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Sample records for alas sacrificial layer

  1. Rolled-Up Nanotech: Illumination-Controlled Hydrofluoric Acid Etching of AlAs Sacrificial Layers

    NASA Astrophysics Data System (ADS)

    Costescu, Ruxandra M.; Deneke, Christoph; Thurmer, Dominic J.; Schmidt, Oliver G.

    2009-12-01

    The effect of illumination on the hydrofluoric acid etching of AlAs sacrificial layers with systematically varied thicknesses in order to release and roll up InGaAs/GaAs bilayers was studied. For thicknesses of AlAs below 10 nm, there were two etching regimes for the area under illumination: one at low illumination intensities, in which the etching and releasing proceeds as expected and one at higher intensities in which the etching and any releasing are completely suppressed. The “etch suppression” area is well defined by the illumination spot, a feature that can be used to create heterogeneously etched regions with a high degree of control, shown here on patterned samples. Together with the studied self-limitation effect, the technique offers a way to determine the position of rolled-up micro- and nanotubes independently from the predefined lithographic pattern.

  2. In-situ deposition of sacrificial layers during ion implantation

    SciTech Connect

    Anders, A.; Anders, S.; Brown, I.G.; Yu, K.M.

    1995-02-01

    The retained dose of implanted ions is limited by sputtering. It is known that a sacrificial layer deposited prior to ion implantation can lead to an enhanced retained dose. However, a higher ion energy is required to obtain a similar implantation depth due to the stopping of ions in the sacrificial layer. It is desirable to have a sacrificial layer of only a few monolayers thickness which can be renewed after it has been sputtered away. We explain the concept and describe two examples: (i) metal ion implantation using simultaneously a vacuum arc ion source and filtered vacuum arc plasma sources, and (ii) Metal Plasma Immersion Ion Implantation and Deposition (MePIIID). In MePIIID, the target is immersed in a metal or carbon plasma and a negative, repetitively pulsed bias voltage is applied. Ions are implanted when the bias is applied while the sacrificial layer suffers sputtering. Low-energy thin film deposition - repair of the sacrificial layer -- occurs between bias pulses. No foreign atoms are incorporated into the target since the sacrificial film is made of the same ion species as used in the implantation phase.

  3. Cleaning graphene with a titanium sacrificial layer

    SciTech Connect

    Joiner, C. A. Roy, T.; Hesabi, Z. R.; Vogel, E. M.; Chakrabarti, B.

    2014-06-02

    Graphene is a promising material for future electronic applications and chemical vapor deposition of graphene on copper is a promising method for synthesizing graphene on the wafer scale. The processing of such graphene films into electronic devices introduces a variety of contaminants which can be difficult to remove. An approach to cleaning residues from the graphene channel is presented in which a thin layer of titanium is deposited via thermal e-beam evaporation and immediately removed. This procedure does not damage the graphene as evidenced by Raman spectroscopy, greatly enhances the electrical performance of the fabricated graphene field effect transistors, and completely removes the chemical residues from the surface of the graphene channel as evidenced by x-ray photoelectron spectroscopy.

  4. Methods of producing free-standing semiconductors using sacrificial buffer layers and recyclable substrates

    SciTech Connect

    Ptak, Aaron Joseph; Lin, Yong; Norman, Andrew; Alberi, Kirstin

    2015-05-26

    A method of producing semiconductor materials and devices that incorporate the semiconductor materials are provided. In particular, a method is provided of producing a semiconductor material, such as a III-V semiconductor, on a spinel substrate using a sacrificial buffer layer, and devices such as photovoltaic cells that incorporate the semiconductor materials. The sacrificial buffer material and semiconductor materials may be deposited using lattice-matching epitaxy or coincident site lattice-matching epitaxy, resulting in a close degree of lattice matching between the substrate material and deposited material for a wide variety of material compositions. The sacrificial buffer layer may be dissolved using an epitaxial liftoff technique in order to separate the semiconductor device from the spinel substrate, and the spinel substrate may be reused in the subsequent fabrication of other semiconductor devices. The low-defect density semiconductor materials produced using this method result in the enhanced performance of the semiconductor devices that incorporate the semiconductor materials.

  5. Polymer films as planarization and sacrificial layers for uncooled infrared focal plane arrays

    NASA Astrophysics Data System (ADS)

    Liu, Huan; Liu, Weiguo; Cai, Changlong; Zhou, Shun

    2010-10-01

    This paper presents a planarization procedure using polymer films to achieve a flat CMOS surface of Readout Integrated Circuit (ROIC) for the integration between uncooled infrared focal plane arrays and ROIC. At the same time, the polymer film is also used as the sacrificial layers. After amorphous Silicon (a-Si) film was deposited using plasma enhanced chemical vapor deposition (PECVD), and patterned using inductively coupled plasma (ICP), the polymer sacrificial layer should be removed to form a-Si self-supporting micro-bridge structure. So the thickness of polymer film determine the height of the micro-bridge; the soft curing temperature determines if the contact hole can be etched by developer during the first photolithography; and the rate of dry etching determines whether the sacrificial layers of the structure can be released successfully. In this paper, the curing temperature, surface roughness, etching process of polymer films are systematically researched. On this basis, polymer film as planarization successfully reduces the 2μm height of the bumps on ROIC to less than 83 nm, over the planarized polymer mesas, bolometer arrays are fabricated. Then the polymer film as sacrificial are removed by ICP and 160x120 self-supporting micro-bridge structure arrays are successfully fabricated.

  6. Polymer films as planarization and sacrificial layers for uncooled infrared focal plane arrays

    NASA Astrophysics Data System (ADS)

    Liu, Huan; Liu, Weiguo; Cai, Changlong; Zhou, Shun

    2011-02-01

    This paper presents a planarization procedure using polymer films to achieve a flat CMOS surface of Readout Integrated Circuit (ROIC) for the integration between uncooled infrared focal plane arrays and ROIC. At the same time, the polymer film is also used as the sacrificial layers. After amorphous Silicon (a-Si) film was deposited using plasma enhanced chemical vapor deposition (PECVD), and patterned using inductively coupled plasma (ICP), the polymer sacrificial layer should be removed to form a-Si self-supporting micro-bridge structure. So the thickness of polymer film determine the height of the micro-bridge; the soft curing temperature determines if the contact hole can be etched by developer during the first photolithography; and the rate of dry etching determines whether the sacrificial layers of the structure can be released successfully. In this paper, the curing temperature, surface roughness, etching process of polymer films are systematically researched. On this basis, polymer film as planarization successfully reduces the 2μm height of the bumps on ROIC to less than 83 nm, over the planarized polymer mesas, bolometer arrays are fabricated. Then the polymer film as sacrificial are removed by ICP and 160x120 self-supporting micro-bridge structure arrays are successfully fabricated.

  7. Preparation of self-supporting Au thin films on perforated substrate by releasing from water-soluble sacrificial layer

    NASA Astrophysics Data System (ADS)

    Miyamoto, Yu; Fujii, Yuma; Yamano, Masafumi; Harigai, Toru; Suda, Yoshiyuki; Takikawa, Hirofumi; Kawano, Takeshi; Nishiuchi, Mamiko; Sakaki, Hironao; Kondo, Kiminori

    2016-07-01

    A self-supporting thin film is useful as a target material for laser-driven ion acceleration experiments. In this study, 100-nm-thick sputtered gold (Au) thin films were released from substrates using water-soluble sacrificial layers, and the released films were subsequently scooped up on perforated substrates. Au thin films were deposited by DC plasma sputtering on the sacrificial layers. In the releasing test, sodium chloride (NaCl) was shown to be most suitable as a sacrificial layer for Au thin films. In addition, sputtered Au thin films with thicknesses of 50 and 150 nm were deposited onto NaCl sacrificial layers, released on water, and scooped up on perforated substrates. Self-supporting Au thin films were obtained for all film thicknesses, but wrinkles and cracks appeared in the 50 nm film.

  8. Soft substrate as a sacrificial layer for fabrication free-standing SU-8-based nanofluidic system

    NASA Astrophysics Data System (ADS)

    Li, Xiaojun; Wang, Xudi; Jin, Jian; Li, Xin; Tian, Yangchao; Fu, Shaojun

    2010-10-01

    In this paper, we describe a new fabrication process utilizing polydimethylesiloxane (PDMS) and polyester (PET) as a sacrificial substrate for fabricating free-standing SU-8-based nanofluidic system. The soft substrate permits SU-8 UV cured patterning and layer-to-layer bonding, and allows the SU-8 structures to be easily peeled off from the substrate after complete fabrication. In the process, PDMS-on glass is used as a handling wafer, on which SU-8 based trenches is imprinted by a flexible film mold using low-pressure nanoimprint lithography. The reservoir pattern of SU-8 is fabricated on the bonding layer, in which PET serves as substrate. The nanochannel is sealed by optimized bonding process, which is flexible and easily controllable with the use of soft substrate as a sacrificial layer. After bonding process, PDMS and PET could be easily peeled off from nanaofluidic system. The SEM results shows that the height of the fully enclosed nanochannels will be about hundreds nanometer. Large area of free standing SU-8 structure layers are successfully fabricated and peeled off from the soft substrate layer as single continuous sheets.

  9. Multifunctional polyelectrolyte multilayers as nanofiltration membranes and as sacrificial layers for easy membrane cleaning.

    PubMed

    Ilyas, Shazia; de Grooth, Joris; Nijmeijer, Kitty; de Vos, Wiebe M

    2015-05-15

    This manuscript investigates the modification of an ultra-filtration (UF) membrane support with polyelectrolyte multilayers (PEMs) consisting of the weak polyelectrolytes poly(allyl amine) hydrochloride (PAH) and poly(acrylic acid) (PAA). These prepared polyelectrolyte multilayer membranes have a dual function: They act as nanofiltration (NF) membranes and as sacrificial layers to allow easy cleaning of the membranes. In order to optimize the conditions for PEM coating and removal, adsorption and desorption of these layers on a model surface (silica) was first studied via optical reflectometry. Subsequently, a charged UF membrane support was coated with a PEM and after each deposited layer, a clear increase in membrane resistance against pure water permeation and a switch of the zeta potential were observed. Moreover these polyelectrolyte multilayer membranes, exhibited rejection of solutes in a range typical for NF membranes. Monovalent ions (NaCl) were hardly rejected (<24%), while rejections of >60% were observed for a neutral organic molecule sulfamethoxazole (SMX) and for the divalent ion SO3(2-). The rejection mechanism of these membranes seems to be dominated by size-exclusion. To investigate the role of these PEMs as sacrificial layers for the cleaning of fouled membranes, the prepared polyelectrolyte multilayers were fouled with silica nano particles. Subsequent removal of the coating using a rinse and a low pressure backwash with pH 3, 3M NaNO3 allowed for a drop in membrane resistance from 1.7⋅10(14)m(-1) (fouled membrane) to 9.9⋅10(12)m(-1) (clean membrane), which is nearly equal to that of the pristine membrane (9.7⋅10(12)m(-1)). Recoating of the support membrane with the same PEMs resulted in a resistance equal to the resistance of the original polyelectrolyte multilayer membrane. Interestingly, less layers were needed to obtain complete foulant removal from the membrane surface, than was the case for the model surface. The possibility for

  10. Film transfer enabled by nanosheet seed layers on arbitrary sacrificial substrates

    SciTech Connect

    Dral, A. P.; Nijland, M.; Koster, G.; Elshof, J. E. ten

    2015-05-01

    An approach for film transfer is demonstrated that makes use of seed layers of nanosheets on arbitrary sacrificial substrates. Epitaxial SrTiO{sub 3}, SrRuO{sub 3}, and BiFeO{sub 3} films were grown on Ca{sub 2}Nb{sub 3}O{sub 10} nanosheet seed layers on phlogopite mica substrates. Cleavage of the mica substrates enabled film transfer to flexible polyethylene terephthalate substrates. Electron backscatter diffraction, X-ray diffraction, and atomic force microscopy confirmed that crystal orientation and film morphology remained intact during transfer. The generic nature of this approach is illustrated by growing films on zinc oxide substrates with a nanosheet seed layer. Film transfer to a flexible substrate was accomplished via acid etching.

  11. Metallization and biopatterning on ultra-flexible substrates via dextran sacrificial layers.

    PubMed

    Tseng, Peter; Pushkarsky, Ivan; Di Carlo, Dino

    2014-01-01

    Micro-patterning tools adopted from the semiconductor industry have mostly been optimized to pattern features onto rigid silicon and glass substrates, however, recently the need to pattern on soft substrates has been identified in simulating cellular environments or developing flexible biosensors. We present a simple method of introducing a variety of patterned materials and structures into ultra-flexible polydimethylsiloxane (PDMS) layers (elastic moduli down to 3 kPa) utilizing water-soluble dextran sacrificial thin films. Dextran films provided a stable template for photolithography, metal deposition, particle adsorption, and protein stamping. These materials and structures (including dextran itself) were then readily transferrable to an elastomer surface following PDMS (10 to 70∶1 base to crosslinker ratios) curing over the patterned dextran layer and after sacrificial etch of the dextran in water. We demonstrate that this simple and straightforward approach can controllably manipulate surface wetting and protein adsorption characteristics of PDMS, covalently link protein patterns for stable cell patterning, generate composite structures of epoxy or particles for study of cell mechanical response, and stably integrate certain metals with use of vinyl molecular adhesives. This method is compatible over the complete moduli range of PDMS, and potentially generalizable over a host of additional micro- and nano-structures and materials. PMID:25153326

  12. Metallization and Biopatterning on Ultra-Flexible Substrates via Dextran Sacrificial Layers

    PubMed Central

    Tseng, Peter; Pushkarsky, Ivan; Di Carlo, Dino

    2014-01-01

    Micro-patterning tools adopted from the semiconductor industry have mostly been optimized to pattern features onto rigid silicon and glass substrates, however, recently the need to pattern on soft substrates has been identified in simulating cellular environments or developing flexible biosensors. We present a simple method of introducing a variety of patterned materials and structures into ultra-flexible polydimethylsiloxane (PDMS) layers (elastic moduli down to 3 kPa) utilizing water-soluble dextran sacrificial thin films. Dextran films provided a stable template for photolithography, metal deposition, particle adsorption, and protein stamping. These materials and structures (including dextran itself) were then readily transferrable to an elastomer surface following PDMS (10 to 70∶1 base to crosslinker ratios) curing over the patterned dextran layer and after sacrificial etch of the dextran in water. We demonstrate that this simple and straightforward approach can controllably manipulate surface wetting and protein adsorption characteristics of PDMS, covalently link protein patterns for stable cell patterning, generate composite structures of epoxy or particles for study of cell mechanical response, and stably integrate certain metals with use of vinyl molecular adhesives. This method is compatible over the complete moduli range of PDMS, and potentially generalizable over a host of additional micro- and nano-structures and materials. PMID:25153326

  13. Multiscale ommatidial arrays with broadband and omnidirectional antireflection and antifogging properties by sacrificial layer mediated nanoimprinting.

    PubMed

    Raut, Hemant Kumar; Dinachali, Saman Safari; Loke, Yee Chong; Ganesan, Ramakrishnan; Ansah-Antwi, Kwadwo Konadu; Góra, Aleksander; Khoo, Eng Huat; Ganesh, V Anand; Saifullah, Mohammad S M; Ramakrishna, Seeram

    2015-02-24

    Moth's eye inspired multiscale ommatidial arrays offer multifunctional properties of great significance in optoelectronic devices. However, a major challenge remains in fabricating these arrays on large-area substrates using a simple and scalable technique. Here we present the fabrication of these multiscale ommatidial arrays over large areas by a distinct approach called sacrificial layer mediated nanoimprinting, which involves nanoimprinting aided by a sacrificial layer. The fabricated arrays exhibited excellent pattern uniformity over the entire patterned area. Optimum dimensions of the multiscale ommatidial arrays determined by the finite-difference time domain simulations served as the design parameters for replicating the arrays on glass. A broadband suppression of reflectance to a minimum of ∼1.4% and omnidirectional antireflection for highly oblique angles of incidence up to 70° were achieved. In addition, superhydrophobicity and superior antifogging characteristics enabled the retention of optical properties even in wet and humid conditions, suggesting reliable optical performance in practical outdoor conditions. We anticipate that these properties could potentially enhance the performance of optoelectronic devices and minimize the influence of in-service conditions. Additionally, as our technique is solely nanoimprinting-based, it may enable scalable and high-throughput fabrication of multiscale ommatidial arrays. PMID:25634665

  14. Generation of cavities in silicon wafers by laser ablation using silicon nitride as sacrificial layer

    NASA Astrophysics Data System (ADS)

    Lerner, B.; Perez, M. S.; Toro, C.; Lasorsa, C.; Rinaldi, C. A.; Boselli, A.; Lamagna, A.

    2012-01-01

    Throughout this investigation, experiments on laser ablation with silicon (Si) wafers have been performed using silicon nitride (Si3N4) as a sacrificial layer to find the optimal fluence capable of removing the Si3N4, which allows the subsequent anisotropic etching in Si with potassium hydroxide. As a result, an alternative to the traditional micromachining techniques that require more steps and processing times has been introduced. The effect of the pulse numbers on Si wafers has been studied and it has been observed that when increasing the pulse numbers at the same fluence, the capacity of the pyramidal cavity formed was greater than using only one pulse at higher fluences. Microcavities were performed with a floating Si3N4 layer. This happens to be very useful for the development of drug delivery systems and the manufacture of microarrays. Microcavities were also used as masters for the fabrication of microionizers in polydimethyl siloxane (PDMS).

  15. Phosphorus diffusion gettering process of multicrystalline silicon using a sacrificial porous silicon layer

    PubMed Central

    2012-01-01

    The aims of this work are to getter undesirable impurities from low-cost multicrystalline silicon (mc-Si) wafers and then enhance their electronic properties. We used an efficient process which consists of applying phosphorus diffusion into a sacrificial porous silicon (PS) layer in which the gettered impurities have been trapped after the heat treatment. As we have expected, after removing the phosphorus-rich PS layer, the electrical properties of the mc-Si wafers were significantly improved. The PS layers, realized on both sides of the mc-Si substrates, were formed by the stain-etching technique. The phosphorus treatment was achieved using a liquid POCl3-based source on both sides of the mc-Si wafers. The realized phosphorus/PS/Si/PS/phosphorus structures were annealed at a temperature ranging between 700°C and 950°C under a controlled O2 atmosphere, which allows phosphorus to diffuse throughout the PS layers and to getter eventual metal impurities towards the phosphorus-doped PS layer. The effect of this gettering procedure was investigated by means of internal quantum efficiency and the dark current–voltage (I-V) characteristics. The minority carrier lifetime measurements were made using a WTC-120 photoconductance lifetime tester. The serial resistance and the shunt resistance carried out from the dark I-V curves confirm this gettering-related solar cell improvement. It has been shown that the photovoltaic parameters of the gettered silicon solar cells were improved with regard to the ungettered one, which proves the beneficial effect of this gettering process on the conversion efficiency of the multicrystalline silicon solar cells. PMID:22846070

  16. Phosphorus diffusion gettering process of multicrystalline silicon using a sacrificial porous silicon layer

    NASA Astrophysics Data System (ADS)

    Lotfi, Derbali; Hatem, Ezzaouia

    2012-07-01

    The aims of this work are to getter undesirable impurities from low-cost multicrystalline silicon (mc-Si) wafers and then enhance their electronic properties. We used an efficient process which consists of applying phosphorus diffusion into a sacrificial porous silicon (PS) layer in which the gettered impurities have been trapped after the heat treatment. As we have expected, after removing the phosphorus-rich PS layer, the electrical properties of the mc-Si wafers were significantly improved. The PS layers, realized on both sides of the mc-Si substrates, were formed by the stain-etching technique. The phosphorus treatment was achieved using a liquid POCl3-based source on both sides of the mc-Si wafers. The realized phosphorus/PS/Si/PS/phosphorus structures were annealed at a temperature ranging between 700°C and 950°C under a controlled O2 atmosphere, which allows phosphorus to diffuse throughout the PS layers and to getter eventual metal impurities towards the phosphorus-doped PS layer. The effect of this gettering procedure was investigated by means of internal quantum efficiency and the dark current-voltage ( I- V) characteristics. The minority carrier lifetime measurements were made using a WTC-120 photoconductance lifetime tester. The serial resistance and the shunt resistance carried out from the dark I- V curves confirm this gettering-related solar cell improvement. It has been shown that the photovoltaic parameters of the gettered silicon solar cells were improved with regard to the ungettered one, which proves the beneficial effect of this gettering process on the conversion efficiency of the multicrystalline silicon solar cells.

  17. Releasing of Sputtered Au Film by Dissolving Sacrificial Layer and Its Self-Standing on Perforated Substrate

    NASA Astrophysics Data System (ADS)

    Miyamoto, Yu; Fujii, Yuma; Yamano, Masafumi; Harigai, Toru; Suda, Yoshiyuki; Takikawa, Hirofumi; Nishiuchi, Mamiko; Sakaki, Hironao; Kondo, Kiminori

    2015-09-01

    Free-standing thin films such as diamond-like carbon (DLC) and gold (Au) have been attracted increasing interests as film targets used in the laser-driven ion acceleration experiment. One of the methods to make the free-standing thin film is to use a soluble sacrifice layer. In this study, the fabrication technique of self-standing Au thin film is presented. Gelatin, oblate, silk fibroin, and NaCl were examined as a. Au thin films were deposited by DC plasma sputtering on sacrifice layers. The gelatin and oblate were used as the sacrificial layer and the supporting substrate. Silk fibroin was coated on glass substrates by a spin coater. The NaCl sacrificial layers were deposited on flat Si substrates by the vacuum vapor deposition system. Sputtered Au thin films were released by immersing the substrates in purified water. Self-standing Au thin films were fabricated by scooping up the released Au thin film on a perforated substrate. The highest quality of the self-standing Au thin film was achieved by using NaCl sacrificial layer. This work was supported by JSPS KAKENHI Grant-in-Aid for Scientific Research and Toukai Foundation for Technology.

  18. UV-Enhanced Sacrificial Layer Stabilised Graphene Oxide Hollow Fibre Membranes for Nanofiltration.

    PubMed

    Chong, J Y; Aba, N F D; Wang, B; Mattevi, C; Li, K

    2015-01-01

    Graphene oxide (GO) membranes have demonstrated great potential in gas separation and liquid filtration. For upscale applications, GO membranes in a hollow fibre geometry are of particular interest due to the high-efficiency and easy-assembly features at module level. However, GO membranes were found unstable in dry state on ceramic hollow fibre substrates, mainly due to the drying-related shrinkage, which has limited the applications and post-treatments of GO membranes. We demonstrate here that GO hollow fibre membranes can be stabilised by using a porous poly(methyl methacrylate) (PMMA) sacrificial layer, which creates a space between the hollow fibre substrate and the GO membrane thus allowing stress-free shrinkage. Defect-free GO hollow fibre membrane was successfully determined and the membrane was stable in a long term (1200 hours) gas-tight stability test. Post-treatment of the GO membranes with UV light was also successfully accomplished in air, which induced the creation of controlled microstructural defects in the membrane and increased the roughness factor of the membrane surface. The permeability of the UV-treated GO membranes was greatly enhanced from 0.07 to 2.8 L m(-2) h(-1) bar(-1) for water, and 0.14 to 7.5 L m(-2) h(-1) bar(-1) for acetone, with an unchanged low molecular weight cut off (~250 Da). PMID:26527173

  19. UV-Enhanced Sacrificial Layer Stabilised Graphene Oxide Hollow Fibre Membranes for Nanofiltration

    NASA Astrophysics Data System (ADS)

    Chong, J. Y.; Aba, N. F. D.; Wang, B.; Mattevi, C.; Li, K.

    2015-11-01

    Graphene oxide (GO) membranes have demonstrated great potential in gas separation and liquid filtration. For upscale applications, GO membranes in a hollow fibre geometry are of particular interest due to the high-efficiency and easy-assembly features at module level. However, GO membranes were found unstable in dry state on ceramic hollow fibre substrates, mainly due to the drying-related shrinkage, which has limited the applications and post-treatments of GO membranes. We demonstrate here that GO hollow fibre membranes can be stabilised by using a porous poly(methyl methacrylate) (PMMA) sacrificial layer, which creates a space between the hollow fibre substrate and the GO membrane thus allowing stress-free shrinkage. Defect-free GO hollow fibre membrane was successfully determined and the membrane was stable in a long term (1200 hours) gas-tight stability test. Post-treatment of the GO membranes with UV light was also successfully accomplished in air, which induced the creation of controlled microstructural defects in the membrane and increased the roughness factor of the membrane surface. The permeability of the UV-treated GO membranes was greatly enhanced from 0.07 to 2.8 L m-2 h-1 bar-1 for water, and 0.14 to 7.5 L m-2 h-1 bar-1 for acetone, with an unchanged low molecular weight cut off (~250 Da).

  20. UV-Enhanced Sacrificial Layer Stabilised Graphene Oxide Hollow Fibre Membranes for Nanofiltration

    PubMed Central

    Chong, J. Y.; Aba, N. F. D.; Wang, B.; Mattevi, C.; Li, K.

    2015-01-01

    Graphene oxide (GO) membranes have demonstrated great potential in gas separation and liquid filtration. For upscale applications, GO membranes in a hollow fibre geometry are of particular interest due to the high-efficiency and easy-assembly features at module level. However, GO membranes were found unstable in dry state on ceramic hollow fibre substrates, mainly due to the drying-related shrinkage, which has limited the applications and post-treatments of GO membranes. We demonstrate here that GO hollow fibre membranes can be stabilised by using a porous poly(methyl methacrylate) (PMMA) sacrificial layer, which creates a space between the hollow fibre substrate and the GO membrane thus allowing stress-free shrinkage. Defect-free GO hollow fibre membrane was successfully determined and the membrane was stable in a long term (1200 hours) gas-tight stability test. Post-treatment of the GO membranes with UV light was also successfully accomplished in air, which induced the creation of controlled microstructural defects in the membrane and increased the roughness factor of the membrane surface. The permeability of the UV-treated GO membranes was greatly enhanced from 0.07 to 2.8 L m−2 h−1 bar−1 for water, and 0.14 to 7.5 L m−2 h−1 bar−1 for acetone, with an unchanged low molecular weight cut off (~250 Da). PMID:26527173

  1. Release of MEMS devices with hard-baked polyimide sacrificial layer

    NASA Astrophysics Data System (ADS)

    Boroumand Azad, Javaneh; Rezadad, Imen; Nath, Janardan; Smith, Evan; Peale, Robert E.

    2013-03-01

    Removal of polyimides used as sacrificial layer in fabricating MEMS devices can be challenging after hardbaking, which may easily result by the end of multiple-step processing. We consider the specific commercial co-developable polyimide ProLift 100 (Brewer Science). Excessive heat hardens this material, so that during wet release in TMAH based solvents, intact sheets break free from the substrate, move around in the solution, and break delicate structures. On the other hand, dry reactive-ion etching of hard-baked ProLift is so slow, that MEMS structures are damaged from undesirably-prolonged physical bombardment by plasma ions. We found that blanket exposure to ultraviolet light allows rapid dry etch of the ProLift surrounding the desired structures without damaging them. Subsequent removal of ProLift from under the devices can then be safely performed using wet or dry etch. We demonstrate the approach on PECVD-grown silicon-oxide cantilevers of 100 micron × 100 micron area supported 2 microns above the substrate by ~100-micron-long 8-micron-wide oxide arms.

  2. Sodium Exposure Tests on Limestone Concrete Used as Sacrificial Protection Layer in FBR

    SciTech Connect

    Parida, F.C.; Das, S.K.; Sharma, A.K.; Rao, P.M.; Ramesh, S.S.; Somayajulu, P.A.; Malarvizhi, B.; Kasinathan, N.

    2006-07-01

    Hot sodium coming in contact with structural concrete in case of sodium leak in FBR system cause damage as a result of thermo-chemical attack by burning sodium. In addition, release of free and bound water from concrete leads to generation of hydrogen gas, which is explosive in nature. Hence limestone concrete, as sacrificial layer on the structural concrete in FBR, needs to be qualified. Four concrete blocks of dimension 600 mm x 600 mm x 300 mm with 300 mm x 300 mm x 150 mm cavity were cast and subjected to controlled sodium exposure tests. They have composition of ordinary portland cement, water, fine and coarse aggregate of limestone in the ratio of 1: 0.58: 2.547: 3.817. These blocks were subjected to preliminary inspection by ultrasonic pulse velocity technique and rebound hammer tests. Each block was exposed for 30 minutes to about 12 kg of liquid sodium ({approx} 120 mm liquid column) at 550 deg. C in open air, after which sodium was sucked back from the cavity of the concrete block into a sodium tank. On-line temperature monitoring was carried out at strategic locations of sodium pool and concrete block. After removing sodium from the cavity and cleaning the surfaces, rebound hammer testing was carried out on each concrete block at the same locations where data were taken earlier at pre-exposed stage. The statistical analysis of rebound hammer data revealed that one of the concrete block alone has undergone damage to the extent of 16%. The loss of mass occurred for all the four blocks varied from 0.6 to 2.4% due to release of water during the test duration. Chemical analysis of sodium in concrete samples collected from cavity floor of each block helped in generation of depth profiles of sodium monoxide concentration for each block. From this it is concluded that a bulk penetration of sodium up to 30 mm depth has taken place. However it was also observed that at few local spots, sodium penetrated into concrete up to 50 mm. Cylindrical core samples of 50 mm

  3. Near-Infrared Light-Stimulus-Responsive Film as a Sacrificial Layer for the Preparation of Free-Standing Films.

    PubMed

    Bao, Chunyang; Ma, Benhua; Liu, Jiale; Wu, Zhennan; Zhang, Hao; Jiang, Yi-Jun; Sun, Junqi

    2016-04-12

    It remains a challenge to fabricate sacrificial films that are stable in most of solvents and can be readily decomposed on demand. Here we report the fabrication of a near-infrared (NIR) light decomposable sacrificial film by layer-by-layer (LbL) assembly of UV-light-decomposable poly((4-(2-bromoethoxy)-5-methoxy-2-nitrobenzyl acrylate) triethylammonium bromide) (PNBA-TEA), poly(sodium 4-styrene-sulfonate) (PSS), branched polyethyleimine (bPEI), and lanthanide-doped upconversion nanoparticles (UCNPs). The [(PNBA-TEA/PSS)*2/(bPEI/UCNPs)*3]*2 films are stable in deposition solutions of various materials and decompose upon NIR light irradiation. In the [(PNBA-TEA/PSS)*2/(bPEI/UCNPs)*3]*2 films, UCNPs can convert NIR light into UV light, which can decompose PNBA-TEA. After immersing the NIR light-irradiated [(PNBA-TEA/PSS)*2/(bPEI/UCNPs)*3]*2 films in 0.1 M aqueous NaHCO3 solution, the disintegration of the entire films occurs because of the repulsive force between the negatively charged photoproduct of PNBA-TEA and PSS. LbL-assembled (PAH/PAA)*50 films deposited on top of the NIR-light-decomposable [(PNBA-TEA/PSS)*2/(bPEI/UCNPs)*3]*2 films can be conveniently released to produce large-area and defect-free (PAH/PAA)*50 free-standing films after NIR light irradiation and subsequent immersion in 0.1 M aqueous NaHCO3 solution. Because of the satisfactory stability and on-demand decomposable property, the [(PNBA-TEA/PSS)*2/(bPEI/UCNPs)*3]*2 films are promising as sacrificial layers for the fabrication of various free-standing films. PMID:27019115

  4. Numerically controlled atmospheric-pressure plasma sacrificial oxidation using electrode arrays for improving silicon-on-insulator layer uniformity

    NASA Astrophysics Data System (ADS)

    Takei, Hiroyasu; Yoshinaga, Keinosuke; Matsuyama, Satoshi; Yamauchi, Kazuto; Sano, Yasuhisa

    2015-01-01

    Silicon-on-insulator (SOI) wafers are important semiconductor substrates in high-performance devices. In accordance with device miniaturization requirements, ultrathin and highly uniform top silicon layers (SOI layers) are required. A novel method involving numerically controlled (NC) atmospheric-pressure plasma sacrificial oxidation using an electrode array system was developed for the effective fabrication of an ultrathin SOI layer with extremely high uniformity. Spatial resolution and oxidation properties are the key factors controlling ultraprecision machining. The controllability of plasma oxidation and the oxidation properties of the resulting experimental electrode array system were examined. The results demonstrated that the method improved the thickness uniformity of the SOI layer over one-sixth of the area of an 8-in. wafer area.

  5. Chemically Compatible Sacrificial Layer-Assisted Lift-Off Patterning Method for Fabrication of Organic Light-Emitting Displays

    NASA Astrophysics Data System (ADS)

    Choi, Wonsuk; Kim, Min-Hoi; Lee, Sin-Doo

    2011-08-01

    We developed a generic platform to pattern combinatorial functional layers composed of different classes of organic materials using a repetitive lift-off method based on a chemically compatible sacrificial layer (SL) for organic light-emitting diodes (OLEDs). The essential features come from the chemically compatible SL of a fluorous-polymer that can be generated by laser-inscription or transfer-printing. The precise registration of lateral patterns of different materials was achieved on a single substrate through a series of SL-assisted lift-off processes. The chemical compatibility of the SL and the stability of the light-emitting characteristics were shown in a fluorous-solvent treated monochrome OLEDs.

  6. BEOL compatible high tunnel magneto resistance perpendicular magnetic tunnel junctions using a sacrificial Mg layer as CoFeB free layer cap

    NASA Astrophysics Data System (ADS)

    Swerts, J.; Mertens, S.; Lin, T.; Couet, S.; Tomczak, Y.; Sankaran, K.; Pourtois, G.; Kim, W.; Meersschaut, J.; Souriau, L.; Radisic, D.; Van Elshocht, S.; Kar, G.; Furnemont, A.

    2015-06-01

    Perpendicularly magnetized MgO-based tunnel junctions are envisaged for future generation spin-torque transfer magnetoresistive random access memory devices. Achieving a high tunnel magneto resistance and preserving it together with the perpendicular magnetic anisotropy during BEOL CMOS processing are key challenges to overcome. The industry standard technique to deposit the CoFeB/MgO/CoFeB tunnel junctions is physical vapor deposition. In this letter, we report on the use of an ultrathin Mg layer as free layer cap to protect the CoFeB free layer from sputtering induced damage during the Ta electrode deposition. When Ta is deposited directly on CoFeB, a fraction of the surface of the CoFeB is sputtered even when Ta is deposited with very low deposition rates. When depositing a thin Mg layer prior to Ta deposition, the sputtering of CoFeB is prevented. The ultra-thin Mg layer is sputtered completely after Ta deposition. Therefore, the Mg acts as a sacrificial layer that protects the CoFeB from sputter-induced damage during the Ta deposition. The Ta-capped CoFeB free layer using the sacrificial Mg interlayer has significantly better electrical and magnetic properties than the equivalent stack without protective layer. We demonstrate a tunnel magneto resistance increase up to 30% in bottom pinned magnetic tunnel junctions and tunnel magneto resistance values of 160% at resistance area product of 5 Ω.μm2. Moreover, the free layer maintains perpendicular magnetic anisotropy after 400 °C annealing.

  7. BEOL compatible high tunnel magneto resistance perpendicular magnetic tunnel junctions using a sacrificial Mg layer as CoFeB free layer cap

    SciTech Connect

    Swerts, J. Mertens, S.; Lin, T.; Couet, S.; Tomczak, Y.; Sankaran, K.; Pourtois, G.; Kim, W.; Meersschaut, J.; Souriau, L.; Radisic, D.; Van Elshocht, S.; Kar, G.; Furnemont, A.

    2015-06-29

    Perpendicularly magnetized MgO-based tunnel junctions are envisaged for future generation spin-torque transfer magnetoresistive random access memory devices. Achieving a high tunnel magneto resistance and preserving it together with the perpendicular magnetic anisotropy during BEOL CMOS processing are key challenges to overcome. The industry standard technique to deposit the CoFeB/MgO/CoFeB tunnel junctions is physical vapor deposition. In this letter, we report on the use of an ultrathin Mg layer as free layer cap to protect the CoFeB free layer from sputtering induced damage during the Ta electrode deposition. When Ta is deposited directly on CoFeB, a fraction of the surface of the CoFeB is sputtered even when Ta is deposited with very low deposition rates. When depositing a thin Mg layer prior to Ta deposition, the sputtering of CoFeB is prevented. The ultra-thin Mg layer is sputtered completely after Ta deposition. Therefore, the Mg acts as a sacrificial layer that protects the CoFeB from sputter-induced damage during the Ta deposition. The Ta-capped CoFeB free layer using the sacrificial Mg interlayer has significantly better electrical and magnetic properties than the equivalent stack without protective layer. We demonstrate a tunnel magneto resistance increase up to 30% in bottom pinned magnetic tunnel junctions and tunnel magneto resistance values of 160% at resistance area product of 5 Ω.μm{sup 2}. Moreover, the free layer maintains perpendicular magnetic anisotropy after 400 °C annealing.

  8. Atomic layer epitaxy of AlAs and AlGaAs

    NASA Astrophysics Data System (ADS)

    Meguro, T.; Iwai, S.; Aoyagi, Y.; Ozaki, K.; Yamamoto, Y.; Suzuki, T.; Okano, Y.; Hirata, A.

    1990-01-01

    Atomic layer epitaxy (ALE) of AlAs and AlGaAs with metalorganic vapor-phase epitaxy (MOVPE) under Ar-ion laser irradiation has been successfully realized in a triethylaluminum (TEA)/AsH 3 system for the first time. Comparison with the growth characteristics of MOVPE with alternative feeding modes of TMA/AsH 3 and TEA/AsH 3 is discussed. Application to laser-ALE of AlGaAs using a triethylgallium (TEG)/TEA/AsH 3 system is also discussed.

  9. Improvement of performance of InAs quantum dot solar cell by inserting thin AlAs layers

    PubMed Central

    2011-01-01

    A new measure to enhance the performance of InAs quantum dot solar cell is proposed and measured. One monolayer AlAs is deposited on top of InAs quantum dots (QDs) in multistack solar cells. The devices were fabricated by molecular beam epitaxy. In situ annealing was intended to tune the QD density. A set of four samples were compared: InAs QDs without in situ annealing with and without AlAs cap layer and InAs QDs in situ annealed with and without AlAs cap layer. Atomic force microscopy measurements show that when in situ annealing of QDs without AlAs capping layers is investigated, holes and dashes are present on the device surface, while capping with one monolayer AlAs improves the device surface. On unannealed samples, capping the QDs with one monolayer of AlAs improves the spectral response, the open-circuit voltage and the fill factor. On annealed samples, capping has little effect on the spectral response but reduces the short-circuit current, while increasing the open-circuit voltage, the fill factor and power conversion efficiency. PMID:21711628

  10. Fabrication of Covalently Crosslinked and Amine-Reactive Microcapsules by Reactive Layer-by-Layer Assembly of Azlactone-Containing Polymer Multilayers on Sacrificial Microparticle Templates

    PubMed Central

    Saurer, Eric M.; Flessner, Ryan M.; Buck, Maren E.; Lynn, David M.

    2011-01-01

    We report on the fabrication of covalently crosslinked and amine-reactive hollow microcapsules using ‘reactive’ layer-by-layer assembly to deposit thin polymer films on sacrificial microparticle templates. Our approach is based on the alternating deposition of layers of a synthetic polyamine and a polymer containing reactive azlactone functionality. Multilayered films composed of branched poly(ethylene imine) (BPEI) and poly(2-vinyl-4,4-dimethylazlactone) (PVDMA) were fabricated layer-by-layer on the surfaces of calcium carbonate and glass microparticle templates. After fabrication, these films contained residual azlactone functionality that was accessible for reaction with amine-containing molecules. Dissolution of the calcium carbonate or glass cores using aqueous ethylenediamine tetraacetic acid (EDTA) or hydrofluoric acid (HF), respectively, led to the formation of hollow polymer microcapsules. These microcapsules were robust enough to encapsulate and retain a model macromolecule (FITC-dextran) and were stable for at least 22 hours in high ionic strength environments, in low and high pH solutions, and in several common organic solvents. Significant differences in the behaviors of capsules fabricated on CaCO3 and glass cores were observed and characterized using scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDS). Whereas capsules fabricated on CaCO3 templates collapsed upon drying, capsules fabricated on glass templates remained rigid and spherical. Characterization using EDS suggested that this latter behavior results, at least in part, from the presence of insoluble metal fluoride salts that are trapped or precipitate within the walls of capsules after etching of the glass cores using HF. Our results demonstrate that the assembly of BPEI/PVDMA films on sacrificial templates can be used to fabricate reactive microcapsules of potential use in a wide range of fields, including catalysis, drug and gene delivery, imaging, and

  11. Fabrication of a three-layer SU-8 mould with inverted T-shaped cavities based on a sacrificial photoresist layer technique.

    PubMed

    Liu, Junshan; Zhang, Dong; Sha, Baoyong; Yin, Penghe; Xu, Zheng; Liu, Chong; Wang, Liding; Xu, Feng; Wang, Lin

    2014-10-01

    A novel method for fabricating a three-layer SU-8 mould with inverted T-shaped cavities is presented. The first two SU-8 layers were spin coated and exposed separately, and simultaneously developed to fabricate the bottom and the horizontal part of the inverted T-shaped cavity. Then, a positive photoresist was filled into the cavity, and a wet lapping process was performed to remove the excess photoresist and make a temporary substrate. The third SU-8 layer was spin coated on the temporary substrate to make the vertical part of the inverted T-shaped cavity. The sacrificial photoresist layer can prevent the first two SU-8 layers from being secondly exposed, and make a temporary substrate for the third SU-8 layer at the same time. Moreover, the photoresist can be easily removed with the development of the third SU-8 layer. A polydimethylsiloxane (PDMS) microchip with arrays of T-shaped cantilevers for studying the mechanics of cells was fabricated by using the SU-8 mould. PMID:24850230

  12. The case for using a sacrificial layer of absorbent insulation in the design of flat and low-sloped roofing

    NASA Astrophysics Data System (ADS)

    Stockton, Gregory R.

    2013-05-01

    Beginning about twenty-five years ago, there was a marked increase in the number of single-ply membrane roof designs used to cover and waterproof flat and low-sloped building roofs. Over the past ten years, there has been a substantial increase in the number of installations of white and more reflective single-ply roof systems, mostly using high density cellular foam insulation in the substrate for insulation. A major factor in the increase in the popularity of these highly insulated and more reflective roof systems is the fact that many governments began offering incentives for building owners to use reflective coverings and better insulated roofs. Now, owing to the energy efficient requirements for the design and construction of new buildings put forth in ASHRAE Standard 90.1, "Energy Standard for Buildings Except Low-Rise Residential Buildings" and the world's apparent desire to be "green" (or at least appear to be), more and more roof designs will include these reflective single-ply membranes, which use the cellular foam insulation boards to meet these requirements. Using a lower density traditional insulation will mean that the roof will have to be very thick to comply, increasing the costs of installation. High density cellular foams do not absorb water until time, vapor pressure drive, UV and thermal shock break down the foam and it becomes more absorbent. This could be 5-7 years or longer, depending on the roof construction and other factors. This means that any water that enters the roof through a breach (leak) in the membrane goes straight into the building. This is not a good consequence since the failure mode of any roof is water entering the building. Keeping the water out of the building is the purpose of the waterproofing layer. This paper reviews the techniques of moisture testing on building roofs and infrared (IR) thermography, and puts forth the idea and reasoning behind having a sacrificial layer of very absorbent insulation installed in every

  13. Screen printing of a capacitive cantilever-based motion sensor on fabric using a novel sacrificial layer process for smart fabric applications

    NASA Astrophysics Data System (ADS)

    Wei, Yang; Torah, Russel; Yang, Kai; Beeby, Steve; Tudor, John

    2013-07-01

    Free-standing cantilevers have been fabricated by screen printing sacrificial and structural layers onto a standard polyester cotton fabric. By printing additional conductive layers, a complete capacitive motion sensor on fabric using only screen printing has been fabricated. This type of free-standing structure cannot currently be fabricated using conventional fabric manufacturing processes. In addition, compared to conventional smart fabric fabrication processes (e.g. weaving and knitting), screen printing offers the advantages of geometric design flexibility and the ability to simultaneously print multiple devices of the same or different designs. Furthermore, a range of active inks exists from the printed electronics industry which can potentially be applied to create many types of smart fabric. Four cantilevers with different lengths have been printed on fabric using a five-layer structure with a sacrificial material underneath the cantilever. The sacrificial layer is subsequently removed at 160 °C for 30 min to achieve a freestanding cantilever above the fabric. Two silver electrodes, one on top of the cantilever and the other on top of the fabric, are used to capacitively detect the movement of the cantilever. In this way, an entirely printed motion sensor is produced on a standard fabric. The motion sensor was initially tested on an electromechanical shaker rig at a low frequency range to examine the linearity and the sensitivity of each design. Then, these sensors were individually attached to a moving human forearm to evaluate more representative results. A commercial accelerometer (Microstrain G-link) was mounted alongside for comparison. The printed sensors have a similar motion response to the commercial accelerometer, demonstrating the potential of a printed smart fabric motion sensor for use in intelligent clothing applications.

  14. Ga0.5In0.5P Barrier Layer for Wet Oxidation of AlAs

    NASA Astrophysics Data System (ADS)

    Lee, Shih-Chang; Lee, Wei-I

    2000-05-01

    We study the stability of Ga0.5In0.5P and Al0.4Ga0.6As barrier layers for wet thermal oxidation of AlAs on GaAs. Samples with a Ga0.5In0.5P or Al0.4Ga0.6As barrier layer are oxidized in a water vapor environment under various oxidation conditions. The results of photoluminescence and secondary-ion mass spectrometry (SIMS) depth profile measurements indicate that the Ga0.5In0.5P barrier layer is more stable than the Al0.4Ga0.6As layer at higher oxidation temperatures and longer periods of oxidation time.

  15. A concave-patterned TiN/PECVD-Si3N4 /TiN diaphragm MEMS acoustic sensor based on a polyimide sacrificial layer

    NASA Astrophysics Data System (ADS)

    Lee, Jaewoo; Jeon, J. H.; Je, C. H.; Kim, Y.-G.; Lee, S. Q.; Yang, W. S.; Lee, J. S.; Lee, S.-G.

    2015-12-01

    In this paper, we present a concave-patterned TiN/PECVD-Si3N4 /TiN diaphragm micro-electro-mechanical system (MEMS) acoustic sensor based on a polyimide sacrificial layer. The use of the spin-coated polyimide eliminates the additional Al pad process of conventional device fabrication due to simple O2 ashing to release the sacrificial layer, simplifying the photolithography process. Also, to adjust the acoustic sensor for a bottom-ported package, its diaphragm was implemented to be placed over the back-plate. The TiN/PECVD-Si3N4/TiN multi-layer diaphragm was formed with the stress controllability of PECVD-Si3N4 from  -162 MPa to  +109 MPa. Furthermore, a parallel-plate capacitance model on the basis of an approximately linearized electric field method (ALEM) is proposed to evaluate the capacitance of two plates. The modelled capacitance showed less than 3.7% error in FEM simulation, demonstrating the validity of the proposed model. At a zero-bias voltage, the effective intrinsic and parasitic capacitances in the active area were 1.656 pF and 0.388 pF, respectively. Moreover, with a pull-in analytical model by using ALEM, the effective tensile stress for the diaphragm was extracted to  +31.5 MPa, where the pull-in voltage was 10.7 V. In succession, the dynamic response for the open-circuit sensitivity was modelled with an equivalent circuit model based on lumped parameters. The measured open-circuit sensitivity of  -45.1 dBV Pa-1 at 1 kHz with a bias of 9.6 V was only slightly different from the modelled sensitivity of  -45.0 dBV Pa-1. Thus, these results demonstrate that the proposed sensor is suitable for a front-end voice capture module.

  16. Impact of an AlAs window layer upon the optical properties of Al x Ga1‑x As photodiodes

    NASA Astrophysics Data System (ADS)

    Kang, T.; Chen, X. J.; Johnson, E. B.; Christian, J. F.; Lee, K.; Hammig, M. D.

    2016-05-01

    Recently developed advanced scintillators, which have the ability to distinguish gamma-ray interaction events from those that accompany neutron impact, require improved quantum efficiency in the blue to near UV region of the spectrum. We utilize GaAs/Al0.8Ga0.2As photodiode elements as components in a wide band-gap solid-state photomultiplier as a lower-cost, lower logistical burden, and higher quantum efficiency replacement for the photomultiplier tube. An AlAs window layer is employed as a means to increase the diode’s optical performance. Relative to structures absent the window layer, simulations and measurements demonstrate that the AlAs layer produces a spatial coincidence between regions of large drift fields with regions of high photon absorption. In addition to the AlAs layer, secondary ion mass spectrometry measurements show that an unexpected high degree of inter-diffusion of GaAs and AlAs quenches the photon-detection efficiency, a decrease that can be avoided by its post-growth removal. With the AlAs layer, the peak external quantum efficiency of 49% is achieved at 450 nm with 10 V reverse bias, which does not fully deplete the device. Simulations show that full depletion can result in efficiencies exceeding 90%. In order to enhance the optical response, a simple anti-reflective coating layer is designed using the existing passivation layer components that successfully minimizes the reflection at the wavelength range of interest (300 nm–500 nm).

  17. Fabrication of 3-nm-thick Si3N4 membranes for solid-state nanopores using the poly-Si sacrificial layer process

    PubMed Central

    Yanagi, Itaru; Ishida, Takeshi; Fujisaki, Koji; Takeda, Ken-ichi

    2015-01-01

    To improve the spatial resolution of solid-state nanopores, thinning the membrane is a very important issue. The most commonly used membrane material for solid-state nanopores is silicon nitride (Si3N4). However, until now, stable wafer-scale fabrication of Si3N4 membranes with a thickness of less than 5 nm has not been reported, although a further reduction in thickness is desired to improve spatial resolution. In the present study, to fabricate thinner Si3N4 membranes with a thickness of less than 5 nm in a wafer, a new fabrication process that employs a polycrystalline-Si (poly-Si) sacrificial layer was developed. This process enables the stable fabrication of Si3N4 membranes with thicknesses of 3 nm. Nanopores were fabricated in the membrane using a transmission electron microscope (TEM) beam. Based on the relationship between the ionic current through the nanopores and their diameter, the effective thickness of the nanopores was estimated to range from 0.6 to 2.2 nm. Moreover, DNA translocation through the nanopores was observed. PMID:26424588

  18. Sacrificial conversion of layered rare-earth hydroxide (LRH) nanosheets into (Y1-xEux)PO4 nanophosphors and investigation of photoluminescence.

    PubMed

    Wang, Zhihao; Li, Ji-Guang; Zhu, Qi; Li, Xiaodong; Sun, Xudong

    2016-03-15

    Ultra-thin nanosheets (2-6 nm) of the (Y1-xEux)2(OH)5NO3·nH2O layered rare-earth hydroxide (LRH), directly crystallized without exfoliation were employed for the first time as a sacrificial precursor to synthesize (Y1-xEux)PO4 orthophosphate red phosphors via nano-conversion, and anion exchange of both the hydroxyls and NO3(-) in the LRH with the phosphate ions from diammonium hydrogen phosphate ((NH4)2HPO4) is discussed. Detailed characterization of the materials was performed by the combined techniques of XRD, FTIR, TG/DSC, FE-SEM, HR-TEM, and photoluminescence spectroscopy. The (Y1-xEux)PO4 phosphors, with crystallite sizes of up to ∼20 nm, were found to exhibit stronger (5)D0 → (7)F2 (621 nm) than (5)D0 → (7)F1 (595 nm) emissions under charge transfer excitation (236 nm) owing to the nano-size effect. The optimal Eu(3+) content was determined to be ∼10 at% (x = 0.10), and concentration quenching of luminescence was analyzed to result from exchange interactions. The effects of the Eu(3+) content and annealing temperature on the structural features and luminescence properties of the (Y1-xEux)PO4 nanophosphors were discussed in detail, including emission intensity, the asymmetry factor of luminescence, fluorescence lifetime, and CIE chromaticity coordinates. PMID:26898332

  19. Sugar-mediated disassembly of mucin/lectin multilayers and their use as pH-Tolerant, on-demand sacrificial layers.

    PubMed

    Polak, Roberta; Crouzier, Thomas; Lim, Rosanna M; Ribbeck, Katharina; Beppu, Marisa M; Pitombo, Ronaldo N M; Cohen, Robert E; Rubner, Michael F

    2014-08-11

    The layer-by-layer (LbL) assembly of thin films on surfaces has proven to be an extremely useful technology for uses ranging from optics to biomedical applications. Releasing these films from the substrate to generate so-called free-standing multilayer films opens a new set of applications. Current approaches to generating such materials are limited because they can be cytotoxic, difficult to scale up, or have undesirable side reactions on the material. In this work, a new sacrificial thin film system capable of chemically triggered dissolution at physiological pH of 7.4 is described. The film was created through LbL assembly of bovine submaxillary mucin (BSM) and the lectin jacalin (JAC) for a (BSM/JAC) multilayer system, which remains stable over a wide pH range (pH 3-9) and at high ionic strength (up to 5 M NaCl). This stability allows for subsequent LbL assembly of additional films in a variety of conditions, which could be released from the substrate by incubation in the presence of a competitive inhibitor sugar, melibiose, which selectively disassembles the (BSM/JAC) section of the film. This novel multilayer system was then applied to generate free-standing, 7 μm diameter, circular ultrathin films, which can be attached to a cell surface as a "backpack". A critical thickness of about 100 nm for the (BSM/JAC) film was required to release the backpacks from the glass substrate, after incubation in melibiose solution at 37 °C for 1 h. Upon their release, backpacks were subsequently attached to murine monocytes without cytotoxicity, thereby demonstrating the compatibility of this mucin-based release system with living cells. PMID:24964165

  20. Sacrificial bridges for MEMS fabrication

    NASA Astrophysics Data System (ADS)

    Chang, Chao-Min; Chen, Yang-Che; Fong, Chien-Fu; Guu, Yunn-Horng; Chen, Rongshun; Yeh, J. Andrew; Hou, Max T.

    2011-09-01

    This study discusses sacrificial bridges that are used to release MEMS devices. Before being released, sacrificial bridges connect all the component structures into an integral structure. Solder bump bonding is used to mount the MEMS chip on another chip or a printed circuit board (PCB) and to maintain the alignment among all component structures after removal of the sacrificial bridges. Two types of sacrificial bridges were designed, analyzed and fabricated. The fabrication process—which used low resistivity single crystal silicon (SCS) wafers as the device material—was developed to implement the sacrificial bridges. Novel SCS through silicon vias (TSVs), which interconnect stacked chips, was made using the same process. An electrostatic comb drive actuator was fabricated and mounted onto a PCB. The fabricated actuator was tested to demonstrate the feasibility of the fabrication process, sacrificial bridges and SCS TSVs. The results show that the actuator worked well. Its maximum displacement and resonant frequency were 69.9 µm and 406 Hz, respectively. This method is promising for the delivery of a novel 3D system in package for MEMS devices.

  1. Application of graphite-based sacrificial layers for fabrication of LTCC (low temperature co-fired ceramic) membranes and micro-channels

    NASA Astrophysics Data System (ADS)

    Birol, H.; Maeder, T.; Ryser, P.

    2007-01-01

    Fabrication of sensors and micro-fluidic structures from low temperature co-fired ceramic (LTCC) sheets is a growing interest in the micro-packaging community. Such devices usually have inner cavities, whose production is quite complicated. The most elegant method to build such structures so far achieved is by a fugitive phase that is introduced into the multilayer and removed during firing. This paper, therefore, is aimed to introduce the graphite-based sacrificial paste developed for this purpose, and it is constructed in two sections: (i) selection of paste and determination of LTCC open-porosity elimination temperature, and (ii) fabrication and characterization of pressure sensitive LTCC membranes. In the former section, it is shown that increased heating rates (and decreasing tape thickness) shift the open porosity elimination temperature of LTCC by 20 °C, which is small compared to the shift of graphite oxidation temperature (about 100 °C). In the latter section, three parameters affecting the balance between the graphite oxidation and LTCC sintering are studied: heating rate, graphite phase thickness and width of the membrane inlet/outlet channels. As expected, larger heating rates and narrow inlet/outlet channels are found to hinder the oxidation of graphite and evacuation of the resulting products, which results in swollen membranes. Large graphite thickness, through the increased channel height, results in lower swelling in spite of the larger amount of graphite to be oxidized. Membranes with low swelling are found to exhibit excellent pressure sensing characteristics, whereas those with high swelling display hysteretic behavior.

  2. Fabrication of a microfluidic system for capillary electrophoresis using a two-stage embossing technique and solvent welding on poly(methyl methacrylate) with water as a sacrificial layer.

    PubMed

    Koesdjojo, Myra T; Tennico, Yolanda H; Remcho, Vincent T

    2008-04-01

    Methods for fabricating poly(methyl methacrylate) microchips using a novel two-stage embossing technique and solvent welding to form microchannels in microfluidic devices are presented. The hot embossing method involves a two-stage process to create the final microchip design. In its simplest form, a mold made of aluminum is fabricated using CNC machining to create the desired microchannel design. In this work, two polymer substrates with different glass transition temperatures (Tg), polyetherimide (PEI) and poly(methyl methacrylate) (PMMA), were used to make the reusable secondary master and the final chip. First, the aluminum mold was used to emboss the PEI, a polymeric substrate with Tg approximately 216 degrees C. The embossed PEI was then used as a secondary mold for embossing PMMA, a polymeric substrate with a lower Tg ( approximately 105 degrees C). The resulting PMMA substrate possessed the same features as those of the aluminum mold. Successful feature transfer from the aluminum mold to the PMMA substrate was verified by profilometry. Bonding of the embossed layer and a blank PMMA layer to generate the microchip was achieved by solvent welding. The embossed piece was first filled with water that formed a solid sacrificial layer when frozen. The ice layer prevented channel deformation when the welding solvent (dichloroethane) was applied between the two chips during bonding. Electrophoretic separations of fluorescent dyes, rhodamine B (Rh B) and fluorescein (FL), were performed on PMMA microchips to demonstrate the feasibility of the fabrication process for microreplication of useful devices for separations. The PMMA micro-chip was tested under an electric field strength of 705 V cm-1. Separations of the test mixture of Rh B and FL generated 55 500 and 66 300 theoretical plates/meter, respectively. PMID:18303914

  3. Improving Efficiency of Aluminium Sacrificial Anode Using Cold Work Process

    NASA Astrophysics Data System (ADS)

    Asmara, Y. P.; Siregar, J. P.; Tezara, C.; Ann, Chang Tai

    2016-02-01

    Aluminium is one of the preferred materials to be used as sacrificial anode for carbon steel protection. The efficiency of these can be low due to the formation of oxide layer which passivate the anodes. Currently, to improve its efficiency, there are efforts using a new technique called surface modifications. The objective of this research is to study corrosion mechanism of aluminium sacrificial anode which has been processed by cold work. The cold works are applied by reducing the thickness of aluminium sacrificial anodes at 20% and 40% of thickness reduction. The cathodic protection experiments were performed by immersion of aluminium connected to carbon steel cylinder in 3% NaCl solutions. Visual inspections using SEM had been conducted during the experiments and corrosion rate data were taken in every week for 8 weeks of immersion time. Corrosion rate data were measured using weight loss and linear polarization technique (LPR). From the results, it is observed that cold worked aluminium sacrificial anode have a better corrosion performance. It shows higher corrosion rate and lower corrosion potential. The anodes also provided a long functional for sacrificial anode before it stop working. From SEM investigation, it is shown that cold works have changed the microstructure of anodes which is suspected in increasing corrosion rate and cause de-passivate of the surface anodes.

  4. Photoluminescence from InGaAs/GaAs quantum well regrown on a buried patterned oxidized AlAs layer

    NASA Astrophysics Data System (ADS)

    Chouchane, F.; Makhloufi, H.; Calvez, S.; Fontaine, C.; Almuneau, G.

    2014-02-01

    We present a quasi-planar technological approach for forming a flexible and versatile confinement scheme based on oxidation of AlGaAs buried layers combined to an epitaxial regrowth. This method improves the electrical and optical confinements compared to the lateral oxidation since it allows to define confinement areas from a planar surface. This technique is suitable for the realization of advanced integrated photonic components arrays with close device-to-device spacing such as two-dimensional arrays of vertical-cavity surface-emitting lasers. Our results prove that the oxidation and epitaxial regrowth can be sequenced in a process flow, leading to viable confinement while preserving good radiative properties.

  5. Photoluminescence from InGaAs/GaAs quantum well regrown on a buried patterned oxidized AlAs layer

    SciTech Connect

    Chouchane, F.; Makhloufi, H.; Calvez, S.; Fontaine, C.; Almuneau, G.

    2014-02-10

    We present a quasi-planar technological approach for forming a flexible and versatile confinement scheme based on oxidation of AlGaAs buried layers combined to an epitaxial regrowth. This method improves the electrical and optical confinements compared to the lateral oxidation since it allows to define confinement areas from a planar surface. This technique is suitable for the realization of advanced integrated photonic components arrays with close device-to-device spacing such as two-dimensional arrays of vertical-cavity surface-emitting lasers. Our results prove that the oxidation and epitaxial regrowth can be sequenced in a process flow, leading to viable confinement while preserving good radiative properties.

  6. ALA Candidates: Presidential Timbre

    ERIC Educational Resources Information Center

    Berry, John N., III

    2010-01-01

    This article presents an interview with two effective spokespeople, notable school librarian Sara Kelly Johns and retired public library administrator Molly Raphael, who compete to be American Library Association (ALA) president. One of them will be elected president of ALA for a year's term beginning in July 2011. Each candidate comes from a…

  7. Parylene C as a Sacrificial Material for Microfabrication

    NASA Technical Reports Server (NTRS)

    Beamesderfer, Michael

    2005-01-01

    Parylene C has been investigated for use as a sacrificial material in microfabrication. Although Parylene C cannot be patterned lithographically like photoresists, it nevertheless extends the range of processing options by offering a set of properties that are suitable for microfabrication and are complementary to those of photoresists. The compatibility of Parylene C with several microfabrication processes was demonstrated in experiments in which a thin film of Parylene C was deposited on a silicon wafer, then several thin metal films were deposited and successfully patterned, utilizing the Parylene C pads as a sacrificial layer. The term "parylene" -- a contraction of "poly(para-xylene)" -- denotes a family of vapor-deposited polymers. In Parylene C (the most common form of parylene), a chlorine atom is substituted for one of the hydrogen atoms on the benzene ring of each para-xylene moiety. Heretofore, parylenes have been used as conformal coating materials in diverse applications.

  8. Condenser optic with sacrificial reflective surface

    DOEpatents

    Tichenor, Daniel A.; Kubiak, Glenn D.; Lee, Sung Hun

    2007-07-03

    Employing collector optics that has a sacrificial reflective surface can significantly prolong the useful life of the collector optics and the overall performance of the condenser in which the collector optics are incorporated. The collector optics is normally subject to erosion by debris from laser plasma source of radiation. The presence of an upper sacrificial reflective surface over the underlying reflective surface effectively increases the life of the optics while relaxing the constraints on the radiation source. Spatial and temporally varying reflectivity that results from the use of the sacrificial reflective surface can be accommodated by proper condenser design.

  9. Condenser optic with sacrificial reflective surface

    DOEpatents

    Tichenor, Daniel A.; Kubiak, Glenn D.; Lee, Sang Hun

    2006-07-25

    Employing collector optics that have a sacrificial reflective surface can significantly prolong the useful life of the collector optics and the overall performance of the condenser in which the collector optics are incorporated. The collector optics are normally subject to erosion by debris from laser plasma source of radiation. The presence of an upper sacrificial reflective surface over the underlying reflective surface effectively increases the life of the optics while relaxing the constraints on the radiation source. Spatial and temporally varying reflectivity that results from the use of the sacrificial reflective surface can be accommodated by proper condenser design.

  10. Use of silicon oxynitride as a sacrificial material for microelectromechanical devices

    DOEpatents

    Habermehl, Scott D.; Sniegowski, Jeffry J.

    2001-01-01

    The use of silicon oxynitride (SiO.sub.x N.sub.y) as a sacrificial material for forming a microelectromechanical (MEM) device is disclosed. Whereas conventional sacrificial materials such as silicon dioxide and silicate glasses are compressively strained, the composition of silicon oxynitride can be selected to be either tensile-strained or substantially-stress-free. Thus, silicon oxynitride can be used in combination with conventional sacrificial materials to limit an accumulation of compressive stress in a MEM device; or alternately the MEM device can be formed entirely with silicon oxynitride. Advantages to be gained from the use of silicon oxynitride as a sacrificial material for a MEM device include the formation of polysilicon members that are substantially free from residual stress, thereby improving the reliability of the MEM device; an ability to form the MEM device with a higher degree of complexity and more layers of structural polysilicon than would be possible using conventional compressively-strained sacrificial materials; and improved manufacturability resulting from the elimination of wafer distortion that can arise from an excess of accumulated stress in conventional sacrificial materials. The present invention is useful for forming many different types of MEM devices including accelerometers, sensors, motors, switches, coded locks, and flow-control devices, with or without integrated electronic circuitry.

  11. Sacrificial Plastic Mold With Electroplatable Base

    DOEpatents

    Domeier, Linda A.; Hruby, Jill M.; Morales, Alfredo M.

    2005-08-16

    A sacrificial plastic mold having an electroplatable backing is provided. One embodiment consists of the infusion of a softened or molten thermoplastic through a porous metal substrate (sheet, screen, mesh or foam) and into the features of a micro-scale molding tool contacting the porous metal substrate. Upon demolding, the porous metal substrate will be embedded within the thermoplastic and will project a plastic structure with features determined by the mold tool. This plastic structure, in turn, provides a sacrificial plastic mold mechanically bonded to the porous metal substrate which provides a conducting support suitable for electroplating either contiguous or non-contiguous metal replicates. After electroplating and lapping, the sacrificial plastic can be dissolved to leave the desired metal structure bonded to the porous metal substrate. Optionally, the electroplated structures may be debonded from the porous substrate by selective dissolution of the porous substrate or a coating thereon.

  12. Sacrificial plastic mold with electroplatable base

    DOEpatents

    Domeier, Linda A.; Hruby, Jill M.; Morales, Alfredo M.

    2002-01-01

    A sacrificial plastic mold having an electroplatable backing is provided. One embodiment consists of the infusion of a softened or molten thermoplastic through a porous metal substrate (sheet, screen, mesh or foam) and into the features of a micro-scale molding tool contacting the porous metal substrate. Upon demolding, the porous metal substrate will be embedded within the thermoplastic and will project a plastic structure with features determined by the mold tool. This plastic structure, in turn, provides a sacrificial plastic mold mechanically bonded to the porous metal substrate which provides a conducting support suitable for electroplating either contiguous or non-contiguous metal replicates. After electroplating and lapping, the sacrificial plastic can be dissolved to leave the desired metal structure bonded to the porous metal substrate. Optionally, the electroplated structures may be debonded from the porous substrate by selective dissolution of the porous substrate or a coating thereon.

  13. Polydimethylglutarimide (PMGI) as a sacrificial material for SU-8 surface-micromachining

    NASA Astrophysics Data System (ADS)

    Foulds, I. G.; Johnstone, R. W.; Parameswaran, M.

    2008-07-01

    SU-8 is finding increased use as a structural polymer MEMS material due to its biocompatibility, mechanical properties and low cost. The goal of this work is to expand the use of SU-8 through the creation of SU-8-based surface-micromachining processes that use polydimethylglutarimide (PMGI) as a sacrificial layer. PMGI is a deep-UV positive resist, used mainly for bilayer lift-off processes. PMGI is a good sacrificial layer candidate, as it is spinable at a wide variety of thicknesses, is photopatternable and has a glass transition temperature greater than the processing temperatures required for SU-8. PMGI is shown to be useful as a sacrificial layer for SU-8 surface micromachining processes with one freestanding layer with patterned metal, single-layer devices with more than one thickness, and two layer devices. Two classes of devices were fabricated with the developed processes. The first class of devices are compliant mechanisms, including bent-beam actuators, thermal isolation platforms and out-of-plane grippers. The second class of devices fabricated are freely moving devices such as hinged plates and gears, which require the use of true kinematic joints, such as scissor hinges, staple hinges and pin joints.

  14. Protective, Sacrificial Coats On Optical Surfaces

    NASA Technical Reports Server (NTRS)

    Babel, Henry W.; Hasegawa, Mark M.; Jones, Cherie A.

    1994-01-01

    Clear, easily cleaned sacrificial coats of polytetrafluoroethylene, polyurethane, silicone, or other low-outgassing organic films help maintain optical properties of surfaces of radiators, solar panels, and other components. Contamination removed by erosion of coats. Applied by conventional spraying or other techniques. Originally coats intended to protect surfaces of radiators on spacecraft in low orbit around the Earth. On Earth, used to protect optical surfaces against damage during manufacture or protect and facilitate cleaning of optical surfaces particularly delicate or otherwise not cleaned easily.

  15. Delta-ALA urine test

    MedlinePlus

    ... increased level of urinary delta-ALA may indicate: Lead poisoning Porphyria (several types) A decreased level may occur ... A.M. Editorial team. Related MedlinePlus Health Topics Lead Poisoning Porphyria Browse the Encyclopedia A.D.A.M., ...

  16. ALA 2010: The Costly Cornucopia

    ERIC Educational Resources Information Center

    Berry, John N., III

    2010-01-01

    Every librarian wants to go to the American Library Association (ALA) annual conference in Washington, DC, June 24-29. Despite that, more than half of those asked informally said they can't afford it. The good news is a cornucopia of programs aimed at nearly every need of librarians of all types and including every best practice in libraries. Many…

  17. Stick to the ALA Plan

    ERIC Educational Resources Information Center

    Berry, John N., III

    2007-01-01

    One candidate for president-elect of the American Library Association (ALA) is a woman, the other is a man. One can tell them apart by looking at them. But Nancy Davenport and James Rettig are not that far apart on the issues that confront the old association and the profession it serves. They have selected slightly different emphases for their…

  18. ALA Conference 2009: Chicago Hope

    ERIC Educational Resources Information Center

    Berry, John N., III

    2009-01-01

    There is joy among those who have the funds to go to Chicago for the American Library Association (ALA) annual conference, July 9-15. Every librarian knows there is nothing better than a Chicago gathering, with the city's wonderful haunts, museums, restaurants, and fine memories of past conferences. The conference program covers nearly every…

  19. Epitaxial Growth of GaN-based LEDs on Simple Sacrificial Substrates

    SciTech Connect

    Ian Ferguson; Chris Summers

    2009-12-31

    The objective of this project is to produce alternative substrate technologies for GaN-based LEDs by developing an ALD interlayer of Al{sub 2}O{sub 3} on sacrificial substrates such as ZnO and Si. A sacrificial substrate is used for device growth that can easily be removed using a wet chemical etchant leaving only the thin GaN epi-layer. After substrate removal, the GaN LED chip can then be mounted in several different ways to a metal heat sink/reflector and light extraction techniques can then be applied to the chip and compared for performance. Success in this work will lead to high efficiency LED devices with a simple low cost fabrication method and high product yield as stated by DOE goals for its solid state lighting portfolio.

  20. Sunset at the ALaMO

    NASA Video Gallery

    A new color all-sky camera has opened its eyes at the ALaMO, or Automated Lunar and Meteor Observatory, at NASA's Marshall Space Flight Center in Huntsville, Ala. Watch its inaugural video below, s...

  1. The possibility of forming a sacrificial anode coating for Mg

    SciTech Connect

    Dudney, Nancy J; Li, Juchuan; Sacci, Robert L; Thomson, Jeffery K

    2014-01-01

    Mg is the most active engineering metal, and is often used as a sacrificial anode/coating to protect other engineering metals from corrosion attack. So far no sacrificial anode coating has been developed or considered for Mg. This study explores the possibility of forming a sacrificial coating for Mg. A lithiated carbon coating and a metaphosphated coating are applied on the Mg surface, respectively, and their open-circuit-potentials are measured in saturated Mg(OH)2 solution. They exhibit more negative potentials than bare Mg. SEM reveals that the metaphosphated coating offers more effective and uniform protection for Mg than the lithiated carbon coating. These preliminary results indicate that development of a sacrificial anode coating for Mg is indeed possible.

  2. Sacrificial Template Synthesis and Properties of 3D Hollow-Silicon Nano- and Microstructures.

    PubMed

    Hölken, Iris; Neubüser, Gero; Postica, Vasile; Bumke, Lars; Lupan, Oleg; Baum, Martina; Mishra, Yogendra Kumar; Kienle, Lorenz; Adelung, Rainer

    2016-08-10

    Novel three-dimensional (3D) hollow aero-silicon nano- and microstructures, namely, Si-tetrapods (Si-T) and Si-spheres (Si-S) were synthesized by a sacrificial template approach for the first time. The new Si-T and Si-S architectures were found as most temperature-stable hollow nanomaterials, up to 1000 °C, ever reported. The synthesized aero-silicon or aerogel was integrated into sensor structures based on 3D networks. A single microstructure Si-T was employed to investigate electrical and gas sensing properties. The elaborated hollow microstructures open new possibilities and a wide area of perspectives in the field of nano- and microstructure synthesis by sacrificial template approaches. The enormous flexibility and variety of the hollow Si structures are provided by the special geometry of the sacrificial template material, ZnO-tetrapods (ZnO-T). A Si layer was deposited onto the surface of ZnO-T networks by plasma-enhanced chemical vapor deposition. All samples demonstrated p-type conductivity; hence, the resistance of the sensor structure increased after introducing the reducing gases in the test chamber. These hollow structures and their unique and superior properties can be advantageous in different fields, such as NEMS/MEMS, batteries, dye-sensitized solar cells, gas sensing in harsh environment, and biomedical applications. This method can be extended for synthesis of other types of hollow nanostructures. PMID:27428091

  3. A sacrificial process for fabrication of biodegradable polymer membranes with submicron thickness.

    PubMed

    Beardslee, Luke A; Stolwijk, Judith; Khaladj, Dimitrius A; Trebak, Mohamed; Halman, Justin; Torrejon, Karen Y; Niamsiri, Nuttawee; Bergkvist, Magnus

    2016-08-01

    A new sacrificial molding process using a single mask has been developed to fabricate ultrathin 2-dimensional membranes from several biocompatible polymeric materials. The fabrication process is similar to a sacrificial microelectromechanical systems (MEMS) process flow, where a mold is created from a material that can be coated with a biodegradable polymer and subsequently etched away, leaving behind a very thin polymer membrane. In this work, two different sacrificial mold materials, silicon dioxide (SiO2 ) and Liftoff Resist (LOR) were used. Three different biodegradable materials; polycaprolactone (PCL), poly(lactic-co-glycolic acid) (PLGA), and polyglycidyl methacrylate (PGMA), were chosen as model polymers. We demonstrate that this process is capable of fabricating 200-500 nm thin, through-hole polymer membranes with various geometries, pore-sizes and spatial features approaching 2.5 µm using a mold fabricated via a single contact photolithography exposure. In addition, the membranes can be mounted to support rings made from either SU8 or PCL for easy handling after release. Cell culture compatibility of the fabricated membranes was evaluated with human dermal microvascular endothelial cells (HDMECs) seeded onto the ultrathin porous membranes, where the cells grew and formed confluent layers with well-established cell-cell contacts. Furthermore, human trabecular meshwork cells (HTMCs) cultured on these scaffolds showed similar proliferation as on flat PCL substrates, further validating its compatibility. All together, these results demonstrated the feasibility of our sacrificial fabrication process to produce biocompatible, ultra-thin membranes with defined microstructures (i.e., pores) with the potential to be used as substrates for tissue engineering applications. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1192-1201, 2016. PMID:26079689

  4. Development of an SU-8 MEMS process with two metal electrodes using amorphous silicon as a sacrificial material

    NASA Astrophysics Data System (ADS)

    Ramadan, Khaled S.; Nasr, Tarek; Foulds, Ian G.

    2013-03-01

    This work presents an SU-8 surface micromachining process using amorphous silicon as a sacrificial material, which also incorporates two metal layers for electrical excitation. SU-8 is a photo-patternable polymer that is used as a structural layer for MEMS and microfluidic applications due to its mechanical properties, biocompatibility and low cost. Amorphous silicon is used as a sacrificial layer in MEMS applications because it can be deposited in large thicknesses, and can be released in a dry method using XeF2, which alleviates release-based stiction problems related to MEMS applications. In this work, an SU-8 MEMS process was developed using α-Si as a sacrificial layer. Two conductive metal electrodes were integrated in this process to allow out-of-plane electrostatic actuation for applications like MEMS switches and variable capacitors. In order to facilitate more flexibility for MEMS designers, the process can fabricate dimples that can be conductive or nonconductive. Additionally, this SU-8 process can fabricate SU-8 MEMS structures of a single layer of two different thicknesses. Process parameters were optimized for two sets of thicknesses: thin (5-10 µm) and thick (130 µm). The process was tested fabricating MEMS switches, capacitors and thermal actuators.

  5. ALA-induced PpIX fluorescence in epileptogenic tissue

    NASA Astrophysics Data System (ADS)

    Kleen, Jonathan K.; Valdes, Pablo A.; Harris, Brent T.; Holmes, Gregory L.; Paulsen, Keith D.; Roberts, David W.

    2011-03-01

    Astrogliotic tissue displays markedly increased levels of ALA-induced PpIX fluorescence, making it useful for fluorescence-guided resection in glioma surgery. In patients with temporal lobe epilepsy (TLE) and corresponding animal models, there are areas of astrogliosis that often co-localize with the epileptic focus, which can be resected to eliminate seizures in the majority of treated patients. If this epileptogenic tissue can exhibit PpIX fluorescence that is sufficiently localized, it could potentially help identify margins in epilepsy surgery. We tested the hypothesis that ALA-induced PpIX fluorescence could visually accentuate epileptogenic tissue, using an established animal model of chronic TLE. An acute dose of pilocarpine was used to induce chronic seizure activity in a rat. This rat and a normal control were given ALA, euthanized, and brains examined post-mortem for PpIX fluorescence and neuropathology. Preliminary evidence indicates increased PpIX fluorescence in areas associated with chronic epileptic changes and seizure generation in TLE, including the hippocampus and parahippocampal areas. In addition, strong PpIX fluorescence was clearly observed in layer II of the piriform cortex, a region known for epileptic reorganization and involvement in the generation of seizures in animal studies. We are further investigating whether ALA-induced PpIX fluorescence can consistently identify epileptogenic zones, which could warrant the extension of this technique to clinical studies for use as an adjuvant guidance technology in the resection of epileptic tissue.

  6. ALA Midwinter 2011 Preview: A Better Place

    ERIC Educational Resources Information Center

    Berry, John N., III

    2010-01-01

    There has been an effort to make the American Library Association (ALA) Midwinter Meeting "member-friendly," so that more ALA members will attend. Held January 7-11 in beautiful San Diego, the conference program is loaded with interesting events that look suspiciously like entertainment, plus learning opportunities, and the usual parties and…

  7. Comparison between mALA- and ALA-PDT in the treatment of basal cell carcinomas

    NASA Astrophysics Data System (ADS)

    Schleier, Peter; Zenk, Witold; Hyckel, Peter; Berndt, Alexander

    2006-02-01

    Introduction: The external application of aminoleavulinic acid (ALA), which is a substrate of physiologic cell metabolism, represents a possible treatment option in superficial basal cell carcinomas (BCC). The development of new ALA-esters (mALA) with potential for higher penetration depths promises higher therapeutic success. This research aimed to prove the following hypothesis: The cytotoxic effect of the mALA- photodynamic therapy (mALA-PDT), when compared to the ALA-PDT, leads to a higher clinical success rate. Material and Methods: 24 patients with multiple facial tumors, after having received several local surgical excisions with known histology, were treated with either ALA- or mALA-PDT, during the past two years. In total, 89 basal cell carcinoma, 45 actinic keratoses, 6 keratoacanthoma, and 2 squamous cell carcinomas were treated. ALA-PDT: A thermo gel with 40 % mALA or ALA was applied from a cooled syringe. Three to five hours after gel application the skin was cleaned from any gel residues. Irradiation was done with a diode laser and was performed in two sessions, each 10 min long. After intervals of 2, 4 and 12 weeks, the patients were recalled to assess therapeutic efficacy. This was followed by photographic documentation. Results: More than 80% of the tumors treated primarily were resolved successfully. A recurrence rate of approximately 15% was observed. Three per cent of the tumors showed no reaction to therapy. There were no statistically significant differences between the two therapeutic groups. Discussion: The advantage of the use of ALA lies foremost in the fast metabolic use of the body's own photosensitizer PpIX. There are no known side effects of this therapy. Moreover, external application is superior to systemic application with regard to patient management. The method can be combined with other therapies. Although the mALA should have a better penetration in tumor tissue, the therapeutic outcome is similar to the use of ALA.

  8. PDT of the endometrium using ALA

    NASA Astrophysics Data System (ADS)

    Gannon, Michael J.; Vernon, David I.; Holroyd, J. Andrew; Stringer, Mark R.; Johnson, Nick; Brown, Stanley B.

    1997-05-01

    There is a widely recognized need for new approaches to effect endometrial ablation as an alternative to hysterectomy for treatment of menorrhagia. Photodynamic therapy (PDT) offers one such approach. We have investigated the use of 5-aminolaevulinic acid (ALA)-based PDT of the endometrium in model systems and in a series of patients. In all of this work, the ALA was administrated directly into the uterine cavity to reduce any possibility of systemic photosensitization. In a series of experiments in perfused ex vivo uteri, ALA was introduced into the cavity and protoporphyrin formation was measured in the endometrium, the underlying myometrium and the perfusate. ALA transfer into the perfusate was also measured. This work demonstrated that protoporphyrin formation in the endometrium was approximately ten fold that in the underlying myometrium and that systemic photosensitization would be unlikely to result form transfer of administered ALA from the uterus into the circulation. Similar results were found in studies carried out in vivo, where ALA was administered to patients scheduled for hysterectomy. Using a specially designed light source, the first patients have now been treated by giving intrauterine ALA followed by laser light. Two series of treatments - 10 in all - have been carried out. Eight patients have one year follow up. A reduction in measured menstrual blood loss was demonstrated in all but one patient. Complete symptomatic relief was obtained in tow women who did not require further treatment.

  9. Increase of the electron mobility in HEMT heterostructures with composite spacers containing AlAs nanolayers

    SciTech Connect

    Vinichenko, A. N. Gladkov, V. P.; Kargin, N. I.; Strikhanov, M. N.; Vasil’evskii, I. S.

    2014-12-15

    The effect of the hybridization of quantum states on electron transport in a two-barrier quantum well δ-doped through a spacer layer at the limit of heavy doping is shown theoretically and experimentally. A method for increasing the electron mobility in the quantum well by suppressing the tunnel coupling with the donor region through the introduction of an AlAs nanobarrier into the spacer layer is proposed. It is experimentally shown that, in the samples with a shallow quantum well, the AlAs nanobarrier introduced into the spacer layer provides a larger than threefold increase in the electron mobility at low temperatures.

  10. Three-dimensional silicone microfluidic interconnection scheme using sacrificial wax filaments

    NASA Astrophysics Data System (ADS)

    Dharmatilleke, Saman; Henderson, H. Thurman; Bhansali, Shekhar; Ahn, Chong H.

    2000-08-01

    A very simple room-temperature procedure is presented herein for formation of true three-dimensionality of microplumbing in plastic (silicone elastomer in this case), by molding the plastic to simply encapsulate a pre-formed network of sacrificial wax threads or other connected wax configurations which are ultimately to become micro channels and cavities in the plastic motherboard. When these wax sacrificial areas are etched away with acetone, precise cavities, channels, and capillaries results with direct arbitrary three- dimensionality for the first time. This method leads also to a simple and effective external interconnect scheme where ordinary fused silica tubes may be press-fitted into the surface opening to withstand high pressure. This method may be extended for connection of multiple levels of silicone motherboards together using small sections of fused silica tubing, with no loss of stacking volume because of the lack of any connector lips or bosses. An array of micro channels having circular cross sections with diameters of 100, 150 and 200 microns were molded on silicone elastomer using wax thread. The wax thread was dissolved in acetone after the silicon elastometer became components (motherboards) while being able to control the channel lengths within the stacks as desired. Mixing chambers were also molded in a single silicone elastomer layer, because true three-dimensionality is trivially possible without the complexity of multi stacked lithography.

