Oral Delivery of Double-Stranded RNA in Larvae of the Yellow Fever Mosquito, Aedes aegypti: Implications for Pest Mosquito Control

PubMed Central

Singh, Aditi D.; Wong, Sylvia; Ryan, Calen P.; Whyard, Steven

2013-01-01

RNA interference has already proven itself to be a highly versatile molecular biology tool for understanding gene function in a limited number of insect species, but its widespread use in other species will be dependent on the development of easier methods of double-stranded RNA (dsRNA) delivery. This study demonstrates that RNA interference can be induced in the mosquito Aedes aegypti L. (Diptera: Culicidae) simply by soaking larvae in a solution of dsRNA for two hours. The mRNA transcripts for β-tubulin, chitin synthase-1 and -2, and heat shock protein 83 were reduced between 30 and 50% three days post-dsRNA treatment. The dsRNA was mixed with a visible dye to identify those individuals that fed on the dsRNA, and based on an absence of RNA interference in those individuals that contained no dye within their guts, the primary route of entry of dsRNA is likely through the gut epithelium. RNA interference was systemic in the insects, inducing measurable knock down of gene expression in tissues beyond the gut. Silencing of the β-tubulin and chitin synthase-1 genes resulted in reduced growth and/or mortality of the larvae, demonstrating the utility of dsRNA as a potential mosquito larvicide. Silencing of chitin synthase-2 did not induce mortality in the larvae, and silencing of heat shock protein 83 only induced mortality in the insects if they were subsequently subjected to a heat stress. Drosophila melanogaster Meigen (Diptera: Drosophilidae) larvae were also soaked in dsRNA designed to specifically target either their own β-tubulin gene, or that of A. aegypti, and significant mortality was only seen in larvae treated with dsRNA targeting their own gene, which suggests that dsRNA pesticides could be designed to be species-limited. PMID:24224468

Delivery of dsRNA through topical feeding for RNA interference in the citrus sap piercing-sucking hemipteran, Diaphorina citri.

PubMed

Killiny, Nabil; Kishk, Abdelaziz

2017-06-01

RNA interference (RNAi) is a powerful means to study functional genomics in insects. The delivery of dsRNA is a challenging step in the development of RNAi assay. Here, we describe a new delivery method to increase the effectiveness of RNAi in the Asian citrus psyllid Diaphorina citri. Bromophenol blue droplets were topically applied to fifth instar nymphs and adults on the ventral side of the thorax between the three pairs of legs. In addition to video recordings that showed sucking of the bromophenol blue by the stylets, dissected guts turned blue indicating that the uptake was through feeding. Thus, we called the method topical feeding. We targeted the abnormal wing disc gene (awd), also called nucleoside diphosphate kinase (NDPK), as a reporter gene to prove the uptake of dsRNA via this method of delivery. Our results showed that dsRNA-awd caused reduction of awd expression and nymph mortality. Survival and lifespan of adults emerged from treated nymphs and treated adults were affected. Silencing awd caused wing malformation in the adults emerged from treated nymphs. Topical feeding as a delivery of dsRNA is highly efficient for both nymphs and adults. The described method could be used to increase the efficiency of RNAi in D. citri and other sap piercing-sucking hemipterans. © 2017 Wiley Periodicals, Inc.

Highly efficient delivery of siRNA to a heart transplant model by a novel cell penetrating peptide-dsRNA binding domain.

PubMed

Li, Hua; Zheng, Xiangtao; Koren, Viktoria; Vashist, Yogesh Kumar; Tsui, Tung Yu

2014-07-20

Small interfering RNAs (siRNAs) delivery remains a bottleneck for RNA interference (RNAi) - based therapies in the clinic. In the present study, a fusion protein with two cell-penetrating peptides (CPP), Hph1-Hph1, and a double-stranded RNA binding domain (dsRBD), was constructed for the siRNA delivery: dsRBD was designed to bind siRNA, and CPP would subsequently transport the dsRBD/siRNA complex into cells. We assessed the efficiency of the fusion protein, Hph1-Hph1-dsRBD, as a siRNA carrier. Calcium-condensed effects were assessed on GAPDH and green fluorescent protein (GFP) genes by western blot, real time polymerase chain reaction (RT-PCR), and flow cytometry analysis in vitro. Evaluations were also made in an in vivo heart transplantation model. The results demonstrated that the fusion protein, Hph1-Hph1-dsRBD, is highly efficient at delivering siRNA in vitro, and exhibits efficiency on GAPDH and GFP genes similar to or greater than lipofectamine. Interestingly, the calcium-condensed effects dramatically enhanced cellular uptake of the protein-siRNA complex. In vivo, Hph1-Hph1-dsRBD transferred and distributed ^ targeted siRNA throughout the whole mouse heart graft. Together, these results indicate that Hph1-Hph1-dsRBD has potential as an siRNA carrier for applications in the clinic or in biomedical research. Copyright © 2014 Elsevier B.V. All rights reserved.

Dextran sulfate nanoparticles as a theranostic nanomedicine for rheumatoid arthritis.

PubMed

Heo, Roun; You, Dong Gil; Um, Wooram; Choi, Ki Young; Jeon, Sangmin; Park, Jong-Sung; Choi, Yuri; Kwon, Seunglee; Kim, Kwangmeyung; Kwon, Ick Chan; Jo, Dong-Gyu; Kang, Young Mo; Park, Jae Hyung

2017-07-01

With the aim of developing nanoparticles for targeted delivery of methotrexate (MTX) to inflamed joints in rheumatoid arthritis (RA), an amphiphilic polysaccharide was synthesized by conjugating 5β-cholanic acid to a dextran sulfate (DS) backbone. Due to its amphiphilic nature, the DS derivative self-assembled into spherical nanoparticles (220 nm in diameter) in aqueous conditions. The MTX was effectively loaded into the DS nanoparticles (loading efficiency: 73.0%) by a simple dialysis method. Interestingly, the DS nanoparticles were selectively taken up by activated macrophages, which are responsible for inflammation and joint destruction, via scavenger receptor class A-mediated endocytosis. When systemically administrated into mice with experimental collagen-induced arthritis (CIA), the DS nanoparticles effectively accumulated in inflamed joints (12-fold more than wild type mice (WT)), implying their high targetability to RA tissues. Moreover, the MTX-loaded DS nanoparticles exhibited significantly improved therapeutic efficacy against CIA in mice compared to free MTX alone. Overall, the data presented here indicate that DS nanoparticles are potentially useful nanomedicines for RA imaging and therapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Stability, Intracellular Delivery, and Release of siRNA from Chitosan Nanoparticles Using Different Cross-Linkers

PubMed Central

Abdul Ghafoor Raja, Maria; Katas, Haliza; Jing Wen, Thum

2015-01-01

Chitosan (CS) nanoparticles have been extensively studied for siRNA delivery; however, their stability and efficacy are highly dependent on the types of cross-linker used. To address this issue, three common cross-linkers; tripolyphosphate (TPP), dextran sulphate (DS) and poly-D-glutamic acid (PGA) were used to prepare siRNA loaded CS-TPP/DS/PGA nanoparticles by ionic gelation method. The resulting nanoparticles were compared with regard to their physicochemical properties including particle size, zeta potential, morphology, binding and encapsulation efficiencies. Among all the formulations prepared with different cross linkers, CS-TPP-siRNA had the smallest particle size (ranged from 127 ± 9.7 to 455 ± 12.9 nm) with zeta potential ranged from +25.1 ± 1.5 to +39.4 ± 0.5 mV, and high entrapment (>95%) and binding efficiencies. Similarly, CS-TPP nanoparticles showed better siRNA protection during storage at 4˚C and as determined by serum protection assay. TEM micrographs revealed the assorted morphology of CS-TPP-siRNA nanoparticles in contrast to irregular morphology displayed by CS-DS-siRNA and CS-PGA-siRNA nanoparticles. All siRNA loaded CS-TPP/DS/PGA nanoparticles showed initial burst release followed by sustained release of siRNA. Moreover, all the formulations showed low and concentration-dependent cytotoxicity with human colorectal cancer cells (DLD-1), in vitro. The cellular uptake studies with CS-TPP-siRNA nanoparticles showed successful delivery of siRNA within cytoplasm of DLD-1 cells. The results demonstrate that ionically cross-linked CS-TPP nanoparticles are biocompatible non-viral gene delivery system and generate a solid ground for further optimization studies, for example with regard to steric stabilization and targeting. PMID:26068222

Delivery of lethal dsRNAs in insect diets by branched amphiphilic peptide capsules.

PubMed

Avila, L A; Chandrasekar, R; Wilkinson, K E; Balthazor, J; Heerman, M; Bechard, J; Brown, S; Park, Y; Dhar, S; Reeck, G R; Tomich, J M

2018-03-10

Development of new and specific insect pest management methods is critical for overcoming pesticide resistance and collateral off-target killings. Gene silencing by feeding dsRNA to insects shows promise in this area. Here we described the use of a peptide nano-material, branched amphiphilic peptide capsules (BAPCs), that facilitates cellular uptake of dsRNA by insects through feeding. The insect diets included dsRNA with and without complexation with BAPCs. The selected insect species come from two different orders with different feeding mechanisms: Tribolium castaneum and Acyrthosiphon pisum. The gene transcripts tested (BiP and Armet) are part of the unfolded protein response (UPR) and suppressing their translation resulted in lethality. For Acyrthosiphon pisum, ingestion of BiP-dsRNA associated with BAPCs led to the premature death of the aphids (t 1/2 =4-5days) compared to ingestion of the same amounts of free BiP-dsRNA (t 1/2 =11-12days). Tribolium castaneum was effectively killed using a combination of BiP-dsRNA and Armet-dsRNA complexed with BAPCs; most dying as larvae or during eclosion (~75%). Feeding dsRNA alone resulted in fewer deaths (~30%). The results show that complexation of dsRNA with BAPCs enhanced the oral delivery of dsRNA over dsRNA alone. Copyright © 2018 Elsevier B.V. All rights reserved.

Induction of Both Local Immune Response in Mice and Protection in a Rabbit Model by Intranasal Immunization with Modified Vaccinia Ankara Virus Expressing a Secreted Form of Bovine Herpesvirus 1 Glycoprotein D.

PubMed

Del Medico Zajac, María Paula; Zanetti, Flavia Adriana; Esusy, María Soledad; Federico, Carlos Rodolfo; Zabal, Osvaldo; Valera, Alejandro Rafael; Calamante, Gabriela

In this study, we evaluated the immunogenicity and efficacy of mucosal delivery of a recombinant modified vaccinia Ankara virus (MVA) expressing the secreted version of bovine herpesvirus type 1 (BoHV-1) glycoprotein D (MVA-gDs) without addition of adjuvant in two animal models. First, we demonstrated the capability of MVA-gDs of inducing both local and systemic anti-gD humoral immune response after intranasal immunization of mice. Then, we confirmed that two doses of MVA-gDs administered intranasally to rabbits induced systemic anti-gD antibodies and conferred protection against BoHV-1 challenge. Our results show the potential of using MVA as a vector for the rational design of veterinary vaccines capable of inducing specific and protective immune responses both at local and systemic level.

An oral colon-targeting controlled release system based on resistant starch acetate: synthetization, characterization, and preparation of film-coating pellets.

PubMed

Pu, Huayin; Chen, Ling; Li, Xiaoxi; Xie, Fengwei; Yu, Long; Li, Lin

2011-05-25

An oral colon-targeting controlled release system based on resistant starch acetate (RSA) as a film-coating material was developed. The RSA was successfully synthesized, and its digestion resistibility could be improved by increasing the degree of substitution (DS), which was favorable for the colon-targeting purpose. As a delivery carrier material, the characteristics of RSA were investigated by polarized light microscopy, FTIR spectroscopy, and X-ray diffraction. The results revealed a decrease of the crystallinity of RSA and a change of its crystalline structure from B + V hydrid type to V type. To evaluate the colon-targeting release performance, the RSA film-coated pellets loaded with different bioactive components were prepared by extrusion-spheronization and then by fluid bed coating. The effects of the DS, plasticizer content, and coating thickness of the RSA film and those of the content and molecular weight of the loaded bioactive component on the colon-targeting release performance of the resulting delivery system were investigated. By adjusting the DS, the coating thickness, and the plasticizer content of the RSA film, either the pellets loaded with a small molecular bioactive component such as 5-aminosalicylic acid or those with a macromolecular bioactive peptide or protein such as bovine serum albumin, hepatocyte growth-promoting factor, or insulin showed a desirable colon-targeting release performance. The release percentage was less than 12% in simulated upper gastrointestinal tract and went up to 70% over a period of 40 h in simulated colonic fluid. This suggests that the delivery system based on RSA film has an excellent colon-targeting release performance and the universality for a wide range of bioactive components.

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Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-08

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Local gene silencing in plants via synthetic dsRNA and carrier peptide.

PubMed

Numata, Keiji; Ohtani, Misato; Yoshizumi, Takeshi; Demura, Taku; Kodama, Yutaka

2014-10-01

Quick and facile transient RNA interference (RNAi) is one of the most valuable plant biotechnologies for analysing plant gene functions. To establish a novel double-strand RNA (dsRNA) delivery system for plants, we developed an ionic complex of synthetic dsRNA with a carrier peptide in which a cell-penetrating peptide is fused with a polycation sequence as a gene carrier. The dsRNA-peptide complex is 100-300 nm in diameter and positively charged. Infiltration of the complex into intact leaf cells of Arabidopsis thaliana successfully induced rapid and efficient down-regulation of exogenous and endogenous genes such as yellow fluorescent protein and chalcone synthase. The present method realizes quick and local gene silencing in specific tissues and/or organs in plants. © 2014 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

Reach Out and Touch Someone: West Alabama Designs a New Emergency Link.

ERIC Educational Resources Information Center

Coogan, Mercy Hardie

1980-01-01

Quality on-the-scene emergency care for a rural area is provided by West Alabama's Emergency Medical Services. The success of this delivery system is attributed to a radio/telephone communications system that provides quick, direct contact between paramedics at the scene and medical doctors miles away. (DS)

Development of RNAi method for screening candidate genes to control emerald ash borer, Agrilus planipennis.

PubMed

Rodrigues, Thais B; Rieske, Lynne K; J Duan, Jian; Mogilicherla, Kanakachari; Palli, Subba R

2017-08-07

The ingestion of double-strand RNAs (dsRNA) targeting essential genes in an insect could cause mortality. Based on this principle, a new generation of insect control methods using RNA interference (RNAi) are being developed. In this work, we developed a bioassay for oral delivery of dsRNA to an invasive forest and urban tree pest, the emerald ash borer (EAB, Agrilus planipennis). EAB feeds and develops beneath the bark, killing trees rapidly. This behavior, coupled with the lack of a reliable artificial diet for rearing larvae and adults, make them difficult to study. We found that dsRNA is transported and processed to siRNAs by EAB larvae within 72 h after ingestion. Also, feeding neonate larvae with IAP (inhibitor of apoptosis) or COP (COPI coatomer, β subunit) dsRNA silenced their target genes and caused mortality. Both an increase in the concentration of dsRNA fed and sequential feeding of two different dsRNAs increased mortality. Here we provide evidence for successful RNAi in EAB, and demonstrate the development of a rapid and effective bioassay for oral delivery of dsRNA to screen additional genes.

Investigating Engineered Ribonucleoprotein Particles to Improve Oral RNAi Delivery in Crop Insect Pests

PubMed Central

Gillet, François-Xavier; Garcia, Rayssa A.; Macedo, Leonardo L. P.; Albuquerque, Erika V. S.; Silva, Maria C. M.; Grossi-de-Sa, Maria F.

2017-01-01

Genetically modified (GM) crops producing double-stranded RNAs (dsRNAs) are being investigated largely as an RNA interference (RNAi)-based resistance strategy against crop insect pests. However, limitations of this strategy include the sensitivity of dsRNA to insect gut nucleases and its poor insect cell membrane penetration. Working with the insect pest cotton boll weevil (Anthonomus grandis), we showed that the chimeric protein PTD-DRBD (peptide transduction domain—dsRNA binding domain) combined with dsRNA forms a ribonucleoprotein particle (RNP) that improves the effectiveness of the RNAi mechanism in the insect. The RNP slows down nuclease activity, probably by masking the dsRNA. Furthermore, PTD-mediated internalization in insect gut cells is achieved within minutes after plasma membrane contact, limiting the exposure time of the RNPs to gut nucleases. Therefore, the RNP provides an approximately 2-fold increase in the efficiency of insect gene silencing upon oral delivery when compared to naked dsRNA. Taken together, these data demonstrate the role of engineered RNPs in improving dsRNA stability and cellular entry, representing a path toward the design of enhanced RNAi strategies in GM plants against crop insect pests. PMID:28503153

Investigating Engineered Ribonucleoprotein Particles to Improve Oral RNAi Delivery in Crop Insect Pests.

PubMed

Gillet, François-Xavier; Garcia, Rayssa A; Macedo, Leonardo L P; Albuquerque, Erika V S; Silva, Maria C M; Grossi-de-Sa, Maria F

2017-01-01

Genetically modified (GM) crops producing double-stranded RNAs (dsRNAs) are being investigated largely as an RNA interference (RNAi)-based resistance strategy against crop insect pests. However, limitations of this strategy include the sensitivity of dsRNA to insect gut nucleases and its poor insect cell membrane penetration. Working with the insect pest cotton boll weevil ( Anthonomus grandis ), we showed that the chimeric protein PTD-DRBD (peptide transduction domain-dsRNA binding domain) combined with dsRNA forms a ribonucleoprotein particle (RNP) that improves the effectiveness of the RNAi mechanism in the insect. The RNP slows down nuclease activity, probably by masking the dsRNA. Furthermore, PTD-mediated internalization in insect gut cells is achieved within minutes after plasma membrane contact, limiting the exposure time of the RNPs to gut nucleases. Therefore, the RNP provides an approximately 2-fold increase in the efficiency of insect gene silencing upon oral delivery when compared to naked dsRNA. Taken together, these data demonstrate the role of engineered RNPs in improving dsRNA stability and cellular entry, representing a path toward the design of enhanced RNAi strategies in GM plants against crop insect pests.

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

Yan, Chen; Jie, Leng; Yongqi, Wang

Nanoparticles are becoming promising carriers for gene delivery because of their high capacity in gene loading and low cell cytotoxicity. In this study, a chitosan-based nanoparticle encapsulated within a recombinant pcDNA3.1-dsNKG2D-IL-15 plasmid was generated. The fused dsNKG2D-IL-15 gene fragment consisted of double extracellular domains of NKG2D with IL-15 gene at downstream. The average diameter of the gene nanoparticles ranged from 200 nm to 400 nm, with mean zeta potential value of 53.8 ± 6.56 mV. The nanoparticles which were loaded with the dsNKG2D-IL-15 gene were uptaken by tumor cells with low cytotoxicity. Tumor cells pre-transfected by gene nanopartilces stimulated NK and T cells in vitro. Intramuscularmore » injection of gene nanoparticles suppressed tumor growth and prolonged survival of tumor-bearing mice through activation of NK and CD8{sup +} T cells. Thus, chitosan-based nanoparticle delivery of dsNKG2D-IL-15 gene vaccine can be potentially used for tumor therapy. - Highlights: • Generation of a nanoparticle for delivery of dsNKG2D-IL-15 gene. • Characterization of the gene nanoparticle. • Antitumor activity mediated by the gene nanoparticle.« less

Reduction in the size of layered double hydroxide nanoparticles enhances the efficiency of siRNA delivery.

PubMed

Chen, Min; Cooper, Helen M; Zhou, Ji Zhi; Bartlett, Perry F; Xu, Zhi Ping

2013-01-15

Small interfering RNAs (siRNAs) are a potentially powerful new class of pharmaceutical drugs for many disease. However, the delivery of unprotected siRNAs is ineffective due to their susceptibility to degradation by ubiquitous nucleases under physiological conditions. Layered double hydroxide nanoparticles (LDHs) have been found to be efficient carriers of anionic drugs and nucleic acids. Our previous research has shown that LDHs (with the Z-average particle size of approximately 110 nm) can mediate siRNA delivery in mammalian cells, resulting in gene silencing. However, short double-stranded nucleic acids are mostly adsorbed onto the external surface and not well protected by LDHs. In order to enhance the intercalation of siRNA into the LDH interlayer and the efficiency of subsequent siRNA delivery, we prepared smaller LDHs (with the Z-average particle size of approximately 45 nm) with an engineered non-aqueous method. We demonstrate here that dsDNA/siRNA is more effectively intercalated into these small LDH nanoparticles, more dsDNA/siRNA is transfected into HEK 293T cells, and more efficient silencing of the target gene is achieved using smaller LDHs. Thus, smaller LDH particles have greater potential as a delivery system for the application of RNA interference. Copyright © 2012 Elsevier Inc. All rights reserved.

Ultradeformable Archaeosomes for Needle Free Nanovaccination with Leishmania braziliensis Antigens.

PubMed

Higa, Leticia H; Arnal, Laura; Vermeulen, Mónica; Perez, Ana Paula; Schilrreff, Priscila; Mundiña-Weilenmann, Cecilia; Yantorno, Osvaldo; Vela, María Elena; Morilla, María José; Romero, Eder Lilia

2016-01-01

Total antigens from Leishmania braziliensis promastigotes, solubilized with sodium cholate (dsLp), were formulated within ultradeformable nanovesicles (dsLp-ultradeformable archaeosomes, (dsLp-UDA), and dsLp-ultradeformable liposomes (dsLp-UDL)) and topically administered to Balb/c mice. Ultradeformable nanovesicles can penetrate the intact stratum corneum up to the viable epidermis, with no aid of classical permeation enhancers that can damage the barrier function of the skin. Briefly, 100 nm unilamellar dsLp-UDA (soybean phosphatidylcholine: Halorubrum tebenquichense total polar lipids (TPL): sodium cholate, 3:3:1 w:w) of -31.45 mV Z potential, containing 4.84 ± 0.53% w/w protein/lipid dsLp, 235 KPa Young modulus were prepared. In vitro, dsLp-UDA was extensively taken up by J774A1 and bone marrow derive cells, and the only that induced an immediate secretion of IL-6, IL-12p40 and TNF-α, followed by IL-1β, by J774A1 cells. Such extensive uptake is a key feature of UDA ascribed to the highly negatively charged archaeolipids of the TPL, which are recognized by a receptor specialized in uptake and not involved in downstream signaling. Despite dsLp alone was also immunostimulatory on J774A1 cells, applied twice a week on consecutive days along 7 weeks on Balb/c mice, it raised no measurable response unless associated to UDL or UDA. The highest systemic response, IgGa2 mediated, 1 log lower than im dsLp Al2O3, was elicited by dsLp-UDA. Such findings suggest that in vivo, UDL and UDA acted as penetration enhancers for dsLp, but only dsLp-UDA, owed to its pronounced uptake by APC, succeeded as topical adjuvants. The actual TPL composition, fully made of sn2,3 ether linked saturated archaeolipids, gives the UDA bilayer resistance against chemical, physical and enzymatic attacks that destroy ordinary phospholipids bilayers. Together, these properties make UDA a promising platform for topical drug targeted delivery and vaccination, that may be of help for countries with a deficient healthcare system.

RNAi-mediated knockdown of the voltage gated sodium ion channel TcNav causes mortality in Tribolium castaneum.

PubMed

Abd El Halim, Hesham M; Alshukri, Baida M H; Ahmad, Munawar S; Nakasu, Erich Y T; Awwad, Mohammed H; Salama, Elham M; Gatehouse, Angharad M R; Edwards, Martin G

2016-07-14

The voltage-gated sodium ion channel (VGSC) belongs to the largest superfamily of ion channels. Since VGSCs play key roles in physiological processes they are major targets for effective insecticides. RNA interference (RNAi) is widely used to analyse gene function, but recently, it has shown potential to contribute to novel strategies for selectively controlling agricultural insect pests. The current study evaluates the delivery of dsRNA targeted to the sodium ion channel paralytic A (TcNav) gene in Tribolium castaneum as a viable means of controlling this insect pest. Delivery of TcNav dsRNA caused severe developmental arrest with larval mortalities up to 73% post injection of dsRNA. Injected larvae showed significant (p < 0.05) knockdown in gene expression between 30-60%. Expression was also significantly (p < 0.05) reduced in pupae following injection causing 30% and 42% knockdown for early and late pupal stages, respectively. Oral delivery of dsRNA caused dose-dependant mortalities of between 19 and 51.34%; this was accompanied by significant (p < 0.05) knockdown in gene expression following 3 days of continuous feeding. The majority of larvae injected with, or fed, dsRNA died during the final larval stage prior to pupation. This work provides evidence of a viable RNAi-based strategy for insect control.

Delivery of human NKG2D-IL-15 fusion gene by chitosan nanoparticles to enhance antitumor immunity.

PubMed

Yan, Chen; Jie, Leng; Yongqi, Wang; Weiming, Xiao; Juqun, Xi; Yanbing, Ding; Li, Qian; Xingyuan, Pan; Mingchun, Ji; Weijuan, Gong

2015-07-31

Nanoparticles are becoming promising carriers for gene delivery because of their high capacity in gene loading and low cell cytotoxicity. In this study, a chitosan-based nanoparticle encapsulated within a recombinant pcDNA3.1-dsNKG2D-IL-15 plasmid was generated. The fused dsNKG2D-IL-15 gene fragment consisted of double extracellular domains of NKG2D with IL-15 gene at downstream. The average diameter of the gene nanoparticles ranged from 200 nm to 400 nm, with mean zeta potential value of 53.8 ± 6.56 mV. The nanoparticles which were loaded with the dsNKG2D-IL-15 gene were uptaken by tumor cells with low cytotoxicity. Tumor cells pre-transfected by gene nanopartilces stimulated NK and T cells in vitro. Intramuscular injection of gene nanoparticles suppressed tumor growth and prolonged survival of tumor-bearing mice through activation of NK and CD8(+) T cells. Thus, chitosan-based nanoparticle delivery of dsNKG2D-IL-15 gene vaccine can be potentially used for tumor therapy. Copyright © 2015 Elsevier Inc. All rights reserved.

Development of reconstitutable suspensions containing diclofenac sodium-loaded microspheres for pediatric delivery.

PubMed

Oz, Umut Can; Devrim, Burcu; Bozkır, Asuman; Canefe, Kandemir

2015-01-01

Effective clinical utilisation of non-steroidal anti-inflammatory drugs, such as diclofenac sodium (DS) is significantly limited by their ulcerogenic potential and poor bioavailability after oral administration. The objective of this work was to develop reconstitutable pediatric suspensions of DS-loaded microspheres prepared with an acrylic polymer (Eudragit RS) for improved pediatric delivery of DS. The microspheres were prepared by the water-in-oil-in-water or solid-in-oil-in-water emulsion techniques. Enviromental scanning electron microscopy observations clearly showed that microspheres have spherical shape. The drug entrapment efficiency of these microspheres was found 47.96 ± 0.79% to 88.57 ± 0.59% and their average particle sizes were 23.94-60.78 µm, which are within the desired range for the development of suspension formulation. The in vitro dissolution indicated prolonged sustained release of DS over 8 h. The results of preliminary characterisation studies of suspensions show that a liquid pharmaceutical preparation for oral administration capable of providing a sustained release of DS was successfully obtained.

Rational design on controlled release ion-exchange polymeric microspheres and polymer-lipid hybrid nanoparticles for the delivery of water-soluble drugs through a multidisciplinary approach

NASA Astrophysics Data System (ADS)

Li, Yongqiang

Sulfopropyl dextran sulfate (SP-DS) microspheres and polymer-lipid hybrid nanoparticles (PLN) for the delivery of water-soluble anticancer drugs and P-glycoprotein inhibitors were developed by our group recently and demonstrated effectiveness in local chemotherapy. To optimize the delivery performance of these particulate systems, particularly PLN, an integrated multidisciplinary approach was developed, based on an in-depth understanding of drug-excipient interactions, internal structure, drug loading and release mechanisms, and application of advanced modeling/optimization techniques. An artificial neural networks (ANN) simulator capable of formulation optimization and drug release prediction was developed. In vitro drug release kinetics of SP-DS microspheres, with various drug loading and in different release media, were predicted by ANN. The effects of independent variables on drug release were evaluated. Good modeling performance suggested that ANN is a useful tool to predict drug release from ion-exchange microspheres. To further improve the performance of PLN, drug-polymer-lipid interactions were characterized theoretically and experimentally using verapamil hydrochloride (VRP) as a model drug and dextran sulfate sodium (DS) as a counter-ion polymer. VRP-DS complexation followed a stoichiometric rule and solid-state transformation of VRP were observed. Dodecanoic acid (DA) was identified as the lead lipid carrier material. Based upon the optimized drug-polymer-lipid interactions, PLN with high drug loading capacity (36%, w/w) and sustained release without initial burst release were achieved. VRP remained amorphous and was molecularly dispersed within PLN. H-bonding contributed to the miscibility between the VRP-DS complex and DA. Drug release from PLN was mainly controlled by diffusion and ion-exchange processes. Drug loading capacity and particle size of PLN depend on the formulation factors of the weight ratio of drug to lipid and concentrations of surfactants applied. A three-factor spherical composite experimental design was used to map the cause-and-effect relationship. PLN with high drug loading efficiency (92%) and small particle size (100 nm) were predicted by ANN and confirmed by experiment. The roles of various factors on the properties of PLN were also investigated. In summary, this thesis demonstrates that an integrated multidisciplinary strategy ranging from preformulation to formulation to optimization is suitable for the rational design of SP-DS microspheres and PLN with desired properties.

Pore-Confined Carriers and Biomolecules in Mesoporous Silica for Biomimetic Separation and Targeting

NASA Astrophysics Data System (ADS)

Zhou, Shanshan

Selectively permeable biological membranes composed of lipophilic barriers inspire the design of biomimetic carrier-mediated membranes for aqueous solute separation. This work imparts selective permeability to lipid-filled pores of silica thin film composite membranes using carrier molecules that reside in the lipophilic self-assemblies. The lipids confined inside the pores of silica are proven to be a more effective barrier than bilayers formed on the porous surface through vesicle fusion, which is critical for quantifying the function of an immobilized carrier. The ability of a lipophilic carrier embedded in the lipid bilayer to reversibly bind the target solute and transport it through the membrane is demonstrated. Through the functionalization of the silica surface with enzymes, enzymatic catalysis and biomimetic separations can be combined on this nanostructured composite platform. The successful development of biomimetic nanocomposite membrane can provide for efficient dilute aqueous solute upgrading or separations using engineered carrier/catalyst/support systems. While the carrier-mediated biomimetic membranes hold great potential, fully understanding of the transport processes in composite synthetic membranes is essential for improve the membrane performance. Electrochemical impedance spectroscopy (EIS) technique is demonstrated to be a useful tool for characterizing the thin film pore accessibility. Furthermore, the effect of lipid bilayer preparation methods on the silica thin film (in the form of pore enveloping, pore filling) on ion transport is explored, as a lipid bilayer with high electrically insulation is essential for detecting activity of proteins or biomimetic carriers in the bilayer. This study provides insights for making better barriers on mesoporous support for carrier-mediated membrane separation process. Porous silica nanoparticles (pSNPs) with pore sizes appropriate for biomolecule loading are potential for encapsulating dsRNA within the pores to achieve effective delivery of dsRNA to insects for RNA interference (RNAi). The mobility of dsRNA in the nanopores of the pSNPs is expected to have a functional effect on delivery of dsRNA to insects. The importance of pores to a mobile dsRNA network is demonstrated by the lack of measurable mobility for both lengths of RNA on nonporous materials. In addition, when the dsRNA could not penetrate the pores, dsRNA mobility is also not measurable at the surface of the particle. Thus, the pores seem to serve as a "sink" in providing a mobile network of dsRNA on the surface of the particle. This work successfully demonstrates the loading of RNA on functionalized pSNPs and identified factors that affects RNA loading and releasing, which provides basis for the delivery of RNA-loaded silica particles in vivo.

Exploitation of novel gum Prunus cerasoides as mucoadhesive beads for a controlled-release drug delivery.

PubMed

Seelan, T Veenus; Kumari, Henry Linda Jeeva; Kishore, Narra; Selvamani, Palanisamy; Lalhlenmawia, H; Thanzami, K; Pachuau, Lalduhsanga; Ruckmani, Kandasamy

2016-04-01

The present study deals with the formulation of pH-sensitive mucoadhesive beads using natural gum isolated from Prunus cerasoides (PC) in combination with sodium alginate (SA) for the controlled release of diclofenac sodium (DS). PC and SA composite (PC-SA), DS loaded SA (DS-SA) and DS loaded PC-SA (DS-PC-SA) beads were prepared by ionotropic gelation method. The absence of interaction between DS and PC-SA was shown by FTIR, DSC and TGA analyses. The optimized DS-PC-SA formulation exhibited mucoadhesive property and the controlled release of DS was achieved 68% in 12h. The in vitro release kinetics follows zero order with anomalous diffusion mechanism. Therefore, the formulated mucoadhesive beads with the novel gum are preferable for the controlled release of DS by prolonging the residence time of the drug in the gastrointestinal tract, overcoming the problems associated with the immediate release dosage forms of DS. Copyright © 2016 Elsevier B.V. All rights reserved.

Synthesis and characterization of a novel cationic hydrogel base on salecan-g-PMAPTAC.

PubMed

Wei, Wei; Qi, Xiaoliang; Li, Junjian; Zhong, Yin; Zuo, Gancheng; Pan, Xihao; Su, Ting; Zhang, Jianfa; Dong, Wei

2017-08-01

Salecan is a biological macromolecular and biocompatible polysaccharide that has been investigated for recent years. Herein, we report a novel cationic hydrogel fabricated by graft-polymerizing 3-(methacryloylamino)propyl-trimethylammonium chloride (MAPTAC) onto salecan chains. The obtained hydrogels were transparent, solid-elastic, macro-porous, ion-sensitive, and non-cytotoxic. The swelling ratios increased with salecan content, while mechanical strength does the opposite. Moreover, drug delivery test was studied as a potential application. Diclofenac sodium (DS) and insulin were selected as model drugs. Interestingly, in drug loading process, DS molecules exhibited highly affinity to these cationic hydrogels. Almost all the DS molecules in loading solution were absorbed and spread into the hydrogel. For drug release profiles, insulin-loaded hydrogel showed an initial rapid release and a sustained release. As a comparison, DS-loaded hydrogel exhibited a more sustained release profile. Results suggested salecan-g-PMAPTAC hydrogel could be a good candidate for anionic drug loading and delivery. Copyright © 2017 Elsevier B.V. All rights reserved.

Dextran sulfate as a drug delivery platform for drug‐coated balloons: Preparation, characterization, in vitro drug elution, and smooth muscle cell response

PubMed Central

Lamichhane, Sujan; Anderson, Jordan; Remund, Tyler; Kelly, Patrick

2015-01-01

Abstract Drug‐coated balloons (DCBs) have now emerged as a promising approach to treat peripheral artery disease. However, a significant amount of drug from the balloon surface is lost during balloon tracking and results in delivering only a subtherapeutic dose of drug at the diseased site. Hence, in this study, the use of dextran sulfate (DS) polymer was investigated as a platform to control the drug release from balloons. An antiproliferative drug, paclitaxel (PAT), was incorporated into DS films (PAT‐DS). The characterizations using SEM, FT‐IR, and DSC showed that the films prepared were smooth and homogenous with PAT molecularly dispersed in the bulk of DS matrix in amorphous form. An investigation on the interaction of smooth muscle cells (SMCs) with control‐DS and PAT‐DS films showed that both films inhibited SMC growth, with a superior inhibitory effect observed for PAT‐DS films. PAT‐DS coatings were then produced on balloon catheters. The integrity of coatings was well‐maintained when the balloons were either deflated or inflated. In this study, up to 2.2 µg/mm2 of PAT was loaded on the balloons using the DS platform. Drug elution studies showed that only 10 to 20% of the total PAT loaded was released from the PAT‐DS coated balloons during the typical time period of balloon tracking (1 min) and then ∼80% of the total PAT loaded was released during the typical time period of balloon inflation and treatment (from 1 min to 4 min). Thus, this study demonstrated the use of DS as a platform to control drug delivery from balloons. © 2015 The Authors Journal of Biomedical Materials Research Part B: Applied Biomaterials Published by Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1416–1430, 2016. PMID:26227252

Multifunctional aptamer-based nanoparticles for targeted drug delivery to circumvent cancer resistance.

PubMed

Liu, Juan; Wei, Tuo; Zhao, Jing; Huang, Yuanyu; Deng, Hua; Kumar, Anil; Wang, Chenxuan; Liang, Zicai; Ma, Xiaowei; Liang, Xing-Jie

2016-06-01

By its unique advantages over traditional medicine, nanomedicine has offered new strategies for cancer treatment. In particular, the development of drug delivery strategies has focused on nanoscale particles to improve bioavailability. However, many of these nanoparticles are unable to overcome tumor resistance to chemotherapeutic agents. Recently, new opportunities for drug delivery have been provided by oligonucleotides that can self-assemble into three-dimensional nanostructures. In this work, we have designed and developed functional DNA nanostructures to deliver the chemotherapy drug doxorubicin (Dox) to resistant cancer cells. These nanostructures have two components. The first component is a DNA aptamer, which forms a dimeric G-quadruplex nanostructure to target cancer cells by binding with nucleolin. The second component is double-stranded DNA (dsDNA), which is rich in -GC- base pairs that can be applied for Dox delivery. We demonstrated that Dox was able to efficiently intercalate into dsDNA and this intercalation did not affect the aptamer's three-dimensional structure. In addition, the Aptamer-dsDNA (ApS) nanoparticle showed good stability and protected the dsDNA from degradation in bovine serum. More importantly, the ApS&Dox nanoparticle efficiently reversed the resistance of human breast cancer cells to Dox. The mechanism circumventing doxorubicin resistance by ApS&Dox nanoparticles may be predominantly by cell cycle arrest in S phase, effectively increased cell uptake and decreased cell efflux of doxorubicin. Furthermore, the ApS&Dox nanoparticles could effectively inhibit tumor growth, while less cardiotoxicity was observed. Overall, this functional DNA nanostructure provides new insights into the design of nanocarriers to overcome multidrug resistance through targeted drug delivery. Copyright © 2016 Elsevier Ltd. All rights reserved.

Intracellular delivery of poly(I:C) induces apoptosis of fibroblast-like synoviocytes via an unknown dsRNA sensor

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

Karpus, Olga N.; Hsiao, Cheng-Chih; Kort, Hanneke de

Fibroblast-like synoviocytes (FLS) express functional membranous and cytoplasmic sensors for double-stranded (ds)RNA. Notably, FLS undergo apoptosis upon transfection with the synthetic dsRNA analog poly(I:C). We here studied the mechanism of intracellular poly(I:C) recognition and subsequent cell death in FLS. FLS responded similarly to poly(I:C) or 3pRNA transfection; however, only intracellular delivery of poly(I:C) induced significant cell death, accompanied by upregulation of pro-apoptotic proteins Puma and Noxa, caspase 3 cleavage, and nuclear segregation. Knockdown of the DExD/H-box helicase MDA5 did not affect the response to intracellular poly(I:C); in contrast, knockdown of RIG-I abrogated the response to 3pRNA. Knockdown of the downstreammore » adaptor proteins IPS, STING, and TRIF or inhibition of TBK1 did not affect the response to intracellular poly(I:C), while knockdown of IFNAR blocked intracellular poly(I:C)-mediated signaling and cell death. We conclude that a so far unknown intracellular sensor recognizes linear dsRNA and induces apoptosis in FLS. - Highlights: • Intracellular poly(I:C) and 3pRNA evoke immune responses in FLS. • Only intracellular delivery of poly(I:C) induces FLS apoptosis. • FLS do not require MDA5 for their response to intracellular poly(I:C). • FLS respond to intracellular poly(I:C) independent of IPS and STING. • An unknown intracellular sensor recognizes linear dsRNA in FLS.« less

Systemic RNAi in the small hive beetle Aethina tumida Murray (Coleoptera: Nitidulidae), a serious pest of the European honey bee Apis mellifera.

PubMed

Powell, Michelle E; Bradish, Hannah M; Gatehouse, John A; Fitches, Elaine C

2017-01-01

Aethina tumida is a serious pest of the European honey bee (Apis mellifera) in North America and Australia. Here we investigate whether Laccase 2, the phenoloxidase gene essential for cuticle sclerotisation and pigmentation in many insects, and vacuolar-ATPase V-type subunit A, vital for the generation of proton gradients used to drive a range of transport processes, could be potential targets for RNAi-mediated control of A. tumida. Injection of V-ATPase subunit A (5 ng) and Laccase 2 (12.5 ng) dsRNAs resulted in 100% larval mortality, and qPCR confirmed significant decreases and enhanced suppression of transcript levels over time. Oral delivery of V-ATPase subunit A dsRNA in solutions resulted in 50% mortality; however, gene suppression could not be verified. We suggest that the inconsistent RNAi effect was a consequence of dsRNA degradation within the gut owing to the presence of extracellular nucleases. Target specificity was confirmed by a lack of effect on survival or gene expression in honey bees injected with A. tumida dsRNAs. This is the first study to show evidence for systemic RNAi in A. tumida in response to injected dsRNA, but further research is required to develop methods to induce RNAi effects via ingestion. © 2016 Crown copyright. Pest Management Science © 2016 Society of Chemical Industry. © 2016 Crown copyright. Pest Management Science © 2016 Society of Chemical Industry.

Therapeutic opportunities of small interfering RNA.

PubMed

Goyal, Bhoomika R; Patel, Mayur M; Soni, Mithil K; Bhadada, Shraddha V

2009-08-01

Formation of small interfering RNA (siRNA) occurs in two steps involving binding of the RNA nucleases to a large double-stranded RNA (dsRNA) and its cleavage into fragments called siRNA. In the second step, these siRNAs join a multinuclease complex, which degrades the homologous single-stranded mRNAs. The delivery of siRNA involves viral- and non-viral-mediated delivery systems; the approaches for chemical modifications have also been developed. It has various therapeutic applications for disorders like cardiovascular diseases, central nervous system (CNS) disorders, cancer, human immunodeficiency virus (HIV), hepatic disorders, etc. The present review gives an overview of the applications of siRNA and their potential for treating many hitherto untreatable diseases.

Nanostructured Layered Terbium Hydroxide Containing NASIDs: In Vitro Physicochemical and Biological Evaluations.

PubMed

Gu, Qing-Yang; Qiu, Xiao; Liu, Jing-Jing; Fu, Min; Chao, Jian-Ping; Ju, Rui-Jun; Li, Xue-Tao

2018-08-01

Diclofenac sodium (abrr. DS) and indomethacin (abrr. IMC) have been intercalated into the layered terbium hydroxide (LTbH) by anion exchange method. Chemical compositions, thermostability, morphology, luminescence property, release behaviors and cytotoxic effects have been investigated. The DS molecules may embed between layers with a bilayered arrangement and the IMC may correspond to a monolayered arrangement. The Tb3+ luminescence in DS-LTbH and IMC-LTbH composites were enhanced compared with LTbH precusor and the luminescence intensity increases with the deprotonation degree. Drug release was measured with HPLC, and LTbH showed sustained release behavior on both drugs. Further In Vitro evaluation were carried out on cancer cells. Cytotoxic effect of LTbH was observed with a sulforhodamine B colorimetric assay on a variety of cancer cell lines, which revealed that the LTbH showed little cytotoxic effect. Results indicate LTbH may offer a potential vehicle as an effective drug delivery system along with diagnostic integration.

WE-D-BRB-00: Basics of Proton Therapy

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

NONE

The goal of this session is to review the physics of proton therapy, treatment planning techniques, and the use of volumetric imaging in proton therapy. The course material covers the physics of proton interaction with matter and physical characteristics of clinical proton beams. It will provide information on proton delivery systems and beam delivery techniques for double scattering (DS), uniform scanning (US), and pencil beam scanning (PBS). The session covers the treatment planning strategies used in DS, US, and PBS for various anatomical sites, methods to address uncertainties in proton therapy and uncertainty mitigation to generate robust treatment plans. Itmore » introduces the audience to the current status of image guided proton therapy and clinical applications of CBCT for proton therapy. It outlines the importance of volumetric imaging in proton therapy. Learning Objectives: Gain knowledge in proton therapy physics, and treatment planning for proton therapy including intensity modulated proton therapy. The current state of volumetric image guidance equipment in proton therapy. Clinical applications of CBCT and its advantage over orthogonal imaging for proton therapy. B. Teo, B.K Teo had received travel funds from IBA in 2015.« less

Double-stranded RNA uptake through topical application, mediates silencing of five CYP4 genes and suppresses insecticide resistance in Diaphorina citri.

PubMed

Killiny, Nabil; Hajeri, Subhas; Tiwari, Siddharth; Gowda, Siddarame; Stelinski, Lukasz L

2014-01-01

Silencing of genes through RNA interference (RNAi) in insects has gained momentum during the past few years. RNAi has been used to cause insect mortality, inhibit insect growth, increase insecticide susceptibility, and prevent the development of insecticide resistance. We investigated the efficacy of topically applied dsRNA to induce RNAi for five Cytochrome P450 genes family 4 (CYP4) in Diaphorina citri. We previously reported that these CYP4 genes are associated with the development of insecticide resistance in D. citri. We targeted five CYP4 genes that share a consensus sequence with one dsRNA construct. Quantitative PCR confirmed suppressed expression of the five CYP4 genes as a result of dsRNA topically applied to the thoracic region of D. citri when compared to the expression levels in a control group. Western blot analysis indicated a reduced signal of cytochrome P450 proteins (45 kDa) in adult D. citri treated with the dsRNA. In addition, oxidase activity and insecticide resistance were reduced for D. citri treated with dsRNA that targeted specific CYP4 genes. Mortality was significantly higher in adults treated with dsRNA than in adults treated with water. Our results indicate that topically applied dsRNA can penetrate the cuticle of D. citri and induce RNAi. These results broaden the scope of RNAi as a mechanism to manage pests by targeting a broad range of genes. The results also support the application of RNAi as a viable tool to overcome insecticide resistance development in D. citri populations. However, further research is needed to develop grower-friendly delivery systems for the application of dsRNA under field conditions. Considering the high specificity of dsRNA, this tool can also be used for management of D. citri by targeting physiologically critical genes involved in growth and development.

Double-Stranded RNA Uptake through Topical Application, Mediates Silencing of Five CYP4 Genes and Suppresses Insecticide Resistance in Diaphorina citri

PubMed Central

Killiny, Nabil; Hajeri, Subhas; Tiwari, Siddharth; Gowda, Siddarame; Stelinski, Lukasz L.

2014-01-01

Silencing of genes through RNA interference (RNAi) in insects has gained momentum during the past few years. RNAi has been used to cause insect mortality, inhibit insect growth, increase insecticide susceptibility, and prevent the development of insecticide resistance. We investigated the efficacy of topically applied dsRNA to induce RNAi for five Cytochrome P450 genes family 4 (CYP4) in Diaphorina citri. We previously reported that these CYP4 genes are associated with the development of insecticide resistance in D. citri. We targeted five CYP4 genes that share a consensus sequence with one dsRNA construct. Quantitative PCR confirmed suppressed expression of the five CYP4 genes as a result of dsRNA topically applied to the thoracic region of D. citri when compared to the expression levels in a control group. Western blot analysis indicated a reduced signal of cytochrome P450 proteins (45 kDa) in adult D. citri treated with the dsRNA. In addition, oxidase activity and insecticide resistance were reduced for D. citri treated with dsRNA that targeted specific CYP4 genes. Mortality was significantly higher in adults treated with dsRNA than in adults treated with water. Our results indicate that topically applied dsRNA can penetrate the cuticle of D. citri and induce RNAi. These results broaden the scope of RNAi as a mechanism to manage pests by targeting a broad range of genes. The results also support the application of RNAi as a viable tool to overcome insecticide resistance development in D. citri populations. However, further research is needed to develop grower-friendly delivery systems for the application of dsRNA under field conditions. Considering the high specificity of dsRNA, this tool can also be used for management of D. citri by targeting physiologically critical genes involved in growth and development. PMID:25330026

Diverse Roads to Relapse: A Discriminative Cue Signaling Cocaine Availability Is More Effective in Renewing Cocaine Seeking in Goal Trackers Than Sign Trackers and Depends on Basal Forebrain Cholinergic Activity.

PubMed

Pitchers, Kyle K; Phillips, Kyra B; Jones, Jonte L; Robinson, Terry E; Sarter, Martin

2017-07-26

Stimuli associated with taking drugs are notorious instigators of relapse. There is, however, considerable variation in the motivational properties of such stimuli, both as a function of the individual and the nature of the stimulus. The behavior of some individuals (sign trackers, STs) is especially influenced by cues paired with reward delivery, perhaps because they are prone to process information via dopamine-dependent, cue-driven, incentive salience systems. Other individuals (goal trackers, GTs) are better able to incorporate higher-order contextual information, perhaps because of better executive/attentional control over behavior, which requires frontal cortical cholinergic activity. We hypothesized, therefore, that a cue that "sets the occasion" for drug taking (a discriminative stimulus, DS) would reinstate cocaine seeking more readily in GTs than STs and that this would require intact cholinergic neurotransmission. To test this, male STs and GTs were trained to self-administer cocaine using an intermittent access schedule with periods of cocaine availability and unavailability signaled by a DS + and a DS - , respectively. Thereafter, half of the rats received an immunotoxic lesion that destroyed 40-50% of basal forebrain cholinergic neurons and later, after extinction training, were tested for the ability of noncontingent presentations of the DS + to reinstate cocaine seeking behavior. The DS + was much more effective in reinstating cocaine seeking in GTs than STs and this effect was abolished by cholinergic losses despite the fact that all rats continued to orient to the DS + We conclude that vulnerability to relapse involves interactions between individual cognitive-motivational biases and the form of the drug cue encountered. SIGNIFICANCE STATEMENT The most predictable outcome of a diagnosis of addiction is a high chance for relapse. When addicts encounter cues previously associated with drug, their attention may be unduly attracted to such cues and these cues can evoke motivational states that instigate and maintain drug-seeking behavior. Although sign-tracking rats were previously demonstrated to exhibit greater relapse vulnerability to Pavlovian drug cues paired with drug delivery, here, we demonstrate that their counterparts, the goal trackers, are more vulnerable if the drug cue acts to signal drug availability and that the forebrain cholinergic system mediates such vulnerability. Given the importance of contextual cues for triggering relapse and the human cognitive-cholinergic capacity for the processing of such cues, goal trackers model essential aspects of relapse vulnerability. Copyright © 2017 the authors 0270-6474/17/377198-11$15.00/0.

A Powder Delivery System (PoDS) for Mars in situ Science

NASA Astrophysics Data System (ADS)

Bryson, C.; Blake, D.; Saha, C.; Sarrazin, P.

2004-12-01

Many instruments proposed for in situ Mars science investigations work best with fine-grained samples of rocks or soils. Such instruments include the mineral analyzer CheMin [1] and any instrument that requires samples having high surface areas (e.g., mass spectrometers, organic analyzers, etc). The Powder Delivery System (PoDS) is designed to deliver powders of selected grain sizes from a sample acquisition device such as an arm-deployed robotic driller or corer to an instrument suite located on the body of a rover/lander. PoDS is capable of size-selective sampling of crushed rocks, soil or drill powder for delivery to instruments that require specific grain sizes (e.g. 5-50 mg of less than150 micron powder for CheMin). Sample material is transported as an aerosol of particles and gas by vacuum advection. In the laboratory a venturi pump driven by compressed air provides the impulse. On Mars, the ambient atmosphere is a source of CO2 that can be captured and compressed by adsorption pumping during diurnal temperature cycling [2]. The lower atmospheric pressure on the surface of Mars (7 torr) will affect fundamental parameters of gas-particle interaction such as Reynolds, Stocks and Knudsen numbers [3]. However, calculations show that the PoDS will operate under both Martian and terrestrial atmospheric conditions. Cyclone separators with appropriate particle size selection ranges remove particles from the aerosol stream. The vortex flow inside the cyclone causes grains larger than a specific size to be collected, while smaller grains remain entrained in the gas. Cyclones are very efficient inertial and centrifugal particle separators with cut sizes (d50) as low as 4 microns. Depending on the particle size ranges desired, a series of cyclones with descending cut sizes may be used, the simplest case being a single cyclone for particle deposition without mass separation. Transmission / membrane filters of appropriate pore sizes may also be used to collect powder from the aerosol stream. Results of a number of tests of the prototype PoDS will be presented. [1] Blake D. F., Sarrazin P., Bish D. L., Feldman S., Chipera S. J, Vaniman D.T., and Collins S., 2004, Definitive Mineralogical Analysis of Mars Analog Rocks Using the CheMin XRD/XRF Instrument, LPSC XXXV abstr. #1794 (CD-ROM). [2] Finn J. E., McKay C. P. and Sridhar R. K., 1999, Martian Atmosphere Utilization by Temperature-Swing Adsorption, University of Arizona, Publication No.961597, http://stl.ame.arizona.edu/publications/961597.pdf [3] Hinds W. C., 1999, Aerosol Technology - Properties, Behavior, and Measurement of Airborne Particles, Second edition, John Wiley & Sons, Inc., pp 15-67, 111-136.

Positively charged biopolymeric nanoparticles for the inhibition of Pseudomonas aeruginosa biofilms

NASA Astrophysics Data System (ADS)

Chronopoulou, Laura; Di Domenico, Enea Gino; Ascenzioni, Fiorentina; Palocci, Cleofe

2016-10-01

Currently, many microbial infections have the potential to become lethal owing to the development of antimicrobial resistance by means of different mechanisms and mainly on the basis of the fact that many drugs are unable to reach therapeutic levels in the target sites. This requires the use of high doses and frequent administrations, causing adverse side effects or in some cases toxicity. The use of nanoparticle systems could help overcome such problems and increase drug efficacy. In the present study, we developed a new drug delivery system based on the use of biopolymeric nanovectors loaded with tobramycin (Tb), which is the standard antibiotic for the treatment of Cystic Fibrosis-associated P. aeruginosa lung infections. Tb-loaded biopolymeric nanoparticles composed by dextran sulfate (DS) and chitosan (CS) were prepared by ionotropic gelation. We optimized drug entrapment in DS/CS nanoparticles, obtaining particles of 170 nm and with a drug loading of 400 µg Tb/mg of nanoparticles. In accord with in vitro release experiments, such preparations were able to release approximately 25 % of their cargo in 60 h. In vitro, the antimicrobial efficacy of the drug delivery system on P. aeruginosa biofilm was tested and compared to the effects of free drug revealing that this formulation can reduce the viability of P. aeruginosa biofilms for 48 h with a single-dose administration.

Phase transition behavior of novel pH-sensitive polyaspartamide derivatives grafted with 1-(3-aminopropyl)imidazole.

PubMed

Seo, Kwangwon; Kim, Dukjoon

2006-09-15

New pH-sensitive polyaspartamide derivatives were synthesized by grafting 1-(3-aminopropyl)imidazole and/or O-(2-aminoethyl)-O'-methylpoly(ethylene glycol) 5000 on polysuccinimide for application in intracellular drug delivery systems. The DS of 1-(3-aminopropyl)imidazole was adjusted by the feed molar ratio, and the structure of the prepared polymer was confirmed using FT-IR and 1H NMR spectroscopy. Their pH-sensitive properties were characterized by light transmittance measurements, and the particle size and its distribution were investigated by dynamic light scattering measurements at varying pH values. The pH-sensitive phase transition was clearly observed in polymer solutions with a high substitution of 1-(3-aminopropyl)imidazole. The prepared polymers showed a high buffering capacity between pH 5 and 7, and this increased with the DS of 1-(3-aminopropyl)imidazole. The pH dependence of the aggregation and de-aggregation behavior was examined using a fluorescence spectrometer. For MPEG/imidazole-g-polyaspartamides with a DS of 1-(3-aminopropyl)imidazole over 82%, self aggregates associated with the hydrophobic interactions of the unprotonated imidazole groups were observed at pH values above 7, and their mean size was over 200 nm, while the aggregates of polymers were dissociated at pH values below 7 by the protonation of imidazole groups. These pH-sensitive polyaspartamide derivatives are potential basic candidates for intracellular drug delivery carriers triggered by small pH changes.

The Effects of a Peer-Delivered Social Skills Intervention for Adults with Comorbid Down Syndrome and Autism Spectrum Disorder.

PubMed

Davis, Matthew A Cody; Spriggs, Amy; Rodgers, Alexis; Campbell, Jonathan

2018-06-01

Deficits in social skills are often exhibited in individuals with comorbid Down syndrome (DS) and autism spectrum disorder (ASD), and there is a paucity of research to help guide intervention for this population. In the present study, a multiple probe study across behaviors, replicated across participants, assessed the effectiveness of peer-delivered simultaneous prompting in teaching socials skills to adults with DS-ASD using visual analysis techniques and Tau-U statistics to measure effect. Peer-mediators with DS and intellectual disability (ID) delivered simultaneous prompting sessions reliably (i.e., > 80% reliability) to teach social skills to adults with ID and a dual-diagnoses of DS-ASD with small (Tau Weighted  = .55, 90% CI [.29, .82]) to medium effects (Tau Weighted  = .75, 90% CI [.44, 1]). Statistical and visual analysis findings suggest a promising social skills intervention for individuals with DS-ASD as well as reliable delivery of simultaneous prompting procedures by individuals with DS.

75 FR 20873 - 60-Day Notice of Proposed Information Collection: DS-2020 Retail Price Schedule, Part 3 and Part...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-21

... Office: Bureau of Administration Office of Allowances (A/OPR/ALS). Form Number: DS-2020. Respondents... submissions): Office of Allowances (A/OPR/ALS), Room L314 SA-1, Department of State, Washington, DC 20522-0103 Fax: (202) 261-8707 or (202) 261-8708 Hand Delivery or Courier: Office of Allowances (A/OPR/ALS) Room...

Inhibition of myostatin gene expression in skeletal muscle of fish by in vivo electrically mediated dsRNA and shRNAi delivery.

PubMed

Terova, Genciana; Rimoldi, Simona; Bernardini, Giovanni; Saroglia, Marco

2013-06-01

Myostatin (MSTN), previously referred to as growth differentiation factor 8 (GDF8), is a negative regulator of skeletal muscle growth. In accordance with this role, natural mutations that inactivate the gene disrupting the function of the protein are associated with excessive muscle growth and double-muscling phenotype in several mammalian species. Recent studies using transgenic MSTN deficient zebrafish and medaka support the idea that this gene inhibits skeletal muscle growth even in fish. If the atrophic actions of mammalian MSTN are indeed conserved in fish, strategies capable of inhibiting the expression of this gene could be applied to enhance growth performance in livestock production. Gene silencing by RNA interference has emerged as a promising new method of inhibiting the expression of targeted genes and inducing knockdown of associated proteins both in vitro and in vivo. Accordingly, we investigated here whether double-stranded RNA (dsRNA) or different plasmids expressing short-hairpin interfering RNAs (shRNAs) against myostatin and transduced by in vivo electroporation would increase skeletal muscle mass in reared European sea bass. After 7 weeks of intramuscular injections on a weekly basis followed by in vivo electrically mediated dsRNA delivery, no increase in the condition factor (K) of fish was observed as compared to the controls. Analogously, mean body weight and K of sea bass injected with three shRNAs were not higher than those of the control fish. On the other hand, MSTN transcript quantification via real-time RT-PCR revealed a significant inhibition of gene expression in the muscle of the dsRNA-injected fish and in the muscle of fish injected with one of the three tested shRNA-expressing vector constructs. In conclusion, in vivo electric-mediated delivery of dsRNA- or shRNA-expressing vectors against MSTN inhibits MSTN gene expression in adult sea bass muscle, but this is associated with an inconsistent double-muscle phenotype.

End-specific strategies of attachment of long double stranded DNA onto gold-coated nanofiber arrays

NASA Astrophysics Data System (ADS)

Peckys, Diana B.; de Jonge, Niels; Simpson, Michael L.; McKnight, Timothy E.

2008-10-01

We report the effective and site-specific binding of long double stranded (ds)DNA to high aspect ratio carbon nanofiber arrays. The carbon nanofibers were first coated with a thin gold layer to provide anchorage for two controllable binding methods. One method was based on the direct binding of thiol end-labeled dsDNA. The second and enhanced method used amine end-labeled dsDNA bound with crosslinkers to a carboxyl-terminated self-assembled monolayer. The bound dsDNA was first visualized with a fluorescent, dsDNA-intercalating dye. The specific binding onto the carbon nanofiber was verified by a high resolution detection method using scanning electron microscopy in combination with the binding of neutravidin-coated fluorescent microspheres to the immobilized and biotinylated dsDNA. Functional activity of thiol end-labeled dsDNA on gold-coated nanofiber arrays was verified with a transcriptional assay, whereby Chinese hamster lung cells (V79) were impaled upon the DNA-modified nanofibers and scored for transgene expression of the tethered template. Thiol end-labeled dsDNA demonstrated significantly higher expression levels than nanofibers prepared with control dsDNA that lacked a gold-binding end-label. Employing these site-specific and robust techniques of immobilization of dsDNA onto nanodevices can be of advantage for the study of DNA/protein interactions and for gene delivery applications.

Development of RNAi methods for Peregrinus maidis, the corn planthopper.

PubMed

Yao, Jianxiu; Rotenberg, Dorith; Afsharifar, Alireza; Barandoc-Alviar, Karen; Whitfield, Anna E

2013-01-01

The corn planthopper, Peregrinus maidis, is a major pest of agronomically-important crops. Peregrinus maidis has a large geographical distribution and transmits Maize mosaic rhabdovirus (MMV) and Maize stripe tenuivirus (MSpV). The objective of this study was to develop effective RNAi methods for P. maidis. Vacuolar-ATPase (V-ATPase) is an essential enzyme for hydrolysis of ATP and for transport of protons out of cells thereby maintaining membrane ion balance, and it has been demonstrated to be an efficacious target for RNAi in other insects. In this study, two genes encoding subunits of P. maidis V-ATPase (V-ATPase B and V-ATPase D) were chosen as RNAi target genes. The open reading frames of V-ATPase B and D were generated and used for constructing dsRNA fragments. Experiments were conducted using oral delivery and microinjection of V-ATPase B and V-ATPase D dsRNA to investigate the effectiveness of RNAi in P. maidis. Real-time quantitative reverse transcriptase-PCR (qRT-PCR) analysis indicated that microinjection of V-ATPase dsRNA led to a minimum reduction of 27-fold in the normalized abundance of V-ATPase transcripts two days post injection, while ingestion of dsRNA resulted in a two-fold reduction after six days of feeding. While both methods of dsRNA delivery resulted in knockdown of target transcripts, the injection method was more rapid and effective. The reduction in V-ATPase transcript abundance resulted in observable phenotypes. Specifically, the development of nymphs injected with 200 ng of either V-ATPase B or D dsRNA was impaired, resulting in higher mortality and lower fecundity than control insects injected with GFP dsRNA. Microscopic examination of these insects revealed that female reproductive organs did not develop normally. The successful development of RNAi in P. maidis to target specific genes will enable the development of new insect control strategies and functional analysis of vital genes and genes associated with interactions between P. maidis and MMV.

WE-D-BRB-02: Proton Treatment Planning and Beam Optimization

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

Pankuch, M.

2016-06-15

The goal of this session is to review the physics of proton therapy, treatment planning techniques, and the use of volumetric imaging in proton therapy. The course material covers the physics of proton interaction with matter and physical characteristics of clinical proton beams. It will provide information on proton delivery systems and beam delivery techniques for double scattering (DS), uniform scanning (US), and pencil beam scanning (PBS). The session covers the treatment planning strategies used in DS, US, and PBS for various anatomical sites, methods to address uncertainties in proton therapy and uncertainty mitigation to generate robust treatment plans. Itmore » introduces the audience to the current status of image guided proton therapy and clinical applications of CBCT for proton therapy. It outlines the importance of volumetric imaging in proton therapy. Learning Objectives: Gain knowledge in proton therapy physics, and treatment planning for proton therapy including intensity modulated proton therapy. The current state of volumetric image guidance equipment in proton therapy. Clinical applications of CBCT and its advantage over orthogonal imaging for proton therapy. B. Teo, B.K Teo had received travel funds from IBA in 2015.« less

WE-D-BRB-03: Current State of Volumetric Image Guidance for Proton Therapy

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

Hua, C.

The goal of this session is to review the physics of proton therapy, treatment planning techniques, and the use of volumetric imaging in proton therapy. The course material covers the physics of proton interaction with matter and physical characteristics of clinical proton beams. It will provide information on proton delivery systems and beam delivery techniques for double scattering (DS), uniform scanning (US), and pencil beam scanning (PBS). The session covers the treatment planning strategies used in DS, US, and PBS for various anatomical sites, methods to address uncertainties in proton therapy and uncertainty mitigation to generate robust treatment plans. Itmore » introduces the audience to the current status of image guided proton therapy and clinical applications of CBCT for proton therapy. It outlines the importance of volumetric imaging in proton therapy. Learning Objectives: Gain knowledge in proton therapy physics, and treatment planning for proton therapy including intensity modulated proton therapy. The current state of volumetric image guidance equipment in proton therapy. Clinical applications of CBCT and its advantage over orthogonal imaging for proton therapy. B. Teo, B.K Teo had received travel funds from IBA in 2015.« less

WE-D-BRB-04: Clinical Applications of CBCT for Proton Therapy

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

Teo, B.

The goal of this session is to review the physics of proton therapy, treatment planning techniques, and the use of volumetric imaging in proton therapy. The course material covers the physics of proton interaction with matter and physical characteristics of clinical proton beams. It will provide information on proton delivery systems and beam delivery techniques for double scattering (DS), uniform scanning (US), and pencil beam scanning (PBS). The session covers the treatment planning strategies used in DS, US, and PBS for various anatomical sites, methods to address uncertainties in proton therapy and uncertainty mitigation to generate robust treatment plans. Itmore » introduces the audience to the current status of image guided proton therapy and clinical applications of CBCT for proton therapy. It outlines the importance of volumetric imaging in proton therapy. Learning Objectives: Gain knowledge in proton therapy physics, and treatment planning for proton therapy including intensity modulated proton therapy. The current state of volumetric image guidance equipment in proton therapy. Clinical applications of CBCT and its advantage over orthogonal imaging for proton therapy. B. Teo, B.K Teo had received travel funds from IBA in 2015.« less

WE-D-BRB-01: Basic Physics of Proton Therapy

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

Arjomandy, B.

The goal of this session is to review the physics of proton therapy, treatment planning techniques, and the use of volumetric imaging in proton therapy. The course material covers the physics of proton interaction with matter and physical characteristics of clinical proton beams. It will provide information on proton delivery systems and beam delivery techniques for double scattering (DS), uniform scanning (US), and pencil beam scanning (PBS). The session covers the treatment planning strategies used in DS, US, and PBS for various anatomical sites, methods to address uncertainties in proton therapy and uncertainty mitigation to generate robust treatment plans. Itmore » introduces the audience to the current status of image guided proton therapy and clinical applications of CBCT for proton therapy. It outlines the importance of volumetric imaging in proton therapy. Learning Objectives: Gain knowledge in proton therapy physics, and treatment planning for proton therapy including intensity modulated proton therapy. The current state of volumetric image guidance equipment in proton therapy. Clinical applications of CBCT and its advantage over orthogonal imaging for proton therapy. B. Teo, B.K Teo had received travel funds from IBA in 2015.« less

NASA's 3D Flight Computer for Space Applications

NASA Technical Reports Server (NTRS)

Alkalai, Leon

2000-01-01

The New Millennium Program (NMP) Integrated Product Development Team (IPDT) for Microelectronics Systems was planning to validate a newly developed 3D Flight Computer system on its first deep-space flight, DS1, launched in October 1998. This computer, developed in the 1995-97 time frame, contains many new computer technologies previously never used in deep-space systems. They include: advanced 3D packaging architecture for future low-mass and low-volume avionics systems; high-density 3D packaged chip-stacks for both volatile and non-volatile mass memory: 400 Mbytes of local DRAM memory, and 128 Mbytes of Flash memory; high-bandwidth Peripheral Component Interface (Per) local-bus with a bridge to VME; high-bandwidth (20 Mbps) fiber-optic serial bus; and other attributes, such as standard support for Design for Testability (DFT). Even though this computer system did not complete on time for delivery to the DS1 project, it was an important development along a technology roadmap towards highly integrated and highly miniaturized avionics systems for deep-space applications. This continued technology development is now being performed by NASA's Deep Space System Development Program (also known as X2000) and within JPL's Center for Integrated Space Microsystems (CISM).

Carboxymethyl starch mucoadhesive microspheres as gastroretentive dosage form.

PubMed

Lemieux, Marc; Gosselin, Patrick; Mateescu, Mircea Alexandru

2015-12-30

Carboxymethyl starch microspheres (CMS-MS) were produced from carboxymethyl starch powder (CMS-P) with a degree of substitution (DS) from 0.1 to 1.5 in order to investigate the influence of DS on physicochemical, drug release and mucoadhesion properties as well as interactions with gastrointestinal tract (GIT) epithelial barrier models. Placebo and furosemide loaded CMS-MS were obtained by emulsion-crosslinking with sodium trimetaphosphate (STMP). DS had an impact on increasing equilibrium water uptake and modulating drug release properties of the CMS-MS according to the surrounding pH. The transepithelial electrical resistance (TEER) of NCI-N87 gastric cell monolayers was not influenced in presence of CMS-MS, whereas that of Caco-2 intestinal cell monolayers decreased with increasing DS but recovered initial values at about 15h post-treatment. CMS-MS with increasing DS also enhanced furosemide permeability across both NCI-N87 and Caco-2 monolayers at pH gradients from 3.0 to 7.4. Mucoadhesion of CMS-MS on gastric mucosa (acidic condition) increased with the DS up to 55% for a DS of 1.0 but decreased on neutral intestinal mucosa to less than 10% with DS of 0.1. The drug release, permeability enhancement and mucoadhesive properties of the CMS-MS suggest CMS-MS with DS between 0.6 and 1.0 as suitable excipient for gastroretentive oral delivery dosage forms. Copyright © 2015 Elsevier B.V. All rights reserved.

Enzyme oxidation of plant galactomannans yielding biomaterials with novel properties and applications, including as delivery systems.

PubMed

Galante, Yves M; Merlini, Luca; Silvetti, Tiziana; Campia, Paola; Rossi, Bianca; Viani, Fiorenza; Brasca, Milena

2018-06-01

New biomaterials from renewable sources and the development of "functionalized biopolymers" are fields of growing industrial interest. Plant polysaccharides represent a valid alternative to traditional synthetic polymers, which are obtained from monomers of fossil, non-renewable origin. Several polysaccharides, either in their natural or chemically/biochemically modified forms, are currently employed in the biomedical, food and feed, and industrial fields, including packaging. Sustainable biochemical reactions, such as enzyme modifications of polysaccharides, open further possibilities for new product and process innovation. In the present review, we summarize the recent progress on enzyme oxidation of galactomannans (GM) from few leguminous plants (performed either with galactose oxidase or laccase) and we focus on the versatile and easily accessible laccase/TEMPO oxidative reaction. The latter causes a steep viscosity increase of GM water solutions and a transition of the gels from a viscous to an elastic form, due to formation of emiacetalic bonds and thus of internal cross-linking of the polymers. Following lyophilization of these hydrogels, stable aerogels can be obtained, which were shown to have good potential as delivery systems (DS) of actives. The active molecules tested and herewith described are polymyxin B, an antibiotic; nisin, an antimicrobial peptide; the enzymes lysozyme, protease and lipase; the mixture of the industrial microbiocides 5-chloro-2-methyl-4-isothiazolin-3-one (CIT) and 2-methyl-4-isothiazolin-3-one (MIT). The advantages of such aerogel systems and the possibilities they open for future developments, including as DS, are described.

Delivery of expression constructs of secreted frizzled-related protein 4 and its domains by chitosan-dextran sulfate nanoparticles enhances their expression and anti-cancer effects.

PubMed

Perumal, Vanathi; Arfuso, Frank; Chen, Yan; Fox, Simon; Dharmarajan, Arun M

2018-06-01

In malignant mesothelioma (MM) cells, secreted frizzled-related protein 4 (SFRP4) expression is downregulated by promoter methylation. In this study, we evaluated the effect of encapsulated chitosan-dextran (CS-DS) nanoparticle formulations of SFRP4 and its cysteine-rich domain (CRD) and netrin-like domain (NLD) as means of SFRP4-GFP protein delivery and their effects in JU77 and ONE58 MM cell lines. CS-DS formulations of SFRP4, CRD, and NLD nanoparticles were prepared by a complex coacervation technique, and particle size ranged from 300 nm for empty particles to 337 nm for particles containing the proteins. Measurement of the zeta potential showed that all preparations were around 25 mV or above, suggesting stable formulation and good affinity for the DNA molecules. The CS-DS nanoparticle formulation maintained high integrity and entrapment efficiency. Gene delivery of SFRP4 and its domains showed enhanced biological effects in both JU77 and ONE58 cell lines when compared to the non-liposomal FUGENE ® HD transfection reagent. In comparison to the CRD nanoparticles, both the SFRP4 and NLD nanoparticles significantly reduced the viability of MM cells, with the NLD showing the greatest effect. The CS-DS nanoparticle effects were observed at an earlier time point and with lower DNA concentrations. Morphological changes in MM cells were characterized by the formation of membrane-associated vesicles and green fluorescent protein expression specific to SFRP4 and the NLD. The findings from our proof-of-concept study provide a stepping stone for further investigations using in vivo models.

Medical problems and oral care of patients with Down syndrome: a literature review.

PubMed

Abanto, Jenny; Ciamponi, Ana Lidia; Francischini, Elizabeth; Murakami, Christiana; de Rezende, Nathalie Pepe Medeiros; Gallottini, Marina

2011-01-01

When planning the dental treatment of patients with Down syndrome (DS), dental practitioners should always consider their general health, in order to achieve a holistic and interdisciplinary approach. This article presents a literature review of the primary medical conditions in patients with DS that may affect their general health care and the appropriate clinical delivery of oral health care. © 2011 Special Care Dentistry Association and Wiley Periodicals, Inc.

Non-Invasive Delivery of dsRNA into De-Waxed Tick Eggs by Electroporation

PubMed Central

Ruiz, Newton; de Abreu, Leonardo Araujo; Parizi, Luís Fernando; Kim, Tae Kwon; Mulenga, Albert; Braz, Gloria Regina Cardoso; Vaz, Itabajara da Silva; Logullo, Carlos

2015-01-01

RNA interference-mediated gene silencing was shown to be an efficient tool for validation of targets that may become anti-tick vaccine components. Here, we demonstrate the application of this approach in the validation of components of molecular signaling cascades, such as the Protein Kinase B (AKT) / Glycogen Synthase Kinase (GSK) axis during tick embryogenesis. It was shown that heptane and hypochlorite treatment of tick eggs can remove wax, affecting corium integrity and but not embryo development. Evidence of AKT and GSK dsRNA delivery into de-waxed eggs of via electroporation is provided. Primers designed to amplify part of the dsRNA delivered into the electroporated eggs dsRNA confirmed its entry in eggs. In addition, it was shown that electroporation is able to deliver the fluorescent stain, 4',6-diamidino-2-phenylindole (DAPI). To confirm gene silencing, a second set of primers was designed outside the dsRNA sequence of target gene. In this assay, the suppression of AKT and GSK transcripts (approximately 50% reduction in both genes) was demonstrated in 7-day-old eggs. Interestingly, silencing of GSK in 7-day-old eggs caused 25% reduction in hatching. Additionally, the effect of silencing AKT and GSK on embryo energy metabolism was evaluated. As expected, knockdown of AKT, which down regulates GSK, the suppressor of glycogen synthesis, decreased glycogen content in electroporated eggs. These data demonstrate that electroporation of de-waxed R. microplus eggs could be used for gene silencing in tick embryos, and improve the knowledge about arthropod embryogenesis. PMID:26091260

Weekly iron as a safe alternative to daily supplementation for nonanemic pregnant women.

