics in a planetary centrifuge.

PubMed

Yasuda, Shoya; Hayakawa, Masayuki; Onoe, Hiroaki; Takinoue, Masahiro

2017-03-15

This paper reports a twisting microfluidic method utilising a centrifuge-based fluid extruding system in a planetary centrifuge which simultaneously generates an orbital rotation and an axial spin. In this method, fluid extrusion from a micro-scale capillary to an 'open-space' solution or air enables release of the fluid from the capillary-based microchannel, which physically means that there is a release of fluids from a confined low-Reynolds-number environment to an open non-low-Reynolds-number environment. As a result, the extruded fluids are separated from the axial spin of the capillary, and the difference in the angular rates of the axial spin between the capillary and the extruded fluids produces the 'twisting' of the fluid. In this study, we achieve control of the twist of highly viscous fluids, and we construct a simple physical model for the fluid twist. In addition, we demonstrate the formation of twisted hydrogel microstructures (stripe-patterned microbeads and multi-helical microfibres) with control over the stripe pattern and the helical pitch length. We believe that this method will enable the generation of more sophisticated microstructures which cannot easily be formed by usual channel-based microfluidic devices. This method can also provide advanced control of microfluids, as in the case of rapid mixing of highly viscous fluids. This method can contribute to a wide range of applications in materials science, biophysics, biomedical science, and microengineering in the future.

Innovative Airbreathing Propulsion Concepts for Access to Space

NASA Technical Reports Server (NTRS)

Whitlow, Jr., Woodrow; Blech, Richard A.; Blankson, Isaiah M.

2001-01-01

This paper will present technologies and concepts for novel aeropropulsion systems. These technologies will enhance the safety of operations, reduce life cycle costs, and contribute to reduced costs of air travel and access to space. One of the goals of the NASA program is to reduce the carbon-dioxide emissions of aircraft engines. Engine concepts that use highly efficient fuel cell/electric drive technologies in hydrogen-fueled engines will be presented in the proposed paper. Carbon-dioxide emissions will be eliminated by replacing hydrocarbon fuel with hydrogen, and reduce NOx emissions through better combustion process control. A revolutionary exoskeletal engine concept, in which the engine drum is rotated, will be shown. This concept has the potential to allow a propulsion system that can be used for subsonic through hypersonic flight. Dual fan concepts that have ultra-high bypass ratios, low noise, and low drag will be presented. Flow-controlled turbofans and control-configured turbofans also will be discussed. To increase efficiency, a system of microengines distributed along lifting surfaces and on the fuselage is being investigated. This concept will be presented in the paper. Small propulsion systems for affordable, safe personal transportation vehicles will be discussed. These low-oil/oilless systems use technologies that enable significant cost and weight reductions. Pulse detonation engine-based hybrid-cycle and combined-cycle propulsion systems for aviation and space access will be presented.

Can organic matter hide from decomposers in the labyrinth of soil aggregates? Micro-engineered Soil Chips challenging foraging fungi

NASA Astrophysics Data System (ADS)

Hammer, Edith C.; Aleklett, Kristin; Arellano Caicedo, Carlos G.; Bengtsson, Martin; Micaela Mafla Endara, Paola; Ohlsson, Pelle

2017-04-01

From the point of view of microorganisms, the soil environment is an enormously complex labyrinth with paths and dead-end streets, where resources and shelters are unevenly distributed. We study foraging strategies of soil organisms, especially fungi, and the possibility of physio-spatial stabilization of organic matter by "hiding" in occluded soil spaces. We manipulate growth habitat microstructure with lab-on-a-chip techniques, where we designed complex environments with channels and obstacle at dimensions of the size of hyphae, and construct them in the transparent, gas-permeable polymer PDMS. We fill those with different nutrient solutions or combine with mineral nutrient gradients, and inoculate them with soil organisms. We analyze organisms and substrates with microscopy, fluorescence microscopy and analytical chemistry. We compared different soil litter decomposers and an arbuscular mycorrhizal fungus for their ability to forage through complex air-gap structures and attempt to classify them into functional traits concerning their mycelium directionality, space-exploring approach and ability to grow through acute angles and narrow constrictions. We identified structures which are very difficult to penetrate for most species, and compounds located behind such features may thus be spatially unavailable for decomposers. We discuss our approach in comparison to soil pore space tomographic analyses and findings we made in the pore space of colonized wood biochar.

Calculations of resonances parameters for the ((2s2) 1Se, (2s2p) 1,3P0) and ((3s2) 1Se, (3s3p) 1,3P0) doubly excited states of helium-like ions with Z≤10 using a complex rotation method implemented in Scilab

NASA Astrophysics Data System (ADS)

Gning, Youssou; Sow, Malick; Traoré, Alassane; Dieng, Matabara; Diakhate, Babacar; Biaye, Mamadi; Wagué, Ahmadou

2015-01-01

In the present work a special computational program Scilab (Scientific Laboratory) in the complex rotation method has been used to calculate resonance parameters of ((2s2) 1Se, (2s2p) 1,3P0) and ((3s2) 1Se, (3s3p) 1,3P0) states of helium-like ions with Z≤10. The purpose of this study required a mathematical development of the Hamiltonian applied to Hylleraas wave function for intrashell states, leading to analytical expressions which are carried out under Scilab computational program. Results are in compliance with recent theoretical calculations.

miR-324-3p promotes gastric cancer development by activating Smad4-mediated Wnt/beta-catenin signaling pathway.

PubMed

Sun, Guang-Li; Li, Zheng; Wang, Wei-Zhi; Chen, Zheng; Zhang, Lei; Li, Qing; Wei, Song; Li, Bo-Wen; Xu, Jiang-Hao; Chen, Liang; He, Zhong-Yuan; Ying, Kai; Zhang, Xuan; Xu, Hao; Zhang, Dian-Cai; Xu, Ze-Kuan

2018-06-01

Emerging evidence suggested that miRNAs can function as oncogenes or tumor suppressors by regulating downstream target genes. miR-324-3p has been reported to function in several carcinomas, but its role in gastric cancer (GC) is still unknown. This study aims to explore the effects of miR-324-3p on the development of GC. Expression of miR-324-3p was examined in GC cells and tissues by qRT-PCR. Effects of miR-324-3p on GC cells were evaluated by cell vitality assay, colony formation assay, cell migration assay, and flow cytometric assay. The dual luciferase assay was used to verify whether miR-324-3p could interact with the potential target genes. Western blot was used to assess the expression level of Smad4 and beta-catenin. Intracellular ATP level was also examined. The tumor xenografts were established using nude mice. A gastric organoid model was made from fresh stomach tissue. miR-324-3p was expressed at higher levels in the tumor tissues compared with adjacent normal tissues. Overexpression of miR-324-3p promoted cell growth, migration, and decreased apoptosis. miR-324-3p repressed the expression of Smad4, and loss of Smad4 activated the Wnt/beta-catenin signaling pathway. Overexpression of Smad4 rescued the effects of miR-324-3p on GC cells. The intracellular ATP level was upregulated with overexpression of miR-324-3p. miR-324-3p facilitated tumor cell colonization and growth in vivo and contributed to the growth of gastric organoids. The results suggested that miR-324-3p promoted GC through activating the Smad4-mediated Wnt/beta-catenin signaling pathway. The miR-324-3p/Smad4/Wnt signaling axis may be a potential therapeutic target to prevent GC progression.

Teaching Petri Nets Using P3

ERIC Educational Resources Information Center

Gasevic, Dragan; Devedzic, Vladan

2004-01-01

This paper presents Petri net software tool P3 that is developed for training purposes of the Architecture and organization of computers (AOC) course. The P3 has the following features: graphical modeling interface, interactive simulation by single and parallel (with previous conflict resolution) transition firing, two well-known Petri net…

U.S. Army Mobility Equipment Research and Development Plan

DTIC Science & Technology

1981-03-01

P LEVEL( ADA 102 7 8 NOIIILITY ISOIIMINT IIISE MICII A DEIIEMOI’MINI COMMAND Al4 198 U.S. ARMY MOBILITY EO,(IJIPME~qNT 1) ITE’V.ZLOPME.NI...8217 PLAN FORT IJELVOIR, VA MAEICII 191 * jDISTII3UTON 3TATE7 N A IAP~rO edIOT U .. ~eI a G Best Available Copy Mobility Equipment Research & DevelopmentC...U.S. ARMY MOBILITY EQUIPMEN9 RESEARCH AND DEVELOPMENT- MOBILITY SURVIVABILITY ENERGI C) LU P= _ _ \\ ii]MAR8I earch & Development Command ~3 QUIPMENT

Development and Testing of the Rigidizable Inflatable Get-Away-Special Experiment

DTIC Science & Technology

2007-06-01

assigned three different drawing numbers: RIGEX- WAVE1-D, RIGEX- WAVE2 -D, and RIGEX-WAVE3-D. The end of wave #3 leaves 20 RIGEX with all structural...intact RIGEX- WAVE2 -P Wave 2 Assembly Complete, main structure and various subassemblies RIGEX-WAVE3-P Wave 3 Assembly Complete RIGEX-HAN2007-P Wave

Patient-Reported Measures for Person-Centered Coordinated Care: A Comparative Domain Map and Web-Based Compendium for Supporting Policy Development and Implementation

PubMed Central

Wheat, Hannah; Horrell, Jane; Sugavanam, Thavapriya; Fosh, Benjamin; Valderas, Jose M

2018-01-01

Background Patient-reported measure (PRM) questionnaires were originally used in research to measure outcomes of intervention studies. They have now evolved into a diverse family of tools measuring a range of constructs including quality of life and experiences of care. Current health and social care policy increasingly advocates their use for embedding the patient voice into service redesign through new models of care such as person-centered coordinated care (P3C). If chosen carefully and used efficiently, these tools can help improve care delivery through a variety of novel ways, including system-level feedback for health care management and commissioning. Support and guidance on how to use these tools would be critical to achieve these goals. Objective The objective of this study was to develop evidence-based guidance and support for the use of P3C-PRMs in health and social care policy through identification of PRMs that can be used to enhance the development of P3C, mapping P3C-PRMs against an existing model of domains of P3C, and integration and organization of the information in a user-friendly Web-based database. Methods A pragmatic approach was used for the systematic identification of candidate P3C-PRMs, which aimed at balancing comprehensiveness and feasibility. This utilized a number of resources, including existing compendiums, peer-reviewed and gray literature (using a flexible search strategy), and stakeholder engagement (which included guidance for relevant clinical areas). A subset of those candidate measures (meeting prespecified eligibility criteria) was then mapped against a theoretical model of P3C, facilitating classification of the construct being measured and the subsequent generation of shortlists for generic P3C measures, specific aspects of P3C (eg, communication or decision making), and condition-specific measures (eg, diabetes, cancer) in priority areas, as highlighted by stakeholders. Results In total, 328 P3C-PRMs were identified, which were used to populate a freely available Web-based database. Of these, 63 P3C-PRMs met the eligibility criteria for shortlisting and were classified according to their measurement constructs and mapped against the theoretical P3C model. We identified tools with the best coverage of P3C, thereby providing evidence of their content validity as outcome measures for new models of care. Transitions and medications were 2 areas currently poorly covered by existing measures. All the information is currently available at a user-friendly web-based portal (p3c.org.uk), which includes all relevant information on each measure, such as the constructs targeted and links to relevant literature, in addition to shortlists according to relevant constructs. Conclusions A detailed compendium of P3C-PRMs has been developed using a pragmatic systematic approach supported by stakeholder engagement. Our user-friendly suite of tools is designed to act as a portal to the world of PRMs for P3C, and have utility for a broad audience, including (but not limited to) health care commissioners, managers, and researchers. PMID:29444767

Meckelin 3 Is Necessary for Photoreceptor Outer Segment Development in Rat Meckel Syndrome

PubMed Central

Tiwari, Sarika; Hudson, Scott; Gattone, Vincent H.; Miller, Caroline; Chernoff, Ellen A. G.; Belecky-Adams, Teri L.

2013-01-01

Ciliopathies lead to multiorgan pathologies that include renal cysts, deafness, obesity and retinal degeneration. Retinal photoreceptors have connecting cilia joining the inner and outer segment that are responsible for transport of molecules to develop and maintain the outer segment process. The present study evaluated meckelin (MKS3) expression during outer segment genesis and determined the consequences of mutant meckelin on photoreceptor development and survival in Wistar polycystic kidney disease Wpk/Wpk rat using immunohistochemistry, analysis of cell death and electron microscopy. MKS3 was ubiquitously expressed throughout the retina at postnatal day 10 (P10) and P21. However, in the mature retina, MKS3 expression was restricted to photoreceptors and the retinal ganglion cell layer. At P10, both the wild type and homozygous Wpk mutant retina had all retinal cell types. In contrast, by P21, cells expressing rod- and cone-specific markers were fewer in number and expression of opsins appeared to be abnormally localized to the cell body. Cell death analyses were consistent with the disappearance of photoreceptor-specific markers and showed that the cells were undergoing caspase-dependent cell death. By electron microscopy, P10 photoreceptors showed rudimentary outer segments with an axoneme, but did not develop outer segment discs that were clearly present in the wild type counterpart. At p21 the mutant outer segments appeared much the same as the P10 mutant outer segments with only a short axoneme, while the wild-type controls had developed outer segments with many well-organized discs. We conclude that MKS3 is not important for formation of connecting cilium and rudimentary outer segments, but is critical for the maturation of outer segment processes. PMID:23516626

Abdominal fat interacts with PNPLA3 I148M, but not with the APOC3 variant in the pathogenesis of liver steatosis in chronic hepatitis C.

PubMed

Zampino, R; Coppola, N; Cirillo, G; Boemio, A; Pisaturo, M; Marrone, A; Macera, M; Sagnelli, E; Perrone, L; Adinolfi, L E; Miraglia del Giudice, E

2013-08-01

The patatin-like phospholipase domain-containing 3 gene (PNPLA3) and the apolipoprotein C3 gene (APOC3) have been studied in relation to liver steatosis and liver disease outcome. The aim of this study was to evaluate the influence of PNPLA3 p.I148M and APOC3 rs2854116 and rs2854117 polymorphisms on the clinical and histological presentation of chronic hepatitis C in an Italian population and their relationship with viral and anthropometric parameters. Patients with hepatitis C (n = 166) entered the study receiving a clinical, histological, virological and biochemical evaluation. APOC3 (rs2854116 and rs2854117) and PNPLA3 (p.I148M) variants were genotyped. PNPLA3 polymorphisms were associated with liver steatosis, which was significantly higher in patients with p.148I/M (P = 0.034) and p.148M/M (P = 0.004) variants than those homozygous for the PNPLA3 wild type. Excluding patients with HCV genotype 3, the association with liver steatosis and PNPLA3 variants was more marked (p.148I/I genotype vs p.148I/M, P = 0.02, and vs p.148M/M, P = 0.005). The APOC3 polymorphism was not associated with any of the evaluated parameters. Among the interacting factors, BMI and waist circumference correlated with liver steatosis (P = 0.008 and 0.004, respectively). Relationship between waist circumference and liver steatosis was analysed for the different PNPLA3 genotypes. Homozygous 148M patients showed a stronger correlation between waist circumference and steatosis than those carrying the other genotypes (P = 0.0047). In our hepatitis C-infected population, the PNPLA3 polymorphism influenced the development of liver steatosis, but not fibrosis progression. APOC3 polymorphisms had no effect on the development of steatosis and no influence on the PNPLA3 polymorphism. The amount of abdominal fat can increase the association of PNPLA3 p.I148M with liver steatosis. © 2013 John Wiley & Sons Ltd.

ArI/ArII laser induced fluorescence system for measurement of neutral and ion dynamics in a large scale helicon plasma

NASA Astrophysics Data System (ADS)

Kelly, R. F.; Meaney, K. D.; Gilmore, M.; Desjardins, T. R.; Zhang, Y.

2016-11-01

In order to investigate the role of both neutral and ion dynamics in large-scale helicon discharges, a laser induced fluorescence (LIF) system capable of measuring both ArI and ArII fluorescence using a single tunable laser is being developed. The system is based on a >250 mW solid state laser. For ArI measurements, the laser pumps the metastable (2P03/2)4s level to the (2P01/2)4p level using 696.7352 nm light, and fluorescence radiation from decay to the (2P01/2)4s level at 772.6333 nm is observed. For ArII, currently in development, the metastable (3P)3d 4F7/2 level will be pumped to the (3P)4p 4D07/2 level using 688.8511 nm, and decay fluorescence to the (3P)4s 4P5/2 level at 434.9285 nm measured. Here all wavelengths are in a vacuum.

Development and validation of P-MODTRAN7 and P-MCScene, 1D and 3D polarimetric radiative transfer models

NASA Astrophysics Data System (ADS)

Hawes, Frederick T.; Berk, Alexander; Richtsmeier, Steven C.

2016-05-01

A validated, polarimetric 3-dimensional simulation capability, P-MCScene, is being developed by generalizing Spectral Sciences' Monte Carlo-based synthetic scene simulation model, MCScene, to include calculation of all 4 Stokes components. P-MCScene polarimetric optical databases will be generated by a new version (MODTRAN7) of the government-standard MODTRAN radiative transfer algorithm. The conversion of MODTRAN6 to a polarimetric model is being accomplished by (1) introducing polarimetric data, by (2) vectorizing the MODTRAN radiation calculations and by (3) integrating the newly revised and validated vector discrete ordinate model VDISORT3. Early results, presented here, demonstrate a clear pathway to the long-term goal of fully validated polarimetric models.

Scaling NASA Applications to 1024 CPUs on Origin 3K

NASA Technical Reports Server (NTRS)

Taft, Jim

2002-01-01

The long and highly successful joint SGI-NASA research effort in ever larger SSI systems was to a large degree the result of the successful development of the MLP scalable parallel programming paradigm developed at ARC: 1) MLP scaling in real production codes justified ever larger systems at NAS; 2) MLP scaling on 256p Origin 2000 gave SGl impetus to productize 256p; 3) MLP scaling on 512 gave SGI courage to build 1024p O3K; and 4) History of MLP success resulted in IBM Star Cluster based MLP effort.

3D Pneumatic and 2D Dynamic Probes: Their Development and Subsequent Use in a Transonic Fan

DTIC Science & Technology

1992-12-01

PROBES: THEIR DEVELOPMENT AND SUBSEQUENT USE IN A TRANSONIC FAN by M. A. Cherrett J. D. Bryce H. P. Hodson* SUMMARY Three different 3D pneumatic...Development & Subsequent Use In A Transonic Fan. by NM A Cherrett & J D Bryce, H P Hodson, Aerodynamics & Propulsion Department, Whittle Laboratory...the dynamic DRA which has been reported by Cherrett 1. Bryce’ A schematic yawmeter ) blockage accounted for approximately 3.0% of the diagram of the

A Prostate Fossa Contouring Instructional Module: Implementation and Evaluation.

PubMed

Gunther, Jillian R; Liauw, Stanley L; Choi, Seungtaek; Mohamed, Abdallah S R; Thaker, Nikhil G; Fuller, Clifton D; Stepaniak, Christopher J; Das, Prajnan; Golden, Daniel W

2016-07-01

Radiation oncology trainees frequently learn to contour through clinical experience and lectures. A hands-on contouring module was developed to teach delineation of the postoperative prostate clinical target volume (CTV) and improve contouring accuracy. Medical students independently contoured a prostate fossa CTV before and after receiving educational materials and live instruction detailing the RTOG approach to contouring this CTV. Metrics for volume overlap and surface distance (Dice similarity coefficient, Hausdorff distance (HD), and mean distance) determined discordance between student and consensus contours. An evaluation assessed perception of session efficacy (1 = "not at all" to 5 = "extremely"; reported as median[interquartile range]). Non-parametric statistical tests were used. Twenty-four students at two institutions completed the module, and 21 completed the evaluation (88% response). The content was rated as "quite" important (4[3.5-5]). The module improved comfort contouring a prostate fossa (pre 1[1-2] vs. post 4[3-4], p<.01), ability to find references (pre 2[1-3] vs. post 4[3.5-4], p<0.01), knowledge of CT prostate/pelvis anatomy (pre 2[1.5-3] vs. post 3[3-4], p<.01), and ability to use contouring software tools (pre 2[2-3.5] vs. post 3[3-4], p=.01). After intervention, mean DSC increased (0.29 to 0.68, p<0.01) and HD and mean distance both decreased, respectively (42.8 to 30.0, p<.01; 11.5 to 1.9, p<.01). A hands-on module to teach CTV delineation to medical students was developed and implemented. Student and expert contours exhibited near "excellent agreement" (as defined in the literature) after intervention. Additional modules to teach target delineation to all educational levels can be developed using this model. Copyright © 2016 American College of Radiology. Published by Elsevier Inc. All rights reserved.

Influence of right ventricular function on the development of primary graft dysfunction after lung transplantation.

PubMed

Pérez-Terán, Purificación; Roca, Oriol; Rodríguez-Palomares, José; Sacanell, Judit; Leal, Sandra; Solé, Joan; Rochera, María I; Román, Antonio; Ruiz-Rodríguez, Juan C; Gea, Joaquim; Evangelista, Arturo; Masclans, Joan R

2015-11-01

Primary graft dysfunction (PGD) remains a significant cause of lung transplant postoperative morbidity and mortality. The underlying mechanisms of PGD development are not completely understood. This study analyzed the effect of right ventricular function (RVF) on PGD development. A retrospective analysis of a prospectively assessed cohort was performed at a single institution between July 2010 and June 2013. The primary outcome was development of PGD grade 3 (PGD3). Conventional echocardiographic parameters and speckle-tracking echocardiography, performed during the pre-transplant evaluation phase up to 1 year before surgery, were used to assess preoperative RVF. Included were 120 lung transplant recipients (LTr). Systolic pulmonary arterial pressure (48 ± 20 vs 41 ± 18 mm Hg; p = 0.048) and ischemia time (349 ± 73 vs 306 ± 92 minutes; p < 0.01) were higher in LTr who developed PGD3. Patients who developed PGD3 had better RVF estimated by basal free wall longitudinal strain (BLS; -24% ± 9% vs -20% ± 6%; p = 0.039) but had a longer intensive care unit length of stay and mechanical ventilation and higher 6-month mortality. BLS ≥ -21.5% was the cutoff that best identified patients developing PGD3 (area under the receiver operating characteristic curve, 0.70; 95% confidence interval, 0.54-0.85; p = 0.020). In the multivariate analysis, a BLS ≥ -21.5% was an independent risk factor for PGD3 development (odds ratio, 4.56; 95% confidence interval, 1.20-17.38; p = 0.026), even after adjusting for potential confounding. A better RVF, as measured by BLS, is a risk factor for severe PGD. Careful preoperative RVF assessment using speckle-tracking echocardiography may identify LTrs with the highest risk of developing PGD. Copyright © 2015 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

The PI3K Isoforms p110α and p110δ are Essential for Pre-B Cell Receptor Signaling and B Cell Development

PubMed Central

Ramadani, Faruk; Bolland, Daniel J.; Garcon, Fabien; Emery, Juliet L.; Vanhaesebroeck, Bart; Corcoran, Anne E.; Okkenhaug, Klaus

2013-01-01

B cell development is controlled by a series of checkpoints that ensure that the immunoglobulin (Ig)-encoding genes are assembled in frame to produce a functional B cell receptor (BCR) and antibodies. The BCR consists of Ig proteins in complex with the immunoreceptor tyrosine-based activation motif (ITAM)-containing Igα and Igβ chains. Whereas the activation of Src and Syk tyrosine kinases is essential for BCR signaling, the pathways that act downstream of these kinases are incompletely defined. Previous work has revealed a key role for the p110δ isoform of phosphoinositide 3-kinase (PI3K) in agonist-induced BCR signaling; however, early B cell development and mature B cell survival, which depend on tonic BCR signaling, are not substantially affected by a deficiency in p110δ. Here, we show that in the absence of p110δ, p110α, but not p110β, can compensate to promote early B cell development in the bone marrow and B cell survival in the spleen. In the absence of both p110α and p110δ activities, pre-BCR signaling fails to suppress the production of recombination-activating gene (Rag) protein and to promote developmental progression of B cell progenitors. By contrast, p110α does not contribute to agonist-induced BCR signaling. These studies indicate that either p110α or p110δ can mediate tonic signaling from the BCR, but that only p110δ can contribute to antigen-dependent activation of B cells. PMID:20699475

Development and Initial Evaluation of a Telephone-Delivered, Behavioral Activation and Problem-solving Treatment Program to Address Functional Goals of Breast Cancer Survivors

PubMed Central

Lyons, Kathleen D.; Hull, Jay G.; Kaufman, Peter A.; Li, Zhongze; Seville, Janette L.; Ahles, Tim A.; Kornblith, Alice B.; Hegel, Mark T.

2015-01-01

The purpose of this research was to develop and pilot test an intervention to optimize functional recovery for breast cancer survivors. Over two studies, 31 women enrolled in a goal-setting program via telephone. All eligible women enrolled (37% of those screened) and 66% completed all study activities. Completers were highly satisfied with the intervention, using it to address, on average, four different challenging activities. The longitudinal analysis showed a main effect of time for overall quality of life (F(5, 43.1) = 5.1, p = 0.001) and improvements in active coping (F (3, 31.7) = 4.9, p = 0.007), planning (F (3, 36.0) = 4.1, p = 0.01), reframing (F (3, 29.3) = 8.5, p < 0.001), and decreases in self-blame (F (3,31.6) = 4.3, p = 0.01). The intervention is feasible and warrants further study to determine its efficacy in fostering recovery and maximizing activity engagement after cancer treatment. PMID:25668509

Efficacy of tebuconazole embedded in biodegradable poly-3-hydroxybutyrate to inhibit the development of Fusarium moniliforme in soil microecosystems.

PubMed

Volova, Tatiana G; Prudnikova, Svetlana V; Zhila, Natalia O; Vinogradova, Olga N; Shumilova, Anna A; Nikolaeva, Elena D; Kiselev, Evgeniy G; Shishatskaya, Ekaterina I

2017-05-01

An important line of research is the development of a new generation of formulations with targeted and controlled release of the pesticide, using matrices made from biodegradable materials. In this study, slow-release formulations of the fungicide tebuconazole (TEB) have been prepared by embedding it into the matrix of poly-3-hydroxybutyrate (P3HB) in the form of films, microgranules and pellets. The average rates of P3HB degradation were determined by the geometry of the formulation, reaching, for 63 days, 0.095-0.116, 0.081-0.083 and 0.030-0.055 mg day -1 for films, microgranules and pellets respectively. The fungicidal activity of P3HB/TEB against the plant pathogen Fusarium moniliforme was compared with that of the commercial formulation Raxil Ultra. A pronounced fungicidal effect of the experimental P3HB/TEB formulations was observed in 2-4 weeks after application, and it was retained for 8 weeks, without affecting significantly the development of soil aboriginal microflora. TEB release can be regulated by the process employed to fabricate the formulation and the fungicide loading, and the TEB accumulates in the soil gradually, as the polymer is degraded. The experimental forms of TEB embedded in the slowly degraded P3HB can be used as a basis for developing slow-release fungicide formulations. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

Provisional in-silico biopharmaceutics classification (BCS) to guide oral drug product development

PubMed Central

Wolk, Omri; Agbaria, Riad; Dahan, Arik

2014-01-01

The main objective of this work was to investigate in-silico predictions of physicochemical properties, in order to guide oral drug development by provisional biopharmaceutics classification system (BCS). Four in-silico methods were used to estimate LogP: group contribution (CLogP) using two different software programs, atom contribution (ALogP), and element contribution (KLogP). The correlations (r2) of CLogP, ALogP and KLogP versus measured LogP data were 0.97, 0.82, and 0.71, respectively. The classification of drugs with reported intestinal permeability in humans was correct for 64.3%–72.4% of the 29 drugs on the dataset, and for 81.82%–90.91% of the 22 drugs that are passively absorbed using the different in-silico algorithms. Similar permeability classification was obtained with the various in-silico methods. The in-silico calculations, along with experimental melting points, were then incorporated into a thermodynamic equation for solubility estimations that largely matched the reference solubility values. It was revealed that the effect of melting point on the solubility is minor compared to the partition coefficient, and an average melting point (162.7°C) could replace the experimental values, with similar results. The in-silico methods classified 20.76% (±3.07%) as Class 1, 41.51% (±3.32%) as Class 2, 30.49% (±4.47%) as Class 3, and 6.27% (±4.39%) as Class 4. In conclusion, in-silico methods can be used for BCS classification of drugs in early development, from merely their molecular formula and without foreknowledge of their chemical structure, which will allow for the improved selection, engineering, and developability of candidates. These in-silico methods could enhance success rates, reduce costs, and accelerate oral drug products development. PMID:25284986

Prognostic significance of nuclear pSTAT3 in oral cancer.

PubMed

Macha, Muzafar A; Matta, Ajay; Kaur, Jatinder; Chauhan, S S; Thakar, Alok; Shukla, Nootan K; Gupta, Siddhartha Datta; Ralhan, Ranju

2011-04-01

Aberrant nuclear accumulation of proteins influences tumor development and may predict biologic aggressiveness and disease prognosis. This study determined the prognostic significance of pSTAT3 (phosphorylayed signal transducer and activator of transcription 3) in oral squamous cell carcinomas (OSCCs). Using immunohistochemistry, a significant increase in nuclear accumulation of pSTAT3 was observed in 49 of 90 leukoplakias (54.4%) and 63/94 OSCCs (67%) (p(trend) < .001). Increased pSTAT3 was associated with tumor stage (p = .01), nodal metastasis (p = .0018), and tobacco consumption (p = .004). Kaplan-Meier analysis demonstrated that OSCC with increased nuclear pSTAT3 showed significantly reduced disease-free survival (13 months), compared with the patients with no nuclear pSTAT3 expression (64 months, p = .019). Cox regression analysis revealed nuclear pSTAT3 as the most significant predictor of poor prognosis (p = .024, hazard ratio [HR] = 2.7). Increased nuclear accumulation of pSTAT3 occurs in early premalignant stages and is a marker for poor prognosis of OSCC. Copyright © 2010 Wiley Periodicals, Inc.

Physical Activity and the Risk of Primary Hyperparathyroidism.

PubMed

Vaidya, Anand; Curhan, Gary C; Paik, Julie M; Wang, Molin; Taylor, Eric N

2016-04-01

Primary hyperparathyroidism (P-HPTH) is relatively common and predominantly affects women. Prior studies have shown that physical activity (PA) can lower PTH levels. Our objective was to evaluate the hypothesis that lower PA is a risk factor for developing P-HPTH. This prospective cohort study included 69 621 female participants in the Nurses' Health Study I followed for 22 years. PA and other dietary and demographic exposures were quantified via detailed, and validated, biennial questionnaires. Incident P-HPTH was confirmed by medical record review after initial assessment by questionnaire. Adjusted Cox proportional hazards models were used to evaluate whether PA was an independent risk factor for developing P-HPTH. We also evaluated the risk of developing P-HPTH when combining low PA (<16 metabolic equivalent hours/week) with a previously identified independent risk factor for developing P-HPTH: low calcium intake (<800 mg/day). The relation between PA and PTH levels was evaluated in 625 participants. We confirmed 302 incident cases of P-HPTH during 1 474 993 person-years of follow-up. Participants in the highest quintile (Q) of PA had a 50% lower risk of developing P-HPTH: age-adjusted relative risks and 95% confidence intervals for incident P-HPTH by lowest to highest of PA were Q1 = 1.0 (reference); Q2 = 0.83 (0.60–1.15); Q3 = 0.84 (0.61–1.15); Q4 = 0.50 (0.34–0.74); Q5 = 0.50 (0.35–0.73); P for trend <.001. Extensive multivariable adjustments did not materially change these findings. The adjusted relative risk for developing P-HPTH among participants with the combination lower PA and lower calcium intake was 2.37-fold (1.60–3.51) higher than in participants with higher PA and higher calcium intake. PA was inversely correlated with serum PTH (ρ = −0.09, P = .03); the mean adjusted serum PTH in Q 2–5 of PA was lower than in Q 1 (36.3 vs 39.1 pg/mL, P = .02). Low physical activity may be a modifiable risk factor for developing P-HPTH in women.

Obtaining P3P privacy policies for composite services.

PubMed

Sun, Yi; Huang, Zhiqiu; Ke, Changbo

2014-01-01

With the development of web services technology, web services have changed from single to composite services. Privacy protection in composite services is becoming an important issue. P3P (platform for privacy preferences) is a privacy policy language which was designed for single web services. It enables service providers to express how they will deal with the privacy information of service consumers. In order to solve the problem that P3P cannot be applied to composite services directly, we propose a method to obtain P3P privacy policies for composite services. In this method, we present the definitions of Purpose, Recipient, and Retention elements as well as Optional and Required attributes for P3P policies of composite services. We also provide an instantiation to illustrate the feasibility of the method.