  11. Phonological activation in anaphoric lexical access (ALA).

    PubMed

    Simner, J; Smyth, R

    Simner and Smyth (1998) propose that anaphoric lexical access (ALA) occurs at an anaphor and targets the lexical entry (specifically, the lemma) of the antecedent. Since the word frequency effect (e.g., Rubenstein et al., 1970) resides at the lexeme (Jescheniak & Levelt, 1994) Simner and Smyth predict, and subsequently illustrate, that ALA exhibits no frequency effect. A problem arises, however: if ALA does not access the lexeme, how do we account for phonological priming at anaphor sites (e.g., Tanenhaus et al., 1985)? We claim that this is the result of "incidental" lemma-to-lexeme activation. Furthermore, we argue that since lexeme activation is not crucial to anaphor comprehension, anaphor reading times indicate lemma search times only (therefore there is no frequency effect). An experiment is presented demonstrating that lemma-access during ALA can cause incidental lexeme activation without invoking a frequency effect. PMID:10433737

  12. Cathodic protection using sacrificial magnesium anodes in prestressed concrete pipelines

    SciTech Connect

    Peris, M.G.; Guillen, M.A.

    1994-12-31

    Two cases of corrosion caused failures in prestressed concrete cylinder pipelines are presented. After determining the nature of the corrosion and its causes, cathodic protection was taken as the only tool that could be applied to try to save the pipeline. This paper describes the methods used to apply cathodic protection using sacrificial magnesium anodes to a pipeline of 800 pipe sections. Also presented are the results of the first year of application.

  13. Nano transfer and nanoreplication using deterministically grown sacrificial nanotemplates

    DOEpatents

    Melechko, Anatoli V.; McKnight, Timothy E.; Guillorn, Michael A.; Ilic, Bojan; Merkulov, Vladimir I.; Doktycz, Mitchel J.; Lowndes, Douglas H.; Simpson, Michael L.

    2012-03-27

    Methods, manufactures, machines and compositions are described for nanotransfer and nanoreplication using deterministically grown sacrificial nanotemplates. An apparatus, includes a substrate and a nanoconduit material coupled to a surface of the substrate. The substrate defines an aperture and the nanoconduit material defines a nanoconduit that is i) contiguous with the aperture and ii) aligned substantially non-parallel to a plane defined by the surface of the substrate.

  14. Sacrificial template method of fabricating a nanotube

    DOEpatents

    Yang, Peidong; He, Rongrui; Goldberger, Joshua; Fan, Rong; Wu, Yi-Ying; Li, Deyu; Majumdar, Arun

    2007-05-01

    Methods of fabricating uniform nanotubes are described in which nanotubes were synthesized as sheaths over nanowire templates, such as using a chemical vapor deposition process. For example, single-crystalline zinc oxide (ZnO) nanowires are utilized as templates over which gallium nitride (GaN) is epitaxially grown. The ZnO templates are then removed, such as by thermal reduction and evaporation. The completed single-crystalline GaN nanotubes preferably have inner diameters ranging from 30 nm to 200 nm, and wall thicknesses between 5 and 50 nm. Transmission electron microscopy studies show that the resultant nanotubes are single-crystalline with a wurtzite structure, and are oriented along the <001> direction. The present invention exemplifies single-crystalline nanotubes of materials with a non-layered crystal structure. Similar "epitaxial-casting" approaches could be used to produce arrays and single-crystalline nanotubes of other solid materials and semiconductors. Furthermore, the fabrication of multi-sheath nanotubes are described as well as nanotubes having multiple longitudinal segments.

  15. Immobilization of ALA-Zn(II) Coordination Polymer Pro-photosensitizers on Magnetite Colloidal Supraparticles for Target Photodynamic Therapy of Bladder Cancer.

    PubMed

    Tan, Jing; Sun, Chuanyu; Xu, Ke; Wang, Changchun; Guo, Jia

    2015-12-16

    5-Aminolevulinic acid (ALA) is a widely used photodynamic therapy (PDT) prodrug in the clinic. It can be metalized to the photosensitizer PpIX, which produces toxic singlet oxygen to kill cancer cells upon visible light irradiation. Herein, a core/shell-structured vehicle is designed to comprise magnetite colloidal supraparticles (MCSPs) as cores and ALA-Zn(II) coordination polymers as shells (Fe3O4@ALA-Zn(II) ) for target pro-photosensitizer delivery. The coordination polymers with 2D layered structures are locally deposited on the MCSPs by the complexation of the ALA and Zn(II) ions, and are readily controlled by varying the feed precursors and reaction temperatures. The maximum conjugated ALA amount is up to 17%. The Fe3O4@ALA-Zn(II) microspheres exhibit pH-sensitive release of ALA in acidic environment and rapid magnetic responsiveness. Cytotoxicity results demonstrate that Fe3O4@ALA-Zn(II) shows a significant inhibitory effect to T24 cells and is nontoxic to 293T normal cells as exposed to the 630 nm visible light for a very short time, which may due to the selective accumulation of ALA-induced PpIX in T24 cancer cells. Compared to the ALA used alone, the coordination polymer form is more efficient because of the bioactivity of incorporated Zn ions despite underlying the same apoptosis mechanism as ALA agent. PMID:26514273

  16. Sacrificial amphiphiles: Eco-friendly chemical herders as oil spill mitigation chemicals.

    PubMed

    Gupta, Deeksha; Sarker, Bivas; Thadikaran, Keith; John, Vijay; Maldarelli, Charles; John, George

    2015-06-01

    Crude oil spills are a major threat to marine biota and the environment. When light crude oil spills on water, it forms a thin layer that is difficult to clean by any methods of oil spill response. Under these circumstances, a special type of amphiphile termed as "chemical herder" is sprayed onto the water surrounding the spilled oil. The amphiphile forms a monomolecular layer on the water surface, reducing the air-sea surface tension and causing the oil slick to retract into a thick mass that can be burnt in situ. The current best-known chemical herders are chemically stable and nonbiodegradable, and hence remain in the marine ecosystem for years. We architect an eco-friendly, sacrificial, and effective green herder derived from the plant-based small-molecule phytol, which is abundant in the marine environment, as an alternative to the current chemical herders. Phytol consists of a regularly branched chain of isoprene units that form the hydrophobe of the amphiphile; the chain is esterified to cationic groups to form the polar group. The ester linkage is proximal to an allyl bond in phytol, which facilitates the hydrolysis of the amphiphile after adsorption to the sea surface into the phytol hydrophobic tail, which along with the unhydrolyzed herder, remains on the surface to maintain herding action, and the cationic group, which dissolves into the water column. Eventual degradation of the phytol tail and dilution of the cation make these sacrificial amphiphiles eco-friendly. The herding behavior of phytol-based amphiphiles is evaluated as a function of time, temperature, and water salinity to examine their versatility under different conditions, ranging from ice-cold water to hot water. The green chemical herder retracted oil slicks by up to ~500, 700, and 2500% at 5°, 20°, and 35°C, respectively, during the first 10 min of the experiment, which is on a par with the current best chemical herders in practice. PMID:26601197

  17. Sacrificial amphiphiles: Eco-friendly chemical herders as oil spill mitigation chemicals

    PubMed Central

    Gupta, Deeksha; Sarker, Bivas; Thadikaran, Keith; John, Vijay; Maldarelli, Charles; John, George

    2015-01-01

    Crude oil spills are a major threat to marine biota and the environment. When light crude oil spills on water, it forms a thin layer that is difficult to clean by any methods of oil spill response. Under these circumstances, a special type of amphiphile termed as “chemical herder” is sprayed onto the water surrounding the spilled oil. The amphiphile forms a monomolecular layer on the water surface, reducing the air–sea surface tension and causing the oil slick to retract into a thick mass that can be burnt in situ. The current best-known chemical herders are chemically stable and nonbiodegradable, and hence remain in the marine ecosystem for years. We architect an eco-friendly, sacrificial, and effective green herder derived from the plant-based small-molecule phytol, which is abundant in the marine environment, as an alternative to the current chemical herders. Phytol consists of a regularly branched chain of isoprene units that form the hydrophobe of the amphiphile; the chain is esterified to cationic groups to form the polar group. The ester linkage is proximal to an allyl bond in phytol, which facilitates the hydrolysis of the amphiphile after adsorption to the sea surface into the phytol hydrophobic tail, which along with the unhydrolyzed herder, remains on the surface to maintain herding action, and the cationic group, which dissolves into the water column. Eventual degradation of the phytol tail and dilution of the cation make these sacrificial amphiphiles eco-friendly. The herding behavior of phytol-based amphiphiles is evaluated as a function of time, temperature, and water salinity to examine their versatility under different conditions, ranging from ice-cold water to hot water. The green chemical herder retracted oil slicks by up to ~500, 700, and 2500% at 5°, 20°, and 35°C, respectively, during the first 10 min of the experiment, which is on a par with the current best chemical herders in practice. PMID:26601197

  18. Method of using sacrificial materials for fabricating internal cavities in laminated dielectric structures

    DOEpatents

    Peterson, Kenneth A.

    2009-02-24

    A method of using sacrificial materials for fabricating internal cavities and channels in laminated dielectric structures, which can be used as dielectric substrates and package mounts for microelectronic and microfluidic devices. A sacrificial mandrel is placed in-between two or more sheets of a deformable dielectric material (e.g., unfired LTCC glass/ceramic dielectric), wherein the sacrificial mandrel is not inserted into a cutout made in any of the sheets. The stack of sheets is laminated together, which deforms the sheet or sheets around the sacrificial mandrel. After lamination, the mandrel is removed, (e.g., during LTCC burnout), thereby creating a hollow internal cavity in the monolithic ceramic structure.

  19. New sacrificial material for ex-vessel core catcher

    NASA Astrophysics Data System (ADS)

    Komlev, Andrei A.; Almjashev, Vyacheslav I.; Bechta, Sevostian V.; Khabensky, Vladimir B.; Granovsky, Vladimir S.; Gusarov, Victor V.

    2015-12-01

    A new functional (sacrificial) material has been developed in the Fe2O3-SrO-Al2O3-CaO system based on strontium hexaferrite ceramic in concrete matrix. The method of producing SM has been advanced technologically; this technological effectiveness allows the SM to be used in ex-vessel core catchers with corium spreading as well as in crucible-type core catchers. Critical properties regarding the efficiency of SM in ex-vessel core catchers, such as porosity, pycnometric density, apparent density, solidus and liquidus temperatures, and water content have been measured. Suitable fractions of SrFe12O19 and high alumina cement (HAC) were found in the SM based on thermodynamic analysis of the SM/corium interaction. The use of sacrificial steel as an additional heat adsorption component in the core catcher allowed us to increase the mass fraction range of SrFe12O19 in the SM from 0.3-0.5 to 0.3-0.85. The activation temperature of the SM/corium interaction has been shown to correspond to the liquidus temperature of the local composition at the SM/corium interface. The calculated value of this temperature was 1716 °C. Analysis of phase transformations in the SrO-Fe2O3 system revealed advantages of the SrFe12O19-based sacrificial material compared with the Fe2O3-contained material owing to the time proximity of SrFe12O19 decomposition and corium interaction activation.

  20. Nanotransfer and nanoreplication using deterministically grown sacrificial nanotemplates

    DOEpatents

    Melechko, Anatoli V.; McKnight, Timothy E. , Guillorn, Michael A.; Ilic, Bojan; Merkulov, Vladimir I.; Doktycz, Mitchel J.; Lowndes, Douglas H.; Simpson, Michael L.

    2011-05-17

    Methods, manufactures, machines and compositions are described for nanotransfer and nanoreplication using deterministically grown sacrificial nanotemplates. A method includes depositing a catalyst particle on a surface of a substrate to define a deterministically located position; growing an aligned elongated nanostructure on the substrate, an end of the aligned elongated nanostructure coupled to the substrate at the deterministically located position; coating the aligned elongated nanostructure with a conduit material; removing a portion of the conduit material to expose the catalyst particle; removing the catalyst particle; and removing the elongated nanostructure to define a nanoconduit.

  1. ALA 2010: Where to Eat in DC

    ERIC Educational Resources Information Center

    Library Journal, 2010

    2010-01-01

    As host to visitors and transplants from around the world, Washington, DC, benefits from the constant infusion of different cultures. Although most neighborhoods lack a unified culinary flavor, make no mistake: DC is a city of distinctive areas, each with its own style, ensuring that hungry American Library Association (ALA) 2010 conference…

  2. Methods for making thin layers of crystalline materials

    DOEpatents

    Lagally, Max G; Paskiewicz, Deborah M; Tanto, Boy

    2013-07-23

    Methods for making growth templates for the epitaxial growth of compound semiconductors and other materials are provided. The growth templates are thin layers of single-crystalline materials that are themselves grown epitaxially on a substrate that includes a thin layer of sacrificial material. The thin layer of sacrificial material, which creates a coherent strain in the single-crystalline material as it is grown thereon, includes one or more suspended sections and one or more supported sections.

  3. 46 CFR 35.01-25 - Sacrificial anode installations-TB/ALL.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... the silicon content limited to trace amounts. (5) The recommended construction of the anode should... 46 Shipping 1 2014-10-01 2014-10-01 false Sacrificial anode installations-TB/ALL. 35.01-25 Section... Provisions; Special Operating Requirements § 35.01-25 Sacrificial anode installations—TB/ALL. (a)...

  4. 46 CFR 35.01-25 - Sacrificial anode installations-TB/ALL.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... the silicon content limited to trace amounts. (5) The recommended construction of the anode should... 46 Shipping 1 2013-10-01 2013-10-01 false Sacrificial anode installations-TB/ALL. 35.01-25 Section... Provisions; Special Operating Requirements § 35.01-25 Sacrificial anode installations—TB/ALL. (a)...

  5. ALA-Butyrate prodrugs for Photo-Dynamic Therapy

    NASA Astrophysics Data System (ADS)

    Berkovitch, G.; Nudelman, A.; Ehenberg, B.; Rephaeli, A.; Malik, Z.

    2010-05-01

    The use of 5-aminolevulinic acid (ALA) administration has led to many applications of photodynamic therapy (PDT) in cancer. However, the hydrophilic nature of ALA limits its ability to penetrate the cells and tissues, and therefore the need for ALA derivatives became an urgent research target. In this study we investigated the activity of novel multifunctional acyloxyalkyl ester prodrugs of ALA that upon metabolic hydrolysis release active components such as, formaldehyde, and the histone deacetylase inhibitory moiety, butyric acid. Evaluation of these prodrugs under photo-irradiation conditions showed that butyryloxyethyl 5-amino-4-oxopentanoate (ALA-BAC) generated the most efficient photodynamic destruction compared to ALA. ALA-BAC stimulated a rapid biosynthesis of protoporphyrin IX (PpIX) in human glioblastoma U-251 cells which resulted in generation of intracellular ROS, reduction of mitochondrial activity, leading to apoptotic and necrotic death of the cells. The apoptotic cell death induced by ALA / ALA-BAC followed by PDT equally activate intrinsic and extrinsic apoptotic signals and both pathways may occur simultaneously. The main advantage of ALA-BAC over ALA stems from its ability to induce photo-damage at a significantly lower dose than ALA.

  6. Plasma assisted synthesis of hollow nanofibers using electrospun sacrificial templates

    NASA Astrophysics Data System (ADS)

    Rahmathullah, Aflal M.; Jason Robinette, E.; Chen, Hong; Elabd, Yossef A.; Palmese, Giuseppe R.

    2007-12-01

    In this work, we describe the synthesis of nanostructured polymeric materials of controlled tubular geometries using oxygen plasma and polysiloxane-grafting onto electrospun fiber sacrificial templates. The fibers were characterized using Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) to determine the extent of grafting, graft chemistry and the influence of plasma treatment. Scanning electron microscopy (SEM) was used to determine the morphology and size of the electrospun fibers and nanotubes. The average diameter of the electrospun fibers employed ranged between 300 nm and 1500 nm. The micrographs revealed differences that are dependent on the type of grafting chemistry as well as plasma treatment times. The template synthesis of polysiloxane nanotubes using polyester track-etched membranes also shows that the technique is applicable to different substrates.

  7. Living Bacterial Sacrificial Porogens to Engineer Decellularized Porous Scaffolds

    PubMed Central

    Xu, Feng; Sridharan, BanuPriya; Durmus, Naside Gozde; Wang, ShuQi; Yavuz, Ahmet Sinan; Gurkan, Umut Atakan; Demirci, Utkan

    2011-01-01

    Decellularization and cellularization of organs have emerged as disruptive methods in tissue engineering and regenerative medicine. Porous hydrogel scaffolds have widespread applications in tissue engineering, regenerative medicine and drug discovery as viable tissue mimics. However, the existing hydrogel fabrication techniques suffer from limited control over pore interconnectivity, density and size, which leads to inefficient nutrient and oxygen transport to cells embedded in the scaffolds. Here, we demonstrated an innovative approach to develop a new platform for tissue engineered constructs using live bacteria as sacrificial porogens. E.coli were patterned and cultured in an interconnected three-dimensional (3D) hydrogel network. The growing bacteria created interconnected micropores and microchannels. Then, the scafold was decellularized, and bacteria were eliminated from the scaffold through lysing and washing steps. This 3D porous network method combined with bioprinting has the potential to be broadly applicable and compatible with tissue specific applications allowing seeding of stem cells and other cell types. PMID:21552485

  8. Experiences in retrofitting sacrificial anodes in offshore Arabian Gulf

    SciTech Connect

    Kiefer, J.H.; Thomason, W.H.; Alansari, N.G.

    1998-12-31

    An analysis was made of the cathodic protection systems of fifteen (15) fixed offshore platforms. These steel template structures are located in the warm waters off the coast of the United Arab Emirates with water depth varying between 125 and 185 feet. The operator employs a systematic survey program to monitor the corrosion protection systems including the assessment of sacrificial anode depletion, and measurement of the anode and platform potentials. These data are used to design new anode retrofits for the older structures to extend the life of the CP systems. This paper presents an analysis of the field survey measurements, the method used to evaluate when new anodes are required, how many are needed, and where to locate retrofit anodes.

  9. Morphological Versatility in the Self-Assembly of Val-Ala and Ala-Val Dipeptides.

    PubMed

    Erdogan, Hakan; Babur, Esra; Yilmaz, Mehmet; Candas, Elif; Gordesel, Merve; Dede, Yavuz; Oren, Ersin Emre; Demirel, Gokcen Birlik; Ozturk, Mustafa Kemal; Yavuz, Mustafa Selman; Demirel, Gokhan

    2015-07-01

    Since the discovery of dipeptide self-assembly, diphenylalanine (Phe-Phe)-based dipeptides have been widely investigated in a variety of fields. Although various supramolecular Phe-Phe-based structures including tubes, vesicles, fibrils, sheets, necklaces, flakes, ribbons, and wires have been demonstrated by manipulating the external physical or chemical conditions applied, studies of the morphological diversity of dipeptides other than Phe-Phe are still required to understand both how these small molecules respond to external conditions such as the type of solvent and how the peptide sequence affects self-assembly and the corresponding molecular structures. In this work, we investigated the self-assembly of valine-alanine (Val-Ala) and alanine-valine (Ala-Val) dipeptides by varying the solvent medium. It was observed that Val-Ala dipeptide molecules may generate unique self-assembly-based morphologies in response to the solvent medium used. Interestingly, when Ala-Val dipeptides were utilized as a peptide source instead of Val-Ala, we observed distinct differences in the final dipeptide structures. We believe that such manipulation may not only provide us with a better understanding of the fundamentals of the dipeptide self-assembly process but also may enable us to generate novel peptide-based materials for various applications. PMID:26086903

  10. ALA Pretreatment Improves Waterlogging Tolerance of Fig Plants

    PubMed Central

    An, Yuyan; Qi, Lin; Wang, Liangju

    2016-01-01

    5-aminolevulinic acid (ALA), a natural and environmentally friendly plant growth regulator, can improve plant tolerance to various environmental stresses. However, whether ALA can improve plant waterlogging tolerance is unknown. Here, we investigated the effects of ALA pretreatment on the waterlogging-induced damage of fig (Ficus carica Linn.) plants, which often suffer from waterlogging stress. ALA pretreatment significantly alleviated stress-induced morphological damage, increased leaf relative water content (RWC), and reduced leaf superoxide anion (O2⋅¯) production rate and malonaldehyde (MDA) content in fig leaves, indicating ALA mitigates waterlogging stress of fig plants. We further demonstrated that ALA pretreatment largely promoted leaf chlorophyll content, photosynthetic electron transfer ability, and photosynthetic performance index, indicating ALA significantly improves plant photosynthetic efficiency under waterlogging stress. Moreover, ALA pretreatment significantly increased activities of leaf superoxide dismutase (SOD) and peroxidase (POD), root vigor, and activities of root alcohol dehydrogenase (ADH), and lactate dehydrogenase (LDH), indicating ALA also significantly improves antioxidant ability and root function of fig plants under waterlogging stress. Taken together, ALA pretreatment improves waterlogging tolerance of fig plants significantly, and the promoted root respiration, leaf photosynthesis, and antioxidant ability may contribute greatly to this improvement. Our data firstly shows that ALA can improve plant waterlogging tolerance. PMID:26789407

  11. ALA Pretreatment Improves Waterlogging Tolerance of Fig Plants.

    PubMed

    An, Yuyan; Qi, Lin; Wang, Liangju

    2016-01-01

    5-aminolevulinic acid (ALA), a natural and environmentally friendly plant growth regulator, can improve plant tolerance to various environmental stresses. However, whether ALA can improve plant waterlogging tolerance is unknown. Here, we investigated the effects of ALA pretreatment on the waterlogging-induced damage of fig (Ficus carica Linn.) plants, which often suffer from waterlogging stress. ALA pretreatment significantly alleviated stress-induced morphological damage, increased leaf relative water content (RWC), and reduced leaf superoxide anion ([Formula: see text]) production rate and malonaldehyde (MDA) content in fig leaves, indicating ALA mitigates waterlogging stress of fig plants. We further demonstrated that ALA pretreatment largely promoted leaf chlorophyll content, photosynthetic electron transfer ability, and photosynthetic performance index, indicating ALA significantly improves plant photosynthetic efficiency under waterlogging stress. Moreover, ALA pretreatment significantly increased activities of leaf superoxide dismutase (SOD) and peroxidase (POD), root vigor, and activities of root alcohol dehydrogenase (ADH), and lactate dehydrogenase (LDH), indicating ALA also significantly improves antioxidant ability and root function of fig plants under waterlogging stress. Taken together, ALA pretreatment improves waterlogging tolerance of fig plants significantly, and the promoted root respiration, leaf photosynthesis, and antioxidant ability may contribute greatly to this improvement. Our data firstly shows that ALA can improve plant waterlogging tolerance. PMID:26789407

  12. Sacrificial adhesive bonding: a powerful method for fabrication of glass microchips

    PubMed Central

    Lima, Renato S.; Leão, Paulo A. G. C.; Piazzetta, Maria H. O.; Monteiro, Alessandra M.; Shiroma, Leandro Y.; Gobbi, Angelo L.; Carrilho, Emanuel

    2015-01-01

    A new protocol for fabrication of glass microchips is addressed in this research paper. Initially, the method involves the use of an uncured SU-8 intermediate to seal two glass slides irreversibly as in conventional adhesive bonding-based approaches. Subsequently, an additional step removes the adhesive layer from the channels. This step relies on a selective development to remove the SU-8 only inside the microchannel, generating glass-like surface properties as demonstrated by specific tests. Named sacrificial adhesive layer (SAB), the protocol meets the requirements of an ideal microfabrication technique such as throughput, relatively low cost, feasibility for ultra large-scale integration (ULSI), and high adhesion strength, supporting pressures on the order of 5 MPa. Furthermore, SAB eliminates the use of high temperature, pressure, or potential, enabling the deposition of thin films for electrical or electrochemical experiments. Finally, the SAB protocol is an improvement on SU-8-based bondings described in the literature. Aspects such as substrate/resist adherence, formation of bubbles, and thermal stress were effectively solved by using simple and inexpensive alternatives. PMID:26293346

  13. Sacrificial adhesive bonding: a powerful method for fabrication of glass microchips

    NASA Astrophysics Data System (ADS)

    Lima, Renato S.; Leão, Paulo A. G. C.; Piazzetta, Maria H. O.; Monteiro, Alessandra M.; Shiroma, Leandro Y.; Gobbi, Angelo L.; Carrilho, Emanuel

    2015-08-01

    A new protocol for fabrication of glass microchips is addressed in this research paper. Initially, the method involves the use of an uncured SU-8 intermediate to seal two glass slides irreversibly as in conventional adhesive bonding-based approaches. Subsequently, an additional step removes the adhesive layer from the channels. This step relies on a selective development to remove the SU-8 only inside the microchannel, generating glass-like surface properties as demonstrated by specific tests. Named sacrificial adhesive layer (SAB), the protocol meets the requirements of an ideal microfabrication technique such as throughput, relatively low cost, feasibility for ultra large-scale integration (ULSI), and high adhesion strength, supporting pressures on the order of 5 MPa. Furthermore, SAB eliminates the use of high temperature, pressure, or potential, enabling the deposition of thin films for electrical or electrochemical experiments. Finally, the SAB protocol is an improvement on SU-8-based bondings described in the literature. Aspects such as substrate/resist adherence, formation of bubbles, and thermal stress were effectively solved by using simple and inexpensive alternatives.

  14. Engineering interconnected 3D vascular networks in hydrogels using molded sodium alginate lattice as the sacrificial template.

    PubMed

    Wang, Xue-Ying; Jin, Zi-He; Gan, Bo-Wen; Lv, Song-Wei; Xie, Min; Huang, Wei-Hua

    2014-08-01

    Engineering 3D perfusable vascular networks in vitro and reproducing the physiological environment of blood vessels is very challenging for tissue engineering and investigation of blood vessel function. Here, we engineer interconnected 3D microfluidic vascular networks in hydrogels using molded sodium alginate lattice as sacrificial templates. The sacrificial templates are rapidly replicated in polydimethylsiloxane (PDMS) microfluidic chips via Ca⁺²-crosslinking and then fully encapsulated in hydrogels. Interconnected channels with well controlled size and morphology are obtained by dissolving the monolayer or multilayer templates with EDTA solution. The human umbilical vein endothelial cells (HUVECs) are cultured on the channel linings and proliferated to form vascular lumens. The strong cell adhesion capability and adaptive response to shear stress demonstrate the excellent cytocompatibility of both the template and template-sacrificing process. Furthermore, the barrier function of the endothelial layer is characterized and the results show that a confluent endothelial monolayer is fully developed. Taken together, we develop a facile and rapid approach to engineer a vascular model that could be potentially used in physiological studies of vascular functions and vascular tissue engineering. PMID:24887141

  15. Bioinspired Interface Engineering in Elastomer/Graphene Composites by Constructing Sacrificial Metal-Ligand Bonds.

    PubMed

    Huang, Jing; Tang, Zhenghai; Yang, Zhijun; Guo, Baochun

    2016-07-01

    It remains a huge challenge to create advanced elastomers combining high strength and great toughness. Despite enhanced strength and stiffness, elastomeric nanocomposites suffer notably reduced extensibility and toughness. Here, inspired by the concept of sacrificial bonding associated with many natural materials, a novel interface strategy is proposed to fabricate elastomer/graphene nanocomposites by constructing a strong yet sacrificial interface. This interface is composed of pyridine-Zn(2+) -catechol coordination motifs, which is strong enough to ensure uniform graphene dispersion and efficient stress transfer from matrix to fillers. Moreover, they are sacrificial under external stress, which dissipates much energy and facilitates chain orientation. As a result, the strength, modulus, and toughness of the elastomeric composites are simultaneously strikingly enhanced relative to elastomeric bulk. This work suggests a promising methodology of designing advanced elastomers with exceptional mechanical properties by engineering sacrificial bonds into the interface. PMID:27229634

  16. Suicide as a derangement of the self-sacrificial aspect of eusociality.

    PubMed

    Joiner, Thomas E; Hom, Melanie A; Hagan, Christopher R; Silva, Caroline

    2016-04-01

    Building upon the idea that humans may be a eusocial species (i.e., rely on multigenerational and cooperative care of young, utilize division of labor for successful survival), we conjecture that suicide among humans represents a derangement of the self-sacrificial aspect of eusociality. In this article, we outline the characteristics of eusociality, particularly the self-sacrificial behavior seen among other eusocial species (e.g., insects, shrimp, mole rats). We then discuss parallels between eusocial self-sacrificial behavior in nonhumans and suicide in humans, particularly with regard to overarousal states, withdrawal phenomena, and perceptions of burdensomeness. In so doing, we make the argument that death by suicide among humans is an exemplar of psychopathology and is due to a derangement of the self-sacrificial behavioral suite found among eusocial species. Implications and future directions for research are also presented. PMID:26524155

  17. 46 CFR 35.01-25 - Sacrificial anode installations-TB/ALL.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... combustible liquids in bulk is prohibited. (b) A sacrificial anode using an aluminum alloy will be permitted... analysis of the alloy composition shall be submitted for approval. The anode should be magnesium free...

  18. 5-ALA based photodynamic management of glioblastoma

    NASA Astrophysics Data System (ADS)

    Rühm, Adrian; Stepp, Herbert; Beyer, Wolfgang; Hennig, Georg; Pongratz, Thomas; Sroka, Ronald; Schnell, Oliver; Tonn, Jörg-Christian; Kreth, Friedrich-Wilhelm

    2014-03-01

    Objective: Improvement of the clinical outcome of glioblastoma (GBM) patients by employment of fluorescence and photosensitization on the basis of 5-aminolevulinic acid (5-ALA) induced protoporphyrin IX (PpIX). Methods: In this report the focus is laid on the use of tumor selective PpIX fluorescence for stereotactic biopsy sampling and intra-operative treatment monitoring. In addition, our current concept for treatment planning is presented. For stereotactic interstitial photodynamic therapy (iPDT), radial diffusers were implanted into the contrast enhancing tumor volume. Spectroscopic measurements of laser light transmission and fluorescence between adjacent fibers were performed prior, during and post PDT. Results: PpIX concentrations in primary glioblastoma tissue show high intra- and inter-patient variability, but are usually sufficient for an effective PDT. During individual treatment attempts with 5-ALA based GBM-iPDT, transmission and fluorescence measurements between radial diffusers gave the following results: 1. In some cases, transmission after PDT is considerably reduced compared to the value before PDT, which may be attributable to a depletion of oxygenated hemoglobin and/or diffuse bleeding. 2. PpIX fluorescence is efficiently photobleached during PDT in all cases. Conclusion: iPDT with assessment of PpIX fluorescence and photobleaching is a promising treatment option. Individualization of treatment parameters appears to bear a potential to further improve clinical outcomes.

  19. Toughening elastomers with sacrificial bonds and watching them break

    NASA Astrophysics Data System (ADS)

    Creton, Costantino

    2014-03-01

    Most unfilled elastomers are relatively brittle, in particular when the average molecular weight between crosslinks is lower than the average molecular weight between entanglements. We created a new class of tough elastomers by introducing isotropically prestretched chains inside ordinary acrylic elastomers by successive swelling and polymerization steps. These new materials combine a high entanglement density with a densely crosslinked structure reaching elastic moduli of 4 MPa and fracture strength of 25 MPa. The highly prestretched chains are the minority in the material and can break in the bulk of the material before catastrophic failure occurs, increasing the toughness of the material by two orders of magnitude up to 5 kJ/m2. To investigate the details of the toughening mechanism we introduced specific sacrificial dioxetane bonds in the prestretched chains that emit light when they break. In uniaxial extension cyclic experiments, we checked that the light emission corresponded exactly and quantitatively to the energy dissipation in each cycle demonstrating that short chains break first and long chains later. We then watched crack propagation in notched samples and mapped spatially the location of bond breakage ahead of the crack tip before and during propagation. This new toughening mechanism for elastomers creates superentangled rubbers and is ideally suited to overcome the trade-off between toughness and stiffness of ordinary elastomers. We gratefully acknowledge funding from DSM Ahead

  20. Struvite precipitation and phosphorus removal using magnesium sacrificial anode.

    PubMed

    Kruk, Damian J; Elektorowicz, Maria; Oleszkiewicz, Jan A

    2014-04-01

    Struvite precipitation using magnesium sacrificial anode as the only source of magnesium is presented. High-purity magnesium alloy cast anode was found to be very effective in recovery of high-quality struvite from water solutions and from supernatant of fermented waste activated sludge from a wastewater treatment plant that does not practice enhanced biological phosphorus removal. Struvite purity was strongly dependent on the pH and the electric current density. Optimum pH of the 24 mM phosphorus and 46 mM ammonia solution (1:1.9 P:N ratio) was in the broad range between 7.5 and 9.3, with struvite purity exceeding 90%. Increasing the current density resulted in elevated struvite purity. No upper limits were observed in the studied current range of 0.05-0.2 A. Phosphorus removal rate was proportional to the current density and comparable for tests with water solutions and with the supernatant from fermented sludge. The highest P-removal rate achieved was 4.0 mg PO4-P cm(-2) h(-1) at electric current density of 45 A m(-2). Initial substrate concentrations affected the rate of phosphorus removal. The precipitated struvite accumulated in bulk liquid with significant portions attached to the anode surface from which regular detachment occurred. PMID:24387911

  1. 33 CFR 110.194 - Mobile Bay, Ala., at entrance.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Mobile Bay, Ala., at entrance. 110.194 Section 110.194 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY ANCHORAGES ANCHORAGE REGULATIONS Anchorage Grounds § 110.194 Mobile Bay, Ala., at entrance. (a) The...

  2. 33 CFR 110.194 - Mobile Bay, Ala., at entrance.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 1 2011-07-01 2011-07-01 false Mobile Bay, Ala., at entrance. 110.194 Section 110.194 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY ANCHORAGES ANCHORAGE REGULATIONS Anchorage Grounds § 110.194 Mobile Bay, Ala., at entrance. (a) The...

  3. Cellulose Nanofibril Hydrogel Tubes as Sacrificial Templates for Freestanding Tubular Cell Constructs.

    PubMed

    Torres-Rendon, Jose Guillermo; Köpf, Marius; Gehlen, David; Blaeser, Andreas; Fischer, Horst; De Laporte, Laura; Walther, Andreas

    2016-03-14

    The merging of defined nanoscale building blocks with advanced additive manufacturing techniques is of eminent importance for the preparation of multiscale and highly functional materials with de novo designed hierarchical architectures. Here, we demonstrate that hydrogels of cellulose nanofibrils (CNF) can be processed into complex shapes, and used as a sacrificial template to prepare freestanding cell constructs. We showcase our approach for the fabrication of hollow fibers using a controlled extrusion through a circular die into a coagulation bath. The dimensions of the hollow fibers are tunable, and the final tubes combine the nanofibrillar porosity of the CNF hydrogel with a submillimeter wall thickness and centimeter-scale length provided by the additive manufacturing technique. We demonstrate that covalent and supramolecular cross-linking of the CNFs can be used to tailor the mechanical properties of the hydrogel tubes within 1 order of magnitude and in an attractive range for the mechanosensation of cells. The resulting tubes are highly biocompatible and allow for the growth of mouse fibroblasts into confluent cell layers in their inner lumen. A detailed screening of several cellulases enables degradation of the scaffolding, temporary CNF hydrogel tube in a quick and highly cell-friendly way, and allows the isolation of coherent cell tubes. We foresee that the growing capabilities of hydrogel printing techniques in combination with the attractive features of CNFs-sustainable, globally abundant, biocompatible and enzymatically degradable-will allow making plant-based biomaterials with hierarchical structures and on-demand degradation useful, for instance, to engineer complex tissue structures to replace animal models, and for implants. PMID:26812393

  4. Structure of vancomycin and a vancomycin/D-Ala-D-Ala complex in solution

    SciTech Connect

    Molinari, H.; Pastore, A. ); Lian, Luyun ); Hawkes, G.E.; Sales, K. )

    1990-03-06

    Restrained molecular dynamics simulations were used to study the interactions between the glycopeptide antibiotic vancomycin and the dipeptide Ac-D-Ala-D-Ala. Restraints were obtained from a combination of homonuclear and heteronuclear two-dimensional NMR experiments (NOESY, ROESY, {sup 1}H-{sup 15}N inverse correlation). The comparison between the structures obtained for vancomycin alone and for the complex suggests a new hypothesis on the binding mode of this system. The numerical simulations were not straightforward because vancomycin is made of building blocks for which standard force-fields are not available. The representation of unusual chemical environments is also mandatory. The authors believe that the extension of the force-field parameters to their system could be of more general interest. Furthermore, they consider vancomycin and its complex a good example for exploring the more general problem of molecular recognition, a challenge that has been widely approached in the past few years but for which no unique and general methodology has, so far, been recognized.

  5. John Ash, ALA., Photographer August 1997. VIEW OF LOS ANGELES ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    John Ash, ALA., Photographer August 1997. VIEW OF LOS ANGELES CITY HALL NINTH FLOOR NORTH OFFICE WING SHOWING PARTITIONS, WINDOWS AND RADIATOR, FACING SOUTHWEST - Los Angeles City Hall, 200 North Spring Street, Los Angeles, Los Angeles County, CA

  6. PARP1 Val762Ala polymorphism reduces enzymatic activity

    SciTech Connect

    Wang Xiaogan; Wang Zhaoqi; Tong Weimin . E-mail: tong@iarc.fr; Shen Yan

    2007-03-02

    Poly(ADP-ribose) polymerase 1 (PARP1) modifies a variety of nuclear proteins by poly(ADP-ribosyl)ation, and plays diverse roles in molecular and cellular processes. A common PARP1 single nucleotide polymorphism (SNP) at codon 762, resulting in the substitution of alanine (Ala) for valine (Val) in the catalytic domain has been implicated in susceptibility to cancer. To characterize the functional effect of this polymorphism on PARP1, we performed in vitro enzymatic analysis on PARP1-Ala762 and PARP1-Val762. We found that PARP1-Ala762 displayed 57.2% of the activity of PARP1-Val762 for auto-poly(ADP-ribosyl)ation and 61.9% of the activity of PARP1-Val762 for trans-poly(ADP-ribosyl)ation of histone H1. The kinetic characterization revealed that the K {sub m} of PARP1-Ala762 was increased to a 1.2-fold of the K {sub m} of PARP1-Val762 for trans-poly(ADP-ribosyl)ation. Thus, the PARP1 Val762Ala polymorphism reduces the enzymatic activity of PARP1 by increasing K {sub m}. This finding suggests that different levels of poly(ADP-ribosyl)ation by PARP1 might aid in understanding Cancer risk of carriers of the PARP1 Val762Ala polymorphism.

  7. 46 CFR 35.01-25 - Sacrificial anode installations-TB/ALL.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Operating Requirements § 35.01-25 Sacrificial anode installations—TB/ALL. (a) The installation of magnesium... submitted for approval. The anode should be magnesium free and the silicon content limited to trace amounts... materials other than those having aluminum and/or magnesium in whole or in part are permitted....

  8. Sidetracked by trolleys: Why sacrificial moral dilemmas tell us little (or nothing) about utilitarian judgment

    PubMed Central

    Kahane, Guy

    2015-01-01

    Research into moral decision-making has been dominated by sacrificial dilemmas where, in order to save several lives, it is necessary to sacrifice the life of another person. It is widely assumed that these dilemmas draw a sharp contrast between utilitarian and deontological approaches to morality, and thereby enable us to study the psychological and neural basis of utilitarian judgment. However, it has been previously shown that some sacrificial dilemmas fail to present a genuine contrast between utilitarian and deontological options. Here, I raise deeper problems for this research paradigm. Even when sacrificial dilemmas present a contrast between utilitarian and deontological options at a philosophical level, it is misleading to interpret the responses of ordinary folk in these terms. What is currently classified as “utilitarian judgment” does not in fact share essential features of a genuine utilitarian outlook, and is better explained in terms of commonsensical moral notions. When subjects deliberate about such dilemmas, they are not deciding between opposing utilitarian and deontological solutions, but engaging in a richer process of weighing opposing moral reasons. Sacrificial dilemmas therefore tell us little about utilitarian decision-making. An alternative approach to studying proto-utilitarian tendencies in everyday moral thinking is proposed. PMID:25791902

  9. Embedded proteins and sacrificial bonds provide the strong adhesive properties of gastroliths

    NASA Astrophysics Data System (ADS)

    Thormann, Esben; MizunoPresent Address: Nihon L'Oreal, Research; Innovation Center, 3-2-1 Sakado, Takatsu, Kawasaki, Kanagawa, Japan., Hiroyasu; Jansson, Kjell; Hedin, Niklas; Fernández, M. Soledad; Arias, José Luis; Rutland, Mark W.; PaiPresent Address: CenterFunctional Nanomaterials, Brookhaven National Laboratory, 735 Brookhaven Avenue, Upton, New York 11973., Ranjith Krishna; Bergström, Lennart

    2012-06-01

    The adhesive properties of gastroliths from a freshwater crayfish (Cherax quadricarinatus) were quantified by colloidal probe atomic force microscopy (AFM) between heavily demineralized gastrolith microparticles and gastrolith substrates of different composition. Combined AFM and transmission electron microscopy studies demonstrated that the sequential detachment and large adhesion energies that characterise the adhesive behaviour of a native gastrolith substrate are dominated by sacrificial bonds between chitin fibres and between chitin fibres and CaCO3. The sacrificial bonds were shown to be strongly related to the gastrolith proteins and when the majority of these proteins were removed by ethylenediaminetetraacetic acid (EDTA), the sequential detachment disappeared and the adhesive energy was reduced by more than two orders of magnitude.The adhesive properties of gastroliths from a freshwater crayfish (Cherax quadricarinatus) were quantified by colloidal probe atomic force microscopy (AFM) between heavily demineralized gastrolith microparticles and gastrolith substrates of different composition. Combined AFM and transmission electron microscopy studies demonstrated that the sequential detachment and large adhesion energies that characterise the adhesive behaviour of a native gastrolith substrate are dominated by sacrificial bonds between chitin fibres and between chitin fibres and CaCO3. The sacrificial bonds were shown to be strongly related to the gastrolith proteins and when the majority of these proteins were removed by ethylenediaminetetraacetic acid (EDTA), the sequential detachment disappeared and the adhesive energy was reduced by more than two orders of magnitude. Electronic supplementary information (ESI) available. See DOI: 10.1039/c2nr30536d

  10. Corrosion control acceptance criteria for sacrificial anode type, cathodic protection systems (user guide)

    NASA Astrophysics Data System (ADS)

    Hock, Vincent F.; Noble, Michael; McLeod, Malcolm E.

    1994-07-01

    The Army currently operates and maintains more than 20,000 underground storage tanks and over 3000 miles of underground gas pipelines, all of which require some form of corrosion control. Cathodic protection is one method of corrosion control used to prevent corrosion-induced leaks when a steel structure is exposed to an aggressive soil. The corrosion control acceptance criteria for sacrificial anode type CP systems provides guidelines for the DEH/DPW cathodic protection installation inspectors whose responsibilities are to ensure that the materials and equipment specified are delivered to the job site and subsequently installed in accordance with the engineering drawings and specifications. The sacrificial anode CP acceptance criteria includes all components for the sacrificial anode system such as insulated conductors, anodes, anode backfills, and auxiliary equipment. The sacrificial anode CP acceptance criteria is composed of a checklist that lists each component and that contains a space for the inspector to either check 'yes' or 'no' to indicate whether the component complies with the job specifications. In some cases, the inspector must measure and record physical dimensions or electrical output and compare the measurements to standards shown in attached tables.

  11. Sacrificial component fabrication for optimised production of micro-vascular polymer composite

    NASA Astrophysics Data System (ADS)

    Dalton, B.; Dixon, D.; McIlhagger, A.; Archer, E.

    2015-02-01

    Smart functional materials are a viable future goal for advanced applications in aerospace, space and medical applications. In this work micro-vascular polymer composite systems have been developed using sacrificial fibres produced from catalyst loaded Poly(lactic acid). The sacrificial fibres have been produced via a published technique which treated PLA in a solvent catalyst mixture of 60% Trifluoroethanol, 40% H2O dispersed with 10 wt% tin (II) oxalate catalyst. A second process of polymer extrusion of PLA using graded fill contents of tin (II) oxalate has also been developed for the up scaled production of fibres as an alternative to solution treatment. Thermal analysis (TGA) was used to compare sacrificial fibre specimens. PLA fibres produced via the polymer extrusion method outperformed solution treated fibres displaying a lower degradation onset temperature (average 25°C lower), higher degradation rates (observed through a derivative curve comparison) and lower residual catalyst content (0.67% solvent treated fibre against 0.16% extruded fibre). The continuous extrusion process is solvent free and is suitable for high volume production. This work has been carried out to fully understand the fabrication issues with sacrificial components.

  12. Offshore sacrificial anode design -- A producers view of limiting factors for success

    SciTech Connect

    Warnock, P.A.

    1995-11-01

    Offshore sacrificial anode designs that could in theory provide an optimized solution are in practice constrained by design limiting factors. Limiting factor recommendations are made for Platform and Bracelet anodes together with the introduction of crack propensity (CPR) indicators that can be used to predict maximum anode length which may be successfully manufactured by good foundry practice.

  13. Sidetracked by trolleys: Why sacrificial moral dilemmas tell us little (or nothing) about utilitarian judgment.

    PubMed

    Kahane, Guy

    2015-01-01

    Research into moral decision-making has been dominated by sacrificial dilemmas where, in order to save several lives, it is necessary to sacrifice the life of another person. It is widely assumed that these dilemmas draw a sharp contrast between utilitarian and deontological approaches to morality, and thereby enable us to study the psychological and neural basis of utilitarian judgment. However, it has been previously shown that some sacrificial dilemmas fail to present a genuine contrast between utilitarian and deontological options. Here, I raise deeper problems for this research paradigm. Even when sacrificial dilemmas present a contrast between utilitarian and deontological options at a philosophical level, it is misleading to interpret the responses of ordinary folk in these terms. What is currently classified as "utilitarian judgment" does not in fact share essential features of a genuine utilitarian outlook, and is better explained in terms of commonsensical moral notions. When subjects deliberate about such dilemmas, they are not deciding between opposing utilitarian and deontological solutions, but engaging in a richer process of weighing opposing moral reasons. Sacrificial dilemmas therefore tell us little about utilitarian decision-making. An alternative approach to studying proto-utilitarian tendencies in everyday moral thinking is proposed. PMID:25791902

  14. 46 CFR 35.01-25 - Sacrificial anode installations-TB/ALL.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 35.01-25 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY TANK VESSELS OPERATIONS Special... prohibited. (b) A sacrificial anode using an aluminum alloy will be permitted in cargo tanks under the... foot-pounds. (2) No anode shall be installed more than 6 feet above the bottom of the tank....

  15. Synthesis, DNA recognition and cleavage studies of novel tetrapeptide complexes, Cu(II)/Zn(II)-Ala-Pro-Ala-Pro

    NASA Astrophysics Data System (ADS)

    Arjmand, Farukh; Jamsheera, A.; Mohapatra, D. K.

    2013-05-01

    New tetrapeptide complexes Cu(II)·Ala-Pro-Ala-Pro (1) and Zn(II)·Ala-Pro-Ala-Pro (2) were synthesized from the reaction of tetrapeptide, Ala-Pro-Ala-Pro and CuCl2/ZnCl2 and were thoroughly characterized by elemental analysis, IR,1H and 13C NMR (in case of 2), ESI-MS, UV and molar conductance measurements. The solution stability study was carried out employing UV-vis absorption titrations over a broad range of pH which suggested the stability of the complexes in solution. In vitro interaction of complexes 1 and 2 with CT-DNA was studied employing UV-vis, fluorescence, circular dichroic and viscometry studies. To throw insight into molecular binding event at the target site, UV-vis titrations of 1 and 2 with mononucleotides of interest viz.; 5'-GMP and 5'-TMP were carried out. Cleavage activity of the complexes with pBR322 plasmid DNA was evaluated by agarose gel electrophoresis and, the electrophoresis pattern demonstrated that both the complexes 1 and 2 are efficient cleavage agents. Further, the Cu(II) complex displayed efficient oxidative cleavage of supercoiled DNA while various reactive oxygen species are responsible for the cleavage in Zn(II) complex.

  16. Electron microscopy of GaAs-based structures with InAs and As quantum dots separated by an AlAs barrier

    SciTech Connect

    Nevedomskiy, V. N. Bert, N. A.; Chaldyshev, V. V.; Preobrazhenskiy, V. V.; Putyato, M. A.; Semyagin, B. R.

    2013-09-15

    Electron microscopy studies of GaAs-based structures grown by molecular beam epitaxy and containing arrays of semiconductor InAs quantum dots and metal As quantum dots are performed. The array of InAs quantum dots is formed by the Stranski-Krastanov mechanism and consists of vertically coupled pairs of quantum dots separated by a GaAs spacer 10 nm thick. To separate the arrays of semiconductor and metal quantum dots and to prevent diffusion-induced mixing, the array of InAs quantum dots is overgrown with an AlAs barrier layer 5 or 10 nm thick, after which a GaAs layer is grown at a comparatively low temperature (180 Degree-Sign C). The array of As quantum dots is formed in an As-enriched layer of the low-temperature GaAs by means of post-growth annealing at 400-760 Degree-Sign C for 15 min. It is established that the AlAs barrier layer has a surface profile corresponding to that of a subbarrier layer with InAs quantum dots. The presence of such a profile causes the formation of V-shaped structural defects upon subsequent overgrowth with the GaAs layer. Besides, it was obtained that AlAs layer is thinned over the InAs quantum dots tops. It is shown that the AlAs barrier layer in the regions between the InAs quantum dots effectively prevents the starting diffusion of excess As at annealing temperatures up to 600 Degree-Sign C. However, the concentration of mechanical stresses and the reduced thickness of the AlAs barrier layer near the tops of the InAs quantum dots lead to local barrier breakthroughs and the diffusion of As quantum dots into the region of coupled pairs of InAs quantum dots at higher annealing temperatures.

  17. The Carboxyl Terminus of Eremomycin Facilitates Binding to the Non-d-Ala-d-Ala Segment of the Peptidoglycan Pentapeptide Stem.

    PubMed

    Chang, James; Zhou, Hongyu; Preobrazhenskaya, Maria; Tao, Peng; Kim, Sung Joon

    2016-06-21

    Glycopeptide antibiotics inhibit cell wall biosynthesis in Gram-positive bacteria by targeting the peptidoglycan (PG) pentapeptide stem structure (l-Ala-d-iso-Gln-l-Lys-d-Ala-d-Ala). Structures of the glycopeptide complexed with a PG stem mimic have shown that the d-Ala-d-Ala segment is the primary drug binding site; however, biochemical evidence suggests that the glycopeptide-PG interaction involves more than d-Ala-d-Ala binding. Interactions of the glycopeptide with the non-d-Ala-d-Ala segment of the PG stem were investigated using solid-state nuclear magnetic resonance (NMR). LCTA-1421, a double (15)N-enriched eremomycin derivative with a C-terminal [(15)N]amide and [(15)N]Asn amide, was complexed with whole cells of Staphylococcus aureus grown in a defined medium containing l-[3-(13)C]Ala and d-[1-(13)C]Ala in the presence of alanine racemase inhibitor alaphosphin. (13)C{(15)N} and (15)N{(13)C} rotational-echo double-resonance (REDOR) NMR measurements determined the (13)C-(15)N internuclear distances between the [(15)N]Asn amide of LCTA-1421 and the (13)C atoms of the bound d-[1-(13)C]Ala-d-[1-(13)C]Ala to be 5.1 and 4.8 Å, respectively. These measurements also determined the distance from the C-terminal [(15)N]amide of LCTA-1421 to the l-[3-(13)C]Ala of PG to be 3.5 Å. The measured REDOR distance constraints position the C-terminus of the glycopeptide in the proximity of the l-Ala of the PG, suggesting that the C-terminus of the glycopeptide interacts near the l-Ala segment of the PG stem. In vivo REDOR measurements provided structural insight into how C-terminally modified glycopeptide antibiotics operate. PMID:27243469

  18. Fluorescence-Guided Resection of Malignant Glioma with 5-ALA

    PubMed Central

    Kaneko, Sadahiro

    2016-01-01

    Malignant gliomas are extremely difficult to treat with no specific curative treatment. On the other hand, photodynamic medicine represents a promising technique for neurosurgeons in the treatment of malignant glioma. The resection rate of malignant glioma has increased from 40% to 80% owing to 5-aminolevulinic acid-photodynamic diagnosis (ALA-PDD). Furthermore, ALA is very useful because it has no serious complications. Based on previous research, it is apparent that protoporphyrin IX (PpIX) accumulates abundantly in malignant glioma tissues after ALA administration. Moreover, it is evident that the mechanism underlying PpIX accumulation in malignant glioma tissues involves an abnormality in porphyrin-heme metabolism, specifically decreased ferrochelatase enzyme activity. During resection surgery, the macroscopic fluorescence of PpIX to the naked eye is more sensitive than magnetic resonance imaging, and the alert real time spectrum of PpIX is the most sensitive method. In the future, chemotherapy with new anticancer agents, immunotherapy, and new methods of radiotherapy and gene therapy will be developed; however, ALA will play a key role in malignant glioma treatment before the development of these new treatments. In this paper, we provide an overview and present the results of our clinical research on ALA-PDD. PMID:27429612

  19. Fluorescence-Guided Resection of Malignant Glioma with 5-ALA.

    PubMed

    Kaneko, Sadahiro; Kaneko, Sadao

    2016-01-01

    Malignant gliomas are extremely difficult to treat with no specific curative treatment. On the other hand, photodynamic medicine represents a promising technique for neurosurgeons in the treatment of malignant glioma. The resection rate of malignant glioma has increased from 40% to 80% owing to 5-aminolevulinic acid-photodynamic diagnosis (ALA-PDD). Furthermore, ALA is very useful because it has no serious complications. Based on previous research, it is apparent that protoporphyrin IX (PpIX) accumulates abundantly in malignant glioma tissues after ALA administration. Moreover, it is evident that the mechanism underlying PpIX accumulation in malignant glioma tissues involves an abnormality in porphyrin-heme metabolism, specifically decreased ferrochelatase enzyme activity. During resection surgery, the macroscopic fluorescence of PpIX to the naked eye is more sensitive than magnetic resonance imaging, and the alert real time spectrum of PpIX is the most sensitive method. In the future, chemotherapy with new anticancer agents, immunotherapy, and new methods of radiotherapy and gene therapy will be developed; however, ALA will play a key role in malignant glioma treatment before the development of these new treatments. In this paper, we provide an overview and present the results of our clinical research on ALA-PDD. PMID:27429612

  20. Development of corrosion resistant aluminum heat exchanger, Part 1: Development of new aluminum alloy sheets for sacrificial anode

    SciTech Connect

    Hagiwara, M.; Baba, Y.; Tanabe, Z.; Miura, T.; Hasegawa, Y.; Iijima, K.

    1986-01-01

    The sacrificial anodic effect of Al-Zn alloy reduced markedly in aluminium heat exchanger as car air conditioner manufactured by vacuum brazing conventionally used, as zinc elements preferentially evaporate in vacuum-heating. It was found that Al-Sn alloy had superior electrochemical characteristics than Al-Zn alloy (AA7072) as the sacrificial anodic material used in vacuum brazing. According to many experimental results, the new brazing sheet-fin with Al-Mn-Sn alloy core metal has been developed. This fin has favorable formability and prominent sacrificial anodic effect. Therefore, this fin is excellent material for car air conditioner manufactured by vacuum brazing.

  1. Application of 5-ALA for differential diagnostics of stomach diseases

    NASA Astrophysics Data System (ADS)

    Okhotnikova, Natalja L.; Dadvany, Sergey A.; Kuszin, Michail I.; Kharnas, Sergey S.; Zavodnov, Victor Y.; Sklyanskaya, Olga A.; Loschenov, Victor B.; Volkova, Anna I.; Agafonov, Valery V.

    2001-01-01

    59 patients with stomach diseases including gastric cancer or polyp, gastritis, esofagus disease were investigated. Before gastroscopy all patients were given 5-ALA in doses 5mg, 10mg and 20mg per 1kg of body weight orally. Fluorescence diagnostics which estimates concentration of ALA-induced PPIX in regular and alternated tissues of gastric mucosa were carried out in 2-4 hours. Using of 5-ALA has shown high diagnostic effectiveness for differential diagnostics of stomach diseases. This technique has proved 10 diagnosis of cancer and revealed 15 malignant stomach diseases including 4 cancer in situ for patients with preliminary diagnosis of gastric ulcer. It also revealed 5 patients with enhanced fluorescence for which aimed biopsy has shown high degree of inflammation process. The latter were assigned as a risk group.

  2. Growth and magnetotransport measurements of triple-valley high mobility, miscut (111) AlAs quantum wells

    NASA Astrophysics Data System (ADS)

    Prabhu-Gaunkar, Sunanda; Grayson, M.; Herzog, F.; Koblmueller, G.

    2012-02-01

    We optimize growth of AlAs on (111)B GaAs substrates and perform magnetotransport measurements on vicinal (111)AlAs quantum wells (QWs). Previous literature reports that MBE growth on exactly oriented GaAs (111)B substrates is difficult, and the grown epi-layers are obscured by pyramid-like surface faceting and twin defect formation; slight substrate miscut results in stable step-flow growth. We perform a combined structural analysis with AFM, TEM and XRD to correlate MBE growth conditions with defect density scaling. We find that a high growth temperature of 690^o C and low As beam fluxes reduce micro-twin formation for exactly oriented substrates and eliminate them for miscut substrates. A slight miscut of 2^o, at which slip-step growth is known to occur, lead to AlAs QWs with record electron mobility μ = 13000 cm^2/Vs at a sheet density n2D = 2.17x10^11 cm-2. Numerical calculations reveal that valley splitting is about 1 meV per degree of miscut, which compares to typical Fermi energies of 2DEGs in AlAs QWs. Signatures in the transport data indicate that not only miscut but also exchange splitting between valleys can play an important role. Magnetotransport data at 15 mK in magnetic fields up to 15 T will also be presented.

  3. Metalorganic chemical vapor deposition of gallium nitride on sacrificial substrates

    NASA Astrophysics Data System (ADS)

    Fenwick, William Edward

    GaN-based light emitting diodes (LEDs) face several challenges if the technology is to continue to make a significant impact in general illumination, and on technology that has become known as solid state lighting (SSL). Two of the most pressing challenges for the continued penetration of SSL into traditional lighting applications are efficacy and total lumens from the device, and their related cost. The development of alternative substrate technologies is a promising avenue toward addressing both of these challenges, as both GaN-based device technology and the associated metalorganic chemical vapor deposition (MOCVD) technology are already relatively mature technologies with a well-understood cost base. Zinc oxide (ZnO) and silicon (Si) are among the most promising alternative substrates for GaN epitaxy. These substrates offer the ability to access both higher efficacy and lumen devices (ZnO) at a much reduced cost. This work focuses on the development of MOCVD growth processes to yield high quality GaN-based materials and devices on both ZnO and Si. ZnO is a promising substrate for growth of low defect-density GaN because of its similar lattice constant and thermal expansion coefficient. The major hurdles for GaN growth on ZnO are the instability of the substrate in a hydrogen atmosphere, which is typical of nitride growth conditions, and the inter-diffusion of zinc and oxygen from the substrate into the GaN-based epitaxial layer. A process was developed for the MOCVD growth of GaN and InxGa 1-xN on ZnO that attempted to address these issues. The structural and optical properties of these films were studied using various techniques. X-ray diffraction (XRD) showed the growth of wurtzite GaN on ZnO, and room-temperature photoluminescence (RT-PL) showed near band-edge luminescence from the GaN and InxGa1-xN layers. However, high zinc and oxygen concentrations due to interdiffusion near the ZnO substrate remained an issue; therefore, the diffusion of zinc and oxygen

  4. Monolithic multilayer microfluidics via sacrificial molding of 3D-printed isomalt†

    PubMed Central

    Gelber, Matthew K.

    2015-01-01

    Here we demonstrate a method for creating multilayer or 3D microfluidics by casting a curable resin around a water-soluble, freestanding sacrificial mold. We use a purpose-built 3D printer to pattern self-supporting filaments of the sugar alcohol isomalt, which we then back-fill with a transparent epoxy resin. Dissolving the sacrificial mold leaves a network of cylindrical channels as well as input and output ports. We use this technique to fabricate a combinatorial mixer capable of producing 8 combinations of two fluids in ratios ranging from 1 : 100 to 100 : 1. This approach allows rapid iteration on microfluidic chip design and enables the use of geometry and materials not accessible using conventional soft lithography. The ability to precisely pattern round channels in all three dimensions in hard and soft media may prove enabling for many organ-on-chip systems. PMID:25671493

  5. Embedded proteins and sacrificial bonds provide the strong adhesive properties of gastroliths.

    PubMed

    Thormann, Esben; Mizuno, Hiroyasu; Jansson, Kjell; Hedin, Niklas; Fernández, M Soledad; Arias, José Luis; Rutland, Mark W; Pai, Ranjith Krishna; Bergström, Lennart

    2012-07-01

    The adhesive properties of gastroliths from a freshwater crayfish (Cherax quadricarinatus) were quantified by colloidal probe atomic force microscopy (AFM) between heavily demineralized gastrolith microparticles and gastrolith substrates of different composition. Combined AFM and transmission electron microscopy studies demonstrated that the sequential detachment and large adhesion energies that characterise the adhesive behaviour of a native gastrolith substrate are dominated by sacrificial bonds between chitin fibres and between chitin fibres and CaCO(3). The sacrificial bonds were shown to be strongly related to the gastrolith proteins and when the majority of these proteins were removed by ethylenediaminetetraacetic acid (EDTA), the sequential detachment disappeared and the adhesive energy was reduced by more than two orders of magnitude. PMID:22653376

  6. Chemical Fouling Reduction of a Submersible Steel Spectrophotometer in Estuarine Environments Using a Sacrificial Zinc Anode.

    PubMed

    Tait, Zachary S; Thompson, Megan; Stubbins, Aron

    2015-07-01

    The availability of in situ spectrophotometers, such as the S::CAN spectro::lyser, has expanded the possibilities for high-frequency water quality data collection. However, biological and chemical fouling can degrade the performance of in situ spectrophotometers, especially in saline environments with rapid flow rates. A complex freshwater washing system has been previously designed to reduce chemical fouling for the S::CAN spectro::lyser spectrophotometer. In the current study, we present a simpler, cheaper alternative: the attachment of a sacrificial zinc anode. Results are presented detailing the S::CAN spectro::lyser performance with and without the addition of the sacrificial anode. Attachment of the zinc anode provided efficient corrosion protection during 2-wk deployments in a highly dynamic (average tidal range, 2.5 m) saline tidal saltmarsh creek at Groves Creek, Skidaway Institute of Oceanography, Savannah, GA. PMID:26437114

  7. Monolithic multilayer microfluidics via sacrificial molding of 3D-printed isomalt.

    PubMed

    Gelber, Matthew K; Bhargava, Rohit

    2015-04-01

    Here we demonstrate a method for creating multilayer or 3D microfluidics by casting a curable resin around a water-soluble, freestanding sacrificial mold. We use a purpose-built 3D printer to pattern self-supporting filaments of the sugar alcohol isomalt, which we then back-fill with a transparent epoxy resin. Dissolving the sacrificial mold leaves a network of cylindrical channels as well as input and output ports. We use this technique to fabricate a combinatorial mixer capable of producing 8 combinations of two fluids in ratios ranging from 1 : 100 to 100 : 1. This approach allows rapid iteration on microfluidic chip design and enables the use of geometry and materials not accessible using conventional soft lithography. The ability to precisely pattern round channels in all three dimensions in hard and soft media may prove enabling for many organ-on-chip systems. PMID:25671493

  8. Sacrificial Microchannel Sealing by Glass-Frit Reflow for Chip Scale Atomic Magnetometer

    NASA Astrophysics Data System (ADS)

    Tsujimoto, Kazuya; Hirai, Yoshikazu; Sugano, Koji; Tsuchiya, Toshiyuki; Tabata, Osamu

    A novel sealing technique using sacrificial microchannels was proposed for atmosphere control in a micromachined alkali gas-filled cell for a chip scale atomic magnetometer. The microchannels act as feedthrough connecting the cell to outside atmosphere during evacuation and gas-filling steps, and eventually they are sealed by glass-frit reflow. Si microchannel dedicated as a sacrificial microchannel was proposed and its feasibility was successfully demonstrated by experiments. The simulation results clarified the glass-frit reflow characteristics and its dependence on cross-sectional shape of the microchannel. Hermeticity of the proposed sealing technique of less than 10-12Pa·m3/s leak rate was verified by a high resolution helium leak test.

  9. The spectre of court-sanctioned sacrificial separation of teenage conjoined twins against their will.

    PubMed

    Davis, Colleen

    2014-06-01

    In a recent decision of the Indian Supreme Court, judges foreshadowed authorising separation of teenage conjoined twins where both would die if not separated but where the operation could save only one. The absence of medical information advising separation precluded such a decision in the case at hand. However, the case raises a number of difficult legal and ethical questions that judges would have to consider before authorising sacrificial separation of these or other non-infant conjoined twins. PMID:25087373

  10. Formation of Spatially and Geometrically Controlled Three-Dimensional Tissues in Soft Gels by Sacrificial Micromolding

    PubMed Central

    Cerchiari, Alec; Garbe, James C.; Todhunter, Michael E.; Jee, Noel Y.; Pinney, James R.; LaBarge, Mark A.

    2015-01-01

    Patterned three-dimensional (3D) cell culture models aim to more accurately represent the in vivo architecture of a tissue for the purposes of testing drugs, studying multicellular biology, or engineering functional tissues. However, patterning 3D multicellular structures within very soft hydrogels (<500 Pa) that mimic the physicochemical environment of many tissues remains a challenge for existing methods. To overcome this challenge, we use a Sacrificial Micromolding technique to temporarily form spatially and geometrically defined 3D cell aggregates in degradable scaffolds before transferring and culturing them in a reconstituted extracellular matrix. Herein, we demonstrate that Sacrificial Micromolding (1) promotes cyst formation and proper polarization of established epithelial cell lines, (2) allows reconstitution of heterotypic cell–cell interactions in multicomponent epithelia, and (3) can be used to control the lumenization-state of epithelial cysts as a function of tissue size. In addition, we discuss the potential of Sacrificial Micromolding as a cell-patterning tool for future studies. PMID:25351430

  11. Sacrificial bonds and hidden length in biomaterials -- a kinetic description of strength and toughness in bone

    NASA Astrophysics Data System (ADS)

    Lieou, Charles K. C.; Elbanna, Ahmed E.; Carlson, Jean M.

    2013-03-01

    Sacrificial bonds and hidden length in structural molecules account for the greatly increased fracture toughness of biological materials compared to synthetic materials without such structural features, by providing a molecular-scale mechanism of energy dissipation. One example of occurrence of sacrificial bonds and hidden length is in the polymeric glue connection between collagen fibrils in animal bone. In this talk, we propose a simple kinetic model that describes the breakage of sacrificial bonds and the revelation of hidden length, based on Bell's theory. We postulate a master equation governing the rates of bond breakage and formation, at the mean-field level, allowing for the number of bonds and hidden lengths to take up non-integer values between successive, discrete bond-breakage events. This enables us to predict the mechanical behavior of a quasi-one-dimensional ensemble of polymers at different stretching rates. We find that both the rupture peak heights and maximum stretching distance increase with the stretching rate. In addition, our theory naturally permits the possibility of self-healing in such biological structures.

  12. 'Utilitarian' judgments in sacrificial moral dilemmas do not reflect impartial concern for the greater good.

    PubMed

    Kahane, Guy; Everett, Jim A C; Earp, Brian D; Farias, Miguel; Savulescu, Julian

    2015-01-01

    A growing body of research has focused on so-called 'utilitarian' judgments in moral dilemmas in which participants have to choose whether to sacrifice one person in order to save the lives of a greater number. However, the relation between such 'utilitarian' judgments and genuine utilitarian impartial concern for the greater good remains unclear. Across four studies, we investigated the relationship between 'utilitarian' judgment in such sacrificial dilemmas and a range of traits, attitudes, judgments and behaviors that either reflect or reject an impartial concern for the greater good of all. In Study 1, we found that rates of 'utilitarian' judgment were associated with a broadly immoral outlook concerning clear ethical transgressions in a business context, as well as with sub-clinical psychopathy. In Study 2, we found that 'utilitarian' judgment was associated with greater endorsement of rational egoism, less donation of money to a charity, and less identification with the whole of humanity, a core feature of classical utilitarianism. In Studies 3 and 4, we found no association between 'utilitarian' judgments in sacrificial dilemmas and characteristic utilitarian judgments relating to assistance to distant people in need, self-sacrifice and impartiality, even when the utilitarian justification for these judgments was made explicit and unequivocal. This lack of association remained even when we controlled for the antisocial element in 'utilitarian' judgment. Taken together, these results suggest that there is very little relation between sacrificial judgments in the hypothetical dilemmas that dominate current research, and a genuine utilitarian approach to ethics. PMID:25460392

  13. Silk gland-specific tRNA(Ala) genes interact more weakly than constitutive tRNA(Ala) genes with silkworm TFIIIB and polymerase III fractions.

    PubMed Central

    Sullivan, H S; Young, L S; White, C N; Sprague, K U

    1994-01-01

    Constitutive and silk gland-specific tRNA(Ala) genes from silkworms have very different transcriptional properties in vitro. Typically, the constitutive type, which encodes tRNA(AlaC), directs transcription much more efficiently than does the silk gland-specific type, which encodes tRNA(AlaSG). We think that the inefficiency of the tRNA(AlaCG) gene underlies its capacity to be turned off in non-silk gland cells. An economical model is that the tRNA(AlaSG) promoter interacts poorly, relative to the tRNA(AlaC) promoter, with one or more components of the basal transcription machinery. As a consequence, the tRNA(AlaSG) gene directs the formation of fewer transcription complexes or of complexes with reduced cycling ability. Here we show that the difference in the number of active transcription complexes accounts for the difference in tRNA(AlaC) and tRNA(AlaSG) transcription rates. To determine whether a particular component of the silkworm transcription machinery is responsible for reduced complex formation on the tRNA(AlaSG) gene, we measured competition by templates for defined fractions of this machinery. We find that the tRNA(AlaSG) gene is greatly impaired, in comparison with the tRNA(AlaC) gene, in competition for either TFIIIB or RNA polymerase III. Competition for each of these fractions is also strongly influenced by the nature of the 5' flanking sequence, the promoter element responsible for the distinctive transcriptional properties of tRNA(AlaSG) and tRNA(AlaC) genes. These results suggest that differential interaction with TFIIIB or RNA polymerase III is a critical functional distinction between these genes. Images PMID:8114713

  14. Observation of reflection high-energy electron diffraction oscillation during metalorganic-molecular-beam epitaxy of AlAs and control of carbon incorporation

    NASA Astrophysics Data System (ADS)

    Ganapathy, Sasikala; Kurimoto, Makoto; Thilakan, Periyasamy; Uesugi, Kasturi; Suemune, Ikuo; Machida, Hideaki; Shimoyama, Norio

    2003-10-01

    The in situ observation of reflection high-energy electron diffraction (RHEED) oscillations during the metalorganic-molecular-beam epitaxy deposition of AlAs and AlGaAs epitaxial layers is reported. In situ RHEED oscillations as well as atomic force microscopy measurements confirmed the layer-by-layer growth of the AlAs as well as the AlGaAs layers on GaAs substrates. RHEED oscillation was successfully applied to the precise control of the AlAs/GaAs superlattices and of the alloy compositions in the AlGaAs alloys. High-resolution x-ray diffraction and Hall effect measurements revealed the unintentional doping of carbon into the AlGaAs layers, but it was found that the increase in the V/III ratio is able to reduce the carbon incorporation.

  15. ALA 2010 Midwinter Meeting: The Price to Participate

    ERIC Educational Resources Information Center

    Berry, John N., III

    2009-01-01

    While the library economy continues its downward slide, the cost of attending the American Library Association (ALA) Midwinter Meeting seems as high as ever. That is the price of professional participation. These days it seems a bit too high and tends to limit involvement in the old association to librarians in the higher echelons of the field.…

  16. ALAM and ALAS: Questioning Error Assignments in Unidimensional Guttman Scaling

    ERIC Educational Resources Information Center

    Wimberley, Ronald C.

    1976-01-01

    When researchers use the Guttman scalogram rather than multidimensional techniques, scalogram error assignment techniques should be questioned. An alternative to the customary minimizing error rule is suggested through ALAM and ALAS criteria which use ordinal information in scalable item marginals. (Author)

  17. [Plastic surgery indications for the repair of nasal tip and nasal alae defects].

    PubMed

    Boudard, Ph

    2010-01-01

    Analyze methods of reconstruction of non-transfixing and transfixing loss of substance of the nasal tip and nasal ala. We would like to share the attitude guiding our selecting of the different methods to rehabilitate this mobile and functional portion of the nose. We retrospectively studied 32 cases of defects of the tip and ala treated between 2007 and 2009. There were 26 basal cell carcinomas, 5 squamous cell carcinomas and 1 melanoma. The minimum postoperative follow-up was one year. For reconstruction we used local flaps: medial dorsal flap, bilobed flap, transverse island flap and regional flaps: fronto-glabellar flap, forehead flap, nasolabial flap. In this study we analyzed the aesthetic and functional result achieved at the nasal orifice. We also studied the histopathological reports regarding safety tissue margins, both in depth and peripherally. Most of the defects of the tip and the alae of less than 1 cm were repaired by local flaps; bilobed or transverse island flaps. For the median region, the Rintala mid-dorsal flap appears to give better results. Tissue losses greater than 1 cm often required the use of a fronto-glabellar flap that allowed delivery of more tissue with less scarring at the donor site. The nasolabial flap may have the disadvantage of removing the crease and sometimes a certain thickness at the arc of rotation, which might require further thinning at a later stage. For transfixing loss of substance, we must repair all the layers: skin, cartilage and mucosa. The forehead flap with respect to the principles of the aesthetic subunits of the nose is the flap of choice. We stress on the importance of ample resection with adequate safety margins peripherally and in depth. PMID:21284228

  18. Surface modification for patterned cell growth on substrates with pronounced topographies using sacrificial photoresist and parylene-C peel-off

    NASA Astrophysics Data System (ADS)

    Larramendy, Florian; Yoshida, Shotaro; Jalabert, Laurent; Takeuchi, Shoji; Paul, Oliver

    2016-09-01

    A range of methods including soft lithography are available for patterning protein layers for cell adhesion on quasi-planar substrates. Suitably structured, these layers favor the geometrically constrained, controlled growth of cells and the development of cellular extensions on them. For this purpose, the ability to control the shape and dimension of cell-adhesive areas with high precision is crucial. For more advanced studies of cell interactions, the surface modification or functionalization of substrates with complex topographies is desirable. This paper describes a simple technique allowing to produce surface modification patterns using delicate molecules such as laminin on substrates exhibiting pronounced topographies with recessed and protruding microstructures. The technique is based on the combination of sacrificial photoresist structures with a connected parylene-C layer. This layer locally adheres to the substrate wherever the substrate needs to be protected against the surface modification. After surface modification, the parylene-C layer is peeled off. Patterns comprising arbitrary networks of modified and unmodified substrate areas can thus be realized. We demonstrate the technique with the guided growth of neuron-like PC12 cells on networks of laminin lines on substrates structured with micropillars and microwells.

  19. Loss of the Arabidopsis thaliana P4-ATPases ALA6 and ALA7 impairs pollen fitness and alters the pollen tube plasma membrane.

    PubMed

    McDowell, Stephen C; López-Marqués, Rosa L; Cohen, Taylor; Brown, Elizabeth; Rosenberg, Alexa; Palmgren, Michael G; Harper, Jeffrey F

    2015-01-01

    Members of the P4 subfamily of P-type ATPases are thought to create and maintain lipid asymmetry in biological membranes by flipping specific lipids between membrane leaflets. In Arabidopsis, 7 of the 12 Aminophospholipid ATPase (ALA) family members are expressed in pollen. Here we show that double knockout of ALA6 and ALA7 (ala6/7) results in siliques with a ~2-fold reduction in seed set with a high frequency of empty seed positions near the bottom. Seed set was reduced to near zero when plants were grown under a hot/cold temperature stress. Reciprocal crosses indicate that the ala6/7 reproductive deficiencies are due to a defect related to pollen transmission. In-vitro growth assays provide evidence that ala6/7 pollen tubes are short and slow, with ~2-fold reductions in both maximal growth rate and overall length relative to wild-type. Outcrosses show that when ala6/7 pollen are in competition with wild-type pollen, they have a near 0% success rate in fertilizing ovules near the bottom of the pistil, consistent with ala6/7 pollen having short and slow growth defects. The ala6/7 phenotypes were rescued by the expression of either an ALA6-YFP or GFP-ALA6 fusion protein, which showed localization to both the plasma membrane and highly-mobile endomembrane structures. A mass spectrometry analysis of mature pollen grains revealed significant differences between ala6/7 and wild-type, both in the relative abundance of lipid classes and in the average number of double bonds present in acyl side chains. A change in the properties of the ala6/7 plasma membrane was also indicated by a ~10-fold reduction of labeling by lipophilic FM-dyes relative to wild-type. Together, these results indicate that ALA6 and ALA7 provide redundant activities that function to directly or indirectly change the distribution and abundance of lipids in pollen, and support a model in which ALA6 and ALA7 are critical for pollen fitness under normal and temperature-stress conditions. PMID:25954280

  20. Loss of the Arabidopsis thaliana P4-ATPases ALA6 and ALA7 impairs pollen fitness and alters the pollen tube plasma membrane

    PubMed Central

    McDowell, Stephen C.; López-Marqués, Rosa L.; Cohen, Taylor; Brown, Elizabeth; Rosenberg, Alexa; Palmgren, Michael G.; Harper, Jeffrey F.

    2015-01-01

    Members of the P4 subfamily of P-type ATPases are thought to create and maintain lipid asymmetry in biological membranes by flipping specific lipids between membrane leaflets. In Arabidopsis, 7 of the 12 Aminophospholipid ATPase (ALA) family members are expressed in pollen. Here we show that double knockout of ALA6 and ALA7 (ala6/7) results in siliques with a ~2-fold reduction in seed set with a high frequency of empty seed positions near the bottom. Seed set was reduced to near zero when plants were grown under a hot/cold temperature stress. Reciprocal crosses indicate that the ala6/7 reproductive deficiencies are due to a defect related to pollen transmission. In-vitro growth assays provide evidence that ala6/7 pollen tubes are short and slow, with ~2-fold reductions in both maximal growth rate and overall length relative to wild-type. Outcrosses show that when ala6/7 pollen are in competition with wild-type pollen, they have a near 0% success rate in fertilizing ovules near the bottom of the pistil, consistent with ala6/7 pollen having short and slow growth defects. The ala6/7 phenotypes were rescued by the expression of either an ALA6-YFP or GFP-ALA6 fusion protein, which showed localization to both the plasma membrane and highly-mobile endomembrane structures. A mass spectrometry analysis of mature pollen grains revealed significant differences between ala6/7 and wild-type, both in the relative abundance of lipid classes and in the average number of double bonds present in acyl side chains. A change in the properties of the ala6/7 plasma membrane was also indicated by a ~10-fold reduction of labeling by lipophilic FM-dyes relative to wild-type. Together, these results indicate that ALA6 and ALA7 provide redundant activities that function to directly or indirectly change the distribution and abundance of lipids in pollen, and support a model in which ALA6 and ALA7 are critical for pollen fitness under normal and temperature-stress conditions. PMID:25954280

  1. Observation of reflection high-energy electron diffraction oscillation during MOMBE growth of AlAs and related modulated semiconductor structures

    NASA Astrophysics Data System (ADS)

    Ganapathy, Sasikala; Thilakan, Periyasamy; Kurimoto, Makoto; Uesugi, Kasturi; Suemune, Ikuo; Shimoyama, Nori

    2004-03-01

    In situ reflection high-energy electron diffraction (RHEED) oscillation was successfully observed during the MOMBE growth of AlAs for different V/III ratios. At higher V/III ratio the growth mode of AlAs was found to be layer-by-layer growth and thus it resulted in clear and long-period RHEED oscillations. High resolution X-ray diffraction and Hall measurements evidenced the presence of C in the AlGaAs layers and its contribution to p-type conductivity. It was found that the higher V/III ratio reduces the C incorporation in the MOMBE grown AlGaAs layers and lattice matched with GaAs. In such a lattice-matched conditions GaAs/AlAs SPSL were successfully grown with monolayer controlled thickness with the help of RHEED oscillations.

  2. Hydroxylation and Epoxidation of Fatty Acids by Bacillus megaterium ALA2

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bacillus megaterium ALA2 produces many new oxygenated fatty acids from linoleic acid. Strain ALA2 hydroxylated palmitic acid to omega-1, omega-2, and omega-3 hydroxy palmitate. Now we found that strain ALA2 also epoxidized linoleic acid to 12,13-epoxy-9(Z)-octadecenoic acid and 9,10-epoxy-12(Z)-oc...

  3. 75 FR 12254 - Official Trail Marker for the Ala Kahakai National Historic Trail

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-15

    ... National Park Service Official Trail Marker for the Ala Kahakai National Historic Trail AGENCY: National.... SUMMARY: This notice issues the official trail marker insignia of the Ala Kahakai National Historic Trail... P. Arakaki, Superintendent, Ala Kahakai National Historic Trail. The insignia depicted below...

  4. Basic principles of fluorescence detection with use of 5-ALA

    NASA Astrophysics Data System (ADS)

    Baumgartner, Reinhold; Stepp, Herbert G.

    2000-06-01

    5-Aminolevulinic acid (5-ALA) has been proven to induce selective accumulation of flourescent Protoporphyrin IX (PPIX) in many types of malignant tissue. According to the target to treatment different routes of topical and systemical application of 5-ALA can be chosen. They include techniques like inhalation, installation and rinsing. For fluorescence detection a lamp based system have been developed in the laser-Forschungslabor in Munich together with Storz company. By skillful balancing of excitation filter centered around 400 nm and the observation filter with transmission above 450 nm images with high color contrast can be obtained. The universal application of the D-LIGHT could be demonstrated in different clinical disciplines like urology, neurosurgery, ENT clinic, gynecology and others.

  5. The complex filling of alae crater, Kilauea Volcano, Hawaii

    USGS Publications Warehouse

    Swanson, D.A.; Duffield, W.A.; Jackson, D.B.; Peterson, D.W.

    1972-01-01

    Since February 1969 Alae Crater, a 165-m-deep pit crater on the east rift of Kilauea Volcano, has been completely filled with about 18 million m3 of lava. The filling was episodic and complex. It involved 13 major periods of addition of lava to the crater, including spectacular lava falls as high as 100 m, and three major periods of draining of lava from the crater. Alae was nearly filled by August 3, 1969, largely drained during a violent ground-cracking event on August 4, 1969, and then filled to the low point on its rim on October 10, 1969. From August 1970 to May 1971, the crater acted as a reservoir for lava that entered through subsurface tubes leading from the vent fissure 150 m away. Another tube system drained the crater and carried lava as far as the sea, 11 km to the south. Much of the lava entered Alae by invading the lava lake beneath its crust and buoying the crust upward. This process, together with the overall complexity of the filling, results in a highly complicated lava lake that would doubtless be misinterpreted if found in the fossil record. ?? 1972 Stabilimento Tipografico Francesco Giannini & Figli.

  6. Update on sacrificial anode cathodic protection on steel reinforced concrete structures in seawater

    SciTech Connect

    Kessler, R.J.; Powers, R.G.; Lasa, I.R.

    1995-12-01

    Various configurations of sacrificial zinc anodes have been successfully used to provide cathodic protection in the tidal zone of steel reinforced concrete structures. Studies conducted by the Florida Department of Transportation have shown that zinc anodes configured in simple fashion can provide long term cathodic protection. These simple systems represent an attractive alternative to conventional cathodic protection where rectifiers are used. This paper discusses a cathodic protection system comprised of zinc sheet anodes used in conjunction with a submerged bulk zinc anode. An overview of long term performance is presented along with estimated service life and costs.