PubMed

Casanueva, Esther; Viteri, Fernando E; Mares-Galindo, Mónica; Meza-Camacho, Carlos; Loría, Alvar; Schnaas, Lourdes; Valdés-Ramos, Roxana

2006-07-01

We undertook this study to compare the effectiveness and safety of antenatal daily and weekly supplementation with iron, folic acid, and vitamin B(12) in healthy, pregnant women who were not anemic at gestational week 20. Women with singleton pregnancies and blood hemoglobin (Hb) >115 g/L at gestational week 20 (equivalent to 105 g/L at sea level) were randomly assigned to two groups, one consuming one tablet containing 60 mg iron, 200 mug folic acid and 1 mug vitamin B(12) daily (DS, n = 56); the other consuming two tablets once weekly (WS, n = 60). Blood Hb and serum ferritin concentrations were measured every 4 weeks from weeks 20 to 36, and pregnancy outcomes were evaluated. Mild anemia and hypoferritinemia throughout pregnancy occurred less frequently in DS than WS. None of the 116 women had Hb concentrations <103 g/L at any evaluation point. In contrast, hemoconcentration (Hb >145 g/L) from gestational week 28 onwards occurred in 11% in DS and 2% in WS. We observed ex post facto that hemoconcentration at gestational week 28 was associated with a significantly higher relative risk of low birth weight (RR 6.23, 95% CI 1.46-26.57) and premature delivery (RR 7.78, 95% CI 1.45-24.74). In women who were nonanemic at gestational week 20, both schemes (DS and WS) prevented the occurrence of Hb levels <100 g/L. DS women had a higher incidence of hemoconcentration. Hemoconcentration was associated with increased risk of low birth weight and premature delivery.

Selective gene silencing by viral delivery of short hairpin RNA

PubMed Central

2010-01-01

RNA interference (RNAi) technology has not only become a powerful tool for functional genomics, but also allows rapid drug target discovery and in vitro validation of these targets in cell culture. Furthermore, RNAi represents a promising novel therapeutic option for treating human diseases, in particular cancer. Selective gene silencing by RNAi can be achieved essentially by two nucleic acid based methods: i) cytoplasmic delivery of short double-stranded (ds) interfering RNA oligonucleotides (siRNA), where the gene silencing effect is only transient in nature, and possibly not suitable for all applications; or ii) nuclear delivery of gene expression cassettes that express short hairpin RNA (shRNA), which are processed like endogenous interfering RNA and lead to stable gene down-regulation. Both processes involve the use of nucleic acid based drugs, which are highly charged and do not cross cell membranes by free diffusion. Therefore, in vivo delivery of RNAi therapeutics must use technology that enables the RNAi therapeutic to traverse biological membrane barriers in vivo. Viruses and the vectors derived from them carry out precisely this task and have become a major delivery system for shRNA. Here, we summarize and compare different currently used viral delivery systems, give examples of in vivo applications, and indicate trends for new developments, such as replicating viruses for shRNA delivery to cancer cells. PMID:20858246

Internet-Based System for Voice Communication With the ISS

NASA Technical Reports Server (NTRS)

Chamberlain, James; Myers, Gerry; Clem, David; Speir, Terri

2005-01-01

The Internet Voice Distribution System (IVoDS) is a voice-communication system that comprises mainly computer hardware and software. The IVoDS was developed to supplement and eventually replace the Enhanced Voice Distribution System (EVoDS), which, heretofore, has constituted the terrestrial subsystem of a system for voice communications among crewmembers of the International Space Station (ISS), workers at the Payloads Operations Center at Marshall Space Flight Center, principal investigators at diverse locations who are responsible for specific payloads, and others. The IVoDS utilizes a communication infrastructure of NASA and NASArelated intranets in addition to, as its name suggests, the Internet. Whereas the EVoDS utilizes traditional circuitswitched telephony, the IVoDS is a packet-data system that utilizes a voice over Internet protocol (VOIP). Relative to the EVoDS, the IVoDS offers advantages of greater flexibility and lower cost for expansion and reconfiguration. The IVoDS is an extended version of a commercial Internet-based voice conferencing system that enables each user to participate in only one conference at a time. In the IVoDS, a user can receive audio from as many as eight conferences simultaneously while sending audio to one of them. The IVoDS also incorporates administrative controls, beyond those of the commercial system, that provide greater security and control of the capabilities and authorizations for talking and listening afforded to each user.

Thermal Stimuli-Triggered Drug Release from a Biocompatible Porous Metal-Organic Framework.

PubMed

Jiang, Ke; Zhang, Ling; Hu, Quan; Zhang, Qi; Lin, Wenxin; Cui, Yuanjing; Yang, Yu; Qian, Guodong

2017-07-26

Drug delivery carriers with a high drug loading capacity and biocompatibility, especially for controlled drug release, are urgently needed due to the side effects and frequently dose in the traditional therapeutic method. In our work, a Zr-based metal-organic framework named ZJU-801, which is isoreticular with NU-801, has been designed and further demonstrated as an excellent drug delivery system (DDS) with a high drug loading of 41.7 %. Such a high drug loading capacity may be ascribed to the appropriate match of the size and the large pore volume of this kind of Zr MOF material. Compared with DS@NU-801, this DDS has successfully achieved on-command heating-activated drug release, which was probably attributed to the bulkier ligand, the better stability, and the intense π-π interaction between ZJU-801 and diclofenac sodium (DS) demonstrated comprehensively by SEM, powder X-ray diffraction (PXRD), FTIR and 13 C solid-state NMR spectroscopy as well as computer simulations. It is worth noting that premature drug release was avoided effectively without any complicated post-modifications. The low cytotoxicity and good biocompatibility of our DDS were certificated by the in vitro favorable results from an MTT assay, a WST-1 assay, and confocal microscopy imaging. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Knock down of Whitefly Gut Gene Expression and Mortality by Orally Delivered Gut Gene-Specific dsRNAs.

PubMed

Vyas, Meenal; Raza, Amir; Ali, Muhammad Yousaf; Ashraf, Muhammad Aleem; Mansoor, Shahid; Shahid, Ahmad Ali; Brown, Judith K

2017-01-01

Control of the whitefly Bemisia tabaci (Genn.) agricultural pest and plant virus vector relies on the use of chemical insecticides. RNA-interference (RNAi) is a homology-dependent innate immune response in eukaryotes, including insects, which results in degradation of the corresponding transcript following its recognition by a double-stranded RNA (dsRNA) that shares 100% sequence homology. In this study, six whitefly 'gut' genes were selected from an in silico-annotated transcriptome library constructed from the whitefly alimentary canal or 'gut' of the B biotype of B. tabaci, and tested for knock down efficacy, post-ingestion of dsRNAs that share 100% sequence homology to each respective gene target. Candidate genes were: Acetylcholine receptor subunit α, Alpha glucosidase 1, Aquaporin 1, Heat shock protein 70, Trehalase1, and Trehalose transporter1. The efficacy of RNAi knock down was further tested in a gene-specific functional bioassay, and mortality was recorded in 24 hr intervals, six days, post-treatment. Based on qPCR analysis, all six genes tested showed significantly reduced gene expression. Moderate-to-high whitefly mortality was associated with the down-regulation of osmoregulation, sugar metabolism and sugar transport-associated genes, demonstrating that whitefly survivability was linked with RNAi results. Silenced Acetylcholine receptor subunit α and Heat shock protein 70 genes showed an initial low whitefly mortality, however, following insecticide or high temperature treatments, respectively, significantly increased knockdown efficacy and death was observed, indicating enhanced post-knockdown sensitivity perhaps related to systemic silencing. The oral delivery of gut-specific dsRNAs, when combined with qPCR analysis of gene expression and a corresponding gene-specific bioassay that relates knockdown and mortality, offers a viable approach for functional genomics analysis and the discovery of prospective dsRNA biopesticide targets. The approach can be applied to functional genomics analyses to facilitate, species-specific dsRNA-mediated control of other non-model hemipterans.

Performance of Complex Spreading MIMO Systems With Interference

DTIC Science & Technology

2011-06-01

14 III. PERFORMANCE ANALYSIS OF DS -PSK MISO ...............................................15 A. SYSTEM DESCRIPTION...15 Figure 9. BER of DS PSK system for broadband jamming and diversity L=1. ..............20 Figure 10. BER of DS PSK system for...broadband jamming and diversity L=2. .............21 Figure 11. BER of DS PSK system for broadband jamming and diversity L=3. ..............22 Figure 12

Effect of varying molecular weight of dextran on acrylic-derivatized dextran and concanavalin A glucose-responsive materials for closed-loop insulin delivery.

PubMed

Sahota, Tarsem; Sawicka, Kirsty; Taylor, Joan; Tanna, Sangeeta

2011-03-01

Dextran methacrylate (dex-MA) and concanavalin A (con A)-methacrylamide were photopolymerized to produce covalently cross-linked glucose-sensitive gels for the basis of an implantable closed-loop insulin delivery device. The viscoelastic properties of these polymerized gels were tested rheologically in the non-destructive oscillatory mode within the linear viscoelastic range at glucose concentrations between 0 and 5% (w/w). For each cross-linked gel, as the glucose concentration was raised, a decrease in storage modulus, loss modulus and complex viscosity (compared at 1 Hz) was observed, indicating that these materials were glucose responsive. The higher molecular weight acrylic-derivatized dextrans [degree of substitution (DS) 3 and 8%] produced higher complex viscosities across the glucose concentration range. These studies coupled with in vitro diffusion experiments show that dex-MA of 70 kDa and DS (3%) was the optimum mass average molar mass to produce gels that show reduced component leach, glucose responsiveness, and insulin transport useful as part of a self-regulating insulin delivery device.

In vitro photodynamic effects of scavenger receptor targeted-photoactivatable nanoagents on activated macrophages.

PubMed

Yi, Bong Gu; Park, Ok Kyu; Jeong, Myeong Seon; Kwon, Seung Hae; Jung, Jae In; Lee, Seongsoo; Ryoo, Sungwoo; Kim, Sung Eun; Kim, Jin Won; Moon, Won-Jin; Park, Kyeongsoon

2017-04-01

Scavenger receptors (SRs) expressed on the activated macrophages in inflammation sites have been considered as the most interesting and important target biomarker for targeted drug delivery, imaging and therapy. In the present study, we fabricated the scavenger receptor-A (SR-A) targeted-photoactivatable nanoagents (termed as Ce6/DS-DOCA) by entrapping chlorin e6 (Ce6) into the amphiphilic dextran sulfate-deoxycholic acid (DS-DOCA) conjugates via physically hydrophobic interactions. Insoluble Ce6 was easily encapsulated into DS-DOCA nanoparticles by a dialysis method and the loading efficiency was approximately 51.7%. The Ce6/DS-DOCA formed nano-sized self-assembled aggregates (28.8±5.6nm in diameter), confirmed by transmission electron microscope, UV/Vis and fluorescence spectrophotometer. The Ce6/DS-DOCA nanoagents could generate highly reactive singlet oxygen under laser irradiation. Also, in vitro studies showed that they were more specifically taken up by lipopolysaccharide (LPS)-induced activated macrophages (RAW 264.7) via a SR-A-mediated endocytosis, relative to by non-activated macrophages, and notably induced cell death of activated macrophages under laser irradiation. Therefore, SR-A targetable and photoactivatable Ce6/DS-DOCA nanoagents with more selective targeting to the activated macrophages will have great potential for treatment of inflammatory diseases. Copyright © 2017 Elsevier B.V. All rights reserved.

Update on Mathematical Modeling Research to Support the Development of Automated Insulin Delivery Systems

DTIC Science & Technology

2010-05-01

that believed the delay is ≤10–15 min, 50% believed that insulin can cause changes in the blood (i.e., plasma)-to-ISF glucose gradient. Also, 50% still...by the R01HL88448-1 grant, which seeks to establish safe pediatric euglycemia after cardiac surgery in neonates using continuous glucose monitoring...2062–7. 9. Burge MR, Castillo KR, Schade DS. Meal composition is a determinant of lispro-induced hypoglycemia in IDDM. Diabetes Care. 1997;20(2):152–5

Dichotomous versus semi-quantitative scoring of ultrasound joint inflammation in rheumatoid arthritis using novel individualized joint selection methods.

PubMed

Tan, York Kiat; Allen, John C; Lye, Weng Kit; Conaghan, Philip G; Chew, Li-Ching; Thumboo, Julian

2017-05-01

The aim of the study is to compare the responsiveness of two joint inflammation scoring systems (dichotomous scoring (DS) versus semi-quantitative scoring (SQS)) using novel individualized ultrasound joint selection methods and existing ultrasound joint selection methods. Responsiveness measured by the standardized response means (SRMs) using the DS and the SQS system (for both the novel and existing ultrasound joint selection methods) was derived using the baseline and the 3-month total inflammatory scores from 20 rheumatoid arthritis patients. The relative SRM gain ratios (SRM-Gains) for both scoring system (DS and SQS) comparing the novel to the existing methods were computed. Both scoring systems (DS and SQS) demonstrated substantial SRM-Gains (ranged from 3.31 to 5.67 for the DS system and ranged from 1.82 to 3.26 for the SQS system). The SRMs using the novel methods ranged from 0.94 to 1.36 for the DS system and ranged from 0.89 to 1.11 for the SQS system. The SRMs using the existing methods ranged from 0.24 to 0.32 for the DS system and ranged from 0.34 to 0.49 for the SQS system. The DS system appears to achieve high responsiveness comparable to SQS for the novel individualized ultrasound joint selection methods.

Pods: a Powder Delivery System for Mars In-situ Organic, Mineralogic and Isotopic Analysis Instruments

NASA Technical Reports Server (NTRS)

Saha, C. P.; Bryson, C. E.; Sarrazin, P.; Blake, D. F.

2005-01-01

Many Mars in situ instruments require fine-grained high-fidelity samples of rocks or soil. Included are instruments for the determination of mineralogy as well as organic and isotopic chemistry. Powder can be obtained as a primary objective of a sample collection system (e.g., by collecting powder as a surface is abraded by a rotary abrasion tool (RAT)), or as a secondary objective (e.g, by collecting drill powder as a core is drilled). In the latter case, a properly designed system could be used to monitor drilling in real time as well as to deliver powder to analytical instruments which would perform complementary analyses to those later performed on the intact core. In addition, once a core or other sample is collected, a system that could transfer intelligently collected subsamples of power from the intact core to a suite of analytical instruments would be highly desirable. We have conceptualized, developed and tested a breadboard Powder Delivery System (PoDS) intended to satisfy the collection, processing and distribution requirements of powder samples for Mars in-situ mineralogic, organic and isotopic measurement instruments.

Neurotransmitter-based strategies for the treatment of cognitive dysfunction in Down syndrome.

PubMed

Das, Devsmita; Phillips, Cristy; Hsieh, Wayne; Sumanth, Krithika; Dang, Van; Salehi, Ahmad

2014-10-03

Down syndrome (DS) is a multisystem disorder affecting the cardiovascular, respiratory, gastrointestinal, neurological, hematopoietic, and musculoskeletal systems and is characterized by significant cognitive disability and a possible common pathogenic mechanism with Alzheimer's disease. During the last decade, numerous studies have supported the notion that the triplication of specific genes on human chromosome 21 plays a significant role in cognitive dysfunction in DS. Here we reviewed studies in trisomic mouse models and humans, including children and adults with DS. In order to identify groups of genes that contribute to cognitive disability in DS, multiple mouse models of DS with segmental trisomy have been generated. Over-expression of these particular genes in DS can lead to dysfunction of several neurotransmitter systems. Therapeutic strategies for DS have either focused on normalizing the expression of triplicated genes with important roles in DS or restoring the function of these systems. Indeed, our extensive review of studies on the pathogenesis of DS suggests that one plausible strategy for the treatment of cognitive dysfunction is to target the cholinergic, serotonergic, GABA-ergic, glutamatergic, and norepinephrinergic system. However, a fundamental strategy for treatment of cognitive dysfunction in DS would include reducing to normal levels the expression of specific triplicated genes in affected systems before the onset of neurodegeneration. Published by Elsevier Inc.

Stability of triptorelin in the presence of dermis and epidermis.

PubMed

Bachhav, Yogeshwar G; Kalia, Yogeshvar N

2009-08-13

An important issue with respect to the transdermal delivery of peptides is their stability during transit through the epidermis and dermis before entry into the systemic circulation. The objective of the present study was to evaluate the effect of epidermal and dermal tissue on the stability of the luteinizing hormone releasing hormone superagonist, triptorelin. The decapeptide was dissolved in PBS (pH 7.4) and placed in contact with (i) heat separated epidermis (HSE), (ii) dermatomed skin (0.75 mm; DS) and (iii) full thickness skin (FTS) and the extent of peptide biotransformation monitored as a function of time by HPLC. The results showed that triptorelin was metabolized when in contact with each of the skin tissues. However, there were marked differences with respect to the extent of peptide degradation. Triptorelin was least stable in the presence of FTS. After 3 h exposure to HSE, DS and FTS, the extent of triptorelin degradation was 15.0+/-6.0%, 64.8+/-9.9% and 100%, respectively. After 24 h, further triptorelin degradation had occurred in the samples in contact with HSE and DS--with 51.3+/-6.0% and 87.8+/-4.4%, respectively, of the peptide being degraded. The chromatograms revealed the presence of a degradation peak at a higher retention time than the parent molecule--most probably the free acid.

Light-Triggered Release of DNA from Plasmon-Resonant Nanoparticles

NASA Astrophysics Data System (ADS)

Huschka, Ryan

Plasmon-resonant nanoparticle complexes show promising potential for lighttriggered, controllable delivery of deoxyribonucleic acids (DNA) for research and therapeutic purposes. For example, the approach of RNA interference (RNAi) . using antisense DNA or RNA oligonucleotides to silence activity of a specific pathogenic gene transcript and reduce expression of the encoded protein . is very useful in dissecting genetic function and holds promise as a molecular therapeutic. Herein, we investigate the mechanism and probe the in vitro therapeutic potential of DNA light-triggered release from plasmonic nanoparticles. First, we investigate the mechanism of light-triggered release by dehybridizing double-stranded (dsDNA) via laser illumination from two types of nanoparticle substrates: gold (Au) nanoshells and Au nanorods. Both light-triggered and thermally induced releases are distinctly observable from nanoshell-based complexes. Surprisingly, no analogous measurable light-triggered release was observable from nanorod-based complexes below the DNA melting temperature. These results suggest that a nonthermal mechanism may play a role in light-triggered DNA release. Second, we demonstrate the in vitro light-triggered release of molecules noncovalently attached within dsDNA bound to the Au nanoshell surface. DAPI (4',6- diamidino-2-phenylindole), a bright blue fluorescent molecule that binds reversibly to double-stranded DNA, was chosen to visualize this intracellular light-induced release process. Illumination through the cell membrane of the nanoshell-dsDNA-DAPI complexes dehybridizes the DNA and releases the DAPI molecules within living cells. The DAPI molecules diffuse to the nucleus and associate with the cell's endogenous DNA. This work could have future applications towards drug delivery of molecules that associate with dsDNA. Finally, we demonstrate an engineered Au nanoshell (AuNS)-based therapeutic oligonucleotide delivery vehicle, designed to release its cargo on demand upon illumination with a near-infrared (NIR) laser. A poly(L)lysine peptide (PLL) epilayer coated onto the AuNS surface (AuNS-PLL) is used to capture intact, single-stranded antisense DNA oligonucleotide, or alternatively, double-stranded short-interfering RNA (siRNA) molecules. A green fluorescent protein (GFP)-expressing human lung cancer H1299 cell line was used to determine cellular uptake and GFP gene silencing mediated by AuNS-PLL delivery vector. The light-triggered release of oligonucleotides could have broad applications in the study of cellular processes and in the development of intracellular targeted therapies.

Systemic Lupus Erythematosus with and without Anti-dsDNA Antibodies: Analysis from a Large Monocentric Cohort.

PubMed

Conti, Fabrizio; Ceccarelli, Fulvia; Perricone, Carlo; Massaro, Laura; Marocchi, Elisa; Miranda, Francesca; Spinelli, Francesca Romana; Truglia, Simona; Alessandri, Cristiano; Valesini, Guido

2015-01-01

The anti-dsDNA antibodies are a marker for Systemic Lupus Erythematosus (SLE) and 70-98% of patients test positive. We evaluated the demographic, clinical, laboratory, and therapeutical features of a monocentric SLE cohort according to the anti-dsDNA status. We identified three groups: anti-dsDNA + (persistent positivity); anti-dsDNA ± (initial positivity and subsequent negativity during disease course); anti-dsDNA - (persistent negativity). Disease activity was assessed by the European Consensus Lupus Activity Measurement (ECLAM). We evaluated 393 patients (anti-dsDNA +: 62.3%; anti-dsDNA ±: 13.3%; anti-dsDNA -: 24.4%). The renal involvement was significantly more frequent in anti-dsDNA + (30.2%), compared with anti-dsDNA ± and anti-dsDNA - (21.1% and 18.7%, resp.; P = 0.001). Serositis resulted significantly more frequent in anti-dsDNA - (82.3%) compared to anti-dsDNA + and anti-dsDNA ± (20.8% and 13.4%, resp.; P < 0.0001). The reduction of C4 serum levels was identified significantly more frequently in anti-dsDNA + and anti-dsDNA ± (40.0% and 44.2%, resp.) compared with anti-dsDNA - (21.8%, P = 0.005). We did not identify significant differences in the mean ECLAM values before and after modification of anti-dsDNA status (P = 0.7). Anti-dsDNA status influences the clinical and immunological features of SLE patients. Nonetheless, it does not appear to affect disease activity.

Oral delivery of double-stranded RNAs induces mortality in nymphs and adults of the Asian citrus psyllid, Diaphorina citri.

PubMed

Galdeano, Diogo Manzano; Breton, Michèle Claire; Lopes, João Roberto Spotti; Falk, Bryce W; Machado, Marcos Antonio

2017-01-01

The Asian citrus psyllid (ACP), Diaphorina citri Kuwayama, is one of the most important citrus pests. ACP is the vector of the phloem-limited bacteria Candidatus Liberibacter americanus and Candidatus Liberibacter asiaticus, the causal agents of the devastating citrus disease huanglongbing (HLB). The management of HLB is based on the use of healthy young plants, eradication of infected plants and chemical control of the vector. RNA interference (RNAi) has proven to be a promising tool to control pests and explore gene functions. Recently, studies have reported that target mRNA knockdown in many insects can be induced through feeding with double-stranded RNA (dsRNA). In the current study, we targeted the cathepsin D, chitin synthase and inhibitor of apoptosis genes of adult and nymph ACP by feeding artificial diets mixed with dsRNAs and Murraya paniculata leaves placed in dsRNAs solutions, respectively. Adult ACP mortality was positively correlated with the amount of dsRNA used. Both nymphs and adult ACP fed dsRNAs exhibited significantly increased mortality over time compared with that of the controls. Moreover, qRT-PCR analysis confirmed the dsRNA-mediated RNAi effects on target mRNAs. These results showed that RNAi can be a powerful tool for gene function studies in ACP and perhaps for HLB control.

Reproductive Health Issues for Adults with a Common Genomic Disorder: 22q11.2 Deletion Syndrome

PubMed Central

Chan, Chrystal; Costain, Gregory; Ogura, Lucas; Silversides, Candice K.; Chow, Eva W.C.

2015-01-01

22q11.2 deletion syndrome (22q11.2DS) is the most common microdeletion syndrome in humans. Survival to reproductive age and beyond is now the norm. Several manifestations of this syndrome, such as congenital cardiac disease and neuropsychiatric disorders, may increase risk for adverse pregnancy outcomes in the general population. However, there are limited data on reproductive health in 22q11.2DS. We performed a retrospective chart review for 158 adults with 22q11.2DS (75 male, 83 female; mean age 34.3 years) and extracted key variables relevant to pregnancy and reproductive health. We present four illustrative cases as brief vignettes. There were 25 adults (21>age 35 years; 21 female) with a history of one or more pregnancies. Outcomes for women with 22q11.2DS, compared with expectations for the general population, showed a significantly elevated prevalence of small for gestational age liveborn offspring (p<0.001), associated mainly with infants with 22q11.2DS. Stillbirths also showed elevated prevalence (p<0.05). Not all observed adverse events appeared to be attributable to transmission of the 22q11.2 deletion. Recurring issues relevant to reproductive health in 22q11.2DS included the potential impact of maternal morbidities, inadequate social support, unsafe sexual practices, and delayed diagnosis of 22q11.2DS and/or lack of genetic counseling. These preliminary results emphasize the importance of early diagnosis and long term follow-up that could help facilitate genetic counseling for men and women with 22q11.2DS. We propose initial recommendations for pre-conception management, educational strategies, pre-natal planning, and preparation for possible high-risk pregnancy and/or delivery. PMID:25579115

Coded DS-CDMA Systems with Iterative Channel Estimation and no Pilot Symbols

DTIC Science & Technology

2010-08-01

ar X iv :1 00 8. 31 96 v1 [ cs .I T ] 1 9 A ug 2 01 0 1 Coded DS - CDMA Systems with Iterative Channel Estimation and no Pilot Symbols Don...sequence code-division multiple-access ( DS - CDMA ) systems with quadriphase-shift keying in which channel estimation, coherent demodulation, and decoding...amplitude, phase, and the interference power spectral density (PSD) due to the combined interference and thermal noise is proposed for DS - CDMA systems

Reliability and validity of the Children's Fear Survey Schedule-Dental Subscale for Arabic-speaking children: a cross-sectional study.

PubMed

El-Housseiny, Azza A; Alsadat, Farah A; Alamoudi, Najlaa M; El Derwi, Douaa A; Farsi, Najat M; Attar, Moaz H; Andijani, Basil M

2016-04-14

Early recognition of dental fear is essential for the effective delivery of dental care. This study aimed to test the reliability and validity of the Arabic version of the Children's Fear Survey Schedule-Dental Subscale (CFSS-DS). A school-based sample of 1546 children was randomly recruited. The Arabic version of the CFSS-DS was completed by children during class time. The scale was tested for internal consistency and test-retest reliability. To test criterion validity, children's behavior was assessed using the Frankl scale during dental examination, and results were compared with children's CFSS-DS scores. To test the scale's construct validity, scores on "fear of going to the dentist soon" were correlated with CFSS-DS scores. Factor analysis was also used. The Arabic version of the CFSS-DS showed high reliability regarding both test-retest reliability (intraclass correlation = 0.83, p < 0.001) and internal consistency (Cronbach's α = 0.88). It showed good criterion validity: children with negative behavior had significantly higher fear scores (t = 13.67, p < 0.001). It also showed moderate construct validity (Spearman's rho correlation, r = 0.53, p < 0.001). Factor analysis identified the following factors: "fear of invasive dental procedures," "fear of less invasive dental procedures" and "fear of strangers." The Arabic version of the CFSS-DS is a reliable and valid measure of dental fear in Arabic-speaking children. Pediatric dentists and researchers may use this validated version of the CFSS-DS to measure dental fear in Arabic-speaking children.

Efficient, Glucose Responsive, and Islet-Specific Transgene Expression by a Modified Rat Insulin Promoter

PubMed Central

Chai, Renjie; Chen, Shuyuan; Ding, Jiahuan; Grayburn, Paul A

2009-01-01

This study was done to improve efficiency and islet specificity of the rat insulin promoter (RIP). Various rat insulin promoter lengths were prepared and tested in vitro to drive luciferase reporter gene expression in INS1-cells, alpha-cells, acinar cells, ductal cells, and fibroblasts. The CMV promoter was used as a positive control. In addition, the DsRed reporter gene was administered in vivo to rat pancreas by ultrasound-targeted microbubble destruction (UTMD). Confocal microscopy was used to detect the presence and distribution of DsRed within the pancreas after UTMD. A modified RIP3.1 promoter, which includes portions of the insulin gene after its transcription start site is 5-fold more active in INS-1 cells than the full length RIP promoter or the CMV promoter. RIP3.1 is regulated by glucose level and various islet transcription factors in vitro, and exhibits activity in alpha-cells, but not exocrine cells. In vivo delivery of RIP3.1-DsRed resulted in expression of DsRed protein in beta-cells, and to a lesser extent alpha cells under normal glucose conditions. No DsRed signal was present in exocrine pancreas under RIP3.1. A modified rat insulin promoter, RIP3.1, efficiently and specifically directs gene expression to endocrine pancreas. PMID:19727136

Aquatic fate of a double-stranded RNA in a sediment---water system following an over-water application.

PubMed

Fischer, Joshua R; Zapata, Fatima; Dubelman, Samuel; Mueller, Geoffrey M; Uffman, Joshua P; Jiang, Changjian; Jensen, Peter D; Levine, Steven L

2017-03-01

Determining the rate of biodegradation of double-stranded RNA (dsRNA) in the environment is an essential element of a comprehensive risk assessment of an RNA-based agricultural product. This information is used during problem formulation to define relevant routes and durations of environmental exposure for in planta-expressed dsRNA. Although exposure to biotechnology-derived crops expressing dsRNA traits in the aquatic environment is predicted to be minimal, little is known regarding the fate of dsRNA in these environments. To assess exposure to aquatic environments, a study was conducted to measure the rate of biodegradation of DvSnf7 dsRNA in aerobic water-sediment systems. Aquatic systems containing natural water and sediments that varied in physical and chemical characteristics were treated with dsRNA by applying DvSnf7 dsRNA directly to the water column. In the present study, DvSnf7 dsRNA dissipated rapidly from the water phase and was undetectable within 7 d as measured by QuantiGene (Affymetrix) and a sensitive insect bioassay in these diverse systems. Degradation kinetics estimated a half-life (time to 50% dissipation [DT50]) of less than 3 d and a time to 90% dissipation of approximately 4 d. Further analysis indicated that DvSnf7 dsRNA had DT50 values of less than 6 d in both sediment-free systems containing natural water and systems with only sediment. Taken together, the results of the present study indicate that dsRNA-based agricultural products rapidly degrade and consequently are unlikely to persist in aquatic environments. Environ Toxicol Chem 2017;36:727-734. © 2016 SETAC. © 2016 SETAC.

Interaction of Poly(l-lysine)/Polysaccharide Complex Nanoparticles with Human Vascular Endothelial Cells.

PubMed

Weber, Dominik; Torger, Bernhard; Richter, Karsten; Nessling, Michelle; Momburg, Frank; Woltmann, Beatrice; Müller, Martin; Schwartz-Albiez, Reinhard

2018-05-23

Angiogenesis plays an important role in both soft and hard tissue regeneration, which can be modulated by therapeutic drugs. If nanoparticles (NP) are used as vectors for drug delivery, they have to encounter endothelial cells (EC) lining the vascular lumen, if applied intravenously. Herein the interaction of unloaded polyelectrolyte complex nanoparticles (PECNP) composed of cationic poly(l-lysine) (PLL) and various anionic polysaccharides with human vascular endothelial cells (HUVEC) was analyzed. In particular PECNP were tested for their cell adhesive properties, their cellular uptake and intracellular localization considering composition and net charge. PECNP may form a platform for both cell coating and drug delivery. PECNP, composed of PLL in combination with the polysaccharides dextran sulfate (DS), cellulose sulfate (CS) or heparin (HEP), either unlabeled or labeled with fluorescein isothiocyanate (FITC) and either with positive or negative net charge were prepared. PECNP were applied to human umbilical cord vein endothelial cells (HUVEC) in both, the volume phase and immobilized phase at model substrates like tissue culture dishes. The attachment of PECNP to the cell surface, their intracellular uptake, and effects on cell proliferation and growth behavior were determined. Immobilized PECNP reduced attachment of HUVEC, most prominently the systems PLL/HEP and PLL/DS. A small percentage of immobilized PECNP was taken up by cells during adhesion. PECNP in the volume phase showed no effect of the net charge sign and only minor effects of the composition on the binding and uptake of PECNP at HUVEC. PECNP were stored in endosomal vesicles in a cumulative manner without apparent further processing. During mitosis, internalized PECNP were almost equally distributed among the dividing cells. Both, in the volume phase and immobilized at the surface, PECNP composed of PLL/HEP and PLL/DS clearly reduced cell proliferation of HUVEC, however without an apparent cytotoxic effect, while PLL/CS composition showed minor impairment. PECNP have an anti-adhesive effect on HUVEC and are taken up by endothelial cells which may negatively influence the proliferation rate of HUVEC. The negative effects were less obvious with the composition PLL/CS. Since uptake and binding for PLL/HEP was more efficient than for PLL/DS, PECNP of PLL/HEP may be used to deliver growth factors to endothelial cells during vascularization of bone reconstitution material, whereas those of PLL/CS may have an advantage for substituting biomimetic bone scaffold material.

SMART-DS: Synthetic Models for Advanced, Realistic Testing: Distribution

Science.gov Websites

statistical summary of the U.S. distribution systems World-class, high spatial/temporal resolution of solar Systems and Scenarios | Grid Modernization | NREL SMART-DS: Synthetic Models for Advanced , Realistic Testing: Distribution Systems and Scenarios SMART-DS: Synthetic Models for Advanced, Realistic

A Charrelation Matrix-Based Blind Adaptive Detector for DS-CDMA Systems

PubMed Central

Luo, Zhongqiang; Zhu, Lidong

2015-01-01

In this paper, a blind adaptive detector is proposed for blind separation of user signals and blind estimation of spreading sequences in DS-CDMA systems. The blind separation scheme exploits a charrelation matrix for simple computation and effective extraction of information from observation signal samples. The system model of DS-CDMA signals is modeled as a blind separation framework. The unknown user information and spreading sequence of DS-CDMA systems can be estimated only from the sampled observation signals. Theoretical analysis and simulation results show that the improved performance of the proposed algorithm in comparison with the existing conventional algorithms used in DS-CDMA systems. Especially, the proposed scheme is suitable for when the number of observation samples is less and the signal to noise ratio (SNR) is low. PMID:26287209

A Charrelation Matrix-Based Blind Adaptive Detector for DS-CDMA Systems.

PubMed

Luo, Zhongqiang; Zhu, Lidong

2015-08-14

In this paper, a blind adaptive detector is proposed for blind separation of user signals and blind estimation of spreading sequences in DS-CDMA systems. The blind separation scheme exploits a charrelation matrix for simple computation and effective extraction of information from observation signal samples. The system model of DS-CDMA signals is modeled as a blind separation framework. The unknown user information and spreading sequence of DS-CDMA systems can be estimated only from the sampled observation signals. Theoretical analysis and simulation results show that the improved performance of the proposed algorithm in comparison with the existing conventional algorithms used in DS-CDMA systems. Especially, the proposed scheme is suitable for when the number of observation samples is less and the signal to noise ratio (SNR) is low.

Synthetic biology approach for plant protection using dsRNA.

PubMed

Niehl, Annette; Soininen, Marjukka; Poranen, Minna M; Heinlein, Manfred

2018-02-26

Pathogens induce severe damages on cultivated plants and represent a serious threat to global food security. Emerging strategies for crop protection involve the external treatment of plants with double-stranded (ds)RNA to trigger RNA interference. However, applying this technology in greenhouses and fields depends on dsRNA quality, stability and efficient large-scale production. Using components of the bacteriophage phi6, we engineered a stable and accurate in vivo dsRNA production system in Pseudomonas syringae bacteria. Unlike other in vitro or in vivo dsRNA production systems that rely on DNA transcription and postsynthetic alignment of single-stranded RNA molecules, the phi6 system is based on the replication of dsRNA by an RNA-dependent RNA polymerase, thus allowing production of high-quality, long dsRNA molecules. The phi6 replication complex was reprogrammed to multiply dsRNA sequences homologous to tobacco mosaic virus (TMV) by replacing the coding regions within two of the three phi6 genome segments with TMV sequences and introduction of these constructs into P. syringae together with the third phi6 segment, which encodes the components of the phi6 replication complex. The stable production of TMV dsRNA was achieved by combining all the three phi6 genome segments and by maintaining the natural dsRNA sizes and sequence elements required for efficient replication and packaging of the segments. The produced TMV-derived dsRNAs inhibited TMV propagation when applied to infected Nicotiana benthamiana plants. The established dsRNA production system enables the broad application of dsRNA molecules as an efficient, highly flexible, nontransgenic and environmentally friendly approach for protecting crops against viruses and other pathogens. © 2018 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

Minimalism in fabrication of self-organized nanogels holding both anti-cancer drug and targeting moiety.

PubMed

Kim, Sungwon; Park, Kyong Mi; Ko, Jin Young; Kwon, Ick Chan; Cho, Hyeon Geun; Kang, Dongmin; Yu, In Tag; Kim, Kwangmeyung; Na, Kun

2008-05-01

Recent researches to develop nano-carrier systems in anti-cancer drug delivery have focused on more complicated design to improve therapeutic efficacy and to reduce side effects. Although such efforts have great impact to biomedical science and engineering, the complexity has been a huddle because of clinical and economic problems. In order to overcome the problems, a simplest strategy to fabricate nano-carriers to deliver doxorubicin (DOX) was proposed in the present study. Two significant subjects (i) formation of nanoparticles loading and releasing DOX and (ii) binding specificity of them to cells, were examined. Folic acid (FA) was directly coupled with pullulan (Pul) backbone by ester linkage (FA/Pul conjugate) and the degree of substitution (DS) was varied, which were confirmed by 1H NMR and UV spectrophotometry. Light scattering results revealed that the nanogels possessed two major size distributions around 70 and 270 nm in an aqueous solution. Their critical aggregation concentrations (CACs) were less than 10 microg/mL, which are lower than general critical micelle concentrations (CMCs) of low-molecular-weight surfactants. Transmission electron microscopy (TEM) images showed well-dispersed nanogel morphology in a dried state. Depending on the DS, the nanogels showed different DOX-loading and releasing profiles. The DOX release rate from FA8/Pul (with the highest DS) for 24h was slower than that from FA4/or FA6/Pul, indicating that the FA worked as a hydrophobic moiety for drug holding. Cellular uptake of the nanogels (KB cells) was also monitored by confocal microscopy. All nanogels were internalized regardless of the DS of FA. Based on the results, the objectives of this study, to suggest a new method overcoming the complications in the drug carrier design, were successfully verified.

Novel adjuvants & delivery vehicles for vaccines development: a road ahead.

PubMed

Mohan, Teena; Verma, Priyanka; Rao, D Nageswara

2013-11-01

The pure recombinant and synthetic antigens used in modern day vaccines are generally less immunogenic than older style live/attenuated and killed whole organism vaccines. One can improve the quality of vaccine production by incorporating immunomodulators or adjuvants with modified delivery vehicles viz. liposomes, immune stimulating complexes (ISCOMs), micro/nanospheres apart from alum, being used as gold standard. Adjuvants are used to augment the effect of a vaccine by stimulating the immune system to respond to the vaccine, more vigorously, and thus providing increased immunity to a particular disease. Adjuvants accomplish this task by mimicking specific sets of evolutionary conserved molecules which include lipopolysaccharides (LPS), components of bacterial cell wall, endocytosed nucleic acids such as dsRNA, ssDNA and unmethylated CpG dinucleotide containing DNA. This review provides information on various vaccine adjuvants and delivery vehicles being developed to date. From literature, it seems that the humoral immune responses have been observed for most adjuvants and delivery platforms while viral-vector, ISCOMs and Montanides have shown cytotoxic T-cell response in the clinical trials. MF59 and MPL® have elicited Th1 responses, and virus-like particles (VLPs), non-degradable nanoparticle and liposomes have also generated cellular immunity. Such vaccine components have also been evaluated for alternative routes of administration with clinical success reported for intranasal delivery of viral-vectors and proteosomes and oral delivery of VLP vaccines.

Novel adjuvants & delivery vehicles for vaccines development: A road ahead

PubMed Central

Mohan, Teena; Verma, Priyanka; Rao, D. Nageswara

2013-01-01

The pure recombinant and synthetic antigens used in modern day vaccines are generally less immunogenic than older style live/attenuated and killed whole organism vaccines. One can improve the quality of vaccine production by incorporating immunomodulators or adjuvants with modified delivery vehicles viz. liposomes, immune stimulating complexes (ISCOMs), micro/nanospheres apart from alum, being used as gold standard. Adjuvants are used to augment the effect of a vaccine by stimulating the immune system to respond to the vaccine, more vigorously, and thus providing increased immunity to a particular disease. Adjuvants accomplish this task by mimicking specific sets of evolutionary conserved molecules which include lipopolysaccharides (LPS), components of bacterial cell wall, endocytosed nucleic acids such as dsRNA, ssDNA and unmethylated CpG dinucleotide containing DNA. This review provides information on various vaccine adjuvants and delivery vehicles being developed to date. From literature, it seems that the humoral immune responses have been observed for most adjuvants and delivery platforms while viral-vector, ISCOMs and Montanides have shown cytotoxic T-cell response in the clinical trials. MF59 and MPL® have elicited Th1 responses, and virus-like particles (VLPs), non-degradable nanoparticle and liposomes have also generated cellular immunity. Such vaccine components have also been evaluated for alternative routes of administration with clinical success reported for intranasal delivery of viral-vectors and proteosomes and oral delivery of VLP vaccines. PMID:24434331

Circulating anti-double-stranded DNA antibody-secreting cells in patients with systemic lupus erythematosus: a novel biomarker for disease activity.

PubMed

Hanaoka, H; Okazaki, Y; Satoh, T; Kaneko, Y; Yasuoka, H; Seta, N; Kuwana, M

2012-10-01

Antibodies against double-stranded DNA (dsDNA) are widely used to diagnose systemic lupus erythematosus (SLE) and evaluate its activity in patients. This study was undertaken to examine the clinical utility of circulating anti-dsDNA antibody-secreting cells for evaluating SLE patients. Anti-dsDNA antibody-secreting cells quantified using an enzyme-linked immunospot assay were detected in the spleen, bone marrow and peripheral blood from MRL/lpr but not in control BALB/c mice. Circulating anti-dsDNA antibody-secreting cells were detected in 29 (22%) of 130 patients with SLE, but in none of 49 with non-SLE connective-tissue disease or 18 healthy controls. The presence of circulating anti-dsDNA antibody-secreting cells was associated with persistent proteinuria, high SLE disease activity index and systemic lupus activity measures, and a high serum anti-dsDNA antibody titre measured with an enzyme-linked immunosorbent assay. The positive predictive value for active disease was 48% for circulating anti-dsDNA antibody-secreting cells versus 17% for serum anti-dsDNA antibodies. A prospective cohort of patients with circulating anti-dsDNA antibodies and inactive SLE showed that the cumulative disease flare-free rate was significantly lower in patients with than without circulating anti-dsDNA antibody-secreting cells (p < 0.001). Circulating anti-dsDNA antibody-secreting cells are a useful biomarker for assessing disease activity in SLE patients.

Visualizing double-stranded RNA distribution and dynamics in living cells by dsRNA binding-dependent fluorescence complementation

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

Cheng, Xiaofei; College of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou, Zhejiang 310036; Deng, Ping

Double-stranded RNA (dsRNA) is an important type of RNA that plays essential roles in diverse cellular processes in eukaryotic organisms and a hallmark in infections by positive-sense RNA viruses. Currently, no in vivo technology has been developed for visualizing dsRNA in living cells. Here, we report a dsRNA binding-dependent fluorescence complementation (dRBFC) assay that can be used to efficiently monitor dsRNA distribution and dynamics in vivo. The system consists of two dsRNA-binding proteins, which are fused to the N- and C-terminal halves of the yellow fluorescent protein (YFP). Binding of the two fusion proteins to a common dsRNA brings themore » split YFP halves in close proximity, leading to the reconstitution of the fluorescence-competent structure and restoration of fluorescence. Using this technique, we were able to visualize the distribution and trafficking of the replicative RNA intermediates of positive-sense RNA viruses in living cells. - Highlights: • A live-cell imaging system was developed for visualizing dsRNA in vivo. • It uses dsRNA binding proteins fused with two halves of a fluorescent protein. • Binding to a common dsRNA enables the reporter to become fluorescent. • The system can efficiently monitor viral RNA replication in living cells.« less

Polyamidoamine Dendrimer Conjugates with Cyclodextrins as Novel Carriers for DNA, shRNA and siRNA

PubMed Central

Arima, Hidetoshi; Motoyama, Keiichi; Higashi, Taishi

2012-01-01

Gene, short hairpin RNA (shRNA) and small interfering RNA (siRNA) delivery can be particularly used for the treatment of diseases by the entry of genetic materials mammalian cells either to express new proteins or to suppress the expression of proteins, respectively. Polyamidoamine (PAMAM) StarburstTM dendrimers are used as non-viral vectors (carriers) for gene, shRNA and siRNA delivery. Recently, multifunctional PAMAM dendrimers can be used for the wide range of biomedical applications including intracellular delivery of genes and nucleic acid drugs. In this context, this review paper provides the recent findings on PAMAM dendrimer conjugates with cyclodextrins (CyDs) for gene, shRNA and siRNA delivery. PMID:24300184

Gene Silencing in Adult Aedes aegypti Mosquitoes Through Oral Delivery of Double-Stranded RNA

DTIC Science & Technology

2012-01-01

utilization of dsRNA as a bio-insecticide against mosquitoes has only recently begun to be evaluated. Double-stranded RNA targeting chitin syn- thase...double- stranded RNA nanoparticle-mediated RNA interference to silence chitin synthase genes through larval feeding in the African malaria mosquito

Dietary supplements: physician knowledge and adverse event reporting.

PubMed

Cellini, Matthew; Attipoe, Selasi; Seales, Paul; Gray, Robert; Ward, Andrew; Stephens, Mark; Deuster, Patricia A

2013-01-01

Dietary supplement (DS) use among US military personnel is widespread. Many consume several different DS with multiple ingredients one or more times each week, representing a potential public health concern. The overall purpose of the study was to assess the knowledge and behaviors of health professionals and physicians regarding patterns of DS use and possible adverse events (AE) associated with DS use. We also determined how providers address the issue of DS with patients and evaluated provider knowledge regarding reporting systems. Two prospective, cross-sectional, web-based questionnaires were administered. First, health care providers who accessed the Natural Medicines Comprehensive Database to gather evidenced-based information on DS and herbal products were queried. Second, physicians who had graduated from the Uniformed Services University were sent a web-based questionnaire regarding DS knowledge, AE knowledge and reporting, and communication with patients about DS. The frequencies of responses were evaluated. Although 60% of the military physicians who responded to the questionnaires believed they had observed AE in association with a DS, only 18% actually reported them. Three of four physician respondents (approximately 73%) did not know how or where to report AE associated with DS. The majority of physicians (66%) routinely asked most of their patients about DS use, and 65% did not have a reliable source of information for herbal and DS products. Information gaps in DS information and AE reporting were identified. A centralized AE reporting system could serve to identify potentially harmful DS for further evaluation. Health professionals need to remain vigilant for AE associated with DS use and better informed on how to report these events.

Knockdown of nuclease activity in the gut enhances RNAi efficiency in the Colorado potato beetle, Leptinotarsa decemlineata, but not in the desert locust, Schistocerca gregaria.

PubMed

Spit, Jornt; Philips, Annelies; Wynant, Niels; Santos, Dulce; Plaetinck, Geert; Vanden Broeck, Jozef

2017-02-01

The responsiveness towards orally delivered dsRNA and the potency of a subsequent environmental RNA interference (RNAi) response strongly differs between different insect species. While some species are very sensitive to dsRNA delivery through the diet, others are not. The underlying reasons for this may vary, but degradation of dsRNA by nucleases in the gut lumen is believed to play a crucial role. The Colorado potato beetle, Leptinotarsa decemlineata, is a voracious defoliator of potato crops worldwide, and is currently under investigation for novel control methods based on dsRNA treatments. Here we describe the identification and characterization of two nuclease genes exclusively expressed in the gut of this pest species. Removal of nuclease activity in adults increased the sensitivity towards dsRNA and resulted in improved protection of potato plants. A similar strategy in the desert locust, Schistocerca gregaria, for which we show a far more potent nuclease activity in the gut juice, did however not lead to an improvement of the RNAi response. Possible reasons for this are discussed. Taken together, the present data confirm a negative effect of nucleases in the gut on the environmental RNAi response, and further suggest that interfering with this activity is a strategy worth pursuing for improving RNAi efficacy in insect pest control applications. Copyright © 2017 Elsevier Ltd. All rights reserved.

Prevention of autoimmune diabetes and islet allograft rejection by beta cell expression of XIAP: Insight into possible mechanisms of local immunomodulation.

PubMed

Obach, Mercè; Hosseini-Tabatabaei, Azadeh; Montane, Joel; Wind, Katarina; Soukhatcheva, Galina; Dai, Derek; Priatel, John J; Orban, Paul C; Verchere, C Bruce

2018-06-05

Overexpression of the X-linked inhibitor of apoptosis (XIAP) prevents islet allograft rejection. We constructed an adeno-associated virus expressing XIAP driven by the rat insulin promoter (dsAAV8-RIP-XIAP) for long-term beta-cell gene expression in vivo. Pancreatic delivery of dsAAV8-RIP-XIAP prevented autoimmune diabetes in 70% of non-obese diabetic (NOD) mice, associated with decreased insulitis. Islets from Balb/c mice transduced with dsAAV8-RIP-XIAP were protected following transplantation into streptozotocin (STZ)-diabetic Bl/6 recipients, associated with decreased graft infiltration. Interestingly, dsAAV8-RIP-XIAP transduction induced expression of lactate dehydrogenase (LDHA) and monocarboxylate transporter 1 (MCT1), two genes normally suppressed in beta cells and involved in production and release of lactate, a metabolite known to suppress local immune responses. Transduction of Balb/c islets with AAV8-RIP-LDHA-MCT1 tended to prolong allograft survival following transplant into STZ-diabetic Bl/6 recipients. These findings suggest that XIAP has therapeutic potential in autoimmune diabetes and raise the possibility that local lactate production may play a role in XIAP-mediated immunomodulation. Copyright © 2018. Published by Elsevier B.V.

Trust information-based privacy architecture for ubiquitous health.

PubMed

Ruotsalainen, Pekka Sakari; Blobel, Bernd; Seppälä, Antto; Nykänen, Pirkko

2013-10-08

Ubiquitous health is defined as a dynamic network of interconnected systems that offers health services independent of time and location to a data subject (DS). The network takes place in open and unsecure information space. It is created and managed by the DS who sets rules that regulate the way personal health information is collected and used. Compared to health care, it is impossible in ubiquitous health to assume the existence of a priori trust between the DS and service providers and to produce privacy using static security services. In ubiquitous health features, business goals and regulations systems followed often remain unknown. Furthermore, health care-specific regulations do not rule the ways health data is processed and shared. To be successful, ubiquitous health requires novel privacy architecture. The goal of this study was to develop a privacy management architecture that helps the DS to create and dynamically manage the network and to maintain information privacy. The architecture should enable the DS to dynamically define service and system-specific rules that regulate the way subject data is processed. The architecture should provide to the DS reliable trust information about systems and assist in the formulation of privacy policies. Furthermore, the architecture should give feedback upon how systems follow the policies of DS and offer protection against privacy and trust threats existing in ubiquitous environments. A sequential method that combines methodologies used in system theory, systems engineering, requirement analysis, and system design was used in the study. In the first phase, principles, trust and privacy models, and viewpoints were selected. Thereafter, functional requirements and services were developed on the basis of a careful analysis of existing research published in journals and conference proceedings. Based on principles, models, and requirements, architectural components and their interconnections were developed using system analysis. The architecture mimics the way humans use trust information in decision making, and enables the DS to design system-specific privacy policies using computational trust information that is based on systems' measured features. The trust attributes that were developed describe the level systems for support awareness and transparency, and how they follow general and domain-specific regulations and laws. The monitoring component of the architecture offers dynamic feedback concerning how the system enforces the polices of DS. The privacy management architecture developed in this study enables the DS to dynamically manage information privacy in ubiquitous health and to define individual policies for all systems considering their trust value and corresponding attributes. The DS can also set policies for secondary use and reuse of health information. The architecture offers protection against privacy threats existing in ubiquitous environments. Although the architecture is targeted to ubiquitous health, it can easily be modified to other ubiquitous applications.

Trust Information-Based Privacy Architecture for Ubiquitous Health

PubMed Central

2013-01-01

Background Ubiquitous health is defined as a dynamic network of interconnected systems that offers health services independent of time and location to a data subject (DS). The network takes place in open and unsecure information space. It is created and managed by the DS who sets rules that regulate the way personal health information is collected and used. Compared to health care, it is impossible in ubiquitous health to assume the existence of a priori trust between the DS and service providers and to produce privacy using static security services. In ubiquitous health features, business goals and regulations systems followed often remain unknown. Furthermore, health care-specific regulations do not rule the ways health data is processed and shared. To be successful, ubiquitous health requires novel privacy architecture. Objective The goal of this study was to develop a privacy management architecture that helps the DS to create and dynamically manage the network and to maintain information privacy. The architecture should enable the DS to dynamically define service and system-specific rules that regulate the way subject data is processed. The architecture should provide to the DS reliable trust information about systems and assist in the formulation of privacy policies. Furthermore, the architecture should give feedback upon how systems follow the policies of DS and offer protection against privacy and trust threats existing in ubiquitous environments. Methods A sequential method that combines methodologies used in system theory, systems engineering, requirement analysis, and system design was used in the study. In the first phase, principles, trust and privacy models, and viewpoints were selected. Thereafter, functional requirements and services were developed on the basis of a careful analysis of existing research published in journals and conference proceedings. Based on principles, models, and requirements, architectural components and their interconnections were developed using system analysis. Results The architecture mimics the way humans use trust information in decision making, and enables the DS to design system-specific privacy policies using computational trust information that is based on systems’ measured features. The trust attributes that were developed describe the level systems for support awareness and transparency, and how they follow general and domain-specific regulations and laws. The monitoring component of the architecture offers dynamic feedback concerning how the system enforces the polices of DS. Conclusions The privacy management architecture developed in this study enables the DS to dynamically manage information privacy in ubiquitous health and to define individual policies for all systems considering their trust value and corresponding attributes. The DS can also set policies for secondary use and reuse of health information. The architecture offers protection against privacy threats existing in ubiquitous environments. Although the architecture is targeted to ubiquitous health, it can easily be modified to other ubiquitous applications. PMID:25099213

Anti-nucleosome antibodies in patients with systemic lupus erythematosus: potential utility as a diagnostic tool and disease activity marker and its comparison with anti-dsDNA antibody.

PubMed

Saigal, Renu; Goyal, Laxmi Kant; Agrawal, Abhishek; Mehta, Archna; Mittal, Pradeep; Yadav, R N; Meena, P D; Wadhvani, Dilip

2013-06-01

To compare the utility of anti-nucleosome antibodies and anti-dsDNA antibodies in diagnosis of Systemic Lupus Erythematosus (SLE) and as a marker of disease activity. This is a hospital based observational study among 40 (37 females and 3 males) selected cases of SLE (> or = 4 ACR criteria) and 80 control. 40 cases of other systemic autoimmune disease (SAD) [e g. 29 cases of Rheumatoid arthritis, 4 cases of Systemic sclerosis/scleroderma, 4 cases of Sjögren syndrome, 3 cases of MCTD and 40 Healthy blood were taken as control. From each patient venous blood samples were collected and submitted for anti-nucleosome and anti-dsDNA antibodies assay by enzyme linked immunosorbent assay (ELISA). Anti-nucleosome antibodies were positive in 19 (47.5%) SLE, 02 (05%) other SAD and none of the healthy persons. Anti dsDNA antibodies were positive in 15 (37.5%) SLE patients, 07 (17.5%) other SAD and 01(2.5%) healthy persons. For diagnosis of SLE, sensitivity of anti-ds DNA and anti-nucleosome antibody was found to be 37.5% and 47.50% respectively. The specificity of anti-nucleosome was 100% and that of anti-dsDNA was 97.50%. So, anti-nucleosome antibody test is more specific and more sensitive for diagnosis of SLE than anti-dsDNA. When SLE cases were compared with SAD, sensitivity of anti-dsDNA and anti-nucleosome antibody, for diagnosis of SLE, found to be 37.50% and 47.50% respectively but the specificity of anti-nucleosome was 95% and that of anti-dsDNA was 82.50%. Both antibodies show positive correlation with SLEDAI score .The correlation coefficient was stronger for anti-dsDNA antibodies (r = +0.550, P = < .001) than anti-nucleosome antibodies (r = +0.332, P = < .05) CONCLUSIONS: Anti-nucleosome antibodies show higher positivity than anti-dsDNA antibodies among SLE than other SAD and healthy population. Anti-nucleosome antibodies are more sensitive and specific for the diagnosis of SLE than anti-dsDNA antibodies. Anti-nucleosome and anti-dsDNA both show positive correlation with SLEDAI. But anti-dsDNA antibodies show stronger correlation with SLEDAI than anti-nucleosome. So, anti-nucleosome antibodies can be used as an additional marker for diagnosis of SLE and SLE disease activity.

Plant insects and mites uptake double-stranded RNA upon its exogenous application on tomato leaves.

PubMed

Gogoi, Anupam; Sarmah, Nomi; Kaldis, Athanasios; Perdikis, Dionysios; Voloudakis, Andreas

2017-12-01

Exogenously applied double-stranded RNA (dsRNA) molecules onto tomato leaves, moved rapidly from local to systemic leaves and were uptaken by agricultural pests namely aphids, whiteflies and mites. Four small interfering RNAs, deriving from the applied dsRNA, were molecularly detected in plants, aphids and mites but not in whiteflies. Double-stranded RNA (dsRNA) acts as the elicitor molecule of the RNA silencing (RNA interference, RNAi), the endogenous and evolutionary conserved surveillance system present in all eukaryotes. DsRNAs and their subsequent degradation products, namely the small interfering RNAs (siRNAs), act in a sequence-specific manner to control gene expression. Exogenous application of dsRNAs onto plants elicits resistance against plant viruses. In the present work, exogenously applied dsRNA molecules, derived from Zucchini yellow mosaic virus (ZYMV) HC-Pro region, onto tomato plants were detected in aphids (Myzus persicae), whiteflies (Trialeurodes vaporariorum) and mites (Tetranychus urticae) that were fed on treated as well as systemic tomato leaves. Furthermore, four siRNAs, deriving from the dsRNA applied, were detected in tomato and the agricultural pests fed on treated tomato plants. More specifically, dsRNA was detected in agricultural pests at 3 and 10 dpt (days post treatment) in dsRNA-treated leaves and at 14 dpt in systemic leaves. In addition, using stem-loop RT-PCR, siRNAs were detected in agricultural pests at 3 and 10 dpt in aphids and mites. Surprisingly, in whiteflies carrying the applied dsRNA, siRNAs were not molecularly detected. Our results showed that, upon exogenous application of dsRNAs molecules, these moved rapidly within tomato and were uptaken by agricultural pests fed on treated tomato. As a result, this non-transgenic method has the potential to control important crop pests via RNA silencing of vital genes of the respective pests.

Polyelectrolyte Multilayer Film Coated Silver Nanorods: An Effective Carrier System for Externally Activated Drug Delivery

NASA Astrophysics Data System (ADS)

Paramasivam, Gokul; Sharma, Varsha; Sundaramurthy, Anandhakumar

2017-08-01

Nanoparticle anisotropy offers unique functions and features in comparison with spherical nanoparticles (NPs) and makes anisotropic nanoparticles (ANPs) promising candidates in applications like drug delivery, imaging, biosensing and theranostics. Presence of surface active groups (e.g. amine, and carboxylate groups) on their surface provides binding sites for ligands or other biomolecules, and hence, this could be targeted for specific part or cells in our body. In the quest of such surface modification, functionalization of ANPs along Layer-by-Layer (LbL) coating of oppositely charged polyelectrolytes (PE) reduces cellular toxicity and promotes easy encapsulation of drugs. In this work, we report the silver nanorods (AgNRs) synthesis by adsorbate directed synthetic approach using cetyltrimethyl ammonium bromide (CTAB). The formed ANPs is investigated by scanning electron microscopy (SEM) and UV-Visible (UV-Vis) spectroscopy revealing the shaping of AgNRs of 3-16 nm aspect ratio with some presence of triangles. These NRs were further coated with bio polymers of chitosan (CH) and dextran sulphate (DS) through LbL approach and used for encapsulation of water soluble anti-bacterial drugs like ciprofloxacin hydrochloride (CFH). The encapsulation of drugs and profiles of drug release were investigated and compared to that of spherical silver nanoparticles (AgNPs). The added advantages of the proposed drug delivery system (DDS) can be externally activated to release the loaded drug and used as contrast agents for biological imaging under exposure to NIR light. Such system shows unique and attractive characteristics required for drug delivery and bioimaging thus offering the scope for further development as theranostic material.

Interference Rejection and Management

DTIC Science & Technology

2009-07-01

performance of a DS CDMA receiver. And it was shown in [34] that in order to successfully have a CDMA system overlay narrowband users, i.e., to deploy... CDMA transmitters and the CDMA receivers. 9.2.1.2 Multicarrier Direct Sequence In a multicarrier DS system, multiple narrowband DS waveforms, each at...1)] mmax(i−1) m=mmin(i−1) Detection of the (i−1)th path Pi,Di Pi−1,Di−1 channel estimator \\ data detector Fig. 9.1 Low-pass equivalent of the DS / CDMA

Assessment of long-term transgene expression in barley: Ds-mediated delivery of bar results in robust, stable, and heritable expression

USDA-ARS?s Scientific Manuscript database

The utility of transgenic plants for both experimental and practical agronomic purposes is highly dependent on stable, predictable, and heritable expression of the introduced genes. This requirement is frequently unfulfilled, and transgenes are frequently subject to silencing. Studies of the charact...

Differential Genetic Associations for Systemic Lupus Erythematosus Based on Anti–dsDNA Autoantibody Production

PubMed Central

Chung, Sharon A.; Taylor, Kimberly E.; Graham, Robert R.; Nititham, Joanne; Lee, Annette T.; Ortmann, Ward A.; Jacob, Chaim O.; Alarcón-Riquelme, Marta E.; Tsao, Betty P.; Harley, John B.; Gaffney, Patrick M.; Moser, Kathy L.; Petri, Michelle; Demirci, F. Yesim; Kamboh, M. Ilyas; Manzi, Susan; Gregersen, Peter K.; Langefeld, Carl D.; Behrens, Timothy W.; Criswell, Lindsey A.

2011-01-01

Systemic lupus erythematosus (SLE) is a clinically heterogeneous, systemic autoimmune disease characterized by autoantibody formation. Previously published genome-wide association studies (GWAS) have investigated SLE as a single phenotype. Therefore, we conducted a GWAS to identify genetic factors associated with anti–dsDNA autoantibody production, a SLE–related autoantibody with diagnostic and clinical importance. Using two independent datasets, over 400,000 single nucleotide polymorphisms (SNPs) were studied in a total of 1,717 SLE cases and 4,813 healthy controls. Anti–dsDNA autoantibody positive (anti–dsDNA +, n = 811) and anti–dsDNA autoantibody negative (anti–dsDNA –, n = 906) SLE cases were compared to healthy controls and to each other to identify SNPs associated specifically with these SLE subtypes. SNPs in the previously identified SLE susceptibility loci STAT4, IRF5, ITGAM, and the major histocompatibility complex were strongly associated with anti–dsDNA + SLE. Far fewer and weaker associations were observed for anti–dsDNA – SLE. For example, rs7574865 in STAT4 had an OR for anti–dsDNA + SLE of 1.77 (95% CI 1.57–1.99, p = 2.0E-20) compared to an OR for anti–dsDNA – SLE of 1.26 (95% CI 1.12–1.41, p = 2.4E-04), with pheterogeneity<0.0005. SNPs in the SLE susceptibility loci BANK1, KIAA1542, and UBE2L3 showed evidence of association with anti–dsDNA + SLE and were not associated with anti–dsDNA – SLE. In conclusion, we identified differential genetic associations with SLE based on anti–dsDNA autoantibody production. Many previously identified SLE susceptibility loci may confer disease risk through their role in autoantibody production and be more accurately described as autoantibody propensity loci. Lack of strong SNP associations may suggest that other types of genetic variation or non-genetic factors such as environmental exposures have a greater impact on susceptibility to anti–dsDNA – SLE. PMID:21408207

Design and assembly of new non-viral RNAi delivery agents by microwave-assisted quaternization (MAQ) of tertiary amines

PubMed Central

Ghosh, Animesh; Mukherjee, Koushik; Jiang, Xinpeng; Zhou, Ying; McCarroll, Joshua; Qu, James; Swain, Pamela M.; Baigude, Huricha; Rana, Tariq M.

2010-01-01

RNA interference (RNAi), a gene-silencing phenomenon whereby double-stranded RNA (dsRNA) triggers the sequence-specific degradation of homologous mRNA. RNAi has been quickly and widely applied to discover gene functions and holds great potential to provide a new class of therapeutic agents. However, new chemistry and delivery approaches are greatly needed to silence disease-causing genes without toxic effects. We reasoned that conjugation of the cholesterol moiety to cationic lipids would enhance RNAi efficiencies and lower the toxic effects of lipid-mediated RNAi delivery. Here, we report the first design and synthesis of new cholesterol-conjugated cationic lipids for RNAi delivery using microwave-assisted quaternization (MAQ) of tertiary amines. This strategy can be employed to develop new classes of non-viral gene delivery agents under safe and fast reaction conditions. PMID:20722369

76 FR 16850 - 60-Day Notice of Proposed Information Collection: Agency Form DS-4127, NEA/PI Online Performance...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-25

... Form DS- 4127, NEA/PI Online Performance Reporting System (PRS), OMB Control Number 1405-0183. ACTION... Collection: NEA/PI Online Performance Reporting System (PRS). OMB Control Number: 1405-0183. Type of Request: Renewal. Originating Office: NEA/PI. Form Number: DS-4127. Respondents: Recipients of NEA/PI grants...

Performance of Improved Channel Allocation for Multicarrier CDMA with Adaptive Frequency Hopping and Multiuser Detection

DTIC Science & Technology

2008-08-29

resulting in much larger system capacity than for a non-adaptive MC direct-sequence ( DS )- CDMA system. This conclusion is confirmed for realistic fading...system capacity than for a non-adaptive MC direct-sequence ( DS )- CDMA system. This conclusion is confirmed for realistic fading channels with correlated...transmission method exploits both frequency and multiuser diversity and improves on non-adaptive MC DS - CDMA sys- tems in [6]. In this paper, we focus on the

Down syndrome screening in assisted conception twins: an iatrogenic medical challenge.

PubMed

Ben-Ami, Ido; Maymon, Ron; Svirsky, Ran; Cuckle, Howard; Jauniaux, Eric

2013-11-01

The objective of this study was to provide a critical analysis of the impact of assisted conception on prenatal screening for Down syndrome (DS) in twin pregnancies and the value of various screening modalities for early detection of anomalies. The literature was searched using PubMed and the Cochrane Library focusing on prenatal screening and antenatal care of assisted-conception twin pregnancies. Serum screening alone is of limited value in detecting aneuploid twins, because the unaffected cotwin can "mask" the abnormal serum results of an affected one. In addition, this test can designate the pregnancy as at high risk but not identify the affected fetus. Nuchal translucency (NT) screening is the best available modality and a highly effective screening method for twin pregnancies. Among twins, NT alone has a 69% DS detection rate, first-trimester combined NT and serum biochemistry has a 72% DS detection rate, and an integrated screen will have an 80% DS detection rate at a 5% FPR. The data in the literature concerning the effect of assisted conception on maternal serum screening markers in twin pregnancies are scarce. Down syndrome screening in assisted-conception twins presents clinical and technical challenges. Therefore, assisted-conception twins need close monitoring from conception to delivery, by a practitioner familiar with the available screening modalities and their relative accuracy.

Associated congenital anomalies among cases with Down syndrome.

PubMed

Stoll, Claude; Dott, Beatrice; Alembik, Yves; Roth, Marie-Paule

2015-12-01

Down syndrome (DS) is the most common congenital anomaly widely studied for at least 150 years. However, the type and the frequency of congenital anomalies associated with DS are still controversial. Despite prenatal diagnosis and elective termination of pregnancy for fetal anomalies, in Europe, from 2008 to 2012 the live birth prevalence of DS per 10,000 was 10. 2. The objectives of this study were to examine the major congenital anomalies occurring in infants and fetuses with Down syndrome. The material for this study came from 402,532 consecutive pregnancies of known outcome registered by our registry of congenital anomalies between 1979 and 2008. Four hundred sixty seven (64%) out of the 728 cases with DS registered had at least one major associated congenital anomaly. The most common associated anomalies were cardiac anomalies, 323 cases (44%), followed by digestive system anomalies, 42 cases (6%), musculoskeletal system anomalies, 35 cases (5%), urinary system anomalies, 28 cases (4%), respiratory system anomalies, 13 cases (2%), and other system anomalies, 26 cases (3.6%). Among the cases with DS with congenital heart defects, the most common cardiac anomaly was atrioventricular septal defect (30%) followed by atrial septum defect (25%), ventricular septal defect (22%), patent ductus arteriosus (5%), coarctation of aorta (5%), and tetralogy of Fallot (3%). Among the cases with DS with a digestive system anomaly recorded, duodenal atresia (67%), Hirschsprung disease (14%), and tracheo-esophageal atresia (10%) were the most common. Fourteen (2%) of the cases with DS had an obstructive anomaly of the renal pelvis, including hydronephrosis. The other most common anomalies associated with cases with DS were syndactyly, club foot, polydactyly, limb reduction, cataract, hydrocephaly, cleft palate, hypospadias and diaphragmatic hernia. Many studies to assess the anomalies associated with DS have reported various results. There is no agreement in the literature as to which associated anomalies are most common in cases with DS with associated anomalies. In this study we observed a higher percentage of associated anomalies than in the other reported series as well as an increase in the incidence of duodenal atresia, urinary system anomalies, musculoskeletal system anomalies, and respiratory system anomalies, and a decrease in the incidence of anal atresia, annular pancreas, and limb reduction defects. In conclusion, we observed a high prevalence of total congenital anomalies and specific patterns of malformations associated with Down syndrome which emphasizes the need to evaluate carefully all cases with Down syndrome for possible associated major congenital anomalies. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

A proto-architecture for innate directionally selective visual maps.

PubMed

Adams, Samantha V; Harris, Chris M

2014-01-01

Self-organizing artificial neural networks are a popular tool for studying visual system development, in particular the cortical feature maps present in real systems that represent properties such as ocular dominance (OD), orientation-selectivity (OR) and direction selectivity (DS). They are also potentially useful in artificial systems, for example robotics, where the ability to extract and learn features from the environment in an unsupervised way is important. In this computational study we explore a DS map that is already latent in a simple artificial network. This latent selectivity arises purely from the cortical architecture without any explicit coding for DS and prior to any self-organising process facilitated by spontaneous activity or training. We find DS maps with local patchy regions that exhibit features similar to maps derived experimentally and from previous modeling studies. We explore the consequences of changes to the afferent and lateral connectivity to establish the key features of this proto-architecture that support DS.

Design and implementation of a 38 kW dish-Stirling concentrated solar power system

NASA Astrophysics Data System (ADS)

Yan, J.; Peng, Y. D.; Cheng, Z. R.; Liu, F. M.; Tang, X. H.

2017-11-01

Dish-Stirling concentrated solar power system (DS-CSP) is an important pathway for converting solar energy into electricity at high efficiency. In this study, a rated power 38 kW DS-CSP system was developed (installed in Xiangtan Electric Manufacturing Group). The heat engine adopted the alpha-type four cylinders double-acting Stirling engine (Stirling Biopower Flexgen S260). The absorber flux distribution simulation was conducted using ray tracing method and then the 204 m2 parabolic dish concentrator system (diameter is 17.70 m and focal length is 9.49 m) with single concentrator plus single pillar supporting has been designed and built. A water-cooled disc target and an absorber imitation device were adopted to test the tracking performance of the dish concentrator system, homogeneity of the focal spot and flux distribution of the absorber. Finally, the S260 Stirling engine was installed on the focal position of the dish concentrator and then the net output power date of the 38 kW DS-CSP system was tested. The absorber overheating problem on the DS-CSP system performance was discussed when the DS-CSP system was installed in different locations. The testing result shows that this system achieved the net output power of 38 kW and solar-to-electricity efficiency (SEE) of 25.3% with the direct normal irradiation (DNI) at 750 W/m2. The net output power can further increase to 40.5 kW with the SEE of 26.6% when the DNI reaches up to the maximum of 761 W/m2. The net output power of the 38 kW DS-CSP system has a linear function relationship with the DNI. The fitting function is Net power output=0.1003×DNI－36.129, where DNI is at the range of 460∼761 W/m2. This function could be used to predict the amount of the 38 kW DS-CSP system annual generation power.

High-solids anaerobic co-digestion of sewage sludge and food waste in comparison with mono digestions: stability and performance.

PubMed

Dai, Xiaohu; Duan, Nina; Dong, Bin; Dai, Lingling

2013-02-01

System stability and performance of high-solids anaerobic co-digestion of dewatered sludge (DS) and food waste (FW) in comparison with mono digestions were investigated. System stability was improved in co-digestion systems with co-substrate acting as a diluting agent to toxic chemicals like ammonia or Na(+). For high-solids digestion of DS, the addition of FW not only improved system stability but also greatly enhanced volumetric biogas production. For high-solids digestion of FW, the addition of DS could reduce Na(+) concentration and help maintain satisfactory stability during the conversion of FW into biogas. System performances of co-digestion systems were mainly determined by the mixing ratios of DS and FW. Biogas production and volatile solids (VSs) reduction in digestion of the co-mixture of DS and FW increased linearly with higher ratios of FW. A kinetic model, which aimed to forecast the performance of co-digestion and to assist reactor design, was developed from long-term semi-continuous experiments. Maximum VS reduction for DS and FW was estimated to be 44.3% and 90.3%, respectively, and first order constant k was found to be 0.17d(-1) and 0.50 d(-1), respectively. Experimental data of co-digestion were in good conformity to the predictions of the model. Copyright © 2012 Elsevier Ltd. All rights reserved.

Neural correlates of reward processing in adults with 22q11 deletion syndrome.

PubMed

van Duin, Esther D A; Goossens, Liesbet; Hernaus, Dennis; da Silva Alves, Fabiana; Schmitz, Nicole; Schruers, Koen; van Amelsvoort, Therese

2016-01-01

22q11.2 deletion syndrome (22q11DS) is caused by a microdeletion on chromosome 22q11.2 and associated with an increased risk to develop psychosis. The gene coding for catechol-O-methyl-transferase (COMT) is located at the deleted region, resulting in disrupted dopaminergic neurotransmission in 22q11DS, which may contribute to the increased vulnerability for psychosis. A dysfunctional motivational reward system is considered one of the salient features in psychosis and thought to be related to abnormal dopaminergic neurotransmission. The functional anatomy of the brain reward circuitry has not yet been investigated in 22q11DS. This study aims to investigate neural activity during anticipation of reward and loss in adult patients with 22q11DS. We measured blood-oxygen-level dependent (BOLD) activity in 16 patients with 22q11DS and 12 healthy controls during a monetary incentive delay task using a 3T Philips Intera MRI system. Data were analysed using SPM8. During anticipation of reward, the 22q11DS group alone displayed significant activation in bilateral middle frontal and temporal brain regions. Compared to healthy controls, significantly less activation in bilateral cingulate gyrus extending to premotor, primary motor and somatosensory areas was found. During anticipation of loss, the 22q11DS group displayed activity in the left middle frontal gyrus and anterior cingulate cortex, and relative to controls, they showed reduced brain activation in bilateral (pre)cuneus and left posterior cingulate. Within the 22q11DS group, COMT Val hemizygotes displayed more activation compared to Met hemizygotes in right posterior cingulate and bilateral parietal regions during anticipation of reward. During anticipation of loss, COMT Met hemizygotes compared to Val hemizygotes showed more activation in bilateral insula, striatum and left anterior cingulate. This is the first study to investigate reward processing in 22q11DS. Our preliminary results suggest that people with 22q11DS engage a fronto-temporal neural network. Compared to healthy controls, people with 22q11DS primarily displayed reduced activity in medial frontal regions during reward anticipation. COMT hemizygosity affects responsivity of the reward system in this condition. Alterations in reward processing partly underlain by the dopamine system may play a role in susceptibility for psychosis in 22q11DS.