77 FR 6811 - Center for Scientific Review; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-09

...: Anti-pathogen drug development and resistance. Date: February 28, 2012. Time: 3 p.m. to 5 p.m. Agenda... Vaccine Development. Date: March 8-9, 2012. Time: 8 a.m. to 6 p.m. Agenda: To review and evaluate grant...

Development of Obesity and Related Diseases in African Refugees After Resettlement to United States.

PubMed

Rhodes, Corinne M; Chang, Yuchiao; Percac-Lima, Sanja

2016-12-01

Despite increases in obesity and related diseases in developing nations, initial refugee clinical visits do not address these issues. We explored the development of obesity and related diseases in a longitudinal prospective cohort of African refugees resettling in northeastern US. Using state Department of Health data, refugees were linked to a health system. Body mass index, diabetes, hypertension, and hyperlipidemia status were extracted from charts. US regional controls from NAMCS/NHAMCS data were matched by age, sex, race, and visit year. African refugee BMI increased after resettlement at 1 (1.7 ± 2.9, p < 0.0001) and 5 years (3.1 ± 3.7, p < 0.0001), a different trend than matched regional controls (p = 0.01). Refugees had increased rates of diabetes (1.0 vs. 10.8 %, p < 0.0001), hypertension (16.7 vs. 21.6 %, p < 0.0001) and hyperlipidemia (3.9 vs. 10.8 %, p < 0.0001) at 5 years not observed in regional controls. Our findings emphasize the need for interventions during resettlement to prevent development of obesity and related disease in this vulnerable population.

Single-Institution Experience With Component Separation for Ventral Hernia Repair: A Retrospective Review.

PubMed

Hill, Brian; Kambeyanda, Rohan; Fewell, Donna; Bryant, Stewart; Delaney, Kevin O; Herrera, Fernando A

2018-06-01

In this study, we reviewed our institution's experience using component separation for repair of ventral hernias. This was a retrospective review of all component separations for ventral hernia between July 2009 and December 2015. Recorded data included body mass index (BMI), preoperative albumin, smoking history, comorbidities, additional procedures, length of surgery, hospitalization, recurrence, and postoperative complications. One hundred ninety-six component separations were performed in the study period. The average patient age was 56 years, and 65.3% of patients were female. The average BMI was 32.6 kg/m; preoperative albumin was 3.59; 18.4% were current smokers; 28.1% were diabetic; and 14.3% had heart disease. Postoperative complications developed in 16.8% of patients. Recurrence developed in 8.7% of patients. Patients who developed a postoperative complication had a higher BMI (P = 0.025) and lower albumin (P = 0.047) compared with patients who did not develop complications. Current smokers were more likely to develop complications (P = 0.008). More than one third of patients had additional procedures at the time of the ventral hernia repair. The addition of a plastic surgery procedure was not associated with an increased risk of developing a complication (P = 0.25). Patients who developed complications had a significantly longer hospital course (P < 0.001) but no difference in total operative time (P = 0.975). Increased number of comorbidities did not statistically correlate with an increased complication rate (P = 0.65) or length of hospital stay (P = 0.43). We identified risk factors that increase the likelihood of postoperative complications and length of hospital stay. In addition, this study suggests that more comorbidities and additional procedures at the time of the hernia repair may not have as large of impact on complication risk as previously thought.

The correlation between lymphocyte/monocyte ratio and coronary collateral circulation in stable coronary artery disease patients.

PubMed

Kurtul, Alparslan; Duran, Mustafa

2017-01-01

Coronary collateral circulation (CCC) has an important impact on cardiovascular prognosis and well-developed CCC is associated with better clinical outcomes. We investigated whether lymphocyte/monocyte ratio (LMR) has an association with CCC in patients with stable coronary artery disease (SCAD). The study population consisted of 245 patients with SCAD. Patients were classified into a poor CCC group (Rentrop grades 0/1, n = 87), or good CCC group (Rentrop grades 2/3, n = 158). LMR values were significantly higher in patients with good CCC than in those with poor CCC (4.41 ± 1.58 vs 2.76 ± 1.10; p < 0.001). In receiver operating characteristic analysis, optimal cutoff of LMR for predicting well-developed CCC was 3.38. In multivariate analysis, LMR >3.38 (OR 4.637; p = 0.004), high sensitivity C-reactive protein (OR 0.810, p < 0.001), dyslipidemia (OR 2.485; p = 0.039), and presence of chronic total occlusion (OR 16.836; p < 0.001) were independent predictors of well-developed CCC. Increased LMR predicts well-developed CCC in SCAD patients.

Mycoplasma pneumoniae Protein P30 Is Required for Cytadherence and Associated with Proper Cell Development

PubMed Central

Romero-Arroyo, Cynthia E.; Jordan, Jarrat; Peacock, Susan J.; Willby, Melisa J.; Farmer, Mark A.; Krause, Duncan C.

1999-01-01

The attachment organelle of Mycoplasma pneumoniae is a polar, tapered cell extension containing an intracytoplasmic, electron-dense core. This terminal structure is the leading end in gliding motility, and its duplication is thought to precede cell division, raising the possibility that mutations affecting cytadherence also confer a defect in motility or cell development. Mycoplasma surface protein P30 is associated with the attachment organelle, and P30 mutants II-3 and II-7 do not cytadhere. In this study, the recombinant wild-type but not the mutant II-3 p30 allele restored cytadherence when transformed into P30 mutants by recombinant transposon delivery. The mutations associated with loss of P30 in mutant II-3 and reacquisition of P30 in cytadhering revertants thereof were identified by nucleotide sequencing of the p30 gene. Morphological abnormalities that included ovoid or multilobed cells having a poorly defined tip structure were associated with loss of P30. Digital image analysis confirmed quantitatively the morphological differences noted visually. Transformation of the P30 mutants with the wild-type p30 allele restored a normal morphology, as determined both visually and by digital image analysis, suggesting that P30 plays a role in mycoplasma cell development. Finally, the P30 mutants localized the adhesin protein P1 to the terminal organelle, indicating that P30 is not involved in P1 trafficking but may be required for its receptor-binding function. PMID:9973332

MicroRNA-140-3p inhibits proliferation, migration and invasion of lung cancer cells by targeting ATP6AP2.

PubMed

Kong, Xiao-Mei; Zhang, Ge-Hong; Huo, Yun-Kui; Zhao, Xiao-Hong; Cao, Da-Wei; Guo, Shu-Fang; Li, Ai-Min; Zhang, Xin-Ri

2015-01-01

MicroRNAs are small noncoding RNA molecules that regulate gene expression at the post-transcriptional level. Compelling evidence reveals that there is a causative link between microRNAs deregulation and lung cancer development and metastasis. The aim of present study was to explore the function of miR-140-3p in the development and metastasis of lung cancer cell. Using real-time PCR, we detected the miR-140-3p expression of lung cancer tissues and its pared non-lung cancer tissue. Then, we evaluated the role of miR-140-3p in cell proliferation, invasion and migration using MTT, colony formation assay, Transwell invasion and Transwell migration assay in lung cancer cell lines. As a result, miR-140-3p expression level was lower in lung cancer tissues compared to adjacent normal lung cancer tissue. After miR-140-3p was upregulated in A549 or H1299 cells, cell proliferation, invasion and migration was notably attenuated. Furthermore, we identified ATP6AP2, which is associated with adenosine triphosphatases (ATPases), was a directly target of miR-140-3p in lung cancer cells. In conclusion, our data suggest miR-140-3p/ATP6AP2 axis might act as a potential therapeutic biomarker for lung cancer.

MicroRNA-140-3p inhibits proliferation, migration and invasion of lung cancer cells by targeting ATP6AP2

PubMed Central

Kong, Xiao-Mei; Zhang, Ge-Hong; Huo, Yun-Kui; Zhao, Xiao-Hong; Cao, Da-Wei; Guo, Shu-Fang; Li, Ai-Min; Zhang, Xin-Ri

2015-01-01

MicroRNAs are small noncoding RNA molecules that regulate gene expression at the post-transcriptional level. Compelling evidence reveals that there is a causative link between microRNAs deregulation and lung cancer development and metastasis. The aim of present study was to explore the function of miR-140-3p in the development and metastasis of lung cancer cell. Using real-time PCR, we detected the miR-140-3p expression of lung cancer tissues and its pared non-lung cancer tissue. Then, we evaluated the role of miR-140-3p in cell proliferation, invasion and migration using MTT, colony formation assay, Transwell invasion and Transwell migration assay in lung cancer cell lines. As a result, miR-140-3p expression level was lower in lung cancer tissues compared to adjacent normal lung cancer tissue. After miR-140-3p was upregulated in A549 or H1299 cells, cell proliferation, invasion and migration was notably attenuated. Furthermore, we identified ATP6AP2, which is associated with adenosine triphosphatases (ATPases), was a directly target of miR-140-3p in lung cancer cells. In conclusion, our data suggest miR-140-3p/ATP6AP2 axis might act as a potential therapeutic biomarker for lung cancer. PMID:26722475

Expression of the invertebrate sea urchin P16 protein into mammalian MC3T3 osteoblasts transforms and reprograms them into "osteocyte-like" cells.

PubMed

Alvares, Keith; Ren, Yinshi; Feng, Jian Q; Veis, Arthur

2016-01-01

P16 is an acidic phosphoprotein important in both sea urchin embryonic spicule development and transient mineralization during embryogenesis, syncytium formation, and mineralization in mature urchin tooth. Anti-P16 has been used to localize P16 to the syncytial membranes and the calcite mineral. Specific amino acid sequence motifs in P16 are similar to sequences in DSPP, a protein common to all vertebrate teeth, and crucial for their mineralization. Here, we examine the effect of P16 on vertebrate fibroblastic NIH3T3 cells and osteoblastic MC3T3 cells. Transfection of NIH3T3 cells with P16 cDNA resulted in profound changes in the morphology of the cells. In culture, the transfected cells sent out long processes that contacted processes from neighboring cells forming networks or syncytia. There was a similar change in morphology in cultured osteoblastic MC3T3 cells. In addition, the MC3T3 developed numerous dendrites as found in osteocytes. Importantly, there was also a change in the expression of the osteoblast and osteocyte specific genes. MC3T3 cells transfected with P16 showed an 18-fold increase in expression of the osteocyte specific Dentin matrix protein (DMP1) gene, accompanied by decreased expression of osteoblast specific genes: Bone sialoprotein (BSP), osteocalcin (OCN), and β-catenin decreased by 70%, 64%, and 68 %, respectively. Thus, invertebrate urchin P16 with no previously known analog in vertebrates was able to induce changes in both cell morphology and gene expression, converting vertebrate-derived osteoblast-like precursor cells to an "osteocyte-like" phenotype, an important process in bone biology. The mechanisms involved are presently under study. © 2015 Wiley Periodicals, Inc.

Expression of the invertebrate sea urchin P16 protein into mammalian MC3T3 osteoblasts transforms and reprograms them into “osteocyte-like” cells

PubMed Central

Alvares, Keith; Ren, Yinshi; Feng, Jian Q.; Veis, Arthur

2015-01-01

P16 is an acidic phosphoprotein important in both sea urchin embryonic spicule development and transient mineralization during embryogenesis, and syncytium formation and mineralization in mature urchin tooth. Anti-P16 has been used to localize P16 to the syncytial membranes and the calcite mineral. Specific amino acid sequence motifs in P16 are similar to sequences in DSPP a protein common to all vertebrate teeth, and crucial for their mineralization. Here we examine the effect of P16 on vertebrate fibroblastic NIH3T3 cells and osteoblastic MC3T3 cells. Transfection of NIH3T3 cells with P16 cDNA resulted in profound changes in the morphology of the cells. In culture the transfected cells sent out long processes that contacted processes from neighboring cells forming networks or syncytia. There was a similar change in morphology in cultured osteoblastic MC3T3 cells. In addition, the MC3T3 developed numerous dendrites as found in osteocytes. Importantly, there was also a change in the expression of the osteoblast and osteocyte specific genes. MC3T3 cells transfected with P16 showed an 18 fold increase in expression of the osteocyte specific Dentin matrix protein (DMP1) gene, accompanied by decreased expression of osteoblast specific genes: Bone sialoprotein (BSP), osteocalcin (OCN) and β-catenin decreased by 70%, 64% and 68 %, respectively. Thus, invertebrate urchin P16 with no previously known analog in vertebrates was able to induce changes in both cell morphology and gene expression, converting vertebrate-derived osteoblast-like precursor cells to an “osteocyte-like” phenotype, an important process in bone biology. The mechanisms involved are presently under study. PMID:26581835

Proneurotrophin-3 promotes cell cycle withdrawal of developing cerebellar granule cell progenitors via the p75 neurotrophin receptor.

PubMed

Zanin, Juan Pablo; Abercrombie, Elizabeth; Friedman, Wilma J

2016-07-19

Cerebellar granule cell progenitors (GCP) proliferate extensively in the external granule layer (EGL) of the developing cerebellum prior to differentiating and migrating. Mechanisms that regulate the appropriate timing of cell cycle withdrawal of these neuronal progenitors during brain development are not well defined. The p75 neurotrophin receptor (p75(NTR)) is highly expressed in the proliferating GCPs, but is downregulated once the cells leave the cell cycle. This receptor has primarily been characterized as a death receptor for its ability to induce neuronal apoptosis following injury. Here we demonstrate a novel function for p75(NTR) in regulating proper cell cycle exit of neuronal progenitors in the developing rat and mouse EGL, which is stimulated by proNT3. In the absence of p75(NTR), GCPs continue to proliferate beyond their normal period, resulting in a larger cerebellum that persists into adulthood, with consequent motor deficits.

Development of Columnar Topography in the Excitatory Layer 4 to Layer 2/3 Projection in Rat Barrel Cortex

PubMed Central

Bender, Kevin J.; Rangel, Juliana; Feldman, Daniel E.

2011-01-01

The excitatory feedforward projection from layer (L) 4 to L2/3 in rat primary somatosensory (S1) cortex exhibits precise, columnar topography that is critical for columnar processing of whisker inputs. Here, we characterize the development of axonal topography in this projection using single-cell reconstructions in S1 slices. In the mature projection [postnatal day (P) 14 –26], axons of L4 cells extending into L2/3 were confined almost entirely to the home barrel column, consistent with previous results. At younger ages (P8 –11), however, axonal topography was significantly less columnar, with a large proportion of branches innervating neighboring barrel columns representing adjacent whisker rows. Mature topography developed from this initial state by targeted axonal growth within the home column and by growth of barrel columns themselves. Raising rats with all or a subset of whiskers plucked from P8 –9, manipulations that induce reorganization of functional whisker maps and synaptic depression at L4 to L2/3 synapses, did not alter normal anatomical development of L4 to L2/3 axons. Thus, development of this projection does not require normal sensory experience after P8, and deprivation-induced reorganization of whisker maps at this age is unlikely to involve physical remodeling of L4 to L2/3 axons. PMID:14507976

Selective amplification and sequencing of cyclic phosphate-containing RNAs by the cP-RNA-seq method

PubMed Central

Honda, Shozo; Morichika, Keisuke; Kirino, Yohei

2016-01-01

RNA digestions catalyzed by many ribonucleases generate RNA fragments containing a 2′,3′-cyclic phosphate (cP) at their 3′-termini. However, standard RNA-seq methods are unable to accurately capture cP-containing RNAs because the cP inhibits the adapter ligation reaction. We recently developed a method named “cP-RNA-seq” that is able to selectively amplify and sequence cP-containing RNAs. Here we describe the cP-RNA-seq protocol in which the 3′-termini of all RNAs, except those containing a cP, are cleaved through a periodate treatment after phosphatase treatment, hence subsequent adapter ligation and cDNA amplification steps are exclusively applied to cP-containing RNAs. cP-RNA-seq takes ~6 d, excluding the time required for sequencing and bioinformatics analyses, such downstream assays are not covered in detail in this protocol. Biochemical validation of the existence of cP in the identified RNAs takes ~3 d. Even though the cP-RNA-seq method was developed to identify angiogenin-generating 5′-tRNA halves as a proof of principle, the method should be applicable to global identification of cP-containing RNA repertoires in various transcriptomes. PMID:26866791

Accurate Quantitative Sensing of Intracellular pH based on Self-ratiometric Upconversion Luminescent Nanoprobe.

PubMed

Li, Cuixia; Zuo, Jing; Zhang, Li; Chang, Yulei; Zhang, Youlin; Tu, Langping; Liu, Xiaomin; Xue, Bin; Li, Qiqing; Zhao, Huiying; Zhang, Hong; Kong, Xianggui

2016-12-09

Accurate quantitation of intracellular pH (pH i ) is of great importance in revealing the cellular activities and early warning of diseases. A series of fluorescence-based nano-bioprobes composed of different nanoparticles or/and dye pairs have already been developed for pH i sensing. Till now, biological auto-fluorescence background upon UV-Vis excitation and severe photo-bleaching of dyes are the two main factors impeding the accurate quantitative detection of pH i . Herein, we have developed a self-ratiometric luminescence nanoprobe based on förster resonant energy transfer (FRET) for probing pH i , in which pH-sensitive fluorescein isothiocyanate (FITC) and upconversion nanoparticles (UCNPs) were served as energy acceptor and donor, respectively. Under 980 nm excitation, upconversion emission bands at 475 nm and 645 nm of NaYF 4 :Yb 3+ , Tm 3+ UCNPs were used as pH i response and self-ratiometric reference signal, respectively. This direct quantitative sensing approach has circumvented the traditional software-based subsequent processing of images which may lead to relatively large uncertainty of the results. Due to efficient FRET and fluorescence background free, a highly-sensitive and accurate sensing has been achieved, featured by 3.56 per unit change in pH i value 3.0-7.0 with deviation less than 0.43. This approach shall facilitate the researches in pH i related areas and development of the intracellular drug delivery systems.

Accurate Quantitative Sensing of Intracellular pH based on Self-ratiometric Upconversion Luminescent Nanoprobe

NASA Astrophysics Data System (ADS)

Li, Cuixia; Zuo, Jing; Zhang, Li; Chang, Yulei; Zhang, Youlin; Tu, Langping; Liu, Xiaomin; Xue, Bin; Li, Qiqing; Zhao, Huiying; Zhang, Hong; Kong, Xianggui

2016-12-01

Accurate quantitation of intracellular pH (pHi) is of great importance in revealing the cellular activities and early warning of diseases. A series of fluorescence-based nano-bioprobes composed of different nanoparticles or/and dye pairs have already been developed for pHi sensing. Till now, biological auto-fluorescence background upon UV-Vis excitation and severe photo-bleaching of dyes are the two main factors impeding the accurate quantitative detection of pHi. Herein, we have developed a self-ratiometric luminescence nanoprobe based on förster resonant energy transfer (FRET) for probing pHi, in which pH-sensitive fluorescein isothiocyanate (FITC) and upconversion nanoparticles (UCNPs) were served as energy acceptor and donor, respectively. Under 980 nm excitation, upconversion emission bands at 475 nm and 645 nm of NaYF4:Yb3+, Tm3+ UCNPs were used as pHi response and self-ratiometric reference signal, respectively. This direct quantitative sensing approach has circumvented the traditional software-based subsequent processing of images which may lead to relatively large uncertainty of the results. Due to efficient FRET and fluorescence background free, a highly-sensitive and accurate sensing has been achieved, featured by 3.56 per unit change in pHi value 3.0-7.0 with deviation less than 0.43. This approach shall facilitate the researches in pHi related areas and development of the intracellular drug delivery systems.

Validating Vegetable Production Unit (VPU) Plants, Protocols, Procedures and Requirements (P3R) using Currently Existing Flight Resources

NASA Technical Reports Server (NTRS)

Bingham, Gail; Bates, Scott; Bugbee, Bruce; Garland, Jay; Podolski, Igor; Levinskikh, Rita; Sychev, Vladimir; Gushin, Vadim

2009-01-01

Validating Vegetable Production Unit (VPU) Plants, Protocols, Procedures and Requirements (P3R) Using Currently Existing Flight Resources (Lada-VPU-P3R) is a study to advance the technology required for plant growth in microgravity and to research related food safety issues. Lada-VPU-P3R also investigates the non-nutritional value to the flight crew of developing plants on-orbit. The Lada-VPU-P3R uses the Lada hardware on the ISS and falls under a cooperative agreement between National Aeronautics and Space Administration (NASA) and the Russian Federal Space Association (FSA). Research Summary: Validating Vegetable Production Unit (VPU) Plants, Protocols, Procedures and Requirements (P3R) Using Currently Existing Flight Resources (Lada-VPU-P3R) will optimize hardware and

APLP2 Regulates Refractive Error and Myopia Development in Mice and Humans

PubMed Central

Verhoeven, Virginie J. M.; Hysi, Pirro G.; Wojciechowski, Robert; Singh, Pawan Kumar; Kumar, Ashok; Thinakaran, Gopal; Williams, Cathy

2015-01-01

Myopia is the most common vision disorder and the leading cause of visual impairment worldwide. However, gene variants identified to date explain less than 10% of the variance in refractive error, leaving the majority of heritability unexplained (“missing heritability”). Previously, we reported that expression of APLP2 was strongly associated with myopia in a primate model. Here, we found that low-frequency variants near the 5’-end of APLP2 were associated with refractive error in a prospective UK birth cohort (n = 3,819 children; top SNP rs188663068, p = 5.0 × 10−4) and a CREAM consortium panel (n = 45,756 adults; top SNP rs7127037, p = 6.6 × 10−3). These variants showed evidence of differential effect on childhood longitudinal refractive error trajectories depending on time spent reading (gene x time spent reading x age interaction, p = 4.0 × 10−3). Furthermore, Aplp2 knockout mice developed high degrees of hyperopia (+11.5 ± 2.2 D, p < 1.0 × 10−4) compared to both heterozygous (-0.8 ± 2.0 D, p < 1.0 × 10−4) and wild-type (+0.3 ± 2.2 D, p < 1.0 × 10−4) littermates and exhibited a dose-dependent reduction in susceptibility to environmentally induced myopia (F(2, 33) = 191.0, p < 1.0 × 10−4). This phenotype was associated with reduced contrast sensitivity (F(12, 120) = 3.6, p = 1.5 × 10−4) and changes in the electrophysiological properties of retinal amacrine cells, which expressed Aplp2. This work identifies APLP2 as one of the “missing” myopia genes, demonstrating the importance of a low-frequency gene variant in the development of human myopia. It also demonstrates an important role for APLP2 in refractive development in mice and humans, suggesting a high level of evolutionary conservation of the signaling pathways underlying refractive eye development. PMID:26313004

Single Chain Antibodies as Tools to Study transforming growth factor-β-Regulated SMAD Proteins in Proximity Ligation-Based Pharmacological Screens.

PubMed

Blokzijl, Andries; Zieba, Agata; Hust, Michael; Schirrmann, Thomas; Helmsing, Saskia; Grannas, Karin; Hertz, Ellen; Moren, Anita; Chen, Lei; Söderberg, Ola; Moustakas, Aristidis; Dübel, Stefan; Landegren, Ulf

2016-06-01

The cellular heterogeneity seen in tumors, with subpopulations of cells capable of resisting different treatments, renders single-treatment regimens generally ineffective. Accordingly, there is a great need to increase the repertoire of drug treatments from which combinations may be selected to efficiently target sets of pathological processes, while suppressing the emergence of resistance mutations. In this regard, members of the TGF-β signaling pathway may furnish new, valuable therapeutic targets. In the present work, we developed in situ proximity ligation assays (isPLA) to monitor the state of the TGF-β signaling pathway. Moreover, we extended the range of suitable affinity reagents for this analysis by developing a set of in-vitro-derived human antibody fragments (single chain fragment variable, scFv) that bind SMAD2 (Mothers against decapentaplegic 2), 3, 4, and 7 using phage display. These four proteins are all intracellular mediators of TGF-β signaling. We also developed an scFv specific for SMAD3 phosphorylated in the linker domain 3 (p179 SMAD3). This phosphorylation has been shown to inactivate the tumor suppressor function of SMAD3. The single chain affinity reagents developed in the study were fused tocrystallizable antibody fragments (Fc-portions) and expressed as dimeric IgG-like molecules having Fc domains (Yumabs), and we show that they represent valuable reagents for isPLA.Using these novel assays, we demonstrate that p179 SMAD3 forms a complex with SMAD4 at increased frequency during division and that pharmacological inhibition of cyclin-dependent kinase 4 (CDK4)(1) reduces the levels of p179SMAD3 in tumor cells. We further show that the p179SMAD3-SMAD4 complex is bound for degradation by the proteasome. Finally, we developed a chemical screening strategy for compounds that reduce the levels of p179SMAD3 in tumor cells with isPLA as a read-out, using the p179SMAD3 scFv SH544-IIC4. The screen identified two kinase inhibitors, known inhibitors of the insulin receptor, which decreased levels of p179SMAD3/SMAD4 complexes, thereby demonstrating the suitability of the recombinant affinity reagents applied in isPLA in screening for inhibitors of cell signaling. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Painful purinergic receptors.

PubMed

Donnelly-Roberts, Diana; McGaraughty, Steve; Shieh, Char-Chang; Honore, Prisca; Jarvis, Michael F

2008-02-01

Multiple P2 receptor-mediated mechanisms exist by which ATP can alter nociceptive sensitivity following tissue injury. Evidence from a variety of experimental strategies, including genetic disruption studies and the development of selective antagonists, has indicated that the activation of P2X receptor subtypes, including P2X(3), P2X(2/3), P2X(4) and P2X(7), and P2Y (e.g., P2Y(2)) receptors, can modulate pain. For example, administration of a selective P2X(3) antagonist, A-317491, has been shown to effectively block both hyperalgesia and allodynia in different animal models of pathological pain. Intrathecally delivered antisense oligonucleotides targeting P2X(4) receptors decrease tactile allodynia following nerve injury. Selective antagonists for the P2X(7) receptor also reduce sensitization in animal models of inflammatory and neuropathic pain, providing evidence that purinergic glial-neural interactions are important modulators of noxious sensory neurotransmission. Furthermore, activation of P2Y(2) receptors leads to sensitization of polymodal transient receptor potential-1 receptors. Thus, ATP acting at multiple purinergic receptors, either directly on neurons (e.g., P2X(3), P2X(2/3), and P2Y receptors) or indirectly through neural-glial cell interactions (P2X(4) and P2X(7) receptors), alters nociceptive sensitivity. The development of selective antagonists for some of these P2 receptors has greatly aided investigations into the nociceptive role of ATP. This perspective highlights some of the recent advances to identify selective P2 receptor ligands, which has enhanced the investigation of ATP-related modulation of pain sensitivity.

EDITORIAL: The 1st International Conference on Nanomanufacturing (NanoMan2008) The 1st International Conference on Nanomanufacturing (NanoMan2008)

NASA Astrophysics Data System (ADS)

Luo, Jack Jiqui; Fang, Fengzhou

2009-05-01

Nanomanufacturing is an emerging technology in the field of synthesis of nanomaterials, manufacture of nanodevices, nanosystems and the relevant characterization technologies, and will greatly impact our society and environment: speeding up scientific discovery, technological development, improving healthcare and living standards and slowing down the exhaustion of energy resources, to name but few. The 1st International Conference on Nanomanufacturing (NanoMan2008) was held on the 13-16 July 2008 in Singapore in conjunction with ThinFilm2008 (The 4th International Conference on Technological Advances of Thin Films & Surface Coatings). Approximately 140 delegates from all over the world have participated in the conference and presented their latest discoveries and technological developments. The main focuses of the conference were modern nanomanufacturing by laser machining, focused ion beam fabrication, nano/micro-molding/imprinting, nanomaterial synthesis and characterization, nanometrology and nano/microsystems fabrication and characterization. There was also great interest in applications of nanomanufacturing technologies in traditional areas such as free form machining, polishing and grinding with nano-scale precision and the smoothness of surfaces of objects, and applications in space exploration, military and medicine. This special issue is devoted to NanoMan2008 with a collection of 9 invited talks presented at the conference, covering all the topics of nanomanufacturing technology and development. These papers have been upgraded by the authors with new results and discoveries since the preparation of the conference manuscripts, hence presenting the latest developments. We would like to take this opportunity to thank all the delegates who attended the conference and made the conference successful, and to the authors who contributed papers to this special issue. Thanks also go to the conference committee for their efforts and devotion to the conference. We would like to express our sincere thanks to Dr Ian Forbes and the other members of editorial board of the Journal of Micromechanics and Microengineering of the Institute of Physics for their help and support in making this special section. The conference was a success. We found there is a great demand for continuation of the conference, and it has been agreed by the conference committee to hold the conference biannually from now on. The 2nd International Conference on Nanomanufacturing (NanoMan2010) is to be held in Tianjin, China in 2010. On behalf of the committee we would like to take this opportunity to welcome everybody to NanoMan2010.

A prospective microbiome-wide association study of food sensitization and food allergy in early childhood.

PubMed

Savage, Jessica H; Lee-Sarwar, Kathleen A; Sordillo, Joanne; Bunyavanich, Supinda; Zhou, Yanjiao; O'Connor, George; Sandel, Megan; Bacharier, Leonard B; Zeiger, Robert; Sodergren, Erica; Weinstock, George M; Gold, Diane R; Weiss, Scott T; Litonjua, Augusto A

2018-01-01

Alterations in the intestinal microbiome are prospectively associated with the development of asthma; less is known regarding the role of microbiome alterations in food allergy development. Intestinal microbiome samples were collected at age 3-6 months in children participating in the follow-up phase of an interventional trial of high-dose vitamin D given during pregnancy. At age 3, sensitization to foods (milk, egg, peanut, soy, wheat, walnut) was assessed. Food allergy was defined as caretaker report of healthcare provider-diagnosed allergy to the above foods prior to age 3 with evidence of IgE sensitization. Analysis was performed using Phyloseq and DESeq2; P-values were adjusted for multiple comparisons. Complete data were available for 225 children; there were 87 cases of food sensitization and 14 cases of food allergy. Microbial diversity measures did not differ between food sensitization and food allergy cases and controls. The genera Haemophilus (log 2 fold change -2.15, P=.003), Dialister (log 2 fold change -2.22, P=.009), Dorea (log 2 fold change -1.65, P=.02), and Clostridium (log 2 fold change -1.47, P=.002) were underrepresented among subjects with food sensitization. The genera Citrobacter (log 2 fold change -3.41, P=.03), Oscillospira (log 2 fold change -2.80, P=.03), Lactococcus (log 2 fold change -3.19, P=.05), and Dorea (log 2 fold change -3.00, P=.05) were underrepresented among subjects with food allergy. The temporal association between bacterial colonization and food sensitization and allergy suggests that the microbiome may have a causal role in the development of food allergy. Our findings have therapeutic implications for the prevention and treatment of food allergy. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

Parallel effects of the inversion In(3R)Payne on body size across the North American and Australian clines in Drosophila melanogaster.

PubMed

Kapun, M; Schmidt, C; Durmaz, E; Schmidt, P S; Flatt, T

2016-05-01

Chromosomal inversions are thought to play a major role in climatic adaptation. In D. melanogaster, the cosmopolitan inversion In(3R)Payne exhibits latitudinal clines on multiple continents. As many fitness traits show similar clines, it is tempting to hypothesize that In(3R)P underlies observed clinal patterns for some of these traits. In support of this idea, previous work in Australian populations has demonstrated that In(3R)P affects body size but not development time or cold resistance. However, similar data from other clines of this inversion are largely lacking; finding parallel effects of In(3R)P across multiple clines would considerably strengthen the case for clinal selection. Here, we have analysed the phenotypic effects of In(3R)P in populations originating from the endpoints of the latitudinal cline along the North American east coast. We measured development time, egg-to-adult survival, several size-related traits (femur and tibia length, wing area and shape), chill coma recovery, oxidative stress resistance and triglyceride content in homokaryon lines carrying In(3R)P or the standard arrangement. Our central finding is that the effects of In(3R)P along the North American cline match those observed in Australia: standard arrangement lines were larger than inverted lines, but the inversion did not influence development time or cold resistance. Similarly, In(3R)P did not affect egg-to-adult survival, oxidative stress resistance and lipid content. In(3R)P thus seems to specifically affect size traits in populations from both continents. This parallelism strongly suggests an adaptive pattern, whereby the inversion has captured alleles associated with growth regulation and clinal selection acts on size across both continents. © 2016 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2016 European Society For Evolutionary Biology.

IMPROVING PUBLIC AWARENESS OF EVERYDAY CHEMICAL EXPOSURES THROUGH A 3-D ONLINE COMPUTER-SIMULATED EDUCATIONAL GAME

EPA Science Inventory

The game we have developed is named Virtual P3 Game, where P3 is interpreted as “play, participation, and protection”, which implies that the game is designed and played in a virtual world and the goal of the game is to promote public participation in the environme...