  7. From Eshu to Obatala: animals used in sacrificial rituals at Candomblé "terreiros" in Brazil

    PubMed Central

    Léo Neto, Nivaldo A; Brooks, Sharon E; Alves, Rômulo RN

    2009-01-01

    Background The practice of sacrifice has occurred in several cultures and religions throughout history and still exists today. Candomblé, a syncretical Afro-Brazilian religion, practices the sacrificial ritual called "Orô" by its adherents. The present work aims to document the use of animal species in these sacrificial practices in the cities of Caruaru (PE) and Campina Grande (PB) in Norteastern Brazil, and to further understand the symbolism of these rituals. Methods Semi-structured and unstructured interviews and informal discussions were held with 11 Candomblé priests and priestesses between the months of August 2007 and June 2008. We attended rituals performed at "terreiros" where animals were sacrificed, in order to obtain photographic material and observe the procedures and techniques adopted. Results A total of 29 animal species were used during sacrificial rituals according to the priests and priestesses. These species were classified in 5 taxanomic groups: Molluscs (n = 1), Amphibians (n = 2), Reptiles (n = 2), Birds (n = 10) and Mammals (n = 14). According to Candomblé beliefs, animals are sacrificed and offered to their deities, known as orishas, for the prosperity of all life. There is a relationship between the colour, sex and behaviour of the animal to be sacrificed, and the orisha to whom the animal is going to be offered. The many myths that form the cosmogony of Candomblé can often explain the symbolism of the rituals observed and the animal species sacrificed. These myths are conveyed to adherants by the priests and priestesses during the ceremonies, and are essential to the continuation of this religion. Conclusion Candomblé is a sacrificial religion that uses animals for its liturgical purposes. The principal reason for sacrifice is to please supernatural deities known as orishas in order to keep life in harmony. This is accomplished through feeding them in a spiritual sense through sacrifice, maintaining a perfect link between men and

  8. Characterization of the l-alanine exporter AlaE of Escherichia coli and its potential role in protecting cells from a toxic-level accumulation of l-alanine and its derivatives

    PubMed Central

    Kim, Seryoung; Ihara, Kohei; Katsube, Satoshi; Hori, Hatsuhiro; Ando, Tasuke; Isogai, Emiko; Yoneyama, Hiroshi

    2015-01-01

    We previously reported that the alaE gene of Escherichia coli encodes the l-alanine exporter AlaE. The objective of this study was to elucidate the mechanism of the AlaE exporter. The minimum inhibitory concentration of l-alanine and l-alanyl-l-alanine in alaE-deficient l-alanine-nonmetabolizing cells MLA301ΔalaE was 4- and >4000-fold lower, respectively, than in the alaE-positive parent cells MLA301, suggesting that AlaE functions as an efflux pump to avoid a toxic-level accumulation of intracellular l-alanine and its derivatives. Furthermore, the growth of the alaE-deficient mutant derived from the l-alanine-metabolizing strain was strongly inhibited in the presence of a physiological level of l-alanyl-l-alanine. Intact MLA301ΔalaE and MLA301ΔalaE/pAlaE cells producing plasmid-borne AlaE, accumulated approximately 200% and 50%, respectively, of the [3H]l-alanine detected in MLA301 cells, suggesting that AlaE exports l-alanine. When 200 mmol/L l-alanine-loaded inverted membrane vesicles prepared from MLA301ΔalaE/pAlaE were placed in a solution containing 200 mmol/L or 0.34 μmol/L l-alanine, energy-dependent [3H]l-alanine accumulation occurred under either condition. This energy-dependent uphill accumulation of [3H]l-alanine was strongly inhibited in the presence of carbonyl cyanide m-chlorophenylhydrazone but not by dicyclohexylcarbodiimide, suggesting that the AlaE-mediated l-alanine extrusion was driven by proton motive force. Based on these results, physiological roles of the l-alanine exporter are discussed. PMID:26073055

  9. Characterization of the l-alanine exporter AlaE of Escherichia coli and its potential role in protecting cells from a toxic-level accumulation of l-alanine and its derivatives.

    PubMed

    Kim, Seryoung; Ihara, Kohei; Katsube, Satoshi; Hori, Hatsuhiro; Ando, Tasuke; Isogai, Emiko; Yoneyama, Hiroshi

    2015-08-01

    We previously reported that the alaE gene of Escherichia coli encodes the l-alanine exporter AlaE. The objective of this study was to elucidate the mechanism of the AlaE exporter. The minimum inhibitory concentration of l-alanine and l-alanyl-l-alanine in alaE-deficient l-alanine-nonmetabolizing cells MLA301ΔalaE was 4- and >4000-fold lower, respectively, than in the alaE-positive parent cells MLA301, suggesting that AlaE functions as an efflux pump to avoid a toxic-level accumulation of intracellular l-alanine and its derivatives. Furthermore, the growth of the alaE-deficient mutant derived from the l-alanine-metabolizing strain was strongly inhibited in the presence of a physiological level of l-alanyl-l-alanine. Intact MLA301ΔalaE and MLA301ΔalaE/pAlaE cells producing plasmid-borne AlaE, accumulated approximately 200% and 50%, respectively, of the [(3) H]l-alanine detected in MLA301 cells, suggesting that AlaE exports l-alanine. When 200 mmol/L l-alanine-loaded inverted membrane vesicles prepared from MLA301ΔalaE/pAlaE were placed in a solution containing 200 mmol/L or 0.34 μmol/L l-alanine, energy-dependent [(3) H]l-alanine accumulation occurred under either condition. This energy-dependent uphill accumulation of [(3) H]l-alanine was strongly inhibited in the presence of carbonyl cyanide m-chlorophenylhydrazone but not by dicyclohexylcarbodiimide, suggesting that the AlaE-mediated l-alanine extrusion was driven by proton motive force. Based on these results, physiological roles of the l-alanine exporter are discussed. PMID:26073055

  10. Optimal control of AlAs oxidation via digital alloy heterostructure compositions

    NASA Astrophysics Data System (ADS)

    Suárez, I.; Almuneau, G.; Condé, M.; Arnoult, A.; Fontaine, C.

    2009-09-01

    A thorough study of wet thermal oxidation in AlAs/AlxGa1-xAs superlattices is presented. The results shown here demonstrate that the final oxidation depth can be finely tuned via the composition and thickness of AlxGa1-xAs into the digital alloy. A complete model of oxidation in these structures is proposed, relying on diffusion through the AlAs layer, its oxidation and an additional effect due to the AlxGa1-xAs intermediate barriers. This barrier contribution is shown to further improve the control of the oxidation rate, and thereby fabrication of sophisticated AlOx/GaAs integrated optoelectronic devices.

  11. Development of size-customized hepatocarcinoma spheroids as a potential drug testing platform using a sacrificial gelatin microsphere system.

    PubMed

    Leong, Wenyan; Kremer, Antje; Wang, Dong-An

    2016-06-01

    Sacrificial gelatin microspheres can be developed as a cell delivery vehicle for non-anchorage dependent cells - its incorporation into a macroscopic scaffold system not only allows the cells to be cultured in suspension within cavities left behind by the sacrificial material, it also allows scaffold-free tissue development to be confined within the cavities. In this study, dense and highly viable hepatocarcinoma spheroids were developed by means of encapsulation in sacrificial gelatin microspheres produced via a simple water-in-oil emulsion technique. By initial selection of microsphere size and distribution, spheroid size can be controlled for various applications such as uniform tumor spheroids as a reproducible three-dimensional drug screening and testing platform that better mimics the in vivo nature of tumors (instead of conventional monolayer culture), as this study has suggested as a proof-of-concept with chemotherapy drug Doxorubicin. PMID:27040260

  12. Fabrication of scalable and structured tissue engineering scaffolds using water dissolvable sacrificial 3D printed moulds.

    PubMed

    Mohanty, Soumyaranjan; Larsen, Layla Bashir; Trifol, Jon; Szabo, Peter; Burri, Harsha Vardhan Reddy; Canali, Chiara; Dufva, Marin; Emnéus, Jenny; Wolff, Anders

    2015-10-01

    One of the major challenges in producing large scale engineered tissue is the lack of ability to create large highly perfused scaffolds in which cells can grow at a high cell density and viability. Here, we explore 3D printed polyvinyl alcohol (PVA) as a sacrificial mould in a polymer casting process. The PVA mould network defines the channels and is dissolved after curing the polymer casted around it. The printing parameters determined the PVA filament density in the sacrificial structure and this density resulted in different stiffness of the corresponding elastomer replica. It was possible to achieve 80% porosity corresponding to about 150 cm(2)/cm(3) surface to volume ratio. The process is easily scalable as demonstrated by fabricating a 75 cm(3) scaffold with about 16,000 interconnected channels (about 1m(2) surface area) and with a channel to channel distance of only 78 μm. To our knowledge this is the largest scaffold ever to be produced with such small feature sizes and with so many structured channels. The fabricated scaffolds were applied for in-vitro culturing of hepatocytes over a 12-day culture period. Smaller scaffolds (6×4 mm) were tested for cell culturing and could support homogeneous cell growth throughout the scaffold. Presumably, the diffusion of oxygen and nutrient throughout the channel network is rapid enough to support cell growth. In conclusion, the described process is scalable, compatible with cell culture, rapid, and inexpensive. PMID:26117791

  13. Process of Making Three-dimensional Microstructures using Vaporization of a Sacrificial Component

    PubMed Central

    Nguyen, Du T.; Leho, Y. T.; Esser-Kahn, Aaron P.

    2013-01-01

    Vascular structures in natural systems are able to provide high mass transport through high surface areas and optimized structure. Few synthetic material fabrication techniques are able to mimic the complexity of these structures while maintaining scalability. The Vaporization of a Sacrificial Component (VaSC) process is able to do so. This process uses sacrificial fibers as a template to form hollow, cylindrical microchannels embedded within a matrix. Tin (II) oxalate (SnOx) is embedded within poly(lactic) acid (PLA) fibers which facilitates the use of this process. The SnOx catalyzes the depolymerization of the PLA fibers at lower temperatures. The lactic acid monomers are gaseous at these temperatures and can be removed from the embedded matrix at temperatures that do not damage the matrix. Here we show a method for aligning these fibers using micromachined plates and a tensioning device to create complex patterns of three-dimensionally arrayed microchannels. The process allows the exploration of virtually any arrangement of fiber topologies and structures. PMID:24300342

  14. Fluorescence distribution and photodynamic effect of ALA-induced PP IX in the DMH rat colonic tumour model.

    PubMed Central

    Bedwell, J.; MacRobert, A. J.; Phillips, D.; Bown, S. G.

    1992-01-01

    Aminolaevulinic acid (ALA) is the first committed step in haem synthesis. In the presence of excess ALA the natural regulatory feedback system is disrupted allowing accumulation of protoporphyrin IX (PP IX) the last intermediate product before haem, and an effective sensitiser. This method of endogenous photosensitisation of cells has been exploited for photodynamic therapy (PDT). We have studied the fluorescence distribution and biological effect of induced PP IX in normal and tumour tissue in the rat colon. Fluorescence in normal colonic tissue was at a peak of 4 h with a rapid fall off by 6 h. The fluorescence had returned to background levels by 24 h. All normal tissue layers followed the same fluorescence profile but the mucosa showed fluorescent levels six times higher than the submucosa, with muscle barely above background values. At 6 h the ratio of fluorescence levels between normal mucosa and viable tumour was approximately 1:6. At this time laser treatment showed necrosis of normal mucosa and tumour with sparing of normal muscle. There was good correlation between the fluorescence distribution and the biological effect of ALA-induced photosensitisation on exposure to red light. ALA may be superior to conventional sensitisers for tumours that produce haem as the PP IX is synthesised in malignant cells while the other sensitisers mainly localise to the vascular stroma of tumours. There is also a greater concentration difference between the PP IX levels in tumours and in normal mucosa and normal muscle than with the other photosensitisers raising the possibility of more selective necrosis in tumours. Images p820-a Figure 2 Figure 3 Figure 4 Figure 7 Figure 8 PMID:1616853

  15. Non-Conserved Residues in Clostridium acetobutylicum tRNAAla Contribute to tRNA Tuning for Efficient Antitermination of the alaS T Box Riboswitch

    PubMed Central

    Liu, Liang-Chun; Grundy, Frank J.; Henkin, Tina M.

    2015-01-01

    The T box riboswitch regulates expression of amino acid-related genes in Gram-positive bacteria by monitoring the aminoacylation status of a specific tRNA, the binding of which affects the folding of the riboswitch into mutually exclusive terminator or antiterminator structures. Two main pairing interactions between the tRNA and the leader RNA have been demonstrated to be necessary, but not sufficient, for efficient antitermination. In this study, we used the Clostridium acetobutylicum alaS gene, which encodes alanyl-tRNA synthetase, to investigate the specificity of the tRNA response. We show that the homologous C. acetobutylicum tRNAAla directs antitermination of the C. acetobutylicum alaS gene in vitro, but the heterologous Bacillus subtilis tRNAAla (with the same anticodon and acceptor end) does not. Base substitutions at positions that vary between these two tRNAs revealed synergistic and antagonistic effects. Variation occurs primarily at positions that are not conserved in tRNAAla species, which indicates that these non-conserved residues contribute to optimal antitermination of the homologous alaS gene. This study suggests that elements in tRNAAla may have coevolved with the homologous alaS T box leader RNA for efficient antitermination. PMID:26426057

  16. Light fractionation increases the efficacy of ALA-PDT but not of MAL-PDT: What is the role of (vascular) endothelial cells?

    NASA Astrophysics Data System (ADS)

    de Bruijn, H. S.; de Vijlder, H. C.; de Haas, E. R. M.; van der Ploeg-van den Heuvel, A.; Kruijt, B.; Poel-Dirks, D.; Sterenborg, H. J. C. M.; ten Hagen, T. L. M.; Robinson, D. J.

    2009-06-01

    Photodynamic therapy (PDT) using protoporpyrin IX (PpIX) precursors like 5-aminolevulinic acid (ALA) or methyl-aminolevulinate (MAL) has shown to be effective in the treatment of various skin diseases. Using ALA we have shown in numerous studies a significantly improved efficacy by applying light fractionation with a long dark interval. In contrast, in the hairless mouse model, the PDT efficacy using MAL is unaffected by adopting this approach. More acute edema is found after ALA-PDT suggesting a difference in response of endothelial cells to PDT. To investigate the role of endothelial cells, cryo-sections of hairless mouse skin after 4 hours of topical MAL or ALA application were stained with a fluorescent endothelial cell marker (CD31). Co-localization of this marker with the PpIX fluorescence was performed using the spectral imaging function of the confocal microscope. We have also used intra-vital confocal microscopy to image the PpIX fluorescence distribution in correlation with the vasculature of live mouse skin. Our results show PpIX fluorescence at depth in cryo-sections of mouse skin after 4 hours of topical application. Co-localization has shown to be difficult due to the changes in tissue organization caused by the staining procedure. As expected we found high PpIX fluorescence levels in the epidermis after both MAL and ALA application using intra-vital microscopy. After ALA application more PpIX fluorescence was found deep in the dermal layer of the skin than after MAL. Furthermore we detected localized fluorescence in unidentified structures that could not be correlated to blood vessels or nerves.

  17. Photosensitization and mechanism of cytotoxicity induced by the use of ALA derivatives in photodynamic therapy

    PubMed Central

    Casas, A; Fukuda, H; Di Venosa, G; Batlle, A

    2001-01-01

    The use of more lipophilic derivatives of 5-aminolevulinic acid (ALA) is expected to have better diffusing properties, and after conversion into the parent ALA, to reach a higher protoporphyrin IX (PPIX) formation rate, thus improving the efficacy of topical photodynamic therapy (PDT). Here we have analysed the behaviour of 3 ALA derivatives (ALA methyl-ester, hexyl ester and a 2-sided derivative) regarding PPIX formation, efficiency in photosensitizing cells and mechanism of cellular death. The maximum amount of porphyrins synthesized from 0.6 mM ALA was 47 ± 8 ng/105 cells. The same amount was formed by a concentration 60-fold lower of hexyl-ALA and 2-fold higher of methyl-ALA. The 2-sided derivative failed to produce PPIX accumulation. Applying a 0.6 J cm−2 light dose, cell viability decreased to 50%. With the 1.5 J cm−2 light dose, less than 20% of the cells survive, and higher light doses produced nearly total cell killing. Comparing the PPIX production and the induced phototoxicity, the more the amount of porphyrins, the greater the cellular killing, and PPIX formed from either ALA or ALA-esters equally sensitize the cells to photoinactivation. ALA-PDT treated cells exhibited features of apoptosis, independently on the pro-photosensitizer employed. ALA-PDT can be improved with the use of ALA derivatives, reducing the amount of ALA necessary to induce efficient photosensitization. ©2001 Cancer Research Campaign http://www.bjcancer.com PMID:11461090

  18. Evidence for a Contribution of ALA Synthesis to Plastid-To-Nucleus Signaling

    SciTech Connect

    Czarnecki, Olaf; Gläßer, Christine; Chen, Jin-Gui; Mayer, Klaus F. X.; Grimm, Bernhard

    2012-01-01

    The formation of 5-aminolevulinic acid (ALA) in tetrapyrrole biosynthesis is widely controlled by environmental and metabolic feedback cues that determine the influx into the entire metabolic path. Because of its central role as the rate-limiting step, we hypothesized a potential role of ALA biosynthesis in tetrapyrrole-mediated retrograde signaling and exploited the direct impact of ALA biosynthesis on nuclear gene expression (NGE) by using two different approaches. Firstly, the Arabidopsis gun1, hy1 (gun2), hy2 (gun3), gun4 mutants showing uncoupled NGE from the physiological state of chloroplasts were thoroughly examined for regulatory modifications of ALA synthesis and transcriptional control in the nucleus. We found that reduced ALA-synthesizing capacity is common to analyzed gun mutants. Inhibition of ALA synthesis by gabaculine (GAB) that inactivates glutamate-1-semialdehyde aminotransferase and ALA feeding of wild-type and mutant seedlings corroborate the expression data of gun mutants. Transcript level of photosynthetic marker genes were enhanced in norflurazon (NF)-treated seedlings upon additional GAB treatment, while enhanced ALA amounts diminish these RNA levels in NF-treated wild-type in comparison to the solely NF-treated seedlings. Secondly, the impact of posttranslationally down-regulated ALA synthesis on NGE was investigated by global transcriptome analysis of GAB-treated Arabidopsis seedlings and the gun4-1 mutant, which is also characterized by reduced ALA formation. A common set of significantly modulated genes was identified indicating ALA synthesis as a potential signal emitter. The over-represented gene ontology categories of genes with decreased or increased transcript abundance highlight a few biological processes and cellular functions, which are remarkably affected in response to plastid-localized ALA biosynthesis. These results support the hypothesis that ALA biosynthesis correlates with retrograde signaling-mediated control of NGE.

  19. Structure of the interface between ErAs, a cubic semimetal and AlAs, a tetrahedral semiconductor

    SciTech Connect

    Tarnow, E.

    1995-06-15

    Using {ital ab} {ital initio} local density calculations, the atomic structure of the (100) interface between ErAs, a semimetal with the sodium-chloride (SC) structure and AlAs, a semiconductor with the zinc-blende (ZB) structure is investigated. Several findings emerge: (1) Eight different high symmetry SC/ZB interfaces are identified and classified. (2) Several low energy interfaces, and combinations thereof, are found for epitaxial growth and for small superlattices. The energies of these interfaces change during epitaxy pointing to importance of kinetics. Calculated structural energies and Er {l_angle}100{r_angle} placements are compared with experimental Rutherford backscattering measurements. (3) The AlAs ZB structure buckles the first ErAs SC layer. There is a strong correlation between the amount of buckling induced in a substrate SC layer and the energy required to add another SC layer. (4) For small superlattices a complete ZB or SC arrangement, removing the SC/ZB interfaces altogether, is sometimes energetically preferred. {copyright} {ital 1995} {ital American} {ital Institute} {ital of} {ital Physics}.

  20. Skin laser treatments enhancing transdermal delivery of ALA.

    PubMed

    Gómez, Clara; Costela, Ángel; García-Moreno, Inmaculada; Llanes, Felipe; Teijón, José M; Blanco, M Dolores

    2011-01-01

    Drug delivery across skin has been limited due to barrier properties of the skin, especially those of the stratum corneum (SC). Use of the laser radiation has been suggested for the controlled removal of the SC. The purpose of this study was to study in vitro the influence of infrared radiation from the erbium:yttrium-aluminum-garnet (Er:YAG) laser (λ = 2940  nm), and visible from the 2nd harmonic of a neodymium:yttrium-aluminum-garnet (Nd:YAG) laser (λ = 532  nm) on transdermal delivery of 5-aminolevulinic acid (ALA). Pinna skin of the inner side of rabbit ear was used for skin permeation. The light sources were an Er:YAG laser (Key III Plus KaVo) and a Q-switched Nd:YAG laser (Lotis TII SL-2132). Permeation study, morphological and structural skin examination by histology and differential scanning calorimetry (DSC) were carried out. Permeation profiles and histological observations obtained after irradiation with infrared and visible laser radiation differed due to different biophysical effects on irradiated skin. Wavelength of 2940  nm required lower energy contribution to produce the same level of permeation than visible radiation at 532  nm. Structural analysis by DSC shows a selective impact on the lipidic structure. Laser pretreatment enhanced the delivery of ALA trough the skin by SC ablation. PMID:20589948

  1. Relationship between occlusal plane and ala-tragus line in dentate individuals: A Clinical pilot study.

    PubMed

    Nayar, Sanjna; Bhuminathan, S; Bhat, Wasim Manzoor; Mahadevan, R

    2015-04-01

    Many methods have been used to establish the occlusal plane in complete denture prosthodontics. However, no single method seems to be fully accepted. Anteriorly, esthetic considerations help define the occlusal plane, and posteriorly the tongue, retromolar pad, and Stenson's duct are considered. Some dentists bisect the space between the residual ridges. The technique of using the ala-tragus line (Camper's line) to establish the occlusal plane is well documented. However, definitions of the ala-tragus line cause confusion, because the exact points of reference do not agree. For example, the glossary of prosthodontic terms states that the ala-tragus line runs from the inferior border of the ala of the nose to the superior border of the tragus of the ear while Spratley' describes it as running from the center of the ala to the center of the tragus. This article concerns us the exact relationship between the occlusal plane and ala-tragus line in dentate individuals. PMID:26015765

  2. Facile preparation of stabilized polymeric nanotubes using sacrificial yttrium hydroxide nanotubes as template and block copolymer micelles as precursor.

    PubMed

    Shen, Wenming; Wang, Hui; Peng, Huisheng; Nie, Lei; Chen, Daoyong; Jiang, Ming

    2007-06-21

    We report here facile preparation of stabilized polymeric nanotubes with a hair-like shell using yttrium hydroxide nanotubes as the sacrificial template and block copolymer micelles as the precursor, and orientation of the polymeric nanotubes encapsulating magnetic particles under magnetic field. PMID:17844746

  3. The Potential to Improve Cell Infiltration in Composite Fiber-Aligned Electrospun Scaffolds by the Selective Removal of Sacrificial Fibers

    PubMed Central

    Baker, Brendon M.; Gee, Albert O.; Metter, Robert B.; Nathan, Ashwin S.; Marklein, Ross L.; Burdick, Jason A.; Mauck, Robert L.

    2008-01-01

    Aligned electrospun scaffolds are a promising tool for engineering fibrous musculoskeletal tissues as they reproduce the mechanical anisotropy of these tissues and can direct ordered neo-tissue formation. However, these scaffolds suffer from a slow cellular infiltration rate, likely due in part to their dense fiber packing. We hypothesized that cell ingress could be expedited in scaffolds by increasing porosity, while at the same time preserving overall scaffold anisotropy. To test this hypothesis, poly(ε-caprolactone) (a slow-degrading polyester) and poly(ethylene oxide) (a water-soluble polymer) were co-electrospun from two separate spinnerets to form dual-polymer composite fiber-aligned scaffolds. Adjusting fabrication parameters produced aligned scaffolds with a full range of sacrificial (PEO) fiber contents. Tensile properties of scaffolds were a function of the ratio of PCL to PEO in the composite scaffolds, and were altered in a predictable fashion with removal of the PEO component. When seeded with mesenchymal stem cells (MSCs), increases in the starting sacrificial fraction (and porosity) improved cell infiltration and distribution after three weeks in culture. In pure PCL scaffolds, cells lined the scaffold periphery, while scaffolds containing >50% sacrificial PEO content had cells present throughout the scaffold. These findings indicate that cell infiltration can be expedited in dense fibrous assemblies with the removal of sacrificial fibers. This strategy may enhance in vitro and in vivo formation and maturation of a functional constructs for fibrous tissue engineering. PMID:18313138

  4. New efficient electrochemical synthesis of 1,5-dithioxylopyranosides in the presence of a sacrificial anode.

    PubMed

    Brevet, David; Mugnier, Yves; Samreth, Soth; Dellis, Philippe

    2003-07-22

    Electroreduction of the disulfide derivative RSSR (5, R= [bond]C(6)H(4)[bond]CO[bond]C(6)H(4)[bond]CN) on a mercury pool or a carbon gauze electrode in the presence of 2,3,4-tri-O-acetyl-5-thio-D-xylopyranosyl bromide (1), using a sacrificial zinc anode gave an alpha,beta anomeric mixture of [4-(4-cyanobenzoylphenyl)] 2,3,4-tri-O-acetyl-1,5-dithio-D-xylopyranoside (6) in 40-70% yield, according to the experimental conditions used (nature of solvent, electrolyte salt, and temperature). High selectivity favouring the alpha anomer of 6 is observed starting from the alpha anomer of 1. Mechanistic aspects are discussed. PMID:12860425

  5. Sacrificial adsorbate for surfactants utilized in chemical floods of enhanced oil recovery operations

    SciTech Connect

    Johnson, J.S.; Westmoreland, C.G.

    1982-02-02

    The present invention is directed to a sacrificial or competitive adsorbate for surfactants contained in chemical flooding emulsions for enhanced oil recovery operations. The adsorbate to be utilized in the method of the present invention is a caustic effluent from the bleach stage or the weak black liquor from the digesters and pulp washers of the kraft pulping process. This effluent or weak black liquor is injected into an oil-bearing subterranean earth formation prior to or concurrent with the chemical flood emulsion and is adsorbed on the active mineral surfaces of the formation matrix so as to effectively reduce adsorption of surfactant in the chemical flood. Alternatively, the effluent or liquor can be injected into the subterranean earth formation subsequent to a chemical flood to displace the surfactant from the mineral surfaces for the recovery thereof.

  6. Sacrificial adsorbate for surfactants utilized in chemical floods of enhanced oil recovery operations

    DOEpatents

    Johnson, J.S. Jr.; Westmoreland, C.G.

    1980-08-20

    The present invention is directed to a sacrificial or competitive adsorbate for surfactants contained in chemical flooding emulsions for enhanced oil recovery operations. The adsorbate to be utilized in the method of the present invention is a caustic effluent from the bleach stage or the weak black liquor from the digesters and pulp washers of the kraft pulping process. This effluent or weak black liquor is injected into an oil-bearing subterranean earth formation prior to or concurrent with the chemical flood emulsion and is adsorbed on the active mineral surfaces of the formation matrix so as to effectively reduce adsorption of surfactant in the chemical flood. Alternatively, the effluent or liquor can be injected into the subterranean earth formation subsequent to a chemical flood to displace the surfactant from the mineral surfaces for the recovery thereof.

  7. Sacrificial adsorbate for surfactants utilized in chemical floods of enhanced oil recovery operations

    DOEpatents

    Johnson, Jr., James S.; Westmoreland, Clyde G.

    1982-01-01

    The present invention is directed to a sacrificial or competitive adsorbate for surfactants contained in chemical flooding emulsions for enhanced oil recovery operations. The adsorbate to be utilized in the method of the present invention is a caustic effluent from the bleach stage or the weak black liquor from the digesters and pulp washers of the kraft pulping process. This effluent or weak black liquor is injected into an oil-bearing subterranean earth formation prior to or concurrent with the chemical flood emulsion and is adsorbed on the active mineral surfaces of the formation matrix so as to effectively reduce adsorption of surfactant in the chemical flood. Alternatively, the effluent or liquor can be injected into the subterranean earth formation subsequent to a chemical flood to displace the surfactant from the mineral surfaces for the recovery thereof.

  8. Can Sacrificial Feeding Areas Protect Aquatic Plants from Herbivore Grazing? Using Behavioural Ecology to Inform Wildlife Management

    PubMed Central

    Wood, Kevin A.; Stillman, Richard A.; Daunt, Francis; O’Hare, Matthew T.

    2014-01-01

    Effective wildlife management is needed for conservation, economic and human well-being objectives. However, traditional population control methods are frequently ineffective, unpopular with stakeholders, may affect non-target species, and can be both expensive and impractical to implement. New methods which address these issues and offer effective wildlife management are required. We used an individual-based model to predict the efficacy of a sacrificial feeding area in preventing grazing damage by mute swans (Cygnus olor) to adjacent river vegetation of high conservation and economic value. The accuracy of model predictions was assessed by a comparison with observed field data, whilst prediction robustness was evaluated using a sensitivity analysis. We used repeated simulations to evaluate how the efficacy of the sacrificial feeding area was regulated by (i) food quantity, (ii) food quality, and (iii) the functional response of the forager. Our model gave accurate predictions of aquatic plant biomass, carrying capacity, swan mortality, swan foraging effort, and river use. Our model predicted that increased sacrificial feeding area food quantity and quality would prevent the depletion of aquatic plant biomass by swans. When the functional response for vegetation in the sacrificial feeding area was increased, the food quantity and quality in the sacrificial feeding area required to protect adjacent aquatic plants were reduced. Our study demonstrates how the insights of behavioural ecology can be used to inform wildlife management. The principles that underpin our model predictions are likely to be valid across a range of different resource-consumer interactions, emphasising the generality of our approach to the evaluation of strategies for resolving wildlife management problems. PMID:25077615

  9. Can sacrificial feeding areas protect aquatic plants from herbivore grazing? Using behavioural ecology to inform wildlife management.

    PubMed

    Wood, Kevin A; Stillman, Richard A; Daunt, Francis; O'Hare, Matthew T

    2014-01-01

    Effective wildlife management is needed for conservation, economic and human well-being objectives. However, traditional population control methods are frequently ineffective, unpopular with stakeholders, may affect non-target species, and can be both expensive and impractical to implement. New methods which address these issues and offer effective wildlife management are required. We used an individual-based model to predict the efficacy of a sacrificial feeding area in preventing grazing damage by mute swans (Cygnus olor) to adjacent river vegetation of high conservation and economic value. The accuracy of model predictions was assessed by a comparison with observed field data, whilst prediction robustness was evaluated using a sensitivity analysis. We used repeated simulations to evaluate how the efficacy of the sacrificial feeding area was regulated by (i) food quantity, (ii) food quality, and (iii) the functional response of the forager. Our model gave accurate predictions of aquatic plant biomass, carrying capacity, swan mortality, swan foraging effort, and river use. Our model predicted that increased sacrificial feeding area food quantity and quality would prevent the depletion of aquatic plant biomass by swans. When the functional response for vegetation in the sacrificial feeding area was increased, the food quantity and quality in the sacrificial feeding area required to protect adjacent aquatic plants were reduced. Our study demonstrates how the insights of behavioural ecology can be used to inform wildlife management. The principles that underpin our model predictions are likely to be valid across a range of different resource-consumer interactions, emphasising the generality of our approach to the evaluation of strategies for resolving wildlife management problems. PMID:25077615

  10. In vivo study of ALA PLGA nanoparticles-mediated PDT for treating cutaneous squamous cell carcinoma

    NASA Astrophysics Data System (ADS)

    Wang, Xiaojie; Shi, Lei; Huang, Zheng; Wang, Xiuli

    2014-09-01

    Background: Squamous cell carcinoma (SCC) is a common skin cancer and its treatment is still a challenge. Although topical photodynamic therapy (PDT) is effective for treating in situ and superficial SCC, the effectiveness of topical ALA delivery to thick SCC can be limited by its bioavailability. Polylactic-co-glycolic acid nanopartieles (PLGA NPs) might provide a promising ALA delivery strategy. The aim of this study was to evaluate the efficacy of ALA PLGA NPs PDT for the treatment of cutaneous SCC in a mouse model. Methods: ALA loaded PLGA NPs were prepared and characterized. The therapeutic efficacy of ALA PLGA NP mediated PDT in treating UV-induced cutaneous SCC in the mice model were examined. Results: In vivo study showed that ALA PLGA NPs PDT were more effective than free ALA of the same concentration in treating mouse cutaneous SCC. Conclusion: ALA PLGA NPs provides a promising strategy for delivering ALA and treating cutaneous SCC.

  11. Delocalization of phonon-plasmon modes in GaAs/AlAs superlattices with tunnel-thin AlAs barriers

    SciTech Connect

    Volodin, V. A. Efremov, M. D.; Sachkov, V. A.

    2006-10-15

    The technique of Raman spectroscopy has been used to investigate doped (n-type) and undoped GaAs/AlAs superlattices with AlAs barrier thicknesses from 17 to 1 monolayers. The peak corresponding to the scattering by a two-dimensional plasmon was found in the Raman spectrum of a doped superlattice with relatively thick barriers. The position of the experimental peak corresponded to the value calculated in the model of plasma oscillations in periodic planes of a two-dimensional electron gas. The electron tunneling effects played an increasingly prominent role as the AlAs barrier thickness decreased. The peaks corresponding to the scattering by coupled phonons with three-dimensional plasmons were found in the Raman spectra for a superlattice with an AlAs thickness of 2 monolayers; i.e., the delocalization of coupled modes was observed. In this case, the folding of acoustic phonons was observed in the superlattice under consideration, indicative of its good periodicity, while the localization of optical phonons in GaAs layers was observed in undoped superlattices with an AlAs thickness of 2 monolayers.

  12. Colloidal semiconductors in systems for the sacrificial photolysis of water: sensitization of TiO/sub 2/ by adsorption of ruthenium complexes

    SciTech Connect

    Furlong, D.N.; Wells, D.; Sasse, W.H.F.

    1986-03-13

    Adsorbed tris(2,2'-bipyridine-4,4'-dicarboxylic acid)ruthenium(II) molecules (Ru/sup II/(acid)/sub 3/) sensitize the production of H/sub 2/ that occurs when Pt/TiO/sub 2/ dispersions are illuminated with visible light in the presence of EDTA as sacrificial electron donor. Ru/sup II/(acid)/sub 3/ adsorbs on TiO/sub 2/ at pH values below the isoelectric point of the TiO/sub 2/ (6.1) in response to electrostatic attraction between its dissociated species and positively charged TiO/sub 2/ particles. In contrast to band-gap systems, sensitized systems are not regenerated by readjustment of pH and addition of electron donor. Clearly, sensitization requires adsorption of sensitizer in the first adsorbed layer in addition to favorable redox potentials for electron injection from sensitizer into the conduction band of the TiO/sub 2/ particles. Multilayers of sensitizer do not assist electron injection but instead reduce the amount of light available to the first adsorbed layer. 50 references, 8 figures, 4 tables.

  13. 5-ALA-assisted photodynamic therapy in canine prostates

    NASA Astrophysics Data System (ADS)

    Sroka, Ronald; Muschter, Rolf; Knuechel, Ruth; Steinbach, Pia; Perlmutter, Aaron P.; Martin, Thomas; Baumgartner, Reinhold

    1996-05-01

    Photodynamic therapy (PDT) and interstitial thermotherapy are well known treatment modalities in urology. The approach of this study is to combine both to achieve a selective treatment procedure for benign prostatic hyperplasia (BPH) and prostate carcinoma. Measurements of thy in-vivo pharmacokinetics of 5-ALA induced porphyrins by means of fiber assisted ratiofluorometry showed a maximum fluorescence intensity at time intervals of 3 - 4 h post administration. Fluorescence microscopy at that time showed bright fluorescence in epithelial cells while in the stroma fluorescence could not be observed. Interstitial PDT using a 635-nm dye laser with an irradiation of 50 J/cm2 resulted in a nonthermic hemorrhagic lesion. The lesion size did not change significantly when an irradiation of 100 J/cm2 was used. The usefulness of PDT for treating BPH as well as prostate carcinoma has to be proven in further studies.

  14. Enhanced photodynamic efficacy of PLGA-encapsulated 5-ALA nanoparticles in mice bearing Ehrlich ascites carcinoma

    NASA Astrophysics Data System (ADS)

    Shaker, Maryam N.; Ramadan, Heba S.; Mohamed, Moustafa M.; El khatib, Ahmed M.; Roston, Gamal D.

    2014-10-01

    Nanoparticles (NPs) fabricated from the biodegradable copolymer poly(lactic- co-glycolic acid) (PLGA) were investigated as a drug delivery system to enhance the photodynamic efficacy of 5-aminolevulinic acid (5-ALA) in mice bearing Ehrlich ascites carcinoma. The PLGA-encapsulated 5-ALA NPs were prepared using binary organic solvent diffusion method and characterized in terms of shape and particle size. The in vivo photodynamic efficiency in Ehrlich ascites-bearing mice was studied. The obtained particles were uniform in size with spherical shape of mean size of 249.5 nm as obtained by particle size analyzer and the in vitro release studies demonstrated a controlled release profile of 5-ALA. Tumor-bearing mice injected with PLGA-encapsulated 5-ALA NPs exhibited significantly smaller mean tumor volume, increased tumor growth delay compared with the control group and the group injected with free 5-ALA during the time course of the experiment. Histopathological examination of tumor from mice treated with PLGA-encapsulated 5-ALA NPs showed regression of tumor cells, in contrast to those obtained from mice treated with free 5-ALA. The results indicate that PLGA-encapsulated 5-ALA NPs are a successful delivery system for improving photodynamic activity in the target tissue.

  15. A Fifty-Five Year Partnership: ALA and the AFL-CIO.

    ERIC Educational Resources Information Center

    Meyers, Arthur S.

    2002-01-01

    Provides a history of the establishment of the AFL-CIO/ALA (American Federation of Labor (AFL)-Congress of Industrial Organizations (CIO)/American Library Association (ALA)) Joint Committee on Library Service to Labor Groups. Topics include public learning, labor, and libraries; services to labor; problems and issues, including conflicts between…

  16. ALA-PDT inhibits proliferation and promotes apoptosis of SCC cells through STAT3 signal pathway.

    PubMed

    Qiao, Li; Mei, Zhusong; Yang, Zhiyong; Li, Xinji; Cai, Hong; Liu, Wei

    2016-06-01

    Previous studies suggest that apoptosis of carcinoma cells led by photodynamics is mainly intrinsic apoptosis, but whether the extrinsic pathway is involved in the treatment of carcinoma by photodynamic therapy is not confirmed. This research investigated the effect of ALA-PDT on the proliferation and apoptosis of SCC cell A431 and COLO-16, and discussed the role played by JAK/STAT3 signal pathway in this process. Our data showed that the expression levels STAT3 and p-STAT3 protein in the cancer tissue are higher than the corresponding adjacent tissue to carcinoma. The expression level of p-STAT3 in cancerous tissue has a correlation with the tumor size and tissue histopathological differentiation. ALA-PDT could inhibit proliferation of A431 and COLO-16 cells, STAT3 knock down could enhance ALA-PDT's inhibition of cell proliferation, and promote apoptosis induced by ALA-PDT. On the other hand, overexpression of STAT3 has the opposite effect. In addition, ALA-PDT can weaken the protein expression of STAT3 and its target gene Bcl-2 mRNA, and ALA-PDT can strengthen the protein expression of STAT3's target gene Bax mRNA. Overexpression of STAT3 can offset the effect on Bcl-2 and Bax by ALA-PDT; on the other hand, STAT3 knocking down can strengthen ALA-PDT's effect on Bcl-2 and Bax. PMID:26805005

  17. Inducible l-Alanine Exporter Encoded by the Novel Gene ygaW (alaE) in Escherichia coli ▿

    PubMed Central

    Hori, Hatsuhiro; Yoneyama, Hiroshi; Tobe, Ryuta; Ando, Tasuke; Isogai, Emiko; Katsumata, Ryoichi

    2011-01-01

    We previously isolated a mutant hypersensitive to l-alanyl-l-alanine from a non-l-alanine-metabolizing Escherichia coli strain and found that it lacked an inducible l-alanine export system. Consequently, this mutant showed a significant accumulation of intracellular l-alanine and a reduction in the l-alanine export rate compared to the parent strain. When the mutant was used as a host to clone a gene(s) that complements the dipeptide-hypersensitive phenotype, two uncharacterized genes, ygaW and ytfF, and two characterized genes, yddG and yeaS, were identified. Overexpression of each gene in the mutant resulted in a decrease in the intracellular l-alanine level and enhancement of the l-alanine export rate in the presence of the dipeptide, suggesting that their products function as exporters of l-alanine. Since ygaW exhibited the most striking impact on both the intra- and the extracellular l-alanine levels among the four genes identified, we disrupted the ygaW gene in the non-l-alanine-metabolizing strain. The resulting isogenic mutant showed the same intra- and extracellular l-alanine levels as observed in the dipeptide-hypersensitive mutant obtained by chemical mutagenesis. When each gene was overexpressed in the wild-type strain, which does not intrinsically excrete alanine, only the ygaW gene conferred on the cells the ability to excrete alanine. In addition, expression of the ygaW gene was induced in the presence of the dipeptide. On the basis of these results, we concluded that YgaW is likely to be the physiologically most relevant exporter for l-alanine in E. coli and proposed that the gene be redesignated alaE for alanine export. PMID:21531828

  18. Evaluation of ALA-induced PpIX as a photosensitizer for PDT in cats

    NASA Astrophysics Data System (ADS)

    Lucroy, Michael D.; Edwards, Benjamin F.; Peavy, George M.; Krasieva, Tatiana B.; Griffey, Stephen M.; Madewell, Bruce R.

    1998-07-01

    Given exogenously, ALA defeats intrinsic regulatory feedback mechanisms allowing intracellular accumulation of protoporphyrin IX (PpIX), a highly efficient photosensitizer. In vivo, PpIX synthesis in neoplastic mammary tissues averages 20-fold higher than in normal mammary tissues. PpIX is retained intracellularly, unlike perivascular localization of other photosensitizers, and it is then cleared quickly from the body. In vitro, ALA induced PpIX production in our laboratory in 6 cell lines tested, including an established feline kidney cell line and dermal fibroblasts from primary skin biopsy explant, resulting in photosensitization. Fluorescent microscopy confirmed PpIX production in skin adnexae following ALA administration in a normal cat. To evaluate toxicity, three cats were treated with a single i.v. dose of ALA (either 100, 200, of 400 mg/kg) and followed for 7 days. Cats receiving 100 or 200 mg/kg ALA i.v. had elevated liver enzymes and bilirubin within 24 hours. Histopathology revealed hydropic changes in the liver and renal fibrosis. The cat receiving 400 mg/kg ALA intravenously had cutaneous flush, bradycardia and apnea associated with ALA administration; within 24 hours the cat was lethargic, anorectic and icteric. ALT, AST and bilirubin concentrations had increased significantly. At necropsy the liver had a prominent lobular pattern; histopathology revealed severe periportal hepatitis and splenic necrosis. Systemically administered ALA induces PpIX production, but toxicity may preclude its clinical application in the cat. PpIX levels seem to be more time dependent than those dependent at these three ALA doses and they are well beyond the saturation point for adequate PpIX conversion. The literature is scant regarding toxicity associated with parenteral administration of ALA.

  19. Sacrificial bonds and hidden length in biomaterials: A kinetic constitutive description of strength and toughness in bone

    NASA Astrophysics Data System (ADS)

    Lieou, Charles K. C.; Elbanna, Ahmed E.; Carlson, Jean M.

    2013-07-01

    Sacrificial bonds and hidden length in structural molecules account for the greatly increased fracture toughness of biological materials compared to synthetic materials without such structural features by providing a molecular-scale mechanism for energy dissipation. One example is in the polymeric glue connection between collagen fibrils in animal bone. In this paper we propose a simple kinetic model that describes the breakage of sacrificial bonds and the release of hidden length, based on Bell's theory. We postulate a master equation governing the rates of bond breakage and formation. This enables us to predict the mechanical behavior of a quasi-one-dimensional ensemble of polymers at different stretching rates. We find that both the rupture peak heights and maximum stretching distance increase with the stretching rate. In addition, our theory naturally permits the possibility of self-healing in such biological structures.

  20. Influence of fouling on the efficiency of sacrificial anodes in providing cathodic protection in Southeast Asian tropical seawater.

    PubMed

    Blackwood, D J; Lim, C S; Teo, S L M

    2010-10-01

    Aluminum and zinc based sacrificial anodes are routinely used to provide corrosion protection to metals (typically steel) exposed to seawater, for example in steel pipelines and storage tanks. However, the high fouling rates experienced in South East Asia means that both the anodes and the metals to be protected rapidly become coated with macrofoulers, which could potentially prevent the anodes from being effective. The present study, involving exposure tests of up to 18 months, indicates that both aluminum and zinc sacrificial anodes remain effective even after being completely coated with biofouling. Furthermore, it was easier to remove the biofouling on the cathodically protected samples than on their unprotected counterparts, possibly due to the higher local pH produced by cathodic protection at the metal and seawater interface. PMID:20818571

  1. Dynamics of Polymer Molecules with Sacrificial Bond and Hidden Length Systems: Towards a Physically-Based Mesoscopic Constitutive Law

    PubMed Central

    Elbanna, Ahmed E.; Carlson, Jean M.

    2013-01-01

    We investigate the entropic force-elongation behavior of a polymer chain in the presence of the sacrificial bond and hidden length (SBHL) system observed experimentally in many biomaterials. We show that in most cases the SBHL system leads to a significant increase in toughness. However, the presence of a large number of bonds or relatively strong bonds in the SBHL system can reduce the net gain in toughness. We also incorporate the polymer model into a network of polymers with random properties (e.g., contour length, number and strength of sacrificial bonds, length of hidden loops). This allows us to derive a physically-based mesoscopic force-displacement law that governs the collective behavior. PMID:23565135

  2. Bioactive gyroid scaffolds formed by sacrificial templating of nanocellulose and nanochitin hydrogels as instructive platforms for biomimetic tissue engineering.

    PubMed

    Torres-Rendon, Jose Guillermo; Femmer, Tim; De Laporte, Laura; Tigges, Thomas; Rahimi, Khosrow; Gremse, Felix; Zafarnia, Sara; Lederle, Wiltrud; Ifuku, Shinsuke; Wessling, Matthias; Hardy, John G; Walther, Andreas

    2015-05-20

    A sacrificial templating process using lithographically printed minimal surface structures allows complex de novo geo-metries of delicate hydrogel materials. The hydrogel scaffolds based on cellulose and chitin nanofibrils show differences in terms of attachment of human mesenchymal stem cells, and allow their differentiation into osteogenic outcomes. The approach here serves as a first example toward designer hydrogel scaffolds viable for biomimetic tissue engineering. PMID:25833165

  3. Wafer-scale epitaxial lift-off of optoelectronic grade GaN from a GaN substrate using a sacrificial ZnO interlayer

    NASA Astrophysics Data System (ADS)

    Rajan, Akhil; Rogers, David J.; Ton-That, Cuong; Zhu, Liangchen; Phillips, Matthew R.; Sundaram, Suresh; Gautier, Simon; Moudakir, Tarik; El-Gmili, Youssef; Ougazzaden, Abdallah; Sandana, Vinod E.; Teherani, Ferechteh H.; Bove, Philippe; Prior, Kevin A.; Djebbour, Zakaria; McClintock, Ryan; Razeghi, Manijeh

    2016-08-01

    Full 2 inch GaN epilayers were lifted off GaN and c-sapphire substrates by preferential chemical dissolution of sacrificial ZnO underlayers. Modification of the standard epitaxial lift-off (ELO) process by supporting the wax host with a glass substrate proved key in enabling full wafer scale-up. Scanning electron microscopy and x-ray diffraction confirmed that intact epitaxial GaN had been transferred to the glass host. Depth-resolved cathodoluminescence (CL) analysis of the bottom surface of the lifted-off GaN layer revealed strong near-band-edge (3.33 eV) emission indicating a superior optical quality for the GaN which was lifted off the GaN substrate. This modified ELO approach demonstrates that previous theories proposing that wax host curling was necessary to keep the ELO etch channel open do not apply to the GaN/ZnO system. The unprecedented full wafer transfer of epitaxial GaN to an alternative support by ELO offers the perspective of accelerating industrial adoption of the expensive GaN substrate through cost-reducing recycling.

  4. Silk as a biocohesive sacrificial binder in the fabrication of hydroxyapatite load bearing scaffolds

    PubMed Central

    McNamara, Stephanie L.; Rnjak-Kovacina, Jelena; Schmidt, Daniel; Lo, Tim J.; Kaplan, David L.

    2014-01-01

    Limitations of current clinical methods for bone repair continue to fuel the demand for a high strength, bioactive bone replacement material. Recent attempts to produce porous scaffolds for bone regeneration have been limited by the intrinsic weakness associated with high porosity materials. In this study, ceramic scaffold fabrication techniques for potential use in load-bearing bone repairs have been developed using naturally derived silk from Bombyx mori. Silk was first employed for ceramic grain consolidation during green body formation, and later as a sacrificial polymer to impart porosity during sintering. These techniques allowed preparation of hydroxyapatite (HA) scaffolds that exhibited a wide range of mechanical and porosity profiles, with some displaying unusually high compressive strength up to 152.4 ± 9.1 MPa. Results showed that the scaffolds exhibited a wide range of compressive strengths and moduli (8.7 ± 2.7 MPa to 152.4 ± 9.1 MPa and 0.3 ± 0.1 GPa to 8.6 ± 0.3 GPa) with total porosities of up to 62.9 ± 2.7% depending on the parameters used for fabrication. Moreover, HA-silk scaffolds could be molded into large, complex shapes, and further machined post-sinter to generate specific three-dimensional geometries. Scaffolds supported bone marrow-derived mesenchymal stem cell attachment and proliferation, with no signs of cytotoxicity. Therefore, silk-fabricated HA scaffolds show promise for load bearing bone repair and regeneration needs. PMID:24881027

  5. Effect of alloying elements on electrochemical properties of magnesium-based sacrificial anodes

    SciTech Connect

    Kim, J.G.; Koo, S.J.

    2000-04-01

    Effects of alloying elements on electrochemical properties of magnesium-based sacrificial anodes were evaluated. Potentiodynamic, galvanostatic, scanning electron microscopy (SEM), and x-ray diffraction (XRD) analyses were used to investigate the corrosion rate, efficiency, and surface characteristics of anodes. Polarization data indicated that alloying with manganese, aluminum, and zinc reduced the corrosion rates of magnesium anodes. All anodes did not undergo passivation but demonstrated only active behavior. Corrosion morphology was changed from localized to uniform attach by the alloying. Addition of manganese to magnesium anodes yielded increased driving potential and efficiency. The efficiency of Mg-Al anodes was improved up to {approximately}6% Al addition. The addition of zinc increased the efficiency of Mg-Al-Zn anodes compared to the efficiency of Mg-Al anodes, but the reversal of this behavior happened as the zinc content exceeded {approximately}3%. The increase in the efficiency of Mg-Al and Mg-Al-Zn anodes was accompanied by a decrease in the driving potential. The decrease of driving potential might have resulted form a somewhat resistive film on the surface, which hindered the transport of ions. The increased corrosion resistance generally improved anode efficiency.

  6. Hydrogel Composites Containing Sacrificial Collapsed Hollow Particles as Dual Action pH-Responsive Biomaterials.

    PubMed

    Pafiti, Kyriaki; Cui, Zhengxing; Adlam, Daman; Hoyland, Judith; Freemont, Anthony J; Saunders, Brian R

    2016-07-11

    In this study hydrogel composites are investigated that contain sacrificial pH-responsive collapsed hollow particles (CHPs) entrapped within a poly(acrylamide) (PAAm) network. The CHPs were prepared using a scalable (mainly) water-based method and had a bowl-like morphology that was comparable to that of red blood cells. The CHPs were constructed from poly(methyl methacrylate-co-methacrylic acid), which is a pH-responsive copolymer. The PAAm/CHP composite morphology was probed with optical microscopy, CLSM and SEM. These data showed the CHPs were dispersed throughout the PAAm network. Inclusion of the CHPs within the gel composites increased the modulus in a tunable manner. The CHPs fragmented at pH values greater than the pKa of the particles, and this process decreased the gel modulus to values similar to that of the parent PAAm hydrogel. CHPs containing a model drug were used to demonstrate pH-triggered release from PAAm/CHP and the release kinetics obeyed Fickian diffusion. The composite gels had low cytotoxicity as evidenced by Live/Dead and MTT assays. The hydrogel composites showed dual action pH-triggered softening with simultaneous drug release which occurred without a volume increase. The hydrogel composites may have potential application as enteric gels or for intra-articular drug delivery. PMID:27267971

  7. A sacrificial millipede altruistically protects its swarm using a drone blood enzyme, mandelonitrile oxidase

    PubMed Central

    Ishida, Yuko; Kuwahara, Yasumasa; Dadashipour, Mohammad; Ina, Atsutoshi; Yamaguchi, Takuya; Morita, Masashi; Ichiki, Yayoi; Asano, Yasuhisa

    2016-01-01

    Soldiers of some eusocial insects exhibit an altruistic self-destructive defense behavior in emergency situations when attacked by large enemies. The swarm-forming invasive millipede, Chamberlinius hualienensis, which is not classified as eusocial animal, exudes irritant chemicals such as benzoyl cyanide as a defensive secretion. Although it has been thought that this defensive chemical was converted from mandelonitrile, identification of the biocatalyst has remained unidentified for 40 years. Here, we identify the novel blood enzyme, mandelonitrile oxidase (ChuaMOX), which stoichiometrically catalyzes oxygen consumption and synthesis of benzoyl cyanide and hydrogen peroxide from mandelonitrile. Interestingly the enzymatic activity is suppressed at a blood pH of 7, and the enzyme is segregated by membranes of defensive sacs from mandelonitrile which has a pH of 4.6, the optimum pH for ChuaMOX activity. In addition, strong body muscle contractions are necessary for de novo synthesis of benzoyl cyanide. We propose that, to protect its swarm, the sacrificial millipede also applies a self-destructive defense strategy—the endogenous rupturing of the defensive sacs to mix ChuaMOX and mandelonitrile at an optimum pH. Further study of defensive systems in primitive arthropods will pave the way to elucidate the evolution of altruistic defenses in the animal kingdom. PMID:27265180

  8. A sacrificial millipede altruistically protects its swarm using a drone blood enzyme, mandelonitrile oxidase.

    PubMed

    Ishida, Yuko; Kuwahara, Yasumasa; Dadashipour, Mohammad; Ina, Atsutoshi; Yamaguchi, Takuya; Morita, Masashi; Ichiki, Yayoi; Asano, Yasuhisa

    2016-01-01

    Soldiers of some eusocial insects exhibit an altruistic self-destructive defense behavior in emergency situations when attacked by large enemies. The swarm-forming invasive millipede, Chamberlinius hualienensis, which is not classified as eusocial animal, exudes irritant chemicals such as benzoyl cyanide as a defensive secretion. Although it has been thought that this defensive chemical was converted from mandelonitrile, identification of the biocatalyst has remained unidentified for 40 years. Here, we identify the novel blood enzyme, mandelonitrile oxidase (ChuaMOX), which stoichiometrically catalyzes oxygen consumption and synthesis of benzoyl cyanide and hydrogen peroxide from mandelonitrile. Interestingly the enzymatic activity is suppressed at a blood pH of 7, and the enzyme is segregated by membranes of defensive sacs from mandelonitrile which has a pH of 4.6, the optimum pH for ChuaMOX activity. In addition, strong body muscle contractions are necessary for de novo synthesis of benzoyl cyanide. We propose that, to protect its swarm, the sacrificial millipede also applies a self-destructive defense strategy-the endogenous rupturing of the defensive sacs to mix ChuaMOX and mandelonitrile at an optimum pH. Further study of defensive systems in primitive arthropods will pave the way to elucidate the evolution of altruistic defenses in the animal kingdom. PMID:27265180

  9. 3D-printed silicate porous bioceramics using a non-sacrificial preceramic polymer binder.

    PubMed

    Zocca, A; Elsayed, H; Bernardo, E; Gomes, C M; Lopez-Heredia, M A; Knabe, C; Colombo, P; Günster, J

    2015-06-01

    Silicate bioceramics possess an excellent bioactivity; however, shaping them into complex geometries is still challenging. Therefore, this paper aims to present a new strategy for the shaping of a bioglass-ceramic with controlled geometry and properties starting from a glass powder combined with a preceramic polymer, i.e. a silicon resin, and reactive fillers. The powder-based three-dimensional (3D)-printing of wollastonite (CaSiO3)-based silicate bioceramic parts was demonstrated in this work. The resin plays a dual role, as it not only acts as a non-sacrificial binder for the filler powders in the printing process but it also reacts with the fillers to generate the desired bioceramic phases. The mechanical and physical properties, i.e. ball-on-three-balls test, density, porosity and morphology, were evaluated in 3D-printed discs. These samples possessed a total porosity around 64 vol% and a biaxial flexural strength around 6 MPa. The raw materials used in this work also enabled the 3D-printing of scaffolds possessing a designed multi-scale porosity, suitable bioceramic phase assemblage and a compressive strength of 1 MPa (for cylindrical scaffolds with total porosity ~80 vol%). Solubility in TRIS/HCl and in vitro assays, i.e. viability, cytotoxicity and apoptosis assays, were also performed. In vitro tests indicated good cell viability and no cytotoxicity effect on the cells. PMID:26000907

  10. Sacrificial Silver Nanoparticles: Reducing GeI2 To Form Hollow Germanium Nanoparticles by Electroless Deposition.

    PubMed

    Nolan, Bradley M; Chan, Eric K; Zhang, Xinming; Muthuswamy, Elayaraja; van Benthem, Klaus; Kauzlarich, Susan M

    2016-05-24

    Herein we report the electroless deposition of Ge onto sacrificial Ag nanoparticle (NP) templates to form hollow Ge NPs. The formation of AgI is a necessary component for this reaction. Through a systematic study of surface passivating ligands, we determined that tri-n-octylphosphine is necessary to facilitate the formation of hollow Ge NPs by acting as a transport agent for GeI2 and the oxidized Ag(+) cation (i.e., AgI product). Annular dark-field (ADF) scanning transmission electron microscopy (STEM) imaging of incomplete reactions revealed Ag/Ge core/shell NPs; in contrast, completed reactions displayed hollow Ge NPs with pinholes which is consistent with the known method for dissolution of the nanotemplate. Characterization of the hollow Ge NPs was performed by transmission electron microscopy, ADF-STEM, energy-dispersive X-ray spectroscopy, UV-vis spectrophotometry, and Raman spectroscopy. The galvanic replacement reaction of Ag with GeI2 offers a versatile method for controlling the structure of Ge nanomaterials. PMID:27096547

  11. Molecular structures of two crystalline forms of the cyclic heptapeptide antibiotic ternatin, cyclo[-beta-OH-D-Leu-D-Ile-(NMe)Ala-(NMe)Leu-Leu-(NMe)Ala-D-(NMe)Ala-].

    PubMed

    Miller, R; Galitsky, N M; Duax, W L; Langs, D A; Pletnev, V Z; Ivanov, V T

    1993-12-01

    The crystal structures of two solvated forms of ternatin, cyclo[-beta-OH-D-Leu-D-Ile-(NMe)Ala-(NMe)Leu-Leu-(NMe)Ala-D-(NMe)Ala-] are reported. The first crystallizes with two molecules of peptide and one of dioxane in the asymmetric unit: P2(1)2(1)2(1), a = 11.563(1), b = 21.863(2), c = 36.330(4) A. The second crystallizes with two molecules of peptide and one of water in the asymmetric unit: P2(1)2(1)2(1), a = 14.067(2), b = 16.695(1), c = 36.824(6) A. N-Methylation of four of the seven residues of ternatin appears to reduce the number of low-energy conformations the molecule can assume. The same H-bonded macrocyclic ring conformation is adopted by the backbone of each of the four molecules observed here. All the amino-acid side chains, with the exception of D-Ile2, have similar orientations in each of the four conformers. The heptapeptide macrocycle is characterized by: (i) a cis peptide between (NMe)Ala3 and (NMe)Leu4, (ii) a type II beta-bend, involving residues Leu5-(NMe)Ala6-D-(NMe)Ala7-beta-OH-D-Leu1, stabilized by two H-bonds, N1-->O5 and N5-->O1, between Leu5 and beta-OH-D-Leu1 residues, (iii) a third intramolecular H-bond, observed in each of the four molecules, between the hydroxyl group of beta-OH-D-Leu1 and the carbonyl oxygen of D-Ile2. PMID:8307686

  12. The role of DAMPS in ALA-PDT for skin squamous cell carcinoma (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Wang, Xiuli; Wang, Xiaojie; Ji, Jie; Zhang, Haiyan; Shi, Lei

    2016-03-01

    5-Aminolevulinic acid mediated photodynamic therapy (ALA-PDT) is an established local approach for skin squamous cell carcinoma. It is believed that dangerous signals damage-associated molecular patterns (DAMPs) play an important role in ALA-PDT. In this study, we evaluated in vitro and in vivo expressions of major DAMPs, calreticulin (CRT), heat shock proteins 70 (HSP70), and high mobility group box 1 (HMGB1), induced by ALA-PDT using immunohistochemistry, western blot, and ELISA in a squamous cell carcinoma (SCC) mouse model. The role of DAMPs in the maturation of DCs potentiated by ALA-PDT-treated tumor cells was detected by FACS and ELISA. Our results showed that ALA-PDT enhanced the expression of CRT, HSP70, and HMGB1. These induced DAMPs played an important role in activating DCs by PDT-treated tumor cells, including phenotypic maturation (upregulation of surface expression of MHC-II, CD80, and CD86) and functional maturation (enhanced capability to secrete IFN-γ and IL-12). Furthermore, injecting ALA-PDT-treated tumor cells into naïve mice resulted in complete protection against cancer cells of the same origin. Our findings indicate that ALA-PDT can upregulate DAMPs and enhance tumor immunogenicity, providing a promising strategy for inducing a systemic anticancer immune response.

  13. Molecular mechanisms associated with ALA-PDT of brain tumor cells

    NASA Astrophysics Data System (ADS)

    Alqawi, Omar; Espiritu, Myrna; Singh, Gurmit

    2009-06-01

    Previous studies have shown that low-dose PDT using 5-aminolevulinic acid (ALA)-induced photoporphyrin IX (PpIX) can induce apoptosis in tumor cells without causing necrosis. In this study we investigated the molecular mechanisms associated with apoptosis after ALA-PDT treatment in two brain glioma cell lines: human U87, and rat CNS-1cells. We used high energy light at a short time (acute PDT) and low energy light at a long time of exposure (metronomic PDT) to treat both cell lines. The cells were treated with 0.25 mM ALA at 5 joules for energy. We found that CNS-1 cells were more resistant to ALA-PDT than U87 cells when treated by both acute and metronomic PDT. To screen possible apoptosis mechanisms associated with acute and metronomic PDT, microarray analysis of gene expression was performed on RNA from glioblastoma cells treated with either acute or metronomic ALA-PDT. Within the set of genes that were negatively or positively regulated by both treatments are tumor necrosis factor receptors. The expression of TNF receptors was investigated further by RT-PCR and western blotting. The apoptosis mechanism of the cell death occurred through different pathways including BCL-2 and TNF receptors, and in part caused by cleaving caspase 3. Interestingly, metronomic ALA-PDT inhibited the expression of LTβR and the transcription factor NFκB. This inhibition was ALA concentration dependent at low concentrations.

  14. The novel dipeptide Tyr-Ala (TA) significantly enhances the lifespan and healthspan of Caenorhabditis elegans.

    PubMed

    Zhang, Z; Zhao, Y; Wang, X; Lin, R; Zhang, Y; Ma, H; Guo, Y; Xu, L; Zhao, B

    2016-04-20

    Food-derived bioactive peptides may have various physiological modulatory and regulatory functions and are now being studied extensively. Recently, the novel dipeptide Tyr-Ala was isolated from hydrolyzed maize protein. Tyr-Ala significantly prolonged the lifespan of wild-type Caenorhabditis elegans and extended the nematode healthspan and lifespan during heat/oxidative stress. Compared with its constituent amino acids, Tyr-Ala was more efficient in enhancing stress resistance. Further studies demonstrated that the significant longevity-extending effects of Tyr-Ala on Caenorhabditis elegans were attributed to its in vitro and in vivo free radical-scavenging effects, in addition to its ability to up-regulate stress resistance-related proteins, such as SOD (Superoxide Dismutase)-3 and HSP (Heat Shock Protein)-16.2. Real-time PCR results showed that the up-regulation of aging-associated genes, such as daf-16, sod-3, hsp-16.2 and skn-1, also contributed to the stress-resistance effect of Tyr-Ala. These results indicate that the novel dipeptide Tyr-Ala can protect against external stress and thus extend the lifespan and healthspan of Caenorhabditis elegans. Thereby, Tyr-Ala could be used as a potential medicine in anti-aging research. PMID:26987062

  15. Association between Manganese Superoxide Dismutase (MnSOD Val-9Ala) genotypes with the risk of generalized aggressive periodontitis disease.

    PubMed

    Kazemi, E; Moradi, M-T; Yari, K; Mousavi, S A R; Kahrizi, D

    2015-01-01

    Generalized aggressive periodontitis (GAP) is a subtype of periodontal diseases that characterized by rapid destruction of periodontal supporting tissues. The MnSOD Val-9Ala mutation of manganese superoxide dismutase gene (MnSOD Val-9Ala) and its correlation with periodontal diseases has been studied in different populations. The purpose of this study was to investigate the possible association of MnSODVal-9Ala polymorphism with periodontitis disease in sample of GAP patients in Iran for the first time. Following a GAP examination, 50 GAP patients and 100 healthy individuals were recruited. Genomic DNA was extracted from peripheral blood leukocytes and the MnSODVal-9Ala polymorphismwas detected using PCR-RFLP method. The frequency of Ala/Ala, Ala/Val and Val/Val genotypes in healthy individuals were 25, 66 and 9%, respectively. In periodontitis patients, frequencies were as Ala/Ala (12%), Ala/Val (50%) and Val/Val (38%) genotypes. There was a significant positive association between distribution of MnSOD Val-9Ala genotypes and the risk of periodontitis disease (p<0.05). Our results indicated that MnSOD Val-9Ala gene polymorphism has a positive association with the risk of periodontitis disease. PMID:26718428

  16. Intervalley scattering of electrons by short-wave phonons in (GaAs)8(AlAs)8(001) superlattice

    NASA Astrophysics Data System (ADS)

    Grinyaev, S. N.; Nikitina, L. N.; Tyuterev, V. G.

    2016-05-01

    Intervalley transitions induced by short-wavelength phonons in the conduction band of a superlattice (GaAs)8(AlAs)8(001) are investigated on the basis of the pseudopotential method and in the phenomenological model of interatomic forces. The main attention in the study centers around the transitions associated with the vibrations confined inside the layers. It is shown that the deformation potentials for the majority of intervalley transitions in a superlattice exceed the potentials of corresponding transitions in the binary crystals because of the localization of atomic displacements and wavefunctions of electrons inside the same layer of the superlattice. The bottom of the conduction band in (GaAs)8(AlAs)8(001) superlattice corresponds to the states Γ1(1), Z3, M1, M4 originating from sphalerite's X bar valleys localized in AlAs layers. Transitions between them are the most intense ones and they are caused by optical vibrations of Al atoms. "Semi-interface" vibrations being mainly localized in the one side of the GaAs layer are involved in the Γ1(2) -X1 , Γ1(2) -R1 and X1-Z1 transitions which are analogs of Γ bar - L bar transitions in binaries. The transitions Γ1(2) -M1 and Γ1(2) -M4 are governed by smooth parts of wave-functions and pseudopotentials. As a consequence their intensities are comparable with those of Γ bar - X bar sphalerite transitions in spite that these states are localized in the different layers of the superlattice.

  17. Age-dependent dichotomous effect of superoxide dismutase Ala16Val polymorphism on oxidized LDL levels

    PubMed Central

    Kanoni, Stavroula; Panagiotakos, Demosthenes B.; Louizou, Eirini; Grigoriou, Efi; Chrysohoou, Christina; Pitsavos, Christos; Stefanadis, Christodoulos

    2008-01-01

    We investigated the association between superoxide dismutase (SOD) Ala16Val polymorphism and the levels of oxidized LDL lipoprotein-C (ox-LDL-C) in two age-different Greek cohorts. Four hundred fifteen middle-aged (n = 147 females: 43.2 ± 13 years, n = 268 males: 43.3 ± 14 years) Caucasian Greek subjects consisted the middle aged cohort. One hundred seventy five elderly (n = 88 females: 79.9 ± 4 years; n = 87 males: 80.6 ± 4 years) were selected from the elderly cohort. Genotype data were obtained for all of them. Multiple linear regression analysis, stratified by gender and adjusted for age, smoking habits and body mass index as covariates, showed higher ox-LDL-C levels for the middle aged men with the Val/Val genotype, compared to the other allele (Ala/Ala and Ala/Val) carriers (65.9 ± 25.7 vs. 55.7 ± 20.5 mg/dl; standardized β coefficient = 0.192, P = 0.012). On the contrary, elderly women with the Val/Val genotype occurred with lower ox-LDL-C levels compared to the Ala/Ala or Ala/Val genotype (74.2 ± 22.1 vs. 86.5 ± 26.6 mg/dl; standardized β coefficient = -0.269, P = 0.015). The same trend was also recorded in elderly men, however without reaching statistical significance (standardized β coefficient = -0.187, P = 0.077). Moreover, elderly men and women with the Ala/Ala or Ala/Val genotype presented higher triglycerides levels compared to Val/Val (women: 145.2 ± 68.7 vs. 114.3 ± 34.3 mg/dl, P = 0.027; men: 147.8 ± 72.4 vs. 103.7 ± 38.0 mg/dl, P = 0.002). Additionally, middle aged men with the Val/Val genotype had higher HDL-C levels compared to the Ala allele carriers. The results suggest that SOD Ala16Val polymorphism is an age-dependent modulator of ox-LDL-C levels in middle-aged men and elderly women. PMID:18305395

  18. New developments in fluorescence detection of ALA-induced protoporphyrin IX for cancer localization

    NASA Astrophysics Data System (ADS)

    Stepp, Herbert G.; Baumgartner, Reinhold; Betz, Christian; Bise, Karl; Brand, P.; Gamarra, Fernando; Haeussinger, Karl; Hillemanns, Peter; Huber, Rudolf M.; Knuechel, Ruth; Kriegmair, M.; Leunig, Andreas; Pichler, J.; Rick, Kai; Schulz, H.; Stanzel, F.; Stocker, Susanne; Wagner, Simon; Weigandt, H.

    1997-12-01

    After the very promising clinical results for the detection of bladder cancer in urology, preclinical and clinical studies on aminolevulinic acid (5-ALA) induced protoporphyrin IX (PPIX) are preformed in various disciplines now. This paper provides a brief overview of the progress on 5-ALA assisted fluorescence diagnosis in urology, pulmonology, neurosurgery, gynecology and ENT performed in collaboration with the Laser Research Laboratory at the Department of Urology of the Ludwig-Maximilians-University in Munich. Five-ALA can be applied either topically or systemically to induce an intracellular accumulation of fluorescing PPIX. With appropriate dosage of 5-ALA, malignant tissue can be stained selectively, and irradiation with violet light excites a bright red fluorescence of the tumor. Optical properties of the tissue tend to hamper the precise identification and demarcation of suspect areas in fluorescence images. Multicolor remission and fluorescence imaging, therefore, seems to be indispensable for a reliable tumor localization.

  19. Latest results of 5-ALA-based fluorescence diagnosis and other medical disciplines

    NASA Astrophysics Data System (ADS)

    Baumgartner, Reinhold

    1999-02-01

    Preclinical and clinical studies on 5-aminolevulinic acid (5- ALA) induced Protoporphyrin IX (PPIX) are performed in various departments now following promising clinical results for the detection of bladder cancer in urology. This paper provides an overview on the progress of 5-ALA assisted fluorescence diagnosis in urology, pulmonology, neurosurgery, gynecology and ENT coordinated by the Laser Research Laboratory of the Ludwig-Maximilians-University in Munich. 5-ALA can be applied either topically or systematically to induce an intracellular accumulation of fluorescing PPIX. With appropriate dosage of 5-ALA, malignant tissue can be stained selectively, and irradiation with violet light excites a bright red fluorescence of the tumor visible with naked eyes. Optical properties of the tissue tend to hamper the precise identification and demarcation of suspect areas in fluorescence images. Multicolor remission and fluorescence imaging, therefore, should improve tumor localization in future.

  20. Design of PDT protocols using delta-aminolevulinic acid (5ALA)

    NASA Astrophysics Data System (ADS)

    Jacques, Steven L.; He, Xiao-Yan; Gofstein, Gary

    1993-06-01

    The kinetics of protoporphyrin IX (PPIX) synthesis, bioconversion to other metabolic products, and photobleaching were measured in cell cultures after incubation in media containing the metabolic precursor for heme synthesis, (delta) -aminolevulinic acid (5 ALA). A compartmental model described the kinetics in terms of rate constants for the three processes. The maximum amount of PPIX that can be attained in the cells and the concentration of 5 ALA in the medium that obtains this maximum were determined. Using this information, two dosimetry protocols are outlined which both involve complete photobleaching of the PPIX: (1) the classical acute protocol using maximum 5 ALA to produce maximum PPIX and a light treatment of about 0.5 - 1 hr, and (2) a novel prolonged protocol using continuous low-level 5 ALA delivery to produce only slightly elevated PPIX and an extended light exposure time of over 24 hrs.

  1. Conversion of the agent-oriented domain-specific language ALAS into JavaScript

    NASA Astrophysics Data System (ADS)

    Sredojević, Dejan; Vidaković, Milan; Okanović, Dušan; Mitrović, Dejan; Ivanović, Mirjana

    2016-06-01

    This paper shows generation of JavaScript code from code written in agent-oriented domain-specific language ALAS. ALAS is an agent-oriented domain-specific language for writing software agents that are executed within XJAF middleware. Since the agents can be executed on various platforms, they must be converted into a language of the target platform. We also try to utilize existing tools and technologies to make the whole conversion process as simple as possible, as well as faster and more efficient. We use the Xtext framework that is compatible with Java to implement ALAS infrastructure - editor and code generator. Since Xtext supports Java, generation of Java code from ALAS code is straightforward. To generate a JavaScript code that will be executed within the target JavaScript XJAF implementation, Google Web Toolkit (GWT) is used.

  2. Treating cutaneous squamous cell carcinoma using ALA PLGA nanoparticle-mediated photodynamic therapy in a mouse model

    NASA Astrophysics Data System (ADS)

    Wang, Xiaojie; Shi, Lei; Tu, Qingfeng; Wang, Hongwei; Zhang, Haiyan; Wang, Peiru; Zhang, Linglin; Huang, Zheng; Wang, Xiuli; Zhao, Feng; Luan, Hansen

    2015-03-01

    Background: Squamous cell carcinoma (SCC) is a common skin cancer and its treatment is still difficult. The aim of this study was to evaluate the effectiveness of nanoparticle (NP)-assisted ALA delivery for topical photodynamic therapy (PDT) of cutaneous SCC. Methods: UV-induced cutaneous SCCs were established in hairless mice. ALA loaded polylactic-co-glycolic acid (PLGA) NPs were prepared and characterized. The kinetics of ALA PLGA NPs-induced protoporphyrin IX (PpIX) fluorescence in SCCs, therapeutic efficacy of ALA NP-mediated PDT, and immune responses were examined. Results: PLGA NPs could enhance PpIX production in SCC. ALA PLGA NP mediated topical PDT was more effective than free ALA of the same concentration in treating cutaneous SCC. Conclusion: PLGA NPs provide a promising strategy for delivering ALA in topical PDT of cutaneous SCC.

  3. First principles predictions of intrinsic defects in aluminum arsenide, AlAs : numerical supplement.

    SciTech Connect

    Schultz, Peter Andrew

    2012-04-01

    This Report presents numerical tables summarizing properties of intrinsic defects in aluminum arsenide, AlAs, as computed by density functional theory. This Report serves as a numerical supplement to the results published in: P.A. Schultz, 'First principles predictions of intrinsic defects in Aluminum Arsenide, AlAs', Materials Research Society Symposia Proceedings 1370 (2011; SAND2011-2436C), and intended for use as reference tables for a defect physics package in device models.

  4. Using a modified nasotracheal tube to prevent nasal ala pressure sore during prolonged nasotracheal intubation.

    PubMed

    Cherng, Chen-Hwan; Chen, Yuan-Wu

    2010-12-01

    Nasotracheal tube induced nasal ala pressure sores or necrosis during prolonged nasotracheal intubation have been reported, and it is a serious but preventable complication. Here we introduce a modified nasotracheal tube to prevent this complication. This modified nasotracheal tube is composed of two parts, an oral endotracheal tube and a proximal part of a preformed nasotracheal tube, which are linked by a connector. The use of this modified nasotracheal tube can prevent nasal ala pressure sores during prolonged nasotracheal intubation. PMID:20809246

  5. ALA-PDT of glioma cell micro-clusters in BD-IX rat brain

    NASA Astrophysics Data System (ADS)

    Madsen, Steen J.; Angell-Petersen, Even; Spetalen, Signe; Carper, Stephen W.; Ziegler, Sarah A.; Hirschberg, Henry

    2006-02-01

    A significant contributory factor to the poor prognosis of patients with glioblastoma multiforme is the inability of conventional treatments to eradicate infiltrating glioma cells. A syngeneic rat brain tumor model is used to investigate the effects of aminolevulinic acid (ALA)-mediated photodynamic therapy (PDT) on small clusters of tumor cells sequestered in normal brain. The intrinsic sensitivity of rat glioma cells to PDT was investigated by exposing ALA-incubated cells to a range of radiant exposures and irradiances using 635 nm light. Biodistribution studies were undertaken on tumor-bearing animals in order to determine the tumor selectivity of the photosensitizer following systemic administration (i.p.) of ALA. Effects of ALA-PDT on normal brain and gross tumor were evaluated using histopathology. Effects of PDT on isolated glioma cells in normal brain were investigated by treating animals 48 h after tumor cell implantation: a time when the micro-clusters of cells are protected by an intact blood-brain-barrier (BBB). Rat glioma cells in monolayer are susceptible to ALA-PDT - lower irradiances are more effective than higher ones. Fluorescence microscopy of frozen tissue sections showed that photosensitizer is produced with better than 200:1 tumor-to-normal tissue selectivity following i.p. ALA administration. ALA-PDT resulted in significant damage to both gross tumor and normal brain, however, the treatment failed to prolong survival of animals with newly implanted glioma cells compared to non-treated controls if the drug was delivered either i.p. or directly into the brain. In contrast, animals inoculated with tumor cells pre-incubated in vitro with ALA showed a significant survival advantage in response to PDT.

  6. ALA-based photodynamic therapy in epithelial tumors: in vivo and in vitro models

    NASA Astrophysics Data System (ADS)

    Casas, Adriana; Fukuda, Haydee; Batlle, Alcira

    2000-03-01

    PDT shows considerable potential as a treatment modality for superficial tumors. PDT is based on the accumulation of a photosensitizer in the target tissue. Subsequent illumination with light of an appropriate wavelength provokes a photochemical reaction that results in tumor destruction. Aminolevulinic acid (ALA) is a porphyrin precursor, and its administration result in the endogenous production of phototoxic porphyrins, which has been exploited for PDT. We assessed PDT efficacy employing both in vivo and in vitro models. We used papillomas, keratoacanthomas and in situ carcinomas chemically induced in the skin of SENCAR mice. Using ALA lotion and cream formulations, the maximal amount of porphyrin accumulation in papillomas was 5.52 (mu) g/g tissue. An energy of 150 of J/cm2 was delivered by a copper-dye laser tuned at 630 nm. Microscopically, we found several signs of tissue destruction, more markedly in the upper strata of the in situ carcinomas. Papillomas, characterized by hyperkeratinization, were resistant to PDT. In our in vitro studies, we used an epithelial adenocarcinoma cell line. We tested ALA and its hexyl and methyl derivatives with the aim of increasing porphyrin synthesis. We found that hexyl-ALA was the best compound. When cultures incubated 3 hours in 0.6 mM ALA and 0.1 mM hexyl-ALA respectively were irradiated with 3 J/cm2 only 5 percent of cells survived.

  7. Topical application of ALA PDT for the treatment of moderate to severe acne vulgaris

    NASA Astrophysics Data System (ADS)

    Wang, Xiu-Li; Wang, Hong-Wei; Zhang, Ling-Lin; Su, Lina; Guo, Ming-Xia; Huang, Zheng

    2009-06-01

    Objectives: To evaluate the effectiveness of topical 5-aminolevulinic acid (ALA)- medicated photodynamic therapy (ALA PDT) for the treatment of moderate to severe acne vulgaris. Methods: Sixteen Chinese patients with moderate to severe facial acne were treated with 1-3 courses of ALA PDT. ALA cream (3%) was freshly prepared and applied to acne lesions for 3-4 h. The lesions were irradiated by a 635 nm diode laser at dose levels of 60 - 80 J/cm2 at 100 mW/cm2. Clinical assessments were conducted before and after treatment up to 3 months. Results: All patents showed response to ALA PDT. Complete clearance was seen in 10 patients (62.5%) and partial clearance in 6 patients (37.5%). One case showed recurrence after complete clearance at 2 months and another two showed recurrence after complete clearance at 3 months. However, the number of new lesions were significantly reduced. Adverse effects were minimal. Conclusions: The results of this preliminary clinical study is encouraging. ALA PDT is a simple, safe and useful therapeutic option for the treatment of moderate to severe acne. Further studies to evaluate the treatment with a larger number of patients and for a longer period of follow-up are needed.

  8. ‘Utilitarian’ judgments in sacrificial moral dilemmas do not reflect impartial concern for the greater good

    PubMed Central

    Kahane, Guy; Everett, Jim A.C.; Earp, Brian D.; Farias, Miguel; Savulescu, Julian

    2015-01-01

    A growing body of research has focused on so-called ‘utilitarian’ judgments in moral dilemmas in which participants have to choose whether to sacrifice one person in order to save the lives of a greater number. However, the relation between such ‘utilitarian’ judgments and genuine utilitarian impartial concern for the greater good remains unclear. Across four studies, we investigated the relationship between ‘utilitarian’ judgment in such sacrificial dilemmas and a range of traits, attitudes, judgments and behaviors that either reflect or reject an impartial concern for the greater good of all. In Study 1, we found that rates of ‘utilitarian’ judgment were associated with a broadly immoral outlook concerning clear ethical transgressions in a business context, as well as with sub-clinical psychopathy. In Study 2, we found that ‘utilitarian’ judgment was associated with greater endorsement of rational egoism, less donation of money to a charity, and less identification with the whole of humanity, a core feature of classical utilitarianism. In Studies 3 and 4, we found no association between ‘utilitarian’ judgments in sacrificial dilemmas and characteristic utilitarian judgments relating to assistance to distant people in need, self-sacrifice and impartiality, even when the utilitarian justification for these judgments was made explicit and unequivocal. This lack of association remained even when we controlled for the antisocial element in ‘utilitarian’ judgment. Taken together, these results suggest that there is very little relation between sacrificial judgments in the hypothetical dilemmas that dominate current research, and a genuine utilitarian approach to ethics. PMID:25460392

  9. Alpha linolenic acid (ALA) from Rosa canina, sacha inchi and chia oils may increase ALA accretion and its conversion into n-3 LCPUFA in diverse tissues of the rat.