Study of the Decay Bs0→Ds(*)Ds(*)

NASA Astrophysics Data System (ADS)

Abazov, V. M.; Abbott, B.; Abolins, M.; Acharya, B. S.; Adams, M.; Adams, T.; Aguilo, E.; Ahn, S. H.; Ahsan, M.; Alexeev, G. D.; Alkhazov, G.; Alton, A.; Alverson, G.; Alves, G. A.; Anastasoaie, M.; Ancu, L. S.; Andeen, T.; Anderson, S.; Andrieu, B.; Anzelc, M. S.; Arnoud, Y.; Arov, M.; Askew, A.; Åsman, B.; Assis Jesus, A. C. S.; Atramentov, O.; Autermann, C.; Avila, C.; Ay, C.; Badaud, F.; Baden, A.; Bagby, L.; Baldin, B.; Bandurin, D. V.; Banerjee, P.; Banerjee, S.; Barberis, E.; Barfuss, A.-F.; Bargassa, P.; Baringer, P.; Barreto, J.; Bartlett, J. F.; Bassler, U.; Bauer, D.; Beale, S.; Bean, A.; Begalli, M.; Begel, M.; Belanger-Champagne, C.; Bellantoni, L.; Bellavance, A.; Benitez, J. A.; Beri, S. B.; Bernardi, G.; Bernhard, R.; Berntzon, L.; Bertram, I.; Besançon, M.; Beuselinck, R.; Bezzubov, V. A.; Bhat, P. C.; Bhatnagar, V.; Binder, M.; Biscarat, C.; Blazey, G.; Blekman, F.; Blessing, S.; Bloch, D.; Bloom, K.; Boehnlein, A.; Boline, D.; Bolton, T. A.; Borissov, G.; Bos, K.; Bose, T.; Brandt, A.; Brock, R.; Brooijmans, G.; Bross, A.; Brown, D.; Buchanan, N. J.; Buchholz, D.; Buehler, M.; Buescher, V.; Burdin, S.; Burke, S.; Burnett, T. H.; Busato, E.; Buszello, C. P.; Butler, J. M.; Calfayan, P.; Calvet, S.; Cammin, J.; Caron, S.; Carvalho, W.; Casey, B. C. K.; Cason, N. M.; Castilla-Valdez, H.; Chakrabarti, S.; Chakraborty, D.; Chan, K.; Chan, K. M.; Chandra, A.; Charles, F.; Cheu, E.; Chevallier, F.; Cho, D. K.; Choi, S.; Choudhary, B.; Christofek, L.; Christoudias, T.; Cihangir, S.; Claes, D.; Clément, B.; Clément, C.; Coadou, Y.; Cooke, M.; Cooper, W. E.; Corcoran, M.; Couderc, F.; Cousinou, M.-C.; Crépé-Renaudin, S.; Cutts, D.; Ćwiok, M.; da Motta, H.; Das, A.; Davies, G.; de, K.; de Jong, P.; de Jong, S. J.; de La Cruz-Burelo, E.; de Oliveira Martins, C.; Degenhardt, J. D.; Déliot, F.; Demarteau, M.; Demina, R.; Denisov, D.; Denisov, S. P.; Desai, S.; Diehl, H. T.; Diesburg, M.; Dominguez, A.; Dong, H.; Dudko, L. V.; Duflot, L.; Dugad, S. R.; Duggan, D.; Duperrin, A.; Dyer, J.; Dyshkant, A.; Eads, M.; Edmunds, D.; Ellison, J.; Elvira, V. D.; Enari, Y.; Eno, S.; Ermolov, P.; Evans, H.; Evdokimov, A.; Evdokimov, V. N.; Ferapontov, A. V.; Ferbel, T.; Fiedler, F.; Filthaut, F.; Fisher, W.; Fisk, H. E.; Ford, M.; Fortner, M.; Fox, H.; Fu, S.; Fuess, S.; Gadfort, T.; Galea, C. F.; Gallas, E.; Galyaev, E.; Garcia, C.; Garcia-Bellido, A.; Gavrilov, V.; Gay, P.; Geist, W.; Gelé, D.; Gerber, C. E.; Gershtein, Y.; Gillberg, D.; Ginther, G.; Gollub, N.; Gómez, B.; Goussiou, A.; Grannis, P. D.; Greenlee, H.; Greenwood, Z. D.; Gregores, E. M.; Grenier, G.; Gris, Ph.; Grivaz, J.-F.; Grohsjean, A.; Grünendahl, S.; Grünewald, M. W.; Guo, F.; Guo, J.; Gutierrez, G.; Gutierrez, P.; Haas, A.; Hadley, N. J.; Haefner, P.; Hagopian, S.; Haley, J.; Hall, I.; Hall, R. E.; Han, L.; Hanagaki, K.; Hansson, P.; Harder, K.; Harel, A.; Harrington, R.; Hauptman, J. M.; Hauser, R.; Hays, J.; Hebbeker, T.; Hedin, D.; Hegeman, J. G.; Heinmiller, J. M.; Heinson, A. P.; Heintz, U.; Hensel, C.; Herner, K.; Hesketh, G.; Hildreth, M. D.; Hirosky, R.; Hobbs, J. D.; Hoeneisen, B.; Hoeth, H.; Hohlfeld, M.; Hong, S. J.; Hooper, R.; Houben, P.; Hu, Y.; Hubacek, Z.; Hynek, V.; Iashvili, I.; Illingworth, R.; Ito, A. S.; Jabeen, S.; Jaffré, M.; Jain, S.; Jakobs, K.; Jarvis, C.; Jesik, R.; Johns, K.; Johnson, C.; Johnson, M.; Jonckheere, A.; Jonsson, P.; Juste, A.; Käfer, D.; Kahn, S.; Kajfasz, E.; Kalinin, A. M.; Kalk, J. M.; Kalk, J. R.; Kappler, S.; Karmanov, D.; Kasper, J.; Kasper, P.; Katsanos, I.; Kau, D.; Kaur, R.; Kaushik, V.; Kehoe, R.; Kermiche, S.; Khalatyan, N.; Khanov, A.; Kharchilava, A.; Kharzheev, Y. M.; Khatidze, D.; Kim, H.; Kim, T. J.; Kirby, M. H.; Klima, B.; Kohli, J. M.; Konrath, J.-P.; Kopal, M.; Korablev, V. M.; Kotcher, J.; Kothari, B.; Koubarovsky, A.; Kozelov, A. V.; Krop, D.; Kryemadhi, A.; Kuhl, T.; Kumar, A.; Kunori, S.; Kupco, A.; Kurča, T.; Kvita, J.; Lam, D.; Lammers, S.; Landsberg, G.; Lazoflores, J.; Lebrun, P.; Lee, W. M.; Leflat, A.; Lehner, F.; Lesne, V.; Leveque, J.; Lewis, P.; Li, J.; Li, L.; Li, Q. Z.; Lietti, S. M.; Lima, J. G. R.; Lincoln, D.; Linnemann, J.; Lipaev, V. V.; Lipton, R.; Liu, Z.; Lobo, L.; Lobodenko, A.; Lokajicek, M.; Lounis, A.; Love, P.; Lubatti, H. J.; Lynker, M.; Lyon, A. L.; Maciel, A. K. A.; Madaras, R. J.; Mättig, P.; Magass, C.; Magerkurth, A.; Makovec, N.; Mal, P. K.; Malbouisson, H. B.; Malik, S.; Malyshev, V. L.; Mao, H. S.; Maravin, Y.; Martin, B.; McCarthy, R.; Melnitchouk, A.; Mendes, A.; Mendoza, L.; Mercadante, P. G.; Merkin, M.; Merritt, K. W.; Meyer, A.; Meyer, J.; Michaut, M.; Miettinen, H.; Millet, T.; Mitrevski, J.; Molina, J.; Mommsen, R. K.; Mondal, N. K.; Monk, J.; Moore, R. W.; Moulik, T.; Muanza, G. S.; Mulders, M.; Mulhearn, M.; Mundal, O.; Mundim, L.; Nagy, E.; Naimuddin, M.; Narain, M.; Naumann, N. A.; Neal, H. A.; Negret, J. P.; Neustroev, P.; Nilsen, H.; Noeding, C.; Nomerotski, A.; Novaes, S. F.; Nunnemann, T.; O'Dell, V.; O'Neil, D. C.; Obrant, G.; Ochando, C.; Oguri, V.; Oliveira, N.; Onoprienko, D.; Oshima, N.; Osta, J.; Otec, R.; Otero Y Garzón, G. J.; Owen, M.; Padley, P.; Pangilinan, M.; Parashar, N.; Park, S.-J.; Park, S. K.; Parsons, J.; Partridge, R.; Parua, N.; Patwa, A.; Pawloski, G.; Perea, P. M.; Peters, K.; Peters, Y.; Pétroff, P.; Petteni, M.; Piegaia, R.; Piper, J.; Pleier, M.-A.; Podesta-Lerma, P. L. M.; Podstavkov, V. M.; Pogorelov, Y.; Pol, M.-E.; Pompoš, A.; Pope, B. G.; Popov, A. V.; Potter, C.; Prado da Silva, W. L.; Prosper, H. B.; Protopopescu, S.; Qian, J.; Quadt, A.; Quinn, B.; Rangel, M. S.; Rani, K. J.; Ranjan, K.; Ratoff, P. N.; Renkel, P.; Reucroft, S.; Rijssenbeek, M.; Ripp-Baudot, I.; Rizatdinova, F.; Robinson, S.; Rodrigues, R. F.; Royon, C.; Rubinov, P.; Ruchti, R.; Sajot, G.; Sánchez-Hernández, A.; Sanders, M. P.; Santoro, A.; Savage, G.; Sawyer, L.; Scanlon, T.; Schaile, D.; Schamberger, R. D.; Scheglov, Y.; Schellman, H.; Schieferdecker, P.; Schmitt, C.; Schwanenberger, C.; Schwartzman, A.; Schwienhorst, R.; Sekaric, J.; Sengupta, S.; Severini, H.; Shabalina, E.; Shamim, M.; Shary, V.; Shchukin, A. A.; Shivpuri, R. K.; Shpakov, D.; Siccardi, V.; Sidwell, R. A.; Simak, V.; Sirotenko, V.; Skubic, P.; Slattery, P.; Smirnov, D.; Smith, R. P.; Snow, G. R.; Snow, J.; Snyder, S.; Söldner-Rembold, S.; Sonnenschein, L.; Sopczak, A.; Sosebee, M.; Soustruznik, K.; Souza, M.; Spurlock, B.; Stark, J.; Steele, J.; Stolin, V.; Stoyanova, D. A.; Strandberg, J.; Strandberg, S.; Strang, M. A.; Strauss, M.; Ströhmer, R.; Strom, D.; Strovink, M.; Stutte, L.; Sumowidagdo, S.; Svoisky, P.; Sznajder, A.; Talby, M.; Tamburello, P.; Tanasijczuk, A.; Taylor, W.; Telford, P.; Temple, J.; Tiller, B.; Tissandier, F.; Titov, M.; Tokmenin, V. V.; Tomoto, M.; Toole, T.; Torchiani, I.; Trefzger, T.; Trincaz-Duvoid, S.; Tsybychev, D.; Tuchming, B.; Tully, C.; Tuts, P. M.; Unalan, R.; Uvarov, L.; Uvarov, S.; Uzunyan, S.; Vachon, B.; van den Berg, P. J.; van Eijk, B.; van Kooten, R.; van Leeuwen, W. M.; Varelas, N.; Varnes, E. W.; Vartapetian, A.; Vasilyev, I. A.; Vaupel, M.; Verdier, P.; Vertogradov, L. S.; Verzocchi, M.; Villeneuve-Seguier, F.; Vint, P.; Vlimant, J.-R.; von Toerne, E.; Voutilainen, M.; Vreeswijk, M.; Wahl, H. D.; Walder, J.; Wang, L.; Wang, M. H. L. S.; Warchol, J.; Watts, G.; Wayne, M.; Weber, G.; Weber, M.; Weerts, H.; Wenger, A.; Wermes, N.; Wetstein, M.; White, A.; Wicke, D.; Wilson, G. W.; Wimpenny, S. J.; Wobisch, M.; Wood, D. R.; Wyatt, T. R.; Xie, Y.; Yacoob, S.; Yamada, R.; Yan, M.; Yasuda, T.; Yatsunenko, Y. A.; Yip, K.; Yoo, H. D.; Youn, S. W.; Yu, C.; Yu, J.; Yurkewicz, A.; Zatserklyaniy, A.; Zeitnitz, C.; Zhang, D.; Zhao, T.; Zhou, B.; Zhu, J.; Zielinski, M.; Zieminska, D.; Zieminski, A.; Zutshi, V.; Zverev, E. G.

2007-12-01

We report a study of the decay Bs0→Ds(*)Ds(*) using a data sample corresponding to 1.3fb-1 of integrated luminosity collected by the D0 experiment in 2002 2006 during run II of the Fermilab Tevatron collider. One Ds(*) meson was partially reconstructed in the decay Ds→ϕμν, and the other Ds(*) meson was identified using the decay Ds→ϕπ where no attempt was made to distinguish Ds and Ds* states. For the branching fraction Br(Bs0→Ds(*)Ds(*)) we obtain a 90% C.L. range [0.002,0.080] and central value 0.039-0.017+0.019(stat)-0.015+0.016(syst). This was subsequently used to make the most precise estimate of the width difference ΔΓsCP in the Bs0-B¯s0 system: ΔΓsCP/Γs=0.079-0.035+0.038(stat)-0.030+0.031(syst).

Social Inclusion of Children With Down Syndrome: Jewish and Muslim Mothers' Knowledge, Attitudes, Beliefs, and Behavioral Intentions.

PubMed

Barnoy, Sivia; Biton, Anna; Itzhaki, Michal

The current study examined mothers' knowledge, beliefs, attitudes, and intention to socially integrate children with Down syndrome (DS) in the family, with children without disabilities and school system. A questionnaire based on a descriptive, cross-sectional design was administered to Jewish and Muslim mothers. The questionnaire included demographics, knowledge, beliefs, attitudes, and intention to integrate children with DS. Analysis included a regression test of intention to integrate children with DS and a one-way ANOVA for differences between Jewish and Muslim mothers. Nearly all the Jewish mothers (93.7%) and about half the Muslim mothers (52.8%) had performed screening tests for DS during their pregnancy. All mothers displayed low knowledge level about DS. Being Jewish (t=2.89; p=0.005) and holding more positive beliefs (t=3.39; p=0.001) were associated with a higher intention to socially integrate children with DS. Significant positive correlations were found between beliefs and attitudes (r=0.65; p<0.001) and between attitudes and intention to socially integrate children with DS (r=0.39; p<0.001). This study shows that Jewish and Muslim mothers' beliefs and attitudes towards social inclusion of children with DS are quite positive and the intention to integrate children with DS in the family, with children without disabilities, and in the mainstream school system is high. However, their level of knowledge about DS is low. Nurses, as a critical source of information about DS, should develop an ethno-cultural sensitivity to diverse populations in order to influence attitudes and beliefs regarding the social integration of children with DS. Copyright © 2017 Elsevier Inc. All rights reserved.

Redox proteomics analysis of HNE-modified proteins in Down syndrome brain: clues for understanding the development of Alzheimer disease.

PubMed

Di Domenico, Fabio; Pupo, Gilda; Tramutola, Antonella; Giorgi, Alessandra; Schininà, Maria Eugenia; Coccia, Raffaella; Head, Elizabeth; Butterfield, D Allan; Perluigi, Marzia

2014-06-01

Down syndrome (DS) is the most common genetic cause of intellectual disability, due to partial or complete triplication of chromosome 21. DS subjects are characterized by a number of abnormalities including premature aging and development of Alzheimer disease (AD) neuropathology after approximately 40 years of age. Several studies show that oxidative stress plays a crucial role in the development of neurodegeneration in the DS population. Increased lipid peroxidation is one of the main events causing redox imbalance within cells through the formation of toxic aldehydes that easily react with DNA, lipids, and proteins. In this study we used a redox proteomics approach to identify specific targets of 4-hydroxynonenal modifications in the frontal cortex from DS cases with and without AD pathology. We suggest that a group of identified proteins followed a specific pattern of oxidation in DS vs young controls, probably indicating characteristic features of the DS phenotype; a second group of identified proteins showed increased oxidation in DS/AD vs DS, thus possibly playing a role in the development of AD. The third group of comparison, DS/AD vs old controls, identified proteins that may be considered specific markers of AD pathology. All the identified proteins are involved in important biological functions including intracellular quality control systems, cytoskeleton network, energy metabolism, and antioxidant response. Our results demonstrate that oxidative damage is an early event in DS, as well as dysfunctions of protein-degradation systems and cellular protective pathways, suggesting that DS subjects are more vulnerable to oxidative damage accumulation that might contribute to AD development. Further, considering that the majority of proteins have been already demonstrated to be oxidized in AD brain, our results strongly support similarities with AD in DS. Copyright © 2014 Elsevier Inc. All rights reserved.

48 CFR 653.219-70 - DOS form DS-1910, Small Business Agency Review-Actions Above the Simplified Acquisition Threshold.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false DOS form DS-1910, Small Business Agency Review-Actions Above the Simplified Acquisition Threshold. 653.219-70 Section 653.219-70 Federal Acquisition Regulations System DEPARTMENT OF STATE CLAUSES AND FORMS FORMS Prescription of Forms 653.219-70 DOS form DS-1910, Small...

48 CFR 653.219-70 - DOS form DS-1910, Small Business Agency Review-Actions Above the Simplified Acquisition Threshold.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 4 2011-10-01 2011-10-01 false DOS form DS-1910, Small Business Agency Review-Actions Above the Simplified Acquisition Threshold. 653.219-70 Section 653.219-70 Federal Acquisition Regulations System DEPARTMENT OF STATE CLAUSES AND FORMS FORMS Prescription of Forms 653.219-70 DOS form DS-1910, Small...

48 CFR 653.219-70 - DOS form DS-1910, Small Business Agency Review-Actions Above the Simplified Acquisition Threshold.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 4 2014-10-01 2014-10-01 false DOS form DS-1910, Small Business Agency Review-Actions Above the Simplified Acquisition Threshold. 653.219-70 Section 653.219-70 Federal Acquisition Regulations System DEPARTMENT OF STATE CLAUSES AND FORMS FORMS Prescription of Forms 653.219-70 DOS form DS-1910, Small...

48 CFR 653.219-70 - DOS form DS-1910, Small Business Agency Review-Actions Above the Simplified Acquisition Threshold.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 4 2013-10-01 2013-10-01 false DOS form DS-1910, Small Business Agency Review-Actions Above the Simplified Acquisition Threshold. 653.219-70 Section 653.219-70 Federal Acquisition Regulations System DEPARTMENT OF STATE CLAUSES AND FORMS FORMS Prescription of Forms 653.219-70 DOS form DS-1910, Small...

SU-E-T-214: Intensity Modulated Proton Therapy (IMPT) Based On Passively Scattered Protons and Multi-Leaf Collimation: Prototype TPS and Dosimetry Study

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

Sanchez-Parcerisa, D; Carabe-Fernandez, A

2014-06-01

Purpose. Intensity-modulated proton therapy is usually implemented with multi-field optimization of pencil-beam scanning (PBS) proton fields. However, at the view of the experience with photon-IMRT, proton facilities equipped with double-scattering (DS) delivery and multi-leaf collimation (MLC) could produce highly conformal dose distributions (and possibly eliminate the need for patient-specific compensators) with a clever use of their MLC field shaping, provided that an optimal inverse TPS is developed. Methods. A prototype TPS was developed in MATLAB. The dose calculation process was based on a fluence-dose algorithm on an adaptive divergent grid. A database of dose kernels was precalculated in order tomore » allow for fast variations of the field range and modulation during optimization. The inverse planning process was based on the adaptive simulated annealing approach, with direct aperture optimization of the MLC leaves. A dosimetry study was performed on a phantom formed by three concentrical semicylinders separated by 5 mm, of which the inner-most and outer-most were regarded as organs at risk (OARs), and the middle one as the PTV. We chose a concave target (which is not treatable with conventional DS fields) to show the potential of our technique. The optimizer was configured to minimize the mean dose to the OARs while keeping a good coverage of the target. Results. The plan produced by the prototype TPS achieved a conformity index of 1.34, with the mean doses to the OARs below 78% of the prescribed dose. This Result is hardly achievable with traditional conformal DS technique with compensators, and it compares to what can be obtained with PBS. Conclusion. It is certainly feasible to produce IMPT fields with MLC passive scattering fields. With a fully developed treatment planning system, the produced plans can be superior to traditional DS plans in terms of plan conformity and dose to organs at risk.« less

Relaxation kinetics of the interaction between RNA and metal-intercalators: the Poly(A).Poly(U)/platinum-proflavine system.

PubMed

Biver, Tarita; Secco, Fernando; Venturini, Marcella

2005-05-15

The interactions of Poly(A).Poly(U) with the cis-platinum derivative of proflavine [{PtCl(tmen)}(2){HNC(13)H(7)(NHCH(2)CH(2))(2)}](+) (PRPt) and proflavine (PR) are investigated by spectrophotometry, spectrofluorimetry and T-jump relaxation at I=0.2M, pH 7.0, and T=25 degrees C. Base-dye interactions prevail at high RNA/dye ratio and binding isotherms analysis reveals that both dyes bind to Poly(A).Poly(U) according to the excluded site model (n=2). Only one relaxation effect is observed for the Poly(A).Poly(U)/PRPt system, whereas two effects are observed with Poly(A).Poly(U)/PR. The results agree with the sequence D+S <==> D, S <==> DS(I) <==> DS(II), where D,S is an external complex, DS(I) is a partially intercalated species, and DS(II) is the fully intercalated complex. Formation of DS(II) could be observed in the case of proflavine only. This result is interpreted by assuming that the platinum-containing residue of PRPt hinders the full intercalation of the acridine residue.

Identification of distinct molecular phenotypes in acute megakaryoblastic leukemia by gene expression profiling

PubMed Central

Bourquin, Jean-Pierre; Subramanian, Aravind; Langebrake, Claudia; Reinhardt, Dirk; Bernard, Olivier; Ballerini, Paola; Baruchel, André; Cavé, Hélène; Dastugue, Nicole; Hasle, Henrik; Kaspers, Gertjan L.; Lessard, Michel; Michaux, Lucienne; Vyas, Paresh; van Wering, Elisabeth; Zwaan, Christian M.; Golub, Todd R.; Orkin, Stuart H.

2006-01-01

Individuals with Down syndrome (DS) are predisposed to develop acute megakaryoblastic leukemia (AMKL), characterized by expression of truncated GATA1 transcription factor protein (GATA1s) due to somatic mutation. The treatment outcome for DS-AMKL is more favorable than for AMKL in non-DS patients. To gain insight into gene expression differences in AMKL, we compared 24 DS and 39 non-DS AMKL samples. We found that non-DS-AMKL samples cluster in two groups, characterized by differences in expression of HOX/TALE family members. Both of these groups are distinct from DS-AMKL, independent of chromosome 21 gene expression. To explore alterations of the GATA1 transcriptome, we used cross-species comparison with genes regulated by GATA1 expression in murine erythroid precursors. Genes repressed after GATA1 induction in the murine system, most notably GATA-2, MYC, and KIT, show increased expression in DS-AMKL, suggesting that GATA1s fail to repress this class of genes. Only a subset of genes that are up-regulated upon GATA1 induction in the murine system show increased expression in DS-AMKL, including GATA1 and BACH1, a probable negative regulator of megakaryocytic differentiation located on chromosome 21. Surprisingly, expression of the chromosome 21 gene RUNX1, a known regulator of megakaryopoiesis, was not elevated in DS-AMKL. Our results identify relevant signatures for distinct AMKL entities and provide insight into gene expression changes associated with these related leukemias. PMID:16492768

Omega Hawaii Antenna System: Modification and Validation Tests. Volume 2. Data Sheets.

DTIC Science & Technology

1979-10-19

a benchmark because of potential hotel construction . DS 5-1 DATA SHEET 5 (DS-5) RADIO FIELD INTENSITY MEASUREMENTS OMEGA STATION: HAWAII SITE NO. C 1A...27.5 1008 11.05 26.5 1007 Ft 11.80 28.1 COMMENT Not considered for a benchmark because of potential hotel construction . DS 5-5 DATA SHEET 5 (DS-5) RADIO

Interplay between alkyl chain asymmetry and cholesterol addition in the rigid ion pair amphiphile bilayer systems

NASA Astrophysics Data System (ADS)

Huang, Fong-yin; Chiu, Chi-cheng

2017-01-01

Ion pair amphiphile (IPA), a molecular complex composed of a pair of cationic and anionic surfactants, has been proposed as a novel phospholipid substitute. Controlling the physical stability of IPA vesicles is important for its application developments such as cosmetic and drug deliveries. To investigate the effects of IPA alkyl chain combinations and the cholesterol additive on the structural and mechanical properties of IPA vesicular bilayers, we conducted a series of molecular dynamics studies on the hexadecyltrimethylammonium-dodecylsulfate (HTMA-DS) and dodecyltrimethylammonium-hexadecylsulfate (DTMA-HS) IPA bilayers with cholesterol. We found that both IPA bilayers are in the gel phase at 298 K, consistent with experimental observations. Compared with the HTMA-DS system, the DTMA-HS bilayer has more disordered alkyl chains in the hydrophobic region. When adding cholesterol, it induces alkyl chain ordering around its rigid sterol ring. Yet, cholesterol increases the molecular areas for all species and disturbs the molecular packing near the hydrophilic region and the bilayer core. Cholesterol also promotes the alkyl chain mismatch between the IPA moieties, especially for the DTMA-HS bilayer. The combined effects lead to non-monotonically enhancement of the membrane mechanical moduli for both IPA-cholesterol systems. Furthermore, cholesterol can form H-bonds with the alkylsulfate and thus enhance the contribution of alkylsulfate to the overall mechanical moduli. Combined results provide valuable molecular insights into the roles of each IPA component and the cholesterol on modulating the IPA bilayer properties.

Reliability and validity of DS-ADHD: A decision support system on attention deficit hyperactivity disorders.

PubMed

Chu, Kuo-Chung; Huang, Yu-Shu; Tseng, Chien-Fu; Huang, Hsin-Jou; Wang, Chih-Huan; Tai, Hsin-Yi

2017-03-01

The purpose of this study is to examine the reliability of the clinical use of the self-built decision support system, diagnosis-supported attention deficit hyperactivity disorder (DS-ADHD), in an effort to develop the DS-ADHD system, by probing into the development of indicating patterns of past screening support systems for ADHD. The study collected data based on 107 subjects, who were divided into two groups, non-ADHD and ADHD, based on the doctor's determination, using the DSM-IV diagnostic standards. The two groups then underwent Test of Variables of Attention (TOVA) and DS-ADHD testing. The survey and testing results underwent one-way ANOVA and split-half method statistical analysis, in order to further understand whether there were any differences between the DS-ADHD and the identification tools used in today's clinical trials. The results of the study are as follows: 1) The ROC area between the TOVA and the clinical identification rate is 0.787 (95% confidence interval: 0.701-0.872); 2) The ROC area between the DS-ADHD and the clinical identification rate is 0.867 (95% confidence interval: 0.801-0.933). The study results show that DS-ADHD has the characteristics of screening for ADHD, based on its reliability and validity. It does not display any statistical differences when compared with TOVA systems that are currently on the market. However, the system is more effective and the accuracy rate is better than TOVA. It is a good tool to screen ADHD not only in Chinese children, but also in western country. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Validation of Risk Scoring System Excluding Female Sex From CHA2DS2-VASc in Japanese Patients With Nonvalvular Atrial Fibrillation – Subanalysis of the J-RHYTHM Registry.

PubMed

Tomita, Hirofumi; Okumura, Ken; Inoue, Hiroshi; Atarashi, Hirotsugu; Yamashita, Takeshi; Origasa, Hideki; Tsushima, Eiki

2015-01-01

Because the current Japanese guideline recommends CHADS2 score-based risk stratification in nonvalvular atrial fibrillation (NVAF) patients and does not list female sex as a risk for thromboembolic events, we designed the present study to compare the CHA2DS2-VASc and CHA2DS2-VA scores in the J-RHYTHM Registry. We prospectively assessed the incidence of thromboembolic events for 2 years in 997 NVAF patients without warfarin treatment (age 68±12 years, 294 females). The predictive value of the CHA2DS2-VASc and CHA2DS2-VA scores for thromboembolic events was evaluated by c-statistic difference and net reclassification improvement (NRI). Thromboembolic events occurred in 7/294 females (1.2%/year) and 23/703 males (1.6%/year) (odds ratio 0.72 for female to male, 95% confidence interval (CI) 0.28-1.62, P=0.44). No sex difference was found in patient groups stratified by CHA2DS2-VASc and CHA2DS2-VA scores. There were significant c-statistic difference (0.029, Z=2.3, P=0.02) and NRI (0.11, 95% CI 0.01-0.20, P=0.02), with the CHA2DS2-VA score being superior to the CHA2DS2-VASc score. In patients with CHA2DS2-VASc scores 0 and 1 (n=374), there were markedly significant c-statistic difference (0.053, Z=6.6, P<0.0001) and NRI (0.11, 95% CI 0.07-0.14, P<0.0001), again supporting superiority of CHA2DS2-VA to CHA2DS2-VASc score. In Japanese NVAF patients, the CHA2DS2-VA score, a risk scoring system excluding female sex from CHA2DS2-VASc, may be more useful in risk stratification for thromboembolic events than CHA2DS2-VASc score, especially in identifying truly low-risk patients.

Chitosan nanoparticle-based delivery of fused NKG2D–IL-21 gene suppresses colon cancer growth in mice

PubMed Central

Tan, Lunmei; Han, Sen; Ding, Shizhen; Xiao, Weiming; Ding, Yanbing; Qian, Li; Wang, Chenming; Gong, Weijuan

2017-01-01

Nanoparticles can be loaded with exogenous DNA for the potential expression of cytokines with immune-stimulatory function. NKG2D identifies major histocompatibility complex class I chain-related protein in human and retinoic acid early induced transcript-1 in mouse, which acts as tumor-associated antigens. Biologic agents based on interleukin 21 (IL-21) have displayed antitumor activities through lymphocyte activation. The NKG2D–IL-21 fusion protein theoretically identifies tumor cells through NKG2D moiety and activates T cells through IL-21 moiety. In this study, double-gene fragments that encode the extracellular domains of NKG2D and IL-21 genes were connected and then inserted into the pcDNA3.1(−) plasmid. PcDNA3.1–dsNKG2D–IL-21 plasmid nanoparticles based on chitosan were generated. Tumor cells pretransfected with dsNKG2D–IL-21 gene nanoparticles can activate natural killer (NK) and CD8+ T cells in vitro. Serum IL-21 levels were enhanced in mice intramuscularly injected with the gene nanoparticles. DsNKG2D–IL-21 gene nanoparticles accumulated in tumor tissues after being intravenously injected for ~4–24 h. Treatment of dsNKG2D–IL-21 gene nanoparticles also retarded tumor growth and elongated the life span of tumor-bearing mice by activating NK and T cells in vivo. Thus, the dsNKG2D–IL-21 gene nanoparticles exerted efficient antitumor activities and would be potentially used for tumor therapy. PMID:28450784

Scavenger receptor mediates systemic RNA interference in ticks.

PubMed

Aung, Kyaw Min; Boldbaatar, Damdinsuren; Umemiya-Shirafuji, Rika; Liao, Min; Xuenan, Xuan; Suzuki, Hiroshi; Galay, Remil Linggatong; Tanaka, Tetsuya; Fujisaki, Kozo

2011-01-01

RNA interference is an efficient method to silence gene and protein expressions. Here, the class B scavenger receptor CD36 (SRB) mediated the uptake of exogenous dsRNAs in the induction of the RNAi responses in ticks. Unfed female Haemaphysalis longicornis ticks were injected with a single or a combination of H. longicornis SRB (HlSRB) dsRNA, vitellogenin-1 (HlVg-1) dsRNA, and vitellogenin receptor (HlVgR) dsRNA. We found that specific and systemic silencing of the HlSRB, HlVg-1, and HlVgR genes was achieved in ticks injected with a single dsRNA of HlSRB, HlVg-1, and HlVgR. In ticks injected first with HlVg-1 or HlVgR dsRNA followed 96 hours later with HlSRB dsRNA (HlVg-1/HlSRB or HlVgR/HlSRB), gene silencing of HlSRB was achieved in addition to first knockdown in HlVg-1 or HlVgR, and prominent phenotypic changes were observed in engorgement, mortality, and hatchability, indicating that a systemic and specific double knockdown of target genes had been simultaneously attained in these ticks. However, in ticks injected with HlSRB dsRNA followed 96 hours later with HlVg-1 or HlVgR dsRNAs, silencing of HlSRB was achieved, but no subsequent knockdown in HlVgR or HlVg-1 was observed. The Westernblot and immunohistochemical examinations revealed that the endogenous HlSRB protein was fully abolished in midguts of ticks injected with HlSRB/HlVg-1 dsRNAs but HlVg-1 was normally expressed in midguts, suggesting that HlVg-1 dsRNA-mediated RNAi was fully inhibited by the first knockdown of HlSRB. Similarly, the abolished localization of HlSRB protein was recognized in ovaries of ticks injected with HlSRB/HlVgR, while normal localization of HlVgR was observed in ovaries, suggesting that the failure to knock-down HlVgR could be attributed to the first knockdown of HlSRB. In summary, we demonstrated for the first time that SRB may not only mediate the effective knock-down of gene expression by RNAi but also play essential roles for systemic RNAi of ticks.

Scavenger Receptor Mediates Systemic RNA Interference in Ticks

PubMed Central

Aung, Kyaw Min; Boldbaatar, Damdinsuren; Umemiya-Shirafuji, Rika; Liao, Min; Xuenan, Xuan; Suzuki, Hiroshi; Linggatong Galay, Remil; Tanaka, Tetsuya; Fujisaki, Kozo

2011-01-01

RNA interference is an efficient method to silence gene and protein expressions. Here, the class B scavenger receptor CD36 (SRB) mediated the uptake of exogenous dsRNAs in the induction of the RNAi responses in ticks. Unfed female Haemaphysalis longicornis ticks were injected with a single or a combination of H. longicornis SRB (HlSRB) dsRNA, vitellogenin-1 (HlVg-1) dsRNA, and vitellogenin receptor (HlVgR) dsRNA. We found that specific and systemic silencing of the HlSRB, HlVg-1, and HlVgR genes was achieved in ticks injected with a single dsRNA of HlSRB, HlVg-1, and HlVgR. In ticks injected first with HlVg-1 or HlVgR dsRNA followed 96 hours later with HlSRB dsRNA (HlVg-1/HlSRB or HlVgR/HlSRB), gene silencing of HlSRB was achieved in addition to first knockdown in HlVg-1 or HlVgR, and prominent phenotypic changes were observed in engorgement, mortality, and hatchability, indicating that a systemic and specific double knockdown of target genes had been simultaneously attained in these ticks. However, in ticks injected with HlSRB dsRNA followed 96 hours later with HlVg-1 or HlVgR dsRNAs, silencing of HlSRB was achieved, but no subsequent knockdown in HlVgR or HlVg-1 was observed. The Westernblot and immunohistochemical examinations revealed that the endogenous HlSRB protein was fully abolished in midguts of ticks injected with HlSRB/HlVg-1 dsRNAs but HlVg-1 was normally expressed in midguts, suggesting that HlVg-1 dsRNA-mediated RNAi was fully inhibited by the first knockdown of HlSRB. Similarly, the abolished localization of HlSRB protein was recognized in ovaries of ticks injected with HlSRB/HlVgR, while normal localization of HlVgR was observed in ovaries, suggesting that the failure to knock-down HlVgR could be attributed to the first knockdown of HlSRB. In summary, we demonstrated for the first time that SRB may not only mediate the effective knock-down of gene expression by RNAi but also play essential roles for systemic RNAi of ticks. PMID:22145043

Health care needs of children with Down syndrome and impact of health system performance on children and their families.

PubMed

Phelps, Randall A; Pinter, Joseph D; Lollar, Donald J; Medlen, Joan Guthrie; Bethell, Christina D

2012-04-01

The functional, financial, and social impact on families of children with Down syndrome (DS) in the United States and the role of the US health care system in ameliorating these impacts have not been well characterized. We sought to describe the demographic characteristics and functional difficulties of these children and to determine whether children with DS, compared with children with "intellectual disability" (ID) generally, and compared with other "children and youth with special health care needs" (CYSHCN), are more or less likely to receive health care that meets quality standards related to care coordination and to have their health care service needs met. This study analyzed data from the 2005-2006 National Survey of Children with Special Health Care Needs (n = 40,723). Children and youth aged 0 to 17 years with special health care need (CYSHCN) who experience DS (n = 395) and/or IDs (n = 4252) were compared with each other and other CYSHCN on a range of functioning, family impact, and health care quality variables using bivariate and multivariate methods. Data were weighted to represent all CYSHCN in the United States. Compared with CYSHCN without DS, children with DS were significantly less likely to receive comprehensive care within a medical home (29.7% vs 47.3%; p < .001). Parents of children with DS were also significantly more likely to cut back or stop work due to their child's health needs (23.5% vs 55.1%; p < .001). Although overall system performance was poorer for children with DS compared with those with ID and no DS after adjustment for family income, prevalence on most aspects of quality of care and family impacts evaluated were similar for these 2 groups. In this study, the families of children with DS, and ID generally, are burdened disproportionately when compared with other CYSHCN, reflecting the combination of impairments intrinsic to DS and ID and impacts of suboptimal medical care coordination and social support.

Non-invasive delivery of dsGST is lethal to the sweet potato whitefly, Bemisia tabaci (G.) (Hemiptera: Aleyrodidae).

PubMed

Asokan, R; Rebijith, K B; Roopa, H K; Kumar, N K Krishna

2015-02-01

The sweet potato whitefly, Bemisia tabaci (G.) biotype B (Hemiptera: Aleyrodidae), is one of the most economically important pest, by being a dreaded vector of Geminiviruses, and also causes direct damage to the crops by sucking phloem sap. Glutathione S-transferase (GST) is a large family of multifunctional enzymes that play pivotal roles in the detoxification of secondary allelochemical produced by the host plants and in insecticide resistance, thus regulates insect growth and development. The objective of this study is to show the potential of RNA interference (RNAi) in the management of B. tabaci. RNAi is a sequence-specific gene silencing mechanism induced by double-stranded RNA (dsRNA) which holds tremendous potential in pest management. In this regard, we sequenced the GST from B. tabaci and synthesized approximately 500-bp dsRNA from the above and delivered through diet to B. tabaci. Real-time quantitative PCR (RT-qPCR) showed that continuous application of dsGST at 1.0, 0.5, and 0.25 μg/μl reduced mRNA expression levels for BtGST by 77.43, 64.86, and 52.95 % which resulted in mortality by 77, 59, and 40 %, respectively, after 72 h of application. Disruption of BtGST expression will enable the development of novel strategies in pest management and functional analysis of vital genes in B. tabaci.

Influence of additional heat exchanger block on directional solidification system for growing multi-crystalline silicon ingot - A simulation investigation

NASA Astrophysics Data System (ADS)

Nagarajan, S. G.; Srinivasan, M.; Aravinth, K.; Ramasamy, P.

2018-04-01

Transient simulation has been carried out for analyzing the heat transfer properties of Directional Solidification (DS) furnace. The simulation results revealed that the additional heat exchanger block under the bottom insulation on the DS furnace has enhanced the control of solidification of the silicon melt. Controlled Heat extraction rate during the solidification of silicon melt is requisite for growing good quality ingots which has been achieved by the additional heat exchanger block. As an additional heat exchanger block, the water circulating plate has been placed under the bottom insulation. The heat flux analysis of DS system and the temperature distribution studies of grown ingot confirm that the established additional heat exchanger block on the DS system gives additional benefit to the mc-Si ingot.

Optical mapping of the brain activity in children with Down's syndrome

NASA Astrophysics Data System (ADS)

Yuan, Zhen; Lu, Fengmei

2018-02-01

Down's syndrome (DS) has been shown to be associated with many neurological complications, including cognitive deficits, seizures, early-onset dementia that resembles Alzheimer's disease, and neurological complications of systemic disorders. DS patients show to have poor performance in executive functions (EF) and fine motor skills. In this study, we examined the brain hemodynamic responses and brain activation patterns of DS children during the completion of EF tasks. Revealing its neural mechanism of DS is not only able to contribute to the early intervention of this children with DS, but also increase understanding of developmental cascades in childhood.

Transcranial magnetic stimulation in developmental stuttering: Relations with previous neurophysiological research and future perspectives.

PubMed

Busan, P; Battaglini, P P; Sommer, M

2017-06-01

Developmental stuttering (DS) is a disruption of the rhythm of speech, and affected people may be unable to execute fluent voluntary speech. There are still questions about the exact causes of DS. Evidence suggests there are differences in the structure and functioning of motor systems used for preparing, executing, and controlling motor acts, especially when they are speech related. Much research has been obtained using neuroimaging methods, ranging from functional magnetic resonance to diffusion tensor imaging and electroencephalography/magnetoencephalography. Studies using transcranial magnetic stimulation (TMS) in DS have been uncommon until recently. This is surprising considering the relationship between the functionality of the motor system and DS, and the wide use of TMS in motor-related disturbances such as Parkinson's Disease, Tourette's Syndrome, and dystonia. Consequently, TMS could shed further light on motor aspects of DS. The present work aims to investigate the use of TMS for understanding DS neural mechanisms by reviewing TMS papers in the DS field. Until now, TMS has contributed to the understanding of the excitatory/inhibitory ratio of DS motor functioning, also helping to better understand and critically review evidence about stuttering mechanisms obtained from different techniques, which allowed the investigation of cortico-basal-thalamo-cortical and white matter/connection dysfunctions. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Thermally driven spin-Seebeck transport in chiral dsDNA-based molecular devices

NASA Astrophysics Data System (ADS)

Nian, L. L.; Zhang, Rong; Tang, F. R.; Tang, Jun; Bai, Long

2018-03-01

By employing the nonequilibrium Green's function technique, we study the thermal-induced spin-Seebeck transport through a chiral double-stranded DNA (dsDNA) connected to a normal-metal and a ferromagnetic lead. How the main parameters of the dsDNA-based system influence the spin-Seebeck transport is analyzed at length, and the thermally created charge (spin-related) current displays the rectification effect and the negative differential thermal conductance feature. More importantly, the spin current exhibits the rectification behavior of the spin-Seebeck effect; even the perfect spin-Seebeck effect can be obtained with the null charge current. Thus, the chiral dsDNA-based system can act as a spin(charge)-Seebeck diode, spin(charge)-Seebeck switch, and spin(charge)-Seebeck transistor. Our results provide new ways to design spin caloritronic devices based on dsDNA or other organic molecules.

SMART-DS: Synthetic Models for Advanced, Realistic Testing: Distribution Systems and Scenarios

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

Palmintier, Bryan: Hodge, Bri-Mathias

This presentation provides a Smart-DS project overview and status update for the ARPA-e GRID DATA program meeting 2017, including distribution systems, models, and scenarios, as well as opportunities for GRID DATA collaborations.

TLR3 Ligand Poly(I:C) Exerts Distinct Actions in Synovial Fibroblasts When Delivered by Extracellular Vesicles

PubMed Central

Frank-Bertoncelj, Mojca; Pisetsky, David S.; Kolling, Christoph; Michel, Beat A.; Gay, Renate E.; Jüngel, Astrid; Gay, Steffen

2018-01-01

Extracellular vesicles (EV) can modulate the responses of cells to toll-like receptor (TLR) ligation; conversely, TLR ligands such as double-stranded RNA (dsRNA) can enhance the release of EV and influence of the composition and functions of EV cargos. Inflamed synovial joints in rheumatoid arthritis (RA) are rich in EV and extracellular RNA; besides, RNA released from necrotic synovial fluid cells can activate the TLR3 signaling in synovial fibroblasts (SFs) from patients with RA. Since EV occur prominently in synovial joints in RA and may contribute to the pathogenesis, we questioned whether EV can interact with dsRNA, a TLR3 ligand, and modify its actions in arthritis. We have used as model the effects on RA SFs, of EV released from monocyte U937 cells and peripheral blood mononuclear cells upon stimulation with Poly(I:C), a synthetic analog of dsRNA. We show that EV released from unstimulated cells and Poly(I:C)-stimulated U937 cells [Poly(I:C) EV] differ in size but bind similar amounts of Annexin V and express comparable levels of MAC-1, the receptor for dsRNA, on the vesicular membranes. Specifically, Poly(I:C) EV contain or associate with Poly(I:C) and at least partially protect Poly(I:C) from RNAse III degradation. Poly(I:C) EV shuttle Poly(I:C) to SFs and reproduce the proinflammatory and antiviral gene responses of SFs to direct stimulation with Poly(I:C). Poly(I:C) EV, however, halt the death receptor-induced apoptosis in SFs, thereby inverting the proapoptotic nature of Poly(I:C). These prosurvival effects sharply contrast with the high toxicity of cationic liposome-delivered Poly(I:C) and may reflect the route of Poly(I:C) delivery via EV or the fine-tuning of Poly(I:C) actions by molecular cargo in EV. The demonstration that EV may safeguard extracellular dsRNA and allow dsRNA to exert antiapoptotic effects on SFs highlights the potential of EV to amplify the pathogenicity of dsRNA in arthritis beyond inflammation (by concurrently enhancing the expansion of the invasive synovial stroma). PMID:29434584

Enhanced rectal absorption and reduced local irritation of the anti-inflammatory drug ethyl 4-biphenylylacetate in rats by complexation with water-soluble beta-cyclodextrin derivatives and formulation as oleaginous suppository.

PubMed

Arima, H; Kondo, T; Irie, T; Uekama, K

1992-11-01

To improve the rectal delivery of ethyl 4-biphenylylacetate (EBA), a prodrug of the anti-inflammatory drug 4-biphenylylacetic acid (BPAA), the use of highly water-soluble 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CyD) and heptakis(2,6-di-O-methyl)-beta-cyclodextrin (DM-beta-CyD) was investigated and compared with the use of the parent beta-cyclodextrin (beta-CyD). Among the three beta-CyDs, HP-beta-CyD was best at improving the rectal bioavailability of EBA in rats after single and multiple administrations of oleaginous suppositories (Witepsol H-5) containing the complexes. To gain insight into the enhancing effect of beta-CyDs, the absorption behaviors of EBA (observed by monitoring BPAA as an active metabolite of EBA) and beta-CyDs themselves were examined in vitro, in situ, and in vivo. The in situ recirculation study revealed that the complexed form of EBA was less absorbable from the rectal lumen in the solution state, but this disadvantageous effect of beta-CyDs was compensated in part by the inhibition of the bioconversion of EBA to BPAA. When beta-CyDs were coadministered with EBA in vivo, however, rather high amounts of HP-beta-CyD (approximately 26% of dose) and DM-beta-CyD (approximately 21% of dose), compared with beta-CyD (approximately 5% of dose), were absorbed from the rat rectum. Thus, the enhancement of rectal absorption of EBA in vivo can be explained by the facts that the hydrophilic beta-CyDs increased the release rate of EBA from the vehicle and stabilized EBA in the rectal lumen and that the drug was partly absorbed in the form of the complex.(ABSTRACT TRUNCATED AT 250 WORDS)

Two classes of silencing RNAs move between C. elegans tissues

PubMed Central

Jose, Antony M; Garcia, Giancarlo A; Hunter, Craig P

2011-01-01

Summary Organism-wide RNA interference (RNAi) is due to the transport of mobile silencing RNA throughout the organism but the identities of these mobile RNA species in animals are unknown. Here we present genetic evidence that both the initial double-stranded RNA (dsRNA), which triggers RNAi, and at least one dsRNA intermediate produced during RNAi can act as or generate mobile silencing RNA in Caenorhabditis elegans. This dsRNA intermediate requires the long dsRNA-binding protein RDE-4, the endonuclease DCR-1, which cleaves long dsRNA into double-stranded short-interfering RNA (ds-siRNA), and the putative nucleotidyltransferase MUT-2 (RDE-3). However, single-stranded siRNA and downstream secondary siRNA produced upon amplification by the RNA-dependent RNA Polymerase RRF-1 do not generate mobile silencing RNA. Restricting inter-tissue transport to long dsRNA and directly processed siRNA intermediates rather than amplified siRNA may serve to modulate the extent of systemic silencing in proportion to available dsRNA. PMID:21984186

Distinct abnormalities in the innate immune system of children with Down syndrome.

PubMed

Bloemers, Beatrijs L P; van Bleek, Grada M; Kimpen, Jan L L; Bont, Louis

2010-05-01

To analyze the frequency and phenotype of cells of the innate immune system in the peripheral blood of children with Down syndrome (DS). Flow cytometric analysis of expression of cell surface markers was performed in children with DS (n = 41) and healthy age-matched controls (n = 41). Compared with controls, children with DS had significantly lower absolute total leukocyte counts, lymphocytes, monocytes, and granulocytes, but 1.5-times higher absolute numbers of CD14(dim)CD16(+) monocytes (147 x 10(6)/L vs 93 x 10(6)/L; P = .02). This difference is fully explained by a higher percentage of CD14(dim)CD16(+) monocytes within the monocyte compartment (28.7% vs 13.4%; P <.001). The absolute numbers of myeloid dendritic cells were lower in DS (13.8 x 10(6)/L vs 22.7 x 10(6)/L; P <.001). The numbers of plasmacytoid dendritic cells and natural killer cells were normal. Absolute numbers of invariant natural killer T cells were very low overall, but significantly lower in children with DS than in controls (1.2 x 10(6)/L vs 3.7 x 10(6)/L; P = .01). Children with DS exhibited distinct abnormalities in cells of the innate immune system. Most strikingly, they had a high number of proinflammatory CD14(dim)CD16(+) monocytes. This elevated level of CD14(dim)CD16(+) monocytes may play an important role in the onset and maintenance of chronic inflammatory disease in DS.

Quadriphase DS-CDMA wireless communication systems employing the generalized detector

NASA Astrophysics Data System (ADS)

Tuzlukov, Vyacheslav

2012-05-01

Probability of bit-error Per performance of asynchronous direct-sequence code-division multiple-access (DS-CDMA) wireless communication systems employing the generalized detector (GD) constructed based on the generalized approach to signal processing in noise is analyzed. The effects of pulse shaping, quadriphase or direct sequence quadriphase shift keying (DS-QPSK) spreading, aperiodic spreading sequences are considered in DS-CDMA based on GD and compared with the coherent Neyman-Pearson receiver. An exact Per expression and several approximations: one using the characterristic function method, a simplified expression for the improved Gaussian approximation (IGA) and the simplified improved Gaussian approximation are derived. Under conditions typically satisfied in practice and even with a small number of interferers, the standard Gaussian approximation (SGA) for the multiple-access interference component of the GD statistic and Per performance is shown to be accurate. Moreover, the IGA is shown to reduce to the SGA for pulses with zero excess bandwidth. Second, the GD Per performance of quadriphase DS-CDMA is shown to be superior to that of bi-phase DS-CDMA. Numerical examples by Monte Carlo simulation are presented to illustrate the GD Per performance for square-root raised-cosine pulses and spreading factors of moderate to large values. Also, a superiority of GD employment in CDMA systems over the Neyman-Pearson receiver is demonstrated

Advancing clinical decision support using lessons from outside of healthcare: an interdisciplinary systematic review.

PubMed

Wu, Helen W; Davis, Paul K; Bell, Douglas S

2012-08-17

Greater use of computerized decision support (DS) systems could address continuing safety and quality problems in healthcare, but the healthcare field has struggled to implement DS technology. This study surveys DS experience across multiple non-healthcare disciplines for new insights that are generalizable to healthcare provider decisions. In particular, it sought design principles and lessons learned from the other disciplines that could inform efforts to accelerate the adoption of clinical decision support (CDS). Our systematic review drew broadly from non-healthcare databases in the basic sciences, social sciences, humanities, engineering, business, and defense: PsychINFO, BusinessSource Premier, Social Sciences Abstracts, Web of Science, and Defense Technical Information Center. Because our interest was in DS that could apply to clinical decisions, we selected articles that (1) provided a review, overview, discussion of lessons learned, or an evaluation of design or implementation aspects of DS within a non-healthcare discipline and (2) involved an element of human judgment at the individual level, as opposed to decisions that can be fully automated or that are made at the organizational level. Clinical decisions share some similarities with decisions made by military commanders, business managers, and other leaders: they involve assessing new situations and choosing courses of action with major consequences, under time pressure, and with incomplete information. We identified seven high-level DS system design features from the non-healthcare literature that could be applied to CDS: providing broad, system-level perspectives; customizing interfaces to specific users and roles; making the DS reasoning transparent; presenting data effectively; generating multiple scenarios covering disparate outcomes (e.g., effective; effective with side effects; ineffective); allowing for contingent adaptations; and facilitating collaboration. The article provides examples of each feature. The DS literature also emphasizes the importance of organizational culture and training in implementation success. The literature contrasts "rational-analytic" vs. "naturalistic-intuitive" decision-making styles, but the best approach is often a balanced approach that combines both styles. It is also important for DS systems to enable exploration of multiple assumptions, and incorporation of new information in response to changing circumstances. Complex, high-level decision-making has common features across disciplines as seemingly disparate as defense, business, and healthcare. National efforts to advance the health information technology agenda through broader CDS adoption could benefit by applying the DS principles identified in this review.

Cognitive remediation for adolescents with 22q11 deletion syndrome (22q11DS): a preliminary study examining effectiveness, feasibility, and fidelity of a hybrid strategy, remote and computer-based intervention.

PubMed

Mariano, Margaret A; Tang, Kerri; Kurtz, Matthew; Kates, Wendy R

2015-08-01

22q11DS is a multiple anomaly syndrome involving intellectual and behavioral deficits, and increased risk for schizophrenia. As cognitive remediation (CR) has recently been found to improve cognition in younger patients with schizophrenia, we investigated the efficacy, feasibility, and fidelity of a remote, hybrid strategy, computerized CR program in youth with 22q11DS. A longitudinal design was implemented in which 21 participants served as their own controls. Following an eight month baseline period in which no interventions were provided, cognitive coaches met with participants remotely for CR via video conferencing three times a week over a targeted 8month timeframe and facilitated their progress through the intervention, offering task-specific strategies. A subset of strategies were examined for fidelity. Outcomes were evaluated using a neurocognitive test battery at baseline, pre-treatment and post-treatment. All participants adhered to the intervention. The mean length of the treatment phase was 7.96months. A moderately high correlation (intraclass correlation coefficient, 0.73) was found for amount and type of strategies offered by coaches. Participants exhibited significant improvements (ES=.36-.55, p≤.009) in working memory, shifting attention and cognitive flexibility. All significant models were driven by improvements in pre to post-treatment scores. Based on our preliminary investigation, a remote, hybrid strategy, computerized CR program can be implemented with 22q11DS youth despite geographic location, health, and cognitive deficits. It appears effective in enhancing cognitive skills during the developmental period of adolescence, making this type of CR delivery useful for youth with 22q11DS transitioning into post-school environments. Copyright © 2015 Elsevier B.V. All rights reserved.

Postnatal diagnosis of Down syndrome: synthesis of the evidence on how best to deliver the news.

PubMed

Skotko, Brian G; Capone, George T; Kishnani, Priya S

2009-10-01

Many parents of children with Down syndrome (DS) have expressed dissatisfaction with how they learned about their child's diagnosis. DS remains the most common chromosomal condition, occurring in 1 of every 733 births, with the majority of children still diagnosed postnatally. Our goal was to review systematically all available evidence regarding how physicians should approach the conversation in which they explain DS for the first time to new parents. We searched online databases from 1960 to 2008, including Medline and PsychInfo, as well as Web sites maintained by academic organizations (eg, American Academy of Pediatrics) and other nonprofit or private organizations (eg, the National Down Syndrome Society), by using the terms "Down syndrome," "trisomy 21," "mongolism," "prenatal diagnosis," "postnatal care," and "delivery of health care." Articles were selected that answered > or =1 research question, established a priori: (1) Who is the best person to communicate the news? (2) When is the best time to share the news? (3) Where is the best place or setting to deliver the news? (4) What information should be delivered? and (5) How should the news be communicated? All studies were evaluated for quality according to the method outlined by the US Preventative Services Task Force. Final recommendations were based on the strength of evidence. Parents prefer to receive the diagnosis together in a joint meeting with their obstetrician and pediatrician. The conversation should take place in a private setting as soon as a physician suspects a diagnosis of DS. Accurate and up-to-date information should be conveyed, including information about local support groups and resources. By implementing a few cost-neutral measures, physicians can deliver a postnatal diagnosis of DS in a manner that will be deemed by new parents as sensitive and appropriate.

Colon-specific pulsatile drug release provided by electrospun shellac nanocoating on hydrophilic amorphous composites

PubMed Central

Yu, Deng-Guang; Wang, Ke; Liu, Ping; Chen, Xiaohong

2018-01-01

Background Colon-specific pulsatile drug release, as a combined drug controlled-release model, is a useful drug delivery manner for a series of diseases. New nanomedicines and related preparation methods are highly desired. Methods With diclofenac sodium (DS) as a model drug, a new type of structural nanocomposite (SC), in which composite polyvinylpyrrolidone (PVP)–DS core was coated by shellac, was fabricated via modified coaxial electrospinning. For comparison, traditional PVP–DS monolithic hydrophilic nanocomposites (HCs) were generated using a traditional blending process. Scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), attenuated total reflectance-Fourier transform infrared (ATR-FTIR), water contact angle (WCA), and in vitro dissolution and ex vivo permeation tests were conducted to characterize the composites. Results SEM images demonstrated that both composites were linear nanofibers with smooth surface morphology and cross sections. TEM disclosed that the SCs had a thin shellac sheath layer of approximately 12 nm. XRD and ATR-FTIR results demonstrated that the crystalline DS was converted into amorphous composites with PVP because of favorable secondary interactions. WCA and in vitro dissolution tests demonstrated that the sheath shellac layers in SC could resist acid conditions and provide typical colon-specific pulsatile release, rather than a pulsatile release of HC under acid conditions. Ex vivo permeation results demonstrated that the SCs were able to furnish a tenfold drug permeation rate than the DS particles on the colon membrane. Conclusion A new SC with a shellac coating on hydrophilic amorphous nanocomposites could furnish a colon-specific pulsatile drug release profile. The modified coaxial process can be exploited as a useful tool to create nanocoatings. PMID:29713169

Colon-specific pulsatile drug release provided by electrospun shellac nanocoating on hydrophilic amorphous composites.

PubMed

Yang, Yao-Yao; Liu, Zhe-Peng; Yu, Deng-Guang; Wang, Ke; Liu, Ping; Chen, Xiaohong

2018-01-01

Colon-specific pulsatile drug release, as a combined drug controlled-release model, is a useful drug delivery manner for a series of diseases. New nanomedicines and related preparation methods are highly desired. With diclofenac sodium (DS) as a model drug, a new type of structural nanocomposite (SC), in which composite polyvinylpyrrolidone (PVP)-DS core was coated by shellac, was fabricated via modified coaxial electrospinning. For comparison, traditional PVP-DS monolithic hydrophilic nanocomposites (HCs) were generated using a traditional blending process. Scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), attenuated total reflectance-Fourier transform infrared (ATR-FTIR), water contact angle (WCA), and in vitro dissolution and ex vivo permeation tests were conducted to characterize the composites. SEM images demonstrated that both composites were linear nanofibers with smooth surface morphology and cross sections. TEM disclosed that the SCs had a thin shellac sheath layer of approximately 12 nm. XRD and ATR-FTIR results demonstrated that the crystalline DS was converted into amorphous composites with PVP because of favorable secondary interactions. WCA and in vitro dissolution tests demonstrated that the sheath shellac layers in SC could resist acid conditions and provide typical colon-specific pulsatile release, rather than a pulsatile release of HC under acid conditions. Ex vivo permeation results demonstrated that the SCs were able to furnish a tenfold drug permeation rate than the DS particles on the colon membrane. A new SC with a shellac coating on hydrophilic amorphous nanocomposites could furnish a colon-specific pulsatile drug release profile. The modified coaxial process can be exploited as a useful tool to create nanocoatings.

EPA Distribution System (DS) Research as It Relates to the TCRDS and the DS Research Partnership ..and more

EPA Science Inventory

An overview of Water Supply and Water Research Division (WSWRD) distribution system water quality research was provided. Specifically, the research topics of corrosion, nitrification, biofilms and contaminant accumulation were discussed.

Impact of gene patents on the cost-effective delivery of care: the case of BRCA1 genetic testing.

PubMed

Sevilla, Christine; Julian-Reynier, Claire; Eisinger, François; Stoppa-Lyonnet, Dominique; Bressac-de Paillerets, Brigitte; Sobol, Hagay; Moatti, Jean-Paul

2003-01-01

In 1994/95, two genes, BRCA1/2, associated with a predisposition to breast or ovarian cancer were identified. Genetic testing of deleterious BRCA1/2 mutations consequently can be proposed to individuals with a family history of breast or ovarian cancer to identify who is at risk. The granting of U.S. patents on BRCA1/2 to a privately owned company has led to the monopoly use of a unique technique (Direct Sequencing of the gene, DS) for BRCA1/2 testing in this country. Alternative strategies using prescreening techniques, however, have been experienced worldwide. On the basis of data collected at three laboratories of French public hospitals, we carried out a cost-effectiveness study comparing DS to 19 alternative strategies with the number of deleterious BRCA1 mutations detected as the outcome. Results show that the DS strategy presents the highest average cost per mutation detected (9,882.5 Euro) and that there exist strategies using prescreening techniques that can reach similar effectiveness while reducing total costs. Moreover, other strategies can obtain a four- to sevenfold reduction in the average cost per mutation detected as soon as some rates of false negatives (2% to 13%) are deemed to be acceptable. Results suggest that gene patents with a very broad scope, covering all potential medical applications, may prevent health care systems from identifying and adopting the most efficient genetic testing strategies due to the monopoly granted for the exploitation of the gene. Policy implications for regulatory authorities, in the current context of the extension of BRCA1/2 patents in other countries, are discussed.

Transferrin-conjugated magnetic dextran-spermine nanoparticles for targeted drug transport across blood-brain barrier.

PubMed

Ghadiri, Maryam; Vasheghani-Farahani, Ebrahim; Atyabi, Fatemeh; Kobarfard, Farzad; Mohamadyar-Toupkanlou, Farzaneh; Hosseinkhani, Hossein

2017-10-01

Application of many vital hydrophilic medicines have been restricted by blood-brain barrier (BBB) for treatment of brain diseases. In this study, a targeted drug delivery system based on dextran-spermine biopolymer was developed for drug transport across BBB. Drug loaded magnetic dextran-spermine nanoparticles (DS-NPs) were prepared via ionic gelation followed by transferrin (Tf) conjugation as targeting moiety. The characteristics of Tf conjugated nanoparticles (TDS-NPs) were analyzed by different methods and their cytotoxicity effects on U87MG cells were tested. The superparamagnetic characteristic of TDS-NPs was verified by vibration simple magnetometer. Capecitabine loaded TDS-NPs exhibited pH-sensitive release behavior with enhanced cytotoxicity against U87MG cells, compared to DS-NPs and free capecitabine. Prussian-blue staining and TEM-imaging showed the significant cellular uptake of TDS-NPs. Furthermore, a remarkable increase of Fe concentrations in brain was observed following their biodistribution and histological studies in vivo, after 1 and 7 days of post-injection. Enhanced drug transport across BBB and pH-triggered cellular uptake of TDS-NPs indicated that these theranostic nanocarriers are promising candidate for the brain malignance treatment. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2851-2864, 2017. © 2017 Wiley Periodicals, Inc.

48 CFR 9903.202-10 - Illustration of Disclosure Statement Form, CASB DS-2.

Code of Federal Regulations, 2012 CFR

2012-10-01

... of Disclosure Statement Form, CASB DS-2. The data which are required to be disclosed by educational institutions are set forth in detail in the Disclosure Statement Form, CASB DS-2, which is illustrated below... 48 Federal Acquisition Regulations System 7 2012-10-01 2012-10-01 false Illustration of Disclosure...

48 CFR 9903.202-10 - Illustration of Disclosure Statement Form, CASB DS-2.

Code of Federal Regulations, 2010 CFR

2010-10-01

... of Disclosure Statement Form, CASB DS-2. The data which are required to be disclosed by educational institutions are set forth in detail in the Disclosure Statement Form, CASB DS-2, which is illustrated below... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Illustration of Disclosure...

75 FR 50791 - 30-Day Notice of Proposed Information Collection: Recording, Reporting, and Data Collection...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-17

...: Recording, Reporting, and Data Collection Requirements Under 22 CFR Part 62, the Exchange Visitor Program--Student and Exchange Visitor Information System (SEVIS); Forms DS-3036, DS-3037, and DS-7000, OMB No. 1405... the Office of Management and Budget (OMB) for approval in accordance with the Paperwork Reduction Act...

Multiple Access Interference Reduction Using Received Response Code Sequence for DS-CDMA UWB System

NASA Astrophysics Data System (ADS)

Toh, Keat Beng; Tachikawa, Shin'ichi

This paper proposes a combination of novel Received Response (RR) sequence at the transmitter and a Matched Filter-RAKE (MF-RAKE) combining scheme receiver system for the Direct Sequence-Code Division Multiple Access Ultra Wideband (DS-CDMA UWB) multipath channel model. This paper also demonstrates the effectiveness of the RR sequence in Multiple Access Interference (MAI) reduction for the DS-CDMA UWB system. It suggests that by using conventional binary code sequence such as the M sequence or the Gold sequence, there is a possibility of generating extra MAI in the UWB system. Therefore, it is quite difficult to collect the energy efficiently although the RAKE reception method is applied at the receiver. The main purpose of the proposed system is to overcome the performance degradation for UWB transmission due to the occurrence of MAI during multiple accessing in the DS-CDMA UWB system. The proposed system improves the system performance by improving the RAKE reception performance using the RR sequence which can reduce the MAI effect significantly. Simulation results verify that significant improvement can be obtained by the proposed system in the UWB multipath channel models.

Evaluation of solar sludge drying alternatives by costs and area requirements.

PubMed

Kurt, Mayıs; Aksoy, Ayşegül; Sanin, F Dilek

2015-10-01

Thermal drying is a common method to reach above 90% dry solids content (DS) in sludge. However, thermal drying requires high amount of energy and can be expensive. A greenhouse solar dryer (GSD) can be a cost-effective substitute if the drying performance, which is typically 70% DS, can be increased by additional heat. In this study feasibility of GSD supported with solar panels is evaluated as an alternative to thermal dryers to reach 90% DS. Evaluations are based on capital and O&M costs as well as area requirements for 37 wastewater treatment plants (WWTPs) with various sludge production rates. Costs for the supported GSD system are compared to that of conventional and co-generation thermal dryers. To calculate the optimal costs associated with the drying system, an optimization model was developed in which area limitation was a constraint. Results showed that total cost was minimum when the DS in the GSD (DS(m,i)) was equal to the maximum attainable value (70% DS). On average, 58% of the total cost and 38% of total required area were associated with the GSD. Variations in costs for 37 WWTPs were due to differences in initial DS (DS(i,i)) and sludge production rates, indicating the importance of dewatering to lower drying costs. For large plants, GSD supported with solar panels provided savings in total costs especially in long term when compared to conventional and co-generation thermal dryers. Copyright © 2015 Elsevier Ltd. All rights reserved.

Knockdown of the Chromatin Remodeling Gene Brahma by RNA Interference Reduces Reproductive Fitness and Lifespan in Common Bed Bug (Hemiptera: Cimicidae).

PubMed

Basnet, Sanjay; Kamble, Shripat T

2018-05-04

The common bed bug, Cimex lectularius L. (Hemiptera: Cimicidae) is a nuisance household pest causing significant medical and economic impacts. RNA interference (RNAi) of genes that are involved in vital physiological processes can serve as potential RNAi targets for insect control. Brahma is an ATPase subunit of a chromatin-remodeling complex involved in transcription of several genes for cellular processes, most importantly the homeotic genes. In this study, we used a microinjection technique to deliver double stranded RNA into female bed bugs. Delivery of 0.05 and 0.5 µg/insect of brahma dsRNA directly into hemocele resulted substantial reduction in oviposition. Eggs laid by bed bugs receiving both doses of brahma dsRNA exhibited significantly lower hatching percentage as compared to controls. In addition, brahma RNAi in female bed bugs caused significant mortality. Our results disclosed the potential of brahma RNAi to suppress bed bug population through injection of specific dsRNA, suggesting a critical function of this gene in bed bugs' reproduction and survival. Based on our data, brahma can be a promising RNAi target for suppression of bed bug population.

Functional bacteria and process metabolism of the Denitrifying Sulfur conversion-associated Enhanced Biological Phosphorus Removal (DS-EBPR) system: An investigation by operating the system from deterioration to restoration.

PubMed

Guo, Gang; Wu, Di; Hao, Tianwei; Mackey, Hamish Robert; Wei, Li; Wang, Haiguang; Chen, Guanghao

2016-05-15

A sulfur conversion-associated Enhanced Biological Phosphorus (P) Removal (EBPR) system is being developed to cater for the increasing needs to treat saline/brackish wastewater resulting from seawater intrusion into groundwater and sewers and frequent use of sulfate coagulants during drinking water treatment, as well as to meet the demand for eutrophication control in warm climate regions. However, the major functional bacteria and metabolism in this emerging biological nutrient removal system are still poorly understood. This study was thus designed to explore the functional microbes and metabolism in this new EBPR system by manipulating the deterioration, failure and restoration of a lab-scale system. This was achieved by changing the mixed liquor suspended solids (MLSS) concentration to monitor and evaluate the relationships among sulfur conversion (including sulfate reduction and sulfate production), P removal, variation in microbial community structures, and stoichiometric parameters. The results show that the stable Denitrifying Sulfur conversion-associated EBPR (DS-EBPR) system was enriched by sulfate-reducing bacteria (SRB) and sulfide-oxidizing bacteria (SOB). These bacteria synergistically participated in this new EBPR process, thereby inducing an appropriate level of sulfur conversion crucial for achieving a stable DS-EBPR performance, i.e. maintaining sulfur conversion intensity at 15-40 mg S/L, corresponding to an optimal sludge concentration of 6.5 g/L. This range of sulfur conversion favors microbial community competition and various energy flows from internal polymers (i.e. polysulfide or elemental sulfur (poly-S(2-)/S(0)) and poly-β-hydroxyalkanoates (PHA)) for P removal. If this range was exceeded, the system might deteriorate or even fail due to enrichment of glycogen-accumulating organisms (GAOs). Four methods of restoring the failed system were investigated: increasing the sludge concentration, lowering the salinity or doubling the COD loading, non of which restored SRB and SOB activities for DS-EBPR; only the final novel approach of adding 25 ± 5 mg S/L of external sulfide into the reactor at the beginning of the anoxic phase could efficiently restore the DS-EBPR system from failure. The present study represents a step towards understanding the DS-EBPR metabolism and provides an effective remedial measure for recovering a deteriorating or failed DS-EBPR system. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effective and lesion-free cutaneous influenza vaccination

PubMed Central

Wang, Ji; Li, Bo; Wu, Mei X.

2015-01-01

The current study details efficient lesion-free cutaneous vaccination via vaccine delivery into an array of micropores in the skin, instead of bolus injection at a single site. Such delivery effectively segregated vaccine-induced inflammation, resulting in rapid resolution of the inflammation, provided that distances between any two micropores were sufficient. When the inoculation site was treated by FDA-approved nonablative fractional laser (NAFL) before insertion of a PR8 model influenza vaccine-packaged, biodegradable microneedle array (MNs), mice displayed vigorous antigen-uptake, eliciting strong Th1-biased immunity. These animals were completely protected from homologous viral challenges, and fully or partially protected from heterologous H1N1 and H3N2 viral challenges, whereas mice receiving MNs alone suffered from severe illnesses or died of similar viral challenges. NAFL-mediated adjuvanicity was ascribed primarily to dsDNA and other “danger” signals released from laser-damaged skin cells. Thus, mice deficient in dsDNA-sensing pathway, but not Toll like receptor (TLR) or inflammasome pathways, showed poor responses to NAFL. Importantly, with this novel approach both mice and swine exhibited strong protective immunity without incurring any appreciable skin irritation, in sharp contrast to the overt skin irritation caused by intradermal injections. The effective lesion-free cutaneous vaccination merits further clinical studies. PMID:25848020

Role of edge activators and surface charge in developing ultradeformable vesicles with enhanced skin delivery.

PubMed

El Zaafarany, Ghada M; Awad, Gehanne A S; Holayel, Samar M; Mortada, Nahed D

2010-09-15

Transfersomes are highly efficient edge activator (EA)-based ultraflexible vesicles capable of, non-invasively, trespassing skin by virtue of their high, self-optimizing deformability. This investigation presents different approaches for the optimization of Transfersomes for enhanced transepidermal delivery of Diclofenac sodium (DS). Different methods of preparation, drug and lipid concentrations and vesicle compositions were employed, resulting in ultraflexible vesicles with diverse membrane characteristics. Evaluation of Transfersomes was implemented in terms of their shapes, sizes, entrapment efficiencies (EE%), relative deformabilities and in vitro skin permeation. Transfersomes prepared with 95:5% (w/w) (PC:EA) ratio showed highest EE% (Span 85>Span 80>Na cholate>Na deoxycholate>Tween 80). Whereas, those prepared using 85:15% (w/w) ratio showed highest deformability (Tween 80 was superior to bile salts and spans). Transfersomes were proved significantly superior in terms of, the amount of drug deposited in the skin and the amount permeated, with an enhancement ratio of 2.45, when compared to a marketed product. The study proved that the type and concentration of EA, as well as, the method of preparation had great influences on the properties of Transfersomes. Hence, optimized Transfersomes can significantly increase transepidermal flux and prolong the release of DS, when applied non-occlusively. Copyright 2010 Elsevier B.V. All rights reserved.

Amphiphilically modified chitosan cationic nanoparticles for drug delivery

NASA Astrophysics Data System (ADS)

You, Jie; Li, Wenfeng; Yu, Chang; Zhao, Chengguang; Jin, Langping; Zhou, Yili; Xu, Xuzhong; Dong, Siyang; Lu, Xincheng; Wang, Ouchen

2013-12-01

A series of amphiphilic N-(2-hydroxy)propyl-3-trimethylammonium-chitosan-cholic acid (HPTA-CHI-CA) polymers were synthesized by grafting cholic acid (CA) and glycidyltrimethylammonium chloride onto chitosan. The self-assembly behavior of HPTA-CHI-CA was studied by fluorescence technique. The polymers were able to self-assemble into NPs in phosphate buffered saline with a critical aggregation concentration (CAC) in the range of 66-26 mg/L and the CAC decreased with the increasing of the degree of substitution (DS) of CA. The size of cationic HPTA-CHI-CA NPs ranges from 170 to 220 nm (PDI < 0.2). It was found that doxorubicin (DOX) could be encapsulated into HPTA-CHI-CA NPs based on self-assembly. The drug loading content and efficiency varies depending on the DS of CA and feeding ratio of DOX to polymer. In vitro release studies suggested that DOX released slowly from HPTA-CHI-CA NPs without any burst initial release. Besides, the confocal microscopic measurements indicated that DOX-HPTA-CHI-CA NPs could easily be uptaken by breast cancer (MCF-7) cells and release DOX in cytoplasm. Anti-tumor efficacy results showed that DOX-HPTA-CHI-CA NPs have a significant activity of inhibition MCF-7 cells growth. These results suggest cationic HPTA-CHI-CA may have great potential for anticancer drug delivery.