Muenke Syndrome Mutation, FgfR3P244R, Causes TMJ Defects

PubMed Central

Yasuda, T.; Nah, H.D.; Laurita, J.; Kinumatsu, T.; Shibukawa, Y.; Shibutani, T.; Minugh-Purvis, N.; Pacifici, M.; Koyama, E.

2012-01-01

Muenke syndrome is characterized by various craniofacial deformities and is caused by an autosomal-dominant activating mutation in fibroblast growth factor receptor 3 (FGFR3P250R). Here, using mice carrying a corresponding mutation (FgfR3P244R), we determined whether the mutation affects temporomandibular joint (TMJ) development and growth. In situ hybridization showed that FgfR3 was expressed in condylar chondroprogenitors and maturing chondrocytes that also expressed the Indian hedgehog (Ihh) receptor and transcriptional target Patched 1(Ptch1). In FgfR3P244R mutants, the condyles displayed reduced levels of Ihh expression, H4C-positive proliferating chondroprogenitors, and collagen type II- and type X-expressing chondrocytes. Primary bone spongiosa formation was also disturbed and was accompanied by increased osteoclastic activity and reduced trabecular bone formation. Treatment of wild-type condylar explants with recombinant FGF2/FGF9 decreased Ptch1 and PTHrP expression in superficial/polymorphic layers and proliferation in chondroprogenitors. We also observed early degenerative changes of condylar articular cartilage, abnormal development of the articular eminence/glenoid fossa in the TMJ, and fusion of the articular disc. Analysis of our data indicates that the activating FgfR3P244R mutation disturbs TMJ developmental processes, likely by reducing hedgehog signaling and endochondral ossification. We suggest that a balance between FGF and hedgehog signaling pathways is critical for the integrity of TMJ development and for the maintenance of cellular organization. PMID:22622662

Rapid and Facile Formation of P3HT Organogels via Spin Coating: Tuning Functional Properties of Organic Electronic Thin Films

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

Lee, Cameron S.; Yin, Wen; Holt, Adam P.

Poly(3-hexyl thiophene) (P3HT) is widely regarded as the benchmark polymer when studying the physics of conjugated polymers used in organic electronic devices. P3HT can self-assemble via stacking of its backbone, leading to an assembly and growth of P3HT fi brils into 3D percolating organogels. These structures are capable of bridging the electrodes, providing multiple pathways for charge transport throughout the active layer. Here, a novel set of conditions is identified and discussed for P3HT organogel network formation via spin coating by monitoring the spin-coating process from various solvents. The development of organogel formation is detected by in situ static lightmore » scattering, which measures both the thinning rate by refl ectance and structural development in the fi lm via off-specular scattering during fi lm formation. Optical microscopy and thermal annealing experiments provide ex situ confi rmation of organogel fabrication. The role of solution characteristics, including solvent boiling point, P3HT solubility, and initial P3HT solution concentration on organogel formation, is examined to correlate these parameters to the rate of film formation, organogel-onset concentration, and overall network size. The correlation of film properties to the fabrication parameters is also analyzed within the context of the hole mobility and density-of-states measured by impedance spectroscopy.« less

Optimizing Available Phosphorus in Calcareous Soils Fertilized with Diammonium Phosphate and Phosphoric Acid Using Freundlich Adsorption Isotherm

PubMed Central

Akhtar, Muhammad

2013-01-01

In calcareous soils, phosphorus (P) retention and immobilization take place due to precipitation and adsorption. Since soil pH is considered a major soil variable affecting the P sorption, an acidic P fertilizer could result in low P adsorption compared to alkaline one. Therefore, P adsorption from DAP and phosphoric acid (PA) required to produce desired soil solution P concentration was estimated using Freundlich sorption isotherms. Two soils from Faisalabad and T. T. Singh districts were spiked with 0, 10, and 20 % CaCO3 for 15 days. Freundlich adsorption isotherms (P = aC b/a) were constructed, and theoretical doses of PA and DAP to develop a desired soil solution P level (i.e., 0.20 mg L−1) were calculated. It was observed that P adsorption in soil increased with CaCO3. Moreover, at all the levels of CaCO3, P adsorption from PA was lower compared to that from DAP in both the soils. Consequently, lesser quantity of PA was required to produce desired solution P, 0.2 mg L−1, compared to DAP. However, extrapolating the developed relationship between soil CaCO3 contents and quantity of fertilizer to other similar textured soils needs confirmation. PMID:24307878

The development of gastric cancer in a patient with polycythemia Vera, 3P deletion, and JAK2 V617F mutation.

PubMed

Ayvaz, Ozlem; Yavasoglu, Irfan; Kadikoylu, Gurhan; Meydan, Nezih; Barutca, Sabri; Bolaman, Zahit

2010-12-01

3p deletion which is frequently associated with solitary tumors and hematological malignancies is a chromosomal abnormality. Recently, Janus kinase-2 (JAK2) V617F mutation has an important role in the diagnosis of myeloproliferative disorders, especially in polycythemia vera (PV). We reported the development of gastric cancer in a 75-year-old patient with PV, 3p 12-14 deletion and JAK2 V617F mutation. PV was diagnosed according to the classification of World Health Organization. JAK2 V617F mutation with polymerase chain reaction and 3p12-14 deletion with cytogenetic examination of the bone marrow were detected. We investigated solitary tumors in the patient using computed tomographies of thorax, neck, ear, nose, and throat. However, they were normal. After 2 years, gastric cancer appeared in the patient. In conclusion, cytogenetic examination may be important in both the development and the diagnosis of hematological malignancies and solitary tumors. So the patients should be followed closely.

Nutrition, hygiene, and stimulation education to improve growth, cognitive, language, and motor development among infants in Uganda: A cluster-randomized trial.

PubMed

Muhoozi, Grace K M; Atukunda, Prudence; Diep, Lien M; Mwadime, Robert; Kaaya, Archileo N; Skaare, Anne B; Willumsen, Tiril; Westerberg, Ane C; Iversen, Per O

2018-04-01

Stunting is associated with impaired cognitive and motor function. The effect of an education intervention including nutrition, stimulation, sanitation, and hygiene on child growth and cognitive/language/motor development, delivered to impoverished mothers in Uganda, was assessed. In a community-based, open cluster-randomized trial, 511 mother/children dyads aged 6-8 months were enrolled to an intervention (n = 263) or control (n = 248) group. The primary outcome was change in length-for-age z-score at age 20-24 months. Secondary outcomes included anthropometry and scores on the 2 developmental scales: Bayley Scales of Infant and Toddler Development-III and the Ages and Stages Questionnaire. There was no evidence of a difference in mean length-for-age z-score at 20-24 months between the 2 study groups: 0.10, 95% CI [-0.17, 0.36], p = .49. The intervention group had higher mean composite development scores than the controls on Bayley Scales of Infant and Toddler Development-III, the mean difference being 15.6, 95% CI [10.9, 20.2], p = .0001; 9.9, 95% CI [6.4, 13.2], p = .0001; and 14.6, 95% CI [10.9, 18.2], p = .0001, for cognitive, language, and motor composite scores, respectively. The mean difference in scores from the Ages and Stages Questionnaire were 7.0, 95% CI [2.9, 11.3], p = .001; 5.9, 95% CI [1.2, 10.3], p = .01; 4.2, 95% CI [1.7, 6.7], p = .001; 8.9, 95% CI [5.3, 12.3], p = .0001; and 4.4, 95% CI [0.0, 8.8], p = .05, for communication, gross motor, fine motor, problem solving, and personal-social development, respectively. The intervention education delivered to mothers promoted early development domains in cognitive, language, and motor development but not linear growth of small children in impoverished rural communities in Uganda. Our study showed that child development may be improved with a relatively low cost intervention strategy. This trial was registered at ClinicalTrials.gov as NCT02098031. © 2017 John Wiley & Sons Ltd.

Analysis of the relationship between the decrease in pH and accumulation of 3-phosphoglyceric acid in developing forespores of Bacillus species.

PubMed

Magill, N G; Cowan, A E; Leyva-Vazquez, M A; Brown, M; Koppel, D E; Setlow, P

1996-04-01

Analysis of the pH decrease and 3-phosphoglyceric acid (3PGA) accumulation in the forespore compartment of sporulating cells of Bacillus subtilis showed that the pH decrease of 1 to 1.2 units at approximately 4 h of sporulation preceded 3PGA accumulation, as observed previously in B. megaterium. These data, as well as analysis of the forespore pH decrease in asporogenous mutants of B. subtilis, indicated that sigma G-dependent forespore transcription, but not sigma K-dependent mother cell transcription, is required for the forespore pH decrease. Further analysis of these asporogenous mutants showed an excellent correlation between the forespore pH decrease and the forespore's accumulation of 3PGA. These latter results are consistent with our previous suggestion that the decrease in forespore pH results in greatly decreased activity of phosphoglycerate mutase in the forespore, which in turn leads to 3PGA accumulation. In further support of this suggestion, we found that (i) elevating the pH of developing forespores of B. megaterium resulted in rapid utilization of the forespore's 3PGA depot and (ii) increasing forespore levels of PGM approximately 10-fold in B. subtilis resulted in a large decrease in the spore's depot of 3PGA. The B. subtilis strain with a high phosphoglycerate mutase level sporulated, and the spores germinated and went through outgrowth normally, indicating that forespore accumulation of a large 3PGA depot is not essential for these processes.

Obtaining P3P Privacy Policies for Composite Services

PubMed Central

Sun, Yi; Huang, Zhiqiu; Ke, Changbo

2014-01-01

With the development of web services technology, web services have changed from single to composite services. Privacy protection in composite services is becoming an important issue. P3P (platform for privacy preferences) is a privacy policy language which was designed for single web services. It enables service providers to express how they will deal with the privacy information of service consumers. In order to solve the problem that P3P cannot be applied to composite services directly, we propose a method to obtain P3P privacy policies for composite services. In this method, we present the definitions of Purpose, Recipient, and Retention elements as well as Optional and Required attributes for P3P policies of composite services. We also provide an instantiation to illustrate the feasibility of the method. PMID:25126609

ULTOR(Registered TradeMark) Passive Pose and Position Engine For Spacecraft Relative Navigation

NASA Technical Reports Server (NTRS)

Hannah, S. Joel

2008-01-01

The ULTOR(Registered TradeMark) Passive Pose and Position Engine (P3E) technology, developed by Advanced Optical Systems, Inc (AOS), uses real-time image correlation to provide relative position and pose data for spacecraft guidance, navigation, and control. Potential data sources include a wide variety of sensors, including visible and infrared cameras. ULTOR(Registered TradeMark) P3E has been demonstrated on a number of host processing platforms. NASA is integrating ULTOR(Registerd TradeMark) P3E into its Relative Navigation System (RNS), which is being developed for the upcoming Hubble Space Telescope (HST) Servicing Mission 4 (SM4). During SM4 ULTOR(Registered TradeMark) P3E will perform realtime pose and position measurements during both the approach and departure phases of the mission. This paper describes the RNS implementation of ULTOR(Registered TradeMark) P3E, and presents results from NASA's hardware-in-the-loop simulation testing against the HST mockup.

Comparison of the ontogeny of the vesicular glutamate transporter 3 (VGLUT3) with VGLUT1 and VGLUT2 in the rat retina.

PubMed

Stella, Salvatore L; Li, Stefanie; Sabatini, Andrea; Vila, Alejandro; Brecha, Nicholas C

2008-06-18

Glutamate is the major excitatory neurotransmitter in the retina, and most glutamatergic neurons express one of the three known vesicular glutamate transporters (VGLUT1, 2, or 3). However, the expression profiles of these transporters vary greatly in the retina. VGLUT1 is expressed by photoreceptor and bipolar cell terminals, and VGLUT2 appears to be predominately expressed by ganglion cells, and perhaps Müller cells, cone photoreceptor terminals, and horizontal cells in some species. The discovery of a third vesicular glutamate transporter, VGLUT3, has brought about speculation concerning its role and function based on its expression in amacrine cells. To address this we studied the postnatal development of VGLUT3 from day 0 through adult in the rat retina, and compared this with the expression patterns of VGLUT1 and VGLUT2. VGLUT3 expression was restricted to a population of amacrine cells. Expression of VGLUT3 was first observed at postnatal day 10 (P10) in the soma and some processes, which extensively arborized in both the ON and OFF sublamina of the IPL by P15. In contrast, VGLUT1 and VGLUT2 expression appeared earlier than VGLUT3; with VGLUT1 initially detected at P5 in photoreceptor terminals and P6 in bipolar terminals, and VGLUT2 immunoreactivity initially detected at P0 in ganglion cell bodies, and remained prominent throughout all stages of development. Interestingly, VGLUT3 has extensive somatic expression throughout development, which could be involved in non-synaptic modulation by glutamate in developing retina, and could influence trophic and extra-synaptic neuronal signaling by glutamate in the inner retina.

Role of group II metabotropic glutamate receptors 2/3 and group I metabotropic glutamate receptor 5 in developing rat medial vestibular nuclei.

PubMed

Grassi, Silvarosa; Frondaroli, Adele; Pettorossi, Vito Enrico

2005-08-22

In brainstem slices from developing rats, metabotropic glutamate receptors mGluR2/3 and mGluR5 play different inhibitory roles in synaptic transmission and plasticity of the medial vestibular nuclei. The mGluR2/3 block (LY341495) reduces the occurrence of long-term depression after vestibular afferent high frequency stimulation at P8-P10, and increases that of long-term potentiation, while the mGluR5 block prevents high frequency stimulation long-term depression. Later on, the receptor block does not influence high frequency stimulation effects. In addition, while mGluR2/3 agonist (APDC) always provokes a transient reduction of synaptic responses, that of mGluR5 (CHPG) induces long-term depression per se at P8-P10. These results show a key role of mGluR5 in inducing high frequency stimulation long-term depression in developing medial vestibular nuclei, while mGluR2/3 modulate synaptic transmission, probably through presynaptic control of glutamate release.

Origin of the Outbreak in France of Pseudomonas syringae pv. actinidiae Biovar 3, the Causal Agent of Bacterial Canker of Kiwifruit, Revealed by a Multilocus Variable-Number Tandem-Repeat Analysis

PubMed Central

Cunty, A.; Cesbron, S.; Poliakoff, F.; Jacques, M.-A.

2015-01-01

The first outbreaks of bacterial canker of kiwifruit caused by Pseudomonas syringae pv. actinidiae biovar 3 were detected in France in 2010. P. syringae pv. actinidiae causes leaf spots, dieback, and canker that sometimes lead to the death of the vine. P. syringae pv. actinidifoliorum, which is pathogenic on kiwi as well, causes only leaf spots. In order to conduct an epidemiological study to track the spread of the epidemics of these two pathogens in France, we developed a multilocus variable-number tandem-repeat (VNTR) analysis (MLVA). MLVA was conducted on 340 strains of P. syringae pv. actinidiae biovar 3 isolated in Chile, China, France, Italy, and New Zealand and on 39 strains of P. syringae pv. actinidifoliorum isolated in Australia, France, and New Zealand. Eleven polymorphic VNTR loci were identified in the genomes of P. syringae pv. actinidiae biovar 3 ICMP 18744 and of P. syringae pv. actinidifoliorum ICMP 18807. MLVA enabled the structuring of P. syringae pv. actinidiae biovar 3 and P. syringae pv. actinidifoliorum strains in 55 and 16 haplotypes, respectively. MLVA and discriminant analysis of principal components revealed that strains isolated in Chile, China, and New Zealand are genetically distinct from P. syringae pv. actinidiae strains isolated in France and in Italy, which appear to be closely related at the genetic level. In contrast, no structuring was observed for P. syringae pv. actinidifoliorum. We developed an MLVA scheme to explore the diversity within P. syringae pv. actinidiae biovar 3 and to trace the dispersal routes of epidemic P. syringae pv. actinidiae biovar 3 in Europe. We suggest using this MLVA scheme to trace the dispersal routes of P. syringae pv. actinidiae at a global level. PMID:26209667

Anticancer activity of the protein kinase C modulator HMI-1a3 in 2D and 3D cell culture models of androgen-responsive and androgen-unresponsive prostate cancer.

PubMed

Jäntti, Maria H; Talman, Virpi; Räsänen, Kati; Tarvainen, Ilari; Koistinen, Hannu; Tuominen, Raimo K

2018-05-01

Prostate cancer is one of the most common cancers in men. Although it has a relatively high 5-year survival rate, development of resistance to standard androgen-deprivation therapy is a significant clinical problem. Therefore, novel therapeutic strategies are urgently needed. The protein kinase C (PKC) family is a putative prostate cancer drug target, but so far no PKC-targeting drugs are available for clinical use. By contrast to the standard approach of developing PKC inhibitors, we have developed isophthalate derivatives as PKC agonists. In this study, we have characterized the effects of the most potent isophthalate, 5-(hydroxymethyl)isophthalate 1a3 (HMI-1a3), on three prostate cancer cell lines (LNCaP, DU145, and PC3) using both 2D and 3D cell culture models. In 2D cell culture, HMI-1a3 reduced cell viability or proliferation in all cell lines as determined by the metabolic activity of the cells (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assay) and thymidine incorporation. However, the mechanism of action in LNCaP cells was different to that in DU145 or PC3 cells. In LNCaP cells, HMI-1a3 induced a PKC-dependent activation of caspase 3/7, indicating an apoptotic response, whereas in DU145 and PC3 cells, it induced senescence, which was independent of PKC. This was observed as typical senescent morphology, increased β-galactosidase activity, and upregulation of the senescence marker p21 and downregulation of E2F transcription factor 1. Using a multicellular spheroid model, we further showed that HMI-1a3 affects the growth of LNCaP and DU145 cells in a 3D culture, emphasizing its potential as a lead compound for cancer drug development.

Immunolocalization of NR1, NR2A, and PSD-95 in rat hippocampal subregions during postnatal development.

PubMed

Ling, Wei; Chang, Lirong; Song, Yizhi; Lu, Tao; Jiang, Yuhua; Li, Youxiang; Wu, Yan

2012-05-01

Although the expression of NMDARs and synaptic-associated proteins has been widely studied, the temporospatial distribution of NMDAR subunits and synaptic proteins in different hippocampal subregions during postnatal development still lacks detailed information, and the relationship between NR1 or NR2 subunits and PSD-95 family proteins is controversial. In this study, we used immunofluorescent staining to assess NR1 or NR2A and PSD-95 expressions and the relationship between them in CA1, CA3, and DG of rat hippocampus on postnatal (P) days: P0, P4, P7, P10, P14, P21, P28, P56. The results showed that from P0 to P56, NR1, NR2A, and PSD-95 expressions increased gradually, and the time points of their expression peak differed in CA1, CA3, and DG during postnatal development. Interestingly, although the expression of PSD-95 was positively correlated to both NR1 and NR2A, the NR1 and PSD-95 coexpressed puncta were greatest in CA3, while NR2A and PSD-95 coexpressed puncta were greatest in CA1, compared to other subregions. Surprisingly, at P21, among different strata of CA1, the area of highest expression of NR2A was dramatically changed from stratum pyramidale to stratum polymorphum and stratum moleculare, and returned to stratum pyramidale gradually on the later observed days again, indicating that P21 may be one critical timepoint during postnatal development in CA1. The specific temporospatial distribution pattern of NR1, NR2A, and PSD-95 might be related to the different physiological functions during postnatal development. Discovering the alteration of the relationship between PSD-95 and NMDAR subunits expression may be helpful for understanding mechanisms and therapy of neurodegenerative diseases. Copyright © 2011 Elsevier GmbH. All rights reserved.

Effects of P3HT concentration on the electrical properties of the Au/PEDOT:PSS/P3HT/n-GaN hybrid junction structure

NASA Astrophysics Data System (ADS)

Noh, Ji-yeon; Lee, Ha Young; Lim, Kyung-won; Ahn, Hyung Soo; Yi, Sam Nyung; Jeon, Hunsoo; Shin, Min Jeong; Yu, Young Moon; Ha, Dong Han

2017-09-01

An inorganic-organic hybrid junction has been fabricated by spin coating the p-type poly(3- hexylthiophene-2,5-diyl)(P3HT) and poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT: PSS) on an n-type GaN layer. The GaN layer was formed on Al2O3 by metal organic chemical vapor deposition(MOCVD) method. To investigate the effects of P3HT concentration on the electrical properties, we changed P3HT solution concentration and speed of spin coater. The currentvoltage (I-V ) characteristic of Au/PEDOT:PSS/P3HT/n-GaN shows rectifying behavior. The I-V characteristic was examined in the frame work of the thermionic emission model. The most proper rectifying behavior was obtained for 0.6 wt% and thickness below 65 nm of P3HT used diode. We expect that such hybrid structures, suitably developed, might be enable the fabrication of highquality electronic and optoelectronic devices.

Risk Factor Burden, Heart Failure, and Survival in Women of Different Ethnic Groups: Insights From the Women's Health Initiative.

PubMed

Breathett, Khadijah; Leng, Iris; Foraker, Randi E; Abraham, William T; Coker, Laura; Whitfield, Keith E; Shumaker, Sally; Manson, JoAnn E; Eaton, Charles B; Howard, Barbara V; Ijioma, Nkechinyere; Cené, Crystal W; Martin, Lisa W; Johnson, Karen C; Klein, Liviu

2018-05-01

The higher risk of heart failure (HF) in African-American and Hispanic women compared with white women is related to the higher burden of risk factors (RFs) in minorities. However, it is unclear if there are differences in the association between the number of RFs for HF and the risk of development of HF and death within racial/ethnic groups. In the WHI (Women's Health Initiative; 1993-2010), African-American (n=11 996), white (n=18 479), and Hispanic (n=5096) women with 1, 2, or 3+ baseline RFs were compared with women with 0 RF within their respective racial/ethnic groups to assess risk of developing HF or all-cause mortality before and after HF, using survival analyses. After adjusting for age, socioeconomic status, and hormone therapy, the subdistribution hazard ratio (95% confidence interval) of developing HF increased as number of RFs increased ( P <0.0001, interaction of race/ethnicity and RF number P =0.18)-African-Americans 1 RF: 1.80 (1.01-3.20), 2 RFs: 3.19 (1.84-5.54), 3+ RFs: 7.31 (4.26-12.56); Whites 1 RF: 1.27 (1.04-1.54), 2 RFs: 1.95 (1.60-2.36), 3+ RFs: 4.07 (3.36-4.93); Hispanics 1 RF: 1.72 (0.68-4.34), 2 RFs: 3.87 (1.60-9.37), 3+ RFs: 8.80 (3.62-21.42). Risk of death before developing HF increased with subsequent RFs ( P <0.0001) but differed by racial/ethnic group (interaction P =0.001). The number of RFs was not associated with the risk of death after developing HF in any group ( P =0.25; interaction P =0.48). Among diverse racial/ethnic groups, an increase in the number of baseline RFs was associated with higher risk of HF and death before HF but was not associated with death after HF. Early RF prevention may reduce the burden of HF across multiple racial/ethnic groups. © 2018 American Heart Association, Inc.

Nanotechnology: MEMS and NEMS and their applications to smart systems and devices

NASA Astrophysics Data System (ADS)

Varadan, Vijay K.

2003-10-01

The microelectronics industry has seen explosive growth during the last thirty years. Extremely large markets for logic and memory devices have driven the development of new materials, and technologies for the fabrication of even more complex devices with features sizes now down at the sub micron and nanometer level. Recent interest has arisen in employing these materials, tools and technologies for the fabrication of miniature sensors and actuators and their integration with electronic circuits to produce smart devices and systems. This effort offers the promise of: (1) increasing the performance and manufacturability of both sensors and actuators by exploiting new batch fabrication processes developed including micro stereo lithographic and micro molding techniques; (2) developing novel classes of materials and mechanical structures not possible previously, such as diamond like carbon, silicon carbide and carbon nanotubes, micro-turbines and micro-engines; (3) development of technologies for the system level and wafer level integration of micro components at the nanometer precision, such as self-assembly techniques and robotic manipulation; (4) development of control and communication systems for MEMS devices, such as optical and RF wireless, and power delivery systems, etc. A novel composite structure can be tailored by functionalizing carbon nano tubes and chemically bonding them with the polymer matrix e.g. block or graft copolymer, or even cross-linked copolymer, to impart exceptional structural, electronic and surface properties. Bio- and Mechanical-MEMS devices derived from this hybrid composite provide a new avenue for future smart systems. The integration of NEMS (NanoElectroMechanical Systems), MEMS, IDTs (Interdigital Transducers) and required microelectronics and conformal antenna in the multifunctional smart materials and composites results in a smart system suitable for sending and control of a variety functions in automobile, aerospace, marine and civil strutures and food and medical industries. This unique combination of technologies also results in novel conformal sensors that can be remotely sensed by an antenna system with the advantage of no power requirements at the sensor site. This paper provides a brief review of MEMS and NEMS based smart systems for various applications mentioned above. Carbon Nano Tubes (CNT) with their unique structure, have already proven to be valuable in their application as tips for scanning probe microscopy, field emission devices, nanoelectronics, H2-storage, electromagnetic absorbers, ESD, EMI films and coatings and structural composites. For many of these applications, highly purified and functionalized CNT which are compatible with many host polymers are needed. A novel microwave CVD processing technique to meet these requirements has been developed at Penn State Center for the Engineering of Electronic and Acoustic Materials and Devices (CEEAMD). This method enables the production of highly purified carbon nano tubes with variable size (from 5 - 40 nm) at low cost (per gram) and high yield. Whereas, carbon nano tubes synthesized using the laser ablation or arc discharge evaporation method always include impurity due to catalyst or catalyst support. The Penn State research is based on the use of zeolites over other metal/metal oxides in the microwave field for a high production and uniformity of the product. An extended coventional purification method has been employed to purify our products in order to remove left over impurity. A novel composite structure can be tailored by functionalizing carbon nano tubes and chemically bonding them with the polymer matrix e.g. block or graft copolymer, or even cross-linked copolymer, to impart exceptional structural, electronic and surface properties. Bio- and Mechanical-MEMS devices derived from this hybrid composites will be presented.

MEMS- and NEMS-based smart devices and systems

NASA Astrophysics Data System (ADS)

Varadan, Vijay K.

2001-11-01

The microelectronics industry has seen explosive growth during the last thirty years. Extremely large markets for logic and memory devices have driven the development of new materials, and technologies for the fabrication of even more complex devices with features sized now don at the sub micron and nanometer level. Recent interest has arisen in employing these materials, tools and technologies for the fabrication of miniature sensors and actuators and their integration with electronic circuits to produce smart devices and systems. This effort offers the promise of: 1) increasing the performance and manufacturability of both sensors and actuators by exploiting new batch fabrication processes developed including micro stereo lithographic an micro molding techniques; 2) developing novel classes of materials and mechanical structures not possible previously, such as diamond like carbon, silicon carbide and carbon nanotubes, micro-turbines and micro-engines; 3) development of technologies for the system level and wafer level integration of micro components at the nanometer precision, such as self-assembly techniques and robotic manipulation; 4) development of control and communication systems for MEMS devices, such as optical and RF wireless, and power delivery systems, etc. A novel composite structure can be tailored by functionalizing carbon nano tubes and chemically bonding them with the polymer matrix e.g. block or graft copolymer, or even cross-linked copolymer, to impart exceptional structural, electronic and surface properties. Bio- and Mechanical-MEMS devices derived from this hybrid composite provide a new avenue for future smart systems. The integration of NEMS (NanoElectroMechanical Systems), MEMS, IDTs (Interdigital Transducers) and required microelectronics and conformal antenna in the multifunctional smart materials and composites results in a smart system suitable for sensing and control of a variety functions in automobile, aerospace, marine and civil structures and food and medical industries. This unique combination of technologies also results in novel conformal sensors that can be remotely sensed by an antenna system with the advantage of no power requirements at the sensor site. This paper provides a brief review of MEMS and NEMS based smart systems for various applications mentioned above. Carbon Nano Tubes (CNT) with their unique structure, have already proven to be valuable in their application as tips for scanning probe microscopy, field emission devices, nanoelectronics, H2-storage, electromagnetic absorbers, ESD, EMI films and coatings and structural composites. For many of these applications, highly purified and functionalized CNT which are compatible with many host polymers are needed. A novel microwave CVD processing technique to meet these requirements has been developed at Penn State Center for the engineering of Electronic and Acoustic Materials and Devices (CEEAMD). This method enables the production of highly purified carbon nano tubes with variable size (from 5-40 nm) at low cost (per gram) and high yield. Whereas, carbon nano tubes synthesized using the laser ablation or arc discharge evaporation method always include impurity due to catalyst or catalyst support. The Penn State research is based on the use of zeolites over other metal/metal oxides in the microwave field for a high production and uniformity of the product. An extended conventional purification method has been employed to purify our products in order to remove left over impurity. A novel composite structure can be tailored by functionalizing carbon nano tubes and chemically bonding them with the polymer matrix e.g. block or graft copolymer, or even cross- linked copolymer, to impart exceptional structural, electronic and surface properties. Bio- and Mechanical-MEMS devices derived from this hybrid composites will be presented.

Disproportionate cardiac hypertrophy during early postnatal development in infants born preterm.

PubMed

Aye, Christina Y L; Lewandowski, Adam J; Lamata, Pablo; Upton, Ross; Davis, Esther; Ohuma, Eric O; Kenworthy, Yvonne; Boardman, Henry; Wopperer, Samuel; Packham, Alice; Adwani, Satish; McCormick, Kenny; Papageorghiou, Aris T; Leeson, Paul

2017-07-01

BackgroundAdults born very preterm have increased cardiac mass and reduced function. We investigated whether a hypertrophic phenomenon occurs in later preterm infants and when this occurs during early development.MethodsCardiac ultrasound was performed on 392 infants (33% preterm at mean gestation 34±2 weeks). Scans were performed during fetal development in 137, at birth and 3 months of postnatal age in 200, and during both fetal and postnatal development in 55. Cardiac morphology and function was quantified and computational models created to identify geometric changes.ResultsAt birth, preterm offspring had reduced cardiac mass and volume relative to body size with a more globular heart. By 3 months, ventricular shape had normalized but both left and right ventricular mass relative to body size were significantly higher than expected for postmenstrual age (left 57.8±41.9 vs. 27.3±29.4%, P<0.001; right 39.3±38.1 vs. 16.6±40.8, P=0.002). Greater changes were associated with lower gestational age at birth (left P<0.001; right P=0.001).ConclusionPreterm offspring, including those born in late gestation, have a disproportionate increase in ventricular mass from birth up to 3 months of postnatal age. These differences were not present before birth. Early postnatal development may provide a window for interventions relevant to long-term cardiovascular health.

Disproportionate cardiac hypertrophy during early postnatal development in infants born preterm

PubMed Central

Aye, Christina Y L; Lewandowski, Adam J; Lamata, Pablo; Upton, Ross; Davis, Esther; Ohuma, Eric O; Kenworthy, Yvonne; Boardman, Henry; Wopperer, Samuel; Packham, Alice; Adwani, Satish; McCormick, Kenny; Papageorghiou, Aris T; Leeson, Paul

2017-01-01

Background Adults born very preterm have increased cardiac mass and reduced function. We investigated whether a hypertrophic phenomenon occurs in later preterm infants and when this occurs during early development. Methods Cardiac ultrasound was performed on 392 infants (33% preterm at mean gestation 34±2 weeks). Scans were performed during fetal development in 137, at birth and 3 months of postnatal age in 200, and during both fetal and postnatal development in 55. Cardiac morphology and function was quantified and computational models created to identify geometric changes. Results At birth, preterm offspring had reduced cardiac mass and volume relative to body size with a more globular heart. By 3 months, ventricular shape had normalized but both left and right ventricular mass relative to body size were significantly higher than expected for postmenstrual age (left 57.8±41.9 vs. 27.3±29.4%, P<0.001; right 39.3±38.1 vs. 16.6±40.8, P=0.002). Greater changes were associated with lower gestational age at birth (left P<0.001; right P=0.001). Conclusion Preterm offspring, including those born in late gestation, have a disproportionate increase in ventricular mass from birth up to 3 months of postnatal age. These differences were not present before birth. Early postnatal development may provide a window for interventions relevant to long-term cardiovascular health. PMID:28399117

The Effects of Early Postnatal Diuretics Treatment on Kidney Development and Long-Term Kidney Function in Wistar Rats.