    PubMed

    Valenzuela B, Rodrigo; Barrera R, Cynthia; González-Astorga, Marcela; Sanhueza C, Julio; Valenzuela B, Alfonso

    2014-07-25

    Alpha-linolenic acid (ALA) is an essential n-3 PUFA; its n-3 LCPUFA derivatives EPA and DHA, which have diverse beneficial effects, are scarce in the human diet. In recent years nontraditional vegetable oils rich in ALA (up to 45%) have been developed as new alternatives to increase ALA consumption. This work evaluated the accretion of ALA, EPA and DHA into the phospholipids extracted from erythrocytes, liver, kidney, small intestine, heart, quadriceps and the brain in rats fed sunflower (SFO), canola (CO), Rosa canina (RCO), sacha inchi (Plukenetia volubilis, SIO) and chia (Salvia hispánica, ChO) oils. Five experimental groups (n = 12 per group) were fed for 21 days with SFO (1% ALA), CO (10% ALA), RCO (33% ALA), SIO (49% ALA), and ChO (64% ALA). SIO and ChO allowed higher ALA accretion in all tissues, except the brain, and a reduction in the content of arachidonic acid in all tissues except the brain. EPA was increased in erythrocytes, liver, kidney, small intestine, heart and quadriceps, but not in the brain. DHA was increased in the liver, small intestine and brain tissues. Our results demonstrate that ALA, when provided in significant amounts, can be converted into n-3 LCPUFA, mostly DHA in the liver and brain. It is suggested that oils rich in ALA, such as SIO and ChO, are good sources for obtaining higher tissue levels of ALA, also allowing its selective conversion into n-3 LCPUFA in some tissues of the rat. PMID:24855655

  10. A potential role for endogenous proteins as sacrificial sunscreens and antioxidants in human tissues.

    PubMed

    Hibbert, Sarah A; Watson, Rachel E B; Gibbs, Neil K; Costello, Patrick; Baldock, Clair; Weiss, Anthony S; Griffiths, Christopher E M; Sherratt, Michael J

    2015-08-01

    as a consequence of an evolutionary pressure to express sacrificial protein sunscreens which reduce UVR penetration and hence mitigate tissue damage. PMID:25911998

  11. A potential role for endogenous proteins as sacrificial sunscreens and antioxidants in human tissues

    PubMed Central

    Hibbert, Sarah A.; Watson, Rachel E.B.; Gibbs, Neil K.; Costello, Patrick; Baldock, Clair; Weiss, Anthony S.; Griffiths, Christopher E.M.; Sherratt, Michael J.

    2015-01-01

    as a consequence of an evolutionary pressure to express sacrificial protein sunscreens which reduce UVR penetration and hence mitigate tissue damage. PMID:25911998

  12. The enzymology of alanine aminotransferase (AlaAT) isoforms from Hordeum vulgare and other organisms, and the HvAlaAT crystal structure.

    PubMed

    Duff, Stephen M G; Rydel, Timothy J; McClerren, Amanda L; Zhang, Wenlan; Li, Jimmy Y; Sturman, Eric J; Halls, Coralie; Chen, Songyang; Zeng, Jiamin; Peng, Jiexin; Kretzler, Crystal N; Evdokimov, Artem

    2012-12-01

    In this paper we describe the expression, purification, kinetics and biophysical characterization of alanine aminotransferase (AlaAT) from the barley plant (Hordeum vulgare). This dimeric PLP-dependent enzyme is a pivotal element of several key metabolic pathways from nitrogen assimilation to carbon metabolism, and its introduction into transgenic plants results in increased yield. The enzyme exhibits a bi-bi ping-pong reaction mechanism with a K(m) for alanine, 2-oxoglutarate, glutamate and pyruvate of 3.8, 0.3, 0.8 and 0.2 mM, respectively. Barley AlaAT catalyzes the forward (alanine-forming) reaction with a k(cat) of 25.6 s(-1), the reverse (glutamate-forming) reaction with k(cat) of 12.1 s(-1) and an equilibrium constant of ~0.5. The enzyme is also able to utilize aspartate and oxaloacetate with ~10% efficiency as compared to the native substrates, which makes it much more specific than related bacterial/archaeal enzymes (that also have lower K(m) values). We have crystallized barley AlaAT in complex with PLP and l-cycloserine and solved the structure of this complex at 2.7 Å resolution. This is the first example of a plant AlaAT structure, and it reveals a canonical aminotransferase fold similar to structures of the Thermotoga maritima, Pyrococcus furiosus, and human enzymes. This structure bridges our structural understanding of AlaAT mechanism between three kingdoms of life and allows us to shed some light on the specifics of the catalysis performed by these proteins. PMID:22750542

  13. Combination therapies in adjuvant with topical ALA-mediated photodynamic therapy for DMBA-induced hamster buccal pouch premalignant lesions

    NASA Astrophysics Data System (ADS)

    Yang, Deng-Fu; Hsu, Yih-Chih

    2012-03-01

    In Taiwan, oral cancer has becomes the fastest growth male cancer disease due to the betel nut chewing habit combing with smoking and alcohol-drinking lifestyle of people. In order to eliminate the systemic phototoxic effect of 5-aminolevulinic acid (ALA), this study was designed to use a topical ALA-mediated PDT for treatment of DMBA-induced hamster buccal pouch precancerous lesions. DMBA was applied to one of the buccal pouches of hamsters thrice a week for 10 to 12 weeks. Cancerous lesions were induced and proven by histological examination. These DMBA-induced cancerous lesions were used for testing the efficacy of topical ALA-mediated PDT. Before PDT, fluorescence spectroscopy was used to determine when ALA reached its peak level in the lesional epithelial cells after topical application of ALA gel. We found that ALA reached its peak level in precancerous lesions about 2.5 hrs after topical application of ALA gel. The cancerous lesions in hamsters were then treated with topical ALA -mediated PDT with light exposure dose of 150 J/cm2 using LED 635 nm fiber-guided light device. Visual examination demonstrated that adjuvant topical ALA -mediated PDT group has shown better therapeutic results in compared to those of non-adjuvant topical ALA-mediated PDT group for DMBA-induced hamster buccal pouch precancerous lesions.

  14. Intensified oxidative and nitrosative stress following combined ALA-based photodynamic therapy and local hyperthermia in rat tumors.

    PubMed

    Frank, Juergen; Lambert, Christine; Biesalski, Hans Konrad; Thews, Oliver; Vaupel, Peter; Kelleher, Debra K

    2003-12-20

    Oxidative stress-related changes in tumors upon localized hyperthermia (HT), 5-aminolevulinic acid-based photodynamic therapy (ALA-PDT) and their combination (ALA+HT) were examined after the observation that the antitumor effects of ALA-PDT could be significantly enhanced upon simultaneous application of HT. Rats bearing s.c. DS-sarcomas (0.6-1.0 ml) on the hind foot dorsum were anesthetized and underwent one of the following treatments: (i) ALA-PDT (375 mg/kg 5-ALA i.v.); (ii) localized HT, 43 degrees C for 60 min; (iii) combined ALA-PDT and HT [=ALA+HT]. Appropriate control experiments were also performed. After treatment, tumors were excised and rapidly frozen for later analysis of nitrosative stress (protein nitration), apoptotic events (TUNEL, caspase activation, DNA and RNA fragmentation), expression of heat shock proteins (hsp70 and HO-1), glutathione (GSH) levels and glutathione peroxidase (GPx) activity. Protein nitration was found to increase upon treatment, being especially pronounced in the ALA+HT group, and could partially be related to areas surrounding microvessels. The extent of nitrosative stress also correlated well with the appearance of the markers of apoptosis and the inhibition of in vivo tumor growth as seen in a previous study. GSH levels decreased upon treatment, the reduction being most prominent in the ALA-PDT and ALA+HT groups. GPx activity, however, showed a significant decrease only in the ALA-PDT group. Whereas hsp70 expression increased upon HT, ALA-PDT caused a decrease, and these opposing effects were nullified with ALA+HT. The results obtained point to a number of cellular mechanisms-including effects on cellular defense mechanisms and an abrogation of the heat shock defense mechanism-that may interact to achieve the potentiated tumor response rate seen in vivo upon combined treatment. PMID:14601053

  15. Combination of 5-ALA and iMRI in re-resection of recurrent glioblastoma.

    PubMed

    Quick-Weller, Johanna; Lescher, Stephanie; Forster, Marie-Therese; Konczalla, Jürgen; Seifert, Volker; Senft, Christian

    2016-06-01

    Background Tumour resection plays a role in the initial treatment but also in the setting of recurrent glioblastoma (rGBM). To achieve maximum resection, 5-aminolevulinic acid (5-ALA) and intraoperative MRI (iMRI) are used as surgical tools. Aiming at complete tumour re-resection, we started combining iMRI with 5-ALA to find out if this leads to better surgical results. Methods We performed tumour resections in seven patients with rGBM, combining 5-ALA (20 mg/kg bodyweight) with iMRI (0.15 T). Radiologically complete resections were intended in all seven patients. We assessed intraoperative fluorescence findings and compared these with intraoperative imaging. All patients had early postoperative MRI (3 T) to verify final iMRI scans and received adjuvant treatment according to interdisciplinary tumour board decision. Results Median patient age was 63 years. Median KPS score was 90, and median tumour volume was 8.2 cm(3). In six of seven patients (85%), 5-ALA induced fluorescence of tumour-tissue was detected intraoperatively. All tumours were good to visualise with iMRI and contrast media. One patient received additional resection of residual contrast enhancing tissue on intraoperative imaging, which did not show fluorescence. Radiologically complete resections according to early postoperative MRI were achieved in all patients. Median survival since second surgery was 7.6 months and overall survival since diagnosis was 27.8 months. Conclusions 5-ALA and iMRI are important surgical tools to maximise tumour resection also in rGBM. However, not all rGBMs exhibit fluorescence after 5-ALA administration. We propose the combined use of 5-ALA and iMRI in the surgery of rGBM. PMID:26743016

  16. Stimulation of dendritic cells by DAMPs in ALA-PDT treated SCC tumor cells

    PubMed Central

    Zhang, Haiyan; Fan, Zhixia; Zhang, Linglin; Shi, Lei; Zhou, Feifan; Chen, Wei R.; Wang, Hongwei; Wang, Xiuli

    2015-01-01

    Photodynamic therapy (PDT) not only kills tumor cells directly but also rapidly recruits and activates immune cells favoring the development of antitumor adaptive immunity. It is believed that Topical 5-aminolevulinic acid mediated photodynamic therapy (ALA-PDT) can induce anti-tumor immune responses through dangerous signals damage-associated molecular patterns (DAMPs). In this study, we investigated the effect of ALA-PDT induced DAMPs on immune cells. We focused on the stimulation of dendritic cells by major DAMPs, enhanced the expression of calreticulin (CRT), heat shock proteins 70 (HSP70), and high mobility group box 1 (HMGB1), either individually or in combination. We evaluated in vitro and in vivo expressions of DAMPs induced by ALA-PDT using immunohistochemistry, western blot, and ELISA in a squamous cell carcinoma (SCC) mouse model. The role of DAMPs in the maturation of DCs potentiated by ALA-PDT-treated tumor cells was detected by FACS and ELISA. Our results showed that ALA-PDT enhanced the expression of CRT, HSP70, and HMGB1. These induced DAMPs played an important part in activating DCs by PDT-treated tumor cells, including phenotypic maturation (increase of surface expression of MHC-II, CD80, and CD86) and functional maturation (enhanced capability to secrete IFN-γ and IL-12). Furthermore, injecting ALA-PDT-treated tumor cells into naïve mice resulted in complete protection against cancer cells of the same origin. Our findings indicate that ALA-PDT can increase DAMPs and enhance tumor immunogenicity, providing a promising strategy for inducing a systemic anticancer immune response. PMID:26625309

  17. Harnessing cellular differentiation to improve ALA-based photodynamic therapy in an artificial skin model

    NASA Astrophysics Data System (ADS)

    Maytin, Edward; Anand, Sanjay; Sato, Nobuyuki; Mack, Judith; Ortel, Bernhard

    2005-04-01

    During ALA-based photodynamic therapy (PDT), a pro-drug (aminolevulinic acid; ALA) is taken up by tumor cells and metabolically converted to a photosensitizing intermediate (protoporphyrin IX; PpIX). ALA-based PDT, while an emerging treatment modality, remains suboptimal for most cancers (e.g. squamous cell carcinoma of the skin). Many treatment failures may be largely due to insufficient conversion of ALA to PpIX within cells. We discovered a novel way to increase the conversion of ALA to PpIX, by administering agents that can drive terminal differentiation (i.e., accelerate cellular maturation). Terminally-differentiated epithelial cells show higher levels of intracellular PpIX, apparently via increased levels of a rate-limiting enzyme, coproporphyrinogen oxidase (CPO). To study these mechanisms in a three-dimensional tissue, we developed an organotypic model that mimics true epidermal physiology in a majority of respects. A line of rat epidermal keratinocytes (REKs), when grown in raft cultures, displays all the features of a fully-differentiated epidermis. Addition of ALA to the culture medium results in ALA uptake and PpIX synthesis, with subsequent death of keratinocytes upon exposure to blue light. Using this model, we can manipulate cellular differentiation via three different approaches. (1) Vitamin D, a hormone that enhances keratinocyte differentiation; (2) Hoxb13, a nuclear transcription factor that affects the genetically-controlled differentiation program of stratifying cells (3) Hyaluronan, an abundant extracellular matrix molecule that regulates epidermal differentiation. Because the raft cultures contain only a single cell type (no blood, fibroblasts, etc.) the effects of terminal differentiation upon CPO, PpIX, and keratinocyte cell death can be specifically defined.

  18. Crystallization of tholeiitic basalt in Alae Lava Lake, Hawaii

    USGS Publications Warehouse

    Peck, D.L.; Wright, T.L.; Moore, J.G.

    1966-01-01

    The eruption of Kilauea Volcano August 21-23, 1963, left 600,000 cubic meters of basaltic lava in a lava lake as much as 15 meters deep in Alae pit crater. Field studies of the lake began August 27 and include repeated core drilling, measurements of temperature in the crust and melt, and precise level surveys of the lake surface. The last interstitial melt in the lake solidified late in September 1964; by mid August 1965 the maximum temperature was 690??C at a depth of 11.5 meters. Pumice air-quenched from about 1140??C contains only 5 percent crystals - clinopyroxene, cuhedral olivine (Fo 80), and a trace of plagioclase, (An 70). Drill cores taken from the zone of crystallization in the lake show that olivine continued crystallizing to about 1070??C; below that it reacts with the melt, becoming corroded and mantled by pyroxene and plagioclase. Below 1070??C, pyroxene and plagioclase crystallized at a constant ratio. Ilmenite first appeared at about 1070??C and was joined by magnetite at about 1050??C; both increased rapidly in abundance to 1000??C. Apatite first appeared as minute needles in interstitial glass at 1000??C. Both the abundance and index of refraction of glass quenched from melt decreased nearly linearly with falling temperature. At 1070??C the quenched lava contains about 65 percent dark-brown glass with an index of 1.61; at 980??C it contains about 8 percent colorless glass with an index of 1.49. Below 980??C, the percentage of glass remained constant. Progressive crystallization forced exsolution of gases from the melt fraction; these formed vesicles and angular pores, causing expansion of the crystallizing lava and lifting the surface of the central part of the lake an average of 19.5 cm. The solidified basalt underwent pneumatolitic alteration, including deposition of cristobalite at 800??C, reddish alteration of olivine at 700??C, tarnishing of ilmenite at 550??C, deposition of anhydrite at 250??C, and deposition of native sulfur at 100??C

  19. The dipeptide alanylphenylalanine ( H-Ala-Phe-OH) - protonation and coordination ability with Au(III)

    NASA Astrophysics Data System (ADS)

    Koleva, B. B.; Kolev, Ts.; Zareva, S. Y.; Spiteller, M.

    2007-04-01

    The dipeptide alanylphenylalanine ( H-Ala-Phe-OH), its hydrochloride ( HCl × H-Ala-Phe-OH) and Au(III)-complex have been characterized structurally. Quantum chemical DFT and ab initio calculations, solid-state linear-dichroic infrared (IR-LD) spectroscopy and 1H and 13C NMR data were employed. The results are confirmed by a single crystal X-ray diffraction analysis of HCl × H-Ala-Phe-OH. The coordination with Au(III) is supported by data from MS, TGV, DSC methods and by elemental analysis. The H-Ala-Phe-OH coordinates in a bidentate manner via an O-atom of the COO --group and N-amide nitrogen, after a previous deprotonation of the NH-group has taken place. Two Cl - ions are attached to the metal center as terminal ligands, yielding a completely planar geometry for the AuNOCl 2 chromophor in the mononuclear [Au(( H-Ala-Phe-OH)H -1)Cl 2] complex.

  20. Simplified and optimized multispectral imaging for 5-ALA-based fluorescence diagnosis of malignant lesions.

    PubMed

    Minamikawa, Takeo; Matsuo, Hisataka; Kato, Yoshiyuki; Harada, Yoshinori; Otsuji, Eigo; Yanagisawa, Akio; Tanaka, Hideo; Takamatsu, Tetsuro

    2016-01-01

    5-aminolevulinic acid (5-ALA)-based fluorescence diagnosis is now clinically applied for accurate and ultrarapid diagnosis of malignant lesions such as lymph node metastasis during surgery. 5-ALA-based diagnosis evaluates fluorescence intensity of a fluorescent metabolite of 5-ALA, protoporphyrin IX (PPIX); however, the fluorescence of PPIX is often affected by autofluorescence of tissue chromophores, such as collagen and flavins. In this study, we demonstrated PPIX fluorescence estimation with autofluorescence elimination for 5-ALA-based fluorescence diagnosis of malignant lesions by simplified and optimized multispectral imaging. We computationally optimized observation wavelength regions for the estimation of PPIX fluorescence in terms of minimizing prediction error of PPIX fluorescence intensity in the presence of typical chromophores, collagen and flavins. By using the fluorescence intensities of the optimized wavelength regions, we verified quantitative detection of PPIX fluorescence by using chemical mixtures of PPIX, flavins, and collagen. Furthermore, we demonstrated detection capability by using metastatic and non-metastatic lymph nodes of colorectal cancer patients. These results suggest the potential and usefulness of the background-free estimation method of PPIX fluorescence for 5-ALA-based fluorescence diagnosis of malignant lesions, and we expect this method to be beneficial for intraoperative and rapid cancer diagnosis. PMID:27149301

  1. Simplified and optimized multispectral imaging for 5-ALA-based fluorescence diagnosis of malignant lesions

    PubMed Central

    Minamikawa, Takeo; Matsuo, Hisataka; Kato, Yoshiyuki; Harada, Yoshinori; Otsuji, Eigo; Yanagisawa, Akio; Tanaka, Hideo; Takamatsu, Tetsuro

    2016-01-01

    5-aminolevulinic acid (5-ALA)-based fluorescence diagnosis is now clinically applied for accurate and ultrarapid diagnosis of malignant lesions such as lymph node metastasis during surgery. 5-ALA-based diagnosis evaluates fluorescence intensity of a fluorescent metabolite of 5-ALA, protoporphyrin IX (PPIX); however, the fluorescence of PPIX is often affected by autofluorescence of tissue chromophores, such as collagen and flavins. In this study, we demonstrated PPIX fluorescence estimation with autofluorescence elimination for 5-ALA-based fluorescence diagnosis of malignant lesions by simplified and optimized multispectral imaging. We computationally optimized observation wavelength regions for the estimation of PPIX fluorescence in terms of minimizing prediction error of PPIX fluorescence intensity in the presence of typical chromophores, collagen and flavins. By using the fluorescence intensities of the optimized wavelength regions, we verified quantitative detection of PPIX fluorescence by using chemical mixtures of PPIX, flavins, and collagen. Furthermore, we demonstrated detection capability by using metastatic and non-metastatic lymph nodes of colorectal cancer patients. These results suggest the potential and usefulness of the background-free estimation method of PPIX fluorescence for 5-ALA-based fluorescence diagnosis of malignant lesions, and we expect this method to be beneficial for intraoperative and rapid cancer diagnosis. PMID:27149301

  2. Supplementation of milled chia seeds increases plasma ALA and EPA in postmenopausal women.

    PubMed

    Jin, Fuxia; Nieman, David C; Sha, Wei; Xie, Guoxiang; Qiu, Yunping; Jia, Wei

    2012-06-01

    Ten postmenopausal women (age 55.6 ± 0.8 years, BMI 24.6 ± 1.1 kg/m²) ingested 25 g/day milled chia seed during a 7-week period, with six plasma samples collected for measurement of α-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA). Subjects operated as their own controls with overnight fasted blood samples taken at baseline (average of two samples), and then after 1, 2, 3, 5, and 7 weeks supplementation. Plasma ALA increased significantly after one week supplementation and was 138 % above baseline levels by the end of the study (overall time effect, P < 0.001). EPA increased 30 % above baseline (overall time effect, P = 0.019) and was correlated across time with ALA (r = 0.84, P = 0.02). No significant change in plasma DPA levels was measured (overall time effect, P = 0.067). Plasma DHA decreased slightly by the end of the study (overall time effect, P = 0.030) and was not correlated with change in ALA. In conclusion, ingestion of 25 g/day milled chia seeds for seven weeks by postmenopausal women resulted in significant increases in plasma ALA and EPA but not DPA and DHA. PMID:22538527

  3. Flourescence analysis of ALA-induced Protoporphyrin IX in psoriatic plaque

    NASA Astrophysics Data System (ADS)

    Stringer, Mark R.; Robinson, Dominic J.; Collins, P.

    1996-01-01

    The success reported for the treatment of superficial skin carcinomas by photodynamic therapy (PDT), following topical application of 5-aminolaevulinic acid (ALA), has therapeutic implications for the treatment of other skin disorders. This presentation describes the accumulation of the photosensitizing agent protoporphyrin IX (PpIX) in areas of psoriatic plaque, by monitoring the fluorescence emission induced by low-intensity laser excitation at 488 nm. We present the results from 15 patients, with a total of 42 plaques. These results show that PpIX fluorescence increases in intensity within the 6 hour period following application of ALA, which implies there is a potential for PDT. The emission is localized to the area of ALA application and the effect of occlusion appears insignificant. Also, the rate of increase, and maximum intensity of fluorescence emission, is not directly related to the applied quantity of ALA. The variability of the fluorescence intensity is as great between plaques at different sites on the same patient as between different patients. We also present measurements of the depletion in intensity of fluorescence emission during PDT treatment, using white light, at an irradiance of 25 mW cm-2, that is a consequence of the molecular photo-oxidation of PpIX. The use of fluorescence measurements in predicting the therapeutic effect of treating plaque psoriasis by ALA-PDT is discussed.

  4. Protective Effect of ALA in Crushed Optic Nerve Cat Retinal Ganglion Cells Using a New Marker RBPMS

    PubMed Central

    Wang, Yanling; Wang, Wenyao; Liu, Jessica; Huang, Xin; Liu, Ruixing; Xia, Huika; Brecha, Nicholas C.; Pu, Mingliang; Gao, Jie

    2016-01-01

    In this study we first sought to determine whether RNA-binding protein with multiple splicing (RBPMS) can serve as a specific marker for cat retina ganglion cells (RGCs) using retrograde labeling and immunohistochemistry staining. RBPM was then used as an RGC marker to study RGC survival after optic nerve crush (ONC) and alpha-lipoic acid (ALA) treatment in cats. ALA treatment yielded a peak density of RBPMS-alpha cells within the peak isodensity zone (>60/mm2) which did not differ from ONC retinas. The area within the zone was significantly enlarged (control: 2.3%, ONC: 0.06%, ONC+ALA: 0.1%). As for the 10-21/mm2 zone, ALA treatment resulted in a significant increase in area (control: 34.5%, ONC: 12.1%, ONC+ALA: 35.9%). ALA can alleviate crush-induced RGC injury. PMID:27504635

  5. Light Fractionation Significantly Increases the Efficacy of Photodynamic Therapy Using BF-200 ALA in Normal Mouse Skin

    PubMed Central

    de Bruijn, Henriëtte S.; Brooks, Sander; van der Ploeg-van den Heuvel, Angélique; ten Hagen, Timo L. M.; de Haas, Ellen R. M.; Robinson, Dominic J.

    2016-01-01

    Background Light fractionation significantly increases the efficacy of 5-aminolevulinic acid (ALA) based photodynamic therapy (PDT) using the nano-emulsion based gel formulation BF-200. PDT using BF-200 ALA has recently been clinically approved and is under investigation in several phase III trials for the treatment of actinic keratosis. This study is the first to compare BF-200 ALA with ALA in preclinical models. Results In hairless mouse skin there is no difference in the temporal and spatial distribution of protoporphyrin IX determined by superficial imaging and fluorescence microscopy in frozen sections. In the skin-fold chamber model, BF-200 ALA leads to more PpIX fluorescence at depth in the skin compared to ALA suggesting an enhanced penetration of BF-200 ALA. Light fractionated PDT after BF-200 ALA application results in significantly more visual skin damage following PDT compared to a single illumination. Both ALA formulations show the same visual skin damage, rate of photobleaching and change in vascular volume immediately after PDT. Fluorescence immunohistochemical imaging shows loss of VE-cadherin in the vasculature at day 1 post PDT which is greater after BF-200 ALA compared to ALA and more profound after light fractionation compared to a single illumination. Discussion The present study illustrates the clinical potential of light fractionated PDT using BF-200 ALA for enhancing PDT efficacy in (pre-) malignant skin conditions such as basal cell carcinoma and vulval intraepithelial neoplasia and its application in other lesion such as cervical intraepithelial neoplasia and oral squamous cell carcinoma where current approaches have limited efficacy. PMID:26872051

  6. Photodynamic therapy (PDT) and photodiagnosis (PD) using endogenous photosensitization induced by 5-aminolevulinic acid (ALA): current clinical and development status

    NASA Astrophysics Data System (ADS)

    Marcus, Stuart L.; Sobel, Russel S.; Golub, Allyn L.; Carroll, Ronald L.; Lundahl, Scott L.; Shulman, D. Geoffrey

    1996-04-01

    Exogenous provision of ALA to many tissues results in the accumulation of sufficient quantities of the endogenous photosensitizer protoporphyrin IX, (PpIX), to produce a photodynamic effect. Therefore, ALA may be considered the only current PDT agent in clinical development which is a biochemical precursor of a photosensitizer. Topical ALA application, followed by exposure to activating light (ALA PDT), has been reported effective for the treatment of a variety of dermatologic diseases including cutaneous T-cell lymphoma, superficial basal cell carcinoma, Bowen's disease, and actinic (solar) keratoses, and is also being examined for treatment of acne and hirsutism. PpIX induced by ALA application also may serve as a fluorescence detection marker for photodiagnosis (PD) of malignant and pre- malignant conditions of the urinary bladder and other organs. Local internal application of ALA has also been used for selective endometrial ablation in animal model systems and is beginning to be examined in human clinical studies. Systemic, oral administration of ALA has been used for ALA PDT of superficial head and neck cancer, various gastrointestinal cancers, and the condition known as Barrett's esophagus. This brief paper reviews the current clinical and development status of ALA PDT.

  7. Assessment of ALA-induced PpIX production in porcine skin pretreated with microneedles.

    PubMed

    Rodrigues, Phamilla Gracielli Sousa; Campos de Menezes, Priscila Fernanda; Fujita, Alessandra Keiko Lima; Escobar, André; Barboza de Nardi, Andrigo; Kurachi, Cristina; Bagnato, Vanderlei S

    2015-09-01

    Photodynamic therapy (PDT) is used for skin treatments of premalignant and cancer lesions and recognized as a non-invasive technique that combines tissue photosensitization and subsequent exposure to light to induce cell death. However, it is limited to the treatment of superficial lesions, mainly due to the low cream penetration. Therefore, the improvement of transdermal distribution of aminolevulinic acid (ALA) is needed. In this study, the kinetics and homogeneity of production of ALA-induced PpIX after the skin pre-treatment with microneedles rollers of 0.5, 1.0 and 1.5 mm length were investigated. An improvement in homogeneity and production of PpIX was shown in a porcine model. Widefield fluorescence imaging three hours after the topical application of ALA-cream in the combined treatment with microeedles rollers. PMID:25319567

  8. ALA PDT for high grade dysplasia in Barrett's oesophagus: review of a decade's experience

    NASA Astrophysics Data System (ADS)

    Bown, Stephen G.; Mackenzie, Gary D.; Dunn, Jason M.; Thorpe, Sally M.; Lovat, Laurence B.

    2009-06-01

    We have been investigating PDT with 5 aminolaevulinic acid (ALA) for the treatment of high grade dysplasia (HGD) in Barrett's oesophagus (BO) for over a decade. This drug has inherent advantages over porfimer sodium (Photofrin), the current approved photosensitiser in the UK and USA, which causes strictures in 18-50% and light sensitivity for up to three months. ALA has a lower rate of oesophageal strictures due to its preferential activity in the mucosa, sparing the underlying muscle, and patients are only light sensitive for 1-2 days. Within a randomised controlled trial, we demonstrated that an ALA dose of 60mg/kg activated by 1000J/cm red laser light is the most effective. Using these values we achieved complete reversal of HGD at 1 year in 89% of 27 patients. A randomised controlled trial of ALA vs porfimer sodium PDT for HGD is currently under way with end points of efficacy and safety. 50 of 66 patients have been recruited. Preliminary data suggest ALA PDT is safer with a trend to higher efficacy. Late relapse can occur in 20% of patients. New prognostic markers, in particular aneuploidy, are helping us to identify and target patients at risk of late relapse. Furthermore optical biopsy techniques such as elastic scattering spectroscopy (ESS) may allow detection of nuclear abnormalities in vivo and enable us to target areas of interest whilst reducing sampling error. PDT faces new challenges for the treatment of HGD in BO, with the recent introduction of balloon based radiofrequency ablation. This technique appears simpler and as effective as PDT, but follow up is currently short and long term safety data is lacking. In our experience ALA PDT is currently the most effective minimally invasive treatment for HGD in BO. This work was undertaken at UCLH/UCL who received a proportion of funding from the Department of Health's NIHR Biomedical Research Centres funding scheme.

  9. Distribution of ALA metabolic products in esophageal carcinoma cells using spectrally resolved confocal laser microscopy

    NASA Astrophysics Data System (ADS)

    Smolka, Jozef; Mateasik, Anton

    2006-08-01

    Aminolevulinic acid (ALA) is an efficient substance used in photodynamic therapy (PDT). It is a precursor of light-sensitive products that can selectively accumulate in malignant cells following the altered activity of the heme biosynthetic pathway enzymes in such cells. These products are synthesized in mitochondria and distributed to various cellular structures [1]. The localization of ALA products in subcellular structures depends on their chemical characteristics as well as on the properties of the intracellular environment [2]. Characterization of such properties is possible by means of fluorescent probes like JC-1 and carboxy SNARF-1. However, the emission spectra of these probes are overlapped with spectral pattern of typical ALA product -protoporphyrin IX (PpIX). Spectral overlap of fluorescence signals prevents to clearly separate a distribution of probes from PpIX distribution what can completely mess the applicability of these probes in characterization of cell properties. The spectrally resolved confocal laser microscopy can be used to overcome this problem. In this study, a distribution of ALA metabolic products in relation to the mitochondrial membrane potential and intracellular pH was examined. Human cell lines (KYSE-450, KYSE-70) from esophageal squamous cell carcinoma were used. Cells were incubated with 1mM solution of ALA for four hours. Two fluorescent probes, carboxy SNARF-1 and JC-1 , were used to monitor intracellular pH levels and to determine membrane potential changes, respectively. The samples were scanned by spectrally resolved laser scanning microscope. Spectral linear unmixing method was used to discriminate and separate regions of accumulation of ALA metabolic products of JC-1 and carboxy SNARF-1.

  10. Photodynamic damage study of HeLa cell line using ALA

    NASA Astrophysics Data System (ADS)

    AlSalhi, M. S.; Atif, M.; AlObiadi, A. A.; Aldwayyan, A. S.

    2011-04-01

    The present study evaluates the photodynamic damage with 5-aminolevulinic acid (5-ALA) using HeLa as experimental model. HeLa cell line was irradiated with red light (He-Ne laser, λ = 632.8 CW nm). The influence of different incubation times and concentrations of 5-ALA, different irradiation doses and various combinations of photosensitizer and light doses on the cellular viability of HeLa cells were studied. The optimal uptake of photosensitizer ALA in HeLa cells was investigated by means of PpIX fluorescence intensity by exciting the HeLa cell suspension at 450 nm and a detection wavelength set at 690 nm. Cells viability was determined by means of trypan blue solution. The spectrometric measurements showed that the maximal cellular uptake of 5-ALA occurred after 4 h in vitro incubation. We found that the combination with 5-ALA and laser irradiation leads to time/concentration-dependent increase of cells death and also energy doses-dependent enlarge the cells death. The fluorescence intensity after PDD of carcinoma cells reduce when compared with the control group. The fluorescence emission spectral profiles after PDD of carcinoma cells showed a dip around 425-525 nm when compared with the control group. This may be due to the damage of mitochondria component of cells. The percentage of HeLa cells after PDD shows that the percentage of cells survival rate as function of laser dose (power). Hence it is clear that at 200 μg/ml ALA and 20 mW laser irradiation, more than 70% of HeLa cells were dead after 15 min.

  11. Differentiation-specific increase in ALA-induced protoporphyrin IX accumulation in primary mouse keratinocytes.

    PubMed Central

    Ortel, B.; Chen, N.; Brissette, J.; Dotto, G. P.; Maytin, E.; Hasan, T.

    1998-01-01

    A treatment regimen that takes advantage of the induction of intracellular porphyrins such as protoporphyrin IX (PPIX) by exposure to exogenous 5-amino-laevulinic acid (ALA) followed by localized exposure to visible light represents a promising new approach to photodynamic therapy (PDT). Acting upon the suggestion that the effectiveness of ALA-dependent PDT may depend upon the state of cellular differentiation, we investigated the effect of terminal differentiation upon ALA-induced synthesis of and the subsequent phototoxicity attributable to PPIX in primary mouse keratinocytes. Induction of keratinocyte differentiation augmented intracellular PPIX accumulation in cells treated with ALA. These elevated PPIX levels resulted in an enhanced lethal photodynamic sensitization of differentiated cells. The differentiation-dependent increase in cellular PPIX levels resulted from several factors including: (a) increased ALA uptake, (b) enhanced PPIX production and (c) decreased PPIX export into the culture media. Simultaneously, steady-state levels of coproporphyrinogen oxidase mRNA increased but aminolaevulinic acid dehydratase mRNA levels remained unchanged. From experiments using 12-o-tetradecanoylphorbol-13-acetate, transforming growth factor beta 1 and calcimycin we demonstrated that the increase in PPIX concentration in terminally differentiating keratinocytes is calcium- and differentiation specific. Stimulation of the haem synthetic capacity is seen in primary keratinocytes, but not in PAM 212 cells that fail to undergo differentiation. Interestingly, increased PPIX formation and elevated coproporphyrinogen oxidase mRNA levels are not limited to differentiating keratinocytes; these were also elevated in the C2C12 myoblast and the PC12 adrenal cell lines upon induction of differentiation. Overall, the therapeutic implications of these results are that the effectiveness of ALA-dependent PDT depends on the differentiation status of the cell and that this may enable

  12. Sacrificial anode stability and polarization potential variation in a ternary Al-xZn-xMg alloy in a seawater-marine environment

    NASA Astrophysics Data System (ADS)

    Muazu, Abubakar; Aliyu, Yaro Shehu; Abdulwahab, Malik; Idowu Popoola, Abimbola Patricia

    2016-04-01

    In this paper, the effects of zinc (Zn) and magnesium (Mg) addition on the performance of an aluminum-based sacrificial anode in seawater were investigated using a potential measurement method. Anodic efficiency, protection efficiency, and polarized potential were the parameters used. The percentages of Zn and Mg in the anodes were varied from 2% to 8% Zn and 1% to 4% Mg. The alloys produced were tested as sacrificial anodes for the protection of mild steel in seawater at room temperature. Current efficiency as high as 88.36% was obtained in alloys containing 6% Zn and 1% Mg. The polarized potentials obtained for the coupled (steel/Al-based alloys) are as given in the Pourbaix diagrams, with steel lying within the immunity region/cathodic region and the sacrificial anodes within the anodic region. The protection offered by the sacrificial anodes to the steel after the 7th and 8th week was measured and protection efficiency values as high as 99.66% and 99.47% were achieved for the Al-6%Zn-1%Mg cast anode. The microstructures of the cast anodes comprise of intermetallic structures of hexagonal Mg3Zn2 and body-centered cubic Al2Mg3Zn3. These are probably responsible for the breakdown of the passive alumina film, thus enhancing the anode efficiency.

  13. Sacrificial anode stability and polarization potential variation in a ternary Al-xZn-xMg alloy in a seawater-marine environment

    NASA Astrophysics Data System (ADS)

    Muazu, Abubakar; Aliyu, Yaro Shehu; Abdulwahab, Malik; Idowu Popoola, Abimbola Patricia

    2016-06-01

    In this paper, the effects of zinc (Zn) and magnesium (Mg) addition on the performance of an aluminum-based sacrificial anode in seawater were investigated using a potential measurement method. Anodic efficiency, protection efficiency, and polarized potential were the parameters used. The percentages of Zn and Mg in the anodes were varied from 2% to 8% Zn and 1% to 4% Mg. The alloys produced were tested as sacrificial anodes for the protection of mild steel in seawater at room temperature. Current efficiency as high as 88.36% was obtained in alloys containing 6% Zn and 1% Mg. The polarized potentials obtained for the coupled (steel/Al-based alloys) are as given in the Pourbaix diagrams, with steel lying within the immunity region/cathodic region and the sacrificial anodes within the anodic region. The protection offered by the sacrificial anodes to the steel after the 7th and 8th week was measured and protection efficiency values as high as 99.66% and 99.47% were achieved for the Al-6%Zn-1%Mg cast anode. The microstructures of the cast anodes comprise of intermetallic structures of hexagonal Mg3Zn2 and body-centered cubic Al2Mg3Zn3. These are probably responsible for the breakdown of the passive alumina film, thus enhancing the anode efficiency.

  14. Stabilization of green bodies via sacrificial gelling agent during electrophoretic deposition

    DOEpatents

    Worsley, Marcus A.; Kuntz, Joshua D.; Rose, Klint A.

    2016-03-22

    In one embodiment, a method for electrophoretic deposition of a three-dimensionally patterned green body includes suspending a first material in a gelling agent above a patterned electrode of an electrophoretic deposition (EPD) chamber, and gelling the suspension while applying a first electric field to the suspension to cause desired patterning of the first material in a resulting gelation. In another embodiment, a ceramic, metal, or cermet includes a plurality of layers, wherein each layer includes a gradient in composition, microstructure, and/or density in an x-y plane oriented parallel to a plane of deposition of the plurality of layers along a predetermined distance in a z-direction perpendicular to the plane of deposition.

  15. 5-ALA Fluorescence Image Guided Resection of Glioblastoma Multiforme: A Meta-Analysis of the Literature

    PubMed Central

    Eljamel, Samy

    2015-01-01

    Background: Glioblastoma multiforme (GBM) is one of the most deadly cancers in humans. Despite recent advances in anti-cancer therapies, most patients with GBM die from local disease progression. Fluorescence image guided surgical resection (FIGR) was recently advocated to enhance local control of GBM. This is meta-analyses of 5-aminolevulinic (5-ALA) induced FIGR. Materials: Review of the literature produced 503 potential publications; only 20 of these fulfilled the inclusion criteria of this analysis, including a total of 565 patients treated with 5-ALA-FIGR reporting on its outcomes and 800 histological samples reporting 5-ALA-FIGR sensitivity and specificity. Results: The mean gross total resection (GTR) rate was 75.4% (95% CI: 67.4–83.5, p < 0.001). The mean time to tumor progression (TTP) was 8.1 months (95% CI: 4.7–12, p < 0.001). The mean overall survival gain reported was 6.2 months (95% CI: −1–13, p < 0.001). The specificity was 88.9% (95% CI: 83.9–93.9, p < 0.001) and the sensitivity was 82.6% (95% CI: 73.9–91.9, p < 0.001). Conclusion: 5-ALA-FIGR in GBM is highly sensitive and specific, and imparts significant benefits to patients in terms of improved GTR and TTP. PMID:25961952

  16. Hey, Small Spender: An Insider's Guide to Navigating ALA's Chicago Conference on the Cheap

    ERIC Educational Resources Information Center

    School Library Journal, 2009

    2009-01-01

    This article presents an insider's guide to navigating the American Library Association's (ALA) annual conference in Chicago on July 9-15. As for the extracurricular activities, Chicago has a lot to offer. This article provides tips from the arts and entertainment bible "Time Out Chicago" on where to go and what to do (on a limited budget) while…

  17. A Circle of Colleagues Meet in the Loop: ALA Midwinter Report.

    ERIC Educational Resources Information Center

    Wilson Library Bulletin, 1987

    1987-01-01

    Highlights the American Library Association (ALA) 1987 Midwinter Conference, including the aftermath of the Attorney General's report on pornography; Congressional pay equity bills; library copying rights; federal librarians' decline in membership and privatization; public library planning, role setting, and output measures manuals; and summaries…

  18. "LJ" Report "Anaheim, ALA 2008": Amid the Fantasy, Doses of Reality

    ERIC Educational Resources Information Center

    Blumenstein, Lynn; Berry, John; Fialkoff, Francine; Fox, Bette-Lee; Hadro, Josh; Horrocks, Norman; Oder, Norman; Roncevic, Mirela

    2008-01-01

    If the resort city of Anaheim, California, home of Disneyland and its "imagineers," marked a departure from the urban reality of the typical American Library Association (ALA) annual conference, it was impossible, at this 2008 meeting, to avoid urgent library issues. How do libraries maintain their value and cultural presence as users turn to the…

  19. ALA Office for Intellectual Freedom: Who We Are and How We Help Librarians

    ERIC Educational Resources Information Center

    Pekoll, Kristin

    2015-01-01

    The American Library Association's (ALA's) Office for Intellectual Freedom (OIF) strives to educate librarians and the public about the nature and importance of intellectual freedom in libraries, and it will celebrate its fiftieth anniversary in 2017. Libraries are a forum for information and ideas (under the First Amendment), and librarians are…

  20. Theoretical site-directed mutagenesis: Asp168Ala mutant of lactate dehydrogenase

    PubMed Central

    Ferrer, Silvia; Tuñón, Iñaki; Moliner, Vicent; Williams, Ian H.

    2008-01-01

    Molecular simulations based on the use of hybrid quantum mechanics/molecular mechanics methods are able to provide detailed information about the complex enzymatic reactions and the consequences of specific mutations on the activity of the enzyme. In this work, the reduction of pyruvate to lactate catalysed by wild-type and Asp168Ala mutant lactate dehydrogenase (LDH) has been studied by means of simulations using a very flexible molecular model consisting of the full tetramer of the enzyme, together with the cofactor NADH, the substrate and solvent water molecules. Our results indicate that the Asp168Ala mutation provokes a shift in the pKa value of Glu199 that becomes unprotonated at neutral pH in the mutant enzyme. This change compensates the loss of the negative charge of Asp168, rendering a still active enzyme. Thus, our methodology gives a calculated barrier height for the Asp168Ala mutant 3 kcal mol−1 higher than that for wild-type LDH, which is in very good agreement with the experiment. The computed potential energy surfaces reveal the reaction pathways and transition structures for the wild-type and mutant enzymes. Hydride transfer is less advanced and the proton transfer is more advanced in the Asp168Ala mutant than in the wild type. This approach provides a very powerful tool for the analysis of the roles of key active-site residues. PMID:18682365

  1. Shifting with the Paradigm: LJ's Picks & Pans for ALA in Disneyland

    ERIC Educational Resources Information Center

    Berry, John N., III

    2008-01-01

    The feelings of librarians planning for the American Library Association (ALA) conference at Disneyland (aka Anaheim, California, June 26-July 2) range from moderate pleasure to dread. Some remember the joys and difficulties of Orlando, especially the exorbitant cab fares and mediocre restaurants. Others quail at screaming kids and tourists in…

  2. ALA-PDT mediated DC vaccine for skin squamous cell carcinoma

    NASA Astrophysics Data System (ADS)

    Ji, Jie; Fan, Zhixia; Zhou, Feifan; Wang, Xiaojie; Shi, Lei; Zhang, Haiyan; Wang, Peiru; Yang, Degang; Zhang, Linglin; Wang, Xiuli; Chen, Wei R.

    2015-03-01

    Dendritic cell (DC) based vaccine has emerged as a promising immunotherapy for cancers. However, most DC vaccines so far have only achieved limited success in cancer treatment. Photodynamic therapy (PDT), an established cancer treatment strategy, can cause immunogenic apoptosis to induce an effective antitumor immune response. In this study, we developed a DC-based cancer vaccine using immunogenic apoptotic tumor cells induced by 5-aminolevulinic acid (ALA) mediated PDT. The maturation of DCs induced by PDT-treated apoptotic cells was evaluated. The anti-tumor immunity of ALA-PDT-DC vaccine was tested with mouse model. We observed the maturations of DCs potentiated by ALA-PDT treated tumor cells, including phenotypic maturation (upregulation of surface expression of MHC-II, DC80, and CD86), and functional maturation (enhanced capability to secret INF-Υ and IL-12). ALA-PDT-DC vaccine mediated by apoptotic cells provided protection against tumor in mice, far stronger than that of DC vaccine obtained from freeze/thaw treated tumor cells. Our results indicate that immunogenic apoptotic tumor cells can be more effective in enhancing DC-based cancer vaccine, which could improve the clinical application of PDT- DC vaccines.

  3. Members of the Club: A Look at One Hundred ALA Presidents. Occasional Paper Number 182.

    ERIC Educational Resources Information Center

    Wiegand, Wayne A.; Steffens, Dorothy

    A survey of the personal, socioeconomic, and professional characteristics of the 100 men and women who served as President to the American Library Association (ALA) between 1876 and 1986 was undertaken to identify those socioeconomic and professional characteristics whose frequency distributions remained relatively constant for all 100 members of…

  4. Studying Online: Student Motivations and Experiences in ALA-Accredited LIS Programs

    ERIC Educational Resources Information Center

    Oguz, Fatih; Chu, Clara M.; Chow, Anthony S.

    2015-01-01

    This paper presents a large scale study of online MLIS students (n = 910), who completed at least one online course and were enrolled in 36 of the 58 ALA-accredited MLIS programs in Canada and the United States. The results indicate that the typical student is female, White, lives in an urban setting, and is in her mid-30s. Online students were…

  5. Preservice Legal Education for Academic Librarians within ALA-Accredited Degree Programs

    ERIC Educational Resources Information Center

    Cross, William M.; Edwards, Phillip M.

    2011-01-01

    In order to explore the current state of legal education for graduates of LIS programs, we present the results of an examination of the curricula and faculty composition at all 57 institutions that offer ALA-accredited graduate degrees. Concluding that, even under the best circumstances, many students graduate with a limited understanding of legal…

  6. Evidence of fully spin polarized ν = 3 in single valley (110)-AlAs quantum wells

    NASA Astrophysics Data System (ADS)

    Prabhu-Gaunkar, S.; Grayson, M.; Dasgupta, S.; Bichler, M.; Morral, A. Fontcuberta I.; Abstreiter, G.

    2010-03-01

    We observe a spike in the longitudinal resistance of a single valley (110)-AlAs quantum well between ν = 3 and 4 which is interpreted as evidence of a quantum Hall ferromagnetic transition. This feature occurs at a magnetic field B = 2.85 T in a sample with densities n = 1.5 - 2.17x10^11 cm-2 in a perpendicular field with no external strain. The spike disappears on further lowering the density of the sample or on raising its temperature above 600 mK. The spike also shows magnetic hysteresis. Since AlAs is a heavy mass system, the exchange enhanced Zeeman energies become comparable to the cyclotron energies and can lead to Landau level crossings even in a purely perpendicular magnetic field. Being a single valley system, there are fewer quantum numbers for the Landau levels than in standard (001) double-valley AlAs wells, and exchange interactions can reorder the levels differently. The spike feature may suggest that up to three completely spin polarized levels exist before the occupation of minority spin levels lowers the exchange interaction energy causing the ground state transition. The (110)-AlAs quantum wells may thus be particularly suited to study exchange enhancement effects.

  7. X-linked macrocytic dyserythropoietic anemia in females with an ALAS2 mutation

    PubMed Central

    Sankaran, Vijay G.; Ulirsch, Jacob C.; Tchaikovskii, Vassili; Ludwig, Leif S.; Wakabayashi, Aoi; Kadirvel, Senkottuvelan; Lindsley, R. Coleman; Bejar, Rafael; Shi, Jiahai; Lovitch, Scott B.; Bishop, David F.; Steensma, David P.

    2015-01-01

    Macrocytic anemia with abnormal erythropoiesis is a common feature of megaloblastic anemias, congenital dyserythropoietic anemias, and myelodysplastic syndromes. Here, we characterized a family with multiple female individuals who have macrocytic anemia. The proband was noted to have dyserythropoiesis and iron overload. After an extensive diagnostic evaluation that did not provide insight into the cause of the disease, whole-exome sequencing of multiple family members revealed the presence of a mutation in the X chromosomal gene ALAS2, which encodes 5′-aminolevulinate synthase 2, in the affected females. We determined that this mutation (Y365C) impairs binding of the essential cofactor pyridoxal 5′-phosphate to ALAS2, resulting in destabilization of the enzyme and consequent loss of function. X inactivation was not highly skewed in wbc from the affected individuals. In contrast, and consistent with the severity of the ALAS2 mutation, there was a complete skewing toward expression of the WT allele in mRNA from reticulocytes that could be recapitulated in primary erythroid cultures. Together, the results of the X inactivation and mRNA studies illustrate how this X-linked dominant mutation in ALAS2 can perturb normal erythropoiesis through cell-nonautonomous effects. Moreover, our findings highlight the value of whole-exome sequencing in diagnostically challenging cases for the identification of disease etiology and extension of the known phenotypic spectrum of disease. PMID:25705881

  8. No association between dysplasminogenemia with p.Ala620Thr mutation and atypical hemolytic uremic syndrome.

    PubMed

    Miyata, Toshiyuki; Uchida, Yumiko; Yoshida, Yoko; Kato, Hideki; Matsumoto, Masanori; Kokame, Koichi; Fujimura, Yoshihiro; Nangaku, Masaomi

    2016-08-01

    Atypical hemolytic uremic syndrome (aHUS), a form of thrombotic microangiopathy, is caused by the uncontrolled activation of the alternative pathway of complement on the cell surface that leads to microangiopathic hemolytic anemia, thrombocytopenia, and renal failure. A recent genetic analysis of aHUS patients identified deleterious mutations not only in complement or complement regulatory genes but also in the plasminogen gene, suggesting that subnormal plasminogen activity may be related to the degradation of thrombi in aHUS. Dysplasminogenemia, which is caused by a genetic variant in the plasminogen gene, PLG:p.Ala620Thr, is commonly observed in the northeast Asian populations, including Japanese. To examine the association between dysplasminogenemia and aHUS, we genotyped PLG:p.Ala620Thr in 103 Japanese patients with aHUS. We identified five aHUS patients with PLG:p.Ala620Thr; the minor allele frequency (MAF) was thus 0.024. The MAF in the patient group was not significantly different from those obtained from a general Japanese population (MAF = 0.020) and the Japanese genetic variation HGDV database (MAF = 0.021) (P = 0.62 and 0.61, respectively). We concluded that, although carriers with PLG:p.Ala620Thr show low plasminogen activity, this is not a predisposing variant for aHUS and that individuals of dysplasminogenemia are not at significantly increased risk of aHUS. PMID:27194432

  9. Exploring the Core: An Examination of Required Courses in ALA-Accredited

    ERIC Educational Resources Information Center

    Hall, Russell A.

    2009-01-01

    This paper examines the required courses of ALA-accredited Library and Information Science programs as published on their websites. The study expands on previous research in this area. Findings show that the typical core curriculum has grown to include both research and information technology in addition to the more traditional subjects. The…

  10. Potentiation of ALA-PDT antitumor activity in mice using topical DMXAA

    NASA Astrophysics Data System (ADS)

    Marrero, Allison; Sunar, Ulas; Sands, Theresa; Oseroff, Allan; Bellnier, David

    2009-06-01

    Photodynamic treatment of subcutaneously implanted Colon 26 tumors in BALB/c mice using the aminolevulinic acid (ALA)-induced photosensitizer protoporphyrin IX (PpIX) was shown to be enhanced by the addition of the vascular disrupting agent 5,6-Dimethylxanthenone-4-acetic-acid (DMXAA; Novartis ASA404). DMXAA increases vascular permeability and decreases blood flow in both murine and human tumors. Sufficiently high parenteral DMXAA doses can lead to tumor collapse and necrosis. We have previously reported marked enhancement of antitumor activity when PDT, using either Photofrin or HPPH, is combined with low-dose intraperitoneal DMXAA. We now describe the first attempt to combine topically-applied DMXAA with PDT. For this, DMXAA was applied two hours before PpIX-activating light delivery. PDT with ALA-PDT alone (ALA 20%; 80 J/cm2 delivered at 75 mW/cm2) caused a 39% decrease in tumor volume compared to unirradiated controls. Addition of topical DMXAA to ALA-PDT resulted in a 74% reduction in tumor volume. Diffuse correlation spectroscopy (DCS), a non-invasive blood flow imaging method, is being used to understand the mechanism of this effect and to aid in the proper design of the therapy. For instance, our most recent DCS data suggests that the 2-hour interval between the DMXAA and light applications may not be optimum. This preliminary study suggests a potential role for topical DMXAA in combination with PDT for dermatologic tumors.

  11. Effect of Surfactants on Production of Oxygenated Unsaturated Fatty Acids by Bacillus megaterium ALA2

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bacillus megaterium ALA2 (NRRL B-21660) produces many oxygenated unsaturated fatty acids from linoleic acid. Its major product, 12,13,17-trihydroxy-9(Z)-octadecenoic acid (12,13,17-THOA), inhibits the growth of some plant pathogenic fungi. Because hydrophobic fatty acids need to be evenly disperse...

  12. Enhancing (L)-isoleucine production by thrABC overexpression combined with alaT deletion in Corynebacterium glutamicum.

    PubMed

    Wang, Jing; Wen, Bing; Wang, Jian; Xu, Qingyang; Zhang, Chenglin; Chen, Ning; Xie, Xixian

    2013-09-01

    L-isoleucine is synthesized from 2-ketobutyrate and pyruvate in Corynebacterium glutamicum, and the supplies of these two precursors are important for L-isoleucine synthesis. C. glutamicum YILWΔalaT with alaT gene deletion (encoding alanine aminotransferase, a principal enzyme for L-alanine synthesis) was constructed to increase intracellular pyruvate availability, and the thrABC genes from Escherichia coli (encoding bifunctional aspartate kinase I-homoserine dehydrogenase I, homoserine kinase, and threonine synthetase) were overexpressed in C. glutamicum YILW and YILWΔalaT to increase the supply of intracellular 2-ketobutyrate. In the fed-batch fermentation, YILWpXMJ19thrABC, YILWΔalaT, and YILWΔalaTpXMJ19thrABC exhibited 5.3, 17.6, and 8.4 % higher L-isoleucine production than the original strain, respectively. Both YILWpXMJ19thrABC and YILWΔalaT excreted lower concentrations of L-lysine, L-alanine, and L-valine. YILWΔalaTpXMJ19thrABC exhibited a cumulative reduction of these by-products excretion, which indicated that thrABC overexpression combined with alaT deletion resulted in the metabolic flux redistribution from 2-ketobutyrate and pyruvate to L-isoleucine synthesis, and decreased the fluxes to by-products synthesis accordingly. PMID:23813403

  13. 78 FR 14414 - The Alabama Great Southern Railroad Company-Abandonment Exemption-in Gadsden, Etowah County, Ala...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-05

    ... Gadsden, Etowah County, Ala.; Tennessee, Alabama, and Georgia Railway Company--Abandonment Exemption--in Gadsden, Etowah County, AL The Alabama Great Southern Railroad Company (AGS) and Tennessee, Alabama, and... approximately 4.25 miles of interconnected rail line in Gadsden, Etowah County, Ala. Specifically, AGS...

  14. Combination Nasolabial Transposition Flap and Island Pedicle Flap Following Mohs Surgery of Simultaneous Basal Cell Carcinomas Involving Both Nasal Alae

    PubMed Central

    Lee, Chae Young; Lee, Yeong Kyu; Choi, Kyu Won; Lee, Chae Wook; Kim, Ki Ho

    2008-01-01

    The nasal ala is a challenging area for surgical reconstruction, with thick sebaceous skin, the lack of an ample tissue reservoir, and an adjacent free margin. Numerous flaps have been reported for the repair of alae defects. A 71-year-old woman with simultaneous basal cell carcinomas involving both nasal alae was treated by Mohs micrographic surgery. The surgical defects measured 1.5×1.5 cm on the center of the right nasal ala and 1.0×1.0 cm on the left nasal ala, including the alar crease and rim. The right nasal ala was used as a nasolabial transposition flap and the left nasal ala was reconstructed by an island pedicle flap. The final shape and texture were satisfactory. The flaps survived and nasal symmetry was preserved. Combined nasolabial transposition and island pedicle flaps thus offer a superior esthetic and functional result owing to minimized tension. This may be a valuable reconstructive option in the repair of bilateral nasal alae defects.

  15. Substitution of the Lys Linker with the β-Ala Linker Dramatically Decreased the Renal Uptake of 99mTc-Labeled Arg-X-Asp-Conjugated and X-Ala-Asp-Conjugated α-Melanocyte Stimulating Hormone Peptides

    PubMed Central

    2015-01-01

    The purpose of this study was to examine whether the substitution of the Lys linker with the β-Ala could reduce the renal uptake of 99mTc-labeled Arg-X-Asp-conjugated and X-Ala-Asp-conjugated α-melanocyte stimulating hormone (α-MSH) peptides. RSD-β-Ala-(Arg11)CCMSH (1) {c[Arg-Ser-Asp-dTyr-Asp]-β-Ala-Cys-Cys-Glu-His-dPhe-Arg-Trp-Cys-Arg-Pro-Val-NH2}, RTD-β-Ala-(Arg11)CCMSH (2), RVD-β-Ala-(Arg11)CCMSH (3), RAD-β-Ala-(Arg11)CCMSH (4), NAD-β-Ala-(Arg11)CCMSH (5), and EAD-β-Ala-(Arg11)CCMSH (6) peptides were synthesized and evaluated for their melanocortin 1 (MC1) receptor binding affinities in B16/F1 melanoma cells. The biodistribution of their 99mTc-conjugates were determined in B16/F1 melanoma-bearing C57 mice. The substitution of the Lys linker with β-Ala linker dramatically reduced the renal uptake of all six 99mTc-peptides. 99mTc-4 exhibited the highest melanoma uptake (15.66 ± 6.19% ID/g) and the lowest kidney uptake (20.18 ± 3.86% ID/g) among these 99mTc-peptides at 2 h postinjection. The B16/F1 melanoma lesions could be clearly visualized by single photon emission computed tomography (SPECT)/CT using 99mTc-4 as an imaging probe. PMID:25290883

  16. ALA-mediated photodynamic therapy of experimental malignant glioma in the BD-IX rat model

    NASA Astrophysics Data System (ADS)

    Hirschberg, Henry; Angell-Petersen, Even; Peng, Qian; Sun, Chung-Ho; Sorensen, Dag R.; Carper, Steven W.; Madsen, Steen J.

    2005-04-01

    Introduction: Failure of treatment for high grade gliomas is usually due to local recurrence at the site of surgical resec-tion indicating that a more aggressive form of local therapy could be of benefit. Photodynamic therapy (PDT) is a local form of treatment involving the administration of a tumor-localizing photosensitizing drug that is activated by light of a specific wavelength The results of in vitro experiments indicated that PDT, given at low fluence rates was substantially more effective at inhibiting glioma spheroid growth than short term high fluence rate regimes. This prompted the initia-tion of in vivo studies of low fluence rate 5-aminolevulinic acid (ALA) PDT in a rat glioma model. Methods:BT4C cell line tumors were established in the brains of inbred BD- IX rats. Eighteen days following tumor induction the animals were injected with 125 mg/kg ALA ip. and four hours later light treatment at various fluences and fluence rates were given after the introduction of an optical fiber. Tumor histology and animal survival were examined. Results: In vitro experiments verified that the cell line was sensitive to ALA PDT. Microfluorometry of frozen tissue sections showed that PpIX is produced with a greater than 20:1 tumor to normal tissue selectivity ratio four hours after ALA injection. Histological examination demonstrated neutrophil infiltration and tumor central necrosis in low fluence rate treated tumors. Conclusions: Low fluence rate long term ALA mediated PDT had a more pronounced effect on tumor histology than single shot short duration treatments at similar total fluence levels.

  17. Characterization of the Ala62Pro polymorphic variant of human cytochrome P450 1A1 using recombinant protein expression

    SciTech Connect

    Lee, Seung Heon; Kang, Sukmo; Dong, Mi Sook; Park, Jung-Duck; Park, Jinseo; Rhee, Sangkee; Ryu, Doug-Young

    2015-06-15

    Cytochrome P450 (CYP) 1A1 is a heme-containing enzyme involved in detoxification of hydrophobic pollutants. Its Ala62Pro variant has been identified previously. Ala62 is located in α-helix A of CYP1A1. Residues such as Pro and Gly are α-helix breakers. In this study, the Ala62Pro variant was characterized using heterologous expression. E. coli expressing the Ala62Pro variant, and the purified variant protein, had lower CYP (i.e. holoenzyme) contents than their wild-type (WT) equivalents. The CYP variant from E. coli and mammalian cells exhibited lower 7-ethoxyresorufin O-dealkylation (EROD) and benzo[a]pyrene hydroxylation activities than the WT. Enhanced supplementation of a heme precursor during E. coli culture did not increase CYP content in E. coli expressing the variant, but did for the WT. As for Ala62Pro, E. coli expressing an Ala62Gly variant had a lower CYP content than the WT counterpart, but substitution of Ala62 with α-helix-compatible residues such as Ser and Val partially recovered the level of CYP produced. Microsomes from mammalian cells expressing Ala62Pro and Ala62Gly variants exhibited lower EROD activities than those expressing the WT or Ala62Val variant. A region harboring α-helix A has interactions with another region containing heme-interacting residues. Site-directed mutagenesis analyses suggest the importance of interactions between the two regions on holoenzyme expression. Together, these findings suggest that the Ala62Pro substitution leads to changes in protein characteristics and function of CYP1A1 via structural disturbance of the region where the residue is located. - Highlights: • Ala62 is located in α-helix A of the carcinogen-metabolizing enzyme CYP1A1. • Pro acts as an α-helix breaker. • A variant protein of CYP1A1, Ala62Pro, had lower heme content than the wild-type. • The variant of CYP1A1 had lower enzyme activities than the wild-type.

  18. Preclinical Development of a Subcutaneous ALAS1 RNAi Therapeutic for Treatment of Hepatic Porphyrias Using Circulating RNA Quantification.

    PubMed

    Chan, Amy; Liebow, Abigail; Yasuda, Makiko; Gan, Lin; Racie, Tim; Maier, Martin; Kuchimanchi, Satya; Foster, Don; Milstein, Stuart; Charisse, Klaus; Sehgal, Alfica; Manoharan, Muthiah; Meyers, Rachel; Fitzgerald, Kevin; Simon, Amy; Desnick, Robert J; Querbes, William

    2015-01-01

    The acute hepatic porphyrias are caused by inherited enzymatic deficiencies in the heme biosynthesis pathway. Induction of the first enzyme 5-aminolevulinic acid synthase 1 (ALAS1) by triggers such as fasting or drug exposure can lead to accumulation of neurotoxic heme intermediates that cause disease symptoms. We have demonstrated that hepatic ALAS1 silencing using siRNA in a lipid nanoparticle effectively prevents and treats induced attacks in a mouse model of acute intermittent porphyria. Herein, we report the development of ALN-AS1, an investigational GalNAc-conjugated RNAi therapeutic targeting ALAS1. One challenge in advancing ALN-AS1 to patients is the inability to detect liver ALAS1 mRNA in the absence of liver biopsies. We here describe a less invasive circulating extracellular RNA detection assay to monitor RNAi drug activity in serum and urine. A striking correlation in ALAS1 mRNA was observed across liver, serum, and urine in both rodents and nonhuman primates (NHPs) following treatment with ALN-AS1. Moreover, in donor-matched human urine and serum, we demonstrate a notable correspondence in ALAS1 levels, minimal interday assay variability, low interpatient variability from serial sample collections, and the ability to distinguish between healthy volunteers and porphyria patients with induced ALAS1 levels. The collective data highlight the potential utility of this assay in the clinical development of ALN-AS1, and in broadening our understanding of acute hepatic porphyrias disease pathophysiology. PMID:26528940

  19. Preclinical Development of a Subcutaneous ALAS1 RNAi Therapeutic for Treatment of Hepatic Porphyrias Using Circulating RNA Quantification

    PubMed Central

    Chan, Amy; Liebow, Abigail; Yasuda, Makiko; Gan, Lin; Racie, Tim; Maier, Martin; Kuchimanchi, Satya; Foster, Don; Milstein, Stuart; Charisse, Klaus; Sehgal, Alfica; Manoharan, Muthiah; Meyers, Rachel; Fitzgerald, Kevin; Simon, Amy; Desnick, Robert J; Querbes, William

    2015-01-01

    The acute hepatic porphyrias are caused by inherited enzymatic deficiencies in the heme biosynthesis pathway. Induction of the first enzyme 5-aminolevulinic acid synthase 1 (ALAS1) by triggers such as fasting or drug exposure can lead to accumulation of neurotoxic heme intermediates that cause disease symptoms. We have demonstrated that hepatic ALAS1 silencing using siRNA in a lipid nanoparticle effectively prevents and treats induced attacks in a mouse model of acute intermittent porphyria. Herein, we report the development of ALN-AS1, an investigational GalNAc-conjugated RNAi therapeutic targeting ALAS1. One challenge in advancing ALN-AS1 to patients is the inability to detect liver ALAS1 mRNA in the absence of liver biopsies. We here describe a less invasive circulating extracellular RNA detection assay to monitor RNAi drug activity in serum and urine. A striking correlation in ALAS1 mRNA was observed across liver, serum, and urine in both rodents and nonhuman primates (NHPs) following treatment with ALN-AS1. Moreover, in donor-matched human urine and serum, we demonstrate a notable correspondence in ALAS1 levels, minimal interday assay variability, low interpatient variability from serial sample collections, and the ability to distinguish between healthy volunteers and porphyria patients with induced ALAS1 levels. The collective data highlight the potential utility of this assay in the clinical development of ALN-AS1, and in broadening our understanding of acute hepatic porphyrias disease pathophysiology. PMID:26528940

  20. Metallopolymer-peptide conjugates: synthesis and self-assembly of polyferrocenylsilane graft and block copolymers containing a beta-sheet forming Gly-Ala-Gly-Ala tetrapeptide segment.

    PubMed

    Vandermeulen, Guido W M; Kim, Kyoung Taek; Wang, Zhuo; Manners, Ian

    2006-04-01

    We describe the synthesis and self-assembly of two beta-sheet forming metallopolymer-peptide conjugates. The ability of the oligotetrapeptide sequence Gly-Ala-Gly-Ala (GAGA) to form antiparallel beta-sheets was retained in PFS-b-AGAG (PFS = polyferrocenylsilane) and PFS-g-AGAG conjugates with block and graft architectures, respectively. In the solid state, DSC experiments suggest a phase separation between the peptide and PFS domains. In toluene, PFS-b-AGAG interestingly forms a fibrous network which consists of a core containing the self-assembled antiparallel beta-sheet peptide and a corona of organometallic PFS. The self-assembly of the peptide into antiparallel beta-sheets is the driving force for the fiber formation, whereas PFS prevents uncontrolled lateral aggregation of the fibers. The use of an oligopeptide to self-assemble an otherwise random coiled organometallic polymer may be a useful strategy to enhance nanostructure formation. In the cases described here, the conjugates may be used to create nanopatterned ceramics, and the redox properties of the resulting supramolecular aggregates are of significant interest. PMID:16602714

  1. Pressure-induced Γ-X electron-transfer rates in a (GaAs)15/(AlAs)5 superlattice

    NASA Astrophysics Data System (ADS)

    Nunnenkamp, J.; Reimann, K.; Kuhl, J.; Ploog, K.

    1991-10-01

    Time-resolved measurements on pressure-induced type-II Γ-X electron transfer in a (GaAs)15/(AlAs)5 superlattice have been performed using the femtosecond pump-and-probe technique. In the case of type-II character, the measured transfer times τΓ-X depend on the energy separation ΔΓX of Γ and X states as τ-1Γ-X~(ΔΓX)1/2, showing that the transfer process consists of (1) relaxation and quasithermalization of the electrons and holes in the GaAs, and (2) transfer of the electrons to the AlAs layer. Well above the crossover pressure Pc the scattering rates are independent of the carrier density. Near Pc=1.2 GPa, a carrier-induced type-I-type-II crossover leads to a shift of Pc towards lower pressures, giving Pc~=0.9 GPa at 1.5×1012 cm-2. This value Pcdyn is explained in terms of the different band-gap renormalizations of the direct Γ and indirect X-point transitions. The renormalization of the X state is found to be twice as large as the Γ-state renormalization.

  2. ALA Inhibits ABA-induced Stomatal Closure via Reducing H2O2 and Ca(2+) Levels in Guard Cells.

    PubMed

    An, Yuyan; Liu, Longbo; Chen, Linghui; Wang, Liangju

    2016-01-01

    5-Aminolevulinic acid (ALA), a newly proved natural plant growth regulator, is well known to improve plant photosynthesis under both normal and stressful conditions. However, its underlying mechanism remains largely unknown. Stomatal closure is one of the major limiting factors for photosynthesis and abscisic acid (ABA) is the most important hormone in provoking stomatal closing. Here, we showed that ALA significantly inhibited ABA-induced stomatal closure using wild-type and ALA-overproducing transgenic Arabidopsis (YHem1). We found that ALA decreased ABA-induced H2O2 and cytosolic Ca(2+) accumulation in guard cells with stomatal bioassay, laser-scanning confocal microscopy and pharmacological methods. The inhibitory effect of ALA on ABA-induced stomatal closure was similar to that of AsA (an important reducing substrate for H2O2 removal), CAT (a H2O2-scavenging enzyme), DPI (an inhibitor of the H2O2-generating NADPH oxidase), EGTA (a Ca-chelating agent), and AlCl3 (an inhibitor of calcium channel). Furthermore, ALA inhibited exogenous H2O2- or Ca(2+)-induced stomatal closure. Taken together, we conclude that ALA inhibits ABA-induced stomatal closure via reducing H2O2, probably by scavenging, and Ca(2+) levels in guard cells. Moreover, the inhibitive effect of ALA on ABA-induced stomatal closure was further confirmed in the whole plant. Finally, we demonstrated that ALA inhibits stomatal closing, but significantly improves plant drought tolerance. Our results provide valuable information for the promotion of plant production and development of a sustainable low-carbon society. PMID:27148309

  3. ALA Inhibits ABA-induced Stomatal Closure via Reducing H2O2 and Ca2+ Levels in Guard Cells

    PubMed Central

    An, Yuyan; Liu, Longbo; Chen, Linghui; Wang, Liangju

    2016-01-01

    5-Aminolevulinic acid (ALA), a newly proved natural plant growth regulator, is well known to improve plant photosynthesis under both normal and stressful conditions. However, its underlying mechanism remains largely unknown. Stomatal closure is one of the major limiting factors for photosynthesis and abscisic acid (ABA) is the most important hormone in provoking stomatal closing. Here, we showed that ALA significantly inhibited ABA-induced stomatal closure using wild-type and ALA-overproducing transgenic Arabidopsis (YHem1). We found that ALA decreased ABA-induced H2O2 and cytosolic Ca2+ accumulation in guard cells with stomatal bioassay, laser-scanning confocal microscopy and pharmacological methods. The inhibitory effect of ALA on ABA-induced stomatal closure was similar to that of AsA (an important reducing substrate for H2O2 removal), CAT (a H2O2-scavenging enzyme), DPI (an inhibitor of the H2O2-generating NADPH oxidase), EGTA (a Ca-chelating agent), and AlCl3 (an inhibitor of calcium channel). Furthermore, ALA inhibited exogenous H2O2- or Ca2+-induced stomatal closure. Taken together, we conclude that ALA inhibits ABA-induced stomatal closure via reducing H2O2, probably by scavenging, and Ca2+ levels in guard cells. Moreover, the inhibitive effect of ALA on ABA-induced stomatal closure was further confirmed in the whole plant. Finally, we demonstrated that ALA inhibits stomatal closing, but significantly improves plant drought tolerance. Our results provide valuable information for the promotion of plant production and development of a sustainable low-carbon society. PMID:27148309

  4. Well-defined hollow nanochanneled-silica nanospheres prepared with the aid of sacrificial copolymer nanospheres and surfactant nanocylinders

    NASA Astrophysics Data System (ADS)

    Kim, Young Yong; Hwang, Bora; Song, Sungjin; Ree, Brian J.; Kim, Yongjin; Cho, Seo Yeon; Heo, Kyuyoung; Kwon, Yong Ku; Ree, Moonhor

    2015-08-01

    A new approach for synthesizing well-defined hollow nanochanneled-silica nanosphere particles is demonstrated, and the structural details of these particles are described for the first time. Positively charged styrene copolymer nanospheres with a clean, smooth surface and a very narrow size distribution are synthesized by surfactant-free emulsion copolymerization and used as a thermal sacrificial core template for the production of core-shell nanoparticles. A surfactant/silica composite shell with a uniform thickness is successfully produced and deposited onto the polymeric core template by charge density matching between the polymer nanosphere template surface and the negatively charged silica precursors and then followed by selective thermal decomposition of the polymeric core and the surfactant cylinder domains in the shell, producing the hollow nanochanneled-silica nanospheres. Comprehensive, quantitative structural analyses collectively confirm that the obtained nanoparticles are structurally well defined with a hollow core and a shell composed of cylindrical nanochannels that provide facile accessibility to the hollow interior space. Overall, the hollow nanochanneled-silica nanoparticles have great potential for applications in various fields.A new approach for synthesizing well-defined hollow nanochanneled-silica nanosphere particles is demonstrated, and the structural details of these particles are described for the first time. Positively charged styrene copolymer nanospheres with a clean, smooth surface and a very narrow size distribution are synthesized by surfactant-free emulsion copolymerization and used as a thermal sacrificial core template for the production of core-shell nanoparticles. A surfactant/silica composite shell with a uniform thickness is successfully produced and deposited onto the polymeric core template by charge density matching between the polymer nanosphere template surface and the negatively charged silica precursors and then

  5. Layer-by-layer Synthesis and Transfer of Freestanding Conjugated Microporous Polymer Nanomembranes.

    PubMed

    Lindemann, Peter; Träutlein, Yannick; Wöll, Christof; Tsotsalas, Manuel

    2015-01-01

    CMP as large surface area materials have attracted growing interest recently, due to their high variability in the incorporation of functional groups in combination with their outstanding thermal and chemical stability, and low densities. However, their insoluble nature causes problems in their processing since usually applied techniques such as spin coating are not available. Especially for membrane applications, where the processing of CMP as thin films is desirable, the processing problems have hindered their commercial application. Here we describe the interfacial synthesis of CMP thin films on functionalized substrates via molecular layer-by-layer (l-b-l) synthesis. This process allows the preparation of films with desired thickness and composition and even desired composition gradients. The use of sacrificial supports allows the preparation of freestanding membranes by dissolution of the support after the synthesis. To handle such ultra-thin freestanding membranes the protection with sacrificial coatings showed great promise, to avoid rupture of the nanomembranes. To transfer the nanomembranes to the desired substrate, the coated membranes are upfloated at the air-liquid interface and then transferred via dip coating. PMID:26710232

  6. Monitoring ALA-induced PpIX photodynamic therapy in the rat esophagus using fluorescence and reflectance spectroscopy.

    PubMed

    Kruijt, Bastiaan; de Bruijn, Henriette S; van der Ploeg-van den Heuvel, Angelique; de Bruin, Ron W F; Sterenborg, Henricus J C M; Amelink, Arjen; Robinson, Dominic J

    2008-01-01

    The presence of phased protoporphyrin IX (PpIX) bleach kinetics has been shown to correlate with esophageal response to 5-aminolevulinic acid-based photodynamic therapy (ALA-PDT) in animal models. Here we confirm the existence of phased PpIX photobleaching by increasing the temporal resolution of the fluorescence measurements using the therapeutic illumination and long wavelength fluorescence detection. Furthermore fluorescence differential pathlength spectroscopy (FDPS) was incorporated to provide information on the effects of PpIX and tissue oxygenation distribution on the PpIX bleach kinetics during illumination. ALA at a dose of 200 mg kg(-1) was orally administered to 15 rats, five rats served as control animals. PDT was performed at an in situ measured fluence rate of 75 mW cm(-2) using a total fluence of 54 J cm(-2). Forty-eight hours after PDT the esophagus was excised and histologically examined for PDT-induced damage. Fluence rate and PpIX photobleaching at 705 nm were monitored during therapeutic illumination with the same isotropic probe. A new method, FDPS, was used for superficial measurement on saturation, blood volume, scattering characteristics and PpIX fluorescence. Results showed two-phased PpIX photobleaching that was not related to a (systematic) change in esophageal oxygenation but was associated with an increase in average blood volume. PpIX fluorescence photobleaching measured using FDPS, in which fluorescence signals are only acquired from the superficial layers of the esophagus, showed lower rates of photobleaching and no distinct phases. No clear correlation between two-phased photobleaching and histologic tissue response was found. This study demonstrates the feasibility of measuring fluence rate, PpIX fluorescence and FDPS during PDT in the esophagus. We conclude that the spatial distribution of PpIX significantly influences the kinetics of photobleaching and that there is a complex interrelationship between the distribution of PpIX and

  7. Photodynamic therapy (ALA-PDT) in the treatment of pathological states of the cornea

    NASA Astrophysics Data System (ADS)

    Switka-Wieclawska, Iwona; Kecik, Tadeusz; Kwasny, Miroslaw; Graczyk, Alfreda

    2003-10-01

    Each year an increasing amount of research is published on the use of photodynamic therapy in medicine. The most recent research has focused mostly on the use of photosensitizer called vertoporphyrin (Visudyne) is the treatment of subretinal neovascularization in age-related macular degeneration (AMD) or myopia, following a substantial amount of ophthalmology research mostly experimental on the application of the method in diagnosis and treatment of some eye tumors. In the Department of Ophthalmology of Polish Medical University in Warsaw, PDT was used as supplementary method in a selected group of patients with chronic virus ulcer of the cornea and keratopathies. During the treatment 5-aminolevulinic acid (5-ALA) was applied in ointment form as a photosensitizer activated with light wave of 633 nm. It appears, on the basis of the results obtained, that photodynamic therapy (ALA-PDT) may become in the future a valuable supplement to the methods being used at the present treating pathological states of the cornea.

  8. Photodynamic diagnosis following intravesical instillation of aminolevulinic acid (ALA): first clinical experiences in urology

    NASA Astrophysics Data System (ADS)

    Baumgartner, Reinhold; Kriegmair, M.; Stepp, Herbert G.; Lumper, W.; Heil, Peter; Riesenberg, Rainer; Stocker, Susanne; Hofstetter, Alfons G.

    1993-06-01

    Delta Aminolevulinic acid (ALA), a precursor of Protoporphyrin IX (PP IX) in hem biosynthesis has been topically applied in urinary bladders in order to study its potential as fluorescent tumor marker. Preclinical experiments have been performed on chemically induced tumors in rats, revealing a ratio of PP IX-fluorescence intensity up to 20:1 in tumors as compared to healthy urothelium. Synthesis of PP IX has been stimulated in 56 patients by intravesical instillation of a pH-neutral ALA-solution. After an incubation time of two to four hours strong red fluorescence was endoscopically observed even in tiny superficial tumors. Brightness and contrast allows visualization of early stage urothelial diseases with naked eyes and without the necessity suppressing background fluorescence or violet excitation light.

  9. Rotation of the Conduction Band Valleys in AlAs due to XX- XY Mixing

    NASA Astrophysics Data System (ADS)

    Im, Hyunsik; Klipstein, P. C.; Grey, R.; Hill, G.

    1999-11-01

    We report resonant magnetotunneling measurements of the energy dispersion near the third X symmetry subband edge in 60 and 70 Å thick AlAs quantum wells with GaAs barriers, grown along z = [001]. An elliptical constant energy surface is observed, oriented parallel to either [110] or [ 1¯10]. This rotation of 45° with respect to the bulk AlAs Fermi surface is explained by interface induced XX-XY mixing. Our results provide new insight into both γ-XZ and XX-XY mixing, showing conclusively that states with both X1 and X3 symmetry contribute. This contrasts with several recent theoretical studies in which the X1 contribution is zero.

  10. Interaction between Pro12Ala polymorphism of PPARγ2 and diet on adiposity phenotypes.

    PubMed

    Lapice, Emanuela; Vaccaro, Olga

    2014-12-01

    The aim of this report is to perform a systematic review and qualitative synthesis of the literature to address whether, and to what extent, diet modulates the effects of the Pro12Ala polymorphism of peroxisome proliferator-activated receptor gamma 2 (PPARγ2) on body weight and other measures of adiposity. A systematic search of the literature was conducted, wherein both observational and experimental studies of adults were reviewed. Overall, the results of the observational studies show little consistency. Methodological differences in their design, conduct and analysis may largely account for the apparently discrepant findings. This notwithstanding, the main picture that emerges is that the energy content and composition of the diet may affect BMI, body composition and metabolic parameters in Ala allele carriers more than in Pro/Pro homozygotes. In most studies, carriers of the Ala allele with an obesogenic lifestyle (i.e. high-energy, high-carbohydrate and, to some extent, high-fat diets) are more obese than Pro homozygotes. Well-designed intervention studies with a sufficiently large sample size consistently show that carriers of the Ala allele are more prone to weight loss when exposed to a healthy lifestyle; however, these individuals do not seem to retain these benefits when returning to a sedentary lifestyle and inadequate dieting behaviours. Some key questions in this area of research have emerged. Carefully designed and adequately powered studies are needed, particularly involving the development and validation of standardized tools for the assessment of dietary exposure, including the use of biomarkers, to move the field forward. PMID:25342491

  11. Conformational preferences of heterochiral peptides. Crystal structures of heterochiral peptides Boc-(D) Val-(D) Ala-Leu-Ala-OMe and Boc-Val-Ala-Leu-(D) Ala-OMe--enhanced stability of beta-sheet through C-H...O hydrogen bonds.

    PubMed

    Fabiola, G F; Bobde, V; Damodharan, L; Pattabhi, V; Durani, S

    2001-02-01

    The crystal structures of Boc-(D) Val-(D) Ala-Leu-Ala-OMe (vaLA) and Boc-Val-Ala-Leu-(D) Ala-OMe (VALa) have been determined. vaLA crystallises in space group P2(1),2(1),2(1), with a = 9.401 (4), b = 17.253 (5), c = 36.276 (9)A. V = 5,884 (3) A3, Z = 8, R = 0.086. VALa crystallises in space group P2(1) with a = 9.683 (9), b = 17.355 (7), c = 18.187 (9) A, beta = 95.84 (8) degrees , V = 3,040(4) A3, Z = 4, R = 0.125. There are two molecules in the asymmetric unit in antiparallel beta-sheet arrangement in both the structures. Several of the Calpha hydrogens are in hydrogen bonding contact with the carbonyl oxygen in the adjacent strand. An analysis of the observed conformational feature of D-chiral amino acid residues in oligopeptides, using coordinates of 123 crystal structures selected from the 1998 release of CSD has been carried out. This shows that all the residues except D-isoleucine prefer both extended and alphaL conformation though the frequence of occurence may not be equal. In addition to this, D-leucine, valine, proline and phenylalanine have assumed alphaR conformations in solid state. D-leucine has a strong preference for helical conformation in linear peptides whereas they prefer an extended conformation in cyclic peptides. PMID:11245253

  12. Feasibility of Raman spectroscopy in vitro after 5-ALA-based fluorescence diagnosis in the bladder

    NASA Astrophysics Data System (ADS)

    Grimbergen, M. C. M.; van Swol, C. F. P.; van Moorselaar, R. J. A.; Mahadevan-Jansen, A.,; Stone, N.