An accurate evaluation of the performance of asynchronous DS-CDMA systems with zero-correlation-zone coding in Rayleigh fading

NASA Astrophysics Data System (ADS)

Walker, Ernest; Chen, Xinjia; Cooper, Reginald L.

2010-04-01

An arbitrarily accurate approach is used to determine the bit-error rate (BER) performance for generalized asynchronous DS-CDMA systems, in Gaussian noise with Raleigh fading. In this paper, and the sequel, new theoretical work has been contributed which substantially enhances existing performance analysis formulations. Major contributions include: substantial computational complexity reduction, including a priori BER accuracy bounding; an analytical approach that facilitates performance evaluation for systems with arbitrary spectral spreading distributions, with non-uniform transmission delay distributions. Using prior results, augmented by these enhancements, a generalized DS-CDMA system model is constructed and used to evaluated the BER performance, in a variety of scenarios. In this paper, the generalized system modeling was used to evaluate the performance of both Walsh- Hadamard (WH) and Walsh-Hadamard-seeded zero-correlation-zone (WH-ZCZ) coding. The selection of these codes was informed by the observation that WH codes contain N spectral spreading values (0 to N - 1), one for each code sequence; while WH-ZCZ codes contain only two spectral spreading values (N/2 - 1,N/2); where N is the sequence length in chips. Since these codes span the spectral spreading range for DS-CDMA coding, by invoking an induction argument, the generalization of the system model is sufficiently supported. The results in this paper, and the sequel, support the claim that an arbitrary accurate performance analysis for DS-CDMA systems can be evaluated over the full range of binary coding, with minimal computational complexity.

Determining the relative contribution of retinal disparity and blur cues to ocular accommodation in Down syndrome.

PubMed

Doyle, Lesley; Saunders, Kathryn J; Little, Julie-Anne

2017-01-10

Individuals with Down syndrome (DS) often exhibit hypoaccommodation alongside accurate vergence. This study investigates the sensitivity of the two systems to retinal disparity and blur cues, establishing the relationship between the two in terms of accommodative-convergence to accommodation (AC/A) and convergence-accommodation to convergence (CA/C) ratios. An objective photorefraction system measured accommodation and vergence under binocular conditions and when retinal disparity and blur cues were removed. Participants were aged 6-16 years (DS n = 41, controls n = 76). Measures were obtained from 65.9% of participants with DS and 100% of controls. Accommodative and vergence responses were reduced with the removal of one or both cues in controls (p < 0.007). For participants with DS, removal of blur was less detrimental to accommodative responses than removal of disparity; accommodative responses being significantly better when all cues were available or when blur was removed in comparison to when proximity was the only available cue. AC/A ratios were larger and CA/C ratios smaller in participants with DS (p < 0.00001). This study demonstrates that retinal disparity is the main driver to both systems in DS and illustrates the diminished influence of retinal blur. High AC/A and low CA/C ratios in combination with disparity-driven responses suggest prioritisation of vergence over accurate accommodation.

Determining the relative contribution of retinal disparity and blur cues to ocular accommodation in Down syndrome

PubMed Central

Doyle, Lesley; Saunders, Kathryn J.; Little, Julie-Anne

2017-01-01

Individuals with Down syndrome (DS) often exhibit hypoaccommodation alongside accurate vergence. This study investigates the sensitivity of the two systems to retinal disparity and blur cues, establishing the relationship between the two in terms of accommodative-convergence to accommodation (AC/A) and convergence-accommodation to convergence (CA/C) ratios. An objective photorefraction system measured accommodation and vergence under binocular conditions and when retinal disparity and blur cues were removed. Participants were aged 6–16 years (DS n = 41, controls n = 76). Measures were obtained from 65.9% of participants with DS and 100% of controls. Accommodative and vergence responses were reduced with the removal of one or both cues in controls (p < 0.007). For participants with DS, removal of blur was less detrimental to accommodative responses than removal of disparity; accommodative responses being significantly better when all cues were available or when blur was removed in comparison to when proximity was the only available cue. AC/A ratios were larger and CA/C ratios smaller in participants with DS (p < 0.00001). This study demonstrates that retinal disparity is the main driver to both systems in DS and illustrates the diminished influence of retinal blur. High AC/A and low CA/C ratios in combination with disparity-driven responses suggest prioritisation of vergence over accurate accommodation. PMID:28071728

48 CFR 653.219-70 - DOS form DS-1910, Small Business Agency Review-Actions Above the Simplified Acquisition Threshold.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 4 2012-10-01 2012-10-01 false DOS form DS-1910, Small Business Agency Review-Actions Above the Simplified Acquisition Threshold. 653.219-70 Section 653.219-70... Threshold. As prescribed in 619.501(c), DS-1910 is prescribed for use in documenting set-aside decisions...

Robust MOE Detector for DS-CDMA Systems with Signature Waveform Mismatch

NASA Astrophysics Data System (ADS)

Lin, Tsui-Tsai

In this letter, a decision-directed MOE detector with excellent robustness against signature waveform mismatch is proposed for DS-CDMA systems. Both the theoretic analysis and computer simulation results demonstrate that the proposed detector can provide better SINR performance than that of conventional detectors.

Flying vaccinator; a transgenic mosquito delivers a Leishmania vaccine via blood feeding.

PubMed

Yamamoto, D S; Nagumo, H; Yoshida, S

2010-06-01

'Flying vaccinator' is the concept of using genetically engineered hematophagous insects to deliver vaccines. Here we show the generation of a transgenic anopheline mosquito that expresses the Leishmania vaccine candidate, SP15, fused to monomeric red fluorescent protein (mDsRed) in its salivary glands. Importantly, mice bitten repeatedly by the transgenic mosquitoes raised anti-SP15 antibodies, indicating delivery of SP15 via blood feeding with its immunogenicity intact. Thus, this technology makes possible the generation of transgenic mosquitoes that match the original concept of a 'flying vaccinator'. However, medical safety issues and concerns about informed consent mitigate the use of the 'flying vaccinator' as a method to deliver vaccines. We propose that this expression system could be applied to elucidate saliva-malaria sporozoite interactions.

Post-fire suspended sediment dynamics in a Mediterranean terraced catchment using a nested approach

NASA Astrophysics Data System (ADS)

Garcia-Comendador, Julián; Fortesa, Josep; Calsamiglia, Aleix; Calvo-Cases, Adolfo; Estrany, Joan

2017-04-01

Wildfires promote serious disturbances in the hydrological and sediment dynamics at catchment scale modifying the runoff generation response and the sediment delivery. The hysteretic loops analyses can help to clarify some landscape changes induced by fire. Accordingly, these spatio-temporal relationships between discharge and sediment transport at event scale enable the location of sediment sources, the availability or depletion of sediment and the precipitation threshold necessary to generate functional hillslope-channel connectivity. In addition, a nested catchment approach allows the characterization of the hydro-sedimentological dynamics in different landscape compartments, observing the incidence of the changes generated in the landscape and its evolution to control soil erosion and to implement useful mitigation practices after fire. In July 2013 a large wildfire (2,450 ha) severely affected the western part of Mallorca (Balearic Islands, Spain). The hydrological and sediment delivery processes were assessed in the first three post-fire hydrological years in a representative catchment when the window of disturbance is typically more open. A nested approach was applied in which two gauging stations (i.e., US 1.2 km2 and DS 4.8 km2) were established in September 2013 with continuous measurement of rainfall, water and sediment yield. At DS, a minimal runoff (i.e., 11 mm with 2% of coefficient) and low sediment yield (i.e., 6.3 t km2 yr-1) were generated on average in the study period in which rainfall averaged amount (i.e., 468 mm ± 141) and intensities were representative of long-term records. The hysteretic analysis allowed a better understanding of the effects of wildfires and terraces in sediment yields. For the whole study period, the percentage distribution was 43% (US; two monitored years) and 40% (DS; three monitored years) for clockwise loops in front of 57% (US) and 60% (DS) for counter clockwise loops. This percentage of counter clockwise loops was high if compared with other studies on non-burned Mediterranean catchments probably related with the increased sensitivity of the landscape after wildfire perturbation. During the following years, this percentage -as well as the sediment yield- showed a significant decrease related to the vegetation recovery. The findings also illustrated a differenced behaviour between nested catchments. For the coincident floods between US and DS, only 40% recorded the same hysteresis behaviour. Counter clock loops were predominant in US because of the higher hillslope-channel connectivity of upstream parts of the catchment, whilst the predominance of clockwise loops in DS were indicative of the mobilization of sediment deposited along the river channel and its adjacent areas. These differenced patterns can be attributed to the sediment conveyance losses and storage along the stream channel between stations as well as the size characteristics and the buffering effect of the nested catchments.

Foot Structure in Boys with Down Syndrome.

PubMed

Puszczałowska-Lizis, Ewa; Nowak, Krzysztof; Omorczyk, Jarosław; Ambroży, Tadeusz; Bujas, Przemysław; Nosiadek, Leszek

2017-01-01

Down syndrome (DS) is associated with numerous developmental abnormalities, some of which cause dysfunctions of the posture and the locomotor system. The analysis of selected features of the foot structure in boys with DS versus their peers without developmental disorders is done. The podoscopic examination was performed on 30 boys with DS aged 14-15 years. A control group consisted of 30 age- and gender-matched peers without DS. The feet of boys with DS are flatter compared to their healthy peers. The hallux valgus angle is not the most important feature differentiating the shape of the foot in the boys with DS and their healthy peers. In terms of the V toe setting, healthy boys had poorer results. Specialized therapeutic treatment in individuals with DS should involve exercises to increase the muscle strength around the foot joints, enhancing the stabilization in the joints and proprioception. Introducing orthotics and proper footwear is also important. It is also necessary to monitor the state of the foot in order to modify undertaken therapies.

The burden of trisomy 21 disrupts the proteostasis network in Down syndrome

PubMed Central

Rauniyar, Abhishek K.; Jiang, Hua; Liggett, L. Alexander; Maclean, Kenneth N.

2017-01-01

Down syndrome (DS) is a genetic disorder caused by trisomy of chromosome 21. Abnormalities in chromosome number have the potential to lead to disruption of the proteostasis network (PN) and accumulation of misfolded proteins. DS individuals suffer from several comorbidities, and we hypothesized that disruption of proteostasis could contribute to the observed pathology and decreased cell viability in DS. Our results confirm the presence of a disrupted PN in DS, as several of its elements, including the unfolded protein response, chaperone system, and proteasomal degradation exhibited significant alterations compared to euploid controls in both cell and mouse models. Additionally, when cell models were treated with compounds that promote disrupted proteostasis, we observed diminished levels of cell viability in DS compared to controls. Collectively our findings provide a cellular-level characterization of PN dysfunction in DS and an improved understanding of the potential pathogenic mechanisms contributing to disrupted cellular physiology in DS. Lastly, this study highlights the future potential of designing therapeutic strategies that mitigate protein quality control dysfunction. PMID:28430800

A dynamic systems approach to psychotherapy: A meta-theoretical framework for explaining psychotherapy change processes.

PubMed

Gelo, Omar Carlo Gioacchino; Salvatore, Sergio

2016-07-01

Notwithstanding the many methodological advances made in the field of psychotherapy research, at present a metatheoretical, school-independent framework to explain psychotherapy change processes taking into account their dynamic and complex nature is still lacking. Over the last years, several authors have suggested that a dynamic systems (DS) approach might provide such a framework. In the present paper, we review the main characteristics of a DS approach to psychotherapy. After an overview of the general principles of the DS approach, we describe the extent to which psychotherapy can be considered as a self-organizing open complex system, whose developmental change processes are described in terms of a dialectic dynamics between stability and change over time. Empirical evidence in support of this conceptualization is provided and discussed. Finally, we propose a research design strategy for the empirical investigation of psychotherapy from a DS approach, together with a research case example. We conclude that a DS approach may provide a metatheoretical, school-independent framework allowing us to constructively rethink and enhance the way we conceptualize and empirically investigate psychotherapy. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Clathrin Heavy Chain Is Important for Viability, Oviposition, Embryogenesis and, Possibly, Systemic RNAi Response in the Predatory Mite Metaseiulus occidentalis

PubMed Central

Wu, Ke; Hoy, Marjorie A.

2014-01-01

Clathrin heavy chain has been shown to be important for viability, embryogenesis, and RNA interference (RNAi) in arthropods such as Drosophila melanogaster. However, the functional roles of clathrin heavy chain in chelicerate arthropods, such as the predatory mite Metaseiulus occidentalis, remain unknown. We previously showed that dsRNA ingestion, followed by feeding on spider mites, induced systemic and robust RNAi in M. occidentalis females. In the current study, we performed a loss-of-function analysis of the clathrin heavy chain gene in M. occidentalis using RNAi. We showed that ingestion of clathrin heavy chain dsRNA by M. occidentalis females resulted in gene knockdown and reduced longevity. In addition, clathrin heavy chain dsRNA treatment almost completely abolished oviposition by M. occidentalis females and the few eggs produced did not hatch. Finally, we demonstrated that clathrin heavy chain gene knockdown in M. occidentalis females significantly reduced a subsequent RNAi response induced by ingestion of cathepsin L dsRNA. The last finding suggests that clathrin heavy chain may be involved in systemic RNAi responses mediated by orally delivered dsRNAs in M. occidentalis. PMID:25329675

Advancing clinical decision support using lessons from outside of healthcare: an interdisciplinary systematic review

PubMed Central

2012-01-01

Background Greater use of computerized decision support (DS) systems could address continuing safety and quality problems in healthcare, but the healthcare field has struggled to implement DS technology. This study surveys DS experience across multiple non-healthcare disciplines for new insights that are generalizable to healthcare provider decisions. In particular, it sought design principles and lessons learned from the other disciplines that could inform efforts to accelerate the adoption of clinical decision support (CDS). Methods Our systematic review drew broadly from non-healthcare databases in the basic sciences, social sciences, humanities, engineering, business, and defense: PsychINFO, BusinessSource Premier, Social Sciences Abstracts, Web of Science, and Defense Technical Information Center. Because our interest was in DS that could apply to clinical decisions, we selected articles that (1) provided a review, overview, discussion of lessons learned, or an evaluation of design or implementation aspects of DS within a non-healthcare discipline and (2) involved an element of human judgment at the individual level, as opposed to decisions that can be fully automated or that are made at the organizational level. Results Clinical decisions share some similarities with decisions made by military commanders, business managers, and other leaders: they involve assessing new situations and choosing courses of action with major consequences, under time pressure, and with incomplete information. We identified seven high-level DS system design features from the non-healthcare literature that could be applied to CDS: providing broad, system-level perspectives; customizing interfaces to specific users and roles; making the DS reasoning transparent; presenting data effectively; generating multiple scenarios covering disparate outcomes (e.g., effective; effective with side effects; ineffective); allowing for contingent adaptations; and facilitating collaboration. The article provides examples of each feature. The DS literature also emphasizes the importance of organizational culture and training in implementation success. The literature contrasts “rational-analytic” vs. “naturalistic-intuitive” decision-making styles, but the best approach is often a balanced approach that combines both styles. It is also important for DS systems to enable exploration of multiple assumptions, and incorporation of new information in response to changing circumstances. Conclusions Complex, high-level decision-making has common features across disciplines as seemingly disparate as defense, business, and healthcare. National efforts to advance the health information technology agenda through broader CDS adoption could benefit by applying the DS principles identified in this review. PMID:22900537

A Versatile Transposon-Based Activation Tag Vector System for Functional Genomics in Cereals and Other Monocot Plants1[OA

PubMed Central

Qu, Shaohong; Desai, Aparna; Wing, Rod; Sundaresan, Venkatesan

2008-01-01

Transposon insertional mutagenesis is an effective alternative to T-DNA mutagenesis when transformation through tissue culture is inefficient as is the case for many crop species. When used as activation tags, transposons can be exploited to generate novel gain-of-function phenotypes without transformation and are of particular value in the study of polyploid plants where gene knockouts will not have phenotypes. We have developed an in cis-activation-tagging Ac-Ds transposon system in which a T-DNA vector carries a Dissociation (Ds) element containing 4× cauliflower mosaic virus enhancers along with the Activator (Ac) transposase gene. Stable Ds insertions were selected using green fluorescent protein and red fluorescent protein genes driven by promoters that are functional in maize (Zea mays) and rice (Oryza sativa). The system has been tested in rice, where 638 stable Ds insertions were selected from an initial set of 26 primary transformants. By analysis of 311 flanking sequences mapped to the rice genome, we could demonstrate the wide distribution of the elements over the rice chromosomes. Enhanced expression of rice genes adjacent to Ds insertions was detected in the insertion lines using semiquantitative reverse transcription-PCR method. The in cis-two-element vector system requires minimal number of primary transformants and eliminates the need for crossing, while the use of fluorescent markers instead of antibiotic or herbicide resistance increases the applicability to other plants and eliminates problems with escapes. Because Ac-Ds has been shown to transpose widely in the plant kingdom, the activation vector system developed in this study should be of utility more generally to other monocots. PMID:17993541

Longitudinal telomere shortening and early Alzheimer's disease progression in adults with down syndrome.

PubMed

Jenkins, Edmund C; Marchi, Elaine J; Velinov, Milen T; Ye, Lingling; Krinsky-McHale, Sharon J; Zigman, Warren B; Schupf, Nicole; Silverman, Wayne P

2017-12-01

Telomere shortening was shown to parallel Alzheimer's disease (AD) associated dementia. By using a dual PNA Probe system we have developed a practical method for comparing telomere length in T-lymphocyte interphases from individuals with Down syndrome (DS) with and without "mild cognitive impairment" (MCI-DS) and demonstrated that telomere length can serve as a valid biomarker for the onset of MCI-DS in this high-risk population. To verify progressive cognitive decline we have now examined sequential changes in telomere length in 10 adults with DS (N = 4 Female, N = 6 Male) developing MCI-DS. Cases were selected blind to telomere length from a sample of adults with DS previously enrolled in a prospective longitudinal study at 18-month intervals with clinical and telomere assessments: (1) MCI-DS group data were collected approximately three years prior to development of MCI-DS; (2) 18 months later; (3) when MCI-DS was first observed. These telomere measures were compared to those from another 10 adults with DS matched by sex and approximate age but without indications of MCI-DS (Controls). PNA (peptide nucleic acid) probes for telomeres together with a chromosome two centromere probe were used. Findings indicated telomere shortening over time for both Cases and Controls. Group differences emerged by 18-months prior to recognition of MCI-DS onset and completely non-overlapping distributions of telomere measures were observed by the time of MCI-DS onset. This study adds to accumulating evidence of the value of telomere length, as an early biomarker of AD progression in adults with Down syndrome. © 2017 Wiley Periodicals, Inc.

Denaturation of proteins by SDS and tetraalkylammonium dodecyl sulfates.

PubMed

Lee, Andrew; Tang, Sindy K Y; Mace, Charles R; Whitesides, George M

2011-09-20

This article describes the use of capillary electrophoresis (CE) to examine the influence of different cations (C(+); C(+) = Na(+) and tetra-n-alkylammonium, NR(4)(+), where R = Me, Et, Pr, and Bu) on the rates of denaturation of bovine carbonic anhydrase II (BCA) in the presence of anionic surfactant dodecylsulfate (DS(-)). An analysis of the denaturation of BCA in solutions of Na(+)DS(-) and NR(4)(+)DS(-) (in Tris-Gly buffer) indicated that the rates of formation of complexes of denatured BCA with DS(-) (BCA(D)-DS(-)(n,sat)) are indistinguishable and independent of the cation below the critical micellar concentration (cmc) and independent of the total concentration of DS(-) above the cmc. At concentrations of C(+)DS(-) above the cmc, BCA denatured at rates that depended on the cation; the rates decreased by a factor >10(4) in the order of Na(+) ≈ NMe(4)(+) > NEt(4)(+) > NPr(4)(+) > NBu(4)(+), which is the same order as the values of the cmc (which decrease from 4.0 mM for Na(+)DS(-) to 0.9 mM for NBu(4)(+)DS(-) in Tris-Gly buffer). The relationship between the cmc values and the rates of formation of BCA(D)-DS(-)(n,sat()) suggested that the kinetics of denaturation of BCA involve the association of this protein with monomeric DS(-) rather than with micelles of (C(+)DS(-))(n). A less-detailed survey of seven other proteins (α-lactalbumin, β-lactoglobulin A, β-lactoglobulin B, carboxypeptidase B, creatine phosphokinase, myoglobin, and ubiquitin) showed that the difference between Na(+)DS(-) and NR(4)(+)DS(-) observed with BCA was not general. Instead, the influence of NR(4)(+) on the association of DS(-) with these proteins depended on the protein. The selection of the cation contributed to the properties (including the composition, electrophoretic mobility, and partitioning behavior in aqueous two-phase systems) of aggregates of denatured protein and DS(-). These results suggest that the variation in the behavior of NR(4)(+)DS(-) with changes in R may be exploited in methods used to analyze and separate mixtures of proteins. © 2011 American Chemical Society

High Avidity dsDNA Autoantibodies in Brazilian Women with Systemic Lupus Erythematosus: Correlation with Active Disease and Renal Dysfunction

PubMed Central

Oliveira, Rodrigo C.; Oliveira, Isabela S.; Santiago, Mittermayer B.; Sousa Atta, Maria L. B.; Atta, Ajax M.

2015-01-01

We investigated in Brazilian women with SLE the prevalence and levels of high avidity (HA) dsDNA antibodies and tested their correlation with lupus activity and biomarkers of renal disease. We also compared these correlations to those observed with total dsDNA antibodies and antibodies against nucleosome (ANuA). Autoantibodies were detected by ELISA, while C3 and C4 levels were determined by nephelometry. Urine protein/creatinine ratio was determined, and lupus activity was measured by SLEDAI-2K. The prevalence of total and HA dsDNA antibodies was similar to but lower than that verified for ANuA. The levels of the three types of antibodies were correlated, but the correlation was more significant between HA dsDNA antibodies and ANuA. High avidity dsDNA antibodies correlated positively with ESR and SLEDAI and inversely with C3 and C4. Similar correlations were observed for ANuA levels, whereas total dsDNA antibodies only correlated with SLEDAI and C3. The levels of HA dsDNA antibodies were higher in patients with proteinuria, but their levels of total dsDNA antibodies and ANuA were unaltered. High avidity dsDNA antibodies can be found in high prevalence in Brazilian women with SLE and are important biomarkers of active disease and kidney dysfunction. PMID:26583157

High Avidity dsDNA Autoantibodies in Brazilian Women with Systemic Lupus Erythematosus: Correlation with Active Disease and Renal Dysfunction.

PubMed

Oliveira, Rodrigo C; Oliveira, Isabela S; Santiago, Mittermayer B; Sousa Atta, Maria L B; Atta, Ajax M

2015-01-01

We investigated in Brazilian women with SLE the prevalence and levels of high avidity (HA) dsDNA antibodies and tested their correlation with lupus activity and biomarkers of renal disease. We also compared these correlations to those observed with total dsDNA antibodies and antibodies against nucleosome (ANuA). Autoantibodies were detected by ELISA, while C3 and C4 levels were determined by nephelometry. Urine protein/creatinine ratio was determined, and lupus activity was measured by SLEDAI-2K. The prevalence of total and HA dsDNA antibodies was similar to but lower than that verified for ANuA. The levels of the three types of antibodies were correlated, but the correlation was more significant between HA dsDNA antibodies and ANuA. High avidity dsDNA antibodies correlated positively with ESR and SLEDAI and inversely with C3 and C4. Similar correlations were observed for ANuA levels, whereas total dsDNA antibodies only correlated with SLEDAI and C3. The levels of HA dsDNA antibodies were higher in patients with proteinuria, but their levels of total dsDNA antibodies and ANuA were unaltered. High avidity dsDNA antibodies can be found in high prevalence in Brazilian women with SLE and are important biomarkers of active disease and kidney dysfunction.

Dental attendance patterns among older people: a retrospective review of records in public and private dental care in Sweden.

PubMed

Derblom, C; Hagman-Gustafsson, M-L; Gabre, P

2017-11-01

Nowadays, older people retain their natural teeth more frequently and so are at increased risk of oral disease. At the same time, discontinued contacts with dental services prevent access to preventive care and increase the risk of undetected disease. This study aims to evaluate how often older people discontinue regular dental visits and to establish the reasons. This study is a retrospective review of records of patients aged ≥75 years from seven Swedish clinics, three in the public dental service (PuDS) and four in the private (PrDS). All patients were examined in 2010, and their dental attendance records from 2010 to 2014 studied. Data included gender, dental insurance system, last performed planned examination, emergency visits, registrations in the recall system, cause of discontinued care and number of teeth and implants. In total, 993 records were studied, 303 in PuDS and 690 in PrDS. In both groups, 10% of patients had no complete dental examinations between 2010 and 2014 after baseline examination in 2010. One-quarter were not registered in the recall system after their last examinations, and this was more common in PrDS than PuDS. In many cases, no reason for discontinued regular visits were described in the records. The mean number of natural teeth was 19.0 in both groups, but there were more implants in the PrDS group. A large proportion of the participants risked losing regular contact with dental services. Dental services appeared to lack strategies for maintaining regular dental care for elderly patients. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Recombinant modified vaccinia virus Ankara generating excess early double-stranded RNA transiently activates protein kinase R and triggers enhanced innate immune responses.

PubMed

Wolferstätter, Michael; Schweneker, Marc; Späth, Michaela; Lukassen, Susanne; Klingenberg, Marieken; Brinkmann, Kay; Wielert, Ursula; Lauterbach, Henning; Hochrein, Hubertus; Chaplin, Paul; Suter, Mark; Hausmann, Jürgen

2014-12-01

Double-stranded RNA (dsRNA) is an important molecular pattern associated with viral infection and is detected by various extra- and intracellular recognition molecules. Poxviruses have evolved to avoid producing dsRNA early in infection but generate significant amounts of dsRNA late in infection due to convergent transcription of late genes. Protein kinase R (PKR) is activated by dsRNA and triggers major cellular defenses against viral infection, including protein synthesis shutdown, apoptosis, and type I interferon (IFN-I) production. The poxviral E3 protein binds and sequesters viral dsRNA and is a major antagonist of the PKR pathway. We found that the highly replication-restricted modified vaccinia virus Ankara (MVA) engineered to produce excess amounts of dsRNA early in infection showed enhanced induction of IFN-β in murine and human cells in the presence of an intact E3L gene. IFN-β induction required a minimum overlap length of 300 bp between early complementary transcripts and was strongly PKR dependent. Excess early dsRNA produced by MVA activated PKR early but transiently in murine cells and induced enhanced systemic levels of IFN-α, IFN-γ, and other cytokines and chemokines in mice in a largely PKR-dependent manner. Replication-competent chorioallantois vaccinia virus Ankara (CVA) generating excess early dsRNA also enhanced IFN-I production and was apathogenic in mice even at very high doses but showed no in vitro host range defect. Thus, genetically adjuvanting MVA and CVA to generate excess early dsRNA is an effective method to enhance innate immune stimulation by orthopoxvirus vectors and to attenuate replicating vaccinia virus in vivo. Efficient cellular sensing of pathogen-specific components, including double-stranded RNA (dsRNA), is an important prerequisite of an effective antiviral immune response. The prototype poxvirus vaccinia virus (VACV) and its derivative modified vaccinia virus Ankara (MVA) produce dsRNA as a by-product of viral transcription. We found that inhibition of cellular dsRNA recognition established by the virus-encoded proteins E3 and K3 can be overcome by directing viral overexpression of dsRNA early in infection without compromising replication of MVA in permissive cells. Early dsRNA induced transient activation of the cellular dsRNA sensor protein kinase R (PKR), resulting in enhanced production of interferons and cytokines in cells and mice. Enhancing the capacity of MVA to activate the innate immune system is an important approach to further improve the immunogenicity of this promising vaccine vector. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

[Diagnostic advantages of the test system "DS-EIA-HBsAg-0.01" for detection of HBV surface antigen].

PubMed

Egorova, N I; Pyrenkova, I Iu; Igolkina, S N; Sharipova, I N; Puzyrev, V F; Obriadina, A P; Burkov, A N; Kornienko, N V; Fields, H A; Korovkin, A S; Shalunova, N V; Bektemirov, T A; Kuznetsov, K V; Koshcheeva, N A; Ulanova, T I

2009-01-01

The new highly sensitive test system "DS-EIA-HBsAg-0.01" (Priority Certificate No. 2006129019 of August 10, 2006) in detecting hepatitis B surface antigen (HBsAg) was assessed. The sensitivity of the test was estimated using the federal standards sample HBsAg 42-28-311-06, panels' samples Boston Biomedica Inc. (West Bridgewater, Mass, USA) and ZeptoMetrix Corp. (Buffalo, NY, USA). The findings have indicated that "DS-EIA-HBsAg-0.01" is equally effective in detecting different subtypes of HBsAg during a seroconversion period earlier than alternative assays. Along with its high analytical and diagnostic sensitivity, the system shows a high diagnostic specificity.

Changing Paradigms in Down Syndrome: The First International Conference of the Trisomy 21 Research Society.

PubMed

Delabar, Jean-Maurice; Allinquant, Bernadette; Bianchi, Diana; Blumenthal, Tom; Dekker, Alain; Edgin, Jamie; O'Bryan, John; Dierssen, Mara; Potier, Marie-Claude; Wiseman, Frances; Guedj, Faycal; Créau, Nicole; Reeves, Roger; Gardiner, Katheleen; Busciglio, Jorge

2016-10-01

Down syndrome (DS) is the most common genetic cause of intellectual disability (ID) in humans with an incidence of ∼1:1,000 live births worldwide. It is caused by the presence of an extra copy of all or a segment of the long arm of human chromosome 21 (trisomy 21). People with DS present with a constellation of phenotypic alterations involving most organs and organ systems. ID is present in all people with DS, albeit with variable severity. DS is also the most frequent genetic cause of Alzheimer's disease (AD), and ∼50% of those with DS will develop AD-related dementia. In the last few years, significant progress has been made in understanding the crucial genotype-phenotype relationships in DS, in identifying the alterations in molecular pathways leading to the various clinical conditions present in DS, and in preclinical evaluations of potential therapies to improve the overall health and well-being of individuals with DS. In June 2015, 230 scientists, advocates, patients, and family members met in Paris for the 1st International Conference of the Trisomy 21 Research Society. Here, we report some of the most relevant presentations that took place during the meeting.

Taking Emergence Seriously: The Centrality of Circular Causality for Dynamic Systems Approaches to Development

ERIC Educational Resources Information Center

Witherington, David C.

2011-01-01

The dynamic systems (DS) approach has emerged as an influential and potentially unifying metatheory for developmental science. Its central platform--the argument against design--suggests that structure spontaneously and without prescription emerges through self-organization. In one of the most prominent accounts of DS, Thelen and her colleagues…

Defect in dermatan sulfate in urine of patients with Ehlers-Danlos syndrome caused by a CHST14/D4ST1 deficiency.

PubMed

Mizumoto, Shuji; Kosho, Tomoki; Hatamochi, Atsushi; Honda, Tomoko; Yamaguchi, Tomomi; Okamoto, Nobuhiko; Miyake, Noriko; Yamada, Shuhei; Sugahara, Kazuyuki

2017-08-01

Dermatan sulfate (DS) plays a number of roles in a wide range of biological activities such as cell signaling and tissue morphogenesis through interactions with various extracellular matrix proteins including collagen. Mutations in the carbohydrate sulfotransferase 14 gene (CHST14) encoding CHST14/dermatan 4-O-sulfotransferase-1 (D4ST1), which is responsible for the biosynthesis of DS, cause a recently delineated form of Ehlers-Danlos syndrome (EDS, musculocontractural type 1), an autosomal recessive connective tissue disorder characterized by congenital malformations (specific craniofacial features, and congenital multiple contractures) and progressive fragility-related complications (skin hyperextensibility, bruisability, and fragility with atrophic scars; recurrent dislocations; progressive talipes or spinal deformities; and large subcutaneous hematomas). In an attempt to develop a diagnostic screening method for this type of EDS, the amount of DS in the urine of patients was analyzed. Urinary DS was quantified by an anion-exchange chromatography after treatment with DS-specific degrading enzyme. DS was not detected in the urine of patients with homo- or compound heterozygous mutations in CHST14. These results suggest that the quantification of DS in urine is applicable to an initial diagnosis of DS-defective EDS. This is the first study to perform a urinary disaccharide compositional analysis of chondroitin sulfate (CS)/DS chains in patients with EDS caused by a CHST14/D4ST1 deficiency, and demonstrated the absence of DS chains. This result suggests systemic DS depletion in this disorder, and also proposes the usefulness of a urinary disaccharide compositional analysis of CS/DS chains as a non-invasive screening method for this disorder. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Single Pore Translocation of Folded, Double-Stranded, and Tetra-stranded DNA through Channel of Bacteriophage Phi29 DNA Packaging Motor

PubMed Central

Haque, Farzin; Wang, Shaoying; Stites, Chris; Chen, Li; Wang, Chi; Guo, Peixuan

2015-01-01

The elegant architecture of the channel of bacteriophage phi29 DNA packaging motor has inspired the development of biomimetics for biophysical and nanobiomedical applications. The reengineered channel inserted into a lipid membrane exhibits robust electrophysiological properties ideal for precise sensing and fingerprinting of dsDNA at the single-molecule level. Herein, we used single channel conduction assays to quantitatively evaluate the translocation dynamics of dsDNA as a function of the length and conformation of dsDNA. We extracted the speed of dsDNA translocation from the dwell time distribution and estimated the various forces involved in the translocation process. A ~35-fold slower speed of translocation per base pair was observed for long dsDNA, a significant contrast to the speed of dsDNA crossing synthetic pores. It was found that the channel could translocate both dsDNA with ~32% of channel current blockage and ~64% for tetra-stranded DNA (two parallel dsDNA). The calculation of both cross-sectional areas of the dsDNA and tetra-stranded DNA suggested that the blockage was purely proportional to the physical space of the channel lumen and the size of the DNA substrate. Folded dsDNA configuration was clearly reflected in their characteristic current signatures. The finding of translocation of tetra-stranded DNA with 64% blockage is in consent with the recently elucidated mechanism of viral DNA packaging via a revolution mode that requires a channel larger than the dsDNA diameter of 2 nm to provide room for viral DNA revolving without rotation. The understanding of the dynamics of dsDNA translocation in the phi29 system will enable us to design more sophisticated single pore DNA translocation devices for future applications in nanotechnology and personal medicine. PMID:25890769

Wireless Technology

DTIC Science & Technology

2009-03-01

section, we use as an illustration vehicle for the proposed GLRT schemes a packet-data DS - CDMA communication system2. At all times, the GLRT detectors...are imple- 2The combined effect of DS - CDMA multiple access interference (MAI) and AWGN is Gaussian-mixture distributed and not plain Gaussian. It is...closely to the SMI detector in (9) and outperforms all other detectors. DS - CDMA Case-study #2 Asynchronous multipath fading channel: Pilot-assisted

Noise-induced creation and annihilation of dissipative solitons (DS) in a passively mode-locked laser

NASA Astrophysics Data System (ADS)

Teamir, Tesfay; Elahi, Parviz; Makey, Ghaith; Fatih, Ilday

Passive mode-locking, resulting in self-organized formation of femtoseconds-long laser pulses, constitutes a far-from-equilibrium steady state. Mode-locking is not only important for laser technology, but also of fundamental interest for broad class of systems. Despite numerous studies on their nonlinear dynamics, there is little understanding of the transitions that intrinsic noise can induce. We show that transitions between single-DS and multi-DS states can be triggered. Near critical points, DS states are observed to repeatedly exchange energy among themselves, form DS clusters with varying or vibrating temporal separation, often followed by random transformations among different states. This critical behavior appears to be caused by soliton-soliton or soliton-generated dispersive wave interactions. Irrespective of the specifics of the state, the measured noise level of the laser starts at a moderate value, is then reduced, as the DS's energy is increased. Further increases in power (nonlinearity) drives it towards a noisy critical state, where creation or annihilation of pulses occurs just before a new steady state is formed. These noise-induced transitions between steady states can shed light on the thermodynamics of far-from-equilibrium systems. TàBITAK (113F319) and ERC CoG (617521).

Foot Structure in Boys with Down Syndrome

PubMed Central

Nowak, Krzysztof; Omorczyk, Jarosław; Ambroży, Tadeusz; Nosiadek, Leszek

2017-01-01

Introduction and Aim Down syndrome (DS) is associated with numerous developmental abnormalities, some of which cause dysfunctions of the posture and the locomotor system. The analysis of selected features of the foot structure in boys with DS versus their peers without developmental disorders is done. Materials and Methods The podoscopic examination was performed on 30 boys with DS aged 14-15 years. A control group consisted of 30 age- and gender-matched peers without DS. Results The feet of boys with DS are flatter compared to their healthy peers. The hallux valgus angle is not the most important feature differentiating the shape of the foot in the boys with DS and their healthy peers. In terms of the V toe setting, healthy boys had poorer results. Conclusions Specialized therapeutic treatment in individuals with DS should involve exercises to increase the muscle strength around the foot joints, enhancing the stabilization in the joints and proprioception. Introducing orthotics and proper footwear is also important. It is also necessary to monitor the state of the foot in order to modify undertaken therapies. PMID:28904967

Sensitivity and specificity of ANA and anti-dsDNA in the diagnosis of systemic lupus erythematosus: a comparison using control sera obtained from healthy individuals and patients with multiple medical problems.

PubMed

Wichainun, Ramjai; Kasitanon, Nuntana; Wangkaew, Suparaporn; Hongsongkiat, Sith; Sukitawut, Waraporn; Louthrenoo, Worawit

2013-12-01

Antinuclear antibodies (ANA) and anti-double stranded DNA (anti-dsDNA) are often tested as a screening tool in patients with suspected systemic lupus erythematosus or connective tissue diseases. ANA can be seen in healthy controls (HC) and patients with multiple medical problems (MMP). To determine the sensitivity and specificity of ANA and anti-dsDNA in SLE patients, using sera from HC and MMP patients. Serum samples from HC, MMP and SLE patients, 100 in each group, were analyzed for the presence of ANA and anti-dsDNA, by indirect immunofluorescent assay, using a HEp-2 cell and Crithidia luciliae as substrates, respectively. The prevalence of ANA at a titer of ≥1:80 and ≥ 1:160 was 8% and 4%, respectively, in HC; and it was 12% and 6% respectively, in MMP patients. The prevalence of anti-dsDNA was 0% in HC and 3% in MMP patients. When using HC sera for the diagnosis of SLE, the sensitivity of ANA at a titer of ≥ 1:80 and ≥ 1:160 was 98% and 90%, respectively, with specificity of 92% and 96%, respectively. The specificity decreased to 88% and 94%, respectively, when using sera from MMP patients. The specificity of anti-dsDNA was 100% and 97%, when using sera from HC and MMP patients, respectively. ANA and anti-dsDNA gave high sensitivity and high specificity in patients with SLE, even when using MMP patient's sera as controls. Physicians should take care in interpreting ANA and anti-dsDNA results in MMP patients who do not have signs or symptoms of SLE or connective tissue diseases.

Common and specific impairments in attention functioning in girls with chromosome 22q11.2 deletion, fragile X or Turner syndromes

PubMed Central

2014-01-01

Background Chromosome 22q11.2 deletion syndrome (22q11.2DS), fragile X syndrome (FXS), and Turner syndrome (TS) are complex and variable developmental syndromes caused by different genetic abnormalities; yet, they share similar cognitive impairments in the domains of numbers, space, and time. The atypical development of foundational neural networks that underpin the attentional system is thought to result in further impairments in higher-order cognitive functions. The current study investigates whether children with similar higher-order cognitive impairments but different genetic disorders also show similar impairments in alerting, orienting, and executive control of attention. Methods Girls with 22q11.2DS, FXS, or TS and typically developing (TD) girls, aged 7 to 15 years, completed an attention network test, a flanker task with alerting and orienting cues. Exploration of reaction times and accuracy allowed us to test for potential commonalities in attentional functioning in alerting, orienting, and executive control. Linear regression models were used to test whether the predictors of group and chronological age were able to predict differences in attention indices. Results Girls with 22q11.2DS, FXS, or TS demonstrated unimpaired function of the alerting system and impaired function of the executive control system. Diagnosis-specific impairments were found such that girls with FXS made more errors and had a reduced orienting index, while girls with 22q11.2DS showed specific age-related deficits in the executive control system. Conclusions These results suggest that the control but not the implementation of attention is selectively impaired in girls with 22q11.2DS, TS or FXS. Additionally, the age effect on executive control in girls with 22q11.2DS implies a possible altered developmental trajectory. PMID:24628892

Double-stranded RNA delivery through soaking mediates silencing of the muscle protein 20 and increases mortality to the Asian citrus psyllid, Diaphorina citri.

PubMed

Yu, Xiudao; Gowda, Siddarame; Killiny, Nabil

2017-09-01

Asian citrus psyllid, Diaphorina citri Kuwayama, is the most important economic pest of citrus because it transmits Candidatus Liberibacter asiaticus (CLas), the causal agent of huanglongbing (HLB). Silencing genes by RNA interference (RNAi) is a promising approach for controlling D. citri. RNAi-based insect management strategies depend on the selection of suitable target genes. The muscle protein 20 gene DcMP20 was characterized from D. citri in an effort to impair proper muscle development through RNAi. Phylogenetic analysis showed that DcMP20 was more closely related to MP20 from Drosophila compared with its counterpart from other insect species. Developmental expression analysis revealed that transcription of DcMP20 was development dependent and reached a maximum level in the last instar (fourth-fifth) of the nymphal stage. The extent of RNAi in D. citri was dose dependent, with dsRNA-DcMP20 at 75 ng µL -1 being sufficient to knock down endogenous DcMP20 expression, which resulted in significant mortality and reduced body weight that positively correlated with the silencing of DcMP20. No effect was found when dsRNA-GFP or water was used, indicating the specific effect of dsRNA-DcMP20. Our results suggest that dsRNA can be delivered to D. citri through soaking, and DcMP20 is an effective RNAi target to be used in the management of D. citri. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Anti-dsDNA antibodies in systemic lupus erythematosus: A combination of two quantitative methods and the ANA pattern is the most efficient strategy of detection.

PubMed

Almeida González, Delia; Roces Varela, Alfredo; Marcelino Rodríguez, Itahisa; González Vera, Alexander; Delgado Sánchez, Mónica; Aznar Esquivel, Antonio; Casañas Rodríguez, Carlos; Cabrera de León, Antonio

2015-12-01

Several methods have been used to measure anti-double-stranded DNA auto-antibody (anti-dsDNA). Our aim was to determine the most efficient strategy to test anti-dsDNA in systemic lupus erythematosus (SLE). In this study, anti-dsDNA and anti-nuclear antibody (ANA) tests were requested for 644 patients. Anti-dsDNA was tested by RIA, ELISA and CLIA in all patients. The results indicated that 78 patients had a positive anti-dsDNA test according to at least one of the methods. After a 3-year follow-up period only 26 patients were diagnosed with SLE. We evaluated each method and combination of methods. Specificity and positive predictive value (PPV) increased with the number of assay methods used (p=0.002 for trend), and PPV was 100% in patients whose results were positive by all three anti-dsDNA assay methods. The proportion of anti-dsDNA-positive patients who had SLE was highest (82%; p b 0.001) among those with a homogeneous pattern of ANA staining, followed by those with a speckled pattern. In ANA positive patients, when only RIA was considered, 59% of anti-dsDNA-positive patients had SLE, but when RIA and CLIA were both considered, all patients with positive results on both tests had SLE. The combination of RIA+CLIA in patients with homogeneous and speckled ANA staining showed a similar cost and higher sensitivity than RIA alone in ANA positive patients (p b 0.001). We conclude that the most efficient strategy was to combine simultaneously two quantitative and sensitive methods but only in patients with a homogeneous or speckled pattern of ANA staining. This approach maximized specificity and PPV, and reduced costs. Copyright © 2015 Elsevier B.V. All rights reserved.

RNA-seq Analysis Reveals Unique Transcriptome Signatures in Systemic Lupus Erythematosus Patients with Distinct Autoantibody Specificities

PubMed Central

Rai, Richa; Chauhan, Sudhir Kumar; Singh, Vikas Vikram; Rai, Madhukar; Rai, Geeta

2016-01-01

Systemic lupus erythematosus (SLE) patients exhibit immense heterogeneity which is challenging from the diagnostic perspective. Emerging high throughput sequencing technologies have been proved to be a useful platform to understand the complex and dynamic disease processes. SLE patients categorised based on autoantibody specificities are reported to have differential immuno-regulatory mechanisms. Therefore, we performed RNA-seq analysis to identify transcriptomics of SLE patients with distinguished autoantibody specificities. The SLE patients were segregated into three subsets based on the type of autoantibodies present in their sera (anti-dsDNA+ group with anti-dsDNA autoantibody alone; anti-ENA+ group having autoantibodies against extractable nuclear antigens (ENA) only, and anti-dsDNA+ENA+ group having autoantibodies to both dsDNA and ENA). Global transcriptome profiling for each SLE patients subsets was performed using Illumina® Hiseq-2000 platform. The biological relevance of dysregulated transcripts in each SLE subsets was assessed by ingenuity pathway analysis (IPA) software. We observed that dysregulation in the transcriptome expression pattern was clearly distinct in each SLE patients subsets. IPA analysis of transcripts uniquely expressed in different SLE groups revealed specific biological pathways to be affected in each SLE subsets. Multiple cytokine signaling pathways were specifically dysregulated in anti-dsDNA+ patients whereas Interferon signaling was predominantly dysregulated in anti-ENA+ patients. In anti-dsDNA+ENA+ patients regulation of actin based motility by Rho pathway was significantly affected. The granulocyte gene signature was a common feature to all SLE subsets; however, anti-dsDNA+ group showed relatively predominant expression of these genes. Dysregulation of Plasma cell related transcripts were higher in anti-dsDNA+ and anti-ENA+ patients as compared to anti-dsDNA+ ENA+. Association of specific canonical pathways with the uniquely expressed transcripts in each SLE subgroup indicates that specific immunological disease mechanisms are operative in distinct SLE patients’ subsets. This ‘sub-grouping’ approach could further be useful for clinical evaluation of SLE patients and devising targeted therapeutics. PMID:27835693

Aqueous solubility of diclofenac diethylamine in the presence of pharmaceutical additives: a comparative study with diclofenac sodium.

PubMed

Khalil, E; Najjar, S; Sallam, A

2000-04-01

Aqueous solubility of diclofenac diethylamine (DDEA), a nonsteroidal anti-inflammatory drug currently formulated as a topical emulgel, was studied in the presence of pharmaceutical additives and compared with diclofenac sodium (DS). Electrolytes at low concentrations exhibited a salting-in effect on DDEA with peak solubility that was attributed to the association of DDEA into micelles, followed by a salting-out effect at higher concentrations, by which structure formation by DDEA molecules increased and precipitation occurred. For DS, which is not capable of forming micelles, the salting-out effect was dominant due to the common ion effect. Cosolvents displayed significant enhancement in solubility of both salts except glycerol, which showed a slight increase in solubility of DDEA and a decrease in solubility of DS due to transformation into the less soluble hydrate form. Ethanol and polyethylene glycol (PEG) 400 cosolvent systems at all concentrations showed positive deviations from the log-linear solubility equation. In the case of propylene glycol (PG) cosolvent systems, negative deviations were observed at low volume fractions of cosolvent, while positive deviations were observed at high volume fractions of cosolvent for DS and DDEA. The parent drug, being less ionizable and highly nonpolar, showed negative deviations up to 90% PG content. Thus, the positive deviations for DS and DDEA could be attributed to the more ionizable carboxylic group and its higher ability for hydrogen bonding at higher fractions of cosolvent. Polyvinylpyrrolidone (PVP) and PEG4000 or PEG6000 enhanced the solubility of DS and DDEA, with PVP exerting higher solubilizing efficiency and DS showing better solubility than DDEA. Solubilities of DS in Tween 80 (T80) and Pluronic F-127 (PF127) aqueous solutions were almost similar, while the solubility of DDEA in the presence of T80 was higher than the solubility in the presence of PF127. DS appeared to be located more in the polyoxyethylene mantle of the micelles, while DDEA was located more in the core of the micelles.

C4 deficiency is a predisposing factor for Streptococcus pneumoniae-induced autoantibody production

PubMed Central

Yammani, Rama D.; Leyva, Marcela A.; Jennings, Ryan N.; Haas, Karen M.

2015-01-01

Reductions in C4 levels may predispose individuals to infection with encapsulated bacteria as well as autoimmunity. In this study, we examined the role C4 has in protection against Streptococcus pneumoniae-induced autoimmunity. Mild respiratory infection with serotype 19F pneumococci selectively induced systemic anti-dsDNA IgA production in naïve C4-/- mice, but not C3-/- or wild type mice. Systemic challenge with virulent serotype 3 pneumococci also induced anti-dsDNA IgA production in immune C4-/- mice. Remarkably, pneumococcal polysaccharide (PPS) vaccination alone induced C4-/- mice to produce increased anti-dsDNA IgA levels that were maintained in some mice for months. These effects were most pronounced in female C4-/- mice. Importantly, immunization-induced increases in anti-dsDNA IgA levels were strongly associated with increased IgA deposition in kidneys. Cross-reactivity between pneumococcal antigens and dsDNA played a partial role in the induction of anti-dsDNA IgA, but a major role for PPS-associated TLR2 agonists was also revealed. Administration of the TLR2/4 antagonist, OxPAPC, at the time of PPS immunization completely blocked the production of anti-dsDNA IgA in C4-/- mice without suppressing PPS-specific Ab production. The TLR2 agonist, Pam3Csk4, similarly induced anti-dsDNA IgA production in C4-/- mice, which OxPAPC also prevented. LPS, a TLR4 agonist, had no effect. Pam3Csk4, but not LPS, also induced dsDNA-specific IgA production by C4-/- splenic IgA+ B cells in vitro, indicating TLR2 agonists can stimulate autoAb production via B cell-intrinsic mechanisms. Collectively, our results show an important role for C4 in suppressing autoAb production elicited by cross-reactive antigens and TLR2 agonists associated with S. pneumoniae. PMID:25339671

Close-loop performance of a high precision deflectometry controlled deformable mirror (DCDM) unit for wavefront correction in adaptive optics system

NASA Astrophysics Data System (ADS)

Huang, Lei; Zhou, Chenlu; Zhao, Wenchuan; Choi, Heejoo; Graves, Logan; Kim, Daewook

2017-06-01

We present a high precision deflectometry system (DS) controlled deformable mirror (DM) solution for optical system. Different from wavefront and non-wavefront system, the DS and the DM are set to be an individual integrated DCDM unit and can be installed in one base plate. In the DCDM unit, the DS can directly provide the influence functions and surface shape of the DM to the industrial computer in any adaptive optics system. As an integrated adaptive unit, the DCDM unit could be put into various optical systems to realize aberration compensation. In this paper, the configuration and principle of the DCDM unit is introduced first. Theoretical simulation on the close-loop performance of the DCDM unit is carried out. Finally, a verification experiment is proposed to verify the compensation capability of the DCDM unit.

The relationship between increased levels of Anti-dsDNA with clinical manifestation in patients with SLE in Haji Adam Malik General Hospital Medan

NASA Astrophysics Data System (ADS)

Marpaung, B.; Patrick, J.

2018-03-01

Systemic Lupus Erythematosus (SLE) is an autoimmune rheumatic disease characterized by widespread inflammation and affects any organism the body. Many autoimmune diseases result in autoantibody production, but Anti-dsDNA antibodies are highly specific to SLE. Previous study found that Anti-dsDNA antibodies are associated with severe clinical manifestations of lupus. The aim of this study was to examine the relationship between anti-dsDNA level with clinical features and laboratory findings in SLE patients. This cross-sectional study was conducted in Hospital Haji Adam Malik Medan in May-October 2016.We examine anti-dsDNA, clinical features and kidney laboratory profile in all patient. Data were statistically analyzed.81 SLE patients with median level of anti-dsDNA 294 (6.1-1317). There was no significant relationship between increased level of Anti-dsDNA with clinical manifestations (p>0.05). There were significant relationships between increased level of Anti-dsDNA with renal impairment (p=0.049), urea level (p=0.016), urine protein (p=0.042) and hematology disorder (p=0.005). Arthritis is the most frequent clinical manifestation (96.3%) followed by malar rash (77.8%). Elevated anti-dsDNA level was not related with clinical manifestations but there was significant relationship with hematology disorder, urea, creatinine, and proteinuria in SLE patents.

Re-thinking the role of the dorsal striatum in egocentric/response strategy.

PubMed

Botreau, Fanny; Gisquet-Verrier, Pascale

2010-01-01

Rats trained in a dual-solution cross-maze task, which can be solved by place and response strategies, predominantly used a response strategy after extensive training. This paper examines the involvement of the medial and lateral dorsal striatum (mDS and lDS) in the choice of these strategies after partial and extensive training. Our results show that rats with lDS and mDS lesions used mainly a response strategy from the early phase of training. We replicated these unexpected data in rats with lDS lesions and confirmed their tendency to use the response strategy in a modified cross-maze task. When trained in a dual-solution water-maze task, however, control and lesioned rats consistently used a place strategy, demonstrating that lDS and mDS lesioned rats can use a place strategy and that the shift towards a response strategy did not systematically result from extensive training. The present data did not show any clear dissociation between the mDS and lDS in dual solution tasks. They further indicate that the dorsal striatum seems to determine the strategies adopted in a particular context but cannot be considered as a neural support for the response memory system. Accordingly, the role of the lateral and medial part of the dorsal striatum in egocentric/response memory should be reconsidered.

Computational design of co-assembling protein-DNA nanowires

NASA Astrophysics Data System (ADS)

Mou, Yun; Yu, Jiun-Yann; Wannier, Timothy M.; Guo, Chin-Lin; Mayo, Stephen L.

2015-09-01

Biomolecular self-assemblies are of great interest to nanotechnologists because of their functional versatility and their biocompatibility. Over the past decade, sophisticated single-component nanostructures composed exclusively of nucleic acids, peptides and proteins have been reported, and these nanostructures have been used in a wide range of applications, from drug delivery to molecular computing. Despite these successes, the development of hybrid co-assemblies of nucleic acids and proteins has remained elusive. Here we use computational protein design to create a protein-DNA co-assembling nanomaterial whose assembly is driven via non-covalent interactions. To achieve this, a homodimerization interface is engineered onto the Drosophila Engrailed homeodomain (ENH), allowing the dimerized protein complex to bind to two double-stranded DNA (dsDNA) molecules. By varying the arrangement of protein-binding sites on the dsDNA, an irregular bulk nanoparticle or a nanowire with single-molecule width can be spontaneously formed by mixing the protein and dsDNA building blocks. We characterize the protein-DNA nanowire using fluorescence microscopy, atomic force microscopy and X-ray crystallography, confirming that the nanowire is formed via the proposed mechanism. This work lays the foundation for the development of new classes of protein-DNA hybrid materials. Further applications can be explored by incorporating DNA origami, DNA aptamers and/or peptide epitopes into the protein-DNA framework presented here.

Effects of chlorhexidine (gel) application on bacterial levels and orthodontic brackets during orthodontic treatment.

PubMed

Al-Bazi, Samar M; Abbassy, Mona A; Bakry, Ahmed S; Merdad, Leena A; Hassan, Ali H

2016-01-01

The objectives of this study were to evaluate the effects of applying 0.50% chlorhexidine (CHX) gel using the dental drug delivery system (3DS) on salivary Streptococcus mutans (S. mutans) and on the surface topography of metal and ceramic orthodontic brackets. The study involved 20 orthodontic patients with high levels of salivary S. mutans. The patients were treated with professional mechanical tooth cleaning followed by application of 0.50% CHX using individual trays (3DS). Salivary S. mutans levels were repeatedly measured 1, 2, 4, and 8 weeks post-treatment. In vitro study utilized forty ceramic and metallic brackets that were immersed in 0.50% CHX gel for 10 min, whereas another untreated forty brackets served as controls. The frictional resistances of stainless steel wires to the brackets before and after CHX treatment were recorded using a universal testing machine. Scanning electron microscopy was used to compare changes in the surface topography of brackets. Statistical analyses were used to determine the effect of CHX on bacterial count and to evaluate the effect of CHX on frictional resistance. According to the results of this study, S. mutans levels were reduced significantly (P < 0.05). There were no significant changes in the frictional resistance and surface topography of brackets before or after application of CHX. (J Oral Sci 58, 35-42, 2016).

Biophysical and electrochemical properties of Self-assembled noncovalent SWNT/DNA hybrid and electroactive nanostructure

NASA Astrophysics Data System (ADS)

Mirzapoor, Aboulfazl; Ranjbar, Bijan

2017-09-01

DNA self-assembled hybrid nanostructures are widely used in recent research in nanobiotechnology. Combination of DNA with carbon based nanoparticles such as single-walled carbon nanotube (SWNT), multi-walled carbon nanotube (MWNT) and carbon quantum dot were applied in important biological applications. Many examples of biosensors, nanowires and nanoelectronic devices, nanomachine and drug delivery systems are fabricated by these hybrid nanostructures. In this study, a new hybrid nanostructure has been fabricated by noncovalent interactions between single or double stranded DNA and SWNT nanoparticles and biophysical properties of these structures were studied comparatively. Biophysical properties of hybrid nanostructures studied by circular dichroism, UV-vis and fluorescence spectroscopy techniques. Also, electrochemical properties studied by cyclic voltammetry, linear sweep voltammetry, square wave voltammetry, choronoamperometry and impedance spectroscopy (EIS). Results revealed that the biophysical and electrochemical properties of SWNT/DNA hybrid nanostructures were different compare to ss-DNA, ds-DNA and SWNT singly. Circular dichroism results showed that ss-DNA wrapped around the nanotubes through π-π stacking interactions. The results indicated that after adding SWNT to ss-DNA and ds-DNA intensity of CD and UV-vis spectrum peaks were decreased. Electrochemical experiments indicated that the modification of single-walled carbon nanotubes by ss-DNA improves the electron transfer rate of hybrid nanostructures. It was demonstrated SWNT/DNA hybrid nanostructures should be a good electroactive nanostructure that can be used for electrochemical detection or sensing.

SU-F-T-142: An Analytical Model to Correct the Aperture Scattered Dose in Clinical Proton Beams

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

Sun, B; Liu, S; Zhang, T

2016-06-15

Purpose: Apertures or collimators are used to laterally shape proton beams in double scattering (DS) delivery and to sharpen the penumbra in pencil beam (PB) delivery. However, aperture-scattered dose is not included in the current dose calculations of treatment planning system (TPS). The purpose of this study is to provide a method to correct the aperture-scattered dose based on an analytical model. Methods: A DS beam with a non-divergent aperture was delivered using a single-room proton machine. Dose profiles were measured with an ion-chamber scanning in water and a 2-D ion chamber matrix with solid-water buildup at various depths. Themore » measured doses were considered as the sum of the non-contaminated dose and the aperture-scattered dose. The non-contaminated dose was calculated by TPS and subtracted from the measured dose. Aperture scattered-dose was modeled as a 1D Gaussian distribution. For 2-D fields, to calculate the scatter-dose from all the edges of aperture, a sum of weighted distance was used in the model based on the distance from calculation point to aperture edge. The gamma index was calculated between the measured and calculated dose with and without scatter correction. Results: For a beam with range of 23 cm and aperture size of 20 cm, the contribution of the scatter horn was ∼8% of the total dose at 4 cm depth and diminished to 0 at 15 cm depth. The amplitude of scatter-dose decreased linearly with the depth increase. The 1D gamma index (2%/2 mm) between the calculated and measured profiles increased from 63% to 98% for 4 cm depth and from 83% to 98% at 13 cm depth. The 2D gamma index (2%/2 mm) at 4 cm depth has improved from 78% to 94%. Conclusion: Using the simple analytical method the discrepancy between the measured and calculated dose has significantly improved.« less

Increased oxidative stress in human fetal membranes overlying the cervix from term non-labouring and post labour deliveries.

PubMed

Chai, M; Barker, G; Menon, R; Lappas, M

2012-08-01

Enzymatic breakdown of the collagen-rich extracellular matrix (ECM) that connects the amnion and chorion layers of the fetal membranes is one of the key events leading to rupture of membranes. Oxidant stress caused by increased formation of reactive oxygen species and/or reduced antioxidant capacity may predispose to membrane rupture, a major cause of preterm birth. The aim of this study was to determine the effect of human labour and supracervical (SC) apposition on antioxidant enzymes and 8-isoprostane (a marker of lipid peroxidation). To determine the effect of human labour on oxidative stress status, fetal membranes from the SC site (SCS) were collected from women at term Caesarean section (no labour), and from the site of membrane rupture (SOR) after spontaneous labour onset and delivery (post labour). To determine the effect of SC apposition on oxidative stress status, amnion was collected from the SCS and a distal site (DS) in women at term Caesarean section in the absence of labour. The release of 8-isoprostane was significantly higher in amnion from the SCS compared to DS, and in fetal membranes from the SOR compared to the SCS. Glutathione peroxidase (GPx) and superoxide dismutase (SOD) activity were lower in amnion from the SC compared to DS. SOD gene expression and enzyme activity were lower in fetal membranes after labour. There was no difference in expression or activity in catalase, GPx and glutathione reductase (GSR) between no labour and post labour fetal membranes. In primary amnion cells, SOD supplementation significantly augmented IL-1β induced MMP-9 expression and activity. In summary, non-labouring SC fetal membranes are characterised by reduced antioxidant enzyme activity when compared to distal membranes, and, as such, may be more susceptible to oxidative damage and thus membrane rupture. Copyright © 2012 Elsevier Ltd. All rights reserved.

Gait patterns in Prader-Willi and Down syndrome patients

PubMed Central

2010-01-01

Background Prader-Willi (PWS) and Down Syndrome (DS) are two genetic disorders characterised by some common clinical and functional features. A quantitative description and comparison of their patterns would contribute to a deeper understanding of the determinants of motor disability in these two syndromes. The aim of this study was to measure gait pattern in PWS and DS in order to provide data for developing evidence-based deficit-specific or common rehabilitation strategies. Methods 19 PWS patients (17.7-40 yr) and 21 DS patients (18-39 yr) were evaluated with an optoelectronic system and force platforms for measuring kinematic and kinetic parameters during walking. The results were compared with those obtained in a group of normal-weight controls (Control Group: CG; 33.4 + 9.6 yr). Results and Discussion The results show that PWS and DS are characterised by different gait strategies. Spatio-temporal parameters indicated a cautious, abnormal gait in both groups, but DS walked with a less stable strategy than PWS. As for kinematics, DS showed a significantly reduced hip and knee flexion, especially at initial contact and ankle range of motion than PWS. DS were characterised by lower ranges of motion (p < 0.05) in all joints than CG and PWS. As for ankle kinetics, both PWS and DS showed a significantly lower push-off during terminal stance than CG, with DS yielding the lowest values. Stiffness at hip and ankle level was increased in DS. PWS showed hip stiffness values close to normal. At ankle level, stiffness was significantly decreased in both groups. Conclusions Our data show that DS walk with a less physiological gait pattern than PWS. Based on our results, PWS and DS patients need targeted rehabilitation and exercise prescription. Common to both groups is the aim to improve hypotonia, muscle strength and motor control during gait. In DS, improving pelvis and hip range of motion should represent a major specific goal to optimize gait pattern. PMID:20565926

Gait patterns in Prader-Willi and Down syndrome patients.

PubMed

Cimolin, Veronica; Galli, Manuela; Grugni, Graziano; Vismara, Luca; Albertini, Giorgio; Rigoldi, Chiara; Capodaglio, Paolo

2010-06-21

Prader-Willi (PWS) and Down Syndrome (DS) are two genetic disorders characterised by some common clinical and functional features. A quantitative description and comparison of their patterns would contribute to a deeper understanding of the determinants of motor disability in these two syndromes. The aim of this study was to measure gait pattern in PWS and DS in order to provide data for developing evidence-based deficit-specific or common rehabilitation strategies. 19 PWS patients (17.7-40 yr) and 21 DS patients (18-39 yr) were evaluated with an optoelectronic system and force platforms for measuring kinematic and kinetic parameters during walking. The results were compared with those obtained in a group of normal-weight controls (Control Group: CG; 33.4 + 9.6 yr). The results show that PWS and DS are characterised by different gait strategies. Spatio-temporal parameters indicated a cautious, abnormal gait in both groups, but DS walked with a less stable strategy than PWS. As for kinematics, DS showed a significantly reduced hip and knee flexion, especially at initial contact and ankle range of motion than PWS. DS were characterised by lower ranges of motion (p < 0.05) in all joints than CG and PWS. As for ankle kinetics, both PWS and DS showed a significantly lower push-off during terminal stance than CG, with DS yielding the lowest values. Stiffness at hip and ankle level was increased in DS. PWS showed hip stiffness values close to normal. At ankle level, stiffness was significantly decreased in both groups. Our data show that DS walk with a less physiological gait pattern than PWS. Based on our results, PWS and DS patients need targeted rehabilitation and exercise prescription. Common to both groups is the aim to improve hypotonia, muscle strength and motor control during gait. In DS, improving pelvis and hip range of motion should represent a major specific goal to optimize gait pattern.

Chirped laser dispersion spectroscopy using a directly modulated quantum cascade laser

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

Hangauer, Andreas, E-mail: hangauer@princeton.edu; Nikodem, Michal; Wysocki, Gerard, E-mail: gwysocki@princeton.edu

2013-11-04

Chirped laser dispersion spectroscopy (CLaDS) utilizing direct modulation of a quantum cascade laser (QCL) is presented. By controlling the laser bias nearly single- and dual-sideband CLaDS operation can be realized in an extremely simplified optical setup with no external optical modulators. Capability of direct single-sideband modulation is a unique feature of QCLs that exhibit a low linewidth enhancement factor. The developed analytical model shows excellent agreement with the experimental, directly modulated CLaDS spectra. This method overcomes major technical limitations of mid-infrared CLaDS systems by allowing significantly higher modulation frequencies and eliminating optical fringes introduced by external modulators.

Polymorphisms of interleukin 6 in Down syndrome individuals: a case-control study.

PubMed

Mattos, M F; Uback, L; Biselli-Chicote, P M; Biselli, J M; Goloni-Bertollo, E M; Pavarino, E C

2017-08-17

Down syndrome (DS) individuals present impaired adaptive immune system. However, the etiology of the immunological deficiency in these individuals is not completely understood. This study investigated the frequency of interleukin 6 polymorphisms (rs1800795, rs1800796, and rs1800797) in individuals with DS and individuals without the syndrome. The study included 282 individuals, 94 with DS attended at the General Genetics Outpatient Service of Hospital de Base, São José do Rio Preto, SP, Brazil, and 188 individuals without DS attended at the Pediatric Service of Hospital de Base de São José do Rio Preto, SP, Brazil. Genotyping was performed by allelic discrimination technique by real-time polymerase chain reaction using TaqMan SNP Genotyping Assays (Applied Biosystems). There was no difference in the genotype frequency between individuals with and without DS for the evaluated polymorphisms (P > 0.05). The frequency of interleukin 6 polymorphisms did not differ significantly between individuals with and without DS in the casuistic analyzed.

The best management of SuDS treatment trains: a holistic approach.

PubMed

Bastien, Nicolas; Arthur, Scott; Wallis, Stephen; Scholz, Miklas

2010-01-01

The use of Sustainable Drainage Systems (SuDS) or Best Management Practice (BMP) is becoming increasingly common. However, rather than adopting the preferred "treatment train" implementation, many developments opt for end of pipe control ponds. This paper discusses the use of SuDS in series to form treatment trains and compares their potential performance and effectiveness with end of pipe solutions. Land-use, site and catchment characteristics have been used alongside up-to-date guidance, Infoworks CS and MUSIC to determine whole-life-costs, land-take, water quality and water quantity for different SuDS combinations. The results presented show that the use of a treatment train allows approaches differing from the traditional use of single SuDS, either source or "end of pipe", to be proposed to treat and attenuate runoff. The outcome is a more flexible solution where the footprint allocated to SuDS, costs and water quality can be managed differently to satisfy more efficiently the holistically stakeholders' objectives.

Development of acute megakaryoblastic leukemia in Down syndrome is associated with sequential epigenetic changes

PubMed Central

Malinge, Sébastien; Chlon, Tim; Doré, Louis C.; Ketterling, Rhett P.; Tallman, Martin S.; Paietta, Elisabeth; Gamis, Alan S.; Taub, Jeffrey W.; Chou, Stella T.; Weiss, Mitchell J.

2013-01-01

Acute megakaryoblastic leukemia (AMKL) is more frequently observed in Down syndrome (DS) patients, in whom it is often preceded by a transient myeloproliferative disorder (TMD). The development of DS-TMD and DS-AMKL requires not only the presence of the trisomy 21 but also that of GATA1 mutations. Despite extensive studies into the genetics of DS-AMKL, the importance of epigenetic deregulation in this disease has been unexplored. We performed DNA methylation profiling at different stages of development of DS-AMKL and analyzed the dynamics of the epigenetic program. Early genome-wide DNA methylation changes can be detected in trisomy 21 fetal liver mononuclear cells, prior to the acquisition of GATA1 mutations. These early changes are characterized by marked loss of DNA methylation at genes associated with developmental disorders, including those affecting the cardiovascular, neurological, and endocrine systems. This is followed by a second wave of changes detected in DS-TMD and DS-AMKL, characterized by gains of methylation. This new wave of hypermethylation targets a distinct set of genes involved in hematopoiesis and regulation of cell growth and proliferation. These findings indicate that the final epigenetic landscape of DS-AMKL is the result of sequential and opposing changes in DNA methylation occurring at specific times in the disease development. PMID:23980066

Shorter telomeres may indicate dementia status in older individuals with Down Syndrome

PubMed Central

Jenkins, Edmund C.; Ye, Lingling; Gu, Hong; Ni, Samantha A.; Velinov, Milen; Pang, Deborah; Krinsky-McHale, Sharon J.; Zigman, Warren B.; Schupf, Nicole; Silverman, Wayne P.

2009-01-01

We have recently reported reduced telomere length in T lymphocytes of individuals with Down syndrome (DS) and dementia due to Alzheimer’s disease (AD). We have now replicated and extended that study by finding that people with DS and mild cognitive impairment (MCI-DS) also have shorter telomeres than people with DS without MCI-DS. Additional new findings demonstrated that light intensity measurements from chromosome 21 alone, or in concert with chromosomes 1, 2, and 16, exhibited shorter telomeres in adults with DS and with either dementia or MCI-DS compared to aging per se. Chromosome 21 measurements appeared to be especially promising for use as a biomarker because there was no overlap in the distribution of light intensity measurement scores between demented or MCI-DS and non-demented participants. Given that early clinical symptoms of AD can be very difficult to recognize in this population of adults due to their pre-existing cognitive impairments, a valid biomarker would be of great value. Early detection is especially important because it would allow treatments to begin before significant damage to the central nervous system has occurred. Our findings suggest that it may be feasible to use telomere shortening as a biomarker for accurately inferring dementia status. PMID:18635289

The medial temporal memory system in Down syndrome: Translating animal models of hippocampal compromise.

PubMed

Clark, Caron A C; Fernandez, Fabian; Sakhon, Stella; Spanò, Goffredina; Edgin, Jamie O

2017-06-01

Recent studies have highlighted the dentate gyrus as a region of increased vulnerability in mouse models of Down syndrome (DS). It is unclear to what extent these findings are reflected in the memory profile of people with the condition. We developed a series of novel tasks to probe distinct medial temporal functions in children and young adults with DS, including object, spatial, and temporal order memory. Relative to mental age-matched controls (n = 45), individuals with DS (n = 28) were unimpaired on subtests involving short-term object or configural recall that was divorced from spatial or temporal contexts. By contrast, the DS group had difficulty recalling spatial locations when contextual information was salient and recalling the order in which objects were serially presented. Results are consistent with dysfunction of spatial and temporal contextual pattern separation abilities in individuals with DS, mediated by the hippocampus, including the dentate gyrus. Amidst increasing calls to bridge human and animal work, the memory profile demonstrated here in humans with DS is strikingly similar to that of the Ts65Dn mouse model of DS. The study highlights the trisynaptic circuit as a potentially fruitful intervention target to mitigate cognitive impairments associated with DS. © 2017 Wiley Periodicals, Inc.

A design of the u-health monitoring system using a Nintendo DS game machine.

PubMed

Lee, Sangjoon; Kim, Jinkwon; Kim, Jungkuk; Lee, Myoungho

2009-01-01

In this paper, we used the hand held type a Nintendo DS Game Machine for consisting of a u-Health Monitoring system. This system is consists of four parts. Biosignal acquire device is the first. The Second is a wireless sensor network device. The third is a wireless base-station for connecting internet network. Displaying units are the last part which were a personal computer and a Nintendo DS game machine. The bio-signal measurement device among the four parts the u-health monitoring system can acquire 7-channels data which have 3-channels ECG(Electrocardiogram), 3-axis accelerometer and tilting sensor data. Acquired data connect up the internet network throughout the wireless sensor network and a base-station. In the experiment, we concurrently display the bio-signals on to a monitor of personal computer and LCD of a Nintendo DS using wireless internet protocol and those monitoring devices placed off to the one side an office building. The result of the experiment, this proposed system effectively can transmit patient's biosignal data as a long time and a long distance. This suggestion of the u-health monitoring system need to operate in the ambulance, general hospitals and geriatric institutions as a u-health monitoring device.

A HER2-targeting antibody-drug conjugate, trastuzumab deruxtecan (DS-8201a), enhances antitumor immunity in a mouse model.

PubMed

Iwata, Tomomi Nakayama; Ishii, Chiaki; Ishida, Saori; Ogitani, Yusuke; Wada, Teiji; Agatsuma, Toshinori

2018-04-27

Trastuzumab deruxtecan (DS-8201a), a HER2-targeting antibody-drug conjugate with a topoisomerase I inhibitor exatecan derivative (DX-8951 derivative, DXd), has been reported to exert potent antitumor effects in xenograft mouse models and clinical trials. In this study, the immune system-activating ability of DS-8201a was assessed. DS-8201a significantly suppressed tumor growth in an immunocompetent mouse model with human HER2-expressing CT26.WT (CT26.WT-hHER2) cells. Cured immunocompetent mice rejected not only re-challenged CT26.WT-hHER2 cells, but also CT26.WT-mock cells. Splenocytes from the cured mice responded to both CT26.WT-hHER2 and CT26.WT-mock cells. Further analyses revealed that DXd up-regulated CD86 expression on bone marrow-derived DCs in vitro, and that DS-8201a increased tumor-infiltrating DCs and up-regulated their CD86 expression in vivo. DS-8201a also increased tumor-infiltrating CD8+ T cells and enhanced PD-L1 and MHC class I expression on tumor cells. Furthermore, combination therapy with DS-8201a and anti-PD-1 antibody was more effective than either monotherapy. In conclusion, DS-8201a enhanced antitumor immunity, as evidenced by the increased expression of DC markers, augmented expression of MHC class I in tumor cells, and rejection of re-challenged tumor cells by adaptive immune cells, suggesting that DS-8201a enhanced tumor recognition by T cells. Furthermore, DS-8201a treatment benefited from combination with anti-PD-1 antibody, possibly due to increased T cell activity and up-regulated PD-L1 expression induced by DS-8201a. Copyright ©2018, American Association for Cancer Research.

Nonrenal and renal activity of systemic lupus erythematosus: a comparison of two anti-C1q and five anti-dsDNA assays and complement C3 and C4.