PubMed

Bueters, Ruud R G; Jeronimus-Klaasen, Annelies; Maicas, Nuria; Florquin, Sandrine; van den Heuvel, Lambertus P; Schreuder, Michiel F

2016-01-01

Diuretics are administered to neonates to control fluid balance. We studied whether clinical doses affected kidney development and function and whether extrauterine growth retardation (EUGR) could be a modulator. Wistar rats were cross-fostered in normal food or food restricted litters at postnatal day (PND) 2 and treated daily with 0.9% NaCl, 5 mg/kg furosemide or 5 mg/kg hydrochlorothiazide (HCTZ) up to PND 8. Kidneys were evaluated on proliferation, apoptosis and a set of mRNA target genes at PND 8, glomerular- and glomerular generation count at PND 35, clinical pathology parameters at 3- and 9 months, neutrophil gelatinase-associated lipocalin at PND 8, 3 and 6 months, monthly blood pressure from 3 months onward and histopathology at study end. Treatment with furosemide or HCTZ did not have relevant effects on measured parameters. EUGR resulted in lower body weight from day 3 onwards (-29% at weaning; p < 0.001, -10% at necropsy; p < 0.001), less glomerular generations (4.4 ± 0.32 vs. 5.0 ± 0.423; p = 0.025, males only), decreased glomerular numbers (27,861 ± 3,468 vs. 30,527 ± 4,096; p = 0.026), higher creatinine clearance (0.84 ± 0.1 vs. 0.77 ± 0.09 ml/min/kg; p = 0.047) at 3 months and lower plasma creatinine (25.7 ± 1.8 vs. 27.5 ± 2.8 µmol/l; p = 0.043) at 9 months. Furosemide and HCTZ did not influence kidney development or function when administered in a clinically relevant dose to rat pups at a stage of ongoing nephrogenesis. EUGR led to impaired kidney development but did not modify furosemide or HCTZ findings. © 2016 S. Karger AG, Basel.

Binding of Y-P30 to Syndecan 2/3 Regulates the Nuclear Localization of CASK

PubMed Central

Landgraf, Peter; Mikhaylova, Marina; Macharadze, Tamar; Borutzki, Corinna; Zenclussen, Ana-Claudia; Wahle, Petra; Kreutz, Michael R.

2014-01-01

The survival promoting peptide Y-P30 has documented neuroprotective effects as well as cell survival and neurite outgrowth promoting activity in vitro and in vivo. Previous work has shown that multimerization of the peptide with pleiotrophin (PTN) and subsequent binding to syndecan (SDC) -2 and -3 is involved in its neuritogenic effects. In this study we show that Y-P30 application regulates the nuclear localization of the SDC binding partner Calcium/calmodulin-dependent serine kinase (CASK) in neuronal primary cultures during development. In early development at day in vitro (DIV) 8 when mainly SDC-3 is expressed supplementation of the culture medium with Y-P30 reduces nuclear CASK levels whereas it has the opposite effect at DIV 18 when SDC-2 is the dominant isoform. In the nucleus CASK regulates gene expression via its association with the T-box transcription factor T-brain-1 (Tbr-1) and we indeed found that gene expression of downstream targets of this complex, like the GluN2B NMDA-receptor, exhibits a corresponding down- or up-regulation at the mRNA level. The differential effect of Y-P30 on the nuclear localization of CASK correlates with its ability to induce shedding of the ectodomain of SDC-2 but not -3. shRNA knockdown of SDC-2 at DIV 18 and SDC-3 at DIV 8 completely abolished the effect of Y-P30 supplementation on nuclear CASK levels. During early development a protein knockdown of SDC-3 also attenuated the effect of Y-P30 on axon outgrowth. Taken together these data suggest that Y-P30 can control the nuclear localization of CASK in a SDC-dependent manner. PMID:24498267

Impact of Transient Acute Hypoxia on the Developing Mouse EEG

PubMed Central

Zanelli, S.; Goodkin, H.P.; Kowalski, S.; Kapur, J.

2015-01-01

Hypoxemic events are common in sick preterm and term infants and represent the most common cause of seizures in the newborn period. Neonatal seizures often lack clinical correlates and are only recognized by electroencephalogram (EEG). The mechanisms leading from a hypoxic/ischemic insult to acute seizures in neonates remain poorly understood. Further, the effects of hypoxia on EEG at various developmental stages have not been fully characterized in neonatal animals, in part due to technical challenges. We evaluated the impact of hypoxia on neonatal mouse EEG to define periods of increased susceptibility to seizures during postnatal development. Hippocampal and cortical electrodes were implanted stereotaxically in C57BL/6 mice from postnatal age 3 (P3) to P15. Following recovery, EEG recording were obtained during baseline, acute hypoxia (4% FiO2 for 4 min) and reoxygenation. In baseline recordings, maturation of EEG was characterized by the appearance of a more continuous background pattern that replaced alternating high and low amplitude activity. Clinical seizures during hypoxia were observed more frequently in younger animals (100% P3-4, 87.5% P5-6, 93% P7-8, 83% P9-10, 33% P11-12, 17% P15, r2=0.81) and also occurred at higher FiO2 in younger animals (11.2±1.1% P3-P6 vs. 8.9±0.8% P7-12, p<0.05). Background attenuation followed the initial hypoxemic seizure; progressive return to baseline during reoxygenation was observed in survivors. Electrographic seizures without clinical manifestations were observed during reoxygenation, again more commonly in younger animals (83% P3-4, 86% P5-6, 75% P7-8, 71% P9-10, 20% P11-12, r2=0.82). All P15 animals died with this duration and degree of hypoxia. Post-ictal abnormalities included burst attenuation and post-anoxic myoclonus and were more commonly seen in older animals. In summary, neonatal mice exposed to brief and severe hypoxia followed by rapid reoxygenation reliably develop seizures and the response to hypoxia varies with postnatal age and maturation. PMID:24636798

Development of the morphology during functional stack build-up of P3HT:PCBM bulk heterojunction solar cells with inverted geometry.

PubMed

Wang, Weijia; Pröller, Stephan; Niedermeier, Martin A; Körstgens, Volker; Philipp, Martine; Su, Bo; Moseguí González, Daniel; Yu, Shun; Roth, Stephan V; Müller-Buschbaum, Peter

2015-01-14

Highly efficient poly(3-hexylthiophene-2,5-diyl) (P3HT):phenyl-C61-butyric acid methyl ester (PCBM) bulk heterojunction solar cells are achieved by using an inverted geometry. The development of the morphology is investigated as a function of the multilayer stack assembling during the inverted solar cell preparation. Atomic force microscopy is used to reveal the surface morphology of each stack, and the inner structure is probed with grazing incidence small-angle X-ray scattering. It is found that the smallest domain size of P3HT is introduced by replicating the fluorine-doped tin oxide structure underneath. The structure sizes of the P3HT:PCBM active layer are further optimized after thermal annealing. Compared to devices with standard geometry, the P3HT:PCBM layer in the inverted solar cells shows smaller domain sizes, which are much closer to the exciton diffusion length in the polymer. The decrease in domain sizes is identified as the main reason for the improvement of the device performance.

Osteoblast differentiation and skeletal development are regulated by Mdm2–p53 signaling

PubMed Central

Lengner, Christopher J.; Steinman, Heather A.; Gagnon, James; Smith, Thomas W.; Henderson, Janet E.; Kream, Barbara E.; Stein, Gary S.; Lian, Jane B.; Jones, Stephen N.

2006-01-01

Mdm2 is required to negatively regulate p53 activity at the peri-implantation stage of early mouse development. However, the absolute requirement for Mdm2 throughout embryogenesis and in organogenesis is unknown. To explore Mdm2–p53 signaling in osteogenesis, Mdm2-conditional mice were bred with Col3.6-Cre–transgenic mice that express Cre recombinase in osteoblast lineage cells. Mdm2-conditional Col3.6-Cre mice die at birth and display multiple skeletal defects. Osteoblast progenitor cells deleted for Mdm2 have elevated p53 activity, reduced proliferation, reduced levels of the master osteoblast transcriptional regulator Runx2, and reduced differentiation. In contrast, p53-null osteoprogenitor cells have increased proliferation, increased expression of Runx2, increased osteoblast maturation, and increased tumorigenic potential, as mice specifically deleted for p53 in osteoblasts develop osteosarcomas. These results demonstrate that p53 plays a critical role in bone organogenesis and homeostasis by negatively regulating bone development and growth and by suppressing bone neoplasia and that Mdm2-mediated inhibition of p53 function is a prerequisite for Runx2 activation, osteoblast differentiation, and proper skeletal formation. PMID:16533949

Cerebral radiation necrosis: incidence, outcomes, and risk factors with emphasis on radiation parameters and chemotherapy.

PubMed

Ruben, Jeremy D; Dally, Michael; Bailey, Michael; Smith, Robin; McLean, Catriona A; Fedele, Pasqual

2006-06-01

To investigate radiation necrosis in patients treated for glioma in terms of incidence, outcomes, predictive and prognostic factors. Records were reviewed for 426 patients followed up until death or for at least 3 years. Logistic regression analysis was performed to identify predictive and prognostic factors. Multivariate survival analysis was conducted using Cox proportional hazards regression. Separate analyses were performed for the subset of 352 patients who received a biologically effective dose (BED) > or =85.5 Gy2 (> or =45 Gy/25 fractions) who were at highest risk for radionecrosis. Twenty-one patients developed radionecrosis (4.9%). Actuarial incidence plateaued at 13.3% after 3 years. In the high-risk subset, radiation parameters confirmed as risk factors included total dose (p < 0.001), BED (p < 0.005), neuret (p < 0.001), fraction size (p = 0.028), and the product of total dose and fraction size (p = 0.001). No patient receiving a BED <96 Gy2 developed radionecrosis. Subsequent chemotherapy significantly increased the risk of cerebral necrosis (p = 0.001) even when adjusted for BED (odds ratio [OR], 5.8; 95% confidence interval [CI], 1.6-20.3) or length of follow-up (OR, 5.4; 95% CI, 1.5-19.3). Concurrent use of valproate appeared to delay the onset of necrosis (p = 0.013). The development of radionecrosis did not affect survival (p = 0.09). Cerebral necrosis is unlikely at doses below 50 Gy in 25 fractions. The risk increases significantly with increasing radiation dose, fraction size, and the subsequent administration of chemotherapy.

14th Annual P3 Awards: A National Student Design ...

EPA Pesticide Factsheets

2017-02-14

EPA as part of its People, Prosperity and the Planet (P3) Award Program – is seeking applications proposing to research, develop, and design solutions to real world challenges involving sustainability.

Development of loop-mediated isothermal amplification with Plasmodium falciparum unique genes for molecular diagnosis of human malaria.

PubMed

Zhang, Yijing; Yao, Yi; Du, Weixing; Wu, Kai; Xu, Wenyue; Lin, Min; Tan, Huabing; Li, Jian

2017-07-01

In order to achieve better outcomes for treatment and in the prophylaxis of malaria, it is imperative to develop a sensitive, specific, and accurate assay for early diagnosis of Plasmodium falciparum infection, which is the major cause of malaria. In this study, we aimed to develop a loop-mediated isothermal amplification (LAMP) assay with P. falciparum unique genes for sensitive, specific, and accurate detection of P. falciparum infection. The unique genes of P. falciparum were randomly selected from PlasmoDB. The LAMP primers of the unique genes were designed using PrimerExplorer V4. LAMP assays with primers from unique genes of P. falciparum and conserved 18S rRNA gene were developed and their sensitivity was assessed. The specificity of the most sensitive LAMP assay was further examined using genomic DNA from Plasmodium vivax, Plasmodium yoelii and Toxoplasma gondii. Finally, the unique gene-based LAMP assay was validated using clinical samples of P. falciparum infection cases. A total of 31 sets of top-scored LAMP primers from nine unique genes were selected from the pools of designed primers. The LAMP assay with PF3D7_1253300-5 was the most sensitive with the detection limit 5 parasites/μl, and it displayed negative LAMP assay with the genomic DNA samples of P. vivax, P. yoelii, and T. gondii. The LAMP assay with PF3D7_0112300 (18S rRNA) was less sensitive with the detection limit 50 parasites/μl, and it displayed negative LAMP assay with the genomic DNA samples of P. yoelii and T. gondii, but displayed positive LAMP detection with P. vivax. The positive detection rate of the LAMP assay with PF3D7_1253300-5 was 90% (27/30), higher than that (80%, 24/30) of the positive rate of PF3D7_0112300 (18S rRNA) in examining clinical samples of P. falciparum infection cases. The LAMP assay with the primer set PF3D7_1253300-5 was more sensitive, specific, and accurate than those with PF3D7_0112300 (18S rRNA) in examining P. falciparum infection, and therefore it is a promising tool for diagnosis of P. falciparum infection.

P2X7R is involved in the progression of atherosclerosis by promoting NLRP3 inflammasome activation

PubMed Central

PENG, KUANG; LIU, LUSHAN; WEI, DANGHENG; LV, YUNCHENG; WANG, GANG; XIONG, WENHAO; WANG, XIAOQING; ALTAF, AFRASYAB; WANG, LILI; HE, DAN; WANG, HONGYAN; QU, PENG

2015-01-01

Purinergic 2X7 receptor (P2X7R) and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) are expressed in macrophages in atherosclerotic lesions. However, the mechanisms through which P2X7R participates in the inflammatory response in atherosclerosis remain largely unknown. The aim of the present study was to investigate the role of P2X7R in atherosclerosis and the mechanisms of action of the NLRP3 inflammasome following stimulation with oxidized low-density lipoprotein (oxLDL). We observed the expression and distribution of P2X7R in the atherosclerotic plaque in the coronary arteries from an autopsy specimen and in that of the aortic sinuses of apoE−/− mice by immunohistochemistry and immunofluorescence staining. The specificity of short interfering RNA (siRNA) was used to suppress P2X7R and NLRP3 mRNA expression. RT-qPCR and western blot analysis were used to analyze mRNA and protein expression, respectively. Co-immunoprecipitation was used to examine the interaction between protein kinase R (PKR) phosphorylation and NLRP3. P2X7R and NLRP3 were expressed at high levels in the atherosclerotic plaque in the coronary arteries. Stimulation with oxLDL upregulated P2X7R, NLRP3 and interleukin (IL)-1β expression. P2X7R knockdown by siRNA suppressed NLRP3 inflammasome activation by inhibiting the PKR phosphorylation mediated by oxLDL. In the atherosclerotic lesions in the aortic sinuses of apoE−/− mice, P2X7R expression was found at high levels. Moreover, P2X7R siRNA attenuated the development of atherosclerosis in the apoE−/− mice. In conclusion, our results demonstrate that P2X7R plays a significant role in the development of atherosclerosis and regulates NLRP3 inflammasome activation by promoting PKR phosphorylation. PMID:25761252

Dietary Patterns and Body Mass Index in Children with Autism and Typically Developing Children

PubMed Central

Evans, E. Whitney; Must, Aviva; Anderson, Sarah E.; Curtin, Carol; Scampini, Renee; Maslin, Melissa; Bandini, Linda

2012-01-01

To determine whether dietary patterns (juice and sweetened non-dairy beverages, fruits, vegetables, fruits & vegetables, snack foods, and kid’s meals) and associations between dietary patterns and body mass index (BMI) differed between 53 children with autism spectrum disorders (ASD) and 58 typically developing children, ages 3 to 11, multivariate regression models including interaction terms were used. Children with ASD were found to consume significantly more daily servings of sweetened beverages (2.6 versus 1.7, p=0.03) and snack foods (4.0 versus 3.0, p=0.01) and significantly fewer daily servings of fruits and vegetables (3.1 versus 4.4, p=0.006) than typically developing children. There was no evidence of statistical interaction between any of the dietary patterns and BMI z-score with autism status. Among all children, fruits and vegetables (p=0.004) and fruits alone (p=0.005) were positively associated with BMI z-score in our multivariate models. Children with ASD consume more energy-dense foods than typically developing children; however, in our sample, only fruits and vegetables were positively associated with BMI z-score. PMID:22936951

Semi-automated De-identification of German Content Sensitive Reports for Big Data Analytics.

PubMed

Seuss, Hannes; Dankerl, Peter; Ihle, Matthias; Grandjean, Andrea; Hammon, Rebecca; Kaestle, Nicola; Fasching, Peter A; Maier, Christian; Christoph, Jan; Sedlmayr, Martin; Uder, Michael; Cavallaro, Alexander; Hammon, Matthias

2017-07-01

Purpose  Projects involving collaborations between different institutions require data security via selective de-identification of words or phrases. A semi-automated de-identification tool was developed and evaluated on different types of medical reports natively and after adapting the algorithm to the text structure. Materials and Methods  A semi-automated de-identification tool was developed and evaluated for its sensitivity and specificity in detecting sensitive content in written reports. Data from 4671 pathology reports (4105 + 566 in two different formats), 2804 medical reports, 1008 operation reports, and 6223 radiology reports of 1167 patients suffering from breast cancer were de-identified. The content was itemized into four categories: direct identifiers (name, address), indirect identifiers (date of birth/operation, medical ID, etc.), medical terms, and filler words. The software was tested natively (without training) in order to establish a baseline. The reports were manually edited and the model re-trained for the next test set. After manually editing 25, 50, 100, 250, 500 and if applicable 1000 reports of each type re-training was applied. Results  In the native test, 61.3 % of direct and 80.8 % of the indirect identifiers were detected. The performance (P) increased to 91.4 % (P25), 96.7 % (P50), 99.5 % (P100), 99.6 % (P250), 99.7 % (P500) and 100 % (P1000) for direct identifiers and to 93.2 % (P25), 97.9 % (P50), 97.2 % (P100), 98.9 % (P250), 99.0 % (P500) and 99.3 % (P1000) for indirect identifiers. Without training, 5.3 % of medical terms were falsely flagged as critical data. The performance increased, after training, to 4.0 % (P25), 3.6 % (P50), 4.0 % (P100), 3.7 % (P250), 4.3 % (P500), and 3.1 % (P1000). Roughly 0.1 % of filler words were falsely flagged. Conclusion  Training of the developed de-identification tool continuously improved its performance. Training with roughly 100 edited reports enables reliable detection and labeling of sensitive data in different types of medical reports. Key Points:   · Collaborations between different institutions require de-identification of patients' data. · Software-based de-identification of content-sensitive reports grows in importance as a result of 'Big data'. · A de-identification software was developed and tested natively and after training. · The proposed de-identification software worked quite reliably, following training with roughly 100 edited reports. · A final check of the texts by an authorized person remains necessary. Citation Format · Seuss H, Dankerl P, Ihle M et al. Semi-automated De-identification of German Content Sensitive Reports for Big Data Analytics. Fortschr Röntgenstr 2017; 189: 661 - 671. © Georg Thieme Verlag KG Stuttgart · New York.

Effects of ocean warming and acidification on survival, growth and skeletal development in the early benthic juvenile sea urchin (Heliocidaris erythrogramma).

PubMed

Wolfe, Kennedy; Dworjanyn, Symon A; Byrne, Maria

2013-09-01

Co-occurring ocean warming, acidification and reduced carbonate mineral saturation have significant impacts on marine biota, especially calcifying organisms. The effects of these stressors on development and calcification in newly metamorphosed juveniles (ca. 0.5 mm test diameter) of the intertidal sea urchin Heliocidaris erythrogramma, an ecologically important species in temperate Australia, were investigated in context with present and projected future conditions. Habitat temperature and pH/pCO2 were documented to place experiments in a biologically and ecologically relevant context. These parameters fluctuated diurnally up to 10 °C and 0.45 pH units. The juveniles were exposed to three temperature (21, 23 and 25 °C) and four pH (8.1, 7.8, 7.6 and 7.4) treatments in all combinations, representing ambient sea surface conditions (21 °C, pH 8.1; pCO2 397; ΩCa 4.7; ΩAr 3.1), near-future projected change (+2-4 °C, -0.3-0.5 pH units; pCO2 400-1820; ΩCa 5.0-1.6; ΩAr 3.3-1.1), and extreme conditions experienced at low tide (+4 °C, -0.3-0.7 pH units; pCO2 2850-2967; ΩCa 1.1-1.0; ΩAr 0.7-0.6). The lowest pH treatment (pH 7.4) was used to assess tolerance levels. Juvenile survival and test growth were resilient to current and near-future warming and acidification. Spine development, however, was negatively affected by near-future increased temperature (+2-4 °C) and extreme acidification (pH 7.4), with a complex interaction between stressors. Near-future warming was the more significant stressor. Spine tips were dissolved in the pH 7.4 treatments. Adaptation to fluctuating temperature-pH conditions in the intertidal may convey resilience to juvenile H. erythrogramma to changing ocean conditions, however, ocean warming and acidification may shift baseline intertidal temperature and pH/pCO2 to levels that exceed tolerance limits. © 2013 John Wiley & Sons Ltd.

Adrenomedullin promotes lung angiogenesis, alveolar development, and repair.

PubMed

Vadivel, Arul; Abozaid, Sameh; van Haaften, Tim; Sawicka, Monika; Eaton, Farah; Chen, Ming; Thébaud, Bernard

2010-08-01

Bronchopulmonary dysplasia (BPD) and emphysema are significant global health problems at the extreme stages of life. Both are characterized by alveolar simplification and abnormal distal airspace enlargement due to arrested development or loss of alveoli, respectively. Both lack effective treatments. Mechanisms that inhibit distal lung growth are poorly understood. Adrenomedullin (AM), a recently discovered potent vasodilator, promotes angiogenesis and has protective effects on the cardiovascular and respiratory system. Its role in the developing lung is unknown. We hypothesized that AM promotes lung angiogenesis and alveolar development. Accordingly, we report that lung mRNA expression of AM increases during normal alveolar development. In vivo, intranasal administration of the AM antagonist, AM22-52 decreases lung capillary density (12.4 +/- 1.5 versus 18 +/- 1.5 in control animals; P < 0.05) and impairs alveolar development (mean linear intercept, 52.3 +/- 1.5 versus 43.8 +/- 1.8 [P < 0.05] and septal counts 62.0 +/- 2.7 versus 90.4 +/- 3.5 [P < 0.05]) in neonatal rats, resulting in larger and fewer alveoli, reminiscent of BPD. This was associated with decreased lung endothelial nitric oxide synthase and vascular endothelial growth factor-A mRNA expression. In experimental oxygen-induced BPD, a model of arrested lung vascular and alveolar growth, AM attenuates arrested lung angiogenesis (vessel density, 6.9 +/- 1.1 versus 16.2 +/- 1.3, P < 0.05) and alveolar development (mean linear intercept, 51.9 +/- 3.2 versus 44.4 +/- 0.7, septal counts 47.6 +/- 3.4 versus 67.7 +/- 4.0, P < 0.05), an effect in part mediated by inhibition of apoptosis. AM also prevents pulmonary hypertension in this model, as assessed by decreased right ventricular hypertrophy and pulmonary artery medial wall thickness. Our findings suggest a role for AM during normal alveolar development. AM may have therapeutic potential in diseases associated with alveolar injury.

Technical Evaluation Report of the Aerospace Medical Panel Working Group WG-08 on Evaluation of Methods to Assess Workload.

DTIC Science & Technology

1980-11-01

Occlusion 3.1 Single Measures 3. Primary Task 3.2 Multiple Measures 3.3 Math Modeling 4.1.1 PFF 4.1.2 CSR 4.1.3 M,0 4.1.4 MW 4.1.5 UG3 4.1.6 ZCP 4.1 Single... modeling methodology; and (4) validation of the analytic/predictive methodology In a system design, development, and test effort." Chapter 9: "A central...2.3 Occlusion P S P S S P -P 3.1 Single Measure-Primary S S S S S S S 3.2 Multiple Measure-Primary S S IS S S S S K 3.3 Math Modeling ~ 4.1.7 Eye and

Development of a ratiometric time-resolved luminescence sensor for pH based on lanthanide complexes.

PubMed

Liu, Mingjing; Ye, Zhiqiang; Xin, Chenglong; Yuan, Jingli

2013-01-25

Time-resolved luminescence bioassay technique using lanthanide complexes as luminescent probes/sensors has shown great utilities in clinical diagnostics and biotechnology discoveries. In this work, a novel terpyridine polyacid derivative that can form highly stable complexes with lanthanide ions in aqueous media, (4'-hydroxy-2,2':6',2''-terpyridine-6,6''-diyl) bis(methylenenitrilo) tetrakis(acetic acid) (HTTA), was designed and synthesized for developing time-resolved luminescence pH sensors based on its Eu(3+) and Tb(3+) complexes. The luminescence characterization results reveal that the luminescence intensity of HTTA-Eu(3+) is strongly dependent on the pH values in weakly acidic to neutral media (pK(a) = 5.8, pH 4.8-7.5), while that of HTTA-Tb(3+) is pH-independent. This unique luminescence response allows the mixture of HTTA-Eu(3+) and HTTA-Tb(3+) (the HTTA-Eu(3+)/Tb(3+) mixture) to be used as a ratiometric luminescence sensor for the time-resolved luminescence detection of pH with the intensity ratio of its Tb(3+) emission at 540 nm to its Eu(3+) emission at 610 nm, I(540 nm)/I(610 nm), as a signal. Moreover, the UV absorption spectrum changes of the HTTA-Eu(3+)/Tb(3+) mixture at different pHs (pH 4.0-7.0) also display a ratiometric response to the pH changes with the ratio of absorbance at 290 nm to that at 325 nm, A(290 nm)/A(325 nm), as a signal. This feature enables the HTTA-Eu(3+)/Tb(3+) mixture to have an additional function for the pH detection with the absorption spectrometry technique. For loading the complexes into the living cells, the acetoxymethyl ester of HTTA was synthesized and used for loading HTTA-Eu(3+) and HTTA-Tb(3+) into the cultured HeLa cells. The luminescence imaging results demonstrated the practical utility of the new sensor for the time-resolved luminescence cell imaging application. Copyright © 2012 Elsevier B.V. All rights reserved.

The two single nucleotide polymorphisms in the H37/RBM5 tumour suppressor gene at 3p21.3 correlated with different subtypes of non-small cell lung cancers

PubMed Central

Oh, Juliana J.; Koegel, Ashley; Phan, Diana T.; Razfar, Ali; Slamon, Dennis J.

2007-01-01

Summary Allele loss and genetic alteration in chromosome 3p, particularly in 3p21.3 region, are the most frequent and the earliest genomic abnormalities found in lung cancer. Multiple 3p21.3 genes exhibit various degrees of tumour suppression activity suggesting that 3p21.3 genes may function as an integrated tumour suppressor region through their diverse biological activities. We have previously demonstrated growth inhibitory effects and tumour suppression mechanism of the H37/RBM5 gene which is one of the 19 genes residing in the 370kb minimal overlap region at 3p21.3. In the current study, in an attempt to find, if any, mutations in the H37 coding region in lung cancer cells, we compared nucleotide sequences of the entire H37 gene in tumour vs. adjacent normal tissues from 17 non-small cell lung cancer (NSCLC) patients. No mutations were detected, instead, we found the two silent single nucleotide polymorphisms (SNPs), C1138T and C2185T, within the coding region of the H37 gene. In addition, we found that specific allele types at these SNP positions are correlated with different histological subtypes of NSCLC; tumours containing heterozygous alleles (C+T) at these SNP positions are more likely to be associated with adenocarcinoma (AC) whereas homozygous alleles (either C or T) are associated with squamous cell carcinoma (SCC) (p=0.0098). We postulate that, these two silent polymorphisms may be in linkage disequilibrium (LD) with a disease causative allele in the 3p21.3 tumour suppressor region which is packed with a large number of important genes affecting lung cancer development. In addition, because of prevalent loss of heterozygosity (LOH) detected at 3p21.3 which precedes lung cancer initiation, these SNPs may be developed into a marker screening for the high risk individuals. PMID:17606309

Increasing dietary vitamin D3 improves the walking ability and welfare status of broiler chickens reared at high stocking densities.

PubMed

Sun, Z W; Yan, L; G, Y Y; Zhao, J P; Lin, H; Guo, Y M

2013-12-01

A study was conducted to evaluate the effects of varying dietary vitamin D3 and stocking density on growing performance, carcass characteristics, bone biomechanical properties, and welfare responses in Ross (308) broilers. Experimental diets, containing 1, 10, or 20 times the NRC recommended level of vitamin D3 (200 IU/kg), were formulated with low, medium, or high vitamin D3 levels for 3 growing phases. Two stocking densities were 10 and 16 birds/m(2). One-day-old hatchlings (1,872 males) were randomly assigned to 6 pens in each treatment. Results showed that high stocking density decreased the feed intake, BW gain (P < 0.01), breast muscle yield (P = 0.010), and tibial development (P < 0.01), whereas increasing feed conversion ratio (P < 0.001), and the scores of gait, footpad and hock burn, and abdominal plumage damage (P < 0.01), particularly toward the age when birds attained their market size. Increasing dietary vitamin D3 improved the birds' walking ability and tibial quality (P < 0.05), and reduced the development of footpad or hock dermatitis and abdominal plumage damage (P < 0.01), some aspects of which were age-dependent and appeared to vary with stocking density. These data indicate that increasing supplemental vitamin D3 has a favorable effect on walking ability and welfare status of high stocking density birds, but not on performance.

Analysis of Sub-Grid Boundary-Layer Processes Observed by the P-3 Doppler Wind Lidar in Support of the Western Pacific Tropical Cyclone Structure 2008 Experiment

DTIC Science & Technology

2012-02-02

flight hours to one significant atmospheric phenomena. OBJECTIVES The P-3 Doppler Wind Lidar (P3DWL) uses the latest version of a coherent ... Doppler transceiver developed at Lockheed Martin Coherent Technologies. The lidar , with the exception of the scanner, is shown on the top in Figure 1...Processes Observed by the P-3 Doppler Wind Lidar in Support of the Western Pacific Tropical Cyclone Structure 2008 Experiment Ralph Foster Applied

Analysis of distortion data from TF30-P-3 mixed compression inlet test

NASA Technical Reports Server (NTRS)

King, R. W.; Schuerman, J. A.; Muller, R. G.

1976-01-01

A program was conducted to reduce and analyze inlet and engine data obtained during testing of a TF30-P-3 engine operating behind a mixed compression inlet. Previously developed distortion analysis techniques were applied to the data to assist in the development of a new distortion methodology. Instantaneous distortion techniques were refined as part of the distortion methodology development. A technique for estimating maximum levels of instantaneous distortion from steady state and average turbulence data was also developed as part of the program.

[Relationship of plasma ghrelin, IGF-1 and insulin with the growth and development of 2 -7 year-old children with small for gestational age at birth].

PubMed

Cheng, Yaying; Song, Guangyao; Zhou, Lixia; Cai, Baoping; Zhao, Xiumian; Yin, Jianying

2012-01-01

To explore the relationship of Ghrelin, insulin-like growth factor-1 (IGF-1) and insulin with the growth and development of 2 -7 year-old children with small for gestational age (SGA) at birth. The levels of ghrelin, IGF-1, IGFBP-3, insulin and glucose were measured in the children with preterm SGA and term SGA and compared with the children with preterm appropriate for gestational age (AGA) and term AGA. The correlation of ghrelin with IGF-1, IGFBP-3 and insulin was analyzed. Plasma ghrelin in preterm SGA was higher than that in term SGA (P < 0.05), and there was no significant difference between preterm SGA and preterm AGA (P > 0.05). Plasma ghrelin in preterm AGA and term SGA was higher than that in term AGA (P < 0.05, P < 0.01 respectively). Serum IGF-1 and IGFBP-3 in preterm SGA were lower than those in term SGA (P < 0.05 for all) and serum IGF-1 and IGFBP-3 in preterm AGA were much lower than those in term AGA (P < 0.0001 for all). The level of serum insulin was the highest in term SGA. The trend of insulin resistance index (IRI) was similar to insulin. There were negative correlations of ghrelin with other indexes (weight SDS, IGF-1, IGFBP-3, insulin and IRI) in preterm SGA and term SGA (in preterm SGA r = -0.683, P < 0.002; r = -0.749, P < 0.001; r = -0.828, P < 0.001; r = -0.694, P < 0.005; r = -0.822, P < 0.001; in term SGA r = -0.792, P < 0.001; r = -0.707, P < 0.002; r = -0.615, P < 0.01; r = -0.648, P < 0.005; r = -0.679, P < 0.005). Ghrelin is involved in the regulation of growth and development of preterm and SGA children, regardless of the magnitude of their catch up growth. As a re-regulatory factor to insulin, ghrelin regulates the energy metabolism in a form of negative feedback.

Sources and mechanisms of nitrate and orthophosphate transport in urban stormwater runoff from residential catchments.