    2006-02-01

    Photodynamic diagnosis (PDD) has become popular in bladder cancer detection. Several studies have however shown an increased false positive biopsies rate under PDD guidance compared to conventional cystoscopy. Raman spectroscopy is an optical technique that utilizes molecular specific, inelastic scattering of light photons to interrogate biological tissues, which can successfully differentiate epithelial neoplasia from normal tissue and inflammations in vitro. This investigation was performed to show the feasibility of NIR Raman spectroscopy in vitro on biopsies obtained under guidance of 5-ALA induced PPIX fluorescence imaging. Raman spectra of a PPIX solution was measured to obtain a characteristic signature for the photosensitzer without contributions from tissue constituents. Biopsies were obtained from patients with known bladder cancer instilled with 50ml, 5mg 5-ALA two hours prior to trans-urethral resection of tumor (TURT). Additional biopsies were obtained at a fluorescent and non-fluorescent area, snap-frozen in liquid nitrogen and stored at -80 °C. Each biopsy was thawed before measurements (10sec integration time) with a confocal Raman system (Renishaw Gloucestershire, UK). The 830 nm excitation (300mW) source is focused on the tissue by a 20X ultra-long-working-distance objective. Differences in fluorescence background between the two groups were removed by means of a special developed fluorescence subtraction algorithm. Raman spectra from ALA biopsies showed different fluorescence background which can be effectively removed by a fluorescence subtraction algorithm. This investigation shows that the interaction of the ALA induced PPIX with Raman spectroscopy in bladder samples. Combination of these techniques in-vivo may lead to a viable method of optical biopsies in bladder cancer detection.

  13. Nuclear transcription factors: a new approach to enhancing cellular responses to ALA-mediated photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Maytin, Edward V.; Anand, Sanjay; Sato, Nobuyuki; Moore, Brian; Mack, Judith; Gasbarre, Christopher; Keevey, Samantha; Ortel, Bernhard; Sinha, Alok; Khachemoune, Amor

    2006-02-01

    Photodynamic therapy (PDT) using aminolevulinic acid (ALA) relies upon the uptake of ALA into cancer cells, where it is converted into a porphyrin intermediate, protoporphyrin IX (PpIX) that is highly photosensitizing. For large or resistant tumors, however, ALA/PDT is often not completely effective due to inadequate PpIX levels. Therefore, new approaches to enhance the intracellular production of PpIX are sought. Here, we describe a general approach to improve intracellular PpIX accumulation via manipulations that increase the expression of an enzyme, coproporphyrinogen oxidase (CPO), that is rate-determining for PpIX production. We show that nuclear hormones that promote terminal differentiation, e.g. vitamin D or androgens, can also increase the accumulation of PpIX and the amount of killing of the target cells upon exposure to light. These hormones bind to intracellular hormone receptors that translocate to the nucleus, where they act as transcription factors to increase the expression of target genes. We have found that several other transcription factors associated with terminal differentiation, including members of the CCAAT enhancer binding (C/EBP) family, and a homeobox protein named Hoxb13, are also capable of enhancing PpIX accumulation. These latter transcription factors appear to interact directly with the CPO gene promoter, resulting in enhanced CPO transcriptional activity. Our data in several different cell systems, including epithelial cells of the skin and prostate cancer cells, indicate that enhancement of CPO expression and PpIX accumulation represents a viable new approach toward improving the efficacy of ALA/PDT.

  14. Challenges for Community-Based Forest Management in the KoloAla Site Manompana

    NASA Astrophysics Data System (ADS)

    Urech, Zora Lea; Sorg, Jean-Pierre; Felber, Hans Rudolph

    2013-03-01

    Following the IUCN 5th World Congress on Protected Areas in 2003, the then-President of Madagascar decided to increase the area of Madagascar's protected areas from 1.7 to 6 million ha. To combine the aims of protection and timber production, a new concept was developed through the establishment of community-based forest management (CBFM) sites, called KoloAla. However, experience shows that similar management transfers to communities in Madagascar have only been successful in a very few cases. We aimed to explore the success to be expected of this new approach in the particular case of the Manompana corridor at Madagascar's eastern coast. In a first step, the readiness of the corridor's resource users for CBFM has been analysed according to the seven resource users' attributes developed by Ostrom that predict an effective self-organized resource management. In a second step, we explored how KoloAla addresses known challenges of Madagascar's CBFM. Analyses lead in a rather sober conclusion. Although KoloAla attempts to address the goals of poverty alleviation, biodiversity conservation and timber production under a single umbrella, it does so in a rather non-innovative way. Challenges with regard to the state's environmental governance, agricultural inefficiency and thus deforestation remain unsolved.

  15. Analysis of mitochondrial haplogroups associated with TTR Val30Ala familial amyloidotic polyneuropathy in Chinese patients.

    PubMed

    Liu, Jing-Yao; Jiang, Xin-Mei; Zhang, Min; Guo, Ying-Jie

    2012-12-01

    Extracellular deposition of abnormal transthyretin (TTR) amyloid fibrils leads to familial amyloidotic polyneuropathy (FAP), an inherited autsomal dominant disease. A large number of protein variants, each caused by a different point mutation in the TTR gene have been identified, including TTR Val30Ala. Since the age of onset, organ involvement, and disease progression are highly variable in FAP, even among individuals with the same TTR genetic variation. it is likely that other genetic and environmental factors influence FAP disease phenotype. One study has found a relationship between mitochondrial haplogroups and age of onset of FAP. In this study, we wondered whether certain mitochondrial haplogroups were associated with the cases of TTR Val30Ala FAP in a Chinese population. Mitochondrial haplogroup analysis was performed on a group of patients and their relatives and on a group of healthy controls. All FAP probands were unrelated in their maternal lineages. The chi-squared test for independence found no difference in mitochondrial haplogroup distribution between FAP and control groups. This is the first study reporting frequency and distribution of different haplogroups in FAP in a Chinese population. Although the study group was small, TTR Val30Ala FAP in China seems unrelated to mitochondrial haplogroup. PMID:22784244

  16. Characterization of a TK6-Bcl-xL gly-159-ala Human Lymphoblast Clone

    SciTech Connect

    Chyall, L.: Gauny, S.; Kronenberg, A.

    2006-01-01

    TK6 cells are a well-characterized human B-lymphoblast cell line derived from WIL-2 cells. A derivative of the TK6 cell line that was stably transfected to express a mutated form of the anti-apoptotic protein Bcl-xL (TK6-Bcl-xL gly-159- ala clone #38) is compared with the parent cell line. Four parameters were evaluated for each cell line: growth under normal conditions, plating efficiency, and frequency of spontaneous mutation to 6‑thioguanine resistance (hypoxanthine phosphoribosyl transferase locus) or trifluorothymidine resistance (thymidine kinase locus). We conclude that the mutated Bcl-xL protein did not affect growth under normal conditions, plating efficiency or spontaneous mutation frequencies at the thymidine kinase (TK) locus. Results at the hypoxanthine phosphoribosyl transferase (HPRT) locus were inconclusive. A mutant fraction for TK6‑Bcl-xL gly-159-ala clone #38 cells exposed to 150cGy of 160kVp x-rays was also calculated. Exposure to x-irradiation increased the mutant fraction of TK6‑Bcl-xL gly-159-ala clone #38 cells.

  17. Laser biospectroscopy and 5-ALA fluorescence navigation as a helpful tool in the meningioma resection.

    PubMed

    Potapov, A A; Goryaynov, S A; Okhlopkov, V A; Shishkina, L V; Loschenov, V B; Savelieva, T A; Golbin, D A; Chumakova, A P; Goldberg, M F; Varyukhina, M D; Spallone, A

    2016-07-01

    5-aminolevulinic acid (5-ALA) is a natural precursor of protoporphyrin IX (PP IX), which possesses fluorescent properties and is more intensively accumulated in tumor cells than in normal tissue. Therefore, the use of 5-ALA in the surgical treatment of intracranial tumors, particularly gliomas, has gained popularity in the last years, whereas its use in other intracranial pathological entities including meningiomas has been reported occasionally. This study describes a series of 28 patients with intracranial meningiomas, who were administered 5-ALA for a better visualization of tumor boundaries. Twelve patients underwent also laser spectroscopic analysis in order to confirm the visual impression of tumor tissue visualization. Bone infiltration was readily demonstrated. In one case, the tumor recurrence could have been prevented by removal of a tumor remnant, which would possibly have been better recognized if spectroscopic analysis had been used. Fluorescent navigation (FN) is a useful method for maximizing the radicality of meningioma surgery, particularly if the tumor infiltrates the bone, the skull base, and/or the surrounding structures. PMID:26887580

  18. Establishment of treatment parameters for ALA-PDT of plaque psoriasis

    NASA Astrophysics Data System (ADS)

    Stringer, Mark R.; Robinson, Dominic J.; Collins, P.

    1996-12-01

    We report an investigation into the use of photodynamic therapy (PDT), following topically applied 5-aminolaevulinic acid (ALA), as a treatment for plaque psoriasis. Treatment was performed 4 hours post-ALA, using white light doses of 2 - 16 J cm-2 delivered at 10 - 40 mW cm-2. The fluorescence emission of protoporphyrin IX was used as an indicator of the relative concentration of photosensitizer within each plaque before, during, and after therapy. Results show that the rate of sensitizer photo- oxidation is proportional to both pre-treatment fluorescence intensity and surface irradiance, consistent with a rate- equation analysis. A correlation of fluorescence measurements with clinical response of plaques indicates that the effectiveness of PDT is dominated by the level of PpIX at the onset of treatment, and is much less dependent upon light dose. Using these findings we have established a PDT treatment protocol that involves the delivery of 8 J cm-2 of white light, at a rate of 15 mW cm-2. The possibility of ALA-PDT being established as the therapy of choice is discussed.

  19. Comparative toxicities of aluminum and zinc from sacrificial anodes or from sulfate salt in sea urchin embryos and sperm.

    PubMed

    Caplat, Christelle; Oral, Rahime; Mahaut, Marie-Laure; Mao, Andrea; Barillier, Daniel; Guida, Marco; Della Rocca, Claudio; Pagano, Giovanni

    2010-09-01

    The toxicity of aluminum or zinc from either sacrificial anodes (SA) or their sulfate salts (SS) was evaluated in sea urchin (Paracentrotus lividus) embryos or sperm exposed to Al(III) or Zn(II) (SA or SS, 0.1-10 microM), scoring developmental defects (DDs), fertilization rate (FR), and mitotic abnormalities. A significant DD increase was observed in SS, but not SA Al(III)- and Zn(II)-exposed embryos vs. controls. Both Al(III) and Zn(II), up to 10 microM, from SA and SS, inhibited mitotic activity and induced mitotic aberrations in exposed embryos. SA-Al(III)-exposed sperm displayed a significant FR increase, unlike Al(III) sulfate overlapping with controls. Both SA-Zn(II) and Zn(II) sulfate sperm exposure resulted in a significant FR increase. The offspring of SA-Al(III)-exposed sperm displayed a significant DD decrease, unlike Al(III) sulfate exposure. Zinc sulfate sperm exposure resulted in a significant increase in offspring DDs, whereas SA-Zn(II) sperm exposure decreased DDs. Together, exposures to SA-dissolved Al(III) or Zn(II) resulted in lesser, if any toxicity, up to hormesis, compared to SS. Studies of metal speciation should elucidate the present results. PMID:20650532

  20. Templating Sol-Gel Hematite Films with Sacrificial Copper Oxide: Enhancing Photoanode Performance with Nanostructure and Oxygen Vacancies.

    PubMed

    Li, Yang; Guijarro, Néstor; Zhang, Xiaoli; Prévot, Mathieu S; Jeanbourquin, Xavier A; Sivula, Kevin; Chen, Hong; Li, Yongdan

    2015-08-12

    Nanostructuring hematite films is a critical step for enhancing photoelectrochemical performance by circumventing the intrinsic limitations on minority carrier transport. Herein, we present a novel sol-gel approach that affords nanostructured hematite films by including CuO as sacrificial templating agent. First, by annealing in air at 450 °C a film comprising an intimate mixture of CuO and Fe2O3 nanoparticles is obtained. The subsequent treatment with NaCl and annealing at 700 °C under Argon reveals a nanostructured highly crystalline hematite film devoid of copper. Photoelectrochemical investigations reveal that the incorporation of CuO as templating agent and the inert conditions employed during the annealing play a crucial role in the performance of the hematite electrodes. Mott-Schottky analysis shows a higher donor concentration when annealing in inert conditions, and even higher when combined with the NaCl treatment. These findings agree well with the presence of an oxygen-deficient shell on the material's surface evidenced by FT-IR and XPS measurements. Likewise, the incorporation of the CuO enhances the photocurrent obtained at 1.23 V from 0.55 to 0.8 mA·cm(-2) because of an improved nanostructure. Optimized films demonstrate an incident photon-to-current efficiency (IPCE) of 52% at 380 nm when applying 1.23 V versus RHE, and a faradaic efficiency for water splitting close to unity. PMID:26186065

  1. Nickel-pincer cofactor biosynthesis involves LarB-catalyzed pyridinium carboxylation and LarE-dependent sacrificial sulfur insertion.

    PubMed

    Desguin, Benoît; Soumillion, Patrice; Hols, Pascal; Hausinger, Robert P

    2016-05-17

    The lactate racemase enzyme (LarA) of Lactobacillus plantarum harbors a (SCS)Ni(II) pincer complex derived from nicotinic acid. Synthesis of the enzyme-bound cofactor requires LarB, LarC, and LarE, which are widely distributed in microorganisms. The functions of the accessory proteins are unknown, but the LarB C terminus resembles aminoimidazole ribonucleotide carboxylase/mutase, LarC binds Ni and could act in Ni delivery or storage, and LarE is a putative ATP-using enzyme of the pyrophosphatase-loop superfamily. Here, we show that LarB carboxylates the pyridinium ring of nicotinic acid adenine dinucleotide (NaAD) and cleaves the phosphoanhydride bond to release AMP. The resulting biscarboxylic acid intermediate is transformed into a bisthiocarboxylic acid species by two single-turnover reactions in which sacrificial desulfurization of LarE converts its conserved Cys176 into dehydroalanine. Our results identify a previously unidentified metabolic pathway from NaAD using unprecedented carboxylase and sulfur transferase reactions to form the organic component of the (SCS)Ni(II) pincer cofactor of LarA. In species where larA is absent, this pathway could be used to generate a pincer complex in other enzymes. PMID:27114550

  2. Sacrificial hydrogen generation from aqueous triethanolamine with Eosin Y-sensitized Pt/TiO2 photocatalyst in UV, visible and solar light irradiation.

    PubMed

    Chowdhury, Pankaj; Gomaa, Hassan; Ray, Ajay K

    2015-02-01

    In this paper, we have studied Eosin Y-sensitized sacrificial hydrogen generation with triethanolamine as electron donor in UV, visible, and solar light irradiation. Aeroxide TiO2 was loaded with platinum metal via solar photo-deposition method to reduce the electron hole recombination process. Photocatalytic sacrificial hydrogen generation was influenced by several factors such as platinum loading (wt%) on TiO2, solution pH, Eosin Y to Pt/TiO2 mass ratio, triethanolamine concentration, and light (UV, visible and solar) intensities. Detailed reaction mechanisms in visible and solar light irradiation were established. Oxidation of triethanolamine and formaldehyde formation was correlated with hydrogen generation in both visible and solar lights. Hydrogen generation kinetics followed a Langmuir-type isotherm with reaction rate constant and adsorption constant of 6.77×10(-6) mol min(-1) and 14.45 M(-1), respectively. Sacrificial hydrogen generation and charge recombination processes were studied as a function of light intensities. Apparent quantum yields (QYs) were compared for UV, visible, and solar light at four different light intensities. Highest QYs were attained at lower light intensity because of trivial charge recombination. At 30 mW cm(-2) we achieved QYs of 10.82%, 12.23% and 11.33% in UV, visible and solar light respectively. PMID:25441927

  3. Short-term supplementation of low-dose gamma-linolenic acid (GLA), alpha-linolenic acid (ALA), or GLA plus ALA does not augment LCP omega 3 status of Dutch vegans to an appreciable extent.

    PubMed

    Fokkema, M R; Brouwer, D A; Hasperhoven, M B; Martini, I A; Muskiet, F A

    2000-11-01

    Vegans do not consume meat and fish and have therefore low intakes of long chain polyunsaturated fatty acids (LCP). They may consequently have little negative feedback inhibition from dietary LCP on conversion of alpha -linolenic acid (ALA) to the LCP omega 3 eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids. We investigated whether supplementation of nine apparently healthy vegans with 2.01 g ALA (4 ml linseed oil), 1.17 g gamma-linolenic acid (GLA) (6 ml borage oil) or their combination increases the LCP omega 3 contents of erythrocytes (RBC) and platelets (PLT), and of plasma phospholipids (PL), cholesterol esters (CE) and triglycerides (TG). The supplements changed the dietary LA/ALA ratio (in g/g) from about 13.7 (baseline) to 6.8 (linseed oil), 14.3 (borage oil) and 6.4 (linseed + borage oil), respectively. ALA or GLA given as single supplements did not increase LCP omega 3 status, but their combination augmented LCP omega 3 (in CE) and EPA (in fasting TG) to a statistically significant, but nevertheless negligible, extent. We conclude that negative feedback inhibition by dietary LCP, if any, does not play an important role in the inability to augment notably DHA status by dietary ALA. The reach of a DHA plateau already at low dietary ALA intakes suggests that dietary DHA causes a non-functional DHA surplus, or is, alternatively, important for maintaining DHA status at a functionally relevant level. PMID:11090255

  4. Hollow Microneedles for Intradermal Injection Fabricated by Sacrificial Micromolding and Selective Electrodeposition

    PubMed Central

    Norman, James J.; Choi, Seong-O; Tong, Nhien T.; Aiyar, Avishek R.; Patel, Samirkumar R.; Prausnitz, Mark R.; Allen, Mark G.

    2012-01-01

    Limitations with standard intradermal injections have created a clinical need for an alternative, low-cost injection device. In this study, we designed a hollow metal microneedle for reliable intradermal injection and developed a high-throughput micromolding process to produce metal microneedles with complex geometries. To fabricate the microneedles, we laser-ablated a 70 μm × 70 μm square cavity near the tip of poly(lactic acid-co-glyoclic acid) (PLGA) microneedles. The master structure was a template for multiple micromolded PLGA replicas. Each replica was sputtered with a gold seed layer with minimal gold deposited in the cavity due to masking effects. In this way, nickel was electrodeposited selectively outside of the cavity, after which the polymer replica was dissolved to produce a hollow metal microneedle. Force-displacement tests showed the microneedles, with 12 μm thick electrodeposition, could penetrate skin with an insertion force 9 times less than their axial failure force. We injected fluid with the microneedles into pig skin in vitro and hairless guinea pig skin in vivo. The injections targeted 90% of the material within the skin with minimal leakage onto the skin surface. We conclude that hollow microneedles made by this simple microfabrication method can achieve targeted intradermal injection. PMID:23053452

  5. Delta-aminolevulinic acid dehydratase (ALAD) polymorphism in lead exposed Bangladeshi children and its effect on urinary aminolevulinic acid (ALA)

    SciTech Connect

    Tasmin, Saira; Furusawa, Hana; Ahmad, Sk. Akhtar; Watanabe, Chiho

    2015-01-15

    Background and objective: Lead has long been recognized as a harmful environmental pollutant. People in developing countries like Bangladesh still have a higher risk of lead exposure. Previous research has suggested that the delta-aminolevulinic acid dehydratase (ALAD) genotype can modify lead toxicity and individual susceptibility. As children are more susceptible to lead-induced toxicity, this study investigated whether the ALAD genotype influenced urinary excretion of delta-aminolevulinic acid (U-ALA) among children exposed to environmental lead in Bangladesh. Methods: Subjects were elementary schoolchildren from a semi-urban industrialized area in Bangladesh. A total of 222 children were studied. Blood and urine were collected to determine ALAD genotypes, blood lead levels and urinary aminolevulinic acid (U-ALA). Results: The mean BPb level was 9.7 µg/dl for the study children. BPb was significantly positively correlated with hemoglobin (p<0.01). In total, allele frequency for ALAD 1 and 2 was 0.83 and 0.17 respectively. The mean U-ALA concentration was lower in ALAD1-2/2-2 carriers than ALAD1-1 carriers for boys (p=0.001). But for girls, U-ALA did not differ significantly by genotype (p=0.26). When U-ALA was compared by genotype at the same exposure level in a multiple linear regression analysis, boys who were ALAD1-2/2-2 carriers still had a lower level of U-ALA compared to ALAD1-1carriers. Conclusion: This study provides information about the influence of ALAD polymorphism and its association with U-ALA in Bangladeshi children. Our results indicate that the ALAD1-2/2-2 genotype may have a protective effect in terms of U-ALA for environmentally lead exposed boys. - Highlights: • High blood lead level for the environmentally exposed schoolchildren. • BPb was significantly correlated with U-ALA and Hb. • Effect of ALAD genotype on U-ALA is differed by sex. • Lower U-ALA in ALAD2 than ALAD1 carriers only for boys at same exposure.

  6. Microsurgical Reconstruction of the Nasal Ala using a Composite Auricular Graft Based on the Superficial Temporal Vessels.

    PubMed

    Stillaert, F; Van Landuyt, K; Blondeel, Ph; Monstrey, S

    2015-01-01

    Full-thickness defects of the nasal ala can be challenging to reconstruct. The original texture, color and shape of this specific aesthetic unit requires careful planning of the surgical approach and technique in order to minimize donor-site morbidity and repetitive procedures. We describe the use of the chondrocutaneous composite auricular graft to -reconstruct a full-thickness defect of the ala of the nose with a successful and aesthetically pleasing outcome. PMID:26560009

  7. In-situ optical monitoring of AlAs wet oxidation using a novel low-temperature low-pressure steam furnace design

    SciTech Connect

    Feld, S.A.; Loehr, J.P.; Sherriff, R.E.; Wiemeri, J.; Kaspi, R.

    1998-02-01

    To reproducibly define small features by oxidizing AlGaAs layers, it is essential to have good control over the oxidation reaction. The authors have integrated a glass viewport into a low-pressure (5 torr) cold-walled oxidation chamber to enable in situ optical monitoring of the sample during oxidation. To gain additional control, they reduced the oxidation temperature to 325 C, consequently slowing the oxidation rate to 2 {micro}m/h. Real-time in situ optical measurements of AlAs oxidation rates were performed using this system and the results were compared with a standard model. Oxide-semiconductor distributed Bragg reflectors (DBRs) were also fabricated and measured, yielding highly reflective mirrors suitable for vertical-cavity surface-emitting laser (VCSEL) fabrication.

  8. Pro12Ala polymorphism of the peroxisome proliferator-activated receptor γ2 in patients with fatty liver diseases

    PubMed Central

    Rey, Johannes W; Noetel, Andrea; Hardt, Aline; Canbay, Ali; Alakus, Hakan; zur Hausen, Axel; Dienes, Hans Peter; Drebber, Uta; Odenthal, Margarete

    2010-01-01

    AIM: To test the occurrence of the Pro12Ala mutation of the peroxisome proliferator-activated receptor-γ (PPARγ)2-gene in patients with non-alcoholic fatty liver disease (NAFLD) or alcoholic fatty liver disease (AFLD). METHODS: DNA from a total of 622 specimens including 259 blood samples of healthy blood donors and 363 histologically categorized liver biopsies of patients with NAFLD (n = 263) and AFLD (n = 100) were analyzed by Real-time polymerase chain reaction using allele-specific probes. RESULTS: In the NAFLD and the AFLD collective, 3% of the patients showed homozygous occurrence of the Ala12 PPARγ2-allele, differing from only 1.5% cases in the healthy population. In NAFLD patients, a high incidence of the Ala12 mutant was not associated with the progression of fatty liver disease. However, we observed a significantly higher risk (odds ratio = 2.50, CI: 1.05-5.90, P = 0.028) in AFLD patients carrying the mutated Ala12 allele to develop inflammatory alterations. The linkage of the malfunctioning Ala12-positive PPARγ2 isoform to an increased risk in patients with AFLD to develop severe steatohepatitis and fibrosis indicates a more prominent anti-inflammatory impact of PPARγ2 in progression of AFLD than of NAFLD. CONCLUSION: In AFLD patients, the Pro12Ala single nuclear polymorphism should be studied more extensively in order to serve as a novel candidate in biomarker screening for improved prognosis. PMID:21155004

  9. Comparsion of light dose on topical ALA-mediated photodynamic therapy for DMBA-induced hamster buccal pouch premalignant lesions

    NASA Astrophysics Data System (ADS)

    Yang, Deng-Fu; Tseng, Meng-Ke; Liu, Chung-Ji; Hsu, Yih-Chih

    2012-03-01

    Oral cancer has becomes the most prominent male cancer disease due to the local betel nut chewing habit combing with smoking and alcohol-drinking lifestyle. In order to minimize the systemic phototoxic effect of 5-aminolevulinic acid (ALA), this study was designed to use a topical ALA-mediated PDT for treatment of DMBA-induced hamster buccal pouch cancerous lesions. DMBA was applied to one of the buccal pouches of hamsters thrice a week for 8 to 10 weeks. Precancerous lesions were induced and proven by histological examination. These DMBA-induced cancerous lesions were used for testing the efficacy of topical ALA -mediated PDT. We found that ALA reached its peak level in cancerous lesions about 2.5 hrs after topical application of ALA gel. The precancerous lesions in hamsters were then treated with topical ALA -mediated PDT with light exposure dose of 75 and 100 J/cm2 using LED 635 nm Wonderlight device. It is suggesting that optimization of the given light dose is critical to the success of PDT results.

  10. Method for forming a layer of synthetic corrosion products on tubing surfaces

    DOEpatents

    Lane, Michael H.; Salamon, Eugene J. M.

    1996-01-01

    A method is provided for forming a synthetic corrosion product layer on tube surfaces. The method utilizes two dissimilar materials with different coefficients of thermal expansion. An object tube and sacrificial tube are positioned one inside the other such that an annular region is created between the two tubes' surfaces. A slurry of synthetic corrosion products is injected into this annular region and the assembly is heat treated. This heat causes the tubes to expand, the inner tube with the higher coefficient of expansion expanding more than the outer tube, thereby creating internal pressures which consolidate the corrosion products and adhere the corrosion products to the tubing surfaces. The sacrificial tube may then be removed by conventional chemical etching or mechanical methods.

  11. Disruption of the blood brain barrier following ALA mediated photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Hirschberg, Henry; Peng, Qian; Uzal, Francisco A.; Chighvinadze, David; Zhang, Michelle J.; Madsen, Steen J.

    2008-02-01

    Introduction: Failure of treatment for high grade gliomas is usually due to local recurrence at the site of surgical resection indicating that a more aggressive form of local therapy, such as PDT, could be of benefit. PDT causes damage to tumor cells as well as degradation of the blood brain barrier (BBB). We have evaluated the ability of ALA mediated PDT to open the BBB in rats. This will permit access of chemotherapeutic agents to brain tumor cells remaining in the resection cavity wall, but limit their penetration into normal brain remote from the site of illumination. Materials and Methods: ALA-PDT was performed on non tumor bearing inbred Fisher rats at increasing fluence levels. T2 weighted MRI scans were used to evaluate edema formation and post-contrast T I MRI scans were used to monitor the degree BBB disruption which could be inferred from the intensity and volume of the contrast agent visualized. Results. PDT at increasing fluence levels between 9J and 26J demonstrated an increasing contrast flow rate. No effect on the BBB was observed if 26J of light were given in the absence of ALA. A similar increased contrast volume was observed with increasing fluence rates. The BBB was found to be disrupted 2hrs. following PDT and 80-100% restored 72hrs later. Conclusion: PDT was highly effective in opening the BBB in a limited region of the brain. The degradation of the BBB was temporary in nature, opening rapidly following treatment and significantly restored during the next 72 hrs.

  12. Hydrologic Modelling of Katsina-Ala River Basin: AN Emerging Scenario from Lake Nyos Threat

    NASA Astrophysics Data System (ADS)

    Akinyede, J. O.; Babamaaji, R.; Vaatough, M.; Adepoju, K. A.

    2012-07-01

    Understanding the hydrologic system surrounding crater lakes is of great importance for prevention of flooding damages, conservation of ecological environment, and assessment of socio-economic impact of dam failure on the civilians in the downstream regions. Lake Nyos is a crater lake formed by volcanic activities at the Oku volcanic field on the Cameroon Volcanic Line. It is a freshwater lake with a maximum depth of 200 meter. In 1986, a limnic eruption at the lake emitted 1.6 million tonnes of carbon dioxide from the bottom of saturated water into the air and suffocated up to 1,800 people and 3,500 livestock at nearby villages. The lake waters are held in place by a natural dam composed of loosely consolidated volcanic rock, which is now at the verge of collapse due to accelerated erosion. This study was carried out to determine the flood risks and vulnerability of population and infrastructure along Katsina-Ala drainage basins. The project integrated both satellite images and field datasets into a hydrologic model for Katsina-Ala River Basin and its vicinity including the Lake Nyos. ArcHydro was used to construct a hydrologic database as 'data models' and MIKE SHE was employed to conduct hydrologic simulations. Vulnerable infrastructures, population and socio-economic activities were identified to assist the Federal and State governments in disaster mitigation and management plans. The result of the project provides comprehensive knowledge of hydrologic system of Katsina-Ala drainage basin to mitigate potential future disasters from a potential dam failure and manage water resources against such disasters.

  13. Imiquimod immunotherapy and ALA photodynamic therapy combination for the treatment of genital bowenoid papulosis

    NASA Astrophysics Data System (ADS)

    Wang, Xiu-Li; Wang, Hong-Wei; Guo, Ming-Xia; Huang, Zheng

    2007-02-01

    To investigate the feasibility and efficacy of combination of imiquimod immunotherapy and 5- aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) for the treatment of genital bowenoid papulosis (BP). A total of twenty seven BP patients were randomized into two groups: (I) fifteen patients (12 male and 3 female, age 22-56 years old) were treated with topical application of 5% imiquimod cream (three times a week) and ALA-PDT (100 J/cm2 at 100 mW/cm2, once a week) for 1-4 times in one week interval. (II) Twelve patients (6 male and 6 female, age 29-58 years old) were treated with CO II laser vaporization as a control. Patients were followed up for 3 to 12 months. Results: In combined therapy group, 60% (9/15) patients showed complete remission and only one recurred (11.1%) during follow up. Local side effects included mild erythema, edema, erosion and burning and/or stinging sensation. No systemic side effect was found. In CO II laser vaporization group, 83.3% (10/12) patients showed complete remission. However, recurrence occurred in 6 patients (60.0%). Local side effects included mild to moderate edema, erosion, ulceration, delayed healing, prolonged pain and scarring. The difference of recurrence rate between two groups was statistically significant (P < 0.05). Topical application of imiquimod cream and ALA-PDT is safe, effective and associated with low recurrence and less side effect. Its true clinical value needs to be further investigated by a long-term follow-up of large scale trial.

  14. Reduction of the invasiveness of human glioma cells by ALA-mediated photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Hirschberg, Henry; Sun, Chung-Ho; Madsen, Steen

    2006-02-01

    Introduction: High grade gliomas are characterised by rapid and invasive growth, that cause massive tissue destruction at both the tumour- brain boarder as well as in regions remote from the tumor core. Eradication or inhibition of infiltrating glioma cells poses a significant clinical challenge that is unlikely to be solved using conventional treatment regimens consisting of ionizing radiation and chemotherapeutic agents. In this study we evaluated the effects of ALA mediated photodynamic therapy (PDT) on the invesivness of human glioma cells migrating from implanted multicell tumor spheroids. Materials and method 3-400nm diameter tumor spheroids, derived from the human glioma cell line ACBT, were implanted into a gel matrix of collagen type I. 24 hours following implantation there was a significant invasion of the surrounding gel by individual tumor cells to an average distance of 400nm. The cultures were incubated in increasing concentrations of ALA (10-1000 ug/ml) for four hours and then exposed to 635nm laser light in a titration of both fluence level and fluence rate. Results Fluences of 25J/cm2 were clearly cytotoxic for both the infiltrating cells as well as the spheroids at all ALA concentrations. Fluence levels of 6J did not stop the spheroid growth or prove cytotoxic to the glioma cells that had previously migrated into the gel, in a majority of cultures but inhibited further migration of the cells by 80-90% compared to control. Conclusion: Measurement of cell survival and cell proliferation indices seemed to indicate a direct migratory inhibition effect on the invading cells and not cytotoxicity as the most likely mechanism for this observation.

  15. The role of D1-Ala344 in charge stabilization and recombination in Photosystem II.

    PubMed

    Cser, Krisztián; Diner, Bruce A; Nixon, Peter J; Vass, Imre

    2005-12-01

    The Ala344 residue of the D1 protein has been identified as a crucial residue of the catalytic cluster of the water-oxidizing complex, however, its function has not been fully clarified. Here we have used thermoluminescence and flash-induced chlorophyll fluorescence measurements to characterize the effect of the D1-Ala344stop mutation on the electron transport of Photosystem II in intact cells of the cyanobacterium Synechocystis 6803. Although the mutant cannot grow photoautotrophically it shows flash-induced thermoluminescence and chlorophyll fluorescence signals reflecting the stabilization of negative and positive charges on the Q(A) and Q(B) quinone electron acceptors, and stable Photosystem II donors, respectively. Decay of flash induced chlorophyll fluorescence yield is multiphasic in the presence of 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU), with 6 ms, 350 ms, and 26 s time constants. When cells are illuminated with repetitive flashes, fired at 1 ms intervals, the 6 ms phase is gradually decreased with the concomitant increase of the 350 ms phase. After 45 min dark adaptation of mutant cells the 6 ms and 350 ms phases were significantly decreased and a very slow decaying component was formed. Flash induced oscillation of the thermoluminescence B band, which reflects the redox cycling of the water-oxidizing complex in the wild-type cells, was completely abolished in the D1-Ala344stop mutant. The results demonstrate that low efficiency photooxidation of Mn occurs in about 60% of the PSII centers. The photooxidizable Mn is unstable in the dark, and formation of higher S states is inhibited. In addition, the Q(A) to Q(B) electron transfer step is slowed down as an indirect consequence of the donor side modification. Our data indicate that the stabilization of a Mn ion by the alpha-carboxylate chain of the D1-Ala344 residue might represent one of the final steps in the assembly of functional catalytic sites for water oxidation. PMID:16307121

  16. Phonon-drag thermopower in anisotropic AlAs quantum wells

    SciTech Connect

    Lehmann, Dietmar; Tsaousidou, Margarita; Kubakaddi, Shrishail

    2013-12-04

    In the present work we have developed a generalized theory of phonon-drag thermopower Ŝ{sup g} for a highly anisotropic two-dimensional electron gas. For electrons confined in AlAs quantum wells we calculate Ŝ{sup g} as function of temperature. We show that Ŝ{sup g} exhibits a strong anisotropic behavior depending on valley occupancy which can be tuned by well width and strain. Also a great enhancement of Ŝ{sup g} is observed compared to GaAs quantum wells.

  17. Anomalous giant piezoresistance in AlAs 2D electron systems with antidot lattices.

    PubMed

    Gunawan, O; Gokmen, T; Shkolnikov, Y P; De Poortere, E P; Shayegan, M

    2008-01-25

    An AlAs two-dimensional electron system patterned with an antidot lattice exhibits a giant piezoresistance effect at low temperatures, with a sign opposite to the piezoresistance observed in the unpatterned region. We suggest that the origin of this anomalous giant piezoresistance is the nonuniform strain in the antidot lattice and the exclusion of electrons occupying the two conduction-band valleys from different regions of the sample. This is analogous to the well-known giant magnetoresistance effect, with valley playing the role of spin and strain the role of magnetic field. PMID:18233015

  18. Dietary polyunsaturated fatty acids and the Pro12Ala polymorphisms of PPARG regulate serum lipids through divergent pathways: a randomized crossover clinical trial.

    PubMed

    Pihlajamäki, Jussi; Schwab, Ursula; Kaminska, Dorota; Ågren, Jyrki; Kuusisto, Johanna; Kolehmainen, Marjukka; Paananen, Jussi; Laakso, Markku; Uusitupa, Matti

    2015-11-01

    Human and animal studies suggest an interaction between the Pro12Ala polymorphism of PPARG and dietary fat. In this randomized crossover clinical trial, we investigated whether subjects with the Pro12Pro and Ala12Ala genotypes of PPARG respond differently to a diet supplemented with high saturated (SAFA) or polyunsaturated fatty acid (PUFA).We recruited non-diabetic men from a population-based METSIM study (including 10,197 men) to obtain men with the Ala12Ala and the Pro12Pro genotypes matched for age and body mass index. Seventeen men with the Pro12Pro genotype and 14 with the Ala12Ala genotype were randomized to both a PUFA diet and a SAFA diet for 8 weeks in a crossover setting. Serum lipids and adipose tissue mRNA expression were measured during the diet intervention. At baseline, subjects with the Ala12Ala genotype had higher levels of HDL cholesterol and lower levels of LDL cholesterol, total triglycerides, and apolipoprotein B compared to those subjects with the Pro12Pro genotype (P < 0.05, FDR < 0.1). The Ala12Ala genotype also associated with higher mRNA expression of PPARG2, LPIN1, and SREBP-1c compared to participants with the Pro12Pro genotype (FDR < 0.001). On the other hand, PUFA diet resulted in lower levels of fasting glucose, total cholesterol, total triglycerides, and apolipoprotein B (P < 0.05, FDR < 0.1) but did not affect PPARG2 mRNA expression in adipose tissue. We conclude that individuals with the Pro12Pro genotype, with higher triglyceride levels at baseline, are more likely to benefit from the PUFA diet. However, the beneficial effects of dietary PUFA and the Ala12Ala genotype of PPARG on serum lipids are mediated through divergent mechanisms. PMID:26446033

  19. Atomic layer epitaxy

    NASA Astrophysics Data System (ADS)

    Goodman, Colin H. L.; Pessa, Markus V.

    1986-08-01

    Atomic layer epitaxy (ALE) is not so much a new technique for the preparation of thin films as a novel modification to existing methods of vapor-phase epitaxy, whether physical [e.g., evaporation, at one limit molecular-beam epitaxy (MBE)] or chemical [e.g., chloride epitaxy or metalorganic chemical vapor deposition (MOCVD)]. It is a self-regulatory process which, in its simplest form, produces one complete molecular layer of a compound per operational cycle, with a greater thickness being obtained by repeated cycling. There is no growth rate in ALE as in other crystal growth processes. So far ALE has been applied to rather few materials, but, in principle, it could have a quite general application. It has been used to prepare single-crystal overlayers of CdTe, (Cd,Mn)Te, GaAs and AlAs, a number of polycrystalline films and highly efficient electroluminescent thin-film displays based on ZnS:Mn. It could also offer particular advantages for the preparation of ultrathin films of precisely controlled thickness in the nanometer range and thus may have a special value for growing low-dimensional structures.

  20. Effects of Ala-Gln feeding strategies on growth, metabolism, and crowding stress resistance of juvenile Cyprinus carpio var. Jian.

    PubMed

    Chen, Xiu-Mei; Guo, Gui-Liang; Sun, Li; Yang, Qiu-Shi; Wang, Gui-Qin; Qin, Gui-Xin; Zhang, Dong-Ming

    2016-04-01

    The present study was conducted to evaluate the effects of different L-alanyl-l-glutamine (Ala-Gln) feeding strategies on the growth performance, metabolism and crowding stress resistance related parameters in juvenile Jian carp (Cyprinus carpio var. Jian) under crowded condition (80 g/L). Juvenile Jian carp (initial weight 26.1 ± 0.6 g) were distributed into five groups which fed with graded concentrations (0% or 1.0%) of Ala-Gln for eight weeks. Control group (I, 0/0) fed with control diet (0% Ala-Gln) throughout the feeding trial. The other four groups employed different control and experimental diet feeding strategies ranging from two weeks control diet fed and two weeks experimental diet (1% Ala-Gln) fed (II, 0/2) to eight weeks experimental diet fed (V, 4/4). Results revealed that Mean weight gain (MEG) under all different feeding strategies of Ala-Gln were significantly higher than that of the control group (p < 0.05), and MEG of group II (201.90%) was even higher than that of group IV (184.70%). Liver glycogen and blood total protein of groups II, III and V were significantly higher than that in groups I and IV (p < 0.05). The highest level of serum thyroxine (10.07 ng/ml), insulin-like growth factor-I (52.40 ng/ml) and insulin (9.73 μ IU/mL) were observed in group V. However, diet supplemented with Ala-Gln did not affect the levels of serum glucose, cortisol and catecholamine in fish. The mRNA expression of GR1a, GR1b and GR2 were also significantly changed in Ala-Gln supplementation groups compared with control group (p < 0.05). After fish intraperitoneally injected with virulent Aeromonas hydrophila, the fish survival rates were significantly increased in all Ala-Gln supplementation groups compared with control group (p < 0.05). Results from the present experiment showed the importance of dietary supplementation of Ala-Gln in benefaction of the growth performance, metabolism and crowding stress resistance in Jian carp breeding. The

  1. Structural and kinetic studies on the Ser101Ala variant of choline oxidase: Catalysis by compromise

    SciTech Connect

    Finnegan, S.; Orville, A.; Yuan, H.; Wang, Y.-F.; Weber, I. T.; Gadda, G.

    2010-09-15

    The oxidation of choline catalyzed by choline oxidase includes two reductive half-reactions where FAD is reduced by the alcohol substrate and by an aldehyde intermediate transiently formed in the reaction. Each reductive half-reaction is followed by an oxidative half-reaction where the reduced flavin is oxidized by oxygen. Here, we have used mutagenesis to prepare the Ser101Ala mutant of choline oxidase and have investigated the impact of this mutation on the structural and kinetic properties of the enzyme. The crystallographic structure of the Ser101Ala enzyme indicates that the only differences between the mutant and wild-type enzymes are the lack of a hydroxyl group on residue 101 and a more planar configuration of the flavin in the mutant enzyme. Kinetics established that replacement of Ser101 with alanine yields a mutant enzyme with increased efficiencies in the oxidative half-reactions and decreased efficiencies in the reductive half-reactions. This is accompanied by a significant decrease in the overall rate of turnover with choline. Thus, this mutation has revealed the importance of a specific residue for the optimization of the overall turnover of choline oxidase, which requires fine-tuning of four consecutive half-reactions for the conversion of an alcohol to a carboxylic acid.

  2. AlaScan: A Graphical User Interface for Alanine Scanning Free-Energy Calculations.

    PubMed

    Ramadoss, Vijayaraj; Dehez, François; Chipot, Christophe

    2016-06-27

    Computation of the free-energy changes that underlie molecular recognition and association has gained significant importance due to its considerable potential in drug discovery. The massive increase of computational power in recent years substantiates the application of more accurate theoretical methods for the calculation of binding free energies. The impact of such advances is the application of parent approaches, like computational alanine scanning, to investigate in silico the effect of amino-acid replacement in protein-ligand and protein-protein complexes, or probe the thermostability of individual proteins. Because human effort represents a significant cost that precludes the routine use of this form of free-energy calculations, minimizing manual intervention constitutes a stringent prerequisite for any such systematic computation. With this objective in mind, we propose a new plug-in, referred to as AlaScan, developed within the popular visualization program VMD to automate the major steps in alanine-scanning calculations, employing free-energy perturbation as implemented in the widely used molecular dynamics code NAMD. The AlaScan plug-in can be utilized upstream, to prepare input files for selected alanine mutations. It can also be utilized downstream to perform the analysis of different alanine-scanning calculations and to report the free-energy estimates in a user-friendly graphical user interface, allowing favorable mutations to be identified at a glance. The plug-in also assists the end-user in assessing the reliability of the calculation through rapid visual inspection. PMID:27214306

  3. The Simplified Aircraft-Based Paired Approach With the ALAS Alerting Algorithm

    NASA Technical Reports Server (NTRS)

    Perry, Raleigh B.; Madden, Michael M.; Torres-Pomales, Wilfredo; Butler, Ricky W.

    2013-01-01

    This paper presents the results of an investigation of a proposed concept for closely spaced parallel runways called the Simplified Aircraft-based Paired Approach (SAPA). This procedure depends upon a new alerting algorithm called the Adjacent Landing Alerting System (ALAS). This study used both low fidelity and high fidelity simulations to validate the SAPA procedure and test the performance of the new alerting algorithm. The low fidelity simulation enabled a determination of minimum approach distance for the worst case over millions of scenarios. The high fidelity simulation enabled an accurate determination of timings and minimum approach distance in the presence of realistic trajectories, communication latencies, and total system error for 108 test cases. The SAPA procedure and the ALAS alerting algorithm were applied to the 750-ft parallel spacing (e.g., SFO 28L/28R) approach problem. With the SAPA procedure as defined in this paper, this study concludes that a 750-ft application does not appear to be feasible, but preliminary results for 1000-ft parallel runways look promising.

  4. Aminolevulinic acid (ALA)-assisted photodynamic diagnosis of subclinical and latent HPV infection of external genital region.

    PubMed

    Wang, Hong-Wei; Wang, Xiu-Li; Zhang, Ling-Lin; Guo, Ming-Xia; Huang, Zheng

    2008-12-01

    The relatively high recurrence rate of genital warts can be attributed to the unsuccessful elimination of viruses in areas of subclinical and latent infection. Therefore, the identification and treatment of the subclinical and latent infection is a key to reduce the recurrence. The goal of this study is to investigate the usefulness of 5-aminolevulinic acid (ALA)-assisted in situ fluorescence diagnosis of subclinical lesion and latent HPV infection. A total of 30 patients with histologically confirmed genital warts (condylomata acuminata) were subjected to topical application of ALA, acetic acid test, histopathologic examination and HPV DNA subtyping. Topical application of ALA was performed by applying 20% ALA cream to the lesion plus 2-cm margin for 2h followed by fluorescence examination. Correlations between histopathologic examination, aceto-whitening test, HPV DNA subtyping and fluorescence were examined. All warty lesions and subclinical lesions (n=25) showed red fluorescence and harbored HPV DNA (HPV6 or 11). Latent HPV infections at 0.5-2 cm away from the warty lesion also showed red fluorescence. Nonspecific fluorescence was associated with mucosa, inflammatory infiltration and erosive lesion. ALA-assisted photodynamic diagnosis could be employed for the detection of the lesion and subclinical lesion of genital warts. It is also useful in detecting latent HPV infection. PMID:19356665

  5. Comparative in vivo study of precursors of PpIX (ALA and MAL) used topically in photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Rego, Raquel F.; Inada, Natalia M.; Ferreira, Juliana; Araújo-Moreira, Fernando M.; Bagnato, Vanderlei S.

    2009-06-01

    The efficacy of Photodynamic Therapy (PDT) combined with aminolevulinic acid (ALA) or methyl aminolevulinate (MAL) in treatment of cancer has been studied for over ten years. However, there is no established dose for the topical use of these drugs in PDT. The purpose of this study was the comparison of induced PDT response of ALAsense (5-aminolevulinic acid - ALA) and Metvix (methyl aminolevulinate - MAL). Depth of necrosis induced by PDT was analyzed in normal liver of male Wistar rats, using different light doses and topical application of both PpIX precursors - ALA and MAL. PDT was performed with a diode laser at 630 nm with different doses of light (20, 50, 100 and 200 J/cm2), and intensity of 250 mW/cm2. Depth of necrosis analysis was used to calculate the threshold dose for each drug. The results showed that MAL-PDT presented a better response than ALA-PDT, mainly due to formulation differences. Moreover, the ability of the ALA PpIX production was more efficient.

  6. Self-sacrificial template-induced modulation of conjugated microporous polymer microcapsules and shape-dependent enhanced photothermal efficiency for ablation of cancer cells.

    PubMed

    Tan, Jing; Wan, Jiaxun; Guo, Jia; Wang, Changchun

    2015-12-21

    The one-step synthesis of nanoscale conjugated microporous polymer (NCMP) capsules is presented by using PMAA microspheres as self-sacrificial templates. Precise control over the morphology, nanostructure and shell thickness makes the NCMPs have a tunable NIR absorption ability and a shape-dependent photothermal conversion efficiency. Upon exposure to 808 nm light, they rapidly generate heat (NCMP concentration: 100 μg mL(-1)) and cause thermal ablation of HeLa cells with less than 10% viability. PMID:26465074

  7. Properties of myelin altered peptide ligand cyclo(87-99)(Ala91,Ala96)MBP87-99 render it a promising drug lead for immunotherapy of multiple sclerosis.

    PubMed

    Deraos, George; Rodi, Maria; Kalbacher, Hubert; Chatzantoni, Kokona; Karagiannis, Fotios; Synodinos, Loukas; Plotas, Panayiotis; Papalois, Apostolos; Dimisianos, Nikolaos; Papathanasopoulos, Panagiotis; Gatos, Dimitrios; Tselios, Theodore; Apostolopoulos, Vasso; Mouzaki, Athanasia; Matsoukas, John

    2015-08-28

    Multiple sclerosis (MS) is an inflammatory, demyelinating disease of the central nervous system, and it has been established that autoreactive T helper (Th) cells play a crucial role in its pathogenesis. Myelin basic protein (MBP) epitopes are major autoantigens in MS, and the sequence MBP87-99 is an immunodominant epitope. We have previously reported that MBP87-99 peptides with modifications at principal T-cell receptor (TCR) contact sites suppressed the induction of EAE symptoms in rats and SJL/J mice, diverted the immune response from Th1 to Th2 and generated antibodies that did not cross react with the native MBP protein. In this study, the linear and cyclic analogs of the MBP87-99 epitope, namely linear (Ala91,Ala96)MBP87-99 (P2) and cyclo(87-99)(Ala91,Ala96)MBP87-99 (P3), were evaluated for their binding to HLA-DR4, stability to lysosomal enzymes, their effect on cytokine secretion by peripheral blood mononuclear cells (PBMC) derived from MS patients or healthy subjects (controls), and their effect in rat EAE. P1 peptide (wild-type, MBP87-99) was used as control. P2 and P3 did not alter significantly the cytokine secretion by control PBMC, in contrast to P1 that induced moderate IL-10 production. In MS PBMC, P2 and P3 induced the production of IL-2 and IFN-γ, with a simultaneous decrease of IL-10, whereas P1 caused a reduction of IL-10 secretion only. The cellular response to P3 indicated that cyclization did not affect the critical TCR contact sites in MS PBMC. Interestingly, the cyclic P3 analog was found to be a stronger binder to HLA-DR4 compared to linear P2. Moreover, cyclic P3 was more stable to proteolysis compared to linear P2. Finally, both P2 and P3 suppressed EAE induced by an encephalitogenic guinea pig MBP74-85 epitope in Lewis rats whereas P1 failed to do so. In conclusion, cyclization of myelin altered peptide ligand (Ala91,Ala96)MBP87-99 improved binding affinity to HLA-DR4, resistance to proteolysis and antigen-specific immunomodulation

  8. Delta-aminolevulinic acid dehydratase activity (ALA-D) in red mullet (Mullus barbatus) from Mediterranean waters as biomarker of lead exposure.

    PubMed

    Fernández, B; Martínez-Gómez, C; Benedicto, J

    2015-05-01

    The enzyme delta-aminolevulinic acid dehydratase (ALA-D) has been investigated as biomarker of lead (Pb) exposure in red mullet (Mullus barbatus) from the Spanish continental shelf. Concentrations of Pb and Zn in muscle and organosomatic indices were also measured to explore causality. Blood ALA-D assay conditions were optimized; the optimum pH for this species has been set to 6.5. Results showed that ALA-D activity ranged from 3.2 to 16.9 nmol PBGmin(-1)mg(-1). No significant differences on ALA-D levels between genders have been detected. ALA-D Baseline level and Background Assessment Criteria (BAC) for this species have been set to 9.1 and 6.6 nmol PBGmin(-1)mg(-1), respectively. There have been detected significant differences on ALA-D activity levels among areas, though the markedly low levels of Pb measured in fish muscle seemed not to be able to produce a relevant suppression on ALA-D. In spite of this, a weak inverse relationship detected between ALA-D and Pb concentrations pointed out the potential of this biomarker in red mullet to reflect Pb bioavailability in marine environment. Nevertheless, subsequent research on ALA-D in marine fish species is recommended to be limited to areas where environmental Pb is effectively accumulated by fish. PMID:25706085

  9. Deuterium NMR of Val1...(2-2H)Ala3...gramicidin A in oriented DMPC bilayers.

    PubMed

    Hing, A W; Adams, S P; Silbert, D F; Norberg, R E

    1990-05-01

    Deuterium NMR is used to study the selectively labeled Val1...(2-2H)Ala3...gramicidin A molecule to investigate the structure and dynamics of the C alpha-2H bond in the Ala3 residue of gramicidin. Val1...(2-2H)Ala3...gramicidin A is synthesized, purified, and characterized and then incorporated into oriented bilayers of dimyristoylphosphatidylcholine sandwiched between glass coverslips. Phosphorus NMR line shapes obtained from this sample are consistent with the presence of the bilayer phase and indicate that no nonbilayer phases are present in significant amounts. Deuterium NMR line shapes obtained from this sample indicate that the motional axis of the gramicidin Ala3 residue is parallel to the coverslip normal, that the distribution of motional axis orientations has a width of 2 degrees, and that only one major conformational and dynamical state of the Ala3 C alpha-2H bond is observed on the NMR time scale. Furthermore, the Ala3 C alpha-2H bond angle relative to the motional axis is 19-20 degrees if fast axial rotation is assumed to be the only motion present but is less than or equal to 19-20 degrees in the absence of such an assumption. This result indicates that various double-stranded, helical dimer models are very unlikely to represent the structure of gramicidin in the sample studied but that the single-stranded, beta 6.3 helical dimer models are consistent with the experimental data. However, a definitive distinction between the left-handed, single-stranded, beta 6.3 helical dimer model and the right-handed, single-stranded, beta 6.3 helical dimer model cannot be made on the basis of the experimental data obtained in this study. PMID:1694457

  10. The current status of 5-ALA fluorescence-guided resection of intracranial meningiomas-a critical review.

    PubMed

    Motekallemi, Arash; Jeltema, Hanne-Rinck; Metzemaekers, Jan D M; van Dam, Gooitzen M; Crane, Lucy M A; Groen, Rob J M

    2015-10-01

    Meningiomas are the second most common primary tumors affecting the central nervous system. Surgical treatment can be curative in case of complete resection. 5-aminolevulinic acid (5-ALA) has been established as an intraoperative tool in malignant glioma surgery. A number of studies have tried to outline the merits of 5-ALA for the resection of intracranial meningiomas. In the present paper, we review the existing literature about the application of 5-ALA as an intraoperative tool for the resection of intracranial meningiomas. PubMed was used as the database for search tasks. We included articles published in English without limitations regarding publication date. Tumor fluorescence can occur in benign meningiomas (WHO grade I) as well as in WHO grade II and WHO grade III meningiomas. Most of the reviewed studies report fluorescence of the main tumor mass with high sensitivity and specificity. However, different parts of the same tumor can present with a different fluorescent pattern (heterogenic fluorescence). Quantitative probe fluorescence can be superior, especially in meningiomas with difficult anatomical accessibility. However, only one study was able to consistently correlate resected tissue with histopathological results and nonspecific fluorescence of healthy brain tissue remains a confounder. The use of 5-ALA as a tool to guide resection of intracranial meningiomas remains experimental, especially in cases with tumor recurrence. The principle of intraoperative fluorescence as a real-time method to achieve complete resection is appealing, but the usefulness of 5-ALA is questionable. 5-ALA in intracranial meningioma surgery should only be used in a protocolled prospective and long-term study. PMID:25736455

  11. Neuroprotective effects of D-Ala2GIP on Alzheimer's disease biomarkers in an APP/PS1 mouse model

    PubMed Central

    2013-01-01

    Introduction Type 2 diabetes mellitus has been identified as a risk factor for Alzheimer's disease (AD). An impairment of insulin signaling as well as a desensitization of its receptor has been found in AD brains. Glucose-dependent insulinotropic polypeptide (GIP) normalises insulin signaling by facilitating insulin release. GIP directly modulates neurotransmitter release, LTP formation, and protects synapses from the detrimental effects of beta-amyloid fragments on LTP formation, and cell proliferation of progenitor cells in the dentate gyrus. Here we investigate the potential therapeutic property of the new long lasting incretin hormone analogue D-Ala2GIP on key symptoms found in a mouse model of Alzheimer' disease (APPswe/PS1detaE9). Methods D-Ala2GIP was injected for 21 days at 25 nmol/kg ip once daily in APP/PS1 male mice and wild type (WT) littermates aged 6 or 12 months of age. Amyloid plaque load, inflammation biomarkers, synaptic plasticity in the brain (LTP), and memory were measured. Results D-Ala2GIP improved memory in WT mice and rescued the cognitive decline of 12 months old APP/PS1 mice in two different memory tasks. Furthermore, deterioration of synaptic function in the dentate gyrus and cortex was prevented in 12 months old APP/PS1 mice. D-Ala2GIP facilitated synaptic plasticity in APP/PS1 and WT mice and reduced the number of amyloid plaques in the cortex of D-Ala2GIP injected APP/PS1 mice. The inflammatory response in microglia was also reduced. Conclusion The results demonstrate that D-Ala2GIP has neuroprotective properties on key hallmarks found in AD. This finding shows that novel GIP analogues have the potential as a novel therapeutic for AD. PMID:23601582

  12. Stability, metabolism and transport of D-Asp(OBzl)-Ala--a model prodrug with affinity for the oligopeptide transporter.

    PubMed

    Steffansen, B; Lepist, E I; Taub, M E; Larsen, B D; Frokjaer, S; Lennernäs, H

    1999-04-01

    The model prodrug D-Asp(OBzl)-Ala has previously been shown to have affinity and to be transported by the oligopeptide transporter PepT1 expressed in Caco-2 cells. The main objective of the present study was to investigate the aqueous stability of D-Asp(OBzl)-Ala and its in vitro metabolism in different gastrointestinal media arising from rats and humans, as well as in human plasma. The second major aim of the study was to evaluate our previous study in Caco-2 cell culture, by determining the effective intestinal permeability (Peff) of D-Asp(OBzl)-Ala in situ using the single-pass rat perfusion model. The aqueous stability studies show water, general buffer, as well as specific acid and base catalysis of D-Asp(OBzl)-Ala. The degradation of the model prodrug was independent of ionic strength. The half-lives in rat jejunal fluid and homogenate were >3 h. In human gastric and intestinal fluids, the half-lives were >3 h and 2.3+/-0. 03 h, respectively. Using the rat single-pass perfusion technique, the effective jejunal permeability (Peff) of D-Asp(OBzl)-Ala was determined to be high (1.29+/-0.5.10-4 cm/s). The 32 times higher Peff value found in the perfusion model compared to Caco-2 cells is most likely due to a higher functional expression of the oligopeptide transporter. Rat jejuna Peff was reduced by approximately 50% in the presence of well known oligopeptide transporter substrates, such as Gly-Sar and cephalexin. It may be that D-Asp(OBzl)-Ala is primarily absorbed intact by the rat jejunal oligopeptide transporter, since the stability in the intestinal homogenate and fluids was rather high (t1/2>2.3 h). PMID:10072480

  13. Laminated metal composite formed from low flow stress layers and high flow stress layers using flow constraining elements and making same

    DOEpatents

    Syn, C.K.; Lesuer, D.R.

    1995-07-04

    A laminated metal composite of low flow stress layers and high flow stress layers is described which is formed using flow constraining elements, preferably in the shape of rings, individually placed around each of the low flow stress layers while pressure is applied to the stack to bond the layers of the composite together, to thereby restrain the flow of the low flow stress layers from the stack during the bonding. The laminated metal composite of the invention is made by the steps of forming a stack of alternate layers of low flow stress layers and high flow stress layers with each layer of low flow stress material surrounded by an individual flow constraining element, such as a ring, and then applying pressure to the top and bottom surfaces of the resulting stack to bond the dissimilar layers together, for example, by compression rolling the stack. In a preferred embodiment, the individual flow constraining elements surrounding the layers of low flow stress material are formed of a material which may either be the same material as the material comprising the high flow stress layers, or have similar flow stress characteristics to the material comprising the high flow stress layers. Additional sacrificial layers may be added to the top and bottom of the stack to avoid damage to the stack during the bonding step; and these additional layers may then be removed after the bonding step. 5 figs.

  14. Laminated metal composite formed from low flow stress layers and high flow stress layers using flow constraining elements and making same

    DOEpatents

    Syn, Chol K.; Lesuer, Donald R.

    1995-01-01

    A laminated metal composite of low flow stress layers and high flow stress layers is described which is formed using flow constraining elements, preferably in the shape of rings, individually placed around each of the low flow stress layers while pressure is applied to the stack to bond the layers of the composite together, to thereby restrain the flow of the low flow stress layers from the stack during the bonding. The laminated metal composite of the invention is made by the steps of forming a stack of alternate layers of low flow stress layers and high flow stress layers with each layer of low flow stress material surrounded by an individual flow constraining element, such as a ring, and then applying pressure to the top and bottom surfaces of the resulting stack to bond the dissimilar layers together, for example, by compression rolling the stack. In a preferred embodiment, the individual flow constraining elements surrounding the layers of low flow stress material are formed of a material which may either be the same material as the material comprising the high flow stress layers, or have similar flow stress characteristics to the material comprising the high flow stress layers. Additional sacrificial layers may be added to the top and bottom of the stack to avoid damage to the stack during the bonding step; and these additional layers may then be removed after the bonding step.

  15. A randomised controlled trial of ALA vs. Photofrin photodynamic therapy for high-grade dysplasia arising in Barrett's oesophagus.

    PubMed

    Dunn, J M; Mackenzie, G D; Banks, M R; Mosse, C A; Haidry, R; Green, S; Thorpe, S; Rodriguez-Justo, M; Winstanley, A; Novelli, M R; Bown, S G; Lovat, L B

    2013-05-01

    Photofrin photodynamic therapy (PDT) is a licenced treatment for Barrett's oesophagus (BE) with high-grade dysplasia (HGD) but causes strictures and photosensitivity and complete reversal of dysplasia (CR-HGD) by 50 % at 5 years. 5-Aminolaevulinic acid (ALA) is an alternative treatment with non-randomised data suggesting 85 % CR-HGD and a low risk of side effects. We aimed to compare efficacy and side effect profile between the drugs. A single-centre randomised controlled trial was conducted. Presence of HGD was confirmed on three occasions by two specialist GI pathologists. Stratification was by length of BE and extent of dysplasia. Standard protocols for ALA and Photofrin-PDT were followed. Endoscopic follow-up with 2-cm four-quadrant biopsy was at 6 weeks, 4 months, and then annually. All adverse event data were collected. Sixty four patients were randomised, 34 ALA and 30 Photofrin-PDT. Median follow-up is 24 months. On intention-to-treat analysis, CR-HGD was 16/34 (47 %) with ALA-PDT and 12/30 (40 %) with Photofrin-PDT. The overall cancer incidence was 14 % (9/64). On sub-group log-rank analysis, for BE ≤ 6 cm, CR-HGD was significantly higher with ALA-PDT than Photofrin-PDT (χ(2) =5.39, p=0.02). Strictures and skin photosensitivity were significantly more common after treatment with Photofrin-PDT than ALA-PDT (33 vs. 9 % and 43 vs. 6 %, respectively, p<0.05). The rate of buried glands with either drug was significantly higher post-PDT (48 % of patients) than pre-PDT (20 %). ALA-PDT has a better risk profile than Photofrin-PDT. In patients with BE length ≤ 6 cm, preliminary results show ALA-PDT is associated with significantly higher CR-HGD. In longer segments of BE, neither PDT drug is sufficiently efficacious to warrant routine use. PMID:22699800

  16. Successful treatment of recalcitrant dissecting cellulitis of the scalp with ALA-PDT: case report and literature review.

    PubMed

    Liu, Ye; Ma, Ying; Xiang, Lei-Hong

    2013-12-01

    A case of refractory dissecting cellulitis of the scalp (DCS) in a forty-one-year-old Chinese female patient was treated with a total of 6 sessions of topical ALA-PDT at one week intervals. The patient tolerated and responded well to this new approach without any adverse events. This suggested that topical ALA-PDT could be an effective and safe alternative for DCS patients who were refractory to other conventional therapies. We also reviewed etiology, pathophysiology, natural history and treatment options for DCS. PMID:24284093

  17. A TiO₂ nanoparticle system for sacrificial solar H₂ production prepared by rational combination of a hydrogenase with a ruthenium photosensitizer.

    PubMed

    Reisner, Erwin; Armstrong, Fraser A

    2011-01-01

    A hybrid system comprising a hydrogenase and a photosensitizer co-attached to a nanoparticle serves as a rational model for fast dihydrogen (H(2)) production using visible light. This chapter describes a stepwise procedure for preparing TiO(2) nanoparticles functionalized with a hydrogenase from Desulfomicrobium baculatum (Db [NiFeSe]-H) and a tris(bipyridyl)ruthenium photosensitizer (RuP). Upon irradiation with visible light, these particles produce H(2) from neutral water at room temperature in the presence of a sacrificial electron donor - a test-system for the cathodic half reaction of water splitting. In particular, we describe how a hydrogenase and a photosensitizer with desired properties, including strong adsorption on TiO(2), can be selected by electrochemical methods. The catalyst Db [NiFeSe]-H is selected for its high H(2) production activity even when H(2) and traces of O(2) are present. Adsorption of Db [NiFeSe]-H and RuP on TiO(2) electrodes results in high electrochemical and photocatalytic activities that translate into nanoparticles exhibiting efficient light harvesting, charge separation, and sacrificial H(2) generation. PMID:21553186

  18. Ala(0)-actagardine, a new lantibiotic from cultures of Actinoplanes liguriae ATCC 31048.

    PubMed

    Vértesy, L; Aretz, W; Bonnefoy, A; Ehlers, E; Kurz, M; Markus, A; Schiell, M; Vogel, M; Wink, J; Kogler, H

    1999-08-01

    The actagardine-producing strain Actinoplanes liguriae ATCC 31048, forms an additional lantibiotic when it is cultured on mannitol and soya meal. The new compound, Ala(0)-actagardine (1), has been isolated by solid-phase extraction followed by a two-step chromatographic separation. The molecular formula of 1 is C84H129N21O25S4. Its chemical structure was determined by 2D-NMR analysis and was further confirmed by an amino acid analysis, Edman degradation, and partial synthesis from actagardine. 1 exhibits a slightly higher biological activity than the parent compound actagardine. The synthetic analogs Lys(0)-actagardine (2) and Ile(0)-actagardine (3) demonstrate also antibacterial activities and emphasize the importance of the N-terminus for further derivatization. PMID:10580386

  19. Effective treatment of d-penicillamine induced elastosis perforans serpiginosa with ALA-PDT.

    PubMed

    Wang, Duoqin; Liang, Jun; Xu, Jinhua; Chen, Lianjun

    2015-03-01

    A case of D-penicillamine(DPA) induced elastosis perforans serpiginosa(EPS) in a 32-year-old Chinese man was reported. The presentation lasted two years and was refractory to traditional medical treatment. He was then commenced on 7.6% 5-aminolevulinic acid (ALA) induced photodynamic therapy(PDT) by a LED light of 633 nm at dose levels of 130J/ cm2 for each session with total 3 sessions at one week interval. The patient was tolerated and responded well to this new approach for DPA-induced EPS without any adverse events. The etiology, pathophysiology, natural history, and treatment options for DPA-induced EPS are reviewed, and the authors suggest this method of treatment to be effective and safe for patients of DPA-induced EPS refractory to conventional therapy. PMID:25463318

  20. Fluorescence endoscopy with 5-amino levulinic acid (ALA) reduces early recurrence rate in superficial bladder cancer

    NASA Astrophysics Data System (ADS)

    Koenig, Frank; Riedl, Claus R.; Daniltchenko, Dmitri; Schnorr, Dietmar

    2003-06-01

    Purpose: Several investigators have demonstrated an approximately 20% higher tumor detection rate by ALA (5-aminolevulinic acid) based fluorescence endoscopy (AFE) compared to standard white light cystoscopy. These data suggest a reduction of residual and recurrent tumor following fluorescence guided transurethral resection (TUR) of bladder carcinoma. The present study was performed to test this hypothesis. Materials and Methods: In a prospective randomized multi-center study, 2 x 51 patients underwent TUR of bladder tumor(s) either with white light (current standard) or assisted by ALA-induced fluorescence. A 2nd look TUR with AFE was performed 6 weeks after the initial operation. Control cystoscopies were performed 3 and 6 months after initial tumor resection. Results: At 2nd look TUR (6 weeks post op) and at control cystoscopies 3 and 6 months following initial TUR in the white light group residual and/or recurrent carcinoma was detected in 20 of 51, in 24 of 48 and in 28 of 48 patients, respectively, and in the AFE group in 8 of 51, in 10 of 47 and in 17 of 47 patients, respectively. The differences were statistically significant (p=0.005, p=0.002 and p=0.01, respectively). Three patients in the white light and four patients in the AFE group were lost to follow up. Conclusions: AFE is a minimally invasive and inexpensive diagnostic procedure that significantly improves bladder tumor detection rates compared to standard white light endoscopy. In the present study AFE reduced the residual/recurrent tumor rate 6 weeks, 3 and 6 months after initial TUR by 59%, 58% and 38%, respectively.

  1. Some Properties of a Self-sufficient Cytochrome P-450 Monooxygenase from Bacillus megaterium NRRL B-21660, Strain ALA2

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bacillus megaterium NRRL B-21660, strain ALA2, produces many new oxygenated unsaturated fatty acids from linoleic acid with potential applications such as specialty chemicals and biomedicals. In order to utilize the enzymes involved in this pathway for the production of these new fatty acid product...

  2. Novel Association of WNK4 Gene, Ala589Ser Polymorphism in Essential Hypertension, and Type 2 Diabetes Mellitus in Malaysia

    PubMed Central

    Ghodsian, Nooshin; Ismail, Patimah; Ahmadloo, Salma; Heidari, Farzad; Haghvirdizadeh, Polin; Ataollahi Eshkoor, Sima; Etemad, Ali

    2016-01-01

    With-no-lysine (K) Kinase-4 (WNK4) consisted of unique serine and threonine protein kinases, genetically associated with an autosomal dominant form of hypertension. Argumentative consequences have lately arisen on the association of specific single nucleotide polymorphisms of WNK4 gene and essential hypertension (EHT). The aim of this study was to determine the association of Ala589Ser polymorphism of WNK4 gene with essential hypertensive patients in Malaysia. WNK4 gene polymorphism was specified utilizing mutagenically separated polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) method in 320 subjects including 163 cases and 157 controls. Close relation between Ala589Ser polymorphism and elevated systolic and diastolic blood pressure (SBP and DBP) was recognized. Sociodemographic factors including body mass index (BMI), age, the level of fasting blood sugar (FBS), low density lipoprotein (LDL), and triglyceride (TG) in the cases and healthy subjects exhibited strong differences (p < 0.05). The distribution of allele frequency and genotype of WNK4 gene Ala589Ser polymorphism showed significant differences (p < 0.05) between EHT subjects with or without type 2 diabetes mellitus (T2DM) and normotensive subjects, statistically. The WNK4 gene variation influences significantly blood pressure increase. Ala589Ser probably has effects on the enzymic activity leading to enhanced predisposition to the disorder. PMID:27314050

  3. Role of Superoxide Dismutase 2 Gene Ala16Val Polymorphism and Total Antioxidant Capacity in Diabetes and its Complications

    PubMed Central

    Pourvali, Katayoun; Abbasi, Mehrnaz; Mottaghi, Azadeh

    2016-01-01

    Diabetes Mellitus (DM) is a chronic heterogeneous disorder and oxidative stress is a key participant in the development and progression of it and its complications. Anti-oxidant status can affect vulnerability to oxidative damage, onset and progression of diabetes and diabetes complications. Superoxide dismutase 2 (SOD2) is one of the major antioxidant defense systems against free radicals. SOD2 is encoded by the nuclear SOD2 gene located on the human chromosome 6q25 and the Ala16Val polymorphism has been identified in exon 2 of the human SOD2 gene. Ala16Val (rs4880) is the most commonly studied SOD2 single nucleotide polymorphism (SNP) in SOD2 gene. This SNP changes the amino acid at position 16 from valine (Val) to alanine (Ala), which has been shown to cause a conformational change in the target sequence of manganese superoxide dismutase (MnSOD) and also affects MnSOD activity in mitochondria. Ala16Val SNP and changes in the activity of the SOD2 antioxidant enzyme have been associated with altered progression and risk of different diseases. Association of this SNP with diabetes and some of its complications have been studied in numerous studies. This review evaluated how rs4880, oxidative stress and antioxidant status are associated with diabetes and its complications although some aspects of this line still remain unclear. PMID:27141263

  4. Some Properties of a Self-Sufficient Cytochrome P-450 Monooxygenase System from Bacillus megaterium Strain ALA2

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We reviewed the many interesting and related in vivo products derived from reactions of the B. megaterium strain ALA2 and various related polyunsaturated fatty acids (PUFA) substrates. Products obtained from the omega-6 PUFAs (linoleic acid, gamma-linolenic acid, and arachidonic acid) possessed die...

  5. The effect of ALA/PpIX PDT on putative cancer stem cells in tumor side populations

    NASA Astrophysics Data System (ADS)

    Morgan, Janet; Petrucci, Cara M.

    2009-06-01

    Protoporphyrin IX (PpIX) synthesized endogenously from 5-aminolevulinic acid (ALA), is effluxed from cells expressing the ATP-dependent transporter ABCG2. Side population (SP) cells (named for their low red/blue fluorescence distribution in flow cytometry plots with ABCG2 substrates such as Hoechst) are postulated to contain cancer stem cells (CSC). The SP in U87 (human gliblastoma cell line) were more resistant to ALA-PDT than NON-SP cells. Inhibiting ABCG2 activity with the tyrosine kinase inhibitor imatinib mesylate (IM, Gleevec) during incubation with ALA increased PpIX in the SP by preventing its efflux and decreased the SP after subsequent PDT, enhancing phototoxicity. Evasion of SP cells from ALA-PDT could cause tumor recurrence from CSC. Manipulation of ABCG2 levels on the SP with small molecule modulators may be a potential strategy for enhancing PDT by decreasing the amount of substrate photosensitizer extruded from cells and lowering the threshold for phototoxicity.

  6. Sensitization and photodynamic therapy of esophageal,duodenal, and colonic tumors with 5-aminolaevulinic acid (ALA) induced protoporphyrin IX (PPIX)

    NASA Astrophysics Data System (ADS)

    Mlkvy, Peter; Messmann, Helmut; Regula, Jaroslaw; Conio, M.; Pauer, M.; Millson, Charles E.; MacRobert, Alexander J.; Bown, Stephen G.

    1995-03-01

    Five aminolaevulinic acid (ALA) is a promising agent for PDT sensitization as it can be given orally and only causes skin photosensitivity for 1 - 2 days. In fluorescence and photodynamic studies 26 patients with benign and malignant gastrointestinal tumors (M 17, F 9; mean age 79) were given 30 - 60 mg ALA orally (single or divided doses) and biopsies taken of tumor and normal tissue at 1 - 24 hours for fluorescence microscopy. With 30 mg/kg, highest protoporphyrin IX (PPIX) levels were seen in oesophagus, duodenum and less in colon, but without tumor selectivity. Better tumor selectivity was seen in the colon after 60 mg/kg (5:1). Six patients had transient rises in transaminases and five mild nausea. Sixteen patients were later treated (after further ALA) with red light (628 nm, bare fiber or diffuser, 50 - 100 J at 50 mW at each site). All but two showed subsequent necrosis, but only 0.5 - 1.5 mm depth. PDT with ALA is simple, safe, and promising for tumors in the GI tract. Modification of treatment parameters may make it suitable for larger lesions.

  7. Books for Gerstner Field Aviators: The Mexican Border Traveling Library Service and ALA in Southwest Louisiana during World War I.

    ERIC Educational Resources Information Center

    Bordelon, Kathie

    This paper examines the efforts made by the American Library Association (ALA) and the Mexican Border Traveling Library Service (MBTLS) to ensure that remote World War I outposts, such as the Gerstner Field aviation and military training camp in Louisiana, would have adequate library service. A history of the MBTLS' early organizational success,…

  8. Comparison of the crystal structure and function to wild-type and His25Ala mutant human heme oxygenase-1.

    PubMed

    Zhou, Wen-Pu; Zhong, Wen-Wei; Zhang, Xue-Hong; Ding, Jian-Ping; Zhang, Zi-Li; Xia, Zhen-Wei

    2009-03-01

    Human heme oxygenase-1 (hHO-1) is a rate-limiting enzyme in heme metabolism. It regulates serum bilirubin level. Site-directed mutagenesis studies indicate that the proximal residue histidine 25 (His25) plays a key role in hHO-1 activity. A highly purified hHO-1 His25Ala mutant was generated and crystallized with a new expression system. The crystal structure of the mutant was determined by X-ray diffraction technology and molecular replacement at the resolution of 2.8 A, and the model of hHO-1 His25Ala mutant was refined. The final crystallographic and free R factors were 0.245 and 0.283, respectively. The standard bond length deviation was 0.007 A, and the standard bond angle deviation was 1.3 degrees . The mutation of His25 to Ala led to an empty pocket underneath the ferric ion in the heme, leading to loss of binding iron ligand. Although this did not cause an overall structural change, the enzymatic activity of the mutant hHO-1 was reduced by 90%. By supplementing imidazole, the HO-1 activity was restored approximately 90% to its normal level. These data suggest that Ala25 remains unchanged in the structure compared to His25, but the important catalytic function of hHO-1 is lost. Thus, it appears that His25 is a crucial residue for proper hHO-1 catalysis. PMID:19212657

  9. An organic solvent-stable lipase from a newly isolated Staphylococcus aureus ALA1 strain with potential for use as an industrial biocatalyst.

    PubMed

    Ben Bacha, Abir; Moubayed, Nadine Ms; Al-Assaf, Alaa

    2016-05-01

    In this study, a new strain, ALA1, was identified as Staphylococcus aureus by biochemical tests, and its 16S ribosomal DNA sequence was isolated from dromedary milk. ALA1 lipase production was optimized in shake flask experiments and measured with varying pH (3-11), temperature (20-55 °C) and substrate concentrations. The maximum lipase production was recorded at pH 8 and 30 °C for up to 30 H of culture period for the S. aureus ALA1 strain. Among the substrates tested, selected carbon sources, xylose, nitrogen source, yeast extract, and olive oil (1%) were suitable for maximizing lipase production. The effects of surfactants were investigated and showed that Tween 20, Tween 80, and Triton X-100 prevented lipase production. Interestingly, isolate ALA1 was able to grow in high concentrations of benzene or toluene (up to 50% (v/v)). Moreover, the lipolytic activity of the S. aureus ALA1 lipase was stimulated by diethyl ether, whereas almost 100% of S. aureus ALA1 lipase activity was retained in 25% acetone, acetonitrile, benzene, 2-propanol, ethanol, methanol, or toluene. Because of its stability in organic solvent, the S. aureus ALA1 lipase was used as a biocatalyst to synthesize high levels of added value molecules. S. aureus ALA1 lipase could be considered as an ideal choice for applications in detergent formulations because of its high stability and compatibility with various surfactants, oxidizing agents, and commercial detergents. PMID:25828848

  10. RNAi-mediated silencing of hepatic Alas1 effectively prevents and treats the induced acute attacks in acute intermittent porphyria mice

    PubMed Central

    Yasuda, Makiko; Gan, Lin; Chen, Brenden; Kadirvel, Senkottuvelan; Yu, Chunli; Phillips, John D.; New, Maria I.; Liebow, Abigail; Fitzgerald, Kevin; Querbes, William; Desnick, Robert J.

    2014-01-01

    The acute hepatic porphyrias are inherited disorders of heme biosynthesis characterized by life-threatening acute neurovisceral attacks. Factors that induce the expression of hepatic 5-aminolevulinic acid synthase 1 (ALAS1) result in the accumulation of the neurotoxic porphyrin precursors 5-aminolevulinic acid (ALA) and porphobilinogen (PBG), which recent studies indicate are primarily responsible for the acute attacks. Current treatment of these attacks involves i.v. administration of hemin, but a faster-acting, more effective, and safer therapy is needed. Here, we describe preclinical studies of liver-directed small interfering RNAs (siRNAs) targeting Alas1 (Alas1-siRNAs) in a mouse model of acute intermittent porphyria, the most common acute hepatic porphyria. A single i.v. dose of Alas1-siRNA prevented the phenobarbital-induced biochemical acute attacks for approximately 2 wk. Injection of Alas1-siRNA during an induced acute attack significantly decreased plasma ALA and PBG levels within 8 h, more rapidly and effectively than a single hemin infusion. Alas1-siRNA was well tolerated and a therapeutic dose did not cause hepatic heme deficiency. These studies provide proof-of-concept for the clinical development of RNA interference therapy for the prevention and treatment of the acute attacks of the acute hepatic porphyrias. PMID:24821812

  11. Association of PPARG Pro12Ala polymorphism with insulin sensitivity and body mass index in patients with polycystic ovary syndrome

    PubMed Central

    BALDANI, DINKA PAVICIC; SKRGATIC, LANA; CERNE, JASMINA Z.; FERK, POLONCA; SIMUNIC, VELIMIR; GERSAK, KSENIJA

    2014-01-01

    Insulin resistance is one of the key factors in the pathogenesis of polycystic ovary syndrome (PCOS). The peroxisome proliferator-activated receptor gamma (PPARG) plays a role in the regulation of insulin sensitivity. The aim of the present study was to establish a possible association of the PPARG Pro12Ala polymorphism with PCOS and its effect on family and personal history, as well as on the metabolic and endocrine parameters in PCOS patients. A total of 151 PCOS patients and 179 healthy women of reproductive age were enrolled. History, body mass index (BMI), waist-to-hip ratio and the presence of phenotypic hyperandrogenism were recorded. Hormonal, metabolic and biochemical profiles were assessed. A molecular analysis for the genetic polymorphism was performed. One third (29.8%) of the PCOS patients were found to be carriers of at least one variant of the Ala allele (X/Ala), while 70.2% carried two wild-type Pro alleles (Pro/Pro), with an equal distribution observed in the control group. The PCOS patients carrying the X/Ala alleles exhibited lower serum fasting insulin levels, homeostatic model assessment of insulin resistance (HOMA-IR) and BMI compared to Pro/Pro carriers. This finding was significant only in the lean PCOS group. The polymorphic genotype exerted no effect on history, hormonal and clinical hyperandrogenism, lipid status or C-reactive protein, leptin, adiponectin, resistin and ghrelin serum levels in women with PCOS. In conclusion, although the PPARG Pro12Ala polymorphism is not a major determinant of PCOS in the Croatian population, it may exert a positive effect on insulin sensitivity and BMI. As these associations were recorded exclusively in the lean group of patients with PCOS, this polymorphism potentially contributes to a protective role against hyperinsulinemia and obesity. PMID:24649096

  12. Three-dimensional ordered TiO2 hollow spheres as scattering layer in dye-sensitized solar cells

    NASA Astrophysics Data System (ADS)

    Chen, Yang; Chen, Zhigang

    2016-03-01

    TiO2 nanostructure was constructed to obtain an improved photoelectric conversion performance. The design was based on the three-dimensional ordered assembly of TiO2 hollow spheres (3D-TiO2 HPs), which were synthesized using polystyrene colloidal crystals as sacrificial templates. Owing to this highly periodic structure and high specific surface area, the double-layered photoanode films derived from 3D-TiO2 HPs as light scattering layer exhibited enhanced conversion efficiency (7.0 %), thus leading to a 46 % increment of photovoltaic performance compared to the cell based on P25 TiO2 photoanode (4.8 %).

  13. Dual catalysis with magnetic chitosan: direct synthesis of cyclic carbonates from olefins with carbon dioxide using isobutyraldehyde as the sacrificial reductant.

    PubMed

    Kumar, Subodh; Singhal, Nikita; Singh, Raj K; Gupta, Piyush; Singh, Raghuvir; Jain, Suman L

    2015-07-14

    Chitosan coated magnetic nanoparticles were synthesized and used as a support for the immobilization of the cobalt(II) acetylacetonate complex [Co(acac)2] and quaternary triphenylphosphonium bromide [P(+)Ph3Br(-)] targeting -NH2 and -OH moieties located on the surface of chitosan. The synthesized material was used as a catalyst for one pot direct synthesis of cyclic carbonates from olefins via an oxidative carboxylation approach with carbon dioxide using isobutyraldehyde as the sacrificial reductant and molecular oxygen as the oxidant. After the reaction, the catalyst was recovered by applying an external magnet and reused for several runs without significant loss in catalytic activity and no leaching was observed during this course. PMID:26055991

  14. Association of Type II 5' Monodeiodinase Thr92Ala Single Nucleotide Gene Polymorphism and Circulating Thyroid Hormones Among Type 2 Diabetes Mellitus Patients.