PubMed

Julkunen, Heikki; Ekblom-Kullberg, Susanne; Miettinen, Aaro

2012-08-01

Associations of different assays for antibodies to C1q (anti-C1q) and to dsDNA (anti-dsDNA) and of complements C3 and C4 with disease activity in patients with systemic lupus erythematosus (SLE) were studied. The clinical manifestations of 223 SLE patients were recorded, and the disease activity was assessed by the SLEDAI score. Anti-C1q were determined by two enzyme-linked immunosorbent assays (ELISA) and anti-dsDNA by a radioimmunoassay (RIA), a Crithidia immunofluorescence (IF) assay and three ELISA assays using human telomere DNA, plasmid DNA circles, or calf thymus DNA as antigens, respectively. Complement C3 and C4 were determined by nephelometry. Control sera were obtained from 98 blood donors. In patients with SLE, the prevalence of anti-C1q was 17-18% and that of anti-dsDNA was 36-69%. Anti-C1q, anti-dsDNA, and complement C3 and C4 correlated well with the overall activity of SLE (r = 0.323-0.351, 0.353-0.566, and -0.372-0.444, respectively; P < 0.001). Sensitivity, specificity, positive predictive value, and negative predictive value for active lupus nephritis among SLE patients were 40-44, 92, 29, and 91-92% for anti-C1q and 48-68, 29-66, 11-16, and 86-91% for anti-dsDNA, respectively. Patients with active nephritis had higher levels of anti-C1q and lower levels of C3 and C4 than patients with inactive nephritis (P = 0.003-0.018). The corresponding associations of anti-dsDNA were somewhat weaker (P = 0.023-0.198). Hematological parameters reflecting disease activity correlated clearly better with anti-dsDNA and complement C3 and C4 than with anti-C1q. Anti-C1q is inferior to anti-dsDNA as a diagnostic test in SLE and in the evaluation of overall clinical activity of the disease. Anti-C1q together with complement C3 and C4 may offer useful additional information to monitor lupus nephritis activity. There are no practical differences between different assays for anti-C1q and anti-dsDNA.

Internet Voice Distribution System (IVoDS) Utilization in Remote Payload Operations

NASA Technical Reports Server (NTRS)

Best, Susan; Bradford, Bob; Chamberlain, Jim; Nichols, Kelvin; Bailey, Darrell (Technical Monitor)

2002-01-01

Due to limited crew availability to support science and the large number of experiments to be operated simultaneously, telescience is key to a successful International Space Station (ISS) science program. Crew, operations personnel at NASA centers, and researchers at universities and companies around the world must work closely together to perform scientific experiments on-board ISS. NASA has initiated use of Voice over Internet Protocol (VoIP) to supplement the existing HVoDS mission voice communications system used by researchers. The Internet Voice Distribution System (IVoDS) connects researchers to mission support "loops" or conferences via Internet Protocol networks such as the high-speed Internet 2. Researchers use IVoDS software on personal computers to talk with operations personnel at NASA centers. IVoDS also has the capability, if authorized, to allow researchers to communicate with the ISS crew during experiment operations. NODS was developed by Marshall Space Flight Center with contractors A2 Technology, Inc. FVC, Lockheed- Martin, and VoIP Group. IVoDS is currently undergoing field-testing with full deployment for up to 50 simultaneous users expected in 2002. Research is currently being performed to take full advantage of the digital world - the Personal Computer and Internet Protocol networks - to qualitatively enhance communications among ISS operations personnel. In addition to the current voice capability, video and data-sharing capabilities are being investigated. Major obstacles being addressed include network bandwidth capacity and strict security requirements. Techniques being investigated to reduce and overcome these obstacles include emerging audio-video protocols and network technology including multicast and quality-of-service.

Bystander killing effect of DS-8201a, a novel anti-human epidermal growth factor receptor 2 antibody-drug conjugate, in tumors with human epidermal growth factor receptor 2 heterogeneity.

PubMed

Ogitani, Yusuke; Hagihara, Katsunobu; Oitate, Masataka; Naito, Hiroyuki; Agatsuma, Toshinori

2016-07-01

Antibody-drug conjugates deliver anticancer agents selectively and efficiently to tumor tissue and have significant antitumor efficacy with a wide therapeutic window. DS-8201a is a human epidermal growth factor receptor 2 (HER2)-targeting antibody-drug conjugate prepared using a novel linker-payload system with a potent topoisomerase I inhibitor, exatecan derivative (DX-8951 derivative, DXd). It was effective against trastuzumab emtansine (T-DM1)-insensitive patient-derived xenograft models with both high and low HER2 expression. In this study, the bystander killing effect of DS-8201a was evaluated and compared with that of T-DM1. We confirmed that the payload of DS-8201a, DXd (1), was highly membrane-permeable whereas that of T-DM1, Lys-SMCC-DM1, had a low level of permeability. Under a coculture condition of HER2-positive KPL-4 cells and negative MDA-MB-468 cells in vitro, DS-8201a killed both cells, whereas T-DM1 and an antibody-drug conjugate with a low permeable payload, anti-HER2-DXd (2), did not. In vivo evaluation was carried out using mice inoculated with a mixture of HER2-positive NCI-N87 cells and HER2-negative MDA-MB-468-Luc cells by using an in vivo imaging system. In vivo, DS-8201a reduced the luciferase signal of the mice, indicating suppression of the MDA-MB-468-Luc population; however, T-DM1 and anti-HER2-DXd (2) did not. Furthermore, it was confirmed that DS-8201a was not effective against MDA-MB-468-Luc tumors inoculated at the opposite side of the NCI-N87 tumor, suggesting that the bystander killing effect of DS-8201a is observed only in cells neighboring HER2-positive cells, indicating low concern in terms of systemic toxicity. These results indicated that DS-8201a has a potent bystander effect due to a highly membrane-permeable payload and is beneficial in treating tumors with HER2 heterogeneity that are unresponsive to T-DM1. © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Molecular interactions between chondroitin-dermatan sulfate and growth factors/receptors/matrix proteins.

PubMed

Mizumoto, Shuji; Yamada, Shuhei; Sugahara, Kazuyuki

2015-10-01

Recent functional studies on chondroitin sulfate-dermatan sulfate (CS-DS) demonstrated its indispensable roles in various biological events including brain development and cancer. CS-DS proteoglycans exert their physiological activity through interactions with specific proteins including growth factors, cell surface receptors, and matrix proteins. The characterization of these interactions is essential for regulating the biological functions of CS-DS proteoglycans. Although amino acid sequences on the bioactive proteins required for these interactions have already been elucidated, the specific saccharide sequences involved in the binding of CS-DS to target proteins have not yet been sufficiently identified. In this review, recent findings are described on the interaction between CS-DS and some proteins which are especially involved in the central nervous system and cancer development/metastasis. Copyright © 2015. Published by Elsevier Ltd.

A case of pediatric age anticholinergic intoxication due to accidental Datura stramonium ingestion admitting with visual hallucination.

PubMed

Şanlıdağ, Burçin; Derinöz, Okşan; Yıldız, Nagehan

2014-01-01

Datura stramonium (DS) is a hallucinogenic plant that can produce anticholinergic toxicity because of its significant concentrations of toxic alkaloids, such as atropine, hyoscyamine, and scopolamine. DS grows in both rural and urban areas in Turkey. Clinical findings of toxicity are similar to those of atropine toxicity. DS abuse is common among adolescents because of its hallucinatory effects. However, accidental DS poisoning from contaminated food is very rare. Accidental poisonings are commonly seen among children. Children are more prone to the toxic effects of atropine; ingestion of even a small amount can cause serious central nervous system symptoms. Treatment is supportive; antidote treatment is given rarely. An eight-year-old male with accidental DS poisoning who presented to the Pediatric Emergency Department with aggression, agitation, delirium, and visual hallucinations is reported.

Polyethylene glycol-coated blue-emitting silicon dots with improved properties for uses in aqueous and biological environments

NASA Astrophysics Data System (ADS)

Rodríguez Sartori, Damián; Lillo, Cristian R.; Romero, Juan J.; Dell‧Arciprete, María Laura; Miñán, Alejandro; de Mele, Mónica Fernández Lorenzo; Gonzalez, Mónica C.

2016-11-01

Grafting of polyethylene glycol (PEG) to ultrasmall photoluminescent silicon dots (SiDs) is expected to improve and expand the applications of these particles to aqueous environments and biological systems. Herein we report a novel one-pot synthesis of robust, highly water compatible PEG-coated SiDs (denoted as PEG-SiDs) of (3.3 ± 0.5) nm size. The nanoparticles’ synthesis is based on the liquid phase oxidation of magnesium silicide using PEG as reaction media and leading to high PEG density grafting. PEG-SiDs enhanced photophysical, photosensitising, and solution properties in aqueous environments are described and compared to those of 2 nm size PEG-coated SiDs with low PEG density grafting (denoted as PEG-NHSiDs) obtained from a multistep synthesis strategy. PEG-SiDs form highly dispersed suspensions in water showing stable photoluminescence and quantum yields of Φ = 0.13 ± 0.04 at 370 nm excitation in air-saturated suspensions. These particles exhibited the capacity of photosensitising the formation of singlet molecular oxygen, not observed for PEG-NHSiDs. PEG robust shielding of the silicon core luminescent properties is further demonstrated in bio-imaging experiments stressing the strong interaction between PEG-SiDs and Staphylococcus aureus smears by observing the photoluminescence of particles. PEG-SiDs were found to be nontoxic to S. aureus cells at concentrations of 100 mg ml-1, though a bacteriostatic effect on S. aureus biofilms was observed upon UV-A irradiation under conditions where light alone has no effect.

Development of Michelson interferometer based spatial phase-shift digital shearography

NASA Astrophysics Data System (ADS)

Xie, Xin

Digital shearography is a non-contact, full field, optical measurement method, which has the capability of directly measuring the gradient of deformation. For high measurement sensitivity, phase evaluation method has to be introduced into digital shearography by phase-shift technique. Catalog by phase-shift method, digital phase-shift shearography can be divided into Temporal Phase-Shift Digital Shearography (TPS-DS) and Spatial Phase-Shift Digital Shearography (SPS-DS). TPS-DS is the most widely used phase-shift shearography system, due to its simple algorithm, easy operation and good phase-map quality. However, the application of TPS-DS is only limited in static/step-by-step loading measurement situation, due to its multi-step shifting process. In order to measure the strain under dynamic/continuous loading situation, a SPS-DS system has to be developed. This dissertation aims to develop a series of Michelson Interferometer based SPS-DS measurement methods to achieve the strain measurement by using only a single pair of speckle pattern images. The Michelson Interferometer based SPS-DS systems utilize special designed optical setup to introduce extra carrier frequency into the laser wavefront. The phase information corresponds to the strain field can be separated on the Fourier domain using a Fourier Transform and can further be evaluated with a Windowed Inverse Fourier Transform. With different optical setups and carrier frequency arrangements, the Michelson Interferometer based SPS-DS method is capable to achieve a variety of measurement tasks using only single pair of speckle pattern images. Catalog by the aimed measurand, these capable measurement tasks can be divided into five categories: 1) measurement of out-of-plane strain field with small shearing amount; 2) measurement of relative out-of-plane deformation field with big shearing amount; 3) simultaneous measurement of relative out-of-plane deformation field and deformation gradient field by using multiple carrier frequencies; 4) simultaneous measurement of two directional strain field using dual measurement channels 5) measurement of pure in-plane strain and pure out-of-plane strain with multiple carrier frequencies. The basic theory, optical path analysis, preliminary studies, results analysis and research plan are shown in detail in this dissertation.

Effects of obesity on gait pattern in young individuals with Down syndrome.

PubMed

Galli, Manuela; Cimolin, Veronica; Rigoldi, Chiara; Condoluci, Claudia; Albertini, Giorgio

2015-03-01

In individuals with Down syndrome (DS), the prevalence of obesity is widespread; despite this, there are no experimental studies on the effect of obesity on gait strategy in DS individuals. The aim of this study is to assess the clinical gait analysis of a group of obese individuals with DS and a group of nonobese individuals with DS to determine whether obesity produces a different gait pattern in these participants. In addition, although females and males share a similar mass, they are characterized by different fat distribution and/or accumulation; thus, the presence of differences between females and males within the two DS groups was investigated. Gait analysis data of a group of 78 young individuals with DS and 20 normal-weight participants in the 5-18-year age range were considered. Among DS individuals, 40 were classified as obese (obese DS group), whereas 38 were classified as normal weight (nonobese groups). A three-dimensional gait analysis was carried out using an optoelectronic system, force platforms and video recording. Spatiotemporal, kinematic and kinetic parameters were identified and calculated for each participant. Our results show that most of the parameters were similar in the two groups of DS participants; the only differences were in terms of stance duration, longer in the obese DS group and dorsiflexion ability during the swing phase, which was limited in the obese DS group. The two DS groups were significantly different in terms of ankle stiffness (Ka index): both groups were characterized by reduced values compared with the control group, but the obese group presented lower values with respect to nonobese participants. The data showed that females were characterized by significant modifications of gait pattern compared with males in both groups, in particular, at proximal levels, such as the hip and the pelvis. Our findings indicate that the presence of obesity exerts effects on gait pattern in DS individuals and in particular on ankle joint stiffness. These results may have special clinical relevance; the biomechanical comparison of gait in young obese and nonobese DS individuals may provide a basis for developing either specific or common rehabilitative strategies.

Neural network approach to time-dependent dividing surfaces in classical reaction dynamics.

PubMed

Schraft, Philippe; Junginger, Andrej; Feldmaier, Matthias; Bardakcioglu, Robin; Main, Jörg; Wunner, Günter; Hernandez, Rigoberto

2018-04-01

In a dynamical system, the transition between reactants and products is typically mediated by an energy barrier whose properties determine the corresponding pathways and rates. The latter is the flux through a dividing surface (DS) between the two corresponding regions, and it is exact only if it is free of recrossings. For time-independent barriers, the DS can be attached to the top of the corresponding saddle point of the potential energy surface, and in time-dependent systems, the DS is a moving object. The precise determination of these direct reaction rates, e.g., using transition state theory, requires the actual construction of a DS for a given saddle geometry, which is in general a demanding methodical and computational task, especially in high-dimensional systems. In this paper, we demonstrate how such time-dependent, global, and recrossing-free DSs can be constructed using neural networks. In our approach, the neural network uses the bath coordinates and time as input, and it is trained in a way that its output provides the position of the DS along the reaction coordinate. An advantage of this procedure is that, once the neural network is trained, the complete information about the dynamical phase space separation is stored in the network's parameters, and a precise distinction between reactants and products can be made for all possible system configurations, all times, and with little computational effort. We demonstrate this general method for two- and three-dimensional systems and explain its straightforward extension to even more degrees of freedom.

Neural network approach to time-dependent dividing surfaces in classical reaction dynamics

NASA Astrophysics Data System (ADS)

Schraft, Philippe; Junginger, Andrej; Feldmaier, Matthias; Bardakcioglu, Robin; Main, Jörg; Wunner, Günter; Hernandez, Rigoberto

2018-04-01

In a dynamical system, the transition between reactants and products is typically mediated by an energy barrier whose properties determine the corresponding pathways and rates. The latter is the flux through a dividing surface (DS) between the two corresponding regions, and it is exact only if it is free of recrossings. For time-independent barriers, the DS can be attached to the top of the corresponding saddle point of the potential energy surface, and in time-dependent systems, the DS is a moving object. The precise determination of these direct reaction rates, e.g., using transition state theory, requires the actual construction of a DS for a given saddle geometry, which is in general a demanding methodical and computational task, especially in high-dimensional systems. In this paper, we demonstrate how such time-dependent, global, and recrossing-free DSs can be constructed using neural networks. In our approach, the neural network uses the bath coordinates and time as input, and it is trained in a way that its output provides the position of the DS along the reaction coordinate. An advantage of this procedure is that, once the neural network is trained, the complete information about the dynamical phase space separation is stored in the network's parameters, and a precise distinction between reactants and products can be made for all possible system configurations, all times, and with little computational effort. We demonstrate this general method for two- and three-dimensional systems and explain its straightforward extension to even more degrees of freedom.

Assessment of the Knowledge of the Decimal Number System Exhibited by Students with Down Syndrome

ERIC Educational Resources Information Center

Noda, Aurelia; Bruno, Alicia

2017-01-01

This paper presents an assessment of the understanding of the decimal numeral system in students with Down Syndrome (DS). We followed a methodology based on a descriptive case study involving six students with DS. We used a framework of four constructs (counting, grouping, partitioning and numerical relationships) and five levels of thinking for…

Interference Analysis for Highly Directional 60 GHz Mesh Networks: The Case for Rethinking Medium Access Control

DTIC Science & Technology

2010-11-24

Helmken, “Performance analysis of coherent DS - CDMA systems in a Nakagami fading channel with arbitrary parameters,” Vehicular Technology, IEEE...Transactions on, vol. 46, no. 2, pp. 289–297, may 1997. [26] M. Sunay and P. McLane, “Calculating error probabilities for DS - CDMA systems: when not to use

Down syndrome's brain dynamics: analysis of fractality in resting state.

PubMed

Hemmati, Sahel; Ahmadlou, Mehran; Gharib, Masoud; Vameghi, Roshanak; Sajedi, Firoozeh

2013-08-01

To the best knowledge of the authors there is no study on nonlinear brain dynamics of down syndrome (DS) patients, whereas brain is a highly complex and nonlinear system. In this study, fractal dimension of EEG, as a key characteristic of brain dynamics, showing irregularity and complexity of brain dynamics, was used for evaluation of the dynamical changes in the DS brain. The results showed higher fractality of the DS brain in almost all regions compared to the normal brain, which indicates less centrality and higher irregular or random functioning of the DS brain regions. Also, laterality analysis of the frontal lobe showed that the normal brain had a right frontal laterality of complexity whereas the DS brain had an inverse pattern (left frontal laterality). Furthermore, the high accuracy of 95.8 % obtained by enhanced probabilistic neural network classifier showed the potential of nonlinear dynamic analysis of the brain for diagnosis of DS patients. Moreover, the results showed that the higher EEG fractality in DS is associated with the higher fractality in the low frequencies (delta and theta), in broad regions of the brain, and the high frequencies (beta and gamma), majorly in the frontal regions.

Cryo-EM Structures Reveal Mechanism and Inhibition of DNA Targeting by a CRISPR-Cas Surveillance Complex.

PubMed

Guo, Tai Wei; Bartesaghi, Alberto; Yang, Hui; Falconieri, Veronica; Rao, Prashant; Merk, Alan; Eng, Edward T; Raczkowski, Ashleigh M; Fox, Tara; Earl, Lesley A; Patel, Dinshaw J; Subramaniam, Sriram

2017-10-05

Prokaryotic cells possess CRISPR-mediated adaptive immune systems that protect them from foreign genetic elements, such as invading viruses. A central element of this immune system is an RNA-guided surveillance complex capable of targeting non-self DNA or RNA for degradation in a sequence- and site-specific manner analogous to RNA interference. Although the complexes display considerable diversity in their composition and architecture, many basic mechanisms underlying target recognition and cleavage are highly conserved. Using cryoelectron microscopy (cryo-EM), we show that the binding of target double-stranded DNA (dsDNA) to a type I-F CRISPR system yersinia (Csy) surveillance complex leads to large quaternary and tertiary structural changes in the complex that are likely necessary in the pathway leading to target dsDNA degradation by a trans-acting helicase-nuclease. Comparison of the structure of the surveillance complex before and after dsDNA binding, or in complex with three virally encoded anti-CRISPR suppressors that inhibit dsDNA binding, reveals mechanistic details underlying target recognition and inhibition. Published by Elsevier Inc.

Faster, Stronger, Healthier: Adolescent-Stated Reasons for Dietary Supplementation.

PubMed

Zdešar Kotnik, Katja; Jurak, Gregor; Starc, Gregor; Golja, Petra

Examine the underlying reasons and sources of recommendation for dietary supplement (DS) use among adolescents. Cross-sectional analysis of children's development in Slovenia in September to October, 2014. Nationally recruited sample. Adolescents aged 14-19 years enrolled in 15 high schools (n = 1,463). Reasons for and sources of recommendation for DS use, sports club membership, sports discipline, and extent of physical activity (PA) were self-reported data. Chi-square test of independence was performed to compare the prevalence of DS use between groups with different extents of PA and nonathletes/athletes, referring to 11 different reasons and 9 different sources of recommendation for DS use. Use of DS was widespread among adolescents (69%), athletes (76%), and nonathletes (66%). Higher prevalence of supplementation was observed in males, who justified it use for sports performance enhancement and better development and function of muscles. In contrast, females emphasized immune system improvement. Higher extent of PA was associated with a higher prevalence of DS use. This was especially evident in males, who participated in team sports. A high percentage of adolescents (41%) decided on their own to use DS and because of advice from parents or relatives (30%). Several reasons for the widespread use of DS in adolescents were associated with sports participation. Therefore, educational programs regarding DS use should be targeted primarily to adolescents and their parents who are involved in sports, and especially team sports. Copyright © 2017 Society for Nutrition Education and Behavior. Published by Elsevier Inc. All rights reserved.

dsRNA binding characterization of full length recombinant wild type and mutants Zaire ebolavirus VP35.

PubMed

Zinzula, Luca; Esposito, Francesca; Pala, Daniela; Tramontano, Enzo

2012-03-01

The Ebola viruses (EBOVs) VP35 protein is a multifunctional major virulence factor involved in EBOVs replication and evasion of the host immune system. EBOV VP35 is an essential component of the viral RNA polymerase, it is a key participant of the nucleocapsid assembly and it inhibits the innate immune response by antagonizing RIG-I like receptors through its dsRNA binding function and, hence, by suppressing the host type I interferon (IFN) production. Insights into the VP35 dsRNA recognition have been recently revealed by structural and functional analysis performed on its C-terminus protein. We report the biochemical characterization of the Zaire ebolavirus (ZEBOV) full-length recombinant VP35 (rVP35)-dsRNA binding function. We established a novel in vitro magnetic dsRNA binding pull down assay, determined the rVP35 optimal dsRNA binding parameters, measured the rVP35 equilibrium dissociation constant for heterologous in vitro transcribed dsRNA of different length and short synthetic dsRNA of 8bp, and validated the assay for compound screening by assessing the inhibitory ability of auryntricarboxylic acid (IC(50) value of 50μg/mL). Furthermore, we compared the dsRNA binding properties of full length wt rVP35 with those of R305A, K309A and R312A rVP35 mutants, which were previously reported to be defective in dsRNA binding-mediated IFN inhibition, showing that the latter have measurably increased K(d) values for dsRNA binding and modified migration patterns in mobility shift assays with respect to wt rVP35. Overall, these results provide the first characterization of the full-length wt and mutants VP35-dsRNA binding functions. Copyright © 2012 Elsevier B.V. All rights reserved.

Despeckle filtering software toolbox for ultrasound imaging of the common carotid artery.

PubMed

Loizou, Christos P; Theofanous, Charoula; Pantziaris, Marios; Kasparis, Takis

2014-04-01

Ultrasound imaging of the common carotid artery (CCA) is a non-invasive tool used in medicine to assess the severity of atherosclerosis and monitor its progression through time. It is also used in border detection and texture characterization of the atherosclerotic carotid plaque in the CCA, the identification and measurement of the intima-media thickness (IMT) and the lumen diameter that all are very important in the assessment of cardiovascular disease (CVD). Visual perception, however, is hindered by speckle, a multiplicative noise, that degrades the quality of ultrasound B-mode imaging. Noise reduction is therefore essential for improving the visual observation quality or as a pre-processing step for further automated analysis, such as image segmentation of the IMT and the atherosclerotic carotid plaque in ultrasound images. In order to facilitate this preprocessing step, we have developed in MATLAB(®) a unified toolbox that integrates image despeckle filtering (IDF), texture analysis and image quality evaluation techniques to automate the pre-processing and complement the disease evaluation in ultrasound CCA images. The proposed software, is based on a graphical user interface (GUI) and incorporates image normalization, 10 different despeckle filtering techniques (DsFlsmv, DsFwiener, DsFlsminsc, DsFkuwahara, DsFgf, DsFmedian, DsFhmedian, DsFad, DsFnldif, DsFsrad), image intensity normalization, 65 texture features, 15 quantitative image quality metrics and objective image quality evaluation. The software is publicly available in an executable form, which can be downloaded from http://www.cs.ucy.ac.cy/medinfo/. It was validated on 100 ultrasound images of the CCA, by comparing its results with quantitative visual analysis performed by a medical expert. It was observed that the despeckle filters DsFlsmv, and DsFhmedian improved image quality perception (based on the expert's assessment and the image texture and quality metrics). It is anticipated that the system could help the physician in the assessment of cardiovascular image analysis. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

A Single RNaseIII Domain Protein from Entamoeba histolytica Has dsRNA Cleavage Activity and Can Help Mediate RNAi Gene Silencing in a Heterologous System.

PubMed

Pompey, Justine M; Foda, Bardees; Singh, Upinder

2015-01-01

Dicer enzymes process double-stranded RNA (dsRNA) into small RNAs that target gene silencing through the RNA interference (RNAi) pathway. Dicer enzymes are complex, multi-domain RNaseIII proteins, however structural minimalism of this protein has recently emerged in parasitic and fungal systems. The most minimal Dicer, Saccharomyces castellii Dicer1, has a single RNaseIII domain and two double stranded RNA binding domains. In the protozoan parasite Entamoeba histolytica 27nt small RNAs are abundant and mediate silencing, yet no canonical Dicer enzyme has been identified. Although EhRNaseIII does not exhibit robust dsRNA cleavage in vitro, it can process dsRNA in the RNAi-negative background of Saccharomyces cerevisiae, and in conjunction with S. castellii Argonaute1 can partially reconstitute the RNAi pathway. Thus, although EhRNaseIII lacks the domain architecture of canonical or minimal Dicer enzymes, it has dsRNA processing activity that contributes to gene silencing via RNAi. Our data advance the understanding of small RNA biogenesis in Entamoeba as well as broaden the spectrum of non-canonical Dicer enzymes that contribute to the RNAi pathway.

A GIS-based methodology for selecting stormwater disconnection opportunities.

PubMed

Moore, S L; Stovin, V R; Wall, M; Ashley, R M

2012-01-01

The purpose of this paper is to introduce a geographic information system (GIS)-based decision support tool that assists the user to select not only areas where (retrofit) sustainable drainage systems (SuDS) could be implemented within a large catchment (>100 ha), but also to allow discrimination between suitable SuDS techniques based on their likely feasibility and effectiveness. The tool is applied to a case study catchment within London, UK, with the aim of increasing receiving water quality by reducing combined sewer overflow (CSO) spill frequency and volume. The key benefit of the tool presented is to allow rapid assessment of the retrofit SuDS potential of large catchments. It is not intended to replace detailed site investigations, but may help to direct attention to sites that have the greatest potential for retrofit SuDS implementation. Preliminary InfoWorks CS modelling of 'global disconnections' within the case study catchment, e.g. the removal of 50% of the total impervious area, showed that CSO spill volume could be reduced by 55 to 78% during a typical year. Using the disconnection hierarchy developed by the authors, the feasibility of retrofit SuDS deployment within the case study catchment is assessed, and the implications discussed.

A Single RNaseIII Domain Protein from Entamoeba histolytica Has dsRNA Cleavage Activity and Can Help Mediate RNAi Gene Silencing in a Heterologous System

PubMed Central

Singh, Upinder

2015-01-01

Dicer enzymes process double-stranded RNA (dsRNA) into small RNAs that target gene silencing through the RNA interference (RNAi) pathway. Dicer enzymes are complex, multi-domain RNaseIII proteins, however structural minimalism of this protein has recently emerged in parasitic and fungal systems. The most minimal Dicer, Saccharomyces castellii Dicer1, has a single RNaseIII domain and two double stranded RNA binding domains. In the protozoan parasite Entamoeba histolytica 27nt small RNAs are abundant and mediate silencing, yet no canonical Dicer enzyme has been identified. Although EhRNaseIII does not exhibit robust dsRNA cleavage in vitro, it can process dsRNA in the RNAi-negative background of Saccharomyces cerevisiae, and in conjunction with S. castellii Argonaute1 can partially reconstitute the RNAi pathway. Thus, although EhRNaseIII lacks the domain architecture of canonical or minimal Dicer enzymes, it has dsRNA processing activity that contributes to gene silencing via RNAi. Our data advance the understanding of small RNA biogenesis in Entamoeba as well as broaden the spectrum of non-canonical Dicer enzymes that contribute to the RNAi pathway. PMID:26230096

Analyses via automated mass spectrometry (MS/DS)

NASA Technical Reports Server (NTRS)

Koenig, T.

1985-01-01

New or improved uses of the Finnigan 4000 quadrupole mass spectrometer (MS) with its associated INCOS data system (DS) were investigated. The first phase involved an evaluative activity in which specific problems with miscalibration and gas chromatographic column conditioning were identified. This also revealed one solution to the problem of detection of substances not visible in the gas chromatography detection mode. A second phase was to seek useful applications of the direct inlet systems. This mode of sample introduction has not been previously utilized on the existing equipment and was successfully applied to the analysis of the components of TONOX 60/40 and in the thermal degradation products of some polymeric materials. Suggestions are made for improving and expanding the use of the MS/DS system in materials development and testing.

Rainfall-Runoff Simulations to Assess the Potential of SuDS for Mitigating Flooding in Highly Urbanized Catchments.

PubMed

Jato-Espino, Daniel; Charlesworth, Susanne M; Bayon, Joseba R; Warwick, Frank

2016-01-21

Sustainable Urban Drainage Systems (SuDS) constitute an alternative to conventional drainage when managing stormwater in cities, reducing the impact of urbanization by decreasing the amount of runoff generated by a rainfall event. This paper shows the potential benefits of installing different types of SuDS in preventing flooding in comparison with the common urban drainage strategies consisting of sewer networks of manholes and pipes. The impact of these systems on urban water was studied using Geographic Information Systems (GIS), which are useful tools when both delineating catchments and parameterizing the elements that define a stormwater drainage system. Taking these GIS-based data as inputs, a series of rainfall-runoff simulations were run in a real catchment located in the city of Donostia (Northern Spain) using stormwater computer models, in order to compare the flow rates and depths produced by a design storm before and after installing SuDS. The proposed methodology overcomes the lack of precision found in former GIS-based stormwater approaches when dealing with the modeling of highly urbanized catchments, while the results demonstrated the usefulness of these systems in reducing the volume of water generated after a rainfall event and their ability to prevent localized flooding and surcharges along the sewer network.

Rainfall–Runoff Simulations to Assess the Potential of SuDS for Mitigating Flooding in Highly Urbanized Catchments

PubMed Central

Jato-Espino, Daniel; Charlesworth, Susanne M.; Bayon, Joseba R.; Warwick, Frank

2016-01-01

Sustainable Urban Drainage Systems (SuDS) constitute an alternative to conventional drainage when managing stormwater in cities, reducing the impact of urbanization by decreasing the amount of runoff generated by a rainfall event. This paper shows the potential benefits of installing different types of SuDS in preventing flooding in comparison with the common urban drainage strategies consisting of sewer networks of manholes and pipes. The impact of these systems on urban water was studied using Geographic Information Systems (GIS), which are useful tools when both delineating catchments and parameterizing the elements that define a stormwater drainage system. Taking these GIS-based data as inputs, a series of rainfall–runoff simulations were run in a real catchment located in the city of Donostia (Northern Spain) using stormwater computer models, in order to compare the flow rates and depths produced by a design storm before and after installing SuDS. The proposed methodology overcomes the lack of precision found in former GIS-based stormwater approaches when dealing with the modeling of highly urbanized catchments, while the results demonstrated the usefulness of these systems in reducing the volume of water generated after a rainfall event and their ability to prevent localized flooding and surcharges along the sewer network. PMID:26805864

The Defense Logistics Agency: Providing Logistics Support throughout the Department of Defense

DTIC Science & Technology

1993-10-01

agencies, as well as its engineer, ordnance, and transportation corps. 6 As the Navy and Army recovered from these losses, the dust seemed to settle, yet... transportation and packaging assis- tance, and surveillance of contractor progress to assure timely delivery of material. To streamline contract management in DOD...Ar Foce ktem Ironsr o Ohr.cloru•e. Aki F-oce Nmw Ciamfe. 1901), 11: and ds eracbd froro Headqueree De .. L ta iercy, Weapon Sys- •mppo f Pr•gwn tohy

Regulation of Mammary Progenitor Cells by p53 and Parity

DTIC Science & Technology

2011-01-01

quantitative PCR system (Stratagene). To knockdown Notch1 in TM40A cells, siRNA (s70698 and s70700) were purchased from Ambion. s70698 siRNA sense sequence: 5...hours after transfect ion and real-tim e quantitative P CR was used to confirm the knockdown efficiency. Results Label and chase progenitor cells...cells contained 0.8% o f DsRed positiv e (DsR +) progenitor cells (Fig. 1B). The mammosphere-forming capacity of DsR+ cells is 3.8-fold greater

Seasonal and spatial variations of source and drinking water quality in small municipal systems of two Canadian regions.

PubMed

Scheili, A; Rodriguez, M J; Sadiq, R

2015-03-01

A one-year sampling program covering twenty-five small municipal systems was carried out in two Canadian regions to improve our understanding of the variability of water quality in small systems from water source to the end of the distribution system (DS). The database obtained was used to develop a global portrait of physical, chemical and microbiological water quality parameters. More precisely, the temporal and the spatial variability of these parameters were investigated. We observed that the levels of natural organic matter (NOM) were variable during different seasons, with maxima in the fall for both provinces. In the regions under study, the highest trihalomethane (THM) and haloacetic acid (HAA) levels were achieved in warmer seasons (summer, fall), as observed in previous studies involving large systems. Observed THM and HAA levels were three times higher in systems in the province of Newfoundland & Labrador than in the province of Quebec. Taste and odor indicators were detected during the summer and fall, and higher heterotrophic plate count (HPC) levels were associated with lower free chlorine levels. To determine spatial variations, stepwise statistical analysis was used to identify parameters and locations in the DS that act as indicators of drinking water quality. As observed for medium and large systems, free chlorine consumption, THM and HAA levels were dependent on their location in the DS. We also observed that the degradation of HAAs is more important in small systems than in medium or large DS reported in the literature, and this degradation can occur from the beginning of the DS. The results of this research may contribute to providing precious information on drinking water quality to small system operators and pave the way for several opportunities to improve water quality management. Copyright © 2014 Elsevier B.V. All rights reserved.

Working Memory Impairments in Chromosome 22q11.2 Deletion Syndrome: The Roles of Anxiety and Stress Physiology.

PubMed

Sanders, Ashley F P; Hobbs, Diana A; Stephenson, David D; Laird, Robert D; Beaton, Elliott A

2017-04-01

Stress and anxiety have a negative impact on working memory systems by competing for executive resources and attention. Broad memory deficits, anxiety, and elevated stress have been reported in individuals with chromosome 22q11.2 deletion syndrome (22q11.2DS). We investigated anxiety and physiological stress reactivity in relation to visuospatial working memory impairments in 20 children with 22q11.2DS and 32 typically developing (TD) children ages 7 to 16. Children with 22q11.2DS demonstrated poorer working memory, reduced post-stress respiratory sinus arrhythmia recovery, and overall increased levels of cortisol in comparison to TD children. Anxiety, but not physiological stress responsivity, mediated the relationship between 22q11.2DS diagnosis and visuospatial working memory impairment. Findings indicate that anxiety exacerbates impaired working memory in children with 22q11.2DS.

Isolation, characterization, and in rats plasma pharmacokinetic study of a new triterpenoid saponin from Dianthus superbus.

PubMed

Ren, Yina; Xu, Xiaobao; Zhang, Qianlan; Lu, Yongzhuang; Li, Ximin; Zhang, Lin; Tian, Jingkui

2017-02-01

One new oleanolic acid triterpenoid saponin, 3-O-β-D-glucopyranosyl olean-11, 13(18)-diene-23,28-dioic acid, (hereafter referred to as DS-1) was isolated from the traditional Chinese medicinal plant Dianthus superbus (D. superbus). DS-1 plays an important role in the bioactivity of D. superbus. Thus, a sensitive, reliable and accurate reversed-phased liquid chromatography with tandem mass spectrometry (LC-MS/MS) in negative ion mode was developed and validated for the quantification and pharmacokinetic study of DS-1 in rats plasma. The pharmacokinetic profile showed that DS-1 was rapidly absorbed and eliminated in plasma, indicating that significant accumulation of the compound in biological specimen is unlikely. In addition, poor absorption into systemic circulation was observed after oral administration of DS-1, resulting in low absolute bioavailability (0.92 %).

Developmental abnormalities and age-related neurodegeneration in a mouse model of Down syndrome

PubMed Central

Holtzman, David M.; Santucci, Daniela; Kilbridge, Joshua; Chua-Couzens, Jane; Fontana, David J.; Daniels, Scott E.; Johnson, Randolph M.; Chen, Karen; Sun, Yuling; Carlson, Elaine; Alleva, Enrico; Epstein, Charles J.; Mobley, William C.

1996-01-01

To study the pathogenesis of central nervous system abnormalities in Down syndrome (DS), we have analyzed a new genetic model of DS, the partial trisomy 16 (Ts65Dn) mouse. Ts65Dn mice have an extra copy of the distal aspect of mouse chromosome 16, a segment homologous to human chromosome 21 that contains much of the genetic material responsible for the DS phenotype. Ts65Dn mice show developmental delay during the postnatal period as well as abnormal behaviors in both young and adult animals that may be analogous to mental retardation. Though the Ts65Dn brain is normal on gross examination, there is age-related degeneration of septohippocampal cholinergic neurons and astrocytic hypertrophy, markers of the Alzheimer disease pathology that is present in elderly DS individuals. These findings suggest that Ts65Dn mice may be used to study certain developmental and degenerative abnormalities in the DS brain. PMID:8917591

Verbal short-term memory in Down's syndrome: an articulatory loop deficit?

PubMed

Vicari, S; Marotta, L; Carlesimo, G A

2004-02-01

Verbal short-term memory, as measured by digit or word span, is generally impaired in individuals with Down's syndrome (DS) compared to mental age-matched controls. Moving from the working memory model, the present authors investigated the hypothesis that impairment in some of the articulatory loop sub-components is at the base of the deficient maintenance and recall of phonological representations in individuals with DS. Two experiments were carried out in a group of adolescents with DS and in typically developing children matched for mental age. In the first experiment, the authors explored the reliance of these subjects on the subvocal rehearsal mechanism during a word-span task and the effects produced by varying the frequency of occurrence of the words on the extension of the word span. In the second experiment, they investigated the functioning of the phonological store component of the articulatory loop in more detail. A reduced verbal span in DS was confirmed. Neither individuals with DS nor controls engaged in spontaneous subvocal rehearsal. Moreover, the data provide little support for defective functioning of the phonological store in DS. No evidence was found suggesting that a dysfunction of the articulatory loop and lexical-semantic competence significantly contributed to verbal span reduction in subjects with DS. Alternative explanations of defective verbal short-term memory in DS, such as a central executive system impairment, must be considered.

[Pharmacological analysis of the effect of natural double-helical nucleic acids on the detoxifying function of the liver].

PubMed

Masycheva, V I; Morozova, E N; Nadolinnaia, I G

1988-10-01

The effect of interferon inductors i.e. double stranded RNAs from S. cerevisiae and phage F6 on the liver detoxicating function was studied on noninbred albino mice. The liver detoxicating function was tested by duration of hexenal sleep. It was shown that intraperitoneal administration of the yeast and phage RNAs in doses of 1/5 LD50 for three times led to increasing of the narcotic sleep duration in the animals by 65 and 207 per cent, respectively. The effect was of the dose-dependent nature. The doses not inducing reliable inhibition of hexenal metabolism were equal to 1/10 LD50 for the yeast dsRNA and 1/27 LD50 for the phage dsRNA. The inhibitory effect of the dsRNAs was retained for 2-3 days after discontinuation of the drug use. When the dsRNAs were administered simultaneously with nembutal, an inductor of the liver microsomal enzymes, the dsRNAs eliminated its inducing effect. Simultaneous administration of alpha-tocopherol lowered the dsRNA effect on hexenal metabolism. The findings suggested that the dsRNA inhibitory effect on the liver detoxicating function was grounded on the mechanisms associated with inhibition of syntheses and activation of lipid peroxidation specific of the monooxygenase system under the action of the dsRNAs.

Comparative Genomic Analysis of Phylogenetically Closely Related Hydrogenobaculum sp. Isolates from Yellowstone National Park

PubMed Central

Romano, Christine; D'Imperio, Seth; Woyke, Tanja; Mavromatis, Konstantinos; Lasken, Roger; Shock, Everett L.

2013-01-01

We describe the complete genome sequences of four closely related Hydrogenobaculum sp. isolates (≥99.7% 16S rRNA gene identity) that were isolated from the outflow channel of Dragon Spring (DS), Norris Geyser Basin, in Yellowstone National Park (YNP), WY. The genomes range in size from 1,552,607 to 1,552,931 bp, contain 1,667 to 1,676 predicted genes, and are highly syntenic. There are subtle differences among the DS isolates, which as a group are different from Hydrogenobaculum sp. strain Y04AAS1 that was previously isolated from a geographically distinct YNP geothermal feature. Genes unique to the DS genomes encode arsenite [As(III)] oxidation, NADH-ubiquinone-plastoquinone (complex I), NADH-ubiquinone oxidoreductase chain, a DNA photolyase, and elements of a type II secretion system. Functions unique to strain Y04AAS1 include thiosulfate metabolism, nitrate respiration, and mercury resistance determinants. DS genomes contain seven CRISPR loci that are almost identical but are different from the single CRISPR locus in strain Y04AAS1. Other differences between the DS and Y04AAS1 genomes include average nucleotide identity (94.764%) and percentage conserved DNA (80.552%). Approximately half of the genes unique to Y04AAS1 are predicted to have been acquired via horizontal gene transfer. Fragment recruitment analysis and marker gene searches demonstrated that the DS metagenome was more similar to the DS genomes than to the Y04AAS1 genome, but that the DS community is likely comprised of a continuum of Hydrogenobaculum genotypes that span from the DS genomes described here to an Y04AAS1-like organism, which appears to represent a distinct ecotype relative to the DS genomes characterized. PMID:23435891

The Amyloid Precursor Protein (APP) Triplicated Gene Impairs Neuronal Precursor Differentiation and Neurite Development through Two Different Domains in the Ts65Dn Mouse Model for Down Syndrome*

PubMed Central

Trazzi, Stefania; Fuchs, Claudia; Valli, Emanuele; Perini, Giovanni; Bartesaghi, Renata; Ciani, Elisabetta

2013-01-01

Intellectual disability in Down syndrome (DS) appears to be related to severe proliferation impairment during brain development. Recent evidence shows that it is not only cellular proliferation that is heavily compromised in DS, but also cell fate specification and dendritic maturation. The amyloid precursor protein (APP), a gene that is triplicated in DS, plays a key role in normal brain development by influencing neural precursor cell proliferation, cell fate specification, and neuronal maturation. APP influences these processes via two separate domains, the APP intracellular domain (AICD) and the soluble secreted APP. We recently found that the proliferation impairment of neuronal precursors (NPCs) from the Ts65Dn mouse model for DS was caused by derangement of the Shh pathway due to overexpression of patched1(Ptch1), its inhibitory regulator. Ptch1 overexpression was related to increased levels within the APP/AICD system. The overall goal of this study was to determine whether APP contributes to neurogenesis impairment in DS by influencing in addition to proliferation, cell fate specification, and neurite development. We found that normalization of APP expression restored the reduced neuronogenesis, the increased astrogliogenesis, and the reduced neurite length of trisomic NPCs, indicating that APP overexpression underpins all aspects of neurogenesis impairment. Moreover, we found that two different domains of APP impair neuronal differentiation and maturation in trisomic NPCs. The APP/AICD system regulates neuronogenesis and neurite length through the Shh pathway, whereas the APP/secreted AP system promotes astrogliogenesis through an IL-6-associated signaling cascade. These results provide novel insight into the mechanisms underlying brain development alterations in DS. PMID:23740250

Uplink Packet-Data Scheduling in DS-CDMA Systems

NASA Astrophysics Data System (ADS)

Choi, Young Woo; Kim, Seong-Lyun

In this letter, we consider the uplink packet scheduling for non-real-time data users in a DS-CDMA system. As an effort to jointly optimize throughput and fairness, we formulate a time-span minimization problem incorporating the time-multiplexing of different simultaneous transmission schemes. Based on simple rules, we propose efficient scheduling algorithms and compare them with the optimal solution obtained by linear programming.

RNA interference technology in crop protection against arthropod pests, pathogens and nematodes.

PubMed

Zotti, Moises; Dos Santos, Ericmar Avila; Cagliari, Deise; Christiaens, Olivier; Taning, Clauvis Nji Tizi; Smagghe, Guy

2018-06-01

Scientists have made significant progress in understanding and unraveling several aspects of double-stranded RNA (dsRNA)-mediated gene silencing during the last two decades. Now that the RNA interference (RNAi) mechanism is well understood, it is time to consider how to apply the acquired knowledge to agriculture and crop protection. Some RNAi-based products are already available for farmers and more are expected to reach the market soon. Tailor-made dsRNA as an active ingredient for biopesticide formulations is considered a raw material that can be used for diverse purposes, from pest control and bee protection against viruses to pesticide resistance management. The RNAi mechanism works at the messenger RNA (mRNA) level, exploiting a sequence-dependent mode of action, which makes it unique in potency and selectivity compared with conventional agrochemicals. Furthermore, the use of RNAi in crop protection can be achieved by employing plant-incorporated protectants through plant transformation, but also by non-transformative strategies such as the use of formulations of sprayable RNAs as direct control agents, resistance factor repressors or developmental disruptors. In this review, RNAi is presented in an agricultural context (discussing products that have been launched on the market or will soon be available), and we go beyond the classical presentation of successful examples of RNAi in pest-insect control and comprehensively explore its potential for the control of plant pathogens, nematodes and mites, and to fight against diseases and parasites in beneficial insects. Moreover, we also discuss its use as a repressor for the management of pesticide-resistant weeds and insects. Finally, this review reports on the advances in non-transformative dsRNA delivery and the production costs of dsRNA, and discusses environmental considerations. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

The CHADS2 and CHA2DS2-VASc scores for predicting ischemic stroke among East Asian patients with atrial fibrillation: A systemic review and meta-analysis.

PubMed

Xiong, Qinmei; Chen, Sisi; Senoo, Keitaro; Proietti, Marco; Hong, Kui; Lip, Gregory Y H

2015-09-15

Both the CHADS2 and CHA2DS2-VASc scores are well-validated in Western populations for predicting risk of stroke among patients with atrial fibrillation (AF). There is some uncertainty as to which risk score is best to guide optimal anticoagulant therapy among Asian populations with AF. A systemic literature search of Cochrane library, Scopus, and PubMed databases was conducted using search terms: atrial fibrillation, CHADS2 and CHA2DS2-VASc. Stroke/thromboembolism (TE) outcome events at low, moderate, and high risk groups were compared in relation to both scores. Statistical analyses were performed using Revman 5.3 software. 493 records were retrieved, of which 6 cohort studies focusing on patients from Asian regions were finally appraised and included. Absolute event rates were usually lower when patients were categorized as CHA2DS2-VASc of 0-1, rather than CHADS2 of 0-1, respectively. Meta-analysis revealed that when compared with the CHA2DS2-VASc score, there was a 1.71-fold elevated risk of stroke when patients were stratified as 'low risk' using a CHADS2 score = 0, or a 1.40-fold increase with a CHADS2 score = 1. A 1.19-fold elevated event rate was observed among CHADS2 score ≥ 2 compared to CHA2DS2-VASc, but the total stroke/TE events were numerically higher in patients categorized as CHA2DS2-VASc ≥ 2. The CHA2DS2-VASc score is superior to the CHADS2 score in identifying 'low risk' East Asian AF patients. Rather than a categorical approach, Asian guidelines should adopt a 2 step approach, by initially identifying the truly low risk patients, following which effective stroke prevention can be offered to those with ≥ 1 additional stroke risk factors. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Assessment of the Study of Army Logistics 1981. Volume II. Analysis of Recommendations.

DTIC Science & Technology

1983-02-01

conceived. This third generation equipment, because of its size, cost and processing characteristics, demands large scale integrated processing with a... generated by DS4. Three systems changes to SAILS ABX have been implemented which reduce the volume of supply status provided to the DS4 system. 15... generated by the wholesale system by 50 percent or nearly 1,000,000 transactions per month. Additional reductions will be generated by selected status

The design of the m-health service application using a Nintendo DS game console.

PubMed

Lee, Sangjoon; Kim, Jungkuk; Lee, Myoungho

2011-03-01

In this article, we developed an m-health monitoring system using a Nintendo DS game console to demonstrate its utility. The proposed system consists of a biosignal acquisition device, wireless sensor network, base-station for signal reception from the sensor network and signal conversion according to Internet protocol, personal computer display program, and the Nintendo DS game console. The system collects three-channel electrocardiogram (ECG) signals for cardiac abnormality detection and three-axis accelerometer signals for fall detection of a person. The collected signals are then transmitted to the base-station through the wireless sensor network, where they are transformed according to the transmission control protocol/Internet protocol (TCP/IP) and sent to the destination IP through Internet network. To test the developed system, the collected signals were displayed on a computer located in different building through wired Internet network and also simultaneously displayed on the Nintendo DS game console connected to Internet network wirelessly. The system was able to collect and transmit signals for more than 24 h without any interruptions or malfunctions, showing the possibility of integrating healthcare monitoring functions into a small handheld-type electronic device developed for different purposes without significant complications. It is expected that the system can be used in an ambulance, nursing home, or general hospital where efficient patient monitoring from long distance is necessary.

Cell death-inducing stresses are required for defense activation in DS1-phosphatidic acid phosphatase-silenced Nicotiana benthamiana.

PubMed

Nakano, Masahito; Yoshioka, Hirofumi; Ohnishi, Kouhei; Hikichi, Yasufumi; Kiba, Akinori

2015-07-20

We previously identified DS1 plants that showed resistance to compatible Ralstonia solanacearum with accelerated defense responses. Here, we describe activation mechanisms of defense responses in DS1 plants. After inoculation with incompatible R. solanacearum 8107, DS1 plants showed hyperinduction of hypersensitive response (HR) and reactive oxygen species (ROS) generation. Transient expression of PopP1 and AvrA induced hyperinduction of HR and ROS generation. Furthermore, Pseudomonas cichorii (Pc) and a type III secretion system (TTSS)-deficient mutant of P. cichorii showed accelerated induction of HR and ROS generation. Chitin and flg22 did not induce either HR or ROS hyperaccumulation; however, INF1 accelerated HR and ROS in DS1 plants. Activation of these defense responses was closely associated with increased phosphatidic acid (PA) content. Our results show that DS1 plants exhibit PA-mediated sensitization of plant defenses and that cell death-inducing stress is required to achieve full activation of defense responses. Copyright © 2015 Elsevier GmbH. All rights reserved.

Deep sedation versus general anesthesia in percutaneous edge-to-edge mitral valve reconstruction using the MitraClip system.

PubMed

de Waha, Suzanne; Seeburger, Joerg; Ender, Joerg; Desch, Steffen; Eitel, Ingo; Reinhardt, Adrian; Pöss, Janine; Fuernau, Georg; Noack, Thilo; Merk, Denis Rouven; Schuler, Gerhard; Sievers, Hans-Hinrich; Mohr, Friedrich-Wilhelm; Thiele, Holger

2016-06-01

Percutaneous edge-to-edge mitral valve reconstruction (PMVR) has emerged as a treatment option in patients with severe mitral regurgitation not considered suitable candidates for surgery. The majority of PMVR procedures are performed under general anesthesia (GA), although deep sedation (DS) appears to be an attractive alternative. We thus sought to assess the impact on intensive care unit (ICU) length of stay, efficacy, and safety of DS in comparison to GA in patients undergoing PMVR using the MitraClip(®) system. Sixty consecutive patients underwent PMVR procedures at two centers. The first 30 patients were treated by GA followed by 30 patients undergoing DS under different settings. The primary clinical endpoint was ICU length of stay. The primary efficacy endpoint included procedural success and procedural duration. The safety endpoint was defined as a composite of death, stroke, cardiogenic shock, moderate and severe bleeding as well as pneumonia. The ICU length of stay was significantly shorter in the DS group in comparison to GA patients (p = 0.001). The hospital length of stay did not differ following DS in comparison to GA (p = 0.96). Procedural success was high in both groups (100 versus 96.7 %, p = 0.34) at similar procedural duration time (p = 0.60). No difference between GA and DS was observed with respect to the occurrence of the combined safety endpoint (p = 0.47). In comparison to GA, DS reduces the ICU length of stay in PMVR without negative effects on safety and efficacy. Prospective randomized trials are needed to confirm these findings.

Genetic Control of L-a and L-(Bc) Dsrna Copy Number in Killer Systems of SACCHAROMYCES CEREVISIAE

PubMed Central

Ball, Steven G.; Tirtiaux, Catherine; Wickner, Reed B.

1984-01-01

M dsRNA in yeast encodes a toxin precursor and immunity protein, whereas L-A dsRNA encodes the 81,000-dalton major protein of the intracellular particles in which both L-A and M are found. L-(BC) dsRNA(s) are found in particles with different coat proteins. We find that M dsRNA lowers the copy number of L-A, but not L-(BC). The SKI gene products lower the copy number of L-(BC), L-A, M1 and M2. This is the first known interaction of L-(BC) with any element of the killer systems. The MAK3, MAK10 and PET18 gene products are necessary for L-A maintenance and replication, but mutations in these genes do not affect L-(BC) copy number. Mutations in MAK1, MAK4, MAK7, MAK17 and MAK24 do not detectably affect copy number of L-(BC) or L-A. PMID:17246214

Ordered DNA-Surfactant Hybrid Nanospheres Triggered by Magnetic Cationic Surfactants for Photon- and Magneto-Manipulated Drug Delivery and Release.

PubMed

Xu, Lu; Wang, Yitong; Wei, Guangcheng; Feng, Lei; Dong, Shuli; Hao, Jingcheng

2015-12-14

Here we construct for the first time ordered surfactant-DNA hybrid nanospheres of double-strand (ds) DNA and cationic surfactants with magnetic counterion, [FeCl3Br](-). The specificity of the magnetic cationic surfactants that can compact DNA at high concentrations makes it possible for building ordered nanospheres through aggregation, fusion, and coagulation. Cationic surfactants with conventional Br(-) cannot produce spheres under the same condition because they lose the DNA compaction ability. When a light-responsive magnetic cationic surfactant is used to produce nanospheres, a dual-controllable drug-delivery platform can be built simply by the applications of external magnetic force and alternative UV and visible light. These nanospheres obtain high drug absorption efficiency, slow release property, and good biocompatibility. There is potential for effective magnetic-field-based targeted drug delivery, followed by photocontrollable drug release. We deduce that our results might be of great interest for making new functional nucleic-acid-based nanomachines and be envisioned to find applications in nanotechnology and biochemistry.

Systems biological approach to investigate the lack of familial link between Down's Syndrome & Neural Tube Disorders.

PubMed

Ragunath, Pk; Abhinand, Pa

2013-01-01

Systems Biology involves the study of the interactions of biological systems and ultimately their functions. Down's syndrome (DS) is one of the most common genetic disorders which are caused by complete, or occasionally partial, triplication of chromosome 21, characterized by cognitive and language dysfunction coupled with sensory and neuromotor deficits. Neural Tube Disorders (NTDs) are a group of congenital malformations of the central nervous system and neighboring structures related to defective neural tube closure during the first trimester of pregnancy usually occurring between days 18-29 of gestation. Several studies in the past have provided considerable evidence that abnormal folate and methyl metabolism are associated with onset of DS & NTDs. There is a possible common etiological pathway for both NTDs and Down's syndrome. But, various research studies over the years have indicated very little evidence for familial link between the two disorders. Our research aimed at the gene expression profiling of microarray datasets pertaining to the two disorders to identify genes whose expression levels are significantly altered in these conditions. The genes which were 1.5 fold unregulated and having a p-value <0.05 were filtered out and gene interaction network were constructed for both NTDs and DS. The top ranked dense clique for both the disorders were recognized and over representation analysis was carried out for each of the constituent genes. The comprehensive manual analysis of these genes yields a hypothetical understanding of the lack of familial link between DS and NTDs. There were no genes involved with folic acid present in the dense cliques. Only - CBL, EGFR genes were commonly present, which makes the allelic variants of these genes - good candidates for future studies regarding the familial link between DS and NTDs. NTD - Neural Tube Disorders, DS - Down's Syndrome, MTHFR - Methylenetetrahydrofolate reductase, MTRR- 5 - methyltetrahydrofolate-homocysteine methyltransferase reductase.

Infectious Complications in Living-Donor Kidney Transplant Recipients Undergoing Multi-Modal Desensitization

PubMed Central

Shafique, Michael; Lobo, Peter I.; Sawyer, Robert G.; Keith, Douglas S.; Brayman, Kenneth L.; Agarwal, Avinash

2014-01-01

Abstract Background: Pre-existing humoral barriers challenge the transplantation of living donor kidneys (LDK) into highly sensitized ABO- and human leukocyte antigen (HLA)-incompatible recipients. Conditioning these LDK recipients' immune systems is required before they undergo transplantation. We hypothesized that medical desensitization would yield higher post-transplantation rates of infection. Methods: We conducted a study in which matched controls consisting of non-desensitized (NDS) LDK recipients were compared with desensitized (DS) receipients. Pre-transplantation desensitization included treatment with rituximab and mycophenolate mofetil followed by intravenous immunoglobulin (IVIg) and plasmapheresis. All participants in the study underwent induction therapy and maintenance immunosuppression. Primary outcomes included infection (opportunistic, local, systemic) within 12 mo after transplantation. Results: Twenty-five patients underwent desensitization and LDK transplantation. Graft survival in the DS and NDS groups of patients was 96% and 98%, respectively. The mean 3- and 12-mo serum creatinine concentrations in the DS and NDS groups were 1.1±0.2 mg/dL and 1.2±0.3 mg/dL and 0.95±0.4mg/dL and 0.73±0.8mg/dL (p=0.3 and p=0.01), respectively. Thirty-six percent of the patients in the DS group had one or more infections, vs. 28% of those in the NDS group (p=0.1). No difference was observed in the frequency of opportunistic or systemic infections in the two groups. Local infections were statistically significantly more frequent in the DS group (60% vs. 30%, respectively; p=0.02). Conclusion: Pre-operative desensitization in highly sensitized LDK recipients is followed by a similar incidence of opportunistic and systemic infections as in NDS patients. Local infections were significantly more frequent in the DS than in the NDS patients in the study. With careful monitoring of infectious complications, pre-transplant desensitization permits LDK transplantation into highly sensitized patients. PMID:24773230

Infectious complications in living-donor kidney transplant recipients undergoing multi-modal desensitization.

PubMed

Turza, Kristin C; Shafique, Michael; Lobo, Peter I; Sawyer, Robert G; Keith, Douglas S; Brayman, Kenneth L; Agarwal, Avinash

2014-06-01

Pre-existing humoral barriers challenge the transplantation of living donor kidneys (LDK) into highly sensitized ABO- and human leukocyte antigen (HLA)-incompatible recipients. Conditioning these LDK recipients' immune systems is required before they undergo transplantation. We hypothesized that medical desensitization would yield higher post-transplantation rates of infection. We conducted a study in which matched controls consisting of non-desensitized (NDS) LDK recipients were compared with desensitized (DS) receipients. Pre-transplantation desensitization included treatment with rituximab and mycophenolate mofetil followed by intravenous immunoglobulin (IVIg) and plasmapheresis. All participants in the study underwent induction therapy and maintenance immunosuppression. Primary outcomes included infection (opportunistic, local, systemic) within 12 mo after transplantation. Twenty-five patients underwent desensitization and LDK transplantation. Graft survival in the DS and NDS groups of patients was 96% and 98%, respectively. The mean 3- and 12-mo serum creatinine concentrations in the DS and NDS groups were 1.1±0.2 mg/dL and 1.2±0.3 mg/dL and 0.95±0.4 mg/dL and 0.73±0.8 mg/dL (p=0.3 and p=0.01), respectively. Thirty-six percent of the patients in the DS group had one or more infections, vs. 28% of those in the NDS group (p=0.1). No difference was observed in the frequency of opportunistic or systemic infections in the two groups. Local infections were statistically significantly more frequent in the DS group (60% vs. 30%, respectively; p=0.02). Pre-operative desensitization in highly sensitized LDK recipients is followed by a similar incidence of opportunistic and systemic infections as in NDS patients. Local infections were significantly more frequent in the DS than in the NDS patients in the study. With careful monitoring of infectious complications, pre-transplant desensitization permits LDK transplantation into highly sensitized patients.

Finding of widespread viral and bacterial revolution dsDNA translocation motors distinct from rotation motors by channel chirality and size

PubMed Central

2014-01-01

Background Double-stranded DNA translocation is ubiquitous in living systems. Cell mitosis, bacterial binary fission, DNA replication or repair, homologous recombination, Holliday junction resolution, viral genome packaging and cell entry all involve biomotor-driven dsDNA translocation. Previously, biomotors have been primarily classified into linear and rotational motors. We recently discovered a third class of dsDNA translocation motors in Phi29 utilizing revolution mechanism without rotation. Analogically, the Earth rotates around its own axis every 24 hours, but revolves around the Sun every 365 days. Results Single-channel DNA translocation conductance assay combined with structure inspections of motor channels on bacteriophages P22, SPP1, HK97, T7, T4, Phi29, and other dsDNA translocation motors such as bacterial FtsK and eukaryotic mimiviruses or vaccinia viruses showed that revolution motor is widespread. The force generation mechanism for revolution motors is elucidated. Revolution motors can be differentiated from rotation motors by their channel size and chirality. Crystal structure inspection revealed that revolution motors commonly exhibit channel diameters larger than 3 nm, while rotation motors that rotate around one of the two separated DNA strands feature a diameter smaller than 2 nm. Phi29 revolution motor translocated double- and tetra-stranded DNA that occupied 32% and 64% of the narrowest channel cross-section, respectively, evidencing that revolution motors exhibit channel diameters significantly wider than the dsDNA. Left-handed oriented channels found in revolution motors drive the right-handed dsDNA via anti-chiral interaction, while right-handed channels observed in rotation motors drive the right-handed dsDNA via parallel threads. Tethering both the motor and the dsDNA distal-end of the revolution motor does not block DNA packaging, indicating that no rotation is required for motors of dsDNA phages, while a small-angle left-handed twist of dsDNA that is aligned with the channel could occur due to the conformational change of the phage motor channels from a left-handed configuration for DNA entry to a right-handed configuration for DNA ejection for host cell infection. Conclusions The revolution motor is widespread among biological systems, and can be distinguished from rotation motors by channel size and chirality. The revolution mechanism renders dsDNA void of coiling and torque during translocation of the lengthy helical chromosome, thus resulting in more efficient motor energy conversion. PMID:24940480

Supportive care utilization and treatment toxicity in children with Down syndrome and acute lymphoid leukaemia at free-standing paediatric hospitals in the United States.

PubMed

Salazar, Elizabeth G; Li, Yimei; Fisher, Brian T; Rheingold, Susan R; Fitzgerald, Julie; Seif, Alix E; Huang, Yuan-Shung; Bagatell, Rochelle; Aplenc, Richard

2016-08-01

Although inferior outcomes of children with Down syndrome (DS) and acute lymphoid leukaemia (ALL) are established, national supportive care patterns for these patients are unknown. A validated retrospective cohort of paediatric patients diagnosed with ALL from 1999 to 2011 was assembled from the US Pediatric Health Information System (PHIS) database to examine organ toxicity, sepsis, and resource utilization in children with and without DS. Among 10699 ALL patients, 298 had DS-ALL (2·8%). In a multivariate model, DS was associated with increased risk of cardiovascular (odds ratio [OR] 2·0, 95% confidence interval [CI] 1·6-2·7), respiratory (OR 2·1, 95% CI: 1·6-2·9), neurologic (OR 3·4, 95% CI 1·9-6·2), and hepatic (OR 1·4, 95% CI 1·0-1·9) dysfunction and sepsis (OR 1·8, 95% CI: 1·4-2·4). Children with DS-ALL used significantly more respiratory support, insulin, and anti-infectives, including broad-spectrum Gram-positive agents, quinolones, and azoles. They used significantly fewer analgesics and antiemetics compared to non-DS-ALL children. Ultimately, this study confirms the increased risk of infectious and end-organ toxicity in children with DS-ALL and quantifies important differences in resource utilization between children with DS and non-DS ALL. These findings highlight the importance of investigating the impact of these care variations and developing specific supportive care guidelines for this population. © 2016 John Wiley & Sons Ltd.

Spectroscopy detection of green and red fluorescent proteins in genetically modified plants using a fiber optics system

NASA Astrophysics Data System (ADS)

Liew, Oi Wah; Asundi, Anand K.; Chen, Jun-Wei; Chew, Yiwen; Yu, Shangjuan; Yeo, Gare H.

2001-05-01

In this paper, fiber optic spectroscopy is developed to detect and quantify recombinant green (EGFP) and red (DsRED) fluorescent proteins in vitro and in vivo. The bacterial expression vectors carrying the coding regions of EGFP and DsRED were introduced into Escherichia coli host cells and fluorescent proteins were produced following induction with IPTG. Soluble EGFP and DsRED proteins were isolated from lysed bacterial cells and serially diluted for quantitative analysis by fiber optic spectroscopy. Fluorescence at the appropriate emission wavelengths could be detected up to 64X dilution for EGFP and 40X dilution for DsRED. To determine the capability of spectroscopy detection in vivo, transgenic potato hairy roots expressing EGFP and DsRED were regenerated. This was achieved by cloning the EGFP and DsRED genes into the plant binary vector, pTMV35S, to create the recombinant vectors pGLOWGreen and pGLOWRed. These latter binary vectors were introduced into Agrobacterium rhizogenes strain A4T. Infection of potato cells with transformed agrobacteria was used to insert the fluorescent protein genes into the potato genome. Genetically modified potato cells were then regenerated into hairy roots. A panel of transformed hairy roots expressing varying levels of fluorescent proteins was selected by fluorescence microscopy. We are now assessing the capability of spectroscopic detection system for in vivo quantification of green and red fluorescence levels in transformed roots.

Molar mass characterization of sodium carboxymethyl cellulose by SEC-MALLS.

PubMed

Shakun, Maryia; Maier, Helena; Heinze, Thomas; Kilz, Peter; Radke, Wolfgang

2013-06-05

Two series of sodium carboxymethyl celluloses (NaCMCs) derived from microcrystalline cellulose (Avicel samples) and cotton linters (BWL samples) with average degrees of substitution (DS) ranging from DS=0.45 to DS=1.55 were characterized by size exclusion chromatography with multi-angle laser light scattering detection (SEC-MALLS) in 100 mmol/L aqueous ammonium acetate (NH4OAc) as vaporizable eluent system. The application of vaporizable NH4OAc allows future use of the eluent system in two-dimensional separations employing evaporative light scattering detection (ELSD). The losses of samples during filtration and during the chromatographic experiment were determined. The scaling exponent as of the relation [Formula: see text] was approx. 0.61, showing that NaCMCs exhibit an expanded coil conformation in solution. No systematic dependencies of as on DS were observed. The dependences of molar mass on SEC-elution volume for samples of different DS can be well described by a common calibration curve, which is of advantage, as it allows the determination of molar masses of unknown samples by using the same calibration curve, irrespective of the DS of the NaCMC sample. Since no commercial NaCMC standards are available, correction factors were determined allowing converting a pullulan based calibration curve into a NaCMC calibration using the broad calibration approach. The weight average molar masses derived using the so established calibration curve closely agree with the ones determined by light scattering, proving the accuracy of the correction factors determined. Copyright © 2013 Elsevier Ltd. All rights reserved.

Network anomaly detection system with optimized DS evidence theory.

PubMed

Liu, Yuan; Wang, Xiaofeng; Liu, Kaiyu

2014-01-01

Network anomaly detection has been focused on by more people with the fast development of computer network. Some researchers utilized fusion method and DS evidence theory to do network anomaly detection but with low performance, and they did not consider features of network-complicated and varied. To achieve high detection rate, we present a novel network anomaly detection system with optimized Dempster-Shafer evidence theory (ODS) and regression basic probability assignment (RBPA) function. In this model, we add weights for each sensor to optimize DS evidence theory according to its previous predict accuracy. And RBPA employs sensor's regression ability to address complex network. By four kinds of experiments, we find that our novel network anomaly detection model has a better detection rate, and RBPA as well as ODS optimization methods can improve system performance significantly.

Combined Effect of Random Transmit Power Control and Inter-Path Interference Cancellation on DS-CDMA Packet Mobile Communications

NASA Astrophysics Data System (ADS)

Kudoh, Eisuke; Ito, Haruki; Wang, Zhisen; Adachi, Fumiyuki

In mobile communication systems, high speed packet data services are demanded. In the high speed data transmission, throughput degrades severely due to severe inter-path interference (IPI). Recently, we proposed a random transmit power control (TPC) to increase the uplink throughput of DS-CDMA packet mobile communications. In this paper, we apply IPI cancellation in addition to the random TPC. We derive the numerical expression of the received signal-to-interference plus noise power ratio (SINR) and introduce IPI cancellation factor. We also derive the numerical expression of system throughput when IPI is cancelled ideally to compare with the Monte Carlo numerically evaluated system throughput. Then we evaluate, by Monte-Carlo numerical computation method, the combined effect of random TPC and IPI cancellation on the uplink throughput of DS-CDMA packet mobile communications.

Network Anomaly Detection System with Optimized DS Evidence Theory

PubMed Central

Liu, Yuan; Wang, Xiaofeng; Liu, Kaiyu

2014-01-01

Network anomaly detection has been focused on by more people with the fast development of computer network. Some researchers utilized fusion method and DS evidence theory to do network anomaly detection but with low performance, and they did not consider features of network—complicated and varied. To achieve high detection rate, we present a novel network anomaly detection system with optimized Dempster-Shafer evidence theory (ODS) and regression basic probability assignment (RBPA) function. In this model, we add weights for each senor to optimize DS evidence theory according to its previous predict accuracy. And RBPA employs sensor's regression ability to address complex network. By four kinds of experiments, we find that our novel network anomaly detection model has a better detection rate, and RBPA as well as ODS optimization methods can improve system performance significantly. PMID:25254258

Mouse Models of Down Syndrome as a Tool to Unravel the Causes of Mental Disabilities

PubMed Central

Rueda, Noemí; Flórez, Jesús; Martínez-Cué, Carmen

2012-01-01

Down syndrome (DS) is the most common genetic cause of mental disability. Based on the homology of Hsa21 and the murine chromosomes Mmu16, Mmu17 and Mmu10, several mouse models of DS have been developed. The most commonly used model, the Ts65Dn mouse, has been widely used to investigate the neural mechanisms underlying the mental disabilities seen in DS individuals. A wide array of neuromorphological alterations appears to compromise cognitive performance in trisomic mice. Enhanced inhibition due to alterations in GABAA-mediated transmission and disturbances in the glutamatergic, noradrenergic and cholinergic systems, among others, has also been demonstrated. DS cognitive dysfunction caused by neurodevelopmental alterations is worsened in later life stages by neurodegenerative processes. A number of pharmacological therapies have been shown to partially restore morphological anomalies concomitantly with cognition in these mice. In conclusion, the use of mouse models is enormously effective in the study of the neurobiological substrates of mental disabilities in DS and in the testing of therapies that rescue these alterations. These studies provide the basis for developing clinical trials in DS individuals and sustain the hope that some of these drugs will be useful in rescuing mental disabilities in DS individuals. PMID:22685678

Measurement of the CP-violating phase ϕs in Bs(0)→Ds(+)Ds(-) decays.