PubMed

Yang, Yun-Ya; Toor, Gurpal S

2017-04-01

Nutrients export from residential catchments contributes to water quality impairment in urban water bodies. We investigated the concentrations, transport mechanisms, and sources of nitrate-nitrogen (NO 3 -N) and orthophosphate-phosphorus (PO 4 -P) in urban stormwater runoff generated in residential catchments in Tampa Bay, Florida, United States. Street runoff samples, collected over 21 storm events, were supplemented with rainfall and roof runoff samples from six representative residential catchments. Samples were analyzed for N and P forms, N and oxygen (O) isotopes of nitrate (δ 18 O-NO 3 - and δ 15 N-NO 3 - ), and δ 18 O and hydrogen (δD) isotopes of water (H 2 O). We found that the main NO 3 -N source in street runoff was atmospheric deposition (range: 35-64%), followed by chemical N fertilizers (range: 1-39%), and soil and organic N (range: 7-33%), whereas PO 4 -P in the street runoff likely originated from erosion of soil particles and mineralization from organic materials (leaves, grass clippings). The variability in the sources and concentrations of NO 3 -N and PO 4 -P across catchments is attributed to different development designs and patterns, use of various fill materials during land development, and landscaping practices. This data can be useful to develop strategies to offset the impacts of urban development (e.g., designs and patterns resulting in variable impervious areas) and management (e.g., fertilizer use, landscaping practices) on NO 3 -N and PO 4 -P transport in urban residential catchments. Copyright © 2017 Elsevier Ltd. All rights reserved.

Nonoverlapping roles of PD-1 and FoxP3 in maintaining immune tolerance in a novel autoimmune pancreatitis mouse model.

PubMed

Zhang, Baihao; Chikuma, Shunsuke; Hori, Shohei; Fagarasan, Sidonia; Honjo, Tasuku

2016-07-26

PD-1 (programmed-death 1), an immune-inhibitory receptor required for immune self-tolerance whose deficiency causes autoimmunity with variable severity and tissue specificity depending on other genetic factors, is expressed on activated T cells, including the transcription factor FoxP3(+) Treg cells known to play critical roles in maintaining immune tolerance. However, whether PD-1 expression by the Treg cells is required for their immune regulatory function, especially in autoimmune settings, is still unclear. We found that mice with partial FoxP3 insufficiency developed early-onset lympho-proliferation and lethal autoimmune pancreatitis only when PD-1 is absent. The autoimmune phenotype was rescued by the transfer of FoxP3-sufficient T cells, regardless of whether they were derived from WT or PD-1-deficient mice, indicating that Treg cells dominantly protect against development of spontaneous autoimmunity without intrinsic expression of PD-1. The absence of PD-1 combined with partial FoxP3 insufficiency, however, led to generation of ex-FoxP3 T cells with proinflammatory properties and expansion of effector/memory T cells that contributed to the autoimmune destruction of target tissues. Altogether, the results suggest that PD-1 and FoxP3 work collaboratively in maintaining immune tolerance mostly through nonoverlapping pathways. Thus, PD-1 is modulating the activation threshold and maintaining the balance between regulatory and effector T cells, whereas FoxP3 is sufficient for dominant regulation through maintaining the integrity of the Treg function. We suggest that genetic or environmental factors that even moderately affect the expression of both PD-1 and FoxP3 can cause life-threatening autoimmune diseases by disrupting the T-cell homeostasis.

Nonoverlapping roles of PD-1 and FoxP3 in maintaining immune tolerance in a novel autoimmune pancreatitis mouse model

PubMed Central

Zhang, Baihao; Chikuma, Shunsuke; Hori, Shohei; Fagarasan, Sidonia; Honjo, Tasuku

2016-01-01

PD-1 (programmed-death 1), an immune-inhibitory receptor required for immune self-tolerance whose deficiency causes autoimmunity with variable severity and tissue specificity depending on other genetic factors, is expressed on activated T cells, including the transcription factor FoxP3+ Treg cells known to play critical roles in maintaining immune tolerance. However, whether PD-1 expression by the Treg cells is required for their immune regulatory function, especially in autoimmune settings, is still unclear. We found that mice with partial FoxP3 insufficiency developed early-onset lympho-proliferation and lethal autoimmune pancreatitis only when PD-1 is absent. The autoimmune phenotype was rescued by the transfer of FoxP3-sufficient T cells, regardless of whether they were derived from WT or PD-1–deficient mice, indicating that Treg cells dominantly protect against development of spontaneous autoimmunity without intrinsic expression of PD-1. The absence of PD-1 combined with partial FoxP3 insufficiency, however, led to generation of ex-FoxP3 T cells with proinflammatory properties and expansion of effector/memory T cells that contributed to the autoimmune destruction of target tissues. Altogether, the results suggest that PD-1 and FoxP3 work collaboratively in maintaining immune tolerance mostly through nonoverlapping pathways. Thus, PD-1 is modulating the activation threshold and maintaining the balance between regulatory and effector T cells, whereas FoxP3 is sufficient for dominant regulation through maintaining the integrity of the Treg function. We suggest that genetic or environmental factors that even moderately affect the expression of both PD-1 and FoxP3 can cause life-threatening autoimmune diseases by disrupting the T-cell homeostasis. PMID:27410049

Regiochemistry of Poly(3-Hexylthiophene): Synthesis and Investigation of a Conducting Polymer

ERIC Educational Resources Information Center

Pappenfus, Ted M.; Hermanson, David L.; Kohl, Stuart G.; Melby, Jacob H.; Thoma, Laura M.; Carpenter, Nancy E.; Filho, Demetrio A. da Silva; Bredas, Jean-Luc

2010-01-01

A series of experiments for undergraduate laboratory courses (e.g., organic, polymer, inorganic) have been developed. These experiments focus on understanding the regiochemistry of the conducting polymer poly(3-hexylthiophene) (P3HT). The substitution patterns in P3HTs control their conformational features, which, in turn, dictates the [pi]…

P-Cable: New High-Resolution 3D Seismic Acquisition Technology

NASA Astrophysics Data System (ADS)

Planke, Sverre; Berndt, Christian; Mienert, Jürgen; Bünz, Stefan; Eriksen, Frode N.; Eriksen, Ola K.

2010-05-01

We have developed a new cost-efficient technology for acquisition of high-resolution 3D seismic data: the P-Cable system. This technology is very well suited for deep water exploration, site surveys, and studies of shallow gas and fluid migration associated with gas hydrates or leaking reservoirs. It delivers unparalleled 3D seismic images of subsurface sediment architectures. The P-Cable system consists of a seismic cable towed perpendicular to a vessel's steaming direction. This configuration allows us to image an up to 150 m wide swath of the sub-surface for each sail line. Conventional 3D seismic technology relies on several very long streamers (up to 10 km long streamers are common), large sources, and costly operations. In contrast, the P-Cable system is light-weight and fast to deploy from small vessels. Only a small source is required as the system is made for relatively shallow imaging, typically above the first water-bottom multiple. The P-Cable system is particularly useful for acquisition of small 3D cubes, 10-50 km2, in focus areas, rather than extensive mapping of large regions. The rapid deployment and recovery of the system makes it possible to acquire several small cubes (10 to 30 km2) with high-resolution (50-250 Hz) seismic data in during one cruise. The first development of the P-Cable system was a cooperative project achieved by Volcanic Basin Petroleum Research (VBPR), University of Tromsø, National Oceanography Centre, Southampton, and industry partners. Field trials using a 12-streamer system were conducted on sites with active fluid-leakage systems on the Norwegian-Barents-Svalbard margin, the Gulf of Cadiz, and the Mediterranean. The second phase of the development introduced digital streamers. The new P-Cable2 system also includes integrated tow and cross cables for power and data transmission and improved doors to spread the larger cross cable. This digital system has been successfully used during six cruises by the University of Tromsø, VBPR, P-Cable 3D Seismic AS (P3S), and IFM-GEOMAR. Presently, a Norwegian national infrastructure consortium (Univ. of Tromsø, P3S, Univ. of Bergen, NGU) assembles a mobile P-Cable2 high-resolution 3D seismic system for fully operational use of the technology for scientific purposes.

Wakefield Computations for the CLIC PETS using the Parallel Finite Element Time-Domain Code T3P

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

Candel, A; Kabel, A.; Lee, L.

In recent years, SLAC's Advanced Computations Department (ACD) has developed the high-performance parallel 3D electromagnetic time-domain code, T3P, for simulations of wakefields and transients in complex accelerator structures. T3P is based on advanced higher-order Finite Element methods on unstructured grids with quadratic surface approximation. Optimized for large-scale parallel processing on leadership supercomputing facilities, T3P allows simulations of realistic 3D structures with unprecedented accuracy, aiding the design of the next generation of accelerator facilities. Applications to the Compact Linear Collider (CLIC) Power Extraction and Transfer Structure (PETS) are presented.

Local and long-range endogenous resting potential gradients antagonistically regulate apoptosis and proliferation in the embryonic CNS.

PubMed

Pai, Vaibhav P; Lemire, Joan M; Chen, Ying; Lin, Gufa; Levin, Michael

2015-01-01

Bioelectric signals, particularly transmembrane voltage potentials (Vmem), play an important role in large-scale patterning during embryonic development. Endogenous bioelectric gradients across tissues function as instructive factors during eye, brain, and other morphogenetic processes. An important and still poorly-understood aspect is the control of cell behaviors by the voltage states of distant cell groups. Here, experimental alteration of endogenous Vmem was induced in Xenopus laevis embryos by misexpression of well-characterized ion channel mRNAs, a strategy often used to identify functional roles of Vmem gradients during embryonic development and regeneration. Immunofluorescence analysis (for activated caspase 3 and phosphor-histone H3P) on embryonic sections was used to characterize apoptosis and proliferation. Disrupting local bioelectric signals (within the developing neural tube region) increased caspase 3 and decreased H3P in the brain, resulting in brain mispatterning. Disrupting remote (ventral, non-neural region) bioelectric signals decreased caspase 3 and highly increased H3P within the brain, with normal brain patterning. Disrupting both the local and distant bioelectric signals produced antagonistic effects on caspase 3 and H3P. Thus, two components of bioelectric signals regulate apoptosis-proliferation balance within the developing brain and spinal cord: local (developing neural tube region) and distant (ventral non-neural region). Together, the local and long-range bioelectric signals create a binary control system capable of fine-tuning apoptosis and proliferation with the brain and spinal cord to achieve correct pattern and size control. Our data suggest a roadmap for utilizing bioelectric state as a diagnostic modality and convenient intervention parameter for birth defects and degenerative disease states of the CNS.

Post-hypercapnic alkalosis is associated with ventilator dependence and increased ICU stay.

PubMed

Banga, Amit; Khilnani, G C

2009-12-01

Posthypercapnic alkalosis (PHA) is frequently overlooked as a complication of mechanical ventilation in patients with exacerbation of chronic obstructive pulmonary disease (COPD). The current study was conducted to determine the incidence, risk factors for development and effect on outcome of PHA. Eighty-four patients (62 +/- 11 years, range 42-78 years, M:F 58: 26) with exacerbation of COPD with underlying chronic hypercapnic respiratory failure requiring mechanical ventilation were included in a retrospective fashion. PHA was defined as static or rising serum bicarbonate levels, 72 hours or more after return of PaCO2 to baseline, with concurrent pH > 7.44. Development of PHA was noted in 17 patients (20.2%). Corticosteroid use >or=10 days during the hospital stay was an independent risk factor for development of PHA (Adjusted OR, 95% CI: 9.4, 1.6-55.3; P = 0.013). Development of PHA was associated with an increased incidence of ventilator dependence (64.7% vs. 37.3%, OR, 95% CI: 3.1, 1.1-9.4, P = 0.04) and duration of ICU stay (14.7 +/- 6.7 vs. 9.5 +/- 5.9, P = 0.01) but no increase in hospital mortality (43.3% vs. 41.2%, P = NS). It is concluded that PHA is a common complication in patients with exacerbation of COPD requiring mechanical ventilation and is associated with increased incidence of ventilator dependence and ICU stay.

Microduplication of 3p26.3 Implicated in Cognitive Development

PubMed Central

Te Weehi, Leah; Maikoo, Raj; Mc Cormack, Adrian; Mazzaschi, Roberto; Ashton, Fern; Zhang, Liangtao; George, Alice M.; Love, Donald R.

2014-01-01

We report here a 34-month-old boy with global developmental delay referred for molecular karyotyping and fragile X studies. Molecular karyotype analysis revealed a microduplication in the 3p26.3 region involving part of the CHL1 and CNTN6 genes. Several deletions, one translocation, and one duplication have previously been described in this region of chromosome 3. The CHL1 gene has been proposed as a dosage-sensitive gene with a central role in cognitive development, and so the microduplication reported here appears to be implicated in our patient's phenotype. PMID:24778888

The Implication of Substance P in the Development of Tendinopathy: A Case Control Study

PubMed Central

Han, Soo-Hong; Choi, Wonchul; Song, Jiye; Kim, Jaehee; Lee, Seungyong; Choi, Youngrak; Byun, Seong-Eun; Ahn, Taekeun; Ahn, Heejung; Ding, Catherine; Baik, Lloyd; Ward, Spencer; Ting, Kang; Lee, Soonchul

2017-01-01

It was reported that substance P had beneficial effects in the healing of acute tendon injury. However, the relationship between substance P and degenerative tendinopathy development remains unclear. The purpose of this study was to determine the role of substance P in the pathogenesis of tendinopathy. Healthy and tendinopathy tendon were harvested from human and tenocytes were cultured individually. The expression levels of genes associated with tendinopathy were compared. Next, substance P was exogenously administered to the healthy tenocyte and the effect was evaluated. The results showed that tendinopathy tenocytes had higher levels of COL3A1, MMP1, COX2, SCX, ACTA2, and substance P gene expression compared to healthy tenocytes. Next, substance P treatment on the healthy tenocyte displayed similar changes to that of the tendinopathy tenocytes. These differences between the two groups were also determined by Western blot. Additionally, cells with substance P had the tendinopathy change morphologically although cellular proliferation was significantly higher compared to that of the control group. In conclusion, substance P enhanced cellular proliferation, but concomitantly increased immature collagen (type 3 collagen). Substance P plays a crucial role in tendinopathy development and could be a future therapeutic target for treatment. PMID:28598390

The Implication of Substance P in the Development of Tendinopathy: A Case Control Study.

PubMed

Han, Soo-Hong; Choi, Wonchul; Song, Jiye; Kim, Jaehee; Lee, Seungyong; Choi, Youngrak; Byun, Seong-Eun; Ahn, Taekeun; Ahn, Heejung; Ding, Catherine; Baik, Lloyd; Ward, Spencer; Ting, Kang; Lee, Soonchul

2017-06-09

It was reported that substance P had beneficial effects in the healing of acute tendon injury. However, the relationship between substance P and degenerative tendinopathy development remains unclear. The purpose of this study was to determine the role of substance P in the pathogenesis of tendinopathy. Healthy and tendinopathy tendon were harvested from human and tenocytes were cultured individually. The expression levels of genes associated with tendinopathy were compared. Next, substance P was exogenously administered to the healthy tenocyte and the effect was evaluated. The results showed that tendinopathy tenocytes had higher levels of COL3A1 , MMP1 , COX2 , SCX , ACTA2 , and substance P gene expression compared to healthy tenocytes. Next, substance P treatment on the healthy tenocyte displayed similar changes to that of the tendinopathy tenocytes. These differences between the two groups were also determined by Western blot. Additionally, cells with substance P had the tendinopathy change morphologically although cellular proliferation was significantly higher compared to that of the control group. In conclusion, substance P enhanced cellular proliferation, but concomitantly increased immature collagen (type 3 collagen). Substance P plays a crucial role in tendinopathy development and could be a future therapeutic target for treatment.

Development of X-Ray Laser Media. Measurement of Gain and Development of Cavity Resonators for Wavelengths near 130 Angstroms. Volume 1.

DTIC Science & Technology

1983-02-01

A2/f ,11= 1.5 x 10- 6 (g u /g )[AU)] 2/f where r is the radius of the electron (2.82 10 A), c is the velocity of light (3 1018 A/sec), X is the...LASER-PRODUCED PLASMA, *2N , . / - . ’ . .. . . .. . .. . -" 4 A’.° 1. Recombination to Hydrogenic Plasma (i.e. one bound electron ). A. Collisional...its inverse (Auger) N(p) + e 0 N (plop2) (plP charge exchange (here one 2 N(zl)+ 0 N (z-2)+ example among many) (p) (plP 2) 3. Free electrons

Human Lung Small Airway-on-a-Chip Protocol.

PubMed

Benam, Kambez H; Mazur, Marc; Choe, Youngjae; Ferrante, Thomas C; Novak, Richard; Ingber, Donald E

2017-01-01

Organs-on-chips are microfluidic cell culture devices created using microchip manufacturing techniques that contain hollow microchannels lined by living cells, which recreate specialized tissue-tissue interfaces, physical microenvironments, and vascular perfusion necessary to recapitulate organ-level physiology in vitro. Here we describe a protocol for fabrication, culture, and operation of a human lung "small airway-on-a-chip," which contains a differentiated, mucociliary bronchiolar epithelium exposed to air and an underlying microvascular endothelium that experiences fluid flow. First, microengineering is used to fabricate a multilayered microfluidic device that contains two parallel elastomeric microchannels separated by a thin rigid porous membrane; this requires less than 1 day to complete. Next, primary human airway bronchiolar epithelial cells isolated from healthy normal donors or patients with respiratory disease are cultured on the porous membrane within one microchannel while lung microvascular endothelial cells are cultured on the opposite side of the same membrane in the second channel to create a mucociliated epithelium-endothelium interface; this process take about 4-6 weeks to complete. Finally, culture medium containing neutrophils isolated from fresh whole human blood are flowed through the microvascular channel of the device to enable real-time analysis of capture and recruitment of circulating leukocytes by endothelium under physiological shear; this step requires less than 1 day to complete. The small airway-on-a-chip represents a new microfluidic tool to model complex and dynamic inflammatory responses of healthy and diseased lungs in vitro.

Octree-based, GPU implementation of a continuous cellular automaton for the simulation of complex, evolving surfaces

NASA Astrophysics Data System (ADS)

Ferrando, N.; Gosálvez, M. A.; Cerdá, J.; Gadea, R.; Sato, K.

2011-03-01

Presently, dynamic surface-based models are required to contain increasingly larger numbers of points and to propagate them over longer time periods. For large numbers of surface points, the octree data structure can be used as a balance between low memory occupation and relatively rapid access to the stored data. For evolution rules that depend on neighborhood states, extended simulation periods can be obtained by using simplified atomistic propagation models, such as the Cellular Automata (CA). This method, however, has an intrinsic parallel updating nature and the corresponding simulations are highly inefficient when performed on classical Central Processing Units (CPUs), which are designed for the sequential execution of tasks. In this paper, a series of guidelines is presented for the efficient adaptation of octree-based, CA simulations of complex, evolving surfaces into massively parallel computing hardware. A Graphics Processing Unit (GPU) is used as a cost-efficient example of the parallel architectures. For the actual simulations, we consider the surface propagation during anisotropic wet chemical etching of silicon as a computationally challenging process with a wide-spread use in microengineering applications. A continuous CA model that is intrinsically parallel in nature is used for the time evolution. Our study strongly indicates that parallel computations of dynamically evolving surfaces simulated using CA methods are significantly benefited by the incorporation of octrees as support data structures, substantially decreasing the overall computational time and memory usage.

Micropatterning tractional forces in living cells

NASA Technical Reports Server (NTRS)

Wang, Ning; Ostuni, Emanuele; Whitesides, George M.; Ingber, Donald E.

2002-01-01

Here we describe a method for quantifying traction in cells that are physically constrained within micron-sized adhesive islands of defined shape and size on the surface of flexible polyacrylamide gels that contain fluorescent microbeads (0.2-microm diameter). Smooth muscle cells were plated onto square (50 x 50 microm) or circular (25- or 50-microm diameter) adhesive islands that were created on the surface of the gels by applying a collagen coating through microengineered holes in an elastomeric membrane that was later removed. Adherent cells spread to take on the size and shape of the islands and cell tractions were quantitated by mapping displacement fields of the fluorescent microbeads within the gel. Cells on round islands did not exhibit any preferential direction of force application, but they exerted their strongest traction at sites where they formed protrusions. When cells were confined to squares, traction was highest in the corners both in the absence and presence of the contractile agonist, histamine, and cell protrusions were also observed in these regions. Quantitation of the mean traction exerted by cells cultured on the different islands revealed that cell tension increased as cell spreading was promoted. These results provide a mechanical basis for past studies that demonstrated a similar correlation between spreading and growth within various anchorage-dependent cells. This new approach for analyzing the spatial distribution of mechanical forces beneath individual cells that are experimentally constrained to defined sizes and shapes may provide additional insight into the biophysical basis of cell regulation. Copyright 2002 Wiley-Liss, Inc.

p3d--Python module for structural bioinformatics.

PubMed

Fufezan, Christian; Specht, Michael

2009-08-21

High-throughput bioinformatic analysis tools are needed to mine the large amount of structural data via knowledge based approaches. The development of such tools requires a robust interface to access the structural data in an easy way. For this the Python scripting language is the optimal choice since its philosophy is to write an understandable source code. p3d is an object oriented Python module that adds a simple yet powerful interface to the Python interpreter to process and analyse three dimensional protein structure files (PDB files). p3d's strength arises from the combination of a) very fast spatial access to the structural data due to the implementation of a binary space partitioning (BSP) tree, b) set theory and c) functions that allow to combine a and b and that use human readable language in the search queries rather than complex computer language. All these factors combined facilitate the rapid development of bioinformatic tools that can perform quick and complex analyses of protein structures. p3d is the perfect tool to quickly develop tools for structural bioinformatics using the Python scripting language.

IGF-1 promotes the development and cytotoxic activity of human NK cells

PubMed Central

Ni, Fang; Sun, Rui; Fu, Binqing; Wang, Fuyan; Guo, Chuang; Tian, Zhigang; Wei, Haiming

2013-01-01

Insulin-like growth factor 1 (IGF-1) is a critical regulator of many physiological functions, ranging from longevity to immunity. However, little is known about the role of IGF-1 in natural killer cell development and function. Here, we identify an essential role for IGF-1 in the positive regulation of human natural killer cell development and cytotoxicity. Specifically, we show that human natural killer cells have the ability to produce IGF-1 and that differential endogenous IGF-1 expression leads to disparate cytotoxicity in human primary natural killer cells. Moreover, miR-483-3p is identified as a critical regulator of IGF-1 expression in natural killer cells. Overexpression of miR-483-3p has an effect similar to IGF-1 blockade and decreased natural killer cell cytotoxicity, whereas inhibition of miR-483-3p has the opposite effect, which is reversible with IGF-1 neutralizing antibody. These findings indicate that IGF-1 and miR-483-3p belong to a new class of natural killer cell functional modulators and strengthen the prominent role of IGF-1 in innate immunity. PMID:23403580

E1-Like Activating Enzyme Atg7 Is Preferentially Sequestered into p62 Aggregates via Its Interaction with LC3-I

PubMed Central

Gao, Wentao; Chen, Zhixia; Wang, Wei; Stang, Michael T.

2013-01-01

p62 is constitutively degraded by autophagy via its interaction with LC3. However, the interaction of p62 with LC3 species in the context of the LC3 lipidation process is not specified. Further, the p62-mediated protein aggregation’s effect on autophagy is unclear. We systemically analyzed the interactions of p62 with all known Atg proteins involved in LC3 lipidation. We find that p62 does not interact with LC3 at the stages when it is being processed by Atg4B or when it is complexed or conjugated with Atg3. p62 does interact with LC3-I and LC3-I:Atg7 complex and is preferentially recruited by LC3-II species under autophagic stimulation. Given that Atg4B, Atg3 and LC3-Atg3 are indispensable for LC3-II conversion, our study reveals a protective mechanism for Atg4B, Atg3 and LC3-Atg3 conjugate from being inappropriately sequestered into p62 aggregates. Our findings imply that p62 could potentially impair autophagy by negatively affecting LC3 lipidation and contribute to the development of protein aggregate diseases. PMID:24023838

E1-like activating enzyme Atg7 is preferentially sequestered into p62 aggregates via its interaction with LC3-I.

PubMed

Gao, Wentao; Chen, Zhixia; Wang, Wei; Stang, Michael T

2013-01-01

p62 is constitutively degraded by autophagy via its interaction with LC3. However, the interaction of p62 with LC3 species in the context of the LC3 lipidation process is not specified. Further, the p62-mediated protein aggregation's effect on autophagy is unclear. We systemically analyzed the interactions of p62 with all known Atg proteins involved in LC3 lipidation. We find that p62 does not interact with LC3 at the stages when it is being processed by Atg4B or when it is complexed or conjugated with Atg3. p62 does interact with LC3-I and LC3-I:Atg7 complex and is preferentially recruited by LC3-II species under autophagic stimulation. Given that Atg4B, Atg3 and LC3-Atg3 are indispensable for LC3-II conversion, our study reveals a protective mechanism for Atg4B, Atg3 and LC3-Atg3 conjugate from being inappropriately sequestered into p62 aggregates. Our findings imply that p62 could potentially impair autophagy by negatively affecting LC3 lipidation and contribute to the development of protein aggregate diseases.

Deregulated Cardiac Specific MicroRNAs in Postnatal Heart Growth.

PubMed

Yu, Pujiao; Wang, Hongbao; Xie, Yuan; Zhou, Jinzhe; Yao, Jianhua; Che, Lin

2016-01-01

The heart is recognized as an organ that is terminally differentiated by adulthood. However, during the process of human development, the heart is the first organ with function in the embryo and grows rapidly during the postnatal period. MicroRNAs (miRNAs, miRs), as regulators of gene expression, play important roles during the development of multiple systems. However, the role of miRNAs in postnatal heart growth is still unclear. In this study, by using qRT-PCR, we compared the expression of seven cardiac- or muscle-specific miRNAs that may be related to heart development in heart tissue from mice at postnatal days 0, 3, 8, and 14. Four miRNAs-miR-1a-3p, miR-133b-3p, miR-208b-3p, and miR-206-3p-were significantly decreased while miR-208a-3p was upregulated during the postnatal heart growth period. Based on these results, GeneSpring GX was used to predict potential downstream targets by performing a 3-way comparison of predictions from the miRWalk, PITA, and microRNAorg databases. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were used to identify potential functional annotations and signaling pathways related to postnatal heart growth. This study describes expression changes of cardiac- and muscle-specific miRNAs during postnatal heart growth and may provide new therapeutic targets for cardiovascular diseases.

Phase II - P3 Award Winners

EPA Pesticide Factsheets

Those teams that win one of EPA's P3 Awards are eligible to receive additional funding from EPA of up $75,000 to further develop their design, move it to the marketplace, or implement it in the field.

The Validation of a Case-Based, Cumulative Assessment and Progressions Examination

PubMed Central

Coker, Adeola O.; Copeland, Jeffrey T.; Gottlieb, Helmut B.; Horlen, Cheryl; Smith, Helen E.; Urteaga, Elizabeth M.; Ramsinghani, Sushma; Zertuche, Alejandra; Maize, David

2016-01-01

Objective. To assess content and criterion validity, as well as reliability of an internally developed, case-based, cumulative, high-stakes third-year Annual Student Assessment and Progression Examination (P3 ASAP Exam). Methods. Content validity was assessed through the writing-reviewing process. Criterion validity was assessed by comparing student scores on the P3 ASAP Exam with the nationally validated Pharmacy Curriculum Outcomes Assessment (PCOA). Reliability was assessed with psychometric analysis comparing student performance over four years. Results. The P3 ASAP Exam showed content validity through representation of didactic courses and professional outcomes. Similar scores on the P3 ASAP Exam and PCOA with Pearson correlation coefficient established criterion validity. Consistent student performance using Kuder-Richardson coefficient (KR-20) since 2012 reflected reliability of the examination. Conclusion. Pharmacy schools can implement internally developed, high-stakes, cumulative progression examinations that are valid and reliable using a robust writing-reviewing process and psychometric analyses. PMID:26941435

Determinant Factors of Long-Term Performance Development in Young Swimmers.

PubMed

Morais, Jorge E; Silva, António J; Marinho, Daniel A; Lopes, Vítor P; Barbosa, Tiago M

2017-02-01

To develop a performance predictor model based on swimmers' biomechanical profile, relate the partial contribution of the main predictors with the training program, and analyze the time effect, sex effect, and time × sex interaction. 91 swimmers (44 boys, 12.04 ± 0.81 y; 47 girls, 11.22 ± 0.98 y) evaluated during a 3-y period. The decimal age and anthropometric, kinematic, and efficiency features were collected 10 different times over 3 seasons (ie, longitudinal research). Hierarchical linear modeling was the procedure used to estimate the performance predictors. Performance improved between season 1 early and season 3 late for both sexes (boys 26.9% [20.88;32.96], girls 16.1% [10.34;22.54]). Decimal age (estimate [EST] -2.05, P < .001), arm span (EST -0.59, P < .001), stroke length (EST 3.82; P = .002), and propelling efficiency (EST -0.17, P = .001) were entered in the final model. Over 3 consecutive seasons young swimmers' performance improved. Performance is a multifactorial phenomenon where anthropometrics, kinematics, and efficiency were the main determinants. The change of these factors over time was coupled with the training plans of this talent identification and development program.

Combined Chlorophyll Fluorescence and Transcriptomic Analysis Identifies the P3/P4 Transition as a Key Stage in Rice Leaf Photosynthetic Development1[OPEN

PubMed Central

Yaapar, Muhammad N.; Wanchana, Samart; Thakur, Vivek; Quick, W. Paul

2016-01-01

Leaves are derived from heterotrophic meristem tissue that, at some point, must make the transition to autotrophy via the initiation of photosynthesis. However, the timing and spatial coordination of the molecular and cellular processes underpinning this switch are poorly characterized. Here, we report on the identification of a specific stage in rice (Oryza sativa) leaf development (P3/P4 transition) when photosynthetic competence is first established. Using a combined physiological and molecular approach, we show that elements of stomatal and vascular differentiation are coordinated with the onset of measurable light absorption for photosynthesis. Moreover, by exploring the response of the system to environmental perturbation, we show that the earliest stages of rice leaf development have significant plasticity with respect to elements of cellular differentiation of relevance for mature leaf photosynthetic performance. Finally, by performing an RNA sequencing analysis targeted at the early stages of rice leaf development, we uncover a palette of genes whose expression likely underpins the acquisition of photosynthetic capability. Our results identify the P3/P4 transition as a highly dynamic stage in rice leaf development when several processes for the initiation of photosynthetic competence are coordinated. As well as identifying gene targets for future manipulation of rice leaf structure/function, our data highlight a developmental window during which such manipulations are likely to be most effective. PMID:26813793

Combined Chlorophyll Fluorescence and Transcriptomic Analysis Identifies the P3/P4 Transition as a Key Stage in Rice Leaf Photosynthetic Development.

PubMed

van Campen, Julia C; Yaapar, Muhammad N; Narawatthana, Supatthra; Lehmeier, Christoph; Wanchana, Samart; Thakur, Vivek; Chater, Caspar; Kelly, Steve; Rolfe, Stephen A; Quick, W Paul; Fleming, Andrew J

2016-03-01

Leaves are derived from heterotrophic meristem tissue that, at some point, must make the transition to autotrophy via the initiation of photosynthesis. However, the timing and spatial coordination of the molecular and cellular processes underpinning this switch are poorly characterized. Here, we report on the identification of a specific stage in rice (Oryza sativa) leaf development (P3/P4 transition) when photosynthetic competence is first established. Using a combined physiological and molecular approach, we show that elements of stomatal and vascular differentiation are coordinated with the onset of measurable light absorption for photosynthesis. Moreover, by exploring the response of the system to environmental perturbation, we show that the earliest stages of rice leaf development have significant plasticity with respect to elements of cellular differentiation of relevance for mature leaf photosynthetic performance. Finally, by performing an RNA sequencing analysis targeted at the early stages of rice leaf development, we uncover a palette of genes whose expression likely underpins the acquisition of photosynthetic capability. Our results identify the P3/P4 transition as a highly dynamic stage in rice leaf development when several processes for the initiation of photosynthetic competence are coordinated. As well as identifying gene targets for future manipulation of rice leaf structure/function, our data highlight a developmental window during which such manipulations are likely to be most effective. © 2016 American Society of Plant Biologists. All Rights Reserved.

Involvement of microRNA miR-2b-3p in regulation of metabolic resistance to insecticides in Plutella xylostella.