    PubMed

    Yalakanti, Dhanunjaya; Dolia, Pragna B

    2016-04-01

    Diabetes mellitus and thyroid disorders are common endocrinopathies, which often occur parallel. Dyslipidemia is very common in both of these conditions. The development of hypothyroidism is well-known in type 1 diabetics, but it was not distinctly understood in type 2 diabetics. Thus we tried to examine the association between type II deiodinase (D2 or DIO2) Thr92Ala single nucleotide gene polymorphism and thyroid function among type 2 diabetes mellitus patients. A total of 130 type 2 diabetics were screened and genotyped for DIO2 Thr92Ala polymorphism. Fasting plasma glucose, Glycosylated haemoglobin, lipid and thyroid profiles, malondialdehyde (MDA) and paraoxonase were estimated according to standard procedures. A significant altered level of thyroid hormones (TH's) was found in Ala/Ala genotype when compared with Thr/Thr or Thr/Ala genotype. DIO2 and T3:T4 ratio significantly decreased, whereas total T4 and thyroid stimulating hormone levels significantly elevated among Ala/Ala genotype (131 ± 30 ng/ml; 0.12 ± 0.05; 7.17 ± 2.05 µg/dl; 4.77 ± 3.1 µIU/ml, respectively) when compared with Thr/Thr + Thr/Ala genotypes (176 ± 33 ng/ml; 0.21 ± 0.05; 5.21 ± 1.1 µg/dl; 2.59 ± 1.61 µIU/ml respectively). Moreover, D2 levels were significantly negatively correlated with TH's levels except total T4 among Ala/Ala genotypes. All the patients were having a poor glycemic control, and their glycemic status was positively correlating with MDA levels. On the other hand, serum paraoxonase activity decreased among Ala/Ala genotype (104 ± 21 vs. 118 ± 18 nmol/min/ml). In conclusion, DIO2 Ala92 homozygous variant found to be associated with altered levels of DIO2, Thyroid profile and paraoxonase. Hence, we recommend to do detail study of genetic factors related to thyroid function and prevent additional diabetic complications. PMID:27069323

  15. The Thr300Ala variant in ATG16L1 is associated with improved survival in human colorectal cancer and enhanced production of type I interferon

    PubMed Central

    Grimm, Wesley A; Messer, Jeannette S; Murphy, Stephen F; Nero, Thomas; Lodolce, James P; Weber, Christopher R; Logsdon, Mark F; Bartulis, Sarah; Sylvester, Brooke E; Springer, Amanda; Dougherty, Urszula; Niewold, Timothy B; Kupfer, Sonia S; Ellis, Nathan; Huo, Dezheng; Bissonnette, Marc; Boone, David L

    2016-01-01

    Objective ATG16L1 is an autophagy gene known to control host immune responses to viruses and bacteria. Recently, a non-synonymous single-nucleotide polymorphism in ATG16L1 (Thr300Ala), previously identified as a risk factor in Crohn's disease (CD), was associated with more favourable clinical outcomes in thyroid cancer. Mechanisms underlying this observation have not been proposed, nor is it clear whether an association between Thr300Ala and clinical outcomes will be observed in other cancers. We hypothesised that Thr300Ala influences clinical outcome in human colorectal cancer (CRC) and controls innate antiviral pathways in colon cancer cells. Design We genotyped 460 patients with CRC and assessed for an association between ATG16L1 Thr300Ala and overall survival and clinical stage. Human CRC cell lines were targeted by homologous recombination to examine the functional consequence of loss of ATG16L1, or introduction of the Thr300Ala variant. Results We found an association between longer overall survival, reduced metastasis and the ATG16L1 Ala/Ala genotype. Tumour sections from ATG16L1 Ala/Ala patients expressed elevated type I interferons (IFN-I)-inducible, MxA, suggesting that differences in cytokine production may influence disease progression. When introduced into human CRC cells by homologous recombination, the Thr300Ala variant did not affect bulk autophagy, but increased basal production of type I IFN. Introduction of Thr300Ala resulted in increased sensitivity to the dsRNA mimic poly(I:C) through a mitochondrial antiviral signalling (MAVS)-dependent pathway. Conclusions The CD-risk allele, Thr300Ala, in ATG16L1 is associated with improved overall survival in human CRC, generating a rationale to genotype ATG16L1 Thr300Ala in patients with CRC. We found that Thr300A alters production of MAVS-dependent type I IFN in CRC cells, providing a mechanism that may influence clinical outcomes. PMID:25645662

  16. CMUTs with High-K Atomic Layer Deposition Dielectric Material Insulation Layer

    PubMed Central

    Xu, Toby; Tekes, Coskun; Degertekin, F. Levent

    2014-01-01

    Use of high-κ dielectric, atomic layer deposition (ALD) materials as an insulation layer material for capacitive micromachined ultrasonic transducers (CMUTs) is investigated. The effect of insulation layer material and thickness on CMUT performance is evaluated using a simple parallel plate model. The model shows that both high dielectric constant and the electrical breakdown strength are important for the dielectric material, and significant performance improvement can be achieved, especially as the vacuum gap thickness is reduced. In particular, ALD hafnium oxide (HfO2) is evaluated and used as an improvement over plasma-enhanced chemical vapor deposition (PECVD) silicon nitride (SixNy) for CMUTs fabricated by a low-temperature, complementary metal oxide semiconductor transistor-compatible, sacrificial release method. Relevant properties of ALD HfO2 such as dielectric constant and breakdown strength are characterized to further guide CMUT design. Experiments are performed on parallel fabricated test CMUTs with 50-nm gap and 16.5-MHz center frequency to measure and compare pressure output and receive sensitivity for 200-nm PECVD SixNy and 100-nm HfO2 insulation layers. Results for this particular design show a 6-dB improvement in receiver output with the collapse voltage reduced by one-half; while in transmit mode, half the input voltage is needed to achieve the same maximum output pressure. PMID:25474786

  17. CMUTs with high-K atomic layer deposition dielectric material insulation layer.

    PubMed

    Xu, Toby; Tekes, Coskun; Degertekin, F

    2014-12-01

    Use of high-κ dielectric, atomic layer deposition (ALD) materials as an insulation layer material for capacitive micromachined ultrasonic transducers (CMUTs) is investigated. The effect of insulation layer material and thickness on CMUT performance is evaluated using a simple parallel plate model. The model shows that both high dielectric constant and the electrical breakdown strength are important for the dielectric material, and significant performance improvement can be achieved, especially as the vacuum gap thickness is reduced. In particular, ALD hafnium oxide (HfO2) is evaluated and used as an improvement over plasma-enhanced chemical vapor deposition (PECVD) silicon nitride (Six)Ny)) for CMUTs fabricated by a low-temperature, complementary metal oxide semiconductor transistor-compatible, sacrificial release method. Relevant properties of ALD HfO2) such as dielectric constant and breakdown strength are characterized to further guide CMUT design. Experiments are performed on parallel fabricated test CMUTs with 50-nm gap and 16.5-MHz center frequency to measure and compare pressure output and receive sensitivity for 200-nm PECVD Six)Ny) and 100-nm HfO2) insulation layers. Results for this particular design show a 6-dB improvement in receiver output with the collapse voltage reduced by one-half; while in transmit mode, half the input voltage is needed to achieve the same maximum output pressure. PMID:25474786

  18. Study of false positives in 5-ALA induced photodynamic diagnosis of bladder carcinoma

    NASA Astrophysics Data System (ADS)

    Draga, Ronald O. P.; Grimbergen, Matthijs C. M.; Kok, Esther T.; Jonges, Trudy G. N.; Bosch, J. L. H. R.

    2009-02-01

    Photodynamic diagnosis (PDD) is a technique that enhances the detection of tumors during cystoscopy using a photosensitizer which accumulates primarily in cancerous cells and will fluoresce when illuminated by violetblue light. A disadvantage of PDD is the relatively low specificity. In this retrospective study we aimed to identify predictors for false positive findings in PDD. Factors such as gender, age, recent transurethral resection of bladder tumors (TURBT), previous intravesical therapy (IVT) and urinary tract infections (UTIs) were examined for association with the false positive rates in a multivariate analysis. Data of 366 procedures and 200 patients were collected. Patients were instilled with 5-aminolevulinic acid (5-ALA) intravesically and 1253 biopsies were taken from tumors and suspicious lesions. Female gender and TURBT are independent predictors of false positives in PDD. However, previous intravesical therapy with Bacille Calmette-Guérin is also an important predictor of false positives. The false positive rate decreases during the first 9-12 weeks after the latest TURBT and the latest intravesical chemotherapy. Although shortly after IVT and TURBT false positives increase, PDD improves the diagnostic sensitivity and results in more adequate treatment strategies in a significant number of patients.

  19. Integration of seismic and petrophysics to characterize reservoirs in "ALA" oil field, Niger Delta.

    PubMed

    Alao, P A; Olabode, S O; Opeloye, S A

    2013-01-01

    In the exploration and production business, by far the largest component of geophysical spending is driven by the need to characterize (potential) reservoirs. The simple reason is that better reservoir characterization means higher success rates and fewer wells for reservoir exploitation. In this research work, seismic and well log data were integrated in characterizing the reservoirs on "ALA" field in Niger Delta. Three-dimensional seismic data was used to identify the faults and map the horizons. Petrophysical parameters and time-depth structure maps were obtained. Seismic attributes was also employed in characterizing the reservoirs. Seven hydrocarbon-bearing reservoirs with thickness ranging from 9.9 to 71.6 m were delineated. Structural maps of horizons in six wells containing hydrocarbon-bearing zones with tops and bottoms at range of -2,453 to -3,950 m were generated; this portrayed the trapping mechanism to be mainly fault-assisted anticlinal closures. The identified prospective zones have good porosity, permeability, and hydrocarbon saturation. The environments of deposition were identified from log shapes which indicate a transitional-to-deltaic depositional environment. In this research work, new prospects have been recommended for drilling and further research work. Geochemical and biostratigraphic studies should be done to better characterize the reservoirs and reliably interpret the depositional environments. PMID:24068883

  20. Is SOD2 Ala16Val polymorphism associated with migraine with aura phenotype?

    PubMed

    Palmirotta, Raffaele; Barbanti, Piero; De Marchis, Maria Laura; Egeo, Gabriella; Aurilia, Cinzia; Fofi, Luisa; Ialongo, Cristiano; Valente, Maria Giovanna; Ferroni, Patrizia; Della-Morte, David; Guadagni, Fiorella

    2015-01-20

    Several studies suggest a role of oxidative stress in the physiopathology of migraine, particularly in the form with aura. In a case-control study, we investigated the association between migraine and superoxide dismutase 1 (SOD1) and superoxide dismutase 2 (SOD2) genes in a cohort of 490 consecutive unrelated Caucasian migraineurs (migraine with aura [MwA], n=107; migraine without aura [MwoA], n=246; chronic migraine [CM], n=137) and 246 healthy controls recruited at our Headache and Pain Unit and stored in the Interinstitutional Multidisciplinary BioBank (BioBIM). Migraine phenotype was carefully detailed using face-to-face interviews. We examined polymorphisms of SOD1 gene (A/C substitution-rs2234694) and SOD2 gene (C/T transition-rs4880-Ala16Val). The rs4880 TT (Val/Val) genotype was associated (p=0.042) with the presence of unilateral cranial autonomic symptoms (UAs) in MwA patients. We also found a mild correlation between SOD2 rs4880 genotype and the type of acute migraine treatment (p=0.048) in MwA patients. Our findings suggest that SOD2 is a disease-modifier gene influencing oxidative mechanisms in MwA. These observations lead to the hypothesis that SOD2 polymorphism may cause a defective control of the oxidative phenomena linked to cortical spreading depression, the neurophysiological hallmark of migraine aura, causing an overstimulation of trigeminal neurons and UAs triggering. PMID:25295643

  1. Study of the efficacy of 5 ALA-mediated photodynamic therapy on human larynx squamous cell carcinoma (Hep2c) cell line

    NASA Astrophysics Data System (ADS)

    Khursid, A.; Atif, M.; Firdous, S.; Zaidi, S. S. Z.; Salman, R.; Ikram, M.

    2010-07-01

    5-aminolevulanic acid (ALA), a precursor of Protoporphyrin IX, was evaluated as an inducer of photodamage on Hep2c, human larynx squamous cell carcinoma, cell line. Porphyrins are used as active cytotoxic antitumor agents in photodynamic therapy (PDT). The present study evaluates the effects of photodynamic therapy (PDT) with 5-aminolevulinic acid (5-ALA) using human larynx cells as experimental model. Hep2c cell line was irradiated with red light (a diode laser, λ = 635 nm). The influence of different incubation times and concentrations of 5-ALA, different irradiation doses and various combinations of photosensitizer and light doses on the cellular viability of Hep2c cells were studied. The optimal uptake of photosensitizer ALA in Hep-2c cells was investigated by means of spectrometric measurement. Cells viability was determined by means of neutral red assay (NR). It was observed that sensitizer or light doses have no significant effect on cells viability when studied independently. The spectrometric measurements showed that the maximal cellular uptake of 5-ALA occurred after 7 h in vitro incubation. The photocytotoxic assay showed that light dose of 85 J/cm2 gives effective PDT outcome for Hep2c cell line incubated with 55 μg/ml of 5-ALA with a conclusion that Hep2c cell line is sensitive to ALA-mediated PDT.

  2. High-level expression, purification and study of bioactivity of fusion protein M-IL-2((88)Arg, (125)Ala) in Pichia pastoris.

    PubMed

    Li, Lin; Qian, Dongmeng; Shao, Guangcan; Yan, Zhiyong; Li, Ronggui; Hua, Xiaomin; Song, Xuxia; Wang, Bin

    2014-09-01

    M-IL-2((88)Arg, (125)Ala) is a fusion protein comprising melittin genetically linked to a mutant human interleukin 2((88)Arg, (125)Ala). In this study, we constructed an expression system of M-IL-2((88)Arg, (125)Ala) in Pichia pastoris: GS115/pPICZα A/M-IL-2((88)Arg, (125)Ala), and achieved the high-level expression of the fusion protein. The maximum yield of the fusion protein M-IL-2((88)Arg, (125)Ala) reached up to 814.5mg/L, higher than the system in Escherichiacoli. The fusion protein was purified by means of ammonium sulfate fractionation, dialysis and nickel ion affinity chromatography. The molecular weight of the fusion protein is about 26kDa, conforming the theoretical value. And M-IL-2((88)Arg, (125)Ala) possesses strong antigen-specificity by Western blot detection. Bioassay results indicated that the fusion protein could directly inhibit the growth of human ovarian cancer SKOV3 cells and Hela cells in vitro. This study provides an alternative strategy for large-scale production of bioactive M-IL-2((88)Arg, (125)Ala) using P. pastoris as an expression host and paves the way to clinical practice. PMID:24955549

  3. Healthy reduced-fat Bologna sausages enriched in ALA and DHA and stabilized with Melissa officinalis extract.

    PubMed

    Berasategi, Izaskun; Navarro-Blasco, Iñigo; Calvo, Maria Isabel; Cavero, Rita Yolanda; Astiasarán, Iciar; Ansorena, Diana

    2014-03-01

    Reduced-energy and reduced-fat Bologna products enriched with ω-3 polyunsaturated fatty acids were formulated by replacing the pork back-fat by an oil-in-water emulsion containing a mixture of linseed-algae oil stabilized with a lyophilized Melissa officinalis extract. Healthier composition and lipid profile was obtained: 85 kcal/100 g, 3.6% fat, 0.6 g ALA and 0.44 g DHA per 100 g of product and ω-6/ω-3 ratio of 0.4. Technological and sensory problems were not detected in the new formulations. Reformulation did not cause oxidation problems during 32 days of storage under refrigeration. The results suggest that it is possible to obtain reduced-fat Bologna-type sausages rich in ALA and DHA and stabilized with natural antioxidants, applying the appropriate technology without significant effects on the sensory quality, yielding interesting products from a nutritional point of view. PMID:24334039

  4. Efficient aminoacylation of the tRNA(Ala) acceptor stem: dependence on the 2:71 base pair.

    PubMed Central

    Beuning, Penny J; Nagan, Maria C; Cramer, Christopher J; Musier-Forsyth, Karin; Gelpí, Josep-Lluis; Bashford, Donald

    2002-01-01

    Specific aminoacylation by aminoacyl-tRNA synthetases requires accurate recognition of cognate tRNA substrates. In the case of alanyl-tRNA synthetase (AlaRS), RNA duplexes that mimic the acceptor stem of the tRNA are efficient substrates for aminoacylation in vitro. It was previously shown that recognition by AlaRS is severely affected by a simple base pair transversion of the G2:C71 pair at the second position in the RNA helix. In this study, we determined the aminoacylation efficiencies of 50 variants of the tRNA(Ala) acceptor stem containing substitutions at the 2:71 position. We find that there is not a single functional group of the wild-type G2:C71 base pair that is critical for positive recognition. Rather, we observed that base-pair orientation plays an important role in recognition. In particular, pyrimidine2:purine71 combinations generally resulted in decreased aminoacylation efficiency compared to the corresponding purine:pyrimidine pair. Moreover, the activity of a pyrimidine:purine variant could be partially restored by the presence of a major groove amino group at position 71. In an attempt to understand this result further, dielectric continuum electrostatic calculations were carried out, in some cases with additional inclusion of van der Waals interaction energies, to determine interaction potentials of the wild-type duplexAla and seven 2:71 variants. This analysis revealed a positive correlation between major groove negative electrostatic potential in the vicinity of the 3:70 base pair and measured aminoacylation efficiency. PMID:12022232

  5. Relation between iron metabolism and antioxidants enzymes and δ-ALA-D activity in rats experimentally infected by Fasciola hepatica.

    PubMed

    Bottari, Nathieli B; Mendes, Ricardo E; Baldissera, Matheus D; Bochi, Guilherme V; Moresco, Rafael N; Leal, Marta L R; Morsch, Vera M; Schetinger, Maria R C; Christ, Ricardo; Gheller, Larissa; Marques, Éder J; Da Silva, Aleksandro S

    2016-06-01

    The aim of this study was to evaluate the iron metabolism in serum, as well as antioxidant enzymes, in addition to the Delta-Aminolevulinic Acid Dehydratase (δ-ALA-D) activity in the liver of rats experimentally infected by Fasciola hepatica. Thirty male adult rats (Wistar) specific pathogen free were divided into four groups: two uninfected group (CTRL 1 and CTRL 2) with five animals each and two infected groups (INF 1 and INF 2) with 10 animals each. Infection was performed orally with 20 metacercariae at day 1. On day 15 (CTRL 1 and INF 1 groups) and 87 PI (CTRL 2 and INF 2 groups) blood and bone marrow were collected and the animals were subsequently euthanized for liver sampling. Blood was allocated in tubes without anticoagulant for serum acquisition to measure iron, transferrin and unsaturated iron binding capacity (UIBC). δ-ALA-D, superoxide dismutase (SOD), and catalase (CAT) activities were measured in the liver. A decrease in iron, transferrin and UIBC levels was observed in all infected animals compared to control groups (P < 0.05). Furthermore, iron accumulation was observed in bone marrow of infected mice. Infected animals showed an increase in δ-ALA-D activity at 87 post-infection (PI) (INF 2) as well as in SOD activity at days 15 (INF 1) and 87 PI (INF 2). On the other hand, CAT activity was reduced in rats infected by F. hepatica during acute and chronic phase of fasciolosis (INF 1 and INF 2 groups), when moderate (acute) and severe necrosis in the liver histopathology were observed. These results may suggest that oxidative damage to tissues along with antioxidant mechanisms might have taken part in fasciolosis pathogenesis and are also involved in iron deficiency associated to changes in δ-ALA-D activity during chronic phase of disease. PMID:26995536

  6. Alpha-linolenic acid (ALA) is inversely related to development of adiposity in school-age children

    PubMed Central

    Perng, Wei; Villamor, Eduardo; Mora-Plazas, Mercedes; Marin, Constanza; Baylin, Ana

    2015-01-01

    Background/Objectives Studies in adults indicate that dietary polyunsaturated fatty acid (PUFA) composition may play a role in development of adiposity. Because adipocyte quantity is established between late childhood and early adolescence, understanding the impact of PUFAs on weight gain during the school-age years is crucial to developing effective interventions. Subjects/Methods We quantified N-3 and N-6 PUFAs in serum samples of 668 Colombian schoolchildren aged 5–12 years at the time of recruitment into a cohort study, using gas-liquid chromatography. Serum concentrations of N-3 (ALA, EPA, DHA) and N-6 PUFAs (LA, GLA, DGLA, AA) were determined as % total fatty acids. Children’s anthropometry was measured annually for a median of 30 months. We used mixed-effects models with restricted cubic splines to construct population body mass index-for-age z-score (BAZ) growth curves for age-and sex-specific quartiles of each PUFA. Results N-3 ALA was inversely related to BAZ gain after adjustment for sex, baseline age and weight status, and household socioeconomic level. Estimated BAZ change between 6 and 14 years among children in the highest quartile of ALA compared to those in the lowest quartile was 0.45 (95% CI: 0.07, 0.83) lower (P-trend=0.006). Conclusions N-3 ALA may be protective against weight gain in school-age children. Whether improvement in PUFA status reduces adiposity in pediatric populations deserves evaluation in randomized trials. PMID:25271016

  7. Insights on the structural perturbations in human MTHFR Ala222Val mutant by protein modeling and molecular dynamics.

    PubMed

    Abhinand, P A; Shaikh, Faraz; Bhakat, Soumendranath; Radadiya, Ashish; Bhaskar, L V K S; Shah, Anamik; Ragunath, P K

    2016-04-01

    Methylenetetrahydrofolate reductase (MTHFR) protein catalyzes the only biochemical reaction which produces methyltetrahydrofolate, the active form of folic acid essential for several molecular functions. The Ala222Val polymorphism of human MTHFR encodes a thermolabile protein associated with increased risk of neural tube defects and cardiovascular disease. Experimental studies have shown that the mutation does not affect the kinetic properties of MTHFR, but inactivates the protein by increasing flavin adenine dinucleotide (FAD) loss. The lack of completely solved crystal structure of MTHFR is an impediment in understanding the structural perturbations caused by the Ala222Val mutation; computational modeling provides a suitable alternative. The three-dimensional structure of human MTHFR protein was obtained through homology modeling, by taking the MTHFR structures from Escherichia coli and Thermus thermophilus as templates. Subsequently, the modeled structure was docked with FAD using Glide, which revealed a very good binding affinity, authenticated by a Glide XP score of -10.3983 (kcal mol(-1)). The MTHFR was mutated by changing Alanine 222 to Valine. The wild-type MTHFR-FAD complex and the Ala222Val mutant MTHFR-FAD complex were subjected to molecular dynamics simulation over 50 ns period. The average difference in backbone root mean square deviation (RMSD) between wild and mutant variant was found to be ~.11 Å. The greater degree of fluctuations in the mutant protein translates to increased conformational stability as a result of mutation. The FAD-binding ability of the mutant MTHFR was also found to be significantly lowered as a result of decreased protein grip caused by increased conformational flexibility. The study provides insights into the Ala222Val mutation of human MTHFR that induces major conformational changes in the tertiary structure, causing a significant reduction in the FAD-binding affinity. PMID:26273990

  8. Liprotides made of α-lactalbumin and cis fatty acids form core-shell and multi-layer structures with a common membrane-targeting mechanism.

    PubMed

    Frislev, Henriette S; Jessen, Christian M; Oliveira, Cristiano L P; Pedersen, Jan Skov; Otzen, Daniel E

    2016-07-01

    α-Lactalbumin (aLA) has been shown to form complexes with oleic acid (OA), which may target cancer cells. We recently showed that aLA and several other proteins all form protein-OA complexes called liprotides with a generic structure consisting of a micellar OA core surrounded by a shell of partially denatured protein. Here we report that a heat treatment and an alkaline treatment method both allow us to prepare liprotide complexes composed of aLA and a range of unsaturated fatty acids (FA), provided the FAs contain cis (but not trans) double bonds. All liprotides containing cis-FA form both small and large species, which all consist of partially denatured aLA, though the overall shape of the species differs. Small liprotides have a simple core-shell structure while the larger liprotides are multi-layered, i.e. they have an additional layer of both FA and aLA surrounding the outside of the core-shell structure. All liprotides can transfer their entire FA content to vesicles, releasing aLA as monomers and softening the lipid membrane. The more similar to OA, the more efficiently the different FAs induce hemolysis. We conclude that aLA can take up and transfer a wide variety of FA to membranes, provided they contain a cis-bond. This highlights liprotides as a general class of complexes where both protein and cis-FA component can be varied without departing from a generic (though sometimes multi-layered) core-shell structure. PMID:27068540

  9. In situ synthesis carbonated hydroxyapatite layers on enamel slices with acidic amino acids by a novel two-step method.

    PubMed

    Wu, Xiaoguang; Zhao, Xu; Li, Yi; Yang, Tao; Yan, Xiujuan; Wang, Ke

    2015-09-01

    In situ fabrication of carbonated hydroxyapatite (CHA) remineralization layer on an enamel slice was completed in a novel, biomimetic two-step method. First, a CaCO3 layer was synthesized on the surface of demineralized enamel using an acidic amino acid (aspartic acid or glutamate acid) as a soft template. Second, at the same concentration of the acidic amino acid, rod-like carbonated hydroxyapatite was produced with the CaCO3 layer as a sacrificial template and a reactant. The morphology, crystallinity and other physicochemical properties of the crystals were characterized using field emission scanning electron microscopy (FESEM), Fourier transform infrared spectrometry (FTIR), X-ray diffraction (XRD) and energy-dispersive X-ray analysis (EDAX), respectively. Acidic amino acid could promote the uniform deposition of hydroxyapatite with rod-like crystals via absorption of phosphate and carbonate ions from the reaction solution. Moreover, compared with hydroxyapatite crystals coated on the enamel when synthesized by a one-step method, the CaCO3 coating that was synthesized in the first step acted as an active bridge layer and sacrificial template. It played a vital role in orienting the artificial coating layer through the template effect. The results show that the rod-like carbonated hydroxyapatite crystals grow into bundles, which are similar in size and appearance to prisms in human enamel, when using the two-step method with either aspartic acid or acidic glutamate (20.00 mmol/L). PMID:26046278

  10. A new, high current output, galvanic (sacrificial) anode, electrochemical rehabilitation system for reinforced and prestressed concrete structures

    SciTech Connect

    Clear, K.C.

    1999-07-01

    This paper summarizes 1995 through 1998 laboratory, outdoor exposure facility, and field data on the subject concrete rehab system. The system shows promise as a means of providing cathodic protection to the reinforcing, as a chloride removal process, as a re-alkalization process, and/or as a lithium injection procedure to minimize alkali-aggregate reactions in the concrete. Unique characteristics of the system include: (1) Surrounding each galvanic anode with a highly corrosive liquid which maintains it (the anode) at peak output voltage throughout its life; and (2) Placing an ionic transfer layer between the anode and the concrete surface that is high volume, low resistivity and deliquescent (i.e. pulls water vapor out of the air at relative humidities of 35% or higher). The ionic transfer layer typically consists of sponge, felt or sand loaded with calcium chloride (and/or other chemicals such as sodium hydroxide, potassium acetate, and lithium-salts). In some cases it also contains a wetting agent and is encapsulated (fully or partially) in vapor permeable, but water impermeable materials. The ionic transfer layer will not freeze at temperatures as low as {minus}20 C ({minus}5 F), and provides sufficient space for all anode corrosion products, thus preventing undesirable stresses on the concrete, the anode assembly and any cosmetic covering.

  11. Association between Ala379Val polymorphism of lipoprotein-associated phospholipase A2 and migraine without aura in Iranian population

    PubMed Central

    Haghdoost, Faraidoon; Gharzi, Mahsa; Faez, Farough; Hosseinzadeh, Elinaz; Tajaddini, Mohamadhasan; Rafiei, Laleh; Asgari, Fatemeh; Banihashemi, Mahboobeh; Masjedi, Samaneh Sadat; Zandifar, Alireza; Haghjooy-Javanmard, Shaghayegh

    2016-01-01

    Background: Migraine is a common neurovascular disorder with multifactorial and polygenic inheritance. The aim of this study was to investigate the association of a migraine without aura and Ala379Val polymorphism of lipoprotein-associated phospholipase A2 (Lp-PLA2) gene in the Iranian population. Methods: In this study, 103 migraine patients and 100 healthy controls were enrolled. DNA samples were extracted and the Ala379Val polymorphism of Lp-PLA2 gene was investigated. To assess severity of a headache, patients filled out the headache impact test (HIT-6) and migraine severity (MIGSEV) questionnaires. Results: Allele V had significantly lower frequency in the case group than control subjects [P = 0.001, odds ratio (OR) = 0.25, confidence interval (CI): 0.15-0.40]. The frequency of migraine patients that were a carrier of V allele (V/V and A/V) was statistically significant lower than the control group (P = 0.003, OR = 2.39, CI: 1.35-4.23). There was no significant difference of alleles frequency between three grades of MIGSEV (P = 0.316). Furthermore, total HIT-6 score was not significantly different between different genotypes (P = 0.466). Conclusion: Our results showed that Ala379Val gene polymorphism of LP-PLA2 is associated with lower risk of migraine but not with severity of headaches in an Iranian population. PMID:27326362

  12. A comparative study of normal inspection, autofluorescence and 5-ALA-induced PPIX fluorescence for oral cancer diagnosis.

    PubMed

    Betz, Christian S; Stepp, Herbert; Janda, Philip; Arbogast, Susanne; Grevers, Gerhard; Baumgartner, Reinhold; Leunig, Andreas

    2002-01-10

    Fluorescence diagnosis aims to improve the management of oral cancer via early detection of the malignant lesions and better delimitation of the tumor margins. This paper presents a comparative study of normal inspection, combined fluorescence diagnosis (CFD) and its 2 main components, autofluorescence and 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PPIX) fluorescence. Biopsy-controlled fluorescence imaging and spectral analysis were performed on a total of 85 patients with suspected or histologically proven oral carcinoma both before and after topical administration of 5-ALA (200 mg 5-ALA dissolved in 50 ml of H(2)0). Fluorescence excitation was accomplished using filtered light of a xenon short arc lamp (lambda = 375-440 nm). As for CFD, a "streetlight" contrast (red to green) was readily found between malignant and healthy tissue on the acquired images. In terms of tumor localization and delimitation properties, CFD was clearly favorable over either normal inspection or its 2 components in fluorescence imaging. The performance of CFD was found to be impeded by tumor keratinization but to be independent of either tumor staging, grading or localization. In spectral analysis, cancerous tissue showed significantly higher PPIX fluorescence intensities and lower autofluorescence intensities than normal mucosa. There is a great potential for CFD in early detection of oral neoplasms and exact delimitation of the tumors' superficial margins and an advantage over white light inspection and each of its 2 main components. The method is noninvasive, safe and easily reproducible. PMID:11774271

  13. Intestinal transport of the lactokinin Ala-Leu-Pro-Met-His-Ile-Arg through a Caco-2 Bbe monolayer.

    PubMed

    Vermeirssen, V; Deplancke, B; Tappenden, K A; Van Camp, J; Gaskins, H R; Verstraete, W

    2002-03-01

    ACE inhibitory peptides are biologically active peptides that play a role in blood pressure regulation. When derived from food proteins during food processing or gastrointestinal digestion, these peptides could function as efficient agents in treating and preventing hypertension. However, in order to exert an antihypertensive effect by inhibition of the ACE enzyme, they have to reach the bloodstream intact. The aim of this research was to assess if the known ACE inhibitory peptide Ala-Leu-Pro-Met-His-Ile-Arg, derived from a tryptic digest of beta-lactoglobulin, could be absorbed through a Caco-2 Bbe cell monolayer in an Ussing chamber and reach the serosal side undegraded. Samples of the mucosal compartment showed high ACE inhibitory activity. No or only little ACE inhibitory activity was detected in the serosal compartment. However, when the serosal sample was concentrated three-fold, a substantial ACE inhibitory activity was registered. Concomitantly, HPLC and MS clearly showed the presence of Ala-Leu-Pro-Met-His-Ile-Arg in the mucosal compartment, whereas in the serosal compartment only MS was able to detect the heptapeptide. In conclusion. under the observed experimental conditions, the ACE inhibitory peptide Ala-Leu-Pro-Met-His-Ile-Arg was transported intact through the Caco-2 Bbe monolayer, but in concentrations too low to exert an ACE inhibitory activity. PMID:11931586

  14. Is SOD2 Ala16Val Polymorphism Associated with Migraine with Aura Phenotype?

    PubMed Central

    Barbanti, Piero; De Marchis, Maria Laura; Egeo, Gabriella; Aurilia, Cinzia; Fofi, Luisa; Ialongo, Cristiano; Valente, Maria Giovanna; Ferroni, Patrizia; Della-Morte, David; Guadagni, Fiorella

    2015-01-01

    Abstract Several studies suggest a role of oxidative stress in the physiopathology of migraine, particularly in the form with aura. In a case-control study, we investigated the association between migraine and superoxide dismutase 1 (SOD1) and superoxide dismutase 2 (SOD2) genes in a cohort of 490 consecutive unrelated Caucasian migraineurs (migraine with aura [MwA], n=107; migraine without aura [MwoA], n=246; chronic migraine [CM], n=137) and 246 healthy controls recruited at our Headache and Pain Unit and stored in the Interinstitutional Multidisciplinary BioBank (BioBIM). Migraine phenotype was carefully detailed using face-to-face interviews. We examined polymorphisms of SOD1 gene (A/C substitution—rs2234694) and SOD2 gene (C/T transition—rs4880—Ala16Val). The rs4880 TT (Val/Val) genotype was associated (p=0.042) with the presence of unilateral cranial autonomic symptoms (UAs) in MwA patients. We also found a mild correlation between SOD2 rs4880 genotype and the type of acute migraine treatment (p=0.048) in MwA patients. Our findings suggest that SOD2 is a disease-modifier gene influencing oxidative mechanisms in MwA. These observations lead to the hypothesis that SOD2 polymorphism may cause a defective control of the oxidative phenomena linked to cortical spreading depression, the neurophysiological hallmark of migraine aura, causing an overstimulation of trigeminal neurons and UAs triggering. Antioxid. Redox Signal. 22, 275–279. PMID:25295643

  15. Saturation Mutagenesis of TsrA Ala4 Unveils a Highly Mutable Residue of Thiostrepton A

    PubMed Central

    Zhang, Feifei; Kelly, Wendy L.

    2016-01-01

    Thiopeptides are posttranslationally processed macrocyclic peptide metabolites, characterized by extensive backbone and side chain modifications that include a six-membered nitrogeneous ring, thiazol(in)e/oxazol(in)e rings, and dehydrated amino acid residues. Thiostrepton A, one of the more structurally complex and well-studied thiopeptides, contains a second macrocycle bearing a quinaldic acid moiety. Antibacterial, antimalarial, and anticancer properties have been described for thiostrepton A and other thiopeptides, although the molecular details for binding the cellular target in each case are not fully elaborated. We previously demonstrated that a mutation of the TsrA core peptide, Ala4Gly, supported the successful production of the corresponding thiostrepton variant. To more thoroughly probe the thiostrepton biosynthetic machinery’s tolerance toward structural variation at the fourth position of the TsrA core peptide, we report here the saturation mutagenesis of this residue using a fosmid-dependent biosynthetic engineering method and the isolation of 16 thiostrepton analogs. Several types of side chain substitutions at the fourth position of TsrA, including those that introduce polar or branched, hydrophobic residues, are accepted, albeit with varied preferences. In contrast, proline and amino acid residues inherently charged at physiological pH are not well-tolerated at the queried site by the thiostrepton biosynthetic system. These newly generated thiostrepton analogs were assessed for their antibacterial activities and abilities to inhibit the proteolytic functions of the eukaryotic 20S proteasome. We demonstrate that the identity of the fourth amino acid residue in the thiostrepton scaffold is not critical for either ribosome or proteasome inhibition. PMID:25572285

  16. The type 2 deiodinase Thr92Ala polymorphism is associated with increased bone turnover and decreased femoral neck bone mineral density.

    PubMed

    Heemstra, Karen A; Hoftijzer, Hendrieke; van der Deure, Wendy M; Peeters, Robin P; Hamdy, Neveen A; Pereira, Alberto; Corssmit, Eleonora P; Romijn, Johannes A; Visser, Theo J; Smit, Johannes W

    2010-06-01

    The role of type 2 deiodinase (D2) in the human skeleton remains unclear. The D2 polymorphism Thr92Ala has been associated with lower enzymatic activity, which could result in lower local triiodothyronine (T(3)) availability in bone. We therefore hypothesized that the D2 Thr92Ala polymorphism may influence bone mineral density (BMD) and bone turnover. We studied 154 patients (29 men, 125 women: 79 estrogen-replete, 46 estrogen-deficient) with cured differentiated thyroid carcinoma. BMD and bone turnover markers [bone-specific alkaline phosphatase (BAP), cross-linking terminal C-telopeptide of type I collagen (CTX), procollagen type 1 amino-terminal propeptide (P1NP), and cross-linked N-telopeptide of type I collagen (NTX)] were measured. Effects of the D2 Thr92Ala polymorphism on BMD and bone turnover markers were assessed by a linear regression model, with age, gender, estrogen state, body mass index (BMI), serum calcium, 25-hydroxyvitamin D, parathyroid hormone (PTH), thyroid-stimulating hormone (TSH), and free triiodothyroxine (T(4)) as covariables. Sixty patients were wild type (Thr/Thr), 66 were heterozygous (Thr/Ala), and 28 were homozygous (Ala/Ala) for the D2 polymorphism. There were no significant differences in any covariables between the three genotypes. Subjects carrying the D2 Thr92Ala polymorphism had consistently lower femoral neck and total hip densities than wild-type subjects (p = .028), and this was accompanied by significantly higher serum P1NP and CTX and urinary NTX/creatinine levels. We conclude that in patients with cured differentiated thyroid carcinoma, the D2 Thr92Ala polymorphism is associated with a decreased femoral neck BMD and higher bone turnover independent of serum thyroid hormone levels, which points to a potential functional role for D2 in bone. PMID:20200941

  17. Identification of a novel erythroid-specific enhancer for the ALAS2 gene and its loss-of-function mutation which is associated with congenital sideroblastic anemia

    PubMed Central

    Kaneko, Kiriko; Furuyama, Kazumichi; Fujiwara, Tohru; Kobayashi, Ryoji; Ishida, Hiroyuki; Harigae, Hideo; Shibahara, Shigeki

    2014-01-01

    Erythroid-specific 5-aminolevulinate synthase (ALAS2) is the rate-limiting enzyme for heme biosynthesis in erythroid cells, and a missense mutation of the ALAS2 gene is associated with congenital sideroblastic anemia. However, the gene responsible for this form of anemia remains unclear in about 40% of patients. Here, we identify a novel erythroid-specific enhancer of 130 base pairs in the first intron of the ALAS2 gene. The newly identified enhancer contains a cis-acting element that is bound by the erythroid-specific transcription factor GATA1, as confirmed by chromatin immunoprecipitation analysis in vivo and by electrophoretic mobility shift assay in vitro. A promoter activity assay in K562 human erythroleukemia cells revealed that the presence of this 130-base pair region increased the promoter activity of the ALAS2 gene by 10–15-fold. Importantly, two mutations, each of which disrupts the GATA-binding site in the enhancer, were identified in unrelated male patients with congenital sideroblastic anemia, and the lower expression level of ALAS2 mRNA in bone marrow erythroblasts was confirmed in one of these patients. Moreover, GATA1 failed to bind to each mutant sequence at the GATA-binding site, and each mutation abolished the enhancer function on ALAS2 promoter activity in K562 cells. Thus, a mutation at the GATA-binding site in this enhancer may cause congenital sideroblastic anemia. These results suggest that the newly identified intronic enhancer is essential for the expression of the ALAS2 gene in erythroid cells. We propose that the 130-base pair enhancer region located in the first intron of the ALAS2 gene should be examined in patients with congenital sideroblastic anemia in whom the gene responsible is unknown. PMID:23935018

  18. Effects of sub-lethal and chronic lead concentrations on blood and liver ALA-D activity and hematological parameters in Nile tilapia.

    PubMed

    Dos Santos, Carlucio Rocha; Cavalcante, Ana Luiza Michel; Hauser-Davis, Rachel Ann; Lopes, Renato Matos; Da Costa Mattos, Rita De Cássia Oliveira

    2016-07-01

    Liver and blood δ-aminolevulinic acid dehydratase (ALA-D) inhibition by exposure to sub-lethal lead concentrations over time in Nile tilapia (Oreochromis niloticus) were investigated. All three lead concentrations (1mgkg(-1), 10mgkg(-1) and 100mgkg(-1)) significantly inhibited ALA-D activity in blood (319±29.2; 180±14.6 and 172±19µmols(-1)h(-1)L(-1) respectively) and liver (302±5.84; 201±41.4 and 93±22.1µmols(-1)h(-1)L(-1)) 24h after injection relative to controls (blood: 597±37.0µmols(-1)h(-1)L(-1); liver: 376±23.1µmols(-1)h(-1)L(-1)). Blood ALA-D was greatly inhibited in all but the highest lead dose. Fish were then exposed to 1mgkg(-1) lead for 9 days, and presented short-term hyperglycemia, decreased hemoglobin and hematocrit values and time-dependent blood ALA-D activity inhibition, corroborating blood ALA-D activity as being more suitable for investigating lead effects, showing dose and time-dependent ALA-D inhibition after lead exposure. The results of the present study also demonstrated that fish size affects blood ALA-D activity, as fish from the 24-h assay, which were slightly smaller (approximately 200g), showed higher ALA-D inhibition in response to lead exposure when compared to the fish from the 9-day assay (approximately 500g). Thus, fish size should always be taken into account both in the field and in laboratory settings, and efforts should be made to obtain uniform fish size samples for biomarker studies. PMID:27054706

  19. Sacrificial template-directed fabrication of superparamagnetic polymer microcontainers for pH-activated controlled release of Daunorubicin.

    PubMed

    Chatzipavlidis, A; Bilalis, P; Efthimiadou, E K; Boukos, N; Kordas, G C

    2011-07-01

    Magnetic pH-sensitive microcontainers were produced by a four-step process. The first step involves the synthesis of citrate-modified magnetic nanoparticles via the coprecipitation method. The second step consists of the encapsulation of magnetic nanoparticles in non-cross-linked poly(methacrylic acid) (PMAA) microspheres through distillation precipitation polymerization, resulting in a core/shell structure. The third step concerns the formation of a poly(N,N'-methylenebis(acrylamide)-co-mathacrylic acid) (P(MBAAm-co-MAA)) layer on the surface of magnetic PMAA microspheres by second distillation precipitation polymerization in order to produce a trilayer hybrid microsphere. The last step deals with the removal of PMAA layer in ethanol and formation of a stable P(MBAAm-co-MAA) microcontainer with magnetic nanoparticles entrapped inside the formed cavity. This process is simple and leads to the formation of superparamagnetic pH-sensitive microcontainers. The structure and properties of the magnetic microcontainers were investigated by X-ray diffraction (XRD), transmission electron microscopy (TEM), scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), vibrating sample magnetometry (VSM), and dynamic light scattering (DLS) to determine the functionalities of the hybrid structure. The magnetic pH-sensitive microcontainers were loaded with Daunorubicin and tested with respect to release rate at different pH values in order to evaluate their functionality as controlled release system. PMID:21648457

  20. Alanine aminotransferase 1 (OsAlaAT1) plays an essential role in the regulation of starch storage in rice endosperm.

    PubMed

    Yang, Jungil; Kim, Sung-Ryul; Lee, Sang-Kyu; Choi, Heebak; Jeon, Jong-Seong; An, Gynheung

    2015-11-01

    Alteration of storage substances, in particular the major storage form starch, leads to floury endosperm. Because floury mutants have physical attributes for milling processes, identification and characterization of those mutants are valuable. In this study we identified a floury endosperm mutant caused by a T-DNA insertion in Oryza sativa alanine-aminotransferase1 (OsAlaAT1). OsAlaAT1 is localized in the cytosol and has aminotransferase enzyme activity. The osalaat1 mutant has less amylose and its amylopectin is structurally altered. OsAlaAT1 is predominantly expressed in developing seeds during active starch synthesis. AlaAT catalyzes the interconversion of pyruvate to alanine, and this pathway is activated under low-oxygen conditions. Consistently, OsAlaAT1 is induced by such conditions. Expression of the starch synthesis genes AGPases, OsSSI, OsSSIIa, and OsPPDKB is decreased in the mutant. Thus, our observations suggest that OsAlaAT1 plays an essential role in starch synthesis in developing seeds that are exposed to low concentrations of oxygen. PMID:26475189

  1. ALA-mediated fluorescence-guided resection (FGR) and PDT of glioma

    NASA Astrophysics Data System (ADS)

    Johansson, Ann; Stepp, Herbert; Beck, Tobias; Beyer, Wolfgang; Pongratz, Thomas; Sroka, Ronald; Meinel, Thomas; Stummer, Walter; Kreth, Friedrich-Wilhelm; Tonn, Jörg-Christian; Baumgartner, Reinhold

    2009-06-01

    A summary of clinical trials employing photodynamic diagnosis (PDD) and photodynamic therapy (PDT) for the diagnosis and treatment of brain malignancies is presented. Intra-cavity PDT has been performed within the surgical cavity following FGR, employing oral administration of 5-aminolevulinic acid (5-ALA), either targeting fluorescing tissue regions that were not removed during FGR due to safety reasons (referred to as focal PDT, n=20) or illuminating the entire resection cavity (referred to as integral PDT, n=9). Both approaches proved technically feasible and safe. Spectroscopic measurements performed pre-, during and post-PDT revealed Protoporphyrin IX (PpIX)-photobleaching of more than 95% after the delivery of 200 J/cm2. This light dose did not induce any side effects. Furthermore, interstitial PDT (iPDT) has been employed within one feasibility trial (n=10) and one Phase I/II trial (n=15). Here, three to six cylindrical light diffusors (20-30 mm length, 200 mW/cm, 720 J/cm) were positioned within the target tissue under stereotactic guidance. Pre-treatment planning was performed with the intent to target the entire tumour volume with a sufficient light dose while also minimising the risk of any light-induced temperature increase. For the feasibility trial patients with small, recurrent gliomas were included, resulting in a median survival of 15 months as well as some unexpected longterm survivals (up to 5 years). The Phase I/II trial employed the same clinical procedures. Here, the 12-month survival was 35% and the median progression-free survival was 6 months. In summary, stereotactic iPDT in combination with treatment-planning could be shown to be a safe and feasible treatment modality. These trials are presently being extended to also include on-line monitoring of PpIX fluorescence and photobleaching kinetics. Preliminary data has revealed dramatically different PpIX levels and photobleaching kinetics. Such data could possibly be employed for realtime

  2. Localized removal of the Au-Si eutectic bonding layer for the selective release of microstructures

    NASA Astrophysics Data System (ADS)

    Gradin, Henrik; Braun, Stefan; Stemme, Göran; van der Wijngaart, Wouter

    2009-10-01

    This paper presents and investigates a novel technique for the footprint and thickness-independent selective release of Au-Si eutectically bonded microstructures through the localized removal of their eutectic bond interface. The technique is based on the electrochemical removal of the gold in the eutectic layer and the selectivity is provided by patterning the eutectic layer and by proper electrical connection or isolation of the areas to be etched or removed, respectively. The gold removal results in a porous silicon layer, acting similar to standard etch holes in a subsequent sacrificial release etching. The paper presents the principle and the design requirements of the technique. First test devices were fabricated and the method successfully demonstrated. Furthermore, the paper investigates the release mechanism and the effects of different gold layouts on both the eutectic bonding and the release procedure.

  3. The β-Lactamase Gene Regulator AmpR Is a Tetramer That Recognizes and Binds the d-Ala-d-Ala Motif of Its Repressor UDP-N-acetylmuramic Acid (MurNAc)-pentapeptide*

    PubMed Central

    Vadlamani, Grishma; Thomas, Misty D.; Patel, Trushar R.; Donald, Lynda J.; Reeve, Thomas M.; Stetefeld, Jörg; Standing, Kenneth G.; Vocadlo, David J.; Mark, Brian L.

    2015-01-01

    Inducible expression of chromosomal AmpC β-lactamase is a major cause of β-lactam antibiotic resistance in the Gram-negative bacteria Pseudomonas aeruginosa and Enterobacteriaceae. AmpC expression is induced by the LysR-type transcriptional regulator (LTTR) AmpR, which activates ampC expression in response to changes in peptidoglycan (PG) metabolite levels that occur during exposure to β-lactams. Under normal conditions, AmpR represses ampC transcription by binding the PG precursor UDP-N-acetylmuramic acid (MurNAc)-pentapeptide. When exposed to β-lactams, however, PG catabolites (1,6-anhydroMurNAc-peptides) accumulate in the cytosol, which have been proposed to competitively displace UDP-MurNAc-pentapeptide from AmpR and convert it into an activator of ampC transcription. Here we describe the molecular interactions between AmpR (from Citrobacter freundii), its DNA operator, and repressor UDP-MurNAc-pentapeptide. Non-denaturing mass spectrometry revealed AmpR to be a homotetramer that is stabilized by DNA containing the T-N11-A LTTR binding motif and revealed that it can bind four repressor molecules in an apparently stepwise manner. A crystal structure of the AmpR effector-binding domain bound to UDP-MurNAc-pentapeptide revealed that the terminal d-Ala-d-Ala motif of the repressor forms the primary contacts with the protein. This observation suggests that 1,6-anhydroMurNAc-pentapeptide may convert AmpR into an activator of ampC transcription more effectively than 1,6-anhydroMurNAc-tripeptide (which lacks the d-Ala-d-Ala motif). Finally, small angle x-ray scattering demonstrates that the AmpR·DNA complex adopts a flat conformation similar to the LTTR protein AphB and undergoes only a slight conformational change when binding UDP-MurNAc-pentapeptide. Modeling the AmpR·DNA tetramer bound to UDP-MurNAc-pentapeptide predicts that the UDP-MurNAc moiety of the repressor participates in modulating AmpR function. PMID:25480792

  4. The β-lactamase gene regulator AmpR is a tetramer that recognizes and binds the D-Ala-D-Ala motif of its repressor UDP-N-acetylmuramic acid (MurNAc)-pentapeptide.

    PubMed

    Vadlamani, Grishma; Thomas, Misty D; Patel, Trushar R; Donald, Lynda J; Reeve, Thomas M; Stetefeld, Jörg; Standing, Kenneth G; Vocadlo, David J; Mark, Brian L

    2015-01-30

    Inducible expression of chromosomal AmpC β-lactamase is a major cause of β-lactam antibiotic resistance in the Gram-negative bacteria Pseudomonas aeruginosa and Enterobacteriaceae. AmpC expression is induced by the LysR-type transcriptional regulator (LTTR) AmpR, which activates ampC expression in response to changes in peptidoglycan (PG) metabolite levels that occur during exposure to β-lactams. Under normal conditions, AmpR represses ampC transcription by binding the PG precursor UDP-N-acetylmuramic acid (MurNAc)-pentapeptide. When exposed to β-lactams, however, PG catabolites (1,6-anhydroMurNAc-peptides) accumulate in the cytosol, which have been proposed to competitively displace UDP-MurNAc-pentapeptide from AmpR and convert it into an activator of ampC transcription. Here we describe the molecular interactions between AmpR (from Citrobacter freundii), its DNA operator, and repressor UDP-MurNAc-pentapeptide. Non-denaturing mass spectrometry revealed AmpR to be a homotetramer that is stabilized by DNA containing the T-N11-A LTTR binding motif and revealed that it can bind four repressor molecules in an apparently stepwise manner. A crystal structure of the AmpR effector-binding domain bound to UDP-MurNAc-pentapeptide revealed that the terminal D-Ala-D-Ala motif of the repressor forms the primary contacts with the protein. This observation suggests that 1,6-anhydroMurNAc-pentapeptide may convert AmpR into an activator of ampC transcription more effectively than 1,6-anhydroMurNAc-tripeptide (which lacks the D-Ala-D-Ala motif). Finally, small angle x-ray scattering demonstrates that the AmpR·DNA complex adopts a flat conformation similar to the LTTR protein AphB and undergoes only a slight conformational change when binding UDP-MurNAc-pentapeptide. Modeling the AmpR·DNA tetramer bound to UDP-MurNAc-pentapeptide predicts that the UDP-MurNAc moiety of the repressor participates in modulating AmpR function. PMID:25480792

  5. Hierarchical assembly of Ti(IV)/Sn(II) co-doped SnO₂ nanosheets along sacrificial titanate nanowires: synthesis, characterization and electrochemical properties.

    PubMed

    Wang, Hongkang; Xi, Liujiang; Tucek, Jiri; Zhan, Yawen; Hung, Tak Fu; Kershaw, Stephen V; Zboril, Radek; Chung, C Y; Rogach, Andrey L

    2013-10-01

    Hierarchical assembly of Ti(IV)/Sn(II)-doped SnO₂ nanosheets along titanate nanowires serving as both sacrificial templates and a Ti(IV) source is demonstrated, using SnCl2 as a tin precursor and Sn(II) dopants and NaF as the morphology controlling agent. Excess fluoride inhibits the hydrolysis of SnCl2, promoting heterogeneous nucleation of Sn(II)-doped SnO₂ on the titanate nanowires due to the insufficient oxidization of Sn(II) to Sn(IV). Simultaneously, titanate nanowires are dissolved forming Ti(4+) species under the etching effect of in situ generated HF resulting in spontaneous Ti(4+) ion doping of SnO₂ nanosheets formed under hydrothermal conditions. Compositional analysis indicates that Ti(4+) ions are incorporated by substitution of Sn sites at a high level (16-18 at.%), with uniform distribution and no phase separation. Mössbauer spectroscopy quantified the relative content of Sn(II) and Sn(IV) in both Sn(II)-doped and Ti(IV)/Sn(II) co-doped SnO₂ samples. Electrochemical properties were investigated as an anode material in lithium ion batteries, demonstrating that Ti-doped SnO₂ nanosheets show improved cycle performance, which is attributed to the alleviation of inherent volume expansion of the SnO₂-based anode materials by substituting part of Sn sites with Ti dopants. PMID:23904051

  6. Surface imprinting on nano-TiO2 as sacrificial material for the preparation of hollow chlorogenic acid imprinted polymer and its recognition behavior

    NASA Astrophysics Data System (ADS)

    Li, Hui; Li, Gui; Li, Zhiping; Lu, Cuimei; Li, Yanan; Tan, Xianzhou

    2013-01-01

    Surface imprinting chlorogenic acid (CGA) on nano-TiO2 particles as sacrificial support material was successfully performed by using 4-vinylpyridine (4-VP) as functional monomer to obtain a hollow CGA-imprinted polymer (H-MIP1). Fourier transmission infrared spectrometry (FTIR) and scanning electron microscopy (SEM) were utilized for structurally characterizing the polymers obtained and adsorption dynamics and thermodynamic behavior investigated according to different models. Binding selectivity, adsorption capacity and the reusability for this H-MIP1 were also evaluated. This hollow CGA imprinted polymer shows rapid binding dynamics and higher binding capability toward the template molecules. The pseudo first-order kinetic model was shown best to describe the binding process of CGA on the H-MIP1 and Langmuir isotherm model best to fit the experimental adsorption isotherm data. Through adsorption isotherms at different temperatures, thermodynamic parameter values were obtained. Selectivity coefficients for the H-MIP1 toward the template were 2.209, 3.213, 1.746 and 2.353 relative to CA, VA, PCA and GA, respectively. This H-MIP1 was also indicated with a good imprint effect and a high capability to capture CGA from methanol extract of Eucommia ulmoides (E. ulmoides) leaves. Additionally, a good reusability for this imprinted polymer was exhibited during repeated adsorption-desorption use.

  7. One-step generation of cell-laden microgels using double emulsion drops with a sacrificial ultra-thin oil shell.

    PubMed

    Choi, Chang-Hyung; Wang, Huanan; Lee, Hyomin; Kim, June Hwan; Zhang, Liyuan; Mao, Angelo; Mooney, David J; Weitz, David A

    2016-04-26

    Cell-laden microgels with highly uniform sizes have significant potential in tissue engineering and cell therapy due to their capability to provide a physiologically relevant three-dimensional (3D) microenvironment for living cells. In this work, we present a simple and efficient microfluidic approach to produce monodisperse cell-laden microgels through the use of double emulsion drops with an ultra-thin oil shell as the sacrificial template. Specifically, the thin oil shell in double emulsion spontaneously dewets upon polymerization of the innermost precursor drop and subsequent transfer into an aqueous solution, resulting in direct dispersion of microgels in the aqueous phase. Compared to conventional single emulsion-based techniques for cell encapsulation, this one-step approach prevents prolonged exposure of cells to the oil phase, leading to high-throughput cell encapsulation in microgels without compromising the cell viability. Moreover, this approach allows us to culture cells within a 3D microgel which mimics the extracellular matrix, thus enabling long-term cell functionality. This microfluidic technique represents a significant step forward in high-throughput cell microencapsulation technology and offers a potentially viable option to produce cell-laden microgels for widespread applications in tissue engineering and cell therapies. PMID:27070224

  8. Solar light-responsive Pt/CdS/TiO2 photocatalysts for hydrogen production and simultaneous degradation of inorganic or organic sacrificial agents in wastewater.

    PubMed

    Daskalaki, Vasileia M; Antoniadou, Maria; Li Puma, Gianluca; Kondarides, Dimitris I; Lianos, Panagiotis

    2010-10-01

    Photocatalytic degradation of waste material in aqueous solutions and simultaneous production of hydrogen was studied with the double purpose of environmental remediation and renewable energy production. Both powdered and immobilized Pt/CdS/TiO(2) photocatalysts were used to oxidize model inorganic (S(2-)/SO(3)(2-)) and organic (ethanol) sacrificial agents/pollutants in water. Powdered Pt/CdS/TiO(2) photocatalysts of variable CdS content (0-100%) were synthesized by precipitation of CdS nanoparticles on TiO(2) (Degussa P25) followed by deposition of Pt (0.5 wt %) and were characterized with BET, XRD, and DRS. Immobilized photocatalysts were deposited either on plain glass slides or on transparent conductive fluorine-doped SnO(2) electrodes. The results show that it is possible to produce hydrogen efficiently (20% quantum efficiency at 470 nm) by using simulated solar light and by photocatalytically consuming either inorganic or organic substances. CdS-rich photocatalysts are more efficient for the photodegradation of inorganics, while TiO(2)-rich materials are more effective for the photodegradation of organic substances. PMID:20423075

  9. Synthesis of hierarchical NiCo2O4 hollow nanorods via sacrificial-template accelerate hydrolysis for electrochemical glucose oxidation.

    PubMed

    Yang, Jiao; Cho, Misuk; Lee, Youngkwan

    2016-01-15

    Hierarchical NiCo2O4 hollow nanorods (HR) were directly grown on stainless steel via a sacrificial template accelerated hydrolysis and post calcination using ZnO nanorod as a template. The composition of the NiCo2O4 HR electrode was determined using X-ray diffraction and X-ray photoelectron spectroscopy. The morphology of the NiCo2O4 HR is comprised of nanoflakes that were characterized with scanning electron microscopy and transmission electron microscopy. The mixed-valence metal oxide and hollow structure provided high chemical reactivity and a large surface area for glucose oxidation in an alkaline solution. Under an optimal applied potential of +0.6 V, the developed NiCo2O4 HR electrode showed a broad detection range of 0.0003–1.0 mM, a sensitivity of 1685.1 μA mM−1 cm−2, and a low detection limit of 0.16 μM. These results represent a significant improvement over both NiO and Co3O4 HR. The developed NiCo2O4 HR electrode not only demonstrated excellent selectivity in the presence of several electro-active species, but also exhibited high stability following a 200 cycles voltammetry test. PMID:26281005

  10. Meta-Analyses of Manganese Superoxide Dismutase Activity, Gene Ala-9Val Polymorphism, and the Risk of Schizophrenia

    PubMed Central

    Wang, Dong-Fang; Cao, Bing; Xu, Mei-Yan; Liu, Ya-Qiong; Yan, Lai-Lai; Liu, Rong; Wang, Jing-Yu; Lu, Qing-Bin

    2015-01-01

    Abstract Schizophrenia is a complex and disabling psychiatric disorder, and tardive dyskinesia (TD) is a severe adverse drug effect occurring in 20% to 40% of schizophrenic patients chronically treated with typical neuroleptics. Previous studies suggested that the manganese superoxide dismutase (MnSOD) activity was associated with the development of schizophrenia. Ala-9Val polymorphism, a functional polymorphism of MnSOD gene, has been reported to be related to the risk of schizophrenia and TD. However, these studies did not lead to consistent results. We performed meta-analyses aiming to assess the association between MnSOD activity and schizophrenia, as well as the association of MnSOD Ala-9Val polymorphism with schizophrenia and TD in schizophrenic patients. We search for the literature on MnSOD and schizophrenia in English or Chinese published up to May 1, 2015 on PubMed, EMBASE, the Cochrane Databases, Chinese National Knowledge Infrastructure, China Biology Medical and Wanfang databases. Two investigators independently reviewed retrieved literature and evaluated eligibility. Discrepancy was resolved by consensus with a third reviewer. Data were pooled using fixed-effect or random-effect models. The standardized mean difference (SMD) and 95% confidence interval (CI) were calculated for the MnSOD activity. Pooled odds ratio (OR) and 95% CI were calculated for Ala-9Val genotype and allele frequencies. There were 6, 6, and 10 studies entering 3 parts of meta-analyses, respectively. The MnSOD activity of patients was significantly lower than that of controls (SMD = −0.94; 95% CI: −1.76, −0.12; P = 0.025). No significant associations of Ala-9Val genotypes (OR = 1.14; 95% CI: 0.97, 1.33; P = 0.109) and alleles (OR = 1.06; 95% CI: 0.94, 1.20; P = 0.361) with the risk of schizophrenia were observed. We also did not reveal significant associations of the genotypes (OR = 0.82; 95% CI: 0.66, 1.02; P = 0.075) and alleles (OR = 0

  11. Scalable imprinting of shape-specific polymeric nanocarriers using a release layer of switchable water solubility.

    PubMed

    Agarwal, Rachit; Singh, Vikramjit; Jurney, Patrick; Shi, Li; Sreenivasan, S V; Roy, Krishnendu

    2012-03-27

    There is increasing interest in fabricating shape-specific polymeric nano- and microparticles for efficient delivery of drugs and imaging agents. The size and shape of these particles could significantly influence their transport properties and play an important role in in vivo biodistribution, targeting, and cellular uptake. Nanoimprint lithography methods, such as jet-and-flash imprint lithography (J-FIL), provide versatile top-down processes to fabricate shape-specific, biocompatible nanoscale hydrogels that can deliver therapeutic and diagnostic molecules in response to disease-specific cues. However, the key challenges in top-down fabrication of such nanocarriers are scalable imprinting with biological and biocompatible materials, ease of particle-surface modification using both aqueous and organic chemistry as well as simple yet biocompatible harvesting. Here we report that a biopolymer-based sacrificial release layer in combination with improved nanocarrier-material formulation can address these challenges. The sacrificial layer improves scalability and ease of imprint-surface modification due to its switchable solubility through simple ion exchange between monovalent and divalent cations. This process enables large-scale bionanoimprinting and efficient, one-step harvesting of hydrogel nanoparticles in both water- and organic-based imprint solutions. PMID:22385068

  12. Quantitative fluorescence in intracranial tumor: implications for ALA-induced PpIX as an intraoperative biomarker

    PubMed Central

    Valdés, Pablo A.; Leblond, Frederic; Kim, Anthony; Harris, Brent T.; Wilson, Brian C.; Fan, Xiaoyao; Tosteson, Tor D.; Hartov, Alex; Ji, Songbai; Erkmen, Kadir; Simmons, Nathan E.; Paulsen, Keith D.; Roberts, David W.

    2011-01-01

    Object Accurate discrimination between tumor and normal tissue is crucial for optimal tumor resection. Qualitative fluorescence of protoporphyrin IX (PpIX), synthesized endogenously following δ-aminolevulinic acid (ALA) administration, has been used for this purpose in high-grade glioma (HGG). The authors show that diagnostically significant but visually imperceptible concentrations of PpIX can be quantitatively measured in vivo and used to discriminate normal from neoplastic brain tissue across a range of tumor histologies. Methods The authors studied 14 patients with diagnoses of low-grade glioma (LGG), HGG, meningioma, and metastasis under an institutional review board–approved protocol for fluorescence-guided resection. The primary aim of the study was to compare the diagnostic capabilities of a highly sensitive, spectrally resolved quantitative fluorescence approach to conventional fluorescence imaging for detection of neoplastic tissue in vivo. Results A significant difference in the quantitative measurements of PpIX concentration occurred in all tumor groups compared with normal brain tissue. Receiver operating characteristic (ROC) curve analysis of PpIX concentration as a diagnostic variable for detection of neoplastic tissue yielded a classification efficiency of 87% (AUC = 0.95, specificity = 92%, sensitivity = 84%) compared with 66% (AUC = 0.73, specificity = 100%, sensitivity = 47%) for conventional fluorescence imaging (p < 0.0001). More than 81% (57 of 70) of the quantitative fluorescence measurements that were below the threshold of the surgeon's visual perception were classified correctly in an analysis of all tumors. Conclusions These findings are clinically profound because they demonstrate that ALA-induced PpIX is a targeting biomarker for a variety of intracranial tumors beyond HGGs. This study is the first to measure quantitative ALA-induced PpIX concentrations in vivo, and the results have broad implications for guidance during resection of

  13. Boundary Layer

    NASA Technical Reports Server (NTRS)

    Loitsianskii. L. G.

    1956-01-01

    The fundamental, practically the most important branch of the modern mechanics of a viscous fluid or a gas, is that branch which concerns itself with the study of the boundary layer. The presence of a boundary layer accounts for the origin of the resistance and lift force, the breakdown of the smooth flow about bodies, and other phenomena that are associated with the motion of a body in a real fluid. The concept of boundary layer was clearly formulated by the founder of aerodynamics, N. E. Joukowsky, in his well-known work "On the Form of Ships" published as early as 1890. In his book "Theoretical Foundations of Air Navigation," Joukowsky gave an account of the most important properties of the boundary layer and pointed out the part played by it in the production of the resistance of bodies to motion. The fundamental differential equations of the motion of a fluid in a laminar boundary layer were given by Prandtl in 1904; the first solutions of these equations date from 1907 to 1910. As regards the turbulent boundary layer, there does not exist even to this day any rigorous formulation of this problem because there is no closed system of equations for the turbulent motion of a fluid. Soviet scientists have done much toward developing a general theory of the boundary layer, and in that branch of the theory which is of greatest practical importance at the present time, namely the study of the boundary layer at large velocities of the body in a compressed gas, the efforts of the scientists of our country have borne fruit in the creation of a new theory which leaves far behind all that has been done previously in this direction. We shall herein enumerate the most important results by Soviet scientists in the development of the theory of the boundary layer.

  14. Polariton Resonances for Ultrastrong Coupling Cavity Optomechanics in GaAs /AlAs Multiple Quantum Wells

    NASA Astrophysics Data System (ADS)

    Jusserand, B.; Poddubny, A. N.; Poshakinskiy, A. V.; Fainstein, A.; Lemaitre, A.

    2015-12-01

    Polariton-mediated light-sound interaction is investigated through resonant Brillouin scattering experiments in GaAs /AlAs multiple-quantum wells. Photoelastic coupling enhancement at exciton-polariton resonance reaches 105 at 30 K as compared to a typical bulk solid room temperature transparency value. When applied to GaAs based cavity optomechanical nanodevices, this result opens the path to huge displacement sensitivities and to ultrastrong coupling regimes in cavity optomechanics with couplings g0 in the range of 100 GHz.

  15. Epidemiological, clinical and biochemical characterization of the p.(Ala359Asp) SMPD1 variant causing Niemann-Pick disease type B.

    PubMed

    Acuña, Mariana; Martínez, Pablo; Moraga, Carol; He, Xingxuan; Moraga, Mauricio; Hunter, Bessie; Nuernberg, Peter; Gutiérrez, Rodrigo A; González, Mauricio; Schuchman, Edward H; Santos, José Luis; Miquel, Juan Francisco; Mabe, Paulina; Zanlungo, Silvana

    2016-02-01

    Niemann-Pick disease type B (NPDB) is a rare, inherited lysosomal storage disorder that occurs due to variants in the sphingomyelin phosphodiesterase 1 (SMPD1) gene and the resultant deficiency of acid sphingomyelinase (ASM) activity. While numerous variants causing NPDB have been described, only a small number have been studied in any detail. Herein, we describe the frequency of the p.(Ala359Asp) variant in the healthy Chilean population, and determine the haplotype background of homozygous patients to establish if this variant originated from a common founder. Genomic DNA samples from 1691 healthy individuals were analyzed for the p.(Ala359Asp) variant. The frequency of p.(Ala359Asp) was found to be 1/105.7, predicting a disease incidence of 1/44 960 in Chile, higher than the incidence estimated by the number of confirmed NPDB cases. We also describe the clinical characteristics of 13 patients homozygous for p.(Ala359Asp) and all of them had moderate to severe NPDB disease. In addition, a conserved haplotype and shared 280 Kb region around the SMPD1 gene was observed in the patients analyzed, indicating that the variant originated from a common ancestor. The haplotype frequency and mitochondrial DNA analysis suggest an Amerindian origin for the variant. To assess the effect of the p.(Ala359Asp) variant, we transfected cells with the ASM-p.(Ala359Asp) cDNA and the activity was only 4.2% compared with the wild-type cDNA, definitively demonstrating the causative effect of the variant on ASM function. Information on common variants such as p.(Ala359Asp) is essential to guide the successful implementation for future therapies and benefit to patients. PMID:25920558

  16. ALA-PpIX variability quantitatively imaged in A431 epidermoid tumors using in vivo ultrasound fluorescence tomography and ex vivo assay

    NASA Astrophysics Data System (ADS)

    DSouza, Alisha V.; Flynn, Brendan P.; Gunn, Jason R.; Samkoe, Kimberley S.; Anand, Sanjay; Maytin, Edward V.; Hasan, Tayyaba; Pogue, Brian W.

    2014-03-01

    Treatment monitoring of Aminolevunilic-acid (ALA) - Photodynamic Therapy (PDT) of basal-cell carcinoma (BCC) calls for superficial and subsurface imaging techniques. While superficial imagers exist for this purpose, their ability to assess PpIX levels in thick lesions is poor; additionally few treatment centers have the capability to measure ALA-induced PpIX production. An area of active research is to improve treatments to deeper and nodular BCCs, because treatment is least effective in these. The goal of this work was to understand the logistics and technical capabilities to quantify PpIX at depths over 1mm, using a novel hybrid ultrasound-guided, fiber-based fluorescence molecular spectroscopictomography system. This system utilizes a 633nm excitation laser and detection using filtered spectrometers. Source and detection fibers are collinear so that their imaging plane matches that of ultrasound transducer. Validation with phantoms and tumor-simulating fluorescent inclusions in mice showed sensitivity to fluorophore concentrations as low as 0.025μg/ml at 4mm depth from surface, as presented in previous years. Image-guided quantification of ALA-induced PpIX production was completed in subcutaneous xenograft epidermoid cancer tumor model A431 in nude mice. A total of 32 animals were imaged in-vivo, using several time points, including pre-ALA, 4-hours post-ALA, and 24-hours post-ALA administration. On average, PpIX production in tumors increased by over 10-fold, 4-hours post-ALA. Statistical analysis of PpIX fluorescence showed significant difference among all groups; p<0.05. Results were validated by exvivo imaging of resected tumors. Details of imaging, analysis and results will be presented to illustrate variability and the potential for imaging these values at depth.

  17. Association between PPAR-γ2 Pro12Ala genotype and insulin resistance is modified by circulating lipids in Mexican children

    PubMed Central

    Stryjecki, Carolina; Peralta-Romero, Jesus; Alyass, Akram; Karam-Araujo, Roberto; Suarez, Fernando; Gomez-Zamudio, Jaime; Burguete-Garcia, Ana; Cruz, Miguel; Meyre, David

    2016-01-01

    The Pro12Ala (rs1801282) polymorphism in peroxisome proliferator-activated receptor-γ2 (PPAR-γ2) has been convincingly associated with insulin resistance (IR) and type 2 diabetes (T2D) among Europeans, in interaction with a high-fat diet. Mexico is disproportionally affected by obesity and T2D however, whether the Pro12Ala polymorphism is associated with early metabolic complications in this population is unknown. We assessed the association of PPAR-γ2 Pro12Ala with metabolic traits in 1457 Mexican children using linear regression models. Interactions between PPAR-γ2 Pro12Ala and circulating lipids on metabolic traits were determined by adding an interaction term to regression models. We observed a high prevalence of overweight/obesity (49.2%), dyslipidemia (34.9%) and IR (11.1%). We detected nominally significant/significant interactions between lipids (total cholesterol, HDL-cholesterol, LDL-cholesterol), the PPAR-γ2 Pro12Ala genotype and waist-to-hip ratio, fasting insulin, HOMA-IR and IR (9.30 × 10−4  ≤ Pinteraction ≤ 0.04). Post-hoc subgroup analyses evidenced that the association between the PPAR-γ2 Pro12Ala genotype and fasting insulin, HOMA-IR and IR was restricted to children with total cholesterol or LDL-cholesterol values higher than the median (0.02 ≤ P ≤ 0.03). Our data support an association of the Pro12Ala polymorphism with IR in Mexican children and suggest that this relationship is modified by dyslipidemia. PMID:27075119

  18. Endopeptidase 3.4.24.11 converts N-1-(R,S)carboxy-3-phenylpropyl-Ala-Ala-Phe-p-carboxyanilide into a potent inhibitor of angiotensin-converting enzyme.

    PubMed Central

    Williams, C H; Yamamoto, T; Walsh, D M; Allsop, D

    1993-01-01

    It was reported recently that N-1-(R,S)carboxy-3-phenylpropyl-Ala-Ala-Phe-p-carboxyanilide (CPP-A-A-F-pAB), an inhibitor of endopeptidase 3.4.24.15 (E-24.15), also inhibits angiotensin-converting enzyme (ACE) from rabbit lung. We have found that this compound is without effect on ACE purified from pig kidney, at a concentration some 1000-fold greater than the Ki reported for inhibition of the enzyme from lung. However, preincubation of CPP-A-A-F-pAB with neutral endopeptidase 3.4.24.11 (E-24.11) does result in potent inhibitory effects on ACE. We have shown this to be due to formation of a fragment, CPP-A-A, the structure of which is closely related to ACE inhibitors such as enalaprilat. CPP-A-A was found to be a potent inhibitor of pig ACE. Under the conditions used it had an IC50 value of 1.6 x 10(-8) M, compared with the value obtained for captopril of 7.5 x 10(-10) M. These results have important implications for studies of E-24.15 when using CPP-A-A-F-pAB in vivo or in crude tissue extracts where E-24.11 might also be present. PMID:8379924

  19. Spallanzani Layers

    NASA Technical Reports Server (NTRS)

    2006-01-01

    31 March 2006 This Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) image shows a layered, light-toned mesa among other layered materials exposed in a mound that covers much of the floor of Spallanzani Crater.

    Location near: 58.3oS, 273.9oW Image width: 3 km (1.9 mi) Illumination from: upper left Season: Southern Summer

  20. Capping and decapping of MBE grown GaAs(001), Al 0.5Ga 0.5As(001), and AlAs(001) investigated with ASP, PES, LEED, and RHEED

    NASA Astrophysics Data System (ADS)

    Bernstein, R. W.; Borg, A.; Husby, H.; Fimland, B.-O.; Grepstad, J. K.

    Arsenic capping and regeneration of MBE-grown GaAs(001), Al 0.5Ga 0.5As(001), and AlAs(001) epilayer surfaces were examined with Auger sputter profiling (ASP), synchrotron radiation and X-ray photoelectron spectroscopy (PES), LEED, and RHEED. It is found that clean, ordered surfaces of different As/Ga(Al) compositions and different surface reconstructions can be prepared in a controlled manner after long-term storage in air, by thermal desorption of the As cap at appropriate annealing temperatures. A protective film of amorphous arsenic was deposited in situ with both As 2 and As 4 molecular beams onto cold substrates. The recorded Auger depth profiles unveil capping layer thicknesses from 0.3 to 3 μm, the thicker for depositions using the As 2 dimer source. The As 3+ surface oxide, formed immediately upon exposure of the passivated wafers to air, remains on the order of 10Åthick, even after storage in atmosphere for several months. Core level photoemission shows selective desorption of this oxide upon annealing in UHV at 250°C. Further heating at 350°C evaporates the protective arsenic cap, and clean, As-terminated Al xGa 1- xAs(001) surfaces with a regular arrayof chemisorbed excess As sbnd As dimers prevail. The recorded LEED and RHEED patterns show a c(4 × 4) surface reconstruction for GaAs(001) and Al 0.5Ga 0.5As(001), whereas this structural phase was observed with RHEED only for the highly reactive AlAs(001) surface. Subsequently annealing in UHV at 450°C causes desorption of the chemisorbed surface arsenic and a concurrent transition from c(4 × 4) to the (2 × 4)/c(2 × 8) surface of As stabilized MBE-grown Al xGa 1- xAs(001). With AlAs(001), surface Al oxidation was observed immediately after annealing at 450°C, in spite of carefully controlled UHV environments

  1. Glyoxalase I Ala111Glu gene polymorphism: No association with breast cancer risk but correlated with absence of progesterone receptor.

    PubMed

    Naidu, Rakesh; Har, Yip Cheng; Taib, Nur Aishah Mohd

    2010-09-01

    The aim of the present study was to evaluate the association between the Glyoxalase I (GLOI) Ala111Glu polymorphism and breast cancer risk among the major Malaysian ethnic groups, the Malays, Chinese and Indians, as well as clinico-pathological characteristics of these patients. Genotyping of GLOI gene was performed on blood samples obtained from 387 patients and 252 normal healthy women who had no history of any malignancy using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The genotype and allele frequencies of GLOI polymorphism were not significantly different between the patients and normal individuals among the Malays (P= 0.721, 0.402), Chinese (P= 0.208, 0.079) and Indians (P= 0.612, 0.349), respectively. The Malay, Chinese and Indian women who were Glu/Glu homozygotes (P= 0.419, 0.093, 0.367), Ala/Glu heterozygotes (P= 0.648, 0.182, 0.402) and carriers of Glu allele (P= 0.402, 0.079, 0.349), respectively, were not associated with breast cancer risk. The Glu allele genotype was significantly associated with absence of progesterone receptor (P= 0.036). Thus, the polymorphic variant of the GLOI gene might not be a useful genetic marker to identify Malaysian Malay, Chinese or Indian women who could be at greater risk of developing breast cancer. PMID:20712647

  2. Inflammatory cytokines in vitro production are associated with Ala16Val superoxide dismutase gene polymorphism of peripheral blood mononuclear cells.

    PubMed

    Montano, Marco Aurélio Echart; da Cruz, Ivana Beatrice Mânica; Duarte, Marta Maria Medeiros Frescura; Krewer, Cristina da Costa; da Rocha, Maria Izabel de Ugalde Marques; Mânica-Cattani, Maria Fernanda; Soares, Felix Alexandre Antunes; Rosa, Guilherme; Maris, Angélica Francesca; Battiston, Francielle Garghetti; Trott, Alexis; Lera, Juan Pablo Barrio

    2012-10-01

    Obesity is considered a chronic low-grade inflammatory state associated with a chronic oxidative stress caused by superoxide production (O(2)(-)). The superoxide dismutase manganese dependent (SOD2) catalyzes O(2)(-) in H(2)O(2) into mitochondria and is encoded by a single gene that presents a common polymorphism that results in the replacement of alanine (A) with a valine (V) in the 16 codon. This polymorphism has been implicated in a decreased efficiency of SOD2 transport into targeted mitochondria in V allele carriers. Previous studies described an association between VV genotype and metabolic diseases, including obesity and diabetes. However, the causal mechanisms to explain this association need to be more elucidated. We postulated that the polymorphism could influence the inflammatory response. To test our hypothesis, we evaluated the in vitro cytokines production by human peripheral blood mononuclear cells (PBMCs) carrier's different Ala16Val-SOD2 genotypes (IL-1, IL-6, IL-10, TNF-α, IFN-γ). Additionally, we evaluated if the culture medium glucose, enriched insulin, could influence the cytokine production. Higher levels of proinflammatory cytokines were observed in VV-PBMCs when compared to AA-PBMCs. However, the culture medium glucose and enriched insulin did not affect cytokine production. The results suggest that Ala16Val-SOD2 gene polymorphism could trigger the PBMCs proinflammatory cytokines level. However, discerning if a similar mechanism occurs in fat cells is an open question. PMID:22688013

  3. Phototoxic effects of zinc oxide nanowires (ZnO NWs) complexed with 5-ALA in RD cell line

    NASA Astrophysics Data System (ADS)

    Fakhar-e-Alam, M.; Ali, S. M. U.; Ibupoto, Z. H.; Atif, M.; Willander, M.

    2011-12-01

    In this current study, we have manifested the photosensitizing effects of zinc oxide nanowires (ZnO NWs) in dark as well as under ultra violet light exposure with 240 nm of UV region, using human muscle cancer (Rhybdomyosarcoma cells, RD) as in vitro experimental model. We have fabricated ZnO-NWs on the tip of borosilicate glass capillaries (0.5 μm diameter) and were conjugated using 5-aminolevulinic acid (ALA) for the efficient intracellular drug delivery. When ZnO NWs were applied on tumor localizing drugs with non ionizing illumination, then excited drug liberates reactive oxygen species (ROS), effecting mitochondria and nucleus resulting in cell necrosis within few minutes. During investigations, we observed that when ZnO-NWs grown on intracellular tip was excited by using 240 nm of UV light, as a resultant 625 nm of emitted red light were used as appetizer in the presence of 5-ALA for chemical reaction, which produces singlet oxygen, responsible for cell necrosis. Morphological changes of necrosed cells were examined under microscopy. Moreover, Viability of controlled and treated RD cells with optimum dose of light (UV-Visible) has been assessed by MTT assay as well as reactive oxygen species (ROS) detection.

  4. Poly(N-isopropylacrylamide-co-allylamine) (PNIPAM-co-ALA) nanospheres for the thermally triggered release of Bacteriophage K.