PubMed

Aaij, R; Abellán Beteta, C; Adeva, B; Adinolfi, M; Affolder, A; Ajaltouni, Z; Akar, S; Albrecht, J; Alessio, F; Alexander, M; Ali, S; Alkhazov, G; Alvarez Cartelle, P; Alves, A A; Amato, S; Amerio, S; Amhis, Y; An, L; Anderlini, L; Anderson, J; Andreassen, R; Andreotti, M; Andrews, J E; Appleby, R B; Aquines Gutierrez, O; Archilli, F; Artamonov, A; Artuso, M; Aslanides, E; Auriemma, G; Baalouch, M; Bachmann, S; Back, J J; Badalov, A; Baesso, C; Baldini, W; Barlow, R J; Barschel, C; Barsuk, S; Barter, W; Batozskaya, V; Battista, V; Bay, A; Beaucourt, L; Beddow, J; Bedeschi, F; Bediaga, I; Belogurov, S; Belous, K; Belyaev, I; Ben-Haim, E; Bencivenni, G; Benson, S; Benton, J; Berezhnoy, A; Bernet, R; Bettler, M-O; van Beuzekom, M; Bien, A; Bifani, S; Bird, T; Bizzeti, A; Bjørnstad, P M; Blake, T; Blanc, F; Blouw, J; Blusk, S; Bocci, V; Bondar, A; Bondar, N; Bonivento, W; Borghi, S; Borgia, A; Borsato, M; Bowcock, T J V; Bowen, E; Bozzi, C; Brambach, T; Brett, D; Britsch, M; Britton, T; Brodzicka, J; Brook, N H; Brown, H; Bursche, A; Busetto, G; Buytaert, J; Cadeddu, S; Calabrese, R; Calvi, M; Calvo Gomez, M; Campana, P; Campora Perez, D; Carbone, A; Carboni, G; Cardinale, R; Cardini, A; Carson, L; Carvalho Akiba, K; Casse, G; Cassina, L; Castillo Garcia, L; Cattaneo, M; Cauet, Ch; Cenci, R; Charles, M; Charpentier, Ph; Chefdeville, M; Chen, S; Cheung, S-F; Chiapolini, N; Chrzaszcz, M; Cid Vidal, X; Ciezarek, G; Clarke, P E L; Clemencic, M; Cliff, H V; Closier, J; Coco, V; Cogan, J; Cogneras, E; Cogoni, V; Cojocariu, L; Collins, P; Comerma-Montells, A; Contu, A; Cook, A; Coombes, M; Coquereau, S; Corti, G; Corvo, M; Counts, I; Couturier, B; Cowan, G A; Craik, D C; Cruz Torres, M; Cunliffe, S; Currie, R; D'Ambrosio, C; Dalseno, J; David, P; David, P N Y; Davis, A; De Bruyn, K; De Capua, S; De Cian, M; De Miranda, J M; De Paula, L; De Silva, W; De Simone, P; Decamp, D; Deckenhoff, M; Del Buono, L; Déléage, N; Derkach, D; Deschamps, O; Dettori, F; Di Canto, A; Dijkstra, H; Donleavy, S; Dordei, F; Dorigo, M; Dosil Suárez, A; Dossett, D; Dovbnya, A; Dreimanis, K; Dujany, G; Dupertuis, F; Durante, P; Dzhelyadin, R; Dziurda, A; Dzyuba, A; Easo, S; Egede, U; Egorychev, V; Eidelman, S; Eisenhardt, S; Eitschberger, U; Ekelhof, R; Eklund, L; El Rifai, I; Elena, E; Elsasser, Ch; Ely, S; Esen, S; Evans, H-M; Evans, T; Falabella, A; Färber, C; Farinelli, C; Farley, N; Farry, S; Fay, R F; Ferguson, D; Fernandez Albor, V; Ferreira Rodrigues, F; Ferro-Luzzi, M; Filippov, S; Fiore, M; Fiorini, M; Firlej, M; Fitzpatrick, C; Fiutowski, T; Fol, P; Fontana, M; Fontanelli, F; Forty, R; Francisco, O; Frank, M; Frei, C; Frosini, M; Fu, J; Furfaro, E; Gallas Torreira, A; Galli, D; Gallorini, S; Gambetta, S; Gandelman, M; Gandini, P; Gao, Y; García Pardiñas, J; Garofoli, J; Garra Tico, J; Garrido, L; Gaspar, C; Gauld, R; Gavardi, L; Gavrilov, G; Geraci, A; Gersabeck, E; Gersabeck, M; Gershon, T; Ghez, Ph; Gianelle, A; Gianì, S; Gibson, V; Giubega, L; Gligorov, V V; Göbel, C; Golubkov, D; Golutvin, A; Gomes, A; Gotti, C; Grabalosa Gándara, M; Graciani Diaz, R; Granado Cardoso, L A; Graugés, E; Graziani, G; Grecu, A; Greening, E; Gregson, S; Griffith, P; Grillo, L; Grünberg, O; Gui, B; Gushchin, E; Guz, Yu; Gys, T; Hadjivasiliou, C; Haefeli, G; Haen, C; Haines, S C; Hall, S; Hamilton, B; Hampson, T; Han, X; Hansmann-Menzemer, S; Harnew, N; Harnew, S T; Harrison, J; He, J; Head, T; Heijne, V; Hennessy, K; Henrard, P; Henry, L; Hernando Morata, J A; van Herwijnen, E; Heß, M; Hicheur, A; Hill, D; Hoballah, M; Hombach, C; Hulsbergen, W; Hunt, P; Hussain, N; Hutchcroft, D; Hynds, D; Idzik, M; Ilten, P; Jacobsson, R; Jaeger, A; Jalocha, J; Jans, E; Jaton, P; Jawahery, A; Jing, F; John, M; Johnson, D; Jones, C R; Joram, C; Jost, B; Jurik, N; Kaballo, M; Kandybei, S; Kanso, W; Karacson, M; Karbach, T M; Karodia, S; Kelsey, M; Kenyon, I R; Ketel, T; Khanji, B; Khurewathanakul, C; Klaver, S; Klimaszewski, K; Kochebina, O; Kolpin, M; Komarov, I; Koopman, R F; Koppenburg, P; Korolev, M; Kozlinskiy, A; Kravchuk, L; Kreplin, K; Kreps, M; Krocker, G; Krokovny, P; Kruse, F; Kucewicz, W; Kucharczyk, M; Kudryavtsev, V; Kurek, K; Kvaratskheliya, T; La Thi, V N; Lacarrere, D; Lafferty, G; Lai, A; Lambert, D; Lambert, R W; Lanfranchi, G; Langenbruch, C; Langhans, B; Latham, T; Lazzeroni, C; Le Gac, R; van Leerdam, J; Lees, J-P; Lefèvre, R; Leflat, A; Lefrançois, J; Leo, S; Leroy, O; Lesiak, T; Leverington, B; Li, Y; Likhomanenko, T; Liles, M; Lindner, R; Linn, C; Lionetto, F; Liu, B; Lohn, S; Longstaff, I; Lopes, J H; Lopez-March, N; Lowdon, P; Lucchesi, D; Luo, H; Lupato, A; Luppi, E; Lupton, O; Machefert, F; Machikhiliyan, I V; Maciuc, F; Maev, O; Malde, S; Malinin, A; Manca, G; Mancinelli, G; Mapelli, A; Maratas, J; Marchand, J F; Marconi, U; Marin Benito, C; Marino, P; Märki, R; Marks, J; Martellotti, G; Martín Sánchez, A; Martinelli, M; Martinez Santos, D; Martinez Vidal, F; Martins Tostes, D; Massafferri, A; Matev, R; Mathe, Z; Matteuzzi, C; Mazurov, A; McCann, M; McCarthy, J; McNab, A; McNulty, R; McSkelly, B; Meadows, B; Meier, F; Meissner, M; Merk, M; Milanes, D A; Minard, M-N; Moggi, N; Molina Rodriguez, J; Monteil, S; Morandin, M; Morawski, P; Mordà, A; Morello, M J; Moron, J; Morris, A-B; Mountain, R; Muheim, F; Müller, K; Mussini, M; Muster, B; Naik, P; Nakada, T; Nandakumar, R; Nasteva, I; Needham, M; Neri, N; Neubert, S; Neufeld, N; Neuner, M; Nguyen, A D; Nguyen, T D; Nguyen-Mau, C; Nicol, M; Niess, V; Niet, R; Nikitin, N; Nikodem, T; Novoselov, A; O'Hanlon, D P; Oblakowska-Mucha, A; Obraztsov, V; Oggero, S; Ogilvy, S; Okhrimenko, O; Oldeman, R; Onderwater, G; Orlandea, M; Otalora Goicochea, J M; Otto, A; Owen, P; Oyanguren, A; Pal, B K; Palano, A; Palombo, F; Palutan, M; Panman, J; Papanestis, A; Pappagallo, M; Pappalardo, L L; Parkes, C; Parkinson, C J; Passaleva, G; Patel, G D; Patel, M; Patrignani, C; Pazos Alvarez, A; Pearce, A; Pellegrino, A; Pepe Altarelli, M; Perazzini, S; Perez Trigo, E; Perret, P; Perrin-Terrin, M; Pescatore, L; Pesen, E; Petridis, K; Petrolini, A; Picatoste Olloqui, E; Pietrzyk, B; Pilař, T; Pinci, D; Pistone, A; Playfer, S; Plo Casasus, M; Polci, F; Poluektov, A; Polycarpo, E; Popov, A; Popov, D; Popovici, B; Potterat, C; Price, E; Price, J D; Prisciandaro, J; Pritchard, A; Prouve, C; Pugatch, V; Puig Navarro, A; Punzi, G; Qian, W; Rachwal, B; Rademacker, J H; Rakotomiaramanana, B; Rama, M; Rangel, M S; Raniuk, I; Rauschmayr, N; Raven, G; Redi, F; Reichert, S; Reid, M M; dos Reis, A C; Ricciardi, S; Richards, S; Rihl, M; Rinnert, K; Rives Molina, V; Robbe, P; Rodrigues, A B; Rodrigues, E; Rodriguez Perez, P; Roiser, S; Romanovsky, V; Romero Vidal, A; Rotondo, M; Rouvinet, J; Ruf, T; Ruiz, H; Ruiz Valls, P; Saborido Silva, J J; Sagidova, N; Sail, P; Saitta, B; Salustino Guimaraes, V; Sanchez Mayordomo, C; Sanmartin Sedes, B; Santacesaria, R; Santamarina Rios, C; Santovetti, E; Sarti, A; Satriano, C; Satta, A; Saunders, D M; Savrie, M; Savrina, D; Schiller, M; Schindler, H; Schlupp, M; Schmelling, M; Schmidt, B; Schneider, O; Schopper, A; Schune, M-H; Schwemmer, R; Sciascia, B; Sciubba, A; Seco, M; Semennikov, A; Sepp, I; Serra, N; Serrano, J; Sestini, L; Seyfert, P; Shapkin, M; Shapoval, I; Shcheglov, Y; Shears, T; Shekhtman, L; Shevchenko, V; Shires, A; Silva Coutinho, R; Simi, G; Sirendi, M; Skidmore, N; Skillicorn, I; Skwarnicki, T; Smith, N A; Smith, E; Smith, E; Smith, J; Smith, M; Snoek, H; Sokoloff, M D; Soler, F J P; Soomro, F; Souza, D; Souza De Paula, B; Spaan, B; Spradlin, P; Sridharan, S; Stagni, F; Stahl, M; Stahl, S; Steinkamp, O; Stenyakin, O; Stevenson, S; Stoica, S; Stone, S; Storaci, B; Stracka, S; Straticiuc, M; Straumann, U; Stroili, R; Subbiah, V K; Sun, L; Sutcliffe, W; Swientek, K; Swientek, S; Syropoulos, V; Szczekowski, M; Szczypka, P; Szilard, D; Szumlak, T; T'Jampens, S; Teklishyn, M; Tellarini, G; Teubert, F; Thomas, C; Thomas, E; van Tilburg, J; Tisserand, V; Tobin, M; Todd, J; Tolk, S; Tomassetti, L; Tonelli, D; Topp-Joergensen, S; Torr, N; Tournefier, E; Tourneur, S; Tran, M T; Tresch, M; Tsaregorodtsev, A; Tsopelas, P; Tuning, N; Ubeda Garcia, M; Ukleja, A; Ustyuzhanin, A; Uwer, U; Vacca, C; Vagnoni, V; Valenti, G; Vallier, A; Vazquez Gomez, R; Vazquez Regueiro, P; Vázquez Sierra, C; Vecchi, S; Velthuis, J J; Veltri, M; Veneziano, G; Vesterinen, M; Viaud, B; Vieira, D; Vieites Diaz, M; Vilasis-Cardona, X; Vollhardt, A; Volyanskyy, D; Voong, D; Vorobyev, A; Vorobyev, V; Voß, C; Voss, H; de Vries, J A; Waldi, R; Wallace, C; Wallace, R; Walsh, J; Wandernoth, S; Wang, J; Ward, D R; Watson, N K; Websdale, D; Whitehead, M; Wicht, J; Wiedner, D; Wilkinson, G; Williams, M P; Williams, M; Wilschut, H W; Wilson, F F; Wimberley, J; Wishahi, J; Wislicki, W; Witek, M; Wormser, G; Wotton, S A; Wright, S; Wyllie, K; Xie, Y; Xing, Z; Xu, Z; Yang, Z; Yuan, X; Yushchenko, O; Zangoli, M; Zavertyaev, M; Zhang, L; Zhang, W C; Zhang, Y; Zhelezov, A; Zhokhov, A; Zhong, L

2014-11-21

We present a measurement of the CP-violating weak mixing phase ϕs using the decay Bs(0)→Ds(+)Ds(-) in a data sample corresponding to 3.0 fb(-1) of integrated luminosity collected with the LHCb detector in pp collisions at center-of-mass energies of 7 and 8 TeV. An analysis of the time evolution of the system, which does not use the constraint |λ|=1 to allow for the presence of CP violation in decay, yields ϕs=0.02±0.17(stat)±0.02(syst)  rad, |λ|=0.91(-0.15)(+0.18)(stat)±0.02(syst). This result is consistent with the standard model expectation.

Lack of Increased Immediate Early Gene Expression in Rats Reinstating Cocaine-Seeking Behavior to Discrete Sensory Cues

PubMed Central

Riedy, Matthew D.; Keefe, Kristen A.

2013-01-01

Drug-seeking behavior elicited by drug-associated cues contributes to relapse in addiction; however, whether relapse elicited by drug-associated conditioned reinforcers (CR) versus discriminative stimuli (DS) involves distinct or overlapping neuronal populations is unknown. To address this question, we developed a novel cocaine self-administration and cue-induced reinstatement paradigm that exposed the same rats to distinct cocaine-associated CR and DS. Rats were trained to self-administer cocaine in separate sessions. In one, a DS signaled cocaine availability; in the other, cocaine delivery was paired with a different CR. After extinction training and reinstatement testing, where both cues were presented in separate sessions, rats were sacrificed and processed for cellular analysis of temporal activity by fluorescent in situ hybridization (CatFISH) for activity regulated cytoskeleton-associated protein (Arc) mRNA and for radioactive in situ hybridization for Arc and zif268 mRNAs. CatFISH did not reveal significant changes in Arc mRNA expression. Similar results were obtained with radioactive in situ hybridization. We have shown that while rats reinstate drug seeking in response to temporally discrete presentations of distinct drug-associated cues, such reinstatement is not associated with increased transcriptional activation of Arc or zif268 mRNAs, suggesting that expression of these genes may not be necessary for cue-induced reinstatement of drug-seeking behavior. PMID:24069163

Blood-Stable, Tumor-Adaptable Disulfide Bonded mPEG-(Cys)4-PDLLA Micelles for Chemotherapy

PubMed Central

Lee, Seung-Young; Kim, Sungwon; Tyler, Jacqueline; Park, Kinam; Cheng, Ji-Xin

2012-01-01

Although targeted delivery mediated by ligand modified or tumor microenvironment sensitive nanocarriers has been extensively pursued for cancer chemotherapy, the efficiency is still limited by premature drug release after systemic administration. Herein we report a highly blood-stable, tumor-adaptable drug carrier made of disulfide (DS) bonded mPEG-(Cys)4-PDLLA micelles. Intravenously injected disulfide bonded micelles stably retained doxorubicin in the bloodstream and efficiently delivered the drug to a tumor, with a 7-fold increase of the drug in the tumor and 1.9-fold decrease in the heart, as compared with self-assembled (SA), non-crosslinked mPEG-PDLLA micelles. In vivo administration of disulfide bonded micelles led to doxorubicin accumulation in cancer cell nuclei, which was not observed after administration of self-assembled micelles. With a doxorubicin dose as low as 2 mg/kg, disulfide bonded micelles almost completely suppressed tumor growth in mice. PMID:23079665

Double-Stranded RNA Is Detected by Immunofluorescence Analysis in RNA and DNA Virus Infections, Including Those by Negative-Stranded RNA Viruses.

PubMed

Son, Kyung-No; Liang, Zhiguo; Lipton, Howard L

2015-09-01

Early biochemical studies of viral replication suggested that most viruses produce double-stranded RNA (dsRNA), which is essential for the induction of the host immune response. However, it was reported in 2006 that dsRNA could be detected by immunofluorescence antibody staining in double-stranded DNA and positive-strand RNA virus infections but not in negative-strand RNA virus infections. Other reports in the literature seemed to support these observations. This suggested that negative-strand RNA viruses produce little, if any, dsRNA or that more efficient viral countermeasures to mask dsRNA are mounted. Because of our interest in the use of dsRNA antibodies for virus discovery, particularly in pathological specimens, we wanted to determine how universal immunostaining for dsRNA might be in animal virus infections. We have detected the in situ formation of dsRNA in cells infected with vesicular stomatitis virus, measles virus, influenza A virus, and Nyamanini virus, which represent viruses from different negative-strand RNA virus families. dsRNA was also detected in cells infected with lymphocytic choriomeningitis virus, an ambisense RNA virus, and minute virus of mice (MVM), a single-stranded DNA (ssDNA) parvovirus, but not hepatitis B virus. Although dsRNA staining was primarily observed in the cytoplasm, it was also seen in the nucleus of cells infected with influenza A virus, Nyamanini virus, and MVM. Thus, it is likely that most animal virus infections produce dsRNA species that can be detected by immunofluorescence staining. The apoptosis induced in several uninfected cell lines failed to upregulate dsRNA formation. An effective antiviral host immune response depends on recognition of viral invasion and an intact innate immune system as a first line of defense. Double-stranded RNA (dsRNA) is a viral product essential for the induction of innate immunity, leading to the production of type I interferons (IFNs) and the activation of hundreds of IFN-stimulated genes. The present study demonstrates that infections, including those by ssDNA viruses and positive- and negative-strand RNA viruses, produce dsRNAs detectable by standard immunofluorescence staining. While dsRNA staining was primarily observed in the cytoplasm, nuclear staining was also present in some RNA and DNA virus infections. The nucleus is unlikely to have pathogen-associated molecular pattern (PAMP) receptors for dsRNA because of the presence of host dsRNA molecules. Thus, it is likely that most animal virus infections produce dsRNA species detectable by immunofluorescence staining, which may prove useful in viral discovery as well. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Characterizing and Detecting Unrevealed Elements of Network Systems

DTIC Science & Technology

2009-03-01

refers to the direct interaction of persons in so far as this affects the future behavior or attitude of participants (such that this differs from... CHARACTERIZING AND DETECTING UNREVEALED ELEMENTS OF NETWORK SYSTEMS DISSERTATION James A. Leinart, Lieutenant Colonel, USAF AFIT/DS/ENS/08-01W...Air Force, Department of Defense or the United States Government. AFIT/DS/ENS/08-01W CHARACTERIZING AND DETECTING UNREVEALED ELEMENTS OF NETWORK

Adaptive Digital Signature Design and Short-Data-Record Adaptive Filtering

DTIC Science & Technology

2008-04-01

rate BPSK binary phase shift keying CA − CFAR cell averaging− constant false alarm rate CDMA code − division multiple − access CFAR constant false...Cotae, “Spreading sequence design for multiple cell synchronous DS-CDMA systems under total weighted squared correlation criterion,” EURASIP Journal...415-428, Mar. 2002. [6] P. Cotae, “Spreading sequence design for multiple cell synchronous DS-CDMA systems under total weighted squared correlation

Fate of hydrocarbon pollutants in source and non-source control sustainable drainage systems.

PubMed

Roinas, Georgios; Mant, Cath; Williams, John B

2014-01-01

Sustainable drainage (SuDs) is an established method for managing runoff from developments, and source control is part of accepted design philosophy. However, there are limited studies into the contribution source control makes to pollutant removal, especially for roads. This study examines organic pollutants, total petroleum hydrocarbons (TPH) and polycyclic aromatic hydrocarbons (PAHs), in paired source and non-source control full-scale SuDs systems. Sites were selected to cover local roads, trunk roads and housing developments, with a range of SuDs, including porous asphalt, swales, detention basins and ponds. Soil and water samples were taken bi-monthly over 12 months to assess pollutant loads. Results show first flush patterns in storm events for solids, but not for TPH. The patterns of removal for specific PAHs were also different, reflecting varying physico-chemical properties. The potential of trunk roads for pollution was illustrated by peak runoff for TPH of > 17,000 μg/l. Overall there was no significant difference between pollutant loads from source and non-source control systems, but the dynamic nature of runoff means that longer-term data are required. The outcomes of this project will increase understanding of organic pollutants behaviour in SuDs. This will provide design guidance about the most appropriate systems for treating these pollutants.

Cyclen-based lipidic oligomers as potential gene delivery vehicles.

PubMed

Yi, Wen-Jing; Zhang, Qin-Fang; Zhang, Ji; Liu, Qiang; Ren, Laifeng; Chen, Qian-Ming; Guo, Liandi; Yu, Xiao-Qi

2014-03-01

A series of cyclen-based linear oligomers bearing hydrophobic long chains (lipopolymers Cy-LC, where Cy and LC represent cyclen-based linear backbone and hydrophobic long chain substituents, respectively) were designed and synthesized. The effects of type and degree of substitution (DS) of hydrophobic long chains on the transfection efficiency were systematically studied. The nitrogen atoms with relatively strong basicity on the cyclen ensure their good DNA binding ability, which was confirmed by gel retardation and ethidium bromide exclusion assays. Lipopolyplexes could be formed as nanoparticles with suitable sizes and zeta potentials for gene transfection. In vitro gene delivery experiments revealed that the linoleic acid (LIN) substituted material Cy-LIN has better transfection efficiency than 25 kDa polyethylenimine in the absence or in the presence of serum. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and hemolysis assays showed low cytotoxicity and good biocompatibility of the lipopolyplexes. Fluorescent labeled DNA was used to study the cellular uptake and intracellular distribution of transfected DNA. Flow cytometry results suggested that a long chain is necessary for efficient cellular uptake, and images from confocal laser scanning microscopy showed that after 4h transfection, most of the fluorescent labeled DNA accumulated in the perinuclear region, which was required for efficient gene expression. Moreover, it was also found that the DS of the hydrophobic moiety can adjust the balance between DNA binding ability and dissociation of polyplexes, significantly affecting the transfection efficiency. Copyright © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Multidisciplinary obstetric simulated emergency scenarios (MOSES): promoting patient safety in obstetrics with teamwork-focused interprofessional simulations.

PubMed

Freeth, Della; Ayida, Gubby; Berridge, Emma Jane; Mackintosh, Nicola; Norris, Beverley; Sadler, Chris; Strachan, Alasdair

2009-01-01

We describe an example of simulation-based interprofessional continuing education, the multidisciplinary obstetric simulated emergency scenarios (MOSES) course, which was designed to enhance nontechnical skills among obstetric teams and, hence, improve patient safety. Participants' perceptions of MOSES courses, their learning, and the transfer of learning to clinical practice were examined. Participants included senior midwives, obstetricians, and obstetric anesthetists, including course faculty from 4 purposively selected delivery suites in England. Telephone or e-mail interviews with MOSES course participants and facilitators were conducted, and video-recorded debriefings that formed integral parts of this 1-day course were analyzed. The team training was well received. Participants were able to check out assumptions and expectations of others and develop respect for different roles within the delivery suite (DS) team. Skillful facilitation of debriefing after each scenario was central to learning. Participants reported acquiring new knowledge or insights, particularly concerning the role of communication and leadership in crisis situations, and they rehearsed unfamiliar skills. Observing peers working in the simulations increased participants' learning by highlighting alternative strategies. The learning achieved by individuals and groups was noticeably dependent on their starting points. Some participants identified limited changes in their behavior in the workplace following the MOSES course. Mechanisms to manage the transfer of learning to the wider team were weakly developed, although 2 DS teams made changes to their regular update training. Interprofessional, team-based simulations promote new learning.

Noradrenergic System in Down Syndrome and Alzheimer's Disease A Target for Therapy.

PubMed

Phillips, Cristy; Fahimi, Atoossa; Das, Devsmita; Mojabi, Fatemeh S; Ponnusamy, Ravikumar; Salehi, Ahmad

2016-01-01

Locus coeruleus (LC) neurons in the brainstem send extensive noradrenergic (NE)-ergic terminals to the majority of brain regions, particularly those involved in cognitive function. Both Alzheimer's disease (AD) and Down syndrome (DS) are characterized by similar pathology including significant LC degeneration and dysfunction of the NE-ergic system. Extensive loss of NE-ergic terminals has been linked to alterations in brain regions vital for cognition, mood, and executive function. While the mechanisms by which NE-ergic abnormalities contribute to cognitive dysfunction are not fully understood, emergent evidence suggests that rescue of NE-ergic system can attenuate neuropathology and cognitive decline in both AD and DS. Therapeutic strategies to enhance NE neurotransmission have undergone limited testing. Among those deployed to date are NE reuptake inhibitors, presynaptic α-adrenergic receptor antagonists, NE prodrugs, and β-adrenergic agonists. Here we examine alterations in the NE-ergic system in AD and DS and suggest that NE-ergic system rescue is a plausible treatment strategy for targeting cognitive decline in both disorders.

An update on the Deep Space 1 power system: SCARLET integration and test results

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

Allen, D.M.; Murphy, D.M.

1998-07-01

The Solar Concentrator Arrays with Refractive Linear Element Technology (SCARLET) system for the Deep Space 1 (DS1) spacecraft have been completed and delivered to JPL for integration with the spacecraft. This paper describes the array assembly, the qualification test program, and the results of the qualification tests. The array will provide power to the DS1 spacecraft and its NSTAR ion electric propulsion system. Launch is scheduled for October, 1998 from Kennedy Space Center, FL.

A Method to Develop Neck Injury Criteria to Aid Design and Test of Escape Systems Incorporating Helmet Mounted Displays

DTIC Science & Technology

2014-09-01

The military aviation community began designing and building ejection seats for high speed aircraft after World War II. As pilot safety became...AFIT-ENV-DS-14-S-22 A METHOD TO DEVELOP NECK INJURY CRITERIA TO AID DESIGN AND TEST OF ESCAPE SYSTEMS...protection in the United States. AFIT-ENV-DS-14-S-22 A METHOD TO DEVELOP NECK INJURY CRITERIA TO AID DESIGN AND TEST OF ESCAPE SYSTEMS

The Electronics and Data Acquisition System of the DarkSide Dark Matter Search

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

Agnes, P.; et al.

2014-12-09

It is generally inferred from astronomical measurements that Dark Matter (DM) comprises approximately 27\\% of the energy-density of the universe. If DM is a subatomic particle, a possible candidate is a Weakly Interacting Massive Particle (WIMP), and the DarkSide-50 (DS) experiment is a direct search for evidence of WIMP-nuclear collisions. DS is located underground at the Laboratori Nazionali del Gran Sasso (LNGS) in Italy, and consists of three active, embedded components; an outer water veto (CTF), a liquid scintillator veto (LSV), and a liquid argon (LAr) time projection chamber (TPC). This paper describes the data acquisition and electronic systems ofmore » the DS detectors, designed to detect the residual ionization from such collisions.« less

Analysis, optimization, and implementation of a hybrid DS/FFH spread-spectrum technique for smart grid communications

DOE PAGES

Olama, Mohammed M.; Ma, Xiao; Killough, Stephen M.; ...

2015-03-12

In recent years, there has been great interest in using hybrid spread-spectrum (HSS) techniques for commercial applications, particularly in the Smart Grid, in addition to their inherent uses in military communications. This is because HSS can accommodate high data rates with high link integrity, even in the presence of significant multipath effects and interfering signals. A highly useful form of this transmission technique for many types of command, control, and sensing applications is the specific code-related combination of standard direct sequence modulation with fast frequency hopping, denoted hybrid DS/FFH, wherein multiple frequency hops occur within a single data-bit time. Inmore » this paper, error-probability analyses are performed for a hybrid DS/FFH system over standard Gaussian and fading-type channels, progressively including the effects from wide- and partial-band jamming, multi-user interference, and varying degrees of Rayleigh and Rician fading. In addition, an optimization approach is formulated that minimizes the bit-error performance of a hybrid DS/FFH communication system and solves for the resulting system design parameters. The optimization objective function is non-convex and can be solved by applying the Karush-Kuhn-Tucker conditions. We also present our efforts toward exploring the design, implementation, and evaluation of a hybrid DS/FFH radio transceiver using a single FPGA. Numerical and experimental results are presented under widely varying design parameters to demonstrate the adaptability of the waveform for varied harsh smart grid RF signal environments.« less

Smart-DS: Synthetic Models for Advanced, Realistic Testing: Distribution Systems and Scenarios

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

Krishnan, Venkat K; Palmintier, Bryan S; Hodge, Brian S

The National Renewable Energy Laboratory (NREL) in collaboration with Massachusetts Institute of Technology (MIT), Universidad Pontificia Comillas (Comillas-IIT, Spain) and GE Grid Solutions, is working on an ARPA-E GRID DATA project, titled Smart-DS, to create: 1) High-quality, realistic, synthetic distribution network models, and 2) Advanced tools for automated scenario generation based on high-resolution weather data and generation growth projections. Through these advancements, the Smart-DS project is envisioned to accelerate the development, testing, and adoption of advanced algorithms, approaches, and technologies for sustainable and resilient electric power systems, especially in the realm of U.S. distribution systems. This talk will present themore » goals and overall approach of the Smart-DS project, including the process of creating the synthetic distribution datasets using reference network model (RNM) and the comprehensive validation process to ensure network realism, feasibility, and applicability to advanced use cases. The talk will provide demonstrations of early versions of synthetic models, along with the lessons learnt from expert engagements to enhance future iterations. Finally, the scenario generation framework, its development plans, and co-ordination with GRID DATA repository teams to house these datasets for public access will also be discussed.« less

Divalent counterion-induced condensation of triple-strand DNA.

PubMed

Qiu, Xiangyun; Parsegian, V Adrian; Rau, Donald C

2010-12-14

Understanding and manipulation of the forces assembling DNA/RNA helices have broad implications for biology, medicine, and physics. One subject of significance is the attractive force between dsDNA mediated by polycations of valence ≥ 3. Despite extensive studies, the physical origin of the "like-charge attraction" remains unsettled among competing theories. Here we show that triple-strand DNA (tsDNA), a more highly charged helix than dsDNA, is precipitated by alkaline-earth divalent cations that are unable to condense dsDNA. We further show that our observation is general by examining several cations (Mg(2+), Ba(2+), and Ca(2+)) and two distinct tsDNA constructs. Cation-condensed tsDNA forms ordered hexagonal arrays that redissolve upon adding monovalent salts. Forces between tsDNA helices, measured by osmotic stress, follow the form of hydration forces observed with condensed dsDNA. Probing a well-defined system of point-like cations and tsDNAs with more evenly spaced helical charges, the counterintuitive observation that the more highly charged tsDNA (vs. dsDNA) is condensed by cations of lower valence provides new insights into theories of polyelectrolytes and the biological and pathological roles of tsDNA. Cations and tsDNAs also hold promise as a model system for future studies of DNA-DNA interactions and electrostatic interactions in general.

Systemic Lupus Erythematosus: Molecular Mimicry between Anti-dsDNA CDR3 Idiotype, Microbial and Self Peptides-As Antigens for Th Cells.

PubMed

Aas-Hanssen, Kristin; Thompson, Keith M; Bogen, Bjarne; Munthe, Ludvig A

2015-01-01

Systemic lupus erythematosus (SLE) is marked by a T helper (Th) cell-dependent B cell hyperresponsiveness, with frequent germinal center reactions, and gammaglobulinemia. A feature of SLE is the finding of IgG autoantibodies specific for dsDNA. The specificity of the Th cells that drive the expansion of anti-dsDNA B cells is unresolved. However, anti-microbial, anti-histone, and anti-idiotype Th cell responses have been hypothesized to play a role. It has been entirely unclear if these seemingly disparate Th cell responses and hypotheses could be related or unified. Here, we describe that H chain CDR3 idiotypes from IgG(+) B cells of lupus mice have sequence similarities with both microbial and self peptides. Matched sequences were more frequent within the mutated CDR3 repertoire and when sequences were derived from lupus mice with expanded anti-dsDNA B cells. Analyses of histone sequences showed that particular histone peptides were similar to VDJ junctions. Moreover, lupus mice had Th cell responses toward histone peptides similar to anti-dsDNA CDR3 sequences. The results suggest that Th cells in lupus may have multiple cross-reactive specificities linked to the IgVH CDR3 Id-peptide sequences as well as similar DNA-associated protein motifs.

A designed recombinant fusion protein for targeted delivery of siRNA to the mouse brain.

PubMed

Haroon, Mohamed Mohamed; Dar, Ghulam Hassan; Jeyalakshmi, Durga; Venkatraman, Uthra; Saba, Kamal; Rangaraj, Nandini; Patel, Anant Bahadur; Gopal, Vijaya

2016-04-28

RNA interference represents a novel therapeutic approach to modulate several neurodegenerative disease-related genes. However, exogenous delivery of siRNA restricts their transport into different tissues and specifically into the brain mainly due to its large size and the presence of the blood-brain barrier (BBB). To overcome these challenges, we developed here a strategy wherein a peptide known to target specific gangliosides was fused to a double-stranded RNA binding protein to deliver siRNA to the brain parenchyma. The designed fusion protein designated as TARBP-BTP consists of a double-stranded RNA-binding domain (dsRBD) of human Trans Activation response element (TAR) RNA Binding Protein (TARBP2) fused to a brain targeting peptide that binds to monosialoganglioside GM1. Conformation-specific binding of TARBP2 domain to siRNA led to the formation of homogenous serum-stable complex with targeting potential. Further, uptake of the complex in Neuro-2a, IMR32 and HepG2 cells analyzed by confocal microscopy and fluorescence activated cell sorting, revealed selective requirement of GM1 for entry. Remarkably, systemic delivery of the fluorescently labeled complex (TARBP-BTP:siRNA) in ΑβPP-PS1 mouse model of Alzheimer's disease (AD) led to distinctive localization in the cerebral hemisphere. Further, the delivery of siRNA mediated by TARBP-BTP led to significant knockdown of BACE1 in the brain, in both ΑβPP-PS1 mice and wild type C57BL/6. The study establishes the growing importance of fusion proteins in delivering therapeutic siRNA to brain tissues. Copyright © 2016 Elsevier B.V. All rights reserved.

Clinical evaluation of cobas core anti-dsDNA EIA quant.

PubMed

González, Concepción; Guevara, Paloma; García-Berrocal, Belén; Alejandro Navajo, José; Manuel González-Buitrago, José

2004-01-01

The measurement of antibodies to double-stranded DNA (anti-dsDNA) is a useful tool for the diagnosis and monitoring of patients with connective tissue diseases, particularly systemic lupus erythematosus (SLE). The aim of the present study was to compare a new enzyme-linked immunosorbent assay (ELISA) for the measurement of anti-dsDNA antibodies, which uses purified double-stranded plasmid DNA as the antigen (anti-dsDNA EIA Quant; Roche Diagnostics, Mannheim, Germany), with an established ELISA. The clinical usefulness of this new ELISA was also assessed. We measured anti-dsDNA antibodies in 398 serum samples that were divided into four groups: 1). routine samples sent to our laboratory for an antinuclear antibody (ANA) test (n=229), 2). samples from blood donors (n=74), 3). samples from patients with SLE (n=48), and 4) samples from patients with other autoimmune diseases (n=47). The methods used were the Cobas Core Anti-dsDNA EIA Quant (Roche Diagnostics, Mannheim, Germany) and the Anti-dsDNA test (Gull Diagnostics, Bois d'Arcy, France). We obtained a kappa index and Spearman correlation coefficient in the comparative study, and sensitivity, specificity, predictive values, and likelihood ratios in the clinical study. The results obtained show a good agreement between the two methods in both the qualitative results (kappa=0.91) and the quantitative data (r=0.854). The best accuracy, predictive values, likelihood ratios, and correlation with active disease were obtained with the Roche anti-dsDNA assay. Copyright 2004 Wiley-Liss, Inc.

Driving simulator validation of driver behavior with limited safe vantage points for data collection in work zones.

PubMed

Bham, Ghulam H; Leu, Ming C; Vallati, Manoj; Mathur, Durga R

2014-06-01

This study is aimed at validating a driving simulator (DS) for the study of driver behavior in work zones. A validation study requires field data collection. For studies conducted in highway work zones, the availability of safe vantage points for data collection at critical locations can be a significant challenge. A validation framework is therefore proposed in this paper, demonstrated using a fixed-based DS that addresses the issue by using a global positioning system (GPS). The validation of the DS was conducted using objective and subjective evaluations. The objective validation was divided into qualitative and quantitative evaluations. The DS was validated by comparing the results of simulation with the field data, which were collected using a GPS along the highway and video recordings at specific locations in a work zone. The constructed work zone scenario in the DS was subjectively evaluated with 46 participants. The objective evaluation established the absolute and relative validity of the DS. The mean speeds from the DS data showed excellent agreement with the field data. The subjective evaluation indicated realistic driving experience by the participants. The use of GPS showed that continuous data collected along the highway can overcome the challenges of unavailability of safe vantage points especially at critical locations. Further, a validated DS can be used for examining driver behavior in complex situations by replicating realistic scenarios. Copyright © 2014 Elsevier Ltd. All rights reserved.

International multi-center evaluation of a novel chemiluminescence assay for the detection of anti-dsDNA antibodies.

PubMed

Bentow, C; Lakos, G; Martis, P; Wahl, E; Garcia, M; Viñas, O; Espinosa, G; Cervera, R; Sjöwall, C; Carmona-Fernandes, D; Santos, M J; Hanly, J G; Mahler, M

2016-07-01

Anti-double stranded desoxyribonucleic acid (anti-dsDNA) antibodies are considered fairly specific for systemic lupus erythematosus (SLE) and their quantification is useful for the clinical management of SLE patients. We assessed the diagnostic performance of the QUANTA Flash dsDNA chemiluminescent immunoassay (CIA) in comparison to an ELISA, using patients from five participating countries. The main focus was to evaluate the correlation between anti-dsDNA antibody results from the CIA and global SLE disease activity, as measured by the SLE Disease Activity Index 2000 (SLEDAI-2K). A total of 1431 samples (SLE, n = 843; disease controls, n = 588) from five countries (Canada, USA, Portugal, Sweden and Spain) were tested with QUANTA Flash dsDNA (Inova Diagnostics, San Diego, CA, USA). Data obtained with the QUANTA Lite dsDNA SC ELISA (Inova Diagnostics) were available for samples from three sites (Canada, USA and Sweden, n = 566). The SLEDAI-2K scores were available for 805 SLE patients and a cut-off of > 4 was used to define active disease. QUANTA Flash dsDNA had a sensitivity of 54.3% for the diagnosis of SLE, combined with 89.8% specificity. Anti-dsDNA antibody levels were significantly higher (p < 0.0001) in active SLE (SLEDAI-2K > 4; n = 232; median value 83.0 IU/mL) versus the inactive patients (n = 573; median value 22.3 IU/mL), and the SLEDAI-2K scoring correlated with their dsDNA antibody levels (Spearman's rho = 0.44, p < 0.0001). Similar but less pronounced findings were also found for the ELISA, in relation to disease activity. The QUANTA Flash dsDNA assay showed good clinical performance in a large international multi-center study. Additionally, the strong correlation between anti-dsDNA antibody results and SLEDAI-2K scores supported the potential utility of QUANTA Flash dsDNA for monitoring disease activity. © The Author(s) 2016.

Ion Thruster Used to Propel the Deep Space 1 Spacecraft to Comet Encounters

NASA Technical Reports Server (NTRS)

Sovey, James S.

2000-01-01

The NASA Solar Electric Propulsion Technology Applications Readiness (NSTAR) Project provided a xenon ion propulsion system to the Deep Space 1 (DS1) spacecraft to validate the propulsion system as well as perform primary propulsion for asteroid and comet encounters. The On-Board Propulsion Branch of the NASA Glenn Research Center at Lewis Field developed engineering model versions of the 30-cm-diameter ion thruster and the 2.5-kW power processor unit (PPU). Glenn then transferred the thruster and PPU technologies to Hughes Electron Dynamics and managed the contract, which supplied two flight sets of thrusters and PPU s to the Deep Space 1 spacecraft and to a ground-based life verification test at the Jet Propulsion Laboratory (JPL). In addition to managing the DS1 spacecraft development, JPL was responsible for the NSTAR Project management, thruster life tests, the feed system, diagnostics, and propulsion subsystem integration. The ion propulsion development team included NASA Glenn, JPL, Hughes Electronics, Moog Inc., and Spectrum Astro Inc. The overall NSTAR subsystem dry mass, including thruster, PPU, controller, cables, and the xenon storage and feed system, is 48 kg. The mass of the xenon stored onboard DS1 was about 81 kg, and the spacecraft wet mass was approximately 500 kg.The DS1 spacecraft was launched on October 24, 1998, and on July 29, 1999, it flew within 16 miles of the small asteroid Braille (formerly 1992KD) at a relative speed of 35,000 mph. As of November 1999, the ion propulsion system had performed flawlessly for nearly 149 days of thrusting. NASA has approved an extension to the mission, which will allow DS1 to continue thrusting to encounters with two comets in 2001. The DS1 optical and plasma diagnostic instruments will be used to investigate the comet and space environments. The spacecraft is scheduled to fly past the dormant comet Wilson- Harrington in January 2001 and the very active comet Borrelly in September 2001, at which time approximately 500 days of ion engine thrusting will have been completed.

Implementation of Distance Support (DS) to Reduce Total Ownership Cost (R-TOC)

DTIC Science & Technology

2012-02-01

ATIS ) for technical documentation,  PMS Scheduling (SKED)  Food Service Management (FSM3). For morale and welfare support, local web content...Development ( TD ) phase and use a systems engineering (SE) approach (similar to Figure 6 above) to help understand ramifications for deleting DS. For

Proline and COMT Status Affect Visual Connectivity in Children with 22q11.2 Deletion Syndrome

PubMed Central

Magnée, Maurice J. C. M.; Lamme, Victor A. F.; de Sain-van der Velden, Monique G. M.; Vorstman, Jacob A. S.; Kemner, Chantal

2011-01-01

Background Individuals with the 22q11.2 deletion syndrome (22q11DS) are at increased risk for schizophrenia and Autism Spectrum Disorders (ASDs). Given the prevalence of visual processing deficits in these three disorders, a causal relationship between genes in the deleted region of chromosome 22 and visual processing is likely. Therefore, 22q11DS may represent a unique model to understand the neurobiology of visual processing deficits related with ASD and psychosis. Methodology We measured Event-Related Potentials (ERPs) during a texture segregation task in 58 children with 22q11DS and 100 age-matched controls. The C1 component was used to index afferent activity of visual cortex area V1; the texture negativity wave provided a measure for the integrity of recurrent connections in the visual cortical system. COMT genotype and plasma proline levels were assessed in 22q11DS individuals. Principal Findings Children with 22q11DS showed enhanced feedforward activity starting from 70 ms after visual presentation. ERP activity related to visual feedback activity was reduced in the 22q11DS group, which was seen as less texture negativity around 150 ms post presentation. Within the 22q11DS group we further demonstrated an association between high plasma proline levels and aberrant feedback/feedforward ratios, which was moderated by the COMT 158 genotype. Conclusions These findings confirm the presence of early visual processing deficits in 22q11DS. We discuss these in terms of dysfunctional synaptic plasticity in early visual processing areas, possibly associated with deviant dopaminergic and glutamatergic transmission. As such, our findings may serve as a promising biomarker related to the development of schizophrenia among 22q11DS individuals. PMID:21998713

Fluorescence correlation spectroscopy analysis for accurate determination of proportion of doubly labeled DNA in fluorescent DNA pool for quantitative biochemical assays.

PubMed

Hou, Sen; Sun, Lili; Wieczorek, Stefan A; Kalwarczyk, Tomasz; Kaminski, Tomasz S; Holyst, Robert

2014-01-15

Fluorescent double-stranded DNA (dsDNA) molecules labeled at both ends are commonly produced by annealing of complementary single-stranded DNA (ssDNA) molecules, labeled with fluorescent dyes at the same (3' or 5') end. Because the labeling efficiency of ssDNA is smaller than 100%, the resulting dsDNA have two, one or are without a dye. Existing methods are insufficient to measure the percentage of the doubly-labeled dsDNA component in the fluorescent DNA sample and it is even difficult to distinguish the doubly-labeled DNA component from the singly-labeled component. Accurate measurement of the percentage of such doubly labeled dsDNA component is a critical prerequisite for quantitative biochemical measurements, which has puzzled scientists for decades. We established a fluorescence correlation spectroscopy (FCS) system to measure the percentage of doubly labeled dsDNA (PDL) in the total fluorescent dsDNA pool. The method is based on comparative analysis of the given sample and a reference dsDNA sample prepared by adding certain amount of unlabeled ssDNA into the original ssDNA solution. From FCS autocorrelation functions, we obtain the number of fluorescent dsDNA molecules in the focal volume of the confocal microscope and PDL. We also calculate the labeling efficiency of ssDNA. The method requires minimal amount of material. The samples have the concentration of DNA in the nano-molar/L range and the volume of tens of microliters. We verify our method by using restriction enzyme Hind III to cleave the fluorescent dsDNA. The kinetics of the reaction depends strongly on PDL, a critical parameter for quantitative biochemical measurements. Copyright © 2013 Elsevier B.V. All rights reserved.

22q11.2 deletion syndrome in diverse populations.

PubMed

Kruszka, Paul; Addissie, Yonit A; McGinn, Daniel E; Porras, Antonio R; Biggs, Elijah; Share, Matthew; Crowley, T Blaine; Chung, Brian H Y; Mok, Gary T K; Mak, Christopher C Y; Muthukumarasamy, Premala; Thong, Meow-Keong; Sirisena, Nirmala D; Dissanayake, Vajira H W; Paththinige, C Sampath; Prabodha, L B Lahiru; Mishra, Rupesh; Shotelersuk, Vorasuk; Ekure, Ekanem Nsikak; Sokunbi, Ogochukwu Jidechukwu; Kalu, Nnenna; Ferreira, Carlos R; Duncan, Jordann-Mishael; Patil, Siddaramappa Jagdish; Jones, Kelly L; Kaplan, Julie D; Abdul-Rahman, Omar A; Uwineza, Annette; Mutesa, Leon; Moresco, Angélica; Obregon, María Gabriela; Richieri-Costa, Antonio; Gil-da-Silva-Lopes, Vera L; Adeyemo, Adebowale A; Summar, Marshall; Zackai, Elaine H; McDonald-McGinn, Donna M; Linguraru, Marius George; Muenke, Maximilian

2017-04-01

22q11.2 deletion syndrome (22q11.2 DS) is the most common microdeletion syndrome and is underdiagnosed in diverse populations. This syndrome has a variable phenotype and affects multiple systems, making early recognition imperative. In this study, individuals from diverse populations with 22q11.2 DS were evaluated clinically and by facial analysis technology. Clinical information from 106 individuals and images from 101 were collected from individuals with 22q11.2 DS from 11 countries; average age was 11.7 and 47% were male. Individuals were grouped into categories of African descent (African), Asian, and Latin American. We found that the phenotype of 22q11.2 DS varied across population groups. Only two findings, congenital heart disease and learning problems, were found in greater than 50% of participants. When comparing the clinical features of 22q11.2 DS in each population, the proportion of individuals within each clinical category was statistically different except for learning problems and ear anomalies (P < 0.05). However, when Africans were removed from analysis, six additional clinical features were found to be independent of ethnicity (P ≥ 0.05). Using facial analysis technology, we compared 156 Caucasians, Africans, Asians, and Latin American individuals with 22q11.2 DS with 156 age and gender matched controls and found that sensitivity and specificity were greater than 96% for all populations. In summary, we present the varied findings from global populations with 22q11.2 DS and demonstrate how facial analysis technology can assist clinicians in making accurate 22q11.2 DS diagnoses. This work will assist in earlier detection and in increasing recognition of 22q11.2 DS throughout the world. © 2017 Wiley Periodicals, Inc.

Antioxidants and biomarkers of oxidative damage in the saliva of patients with Down's syndrome.

PubMed

de Sousa, Michelle Cardoso; Vieira, Rafael Brizola; Dos Santos, Danielle Sá; Carvalho, Claudio Antonio Talge; Camargo, Samira Esteves Afonso; Mancini, Maria Nadir Gasparoto; de Oliveira, Luciane Dias

2015-04-01

The aim of this study was to investigate enzymatic and non-enzymatic antioxidant systems and levels of biomarker levels of oxidative damage in the saliva of patients with Down's syndrome (DS). Saliva samples were collected from 30 patients with DS and control group (age: 14-24 years). Subsequently, the concentrations of superoxide dismutase, concentration of malondialdehyde, carbonylated proteins, uric acid, vitamin C and total protein, peroxidase activity and total antioxidant capacity were analyzed. Patients with DS presented significantly higher concentrations of superoxide dismutase, higher levels of malondialdehyde and salivary total protein content than controls (p<0.05). Conversely, no difference in carbonylated proteins or antioxidants (uric acid, vitamin C, peroxidase, and total antioxidant capacity) was observed between DS patients and controls (p>0.05). Patients with DS are more vulnerable to oxidative stress in saliva as indicated by the significant increase in malondialdehyde and superoxide dismutase concentrations found in this study. Copyright © 2014 Elsevier Ltd. All rights reserved.

ROSA: Distributed Joint Routing and Dynamic Spectrum Allocation in Cognitive Radio Ad Hoc Networks

DTIC Science & Technology

2010-03-01

Aug. 1999. [20] I. N. Psaromiligkos and S. N. Batalama. Rapid Combined Synchronization/Demodulation Structures for DS - CDMA Systems - Part II: Finite...Medley. Rapid Combined Synchronization/Demodulation Structures for DS - CDMA Systems - Part I: Algorithmic developments. IEEE Transactions on...multiple access ( CDMA ) [21][20] al- low concurrent co-located communications so that a message from node i to node j can be correctly received even if

Costs to Health Services and the Patient of Treating Tuberculosis: A Systematic Literature Review.

PubMed

Laurence, Yoko V; Griffiths, Ulla K; Vassall, Anna

2015-09-01

Novel tuberculosis (TB) drugs and the need to treat drug-resistant tuberculosis (DR-TB) are likely to bring about substantial transformations in TB treatment in coming years. An evidence base for cost and cost-effectiveness analyses of these developments is needed. Our objective was to perform a review of papers assessing provider-incurred as well as patient-incurred costs of treating both drug-susceptible (DS) and multidrug-resistant (MDR)-TB. Five databases (EMBASE, Medline, the National Health Service Economic Evaluation Database, the Cost-Effectiveness Analysis Registry, and Latin American and Caribbean Health Services Literature) were searched for cost and economic evaluation full-text papers containing primary DS-TB and MDR-TB treatment cost data published in peer-reviewed journals between January 1990 and February 2015. No language restrictions were set. The search terms were a combination of 'tuberculosis', 'multidrug-resistant tuberculosis', 'cost', and 'treatment'. In the selected papers, study methods and characteristics, quality indicators and costs were extracted into summary tables according to pre-defined criteria. Results were analysed according to country income groups and for provider costs, patient costs and productivity losses. All values were converted to $US, year 2014 values, so that studies could be compared. We selected 71 treatment cost papers on DS-TB only, ten papers on MDR-TB only and nine papers that included both DS-TB and MDR-TB. These papers provided evidence on the costs of treating DS-TB and MDR-TB in 50 and 16 countries, respectively. In 31 % of the papers, only provider costs were included; 26 % included only patient-incurred costs, and the remaining 43 % estimated costs incurred by both. From the provider perspective, mean DS-TB treatment costs per patient were US$14,659 in high-income countries (HICs), US$840 in upper middle-income countries (UMICs), US$273 in lower middle-income (LMICs), and US$258 in low-income countries (LICs), showing a strong positive correlation. The respective costs for treating MDR-TB were US$83,365, US$5284, US$6313 and US$1218. Costs incurred by patients when seeking treatment for DS-TB accounted for an additional 3 % of the provider costs in HICs. A greater burden was seen in the other income groups, increasing the costs of DS-TB treatment by 72 % in UMICs, 60 % in LICs and 31 % in LMICs. When provider costs, patient costs and productivity losses were combined, productivity losses accounted for 16 % in HICs, 29 % in UMICs, 40 % in LMICs and 38 % in LICs. Cost data for MDR-TB treatment are limited, and the variation in delivery mechanisms, as well as the rapidly evolving diagnosis and treatment regimens, means that it is essential to increase the number of studies assessing the cost from both provider and patient perspectives. There is substantial evidence available on the costs of DS-TB treatment from all regions of the world. The patient-incurred costs illustrate that the financial burden of illness is relatively greater for patients in poorer countries without universal healthcare coverage.

A performance analysis of DS-CDMA and SCPC VSAT networks

NASA Technical Reports Server (NTRS)

Hayes, David P.; Ha, Tri T.

1990-01-01

Spread-spectrum and single-channel-per-carrier (SCPC) transmission techniques work well in very small aperture terminal (VSAT) networks for multiple-access purposes while allowing the earth station antennas to remain small. Direct-sequence code-division multiple-access (DS-CDMA) is the simplest spread-spectrum technique to use in a VSAT network since a frequency synthesizer is not required for each terminal. An examination is made of the DS-CDMA and SCPC Ku-band VSAT satellite systems for low-density (64-kb/s or less) communications. A method for improving the standardf link analysis of DS-CDMA satellite-switched networks by including certain losses is developed. The performance of 50-channel full mesh and star network architectures is analyzed. The selection of operating conditions producing optimum performance is demonstrated.

Small Satellite Constellations for Geospace Sciences

NASA Astrophysics Data System (ADS)

Spence, H. E.

2016-12-01

The recent National Academy of Sciences Solar and Space Physics Decadal Survey (DS) identified community-consensus science priorities for the decade spanning 2013 - 2022. In this talk, we discuss the ways by which small satellite constellations are already and may soon accelerate progress toward achieving many of these science targets. The DS outlined four overarching science goals: (1) determine the origins of the Sun's activity and predict the variations in the space environment; (2) determine the dynamics and coupling of Earth's magnetosphere, ionosphere, and atmosphere and their response to solar and terrestrial inputs; (3) determine the interaction of the Sun with the solar system and the interstellar medium; and, (4) discover and characterize fundamental processes that occur both within the heliosphere and throughout the universe. These DS science goals provide the context for key science challenges in the three connected parts of the system that encompass all of solar and space physics, herein referred to as geospace: the Sun and heliosphere; the coupled solar wind-magnetosphere system; and, the coupled atmosphere-ionosphere-magnetosphere system. The DS further presented the role that small satellites play in resolving many of these science challenges, with a particular emphasis on the role that constellations of small satellites will play. While once considered by many as being "futuristic" or even "unrealizable", constellations of small satellites are already making important contributions to geospace science and with the promise for more to come. Using the DS as a guidepost, in this presentation, we outline representative small satellite constellation missions alread underway, some in development, and others notionally proposed over the next several years that employ small satellite constellations to tackle large science imperatives. Finally, we give examples of key small satellite technologies in development that will potentially enable great scientific return with comparatively low investments in small satellite missions.

Probing Phosphorus Efficient Low Phytic Acid Content Soybean Genotypes with Phosphorus Starvation in Hydroponics Growth System.

PubMed

Kumar, Varun; Singh, Tiratha Raj; Hada, Alkesh; Jolly, Monica; Ganapathi, Andy; Sachdev, Archana

2015-10-01

Phosphorus is an essential nutrient required for soybean growth but is bound in phytic acid which causes negative effects on both the environment as well as the animal nutrition. Lowering of phytic acid levels is associated with reduced agronomic characteristics, and relatively little information is available on the response of soybean plants to phosphorus (P) starvation. In this study, we evaluated the effects of different P starvation concentrations on the phytic acid content, growth, and yield of seven mutant genotypes along with the unirradiated control, JS-335, in a hydroponics growth system. The low phytic acid containing mutant genotypes, IR-JS-101, IR-DS-118, and IR-V-101, showed a relatively high growth rate in low P concentration containing nutrient solution (2 μM), whereas the high P concentration (50 μM) favored the growth of IR-DS-111 and IR-DS-115 mutant genotypes containing moderate phytate levels. The mutant genotypes with high phytic acid content, IR-DS-122, IR-DS-114, and JS-335, responded well under P starvation and did not have any significant effect on the growth and yield of plants. Moreover, the reduction of P concentration in nutrient solution from 50 to 2 μM also reduced the phytic acid content in the seeds of all the soybean genotypes under study. The desirable agronomic performance of low phytic acid containing mutant genotype IR-DS-118 reported in this study suggested it to be a P-efficient genotype which could be considered for agricultural practices under P limiting soils.

Contribution of dietary starch to hepatic and systemic carbohydrate fluxes in European seabass (Dicentrarchus labrax L.).

PubMed

Viegas, Ivan; Rito, João; Jarak, Ivana; Leston, Sara; Caballero-Solares, Albert; Metón, Isidoro; Pardal, Miguel A; Baanante, Isabel V; Jones, John G

2015-05-14

In the present study, the effects of partial substitution of dietary protein by digestible starch on endogenous glucose production were evaluated in European seabass (Dicentrarchus labrax). The fractional contribution of dietary carbohydrates v. gluconeogenesis to blood glucose appearance and hepatic glycogen synthesis was quantified in two groups of seabass fed with a diet containing 30% digestible starch (DS) or without a carbohydrate supplement as the control (CTRL). Measurements were performed by transferring the fish to a tank containing water enriched with 5% (2)H2O over the last six feeding days, and quantifying the incorporation of (2)H into blood glucose and hepatic glycogen by (2)H NMR. For CTRL fish, gluconeogenesis accounted for the majority of circulating glucose while for the DS fish, this contribution was significantly lower (CTRL 85 (SEM 4) % v. DS 54 (SEM 2) %; P < 0.001). Hepatic glycogen synthesis via gluconeogenesis (indirect pathway) was also significantly reduced in the DS fish, in both relative (CTRL 100 (SEM 1) % v. DS 72 (SEM 1) %; P < 0.001) and absolute terms (CTRL 28 (SEM 1) v. DS 17 (sem 1) μmol/kg per h; P < 0.001). A major fraction of the dietary carbohydrates that contributed to blood glucose appearance (33 (sem 1) % of the total 47 (SEM 2) %) had undergone exchange with hepatic glucose 6-phosphate. This indicated the simultaneous activity of hepatic glucokinase and glucose 6-phosphatase. In conclusion, supplementation of digestible starch resulted in a significant reduction of gluconeogenic contributions to systemic glucose appearance and hepatic glycogen synthesis.

Revolution rather than rotation of AAA+ hexameric phi29 nanomotor for viral dsDNA packaging without coiling☆

PubMed Central

Schwartz, Chad; De Donatis, Gian Marco; Zhang, Hui; Fang, Huaming; Guo, Peixuan

2013-01-01

It has long been believed that the DNA-packaging motor of dsDNA viruses utilizes a rotation mechanism. Here we report a revolution rather than rotation mechanism for the bacteriophage phi29 DNA packaging motor. The phi29 motor contains six copies of the ATPase (Schwartz et al., this issue); ATP binding to one ATPase subunit stimulates the ATPase to adopt a conformation with a high affinity for dsDNA. ATP hydrolysis induces a new conformation with a lower affinity, thus transferring the dsDNA to an adjacent subunit by a power stroke. DNA revolves unidirectionally along the hexameric channel wall of the ATPase, but neither the dsDNA nor the ATPase itself rotates along its own axis. One ATP is hydrolyzed in each transitional step, and six ATPs are consumed for one helical turn of 360°. Transition of the same dsDNA chain along the channel wall, but at a location 60° different from the last contact, urges dsDNA to move forward 1.75 base pairs each step (10.5 bp per turn/6ATP=1.75 bp per ATP). Each connector subunit tilts with a left-handed orientation at a 30° angle in relation to its vertical axis that runs anti-parallel to the right-handed dsDNA helix, facilitating the one-way traffic of dsDNA. The connector channel has been shown to cause four steps of transition due to four positively charged lysine rings that make direct contact with the negatively charged DNA phosphate backbone. Translocation of dsDNA into the procapsid by revolution avoids the difficulties during rotation that are associated with DNA supercoiling. Since the revolution mechanism can apply to any stoichiometry, this motor mechanism might reconcile the stoichiometry discrepancy in many phage systems where the ATPase has been found as a tetramer, hexamer, or nonamer. PMID:23763768

Modulation of Human Leukocyte Antigen-C by Human Cytomegalovirus Stimulates KIR2DS1 Recognition by Natural Killer Cells

PubMed Central

van der Ploeg, Kattria; Chang, Chiwen; Ivarsson, Martin A.; Moffett, Ashley; Wills, Mark R.; Trowsdale, John

2017-01-01

The interaction of inhibitory killer cell Ig-like receptors (KIRs) with human leukocyte antigen (HLA) class I molecules has been characterized in detail. By contrast, activating members of the KIR family, although closely related to inhibitory KIRs, appear to interact weakly, if at all, with HLA class I. KIR2DS1 is the best studied activating KIR and it interacts with C2 group HLA-C (C2-HLA-C) in some assays, but not as strongly as KIR2DL1. We used a mouse 2B4 cell reporter system, which carries NFAT-green fluorescent protein with KIR2DS1 and a modified DAP12 adaptor protein. KIR2DS1 reporter cells were not activated upon coculture with 721.221 cells transfected with different HLA-C molecules, or with interferon-γ stimulated primary dermal fibroblasts. However, KIR2DS1 reporter cells and KIR2DS1+ primary natural killer (NK) cells were activated by C2-HLA-C homozygous human fetal foreskin fibroblasts (HFFFs) but only after infection with specific clones of a clinical strain of human cytomegalovirus (HCMV). Active viral gene expression was required for activation of both cell types. Primary NKG2A−KIR2DS1+ NK cell subsets degranulated after coculture with HCMV-infected HFFFs. The W6/32 antibody to HLA class I blocked the KIR2DS1 reporter cell interaction with its ligand on HCMV-infected HFFFs but did not block interaction with KIR2DL1. This implies a differential recognition of HLA-C by KIR2DL1 and KIR2DS1. The data suggest that modulation of HLA-C by HCMV is required for a potent KIR2DS1-mediated NK cell activation. PMID:28424684

Dietary salt restriction improves cardiac and adipose tissue pathology independently of obesity in a rat model of metabolic syndrome.

PubMed

Hattori, Takuya; Murase, Tamayo; Takatsu, Miwa; Nagasawa, Kai; Matsuura, Natsumi; Watanabe, Shogo; Murohara, Toyoaki; Nagata, Kohzo

2014-12-02

Metabolic syndrome (MetS) enhances salt sensitivity of blood pressure and is an important risk factor for cardiovascular disease. The effects of dietary salt restriction on cardiac pathology associated with metabolic syndrome remain unclear. We investigated whether dietary salt restriction might ameliorate cardiac injury in DahlS.Z-Lepr(fa)/Lepr(fa) (DS/obese) rats, which are derived from a cross between Dahl salt-sensitive and Zucker rats and represent a model of metabolic syndrome. DS/obese rats were fed a normal-salt (0.36% NaCl in chow) or low-salt (0.0466% NaCl in chow) diet from 9 weeks of age and were compared with similarly treated homozygous lean littermates (DahlS.Z-Lepr(+)/Lepr(+), or DS/lean rats). DS/obese rats fed the normal-salt diet progressively developed hypertension and showed left ventricular hypertrophy, fibrosis, and diastolic dysfunction at 15 weeks. Dietary salt restriction attenuated all of these changes in DS/obese rats. The levels of cardiac oxidative stress and inflammation and the expression of cardiac renin-angiotensin-aldosterone system genes were increased in DS/obese rats fed the normal-salt diet, and dietary salt restriction downregulated these parameters in both DS/obese and DS/lean rats. In addition, dietary salt restriction attenuated the increase in visceral adipose tissue inflammation and the decrease in insulin signaling apparent in DS/obese rats without reducing body weight or visceral adipocyte size. Dietary salt restriction did not alter fasting serum glucose levels but it markedly decreased the fasting serum insulin concentration in DS/obese rats. Dietary salt restriction not only prevents hypertension and cardiac injury but also ameliorates insulin resistance, without reducing obesity, in this model of metabolic syndrome. © 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Trying to see, failing to focus: near visual impairment in Down syndrome

PubMed Central

Doyle, Lesley; Saunders, Kathryn J.; Little, Julie-Anne

2016-01-01

The majority of individuals with Down syndrome (DS) do not exhibit accurate accommodation, with the aetiology of this deficit unknown. This study examines the mechanism underlying hypoaccommodation in DS by simultaneously investigating the ‘near triad’ – accommodation, vergence and pupillary response. An objective photorefraction system measured accommodation, pupil size and gaze position (vergence) under binocular conditions while participants viewed an animated movie at 50, 33, 25 and 20 cm. Participants were aged 6–16 years (DS = 41, controls = 76). Measures were obtained from 59% of participants with DS and 99% of controls. Accommodative response was significantly less in DS (p < 0.001) and greater accommodative deficits were associated with worsening visual acuity (p = 0.02). Vergence responses were as accurate in DS as in controls (p = 0.90). Habitual pupil diameter did not differ between groups (p = 0.24) but reduced significantly with increasing accommodative demand in both participants with and without DS (p < 0.0001). This study is the first to report simultaneous binocular measurement of the near triad in DS demonstrating that hypoaccommodation is linked to poor visual acuity. Vergence responses were accurate indicating that hypoaccommodation cannot be dismissed as a failure to visually engage with near targets, but rather is a consequence of underlying neurological or physiological deficits. PMID:26847360

Intracellular generation of single-strand template increases the knock-in efficiency by combining CRISPR/Cas9 with AAV.

PubMed

Xiao, Qing; Min, Taishan; Ma, Shuangping; Hu, Lingna; Chen, Hongyan; Lu, Daru

2018-04-18

Targeted integration of transgenes facilitates functional genomic research and holds prospect for gene therapy. The established microhomology-mediated end-joining (MMEJ)-based strategy leads to the precise gene knock-in with easily constructed donor, yet the limited efficiency remains to be further improved. Here, we show that single-strand DNA (ssDNA) donor contributes to efficient increase of knock-in efficiency and establishes a method to achieve the intracellular linearization of long ssDNA donor. We identified that the CRISPR/Cas9 system is responsible for breaking double-strand DNA (dsDNA) of palindromic structure in inverted terminal repeats (ITRs) region of recombinant adeno-associated virus (AAV), leading to the inhibition of viral second-strand DNA synthesis. Combing Cas9 plasmids targeting genome and ITR with AAV donor delivery, the precise knock-in of gene cassette was achieved, with 13-14% of the donor insertion events being mediated by MMEJ in HEK 293T cells. This study describes a novel method to integrate large single-strand transgene cassettes into the genomes, increasing knock-in efficiency by 13.6-19.5-fold relative to conventional AAV-mediated method. It also provides a comprehensive solution to the challenges of complicated production and difficult delivery with large exogenous fragments.

Next generation communications satellites: Multiple access and network studies

NASA Technical Reports Server (NTRS)

Stern, T. E.; Schwartz, M.; Meadows, H. E.; Ahmadi, H. K.; Gadre, J. G.; Gopal, I. S.; Matsmo, K.

1980-01-01

Following an overview of issues involved in the choice of promising system architectures for efficient communication with multiple small inexpensive Earth stations serving hetergeneous user populations, performance evaluation via analysis and simulation for six SS/TDMA (satellite-switched/time-division multiple access) system architectures is discussed. These configurations are chosen to exemplify the essential alternatives available in system design. Although the performance evaluation analyses are of fairly general applicability, whenever possible they are considered in the context of NASA's 30/20 GHz studies. Packet switched systems are considered, with the assumption that only a part of transponder capacit is devoted to packets, the integration of circuit and packet switched traffic being reserved for further study. Three types of station access are distinguished: fixed (FA), demand (DA), and random access (RA). Similarly, switching in the satellite can be assigned on a fixed (FS) or demand (DS) basis, or replaced by a buffered store-and-forward system (SF) onboard the satellite. Since not all access/switching combinations are practical, six systems are analyzed in detail: three FS SYSTEMS, FA/FS, DA/ES, RA/FS; one DS system, DA/DS; and two SF systems, FA/SF, DA/SF. Results are presented primarily in terms of delay-throughput characteristics.

Linguistic profile of individuals with Down syndrome: comparing the linguistic performance of three developmental disorders.

PubMed

Ypsilanti, A; Grouios, G

2008-03-01

An increasing number of studies, addressing the linguistic abilities of individuals with Down syndrome (DS) suggest that they exhibit strengths and weaknesses within the linguistic domain. This article critically reviews the literature on the linguistic profile of individuals with DS, with particular emphasis on the expression and reception of vocabulary and grammar, including nonverbal linguistic expression during infant development. In doing so, attention is given to recent comparative studies of the linguistic abilities of individuals with DS, Specific Language Impairment (SLI), and Williams syndrome (WS). The possibility that deficits in one cognitive system may have consequences in another cognitive system, and that these consequences may define the nature of the impairment in each clinical syndrome is further discussed with suggestions for future research.

22 CFR 62.71 - Control and production of the electronic Form DS-2019.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Control and production of the electronic Form DS-2019. 62.71 Section 62.71 Foreign Relations DEPARTMENT OF STATE PUBLIC DIPLOMACY AND EXCHANGES EXCHANGE VISITOR PROGRAM Student and Exchange Visitor Information System (SEVIS) § 62.71 Control and...

Cellulose esters synthesized using a tetrabutylammonium acetate and dimethylsulfoxide solvent system

NASA Astrophysics Data System (ADS)

Yu, Yongqi; Miao, Jiaojiao; Jiang, Zeming; Sun, Haibo; Zhang, Liping

2016-07-01

Cellulose acetate (CA) and cellulose acetate propionate (CAP) were homogeneously synthesized in a novel tetrabutylammonium acetate/dimethyl sulfoxide (DMSO) solvent system, without any catalyst, at temperatures below 70 °C. The molecular structures of the cellulose esters (CEs) and distributions of the substituents in the anhydroglucose repeating units were determined using 13C cross-polarization magic angle spinning nuclear magnetic resonance spectroscopy, and the degree of substitution (DS) values were determined using 1H nuclear magnetic resonance spectroscopy. The structures of the CEs, regenerated cellulose (RC), and pulp were determined using Fourier transform infrared spectroscopy. The thermal properties of the products were determined using thermogravimetric analysis. The temperatures of initial decomposition of the CEs were up to 40 °C higher than those of the RC and pulp. All the CEs were highly soluble in DMSO, but were insoluble in acetone. CAs with DS values less than 2.6 swelled or were poorly dissolved in CHCl3, but those with DS values above 2.9 dissolved rapidly. CAPs with DS values above 2.6 had good solubilities in ethyl acetate.

AB119. Computer-aided facial recognition of Chinese individuals with 22q11.2 deletion-algorithm training using NIH atlas of human malformation syndromes from diverse population

PubMed Central

Mok, Gary Tsz Kin; Chung, Brian Hon-Yin

2017-01-01

Background 22q11.2 deletion syndrome (22q11.2DS) is a common genetic disorder with an estimated frequency of 1/4,000. It is a multi-systemic disorder with high phenotypic variability. Our previous work showed substantial under-diagnosis of 22q11.2DS as 1 in 10 adult patients with conotruncal defects were found to have 22q11.2DS. The National Institute of Health (NIH) has created an atlas of human malformation syndrome from diverse populations to provide an easy tool to assist clinician in diagnosing the syndromic across various populations. In this study, we seek to determine whether training the computer-aided facial recognition technology using images from ethnicity-matched patients from the NIH Atlas can improve the detection performance of this technology. Methods Clinical photographs of 16 Chinese subjects with molecularly confirmed 22q11.2DS, from the NIH atlas and its related publication were used for training the facial recognition technology. The system automatically localizes hundreds of facial fiducial points and takes measurements. The final classification is based on these measurements, as well as an estimated probability of subjects having 22q11.2DS based on the entire facial image. Clinical photographs of 7 patients with molecularly confirmed 22q11.2DS were obtained with informed consent and used for testing the performance in recognizing facial profiles of the Chinese subjects before and after training. Results All 7 test cases were improved in ranking and scoring after the software training. In 4 cases, 22q11.2DS did not appear as one possible syndrome match before the training; however, it appeared within the first 10 syndrome matches after training. Conclusions The present pilot data shows that this technology can be trained to recognize patients with 22q11.2DS. It also highlights the need to collect clinical photographs of patients from diverse populations to be used as resources for training the software which can lead to improvement of the performance of computer-aided facial recognition technology.

Performance Analysis of Iterative Channel Estimation and Multiuser Detection in Multipath DS-CDMA Channels

NASA Astrophysics Data System (ADS)

Li, Husheng; Betz, Sharon M.; Poor, H. Vincent

2007-05-01

This paper examines the performance of decision feedback based iterative channel estimation and multiuser detection in channel coded aperiodic DS-CDMA systems operating over multipath fading channels. First, explicit expressions describing the performance of channel estimation and parallel interference cancellation based multiuser detection are developed. These results are then combined to characterize the evolution of the performance of a system that iterates among channel estimation, multiuser detection and channel decoding. Sufficient conditions for convergence of this system to a unique fixed point are developed.

Manufacturing cost/design system: A CAD/CAM dialogue

NASA Technical Reports Server (NTRS)

Loshigian, H. H.; Rachowitz, B. I.; Judson, D.

1980-01-01

The development of the Manufacturing Cost/Design System (MC/DS) will provide the aerospace design engineer a tool with which to perform heretofore impractical design manufacturing cost tradeoffs. The Air Force Integrated Computer Aided Manufacturing (ICAM) Office has initiated the development and demonstration of an MC/DS which, when fully implemented, will integrate both design and manufacturing data bases to provide real time visibility into the manufacturing costs associated with various design options. The first release of a computerized system will be made before the end of 1981.

Use of a novel drainage flow servo-controlled CPB for mitral valve replacement in a Jehovah's Witness.

PubMed

Niimi, Yoshinari; Murata, Seiichiro; Mitou, Yumi; Ohno, Yusuke

2018-03-01

We developed a novel open cardiopulmonary bypass (CPB) system, a drainage flow servo-controlled CPB system (DS-CPB), in which rotational speed of the main roller pump is servo-controlled to generate the same amount of flow as the systemic venous drainage. It was designed to safely decrease the priming volume while maintaining a constant reservoir level, even during fluctuations of the drainage flow. We report a successful use of a novel DS-CPB system in an elderly Jehovah's Witness patient with dehydration who underwent mitral valve replacement.

Crescent pyramid and drop-set systems do not promote greater strength gains, muscle hypertrophy, and changes on muscle architecture compared with traditional resistance training in well-trained men.

PubMed

Angleri, Vitor; Ugrinowitsch, Carlos; Libardi, Cleiton Augusto

2017-02-01

The aim of this study was to compare the effects of crescent pyramid (CP) and drop-set (DS) systems with traditional resistance training (TRAD) with equalized total training volume (TTV) on maximum dynamic strength (1-RM), muscle cross-sectional area (CSA), pennation angle (PA), and fascicle length (FL). Thirty-two volunteers had their legs randomized in a within-subject design in TRAD (3-5 sets of 6-12 repetitions at 75% 1-RM), CP (3-5 sets of 6-15 repetitions at 65-85% 1-RM), and DS (3-5 sets of ~50-75% 1-RM to muscle failure) protocols. Each leg was trained for 12 weeks. Participants had one leg fixed in the TRAD while the contralateral leg performed either CP or DS to allow for TTV equalization. The CSA increased significantly and similarly for all protocols (TRAD: 7.6%; CP: 7.5%; DS: 7.8%). All protocols showed significant and similar increases in leg press (TRAD = 25.9%; CP = 25.9%; DS = 24.9%) and leg extension 1-RM loads (TRAD = 16.6%; CP = 16.4%; DS = 17.1%). All protocols increased PA (TRAD = 10.6%; CP = 11.0%; DS = 10.3%) and FL (TRAD = 8.9%; CP = 8.9%; DS = 9.1%) similarly. CP and DS systems do not promote greater gains in strength, muscle hypertrophy and changes in muscle architecture compared to traditional resistance training.

[Results of the epidemiological surveillance of diabetes mellitus in hospitals in Peru, 2012].

PubMed

Ramos, Willy; López, Tania; Revilla, Luis; More, Luis; Huamaní, María; Pozo, Milagros

2014-01-01

To describe the findings of a year of epidemiological surveillance in pilot hospitals in Peru belonging to the diabetes surveillance (DS) system. Cross-sectional study involving diabetic patients in the DS system from 18 hospitals during 2012. The DS database was assessed and epidemiological and laboratory variables were obtained including age, sex, type of diabetes, complications, comorbidity, microalbuminuria, fasting blood glucose and glycosylated hemoglobin (HbA1c) at two time points - at the time of enrollment and the last followup. 2,959 cases were found. At the time of enrollment into the DS system, 91.2% had a fasting blood glucose test of which 65.4% had a level 130 mg/dL. 8.9% had a microalbuminuria test of which 20.5% had microalbuminuria and 6.5% proteinuria. In total, 1025 patients had a follow-up visit; 93.1% had a fasting blood glucose test and 22.3% had HbA1c test. 63.5% had a fasting glycemia level 130 mg/dL and 73.4% HbA1c level 7.0%. The most common complication was neuropathy (21.4 %) and the most frequent comorbidity was high blood pressure (10.5%). Tuberculosis and cancer cases were observed; the most frequent cancer was breast cancer, particularly in postmenopausal women. The DS shows that among diabetics of the pilot hospitals, which have laboratory results, there is a high frequency of inadequate glycemic control and poor adherence to treatment. The high frequency of complications found highlights the need to strengthen early diagnosis.

Increasing the yield of middle silk gland expression system through transgenic knock-down of endogenous sericin-1.

PubMed

Ma, Sanyuan; Xia, Xiaojuan; Li, Yufeng; Sun, Le; Liu, Yue; Liu, Yuanyuan; Wang, Xiaogang; Shi, Run; Chang, Jiasong; Zhao, Ping; Xia, Qingyou

2017-08-01

Various genetically modified bioreactor systems have been developed to meet the increasing demands of recombinant proteins. Silk gland of Bombyx mori holds great potential to be a cost-effective bioreactor for commercial-scale production of recombinant proteins. However, the actual yields of proteins obtained from the current silk gland expression systems are too low for the proteins to be dissolved and purified in a large scale. Here, we proposed a strategy that reducing endogenous sericin proteins would increase the expression yield of foreign proteins. Using transgenic RNA interference, we successfully reduced the expression of BmSer1 to 50%. A total 26 transgenic lines expressing Discosoma sp. red fluorescent protein (DsRed) in the middle silk gland (MSG) under the control of BmSer1 promoter were established to analyze the expression of recombinant. qRT-PCR and western blotting showed that in BmSer1 knock-down lines, the expression of DsRed had significantly increased both at mRNA and protein levels. We did an additional analysis of DsRed/BmSer1 distribution in cocoon and effect of DsRed protein accumulation on the silk fiber formation process. This study describes not only a novel method to enhance recombinant protein expression in MSG bioreactor, but also a strategy to optimize other bioreactor systems.