PubMed

Etebari, K; Afrad, M H; Tang, B; Silva, R; Furlong, M J; Asgari, S

2018-03-24

The diamondback moth, Plutella xylostella, has developed extremely high levels of resistance to chlorantraniliprole and other classes of insecticides in the field. As microRNAs (miRNAs) play important roles in various biological processes through gene regulation, we examined the miRNA profile of P. xylostella in response to chlorantraniliprole exposure. RNA sequencing analysis showed that insecticide treatment caused significant changes in the abundance of some miRNAs. Increasing exposure time and insecticide concentration induced more dysregulated miRNAs in P. xylostella larvae. We also screened potential target genes for some of the differentially expressed miRNAs (such as miR-2b-3p, miR-14b-5p and let-7-5p), which may play important roles in insecticide resistance development. Exposure of P. xylostella larvae to chlorantraniliprole caused considerable overexpression in the transcript levels of potential target genes cytochrome P450 9f2 (CYP9F2) and 307a1 (CYP307a1). Application of miR-2b-3p and miR-14b-5p mimics significantly suppressed the relative transcript levels of CYP9F2 and CYP307a1, respectively, in a P. xylostella cell line. Furthermore, enrichment of P. xylostella diet with miR-2b-3p mimics significantly increased mortality in deltamethrin-resistant larvae when exposed to deltamethrin. The results suggest that miR-2b-3p may suppress CYP9F2 transcript levels in P. xylostella and consequently inhibit larval detoxification pathways. The findings provide an insight into possible role of miRNAs in regulation of metabolic resistance of insects to insecticides. © 2018 The Royal Entomological Society.

[Evaluation of mental development of children with congenital hypothyroidism detected in screening test--personal observations].

PubMed

Kik, Eugenia; Noczyńska, Anna

2010-01-01

Thyroid hormones are crucial for a proper development of the central nervous system (CNS), skeleton and tooth buds. They are important from the early stages of fetal development. The aim of the study was to evaluate the mental development of children with congenital hypothyroidism detected in screening and to determine the effect of TSH, level of thyroid hormones during observation, perinatal factors as well as parental and environmental factors on the children's IQ. 44 children (28 girls and 16 boys) aged 3.5-18 years (mean age 7.3+/- 3.5) were enrolled in the study. The subjects' mental development was analyzed. General intelligence quotient was measured on verbal and non-verbal scale and chosen parameters of mental development were measured. The evaluation of mental development was performed in two age groups: group A - 20 patients in the age range 3.5-5.9 years (mean age 5.3+/-0.8) tested using the Columbus method, and group B - 24 patients in the age range 6-18 years (mean age 10.3+/-2.2) tested on the Wechsler Scale. The intelligence quotient (IQ) in both groups was within the average IQ range on Wechsler scale. Mean IQ values on verbal and non-verbal scale were comparable and within the average IQ range on Wechsler scale. The level of intelligence in group A correlated, on the brink of statistical significance (IS), with the education level of the parents (r=0.32; p=0.0934), while in the group B - IS correlated with birth weight (r=0.62; p=0.00247), it correlated on the brink of statistical significance with the education level of parents (r=0.4; p=0.0532) and mother's age (r=0.41; p=0.0514). The level of intelligence on verbal scale in group B, statistically significant, positively correlated with the body mass at birth (r=0.62; p=0.00147) and negatively with the mean value of TSH in 2-year follow-up period (r=-0.47; p=0.0381). The level of general intelligence and on verbal and non-verbal scale did not correlate with the time of commencement of therapy with LT4, place of residence or TSH value in the screening test. 1. Mental development of the studied children with CH was within normal range. 2. Out of all measured parameters determining mental development, tasks in mathematics, analysis and synthesis, visual concentration and concentration on the hearing level had worst results. 3. The level of TSH in the screening test had no effect on the mental development of children with CH. 4. Out of all environmental factors, parental education influenced the mental development of the studied children.

Effects of interdisciplinary training on MCH professionals, organizations and systems.

PubMed

Margolis, Lewis H; Rosenberg, Angela; Umble, Karl; Chewning, Linda

2013-07-01

We studied the effects of the Interdisciplinary Leadership Development Program (ILDP) on MCH trainees from five MCHB-funded training programs at the UNC-Chapel Hill from the years 2001-2008. Specifically, we examined attitudes/beliefs about interdisciplinary practice and the frequency of use of interdisciplinary skills; identified effects of interdisciplinary training on career choices; and, examined the ways in which graduates used their interdisciplinary skills to effect change in MCH organizations and systems, up to 8 years after completion of training. Using a post-test design, participants in the ILDP were contacted to complete a web-based survey. Non-participating LEND and public health graduates were recruited for comparison. Guided by EvaluLEAD, we designed questions that asked graduates to rate the influence of their programs on their attitudes/beliefs and skills (on 5-point Likert scales), and to describe those influences in some detail in open-ended questions. The 208 respondents represented 59.6 % of the graduates from 2001 through 2008. Model-predicted mean levels of frequency of use of interdisciplinary skilIs was associated with ILDP participation (p = 0.008) and nearly so for interdisciplinary attitudes/beliefs (p = 0.067). There is an association between four domains of systems changes and frequency of skill use: develop/improve a program (3.24 vs. 2.74, p < 0.0001); improve the way an organization works (3.31 vs. 2.88, p < 0.0001); develop/improve a partnership (3.22 vs. 2.83, p < 0.0003); and, develop a policy (3.32 vs. 2.98, p < 0.0013). Graduates used interdisciplinary training to improve outcomes for families and to effect change in MCH systems. MCH leaders should disseminate, more broadly, rigorous assessments of the training intended to develop leadership competencies that underpin effective interdisciplinary practice.

Intravenous Vancomycin Associated With the Development of Nephrotoxicity in Patients With Class III Obesity.

PubMed

Choi, Yookyung Christy; Saw, Stephen; Soliman, Daniel; Bingham, Angela L; Pontiggia, Laura; Hunter, Krystal; Chuang, Linda; Siemianowski, Laura A; Ereshefsky, Benjamin; Hollands, James M

2017-11-01

A consensus statement recommends initial intravenous (IV) vancomycin dosing of 15-20 mg/kg every 8- 24 hours, with an optional 25- to 30-mg/kg loading dose. Although some studies have shown an association between weight and the development of vancomycin-associated nephrotoxicity, results have been inconsistent. To evaluate the correlation between incidence of nephrotoxicity associated with weight-based IV vancomycin dosing strategies in nonobese and obese patients. This retrospective cohort study evaluated hospitalized adult patients admitted who received IV vancomycin. Patients were stratified into nonobese (body mass index [BMI] <25 kg/m 2 ), obesity class I and II (BMI 30-39.9kg/m 2 ), and obesity class III (BMI≥40 kg/m 2 ) groups; patients who were overweight but not obese were excluded. Incidence of nephrotoxicity and serum vancomycin trough concentrations were evaluated. Of a total of 62 documented cases of nephrotoxicity (15.1%), 13 (8.7%), 23 (14.3%), and 26 (26.3%) cases were observed in nonobese, obesity class I and II, and obesity class III groups, respectively ( P=0.002). Longer durations of therapy ( P<0.0001), higher initial maintenance doses in both total milligrams/day ( P=0.0137) and milligrams/kilogram ( P=0.0307), and any trough level >20 mg/L ( P<0.0001) were identified as predictors of development of nephrotoxicity. Concomitant administration of piperacillin/tazobactam, diuretics, and IV contrast were associated with development of nephrotoxicity ( P<0.005, all). Patients with class III obesity were 3-times as likely to develop nephrotoxicity when compared with nonobese patients (odds ratio [OR]=2.99; CI=1.12-7.94) and obesity class I and II patients (OR=3.14; CI=1.27-7.75). Obesity and other factors are associated with a higher risk of vancomycin-associated nephrotoxicity.

Does enhanced diabetes management reduce the risk and improve the outcome of tuberculosis?

PubMed

Lo, H-Y; Yang, S-L; Lin, H-H; Bai, K-J; Lee, J-J; Lee, T-I; Chiang, C-Y

2016-03-01

The Bureau of National Health Insurance (NHI) has implemented a pay-for-performance (p4p) programme for diabetes mellitus (DM) in Taiwan. To investigate whether patients with DM enrolled in the p4p programme (DM-p4p) are less likely to develop tuberculosis (TB) and whether they have a better outcome than patients with DM not enrolled in the p4p programme (DM-non-p4p) if they do develop TB. A random sample of 79,471 DM-p4p, 100,000 DM-non-p4p and 100,000 non-diabetic patients (non-DM) was obtained from the 2008-2009 NHI database, and the patients were matched with the National TB Registry to determine whether they had developed TB by the end of 2010. The average annual incidence of TB was respectively 259.9 (95%CI 230.2-293.4), 137.5 (95%CI 116.4-162.5) and 74.1 (95%CI 59.0-93.0) per 100,000 population among DM-non-p4p, DM-p4p and non-DM patients. The relative risk of death over treatment success was 1.79 (95%CI 1.05-3.04) among DM-non-p4p and 1.69 (95%CI 0.84-3.40) among non-DM patients, relative to DM-p4p patients. Enhanced case management of DM reduced risk and improved outcomes of TB among patients with DM.

Risk factors for the development of uterine cancer in breast cancer survivors: an army of women study.

PubMed

Torres, Diogo; Myers, John A; Eshraghi, Leah W; Riley, Elizabeth C; Soliman, Pamela T; Milam, Michael R

2015-01-01

Our study compares breast cancer survivors without a secondary diagnosis of uterine cancer (BC) to breast cancer survivors with a diagnosis of uterine cancer (BUC) to determine clinical characteristics that increase the odds of developing uterine cancer. A total of 7,228 breast cancer survivors were surveyed. A case-control study was performed with 173 BUC patients matched by age and race in a 1:5 ratio to 865 BC patients. Multivariable logistic regression examined which factors influence the odds of developing uterine cancer. A total of 5,980 (82.3 %) women did not have a previous hysterectomy at the time of breast cancer diagnosis, of which 173 (2.9 %) subsequently developed uterine cancer. There was no significant difference in body mass index (BMI) (34.4 vs. 34.1, p = 0.388) or age (52.3 vs. 52.3 years, p = 0.999) between the two groups. Increased odds for developing uterine cancer were found in patients with a personal history of hypertension [odds ratio (OR) = 1.62, 95 % confidence interval (CI) 1.45-2.70, p < 0.001], gallbladder disease (OR = 1.30, 95 % CI 1.14-1.55, p = 0.005), and thyroid disease (OR = 1.55, 95 % CI 1.37-1.69, p < 0.001). More than 80 % of women in both groups expressed a desire for a blood test to estimate the risk of uterine cancer (80.4 % BUC vs. 91.2 % BC, p < 0.001). Hypertension, gallbladder disease, and thyroid disease in breast cancer survivors increase the odds of developing uterine cancer. Breast cancer survivors also express significant interest in potential serum tests to assess the risk of developing uterine cancer.

Sepsis Within 30 Days of Geriatric Hip Fracture Surgery.

PubMed

Bohl, Daniel D; Iantorno, Stephanie E; Saltzman, Bryan M; Tetreault, Matthew W; Darrith, Brian; Della Valle, Craig J

2017-10-01

Sepsis after hip fracture typically develops from one of the 3 potential infectious sources: urinary tract infection (UTI), pneumonia, and surgical site infection (SSI). The purpose of this investigation is to determine (1) the proportion of cases of sepsis that arises from each of these potential infectious sources; (2) baseline risk factors for developing each of the potential infectious sources; and (3) baseline risk factors for developing sepsis. The National Surgical Quality Improvement Program database was searched for geriatric patients (aged >65 years) who underwent surgery for hip fracture during 2005-2013. Patients subsequently diagnosed with sepsis were categorized according to concomitant diagnosis with UTI, SSI, and/or pneumonia. Multivariate regression was used to test for associations while adjusting for baseline characteristics. Among the 466 patients who developed sepsis (2.4% of all patients), 157 (33.7%) also had a UTI, 135 (29.0%) also had pneumonia, and 36 (7.7%) also had SSI. The rate of sepsis was elevated in patients who developed UTI (13.0% vs 1.7%; P < .001), pneumonia (18.2% vs 1.8%; P < .001), or SSI (14.8% vs 2.3%; P < .001). The mortality rate was elevated among those who developed sepsis (21.0% vs 3.8%; P < .001). Sepsis occurs in about 1 in 40 patients after geriatric hip fracture surgery. Of these septic cases, 1 in 3 is associated with UTI, 1 in 3 with pneumonia, and 1 in 15 with SSI. The cause of sepsis is often unknown on clinical diagnosis, and this distribution of potential infectious sources allows clinicians for direct identification and treatment. Copyright © 2017 Elsevier Inc. All rights reserved.

Mixed-Substituent Cyclophosphazenes with Calamitic and Polycatenar Mesogens.

PubMed

Jiménez, J; Callizo, L; Serrano, J L; Barberá, J; Oriol, L

2017-07-17

A synthetic strategy has been developed to prepare liquid crystalline cyclotriphosphazenes that have two different types of mesogenic units linked to the same phosphorus atom. Hexachlorocyclotriphosphazene, N 3 P 3 Cl 6 , was reacted with 3 mol of the calamitic unit 4-cyano-4'-hydroxybiphenyl to give a mixture of compounds in which the nongem-trans-trisubstituted derivative N 3 P 3 Cl 3 (OC 6 H 4 C 6 H 4 {CN}-p) 3 was the major product. The substitution of all three chlorine atoms in this nongeminal compound gave rise to the hydroxyl-functional phosphazenes, nongem-trans-N 3 P 3 (OC 6 H 4 C 6 H 4 {CN}-p) 3 (OC 6 H 4 {OH}-p) 3 or nongem-trans-N 3 P 3 (OC 6 H 4 C 6 H 4 {CH 3 }-p) 3 (OC 6 H 4 {OH}-p) 3 , from which the second mesogenic unit, a polycatenar one, was introduced. The chemical structure of the resulting materials, deduced from spectroscopic and MALDI-TOF techniques, was in accordance with monodisperse, fully functionalized cyclotriphosphazenes. Mesomorphism is highly dependent on the terminal group of the calamitic units, and liquid crystal phases were only detected on the cyano-derivatives. The calamitic or columnar nature of the mesophase depends on the number of alkyl chains of the polycatenar moieties.

[Molecular genetics of functional articulation disorder in children].

PubMed

Zhao, Yun-Jing; Ma, Hong-Wei

2012-04-01

Genetic factors are an important cause of functional articulation disorder in children. This article reviews some genes and chromosome regions associated with a genetic susceptibility to functional articulation disorders. The forkhead box P2 (FOXP2) gene on chromosome 7 is introduced in details including its structure, expression and function. The relationship between the FOXP2 gene and developmental apraxia of speech is discussed. As a transcription factor, FOXP2 gene regulates the expression of many genes. CNTNAP2 as an important target gene of FOXP2 is a key gene influencing language development. Functional articulation disorder may be developed to dyslexia, therefore some candidate regions and genes related to dyslexia, such as 3p12-13, 15q11-21, 6p22 and 1p34-36, are also introduced. ROBO1 gene in 3p12.3, ZNF280D gene, TCF12 gene, EKN1 gene in 15q21, and KIAA0319 gene in 6p22 have been candidate genes for the study of functional articulation disorder.

Phosphorylated Smad2 and Smad3 signaling: Shifting between tumor suppression and fibro-carcinogenesis in chronic hepatitis C.

PubMed

Yamaguchi, Takashi; Matsuzaki, Koichi; Inokuchi, Ryosuke; Kawamura, Rinako; Yoshida, Katsunori; Murata, Miki; Fujisawa, Junichi; Fukushima, Nobuyoshi; Sata, Michio; Kage, Masayoshi; Nakashima, Osamu; Tamori, Akihiro; Kawada, Norifumi; Tsuneyama, Koichi; Dooley, Steven; Seki, Toshihito; Okazaki, Kazuichi

2013-12-01

Insight into hepatic fibrogenesis and carcinogenesis (fibro-carcinogenesis) caused by hepatitis C virus (HCV) infection has come from recent analyses of transforming growth factor (TGF)-β signaling. TGF-β type I receptor and pro-inflammatory cytokine-activated kinases differentially phosphorylate Smad2 and Smad3 to create C-terminally (C), linker (L) or dually (L/C) phosphorylated (p) isoforms. This study aimed to elucidate how HCV infection affected hepatic fibro-carcinogenesis, particularly via phospho-Smad signaling. We first studied phospho-Smad2/3 positivity of 100 patients in different stages of HCV-related chronic liver disease. To examine changes in phospho-Smad2/3 after HCV clearance, we analyzed 32 paired liver biopsy samples obtained before and after sustained virological response (SVR), dividing patients into two groups: 20 patients not developing hepatocellular carcinoma (HCC) after attaining SVR (non-HCC group), and 12 patients who developed HCC despite SVR (HCC group). Hepatocytic tumor-suppressive pSmad3C signaling shifted to carcinogenic pSmad3L and fibrogenic pSmad2L/C signaling as liver diseases progressed. In the non-HCC group, 13 patients (65%) displayed fibrotic regression and inflammation reduction after SVR. Interestingly, SVR restored cytostatic pSmad3C signaling in hepatocytes, while eliminating prior carcinogenic pSmad3L and fibrogenic pSmad2L/C signaling. In the HCC group, seven patients (58%) displayed unchanged or even progressed fibrosis despite smoothened inflammatory activity, reflecting persistently high numbers of hepatocytes with pSmad3L- and pSmad2L/C-signaling and low pSmad3C-signaling. HCV clearance limits fibrosis and reduces HCC incidence by switching inflammation-dependent phospho-Smad signaling from fibro-carcinogenesis to tumor suppression. However, progression to HCC would occur in severely fibrotic livers if an inflammation-independent fibro-carcinogenic process has already begun before HCV clearance. © 2013 The Japan Society of Hepatology.

IDO-expressing Fibroblasts Suppress the Development of Imiquimod-induced Psoriasis-like Dermatitis.

PubMed

Elizei, Sanam Salimi; Pakyari, Mohammadreza; Ghoreishi, Mehraneh; Kilani, Ruhangiz; Mahmoudi, Sanaz; Ghahary, Aziz

2018-01-01

Psoriasis is a chronic skin condition whose pathogenesis is reported to be due to the activation of the interleukin-23/interleukin-17 (IL-23/IL-17) pathway. Here, we report that indoleamine 2,3-dioxygenase (IDO)-expressing fibroblasts reduce the activity of this pathway in activated immune cells. The findings showed that intralesional injection of IDO-expressing fibroblasts in imiquimod-induced psoriasis-like dermatitis on the back and ear (Pso. ear group) in mice significantly improves the clinical lesional appearance by reducing the number of skin-infiltrated IL-17+ CD4+ T cells (1.9% ± 0.3% vs. 6.9% ± 0.6%, n = 3, P value < 0.01), IL-17+ γδ+ T cells (2.8% ± 0.3% vs. 11.6% ± 1.2%, n = 3, P value < 0.01), IL-23+ activated dendritic cells (7.6% ± 0.9% vs. 14.0% ± 0.5%, n = 3, P < 0.01), macrophages (4.3% ± 0.1% vs. 11.3% ± 1.0%, n = 3, P value < 0.01), and granulocytes (2.5% ± 0.4% vs. 4.5% ± 0.3%, n = 3, P value < 0.01) as compared to untreated psoriatic mice. This finding suggests that IDO-expressing fibroblasts, and to a lesser extent, non-IDO primary fibroblasts suppress the psoriatic-like symptoms by inhibiting the infiltration of key immune cells involved in the development of psoriasis.

Laboratory Studies in UV and EUV Solar Physics

NASA Technical Reports Server (NTRS)

Wagner, William J. (Technical Monitor); Kohl, John L.

2005-01-01

A new 5 GHZ Electron Cyclotron Resonance (ECR) ion source for SAO's Ion Beam Experiment was designed, built and tested. Absolute cross sections were measured for electron impact excitation (EIE) in C(2+) (2s2p (3)P(sup o) - 2p(sup 2) (3)P), and empirical EIE rate coefficients were derived. The absolute cross section for EIE in Si(2+) (3s3p (3)P(sup o) - 3s3p (1)P(sup o)) was measured, and our experimental values for absolute cross sections for EIE in C(3+) (2s (2)S - 2p (2)P(sup o)) were reanalyzed and compared to values obtained by other experimental methods and by theory. In addition, a paper was published. The development and testing of the new ion source, the Si(2+) EIE measurements, and the reevaluation of the cross sections for C(3+) resulted from the Ph.D. research of Paul H. Janzen who completed the degree requirements for the Harvard University Department of Physics in 2002. John Kohl served as the Ph.D.Thesis Advisor. Because of delays in bringing the new ion source on line, the measurements of EIE in C(2+) (2s2p (3)P(sup o) - (2)p(sup 2) (3)P) were not completed until 2004. Preparations for measurements of EIE in C(2+) (1s(sup 2) (1)S - 2s2p (1)P(sup o)) are currently underway.

Effects of seawater acidification on the early development of sea urchin Glyptocidaris crenularis

NASA Astrophysics Data System (ADS)

Zhan, Yaoyao; Hu, Wanbin; Duan, Lizhu; Liu, Minbo; Zhang, Weijie; Chang, Yaqing; Li, Cong

2017-10-01

In this study, we evaluated the effects of CO2-induced seawater acidification on fertilization, embryogenesis and early larval development in the sea urchin Glyptocidaris crenularis, that inhabits subtidal coastal areas in northern China. The range in seawater pH used in experiments was based on the projections of the Intergovernmental Panel on Climate Change (IPCC), to the year 2100. A natural seawater treatment (pHnbs=7.98±0.03) and three laboratory-controlled acidified treatments (OA1, ΔpHnbs=-0.3 units; OA2, ΔpHnbs=-0.4 units; OA3, ΔpHnbs=-0.5 units) were used in experiments. Results show that: (1) there was a negative effect of seawater acidification on fertilization and on the percentage of abnormal fertilized eggs; (2) the size of early cleavage stage embryos decreased in a dose-dependent manner with decreasing pH; (3) both the hatching rate of blastulae and the survival rate of four-armed pluteus larvae decreased as pH declined; (4) larval abnormalities including asymmetrical development, changes in the length of skeletal elements, and corroded spicules were observed in all seawater acidified-treatments compared with the control. These data indicate that seawater acidification has a negative impact on the early development of G. crenularis, and supports the hypothesis that the response of echinoderms to ocean acidification (OA) varies among species. Further research is required to clarify the specific cellular mechanisms involved.

13th Annual P3 Awards: A National Student Design ...

EPA Pesticide Factsheets

2017-02-14

The EPA, as part of the P3-People, Prosperity and the Planet Award Program, is seeking applications proposing to research, develop, and design solutions to real world challenges involving the overall sustainability of human society.

p,p\\'-Dichlorodiphenyltrichloroethane (DDT)

Integrated Risk Information System (IRIS)

p , p ' - Dichlorodiphenyltrichloroethane ( DDT ) ; CASRN 50 - 29 - 3 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard

Development of an analytical method for quantitative comparison of the e-waste management systems in Thailand, Laos, and China.

PubMed

Liang, Li; Sharp, Alice

2016-11-01

This study employed a set of quantitative criteria to analyse the three parameters; namely policy, process, and practice; of the respective e-waste management systems adopted in Thailand, Laos, and China. Questionnaire surveys were conducted to determine the current status of the three parameters in relation to mobile phones. A total of five, three, and six variables under Policy (P 1 ), Process (P 2 ), and Practice (P 3 ), respectively, were analysed and their weighted averages were calculated. The results showed that among the three countries surveyed, significant differences at p<0.01 were observed in all the P 1 , P 2 , and P 3 variables, except P 305 (sending e-waste to recovery centres) and P 306 (treating e-waste by retailers themselves). Based on the quantitative method developed in this study, Laos' e-waste management system received the highest scores in both P 1 average (0.130) and P 3 average (0.129). However, in the combined P total , China scored the highest (0.141), followed by Laos (0.132) and Thailand (0.121). This method could be used to assist decision makers in performing quantitative analysis of complex issues associating with e-waste management in a country. © The Author(s) 2016.

Ab initio study of the operating mechanisms of tris(trimethylsilyl) phosphite as a multifunctional additive for Li-ion batteries

NASA Astrophysics Data System (ADS)

Kim, Dong Young; Park, Hosang; Choi, Woon Ih; Roy, Basab; Seo, Jinah; Park, Insun; Kim, Jin Hae; Park, Jong Hwan; Kang, Yoon-Sok; Koh, Meiten

2017-07-01

Tris(trimethylsilyl) phosphite (P(OSi(CH3)3)3) is a multifunctional electrolyte additive for scavenging HF and forming a cathode electrolyte interphase (CEI). Systematic analysis of the HF reaction pathways and redox potentials of P(OSi(CH3)3)3, OP(OSi(CH3)3)3, P(OSiF3)3, and OP(OSiF3)3, and their reaction products, using ab initio calculations allowed us to elucidate the operating mechanism of P(OSi(CH3)3)3 and verify the rules that determine its HF reaction pathways and electrochemical stability. While Osbnd Si cleavage is the predominant HF scavenging pathway for P(OSi(CH3)3)3, Osbnd P cleavage is stabilized by replacing CH3 with an electron-withdrawing group. Thus, P(OSiF3)3 scavenges HF mainly through Osbnd P cleavage to produce PF3, which has high oxidation stability. However, the Osbnd Si cleavage pathway produces P(OSi(CH3)3)2OH, P(OSi(CH3)3) (OH)2, and P(OH)3 sequentially, along with Si(CH3)3F. These PO3 systems, which are oxidized earlier than carbonate solutions and form tightly bonded units following oxidation, act as seed units for compact CEI growth. Moreover, the HF scavenging ability of PO3 systems is maintained during oxidation until all Osbnd Si bonds are broken. As a strategy for developing additives with enhanced functionality, modifying P(OSi(CH3)3)3 by replacing CH3 with an electron-donating group to exclusively utilize the Osbnd Si cleavage pathway for HF scavenging is recommended.

Identification of De Novo Copy Number Variants Associated with Human Disorders of Sexual Development

PubMed Central

Tannour-Louet, Mounia; Han, Shuo; Corbett, Sean T.; Louet, Jean-Francois; Yatsenko, Svetlana; Meyers, Lindsay; Shaw, Chad A.; Kang, Sung-Hae L.; Cheung, Sau Wai; Lamb, Dolores J.

2010-01-01

Disorders of sexual development (DSD), ranging in severity from genital abnormalities to complete sex reversal, are among the most common human birth defects with incidence rates reaching almost 3%. Although causative alterations in key genes controlling gonad development have been identified, the majority of DSD cases remain unexplained. To improve the diagnosis, we screened 116 children born with idiopathic DSD using a clinically validated array-based comparative genomic hybridization platform. 8951 controls without urogenital defects were used to compare with our cohort of affected patients. Clinically relevant imbalances were found in 21.5% of the analyzed patients. Most anomalies (74.2%) evaded detection by the routinely ordered karyotype and were scattered across the genome in gene-enriched subtelomeric loci. Among these defects, confirmed de novo duplication and deletion events were noted on 1p36.33, 9p24.3 and 19q12-q13.11 for ambiguous genitalia, 10p14 and Xq28 for cryptorchidism and 12p13 and 16p11.2 for hypospadias. These variants were significantly associated with genitourinary defects (P = 6.08×10−12). The causality of defects observed in 5p15.3, 9p24.3, 22q12.1 and Xq28 was supported by the presence of overlapping chromosomal rearrangements in several unrelated patients. In addition to known gonad determining genes including SRY and DMRT1, novel candidate genes such as FGFR2, KANK1, ADCY2 and ZEB2 were encompassed. The identification of risk germline rearrangements for urogenital birth defects may impact diagnosis and genetic counseling and contribute to the elucidation of the molecular mechanisms underlying the pathogenesis of human sexual development. PMID:21048976

Nomogram for individualized prediction of hepatocellular carcinoma occurrence in hepatitis C virus cirrhosis (ANRS CO12 CirVir).

PubMed

Ganne-Carrié, Nathalie; Layese, Richard; Bourcier, Valérie; Cagnot, Carole; Marcellin, Patrick; Guyader, Dominique; Pol, Stanislas; Larrey, Dominique; de Lédinghen, Victor; Ouzan, Denis; Zoulim, Fabien; Roulot, Dominique; Tran, Albert; Bronowicki, Jean-Pierre; Zarski, Jean-Pierre; Riachi, Ghassan; Calès, Paul; Péron, Jean-Marie; Alric, Laurent; Bourlière, Marc; Mathurin, Philippe; Blanc, Jean-Frédéric; Abergel, Armand; Serfaty, Lawrence; Mallat, Ariane; Grangé, Jean-Didier; Attali, Pierre; Bacq, Yannick; Wartelle, Claire; Dao, Thông; Benhamou, Yves; Pilette, Christophe; Silvain, Christine; Christidis, Christos; Capron, Dominique; Bernard-Chabert, Brigitte; Zucman, David; Di Martino, Vincent; Trinchet, Jean-Claude; Nahon, Pierre; Roudot-Thoraval, Françoise

2016-10-01

The aim of this work was to develop an individualized score for predicting hepatocellular carcinoma (HCC) in patients with hepatitis C (HCV)-compensated cirrhosis. Among 1,323 patients with HCV cirrhosis enrolled in the French prospective ANRS CO12 CirVir cohort, 720 and 360 were randomly assigned to training and validation sets, respectively. Cox's multivariate model was used to predict HCC, after which a nomogram was computed to assess individualized risk. During follow-up (median, 51.0 months), 103 and 39 patients developed HCC in the training and validation sets, respectively. Five variables were independently associated with occurrence of HCC: age > 50 years (hazard ratio [HR], 1.94; 95% confidence interval [CI], 1.16; 3.25; P = 0.012); past excessive alcohol intake (HR, 1.55; 95% CI, 1.02; 2.36; P = 0.041); low platelet count (<100 Giga/mm(3) : HR, 2.70; 95% CI, 1.62; 4.51; P < 0.001; [100; 150] Giga/mm(3) : HR, 1.87; 95% CI, 1.10; 3.18; P = 0.021); gamma-glutamyl transpeptidase above the upper limit of normal (HR, 1.96; 95% CI, 1.11; 3.47; P = 0.021); and absence of a sustained virological response during follow-up (HR, 3.02; 95% CI, 1.67; 5.48; P < 0.001). An 11-point risk score was derived from the training cohort and validated in the validation set. Based on this score, the population was stratified into three groups, in which HCC development gradually increased, from 0% to 30.1% at 5 years for patients with the lowest (≤3) and highest (≥8) scores (P < 0.001). Using this score, a nomogram was built enabling individualized prediction of HCC occurrence at 1, 3, and 5 years. This HCC score can accurately predict HCC at an individual level in French patients with HCV cirrhosis. (Hepatology 2016;64:1136-1147). © 2016 by the American Association for the Study of Liver Diseases.

Brain Growth Rate Abnormalities Visualized in Adolescents with Autism

PubMed Central

Hua, Xue; Thompson, Paul M.; Leow, Alex D.; Madsen, Sarah K.; Caplan, Rochelle; Alger, Jeffry R.; O’Neill, Joseph; Joshi, Kishori; Smalley, Susan L.; Toga, Arthur W.; Levitt, Jennifer G.

2014-01-01

Autism spectrum disorder (ASD) is a heterogeneous disorder of brain development with wide-ranging cognitive deficits. Typically diagnosed before age 3, ASD is behaviorally defined but patients are thought to have protracted alterations in brain maturation. With longitudinal magnetic resonance imaging (MRI), we mapped an anomalous developmental trajectory of the brains of autistic compared to those of typically developing children and adolescents. Using tensor-based morphometry (TBM), we created 3D maps visualizing regional tissue growth rates based on longitudinal brain MRI scans of 13 autistic and 7 typically developing boys (mean age/inter-scan interval: autism 12.0 ± 2.3 years/2.9 ± 0.9 years; control 12.3 ± 2.4/2.8 ± 0.8). The typically developing boys demonstrated strong whole-brain white matter growth during this period, but the autistic boys showed abnormally slowed white matter development (p = 0.03, corrected), especially in the parietal (p = 0.008), temporal (p = 0.03) and occipital lobes (p =0.02). We also visualized abnormal overgrowth in autism in some gray matter structures, such as the putamen and anterior cingulate cortex. Our findings reveal aberrant growth rates in brain regions implicated in social impairment, communication deficits and repetitive behaviors in autism, suggesting that growth rate abnormalities persist into adolescence. TBM revealed persisting growth rate anomalies long after diagnosis, which has implications for evaluation of therapeutic effects. PMID:22021093

Brain growth rate abnormalities visualized in adolescents with autism.