    PubMed

    Hathaway, Hollie; Alves, Diana R; Bean, Jessica; Esteban, Patricia P; Ouadi, Khadija; Sutton, J Mark; Jenkins, A Toby A

    2015-10-01

    Due to the increased prevalence of resistant bacterial isolates which are no longer susceptible to antibiotic treatment, recent emphasis has been placed on finding alternative modes of treatment of wound infections. Bacteriophage have long been investigated for their antimicrobial properties, yet the utilization of phage therapy for the treatment of wound infections relies on a suitable delivery system. Poly(N-isopropylacrylamide) (PNIPAM) is a thermally responsive polymer which undergoes a temperature dependent phase transition at a critical solution temperature. Bacteriophage K has been successfully formulated with PNIPAM nanospheres copolymerized with allylamine (PNIPAM-co-ALA). By utilizing a temperature responsive polymer it has been possible to engineer the nanospheres to collapse at an elevated temperature associated with a bacterial skin infection. The nanogels were reacted with surface deposited maleic anhydride in order to anchor the nanogels to non-woven fabric. Bacteriophage incorporated PNIPAM-co-ALA nanospheres demonstrated successful bacterial lysis of a clinically relevant bacterial isolate - Staphylococcus aureus ST228 at 37°C, whilst bacterial growth was unaffected at 25°C, thus providing a thermally triggered release of bacteriophage. PMID:26423908

  5. Development of an orexin-2 receptor selective agonist, [Ala(11), D-Leu(15)]orexin-B.

    PubMed

    Asahi, Shuichi; Egashira, Shin-Ichiro; Matsuda, Masao; Iwaasa, Hisashi; Kanatani, Akio; Ohkubo, Mitsuru; Ihara, Masaki; Morishima, Hajime

    2003-01-01

    Investigation of L-alanine and D-amino acid replacement of orexin-B revealed that three L-leucine residues at the positions of 11, 14, and 15 in orexin-B were important to show selectivity for the orexin-2 receptor (OX(2)) over the orexin-1 receptor (OX(1)). L-Alanine substitution at position 11 and D-leucine substitution at positions 14 and 15 maintained the potency of orexin-B to mobilize [Ca(2+)](i) in CHO cells expressing the OX(2), while their potency for the OX(1) was significantly reduced. In combined substitutions, we identified that [Ala(11), D-Leu(15)]orexin-B showed a 400-fold selectivity for the OX(2) (EC(50)=0.13nM) over OX(1) (EC(50)=52nM). [Ala(11), D-Leu(15)]orexin-B is a beneficial tool for addressing the functional roles of the OX(2). PMID:12467628

  6. Use of 5-ALA fluorescence guided endoscopic biopsy of a deep-seated primary malignant brain tumor.

    PubMed

    Ritz, Rainer; Feigl, Guenther C; Schuhmann, Martin U; Ehrhardt, André; Danz, Soeren; Noell, Susan; Bornemann, Antje; Tatagiba, Marcos S

    2011-05-01

    The introduction of fluorescence-guided resection of primary malignant brain tumors was a milestone in neurosurgery. Deep-seated malignant brain tumors are often not approachable for microsurgical resection. For diagnosis and therapy, new strategies are recommended. The combination of endoscopy and 5-aminolevulinic acid-induced protoporphyrin IX (5-ALA-induced Pp IX) fluorescence-guided procedures supported by neuronavigation seems an interesting option. Here the authors report on a combined approach for 5-ALA fluorescence-guided biopsy in which they use an endoscopy system based on an Xe lamp (excitation approximately λ = 407 nm; dichroic filter system λ = 380-430 nm) to treat a malignant tumor of the thalamus and perform a ventriculostomy and septostomy. The excitation filter and emission filter are adapted to ensure that the remaining visible blue remission is sufficient to superimpose on or suppress the excited red fluorescence of the endogenous fluorochromes. The authors report that the lesion was easily detectable in the fluorescence mode and that biopsy led to histological diagnosis. PMID:21166571

  7. Effects of mass anisotropy, thickness and disorder on the spin susceptibility of the 2DEG in AlAs QWs

    NASA Astrophysics Data System (ADS)

    Marchi, Mariapia; de Palo, Stefania; Senatore, Gaetano; Moroni, Saverio

    2008-03-01

    We present predictions of the spin susceptibility χs, obtained from extensive DMC simulations, for a two dimensional (2D) electron gas (EG) with mass anisotropy appropriate to AlAs QWs[1], both in the strictly 2D limit and with thickness included. We demonstrate that in the one-valley case anisotropy suppresses χs substantially at all densities and in particular at those relevant to experiments[1], the effect being larger at lower density. This suppression adds onto the one due to thickness[2,1]. The comparison of our results for a model EG including both thickness and anisotropy with experiments for AlAs QW's[1] reveals the role of disorder in determining the measured spin susceptibility. In the two-valley case we find an interesting interplay of anisotropy and valley degree of freedom in determining the EG properties and in particular the spin susceptibility. [1] T. Gokmen et. al., Phys. Rev. B in press and cond-mat 0711.1294. [2] S. De Palo et. al., Phys. Rev. Lett. 94, 226405 (2005); and to be published

  8. vanI: a novel D-Ala-D-Lac vancomycin resistance gene cluster found in Desulfitobacterium hafniense.

    PubMed

    Kruse, Thomas; Levisson, Mark; de Vos, Willem M; Smidt, Hauke

    2014-09-01

    The glycopeptide vancomycin was until recently considered a drug of last resort against Gram-positive bacteria. Increasing numbers of bacteria, however, are found to carry genes that confer resistance to this antibiotic. So far, 10 different vancomycin resistance clusters have been described. A chromosomal vancomycin resistance gene cluster was previously described for the anaerobic Desulfitobacterium hafniense Y51. We demonstrate that this gene cluster, characterized by its d-Ala-d-Lac ligase-encoding vanI gene, is present in all strains of D. hafniense, D. chlororespirans and some strains of Desulfosporosinus spp. This gene cluster was not found in vancomycin-sensitive Desulfitobacterium or Desulfosporosinus spp., and we show that this antibiotic resistance can be exploited as an intrinsic selection marker for Desulfitobacterium hafniense and D. chlororespirans. The gene cluster containing vanI is phylogenetically only distantly related with those described from soil and gut bacteria, but clusters instead with vancomycin resistance genes found within the phylum Actinobacteria that include several vancomycin-producing bacteria. It lacks a vanH homologue, encoding a D-lactate dehydrogenase, previously thought to always be present within vancomycin resistance gene clusters. The location of vanH outside the resistance gene cluster likely hinders horizontal gene transfer. Hence, the vancomycin resistance cluster in D. hafniense should be regarded a novel one that we here designated vanI after its unique d-Ala-d-Lac ligase. PMID:25042042

  9. The Synonymous Ala87 Mutation of Estrogen Receptor Alpha Modifies Transcriptional Activation Through Both ERE and AP1 Sites.

    PubMed

    Fernández-Calero, Tamara; Flouriot, Gilles; Marín, Mónica

    2016-01-01

    Estrogen receptor α (ERα) exerts regulatory actions through genomic mechanisms. In the classical pathway, ligand-activated ERα binds directly to DNA through estrogen response elements (ERE) located in the promoter of target genes. ERα can also exert indirect regulation of transcription via protein-protein interaction with other transcription factors such as AP-1.S everal ERα synonymous polymorphisms have been identified and efforts to understand their implications have been made. Nevertheless effects of synonymous polymorphisms are still neglected. This chapter focuses on the experimental procedure employed in order to characterize the transcriptional activity of a synonymous polymorphism of the ERα (rs746432) called Alanine 87 (Ala87). Activity of both WT and Ala87 ERα isoforms on transcriptional pathways can be analyzed in transiently transfected cells using different reporter constructs. ERα efficiency on the classical genomic pathway can be analyzed by determining its transactivation activity on an ERE-driven thymidine kinase (TK) promoter controlling the expression of the luciferase reporter gene. Transcriptional activity through the indirect genomic pathway can be analyzed by employing an AP-1 DNA response element-driven promoter also controlling the expression of luciferase reporter gene. PMID:26585143

  10. The Pro12Ala Polymorphism of the Peroxisome Proliferator-Activated Receptor Gamma Gene Modifies the Association of Physical Activity and Body Mass Changes in Polish Women

    PubMed Central

    Zarebska, Aleksandra; Jastrzebski, Zbigniew; Cieszczyk, Pawel; Leonska-Duniec, Agata; Kotarska, Katarzyna; Kaczmarczyk, Mariusz; Sawczuk, Marek; Maciejewska-Karlowska, Agnieszka

    2014-01-01

    Peroxisome proliferator-activated receptor γ is a key regulator of adipogenesis, responsible for fatty acid storage and maintaining energy balance in the human body. Studies on the functional importance of the PPARG Pro12Ala polymorphic variants indicated that the observed alleles may influence body mass measurements; however, obtained results were inconsistent. We have decided to check if body mass changes observed in physically active participants will be modulated by the PPARG Pro12Ala genotype. The genotype distribution of the PPARG Pro12Ala allele was examined in a group of 201 Polish women measured for selected body mass variables before and after the completion of a 12-week training program. The results of our experiment suggest that PPARG genotype can modulate training-induced body mass measurements changes: after completion of the training program, Pro12/Pro12 homozygotes were characterised by a greater decrease of body fat mass measurements in comparison with 12Ala allele carriers. These results indicate that the PPARG 12Ala variant may impair the training-induced positive effects on body mass measurements; however, the detailed mechanism of such interaction remained unclear and observed correlation between PPARG genotype and body mass differential effects should be interpreted with caution. PMID:25371663

  11. Interaction Effects of the Leu162Val PPARα and Pro12Ala PPARγ2 Gene Variants with Renal Function in Metabolic Syndrome Population

    PubMed Central

    Mohamed Youssef, Sarraj; Mohamed, Najah; Afef, Slimani; Khaldoun, Ben Hamda; Fadoua, Neffati; Fadhel, Najjar Mohamed; Naceur, Slimane Mohamed

    2013-01-01

    Leu162Val PPARα and Pro12Ala PPARγ2 were investigated for their individual and their interactive impact on MS and renal functionality (RF). 522 subjects were investigated for biochemical and anthropometric measurements. The diagnosis of MS was based on the IDF definition (2009). The HOMA 2 was used to determine HOMA-β, HOMA-S and HOMA-IR from FPG and FPI concentrations. RF was assessed by estimating the GFR. PCR-RFLP was performed for DNA genotyping. Allele frequencies were 0.845 for Pro and 0.155 for Ala, and were 0.915 for Leu and 0.085 for Val. We showed that carriers of the PPARα Val 162 allele had lower urea, UA and higher GFR compared to those homozygous for the Leu162 allele. Subjects carried by PPARγ2Ala allele had similar results. They also had reduced FPG, FPI and HOMA-IR, and elevated HOMA-β and HOMA-S compared to those homozygous for the Pro allele. Subjects were divided into 4 groups according to the combinations of genetic alleles of the 2 polymorphisms. Subjects carrying the Leu/Val with an Ala allele had lower FPG, PPI, HOMA-IR, urea, UA levels, higher HOMA-β, HOMA-S and GFR than different genotype combinations. Leu162Val PPARα and Pro12Ala PPARγ2 can interact with each other to modulate glucose and insulin homeostasis and expand their association with overall better RF. PMID:23690758

  12. The presenilin 1 p.Gly206Ala mutation is a frequent cause of early-onset Alzheimer’s disease in Hispanics in Florida

    PubMed Central

    Ravenscroft, Thomas A; Pottier, Cyril; Murray, Melissa E; Baker, Matt; Christopher, Elizabeth; Levitch, Denise; Brown, Patricia H; Barker, Warren; Duara, Ranjan; Greig-Custo, Maria; Betancourt, Ana; English, Mara; Sun, Xiaoyan; Ertekin-Taner, Nilüfer; Graff-Radford, Neill R; Dickson, Dennis W; Rademakers, Rosa

    2016-01-01

    Mutations in the gene encoding the presenilin-1 protein (PSEN1) were first discovered to cause Alzheimer’s disease (AD) 20 years ago. Since then more than 200 different pathogenic mutations have been reported, including a p.Gly206Ala founder mutation in the Hispanic population. Here we report mutation analysis of known AD genes in a cohort of 27 early-onset (age of onset ≤65, age of death ≤70) Hispanic patients ascertained in Florida. The PSEN1 p.Gly206Ala mutation was identified in 13 out of 27 patients (48.1%), emphasizing the importance of this specific mutation in the etiology of early-onset AD in this population. One other patient carried the known PSEN1 p.Gly378Val mutation. Genotyping of the PSEN1 p.Gly206Ala and p.Gly378Val mutations in 63 late-onset Hispanic AD patients did not identify additional mutation carriers. All p.Gly206Ala mutation carriers shared rare alleles at two microsatellite markers flanking PSEN1 supporting a common founder. This study confirms the p.Gly206Ala variant as a frequent cause of early onset AD in the Hispanic population and for the first time reports the high frequency of this mutation in Hispanics in Florida. PMID:27073747

  13. Hierarchical assembly of Ti(iv)/Sn(ii) co-doped SnO2 nanosheets along sacrificial titanate nanowires: synthesis, characterization and electrochemical properties

    NASA Astrophysics Data System (ADS)

    Wang, Hongkang; Xi, Liujiang; Tucek, Jiri; Zhan, Yawen; Hung, Tak Fu; Kershaw, Stephen V.; Zboril, Radek; Chung, C. Y.; Rogach, Andrey L.

    2013-09-01

    Hierarchical assembly of Ti(iv)/Sn(ii)-doped SnO2 nanosheets along titanate nanowires serving as both sacrificial templates and a Ti(iv) source is demonstrated, using SnCl2 as a tin precursor and Sn(ii) dopants and NaF as the morphology controlling agent. Excess fluoride inhibits the hydrolysis of SnCl2, promoting heterogeneous nucleation of Sn(ii)-doped SnO2 on the titanate nanowires due to the insufficient oxidization of Sn(ii) to Sn(iv). Simultaneously, titanate nanowires are dissolved forming Ti4+ species under the etching effect of in situ generated HF resulting in spontaneous Ti4+ ion doping of SnO2 nanosheets formed under hydrothermal conditions. Compositional analysis indicates that Ti4+ ions are incorporated by substitution of Sn sites at a high level (16-18 at.%), with uniform distribution and no phase separation. Mössbauer spectroscopy quantified the relative content of Sn(ii) and Sn(iv) in both Sn(ii)-doped and Ti(iv)/Sn(ii) co-doped SnO2 samples. Electrochemical properties were investigated as an anode material in lithium ion batteries, demonstrating that Ti-doped SnO2 nanosheets show improved cycle performance, which is attributed to the alleviation of inherent volume expansion of the SnO2-based anode materials by substituting part of Sn sites with Ti dopants.Hierarchical assembly of Ti(iv)/Sn(ii)-doped SnO2 nanosheets along titanate nanowires serving as both sacrificial templates and a Ti(iv) source is demonstrated, using SnCl2 as a tin precursor and Sn(ii) dopants and NaF as the morphology controlling agent. Excess fluoride inhibits the hydrolysis of SnCl2, promoting heterogeneous nucleation of Sn(ii)-doped SnO2 on the titanate nanowires due to the insufficient oxidization of Sn(ii) to Sn(iv). Simultaneously, titanate nanowires are dissolved forming Ti4+ species under the etching effect of in situ generated HF resulting in spontaneous Ti4+ ion doping of SnO2 nanosheets formed under hydrothermal conditions. Compositional analysis indicates that Ti4

  14. Copper(ii) tungstate nanoflake array films: sacrificial template synthesis, hydrogen treatment, and their application as photoanodes in solar water splitting

    NASA Astrophysics Data System (ADS)

    Hu, Dianyi; Diao, Peng; Xu, Di; Xia, Mengyang; Gu, Yue; Wu, Qingyong; Li, Chao; Yang, Shubin

    2016-03-01

    We report the preparation of CuWO4 nanoflake (NF) array films by using a solid phase reaction method in which WO3 NFs were employed as sacrificial templates. The SEM, TEM and XRD results demonstrated that the obtained CuWO4 films possessed a network structure that was composed of single crystalline NFs intersected with each other. The CuWO4 NF films showed superior photoelectrochemical (PEC) activity to other CuWO4 photoanodes reported recently for the oxygen evolution reaction (OER). We attributed the high activity to the unique morphological and crystalline structure of the CuWO4 film, which enhanced the photoactivity by providing a large specific area, a short hole transport distance from the inside of CuWO4 to the CuWO4/solution interface, and a low grain boundary density. Hydrogen treatment by annealing the CuWO4 NF film in mixed gases of H2 and Ar could further enhance the photoactivity, as hydrogen treatment significantly increased the electron density of CuWO4 by generating oxygen vacancy in the lattice. The photocurrent density for OER obtained on the hydrogen-treated (H-treated) CuWO4 NF film is the largest ever reported on CuWO4 photoanodes in the literature. Moreover, the CuWO4 photoanodes exhibit good stability in weak alkaline solution, while the H-treated CuWO4 photoanodes exhibit acceptable stability. This work not only reveals the potential of CuWO4 as a photoanode material for solar water splitting but also shows that the construction of nanostructured CuWO4 photoanodes is a promising method to achieve high PEC activity toward OER.We report the preparation of CuWO4 nanoflake (NF) array films by using a solid phase reaction method in which WO3 NFs were employed as sacrificial templates. The SEM, TEM and XRD results demonstrated that the obtained CuWO4 films possessed a network structure that was composed of single crystalline NFs intersected with each other. The CuWO4 NF films showed superior photoelectrochemical (PEC) activity to other CuWO4

  15. Copper(II) tungstate nanoflake array films: sacrificial template synthesis, hydrogen treatment, and their application as photoanodes in solar water splitting.

    PubMed

    Hu, Dianyi; Diao, Peng; Xu, Di; Xia, Mengyang; Gu, Yue; Wu, Qingyong; Li, Chao; Yang, Shubin

    2016-03-21

    We report the preparation of CuWO4 nanoflake (NF) array films by using a solid phase reaction method in which WO3 NFs were employed as sacrificial templates. The SEM, TEM and XRD results demonstrated that the obtained CuWO4 films possessed a network structure that was composed of single crystalline NFs intersected with each other. The CuWO4 NF films showed superior photoelectrochemical (PEC) activity to other CuWO4 photoanodes reported recently for the oxygen evolution reaction (OER). We attributed the high activity to the unique morphological and crystalline structure of the CuWO4 film, which enhanced the photoactivity by providing a large specific area, a short hole transport distance from the inside of CuWO4 to the CuWO4/solution interface, and a low grain boundary density. Hydrogen treatment by annealing the CuWO4 NF film in mixed gases of H2 and Ar could further enhance the photoactivity, as hydrogen treatment significantly increased the electron density of CuWO4 by generating oxygen vacancy in the lattice. The photocurrent density for OER obtained on the hydrogen-treated (H-treated) CuWO4 NF film is the largest ever reported on CuWO4 photoanodes in the literature. Moreover, the CuWO4 photoanodes exhibit good stability in weak alkaline solution, while the H-treated CuWO4 photoanodes exhibit acceptable stability. This work not only reveals the potential of CuWO4 as a photoanode material for solar water splitting but also shows that the construction of nanostructured CuWO4 photoanodes is a promising method to achieve high PEC activity toward OER. PMID:26912373

  16. A trilogy on. delta. -aminolevulinic acid biosynthesis in plants and algae: I. Glutamate is the sole precursor to protoheme and heme a in maize. II. The UUC glutamate anticodon is a general feature of the tRNA required for ALA biosynthesis. III. Protein and ALA biosynthesis use the same tRNA

    SciTech Connect

    Schneegurt, M.A.

    1989-01-01

    Specifically radiolabeled substrates can be used to determine whether the heme and chlorophyll precursor {delta}-aminolevulinic acid (ALA) is synthesized via the fife-carbon pathway (incorporation from L-1-({sup 14}C)glutamate) or ALA synthase (incorporation from 2-({sup 14}C)glycine). In etiolated maize epicotyl sections, highly purified total cellular protoheme was labeled 29.7 times more effectively by glutamate than by glycine. Mitochondrial heme {alpha} was labeled 4.1 times more effectively by glutamate than by glycine. Cell-free plant and algal preparations require tRNA for the enzymatic conversion of glutamate to ALA. The tRNA required for ALA biosynthesis ahs been shown to contain the UUC glutamate anticodon, as determined by its specific retention through anticodon:anticodon interactions by tRNA{sup Phe(GAA)}-acrylamide. A fraction that was highly enriched in the RNA which supported ALA formation was obtained by affinity chromatography of RNA extracts from Chlorella vulgaris, Euglena garcilis, Cyanidium caldarium, Synechocystis, sp. PCC 6803, pea, and spinach. Other glutamate-accepting RNAs that were not retained by the affinity column were ineffective in supporting ALA formation.

  17. The potential applications of ZnO nanoparticles conjugated with ALA and photofrin as a biomarker in HepG2 cells

    NASA Astrophysics Data System (ADS)

    Fakhar-E-Alam, M.; Firdous, S.; Atif, M.; Khan, Y.; Zaidi, S. S. Z.; Suleman, R.; Rehman, A.; Khan, R. U.; Nawaz, M.; Ikram, M.

    2011-12-01

    Drug delivery into the malignant cell is a basic requirement for effectiveness of photosensitizing systems for photodynamic therapy (PDT). For anticancer tumoricidal drugs, e.g., 5-aminolevulinic acid (ALA), zinc oxide (ZnO) nanoparticles (NPs) are used as efficient intracellular photosensitizer carriers. Apoptotic effect of tumoricidal drugs (ALA and Photofrin cells in the presence and absence of ZnO NPs using confocal microscopy as well as Neutral Red Assay (NRA). In dark, ZnO NPs conjugated with ALA or Photofrinhas been found to have a remarkable fluorescence in Hepatucellular carcinoma (HepG2) cells. This fact illustrates the great potential of ZnO NPs as biomarker in relevant clinical and biomedical applications.

  18. Performance, 5-aminolevulinic acid (ALA) yield and microbial population dynamics in a photobioreactor system treating soybean wastewater: Effect of hydraulic retention time (HRT) and organic loading rate (OLR).

    PubMed

    Liu, Shuli; Zhang, Guangming; Zhang, Jie; Li, Xiangkun; Li, Jianzheng

    2016-06-01

    Effects of hydraulic retention time (HRT) and influent organic loading rate (OLR) were investigated in a photobioreactor containing PNSB (Rhodobacter sphaeroides)-chemoheterotrophic bacteria to treat soybean wastewater. Pollutants removal, biomass production and ALA yield in different phases were investigated in together with functional microbial population dynamics. The results showed that proper HRT and OLR increased the photobioreactor performance including pollutants removal, biomass and ALA productions. 89.5% COD, 90.6% TN and 91.2% TP removals were achieved as well as the highest biomass production of 2655mg/L and ALA yield of 7.40mg/g-biomass under the optimal HRT of 60h and OLR of 2.48g/L/d. In addition, HRT and OLR have important impacts on PNSB and total bacteria dynamics. PMID:26818577

  19. Enhancement of tumor responsiveness to aminolevulinate-photodynamic therapy (ALA-PDT) using differentiation-promoting agents in mouse models of skin carcinoma

    NASA Astrophysics Data System (ADS)

    Anand, Sanjay; Honari, Golara; Paliwal, Akshat; Hasan, Tayyaba; Maytin, Edward V.

    2009-06-01

    Aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) is an emerging treatment for cancers. ALA, given as a prodrug, selectively accumulates and is metabolized in cancer cells to form protoporphyrin IX (PpIX). Targeted local irradiation with light induces cell death. Since the efficacy of ALA-PDT for large or deep tumors is currently limited, we are developing a new approach that combines differentiation-inducing agents with ALA-PDT to improve the clinical response. Here, we tested this new combination paradigm in the following two models of skin carcinoma in mice: 1) tumors generated by topical application of chemical carcinogens (DMBA-TPA); 2) human SCC cells (A431) implanted subcutaneously. To achieve a differentiated state of the tumors, pretreatment with a low concentration of methotrexate (MTX) or Vitamin D (Vit D) was administered for 72 h prior to exposure to ALA. Confocal images of histological sections were captured and digitally analyzed to determine relative PpIX levels. PpIX in the tumors was also monitored by real-time in vivo fluorescence dosimetry. In both models, a significant increase in levels of PpIX was observed following pretreatment with MTX or Vit D, as compared to no-pretreatment controls. This enhancing effect was observed at very low, non-cytotoxic concentrations, and was highly specific to cancer cells as compared to normal cells. These results suggest that use of differentiating agents such as MTX or Vit D, as a short-term combination therapy given prior to ALA-PDT, can increase the production of PpIX photosensitizer and enhance the therapeutic response of skin cancers.

  20. The Mediterranean diet protects against waist circumference enlargement in 12Ala carriers for the PPARgamma gene: 2 years' follow-up of 774 subjects at high cardiovascular risk.

    PubMed

    Razquin, Cristina; Alfredo Martinez, J; Martinez-Gonzalez, Miguel A; Corella, Dolores; Santos, José Manuel; Marti, Amelia

    2009-09-01

    The PPARgamma gene regulates insulin sensitivity and adipogenesis. The Pro12Ala polymorphism of this gene has been related to fat accumulation. Our aim was to analyse the effects of a 2-year nutritional intervention with Mediterranean-style diets on adiposity in high-cardiovascular risk patients depending on the Pro12Ala polymorphism of the PPARgamma gene. The population consisted of a substudy (774 high-risk subjects aged 55-80 years) of the Prevención con Dieta Mediterránea (PREDIMED) randomised trial aimed at assessing the effect of the Mediterranean diet for CVD prevention. There were three nutritional intervention groups: two of them of a Mediterranean-style diet and the third was a control group advised to follow a conventional low-fat diet. All the participants were genotyped by PCR-restriction fragment length polymorphism (RFLP). The results showed that carriers of the 12Ala allele allocated to the control group had a statistically significant higher change in waist circumference (adjusted difference coefficient = 2.37 cm; P = 0.014) compared with wild-type subjects after 2 years of nutritional intervention. This adverse effect was not observed among 12Ala carriers allocated to both Mediterranean diet groups. In diabetic patients a statistically significant interaction between Mediterranean diet and the 12Ala allele regarding waist circumference change was observed ( - 5.85 cm; P = 0.003). In conclusion, the Mediterranean diet seems to be able to reduce waist circumference in a high-cardiovascular risk population, reversing the negative effect that the 12Ala allele carriers of the PPARgamma gene appeared to have. The beneficial effect of this dietary pattern seems to be higher among type 2 diabetic subjects. PMID:19267951

  1. Direct Selective Laser Sintering/Melting of High Density Alumina Powder Layers at Elevated Temperatures

    NASA Astrophysics Data System (ADS)

    Deckers, J.; Meyers, S.; Kruth, J. P.; Vleugels, J.

    Direct selective laser sintering (SLS) or selective laser melting (SLM) are additive manufacturing techniques that can be used to produce three-dimensional ceramic parts directly, without the need for a sacrificial binder. In this paper, a low laser energy density is applied to SLS/SLM high density powder layers of sub-micrometer alumina at elevated temperatures (up to 800̊C). In order to achieve this, a furnace was designed and built into a commercial SLS machine. This furnace was able to produce a homogeneously heated cylindrical zone with a height of 60 mm and a diameter of 32 mm. After optimizing the layer deposition and laser scanning parameters, two ceramic parts with a density up to 85% and grain sizes as low as 5 μm were successfully produced.

  2. Layered materials

    NASA Astrophysics Data System (ADS)

    Johnson, David; Clarke, Simon; Wiley, John; Koumoto, Kunihito

    2014-06-01

    Layered compounds, materials with a large anisotropy to their bonding, electrical and/or magnetic properties, have been important in the development of solid state chemistry, physics and engineering applications. Layered materials were the initial test bed where chemists developed intercalation chemistry that evolved into the field of topochemical reactions where researchers are able to perform sequential steps to arrive at kinetically stable products that cannot be directly prepared by other approaches. Physicists have used layered compounds to discover and understand novel phenomena made more apparent through reduced dimensionality. The discovery of charge and spin density waves and more recently the remarkable discovery in condensed matter physics of the two-dimensional topological insulating state were discovered in two-dimensional materials. The understanding developed in two-dimensional materials enabled subsequent extension of these and other phenomena into three-dimensional materials. Layered compounds have also been used in many technologies as engineers and scientists used their unique properties to solve challenging technical problems (low temperature ion conduction for batteries, easy shear planes for lubrication in vacuum, edge decorated catalyst sites for catalytic removal of sulfur from oil, etc). The articles that are published in this issue provide an excellent overview of the spectrum of activities that are being pursued, as well as an introduction to some of the most established achievements in the field. Clusters of papers discussing thermoelectric properties, electronic structure and transport properties, growth of single two-dimensional layers, intercalation and more extensive topochemical reactions and the interleaving of two structures to form new materials highlight the breadth of current research in this area. These papers will hopefully serve as a useful guideline for the interested reader to different important aspects in this field and

  3. Adsorption of Amino Acids (Ala, Cys, His, Met) on Zeolites: Fourier Transform Infrared and Raman Spectroscopy Investigations

    NASA Astrophysics Data System (ADS)

    Carneiro, Cristine E. A.; de Santana, Henrique; Casado, Clara; Coronas, Joaquin; Zaia, Dimas A. M.

    2011-06-01

    Minerals adsorb more amino acids with charged R-groups than amino acids with uncharged R-groups. Thus, the peptides that form from the condensation of amino acids on the surface of minerals should be composed of amino acid residues that are more charged than uncharged. However, most of the amino acids (74%) in today's proteins have an uncharged R-group. One mechanism with which to solve this paradox is the use of organophilic minerals such as zeolites. Over the range of pH (pH 2.66-4.50) used in these experiments, the R-group of histidine (His) is positively charged and neutral for alanine (Ala), cysteine (Cys), and methionine (Met). In acidic hydrothermal environments, the pH could be even lower than those used in this study. For the pH range studied, the zeolites were negatively charged, and the overall charge of all amino acids was positive. The conditions used here approximate those of prebiotic Earth. The most important finding of this work is that the relative concentrations of each amino acid (X=His, Met, Cys) to alanine (X/Ala) are close to 1.00. This is an important result with regard to prebiotic chemistry because it could be a solution for the paradox stated above. Pore size did not affect the adsorption of Cys and Met on zeolites, and the Si/Al ratio did not affect the adsorption of Cys, His, and Met. ZSM-5 could be used for the purification of Cys from other amino acids (Student-Newman-Keuls test, p<0.05), and mordenite could be used for separation of amino acids from each other (Student-Newman-Keuls test, p<0.05). As shown by Fourier transform infrared (FT-IR) spectra, Ala interacts with zeolites through the group, and methionine-zeolite interactions involve the COO, , and CH3 groups. FT-IR spectra show that the interaction between the zeolites and His is weak. Cys showed higher adsorption on all zeolites; however, the hydrophobic Van der Waals interaction between zeolites and Cys is too weak to produce any structural changes in the Cys groups (amine

  4. SLC6A3 coding variant Ala559Val found in two autism probands alters dopamine transporter function and trafficking.

    PubMed

    Bowton, E; Saunders, C; Reddy, I A; Campbell, N G; Hamilton, P J; Henry, L K; Coon, H; Sakrikar, D; Veenstra-VanderWeele, J M; Blakely, R D; Sutcliffe, J; Matthies, H J G; Erreger, K; Galli, A

    2014-01-01

    Emerging evidence associates dysfunction in the dopamine (DA) transporter (DAT) with the pathophysiology of autism spectrum disorder (ASD). The human DAT (hDAT; SLC6A3) rare variant with an Ala to Val substitution at amino acid 559 (hDAT A559V) was previously reported in individuals with bipolar disorder or attention-deficit hyperactivity disorder (ADHD). We have demonstrated that this variant is hyper-phosphorylated at the amino (N)-terminal serine (Ser) residues and promotes an anomalous DA efflux phenotype. Here, we report the novel identification of hDAT A559V in two unrelated ASD subjects and provide the first mechanistic description of its impaired trafficking phenotype. DAT surface expression is dynamically regulated by DAT substrates including the psychostimulant amphetamine (AMPH), which causes hDAT trafficking away from the plasma membrane. The integrity of DAT trafficking directly impacts DA transport capacity and therefore dopaminergic neurotransmission. Here, we show that hDAT A559V is resistant to AMPH-induced cell surface redistribution. This unique trafficking phenotype is conferred by altered protein kinase C β (PKCβ) activity. Cells expressing hDAT A559V exhibit constitutively elevated PKCβ activity, inhibition of which restores the AMPH-induced hDAT A559V membrane redistribution. Mechanistically, we link the inability of hDAT A559V to traffic in response to AMPH to the phosphorylation of the five most distal DAT N-terminal Ser. Mutation of these N-terminal Ser to Ala restores AMPH-induced trafficking. Furthermore, hDAT A559V has a diminished ability to transport AMPH, and therefore lacks AMPH-induced DA efflux. Pharmacological inhibition of PKCβ or Ser to Ala substitution in the hDAT A559V background restores AMPH-induced DA efflux while promoting intracellular AMPH accumulation. Although hDAT A559V is a rare variant, it has been found in multiple probands with neuropsychiatric disorders associated with imbalances in DA neurotransmission

  5. Biological evaluation of (177)Lu-labeled DOTA-Ala(SO3H)-Aminooctanoyl-Gln-Trp-Ala-Val-N methyl Gly-His-Statine-Leu-NH2 for gastrin-releasing peptide receptor-positive prostate tumor targeting.

    PubMed

    Lim, Jae Cheong; Cho, Eun Ha; Kim, Jin Joo; Choi, Sang Mu; Lee, So young; Nam, Sung Soo; Park, Ul Jae; Park, Soo Hyun

    2015-02-01

    Bombesin binds with selectivity and high affinity to a Gastrin-releasing peptide receptor (GRPR), which is highly overexpressed in prostate cancer cells. The present study describes the in vitro and in vivo biological characteristics of DOTA-Ala(SO3H)-Aminooctanoyl-Gln-Trp-Ala-Val-N methyl Gly-His-Statine-Leu-NH2 (DOTA-sBBNA), an antagonist analogue of bombesin peptide for the targeting of GRPR. DOTA-sBBNA was synthesized and labeled with (177)Lu as previously published. A saturation assay on PC-3 human prostate cancer cells revealed that the Kd value of the radiolabeled peptide was 1.88 nM with a maximum binding capacity (Bmax) of 289.3 fmol/10(6) cells. The radio-peptide slowly internalized, and 24.4±0.5% of the total binding was internalized in 4hr. Biodistribution studies were conducted in healthy and PC-3 xenografted balb/c mice, which showed high uptake and retention of tumor-associated radioactivity in PC-3 xenografted mice. The tumor-to-blood ratio was 126.02±9.36 at 1.5hr p.i., and was increased to 216.33±61.58 at 24hr p.i., which means that the radiolabeled peptide was highly accumulated in a tumor and rapidly cleared from the blood pool. The GRPR is also over-expressed in Korean prostate cancer patients. These results suggest that this (177)Lu-labeled peptide has promising characteristics for application in nuclear medicine, namely for the diagnosis and treatment of GRPR over-expressing prostate tumors. PMID:25457455

  6. Exploring the conformational preferences of 20-residue peptides in isolation: Ac-Ala19-Lys + H(+)vs. Ac-Lys-Ala19 + H(+) and the current reach of DFT.

    PubMed

    Schubert, Franziska; Rossi, Mariana; Baldauf, Carsten; Pagel, Kevin; Warnke, Stephan; von Helden, Gert; Filsinger, Frank; Kupser, Peter; Meijer, Gerard; Salwiczek, Mario; Koksch, Beate; Scheffler, Matthias; Blum, Volker

    2015-03-21

    Reliable, quantitative predictions of the structure of peptides based on their amino-acid sequence information are an ongoing challenge. We here explore the energy landscapes of two unsolvated 20-residue peptides that result from a shift of the position of one amino acid in otherwise the same sequence. Our main goal is to assess the performance of current state-of-the-art density-functional theory for predicting the structure of such large and complex systems, where weak interactions such as dispersion or hydrogen bonds play a crucial role. For validation of the theoretical results, we employ experimental gas-phase ion mobility-mass spectrometry and IR spectroscopy. While unsolvated Ac-Ala19-Lys + H(+) will be shown to be a clear helix seeker, the structure space of Ac-Lys-Ala19 + H(+) is more complicated. Our first-principles structure-screening strategy using the dispersion-corrected PBE functional (PBE + vdW(TS)) identifies six distinctly different structure types competing in the low-energy regime (≈16 kJ mol(-1)). For these structure types, we analyze the influence of the PBE and the hybrid PBE0 functional coupled with either a pairwise dispersion correction (PBE + vdW(TS), PBE0 + vdW(TS)) or a many-body dispersion correction (PBE + MBD*, PBE0 + MBD*). We also take harmonic vibrational and rotational free energy into account. Including this, the PBE0 + MBD* functional predicts only one unique conformer to be present at 300 K. We show that this scenario is consistent with both experiments. PMID:25700010

  7. Conformation-Specific Infrared Spectroscopy of γ2-PEPTIDE Foldamers: Ac-γ2-hPhe-γ2-hAla-NHMe and Ac-γ2-hAla-γ2-hPhe-NHMe

    NASA Astrophysics Data System (ADS)

    James, William H., III; Buchanan, Evan G.; Müller, Christian W.; Zwier, Timothy S.; Guo, Li; Gellman, Samuel H.

    2010-06-01

    IR/UV double-resonance spectroscopy has been used to study the intrinsic conformational preferences of naturally occurring and synthetic peptides. These studies demonstrated the power of double-resonance methods and highlighted the ability of even short peptide mimics to form a variety of intramolecular hydrogen bonded architectures. Currently, we are extending these studies to a series of model γ2-peptides, which differ from α-peptides by virtue of having two additional, substitutable methylene units separating amide groups in the peptide backbone. Initial studies centered on the conformation-specific infrared spectra of Ac-γ2-hPhe-NHMe, where three unique conformational isomers (two hydrogen-bonded and one intramolecular amide stacked) were observed under the isolated-molecule conditions of a jet-cooled environment. This talk will focus on on two larger γ2-peptides, Ac-γ2-hPhe-γ2-hAla-NHMe and Ac-γ2-hAla-γ2-hPhe-NHMe. Utilizing resonant ion-dip infrared spectroscopy, the single-conformation infrared spectra of eight resolved conformers of the two molecules were recorded in the amide NH stretch region. The resulting infrared spectra of the tri-amides contain evidence for structures comprised of one, two, and three intramolecular amide-amide hydrogen bonds, the last of which is unprecedented for a tri-amide. In an effort to make firm conformational assignments, the spectroscopic data will be compared to the results of harmonic vibrational frequency calculations using traditional DFT and dispersion-corrected DFT methods, the results of which will be discussed.

  8. Development and characterization of a highly selective neuropeptide Y Y5 receptor agonist radioligand: [125I][hPP1-17, Ala31, Aib32]NPY.

    PubMed

    Dumont, Yvan; Thakur, Mira; Beck-Sickinger, Annette; Fournier, Alain; Quirion, Rémi

    2003-08-01

    (1) The existence of multiple classes of neuropeptide Y (NPY) receptors (Y(1), Y(2), Y(4), Y(5) and y(6)) is now well established. However, one of the major difficulties in the study of these various receptor subtypes is the current lack of highly selective probes to investigate a single receptor class. Up to most recently, this was particularly true for the Y(4) and Y(5) subtypes. (2) [hPP(1-17), Ala(31), Aib(32)]NPY, the first highly selective Y(5) agonist, was iodinated using the chloramine T method and purified by high-pressure liquid chromatography. (3) Binding performed in rat brain homogenates revealed that equilibrium was reached after 120 min (t(1/2)=21 min) and 60 min (t(1/2)=12 min) at 25 and 100 pM [(125)I][hPP(1-17), Ala(31), Aib(32)]NPY, respectively. (4) Isotherm saturation binding experiments demonstrated that [(125)I][hPP(1-17), Ala(31), Aib(32)]NPY binds to an apparent single population with high-affinity (K(D) of 1.2 and 1.7 nM) and low-capacity (B(max) of 14+/-3 fmol/100,000 cells and 20+/-5 fmol/mg protein) sites in Y(5) receptor HEK293-transfected cells and rat brain membrane homogenates, respectively. No specific [(125)I][hPP(1-17), Ala(31), Aib(32)]NPY binding sites could be detected in Y(1), Y(2) or Y(4) receptors transfected HEK293 cells, demonstrating the high selectivity of this ligand for the Y(5) subtype. (5) Competition binding experiments performed in rat brain membrane homogenates and Y(5)-receptor transfected HEK293 cells demonstrated that specific [(125)I][hPP(1-17), Ala(31), Aib(32)]NPY binding was competed with high affinity by Y(5) agonists and antagonists such as [Ala(31), Aib(32)]NPY, [hPP(1-17), Ala(31), Aib(32)]NPY, hPP, CGP71683A and JCF109, but not by Y(1) (BIBP3226), Y(2) (BIIE0246) and Y(1)/Y(4) (GR231118) preferential ligands. (6) Taken together, these data demonstrate that [(125)I][hPP(1-17), Ala(31), Aib(32)]NPY is the first highly selective Y(5) radioligand to be developed. This new probe should prove most useful

  9. Binding stability of peptides derived from 1ALA residue and 7GLY residues to sites near active center of fluctuating papain

    NASA Astrophysics Data System (ADS)

    Nishiyama, Katsuhiko

    2012-05-01

    We investigated the binding stability of peptides derived from 1ALA residue and 7GLY residues to sites near active center of fluctuating papain via molecular dynamics and docking simulations. Replacing GLY residue in 8GLY with ALA residue had a positive effect on binding stability to the sites in some cases although the replacing had a negative effect on it in other cases. Furthermore the replacing had a negative effect on the chance of binding to the sites. Residue in peptide should be replaced on the basis of systematic exploration of its position.

  10. The p.Ala510Val mutation in the SPG7 (paraplegin) gene is the most common mutation causing adult onset neurogenetic disease in patients of British ancestry.

    PubMed

    Roxburgh, Richard H; Marquis-Nicholson, Renate; Ashton, Fern; George, Alice M; Lea, Rod A; Eccles, David; Mossman, Stuart; Bird, Thomas; van Gassen, Koen L; Kamsteeg, Erik-Jan; Love, Donald R

    2013-05-01

    The c.1529C >T change in the SPG7 gene, encoding the mutant p.Ala510Val paraplegin protein, was first described as a polymorphism in 1998. This was based on its frequency of 3 % and 4 % in two separate surveys of controls in the United Kingdom (UK) population. Subsequently, it has been found to co-segregate with disease in a number of different populations. Yeast expression studies support its having a deleterious effect. In this paper a consanguineous sibship is described in which four members who are homozygous for the p.Ala510Val variant present with a spectrum of disease. This spectrum encompasses moderately severe hereditary spastic paraparesis (HSP) with more minor ataxia in two siblings, moderately severe ataxia without spasticity in the third, and a very mild gait ataxia in the fourth. Two of the siblings also manifest vestibular failure. The remaining eight unaffected siblings are either heterozygous for the p.Ala510Val variant, or do not carry it at all. Homozygosity mapping using a high-density SNP array across the whole genome found just 11 genes (on two regions of chromosome 3) outside the SPG7 region on chromosome 16, which were homozygously shared by the affected siblings, but not shared by the unaffected siblings; none of them are likely to be causative. The weight of evidence is strongly in favour of the p.Ala510Val variant being a disease-causing mutation. We present additional data from the Auckland City Hospital neurogenetics clinic to show that the p.Ala510Val mutation is prevalent amongst HSP patients of UK extraction belying any suggestion that European p.Ala510Val haplotypes harbour a disease-causing mutation which the UK p.Ala510Val haplotypes do not. Taken together with previous findings of a carrier frequency of 3-4 % in the UK population (giving a homozygosity rate of 20-40/100,000), the data imply that the p.Ala510Val is the most common mutation causing neurogenetic disease in adults of UK ancestry, albeit the penetrance may be low or

  11. Shape-selective sieving layers on an oxide catalyst surface.

    PubMed

    Canlas, Christian P; Lu, Junling; Ray, Natalie A; Grosso-Giordano, Nicolas A; Lee, Sungsik; Elam, Jeffrey W; Winans, Randall E; Van Duyne, Richard P; Stair, Peter C; Notestein, Justin M

    2012-12-01

    New porous materials such as zeolites, metal-organic frameworks and mesostructured oxides are of immense practical utility for gas storage, separations and heterogeneous catalysis. Their extended pore structures enable selective uptake of molecules or can modify the product selectivity (regioselectivity or enantioselectivity) of catalyst sites contained within. However, diffusion within pores can be problematic for biomass and fine chemicals, and not all catalyst classes can be readily synthesized with pores of the correct dimensions. Here, we present a novel approach that adds reactant selectivity to existing, non-porous oxide catalysts by first grafting the catalyst particles with single-molecule sacrificial templates, then partially overcoating the catalyst with a second oxide through atomic layer deposition. This technique is used to create sieving layers of Al(2)O(3) (thickness, 0.4-0.7 nm) with 'nanocavities' (<2 nm in diameter) on a TiO(2) photocatalyst. The additional layers result in selectivity (up to 9:1) towards less hindered reactants in otherwise unselective, competitive photocatalytic oxidations and transfer hydrogenations. PMID:23174984

  12. Shape-selective sieving layers on an oxide catalyst surface

    NASA Astrophysics Data System (ADS)

    Canlas, Christian P.; Lu, Junling; Ray, Natalie A.; Grosso-Giordano, Nicolas A.; Lee, Sungsik; Elam, Jeffrey W.; Winans, Randall E.; van Duyne, Richard P.; Stair, Peter C.; Notestein, Justin M.

    2012-12-01

    New porous materials such as zeolites, metal-organic frameworks and mesostructured oxides are of immense practical utility for gas storage, separations and heterogeneous catalysis. Their extended pore structures enable selective uptake of molecules or can modify the product selectivity (regioselectivity or enantioselectivity) of catalyst sites contained within. However, diffusion within pores can be problematic for biomass and fine chemicals, and not all catalyst classes can be readily synthesized with pores of the correct dimensions. Here, we present a novel approach that adds reactant selectivity to existing, non-porous oxide catalysts by first grafting the catalyst particles with single-molecule sacrificial templates, then partially overcoating the catalyst with a second oxide through atomic layer deposition. This technique is used to create sieving layers of Al2O3 (thickness, 0.4-0.7 nm) with ‘nanocavities’ (<2 nm in diameter) on a TiO2 photocatalyst. The additional layers result in selectivity (up to 9:1) towards less hindered reactants in otherwise unselective, competitive photocatalytic oxidations and transfer hydrogenations.

  13. Mechanism of the antistress action of d-ala/sup 2/-leu/sup 5/-arg/sup 6/-enkephalin

    SciTech Connect

    Lishmanov, Yu.B.; Maslov, L.N.; Titov, M.I.

    1986-02-01

    The authors study the effect of the arginine-containing hexapeptide analog of Leu-enkephalin - D-Ala/sup 2/-Leu/sup 5/-Ar/sup 6/--enkephalin (enkephalin) on blood plasma levels of ACTH, cortisol, and hormones of the pituitary-thyroid complex, and the cAMP concentration in adrenal and thymus tissues during stress induced by crushing the soft tissues (CST). The experiments were carried out on noninbred male albino rats. The plasma ACTH and cortisol levels were determined by radioimmunoassay using kits from France, thyroxine (T/sub 4/) and tri-iodothyronine (T/sub 3/), and pituitary thyrotropic hormone. A gamma-spectrometer and beta-scintillation counter were used.

  14. Structural requirements of acylated Gly-l-Ala-d-Glu analogs for activation of the innate immune receptor NOD2.

    PubMed

    Gobec, Martina; Mlinarič-Raščan, Irena; Dolenc, Marija Sollner; Jakopin, Žiga

    2016-06-30

    The fragment of bacterial peptidoglycan muramyl dipeptide (MDP) has long been known for its adjuvant activity, however the underlying mechanism of this action has only recently been elucidated. It is ascribed to its agonist action on the nucleotide-binding oligomerization domain-containing protein 2 (NOD2). In spite of the pressing need for novel adjuvants for human use, this discovery is hampered, by not knowing the structural requirements underlying the immunostimulatory activity. We have investigated how minor modifications of hit compound acyl Gly-L-Ala-D-Glu derivative I modulate the molecular recognition by NOD2. A series of novel desmuramyldipeptides has been designed and synthesized leading to the identification of compound 16, in which the sugar moiety is replaced by a 6-phenylindole moiety, that exhibits the strongest NOD2 activation to date sans the carbohydrate moiety. The results have enabled a deeper understanding of the structural requirements of desmuramylpeptides for NOD2 activation. PMID:27039337

  15. Initial evaluation of whole bladder wall photodynamic therapy after intravesical ALA sensitization for carcinoma in situ of the bladder

    NASA Astrophysics Data System (ADS)

    D'Hallewin, Marie-Ange; Star, Willem M.; Baert, Luc

    1997-12-01

    Carcinoma in situ (CIS) of the bladder is a treacherous entity, that will develop into invasive cancer. Early treatment is mandatory in order to prevent progression. When conservative measures, such as Bacillus Calmette Querin (BCG) instillations have failed, radical cystectomy and urinary diversion is recommended. Whole bladder wall photodynamic therapy (PDT) with Photofrin II has been shown to be effective in eradicating carcinoma in situ, but often resulted in bladder shrinking. We wanted to evaluate the effects of PDT after aminolevulinic acid (ALA) sensitization. Six patients with refractory carcinoma in situ of the bladder were treated with whole bladder wall photodynamic therapy, after intravesical sensitization with aminolevulinic acid. The total light dose (scattered plus non scattered) was 75 J/cm2. No skin sensitization occurred, nor loss of bladder capacity. One patient did not respond and was successfully treated with BCG. Another patient developed distant metastases. Carcinoma in situ was completely absent after 3 months in four patients (66%).

  16. Hemoglobin Djelfa beta98 (FG 5) Val leads to Ala: isolation and functional properties of the heme saturated form.

    PubMed

    Gacon, G; Krishnamoorthy, R; Wajcman, H; Labie, D; Tapon, J; Cosson, A

    1977-01-25

    Hemoglobin Djelfa beta98 (FG 5) Val leads to Ala is a neutrally substituted unstable hemoglobin, exhibiting the same gross features as hemoglobin Köln beta98 (FG 5) Val leads to Met. In addition to the presence of a deheminized fraction, a heme saturated abnormal hemoglobin was visualized and isolated by high resolution electrofocusing. By functional studies of the fully heminized form, a slightly increased oxygen affinity, an impairment of heme-heme interaction and a decreased response to organic phosphates were demonstrated. These functional perturbations point out the importance of the beta98 invariant valyl residue, in the quaternary contacts. They can account for the poor oxygen delivery of erythrocytes. PMID:13850

  17. Contribution of the hydrophobic effect to protein stability: analysis based on simulations of the Ile-96----Ala mutation in barnase.

    PubMed Central

    Prevost, M; Wodak, S J; Tidor, B; Karplus, M

    1991-01-01

    Molecular dynamics simulations have been used to compute the difference in the unfolding free energy between wild-type barnase and the mutant in which Ile-96 is replaced by alanine. The simulations yield results (-3.42 and -5.21 kcal/mol) that compare favorably with experimental values (-3.3 and -4.0 kcal/mol). The major contributions to the free energy difference arise from bonding terms involving degrees of freedom of the mutated side chain and from nonbonded interactions of that side chain with its environment in the folded protein. By comparison with simulations of an extended peptide in the absence of solvent, used as a reference state, hydration effects are shown to play a minor role in the overall free energy balance for the Ile----Ala transformation. The implications of these results for our understanding of the hydrophobic effect and its contribution to protein stability are discussed. Images PMID:1961758

  18. Endoscopy imaging of 5-ALA-induced PPIX fluorescence for detecting early neoplasms in the oral cavity

    NASA Astrophysics Data System (ADS)

    Zheng, Wei; Olivo, Malini; Sivanandan, Ranjiv; Karuman, Philip; Lim, Tuan-Kay; Soo, K. C.

    2001-10-01

    A digitized fluorescence endoscopy imaging system combined with 5-Aminolevulinic Acid (5-ALA) induced Protoporphyrin IX (PPIX) has been developed for the detection of neoplasms in oral cavity. It mainly consists of the illumination console, fluorescence detection unit, computer system for image acquisition, processing and analysis, and online image display system as well. The developed system can produce both the digital and video fluorescence images in real time, and can be used to quantify fluorescence images acquired. Preliminary results from the Head and Neck clinic show that high sensitivity and high specificity can be achieved. Furthermore, applying the intensity ratios at two different wavelength regions, the developed system shows the capability of differentiating between different histopathological stages of oral lesions, suggesting a significant potential for realizing the non-invasive optical biopsy for early cancer diagnosis.

  19. Racial and tissue-specific cancer risk associated with PARP1 (ADPRT) Val762Ala polymorphism: a meta-analysis.

    PubMed

    Pabalan, Noel; Francisco-Pabalan, Ofelia; Jarjanazi, Hamdi; Li, Hong; Sung, Lillian; Ozcelik, Hilmi

    2012-12-01

    The Val762Ala polymorphism poly [ADP-ribose] polymerase 1 (PARP1) gene [ADPRT (adenosine diphosphate ribosyltransferase) gene] affects enzymatic activity, which modulates cancer susceptibility among human populations. Individual data on 13,745 cases and 16,947 controls from 28 published case-control studies were re-evaluated. Odds ratios (OR) were estimated for ethnic group, cancer type, smoking joint effects and studies confined to the Hardy-Weinberg equilibrium. We applied subgroup, sensitivity and outlier analyses as well as the Bonferroni correction for multiple testing. The results show strong evidence that the variant (C) allele confers significant increased risk in the Chinese (OR 1.20-1.44, P < 0.0001-0.002), exacerbated by smoking (OR 1.66-2.53, P < 0.0001) and joint interaction with XRCC1 Arg399Gln (OR 1.39, P < 0.0001) as well as adjustment for tumor type (gastric carcinoma ORs 1.39-2.01, P < 0.0001). These significant effects were unaltered following conservative correction for multiple tests. By contrast, this procedure erased the protective significance in Caucasians, but not in two American subgroups, (i) those in the brain tumor category (0.77-0.79, P < 0.0001) and (ii) smokers in the dominant model (OR 0.86, P < 0.0001). These differential findings between the two ethnicities maybe correlated with significantly (P < 0.0001) greater allele frequency of the variant allele (C) among the Chinese compared to Caucasians. Our racial and tissue-specific summary estimates imply consideration of the Val762Ala polymorphism as candidate gene marker for screening cancer patients' best suited for PARP inhibitor therapy. PMID:23073772

  20. Polar Layers

    NASA Technical Reports Server (NTRS)

    2006-01-01

    [figure removed for brevity, see original site] Context image for PIA02153 Polar Layers

    This image of the south polar region shows layered material. It is not known if the layers are formed yearly or if they form over the period of 10s to 100s of years or more.

    Image information: VIS instrument. Latitude -80.3N, Longitude 296.2E. 17 meter/pixel resolution.

    Note: this THEMIS visual image has not been radiometrically nor geometrically calibrated for this preliminary release. An empirical correction has been performed to remove instrumental effects. A linear shift has been applied in the cross-track and down-track direction to approximate spacecraft and planetary motion. Fully calibrated and geometrically projected images will be released through the Planetary Data System in accordance with Project policies at a later time.

    NASA's Jet Propulsion Laboratory manages the 2001 Mars Odyssey mission for NASA's Office of Space Science, Washington, D.C. The Thermal Emission Imaging System (THEMIS) was developed by Arizona State University, Tempe, in collaboration with Raytheon Santa Barbara Remote Sensing. The THEMIS investigation is led by Dr. Philip Christensen at Arizona State University. Lockheed Martin Astronautics, Denver, is the prime contractor for the Odyssey project, and developed and built the orbiter. Mission operations are conducted jointly from Lockheed Martin and from JPL, a division of the California Institute of Technology in Pasadena.

  1. Photocatalytic O{sub 2} evolution from water over Zn–Cr layered double hydroxides intercalated with inorganic anions

    SciTech Connect

    Hirata, Naoya; Tadanaga, Kiyoharu; Tatsumisago, Masahiro

    2015-02-15

    Graphical abstract: The photocatalytic activity of Zn–Cr LDHs intercalated with various inorganic anions was studied by O{sub 2} evolution from aqueous solution of AgNO{sub 3} as a sacrificial agent. All the prepared LDHs showed photocatalytic activity under either UV and/or visible light irradiation. The interlayer anions affected the photocatalytic activity of the LDHs. - Highlights: • Zn–Cr layered double hydroxides intercalated with inorganic anions were synthesized. • Photocatalytic activity of the LDHs was studied by O{sub 2} evolution. • All the prepared LDHs showed photocatalytic activity under either UV and/or visible light irradiation. • The interlayer anions affected the photocatalytic activity of the LDHs. - Abstract: Zn–Cr layered double hydroxides (LDHs) intercalated with inorganic anions (CO{sub 3}{sup 2−}, Cl{sup −}, SO{sub 4}{sup 2−} and NO{sub 3}{sup −}) were synthesized by the co-precipitation method and the anion exchange process. The photocatalytic activity of the LDHs was studied by O{sub 2} evolution from aqueous solution of AgNO{sub 3} as a sacrificial agent. All the prepared LDHs showed photocatalytic activity under either UV and/or visible light irradiation. Besides, the interlayer anions affected the photocatalytic activity of the LDHs. After irradiation, Ag particles were formed on the LDHs by accepting the electrons generated during the photocatalytic reaction.

  2. Infrared sensor with precisely patterned Au black absorption layer

    NASA Astrophysics Data System (ADS)

    Hirota, Masaki; Morita, Shinichi

    1998-10-01

    Thermoelectric infrared sensors has been fabricated by adding to the CMOS process a surface micromachining technique and a highly accurate process for forming an infrared radiation absorbing layer. The sensor, or thermopile, consists of alternating areas of p-type and n-type polysilicon connected in series on a Si3N4 layer. An anisotropic etching technique using hydrazine is employed to form a thermally isolated membrane. While a Au-black layer for infrared radiation absorption provides the best absorption efficiency over a broad infrared wavelength region, it has been difficult to pattern the layer precisely. Patterning is accomplished by forming the Au-black layer by a low-pressure vapor deposition technique on amorphous Si and a PSG sacrificial layer and then removing it on PSG by the lift-off technique or wet etching PSG. This technique makes it possible to obtain a Au-black pattern with the same degree of accuracy as with the CMOS process. As a result, sensor performance has been improved and a device array has also been achieved. A simple sensor design method has been established by which simulations are easily conducted using a thermal equivalent circuit based on the CMOS process. Prototype sensors, having external dimensions of 160 micrometer X 160 micrometer, achieved responsivity of 300, 149 and 60 V/W and a time constant of 2.0, 0.46 and 0.27 msec in the air, respectively. These performance figures surpass the performance reported to date for thermoelectric infrared sensors.

  3. XPC Ala499Val and XPG Asp1104His polymorphisms and digestive system cancer risk: a meta-analysis based on model-free approach

    PubMed Central

    Yu, Guangsheng; Wang, Jianlu; Dong, Jiahong; Liu, Jun

    2015-01-01

    Many studies have reported the association between XPC Ala499Val and XPG Asp1104His polymorphisms and digestive system cancer susceptibility, but the results were inconclusive. We performed a meta-analysis, using a comprehensive strategy based on the allele model and a model-free approach, to derive a more precise estimation of the relationship between XPC Ala499Val and XPG Asp1104His polymorphisms with digestive system cancer risk. For XPC Ala499Val, no significant cancer risk was found in the allele model (OR = 0.98, 95% CI: 0.86-1.11) and with model-free approach (ORG = 0.97, 95% CI: 0.83-1.13). For XPG Asp1104His, there was also no association between this polymorphism and cancer risk in the allele model (OR = 1.03, 95% CI: 0.96-1.11) and with the model-free approach (ORG = 1.04, 95% CI: 0.95-1.14). Therefore, this meta-analysis suggests that the XPC Ala499Val and XPG Asp1104His polymorphisms were not associated with digestive system cancer risk. Further large and well-designed studies are needed to confirm these findings. PMID:26131294

  4. Evaluation of Acoustic Emission NDE of Composite Crew Module Service Module/Alternate Launch Abort System (CCM SM/ALAS) Test Article Failure Tests

    NASA Technical Reports Server (NTRS)

    Horne, Michael R.; Madaras, Eric I.

    2010-01-01

    Failure tests of CCM SM/ALAS (Composite Crew Module Service Module / Alternate Launch Abort System) composite panels were conducted during July 10, 2008 and July 24, 2008 at Langley Research Center. This is a report of the analysis of the Acoustic Emission (AE) data collected during those tests.

  5. Geranylgeranylated Rab proteins terminating in Cys-Ala-Cys, but not Cys-Cys, are carboxyl-methylated by bovine brain membranes in vitro.

    PubMed Central

    Smeland, T E; Seabra, M C; Goldstein, J L; Brown, M S

    1994-01-01

    Geranylgeranylated Rab proteins usually terminate in either Cys-Cys or Cys-Xaa-Cys, where Xaa is Ala, Ser, or Gly. In both classes of proteins, the two cysteines are geranylgeranylated, but only the Cys-Xaa-Cys class has been shown to be carboxyl-methylated on the terminal cysteine in vivo. In the current study, we used recombinant Rab geranylgeranyltransferase and a Rab escort protein (REP-1) to attach geranylgeranyl residues to the two cysteines at the carboxyl terminus of Rab3A (Cys-Ala-Cys) and Rab1A (Cys-Cys). The geranylgeranylated proteins were then incubated with bovine cerebellar membranes that contain an enzyme that transfers [3H]methyl from S-[methyl-3H]adenosyl-L-methionine to geranylgeranylated cysteine. The enzyme transferred [3H]methyl to geranylgeranylated Rab3A but not to geranylgeranylated Rab1A. Replacement of the Cys-Ala-Cys terminus of Rab3A with Cys-Cys abolished methylation, and the opposite result was obtained when the Cys-Cys of Rab1A was replaced with Cys-Ala-Cys. When the Cys-Cys terminus of Rab1A was changed to Ser-Cys, methylation was restored. These studies suggest that the carboxyl-terminal cysteine of Rab proteins terminating in Cys-Xaa-Cys but not Cys-Cys is methylated and that the resistance of Cys-Cys proteins to methylation is attributable to the vicinal geranylgeranylated cysteines. Images PMID:7938016

  6. Estudio de NIH señala que la sigmoidoscopia reduce los índices de cáncer colorrectal

    Cancer.gov

    Estudio señala que la sigmoidoscopia flexible es efectiva para reducir los índices de casos nuevos y de muertes por cáncer colorrectal. Los investigadores encontraron que la mortalidad general por cáncer colorrectal se redujo 26% y que la incidencia se re

  7. Posttranslational Control of ALA Synthesis Includes GluTR Degradation by Clp Protease and Stabilization by GluTR-Binding Protein1[OPEN

    PubMed Central

    Apitz, Janina; Nishimura, Kenji; Wolf, Anja; Hedtke, Boris

    2016-01-01

    5-Aminolevulinic acid (ALA) is the first committed substrate of tetrapyrrole biosynthesis and is formed from glutamyl-tRNA by two enzymatic steps. Glutamyl-tRNA reductase (GluTR) as the first enzyme of ALA synthesis is encoded by HEMA genes and tightly regulated at the transcriptional and posttranslational levels. Here, we show that the caseinolytic protease (Clp) substrate adaptor ClpS1 and the ClpC1 chaperone as well as the GluTR-binding protein (GBP) interact with the N terminus of GluTR. Loss-of function mutants of ClpR2 and ClpC1 proteins show increased GluTR stability, whereas absence of GBP results in decreased GluTR stability. Thus, the Clp protease system and GBP contribute to GluTR accumulation levels, and thereby the rate-limiting ALA synthesis. These findings are supported with Arabidopsis (Arabidopsis thaliana) hema1 mutants expressing a truncated GluTR lacking the 29 N-terminal amino acid residues of the mature protein. Accumulation of this truncated GluTR is higher in dark periods, resulting in increased protochlorophyllide content. It is proposed that the proteolytic activity of Clp protease counteracts GBP binding to assure the appropriate content of GluTR and the adequate ALA synthesis for chlorophyll and heme in higher plants. PMID:26884485

  8. Layered Slope

    NASA Technical Reports Server (NTRS)

    2005-01-01

    28 August 2005 This Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) image shows a frost-covered slope in the south polar region of Mars. The layered nature of the terrain in the south polar region is evident in a series of irregular, somewhat stair-stepped bands that run across the image.

    Location near: 84.3oS, 27.2oW Image width: width: 3 km (1.9 mi) Illumination from: upper left Season: Southern Spring

  9. Microneedles rollers as a potential device to increase ALA diffusion and PpIX production: evaluations by wide-field fluorescence imaging and fluorescence spectroscopy

    NASA Astrophysics Data System (ADS)

    Gracielli Sousa, R. Phamilla; de Menezes, Priscila F. C.; Fujita, Alessandra K. L.; Requena, Michelle B.; Govone, Angelo Biassi; Escobar, André; de Nardi, Andrigo B.; Kurachi, Cristina; Bagnato, Vanderlei Salvador

    2014-03-01

    One of the limitations of topical photodynamic therapy (PDT) using 5-aminolevulinic acid (ALA) is the poor ability to penetrate biological barriers of skin and the recurrence rates in treatments. This study aimed to identify possible signs of increased diffusion of ALA-induced PpIX by fluorescence images and fluorescence spectroscopy. The research was done using in vivo porcine skin model. Before the cream application, microholes was performed with microneedles rollers in only one direction, afterward the ALA cream was applied at a 2.5cm2 area in triplicate and an occlusive dressing was placed. PpIX production was monitored using fluorescence spectroscopy collected at skin surface after 70, 100, 140, and 180 minutes of ALA incubation. About 100 fluorescence spectra of each treatment were collected, distributed by about five points for each site. Wide-field fluorescence imaging was made after 70, 90, and 170 minutes after treatment. The results obtained by imaging analysis indicated increase of the PpIX diffusion in the skin surface using the microneedles rollers (MNs) before ALA application. Circular regions of red fluorescence around the microholes were observed. In addition, the fluorescence spectra showed a greater intensity (2 times as many) in groups microneedles rollers associated. In conclusion, our data shown greater homogeneity and PpIX production in the groups pre-treated with microneedles indicating that the technique can be used to greater uniformity of PpIX production throughout the area to be treated reducing the chances of recurrent tumor as well as has potential for decreasing the time of therapy. (FUNDING SUPPORT:CAPES, CNPq and FAPESP)

  10. The Ala54Thr Polymorphism of the Fatty Acid Binding Protein 2 Gene Modulates HDL Cholesterol in Mexican-Americans with Type 2 Diabetes

    PubMed Central

    Salto, Lorena M.; Bu, Liming; Beeson, W. Lawrence; Firek, Anthony; Cordero-MacIntyre, Zaida; De Leon, Marino

    2015-01-01

    The alanine to threonine amino acid substitution at codon 54 (Ala54Thr) of the intestinal fatty acid binding protein (FABP2) has been associated with elevated levels of insulin and blood glucose as well as with dyslipidemia. The aim of this study was to characterize the effect of this FABP2 polymorphism in Mexican-Americans with type 2 diabetes (T2D) in the context of a three-month intervention to determine if the polymorphism differentially modulates selected clinical outcomes. For this study, we genotyped 43 participant samples and performed post-hoc outcome analysis of the profile changes in fasting blood glucose, HbA1c, insulin, lipid panel and body composition, stratified by the Ala54Thr polymorphism. Our results show that the Thr54 allele carriers (those who were heterozygous or homozygous for the threonine-encoding allele) had lower HDL cholesterol and higher triglyceride levels at baseline compared to the Ala54 homozygotes (those who were homozygous for the alanine-encoding allele). Both groups made clinically important improvements in lipid profiles and glycemic control as a response to the intervention. Whereas the Ala54 homozygotes decreased HDL cholesterol in the context of an overall total cholesterol decrease, Thr54 allele carriers increased HDL cholesterol as part of an overall total cholesterol decrease. We conclude that the Ala54Thr polymorphism of FABP2 modulates HDL cholesterol in Mexican-Americans with T2D and that Thr54 allele carriers may be responsive in interventions that include dietary changes. PMID:26703680

  11. Photodynamic treatment (ALA-PDT) suppresses the expression of the oncogenic Bcr-Abl kinase and affects the cytoskeleton organization in K562 cells.

    PubMed

    Pluskalová, Michaela; Peslová, Gabriela; Grebenová, Dana; Halada, Petr; Hrkal, Zbynek

    2006-06-01

    K562 is the chronic myelogenous leukemia (CML)-derived cell line that expresses high levels of chimeric oncoprotein Bcr-Abl. The deregulated (permanent) kinase activity of Bcr-Abl leads to continuous proliferation of K562 cells and their resistance to the apoptosis promotion by conventional drugs. The photodynamic treatment (PDT) based on the application of 5-aminolevulinic acid (ALA) and irradiation with blue light (ALA-PDT) resulted in the suppression of K562 cells proliferation. It was followed by a necrosis-like cell death [K. Kuzelová, D. Grebenová, M. Pluskalová, I. Marinov, Z. Hrkal, J. Photochem. Photobiol. B 73 (2004) 67-78]. ALA-PDT led to the perturbation of the Hsp90/p23 multichaperone complex of which the Bcr-Abl is the client protein. Bcr-Abl protein was suppressed whereas the bcr-abl mRNA level was not affected. Further on, we observed several changes in the cytoskeleton organization. We detected ALA-PDT-mediated disruption of filamental actin structure using FITC-Phalloidin staining. In connection with this we uncovered certain cytoskeleton organizing proteins involved in the cell response to the treatment. Among these proteins, Septin2, which plays a role in maintaining actin bundles, was suppressed. Another one, PDZ-LIM domain protein 1 (CLP36) was altered. This protein acts as an adaptor molecule for LIM-kinase which phosphorylates and thus inactivates cofilin. Cofilin was indeed dephosphorylated and could thus be activated and operate as an actin-depolymerizing factor. We propose the scheme of molecular response of K562 cells to ALA-PDT. PMID:16495075

  12. SnO{sub 2} films: In-situ template-sacrificial growth and photovoltaic property based on SnO{sub 2}/poly(3-hexyl-thiophene) for hybrid solar cell

    SciTech Connect

    Zhang, Yange; Li, Pinjiang; Xu, Xiaoyun; Wang, Min; Shen, Jinfeng; Zhang, Fujuan; Zheng, Zhi

    2015-10-15

    Highlights: • SnO{sub 2} nanocrystals/thin films were fabricated on ITO glass substrate from preformed SnS thin film as sacrificial template. • The SnO{sub 2} film and SnO{sub 2}/P3HT was characterized by several techniques. • The new hybrid solar cell device was based on the hybrid thin film of SnO{sub 2} NCs and P3HT composites. - Abstract: we described a facile in-situ wet chemical method to prepare SnO{sub 2} thin film on ITO glass substrate from preformed SnS thin film as sacrificial template. The chemical conversion process of SnS to SnO{sub 2} was studied. The SnO{sub 2} film and SnO{sub 2}/P3HT was characterized by several techniques, such as powder X-ray diffract meter (XRD), Raman spectrometer, scanning electron microscope (SEM), atomic force microscope (AFM) and UV–vis spectrophotometer in detail. The new SnO{sub 2}/P3HT hybrid solar cell device showed an open-circuit voltage of 0.185 V, a short-circuit current density of 0.366 mA/cm{sup 2} and a fill factor of 0.247, corresponding to a power conversion efficiency of 0.0167%.

  13. Double Layers in Astrophysics

    NASA Technical Reports Server (NTRS)

    Williams, Alton C. (Editor); Moorehead, Tauna W. (Editor)

    1987-01-01

    Topics addressed include: laboratory double layers; ion-acoustic double layers; pumping potential wells; ion phase-space vortices; weak double layers; electric fields and double layers in plasmas; auroral double layers; double layer formation in a plasma; beamed emission from gamma-ray burst source; double layers and extragalactic jets; and electric potential between plasma sheet clouds.

  14. [Transaminase activity of the cortical layer of the kidney of rats of different ages and sex after administration of hydrocortisone and insulin].

    PubMed

    Poletaeva, K A

    1971-01-01

    Response of cortical layer of rat kidney to separate and combined administration of hydrocortisone and insulin, as manifested by the activity of aspartate-alpha-ketoglutarate transaminase (Asp-T) and alanine-alpha-ketoglutarate transaminase (Ala-T), varied in males and females of different age. Prolonged administration of insulin to normal preadolescent rats and to adult males and females did not affect the activity of Asp-T and Ala-T in the cortical layer of kidney. During simultaneous prolonged administration of hydrocortisone and insulin to preadolescent male rats, there occurred no increase in the activity of Asp-T induced by administration of hydrocortisone alone. During simultaneous prolonged administration of hydrocortisone and insulin to adult male rats, activity of Asp-T of the cortical layer of kidney remained at the same level at after administration of hydrocortisone alone. PMID:5317624

  15. Both Perelmans Thrown Down Gauntlets Versus Would-Be ``Science'' But Alas Sadly Mere ``SEANCES'' Put Jargonial-Obfuscation Sociological-Dysfunctionality(S-D) Ridden/Dominated Would-Be ``Sciences'' But Alas Sadly Mere SEANCES in ``Peril, Man''!!!

    NASA Astrophysics Data System (ADS)

    Carlson, J.; Young, F.; Clay, London; Siegel, Edward Carl-Ludwig (Physical-Mathematicist/Mathsicist)

    2011-03-01

    Both Perelman (Grigory[Poincare-conjecture: partial(with Richard Hamilton!!!)-"sole"-prover: by turning down first the Fields Medal at International Congress of [S-D right there: not mathematICS, but mathematicIANS!!!] Mathematicians (2007: Madrid); then the million-dollar Clay-Institute of Mathemat"ICS" (but really mathematicIANS POLITICIANS: Carlson, Yau,...et. al.) millennium-problem prize, revealing that it and its INSIDER POLITICS/POLITICIANS has/have "Feet of Clay"!!!], as sumarized by Naser-Gruber[Manfold-Destiny, The New Yorker, (August, 2007)] and separately Carlos Castro[with Corredoira: Against the Tid (2008)] put, by revealing the Jargonial-Obfuscation(J.-O.) (Bradshaw[Healing the SHAME that BINDS You, Hazelden(1980s)]-Martin[Brian, Wollongong University]-...ad INFINITUM (i.e. most if not all scientists), ad NAUSEUM!!! (disgusted with "games people play!!!)) S-D ridden/ dominated "games people play" would-be "sciences" (maths, physics,...: ad infinitum; ad NAUSEUM!!!) but alas sadly only mere Bradshaw-Martin S-D DOMINATED "SEANCES"!!!, in "peril, man"!!!

  16. Petrogenetic evolution of the Early Miocene Alaçamdağ volcano-plutonic complex, northwestern Turkey: implications for the geodynamic framework of the Aegean region

    NASA Astrophysics Data System (ADS)

    Erkül, Sibel Tatar

    2012-01-01

    Extensional-tectonic processes have generated extensive magmatic activity that produced volcanic/plutonic rocks along an E-W-trending belt across north-western Turkey; this belt includes granites and coeval volcanic rocks of the Alaçamdağ volcano-plutonic complex. The petrogenesis of the Early Miocene Alaçamdağ granitic and volcanic rocks are here investigated by means of whole-rock Sr-Nd isotopic data along with field, petrographic and whole-rock geochemical studies. Geological and geochemical data indicate two distinct granite facies having similar mineral assemblages, their major distinguishing characteristic being the presence or absence of porphyritic texture as defined by K-feldspar megacrysts. I-type Alaçamdağ granitic stocks have monzogranitic-granodioritic compositions and contain a number of mafic microgranular enclaves of monzonitic, monzodioritic/monzogabbroic composition. Volcanic rocks occur as intrusions, domes, lava flows, dykes and volcanogenic sedimentary rocks having (first episode) andesitic and dacitic-trachyandesitic, and (second episode) dacitic, rhyolitic and trachytic-trachydacitic compositions. These granitic and volcanic rocks are metaluminous, high-K, and calc-alkaline in character. Chondrite-normalised rare earth element patterns vary only slightly such that all of the igneous rocks of the Alaçamdağ have similar REE patterns. Primitive-mantle-normalised multi-element diagrams show that these granitic and volcanic rocks are strongly enriched in LILE and LREE pattern, high (87Sr/86Sr)i and low ɛ Nd( t) ratios suggesting Alaçamdağ volcano-plutonic rocks to have been derived from hybrid magma that originated mixing of co-eval lower crustal-derived more felsic magma and enriched subcontinental lithospheric mantle-derived more mafic magmas during extensional processes, and the crustal material was more dominant than the mantle contribution. The Alaçamdağ volcano-plutonic complex rocks may form by retreat of the Hellenic

  17. Increased Histone Deacetylase Activity Involved in the Suppressed Invasion of Cancer Cells Survived from ALA-Mediated Photodynamic Treatment

    PubMed Central

    Li, Pei-Tzu; Tsai, Yi-Jane; Lee, Ming-Jen; Chen, Chin-Tin

    2015-01-01

    Previously, we have found that cancer cells survived from 5-Aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) have abnormal mitochondrial function and suppressed cellular invasiveness. Here we report that both the mRNA expression level and enzymatic activity of histone deacetylase (HDAC) were elevated in the PDT-derived variants with dysfunctional mitochondria. The activated HDAC deacetylated histone H3 and further resulted in the reduced migration and invasion, which correlated with the reduced expression of the invasion-related genes, matrix metalloproteinase 9 (MMP9), paternally expressed gene 1 (PEG1), and miR-355, the intronic miRNA. Using chromatin immunoprecipitation, we further demonstrate the reduced amount of acetylated histone H3 on the promoter regions of MMP9 and PEG1, supporting the down-regulation of these two genes in PDT-derived variants. These results indicate that HDAC activation induced by mitochondrial dysfunction could modulate the cellular invasiveness and its related gene expression. This argument was further verified in the 51-10 cybrid cells with the 4977 bp mtDNA deletion and A375 ρ0 cells with depleted mitochondria. These results indicate that mitochondrial dysfunction might suppress tumor invasion through modulating histone acetylation. PMID:26473836

  18. Fluorescence excitation and emission spectra of ALA-induced protoporphyrin IX in normal and tumoral tissue of the human bladder

    NASA Astrophysics Data System (ADS)

    Forrer, Martin; Glanzmann, Thomas M.; Mizeret, Jerome C.; Braichotte, Daniel; Wagnieres, Georges A.; van den Bergh, Hubert; Jichlinski, Patrice; Leisinger, Hans-Juerg

    1995-01-01

    In vivo spectrofluorometric analysis represents a tool to obtain information about fluorophore distribution in tissue. Based on a Peltier-cooled CCD we designed a fluorescence excitation and emission spectrograph which allows to obtain tissue spectra endoscopically and in a clinical environment. Clinical studies were performed on patients with positive cytology or tumor recurrence in the urinary bladder. Patients received a 50 ml instillation of 3% ALA solution at pH 5.5 during 3 to 4 hours and underwent a normal white light cystoscopic examination together with light induced fluorescence photodetection at 5 to 8 hours after the beginning of the instillation. Local fluorescence measurements with a single fiber were performed before photodetection. These showed fluorescence ratios between tumor and normal tissue of 1.5 to 20 with the strongest ratios for exophytic papillary tumors. Fluorescence excitation between 380 nm and 450 nm revealed that the higher Protoporphyrin IX (PPIX) signal on tumor tissue is accompanied by a decrease of the autofluorescence at the emission wavelength of 500 nm.

  19. [Dysfibrinogenemia developed in a pregnant woman who has fibrinogen AαThr312Ala (ACT/GCT) polymorphism].

    PubMed

    Yamaguchi, Ayaka; Taga, Atsuko; Kamei, Saori; Wada, Michiko; Fujita, Yohta; Wada, Hideo; Fujita, Kohei

    2016-01-01

    Blood coagulation factors play an essential role in pregnancy. We describe a 30-year-old pregnant woman whose course was complicated by dysfibrinogenemia with polymorphism of fibrinogen AαThr312Ala (rs6050) GG genotype. She was admitted to our hospital for genital bleeding and a huge subchorionic hematoma at 6 gestational weeks. Her first pregnancy and delivery had been uneventful, whereas her second and third pregnancies had resulted in spontaneous abortions with massive subchorionic hematomas. Her fibrinogen activity level was 125 mg/dl and this was lower than her fibrinogen antigen level. We administered tranexamic acid early in the pregnancy, and the subchorionic hematoma diminished in size in accordance with the increase of her fibrinogen level. At 16 gestational weeks, her D-dimer levels were elevated, and heparin treatment was initiated as an alternative. A male infant was delivered at 36 gestational weeks. Intrapartum hemorrhage was 600 g. Patients with coagulation abnormalities are often asymptomatic in the absence of pregnancy. However, when they become pregnant, the spontaneous abortion rate is high. Careful observation and effective management of coagulation abnormalities are essential for such patients to carry their pregnancies to term. PMID:26861101

  20. Pressure dependence of backbone chemical shifts in the model peptides Ac-Gly-Gly-Xxx-Ala-NH2.

    PubMed

    Erlach, Markus Beck; Koehler, Joerg; Crusca, Edson; Kremer, Werner; Munte, Claudia E; Kalbitzer, Hans Robert

    2016-06-01

    For a better understanding of nuclear magnetic resonance (NMR) detected pressure responses of folded as well as unstructured proteins the availability of data from well-defined model systems are indispensable. In this work we report the pressure dependence of chemical shifts of the backbone atoms (1)H(α), (13)C(α) and (13)C' in the protected tetrapeptides Ac-Gly-Gly-Xxx-Ala-NH2 (Xxx one of the 20 canonical amino acids). Contrary to expectation the chemical shifts of these nuclei have a nonlinear dependence on pressure in the range from 0.1 to 200 MPa. The polynomial pressure coefficients B 1 and B 2 are dependent on the type of amino acid studied. The coefficients of a given nucleus show significant linear correlations suggesting that the NMR observable pressure effects in the different amino acids have at least partly the same physical cause. In line with this observation the magnitude of the second order coefficients of nuclei being direct neighbors in the chemical structure are also weakly correlated. PMID:27335085

  1. Nonconserved Residues Ala287 and Ser290 of the Cryptosporidium hominis Thymidylate Synthase Domain Facilitate Its Rapid Rate of Catalysis

    SciTech Connect

    Doan,L.; Martucci, W.; Vargo, M.; Atreya, C.; Anderson, K.

    2007-01-01

    Cryptosporidium hominis TS-DHFR exhibits an unusually high rate of catalysis at the TS domain, at least 10-fold greater than those of other TS enzymes. Using site-directed mutagenesis, we have mutated residues Ala287 and Ser290 in the folate-binding helix to phenylalanine and glycine, respectively, the corresponding residues in human and most other TS enzymes. Our results show that the mutant A287F, the mutant S290G, and the double mutant all have reduced affinities for methylene tetrahydrofolate and reduced rates of reaction at the TS domain. Interestingly, the S290G mutant enzyme had the lowest TS activity, with a catalytic efficiency {approx}200-fold lower than that of the wild type (WT). The rate of conformational change of the S290G mutant is {approx}80 times slower than that of WT, resulting in a change in the rate-limiting step from hydride transfer to covalent ternary complex formation. We have determined the crystal structure of ligand-bound S290G mutant enzyme, which shows that the primary effect of the mutation is an increase in the distance between the TS ligands. The kinetic and crystal structure data presented here provide the first evidence explaining the unusually fast TS rate in C. hominis.

  2. Crystal structure of Boc-(S)-ABOC-(S)-Ala-(S)-ABOC-(S)-Phe-OBn chloro-form monosolvate.

    PubMed

    Wenger, Emmanuel; Moulat, Laure; Legrand, Baptiste; Amblard, Muriel; Calmès, Monique; Didierjean, Claude

    2015-10-01

    In the title compound, phenyl (S)-2-[(S)-(1-{2-[(S)-(1-{[(tert-but-oxy)carbon-yl]amino}-bicyclo-[2.2.2]octan-2-yl)formamido]-propanamido}-bicyclo-[2.2.2]octan-2-yl)formamido]-3-phenyl-propano-ate chloro-form monosolvate, C42H56N4O7·CHCl3, the α,β-hybrid peptide contains two non-proteinogenic amino acid residues of (S)-1-amino-bicyclo-[2.2.2]octane-2-carb-oxy-lic acid [(S)-ABOC], two amino acid residues of (S)-2-amino-propanoic acid [(S)-Ala] and (S)-2-amino-3-phenyl-propanoic acid [(S)-Phe], and protecting groups of tert-but-oxy-carbonyl (Boc) and benzyl ester (OBn). The tetra-mer folds into a right-handed mixed 11/9 helix stabilized by intra-molecular i,i + 3 and i,i - 1 C=O⋯H-N hydrogen bonds. In the crystal, the oligomers are linked by N-H⋯O=C hydrogen bonds into chains along the a-axis direction. The chloro-form solvent mol-ecules are inter-calated between the folded chains via C-H⋯O=C inter-actions. PMID:26594404

  3. Photoreflectance and surface photovoltage spectroscopy of beryllium-doped GaAs /AlAs multiple quantum wells

    NASA Astrophysics Data System (ADS)

    Čechavičius, B.; Kavaliauskas, J.; Krivaitė, G.; Seliuta, D.; Valušis, G.; Halsall, M. P.; Steer, M. J.; Harrison, P.