Discoveries in Down syndrome: moving basic science to clinical care.

PubMed

Kleschevnikov, A M; Belichenko, P V; Salehi, A; Wu, C

2012-01-01

This review describes recent discoveries in neurobiology of Down syndrome (DS) achieved with use of mouse genetic models and provides an overview of experimental approaches aimed at development of pharmacological restoration of cognitive function in people with this developmental disorder. Changes in structure and function of synaptic connections within the hippocampal formation of DS model mice, as well as alterations in innervations of the hippocampus by noradrenergic and cholinergic neuromodulatory systems, provided important clues for potential pharmacological treatments of cognitive disabilities in DS. Possible molecular and cellular mechanisms underlying this genetic disorder have been addressed. We discuss novel mechanisms engaging misprocessing of amyloid precursor protein (App) and other proteins, through their affect on axonal transport and endosomal dysfunction, to "Alzheimer-type" neurodegenerative processes that affect cognition later in life. In conclusion, a number of therapeutic strategies have been defined that may restore cognitive function in mouse models of DS. In the juvenile and young animals, these strategists focus on restoration of synaptic plasticity, rate of adult neurogenesis, and functions of the neuromodulatory subcortical systems. Later in life, the major focus is on recuperation of misprocessed App and related proteins. It is hoped that the identification of an increasing number of potential targets for pharmacotherapy of cognitive deficits in DS will add to the momentum for creating and completing clinical trials. Copyright © 2012 Elsevier B.V. All rights reserved.

OLED study for military applications

NASA Astrophysics Data System (ADS)

Barre, F.; Chiquard, A.; Faure, S.; Landais, L.; Patry, P.

2005-07-01

The presentation deals with some applications of OLED displays in military optronic systems, which are scheduled by SAGEM DS (Defence and Security). SAGEM DS, one of the largest group in the defence and security market, is currently investigating OLED Technologies for military programs. This technology is close from being chosen for optronic equipment such as future infantry night vision goggles, rifle-sight, or, more generally, vision enhancement systems. Most of those applications requires micro-display with an active matrix size below 1". Some others, such as, for instance, ruggedized flat displays do have a need for higher active matrix size (1,5" to 15"). SAGEM DS takes advantages of this flat, high luminance and emissive technology in highly integrated systems. In any case, many requirements have to be fulfilled: ultra-low power consumption, wide viewing angle, good pixel to pixel uniformity, and satisfactory behaviour in extreme environmental conditions.... Accurate measurements have been achieved at SAGEM DS on some micro display OLEDs and will be detailed: luminance (over 2000 cd/m2 achieved), area uniformity and pixel to pixel uniformity, robustness at low and high temperature (-40°C to +60°C), lifetime. These results, which refer to military requirements, provide a valuable feedback representative of the state of the art OLED performances.

Genetic Transformation of Hordeum vulgare ssp. spontaneum for the Development of a Transposon-Based Insertional Mutagenesis System.

PubMed

Cardinal, Marie-Josée; Kaur, Rajvinder; Singh, Jaswinder

2016-10-01

Domestication and intensive selective breeding of plants has triggered erosion of genetic diversity of important stress-related alleles. Researchers highlight the potential of using wild accessions as a gene source for improvement of cereals such as barley, which has major economic and social importance worldwide. Previously, we have successfully introduced the maize Ac/Ds transposon system for gene identification in cultivated barley. The objective of current research was to investigate the response of Hordeum vulgare ssp. spontaneum wild barley accessions in tissue culture to standardize parameters for introduction of Ac/Ds transposons through genetic transformation. We investigated the response of ten wild barley genotypes for callus induction, regenerative green callus induction and regeneration of fertile plants. The activity of exogenous Ac/Ds elements was observed through a transient assay on immature wild barley embryos/callus whereby transformed embryos/calli were identified by the expression of GUS. Transient Ds expression bombardment experiments were performed on 352 pieces of callus (3-5 mm each) or immature embryos in 4 genotypes of wild barley. The transformation frequency of putative transgenic callus lines based on transient GUS expression ranged between 72 and100 % in wild barley genotypes. This is the first report of a transformation system in H. vulgare ssp. spontaneum.

Molecular dynamics simulations of diffusion and clustering along critical isotherms of medium-chain n-alkanes.

PubMed

Mutoru, J W; Smith, W; O'Hern, C S; Firoozabadi, A

2013-01-14

Understanding the transport properties of molecular fluids in the critical region is important for a number of industrial and natural systems. In the literature, there are conflicting reports on the behavior of the self diffusion coefficient D(s) in the critical region of single-component molecular systems. For example, D(s) could decrease to zero, reach a maximum, or remain unchanged and finite at the critical point. Moreover, there is no molecular-scale understanding of the behavior of diffusion coefficients in molecular fluids in the critical regime. We perform extensive molecular dynamics simulations in the critical region of single-component fluids composed of medium-chain n-alkanes-n-pentane, n-decane, and n-dodecane-that interact via anisotropic united-atom potentials. For each system, we calculate D(s), and average molecular cluster sizes κ(cl) and numbers N(cl) at various cluster lifetimes τ, as a function of density ρ in the range 0.2ρ(c) ≤ ρ ≤ 2.0ρ(c) at the critical temperature T(c). We find that D(s) decreases with increasing ρ but remains finite at the critical point. Moreover, for any given τ < 1.2 × 10(-12) s, κ(cl) increases with increasing ρ but is also finite at the critical point.

Evaluation of a new automated enzyme fluoroimmunoassay using recombinant plasmid dsDNA for the detection of anti-dsDNA antibodies in SLE.

PubMed

Villalta, D; Bizzaro, N; Corazza, D; Tozzoli, R; Tonutti, E

2002-01-01

ELISA methods to detect anti-double-stranded DNA (anti-dsDNA) antibodies are highly sensitive, but are less specific for the diagnosis of SLE than the immunofluorescence test on Crithidia luciliae (CLIFT) and the Farr assay because they also detect low-avidity antibodies. This study evaluated the specificity, sensitivity, positive predictive value (PPV), and negative predictive value (NPV) of a new automated fluoroimmunoassay (EliA dsDNA; Pharmacia, Freiburg, Germany). We compared the results with those obtained using a commercial CLIFT and an in-house anti-dsDNA IgG ELISA method, and verified its putative ability to detect only high-avidity anti-dsDNA antibodies. Sera from 100 SLE patients and 120 controls were studied. The control group included 20 healthy donors, 70 patients with other rheumatic diseases (32 systemic sclerosis (SSc); 18 primary Sjögren syndrome (pSS), 20 rheumatoid arthritis (RA)), and 30 patients with various infectious diseases (ID). Anti-dsDNA avidity was estimated using an ELISA method based upon the law of mass action, and a simplified Scatchard plot analysis for data elaboration; the apparent affinity constant (Kaa) was calculated and expressed as arbitrary units (L/U). Sensitivity, specificity, PPV, and NPV for SLE were 64%, 95.8%, 93.8% and 72.7%, respectively, for the EliA anti-dsDNA assay; 55%, 99.2%, 98.5%, and 68.8%, respectively, for the CLIFT; and 64%, 93.3%, 90.6%, and 72.3%, respectively, for the in-house ELISA. Although EliA anti-dsDNA was positive mainly in SLE patients with high- (Kaa>80 L/U) and intermediate- (Kaa 30-80 L/U) avidity antibodies (45.3% and 49.9%, respectively), it was also positive in five (7.8%) SLE patients with low-avidity anti-dsDNA antibodies, and five controls (three SSc, one pSS, and one ID) (mean Kaa = 16.4 +/- 9.04 L/U). In conclusion, EliA anti-dsDNA assay showed a higher sensitivity than the CLIFT, and a good specificity and PPV for SLE. Its putative ability to detect only high-avidity anti-dsDNA antibodies remains questionable. Copyright 2002 Wiley-Liss, Inc.

Dandy-Walker Malformation and Down Syndrome Association: Good Developmental Outcome and Successful Endoscopic Treatment of Hydrocephalus

PubMed Central

Nigri, Flavio; Cabral, Isaias Fiuza; da Silva, Raquel Tavares Boy; Pereira, Heloisa Viscaíno; Ribeiro, Carlos Roberto Telles

2014-01-01

The association of Down syndrome (DS) with Dandy Walker malformation (DWM) is extremely rare, with only 3 cases reported to date. All cases reported have shown a bad life expectancy and a bad developmental outcome. The present case reveals the possibility of a good prognosis. A 19-month-old male patient had successful endoscopic hydrocephalus treatment and a good developmental outcome. He probably had a better outcome because of good DS and DWM prognostic parameters. Our patient suffered from a DWM with vermis identification of 2 fissures and 3 lobes and a DS with a well-preserved tonus, which was not associated with other congenital systemic defects. We may conclude that the prognosis of DS-DWM association may separately depend on the degree of clinical and neurological involvement of each malformation. PMID:24932176

Dandy-walker malformation and down syndrome association: good developmental outcome and successful endoscopic treatment of hydrocephalus.

PubMed

Nigri, Flavio; Cabral, Isaias Fiuza; da Silva, Raquel Tavares Boy; Pereira, Heloisa Viscaíno; Ribeiro, Carlos Roberto Telles

2014-05-01

The association of Down syndrome (DS) with Dandy Walker malformation (DWM) is extremely rare, with only 3 cases reported to date. All cases reported have shown a bad life expectancy and a bad developmental outcome. The present case reveals the possibility of a good prognosis. A 19-month-old male patient had successful endoscopic hydrocephalus treatment and a good developmental outcome. He probably had a better outcome because of good DS and DWM prognostic parameters. Our patient suffered from a DWM with vermis identification of 2 fissures and 3 lobes and a DS with a well-preserved tonus, which was not associated with other congenital systemic defects. We may conclude that the prognosis of DS-DWM association may separately depend on the degree of clinical and neurological involvement of each malformation.

Language Development in Down Syndrome: From the Prelinguistic Period to the Acquisition of Literacy

ERIC Educational Resources Information Center

Abbeduto, Leonard; Warren, Steven F.; Conners, Frances A.

2007-01-01

Down syndrome (DS) is associated with abnormalities in multiple organ systems and a characteristic phenotype that includes numerous behavioral features. Language, however, is among the most impaired domains of functioning in DS and, perhaps, also the greatest barrier to independent meaningful inclusion in the community. In this article, we review…

A Combined MIS/DS Course Uses Lecture Capture Technology to "Level the Playing Field" in Student Numeracy

ERIC Educational Resources Information Center

Popovich, Karen

2012-01-01

This paper describes the process taken to develop a quantitative-based and Excel™-driven course that combines "BOTH" Management Information Systems (MIS) and Decision Science (DS) modeling outcomes and lays the foundation for upper level quantitative courses such as operations management, finance and strategic management. In addition,…

Epidemiological characteristics of children born with Down syndrome in western Herzegovina in the period of the last twenty years (1994-2013).

PubMed

Sumanović-Glamuzina, Darinka; Zovko, Ana; Letica, Ivona; Jerković-Raguž, Marjana; Mustapić, Antonija; Božić, Tomica; Vukojević, Mladenka

2014-12-01

Children with Down syndrome (DS) are an everyday casuistry of pediatric clinical medicine. The prevalence of DS is dependent on socio-demographic and cultural conditions of a community. Antenatal screening is not carried out mainly due to religious views, and the prevalence of DS in our region is really considered a "natural phenomenon". The aim of the study was to analyze some epidemiological characteristics of infants with Down syndrome in the western region of Herzegovina in the period between year 1994-2013. We performed a retrospective analysis of hospital records of children who were supervised and treated at Children's Hospital through the twenty-year period. In this period there were 44,100 liveborn infants. Down syndrome was detected in 78 children (54 male and 24 female). The prevalence is estimated at 1.8/1,000 of live births. Aborted fetuses and stillbirths were not analyzed. 37 (47%) of the parent couples were over 35 years of age. Out of that 65 cytogenetic analysis, a regular type of trisomy 21 was found in 94% of cases, and the translocation in 6%. From major malformations (MM) heart failure was more often present (47%), then the anomaly of the gastrointestinal and genitourinary systems. Ten children (12%) died, most often in the early period of infancy due to complications of the cardiovascular system. The prevalence of DS throughout these two decades has been uniform in the region of western Herzegovina. Improvement in perinatal care in recent years caused higher survival and a better quality of life for the children with DS and thus their families. DS is less a desirable family tragedy, and increasingly a tolerable family fate.

Postural Stability in Young Adults with Down Syndrome in Challenging Conditions

PubMed Central

Bieć, Ewa; Zima, Joanna; Wójtowicz, Dorota; Wojciechowska-Maszkowska, Bożena; Kręcisz, Krzysztof; Kuczyński, Michał

2014-01-01

To evaluate postural control and performance in subjects with Down syndrome (SwDS), we measured postural sway (COP) in quiet stance in four 20-second tests: with eyes open or closed and on hard or foam surface. Ten SwDS and eleven healthy subjects participated, aged 29.8 (4.8) and 28.4 (3.9), respectively. The time-series recorded with the sampling rate of 100 Hz were used to evaluate postural performance (COP amplitude and mean velocity) and strategies (COP frequency, fractal dimension and entropy). There were no intergroup differences in the amplitude except the stance on foam pad with eyes open when SwDS had larger sway. The COP velocity and frequency were larger in SwDS than controls in all trials on foam pad. During stances on the foam pad SwDS increased fractal dimension showing higher complexity of their equilibrium system, while controls decreased sample entropy exhibiting more conscious control of posture in comparison to the stances on hard support surface. This indicated that each group used entirely different adjustments of postural strategies to the somatosensory challenge. It is proposed that the inferior postural control of SwDS results mainly from insufficient experience in dealing with unpredictable postural stimuli and deficit in motor learning. PMID:24728178

A framework to support decision making in the selection of sustainable drainage system design alternatives.

PubMed

Wang, Mingming; Sweetapple, Chris; Fu, Guangtao; Farmani, Raziyeh; Butler, David

2017-10-01

This paper presents a new framework for decision making in sustainable drainage system (SuDS) scheme design. It integrates resilience, hydraulic performance, pollution control, rainwater usage, energy analysis, greenhouse gas (GHG) emissions and costs, and has 12 indicators. The multi-criteria analysis methods of entropy weight and Technique for Order Preference by Similarity to Ideal Solution (TOPSIS) were selected to support SuDS scheme selection. The effectiveness of the framework is demonstrated with a SuDS case in China. Indicators used include flood volume, flood duration, a hydraulic performance indicator, cost and resilience. Resilience is an important design consideration, and it supports scheme selection in the case study. The proposed framework will help a decision maker to choose an appropriate design scheme for implementation without subjectivity. Copyright © 2017 Elsevier Ltd. All rights reserved.

Differences between clinical and laboratory findings in patients with recent diagnosis of SLE according to the positivity of anti-dsDNA by the Crithidia luciliae method.

PubMed

Sarbu, M I; Salman-Monte, T C; Rubio Muñoz, P; Lisbona, M P; Almirall Bernabé, M; Carbonell, J

2015-10-01

Of all anti-dsDNA antibody detection methods, the Crithidia luciliae immunofluorescence test (CLIF) is considered to have the highest specificity for systemic lupus erythematosus (SLE). The objective of this report is to evaluate whether the presence of anti-dsDNA antibodies detected by the CLIF method is associated with a specific clinical phenotype in recently diagnosed SLE. This retrospective cross-sectional study included all patients with newly diagnosed SLE between 1990 and 2011 and followed up in our institution. Demographic, clinical and laboratory findings were assessed. Correlations between positivity of anti-dsDNA by the CLIF method, clinical and laboratory data were analyzed. A total of 104 patients were included in the analysis. Patients who were positive for anti-dsDNA by the CLIF method at the time of diagnosis had (statistically) significantly higher titers of anti-dsDNA by the ELISA method, antinuclear (ANA) and anticardiolipin antibodies, lymphopenia and complement consumption compared with the other two groups. Also they presented significantly more musculoskeletal symptoms at baseline. The presence of anti-dsDNA by the CLIF method in newly diagnosed SLE was associated with certain markers of increased disease activity. Its use could be a useful biomarker for a specific clinical phenotype suggestive of a more severe involvement at the time of the diagnosis. © The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Poly(hydroxyethyl methacrylate) based affinity membranes for in vitro removal of anti-dsDNA antibodies from SLE plasma.

PubMed

Uzun, Lokman; Yavuz, Handan; Osman, Bilgen; Celik, Hamdi; Denizli, Adil

2010-07-01

The preparation of polymeric membrane using affinity technology for application in blood filtration devices is described here. DNA attached poly(hydroxyethyl methacrylate) (PHEMA) based microporous affinity membrane was prepared for selective removal of anti-dsDNA antibodies from systemic lupus erythematosus (SLE) patient plasma in in vitro. In order to further increase blood-compatibility of affinity membrane, aminoacid based comonomer N-methacryloyl-L-alanine (MAAL) was included in the polymerization recipe. PHEMAAL membrane was produced by a photopolymerization technique and then characterized by swelling tests and scanning electron microscope (SEM) studies. Blood-compatibility tests were also performed. The water swelling ratio of PHEMAAL membrane increased significantly (133.2%) compared with PHEMA (58%). PHEMAAL membrane has large pores around in the range of 5-10 microm. All the clotting times increased when compared with PHEMA membrane. Loss of platelets and leukocytes was very low. DNA loading was 7.8 mg/g. There was a very low anti-dsDNA-antibody adsorption onto the plain PHEMAAL membrane, about 78 IU/g. The PHEMAAL-DNA membrane adsorbed anti-dsDNA-antibody in the range of 10-68 x 10(3)IU/g from SLE plasma. Anti-dsDNA-antibody concentration decreased significantly from 875 to 144 IU/ml with the time. Anti-dsDNA-antibodies could be repeatedly adsorbed and eluted without noticeable loss in the anti-dsDNA-antibody adsorption amount. (c) 2010 Elsevier B.V. All rights reserved.

75 FR 77936 - 60-Day Notice of Proposed Information Collection: Forms DS-2053, DS-2054; Medical Examination for...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-14

... DS-2053, DS-2054; Medical Examination for Immigrant or Refugee Applicant; DS- 3024, DS-3030, Chest X... Instructions); Form DS- 3024, Chest X-Ray and Classification Worksheet (1991 Technical Instructions); Form DS-3030, Chest X-Ray and Classification Worksheet (2007 Technical Instructions); Form DS-3025, Vaccination...

Clumsiness in fine motor tasks: evidence from the quantitative drawing evaluation of children with Down Syndrome.

PubMed

Vimercati, S L; Galli, M; Stella, G; Caiazzo, G; Ancillao, A; Albertini, G

2015-03-01

Drawing tests are commonly used for the clinical evaluation of cognitive capabilities in children with learning disabilities. We analysed quantitatively the drawings of children with Down Syndrome (DS) and of healthy, mental age-matched controls to characterise the features of fine motor skills in DS during a drawing task, with particular attention to clumsiness, a well-known feature of DS gross movements. Twenty-three children with DS and 13 controls hand-copied the figures of a circle, a cross and a square on a sheet. An optoelectronic system allowed the acquisition of the three-dimensional track of the drawing. The participants' posture and upper limb movements were analysed as well. Results showed that the participants with DS tended to draw faster but with less accuracy than controls. While clumsiness in gross movements manifests mainly as slow, less efficient movements, it manifests as high velocity and inaccurate movements in fine motor tasks such as drawing. © 2014 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.

Differential representation of Pavlovian-instrumental transfer by prefrontal cortex subregions and striatum.

PubMed

Homayoun, Houman; Moghaddam, Bita

2009-04-01

Environmental cues that once predicted reward can restore extinguished behavior directed toward that reward. This process may be modeled by the Pavlovian-instrumental transfer (PIT) paradigm where a previously learned Pavlovian conditioned stimulus (CS) elicits a representation of the reward associated with that CS, prompts motivation toward the absent reward, and triggers an instrumental action. We recorded in the medial and orbital prefrontal cortex (mPFC and OFC) and dorsal striatum (DS) of freely moving rats during PIT and found that a Pavlovian CS, as compared with neutral or no stimuli, amplified the phasic neuronal responses to instrumental nosepokes ('transfer' event). In mPFC and OFC, but not the DS, representation of the transfer event correlated with the strength of PIT behavior. Neurons in all three regions showed CS-selective amplification of Pavlovian approaches toward the reward delivery site. Whereas striatal neurons represented transfer and approach behavior through mostly segregated neuronal subsets, overlapping subsets represented these events in the mPFC and OFC. These findings suggest that parallel phasic activation of mPFC and OFC neuronal subsets participates in the transfer from Pavlovian incentives to instrumental actions.

Therapy reduction in patients with Down syndrome and myeloid leukemia: the international ML-DS 2006 trial.

PubMed

Uffmann, Madita; Rasche, Mareike; Zimmermann, Martin; von Neuhoff, Christine; Creutzig, Ursula; Dworzak, Michael; Scheffers, Lenie; Hasle, Henrik; Zwaan, C Michel; Reinhardt, Dirk; Klusmann, Jan-Henning

2017-06-22

Children with myeloid leukemia associated with Down syndrome (ML-DS) have superior outcome compared with non-DS patients, but suffer from higher constitutional cytotoxic drug susceptibility. We analyzed the outcome of 170 pediatric patients with ML-DS enrolled in the prospective, multicenter, open-label, nonrandomized ML-DS 2006 trial by Nordic Society for Pediatric Hematology and Oncology (NOPHO), Dutch Childhood Oncology Group (DCOG), and Acute Myeloid Leukemia-Berlin-Frankfurt-Münster (AML-BFM) study group. Compared with the historical control arm (reduced-intensity protocol for ML-DS patients from the AML-BFM 98 trial), treatment intensity was reduced by lowering the cumulative dose of etoposide (950 to 450 mg/m 2 ) and intrathecal central nervous system prophylaxis while omitting maintenance therapy. Still, 5-year overall survival (89% ± 3% vs 90% ± 4%; P log-rank = .64), event-free survival (EFS; 87% ± 3% vs 89% ± 4%; P log-rank = .71), and cumulative incidence of relapse/nonresponse (CIR/NR; 6% ± 3% vs 6% ± 2%; P Gray = .03) did not significantly differ between the ML-DS 2006 trial and the historical control arm. Poor early treatment response (5-year EFS, 58% ± 16% vs 88% ± 3%; P log rank = .0008) and gain of chromosome 8 (CIR/NR, 16% ± 7% vs 3% ± 2%, P Gray = .02; 5-year EFS, 73% ± 8% vs 91% ± 4%, P log rank = .018) were identified as independent prognostic factors predicting a worse EFS. Five of 7 relapsed patients (71%) with cytogenetic data had trisomy 8. Our study reveals prognostic markers for children with ML-DS and illustrates that reducing therapy did not impair excellent outcome. The trial was registered at EudraCT as #2007-006219-2. © 2017 by The American Society of Hematology.

The dimensional structure of psychopathology in 22q11.2 Deletion Syndrome.

PubMed

Niarchou, Maria; Moore, Tyler M; Tang, Sunny X; Calkins, Monica E; McDonald-McGuinn, Donna M; Zackai, Elaine H; Emanuel, Beverly S; Gur, Ruben C; Gur, Raquel E

2017-09-01

22q11.2 Deletion Syndrome (22q11.2DS) is one of the strongest known genetic risk factors for developing schizophrenia. Individuals with 22q11.2DS have high rates of neurodevelopmental disorders in childhood, while in adulthood ∼25% develop schizophrenia. Similar to the general population, high rates of comorbidity are common in 22q11.2DS. Employing a dimensional approach where psychopathology is examined at the symptom-level as complementary to diagnostic categories in a population at such high genetic risk for schizophrenia can help gain a better understanding of how psychopathology is structured as well as its genetic underpinnings. This is the first study to examine the dimensional structure of a wide spectrum of psychopathology in the context of a homogeneous genetic etiology like 22q11.2DS. We evaluated 331 individuals with 22q11.2DS, mean age (SD) = 16.9(8.7); 51% males, who underwent prospective comprehensive phenotyping. We sought to replicate previous findings by examining a bi-factor model that derives a general factor of psychopathology in addition to more specific dimensions of psychopathology (i.e., internalizing, externalizing and thought disorder). Psychopathology in 22q11.2DS was divided into one 'general psychopathology' factor and four specific dimensions (i.e., 'anxiety', 'mood', 'ADHD' and 'psychosis'). The 'psychosis' symptoms loaded strongly on the 'general psychopathology' factor. The similarity of the symptom structure of psychopathology between 22q11.2DS and community and clinical populations without the deletion indicate that 22q11.2DS can provide a model to explore alternative approaches to our current nosology. Our findings add to a growing literature indicating the need to reorganize current diagnostic classification systems. Copyright © 2017 Elsevier Ltd. All rights reserved.

Suppressed Decays of Ds+ Mesons to Two Pseudoscalar Mesons

NASA Astrophysics Data System (ADS)

Adams, G. S.; Anderson, M.; Cummings, J. P.; Danko, I.; Hu, D.; Moziak, B.; Napolitano, J.; He, Q.; Insler, J.; Muramatsu, H.; Park, C. S.; Thorndike, E. H.; Yang, F.; Artuso, M.; Blusk, S.; Khalil, S.; Li, J.; Menaa, N.; Mountain, R.; Nisar, S.; Randrianarivony, K.; Sia, R.; Skwarnicki, T.; Stone, S.; Wang, J. C.; Bonvicini, G.; Cinabro, D.; Dubrovin, M.; Lincoln, A.; Asner, D. M.; Edwards, K. W.; Naik, P.; Briere, R. A.; Ferguson, T.; Tatishvili, G.; Vogel, H.; Watkins, M. E.; Rosner, J. L.; Adam, N. E.; Alexander, J. P.; Cassel, D. G.; Duboscq, J. E.; Ehrlich, R.; Fields, L.; Gibbons, L.; Gray, R.; Gray, S. W.; Hartill, D. L.; Heltsley, B. K.; Hertz, D.; Jones, C. D.; Kandaswamy, J.; Kreinick, D. L.; Kuznetsov, V. E.; Mahlke-Krüger, H.; Mohapatra, D.; Onyisi, P. U. E.; Patterson, J. R.; Peterson, D.; Riley, D.; Ryd, A.; Sadoff, A. J.; Shi, X.; Stroiney, S.; Sun, W. M.; Wilksen, T.; Athar, S. B.; Patel, R.; Yelton, J.; Rubin, P.; Eisenstein, B. I.; Karliner, I.; Lowrey, N.; Selen, M.; White, E. J.; Wiss, J.; Mitchell, R. E.; Shepherd, M. R.; Besson, D.; Pedlar, T. K.; Cronin-Hennessy, D.; Gao, K. Y.; Hietala, J.; Kubota, Y.; Klein, T.; Lang, B. W.; Poling, R.; Scott, A. W.; Zweber, P.; Dobbs, S.; Metreveli, Z.; Seth, K. K.; Tomaradze, A.; Ernst, J.; Ecklund, K. M.; Severini, H.; Love, W.; Savinov, V.; Lopez, A.; Mehrabyan, S.; Mendez, H.; Ramirez, J.; Ge, J. Y.; Miller, D. H.; Sanghi, B.; Shipsey, I. P. J.; Xin, B.

2007-11-01

Using data collected near the Ds*+Ds- peak production energy Ecm=4170MeV by the CLEO-c detector, we study the decays of Ds+ mesons to two pseudoscalar mesons. We report on searches for the singly Cabibbo-suppressed Ds+ decay modes K+η, K+η', π+KS0, K+π0, and the isospin-forbidden decay mode Ds+→π+π0. We normalize with respect to the Cabibbo-favored Ds+ modes π+η, π+η', and K+KS0, and obtain ratios of branching fractions: B(Ds+→K+η)/B(Ds+→π+η)=(8.9±1.5±0.4)%, B(Ds+→K+η')/B(Ds+→π+η')=(4.2±1.3±0.3)%, B(Ds+→π+KS0)/B(Ds+→K+KS0)=(8.2±0.9±0.2)%, B(Ds+→K+π0)/B(Ds+→K+KS0)=(5.5±1.3±0.7)%, and B(Ds+→π+π0)/B(Ds+→K+KS0)<4.1% at 90% C.L., where the uncertainties are statistical and systematic, respectively.

Autistic-spectrum disorders in Down syndrome: further delineation and distinction from other behavioral abnormalities.

PubMed

Carter, John C; Capone, George T; Gray, Robert M; Cox, Christiane S; Kaufmann, Walter E

2007-01-05

The present study extends our previous work characterizing the behavioral features of autistic-spectrum disorder (ASD) in Down syndrome (DS) using the Aberrant Behavior Checklist (ABC) and Autism Behavior Checklist (AutBehav). We examined which specific behaviors distinguished the behavioral phenotype of DS + ASD from other aberrant behavior disorders in DS, by determining the relative contribution of ABC and AutBehav subscales and items to the diagnosis of ASD. A total of 127 subjects (aged 2-24 years; mean age: 8.4 years; approximately 70% male), comprising: a cohort of 64 children and adolescents with DS and co-morbid ASD (DS + ASD), 19 with DS and stereotypic movement disorder (DS + SMD), 18 with DS and disruptive behaviors (DS + DB), and 26 with DS and no co-morbid behavior disorders (DS + none) were examined using the aforementioned measures of aberrant behavior. We found that subjects with DS + ASD showed the most severe aberrant behavior, especially stereotypy compared to DS + none and lethargy/social withdrawal and relating problems compared to DS + SMD. Specifically, relatively simple stereotypic behavior differentiated DS + ASD from DS + DB, whereas odd/bizarre stereotypic and anxious behavior characterized DS + ASD relative to DS + SMD and DS + none. Additionally, in a subset of subjects with DS + ASD and anxiety, social withdrawal was particularly pronounced. Overall, our findings indicate that a diagnosis of DS + ASD represents a distinctive set of aberrant behaviors marked by characteristic odd/bizarre stereotypic behavior, anxiety, and social withdrawal.

Meta-analysis of CHADS2 versus CHA2DS2-VASc for predicting stroke and thromboembolism in atrial fibrillation patients independent of anticoagulation.

PubMed

Zhu, Wen-Gen; Xiong, Qin-Mei; Hong, Kui

2015-02-01

Two validated scoring systems for predicting embolic risk, CHADS2 and CHA2DS2-VASc, contribute to optimizing antithrombotic prescription practices in patients who have atrial fibrillation. However, data about anticoagulated patients are sparse. We compared CHADS2 and CHA2DS2-VASc, in terms of their predictive risk evaluation, in patients with atrial fibrillation who were and were not taking anticoagulants. We systematically searched the Cochrane Library, PubMed, and Embase databases for studies of the comparative diagnostic performance of CHADS2 and CHA2DS2-VASc. We identified 12 cohort studies for meta-analysis. With regard to the occurrence of cardiovascular events individually, patients with CHA2DS2-VASc scores ≥2 have a greater risk of stroke (risk ratio [RR]=5.15; 95% confidence interval [CI], 3.85-6.88; P <0.00001) and thromboembolism (RR=5.96; 95% CI, 5.50-6.45; P <0.00001) (P diff=0.34) than do patients with CHA2DS2-VASc scores <2, independent of anticoagulation therapy (RR=5.76; 95% CI, 5.23-6.35; P <0.00001 in anticoagulated patients; and RR=6.12; 95% CI, 5.40-6.93; P <0.00001 in patients not taking anticoagulants; P diff=0.45). The pooled RR estimates indicate an approximate 6-fold increase in the risk of endpoint events in patients with CHA2DS2-VASc scores ≥2 (RR=5.90; 95% CI, 5.46-6.37; P <0.0001). These results clearly indicate the discriminative capacity of the CHA2DS2-VASc score for stroke, thromboembolic events, or both, independent of optimal anticoagulation. The CHA2DS2-VASc score enables the identification of patients who are at genuinely high risk and can direct the selection of appropriate therapeutic approaches.

Structure of RDE-4 dsRBDs and mutational studies provide insights into dsRNA recognition in the Caenorhabditis elegans RNAi pathway.

PubMed

Chiliveri, Sai Chaitanya; Deshmukh, Mandar V

2014-02-15

The association of RDE-4 (RNAi defective 4), a protein containing two dsRBDs (dsRNA-binding domains), with long dsRNA and Dcr-1 (Dicer1 homologue) initiates the siRNA pathway in Caenorhabditis elegans. Unlike its homologues in higher eukaryotes, RDE-4 dsRBDs possess weak (micromolar) affinity for short dsRNA. With increasing length of dsRNA, RDE-4 exhibits enhanced affinity due to co-operativity. The linker and dsRBD2 are indispensable for RDE-4's simultaneous interaction with dsRNA and Dcr-1. In the present study, we have determined the solution structures of RDE-4 constructs that contain both dsRBDs and the linker region. In addition to the canonical dsRBD fold, both dsRBDs of RDE-4 show modified structural features such as truncation in the β1-β2 loop that rationalize RDE-4's relatively weak dsRNA affinity. Structure and binding studies demonstrate that dsRBD2 plays a decisive role in the RDE-4-dsRNA interaction; however, in contrast with previous findings, we found ephemeral interaction of RDE-4 dsRBD1 with dsRNA. More importantly, mutations in two tandem lysine residues (Lys217 and Lys218) in dsRBD2 impair RDE-4's dsRNA-binding ability and could obliterate RNAi initiation in C. elegans. Additionally, we postulate a structural basis for the minimal requirement of linker and dsRBD2 for RDE-4's association with dsRNA and Dcr-1.

75 FR 36463 - 60-Day Notice of Proposed Information Collection: Form DS-1622, DS-1843, DS-1622P, and DS-1843P...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-25

... decisions on medical suitability for a federal employee and family members for assignment abroad. DS-1622 is... maintain the health and fitness of the individual and family members within the Department of State medical... DS-1622, DS-1843, DS-1622P, and DS-1843P: Medical History and Examination for Foreign Service, OMB...

Ultrastructural observation of the acid-base resistant zone of all-in-one adhesives using three different acid-base challenges.

PubMed

Tsujimoto, Miho; Nikaido, Toru; Inoue, Go; Sadr, Alireza; Tagami, Junji

2010-11-01

The aim of this study was to analyze the ultrastructure of the dentin-adhesive interface using two all-in-one adhesive systems (Clearfil Tri-S Bond, TB; Tokuyama Bond Force, BF) after different acid-base challenges. Three solutions were used as acidic solutions for the acid-base challenges: a demineralizing solution (DS), a phosphoric acid solution (PA), and a hydrochloric acid solution (HCl). After the acid-base challenges, the bonded interfaces were examined by scanning electron microscopy. Thickness of the acid-base resistant zone (ABRZ) created in PA and HCl was thinner than in DS for both adhesive systems. For BF adhesive, an eroded area was observed beneath the ABRZ after immersion in PA and HCl, but not in DS. Conversely for TB adhesive, the eroded area was observed only after immersion in PA. In conclusion, although the ABRZ was observed for both all-in-one adhesive systems, its morphological features were influenced by the ingredients of both the adhesive material and acidic solution.

Nano-bio assemblies for artificial light harvesting systems

NASA Astrophysics Data System (ADS)

Bain, Dipankar; Maity, Subarna; Patra, Amitava

2018-02-01

Ultrasmall fluorescent gold nanoclusters (Au NCs) have drawn considerable research interest owing to their molecular like properties such as d-sp and sp-sp transitions, and intense fluorescence. Fluorescent Au NCs have especial attraction in biological system owing to their biocompatibility and high photostability. Recently, several strategies have been adapted to design an artificial light-harvesting system using Au NCs for potential applications. Here, we have designed Au nanoclusters based dsDNA (double stranded deoxyribonucleic acid) nano assemblies where the Au nanocluster is covalently attached with Alexa Fluor 488 (A488) dye tagged dsDNA. Investigation reveals that the incorporation of Ag+ into dsDNA enhances the rate of energy transfer from A488 to Au NCs. In addition cadmium telluride quantum dot (CdTe QDs) based Au NCs hybrid material shows the significant enhancement of energy transfer 35% to 83% with changing the capping ligand of Au NCs from glutathione (GSH) to bovine serum albumin (BSA) protein. Another hybrid system is developed using carbon dots and dye encapsulated BSA-protein capped Au NCs for efficient light harvesting system with 83% energy transfer efficiency. Thus, Au NCs base nano bio assemblies may open up new possibilities for the construction of artificial light harvesting system.

Penetration enhancement of ibuprofen from supersaturated solutions through human skin.

PubMed

Iervolino, M; Cappello, B; Raghavan, S L; Hadgraft, J

2001-01-05

Systematic investigations on the diffusion of ibuprofen (IBU) from supersaturated solutions through human epidermis are reported. Significant flux enhancement was obtained from supersaturated solutions compared to the saturated solution. Hydroxypropyl methylcellulose (HPMC), when used as an additive was found to be effective in maintaining the high activity state at high degrees of saturation (DS). The increase in the flux was proportional to the DS. In the presence of 2-hydroxypropyl-beta-cyclodextrin (CD) at DS 2 and 3 a lower flux was observed compared to HPMC. At DS 5 a higher flux enhancement was found suggesting that CD might act as a penetration enhancer at certain CD/drug ratios. Studies on the mechanism of stabilisation of HPMC and CD on IBU crystallisation from supersaturated systems showed that HPMC acts as a growth inhibitor and habit modifier whereas CD does not influence the crystallisation process.

Belimumab in the treatment of systemic lupus erythematosus: high disease activity predictors of response.

PubMed

van Vollenhoven, Ronald F; Petri, Michelle A; Cervera, Ricard; Roth, David A; Ji, Beulah N; Kleoudis, Christi S; Zhong, Z John; Freimuth, William

2012-08-01

To identify factors that predict response to belimumab treatment in the phase 3 BLISS trials of autoantibody-positive systemic lupus erythematosus (SLE) and further analyse clinical efficacy in various patient subsets. The BLISS trials compared belimumab 1 and 10 mg/kg versus placebo, all plus standard SLE therapy, over 52 or 76 weeks. Pooled subgroup analyses of week 52 SLE responder index rates (the primary endpoint in both trials) were performed based on demographic characteristics and baseline disease activity indicators. Pooled multivariate analysis was performed to determine predictors of response and treatment effect. Pooled univariate and multivariate analyses (N=1684) identified baseline factors associated with an increased benefit of belimumab versus placebo. These factors included the Safety Of Estrogens In Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) ≥10, low complement, anti-dsDNA positivity and corticosteroid use. Efficacy outcomes were assessed in the low complement/anti-dsDNA-positive and SELENA-SLEDAI ≥10 subgroups. Week 52 SLE Responder Index rates in the low complement/anti-dsDNA-positive subgroup were 31.7%, 41.5% (p=0.002) and 51.5% (p<0.001) with placebo and belimumab 1 mg/kg and 10 mg/kg, respectively; corresponding rates in the SELENA-SLEDAI ≥10 subgroup were 44.3%, 58.0% (p<0.001) and 63.2% (p<0.001). Further analysis of secondary endpoints in the low complement/anti-dsDNA-positive subgroup showed that compared with placebo, belimumab produced greater benefits regarding severe flares, corticosteroid use and health-related quality of life. These findings suggest that belimumab has greater therapeutic benefit than standard therapy alone in patients with higher disease activity, anti-dsDNA positivity, low complement or corticosteroid treatment at baseline. CLINICALTRIALS.GOV: identifiers NCT00424476 and NCT00410384.

Comparison of three anti-dsDNA assays: performance and correlation with systemic lupus erythematosus disease activity.

PubMed

Venner, Allison A; Ibañez, Dominique; Gladman, Dafna D; Urowitz, Murray B; MacKinnon, Anne; Blasutig, Ivan M; Yip, Paul M

2013-03-01

To investigate the BioPlex 2200 multiplex immunoassay and Farrzyme ELISA assays as alternatives to the established Farr radioimmunoassay for the correlation of anti-dsDNA antibodies in the assessment of disease activity in systemic lupus erythematosus (SLE). Standard protocols were used to verify analytical performance claims. Anti-dsDNA antibody levels in SLE patient specimens (N=105) were measured and assessed for clinical performance using manufacturer cut-off limits along with the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score. Assay precision, measurable range and normal reference interval met the manufacturers' stated claims. Agreement between Farr and BioPlex assays was moderate (positive agreement=62%; negative agreement=85%; kappa=0.48), as was agreement between Farr and Farrzyme assays (positive agreement=56%; negative agreement=91%; kappa=0.51). Mean SLEDAI-2K scores differed significantly between the anti-dsDNA positive and negative groups for BioPlex (p=0.0006), but not Farr (p=0.11) or Farrzyme (p=0.34). ROC curve analysis showed a similar area under the curve (AUC) for all three assays (0.76, 0.74, and 0.73 for Farr, BioPlex, and Farrzyme, respectively) in the discrimination of clinically active disease. Furthermore, increased anti-dsDNA levels from BioPlex showed significant correlation with active renal disease. However, results suggested a lower cut-off for the Farrzyme assay for assessment of global disease activity. BioPlex and Farrzyme assays had similar overall agreement with the Farr assay, with BioPlex best reflecting disease activity in SLE patients. Copyright © 2012 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Associations of the Levels of C4d-bearing Reticulocytes and High-avidity Anti-dsDNA Antibodies with Disease Activity in Systemic Lupus Erythematosus.

PubMed

Mora, Claudia; Medina-Rosas, Jorge; Santos, Ana Maria; Jaimes, Diego A; Arbeláez, Ana M; Romero, Consuelo; Cortes, Annie; Londono, John

2016-09-01

There are no laboratory tools that detect early flares in systemic lupus erythematosus (SLE). Our aim was to validate in our population the previous findings of the association of C4d-bearing reticulocytes (R-C4d) compared to anti-dsDNA antibodies, with disease activity assessed by the Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) and the British Isles Lupus Assessment Group (BILAG) 2004 scales. All patients who met the 1987 American College of Rheumatology classification criteria and were seen consecutively in 2013 at a specialized SLE care clinic were included. Disease activity was established by the SELENA-SLEDAI and BILAG 2004. Anti-dsDNA and R-C4d were quantified in peripheral blood. Comparisons were made between values of active and inactive patients, and the correlations between the SELENA-SLEDAI and serum levels of anti-dsDNA and R-C4d were measured. Sixty-two patients (83.9% women) were included. A total of 32.3% had active disease according to the SELENA-SLEDAI. There was a significant statistical difference (p = 0.0001) in the distribution of R-C4d between disease activity groups. The correlation coefficient between R-C4d and the SELENA-SLEDAI score was rs = 0.738 (p = 0.0001). R-C4d differed between patients with and without activity in the BILAG 2004 constitutional, mucocutaneous, gastrointestinal, renal, and hematological domains. R-C4d showed a higher correlation with SLE activity measured by the SELENA-SLEDAI and BILAG 2004 than anti-dsDNA did, suggesting a possible involvement in diagnosing disease activity. Prospective studies that confirm these findings and evaluate its involvement in followup are needed.

Immunoserological parameters in SLE: high-avidity anti-dsDNA detected by ELISA are the most closely associated with the disease activity.

PubMed

Andrejevic, Sladjana; Jeremic, Ivica; Sefik-Bukilica, Mirjana; Nikolic, Milos; Stojimirovic, Biljana; Bonaci-Nikolic, Branka

2013-11-01

We assessed the relationship between the serum levels of antibodies against double-stranded DNA (dsDNA), C1q, nucleosomes, histones, C3 and C4 complement components with one another, with organ involvement and overall disease activity in patients with systemic lupus erythematosus (SLE). One hundred seventy-five sera from 99 patients with SLE, 31 sera of patients with other connective tissue diseases, and 20 sera from healthy blood donors were tested. SLE disease activity was assessed by modified SLEDAI-2K (M-SLEDAI-2K), not including complement and anti-dsDNA descriptors. Anti-dsDNA antibodies were measured by indirect immunofluorescence on Crithidia luciliae (CLIFT), standard enzyme-linked immunosorbent assay (ELISA) and ELISA for high-avidity antibodies. The most significant risk factor for renal involvement were anti-C1q antibodies (OR = 3.88, p < 0.05), high-avidity anti-dsDNA antibodies for polyserositis (OR = 7.99, p < 0.01), anti-histone antibodies for joint involvement (OR = 2.75, p < 0.05), and low C3 for cytopenia (OR = 11.96, p < 0.001) and mucocutaneous lesions (OR = 3.32, p < 0.01). Multiple linear regression analysis showed that disease activity in SLE could be predicted by the levels of antibodies against dsDNA determined by standard (p < 0.05) and high-avidity (p < 0.001) ELISA, and inversely associated with concentration of C3 (p < 0.001). Using stepwise method, high-avidity anti-dsDNA antibodies were found to be in the closest association to M-SLEDAI-2K. Moreover, positive test for high-avidity anti-dsDNA antibodies appeared as an independent risk factor for moderately to severely active disease (M-SLEDAI-2K>5) (OR = 5.5, p < 0.01). The presence of high-avidity anti-dsDNA antibodies represented a risk for renal, joint, and most importantly for serosal involvement. Our results suggest that simple and reliable ELISA for high-avidity anti-dsDNA antibodies is the test of good clinical utility for the assessment of global SLE activity.

Discriminating styles (DS) and pollen-mediated pseudo-self-compatibility (PMPSC) in Nemesia strumosa Benth. : Part 1: Characteristics and inheritance of DS.

PubMed

Robacker, C D; Ascher, P D

1981-09-01

Nemesia strumosa plants were discovered which had styles capable of discriminating among incompatible pollen tubes from different pollinators, allowing growth of some but not others. All but 3 of 26 families tested had at least some members with discriminating styles (DS). Presence and level of DS was independent of S genotype. Plants with pseudo-self-compatiblity (PSC) levels greater than 10% had the trait, though many plants with strong DS had PSC levels less than 10%. Self pollination of highly DS plants produced mostly DS offspring, but of differing sensitivities. Some progenies from crosses between a family of highly DS plants and unrelated, probably low DS plants segregated half DS and half non-DS, while others consisted of mostly DS or mostly non-DS. The DS phenomenon is probably caused by PSC genes.

76 FR 39465 - 30-Day Notice of Proposed Information Collection: DS-573, DS-574, DS-575, and DS-576, Overseas...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-06

... DEPARTMENT OF STATE [Public Notice 7515] 30-Day Notice of Proposed Information Collection: DS-573, DS-574, DS-575, and DS-576, Overseas Schools--Grant Request Automated Submissions Program (GRASP.... Title of Information Collection: Grant Request Automated Submissions Program (GRASP). OMB Control Number...

Logistics Management Systems in Desert Shield/Desert Storm - How Well Did They Do?

DTIC Science & Technology

1992-04-07

were grovped into five major categories: Containerization and Packaging; Distribution Management ; Automation/Communications; Peace versus War Operations...incorporated into normal operating procedures. Distribution ManaQement. Distribution management was plagued with confusion throughout DS\\DS. This...to carrier terminals, depots and vendors. TDS recommendations to address the distribution management issue focused on: 1. Authorization of direct

Assessment of the potential noncancer health hazards of PCBs for inclusion on EPA’s Integrated Risk Information System (IRIS)

EPA Science Inventory

At present, there are IRIS RfDs for two commercial PCB mixtures: Aroclor 1016 and Aroclor 1254. There is no IRIS RfD for complex PCB mixtures in general; and the RfDs for Aroclor 1016 and Aroclor 1254 were last updated in 1993 and 1994, respectively. The new assessment will integ...

β-cell-specific IL-2 therapy increases islet Foxp3+Treg and suppresses type 1 diabetes in NOD mice.

PubMed

Johnson, Mark C; Garland, Alaina L; Nicolson, Sarah C; Li, Chengwen; Samulski, R Jude; Wang, Bo; Tisch, Roland

2013-11-01

Interleukin-2 (IL-2) is a critical cytokine for the homeostasis and function of forkhead box p3-expressing regulatory T cells (Foxp3(+)Tregs). Dysregulation of the IL-2-IL-2 receptor axis is associated with aberrant Foxp3(+)Tregs and T cell-mediated autoimmune diseases such as type 1 diabetes. Treatment with recombinant IL-2 has been reported to enhance Foxp3(+)Tregs and suppress different models of autoimmunity. However, efficacy of IL-2 therapy is dependent on achieving sufficient levels of IL-2 to boost tissue-resident Foxp3(+)Tregs while avoiding the potential toxic effects of systemic IL-2. With this in mind, adeno-associated virus (AAV) vector gene delivery was used to localize IL-2 expression to the islets of NOD mice. Injection of a double-stranded AAV vector encoding IL-2 driven by a mouse insulin promoter (dsAAVmIP-IL2) increased Foxp3(+)Tregs in the islets but not the draining pancreatic lymph nodes. Islet Foxp3(+)Tregs in dsAAVmIP-IL2-treated NOD mice exhibited enhanced fitness marked by increased expression of Bcl-2, proliferation, and suppressor function. In contrast, ectopic IL-2 had no significant effect on conventional islet-infiltrating effector T cells. Notably, β-cell-specific IL-2 expression suppressed late preclinical type 1 diabetes in NOD mice. Collectively, these findings demonstrate that β-cell-specific IL-2 expands an islet-resident Foxp3(+)Tregs pool that effectively suppresses ongoing type 1 diabetes long term.

Unique Thermal Stability of Unnatural Hydrophobic Ds Bases in Double-Stranded DNAs.

PubMed

Kimoto, Michiko; Hirao, Ichiro

2017-10-20

Genetic alphabet expansion technology, the introduction of unnatural bases or base pairs into replicable DNA, has rapidly advanced as a new synthetic biology area. A hydrophobic unnatural base pair between 7-(2-thienyl)imidazo[4,5-b]pyridine (Ds) and 2-nitro-4-propynylpyrrole (Px) exhibited high fidelity as a third base pair in PCR. SELEX methods using the Ds-Px pair enabled high-affinity DNA aptamer generation, and introducing a few Ds bases into DNA aptamers extremely augmented their affinities and selectivities to target proteins. Here, to further scrutinize the functions of this highly hydrophobic Ds base, the thermal stabilities of double-stranded DNAs (dsDNA) containing a noncognate Ds-Ds or G-Ds pair were examined. The thermal stability of the Ds-Ds self-pair was as high as that of the natural G-C pair, and apart from the generally higher stability of the G-C pair than that of the A-T pair, most of the 5'-pyrimidine-Ds-purine-3' sequences, such as CDsA and TDsA, exhibited higher stability than the 5'-purine-Ds-pyrimidine-3' sequences, such as GDsC and ADsC, in dsDNAs. This trait enabled the GC-content-independent control of the thermal stability of the designed dsDNA fragments. The melting temperatures of dsDNA fragments containing the Ds-Ds pair can be predicted from the nearest-neighbor parameters including the Ds base. In addition, the noncognate G-Ds pair can efficiently distinguish its neighboring cognate natural base pairs from noncognate pairs. We demonstrated that real-time PCR using primers containing Ds accurately detected a single-nucleotide mismatch in target DNAs. These unique properties of the Ds base that affect the stabilities of the neighboring base pairs could impart new functions to DNA molecules and technologies.

[Detecting the markers of HIV infection with the new enzyme immunoassay diagnostic kit "DS-EIA-HIV-AB-AG-SPECTRUM" at the laboratories of AIDS prevention and control centers in the Volga Federal District].

PubMed

Ivanova, N I; Peksheva, O Iu

2009-03-01

A possibility of simultaneously detecting specific antibodies to HIV-1 and HIV-2 by enzyme immunoassay (EIA) at lower concentrations than those by immunoblotting (IB), and well as an additional possibility of earlier diagnosis of HIV infection, by identifying the HIV-1 antigen p24 lay the foundation of the "DS-EIA-HIV-AB-AG-SPECTRUM" test system made by OOO "Research-and-Production Association "Diagnosticheskiye Sistemy" (Diagnostic Systems). These peculiarities were compared with those of IB at a number of laboratories of AIDS prevention and control centers in the Volga Federal District, by using native serum/plasma samples and a specially designed control panel. The analysis of the conducted studies to identify HIV-1 and HIV-2 antibodies and HIV-1 antigen p24 in 65 plasma/serum samples in the "DS-EIA-HIV-AB-AG-SPECTRUM" and "LIA-HIV-1/2" (OOO "Niarmedik plus") test systems while confirming the positive result indicated agreement in 57 (87.7%) cases. The diagnostic possibilities of the "DS-EIA-HIV-AB-AG-SPECTRUM" test system versus the "New Lav-Blot I" one to make a laboratory diagnosis of HIV infection were studied. Irrefragable answers as to the availability of HIV-1 markers in the study serum samples on the enciphered panel were provided by IB in 73.3% of cases and EIA in 92%.

Materiel requirements for airborne minefield detection system

NASA Astrophysics Data System (ADS)

Bertsche, Karl A.; Huegle, Helmut

1997-07-01

Within the concept study, Material Requirements for an airborne minefield detection systems (AMiDS) the following topics were investigated: (i) concept concerning airborne minefield detection technique sand equipment, (ii) verification analysis of the AMiDS requirements using simulation models and (iii) application concept of AMiDS with regard o tactics and military operations. In a first approach the problems concerning unmanned airborne minefield detection techniques within a well-defined area were considered. The complexity of unmanned airborne minefield detection is a result of the following parameters: mine types, mine deployment methods, tactical requirements, topography, weather conditions, and the size of the area to be searched. In order to perform the analysis, a simulation model was developed to analyze the usability of the proposed remote controlled air carriers. The basic flight patterns for the proposed air carriers, as well as the preparation efforts of military operations and benefits of such a system during combat support missions were investigated. The results of the conceptual study showed that a proposed remote controlled helicopter drone could meet the stated German MOD scanning requirements of mine barriers. Fixed wing air carriers were at a definite disadvantage because of their inherently large turning loops. By implementing a mine detection system like AMiDS minefields can be reconnoitered before an attack. It is therefore possible either to plan, how the minefields can be circumvented or where precisely breaching lanes through the mine barriers are to be cleared for the advancing force.

Bacillus sp. Acting as Dual Role for Corrosion Induction and Corrosion Inhibition with Carbon Steel (CS)

PubMed Central

Karn, Santosh K.; Fang, Guan; Duan, Jizhou

2017-01-01

Present work investigated the role of five different bacteria species as a corrosion inducer as well as corrosion inhibitor with carbon steel (CS). We observed the ability of different bacteria species on the metal surface attachment, biofilm formation, and determined Peroxidase, Catalase enzyme activity in the detached biofilm from the CS surface. We found that each strain has diverse conduct for surface attachment like DS1 3.3, DS2 2.5, DS3 4.3, DS4 4.0, and DS5 4.71 log cfu/cm2 and for biofilm 8.3 log cfu/cm2. The enzyme Peroxidase, Catalase was found in huge concentration inside the biofilm Peroxidase was maximum for DS4 36.0 U/ml and least for DS3 19.54 U/ml. Whereas, Catalase was highest for DS4, DS5 70.14 U/ml and least 57.2 U/ml for DS2. Scanning electron microscopy (SEM) was conducted to examine the biofilm and electrochemical impedance spectroscopy (EIS) were utilized to observe corrosion in the presence of bacteria. The electrochemical results confirmed that DS1, DS3, DS4, and DS5 strains have statistically significant MIC-factors (Microbially Influenced Corrosion) of 5.46, 8.51, 2.36, and 1.04, while DS2 protective effect factor of 0.89. Weight reduction results with carbon steel likewise supports that corrosion was initiated by DS1 and DS3, while DS2 and DS5 have no any impact though with DS4 we watched less weight reduction however assumed no role in the corrosion. We established the relation of Peroxidase enzyme activity of the isolates. DS1, DS3 and having Peroxidase in the range 22.18, 19.54 U/ml which induce the corrosion whereas DS2 and DS5 having 28.57 and 27.0 U/ml has no any effect and DS4 36 U/ml has inhibitory effect, increasing concentration inhibiting the corrosion. For Catalase DS1, DS3 have 67.28, 61.57 U/ml which induce corrosion while DS2 and DS5 57.71 and 59.14 U/ml also has no effect whereas DS4 70.14 U/ml can inhibit corrosion. Results clearly express that in a specific range both enzymes can induce the corrosion. Our goals are to pursuit and locate the potential role of the enzyme in corrosion induction and inhibition. There is still further work is proceeded for the more profound perception. PMID:29114242

Body and organ dimensions of the 1945 Japanese population used in dosimetry system DS86 and data available for an expanded series of phantoms.

PubMed

Cullings, Harry M; Kawamura, Hisao; Chen, Jing

2012-03-01

The computational phantoms used in dosimetry system DS86 and re-used in DS02 were derived from models and methods developed at Oak Ridge National Laboratories (ORNL) in the US, but referred to Japanese anthropometric data for the Japanese population of 1945, from studies conducted at the Japanese National Institute of Radiological Sciences and other sources. The phantoms developed for DS86 were limited to three hermaphroditic models: infant, child and adult. After comparing data from Japanese and Western populations, phantoms were adapted from the pre-existing ORNL series, adjusting some organs in the adult phantom to reflect differences between Japanese and Western data, but not in the infant and child phantoms. To develop a new and larger series of more age- and sex-specific models, it appears necessary to rely on the original Japanese data and values derived from them, which can directly provide population-average body dimensions for various ages. Those data were re-analysed in conjunction with other Asian data for an Asian Reference Man model, providing a rather complete table of organ weights that could be used to scale organs for growth during childhood and adolescence. Although the resulting organ volumes might have some inaccuracies in relation to true population-average values, this is a minor concern because in the DS02 context organ size per se is less important than the correct body size and correct placement of the organ in the body.

All-optical virtual private network system in OFDM based long-reach PON using RSOA re-modulation technique

NASA Astrophysics Data System (ADS)

Kim, Chang-Hun; Jung, Sang-Min; Kang, Su-Min; Han, Sang-Kook

2015-01-01

We propose an all-optical virtual private network (VPN) system in an orthogonal frequency division multiplexing (OFDM) based long reach PON (LR-PON). In the optical access network field, technologies based on fundamental upstream (U/S) and downstream (D/S) have been actively researched to accommodate explosion of data capacity. However, data transmission among the end users which is arisen from cloud computing, file-sharing and interactive game takes a large weight inside of internet traffic. Moreover, this traffic is predicted to increase more if Internet of Things (IoT) services are activated. In a conventional PON, VPN data is transmitted through ONU-OLT-ONU via U/S and D/S carriers. It leads to waste of bandwidth and energy due to O-E-O conversion in the OLT and round-trip propagation between OLT and remote node (RN). Also, it causes inevitable load to the OLT for electrical buffer, scheduling and routing. The network inefficiency becomes more critical in a LR-PON which has been researched as an effort to reduce CAPEX and OPEX through metro-access consolidation. In the proposed system, the VPN data is separated from conventional U/S and re-modulated on the D/S carrier by using RSOA in the ONUs to avoid bandwidth consumption of U/S and D/S unlike in previously reported system. Moreover, the transmitted VPN data is re-directed to the ONUs by wavelength selective reflector device in the RN without passing through the OLT. Experimental demonstration for the VPN communication system in an OFDM based LR-PON has been verified.

First observation of the decay Bs0-->Ds-Ds+ and measurement of its branching ratio.

PubMed

Aaltonen, T; Adelman, J; Akimoto, T; Albrow, M G; Alvarez González, B; Amerio, S; Amidei, D; Anastassov, A; Annovi, A; Antos, J; Aoki, M; Apollinari, G; Apresyan, A; Arisawa, T; Artikov, A; Ashmanskas, W; Attal, A; Aurisano, A; Azfar, F; Azzi-Bacchetta, P; Azzurri, P; Bacchetta, N; Badgett, W; Barbaro-Galtieri, A; Barnes, V E; Barnett, B A; Baroiant, S; Bartsch, V; Bauer, G; Beauchemin, P-H; Bedeschi, F; Bednar, P; Behari, S; Bellettini, G; Bellinger, J; Belloni, A; Benjamin, D; Beretvas, A; Beringer, J; Berry, T; Bhatti, A; Binkley, M; Bisello, D; Bizjak, I; Blair, R E; Blocker, C; Blumenfeld, B; Bocci, A; Bodek, A; Boisvert, V; Bolla, G; Bolshov, A; Bortoletto, D; Boudreau, J; Boveia, A; Brau, B; Bridgeman, A; Brigliadori, L; Bromberg, C; Brubaker, E; Budagov, J; Budd, H S; Budd, S; Burkett, K; Busetto, G; Bussey, P; Buzatu, A; Byrum, K L; Cabrera, S; Campanelli, M; Campbell, M; Canelli, F; Canepa, A; Carlsmith, D; Carosi, R; Carrillo, S; Carron, S; Casal, B; Casarsa, M; Castro, A; Catastini, P; Cauz, D; Cavalli-Sforza, M; Cerri, A; Cerrito, L; Chang, S H; Chen, Y C; Chertok, M; Chiarelli, G; Chlachidze, G; Chlebana, F; Cho, K; Chokheli, D; Chou, J P; Choudalakis, G; Chuang, S H; Chung, K; Chung, W H; Chung, Y S; Ciobanu, C I; Ciocci, M A; Clark, A; Clark, D; Compostella, G; Convery, M E; Conway, J; Cooper, B; Copic, K; Cordelli, M; Cortiana, G; Crescioli, F; Cuenca Almenar, C; Cuevas, J; Culbertson, R; Cully, J C; Dagenhart, D; Datta, M; Davies, T; de Barbaro, P; De Cecco, S; Deisher, A; De Lentdecker, G; De Lorenzo, G; Dell'Orso, M; Demortier, L; Deng, J; Deninno, M; De Pedis, D; Derwent, P F; Di Giovanni, G P; Dionisi, C; Di Ruzza, B; Dittmann, J R; D'Onofrio, M; Donati, S; Dong, P; Donini, J; Dorigo, T; Dube, S; Efron, J; Erbacher, R; Errede, D; Errede, S; Eusebi, R; Fang, H C; Farrington, S; Fedorko, W T; Feild, R G; Feindt, M; Fernandez, J P; Ferrazza, C; Field, R; Flanagan, G; Forrest, R; Forrester, S; Franklin, M; Freeman, J C; Furic, I; Gallinaro, M; Galyardt, J; Garberson, F; Garcia, J E; Garfinkel, A F; Gerberich, H; Gerdes, D; Giagu, S; Giakoumopolou, V; Giannetti, P; Gibson, K; Gimmell, J L; Ginsburg, C M; Giokaris, N; Giordani, M; Giromini, P; Giunta, M; Glagolev, V; Glenzinski, D; Gold, M; Goldschmidt, N; Golossanov, A; Gomez, G; Gomez-Ceballos, G; Goncharov, M; González, O; Gorelov, I; Goshaw, A T; Goulianos, K; Gresele, A; Grinstein, S; Grosso-Pilcher, C; Grundler, U; Guimaraes da Costa, J; Gunay-Unalan, Z; Haber, C; Hahn, K; Hahn, S R; Halkiadakis, E; Hamilton, A; Han, B-Y; Han, J Y; Handler, R; Happacher, F; Hara, K; Hare, D; Hare, M; Harper, S; Harr, R F; Harris, R M; Hartz, M; Hatakeyama, K; Hauser, J; Hays, C; Heck, M; Heijboer, A; Heinemann, B; Heinrich, J; Henderson, C; Herndon, M; Heuser, J; Hewamanage, S; Hidas, D; Hill, C S; Hirschbuehl, D; Hocker, A; Hou, S; Houlden, M; Hsu, S-C; Huffman, B T; Hughes, R E; Husemann, U; Huston, J; Incandela, J; Introzzi, G; Iori, M; Ivanov, A; Iyutin, B; James, E; Jayatilaka, B; Jeans, D; Jeon, E J; Jindariani, S; Johnson, W; Jones, M; Joo, K K; Jun, S Y; Jung, J E; Junk, T R; Kamon, T; Kar, D; Karchin, P E; Kato, Y; Kephart, R; Kerzel, U; Khotilovich, V; Kilminster, B; Kim, D H; Kim, H S; Kim, J E; Kim, M J; Kim, S B; Kim, S H; Kim, Y K; Kimura, N; Kirsch, L; Klimenko, S; Klute, M; Knuteson, B; Ko, B R; Koay, S A; Kondo, K; Kong, D J; Konigsberg, J; Korytov, A; Kotwal, A V; Kraus, J; Kreps, M; Kroll, J; Krumnack, N; Kruse, M; Krutelyov, V; Kubo, T; Kuhlmann, S E; Kuhr, T; Kulkarni, N P; Kusakabe, Y; Kwang, S; Laasanen, A T; Lai, S; Lami, S; Lammel, S; Lancaster, M; Lander, R L; Lannon, K; Lath, A; Latino, G; Lazzizzera, I; Lecompte, T; Lee, J; Lee, J; Lee, Y J; Lee, S W; Lefèvre, R; Leonardo, N; Leone, S; Levy, S; Lewis, J D; Lin, C; Lin, C S; Linacre, J; Lindgren, M; Lipeles, E; Lister, A; Litvintsev, D O; Liu, T; Lockyer, N S; Loginov, A; Loreti, M; Lovas, L; Lu, R-S; Lucchesi, D; Lueck, J; Luci, C; Lujan, P; Lukens, P; Lungu, G; Lyons, L; Lys, J; Lysak, R; Lytken, E; Mack, P; Macqueen, D; Madrak, R; Maeshima, K; Makhoul, K; Maki, T; Maksimovic, P; Malde, S; Malik, S; Manca, G; Manousakis, A; Margaroli, F; Marino, C; Marino, C P; Martin, A; Martin, M; Martin, V; Martínez, M; Martínez-Ballarín, R; Maruyama, T; Mastrandrea, P; Masubuchi, T; Mattson, M E; Mazzanti, P; McFarland, K S; McIntyre, P; McNulty, R; Mehta, A; Mehtala, P; Menzemer, S; Menzione, A; Merkel, P; Mesropian, C; Messina, A; Miao, T; Miladinovic, N; Miles, J; Miller, R; Mills, C; Milnik, M; Mitra, A; Mitselmakher, G; Miyake, H; Moed, S; Moggi, N; Moon, C S; Moore, R; Morello, M; Movilla Fernandez, P; Mülmenstädt, J; Mukherjee, A; Muller, Th; Mumford, R; Murat, P; Mussini, M; Nachtman, J; Nagai, Y; Nagano, A; Naganoma, J; Nakamura, K; Nakano, I; Napier, A; Necula, V; Neu, C; Neubauer, M S; Nielsen, J; Nodulman, L; Norman, M; Norniella, O; Nurse, E; Oh, S H; Oh, Y D; Oksuzian, I; Okusawa, T; Oldeman, R; Orava, R; Osterberg, K; Pagan Griso, S; Pagliarone, C; Palencia, E; Papadimitriou, V; Papaikonomou, A; Paramonov, A A; Parks, B; Pashapour, S; Patrick, J; Pauletta, G; Paulini, M; Paus, C; Pellett, D E; Penzo, A; Phillips, T J; Piacentino, G; Piedra, J; Pinera, L; Pitts, K; Plager, C; Pondrom, L; Portell, X; Poukhov, O; Pounder, N; Prakoshyn, F; Pronko, A; Proudfoot, J; Ptohos, F; Punzi, G; Pursley, J; Rademacker, J; Rahaman, A; Ramakrishnan, V; Ranjan, N; Redondo, I; Reisert, B; Rekovic, V; Renton, P; Rescigno, M; Richter, S; Rimondi, F; Ristori, L; Robson, A; Rodrigo, T; Rogers, E; Rolli, S; Roser, R; Rossi, M; Rossin, R; Roy, P; Ruiz, A; Russ, J; Rusu, V; Saarikko, H; Safonov, A; Sakumoto, W K; Salamanna, G; Saltó, O; Santi, L; Sarkar, S; Sartori, L; Sato, K; Savoy-Navarro, A; Scheidle, T; Schlabach, P; Schmidt, E E; Schmidt, M A; Schmidt, M P; Schmitt, M; Schwarz, T; Scodellaro, L; Scott, A L; Scribano, A; Scuri, F; Sedov, A; Seidel, S; Seiya, Y; Semenov, A; Sexton-Kennedy, L; Sfyria, A; Shalhout, S Z; Shapiro, M D; Shears, T; Shepard, P F; Sherman, D; Shimojima, M; Shochet, M; Shon, Y; Shreyber, I; Sidoti, A; Sinervo, P; Sisakyan, A; Slaughter, A J; Slaunwhite, J; Sliwa, K; Smith, J R; Snider, F D; Snihur, R; Soderberg, M; Soha, A; Somalwar, S; Sorin, V; Spalding, J; Spinella, F; Spreitzer, T; Squillacioti, P; Stanitzki, M; St Denis, R; Stelzer, B; Stelzer-Chilton, O; Stentz, D; Strologas, J; Stuart, D; Suh, J S; Sukhanov, A; Sun, H; Suslov, I; Suzuki, T; Taffard, A; Takashima, R; Takeuchi, Y; Tanaka, R; Tecchio, M; Teng, P K; Terashi, K; Thom, J; Thompson, A S; Thompson, G A; Thomson, E; Tipton, P; Tiwari, V; Tkaczyk, S; Toback, D; Tokar, S; Tollefson, K; Tomura, T; Tonelli, D; Torre, S; Torretta, D; Tourneur, S; Trischuk, W; Tu, Y; Turini, N; Ukegawa, F; Uozumi, S; Vallecorsa, S; van Remortel, N; Varganov, A; Vataga, E; Vázquez, F; Velev, G; Vellidis, C; Veszpremi, V; Vidal, M; Vidal, R; Vila, I; Vilar, R; Vine, T; Vogel, M; Volobouev, I; Volpi, G; Würthwein, F; Wagner, P; Wagner, R G; Wagner, R L; Wagner-Kuhr, J; Wagner, W; Wakisaka, T; Wallny, R; Wang, S M; Warburton, A; Waters, D; Weinberger, M; Wester, W C; Whitehouse, B; Whiteson, D; Wicklund, A B; Wicklund, E; Williams, G; Williams, H H; Wilson, P; Winer, B L; Wittich, P; Wolbers, S; Wolfe, C; Wright, T; Wu, X; Wynne, S M; Yagil, A; Yamamoto, K; Yamaoka, J; Yamashita, T; Yang, C; Yang, U K; Yang, Y C; Yao, W M; Yeh, G P; Yoh, J; Yorita, K; Yoshida, T; Yu, G B; Yu, I; Yu, S S; Yun, J C; Zanello, L; Zanetti, A; Zaw, I; Zhang, X; Zheng, Y; Zucchelli, S

2008-01-18

We report the observation of the exclusive decay Bs0-->Ds-Ds+ at the 7.5 standard deviation level using 355 pb(-1) of data collected by the CDF II detector in pp collisions at sqrt[s]=1.96 TeV at the Fermilab Tevatron. We measure the relative branching ratio B(Bs0-->Ds-Ds+)/B(B0-->D-Ds+)=1.44(-0.44)(+0.48). Using the world average value for B(B0-->D-Ds+), we find B(Bs0-->Ds-Ds+)=(9.4(-4.2)(+4.4))x10(-3). This provides a lower bound DeltaGammasCP/Gammas>or=2B(Bs0-->Ds-Ds+)>1.2x10(-2) at 95% C.L.

[Establishment of database with standard 3D tooth crowns based on 3DS MAX].

PubMed

Cheng, Xiaosheng; An, Tao; Liao, Wenhe; Dai, Ning; Yu, Qing; Lu, Peijun

2009-08-01

The database with standard 3D tooth crowns has laid the groundwork for dental CAD/CAM system. In this paper, we design the standard tooth crowns in 3DS MAX 9.0 and create a database with these models successfully. Firstly, some key lines are collected from standard tooth pictures. Then we use 3DS MAX 9.0 to design the digital tooth model based on these lines. During the design process, it is important to refer to the standard plaster tooth model. After some tests, the standard tooth models designed with this method are accurate and adaptable; furthermore, it is very easy to perform some operations on the models such as deforming and translating. This method provides a new idea to build the database with standard 3D tooth crowns and a basis for dental CAD/CAM system.

Interpretation with a Donnan-based concept of the influence of simple salt concentration on the apparent binding of divalent ions to the polyelectrolytes polystyrenesulfonate and dextran sulfate

USGS Publications Warehouse

Marinsky, J.A.; Baldwin, Robert F.; Reddy, M.M.

1985-01-01

It has been shown that the apparent enhancement of divalent metal ion binding to polyions such as polystyrenesulfonate (PSS) and dextran sulfate (DS) by decreasing the ionic strength of these mixed counterion systems (M2+, M+, X-, polyion) can be anticipated with the Donnan-based model developed by one of us (J.A.M.). Ion-exchange distribution methods have been employed to measure the removal by the polyion of trace divalent metal ion from simple salt (NaClO4)-polyion (NaPSS) mixtures. These data and polyion interaction data published earlier by Mattai and Kwak for the mixed counterion systems MgCl2-LiCl-DS and MgCl2-CsCl-DS have been shown to be amenable to rather precise analysis by this model. ?? 1985 American Chemical Society.

N-acetyltransferase (nat) is a critical conjunct of photoperiodism between the circadian system and endocrine axis in Antheraea pernyi.

PubMed

Mohamed, Ahmed A M; Wang, Qiushi; Bembenek, Jadwiga; Ichihara, Naoyuki; Hiragaki, Susumu; Suzuki, Takeshi; Takeda, Makio

2014-01-01

Since its discovery in 1923, the biology of photoperiodism remains a mystery in many ways. We sought the link connecting the circadian system to an endocrine switch, using Antheraea pernyi. PER-, CLK- and CYC-ir were co-expressed in two pairs of dorsolateral neurons of the protocerebrum, suggesting that these are the circadian neurons that also express melatonin-, NAT- and HIOMT-ir. The results suggest that a melatonin pathway is present in the circadian neurons. Melatonin receptor (MT2 or MEL-1B-R)-ir in PTTH-ir neurons juxtaposing clock neurons suggests that melatonin gates PTTH release. RIA showed a melatonin rhythm with a peak four hours after lights off in adult brain both under LD16:8 (LD) and LD12:12 (SD), and both the peak and the baseline levels were higher under LD than SD, suggesting a photoperiodic influence. When pupae in diapause were exposed to 10 cycles of LD, or stored at 4 °C for 4 months under constant darkness, an increase of NAT activity was observed when PTTH released ecdysone. DNA sequence upstream of nat contained E-boxes to which CYC/CLK could bind, and nat transcription was turned off by clk or cyc dsRNA. dsRNA(NAT) caused dysfunction of photoperiodism. dsRNA(PER) upregulated nat transcription as anticipated, based on findings in the Drosophila melanogaster circadian system. Transcription of nat, cyc and clk peaked at ZT12. RIA showed that dsRNA(NAT) decreased melatonin while dsRNA(PER) increased melatonin. Thus nat, a clock controlled gene, is the critical link between the circadian clock and endocrine switch. MT-binding may release PTTH, resulting in termination of diapause. This study thus examined all of the basic functional units from the clock: a photoperiodic counter as an accumulator of mRNA(NAT), to endocrine switch for photoperiodism in A. pernyi showing this system is self-complete without additional device especially for photoperiodism.