PubMed

Hua, Xue; Thompson, Paul M; Leow, Alex D; Madsen, Sarah K; Caplan, Rochelle; Alger, Jeffry R; O'Neill, Joseph; Joshi, Kishori; Smalley, Susan L; Toga, Arthur W; Levitt, Jennifer G

2013-02-01

Autism spectrum disorder is a heterogeneous disorder of brain development with wide ranging cognitive deficits. Typically diagnosed before age 3, autism spectrum disorder is behaviorally defined but patients are thought to have protracted alterations in brain maturation. With longitudinal magnetic resonance imaging (MRI), we mapped an anomalous developmental trajectory of the brains of autistic compared with those of typically developing children and adolescents. Using tensor-based morphometry, we created 3D maps visualizing regional tissue growth rates based on longitudinal brain MRI scans of 13 autistic and seven typically developing boys (mean age/interscan interval: autism 12.0 ± 2.3 years/2.9 ± 0.9 years; control 12.3 ± 2.4/2.8 ± 0.8). The typically developing boys demonstrated strong whole brain white matter growth during this period, but the autistic boys showed abnormally slowed white matter development (P = 0.03, corrected), especially in the parietal (P = 0.008), temporal (P = 0.03), and occipital lobes (P = 0.02). We also visualized abnormal overgrowth in autism in gray matter structures such as the putamen and anterior cingulate cortex. Our findings reveal aberrant growth rates in brain regions implicated in social impairment, communication deficits and repetitive behaviors in autism, suggesting that growth rate abnormalities persist into adolescence. Tensor-based morphometry revealed persisting growth rate anomalies long after diagnosis, which has implications for evaluation of therapeutic effects. Copyright © 2011 Wiley Periodicals, Inc.

p38 MAP kinase is required for Wnt3a-mediated osterix expression independently of Wnt-LRP5/6-GSK3β signaling axis in dental follicle cells

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

Sakisaka, Yukihiko; Kanaya, Sousuke; Liason Center for Innovative Dentistry, Tohoku University Graduate School of Dentistry, Sendai 980-8575

Wnt3a is a secreted glycoprotein that activates the glycogen synthase kinase-3β (GSK3β)/β-catenin signaling pathway through low-density-lipoprotein receptor-related protein (LRP)5/6 co-receptors. Wnt3a has been implicated in periodontal development and homeostasis, as well as in cementum formation. Recently, we have reported that Wnt3a increases alkaline phosphatase expression through the induction of osterix (Osx) expression in dental follicle cells, a precursor of cementoblasts. However, the molecular mechanism by which Wnt3a induces Osx expression is still unknown. In this study, we show that Wnt3a-induced Osx expression was inhibited in the presence of p38 mitogen-activated protein kinase (MAPK) inhibitors (SB203580 and SB202190) at gene andmore » protein levels, as assessed by real-time PCR and immunocytohistochemistry, respectively. Pretreatment of cells with Dickkopf-1, a potent canonical Wnt antagonist binding to LRP5/6 co-receptors, did not influence Wnt3a-mediated p38 MAPK phosphorylation, suggesting that Wnt3a activates p38 MAPK through LRP5/6-independent signaling. On the other hand, pretreatment with p38 MAPK inhibitors had no effects on the phosphorylated status of GSK3β and β-catenin as well as β-catenin nuclear translocation, but inhibited Wnt3a-mediated β-catenin transcriptional activity. These findings suggest that p38 MAPK modulates canonical Wnt signaling at the β-catenin transcriptional level without any crosstalk with the Wnt3a-mediated LRP5/6-GSK3β signaling axis and subsequent β-catenin nuclear translocation. These findings expand our knowledge of the mechanisms controlling periodontal development and regeneration. - Highlights: • Wnt3a induces Osx expression via p38 MAPK signaling in dental follicle cells. • p38 MAPK has no crosstalk with Wnt3a-mediated LRP5/6 and GSK3β signaling. • p38 MAPK is required for Wnt signaling at the β-catenin transcriptional level.« less

Development of a Novel Escherichia coli-Kocuria Shuttle Vector Using the Cryptic pKPAL3 Plasmid from K. palustris IPUFS-1 and Its Utilization in Producing Enantiopure (S)-Styrene Oxide.

PubMed

Toda, Hiroshi; Itoh, Nobuya

2017-01-01

The novel cryptic pKPAL3 plasmid was isolated from the Gram-positive microorganism Kocuria palustris IPUFS-1 and characterized in detail. pKPAL3 is a circular plasmid that is 4,443 bp in length. Open reading frame (ORF) and homology search analyses indicated that pKPAL3 possesses four ORFs; however, there were no replication protein coding genes predicted in the plasmid. Instead, there were two nucleotide sequence regions that showed significant identities with untranslated regions of K. rhizophila DC2201 (NBRC 103217) genomic sequences, and these sequences were essential for autonomous replication of pKPAL3 in Kocuria cells. Based on these findings, we constructed the novel Escherichia coli - Kocuria shuttle vectors pKITE301 (kanamycin resistant) and pKITE303 (thiostrepton resistant) from pKPAL3. The copy numbers of the constructed shuttle vectors were estimated to be 20 per cell, and they exhibited low segregation stability in Kocuria transformant cells in the absence of antibiotics. Moreover, constructed vectors showed compatibility with the other K. rhizophila shuttle vector pKITE103. We successfully expressed multiple heterologous genes, including the styrene monooxygenase gene from Rhodococcus sp. ST-10 ( rhsmo ) and alcohol dehydrogenase gene from Leifsonia sp. S749 ( lsadh ), in K . rhizophila DC2201 using the pKITE301P and pKITE103P vectors under the control of the glyceraldehyde 3-phosphate dehydrogenase ( gapdh ) promotor. The RhSMO-LSADH co-expressing K. rhizophila was used as a biocatalyst in an organic solvent-water biphasic reaction system to efficiently convert styrene into ( S )-styrene oxide with 99% ee in the presence of 2-propanol as a hydrogen donor. The product concentration of the reaction in the organic solvent reached 235 mM after 30 h under optimum conditions. Thus, we demonstrated that this novel shuttle vector is useful for developing biocatalysts based on organic solvent-tolerant Kocuria cells.

Origin of the Outbreak in France of Pseudomonas syringae pv. actinidiae Biovar 3, the Causal Agent of Bacterial Canker of Kiwifruit, Revealed by a Multilocus Variable-Number Tandem-Repeat Analysis.

PubMed

Cunty, A; Cesbron, S; Poliakoff, F; Jacques, M-A; Manceau, C

2015-10-01

The first outbreaks of bacterial canker of kiwifruit caused by Pseudomonas syringae pv. actinidiae biovar 3 were detected in France in 2010. P. syringae pv. actinidiae causes leaf spots, dieback, and canker that sometimes lead to the death of the vine. P. syringae pv. actinidifoliorum, which is pathogenic on kiwi as well, causes only leaf spots. In order to conduct an epidemiological study to track the spread of the epidemics of these two pathogens in France, we developed a multilocus variable-number tandem-repeat (VNTR) analysis (MLVA). MLVA was conducted on 340 strains of P. syringae pv. actinidiae biovar 3 isolated in Chile, China, France, Italy, and New Zealand and on 39 strains of P. syringae pv. actinidifoliorum isolated in Australia, France, and New Zealand. Eleven polymorphic VNTR loci were identified in the genomes of P. syringae pv. actinidiae biovar 3 ICMP 18744 and of P. syringae pv. actinidifoliorum ICMP 18807. MLVA enabled the structuring of P. syringae pv. actinidiae biovar 3 and P. syringae pv. actinidifoliorum strains in 55 and 16 haplotypes, respectively. MLVA and discriminant analysis of principal components revealed that strains isolated in Chile, China, and New Zealand are genetically distinct from P. syringae pv. actinidiae strains isolated in France and in Italy, which appear to be closely related at the genetic level. In contrast, no structuring was observed for P. syringae pv. actinidifoliorum. We developed an MLVA scheme to explore the diversity within P. syringae pv. actinidiae biovar 3 and to trace the dispersal routes of epidemic P. syringae pv. actinidiae biovar 3 in Europe. We suggest using this MLVA scheme to trace the dispersal routes of P. syringae pv. actinidiae at a global level. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Previous cryopreservation alters the natural history of the red blood cell storage lesion

PubMed Central

Chang, Alex L.; Hoehn, Richard S.; Jernigan, Peter; Cox, Daniel; Schreiber, Martin; Pritts, Timothy A.

2016-01-01

Background During storage, packed red blood cells (pRBCs) undergo a number of biochemical, metabolic and morphologic changes, collectively known as the “storage lesion”. We aimed to determine the effect of cryopreservation on the red blood cell storage lesion compared to traditional 4°C storage. Methods Previously cryopreserved human packed red blood cells were compared to age matched never frozen packed red blood cells obtained from the local blood bank. The development of the red cell storage lesion was evaluated after 7, 14, 21, 28, and 42 days of storage at 4°C in AS-3 storage medium. We measured physiological parameters including cell counts, lactic acid and potassium concentrations as well as signs of eryptosis including loss of phosphatidylserine (PS) asymmetry, microparticle production and osmotic fragility in hypotonic saline. Results Compared to controls, previously cryopreserved pRBC at 7 days of storage in AS-3 showed lower red cell counts (3.7 vs 5.3 ×10^6 cells/uL, p(<0.01), hemoglobin (12.0 vs 16.5 g/dL, p<0.01), hematocrit (33.0 vs 46.5%, p<0.01), and pH (6.27 vs 6.72, p<0.01). Over 28 days of storage, storage cryopreserved pRBC developed increased cell free hemoglobin (0.7 vs 0.3 g/dL, p<0.01), greater PS exposure (10.1 vs 3.3%, p<0.01), and microparticle production (30,836 vs 1,802 MP/uL, p<0.01). Previously cryopreserved cells were also less resistant to osmotic stress. Conclusion The red blood cell storage lesion is accelerated in previously cryopreserved pRBC after thawing. Biochemical deterioration of thawed and deglycerolized red cells suggests that storage time prior to transfusion should be limited in order to achieve similar risk profiles as never frozen standard liquid storage pRBC units. PMID:27380532

Marmoset Cytochrome P450 3A4 Ortholog Expressed in Liver and Small-Intestine Tissues Efficiently Metabolizes Midazolam, Alprazolam, Nifedipine, and Testosterone.

PubMed

Uehara, Shotaro; Uno, Yasuhiro; Nakanishi, Kazuyuki; Ishii, Sakura; Inoue, Takashi; Sasaki, Erika; Yamazaki, Hiroshi

2017-05-01

Common marmosets ( Callithrix jacchus ), small New World primates, are increasingly attracting attention as potentially useful animal models for drug development. However, characterization of cytochrome P450 (P450) 3A enzymes involved in the metabolism of a wide variety of drugs has not investigated in marmosets. In this study, sequence homology, tissue distribution, and enzymatic properties of marmoset P450 3A4 ortholog, 3A5 ortholog, and 3A90 were investigated. Marmoset P450 3A forms exhibited high amino acid sequence identities (88-90%) to the human and cynomolgus monkey P450 3A orthologs and evolutionary closeness to human and cynomolgus monkey P450 3A orthologs compared with other P450 3A enzymes. Among the five marmoset tissues examined, P450 3A4 ortholog mRNA was abundant in livers and small intestines where P450 3A4 ortholog proteins were immunologically detected. Three marmoset P450 3A proteins heterologously expressed in Escherichia coli membranes catalyzed midazolam 1'- and 4-hydroxylation, alprazolam 4-hydroxylation, nifedipine oxidation, and testosterone 6 β -hydroxylation, similar to cynomolgus monkey and human P450 3A enzymes. Among the marmoset P450 3A enzymes, P450 3A4 ortholog effectively catalyzed midazolam 1'-hydroxylation, comparable to microsomes from marmoset livers and small intestines. Correlation analyses with 23 individual marmoset liver microsomes suggested contributions of P450 3A enzymes to 1'-hydroxylation of both midazolam (human P450 3A probe) and bufuralol (human P450 2D6 probe), similar to cynomolgus monkey P450 3A enzymes. These results indicated that marmoset P450 3A forms had functional characteristics roughly similar to cynomolgus monkeys and humans in terms of tissue expression patterns and catalytic activities, suggesting marmosets as suitable animal models for P450 3A-dependent drug metabolism. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

Growth, development, puberty and adult height of patients with congenital multiple pituitary hormone deficiencies.

PubMed

Haim-Pinhas, Hadar; Kauli, Rivka; Lilos, Pearl; Laron, Zvi

2016-04-01

Congenital MPHD is a rare condition caused by mutations in pituitary transcription factors genes: PROP1, POU1F1 (PIT1), HESX1, LHX3, LHX4. We evaluated in a retrospective study the effects on growth and development in 29 patients with congenital MPHD (cMPHD), during hGH replacement therapy alone and combined with sex hormones. Twenty nine patients with cMPHD were included and diagnosed, treated and followed in our clinic from diagnosis to adult age. Measurements on growth and development were taken by the same medical team. Mean birth weight of 21/29 neonates was 3126 ± 536 g. Mean birth length of 7/29 neonates was 48.7 ± 2 cm. Neuromotor development was normal or slightly delayed. Mean age at referral was 9.5 ± 7 years (m), 6.7 ± 3.5 years (f) (p=0.17). Height (SDS) before treatment was -2.8 ± 1.0 (m), -2.8 ± 1.0 (f) (p=0.99). Mean age at initiation of hGH treatment was 9.9 ± 6.7 years (m), 10.3 ± 4.2 years (f) (p=0.85). Mean age at initiation of sex hormone treatment was 17.0 ± 3.5 years (m), 17.1 ± 2.3 years (f) (p=0.88). Penile and testicular sizes were below normal before and after treatment. Head circumference (SD) was -1.9 ± 0.9 before and -0.6 ± 1.8 at end of treatment (p<0.001). Adult height (SDS) reached -1.1 ± 0.6 (p<0.001) for both males and females. Despite the multiple pituitary hormone deficiencies including hGH, children with congenital MPHD present with a better auxological development than children with congenital IGHD or congenital IGF-1 deficiency. These findings may be due to irregular and incomplete hormone deficiencies increasing with progressive age and late initiation of puberty. Copyright © 2016. Published by Elsevier Ltd.

Overweight adolescents eat what? And when? Analysis of consumption patterns to guide dietary message development for intervention.

PubMed

Smith, K L; Straker, L M; Kerr, D A; Smith, A J

2015-02-01

Little is known about overweight adolescent dietary consumption patterns, with challenges to collecting meaningful data making it difficult to develop targeted obesity interventions. The present study aimed to examine the timing and consumption of fruit, vegetables and junk food by time of the day and day of the week. Overweight adolescents (n = 61), aged 12-16 years, completed 3-day food records. Negative binomial and binary logistic regression using generalised estimating equations were used to compare the amount and likelihood of the consumption of each food group between time periods. Overweight adolescent girls were more likely to eat fruit on weekdays than weekends [odds ratio (OR) = 5.0. P < 0.001], as were boys (OR = 2.5, P = 0.034). Adolescents consumed more fruit at school than other meals [girls: incident rate ratio (IRR) = 7.5, P < 0.001; boys: IRR = 4.0, P = 0.050]. Weekday dinner was the meal where girls were most likely to consume vegetables (OR = 3.0, P = 0.009) and when boys consumed the most vegetables (IRR = 30.9, P = 0.006). Fast food consumption was most likely for girls at dinner on the weekend (OR = 9.6, P = 0.042), whereas fast food intake for boys increased overall on the weekend (IRR = 3.6, P = 0.001). Intake of 'other junk' (e.g. crisps) peaked during school hours for girls (IRR = 7.2, P < 0.001) and sugar-sweetened beverage consumption increased for boys on the weekend (IRR = 3.3, P = 0.001). Overall, trends in fruit intake showed opposing times for high and low consumption compared to vegetable intake. These results represent the next step in using time of day and day of week consumption patterns to develop targeted, evidence-based dietary messages for interventions in overweight adolescents. © 2014 The British Dietetic Association Ltd.

Localization of the calcium channel subunits Cav1.2 (alpha1C) and Cav2.3 (alpha1E) in the mouse organ of Corti.

PubMed

Waka, N; Knipper, M; Engel, J

2003-10-01

Voltage-activated Ca2+ channels play an important role in synaptic transmission, signal processing and development. The immunohistochemical localization of Cav1.2 (alpha1C) and Cav2.3 (alpha1E) Ca2+ channels was studied in the developing and adult mouse organ of Corti using subunit-specific antibodies and fluorescent secondary antibodies with cochlear cryosections. Cav1.2 immunoreactivity has been detected from postnatal day 14 (P14) onwards at the synapses between cholinergic medial efferents and outer hair cells as revealed by co-staining with anti-synaptophysin and anti-choline acetyltransferase. Most likely the Cav1.2 immunoreactivity was located presynaptically at the site of contact of the efferent bouton with the outer hair cell which suggests a role for class C L-type Ca2+ channels in synaptic transmission of the medial efferent system. The localization of the second Ca2+ channel tested, Cav2.3, showed a pronounced change during cochlear development. From P2 until P10, Cav2.3 immunoreactivity was found in the outer spiral bundle followed by the inner spiral bundle, efferent endings and by medial efferent fibers. Around P14, Cav2.3 immunoreactivity disappeared from these structures and from P19 onwards it was observed in the basal poles of the outer hair cell membranes.

The impact of PNPLA3 (rs738409 C>G) polymorphisms on liver histology and long-term clinical outcome in chronic hepatitis B patients.

PubMed

Brouwer, Willem P; van der Meer, Adriaan J; Boonstra, Andre; Pas, Suzan D; de Knegt, Robert J; de Man, Rob A; Hansen, Bettina E; ten Kate, Fiebo J W; Janssen, Harry L A

2015-02-01

We aimed to assess the association between the patatin-like phospholipase domain-containing-3 (PNPLA3) I148M polymorphism, liver histology and long-term outcome in chronic hepatitis B (CHB) patients. We enrolled 531 consecutive treatment naïve CHB patients diagnosed from 1985 to 2012 with an available liver biopsy for reassessment, and sample for genetic testing. Data on all-cause mortality and hepatocellular carcinoma (HCC) at long-term follow-up were obtained from national database registries. The prevalence of steatohepatitis increased with PNPLA3 CC (14%), CG (20%) and GG (43%) (P < 0.001). The association was altered by both gender (P = 0.010) and overweight (P = 0.015): the effect of PNPLA3 on steatohepatitis was most pronounced among non-overweight females (adjusted OR 13.4, 95%CI: 3.7-51.6, P < 0.001), and non-overweight males (adjusted OR 2.4, 95%CI: 1.4-4.3, P = 0.002). Furthermore, PNPLA3 GG genotype was associated with iron depositions (OR 2.8, 95%CI: 1.2-6.4, P = 0.014) and lobular inflammation (OR 2.2, 95%CI: 1.1-4.5, P = 0.032), but not with advanced fibrosis (OR 1.1, 95%CI: 0.7-1.8, P = 0.566). The median follow-up was 10.1 years (interquartile range 5.6 - 15.8), during which 13 patients developed HCC and 28 died. Steatohepatitis was associated with all-cause mortality [Hazard ratio (HR) 3.1, 95%CI: 1.3-7.3, P = 0.006] and HCC (HR 2.8, 95%CI: 0.9-9.2, P = 0.078), but no significant association was observed for PNPLA3. In this cohort of biopsied CHB patients, PNPLA3 was independently associated with steatosis, steatohepatitis, lobular inflammation and iron depositions, but not with advanced fibrosis, HCC development or all-cause mortality. The effect of PNPLA3 on steatohepatitis was particularly pronounced among female patients without severe overweight. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Early motor development and cognitive abilities among Mexican preschoolers.

PubMed

Osorio-Valencia, Erika; Torres-Sánchez, Luisa; López-Carrillo, Lizbeth; Rothenberg, Stephen J; Schnaas, Lourdes

2017-07-18

Psychomotricity plays a very important role in children's development, especially for learning involving reading-writing and mathematical calculations. Evaluate motor development in children 3 years old and its relationship with their cognitive abilities at the age of 5 years. Based on a cohort study, we analyzed the information about motor performance evaluated at 3 years old by Peabody Motor Scale and cognitive abilities at 5 years old. The association was estimated using linear regression models adjusted by mother's intelligence quotient, sex, Bayley mental development index at 18 months, and quality of the environment at home (HOME scale). 148 children whose motor performance was determined at age 3 and was evaluated later at age 5 to determine their cognitive abilities. Cognitive abilities (verbal, quantitative, and memory) measured by McCarthy Scales. Significant positive associations were observed between stationary balance at age 3 with verbal abilities (β = 0.67, p = .04) and memory (β = 0.81, p = .02) at 5 years. Grasping and visual-motor integration were significant and positively associated with quantitative abilities (β = 0.74, p = .005; β = 0.61, p = .01) and memory (β = 2.11, p = .001; β = 1.74, p = .004). The results suggest that early motor performance contributes to the establishment of cognitive abilities at 5 years. Evaluation and early motor stimulation before the child is faced with formal learning likely helps to create neuronal networks that facilitate the acquisition of academic knowledge.

UTILIZATION OF A PBPK MODEL TO PREDICT THE DISTRIBUTION OF 2, 3, 7-8 TETRACHLORODIBENZO-P-DIOXIN (TCDD) IN HUMANS DURING CRITICAL WINDOWS OF DEVELOPMENT

EPA Science Inventory

Utilization of A PBPK model to predict the distribution of 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) in humans during critical windows of development.
C Emond1, MJ DeVito2 and LS Birnbaum2
1National Research Council, US EPA, ORD, NHEERL, (ETD, PK), RTP, NC, 27711, USA 2 US...

PI3K-mediated PDGFRα signaling regulates survival and proliferation in skeletal development through p53-dependent intracellular pathways

PubMed Central

Fantauzzo, Katherine A.; Soriano, Philippe

2014-01-01

Previous studies have identified phosphatidylinositol 3-kinase (PI3K) as the main downstream effector of PDGFRα signaling during murine skeletal development. Autophosphorylation mutant knock-in embryos in which PDGFRα is unable to bind PI3K (PdgfraPI3K/PI3K) exhibit skeletal defects affecting the palatal shelves, shoulder girdle, vertebrae, and sternum. To identify proteins phosphorylated by Akt downstream from PI3K-mediated PDGFRα signaling, we immunoprecipitated Akt phosphorylation substrates from PDGF-AA-treated primary mouse embryonic palatal mesenchyme (MEPM) lysates and analyzed the peptides by nanoliquid chromatography coupled to tandem mass spectrometry (nano-LC-MS/MS). Our analysis generated a list of 56 proteins, including 10 that regulate cell survival and proliferation. We demonstrate that MEPM cell survival is impaired in the presence of a PI3K inhibitor and that PdgfraPI3K/PI3K-derived MEPMs do not proliferate in response to PDGF-AA treatment. Several of the identified Akt phosphorylation targets, including Ybox1, mediate cell survival through regulation of p53. We show that Ybox1 binds both the Trp53 promoter and the p53 protein and that expression of Trp53 is significantly decreased upon PDGF-AA treatment in MEPMs. Finally, we demonstrate that introduction of a Trp53-null allele attenuates the vertebral defects found in PdgfraPI3K/PI3K neonates. Our findings identify p53 as a novel effector downstream from PI3K-engaged PDGFRα signaling that regulates survival and proliferation during skeletal development in vivo. PMID:24788519

Up-regulation of miR-325-3p suppresses pineal aralkylamine N-acetyltransferase (Aanat) after neonatal hypoxia-ischemia brain injury in rats.

PubMed

Yang, Yuanyuan; Sun, Bin; Huang, Jian; Xu, Lixiao; Pan, Jian; Fang, Chen; Li, Mei; Li, Gen; Tao, Yanfang; Yang, Xiaofeng; Wu, Ying; Miao, Po; Wang, Ying; Li, Hong; Ren, Jing; Zhan, Meiqin; Fang, Yiping; Feng, Xing; Ding, Xin

2017-08-01

Survivors of hypoxic-ischemic brain damage (HIBD), besides impairment of psychomotor development, often develop circadian rhythm disorders, although the underlying mechanisms are largely unknown. Here, we first verified that mRNA and protein expression of pineal aralkylamine N-acetyltransferase (Aanat), a key regulator for melatonin (MT) synthesis, along with MT, were severely impaired after HIBD. In addition, we demonstrated that neonatal HIBD disrupted the circadian rhythmicity of locomotor activities in juvenile rats. Based on bioinformatics analysis of a high throughput screening of miRNA expression changes after HIBD (Ding et al., 2015), we identified one microRNA, miR-325-3p, as a potential candidate responsible for the down regulation of Aanat after HIBD. Luciferase reporter assays demonstrated a specific interaction between miR-325-3p and Aanat mRNA 3'-UTR. miR-325-3p blocked norepinephrine (NE) induced Aanat activation in cultured pinealocytes. In addition, miR-325-3p inhibition partially rescued Aanat induction by NE, which was significantly reduced under oxygen glucose deprivation. By elucidating the role of pineal miR-325-3p on Aanat expression upon injury, our study provides new insights into the pathophysiological mechanisms of circadian dysfunction and potential therapeutic targets after HIBD. Copyright © 2017 Elsevier B.V. All rights reserved.

Systematically convergent basis sets for transition metals. I. All-electron correlation consistent basis sets for the 3d elements Sc-Zn

NASA Astrophysics Data System (ADS)

Balabanov, Nikolai B.; Peterson, Kirk A.

2005-08-01

Sequences of basis sets that systematically converge towards the complete basis set (CBS) limit have been developed for the first-row transition metal elements Sc-Zn. Two families of basis sets, nonrelativistic and Douglas-Kroll-Hess (-DK) relativistic, are presented that range in quality from triple-ζ to quintuple-ζ. Separate sets are developed for the description of valence (3d4s) electron correlation (cc-pVnZ and cc-pVnZ-DK; n =T,Q, 5) and valence plus outer-core (3s3p3d4s) correlation (cc-pwCVnZ and cc-pwCVnZ-DK; n =T,Q, 5), as well as these sets augmented by additional diffuse functions for the description of negative ions and weak interactions (aug-cc-pVnZ and aug-cc-pVnZ-DK). Extensive benchmark calculations at the coupled cluster level of theory are presented for atomic excitation energies, ionization potentials, and electron affinities, as well as molecular calculations on selected hydrides (TiH, MnH, CuH) and other diatomics (TiF, Cu2). In addition to observing systematic convergence towards the CBS limits, both 3s3p electron correlation and scalar relativity are calculated to strongly impact many of the atomic and molecular properties investigated for these first-row transition metal species.

Newly developed glycogen synthase kinase-3 (GSK-3) inhibitors protect neuronal cells death in amyloid-beta induced cell model and in a transgenic mouse model of Alzheimer's disease.

PubMed

Noh, Min-Young; Chun, Kwangwoo; Kang, Byung Yong; Kim, Heejaung; Park, Ji-Seon; Lee, Han-Chang; Kim, Young-Ha; Ku, Saekwang; Kim, Seung Hyun

2013-05-31

Glycogen synthase kinase-3 (GSK-3) is emerging as a prominent therapeutic target of Alzheimer's disease (AD). A number of studies have been undertaken to develop GSK-3 inhibitors for clinical use. We report two novel GSK-3 inhibitors (C-7a and C-7b) showing good activity and pharmacokinetic (PK) profiles. IC50 of new GSK-3 inhibitors were in the range of 120-130 nM, and they effectively reduced the Aβ-oligomers induced neuronal toxicity. Also, new GSK-3 inhibitors decreased the phosphorylated tau at pThr231, pSer396, pThr181, and pSer202, and inhibited the GSK-3 activity against Aβ-oligomers induced neuronal cell toxicity. In B6;129-Psen1(tm1Mpm) Tg(APPSwe, tauP301L)1Lfa/Mmjax model of AD, oral administration of C-7a (20 mg/kg, 50 mg/kg) showed increased total arm entries and spontaneous alteration of Y-maze which was regarded as short-term memory. In particular, 50 mg/kg C-7a treated mice significantly decreased the level of phosphorylated tau (Ser396) in brain hippocampus. We suggest that new GSK-3 inhibitor (C-7a) is potential candidates for the treatment of AD. Copyright © 2013 The Author. Published by Elsevier Inc. All rights reserved.

A patient with interstitial deletion of the short arm of chromosome 3 (pter{yields}p21.2::p12{yields}qter) and a CHARGE-like phenotype

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

Wieczorek, D.; Gillessen-Kaesbach, G.

1997-04-14

We report on a 4-month-old boy with a de novo interstitial deletion of the short arm of chromosome 3 (pter {r_arrow} p21.2::p12 {r_arrow} qter) and clinical findings typical of proximal 3p deletion together with coloboma of iris, heart defect, choanal atresia, retardation of growth and development, genital hypoplasia, and ear anomalies. Family history was unremarkable and parental chromosomes were normal. The clinical manifestations of the patient are compared with those of 10 patients previously described with a proximal 3p deletion. The additional CHARGE- like phenotype is discussed. 20 refs., 4 figs., 1 tab.

DIPA-family coiled-coils bind conserved isoform-specific head domain of p120-catenin family: potential roles in hydrocephalus and heterotopia.

PubMed

Markham, Nicholas O; Doll, Caleb A; Dohn, Michael R; Miller, Rachel K; Yu, Huapeng; Coffey, Robert J; McCrea, Pierre D; Gamse, Joshua T; Reynolds, Albert B

2014-09-01

p120-catenin (p120) modulates adherens junction (AJ) dynamics by controlling the stability of classical cadherins. Among all p120 isoforms, p120-3A and p120-1A are the most prevalent. Both stabilize cadherins, but p120-3A is preferred in epithelia, whereas p120-1A takes precedence in neurons, fibroblasts, and macrophages. During epithelial-to-mesenchymal transition, E- to N-cadherin switching coincides with p120-3A to -1A alternative splicing. These isoforms differ by a 101-amino acid "head domain" comprising the p120-1A N-terminus. Although its exact role is unknown, the head domain likely mediates developmental and cancer-associated events linked to p120-1A expression (e.g., motility, invasion, metastasis). Here we identified delta-interacting protein A (DIPA) as the first head domain-specific binding partner and candidate mediator of isoform 1A activity. DIPA colocalizes with AJs in a p120-1A- but not 3A-dependent manner. Moreover, all DIPA family members (Ccdc85a, Ccdc85b/DIPA, and Ccdc85c) interact reciprocally with p120 family members (p120, δ-catenin, p0071, and ARVCF), suggesting significant functional overlap. During zebrafish neural tube development, both knockdown and overexpression of DIPA phenocopy N-cadherin mutations, an effect bearing functional ties to a reported mouse hydrocephalus phenotype associated with Ccdc85c. These studies identify a novel, highly conserved interaction between two protein families that may participate either individually or collectively in N-cadherin-mediated development. © 2014 Markham et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Concordance between isolated cleft palate in mice and alterations within a region including the gene encoding the [beta][sub 3] subunit of the type A [gamma]-aminobutyric acid receptor

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

Culiat, C.T.; Stubbs, L.; Nicholls, R.D.

1993-06-01

Genetic and molecular analyses of a number of radiation-induced deletion mutations of the pink-eyed dilution (p) locus in mouse chromosome 7 have identified a specific interval on the genetic map associated with a neonatally lethal mutation that results in cleft palate. This interval, closely linked and distal to p, and bracketed by the genes encoding the [alpha][sub 5] and [beta][sub 3] subunits of the type A [gamma]-aminobutyric acid receptor (Gabra5 and Gabrb3, respectively), contains a gene(s) (cp1; cleft palate 1) necessary for normal palate development. The cp1 interval extends from the distal breakpoint of the prenatally lethal p[sup 83FBFo] deletionmore » to the Gabrb3 locus. Among 20 p deletions tested, there was complete concordance between alterations at the Gabrb3 transcription unit and inability to complement the cleft-palate defect. These mapping data, along with previously described in vivo and in vitro teratological effects of [gamma]-aminobutyric acid or its agonists on palate development, suggest the possibility that a particular type A [gamma]-aminobutyric acid receptor that includes the [beta][sub 3] subunit may be necessary for normal palate development. The placement of the cp1 gene within a defined segment of the larger D15S12h (p)-D15S9h-1 interval in the mouse suggests that the highly homologous region of the human genome, 15q11-q13, be evaluated for a role(s) in human fetal facial development. 29 refs., 4 figs., 1 tab.« less

p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy.