    2005-07-01

    We present an optical study of beryllium δ-doped GaAs /AlAs multiple quantum well (QW) structures designed for sensing terahertz (THz) radiation. Photoreflectance (PR), surface photovoltage (SPV), and wavelength-modulated differential surface photovoltage (DSPV) spectra were measured in the structures with QW widths ranging from 3to20nm and doping densities from 2×1010to5×1012cm-2 at room temperature. The PR spectra displayed Franz-Keldysh oscillations which enabled an estimation of the electric-field strength of ˜20kV/cm at the sample surface. By analyzing the SPV spectra we have determined that a buried interface rather than the sample surface mainly governs the SPV effect. The DSPV spectra revealed sharp features associated with excitonic interband transitions which energies were found to be in a good agreement with those calculated including the nonparabolicity of the energy bands. The dependence of the exciton linewidth broadening on the well width and the quantum index has shown that an average half monolayer well width fluctuations is mostly predominant broadening mechanism for QWs thinner than 10nm. The line broadening in lightly doped QWs, thicker than 10nm, was found to arise from thermal broadening with the contribution from Stark broadening due to random electric fields of the ionized impurities in the structures. We finally consider the possible influence of strong internal electric fields, QW imperfections, and doping level on the operation of THz sensors fabricated using the studied structures.

  4. Phase Transitions and Magnetoelectric Coupling in Bi1-xAxFeO3 (A=La, Nd) Multiferroic Ceramics

    NASA Astrophysics Data System (ADS)

    Amirov, A. A.; Kamilov, I. K.; Yusupov, D. M.; Reznichenko, L. A.; Razumovskaya, O. N.; Verbenko, I. A.

    The polycrystalline samples of Bi1-xAxFeO3 (A=La, Nd; x=0-0.2) were prepared by a conventional solid-state reaction method. The effects of varying the Nd and La doping concentration on the crystalline structures, magnetic properties and temperature of antiferromagnetic phase transition TN of the Bi1-xAxFeO3 compounds have been investigated. It is found that Nd doping resulted in a sequence of structural phase transitions and the destruction of the space modulated spin structure near x=0.15 in these materials. The temperature dependences of the magnetic ac-susceptibilities of the samples were obtained. The ac-susceptibility vs. temperature curve of BiFeO3 has a sharp peak at 646 K that corresponds to the antiferromagnetic phase transition TN. With the increase of rare-element doping concentration for both series of samples the Neel temperature TN shifts toward high temperatures. Specific heat capacity for all series of samples was measured in the temperature range of 350-750 K with the modulated-temperature differential scanning calorimeter. The phase transitions from antiferromagnetic to paramagnetic state were observed for all samples. The measurements of magnetocapacitance indicated the dependence of the magnetodielectric effect from the doping level of the rare-earth substitution x.

  5. Validation challenge of density-functional theory for peptides-example of Ac-Phe-Ala5-LysH(+).

    PubMed

    Rossi, Mariana; Chutia, Sucismita; Scheffler, Matthias; Blum, Volker

    2014-09-01

    We assess the performance of a group of exchange-correlation functionals for predicting the secondary structure of peptide chains, up to a new many-body dispersion corrected hybrid density functional, dubbed PBE0+MBD* by its original authors. For the purpose of validation, we first compare to published, high-level benchmark conformational energy hierarchies (coupled cluster at the singles, doubles, and perturbative triples level, CCSD(T)) for 73 conformers of small three-residue peptides, establishing that the van der Waals corrected PBE0 functional yields an average error of only ∼20 meV (∼0.5 kcal/mol). This compares to ∼40-50 meV for nondispersion corrected PBE0 and 40-100 meV for different empirical force fields (estimated for the alanine tetrapeptide). For longer peptide chains that form a secondary structure, CCSD(T) level benchmark data are currently unaffordable. We thus turn to the experimentally well studied Ac-Phe-Ala5-LysH(+) peptide, for which four closely competing conformers were established by infrared spectroscopy. For comparison, an exhaustive theoretical conformational space exploration yields at least 11 competing low energy minima. We show that (i) the many-body dispersion correction, (ii) the hybrid functional nature of PBE0+MBD*, and (iii) zero-point corrections are needed to reveal the four experimentally observed structures as the minima that would be populated at low temperature. PMID:24405171

  6. The transcriptional activities and cellular localization of the human estrogen receptor alpha are affected by the synonymous Ala87 mutation.

    PubMed

    Fernández-Calero, Tamara; Astrada, Soledad; Alberti, Alvaro; Horjales, Sofía; Arnal, Jean Francois; Rovira, Carlos; Bollati-Fogolín, Mariela; Flouriot, Gilles; Marin, Mónica

    2014-09-01

    Until recently, synonymous mutations (which do not change amino acids) have been much neglected. Some evidence suggests that this kind of mutations could affect mRNA secondary structure or stability, translation kinetics and protein structure. To explore deeper the role of synonymous mutations, we studied their consequence on the functional activity of the estrogen receptor alpha (ERα). The ERα is a ligand-inducible transcription factor that orchestrates pleiotropic cellular effects, at both genomic and non-genomic levels in response to estrogens. In this work we analyzed in transient transfection experiments, the activity of ERα carrying the synonymous mutation Ala87, a polymorphism involving about 5-10% of the population. In comparison to the wild type receptor, our results show that ERαA87 mutation reduces the transactivation efficiency of ERα on an ERE reporter gene while its expression level remains similar. This mutation enhances 4-OHT-induced transactivation of ERα on an AP1 reporter gene. Finally, the mutation affects the subcellular localization of ERα in a cell type specific manner. It enhances the cytoplasmic location of ERα without significant changes in non-genomic effects of E2. The functional alteration of the ERαA87 determined in this work highlights the relevance of synonymous mutations for biomedical and pharmacological points of view. PMID:24607813

  7. Layered Fan

    NASA Technical Reports Server (NTRS)

    2006-01-01

    [figure removed for brevity, see original site] Context image for PIA03692 Layered Fan

    This beautiful fan deposit is located at the end of a mega-gully that empties into the southern trough of Coprates Chasma.

    Image information: VIS instrument. Latitude -14.9N, Longitude 299.8E. 17 meter/pixel resolution.

    Note: this THEMIS visual image has not been radiometrically nor geometrically calibrated for this preliminary release. An empirical correction has been performed to remove instrumental effects. A linear shift has been applied in the cross-track and down-track direction to approximate spacecraft and planetary motion. Fully calibrated and geometrically projected images will be released through the Planetary Data System in accordance with Project policies at a later time.

    NASA's Jet Propulsion Laboratory manages the 2001 Mars Odyssey mission for NASA's Office of Space Science, Washington, D.C. The Thermal Emission Imaging System (THEMIS) was developed by Arizona State University, Tempe, in collaboration with Raytheon Santa Barbara Remote Sensing. The THEMIS investigation is led by Dr. Philip Christensen at Arizona State University. Lockheed Martin Astronautics, Denver, is the prime contractor for the Odyssey project, and developed and built the orbiter. Mission operations are conducted jointly from Lockheed Martin and from JPL, a division of the California Institute of Technology in Pasadena.

  8. Enhancing photocatalytic activity of LaTiO2N by removal of surface reconstruction layer.

    PubMed

    Matsukawa, Michinori; Ishikawa, Ryo; Hisatomi, Takashi; Moriya, Yosuke; Shibata, Naoya; Kubota, Jun; Ikuhara, Yuichi; Domen, Kazunari

    2014-02-12

    LaTiO2N is an oxynitride photocatalyst that has ability to generate H2 and O2 from water under irradiation of light with wavelengths up to 600 nm. However, LaTiO2N necessitates sacrificial reagents that capture either photoexcited electrons or holes efficiently to be active in the photocatalytic reactions because of a considerable number of defects that cause trapping and recombination of photoexcited carriers. Therefore, identifying defect structures of LaTiO2N is important. In this study, using atomic-resolution scanning transmission electron microscopy, we evidence that eliminating defective surface reconstructed layers of LaTiO2N particles by the treatment with aqua regia can double the photocatalytic activity. PMID:24460145

  9. Benchmark dose approach for low-level lead induced haematogenesis inhibition and associations of childhood intelligences with ALAD activity and ALA levels.

    PubMed

    Wang, Q; Ye, L X; Zhao, H H; Chen, J W; Zhou, Y K

    2011-04-15

    Lead (Pb) levels, delta-aminolevulinic acid dehydratase (ALAD) activities, zinc protoporphyrin (ZPP) levels in blood, and urinary delta-aminolevulinic acid (ALA) and coproporphyrin (CP) concentrations were measured for 318 environmental Pb exposed children recruited from an area of southeast China. The mean of blood lead (PbB) levels was 75.0μg/L among all subjects. Benchmark dose (BMD) method was conducted to present a lower PbB BMD (lower bound of BMD) of 32.4μg/L (22.7) based on ALAD activity than those based on the other three haematological indices, corresponding to a benchmark response of 1%. Childhood intelligence degrees were not associated significantly with ALAD activities or ALA levels. It was concluded that blood ALAD activity is a sensitive indicator of early haematological damage due to low-level Pb exposures for children. PMID:21334730

  10. The Simultaneous Electrochemical Detection of Catechol and Hydroquinone with [Cu(Sal-β-Ala)(3,5-DMPz)2]/SWCNTs/GCE

    PubMed Central

    Alshahrani, Lina Abdullah; Li, Xi; Luo, Hui; Yang, Linlin; Wang, Mengmeng; Yan, Songling; Liu, Peng; Yang, Yuqin; Li, Quanhua

    2014-01-01

    A glassy carbon electrode was modified with a copper(II) complex [Cu(Sal-β-Ala) (3,5-DMPz)2] (Sal = salicylaldehyde, β-Ala = β-alanine, 3,5-DMPz = 3,5-dimethylpyrazole) and single-walled carbon nanotubes (SWCNTs). The modified electrode was used to detect catechol (CT) and hydroquinone (HQ) and exhibited good electrocatalytic activities toward the oxidation of CT and HQ. The peak currents were linear with the CT and HQ concentrations over the range of 5–215 μmol·L−1 and 5–370 μmol·L−1 with corresponding detection limits of 3.5 μmol·L−1 and 1.46 μmol·L−1 (S/N = 3) respectively. Moreover, the modified electrode exhibited good sensitivity, stability and reproducibility for the determination of CT and HQ, indicating the promising applications of the modified electrode in real sample analysis. PMID:25429411

  11. Rapid inactivation of cathepsin L by Z-Phe-PheCHN/sub 2/ and Z-Phe-AlaCHN/sub 2/

    SciTech Connect

    Kirschke, H.; Shaw, E.

    1981-07-30

    Z-Phe-PheCHN/sub 2/ and Z-Phe-AlaCHN/sub 2/ were found to react extremely rapidly with cathepsin L from rat liver lysosomes. For measuring the inactivation time it was necessary to work with dilute enzyme and inhibitor solutions, that is in the range of 10/sup -9/ M. These conditions were made possible through the use of Z-Phe-Arg-4-methyl-7-coumarylamide, a very sensitive substrate suitable for assays of cathepsin L in about 10/sup -12/ M solutions. Z-Phe-AlaCHN/sub 2/ has an affinity for cathepsin L which is about 2000-fold higher than for cathepsin B from rat and human. Z-Phe-PheCHN/sub 2/ proved to be a selective inactivator of cathepsin L in a certain concentration range. Z-Phe-PheCHN/sub 2/ reacts reversibly with cathepsin B from several species.

  12. Short Communication Molecular cloning and expression pattern of the porcine 5-aminolevulinate synthase 1 (ALAS1) gene and its association with reproductive traits.

    PubMed

    Liu, L Q; Li, F E; Deng, C Y

    2016-01-01

    5-Aminolevulinate synthase 1 (ALAS1) is the first enzyme in the heme biosynthetic pathway and is upregulated in follicular tissue during the early stages of ovulation. In this study, we isolated the complete coding sequence of the porcine ALAS1 gene and its 2-9 intron sequence, identified a single nucleotide polymorphism (SNP; T/C) in intron 9, and developed a PCR-MspI-restriction fragment length polymorphism genotyping assay. Association of the SNP with litter size was assessed in two populations [purebred Large White and the experimental synthetic (DIV) line]. Statistical analysis demonstrated that for total number of piglets born (TNB) in all parities, pigs with the CC genotype had an additional 0.68 and 0.74 piglets compared to the TC and TT animals (P < 0.05) in the DIV line, respectively. Purebred Large White sows inheriting the CC and TC genotypes gave birth to an additional 0.96 and 0.70 piglets compared to the TT animals (P < 0.05) in all parities, respectively. In addition, for TNB in all parities, a significant additive effect of 0.48 ± 0.23 and 0.37 ± 0.17 piglets/ litter was detected in sows of both populations (P < 0.05), respectively. The highest levels of ALAS1 gene expression were observed in isolated ovarian granulosa cells 2 and 12 h after stimulation with pregnant mare serum gonadotropin human chorionic gonadotropin, which represents the time of follicular development and ovulation, respectively. Therefore, the ALAS1 gene was significantly associated with litter size in two populations and could be a useful molecular marker for the selection of increasing litter size in pigs. PMID:26910002

  13. Environment of copper in Pseudomonas aeruginosa azurin probed by binding of exogenous ligands to Met121X (X = Gly, Ala, Val, Leu, or Asp) mutants.

    PubMed

    Bonander, N; Karlsson, B G; Vänngård, T

    1996-02-20

    The binding of small exogenous ligands to mutants of the blue copper protein azurin from Pseudomonas aeruginosa, altered in the axial position, Met121X (X = Gly, Ala, Val, Leu, or Asp), has been studied with optical and electron paramagnetic resonance (EPR) spectroscopy. The results show that small molecules can enter the pocket left by the side chain of Met121. For azide, the dissociation constants are Leu > Val > Ala, reflecting the increasing space available. The Gly and Asp mutants bind azide less strongly than the Ala mutant, due to competition with water (Gly) and the polar side chain (Asp). Similar trends are found for thiocyanate. Cyanide binds equally well to the Ala and Val mutants. A number of other small potential ligands were tried. Alcohols do not affect room-temperature optical spectra, but at low temperatures, the EPR spectrum is stellacyanin-like, indicative of a weak axial interaction. Ligands binding with a carboxyl group or nitrogen (e.g. acetate or azide) convert the metal center to a form intermediate between regular types 1 and 2, presumably by pulling the copper ion out of the trigonal plane formed by Cys(S) and two His(N). Cyanide interacts strongly as shown by the hyperfine coupling to the 13C nucleus. With increasing strength of the axial interaction, the two major bands in the visible region (600 and 400-500 nm) shift in parallel to higher energy, and at the same time, the strength of the latter transition increases at the expense of the former. This demonstrates that these transitions have a common origin, namely S-to-Cu charge transfer transition. PMID:8652586

  14. Effects Ala54Thr polymorphism of FABP2 on obesity index and biochemical variable in response to a aerobic exercise training

    PubMed Central

    Han, Tae Kyung

    2013-01-01

    The purpose of the current study was to investigate whether or not the FABP2 gene polymorphism modulated obesity indices, hemodynamic factor, blood lipid factor, and insulin resistance markers through 12-week aerobic exercise training in abdominal obesity group of Korean mid-life women. A total of 243 abdominally obese subjects of Korean mid-life women voluntarily participated in aerobic exercise training program for 12 weeks. Polymerase Chain Reaction with Restriction Fragment Length Polymorphism (PCR-RFLP) assay was used to assess the FABP2 genotype of the participants (117 of AA homozygotes, 100 of AT heterozygotes, 26 of TT homozygotes). Prior to the participation of the exercise training program, baseline obesity indices, hemodynamic factor, blood lipid factor, and insulin resistance markers were measured. All the measurements were replicated following the 12-week aerobic exercise training program, and then the following results were found. After 12-week aerobic exercise training program, wild type (Ala54Ala) and mutant type (Ala54Thr+Thr54Thr) significantly decreased weight (P > .001), BMI (P > .001), %bf (P > .001), waist circumference (P > .001), WHR (P > .001), muscle mass (wild type p < .022; mutant type P > .001), RHR (P > .001), viseceral adipose area (wild type p < .005; mutant type P > .001), subcutaneous area (P > .001), insulin (wild type p < .005; mutant type P > .001) and significantly increased VO2max (P > .001). And wild type significantly decresed NEFA (P > .05), glucose (P > .05), OGTT 120min glucose (P > .05) and significantly increased HDLC (p > .005). Mutant type significantly decreased SBP (P > .001), DBP (P > .01), TC (P > .01), LPL (P > .05), LDL (P > .001), HOMA index (P > .01). The result of the present study represents that regular aerobic exercise training may beneficially prevent obesity index, blood pressure, blood lipids and insulin resistance markers independent of FABP Ala54Thr wild type and mutant type. PMID:25566432

  15. Photodynamic therapy for difficult-to-treat basal cell carcinomas: Do poorly responding BCCs lack accumulation of protoporphyrin IX after ALA/MAL application?

    NASA Astrophysics Data System (ADS)

    Sandberg, Carin; Paoli, John; Halldin, Christina B.; Gillstedt, Martin; Larkö, Olle; Wennberg, Ann-Marie; Ericson, Marica B.

    2009-06-01

    Photodynamic therapy (PDT) using topical application of aminolevulinic acid (ALA) and methylaminolevulinate (MAL) has become a popular therapeutic method for the treatment of non-melanoma skin cancers such as basal cell carcinomas (BCCs); however, the treatment response varies. An important question is if BCCs which respond poorly to PDT lack accumulation of protoporhyrin IX (PpIX) after ALA/MAL application. In connection to PDT, fluorescence diagnostics (FD) can be performed to detect PpIX within human skin. We investigated fluorescence images from 22 patients with 35 BCCs. They were evaluated with respect to the fluorescence contrast based on image analysis, which was considered to be a tool to non-invasively measure the PpIX-concentration. As expected the fluorescence contrast between tumor and normal skin was elevated after MAL-application; although no correlation between low fluorescence contrast and lack of treatment response could be observed. In a former study, we have also investigated the transdermal penetration of ALA and MAL in 27 BCCs in vivo using a microdialysis technique. In 15 of 16 BCCs in which the microdialysis catheter was located superficially (i.e. at a depth of less than 1 mm), therapeutic drug concentrations were detected;.however, in the 11 lesions with a deeper catheter location (below 1 mm) drug concentrations above the detection limit of the system were only obtained in 6 lesions (p=0.026). No difference between the transdermal penetration of MAL and ALA could be seen. Conclusions: Lack of PpIX fluorescence cannot entirely explain why some BCCs don't respond to PDT, but inadecuate concentrations within the full thickness of the tumor may play a role as microdialysis has shown.

  16. A genetic association study of two genes linked to neurodegeneration in a Sardinian multiple sclerosis population: the TARDBP Ala382Thr mutation and C9orf72 expansion.

    PubMed

    Lorefice, L; Murru, M R; Fenu, G; Corongiu, D; Frau, J; Cuccu, S; Coghe, G C; Tranquilli, S; Cocco, E; Marrosu, M G

    2015-10-15

    Multiple sclerosis (MS) is a chronic disease of the central nervous system characterized by inflammation and accompanied and followed by neurodegeneration. Missense mutations of the TAR DNA Binding Protein gene (TARDBP) located in the chromosome 1p36.22 region, and the hexanucleotide repeat expansions in chromosome 9 open reading frame 72 (C9orf72) are pathogenic in other neurodegenerative diseases such as amyotrophic lateral sclerosis and frontotemporal lobar degeneration. Assuming that TARDBP Ala382Thr mutation and C9orf72 expansion may underlie MS, we evaluated their frequency in a large cohort of MS patients and controls from Sardinia, an island characterized by a very high frequency of MS and an unusual genetic background. Genomic DNA was extracted from peripheral blood and analyzed for the presence of a TARDBP Ala382Thr mutation and C9orf72 expansion. Difference in the frequency of these mutations between MS patients and controls was calculated using the χ(2) test with a standard 2×2 table. The Ala382Thr mutation in its heterozygous state was found in 27/1833 patients (1.4%) and 20/1475 controls (1.3%), whereas C9orf72 pathogenic repeat expansion was found in 6/1014 MS patients (0.6%) and 2/333 controls (0.6%). Individuals carrying the mutations did not present with other neurodegenerative conditions and any differences were reported between groups. TARDBP Ala382Thr mutation and C9orf72 expansion do not play a major role in MS pathogenesis in the Sardinian population. Further analyses on larger samples of MS patients from other populations are needed to better define the possible role of these genes in the complex interplay between neuroinflammation and neurodegeneration in MS. PMID:26233805

  17. LA and ALA prevent glucose intolerance in obese male rats without reducing reactive lipid content, but cause tissue-specific changes in fatty acid composition.

    PubMed

    Matravadia, Sarthak; Zabielski, Piotr; Chabowski, Adrian; Mutch, David M; Holloway, Graham P

    2016-04-01

    While the cause of Type 2 diabetes remains poorly defined, the accumulation of reactive lipids within white adipose tissue, skeletal muscle, and liver have been repeatedly implicated as underlying mechanisms. The ability of polyunsaturated fatty acids (PUFAs) to prevent the development of insulin resistance has gained considerable interest in recent years; however, the mechanisms-of-action remain poorly described. Therefore, we determined the efficacy of diets supplemented with either linoleic acid (LA) or α-linolenic acid (ALA) in preventing insulin resistance and reactive lipid accumulation in key metabolic tissues of the obese Zucker rat. Obese Zucker rats displayed impaired glucose homeostasis and reduced n-3 and n-6 PUFA content in the liver and epididymal white adipose tissue (EWAT). After the 12-wk feeding intervention, both LA- and ALA-supplemented diets prevented whole body glucose and insulin intolerance; however, ALA had a more pronounced effect. These changes occurred in association with n-3 and n-6 accumulation in all tissues studied, albeit to different extents (EWAT > liver > muscle). Triacylglycerol (TAG), diacylglycerol (DAG), ceramide, and sphingolipid accumulation were not attenuated in obese animals supplemented with either LA or ALA, suggesting that preservation of glucose homeostasis occurred independent of changes in reactive lipid content. However, PUFA-supplemented diets differentially altered the fatty acid composition of TAGs, DAGs, and PLs in a tissue-specific manner, suggesting essential fatty acid metabolism differs between tissues. Together, our results indicate that remodeling of the fatty acid composition of various lipid fractions may contribute to the improved glucose tolerance observed in obese rats fed PUFA-supplemented diets. PMID:26764053

  18. Characterization of rat brain opioid receptors by (Tyr-3,5-/sup 3/H)1, D-Ala2, Leu5-enkephalin binding

    SciTech Connect

    Benyhe, S.; Toth, G.; Kevei, J.; Szuecs, M.B.; Borsodi, A.; Di Gleria, K.; Szecsi, J.; Sueli-Vargha, H.M.; Medzihradszky, K.

    1985-05-01

    (Tyr-3,5-/sup 3/H)1, D-Ala2, Leu5-enkephalin ((/sup 3/H)DALA) was used for labeling the opioid receptors of rat brain plasma membranes. The labeled ligand was prepared from (Tyr-3,5-diiodo)1, D-Ala2, Leu5-enkephalin by catalytic reductive dehalogenation in the presence of Pd catalyst. The resulting (Tyr-3,5-/sup 3/H)1, D-Ala2, Leu5-enkephalin had a specific activity of 37.3 Ci/mmol. In the binding experiments steady-state level was reached at 24 degrees C within 45 min. The pseudo first order association rate constant was 0.1 min-1. The dissociation of the receptor-ligand complex was biphasic with k-1-s of 0.009 and 0.025 min-1. The existence of two binding sites was proved by equilibrium studies. The high affinity site showed a KD = 0.7 nM and Bmax = 60 fmol/mg protein; the low affinity site had a KD = 5 nM and Bmax = 160 fmol/mg protein. A series of opioid peptides inhibited (/sup 3/H)DALA binding more efficiently than morphine-like drugs suggesting that labeled ligand binds preferentially to the delta subtype of opioid receptors. Modification of the original peptides either at the C or N terminal ends of the molecules resulted in a decrease in their affinity.

  19. Wide mutation spectrum and frequent variant Ala27Thr of FBN1 identified in a large cohort of Chinese patients with sporadic TAAD

    PubMed Central

    Guo, Jun; Cai, Lun; Jia, Lixin; Li, Xiaoyan; Xi, Xin; Zheng, Shuai; Liu, Xuxia; Piao, Chunmei; Liu, Tingting; Sun, Zhongsheng; Cai, Tao; Du, Jie

    2015-01-01

    Genetic etiology in majority of patients with sporadic thoracic aortic aneurysm and dissections (STAAD) remains unknown. Recent GWAS study suggested common variant(s) in FBN1 is associated with STAAD. The present study aims to test this hypothesis and to identify mutation spectrum by targeted exome sequencing of the FBN1 gene in 146 unrelated patients with STAAD. Totally, 15.75% of FBN1 variants in STAAD were identified, including 5 disruptive and 18 missense mutations. Most of the variants were novel. Genotype-phenotype correlation analysis suggested that the maximum aortic diameter in the disruptive mutation group was significantly larger than that in the non-Cys missense mutation group. Interestingly, the variant Ala27Thr at −1 position, which is predicted to change the cleavage site of the signal peptidase of fibrillin-1, was detected in two unrelated patients. Furthermore, genotyping analysis of this variant detected 10 heterozygous Ala27Thr from additional 666 unrelated patients (1.50%), versus 7 from 1500 controls (0.47%), indicating a significant association of this variant with STAAD. Collectively, the identification of the variant Ala27Thr may represent a relatively common genetic predisposition and a novel pathogenetic mechanism for STAAD. Also, expansion of the mutation spectrum in FBN1 will be helpful in genetic counselling for Chinese patients with STAAD. PMID:26272055

  20. Dexamethasone alone and in combination with desipramine, phenytoin, valproic acid or levetiracetam interferes with 5-ALA-mediated PpIX production and cellular retention in glioblastoma cells.

    PubMed

    Lawrence, Johnathan E; Steele, Christopher J; Rovin, Richard A; Belton, Robert J; Winn, Robert J

    2016-03-01

    Extent of resection of glioblastoma (GBM) correlates with overall survival. Fluorescence-guided resection (FGR) using 5-aminolevulinic acid (5-ALA) can improve the extent of resection. Unfortunately not all patients given 5-ALA accumulate sufficient quantities of protoporphyrin IX (PpIX) for successful FGR. In this study, we investigated the effects of dexamethasone, desipramine, phenytoin, valproic acid, and levetiracetam on the production and accumulation of PpIX in U87MG cells. All of these drugs, except levetiracetam, reduce the total amount of PpIX produced by GBM cells (p < 0.05). When dexamethasone is mixed with another drug (desipramine, phenytoin, valproic acid or levetiracetam) the amount of PpIX produced is further decreased (p < 0.01). However, when cells are analyzed for PpIX cellular retention, dexamethasone accumulated significantly more PpIX than the vehicle control (p < 0.05). Cellular retention of PpIX was not different from controls in cells treated with dexamethasone plus desipramine, valproic acid or levetiracetam, but was significantly less for dexamethasone plus phenytoin (p < 0.01). These data suggest that medications given before and during surgery may interfere with PpIX accumulation in malignant cells. At this time, levetiracetam appears to be the best medication in its class (anticonvulsants) for patients undergoing 5-ALA-mediated FGR. PMID:26643803

  1. Clostridium difficile toxin A induces intestinal epithelial cell apoptosis and damage: role of Gln and Ala-Gln in toxin A effects.

    PubMed

    Brito, Gerly A C; Carneiro-Filho, Benedito; Oriá, Reinaldo B; Destura, Raul V; Lima, Aldo A M; Guerrant, Richard L

    2005-07-01

    The aim of this study was to investigate the effect of Clostridium difficile toxin A (TxA) on intestinal epithelial cell migration, apoptosis, and transepithelial resistance and to evaluate the effect of glutamine (Gln) and its stable derivative, alanyl-glutamine (Ala-Gln), on TxA-induced damage. Migration was measured in rat intestinal epithelial cells (IEC-6) 6 and 24 hr after a razor scrape of the cell monolayer. Cell proliferation was indirectly measured utilizing the tetrazolium salt WST-1. The cells were incubated with TxA (1-100 ng/ml) in medium without Gln or medium containing Gln or Ala-Gln (1-30 mM). Apoptosis was quantified in IEC-6 cells using annexin V assay. Transepithelial resistance was measured using an epithelial voltohmmeter across T84 cells seeded on a transwell filter. TxA-induced a dose-dependent reduction of migration and also caused dose and time-dependent apoptosis in IEC-6 cells. Gln and Aln-Gln significantly enhanced IEC-6 cell migration and proliferation. Gln and Ala-Gln also prevented the inhibition of migration, apoptosis, and the initial drop in transepithelial resistance induced by TxA. In conclusion, both peptides reduced toxin-induced epithelial damage and thus might play an adjunctive role in C. difficile-induced colitis therapy. PMID:16047471

  2. A Novel Approach for Full-Thickness Defect of the Nasal Alar Rim: Primary Closure of the Defect and Reduction of the Contralateral Normal Ala for Symmetry

    PubMed Central

    Choe, Yun Seon; Kim, Min-Woo

    2015-01-01

    In full-thickness defects of the nasal alar rim, to achieve projection and maintain airway patency, cartilage graft is frequently needed. However, cartilage graft presents a challenge in considerations such as appropriate donor site, skeletal shape and size, and healing of the donor area. To avoid these demerits, we tried primary closure of alar rim defects by also making the contralateral normal ala smaller. We treated two patients who had a full-thickness nasal alar defect after tumor excision. Cartilage graft was considered for the reconstruction. However, their alar rims were overly curved and their nostril openings were large. To utilize their nasal shape, we did primary closure of the defect rather than cartilage graft, and then downsized the contralateral nasal ala by means of wedge resection to make the alae symmetric. Both patients were satisfied with their aesthetic results, which showed a smaller nostril and nearly straight alar rims. Moreover, functionally, there was no discomfort during breathing in both patients. We propose our idea as one of the reconstruction options for nasal alar defects. It is a simple and easy-to-perform procedure, in addition to enhancing the nasal contour. This method would be useful for patients with a large nostril and an overly curved alar rim. PMID:26719646

  3. Optical detection of human urinary bladder carcinoma utilising tissue autoflurescence and protoporphyrin IX-induced fluorescence following low dose ALA instillation

    NASA Astrophysics Data System (ADS)

    Rokahr, Ingrid; Andersson-Engels, Stefan; Svanberg, Sune; D'Hallewin, Marie-Ange; Baert, Luc; Wang-Nordman, Ingrid; Svanberg, Katarina

    1995-12-01

    Laser-induced fluorescence spectra were recorded in patients undergoing urinary bladder cystoscopy. The measurements were performed in vivo and the spectra were collected from normal and diseased tissue. The patients were divided into two groups. An instillation of a 1% delta-amino-levulinic acid (ALA) solution was performed 2 - 4 hours prior to the investigation of one group of patients. A second group of patients was investigated without any tumor marking substance. The fluorescence was detected following laser excitation at 405 and 337 nm. Fluorescence emission related to ALA-induced protoporphyrin IX (PpIX) was detected in the ALA group for 405 nm excitation. The data were evaluated at the PpIX emission peak at 635 nm and at 490 nm, which approximately corresponds to the peak of the tissue autofluorescence. The data obtained with 337 nm excitation were evaluated at 400 and 460 nm as well as at 390 and 431 nm. The ratios of the respective wavelength pairs were formed in order to investigate the demarcation between tumor and normal tissue. The tumor demarcation results were better and more consistent utilizing the autofluorescence signal following excitation at 337 nm than the PpIX-related signal excited at 405 nm.

  4. The mutation G298A-->Ala100Thr on the coding sequence of the Duffy antigen/chemokine receptor gene in non-caucasian Brazilians.

    PubMed

    Estalote, Angela Cristina; Proto-Siqueira, Rodrigo; Silva, Wilson Araújo Da; Zago, Marco Antonio; Palatnik, Marcos

    2005-01-01

    Ala100Thr has been suggested to be a Caucasian genetic marker on the FY*B allele. As the Brazilian population has arisen from miscegenation among Portuguese, Africans, and Indians, this mutation could possibly be found in Euro- and Afro-Brazilians, or in Brazilian Indians. Fifty-three related individuals and a random sample of 100 subjects from the Brazilian population were investigated using the polymerase chain reaction and four restriction fragment length polymorphisms. Confirming the working hypothesis, among the related individuals three Afro-Brazilians (two of them a mother and daughter) and a woman of Amerindian descent had the Ala100Thr mutation on the FY*B allele. Five non-related Euro-Brazilians also carried the mutation. All nine individuals presented the Fy(a-b+) phenotype. We conclude that the Ala100Thr mutation can occur in populations other than Caucasians and that this mutation does not affect Duffy expression on red blood cells. Gene frequencies for this allele in the non-related individuals were in agreement with those of other populations. The Duffy frequencies of two Amerindian tribes were also investigated. PMID:16110438

  5. Description of a primitive valley scattering unit cell to understand anisotropic inter-valley scattering in AlAs quantum wells

    NASA Astrophysics Data System (ADS)

    Prabhu-Gaunkar, S.; Grayson, M.

    2011-03-01

    Valley degenerate systems have an extra scattering channel not present in single valley systems, namely inter-valley scattering. To help classify anisotropic inter-valley scattering in degenerate multi-valley systems, such as AlAs quantum wells (QWs), we define a valley scattering primitive unit cell in momentum space which allows one to distinguish purely in-plane momentum scattering from scattering requiring an out-of-plane momentum component. The standard depiction of a 2D Brillouin zone of a quantum confined valley-degenerate system projects all valleys to a single plane and this depiction loses information about the momentum scattering component that was projected out. Because QW confinement potentials are inherently anisotropic, the disorder potential characteristic of quantum confinement can create anisotropic short-wavelength inter- valley scattering potentials favoring in-plane momentum scattering. We demonstrate that the valley scattering cell for AlAs QWs grown along various orientations is particularly useful in identifying relevant scattering vectors. Initial estimates will be shown of the role of strong electron-electron interactions in AlAs QWs on inter-valley scattering parameters such as inter-valley scattering time, probabilities and rates.

  6. Structures of an alanine racemase from Bacillus anthracis (BA0252) in the presence and absence of (R)-1-aminoethylphosphonic acid (l-Ala-P)

    SciTech Connect

    Au, Kinfai; Ren, Jingshan; Walter, Thomas S.; Harlos, Karl; Nettleship, Joanne E.; Owens, Raymond J.; Stuart, David I.; Esnouf, Robert M.

    2008-05-01

    Structures of BA0252, an alanine racemase from B. anthracis, in the presence and absence of the inhibitor (R)-1-aminoethylphosphonic acid (l-Ala-P) and determined by X-ray crystallography to resolutions of 2.1 and 1.47 Å, respectively, are described. Bacillus anthracis, the causative agent of anthrax, has been targeted by the Oxford Protein Production Facility to validate high-throughput protocols within the Structural Proteomics in Europe project. As part of this work, the structures of an alanine racemase (BA0252) in the presence and absence of the inhibitor (R)-1-aminoethylphosphonic acid (l-Ala-P) have determined by X-ray crystallo@@graphy to resolutions of 2.1 and 1.47 Å, respectively. Difficulties in crystallizing this protein were overcome by the use of reductive methylation. Alanine racemase has attracted much interest as a possible target for anti-anthrax drugs: not only is d-alanine a vital component of the bacterial cell wall, but recent studies also indicate that alanine racemase, which is accessible in the exosporium, plays a key role in inhibition of germination in B. anthracis. These structures confirm the binding mode of l-Ala-P but suggest an unexpected mechanism of inhibition of alanine racemase by this compound and could provide a basis for the design of improved alanine racemase inhibitors with potential as anti-anthrax therapies.

  7. Evaluation of 99mTc-HYNIC-βAla-Bombesin(7-14) as an agent for pancreas tumor detection in mice

    PubMed Central

    Carlesso, F.N.; Fuscaldi, L.L.; Araújo, R.S.; Teixeira, C.S.; Oliveira, M.C.; Fernandes, S.O.A.; Cassali, G.D.; Reis, D.C.; Barros, A.L.B.; Cardoso, V.N.

    2015-01-01

    Pancreatic adenocarcinoma is important in oncology because of its high mortality rate. Deaths may be avoided if an early diagnosis could be achieved. Several types of tumors overexpress gastrin-releasing peptide receptors (GRPr), including pancreatic cancer cells. Thus, a radiolabeled peptide derivative of gastrin-releasing peptide (GRP) may be useful as a specific imaging probe. The purpose of the present study was to evaluate the feasibility of using99mTc-HYNIC-βAla-Bombesin(7-14)as an imaging probe for Capan-1 pancreatic adenocarcinoma. Xenographic pancreatic tumor was developed in nude mice and characterized by histopathological analysis. Biodistribution studies and scintigraphic images were carried out in tumor-bearing nude mice. The two methods showed higher uptake by pancreatic tumor when compared to muscle (used as control), and the tumor-to-muscle ratio indicated that99mTc-HYNIC-βAla-Bombesin(7-14)uptake was four-fold higher in tumor cells than in other tissues. Scintigraphic images also showed a clear signal at the tumor site. The present data indicate that99mTc-HYNIC-βAla-Bombesin(7-14)may be useful for the detection of pancreatic adenocarcinoma. PMID:26445336

  8. Thermally activated decomposition of (Ga,Mn)As thin layer at medium temperature post growth annealing

    NASA Astrophysics Data System (ADS)

    Melikhov, Y.; Konstantynov, P.; Domagala, J.; Sadowski, J.; Chernyshova, M.; Wojciechowski, T.; Syryanyy, Y.; Demchenko, I. N.

    2016-05-01

    The redistribution of Mn atoms in Ga1-xMnxAs layer during medium-temperature annealing, 250-450 oC, by Mn K-edge X-ray absorption fine structure (XAFS) recorded at ALBA facility, was studied. For this purpose Ga1-xMnxAs thin layer with x=0.01 was grown on AlAs buffer layer deposited on GaAs(100) substrate by molecular beam epitaxy (MBE) followed by annealing. The examined layer was detached from the substrate using a “lift-off” procedure in order to eliminate elastic scattering in XAFS spectra. Fourier transform analysis of experimentally obtained EXAFS spectra allowed to propose a model which describes a redistribution/diffusion of Mn atoms in the host matrix. Theoretical XANES spectra, simulated using multiple scattering formalism (FEFF code) with the support of density functional theory (WIEN2k code), qualitatively describe the features observed in the experimental fine structure.

  9. Fluorometric sensing of ultralow As(III) concentrations using Ag doped hollow CdS/ZnS bi-layer nanoparticles.

    PubMed

    Boxi, Siddhartha Sankar; Paria, Santanu

    2015-12-21

    Arsenic poisoning from drinking water has been an important global issue in recent years. Because of the high level toxicity of arsenic to human health, an easy, inexpensive, low level and highly selective detection technique is of great importance to take any early precautions. This study reports the synthesis of Ag doped hollow CdS/ZnS bi-layer (Ag-h-CdS/ZnS) nanoparticles for the easy fluorometric determination of As(iii) ions in the aqueous phase. The hollow bi-layer structures were synthesized by a sacrificial core method using AgBr as the sacrificial core and the core was removed by dissolution in an ammonium hydroxide solution. The synthesized nanoparticles were characterized using different instrumental techniques. A good linear relationship was obtained between fluorescence quenching intensity and As(iii) concentration in the range of 0.75-22.5 μg L(-1) at neutral pH with a limit of detection as low as 0.226 μg L(-1). PMID:26541652

  10. Nonenzymatic anticoagulant activity of the mutant serine protease Ser360Ala-activated protein C mediated by factor Va.

    PubMed Central

    Gale, A. J.; Sun, X.; Heeb, M. J.; Griffin, J. H.

    1997-01-01

    The human plasma serine protease, activated protein C (APC), primarily exerts its anticoagulant function by proteolytic inactivation of the blood coagulation cofactors Va and VIIIa. A recombinant active site Ser 360 to Ala mutation of protein C was prepared, and the mutant protein was expressed in human 293 kidney cells and purified. The activation peptide of the mutant protein C zymogen was cleaved by a snake venom activator, Protac C, but the "activated" S360A APC did not have amidolytic activity. However, it did exhibit significant anticoagulant activity both in clotting assays and in a purified protein assay system that measured prothrombinase activity. The S360A APC was compared to plasma-derived and wild-type recombinant APC. The anticoagulant activity of the mutant, but not native APC, was resistant to diisopropyl fluorophosphate, whereas all APCs were inhibited by monoclonal antibodies against APC. In contrast to native APC, S360A APC was not inactivated by serine protease inhibitors in plasma and did not bind to the highly reactive mutant protease inhibitor M358R alpha 1 antitrypsin. Since plasma serpins provide the major mechanism for inactivating APC in vivo, this suggests that S360A APC would have a long half-life in vivo, with potential therapeutic advantages. S360A APC rapidly inhibited factor Va in a nonenzymatic manner since it apparently did not proteolyze factor Va. These data suggest that native APC may exhibit rapid nonenzymatic anticoagulant activity followed by enzymatic irreversible proteolysis of factor Va. The results of clotting assays and prothrombinase assays showed that S360A APC could not inhibit the variant Gln 506-FVa compared with normal Arg 506-FVa, suggesting that the active site of S360A APC binds to FVa at or near Arg 506. PMID:9007985

  11. Creep Properties of the As-Cast Al-A319 Alloy: T4 and T7 Heat Treatment Effects

    NASA Astrophysics Data System (ADS)

    Erfanian-Naziftoosi, Hamid R.; Rincón, Ernesto J.; López, Hugo F.

    2016-05-01

    In this work, the creep behavior of a commercial Al-A319 alloy was investigated in the temperature range of 413 K to 533 K (140 °C to 260 °C). Tensile creep specimens in the as-cast condition and after heat treating by solid solution (T4) and by aging (T7) were tested in a stress range varying from 60 to 170 MPa. It was found that steady-state creep strain rate was significantly low in the T7 condition when compared with either the T4 or as-cast alloy conditions. As a result, the time to failure behavior considerably increased. The experimentally determined creep exponents measured from the stress-strain curves were 4 for the as-cast alloy, 7.5 in the solid solution, and 9.5 after aging. In particular, after solid solution a grain substructure was found to develop which indicated that creep in a constant subgrain structure was active, thus accounting for the n exponent of 7.5. In the aged condition, a stress threshold is considered to account for the power law creep exponent n of 9.5. Moreover, It was found that the creep activation energy values were rather similar for the alloys in the as-cast (134 kJ/mol) and T4 (146 kJ/mol) conditions. These values are close to the one corresponding to pure Al self-diffusion (143 kJ/mol). In the aged alloy, the apparent creep activation energy (202 kJ/mol) exceeded that corresponding to Al self-diffusion. This deviation in activation energy is attributed to the effect of temperature on the alloy elastic modulus. Microstructural observations using transmission electron microscopy provided further support for the various dislocation-microstructure interactions exhibited by the alloy under the investigated creep conditions and implemented heat treatments.

  12. Creep Properties of the As-Cast Al-A319 Alloy: T4 and T7 Heat Treatment Effects

    NASA Astrophysics Data System (ADS)

    Erfanian-Naziftoosi, Hamid R.; Rincón, Ernesto J.; López, Hugo F.

    2016-08-01

    In this work, the creep behavior of a commercial Al-A319 alloy was investigated in the temperature range of 413 K to 533 K (140 °C to 260 °C). Tensile creep specimens in the as-cast condition and after heat treating by solid solution (T4) and by aging (T7) were tested in a stress range varying from 60 to 170 MPa. It was found that steady-state creep strain rate was significantly low in the T7 condition when compared with either the T4 or as-cast alloy conditions. As a result, the time to failure behavior considerably increased. The experimentally determined creep exponents measured from the stress-strain curves were 4 for the as-cast alloy, 7.5 in the solid solution, and 9.5 after aging. In particular, after solid solution a grain substructure was found to develop which indicated that creep in a constant subgrain structure was active, thus accounting for the n exponent of 7.5. In the aged condition, a stress threshold is considered to account for the power law creep exponent n of 9.5. Moreover, It was found that the creep activation energy values were rather similar for the alloys in the as-cast (134 kJ/mol) and T4 (146 kJ/mol) conditions. These values are close to the one corresponding to pure Al self-diffusion (143 kJ/mol). In the aged alloy, the apparent creep activation energy (202 kJ/mol) exceeded that corresponding to Al self-diffusion. This deviation in activation energy is attributed to the effect of temperature on the alloy elastic modulus. Microstructural observations using transmission electron microscopy provided further support for the various dislocation-microstructure interactions exhibited by the alloy under the investigated creep conditions and implemented heat treatments.

  13. Degradation, receptor binding, insulin secreting and antihyperglycaemic actions of palmitate-derivatised native and Ala8-substituted GLP-1 analogues.

    PubMed

    Green, Brian D; Gault, Victor A; Mooney, Mark H; Irwin, Nigel; Harriott, Patrick; Greer, Brett; Bailey, Cliff J; O'Harte, Finbarr P M; Flatt, Peter R

    2004-02-01

    The hormone glucagon-like peptide-1(7-36)amide (GLP-1) is released in response to ingested nutrients and acts to promote glucose-dependent insulin secretion ensuring efficient postprandial glucose homeostasis. Unfortunately, the beneficial actions of GLP-1 which give this hormone many of the desirable properties of an antidiabetic drug are short lived due to degradation by dipeptidyl-peptidase IV (DPP IV) and rapid clearance by renal filtration. In this study we have attempted to extend GLP-1 action through the attachment of palmitoyl moieties to the epsilon-amino group in the side chain of the Lys26 residue and to combine this modification with substitutions of the Ala8 residue, namely Val or amino-butyric acid (Abu). In contrast to native GLP-1, which was rapidly degraded, [Lys(pal)26]GLP-1, [Abu8, Lys(pal)26]GLP-1 and [Val8 Lys(pal)26]GLP-1 all exhibited profound stability during 12 h incubations with DPP IV and human plasma. Receptor binding affinity and the ability to increase cyclic AMP in the clonal beta-cell line BRIN-BD11 were decreased by 86- to 167-fold and 15- to 62-fold, respectively compared with native GLP-1. However, insulin secretory potency tested using BRIN-BD11 cells was similar, or in the case of [Val8,Lys(pal)26]GLP-1 enhanced. Furthermore, when administered in vivo together with glucose to diabetic (ob/ob) mice, [Lys(pal)26]GLP-1, [Abu8,Lys(pal)26]GLP-1 and [Val8,Lys(pal)26]GLP-1 did not demonstrate acute glucose-lowering or insulinotropic activity as observed with native GLP-1. These studies support the potential usefulness of fatty acid linked analogues of GLP-1 but indicate the importance of chain length for peptide kinetics and bioavailability. PMID:15101559

  14. Selective Cu4Pd alloy nanoparticles anchoring on amine functionalized graphite nanosheets and their use as reusable catalysts for a C-C coupling reaction with the sacrificial role of Cu for Pd-regeneration.

    PubMed

    Chakravarty, Amrita; De, Goutam

    2016-08-01

    A facile method for the synthesis of phase selective alloy nanoparticles (NPs), Cu4Pd and their in situ anchoring on the surface of amine functionalized graphite nanosheets (AFGNS) by solvothermal process has been demonstrated. It has been seen that upon adding CuCl2·H2O and PdCl2 into the reaction medium containing AFGNS, the -NH2 group initially helps to immobilize Cu(2+) ions from CuCl2·H2O. During the solvothermal reaction in presence of N,N-dimethylformamide (DMF; solvent cum reducing agent) Pd(2+) gets reduced first due to its higher reduction potential. These Pd NPs in turn help in the reduction of Cu(2+) to Cu in an epitaxial manner. Finally at high temperature and long reaction time Cu and Pd combine to form the Cu4Pd alloy NPs along with a small fraction of Cu NPs. The conditions to obtain Cu4Pd NPs have been optimized through controlled reactions. The as prepared Cu4Pd@AFGNS composite has been successfully used for Suzuki-Miyuara C-C coupling reaction with sufficiently high yield and reusability of up to five cycles. The progress of the reaction was monitored using a fluorimeter. Interestingly, it has been observed that the small fraction of the Cu NPs present in the system played a sacrificial role in regenerating metallic Pd NPs in the first and second reaction cycles, followed by Cu from the Cu4Pd alloy itself from the third cycle onwards which played the sacrificial role to regenerate Pd(0). A probable reaction mechanism of the catalytic reaction with Cu4Pd@AFGNS has been suggested. PMID:27435633

  15. Layer-by-layer self-assembly of micro-capsules for the magnetic activation of semi-permeable nano-shells

    NASA Astrophysics Data System (ADS)

    Prouty, Malcolm D.

    2007-12-01

    Layer-by-layer (LbL) self-assembly has demonstrated broad perspectives for encapsulating, and the controllable delivery, of drugs. The nano-scale polymer layers have the capability of material protection. Magnetic nanoparticles have great potential to be applied with LbL technology to achieve both "focusing" of the encapsulated drugs to a specific location followed by "switching" them on to release the encapsulated drugs. In this work, Phor21-betaCG(ala), dextran, and dexamethasone were used as model drugs. Encapsulation of these drugs with layer-by-layer self-assembly formed biolnano robotic capsules for controlled delivery and drug release. Silica nanoparticles coated with polyelectrolyte layers of sodium carboxymethyl cellulose (CMC) or gelatin B, along with an oppositely charged peptide drug (Phor2l-betaCG(ala)), were prepared using LbL self-assembly and confirmed using QCM and zeta potential measurements. The peptide drug was assembled as a component of the multilayer walls. The release kinetics of the embedded peptide were determined. Up to 18% of the embedded Phor21-betaCG(ala) was released from the CMC multilayers over a period of 28 hours. The release was based on physiological conditions, and an external control mechanism using magnetic nanoparticles needed to be developed. Magnetic permeability control experiments were setup by applying LbL self-assembly on MnCO3 micro-cores to fabricate polyelectrolyte microcapsules embedded with superparamagnetic gold coated cobalt (Co Au) nanoparticles. An alternating magnetic field was applied to the microcapsules to check for changes in permeability. Permeability experiments were achieved by adding fluorescein isothiocyanate (FITC) labeled dextran to the microcapsule solution. Before an alternating magnetic field was applied, the capsules remained impermeable to the FITC-dextran; however, after an alternating magnetic field was applied for 30 minutes, approximately 99% of the capsules were filled with FITC

  16. Layer-by-Layer Assembly of Multifunctional Flame Retardant Based on Brucite, 3-Aminopropyltriethoxysilane, and Alginate and Its Applications in Ethylene-Vinyl Acetate Resin.

    PubMed

    Wang, Yiliang; Yang, Xiaomei; Peng, Hui; Wang, Fang; Liu, Xiu; Yang, Yunguo; Hao, Jianwei

    2016-04-20

    An efficient and multifunctional brucite/3-aminopropyltriethoxysilane (APTES)/nickel alginate/APTES (B/A/Nia/A) hybrid flame retardant was fabricated via the layer-by-layer assembly technique with brucite, silane coupling agents, nickel chloride, and sodium alginate. The morphology, chemical composition, and structure of the hybrid flame retardant were characterized. The results confirmed the multilayer structure and indicated that the assembled driving forces were electrostatic interactions, dehydration condensation, hydrogen bonds, and coordination bonds. When used in ethylene-vinyl acetate (EVA) resin, the multifunctional flame retardant had better performance than brucite in improving the flame retardancy, smoke suppression, and mechanical properties. With 130 phr loading, the multifunctional flame retardant achieved a limiting oxygen index value of 32.3% and a UL 94 V-0 rating, whereas the brucite achieved only 31.1% and a V-2 rating, respectively. The peak heat release rate and total heat released decreased by 41.5% and 8.9%, respectively. The multifunctional flame retardant had an excellent performance in reducing the smoke, CO, and CO2 production rates. These improvements could be attributed to the catalyzing carbonization of nickel compounds and the formation of more protective char layers. Moreover, the elongation at break increased by 97.5%, which benefited from the improved compatibility and the sacrificial bonds in the nickel alginate. The mechanism of flame retardant, smoke suppression, and toughening is proposed. PMID:27002922

  17. Functional studies and polymerization of recombinant hemoglobin Glu-alpha2beta26(A3) --> Val/Glu-7(A4) --> Ala.

    PubMed

    Lesecq, S; Baudin, V; Kister, J; Marden, M C; Poyart, C; Pagnier, J

    1996-07-19

    In hemoglobin (Hb) S the hydrophobic mutated residue Val-beta6(A3) (donor site) closely interacts with the hydrophobic side groups of Phe-beta85(F1) and Leu-beta88(F4) (EF pocket, acceptor site) of a neighboring tetramer, resulting in decreased solubility and polymerization of the deoxy-Hb. The beta6(A3) residue is followed by two charged residues Glu-beta7(A4) and Lys-beta8(A5). This cluster has no attraction for the hydrophobic EF pocket. We have modified the beta7(A4) residue next to the donor site Val-beta6(A3), replacing the charged Glu by a hydrophobic Ala-(rHb betaE6V/E7A). The single mutant Glu-beta7 --> Ala-(rHb betaE7A) was also engineered. Both rHbs exhibit a heat instability and an increased oxygen affinity compared to Hb A and Hb S. There was a concentration dependence of the ligand binding properties (1-300 microM in heme) indicating an increased amount of dimers relative to Hb A. The deoxy form of rHb betaE6V/E7A polymerizes in vitro, with a decreased rate of polymer formation relative to Hb S, while the single mutant betaE7A does not polymerize in the same experimental conditions. The Glu-beta7(A4) --> Ala substitution does not increase the hydrophobic interaction between donor and acceptor site. We speculate that the loss of the normal saline bridge between Glu-beta7(A4) and Lys-beta132(H10) leads to an increased flexibility of the A helix and may account for the difference of the polymerization for this Hb S mutant. PMID:8663330

  18. Combination ALA-PDT and Ablative Fractional Er:YAG Laser (2,940 nm) on the Treatment of Severe Acne

    PubMed Central

    Yin, Rui; Lin, Lin; Xiao, Yan; Hao, Fei; Hamblin, Michael R.

    2014-01-01

    Background Scarring is a very common complication of severe acne and is difficult to treat by conventional methods. 5-Aminolevulinic acid (ALA) photodynamic therapy (PDT) is a novel treatment for improving acne lesions. Fractional laser resurfacing is a promising treatment for scar treatment because of its unique ability to stimulate the wound healing response and its depth of penetration. Objective To evaluate the efficacy of combination therapies of ALA-PDT and ablative fractional Er:YAG laser (2,940 nm) for scarring lesions in severe acne patients. Methods A prospective, single-arm, pilot study. Forty subjects with severe acne were treated with 15% ALA-PDT for four times at 10-day intervals. They then received ablative fractional Er:YAG laser treatment five times at 4-week intervals. Three independent investigators evaluated subject outcomes at 1, 3, 6, and 12 months post-treatment (primary outcome); patients also provided self-assessments of improvement (secondary outcome). Results Significant reductions in acne score (P<0.01) were obtained at follow-up visits after 1, 3, 6, and 12 months. After 6 month, the lesions showed overall improvement in all of subjects (good to excellent in acne inflammatory lesions), 80% overall improvement in acne scars. After 12 months, most of subjects had improved hypertrophic/atrophic scars (good to excellent in 85%) and no one had recurrent acne inflammatory lesions. Patient self-evaluation also revealed good to excellent improvements (on average) in acne lesions and scarring, with significant improvements in self-esteem after 6 months post-treatment. Conclusions PDT can control the inflammation and improve the severity of acne lesions. Fractional resurfacing is a promising new treatment modality for scars by stimulating wound healing and remodeling. The combination therapy is a promising option for severe acne to prevent and improve car formation. PMID:24391075

  19. Site-Directed Mutations and the Polymorphic Variant Ala160Thr in the Human Thromboxane Receptor Uncover a Structural Role for Transmembrane Helix 4

    PubMed Central

    Chakraborty, Raja; Pydi, Sai Prasad; Gleim, Scott; Dakshinamurti, Shyamala; Hwa, John; Chelikani, Prashen

    2012-01-01

    The human thromboxane A2 receptor (TP), belongs to the prostanoid subfamily of Class A GPCRs and mediates vasoconstriction and promotes thrombosis on binding to thromboxane (TXA2). In Class A GPCRs, transmembrane (TM) helix 4 appears to be a hot spot for non-synonymous single nucleotide polymorphic (nsSNP) variants. Interestingly, A160T is a novel nsSNP variant with unknown structure and function. Additionally, within this helix in TP, Ala1604.53 is highly conserved as is Gly1644.57. Here we target Ala1604.53 and Gly1644.57 in the TP for detailed structure-function analysis. Amino acid replacements with smaller residues, A160S and G164A mutants, were tolerated, while bulkier beta-branched replacements, A160T and A160V showed a significant decrease in receptor expression (Bmax). The nsSNP variant A160T displayed significant agonist-independent activity (constitutive activity). Guided by molecular modeling, a series of compensatory mutations were made on TM3, in order to accommodate the bulkier replacements on TM4. The A160V/F115A double mutant showed a moderate increase in expression level compared to either A160V or F115A single mutants. Thermal activity assays showed decrease in receptor stability in the order, wild type>A160S>A160V>A160T>G164A, with G164A being the least stable. Our study reveals that Ala1604.53 and Gly1644.57 in the TP play critical structural roles in packing of TM3 and TM4 helices. Naturally occurring mutations in conjunction with site-directed replacements can serve as powerful tools in assessing the importance of regional helix-helix interactions. PMID:22272267

  20. Site-directed mutations and the polymorphic variant Ala160Thr in the human thromboxane receptor uncover a structural role for transmembrane helix 4.

    PubMed

    Chakraborty, Raja; Pydi, Sai Prasad; Gleim, Scott; Dakshinamurti, Shyamala; Hwa, John; Chelikani, Prashen

    2012-01-01

    The human thromboxane A2 receptor (TP), belongs to the prostanoid subfamily of Class A GPCRs and mediates vasoconstriction and promotes thrombosis on binding to thromboxane (TXA2). In Class A GPCRs, transmembrane (TM) helix 4 appears to be a hot spot for non-synonymous single nucleotide polymorphic (nsSNP) variants. Interestingly, A160T is a novel nsSNP variant with unknown structure and function. Additionally, within this helix in TP, Ala160(4.53) is highly conserved as is Gly164(4.57). Here we target Ala160(4.53) and Gly164(4.57) in the TP for detailed structure-function analysis. Amino acid replacements with smaller residues, A160S and G164A mutants, were tolerated, while bulkier beta-branched replacements, A160T and A160V showed a significant decrease in receptor expression (Bmax). The nsSNP variant A160T displayed significant agonist-independent activity (constitutive activity). Guided by molecular modeling, a series of compensatory mutations were made on TM3, in order to accommodate the bulkier replacements on TM4. The A160V/F115A double mutant showed a moderate increase in expression level compared to either A160V or F115A single mutants. Thermal activity assays showed decrease in receptor stability in the order, wild type>A160S>A160V>A160T>G164A, with G164A being the least stable. Our study reveals that Ala160(4.53) and Gly164(4.57) in the TP play critical structural roles in packing of TM3 and TM4 helices. Naturally occurring mutations in conjunction with site-directed replacements can serve as powerful tools in assessing the importance of regional helix-helix interactions. PMID:22272267

  1. The cisproline(i - 1)-aromatic(i) interaction: folding of the Ala-cisPro-Tyr peptide characterized by NMR and theoretical approaches.

    PubMed

    Nardi, F; Kemmink, J; Sattler, M; Wade, R C

    2000-05-01

    Cisproline(i - 1)-aromatic(i) interactions have been detected in several short peptides in aqueous solution by analysis of anomalous chemical shifts measured by 1H-NMR spectroscopy. This formation of local structure is of importance for protein folding and binding properties. To obtain an atomic-detail characterisation of the cisproline(i - 1)-aromatic(i) interaction in terms of structure, energetics and dynamics, we studied the minimal peptide unit, blocked Ala-cisPro-Tyr, using computational and experimental techniques. Structural database analyses and a systematic search revealed two groups of conformations displaying a cisproline(i - 1)-aromatic(i) interaction. These conformations were taken as seeds for molecular dynamics simulations in explicit solvent at 278 K. During a total of 33.6 ns of simulation, all the 'folded' conformations and some 'unfolded' states were sampled. 1H- and 13C-chemical shifts and 3J-coupling constants were measured for the Ala-Pro-Tyr peptide. Excellent agreement was found between all the measured and computed NMR properties, showing the good quality of the force field. We find that under the experimental and simulation conditions, the Ala-cisPro-Tyr peptide is folded 90% of the time and displays two types of folded conformation which we denote 'a' and 'b'. The type a conformations are twice as populated as the type b conformations. The former have the tyrosine ring interacting with the alanine alpha proton and are enthalpically stabilised. The latter have the aromatic ring interacting with the proline side chain and are entropically stabilised. The combined and complementary use of computational and experimental techniques permitted derivation of a detailed scenario of the 'folding' of this peptide. PMID:10909867

  2. A novel factor X gene mutation Val (GTC) 384Ala (GCC) in a Chinese family resulting in congenital factor X deficiency

    PubMed Central

    Wang, Yanming; Ma, Junjie; Liu, Xinguang; Wang, Yan; Wang, Hui; Wang, Li; Ding, Qiulan; Chu, Xiaoxia; Hou, Ming

    2015-01-01

    FX is a vitamin K-dependent coagulation protease critically essential for the coagulation cascade. FXD (congenital deficiency of factor X) is a rare coagulation disorder that inherited as an autosomal recessive trait. Here we reported a patient with bleeding diathesis from infant. The proband with pseudotumor in cerebral articular and cavity were identified as encapsulated hematocele ultimately. FX sequence analysis revealed that the patient carried a novel homozygous missense mutation that resulted in the Val384Ala substitution. Further investigation of the novel mutation would deepen our understanding of the bleeding mechanism involved in FXD. PMID:26309706

  3. Substitution of Thr for Ala-237 in TEM-17, TEM-12 and TEM-26: alterations in beta-lactam resistance conferred on Escherichia coli.

    PubMed

    Giakkoupi, P; Hujer, A M; Miriagou, V; Tzelepi, E; Bonomo, R A; Tzouvelekis, L S

    2001-07-10

    Non-naturally occurring mutants of TEM-17 (E104K), TEM-12 (R164S) and TEM-26 (E104K:R164S) extended-spectrum (ES) beta-lactamases bearing threonine at position 237 were constructed by site-specific mutagenesis and expressed under isogenic conditions in Escherichia coli. Quantification of beta-lactamase activities and immunoblotting indicated that Ala-237-->Thr did not significantly affect expression levels of these ES enzymes. Minimum inhibitory concentrations of beta-lactam antibiotics showed that the presence of threonine at position 237 exerted a dominant effect increasing the enzymes' preference for various early generation cephalosporins over penicillins. Activity against broad-spectrum oxyimino-beta-lactams was also changed. The effect of Ala-237-->Thr on the activity against ceftazidime, aztreonam, cefepime and cefpirome of all three ES TEM enzymes was detrimental. Introduction of Thr-237 improved activity against cefotaxime and ceftriaxone in TEM-12 and TEM-26, but not in TEM-17. PMID:11445164

  4. Research of ALA combined with HpD-PDT which induced s180 ascitic tumor cells, death or apoptosis on cytology

    NASA Astrophysics Data System (ADS)

    Zhu, Jing; Yan, Min; Zhang, Hui-Guo; Li, Enling; Luo, Hongyu

    2005-07-01

    To ascertain the adequate dosage of ALA combined with HpD-PDT which induced tumor cell death or apoptosis on cytology. And to study the different effect of ALA-PDT and HPD-PDT used only. Rat ascitic tumor cells(S180) were randomly divided into several groups and incubated with ALA(20μg/ml 、40μg/ml、80μg/ml 、160μg/ml)、HPD(2.5μg/ml、5μg/ml、10μg/ml)and their combination dosages. 630nm light (total output 2W) was delivered to tumor cells at a constant fluence rate: 200mw/cm2 and a constant irradiated time period: 20 minutes. We set 3 groups (no photosensitizers or no irradiation or neither) to be the control groups. We used inversion microscopy to observe the morphological change of tumor cells and flow cytometry technology to detect the death or apoptosis of tumor cells during the experiment. ..

  5. Interspecific adaptation by binary choice at de novo polyomavirus T antigen site through accelerated codon-constrained Val-Ala toggling within an intrinsically disordered region

    PubMed Central

    Lauber, Chris; Kazem, Siamaque; Kravchenko, Alexander A.; Feltkamp, Mariet C.W.; Gorbalenya, Alexander E.

    2015-01-01

    It is common knowledge that conserved residues evolve slowly. We challenge generality of this central tenet of molecular biology by describing the fast evolution of a conserved nucleotide position that is located in the overlap of two open reading frames (ORFs) of polyomaviruses. The de novo ORF is expressed through either the ALTO protein or the Middle T antigen (MT/ALTO), while the ancestral ORF encodes the N-terminal domain of helicase-containing Large T (LT) antigen. In the latter domain the conserved Cys codon of the LXCXE pRB-binding motif constrains codon evolution in the overlapping MT/ALTO ORF to a binary choice between Val and Ala codons, termed here as codon-constrained Val-Ala (COCO-VA) toggling. We found the rate of COCO-VA toggling to approach the speciation rate and to be significantly accelerated compared to the baseline rate of chance substitution in a large monophyletic lineage including all viruses encoding MT/ALTO and three others. Importantly, the COCO-VA site is located in a short linear motif (SLiM) of an intrinsically disordered region, a typical characteristic of adaptive responders. These findings provide evidence that the COCO-VA toggling is under positive selection in many polyomaviruses, implying its critical role in interspecific adaptation, which is unprecedented for conserved residues. PMID:25904630

  6. Abnormal Paraplegin Expression in Swollen Neurites, τ- and α-Synuclein Pathology in a Case of Hereditary Spastic Paraplegia SPG7 with an Ala510Val Mutation.

    PubMed

    Thal, Dietmar R; Züchner, Stephan; Gierer, Stephan; Schulte, Claudia; Schöls, Ludger; Schüle, Rebecca; Synofzik, Matthis

    2015-01-01

    Mutations in the SPG7 gene are the most frequent cause of autosomal recessive hereditary spastic paraplegias and spastic ataxias. Ala510Val is the most common SPG7 mutation, with a frequency of up to 1% in the general population. Here we report the clinical, genetic, and neuropathological findings in a homozygous Ala510Val SPG7 case with spastic ataxia. Neuron loss with associated gliosis was found in the inferior olivary nucleus, the dentate nucleus of the cerebellum, the substantia nigra and the basal nucleus of Meynert. Neurofilament and/or paraplegin accumulation was observed in swollen neurites in the cerebellar and cerebral cortex. This case also showed subcortical τ-pathology in an unique distribution pattern largely restricted to the brainstem. α-synuclein containing Lewy bodies (LBs) were observed in the brainstem and the cortex, compatible with a limbic pattern of Braak LB-Disease stage 4. Taken together, this case shows that the spectrum of pathologies in SPG7 can include neuron loss of the dentate nucleus and the inferior olivary nucleus as well as neuritic pathology. The progressive supranuclear palsy-like brainstem predominant pattern of τ pathology and α-synuclein containing Lewy bodies in our SPG7 cases may be either coincidental or related to SPG7 in addition to neuron loss and neuritic pathology. PMID:26506339

  7. Use of micro samples of finger prick blood dried on filter paper for a quick and simple dipstick dot-EIA for diagnosis of amebic liver abscess (ALA).

    PubMed

    Sharma, M; Ghosh, S; Singal, A K; Anand, B S; Talwar, G P

    1994-01-01

    Filter paper was used as a support to absorb micro samples of finger prick blood for detection of antibodies to Entamoeba histolytica (causative organism of amebiasis) by a rapid dipstick dot-EIA technique; 8 microliters of blood was sufficient to saturate discs (diameter 6 mm) of Whatman paper No. 3. Conditions of elution of blood from the discs were optimized and the best results were obtained when 0.4 ml of buffer was used for elution for 30 minutes at room temperature. The filter paper technique is extremely useful for field use and for diagnosis of amebic liver abscess on a large scale since it does not involve centrifugation of blood and use of sterile vials because blood dried on paper can be stored in polythene bags at room temperature for up to 3 months and for a week at 42 degrees C without significant loss of antibody activity, thereby eliminating the need of refrigeration of samples for storage or transportation to a reference laboratory. Elution of blood from different discs of the same patient was found to be highly reproducible without appreciable loss of sensitivity or specificity. Twenty-four confirmed ALA, 29 non-ALA, and 25 apparently normal healthy controls, with no previous history of amebiasis, were tested. Sensitivity and specificity of the test was found to be 96% and 92%, respectively. PMID:8189328

  8. An insulin receptor mutant (Asp707 --> Ala), involved in leprechaunism, is processed and transported to the cell surface but unable to bind insulin.

    PubMed

    Hart, L M; Lindhout, D; Van der Zon, G C; Kayserilli, H; Apak, M Y; Kleijer, W J; Van der Vorm, E R; Maassen, J A

    1996-08-01

    We have identified a homozygous mutation near the carboxyl terminus of the insulin receptor (IR) alpha subunit from a leprechaun patient, changing Asp707 into Ala. Fibroblasts from this patient had no high affinity insulin binding sites. To examine the effect of the mutation on IR properties, the mutant IR was stably expressed in Chinese hamster ovary cells. Western blot analysis and metabolic labeling showed a normal processing of the mutant receptor to alpha and beta subunits. No increase in high affinity insulin binding sites was observed on Chinese hamster ovary cells expressing the mutant receptor, and also, affinity cross-linking of 125I-labeled insulin by disuccinimidyl suberate to these cells failed to label the mutant alpha subunit. Biotinylation of cell surface proteins by biotin succinimidyl ester resulted in efficient biotinylation of the mutant IR alpha and beta subunits, showing its presence on the cell surface. On solubilization of the mutant insulin receptor in Triton X-100-containing buffers, 125I-insulin was efficiently cross-linked to the receptor alpha subunit by disuccinimidyl suberate. These studies demonstrate that Ala707 IR is normally processed and transported to the cell surface and that the mutation distorts the insulin binding site. Detergent restores this site. This is an example of a naturally occurring mutation in the insulin receptor that affects insulin binding without affecting receptor transport and processing. This mutation points to a major contribution of the alpha subunit carboxyl terminus to insulin binding. PMID:8702527

  9. Process and performance of hot dip zinc coatings containing ZnO and Ni-P under layers as barrier protection

    NASA Astrophysics Data System (ADS)

    Hamid, Z. Abdel; Aal, A. Abdel; Hassan, H. B.; Shaaban, A.

    2010-04-01

    A new coating system of under layer for hot dip zinc coating was explored as an effective coating for steel especially for application in relatively high aggressive environments. The influence of different barrier layers formed prior to hot dip galvanization was investigated to optimize high performance protective galvanic coatings. The deposition of ZnO and Ni-P inner layers and characteristics of hotdip zinc coatings were explored in this study. The coating morphology was characterized by scanning electron microscope (SEM) analysis. The hot dip zinc coatings containing under layer showed substantial improvement in their properties such as good adhesion, and high hardness. In addition, a decrease in the thickness of the coating layer and an enhancement of the corrosion resistance were found. Open circuit potential (OCP) of different galvanized layers in different corrosive media viz. 5% NaCl and 0.5 M H 2SO 4 solutions at 25 ± 1 °C was measured as a function of time. A nobler OCP was exhibited for samples treated with ZnO and Ni than sample of pure Zn; this indicates a dissolution process followed by passivation due to the surface oxide formation. The high negative OCP can be attributed to the better alloying reaction between Zn and Fe and to the sacrificial nature of the top pure zinc layer.

  10. Burning Graphene Layer-by-Layer

    PubMed Central

    Ermakov, Victor A.; Alaferdov, Andrei V.; Vaz, Alfredo R.; Perim, Eric; Autreto, Pedro A. S.; Paupitz, Ricardo; Galvao, Douglas S.; Moshkalev, Stanislav A.

    2015-01-01

    Graphene, in single layer or multi-layer forms, holds great promise for future electronics and high-temperature applications. Resistance to oxidation, an important property for high-temperature applications, has not yet been extensively investigated. Controlled thinning of multi-layer graphene (MLG), e.g., by plasma or laser processing is another challenge, since the existing methods produce non-uniform thinning or introduce undesirable defects in the basal plane. We report here that heating to extremely high temperatures (exceeding 2000 K) and controllable layer-by-layer burning (thinning) can be achieved by low-power laser processing of suspended high-quality MLG in air in “cold-wall” reactor configuration. In contrast, localized laser heating of supported samples results in non-uniform graphene burning at much higher rates. Fully atomistic molecular dynamics simulations were also performed to reveal details of oxidation mechanisms leading to uniform layer-by-layer graphene gasification. The extraordinary resistance of MLG to oxidation paves the way to novel high-temperature applications as continuum light source or scaffolding material. PMID:26100466

  11. Burning Graphene Layer-by-Layer.

    PubMed

    Ermakov, Victor A; Alaferdov, Andrei V; Vaz, Alfredo R; Perim, Eric; Autreto, Pedro A S; Paupitz, Ricardo; Galvao, Douglas S; Moshkalev, Stanislav A

    2015-01-01

    Graphene, in single layer or multi-layer forms, holds great promise for future electronics and high-temperature applications. Resistance to oxidation, an important property for high-temperature applications, has not yet been extensively investigated. Controlled thinning of multi-layer graphene (MLG), e.g., by plasma or laser processing is another challenge, since the existing methods produce non-uniform thinning or introduce undesirable defects in the basal plane. We report here that heating to extremely high temperatures (exceeding 2000 K) and controllable layer-by-layer burning (thinning) can be achieved by low-power laser processing of suspended high-quality MLG in air in "cold-wall" reactor configuration. In contrast, localized laser heating of supported samples results in non-uniform graphene burning at much higher rates. Fully atomistic molecular dynamics simulations were also performed to reveal details of oxidation mechanisms leading to uniform layer-by-layer graphene gasification. The extraordinary resistance of MLG to oxidation paves the way to novel high-temperature applications as continuum light source or scaffolding material. PMID:26100466

  12. Late Miocene termination of tectonic activity on the detachment in the Alaşehir Rift, Western Anatolia: Depositional records of the Göbekli Formation and high-angle cross-cutting faults

    NASA Astrophysics Data System (ADS)

    Sen, Fatih

    2016-04-01

    Western Anatolia is a well-known province of continental extension in the world. Most distinctive structural elements of the region are E-W trending grabens. The Alaşehir Rift/Graben is an asymmetric rift/graben trending E-W between Ahmetli and Turgutlu in its western part and continues eastwardly in a NW-SE direction to Alaşehir (Philadelphia in ancient Greek). The stratigraphy of the region consists of metamorphic rocks of the Menderes Massif (Paleozoic-lower Cenozoic) and the syn-extensional Salihli granitoid (middle Miocene) forming the basement unit and overlying sedimentary cover rocks of Neogene-Quaternary. These rocks are cut and deformed by the Karadut detachment fault and various low-angle normal faults (antithetic and synthetic faults of the Karadut detachment fault), which are also cut by various younger high-angle normal faults. It is possible to observe two continuous sequences of different time intervals in that Miocene deposits of the first rifting phase are covered by Plio-Quaternary sediments of second rifting phase with a "break-up" unconformity. In lower levels of a measured stratigraphic section (583 m) of the Göbekli formation which has lower age of late Miocene and upper age of early Pliocene, the presence of angular to sub-angular clasts of the blocks and conglomerates suggests alluvial-fun origin during an initial stage of deposition. Existence of normal-reverse graded, cross-bedding, pebble imbrications in layers of the pebbly sandstone demonstrates fluvial environment in following levels of the sequence. Existence of lenses and normal graded conglomerates in pebbly sandstones and fine grained sandstones strata evidences a low energy environment. Observed siltstone-claystone intercalations on the middle levels of the sequence indicate an environment with low dipping morphology to be formed as flat plains during this period. In the uppermost levels of the sequence, existence of the pebble imbrications inside pebbly sandstones overlying

  13. Modelling Layer parallel stylolites

    NASA Astrophysics Data System (ADS)

    Koehn, Daniel; Pataki Rood, Daisy; Beaudoin, Nicolas

    2016-04-01

    We modeled the geometrical roughening of mainly layer-dominated stylolites in order to understand their structural evolution, to present an advanced classification of stylolite shapes and to relate this classification to chemical compaction and stylolite sealing capabilities. Our simulations show that layer-dominated stylolites can grow in three distinct stages, an initial slow nucleation, a fast layer-pinning phase and a final freezing stage if the layer dissolves completely during growth. Dissolution of the pinning layer and thus destruction of the compaction tracking capabilities is a function of the background noise in the rock and the dissolution rate of the layer itself. Low background noise needs a slower dissolving layer for pinning to be successful but produces flatter teeth than higher background noise. We present an advanced classification based on our simulations and separate stylolites into four classes: rectangular layer type, seismogram pinning type, suture/sharp peak type and simple wave-like type.

  14. Improvement in etching rate for epilayer lift-off with surfactant

    NASA Astrophysics Data System (ADS)

    Wu, Fan-Lei; Horng, Ray-Hua; Lu, Jian-Heng; Chen, Chun-Li; Kao, Yu-Cheng

    2013-03-01

    In this study, the GaAs epilayer is quickly separated from GaAs substrate by epitaxial lift-off (ELO) process with mixture etchant solution. The HF solution mixes with surfactant as mixture etchant solution to etch AlAs sacrificial layer for the selective wet etching of AlAs sacrificial layer. Addiction surfactants etchant significantly enhance the etching rate in the hydrofluoric acid etching solution. It is because surfactant provides hydrophilicity to change the contact angle with enhances the fluid properties of the mixture etchant between GaAs epilayer and GaAs substrate. Arsine gas was released from the etchant solution because the critical reaction product in semiconductor etching is dissolved arsine gas. Arsine gas forms a bubble, which easily displaces the etchant solution, before the AlAs layer was undercut. The results showed that acetone and hydrofluoric acid ratio of about 1:1 for the fastest etching rate of 13.2 μm / min. The etching rate increases about 4 times compared with pure hydrofluoric acid, moreover can shorten the separation time about 70% of GaAs epilayer with GaAs substrate. The results indicate that etching ratio and stability are improved by mixture etchant solution. It is not only saving the epilayer and the etching solution exposure time, but also reducing the damage to the epilayer structure.

  15. Layer-by-layer cell membrane assembly

    NASA Astrophysics Data System (ADS)

    Matosevic, Sandro; Paegel, Brian M.

    2013-11-01

    Eukaryotic subcellular membrane systems, such as the nuclear envelope or endoplasmic reticulum, present a rich array of architecturally and compositionally complex supramolecular targets that are as yet inaccessible. Here we describe layer-by-layer phospholipid membrane assembly on microfluidic droplets, a route to structures with defined compositional asymmetry and lamellarity. Starting with phospholipid-stabilized water-in-oil droplets trapped in a static droplet array, lipid monolayer deposition proceeds as oil/water-phase boundaries pass over the droplets. Unilamellar vesicles assembled layer-by-layer support functional insertion both of purified and of in situ expressed membrane proteins. Synthesis and chemical probing of asymmetric unilamellar and double-bilayer vesicles demonstrate the programmability of both membrane lamellarity and lipid-leaflet composition during assembly. The immobilized vesicle arrays are a pragmatic experimental platform for biophysical studies of membranes and their associated proteins, particularly complexes that assemble and function in multilamellar contexts in vivo.

  16. Photonic layered media

    DOEpatents

    Fleming, James G.; Lin, Shawn-Yu

    2002-01-01

    A new class of structured dielectric media which exhibit significant photonic bandstructure has been invented. The new structures, called photonic layered media, are easy to fabricate using existing layer-by-layer growth techniques, and offer the ability to significantly extend our practical ability to tailor the properties of such optical materials.

  17. Thrombomodulin Ala455Val Polymorphism and the risk of cerebral infarction in a biracial population: the Stroke Prevention in Young Women Study

    PubMed Central

    Cole, John W; Roberts, Stacy C; Gallagher, Margaret; Giles, Wayne H; Mitchell, Braxton D; Steinberg, Karen K; Wozniak, Marcella A; Macko, Richard F; Reinhart, Laurie J; Kittner, Steven J

    2004-01-01

    Background The genes encoding proteins in the thrombomodulin-protein C pathway are promising candidate genes for stroke susceptibility because of their importance in thrombosis regulation and inflammatory response. Several published studies have shown that the Ala455Val thrombomodulin polymorphism is associated with ischemic heart disease, but none has examined the association with stroke. Using data from the Stroke Prevention in Young Women Study, we sought to determine the association between the Ala455Val thrombomodulin polymorphism and the occurrence of ischemic stroke in young women. Methods All 59 hospitals in the greater Baltimore-Washington area participated in a population-based case-control study of stroke in young women. We compared 141 cases of first ischemic stroke (44% black) among women 15 to 44 years of age with 210 control subjects (35% black) who were identified by random digit dialing and frequency matched to the cases by age and geographical region of residence. Data on historical risk factors were collected by standardized interview. Genotyping of the thrombomodulin Ala455Val polymorphism was performed by pyrosequencing. Results The A allele (frequency = 0.85) was associated with stroke under the recessive model. After adjustment for age, race, cigarette smoking, hypertension, and diabetes, the AA genotype, compared with the AV and VV genotypes combined, was significantly associated with stroke (odds ratio 1.9, 95% CI 1.1–3.3). The AA genotype was more common among black than white control subjects (81% versus 68%) but there was no significant interaction between the risk genotype and race (adjusted odds ratio 2.7 for blacks and 1.6 for whites). A secondary analysis removing all probable (n = 16) and possible (n = 15) cardioembolic strokes demonstrated an increased association (odds ratio 2.2, 95% CI 1.2–4.2). Conclusions Among women aged 15 to 44 years, the AA genotype is more prevalent among blacks than whites and is associated with

  18. Scintillator reflective layer coextrusion

    SciTech Connect

    Yun, Jae-Chul; Para, Adam

    2001-01-01

    A polymeric scintillator has a reflective layer adhered to the exterior surface thereof. The reflective layer comprises a reflective pigment and an adhesive binder. The adhesive binder includes polymeric material from which the scintillator is formed. A method of forming the polymeric scintillator having a reflective layer adhered to the exterior surface thereof is also provided. The method includes the steps of (a) extruding an inner core member from a first amount of polymeric scintillator material, and (b) coextruding an outer reflective layer on the exterior surface of the inner core member. The outer reflective layer comprises a reflective pigment and a second amount of the polymeric scintillator material.

  19. Two-peaked 5-ALA-induced PpIX fluorescence emission spectrum distinguishes glioblastomas from low grade gliomas and infiltrative component of glioblastomas

    PubMed Central

    Montcel, Bruno; Mahieu-Williame, Laurent; Armoiry, Xavier; Meyronet, David; Guyotat, Jacques

    2013-01-01

    5-ALA-induced protoporphyrin IX (PpIX) fluorescence enables to guiding in intra-operative surgical glioma resection. However at present, it has yet to be shown that this method is able to identify infiltrative component of glioma. In extracted tumor tissues we measured a two-peaked emission in low grade gliomas and in the infiltrative component of glioblastomas due to multiple photochemical states of PpIX. The second emission peak appearing at 620 nm (shifted by 14 nm from the main peak at 634 nm) limits the sensibility of current methods to measured PpIX concentration. We propose new measured parameters, by taking into consideration the two-peaked emission, to overcome these limitations in sensitivity. These parameters clearly distinguish the solid component of glioblastomas from low grade gliomas and infiltrative component of glioblastomas. PMID:23577290

  20. Photodynamic Therapy (PDT) using intratumoral injection of the 5- aminolevulinic acid (5-ALA) for the treatment of eye cancer in cattle

    NASA Astrophysics Data System (ADS)

    Hage, Raduan; Mancilha, Geraldo; Zângaro, Renato A.; Munin, Egberto; Plapler, Hélio

    2007-02-01

    A six-year old Holstein cow with an eye cancer (ocular squamous cell carcinoma) involving the third eyelid and conjunctiva was submitted to photodynamic therapy using intratumoral 20% aminolevulinic acid (5-ALA - Aldrich Chemical Company, Milwaukee, USA) and a light emitting diode (LED - VET LED - MMOptics (R)) with wavelength between 600 and 700 nm, 2 cm diameter circular light beam, power of 150 mW, light dose of 50 J/cm2 as a source of irradiation. Fifteen days after the experimental procedure we observed about 50% tumor reduction and complete remission after 3 months. Relapse was not observed up to 12 months after the treatment. Although the study only includes one animal not allowing definite conclusions, it indicates that PDT represents a safe and technically feasible approach in the treatment of eye cancer in cattle.