PubMed

Pankiv, Serhiy; Clausen, Terje Høyvarde; Lamark, Trond; Brech, Andreas; Bruun, Jack-Ansgar; Outzen, Heidi; Øvervatn, Aud; Bjørkøy, Geir; Johansen, Terje

2007-08-17

Protein degradation by basal constitutive autophagy is important to avoid accumulation of polyubiquitinated protein aggregates and development of neurodegenerative diseases. The polyubiquitin-binding protein p62/SQSTM1 is degraded by autophagy. It is found in cellular inclusion bodies together with polyubiquitinated proteins and in cytosolic protein aggregates that accumulate in various chronic, toxic, and degenerative diseases. Here we show for the first time a direct interaction between p62 and the autophagic effector proteins LC3A and -B and the related gamma-aminobutyrate receptor-associated protein and gamma-aminobutyrate receptor-associated-like proteins. The binding is mediated by a 22-residue sequence of p62 containing an evolutionarily conserved motif. To monitor the autophagic sequestration of p62- and LC3-positive bodies, we developed a novel pH-sensitive fluorescent tag consisting of a tandem fusion of the red, acid-insensitive mCherry and the acid-sensitive green fluorescent proteins. This approach revealed that p62- and LC3-positive bodies are degraded in autolysosomes. Strikingly, even rather large p62-positive inclusion bodies (2 microm diameter) become degraded by autophagy. The specific interaction between p62 and LC3, requiring the motif we have mapped, is instrumental in mediating autophagic degradation of the p62-positive bodies. We also demonstrate that the previously reported aggresome-like induced structures containing ubiquitinated proteins in cytosolic bodies are dependent on p62 for their formation. In fact, p62 bodies and these structures are indistinguishable. Taken together, our results clearly suggest that p62 is required both for the formation and the degradation of polyubiquitin-containing bodies by autophagy.

The Genital Tract Virulence Factor pGP3 Is Essential for Chlamydia muridarum Colonization in the Gastrointestinal Tract.

PubMed

Shao, Lili; Zhang, Tianyuan; Melero, Jose; Huang, Yumeng; Liu, Yuanjun; Liu, Quanzhong; He, Cheng; Nelson, David E; Zhong, Guangming

2018-01-01

The cryptic plasmid is essential for Chlamydia muridarum dissemination from the genital tract to the gastrointestinal (GI) tract. Following intravaginal inoculation, a C. muridarum strain deficient in plasmid-encoded pGP3 or pGP4 but not pGP5, pGP7, or pGP8 failed to spread to the mouse gastrointestinal tract, although mice infected with these strains developed productive genital tract infections. pGP3- or pGP4-deficient strains also failed to colonize the gastrointestinal tract when delivered intragastrically. pGP4 regulates pGP3, while pGP3 does not affect pGP4 expression, indicating that pGP3 is critical for C. muridarum colonization of the gastrointestinal tract. Mutants deficient in GlgA, a chromosome-encoded protein regulated by pGP4, also consistently colonized the mouse gastrointestinal tract. Interestingly, C. muridarum colonization of the gastrointestinal tract positively correlated with pathogenicity in the upper genital tract. pGP3-deficient C. muridarum strains did not induce hydrosalpinx or spread to the GI tract even when delivered to the oviduct by intrabursal inoculation. Thus, the current study not only has revealed that pGP3 is a novel chlamydial colonization factor in the gastrointestinal tract but also has laid a foundation for investigating the significance of gastrointestinal Chlamydia . Copyright © 2017 American Society for Microbiology.

Impact of ocean warming and ocean acidification on larval development and calcification in the sea urchin Tripneustes gratilla.

PubMed

Sheppard Brennand, Hannah; Soars, Natalie; Dworjanyn, Symon A; Davis, Andrew R; Byrne, Maria

2010-06-29

As the oceans simultaneously warm, acidify and increase in P(CO2), prospects for marine biota are of concern. Calcifying species may find it difficult to produce their skeleton because ocean acidification decreases calcium carbonate saturation and accompanying hypercapnia suppresses metabolism. However, this may be buffered by enhanced growth and metabolism due to warming. We examined the interactive effects of near-future ocean warming and increased acidification/P(CO2) on larval development in the tropical sea urchin Tripneustes gratilla. Larvae were reared in multifactorial experiments in flow-through conditions in all combinations of three temperature and three pH/P(CO2) treatments. Experiments were placed in the setting of projected near future conditions for SE Australia, a global change hot spot. Increased acidity/P(CO2) and decreased carbonate mineral saturation significantly reduced larval growth resulting in decreased skeletal length. Increased temperature (+3 degrees C) stimulated growth, producing significantly bigger larvae across all pH/P(CO2) treatments up to a thermal threshold (+6 degrees C). Increased acidity (-0.3-0.5 pH units) and hypercapnia significantly reduced larval calcification. A +3 degrees C warming diminished the negative effects of acidification and hypercapnia on larval growth. This study of the effects of ocean warming and CO(2) driven acidification on development and calcification of marine invertebrate larvae reared in experimental conditions from the outset of development (fertilization) shows the positive and negative effects of these stressors. In simultaneous exposure to stressors the dwarfing effects of acidification were dominant. Reduction in size of sea urchin larvae in a high P(CO2) ocean would likely impair their performance with negative consequent effects for benthic adult populations.

Impact of Ocean Warming and Ocean Acidification on Larval Development and Calcification in the Sea Urchin Tripneustes gratilla

PubMed Central

Sheppard Brennand, Hannah; Soars, Natalie; Dworjanyn, Symon A.; Davis, Andrew R.; Byrne, Maria

2010-01-01

Background As the oceans simultaneously warm, acidify and increase in P CO2, prospects for marine biota are of concern. Calcifying species may find it difficult to produce their skeleton because ocean acidification decreases calcium carbonate saturation and accompanying hypercapnia suppresses metabolism. However, this may be buffered by enhanced growth and metabolism due to warming. Methodology/Principal Findings We examined the interactive effects of near-future ocean warming and increased acidification/P CO2 on larval development in the tropical sea urchin Tripneustes gratilla. Larvae were reared in multifactorial experiments in flow-through conditions in all combinations of three temperature and three pH/P CO2 treatments. Experiments were placed in the setting of projected near future conditions for SE Australia, a global change hot spot. Increased acidity/P CO2 and decreased carbonate mineral saturation significantly reduced larval growth resulting in decreased skeletal length. Increased temperature (+3°C) stimulated growth, producing significantly bigger larvae across all pH/P CO2 treatments up to a thermal threshold (+6°C). Increased acidity (-0.3-0.5 pH units) and hypercapnia significantly reduced larval calcification. A +3°C warming diminished the negative effects of acidification and hypercapnia on larval growth. Conclusions and Significance This study of the effects of ocean warming and CO2 driven acidification on development and calcification of marine invertebrate larvae reared in experimental conditions from the outset of development (fertilization) shows the positive and negative effects of these stressors. In simultaneous exposure to stressors the dwarfing effects of acidification were dominant. Reduction in size of sea urchin larvae in a high P CO2 ocean would likely impair their performance with negative consequent effects for benthic adult populations. PMID:20613879

Neurotrophin responsiveness of sympathetic neurons is regulated by rapid mobilization of the p75 receptor to the cell surface through TrkA activation of Arf6.

PubMed

Edward Hickman, F; Stanley, Emily M; Carter, Bruce D

2018-05-22

The p75 neurotrophin receptor (p75NTR) plays an integral role in patterning the sympathetic nervous system during development. Initially, p75NTR is expressed at low levels as sympathetic axons project toward their targets, which enables neurotrophin-3 (NT3) to activate TrkA receptors and promote growth. Upon reaching nerve growth factor (NGF) producing tissues, p75NTR is up regulated resulting in formation of TrkA-p75 complexes, which are high affinity binding sites selective for NGF, thereby blunting NT3 signaling. The level of p75NTR expressed on the neuron surface is instrumental in regulating trophic factor response; however, the mechanisms by which p75NTR expression is regulated are poorly understood. Here, we demonstrate a rapid, translation independent increase in surface expression of p75NTR in response to NGF in rat sympathetic neurons. p75NTR was mobilized to the neuron surface from GGA3-postitive vesicles through activation of the GTPase Arf6, which was stimulated by NGF, but not NT3 binding to TrkA. Arf6 activation required PI3 kinase activity and was prevented by an inhibitor of the cytohesin family of Arf6 GEFs. Overexpression of a constitutively active Arf6 mutant (Q67L) was sufficient to significantly increase surface expression of p75NTR even in the absence of NGF. Functionally, expression of active Arf6 markedly attenuated the ability of NT3 to promote neuronal survival and neurite outgrowth while the NGF response was unaltered. These data suggest that NGF activation of Arf6 through TrkA is critical for the increase in p75NTR surface expression that enables the switch in neurotrophin responsiveness during development in the sympathetic nervous system. SIGNIFICANCE STATEMENT p75NTR is instrumental in the regulation of neuronal survival and apoptosis during development and is also implicated as a contributor to aberrant neurodegeneration in numerous conditions. Therefore, a better understanding of the mechanisms that mediate p75NTR surface availability, may provide insight into how and why neurodegenerative processes manifest and reveal new therapeutic targets. Results from this study indicate a novel mechanism by which p75NTR can be rapidly shuttled to the cell surface from existing intracellular pools and explores a unique pathway by which NGF regulates the sympathetic innervation of target tissues, which has profound consequences for the function of these organs. Copyright © 2018 the authors.

Subsequent development of fibroatheromas with inflamed fibrous caps can be predicted by intracoronary near infrared spectroscopy.

PubMed

Patel, Dhavalkumar; Hamamdzic, Damir; Llano, Raul; Patel, Daivesh; Cheng, Lan; Fenning, Robert S; Bannan, Khalid; Wilensky, Robert L

2013-02-01

To prospectively evaluate whether the development of fibroatheromas exhibiting features of potential instability can be detected and predicted by serial invasive imaging. Multivessel intravascular ultrasound and near infrared spectroscopy (NIRS) were performed in diabetic/hypercholesterolemic pigs 3, 6, and 9 months after induction. Animals were euthanized at 9 months and histological/immunohistochemical evaluation of the arteries was performed (n=304 arterial segments). Intravascular ultrasound demonstrated, over time, a progressive increase in plaque + media and necrotic core areas and positive vascular remodeling. By histology, NIRS+ lesions were significantly more likely to be a high-risk fibroatheroma (P=0.0001) containing larger plaque (P<0.0001) and necrotic core areas (P<0.0019) and thinner fibrous caps (P=0.04). NIRS + fibroatheromas possessed a greater concentration of inflammatory cells demonstrating protease activity (P=0.006), and proliferating (P=0.016), and apoptotic cells (P=0.04) within the fibrous cap. Eighty-eight percent of NIRS+ lesions at 3 and 6 months subsequently developed into a fibroatheroma at 9 months (P<0.01). By multivariate analysis NIRS positivity at 6 months predicted the subsequent presence of a fibroatheroma at 9 months (P=0.005; odds ratio, 2.71). The future development of inflamed fibroatheromas with thinner fibrous caps, greater plaque, and necrotic core areas, and posessing characteristics of increased plaque instability were detected by intravascular ultrasound/NIRS imaging.

Clinical utility of LC3 and p62 immunohistochemistry in diagnosis of drug-induced autophagic vacuolar myopathies: a case-control study.

PubMed

Lee, Han S; Daniels, Brianne H; Salas, Eduardo; Bollen, Andrew W; Debnath, Jayanta; Margeta, Marta

2012-01-01

Some patients treated with chloroquine, hydroxychloroquine, or colchicine develop autophagic vacuolar myopathy, the diagnosis of which currently requires electron microscopy. The goal of the current study was to develop an immunohistochemical diagnostic marker for this pathologic entity. Microtubule-associated protein light chain 3 (LC3) has emerged as a robust marker of autophagosomes. LC3 binds p62/SQSTM1, an adapter protein that is selectively degraded via autophagy. In this study, we evaluated the utility of immunohistochemical stains for LC3 and p62 as diagnostic markers of drug-induced autophagic vacuolar myopathy. The staining was performed on archival muscle biopsy material, with subject assignment to normal control, drug-treated control, and autophagic myopathy groups based on history of drug use and morphologic criteria. In all drug-treated subjects, but not in normal controls, LC3 and p62 showed punctate staining characteristic of autophagosome buildup. In the autophagic myopathy subjects, puncta were coarser and tended to coalesce into linear structures aligned with the longitudinal axis of the fiber, often in the vicinity of vacuoles. The percentage of LC3- and p62-positive fibers was significantly higher in the autophagic myopathy group compared to either the normal control (p<0.001) or the drug-treated control group (p<0.05). With the diagnostic threshold set between 8% and 15% positive fibers (depending on the desired level of sensitivity and specificity), immunohistochemical staining for either LC3 or p62 could be used to identify subjects with autophagic vacuolar myopathy within the drug-treated subject group (p ≤ 0.001). Immunohistochemistry for LC3 and p62 can facilitate tissue-based diagnosis of drug-induced autophagic vacuolar myopathies. By limiting the need for electron microscopy (a time consuming and costly technique with high specificity, but low sensitivity), clinical use of these markers will improve the speed and accuracy of diagnosis, resulting in significantly improved clinical care.

Single Wall Carbon Nanotube-polymer Solar Cells

NASA Technical Reports Server (NTRS)

Bailey, Sheila G.; Castro, Stephanie L.; Landi, Brian J.; Gennett, Thomas; Raffaelle, Ryne P.

2005-01-01

Investigation of single wall carbon nanotube (SWNT)-polymer solar cells has been conducted towards developing alternative lightweight, flexible devices for space power applications. Photovoltaic devices were constructed with regioregular poly(3-octylthiophene)-(P3OT) and purified, >95% w/w, laser-generated SWNTs. The P3OT composites were deposited on ITO-coated polyethylene terapthalate (PET) and I-V characterization was performed under simulated AM0 illumination. Fabricated devices for the 1.0% w/w SWNT-P3OT composites showed a photoresponse with an open-circuit voltage (V(sub oc)) of 0.98 V and a short-circuit current density (I(sub sc)) of 0.12 mA/sq cm. Optimization of carrier transport within these novel photovoltaic systems is proposed, specifically development of nanostructure-SWNT complexes to enhance exciton dissociation.

Crohn's disease and smoking: is it ever too late to quit?

PubMed

Lawrance, Ian C; Murray, Kevin; Batman, Birol; Gearry, Richard B; Grafton, Rachel; Krishnaprasad, Krupa; Andrews, Jane M; Prosser, Ruth; Bampton, Peter A; Cooke, Sharon E; Mahy, Gillian; Radford-Smith, Graham; Croft, Anthony; Hanigan, Katherine

2013-12-01

Smoking increases CD risk. The aim was to determine if smoking cessation at, prior to, or following, CD diagnosis affects medication use, disease phenotypic progression and/or surgery. Data on CD patients with disease for ≥5 yrs were collected retrospectively including the Montreal classification, smoking history, CD-related abdominal surgeries, family history, medication use and disease behaviour at diagnosis and the time when the disease behaviour changed. 1115 patients were included across six sites (mean follow-up-16.6 yrs). More non-smokers were male (p=0.047) with A1 (p<0.0001), L4 (p=0.028) and perianal (p=0.03) disease. Non-smokers more frequently received anti-TNF agents (p=0.049). (p=0.017: OR 2.5 95%CI 1.18-5.16) and those who ceased smoking prior to diagnosis (p=0.045: OR 2.3 95%CI 1.02-5.21) progressed to complicated (B2/B3) disease as compared to those quitting at diagnosis. Patients with uncomplicated terminal ileal disease at diagnosis more frequently developed B2/B3 disease than isolated colonic CD (p<0.0001). B2/B3 disease was more frequent with perianal disease (p<0.0001) and if i.v. steroids (p=0.004) or immunosuppressants (p<0.0001) were used. 49.3% (558/1115) of patients required at least one intestinal surgery. More smokers had a 2nd surgical resection than patients who quit at, or before, the 1st resection and non-smokers (p=0.044: HR=1.39 95%CI 1.01-1.91). Patients smoking >3 cigarettes/day had an increased risk of developing B2/B3 disease (p=0.012: OR 3.8 95%CI 1.27-11.17). Progression to B2/B3 disease and surgery is reduced by smoking cessation. All CD patients regardless of when they were diagnosed, or how many surgeries, should be strongly encouraged to cease smoking. Copyright © 2013 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

pV3-Gold Visualization Environment for Computer Simulations

NASA Technical Reports Server (NTRS)

Babrauckas, Theresa L.

1997-01-01

A new visualization environment, pV3-Gold, can be used during and after a computer simulation to extract and visualize the physical features in the results. This environment, which is an extension of the pV3 visualization environment developed at the Massachusetts Institute of Technology with guidance and support by researchers at the NASA Lewis Research Center, features many tools that allow users to display data in various ways.

Expression and activation of STAT3 in ischemia-induced retinopathy.

PubMed

Mechoulam, Hadas; Pierce, Eric A

2005-12-01

Signal transducer and activator of transcription protein-3 (STAT3) is a transcription factor that participates in many biological processes, including tumor angiogenesis. The expression and activation of Stat3 in the mouse model of ischemia-induced retinal neovascularization was investigated to evaluate the possible role of STAT3 in retinal vascular disease. Retinal neovascularization was induced in mice pups by exposure to hyperoxia. Gene microarrays were used to identify genes whose expression in the retina is altered at postnatal day (P)12 and P18. The relative levels of Stat3 mRNA were determined by semiquantitative RT-PCR. Stat3 protein levels and the levels of the activated form of Stat3 (pStat3) at P12, P15, P18, and P22 were determined by immunoblot analysis. Stat3 and pStat3 were demonstrated by immunofluorescence in retinal sections at P12, P15, and P18. In a series of microarray experiments, increased Stat3 mRNA levels in the retina were detected at P18. This result was validated by RT-PCR and demonstrated that Stat3 and pStat3 protein levels also increase during the development of neovascularization. Stat3 partially colocalized with blood vessels at the peak of neovascularization. pStat3 colocalized completely with blood vessels in both experimental samples and age-matched controls. pStat3 staining increased notably in the neovascular vessels at P15 and P18 and was more strongly associated with the epiretinal vessels than with inner retinal vessels. It was not detected in larger blood vessels, such as those of the optic nerve. The level of Stat3 expression increased, and pStat3 was observed in association with retinal neovascularization. Activated Stat3 was preferentially localized to neovascular retinal vessels. These data suggest that STAT3 may have a role in proliferative retinopathy.

The homeoprotein DLX3 and tumor suppressor p53 co-regulate cell cycle progression and squamous tumor growth.

PubMed

Palazzo, E; Kellett, M; Cataisson, C; Gormley, A; Bible, P W; Pietroni, V; Radoja, N; Hwang, J; Blumenberg, M; Yuspa, S H; Morasso, M I

2016-06-16

Epidermal homeostasis depends on the coordinated control of keratinocyte cell cycle. Differentiation and the alteration of this balance can result in neoplastic development. Here we report on a novel DLX3-dependent network that constrains epidermal hyperplasia and squamous tumorigenesis. By integrating genetic and transcriptomic approaches, we demonstrate that DLX3 operates through a p53-regulated network. DLX3 and p53 physically interact on the p21 promoter to enhance p21 expression. Elevating DLX3 in keratinocytes produces a G1-S blockade associated with p53 signature transcriptional profiles. In contrast, DLX3 loss promotes a mitogenic phenotype associated with constitutive activation of ERK. DLX3 expression is lost in human skin cancers and is extinguished during progression of experimentally induced mouse squamous cell carcinoma (SCC). Reinstatement of DLX3 function is sufficient to attenuate the migration of SCC cells, leading to decreased wound closure. Our data establish the DLX3-p53 interplay as a major regulatory axis in epidermal differentiation and suggest that DLX3 is a modulator of skin carcinogenesis.

The homeoprotein DLX3 and tumor suppressor p53 co-regulate cell cycle progression and squamous tumor growth

PubMed Central

Palazzo, Elisabetta; Kellett, Meghan; Cataisson, Christophe; Gormley, Anna; Bible, Paul W.; Pietroni, Valentina; Radoja, Nadezda; Hwang, Joonsung; Blumenberg, Miroslav; Yuspa, Stuart H.; Morasso, Maria

2015-01-01

Epidermal homeostasis depends on the coordinated control of keratinocyte cell cycle. Differentiation and the alteration of this balance can result in neoplastic development. Here we report on a novel DLX3-dependent network that constrains epidermal hyperplasia and squamous tumorigenesis. By integrating genetic and transcriptomic approaches, we demonstrate that DLX3 operates through a p53-regulated network. DLX3 and p53 physically interact on the p21 promoter to enhance p21 expression. Elevating DLX3 in keratinocytes produces a G1-S blockade associated with p53 signature transcriptional profiles. In contrast, DLX3 loss promotes a mitogenic phenotype associated with constitutive activation of ERK. DLX3 expression is lost in human skin cancers and is extinquished during progression of experimentally induced mouse squamous cell carcinoma (SCC). Reinstatement of DLX3 function is sufficient to attenuate the migration of SCC cells, leading to decreased wound closure. Our data establish the DLX3-p53 interplay as a major regulatory axis in epidermal differentiation and suggest that DLX3 is a modulator of skin carcinogenesis. PMID:26522723

Collaboration of Antibody and Inflammation in Clearance of Rabies Virus from the Central Nervous System

PubMed Central

Hooper, D. Craig; Morimoto, Kinjiro; Bette, Michael; Weihe, Eberhard; Koprowski, Hilary; Dietzschold, Bernhard

1998-01-01

To investigate the involvement of various cellular and humoral aspects of immunity in the clearance of rabies virus from the central nervous system, (CNS), we studied the development of clinical signs and virus clearance from the CNS in knockout mice lacking either B and T cells, CD8+ cytotoxic T cells, B cells, alpha/beta interferon (IFN-α/β) receptors, IFN-γ receptors, or complement components C3 and C4. Following intranasal infection with the attenuated rabies virus CVS-F3, normal adult mice of different genetic backgrounds developed a transient disease characterized by loss of body weight and appetite depression which peaked at 13 days postinfection (p.i.). While these animals had completely recovered by day 21 p.i., mice lacking either B and T cells or B cells alone developed a progressive disease and succumbed to infection. Mice lacking either CD8+ T cells, IFN receptors, or complement components C3 and C4 showed no significant differences in the development of clinical signs by comparison with intact counterparts having the same genetic background. However, while infectious virus and viral RNA could be detected in normal control mice only until day 8 p.i., in all of the gene knockout mice studied except those lacking C3 and C4, virus infection persisted through day 21 p.i. Analysis of rabies virus-specific antibody production together with histological assessment of brain inflammation in infected animals revealed that clearance of CVS-F3 by 21 days p.i. correlated with both a strong inflammatory response in the CNS early in the infection (day 8 p.i.), and the rapid (day 10 p.i.) production of significant levels of virus-neutralizing antibody (VNA). These studies confirm that rabies VNA is an absolute requirement for clearance of an established rabies virus infection. However, for the latter to occur in a timely fashion, collaboration between VNA and inflammatory mechanisms is necessary. PMID:9557653

Highly Sensitive Ammonia Gas Sensor Based on Single-Crystal Poly(3-hexylthiophene) (P3HT) Organic Field Effect Transistor.

PubMed

Mun, Seohyun; Park, Yoonkyung; Lee, Yong-Eun Koo; Sung, Myung Mo

2017-11-28

A highly sensitive organic field-effect transistor (OFET)-based sensor for ammonia in the range of 0.01 to 25 ppm was developed. The sensor was fabricated by employing an array of single-crystal poly(3-hexylthiophene) (P3HT) nanowires as the organic semiconductor (OSC) layer of an OFET with a top-contact geometry. The electrical characteristics (field-effect mobility, on/off current ratio) of the single-crystal P3HT nanowire OFET were about 2 orders of magnitude larger than those of the P3HT thin film OFET with the same geometry. The P3HT nanowire OFET showed excellent sensitivity to ammonia, about 3 times higher than that of the P3HT thin film OFET at 25 ppm ammonia. The ammonia response of the OFET was reversible and was not affected by changes in relative humidity from 45 to 100%. The high ammonia sensitivity of the P3HT nanowire OFET is believed to result from the single crystal nature and high surface/volume ratio of the P3HT nanowire used in the OSC layer.

Attentional but not pre-attentive neural measures of auditory discrimination are atypical in children with developmental language disorder.

PubMed

Kornilov, Sergey A; Landi, Nicole; Rakhlin, Natalia; Fang, Shin-Yi; Grigorenko, Elena L; Magnuson, James S

2014-01-01

We examined neural indices of pre-attentive phonological and attentional auditory discrimination in children with developmental language disorder (DLD, n = 23) and typically developing (n = 16) peers from a geographically isolated Russian-speaking population with an elevated prevalence of DLD. Pre-attentive phonological MMN components were robust and did not differ in two groups. Children with DLD showed attenuated P3 and atypically distributed P2 components in the attentional auditory discrimination task; P2 and P3 amplitudes were linked to working memory capacity, development of complex syntax, and vocabulary. The results corroborate findings of reduced processing capacity in DLD and support a multifactorial view of the disorder.

Ectopic expression of pMADS3 in transgenic petunia phenocopies the petunia blind mutant.

PubMed Central

Tsuchimoto, S; van der Krol, A R; Chua, N H

1993-01-01

We cloned a MADS-box gene, pMADS3, from Petunia hybrida, which shows high sequence homology to the Arabidopsis AGAMOUS and Antirrhinum PLENA. pMADS3 is expressed exclusively in stamens and carpels of wild-type petunia plants. In the petunia mutant blind, which shows homeotic conversions of corolla limbs into antheroid structures with pollen grains and small parts of sepals into carpelloid tissue, pMADS3 is expressed in all floral organs as well as in leaves. Ectopic expression of pMADS3 in transgenic petunia leads to phenocopies of the blind mutant, i.e., the formation of antheroid structures on limbs and carpelloid tissue on sepals. Transgenic tobacco plants that overexpress pMADS3 exhibit an even more severe phenotype, with the sepals forming a carpel-like structure encasing the interior floral organs. Our results identify BLIND as a negative regulator of pMADS3, which specifies stamens and carpels during petunia flower development. PMID:8104573

Impact of body mass index and waist circumference on the long-term risk of diabetes mellitus, hypertension, and cardiac organ damage.

PubMed

Bombelli, Michele; Facchetti, Rita; Sega, Roberto; Carugo, Stefano; Fodri, Danilo; Brambilla, Gianmaria; Giannattasio, Cristina; Grassi, Guido; Mancia, Giuseppe

2011-12-01

Obesity is associated with a higher risk of developing diabetes mellitus (DM), hypertension (HT), and left ventricular hypertrophy (LVH). The present study assessed in the general population the impact of body weight and visceral obesity on the development of alterations in glucose metabolism and cardiac structure, as well as of elevation in blood pressure. In 1412 subjects randomly selected and representative of the general population of Monza, we assessed twice (in 1990/1991 and 2000/2001) body mass index (BMI); waist circumference; office, home, and 24-hour ambulatory (24-hour) blood pressure, fasting glycemia, and left ventricular mass (echocardiography). New-onset high-risk conditions were DM; impaired fasting glucose; office, home, and 24-hour HT; and LVH. The incidence of new-onset DM; impaired fasting glucose; office, home, and 24-hour HT; and LVH increased progressively from the quintile with the lowest to the quintile with the highest BMI values. Adjusting for confounders, the risk of developing new-onset DM; impaired fasting glucose; office, home, and 24-hour HT; and LVH increased significantly for an increase of 1 kg/m(2) of BMI and 1 cm of waist circumference (respectively, 8.4% [P<0.01], 9.5% [P<0.0001], 4.2% [P<0.0001], 3.9% [P<0.001], 2.5% [P<0.05], and 5.1% [P<0.001] for BMI and 3.2% [P<0.001], 3.5% [P<0.0001], 1.8% [P<0.0001], 1.5% [P<0.0001], 1.4% [P<0.001], and 2.6% [P<0.0001]). These data provide evidence that an increase in BMI and waist circumference is associated with a linearly increased adjusted risk of developing conditions with high cardiovascular risk, such as DM, impaired fasting glucose, in- and out-of-office HT, and LVH.

Quenching of I(2P1/2) by O3 and O(3P).

PubMed

Azyazov, Valeriy N; Antonov, Ivan O; Heaven, Michael C

2007-04-26

Oxygen-iodine lasers that utilize electrical or microwave discharges to produce singlet oxygen are currently being developed. The discharge generators differ from conventional chemical singlet oxygen generators in that they produce significant amounts of atomic oxygen. Post-discharge chemistry includes channels that lead to the formation of ozone. Consequently, removal of I(2P1/2) by O atoms and O3 may impact the efficiency of discharge driven iodine lasers. In the present study, we have measured the rate constants for quenching of I(2P1/2) by O(3P) atoms and O3 using pulsed laser photolysis techniques. The rate constant for quenching by O3, (1.8 +/- 0.4) x 10(-12) cm3 s-1, was found to be a factor of 5 smaller than the literature value. The rate constant for quenching by O(3P) was (1.2 +/- 0.2) x 10(-11) cm3 s-1.

An interplay between 2 signaling pathways: Melatonin-cAMP and IP{sub 3}–Ca{sup 2+} signaling pathways control intraerythrocytic development of the malaria parasite Plasmodium falciparum

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

Furuyama, Wakako; Enomoto, Masahiro; Mossaad, Ehab

Highlights: • A melatonin receptor antagonist blocked Ca{sup 2+} oscillation in P. falciparum and inhibited parasite growth. • P. falciparum development is controlled by Ca{sup 2+}- and cAMP-signaling pathways. • The cAMP-signaling pathway at ring form and late trophozoite stages governs parasite growth of P. falciparum. - Abstract: Plasmodium falciparum spends most of its asexual life cycle within human erythrocytes, where proliferation and maturation occur. Development into the mature forms of P. falciparum causes severe symptoms due to its distinctive sequestration capability. However, the physiological roles and the molecular mechanisms of signaling pathways that govern development are poorly understood. Ourmore » previous study showed that P. falciparum exhibits stage-specific spontaneous Calcium (Ca{sup 2+}) oscillations in ring and early trophozoites, and the latter was essential for parasite development. In this study, we show that luzindole (LZ), a selective melatonin receptor antagonist, inhibits parasite growth. Analyses of development and morphology of LZ-treated P. falciparum revealed that LZ severely disrupted intraerythrocytic maturation, resulting in parasite death. When LZ was added at ring stage, the parasite could not undergo further development, whereas LZ added at the trophozoite stage inhibited development from early into late schizonts. Live-cell Ca{sup 2+} imaging showed that LZ treatment completely abolished Ca{sup 2+} oscillation in the ring forms while having little effect on early trophozoites. Further, the melatonin-induced cAMP increase observed at ring and late trophozoite stage was attenuated by LZ treatment. These suggest that a complex interplay between IP{sub 3}–Ca{sup 2+} and cAMP signaling pathways is involved in intraerythrocytic development of P. falciparum.« less

Role of uncontrolled HIV RNA level and immunodeficiency in the occurrence of malignancy in HIV-infected patients during the combination antiretroviral therapy era: Agence Nationale de Recherche sur le Sida (ANRS) CO3 Aquitaine Cohort.

PubMed

Bruyand, Mathias; Thiébaut, Rodolphe; Lawson-Ayayi, Sylvie; Joly, Pierre; Sasco, Annie Jeanne; Mercié, Patrick; Pellegrin, Jean Luc; Neau, Didier; Dabis, François; Morlat, Philippe; Chêne, Geneviève; Bonnet, Fabrice

2009-10-01

Human immunodeficiency virus (HIV)-infected patients are at higher risk of malignancies. In addition to traditional determinants, a specific deleterious effect of HIV and immunodeficiency is speculated. We aimed at studying the association between immunological and virological characteristics of HIV-infected patients in care and the risk of acquired immunodeficiency syndrome (AIDS)-defining and non-AIDS-defining malignancies. Patients consecutively enrolled in the hospital-based Agence Nationale de Recherche sur le Sida (ANRS) CO3 Aquitaine Cohort were included if the duration of follow-up was >3 months during the period 1998-2006. Multivariate modeling used an extended Cox proportional hazards model for time-dependent covariates and delayed entry. The 4194 patients included in the study developed 251 first malignancies during 22,389 person-years. A higher incidence of AIDS-defining malignancies (107 cases) was independently associated with (1) both longer and current exposures to a plasma HIV RNA level >500 copies/mL (hazard ratio [HR], 1.27 per year [P<.001] and 3.30 [P<.001], respectively) and (2) both longer and current exposure to a CD4(+) cell count <200 cells/mm(3) (HR, 1.36 per year [P<.001] and 6.33 [P<.001], respectively). A higher incidence of non-AIDS-defining malignancies (144 cases) was independently associated with longer and current exposure to a CD4(+) cell count <500 cells/mm(3) (HR, 1.13 per year [P=.01] and 2.07 [P<.001], respectively) and male sex (HR, 1.69; P=.02) but not with plasma HIV RNA level (P=.49 and P=.10 for cumulative and current exposures, respectively). Uncontrolled plasma HIV RNA level was independently associated with a higher likelihood of developing AIDS-defining malignancies, whereas immunosuppression was associated with a higher risk of developing any type of malignancies. Antiretroviral treatment should aim at reaching and maintaining a CD4(+) count >500 cells/mm(3) to prevent the occurrence of malignancy, this should be integrated to malignancy-prevention policies.