N-acetyltransferase (nat) Is a Critical Conjunct of Photoperiodism between the Circadian System and Endocrine Axis in Antheraea pernyi

PubMed Central

Bembenek, Jadwiga; Hiragaki, Susumu; Suzuki, Takeshi; Takeda, Makio

2014-01-01

Since its discovery in 1923, the biology of photoperiodism remains a mystery in many ways. We sought the link connecting the circadian system to an endocrine switch, using Antheraea pernyi. PER-, CLK- and CYC-ir were co-expressed in two pairs of dorsolateral neurons of the protocerebrum, suggesting that these are the circadian neurons that also express melatonin-, NAT- and HIOMT-ir. The results suggest that a melatonin pathway is present in the circadian neurons. Melatonin receptor (MT2 or MEL-1B-R)-ir in PTTH-ir neurons juxtaposing clock neurons suggests that melatonin gates PTTH release. RIA showed a melatonin rhythm with a peak four hours after lights off in adult brain both under LD16∶8 (LD) and LD12∶12 (SD), and both the peak and the baseline levels were higher under LD than SD, suggesting a photoperiodic influence. When pupae in diapause were exposed to 10 cycles of LD, or stored at 4°C for 4 months under constant darkness, an increase of NAT activity was observed when PTTH released ecdysone. DNA sequence upstream of nat contained E-boxes to which CYC/CLK could bind, and nat transcription was turned off by clk or cyc dsRNA. dsRNANAT caused dysfunction of photoperiodism. dsRNAPER upregulated nat transcription as anticipated, based on findings in the Drosophila melanogaster circadian system. Transcription of nat, cyc and clk peaked at ZT12. RIA showed that dsRNANAT decreased melatonin while dsRNAPER increased melatonin. Thus nat, a clock controlled gene, is the critical link between the circadian clock and endocrine switch. MT-binding may release PTTH, resulting in termination of diapause. This study thus examined all of the basic functional units from the clock: a photoperiodic counter as an accumulator of mRNANAT, to endocrine switch for photoperiodism in A. pernyi showing this system is self-complete without additional device especially for photoperiodism. PMID:24667367

Bioelectrochemically-assisted mitigation of salinity buildup and recovery of reverse-fluxed draw solute in an osmotic membrane bioreactor.

PubMed

Yang, Yuli; Yang, Xiaoli; He, Zhen

2018-05-14

A key challenge for osmotic membrane bioreactors (OMBRs) application is reverse solute flux and consequent salt accumulation in the feed side. Herein, a bioelectrochemical system (BES) was employed to drive reverse-fluxed solutes from the feed of an OMBR into a cathode compartment for recovery and subsequent reuse as a draw solute (DS). Compared to an OMBR without BES function, the present OMBR system enhanced water recovery from 925 to 1688 mL and increased the chemical oxygen demand (COD) removal efficiency from 40.2 ± 8.1 to 75.2 ± 3.3%, benefited from its lower anolyte conductivity of 9.0 mS cm -1 than that of the control system (24.1 mS cm -1 ). The CO 2 addition significantly improved the ammonia recovery rate to 93.3-116.7 g N m -3 h -1 (or 248.0-307.4 g N m -2 d -1 ), 12.1-14.5 times higher than that without CO 2 addition. The recovered DS was successfully applied to accomplish water extraction in the reuse test, and such a recovery/reuse process could result in a normalized water recovery of 3870 mL mol DS -1 or a DS usage of 0.26 mol L -1 (of the recovered water). The energy consumption of the system might be compensated by the production of bioenergy, and the net specific energy consumption was estimated to be 0.004-0.112 kWh m -3 wastewater, 0.007-0.179 kWh kg -1 removed COD, or 0.001-0.020 kWh kg -1 recovered NH 4 + -N. Those results have demonstrated that bioelectrochemical processes can be an effective approach for in situ mitigation of reverse-fluxed solute in OMBR and recovering "the lost DS" towards both reuse and reduced operational expense. Copyright © 2018 Elsevier Ltd. All rights reserved.

75 FR 55625 - 30-Day Notice of Proposed Information Collection: Form DS-1622, DS-1843, DS-1622P, and DS-1843P...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-13

... DEPARTMENT OF STATE [Public Notice: 7156] 30-Day Notice of Proposed Information Collection: Form DS-1622, DS-1843, DS-1622P, and DS-1843P: Medical History and Examination for Foreign Service, OMB... of Information Collection: Medical History and Examination for Foreign Service . OMB Control Number...

76 FR 56271 - 30-Day Notice of Proposed Information Collection: Forms DS-1622, DS-1843, DS-1622P and DS-1843P...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-12

... DEPARTMENT OF STATE [Public Notice: 7578] 30-Day Notice of Proposed Information Collection: Forms DS-1622, DS-1843, DS-1622P and DS-1843P: Medical History and Examination for Foreign Service ACTION... Collection: Medical History and Examination for Foreign Service. OMB Control Number: 1405-0068. Type of...

Hibernation, a State of Natural Tolerance to Profound Reduction in Organ Blood Flow and Oxygen Delivery Capacity

DTIC Science & Technology

2001-01-01

reperfusion injury (Bolling et at., 1998). In our also inhil current experiments, pooled plasma samples from... bcl - 2 mediated mechanism. Clin. Immunol. Immunopathol. 89: 205-213. Ta Ruit, K.A., Broce, D.S., Chiang, ~~, Oeltgen, ~R., Welborn, J.R. and Nilekani, S...Publishers Ltd, Oxford. 23 .II . "’-C"",,""’’""’c""""""" ,,_. 5(3257’ 2 &80(17$7,213$*( )RUP$SSURYHG 20%1R 5(3257’$7( ’󈧄<<<<

Maternal choline supplementation differentially alters the basal forebrain cholinergic system of young-adult Ts65Dn and disomic mice.

PubMed

Kelley, Christy M; Powers, Brian E; Velazquez, Ramon; Ash, Jessica A; Ginsberg, Stephen D; Strupp, Barbara J; Mufson, Elliott J

2014-04-15

Down syndrome (DS), trisomy 21, is a multifaceted condition marked by intellectual disability and early presentation of Alzheimer's disease (AD) neuropathological lesions including degeneration of the basal forebrain cholinergic neuron (BFCN) system. Although DS is diagnosable during gestation, there is no treatment option for expectant mothers or DS individuals. Using the Ts65Dn mouse model of DS that displays age-related degeneration of the BFCN system, we investigated the effects of maternal choline supplementation on the BFCN system in adult Ts65Dn mice and disomic (2N) littermates at 4.3-7.5 months of age. Ts65Dn dams were maintained on a choline-supplemented diet (5.1 g/kg choline chloride) or a control, unsupplemented diet with adequate amounts of choline (1 g/kg choline chloride) from conception until weaning of offspring; post weaning, offspring were fed the control diet. Mice were transcardially perfused with paraformaldehyde, and brains were sectioned and immunolabeled for choline acetyltransferase (ChAT) or p75-neurotrophin receptor (p75(NTR) ). BFCN number and size, the area of the regions, and the intensity of hippocampal labeling were determined. Ts65Dn-unsupplemented mice displayed region- and immunolabel-dependent increased BFCN number, larger areas, smaller BFCNs, and overall increased hippocampal ChAT intensity compared with 2N unsupplemented mice. These effects were partially normalized by maternal choline supplementation. Taken together, the results suggest a developmental imbalance in the Ts65Dn BFCN system. Early maternal-diet choline supplementation attenuates some of the genotype-dependent alterations in the BFCN system, suggesting this naturally occurring nutrient as a treatment option for pregnant mothers with knowledge that their offspring is trisomy 21. Copyright © 2013 Wiley Periodicals, Inc.

Utilization of Internet Protocol-Based Voice Systems in Remote Payload Operations

NASA Technical Reports Server (NTRS)

Chamberlain, jim; Bradford, Bob; Best, Susan; Nichols, Kelvin

2002-01-01

Due to limited crew availability to support science and the large number of experiments to be operated simultaneously, telescience is key to a successful International Space Station (ISS) science program. Crew, operations personnel at NASA centers, and researchers at universities and companies around the world must work closely together to per orm scientific experiments on-board ISS. The deployment of reliable high-speed Internet Protocol (IP)-based networks promises to greatly enhance telescience capabilities. These networks are now being used to cost-effectively extend the reach of remote mission support systems. They reduce the need for dedicated leased lines and travel while improving distributed workgroup collaboration capabilities. NASA has initiated use of Voice over Internet Protocol (VoIP) to supplement the existing mission voice communications system used by researchers at their remote sites. The Internet Voice Distribution System (IVoDS) connects remote researchers to mission support "loopsll or conferences via NASA networks and Internet 2. Researchers use NODS software on personal computers to talk with operations personnel at NASA centers. IVoDS also has the ;capability, if authorized, to allow researchers to communicate with the ISS crew during experiment operations. NODS was developed by Marshall Space Flight Center with contractors & Technology, First Virtual Communications, Lockheed-Martin, and VoIP Group. NODS is currently undergoing field-testing with full deployment for up to 50 simultaneous users expected in 2002. Research is being performed in parallel with IVoDS deployment for a next-generation system to qualitatively enhance communications among ISS operations personnel. In addition to the current voice capability, video and data/application-sharing capabilities are being investigated. IVoDS technology is also being considered for mission support systems for programs such as Space Launch Initiative and Homeland Defense.

Maternal choline supplementation differentially alters the basal forebrain cholinergic system of young-adult Ts65Dn and disomic mice

PubMed Central

Kelley, Christy M.; Powers, Brian E.; Velazquez, Ramon; Ash, Jessica A.; Ginsberg, Stephen D.; Strupp, Barbara J.; Mufson, Elliott J.

2014-01-01

Down syndrome (DS), trisomy 21, is a multifaceted condition marked by intellectual disability and early presentation of Alzheimer’s disease (AD) neuropathological lesions including degeneration of the basal forebrain cholinergic neuron (BFCN) system. While DS is diagnosable during gestation, there is no treatment option for expectant mothers or DS individuals. Using the Ts65Dn mouse model of DS that displays age-related degeneration of the BFCN system, we investigated the effects of maternal choline supplementation on the BFCN system in adult Ts65Dn mice and disomic (2N) littermates at 4.3–7.5 mos of age. Ts65Dn dams were maintained on a choline supplemented diet (5.1 g/kg choline chloride) or a control, unsupplemented diet with adequate amounts of choline (1 g/kg choline chloride) from conception until weaning of offspring; postweaning, offspring were fed the control diet. Mice were transcardially perfused with paraformaldehyde, brains were sectioned, and immunolabeled for choline acetyltransferase (ChAT) or p75-neurotrophin receptor (p75NTR). BFCN number and size, the area of the regions, and the intensity of hippocampal labeling were determined. Ts65Dn unsupplemented mice displayed region- and immunolabel-dependent increased BFCN number, larger areas, smaller BFCNs, and overall increased hippocampal ChAT intensity compared with 2N unsupplemented mice. These effects were partially normalized by maternal choline supplementation. Taken together, the results suggest a developmental imbalance in the Ts65Dn BFCN system. Early maternal-diet choline supplementation attenuates some of the genotype-dependent alterations in the BFCN system, suggesting this naturally occurring nutrient as a treatment option for pregnant mothers with knowledge that their offspring is trisomy 21. PMID:24178831

A "turn-on" fluorescent microbead sensor for detecting nitric oxide.

PubMed

Yang, Lan-Hee; Ahn, Dong June; Koo, Eunhae

2015-01-01

Nitric oxide (NO) is a messenger molecule involved in numerous physical and pathological processes in biological systems. Therefore, the development of a highly sensitive material able to detect NO in vivo is a key step in treating cardiovascular and a number of types of cancer-related diseases, as well as neurological dysfunction. Here we describe the development of a fluorescent probe using microbeads to enhance the fluorescence signal. Microbeads are infused with the fluorophore, dansyl-piperazine (Ds-pip), and quenched when the fluorophore is coordinated with a rhodium (Rh)-complex, ie, Rh2(AcO(-))4(Ds-pip). In contrast, they are able to fluoresce when the transition-metal complex is replaced by NO. To confirm the "on/off" mechanism for detecting NO, we investigated the structural molecular properties using the Fritz Haber Institute ab initio molecular simulations (FHI-AIMS) package. According to the binding energy calculation, NO molecules bind more strongly and rapidly with the Rh-core of the Rh-complex than with Ds-pip. This suggests that NO can bond strongly with the Rh-core and replace Ds-pip, even though Ds-pip is already near the Rh-core. However, the recovery process takes longer than the quenching process because the recovery process needs to overcome the energy barrier for formation of the transition state complex, ie, NO-(AcO(-))4-(Ds-pip). Further, we confirm that the Rh-complex with the Ds-pip structure has too small an energy gap to give off visible light from the highest unoccupied molecular orbital/lowest unoccupied molecular orbital energy level.

Biomimetic mineralization: long-term observations in patients with dentin sensitivity.

PubMed

Guentsch, Arndt; Seidler, Karin; Nietzsche, Sandor; Hefti, Arthur F; Preshaw, Philip M; Watts, David C; Jandt, Klaus D; Sigusch, Bernd W

2012-04-01

Cervical tooth erosion is increasingly observed among adults and frequently associated with dentin sensitivity (DS). This study evaluated the effectiveness on DS of a biomimetic mineralization system (BIMIN) in comparison to the current standard treatment (Gluma(®) Desensitizer, Gluma). In this single-blind, 2-arm study, 40 patients with confirmed cervical DS were randomized to either the test group or the positive control group. A Visual-Analog-Scale (VAS) was used to assess DS following stimulation of the exposed dentin with a 2-s air blast. Assessments were made at baseline (pre-treatment), 2 days, 4, 8 and 12 weeks, and 12 months after treatment. Two-stage replicas were obtained from the treated teeth and gold sputtered at baseline, and 2 days, 3 and 12 months after treatment. Surface topography of the treated cervical lesions and occlusion of dentinal tubules were investigated using scanning electron microscopy (SEM). Both treatments led to a statistically significant reduction (P<0.0001) in DS that persisted over the entire 12-month observation period. Differences in DS between the treatments were not statistically significant. SEM photomicrographs demonstrated that a mineral layer concealed the dentinal tubules in the test group. In contrast, numerous dentinal tubules remained visible in cervical defects that were treated with Gluma. A biomimetic mineralization kit was successfully used to treat patients exhibiting DS. The effect was similar to using Gluma, and was likely the result of the deposition of an enamel-like layer on the exposed cervical dentin. Copyright © 2012 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

Silencing of ecdysone receptor, insect intestinal mucin and sericotropin genes by bacterially produced double-stranded RNA affects larval growth and development in Plutella xylostella and Helicoverpa armigera.

PubMed

Israni, B; Rajam, M V

2017-04-01

RNA interference mediated gene silencing, which is triggered by double-stranded RNA (dsRNA), has become a important tool for functional genomics studies in various systems, including insects. Bacterially produced dsRNA employs the use of a bacterial strain lacking in RNaseIII activity and harbouring a vector with dual T7 promoter sites, which allow the production of intact dsRNA molecules. Here, we report an assessment of the functional relevance of the ecdysone receptor, insect intestinal mucin and sericotropin genes through silencing by dsRNA in two lepidopteran insect pests, Helicoverpa armigera and Plutella xylostella, both of which cause serious crop losses. Oral feeding of dsRNA led to significant reduction in transcripts of the target insect genes, which caused significant larval mortality with various moulting anomalies and an overall developmental delay. We also found a significant decrease in reproductive potential in female moths, with a drop in egg laying and compromised egg hatching from treated larvae as compared to controls. dsRNA was stable in the insect gut and was efficiently processed into small interfering RNAs (siRNAs), thus accounting for the phenotypes observed in the present work. The study revealed the importance of these genes in core insect processes, which are essential for insect development and survival. © 2016 The Royal Entomological Society.

Intracerebral haemorrhage in Down syndrome: protected or predisposed?

PubMed Central

Buss, Lewis; Fisher, Elizabeth; Hardy, John; Nizetic, Dean; Groet, Jurgen; Pulford, Laura; Strydom, André

2016-01-01

Down syndrome (DS), which arises from trisomy of chromosome 21, is associated with deposition of large amounts of amyloid within the central nervous system. Amyloid accumulates in two compartments: as plaques within the brain parenchyma and in vessel walls of the cerebral microvasculature. The parenchymal plaque amyloid is thought to result in an early onset Alzheimer’s disease (AD) dementia, a phenomenon so common amongst people with DS that it could be considered a defining feature of the condition. The amyloid precursor protein ( APP) gene lies on chromosome 21 and its presence in three copies in DS is thought to largely drive the early onset AD. In contrast, intracerebral haemorrhage (ICH), the main clinical consequence of vascular amyloidosis, is a more poorly defined feature of DS. We review recent epidemiological data on stroke (including haemorrhagic stroke) in order to make comparisons with a rare form of familial AD due to duplication (i.e. having three copies) of the APP region on chromosome 21, here called ‘dup-APP’, which is associated with more frequent and severe ICH. We conclude that although people with DS are at increased risk of ICH, this is less common than in dup-APP, suggesting the presence of mechanisms that act protectively. We review these mechanisms and consider comparative research into DS and dup-APP that may yield further pathophysiological insight. PMID:27239286

Hybrid lipid-based nanostructures

NASA Astrophysics Data System (ADS)

Dayani, Yasaman

Biological membranes serve several important roles, such as structural support of cells and organelles, regulation of ionic and molecular transport, barriers to non-mediated transport, contact between cells within tissues, and accommodation of membrane proteins. Membrane proteins and other vital biomolecules incorporated into the membrane need a lipid membrane to function. Due to importance of lipid bilayers and their vital function in governing many processes in the cell, the development of various models as artificial lipid membranes that can mimic cell membranes has become a subject of great interest. Using different models of artificial lipid membranes, such as liposomes, planar lipid bilayers and supported or tethered lipid bilayers, we are able to study many biophysical processes in biological membranes. The ability of different molecules to interact with and change the structure of lipid membranes can be also investigated in artificial lipid membranes. An important application of lipid bilayer-containing interfaces is characterization of novel membrane proteins for high throughput drug screening studies to investigate receptor-drug interactions and develop biosensor systems. Membrane proteins need a lipid bilayer environment to preserve their stability and functionality. Fabrication of materials that can interact with biomolecules like proteins necessitates the use of lipid bilayers as a mimic of cell membranes. The objective of this research is to develop novel hybrid lipid-based nanostructures mimicking biological membranes. Toward this aim, two hybrid biocompatible structures are introduced: lipid bilayer-coated multi-walled carbon nanotubes (MWCNTs) and hydrogel-anchored liposomes with double-stranded DNA anchors. These structures have potential applications in biosensing, drug targeting, drug delivery, and biophysical studies of cell membranes. In the first developed nanostructure, lipid molecules are covalently attached to the surfaces of MWCNTs, and then, using a sonication process, a uniform lipid bilayer that supports the incorporation of membrane proteins is formed. These bilayer-coated carbon nanotubes are highly dispersible and stable in aqueous solution, and they can be used in development of various biosensors and energy producing devices. In the other hybrid nanostructure, the lipid bilayer of a liposome is covalently anchored to a biocompatible poly(ethylene) glycol (PEG) hydrogel core using double-stranded DNA (dsDNA) linkers. Release studies shows that nano-size hydrogel-anchored liposomes are exceptionally stable, and they can be used as biomimetic model membranes that mimic the connectivity between the cytoskeleton and the plasma membrane. After lipid bilayer removal, dsDNA linkers can provide programmable nanogels decorated with oligonucleotides with potential sites for further molecular assembly. These stable nanostructures can be useful for oligonucleotide and drug delivery applications. The developed hydrogel-anchored liposomes are exploited for encapsulation and intracellular delivery of therapeutic peptide. Peptides with anti-cancer properties are successfully encapsulated in hydrogel core of pH-sensitive liposomes during rehydration process. Liposomes release their cargo at acidic pH. Confocal microscopy confirms the intracellular delivery of liposomes through an endocytotic pathway.

Tidal Channel Dynamics and Muddy Substrates: a Comparison Between a Wave Dominated and a Tidal Dominated System

DTIC Science & Technology

2011-09-30

McGlathery, J.T. Morris, T.J. Tolhurst, L.A. Deegan , D.S. Johnson, Ecogeomorphology of Salt Marshes (in press) Fagherazzi S., D.M. FitzGerald, R.W...Fulweiler, Z. Hughes, P.L. Wiberg, K.J. McGlathery, J.T. Morris, T.J. Tolhurst, L.A. Deegan , D.S. Johnson, Ecogeomorphology of Tidal Flats (in press

Cognitive Radio for Tactical Wireless Communication Networks

DTIC Science & Technology

2011-10-09

Pursley. Demodulator Statistics for Enhanced Soft-Decision Decoding in CDMA Packet Radio Systems, ICC 2010 - 2010 IEEE International Conference on...likelihood ratio (LLR) metrics and distance metrics. In [BPR08], [BoP09], and [BPR11], we investigated direct-sequence spread-spectrum ( DS -SS...modulation formats, which are among the most robust formats for tactical cognitive radio networks. DS -SS modulation with adaptive soft-decision decoding is

Induced pluripotent stem cells as a cellular model for studying Down Syndrome

PubMed Central

Brigida, Anna Lisa; Siniscalco, Dario

2016-01-01

Down Syndrome (DS), or Trisomy 21 Syndrome, is one of the most common genetic diseases. It is a chromosomal abnormality caused by a duplication of chromosome 21. DS patients show the presence of a third copy (or a partial third copy) of chromosome 21 (trisomy), as result of meiotic errors. These patients suffer of many health problems, such as intellectual disability, congenital heart disease, duodenal stenosis, Alzheimer’s disease, leukemia, immune system deficiencies, muscle hypotonia and motor disorders. About one in 1000 babies born each year are affected by DS. Alterations in the dosage of genes located on chromosome 21 (also called HSA21) are responsible for the DS phenotype. However, the molecular pathogenic mechanisms of DS triggering are still not understood; newest evidences suggest the involvement of epigenetic mechanisms. For obvious ethical reasons, studies performed on DS patients, as well as on human trisomic tissues are limited. Some authors have proposed mouse models of this syndrome. However, not all the features of the syndrome are represented. Stem cells are considered the future of molecular and regenerative medicine. Several types of stem cells could provide a valid approach to offer a potential treatment for some untreatable human diseases. Stem cells also represent a valid system to develop new cell-based drugs and/or a model to study molecular disease pathways. Among stem cell types, patient-derived induced pluripotent stem (iPS) cells offer some advantages for cell and tissue replacement, engineering and studying: self-renewal capacity, pluripotency and ease of accessibility to donor tissues. These cells can be reprogrammed into completely different cellular types. They are derived from adult somatic cells via reprogramming with ectopic expression of four transcription factors (Oct3/4, Sox2, c-Myc and Klf4; or, Oct3/4, Sox2, Nanog, and Lin28). By reprogramming cells from DS patients, it is possible to obtain new tissue with the same genetic background, offering a valuable tool for studying this genetic disease and to design customized patient-specific stem cell therapies. PMID:28096629

Measurement of B(Ds+→l+ν) and the decay constant fDS+

NASA Astrophysics Data System (ADS)

Pedlar, T. K.; Cronin-Hennessy, D.; Gao, K. Y.; Hietala, J.; Kubota, Y.; Klein, T.; Lang, B. W.; Poling, R.; Scott, A. W.; Smith, A.; Zweber, P.; Dobbs, S.; Metreveli, Z.; Seth, K. K.; Tomaradze, A.; Ernst, J.; Ecklund, K. M.; Severini, H.; Love, W.; Savinov, V.; Aquines, O.; Lopez, A.; Mehrabyan, S.; Mendez, H.; Ramirez, J.; Huang, G. S.; Miller, D. H.; Pavlunin, V.; Sanghi, B.; Shipsey, I. P. J.; Xin, B.; Adams, G. S.; Anderson, M.; Cummings, J. P.; Danko, I.; Hu, D.; Moziak, B.; Napolitano, J.; He, Q.; Insler, J.; Muramatsu, H.; Park, C. S.; Thorndike, E. H.; Yang, F.; Artuso, M.; Blusk, S.; Butt, J.; Khalil, S.; Li, J.; Menaa, N.; Mountain, R.; Nisar, S.; Randrianarivony, K.; Sia, R.; Skwarnicki, T.; Stone, S.; Wang, J. C.; Bonvicini, G.; Cinabro, D.; Dubrovin, M.; Lincoln, A.; Asner, D. M.; Edwards, K. W.; Naik, P.; Briere, R. A.; Ferguson, T.; Tatishvili, G.; Vogel, H.; Watkins, M. E.; Rosner, J. L.; Adam, N. E.; Alexander, J. P.; Cassel, D. G.; Duboscq, J. E.; Ehrlich, R.; Fields, L.; Gibbons, L.; Gray, R.; Gray, S. W.; Hartill, D. L.; Heltsley, B. K.; Hertz, D.; Jones, C. D.; Kandaswamy, J.; Kreinick, D. L.; Kuznetsov, V. E.; Mahlke-Krüger, H.; Mohapatra, D.; Onyisi, P. U. E.; Patterson, J. R.; Peterson, D.; Pivarski, J.; Riley, D.; Ryd, A.; Sadoff, A. J.; Schwarthoff, H.; Shi, X.; Stroiney, S.; Sun, W. M.; Wilksen, T.; Athar, S. B.; Patel, R.; Yelton, J.; Rubin, P.; Cawlfield, C.; Eisenstein, B. I.; Karliner, I.; Kim, D.; Lowrey, N.; Selen, M.; White, E. J.; Wiss, J.; Mitchell, R. E.; Shepherd, M. R.; Besson, D.

2007-10-01

We examine e+e-→Ds-Ds*+ and Ds*-Ds+ interactions at 4170 MeV using the CLEO-c detector in order to measure the decay constant fDs+. We use the Ds+→ℓ+ν channel, where the ℓ+ designates either a μ+ or a τ+, when the τ+→π+ν¯. Analyzing both modes independently, we determine B(Ds+→μ+ν)=(0.594±0.066±0.031)%, and B(Ds+→τ+ν)=(8.0±1.3±0.4)%. We also analyze them simultaneously to find an effective value of Beff(Ds+→μ+ν)=(0.638±0.059±0.033)% and extract fDs+=274±13±7MeV. Combining with our previous determination of B(D+→μ+ν), we also find the ratio fDs+/fD+=1.23±0.11±0.04. We compare to current theoretical estimates. Finally, we find B(Ds+→e+ν)<1.3×10-4 at 90% confidence level.

[Prevalence of Down syndrome using certificates of live births and fetal deaths in México 2008-2011].

PubMed

Sierra Romero, María Del Carmen; Navarrete Hernández, Eduardo; Canún Serrano, Sonia; Reyes Pablo, Aldelmo E; Valdés Hernández, Javier

Down syndrome (DS) or trisomy 21 is the most common genetic cause of mental retardation with the clinical presentation of a series of well-defined characteristics. Advanced maternal age has been associated with DS. The databases of all the certificates of live births and fetal deaths in Mexico were combined. Codes based on the International Classification of Diseases 10 th Revision (ICD-10) in Chapter XVII "Congenital malformations, deformations and chromosomal abnormalities" were selected. A database of 8,250,375 births during the period 2008-2011 was constructed: 99.2% were live births with 0.8% of fetal deaths and 3,076 cases diagnosed with DS. The importance of this report is to initiate an epidemiological surveillance of newborn cases of DS nationwide and by state using census information systems available in the country since 2008. An increased risk has been observed for having a child with DS since the mother is ≥ 35 years, as has been reported in other studies. Copyright © 2014 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

The General Movements in children with Down syndrome.

PubMed

Mazzone, Luigi; Mugno, Diego; Mazzone, Domenico

2004-09-01

Aim of our study was to describe the character of General Movements (GMs) in children with Down Syndrome (DS). GMs of 23 children with DS and of 30 healthy full-term infants were assessed from birth to 6th month corrected age. A qualitative and a semi-quantitative evaluation of GMs were achieved for each child. Data were graphically displayed to obtain growth curves of motor optimality scores. GMs in children with DS are characterised by low-low/moderate speed, large-large/moderate amplitude, partially creating impression of fluency, smoothness and complexity, abrupt beginning and end, few other concurrent gross movements. During the 6 months, all children showed an improvement of qualitative and semi-quantitative evaluation, but it was possible to observe great heterogeneity among children in the evolutionary course. GMs evaluation of children with no known motor problems was normal, showing only slight and transient abnormalities at first months. GMs character of children with DS could be related to central nervous system and peripheral abnormalities characterizing this syndrome. The evaluation of GMs in children with DS could be an early marker of motor impairment and help in early management decisions making.

ssDNA-dsRNAs are cleaved at the next to its chimera-junction point by an unknown RNase activity.

PubMed

Mochizuki, Shinichi; Higuchi, Sadaharu; Sakurai, Kazuo

2012-11-30

We found that there is an unknown aspect in serum RNases that cleaves ssDNA-dsRNA and ssRNA-dsRNA. In the first step, RNase cleaves the phosphodiester linkage between the first and second RNA, where the first one is connected to the single stranded RNA or DNA. In the second step, the ssRNA overhang attached siRNA is cleaved. When the 2' hydroxyl of the first RNA was replaced with methoxy, the cleavage did not occur. This RNase activity can be considered related to defense system against exogenous genetic materials. Copyright © 2012 Elsevier Inc. All rights reserved.

Integrating hydrologic modeling web services with online data sharing to prepare, store, and execute models in hydrology

NASA Astrophysics Data System (ADS)

Gan, T.; Tarboton, D. G.; Dash, P. K.; Gichamo, T.; Horsburgh, J. S.

2017-12-01

Web based apps, web services and online data and model sharing technology are becoming increasingly available to support research. This promises benefits in terms of collaboration, platform independence, transparency and reproducibility of modeling workflows and results. However, challenges still exist in real application of these capabilities and the programming skills researchers need to use them. In this research we combined hydrologic modeling web services with an online data and model sharing system to develop functionality to support reproducible hydrologic modeling work. We used HydroDS, a system that provides web services for input data preparation and execution of a snowmelt model, and HydroShare, a hydrologic information system that supports the sharing of hydrologic data, model and analysis tools. To make the web services easy to use, we developed a HydroShare app (based on the Tethys platform) to serve as a browser based user interface for HydroDS. In this integration, HydroDS receives web requests from the HydroShare app to process the data and execute the model. HydroShare supports storage and sharing of the results generated by HydroDS web services. The snowmelt modeling example served as a use case to test and evaluate this approach. We show that, after the integration, users can prepare model inputs or execute the model through the web user interface of the HydroShare app without writing program code. The model input/output files and metadata describing the model instance are stored and shared in HydroShare. These files include a Python script that is automatically generated by the HydroShare app to document and reproduce the model input preparation workflow. Once stored in HydroShare, inputs and results can be shared with other users, or published so that other users can directly discover, repeat or modify the modeling work. This approach provides a collaborative environment that integrates hydrologic web services with a data and model sharing system to enable model development and execution. The entire system comprised of the HydroShare app, HydroShare and HydroDS web services is open source and contributes to capability for web based modeling research.

Systemic lupus erythematosus in a multiethnic cohort (LUMINA): XXIX. Elevation of erythrocyte sedimentation rate is associated with disease activity and damage accrual.

PubMed

Vilá, Luis M; Alarcón, Graciela S; McGwin, Gerald; Bastian, Holly M; Fessler, Barri J; Reveille, John D

2005-11-01

To determine if different categories of erythrocyte sedimentation rate (ESR) elevation are associated with disease activity and/or damage in systemic lupus erythematosus (SLE). We studied 2317 study visits in 553 SLE patients (> or = 4 American College of Rheumatology criteria, < or = 5 years' disease duration at enrollment) from a multiethnic (Hispanic, African American, and Caucasian) longitudinal study of outcome. A study visit was done every 6 months for the first year and annually thereafter. Erythrocyte sedimentation rate (ESR) was measured using the Westergren method; results were expressed in 4 categories: < 25 (normal), 25-50 (mild elevation), 51-75 (moderate elevation), and > 75 (marked elevation) mm/h. Anti-dsDNA antibodies were measured at enrollment with the Crithidia luciliae assay. Disease activity was assessed with the Systemic Lupus Activity Measure (SLAM) and the Physician's Global Assessment (PGA). Because ESR is one of the measures evaluated in the SLAM, it was excluded from the total SLAM score. Disease damage was assessed with the Systemic Lupus International Collaborating Clinics damage index (SDI). The relationship between the SLAM (total and PGA) and SDI scores (at baseline and for all visits) and anti-dsDNA antibodies (at enrollment) with ESR was examined by univariable and generalized estimating equation (GEE) regression analyses. Ethnicity, age, and sex were entered in all regression models. The cohort consisted of 89.7% women with mean age 36.8 (SD 12.6) years and disease duration 4.6 (SD 3.2) years. GEE analyses showed that increasing levels of ESR and anti-dsDNA antibody positivity were independently associated with SLAM and PGA scores, at enrollment and for all visits. Overall, the associations of ESR with SLAM and PGA scores were stronger than for the presence of anti-dsDNA antibodies. At baseline, there was no relationship of ESR elevation or anti-dsDNA positivity with SDI scores. However, when all visits were studied, moderate and marked elevations of ESR were independently associated with SDI scores. Mild, moderate, and marked ESR elevations are strongly associated with disease activity in SLE. Moderate and marked ESR elevations are also associated with damage accrual. These associations are stronger than those for the presence of anti-dsDNA antibodies. Our data suggest that ESR could be used to assess disease activity and predict organ/system damage in a relatively rapid and inexpensive manner in SLE.

Interference Cancellation Technique Based on Discovery of Spreading Codes of Interference Signals and Maximum Correlation Detection for DS-CDMA System

NASA Astrophysics Data System (ADS)

Hettiarachchi, Ranga; Yokoyama, Mitsuo; Uehara, Hideyuki

This paper presents a novel interference cancellation (IC) scheme for both synchronous and asynchronous direct-sequence code-division multiple-access (DS-CDMA) wireless channels. In the DS-CDMA system, the multiple access interference (MAI) and the near-far problem (NFP) are the two factors which reduce the capacity of the system. In this paper, we propose a new algorithm that is able to detect all interference signals as an individual MAI signal by maximum correlation detection. It is based on the discovery of all the unknowing spreading codes of the interference signals. Then, all possible MAI patterns so called replicas are generated as a summation of interference signals. And the true MAI pattern is found by taking correlation between the received signal and the replicas. Moreover, the receiver executes MAI cancellation in a successive manner, removing all interference signals by single-stage. Numerical results will show that the proposed IC strategy, which alleviates the detrimental effect of the MAI and the near-far problem, can significantly improve the system performance. Especially, we can obtain almost the same receiving characteristics as in the absense of interference for asynchrnous system when received powers are equal. Also, the same performances can be seen under any received power state for synchronous system.

Clinical and genetic features of pediatric acute lymphoblastic leukemia in Down syndrome in the Nordic countries

PubMed Central

2014-01-01

Background Children with Down syndrome (DS) have an increased risk for acute lymphoblastic leukemia (ALL). Although previous studies have shown that DS-ALL differs clinically and genetically from non-DS-ALL, much remains to be elucidated as regards genetic and prognostic factors in DS-ALL. Methods To address clinical and genetic differences between DS-ALL and non-DS-ALL and to identify prognostic factors in DS-ALL, we ascertained and reviewed all 128 pediatric DS-ALL diagnosed in the Nordic countries between 1981 and 2010. Their clinical and genetic features were compared with those of the 4,647 B-cell precursor (BCP) ALL cases diagnosed during the same time period. Results All 128 DS-ALL were BCP ALL, comprising 2.7% of all such cases. The 5-year event-free survival (EFS) and overall survival (OS) were significantly (P = 0.026 and P = 0.003, respectively) worse for DS-ALL patients with white blood cell counts ≥50 × 109/l. The age distributions varied between the DS and non-DS cases, with age peaks at 2 and 3 years, respectively; none of the DS patients had infant ALL (P = 0.029). The platelet counts were lower in the DS-ALL group (P = 0.005). Abnormal karyotypes were more common in non-DS-ALL (P < 0.0001), and there was a significant difference in the modal number distribution, with only 2% high hyperdiploid DS-ALL cases (P < 0.0001). The 5-year EFS and 5-year OS were significantly worse for DS-ALL (0.574 and 0.691, respectively) compared with non-DS-ALL (0.783 and 0.894, respectively) in the NOPHO ALL-1992/2000 protocols (P < 0.001). Conclusions The present study adds further support for genetic and clinical differences between DS-ALL and non-DS-ALL. PMID:24726034

[Derivative spectrophotometric and NMR spectroscopic study in pharmaceutical science].

PubMed

Kitamura, Keisuke

2007-10-01

This review starts with an introduction of derivative spectrophotometry followed by a description on the construction of a personal computer-assisted derivative spectrophotometric (DS) system. An acquisition system for inputting digitalized absorption spectra into personal computers and a BASIC program for calculating derivative spectra were developed. Then, applications of the system to drug analyses that are difficult with traditional absorption methods are described. Following this, studies on the interactions of drugs with biological macromolecules by the DS and NMR methods were discussed. An (1)H NMR study elucidated that the small unilamellar vesicle (SUV) has a single membrane made of a phosphatidylcholine bilayer, and that chlorpromazine interacts with both the outer and inner layers. (13)C NMR revealed a reduction of the dissociation constants of phenothiazine drugs due to their interaction with SUV. The partition coefficients of phenothiazine, benzodiazepine and steroid drugs in an SUV-water system and the effects of cholesterol or amino lipids content on these partition coefficients were examined by the DS method. The binding constants of phenothiazine drugs to bovine serum albumin (BSA) and the influence of Na(+), K(+), Cl(-), Br(-), and I(-) on these binding constants were determined by DS. It was found that I(-), Br(-), Cl(-) reduce the binding constants in this order, and that Na(+) and K(+) have no effect. A (19)F NMR study revealed that triflupromazine binds to BSA and human serum albumin in two regions including Site II with different populations, and that a nonsteroidal anti-inflammatory drug, niflumic acid, binds Sites Ia and Ib.

Florbetapir PET, FDG PET, and MRI in Down syndrome individuals with and without Alzheimer's dementia.

PubMed

Sabbagh, Marwan N; Chen, Kewei; Rogers, Joseph; Fleisher, Adam S; Liebsack, Carolyn; Bandy, Dan; Belden, Christine; Protas, Hillary; Thiyyagura, Pradeep; Liu, Xiaofen; Roontiva, Auttawut; Luo, Ji; Jacobson, Sandra; Malek-Ahmadi, Michael; Powell, Jessica; Reiman, Eric M

2015-08-01

Down syndrome (DS) is associated with amyloid b (Ab) deposition. We characterized imaging measurements of regional fibrillar Ab burden, cerebral metabolic rate for glucose (rCMRgl), gray matter volumes (rGMVs), and age associations in 5 DS with dementia (DS/AD1), 12 DS without dementia (DS/AD2), and 9 normal controls (NCs). There were significant group differences in mean standard uptake value ratios (SUVRs) for florbetapir with DS/AD1 having the highest, followed by DS/AD2, followed by NC. For [18F]-fluorodeoxyglucose positron emission tomography, posterior cingulate rCMRgl in DS/AD1 was significantly reduced compared with DS/AD2 and NC. For volumetric magnetic resonance imaging (vMRI), hippocampal volumes were significantly reduced for the DS/AD1 compared with DS/AD2 and NC. Age-related SUVR increases and rCMRgl reductions were greater in DS participants than in NCs. DS is associated with fibrillar Ab, rCMRgl, and rGMV alterations in the dementia stage and before the presence of clinical decline. This study provides a foundation for the studies needed to inform treatment and prevention in DS. Copyright © 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

Upriver transport of dissolved substances in an estuary and sub-estuary system of the lower James River, Chesapeake Bay

NASA Astrophysics Data System (ADS)

Hong, Bo; Shen, Jian; Xu, Hongzhou

2018-01-01

The water exchange between the James River and the Elizabeth River, an estuary and sub-estuary system in the lower Chesapeake Bay, was investigated using a 3D numerical model. The conservative passive tracers were used to represent the dissolved substances (DS) discharged from the Elizabeth River. The approach enabled us to diagnose the underlying physical processes that control the expansion of the DS, which is representative of potential transport of harmful algae blooms, pollutants from the Elizabeth River to the James River without explicitly simulating biological processes. Model simulations with realistic forcings in 2005, together with a series of processoriented numerical experiments, were conducted to explore the correlations of the transport process and external forcing. Model results show that the upriver transport depends highly on the freshwater discharge on a seasonal scale and maximum upriver transport occurs in summer with a mean transport time ranging from 15-30 days. The southerly/easterly wind, low river discharge, and neap tidal condition all act to strengthen the upriver transport. On the other hand, the northerly/westerly wind, river pulse, water level pulse, and spring tidal condition act to inhibit the upriver transport. Tidal flushing plays an important role in transporting the DS during spring tide, which shortens the travel time in the lower James River. The multivariable regression analysis of volume mean subtidal DS concentration in the mesohaline portion of the James River indicates that DS concentration in the upriver area can be explained and well predicted by the physical forcings (r = 0.858, p = 0.00001).

Increased susceptibility to in vitro ultraviolet B radiation in fibroblasts and lymphocytes cultured from systemic lupus erythematosus patients

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

Golan, T.D.; Foltyn, V.; Roueff, A.

1991-02-01

Sunlight is known to induce exacerbations of systemic lupus erythematosus (SLE) but its mechanism remains unclear. We have previously reported that ultraviolet A (UVA) exposure induces an increase in total DNA synthesis (DS) in vitro but a decrease in unscheduled DNA repair synthesis (UDRS) of splenocytes of murine SLE strains. In order to investigate whether similar observations are characteristic of human SLE, peripheral blood lymphocytes (PBL) and dermal fibroblast (DF) cultures of 20 patients and 15 matched controls were exposed in vitro to UVA or UVB at different doses. Thirteen (65%) SLE DF cultures exposed to UVB light (12-24 J/m2)more » showed an increase in DS compared to paired unirradiated cultures. In contrast, UVB-irradiated DF from normal individuals had no significant increase in DS following UVB irradiation. When SLE DF were exposed to higher doses of UVB (48-96 J/m2), 90% of cultures showed a decrease in DS compared to only 20% in the control group. All of the SLE DF cultures showed a decrease of their unscheduled DNA repair capacity following UVB (24-48 J/m2) irradiation whereas no UDRS was apparent in 74% of controls under the same conditions. Similar findings regarding UDRS were observed in SLE PBL cultures and were also confirmed by autoradiography. UVA exposure (0-3840 J/m2) had no effect on DS nor on UDRS in DF or PBL cultured from SLE and controls. The relevance of these in vitro findings to the in vivo pathogenesis of the disease is discussed.« less

The economic impact of battery longevity in implantable cardioverter-defibrillators for cardiac resynchronization therapy: the hospital and healthcare system perspectives.

PubMed

Landolina, Maurizio; Morani, Giovanni; Curnis, Antonio; Vado, Antonello; D'Onofrio, Antonio; Bianchi, Valter; Stabile, Giuseppe; Crosato, Martino; Petracci, Barbara; Ceriotti, Carlo; Bontempi, Luca; Morosato, Martina; Ballari, Gian Paolo; Gasparini, Maurizio

2017-08-01

Patients receiving cardiac resynchronization therapy defibrillators (CRT-Ds) are likely to undergo one or more device replacements, mainly for battery depletion. We assessed the economic impact of battery depletion on the overall cost of CRT-D treatment from the perspectives of the healthcare system and the hospital. We also compared devices of different generations and from different manufacturers in terms of therapy cost. We analysed data on 1792 CRT-Ds implanted in 1399 patients in 9 Italian centres. We calculated the replacement probability and the total therapy cost over 6 years, stratified by device generation and manufacturer. Public tariffs from diagnosis-related groups were used together with device prices and hospitalization costs. Generators were from 3 manufacturers: Boston Scientific (667, 37%), Medtronic (973, 54%), and St Jude Medical (152, 9%). The replacement probability at 6 years was 83 and 68% for earlier- and recent-generation devices, respectively. The need for replacement increased total therapy costs by more than 50% over the initial implantation cost for hospitals and by more than 30% for healthcare system. The improved longevity of recent-generation CRT-Ds reduced the therapy cost by ∼6% in both perspectives. Among recent-generation CRT-Ds, the replacement probability of devices from different manufacturers ranged from 12 to 70%. Consequently, the maximum difference in therapy cost between manufacturers was 40% for hospitals and 19% for the healthcare system. Differences in CRT-D longevity strongly affect the overall therapy cost. While the use of recent-generation devices has reduced the cost, significant differences exist among currently available systems. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Cardiology.

Construction and validation of a three-dimensional finite element model of degenerative scoliosis.

PubMed

Zheng, Jie; Yang, Yonghong; Lou, Shuliang; Zhang, Dongsheng; Liao, Shenghui

2015-12-24

With the aging of the population, degenerative scoliosis (DS) incidence rate is increasing. In recent years, increasing research on this topic has been carried out, yet biomechanical research on the subject is seldom seen and in vitro biomechanical model of DS nearly cannot be available. The objective of this study was to develop and validate a complete three-dimensional finite element model of DS in order to build the digital platform for further biomechanical study. A 55-year-old female DS patient (Suer Pan, ID number was P141986) was selected for this study. This study was performed in accordance with the ethical standards of Declaration of Helsinki and its amendments and was approved by the local ethics committee (117 hospital of PLA ethics committee). Spiral computed tomography (CT) scanning was conducted on the patient's lumbar spine from the T12 to S1. CT images were then imported into a finite element modeling system. A three-dimensional solid model was then formed from segmentation of the CT scan. The three-dimensional model of each vertebra was then meshed, and material properties were assigned to each element according to the pathological characteristics of DS. Loads and boundary conditions were then applied in such a manner as to simulate in vitro biomechanical experiments conducted on lumbar segments. The results of the model were then compared with experimental results in order to validate the model. An integral three-dimensional finite element model of DS was built successfully, consisting of 113,682 solid elements, 686 cable elements, 33,329 shell elements, 4968 target elements, 4968 contact elements, totaling 157,635 elements, and 197,374 nodes. The model accurately described the physical features of DS and was geometrically similar to the object of study. The results of analysis with the finite element model agreed closely with in vitro experiments, validating the accuracy of the model. The three-dimensional finite element model of DS built in this study is clear, reliable, and effective for further biomechanical simulation study of DS.

Elevated Subclinical Double-Stranded DNA Antibodies and Future Proliferative Lupus Nephritis

PubMed Central

Lee, Jessica J.; Prince, Lisa K.; Baker, Thomas P.; Papadopoulos, Patricia; Edison, Jess; Abbott, Kevin C.

2013-01-01

Summary Background and objectives Elevated anti–double-stranded DNA (dsDNA) antibody and C-reactive protein are associated with proliferative lupus nephritis (PLN). Progression of quantitative anti-dsDNA antibody in patients with PLN has not been compared with that in patients with systemic lupus erythematosus (SLE) without LN before diagnosis. The temporal relationship between anti-dsDNA antibody and C-reactive protein elevation has also not been evaluated. Design, setting, participants, & measurements This case-control Department of Defense Serum Repository (established in 1985) study compared longitudinal prediagnostic quantitative anti-dsDNA antibody and C-reactive protein levels in 23 patients with biopsy-proven PLN (Walter Reed Army Medical Center, 1993–2009) with levels in 21 controls with SLE but without LN matched for patient age, sex, race, and age of serum sample. The oldest (median, 2601 days; 25%, 1245 days, 75%, 3075 days), the second to last (368; 212, 635 days), and the last (180; 135, 477 days) serum sample before diagnosis were analyzed. Results More patients with PLN had an elevated anti-dsDNA antibody level than did the matched controls at any point (78% versus 5%; P<0.001), <1 year (82% versus 8%; P<0.001), 1–4 years (53% versus 0%; P<0.001), and >4 years (33% versus 0%; P=0.04) before diagnosis. A rate of increase >1 IU/ml per year (70% versus 0%; P<0.001) was most specific for PLN. The anti-dsDNA antibody levels increased before C-reactive protein did in most patients with an antecedent elevation (92% versus 8%; P<0.001). Conclusions Elevated anti-dsDNA antibody usually precedes both clinical and subclinical evidence of proliferative LN, which suggests direct pathogenicity. Absolute anti-dsDNA antibody level and rate of increase could better establish risk of future PLN in patients with SLE. PMID:23833315

Study of radially excited Ds(21 S 0) and Ds(3P)

NASA Astrophysics Data System (ADS)

Tian, Yu; Zhao, Ze; Zhang, Ai-Lin

2017-08-01

The unobserved JP = 0- radial excitation Ds(21 S 0) is anticipated to have mass 2650 MeV (denoted as Ds(2650)). Study of hadronic production is an important way to identify highly excited states. We study hadronic production of Ds(2650) from higher excited resonances in a 3 P 0 model. Relevant hadronic partial decay widths are found to be very small, which implies it is difficult to observe Ds(2650) in hadronic decays of higher excited resonances. Hadronic decay widths of radially excited Ds(3P) have also been estimated. The total decay widths of four Ds(3P) are large, but the branching ratios in the Ds(2650)η channel are very small, which implies that it seems impossible to observe Ds(2650) in hadronic decays of Ds(3P). The dominant decay channels of the four Ds(3P) have been pointed out, and D1(2420), D1(2430), , D(2550), D(2600), (11D2)D(2750) and are possible to observe in hadronic production from Ds(3P). Supported by National Natural Science Foundation of China (11475111)

The autistic phenotype in Down syndrome: differences in adaptive behaviour versus Down syndrome alone and autistic disorder alone.

PubMed

Dressler, Anastasia; Perelli, Valentina; Bozza, Margherita; Bargagna, Stefania

2011-01-01

The autistic phenotype in Down syndrome (DS) is marked by a characteristic pattern of stereotypies, anxiety and social withdrawal. Our aim was to study adaptive behaviour in DS with and without autistic comorbidity using the Vineland Adaptive Behaviour Scales (VABS), the Childhood Autism Rating Scales (CARS) and the DSM IV-TR criteria. We assessed 24 individuals and established three groups: Down syndrome (DS), DS and autistic disorder (DS-AD), and autistic disorder (AD). The DS and DS-AD groups showed statistically significantly similar strengths on the VABS (in receptive and domestic skills). The DS and DS-AD subjects also showed similar strengths on the CARS (in imitation and relating), differing significantly from the AD group. The profile of adaptive functioning and symptoms in DS-AD seemed to be more similar to that found in DS than to the profile emerging in AD. We suggest that the comorbidity of austistic symptoms in DS hampered the acquisition of adaptive skills more than did the presence of DS alone.

The autistic phenotype in Down syndrome: differences in adaptive behaviour versus Down syndrome alone and autistic disorder alone

PubMed Central

Dressler, Anastasia; Perelli, Valentina; Bozza, Margherita; Bargagna, Stefania

Summary The autistic phenotype in Down syndrome (DS) is marked by a characteristic pattern of stereotypies, anxiety and social withdrawal. Our aim was to study adaptive behaviour in DS with and without autistic comorbidity using the Vineland Adaptive Behaviour Scales (VABS), the Childhood Autism Rating Scales (CARS) and the DSM IV-TR criteria. We assessed 24 individuals and established three groups: Down syndrome (DS), DS and autistic disorder (DS-AD), and autistic disorder (AD). The DS and DS-AD groups showed statistically significantly similar strengths on the VABS (in receptive and domestic skills). The DS and DS-AD subjects also showed similar strengths on the CARS (in imitation and relating), differing significantly from the AD group. The profile of adaptive functioning and symptoms in DS-AD seemed to be more similar to that found in DS than to the profile emerging in AD. We suggest that the comorbidity of austistic symptoms in DS hampered the acquisition of adaptive skills more than did the presence of DS alone. PMID:22152436

A statistical comparison of cirrus particle size distributions measured using the 2-D stereo probe during the TC4, SPARTICUS, and MACPEX flight campaigns with historical cirrus datasets

NASA Astrophysics Data System (ADS)

Schwartz, M. Christian

2017-08-01

This paper addresses two straightforward questions. First, how similar are the statistics of cirrus particle size distribution (PSD) datasets collected using the Two-Dimensional Stereo (2D-S) probe to cirrus PSD datasets collected using older Particle Measuring Systems (PMS) 2-D Cloud (2DC) and 2-D Precipitation (2DP) probes? Second, how similar are the datasets when shatter-correcting post-processing is applied to the 2DC datasets? To answer these questions, a database of measured and parameterized cirrus PSDs - constructed from measurements taken during the Small Particles in Cirrus (SPARTICUS); Mid-latitude Airborne Cirrus Properties Experiment (MACPEX); and Tropical Composition, Cloud, and Climate Coupling (TC4) flight campaigns - is used.Bulk cloud quantities are computed from the 2D-S database in three ways: first, directly from the 2D-S data; second, by applying the 2D-S data to ice PSD parameterizations developed using sets of cirrus measurements collected using the older PMS probes; and third, by applying the 2D-S data to a similar parameterization developed using the 2D-S data themselves. This is done so that measurements of the same cloud volumes by parameterized versions of the 2DC and 2D-S can be compared with one another. It is thereby seen - given the same cloud field and given the same assumptions concerning ice crystal cross-sectional area, density, and radar cross section - that the parameterized 2D-S and the parameterized 2DC predict similar distributions of inferred shortwave extinction coefficient, ice water content, and 94 GHz radar reflectivity. However, the parameterization of the 2DC based on uncorrected data predicts a statistically significantly higher number of total ice crystals and a larger ratio of small ice crystals to large ice crystals than does the parameterized 2D-S. The 2DC parameterization based on shatter-corrected data also predicts statistically different numbers of ice crystals than does the parameterized 2D-S, but the comparison between the two is nevertheless more favorable. It is concluded that the older datasets continue to be useful for scientific purposes, with certain caveats, and that continuing field investigations of cirrus with more modern probes is desirable.

Internal coating of air cooled gas turbine blades

NASA Technical Reports Server (NTRS)

Ahuja, P. L.

1979-01-01

Six coating systems were evaluated for internal coating of decent stage (DS) eutectic high pressure turbine blades. Sequential deposition of electroless Ni by the hydrazine process, slurry Cr, and slurry Al, followed by heat treatment provided the coating composition and thickness for internal coating of DS eutectic turbine blades. Both NiCr and NiCrAl coating compositions were evaluated for strain capability and ductile to brittle transition temperature.

Use of geological mapping tools to improve the hydraulic performance of SuDS.

PubMed

Bockhorn, Britta; Klint, Knud Erik Strøyberg; Jensen, Marina Bergen; Møller, Ingelise

2015-01-01

Most cities in Denmark are situated on low permeable clay rich deposits. These sediments are of glacial origin and range among the most heterogeneous, with hydraulic conductivities spanning several orders of magnitude. This heterogeneity has obvious consequences for the sizing of sustainable urban drainage systems (SuDS). We have tested methods to reveal geological heterogeneity at field scale to identify the most suitable sites for the placement of infiltration elements and to minimize their required size. We assessed the geological heterogeneity of a clay till plain in Eastern Jutland, Denmark measuring the shallow subsurface resistivity with a geoelectrical multi-electrode system. To confirm the resistivity data we conducted a spear auger mapping. The exposed sediments ranged from clay tills over sandy clay tills to sandy tills and correspond well to the geoelectrical data. To verify the value of geological information for placement of infiltration elements we carried out a number of infiltration tests on geologically different areas across the field, and we observed infiltration rates two times higher in the sandy till area than in the clay till area, thus demonstrating that the hydraulic performance of SuDS can be increased considerably and oversizing avoided if field geological heterogeneity is revealed before placing SuDS.

Treatment of greywater by forward osmosis technology: role of the operating temperature.

PubMed

Wang, Ce; Li, Yongmei; Wang, Yanqiang

2018-06-04

Effects of operating conditions were investigated in terms of water flux, reverse salt flux (RSF) and pollutant rejection in a forward osmosis (FO) membrane system treating synthetic greywater. Changing cross-flow velocity had a slight impact on the performance of the FO membrane. Elevating operating temperature was more effective than increasing draw solution concentration to enhance the water flux. Further observation on the effect of heating mode showed that when the temperature was increased from 20 to 30°C, heating the feed solution (FS) side was better than heating the draw solution (DS) side or heating both sides; further increasing the temperature to 40 and 50°C, heating both the FS and DS achieved much higher water flux compared with only increasing the FS or DS temperature. Under isothermal conditions, a higher water flux and a lower RSF were achieved at 40°C than at other temperatures. Changing either FS or DS temperature had similar influences on water flux and RSF. The FO process revealed high rejection of nitrate (95.7%-100%), ammonia nitrogen (98.8%-100%), total nitrogen (97.4%-99.9%), linear alkylbenzene sulfonate (100%) and Mg (97.5%-100%). A mathematical model that could well simulate the water flux evolution in the present FO system was recommended.

The Caenorhabditis elegans rsd-2 and rsd-6 genes are required for chromosome functions during exposure to unfavorable environments.

PubMed

Han, Wang; Sundaram, Prema; Kenjale, Himanshu; Grantham, James; Timmons, Lisa

2008-04-01

In Caenorhabditis elegans, exogenous dsRNA can elicit systemic RNAi, a process that requires the function of many genes. Considering that the activities of many of these genes are also required for normal development, it is surprising that exposure to high concentrations of dsRNA does not elicit adverse consequences to animals. Here, we report inducible phenotypes in attenuated C. elegans strains reared in environments that include nonspecific dsRNA and elevated temperature. Under these conditions, chromosome integrity is compromised in RNAi-defective strains harboring mutations in rsd-2 or rsd-6. Specifically, rsd-2 mutants display defects in transposon silencing, while meiotic chromosome disjunction is affected in rsd-6 mutants. RSD-2 proteins localize to multiple cellular compartments, including the nucleolus and cytoplasmic compartments that, in part, are congruent with calreticulin and HAF-6. We considered that the RNAi defects in rsd-2 mutants might have relevance to membrane-associated functions; however, endomembrane compartmentalization and endocytosis/exocytosis markers in rsd-2 and rsd-6 mutants appear normal. The mutants also possess environmentally sensitive defects in cell-autonomous RNAi elicited from transgene-delivered dsRNAs. Thus, the ultimate functions of rsd-2 and rsd-6 in systemic RNAi are remarkably complex and environmentally responsive.

Using a Family of Dividing Surfaces Normal to the Minimum EnergyPath for Quantum Instanton Rate Constants

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

Li, Yimin; Miller, Wlliam H.

2006-02-22

One of the outstanding issues in the quantum instanton (QI) theory (or any transition state-type theory) for thermal rate constants of chemical reactions is the choice of an appropriate ''dividing surface'' (DS) that separates reactants and products. (In the general version of the QI theory, there are actually two dividing surfaces involved.) This paper shows one simple and general way for choosing DS's for use in QI Theory, namely using the family of (hyper) planes normal to the minimum energy path (MEP) on the potential energy surface at various distances s along it. Here the reaction coordinate is not onemore » of the dynamical coordinates of the system (which will in general be the Cartesian coordinates of the atoms), but rather simply a parameter which specifies the DS. It is also shown how this idea can be implemented for an N-atom system in 3d space in a way that preserves overall translational and rotational invariance. Numerical application to a simple system (the colliner H + H{sub 2} reaction) is presented to illustrate the procedure.« less

A study of the application of permeable pavements as a sustainable technique for the mitigation of soil sealing in cities: A case study in the south of Spain.

PubMed

Rodríguez-Rojas, M I; Huertas-Fernández, F; Moreno, B; Martínez, G; Grindlay, A L

2018-01-01

The use of 'Sustainable Urban Drainage Systems' (SuDS) has become a more sustainable alternative for managing stormwater, greatly reducing the effects of soil sealing. However, the lack of monitored projects is a barrier to their implementation, as the companies which manage sewer systems cannot quantify the impact and cost-efficiency of SuDS. This paper presents a project developed in the south of Spain, in which the hydrological performance of 3 types of permeable pavements has been analyzed. The efficiencies obtained (over 70%), are higher than or similar to the efficiencies of vegetated SuDS, demonstrating the capacity of these pavements for delaying catchment area response and slow flow velocities, reducing the operating costs of sewer systems and the flood risk, while also ensuring service conditions for cities and safety for pedestrian and vehicular circulation. This pilot site has generated results which are sufficiently consistent so as to be representative, and serve as a reference for other cities with a similar climate. Copyright © 2017 Elsevier Ltd. All rights reserved.

Multifunctional benefits of SuDS: techno-economic evaluation of decentralised solutions for urban water management

NASA Astrophysics Data System (ADS)

Mijic, Ana; Ossa-Moreno, Juan; Smith, Karl M.

2016-04-01

The increased frequency of extreme weather events associated with climate change poses a significant threat to the integrity and function of critical urban infrastructure - rail, road, telecommunications, power and water supply/sewerage networks. A key threat within the United Kingdom (UK) is the increased risk of pluvial flooding; the conventional approach of channeling runoff to an outfall has proven to be unsustainable during severe storm events. Green infrastructure, in the form of Sustainable Urban Drainage Systems (SuDS), has been proposed as a means of minimising the risk of pluvial flooding. However, despite their technical performance, SuDS uptake in the UK has not reached its full capacity yet, mostly due to reasons that go beyong the engineering realm. This work investigated the strategic role of SuDS retrofit in managing environmental risks to urban infrastructure in London at a catchment level, through an economic appraisal of multifunctional benefits. It was found that by including the multifunctional benefits of SuDS, the economic feasibility of the project improves considerably. The case study has also shown a mechanism towards achieving wider-scale SuDS retrofit, whereby the investments are split amongst multiple stakeholder groups by highlighting the additional benefits each group derives. Groups include water utilities and their users, local government and critical infrastructure owners. Finally, limitations to the existing cost-benefit methdology in the UK were identified, and recommendations made regarding incentives and governmental regulations to enhance the uptake of SuDS in London. The proposed methodology provides compelling and robust, cost-benefit based evidence of SUDS' effectiveness within the flood risk management planning framework, but also with regard to the additional benefits of Nature Based Solutions in urban environments.

Amino acid metabolic processes in the temporal lobes assessed by proton magnetic resonance spectroscopy (1H MRS) in children with Down syndrome.

PubMed

Śmigielska-Kuzia, Joanna; Boćkowski, Leszek; Sobaniec, Wojciech; Kułak, Wojciech; Sendrowski, Krzysztof

2010-01-01

Down syndrome (DS), or trisomy 21, is one of the most common autosomal mutations. The overexpression of the β-amyloid precursor protein gene, located on chromosome 21, causes an increased production of the specific amyloid. The current study is a continuation of our earlier investigations relating to the profile of metabolic changes in the frontal lobes of DS patients as assessed by proton magnetic resonance spectroscopy ((1)H MRS). The aims of the study were the morphological assessment of the brain using magnetic resonance imaging (MRI) and the evaluation of metabolic disorders of the temporal lobes using (1)H MRS in DS children. The study group included 20 children with DS aged 3-15 years and treated in the Department of Pediatric Neurology and Rehabilitation, Medical University of Białystok. The control group included healthy children (n = 20). MRI scans of the heads of DS children were performed using a 1.5 T MR scanner under standard conditions. (1)H MRS investigations were also carried out to assess metabolic changes in the temporal lobes. Metabolites, such as N-acetylaspartate (NAA), glutamate-glutamine complex (Glx), choline (Cho), myoinositol (mI) and γ-aminobutyric acid (GABA), were determined in both temporal lobes with reference to the internal marker creatine (Cr). Results were compared with the control group.We found a statistically significant decrease in NAA/Cr, Cho/Cr, mI/Cr and GABA/Cr ratios. The Glx/Cr ratio in both temporal lobes of DS patients did not differ from the control group. Our results indicate metabolic neurotransmitter disorders in the central nervous system in children with DS.

An active ac/ds transposon system for activation tagging in tomato cultivar m82 using clonal propagation.

PubMed

Carter, Jared D; Pereira, Andy; Dickerman, Allan W; Veilleux, Richard E

2013-05-01

Tomato (Solanum lycopersicum) is a model organism for Solanaceae in both molecular and agronomic research. This project utilized Agrobacterium tumefaciens transformation and the transposon-tagging construct Activator (Ac)/Dissociator (Ds)-ATag-Bar_gosGFP to produce activation-tagged and knockout mutants in the processing tomato cultivar M82. The construct carried hygromycin resistance (hyg), green fluorescent protein (GFP), and the transposase (TPase) of maize (Zea mays) Activator major transcript X054214.1 on the stable Ac element, along with a 35S enhancer tetramer and glufosinate herbicide resistance (BAR) on the mobile Ds-ATag element. An in vitro propagation strategy was used to produce a population of 25 T0 plants from a single transformed plant regenerated in tissue culture. A T1 population of 11,000 selfed and cv M82 backcrossed progeny was produced from the functional T0 line. This population was screened using glufosinate herbicide, hygromycin leaf painting, and multiplex polymerase chain reaction (PCR). Insertion sites of transposed Ds-ATag elements were identified through thermal asymmetric interlaced PCR, and resulting product sequences were aligned to the recently published tomato genome. A population of 509 independent, Ds-only transposant lines spanning all 12 tomato chromosomes has been developed. Insertion site analysis demonstrated that more than 80% of these lines harbored Ds insertions conducive to activation tagging. The capacity of the Ds-ATag element to alter transcription was verified by quantitative real-time reverse transcription-PCR in two mutant lines. The transposon-tagged lines have been immortalized in seed stocks and can be accessed through an online database, providing a unique resource for tomato breeding and analysis of gene function in the background of a commercial tomato cultivar.

Functional mapping of protein-protein interactions in an enzyme complex by directed evolution.

PubMed

Roderer, Kathrin; Neuenschwander, Martin; Codoni, Giosiana; Sasso, Severin; Gamper, Marianne; Kast, Peter

2014-01-01

The shikimate pathway enzyme chorismate mutase converts chorismate into prephenate, a precursor of Tyr and Phe. The intracellular chorismate mutase (MtCM) of Mycobacterium tuberculosis is poorly active on its own, but becomes >100-fold more efficient upon formation of a complex with the first enzyme of the shikimate pathway, 3-deoxy-d-arabino-heptulosonate-7-phosphate synthase (MtDS). The crystal structure of the enzyme complex revealed involvement of C-terminal MtCM residues with the MtDS interface. Here we employed evolutionary strategies to probe the tolerance to substitution of the C-terminal MtCM residues from positions 84-90. Variants with randomized positions were subjected to stringent selection in vivo requiring productive interactions with MtDS for survival. Sequence patterns identified in active library members coincide with residue conservation in natural chorismate mutases of the AroQδ subclass to which MtCM belongs. An Arg-Gly dyad at positions 85 and 86, invariant in AroQδ sequences, was intolerant to mutation, whereas Leu88 and Gly89 exhibited a preference for small and hydrophobic residues in functional MtCM-MtDS complexes. In the absence of MtDS, selection under relaxed conditions identifies positions 84-86 as MtCM integrity determinants, suggesting that the more C-terminal residues function in the activation by MtDS. Several MtCM variants, purified using a novel plasmid-based T7 RNA polymerase gene expression system, showed that a diminished ability to physically interact with MtDS correlates with reduced activatability and feedback regulatory control by Tyr and Phe. Mapping critical protein-protein interaction sites by evolutionary strategies may pinpoint promising targets for drugs that interfere with the activity of protein complexes.

Functional Mapping of Protein-Protein Interactions in an Enzyme Complex by Directed Evolution

PubMed Central

Roderer, Kathrin; Neuenschwander, Martin; Codoni, Giosiana; Sasso, Severin; Gamper, Marianne; Kast, Peter

2014-01-01

The shikimate pathway enzyme chorismate mutase converts chorismate into prephenate, a precursor of Tyr and Phe. The intracellular chorismate mutase (MtCM) of Mycobacterium tuberculosis is poorly active on its own, but becomes >100-fold more efficient upon formation of a complex with the first enzyme of the shikimate pathway, 3-deoxy-d-arabino-heptulosonate-7-phosphate synthase (MtDS). The crystal structure of the enzyme complex revealed involvement of C-terminal MtCM residues with the MtDS interface. Here we employed evolutionary strategies to probe the tolerance to substitution of the C-terminal MtCM residues from positions 84–90. Variants with randomized positions were subjected to stringent selection in vivo requiring productive interactions with MtDS for survival. Sequence patterns identified in active library members coincide with residue conservation in natural chorismate mutases of the AroQδ subclass to which MtCM belongs. An Arg-Gly dyad at positions 85 and 86, invariant in AroQδ sequences, was intolerant to mutation, whereas Leu88 and Gly89 exhibited a preference for small and hydrophobic residues in functional MtCM-MtDS complexes. In the absence of MtDS, selection under relaxed conditions identifies positions 84–86 as MtCM integrity determinants, suggesting that the more C-terminal residues function in the activation by MtDS. Several MtCM variants, purified using a novel plasmid-based T7 RNA polymerase gene expression system, showed that a diminished ability to physically interact with MtDS correlates with reduced activatability and feedback regulatory control by Tyr and Phe. Mapping critical protein-protein interaction sites by evolutionary strategies may pinpoint promising targets for drugs that interfere with the activity of protein complexes. PMID:25551646

A set of GFP-based organelle marker lines combined with DsRed-based gateway vectors for subcellular localization study in rice (Oryza sativa L.).

PubMed

Wu, Tsung-Meng; Lin, Ke-Chun; Liau, Wei-Shiang; Chao, Yun-Yang; Yang, Ling-Hung; Chen, Szu-Yun; Lu, Chung-An; Hong, Chwan-Yang

2016-01-01

In the post-genomic era, many useful tools have been developed to accelerate the investigation of gene functions. Fluorescent proteins have been widely used as protein tags for studying the subcellular localization of proteins in plants. Several fluorescent organelle marker lines have been generated in dicot plants; however, useful and reliable fluorescent organelle marker lines are lacking in the monocot model rice. Here, we developed eight different GFP-based organelle markers in transgenic rice and created a set of DsRed-based gateway vectors for combining with the marker lines. Two mitochondrial-localized rice ascorbate peroxidase genes fused to DsRed and successfully co-localized with mitochondrial-targeted marker lines verified the practical use of this system. The co-localization of GFP-fusion marker lines and DsRed-fusion proteins provide a convenient platform for in vivo or in vitro analysis of subcellular localization of rice proteins.

Discovery of a new motion mechanism of biomotors similar to the earth revolving around the sun without rotation

PubMed Central

Guo, Peixuan; Schwartz, Chad; Haak, Jeannie; Zhao, Zhengyi

2013-01-01

Biomotors have been classified into linear and rotational motors. For 35 years, it has been popularly believed that viral dsDNA-packaging apparatuses are pentameric rotation motors. Recently, a third class of hexameric motor has been found in bacteriophage phi29 that utilizes a mechanism of revolution without rotation, friction, coiling, or torque. This review addresses how packaging motors control dsDNA one-way traffic; how four electropositive layers in the channel interact with the electronegative phosphate backbone to generate four steps in translocating one dsDNA helix; how motors resolve the mismatch between 10.5 bases and 12 connector subunits per cycle of revolution; and how ATP regulates sequential action of motor ATPase. Since motors with all number of subunits can utilize the revolution mechanism, this finding helps resolve puzzles and debates concerning the oligomeric nature of packaging motors in many phage systems. This revolution mechanism helps to solve the undesirable dsDNA supercoiling issue involved in rotation. PMID:24074575

Iterative MMSE Detection for MIMO/BLAST DS-CDMA Systems in Frequency Selective Fading Channels - Achieving High Performance in Fully Loaded Systems

NASA Astrophysics Data System (ADS)

Silva, João Carlos; Souto, Nuno; Cercas, Francisco; Dinis, Rui

A MMSE (Minimum Mean Square Error) DS-CDMA (Direct Sequence-Code Division Multiple Access) receiver coupled with a low-complexity iterative interference suppression algorithm was devised for a MIMO/BLAST (Multiple Input, Multiple Output / Bell Laboratories Layered Space Time) system in order to improve system performance, considering frequency selective fading channels. The scheme is compared against the simple MMSE receiver, for both QPSK and 16QAM modulations, under SISO (Single Input, Single Output) and MIMO systems, the latter with 2Tx by 2Rx and 4Tx by 4Rx (MIMO order 2 and 4 respectively) antennas. To assess its performance in an existing system, the uncoded UMTS HSDPA (High Speed Downlink Packet Access) standard was considered.

Confidence in the efficacy and safety of dietary supplements among United States active duty army personnel.

PubMed

Carvey, Christina E; Farina, Emily K; Lieberman, Harris R

2012-10-10

United States Army Soldiers regularly use dietary supplements (DS) to promote general health, enhance muscle strength, and increase energy, but limited scientific evidence supports the use of many DS for these benefits. This study investigated factors associated with Soldiers' confidence in the efficacy and safety of DS, and assessed Soldiers' knowledge of federal DS regulatory requirements. Between 2006 and 2007, 990 Soldiers were surveyed at 11 Army bases world-wide to assess their confidence in the effectiveness and safety of DS, knowledge of federal DS regulations, demographic characteristics, lifestyle-behaviors and DS use. A majority of Soldiers were at least somewhat confident that DS work as advertised (67%) and thought they are safe to consume (71%). Confidence in both attributes was higher among regular DS users than non-users. Among users, confidence in both attributes was positively associated with rank, self-rated diet quality and fitness level, education, and having never experienced an apparent DS-related adverse event. Fewer than half of Soldiers knew the government does not require manufacturers to demonstrate efficacy, and almost a third incorrectly believed there are effective pre-market federal safety requirements for DS. Despite limited scientific evidence supporting the purported benefits and safety of many popular DS, most Soldiers were confident that DS are effective and safe. The positive associations between confidence and DS use should be considered when developing DS-related interventions or policies. Additionally, education to clarify Soldiers' misperceptions about federal DS safety and efficacy regulations is warranted.

Recommended improvements to the DS02 dosimetry system's calculation of organ doses and their potential advantages for the Radiation Effects Research Foundation.

PubMed

Cullings, Harry M

2012-03-01

The Radiation Effects Research Foundation (RERF) uses a dosimetry system to calculate radiation doses received by the Japanese atomic bomb survivors based on their reported location and shielding at the time of exposure. The current system, DS02, completed in 2003, calculates detailed doses to 15 particular organs of the body from neutrons and gamma rays, using new source terms and transport calculations as well as some other improvements in the calculation of terrain and structural shielding, but continues to use methods from an older system, DS86, to account for body self-shielding. Although recent developments in models of the human body from medical imaging, along with contemporary computer speed and software, allow for improvement of the calculated organ doses, before undertaking changes to the organ dose calculations, it is important to evaluate the improvements that can be made and their potential contribution to RERF's research. The analysis provided here suggests that the most important improvements can be made by providing calculations for more organs or tissues and by providing a larger series of age- and sex-specific models of the human body from birth to adulthood, as well as fetal models.

An expert system for the quantification of fault rates in construction fall accidents.

PubMed

Talat Birgonul, M; Dikmen, Irem; Budayan, Cenk; Demirel, Tuncay

2016-01-01

Expert witness reports, prepared with the aim of quantifying fault rates among parties, play an important role in a court's final decision. However, conflicting fault rates assigned by different expert witness boards lead to iterative objections raised by the related parties. This unfavorable situation mainly originates due to the subjectivity of expert judgments and unavailability of objective information about the causes of accidents. As a solution to this shortcoming, an expert system based on a rule-based system was developed for the quantification of fault rates in construction fall accidents. The aim of developing DsSafe is decreasing the subjectivity inherent in expert witness reports. Eighty-four inspection reports prepared by the official and authorized inspectors were examined and root causes of construction fall accidents in Turkey were identified. Using this information, an evaluation form was designed and submitted to the experts. Experts were asked to evaluate the importance level of the factors that govern fall accidents and determine the fault rates under different scenarios. Based on expert judgments, a rule-based expert system was developed. The accuracy and reliability of DsSafe were tested with real data as obtained from finalized court cases. DsSafe gives satisfactory results.

The Interactive Roles of Lipopolysaccharides and dsRNA/Viruses on Respiratory Epithelial Cells and Dendritic Cells in Allergic Respiratory Disorders: The Hygiene Hypothesis.

PubMed

Lin, Tsang-Hsiung; Su, Hsing-Hao; Kang, Hong-Yo; Chang, Tsung-Hsien

2017-10-23

The original hygiene hypothesis declares "more infections in early childhood protect against later atopy". According to the hygiene hypothesis, the increased incidence of allergic disorders in developed countries is explained by the decrease of infections. Epithelial cells and dendritic cells play key roles in bridging the innate and adaptive immune systems. Among the various pattern-recognition receptor systems of epithelial cells and dendritic cells, including toll-like receptors (TLRs), nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) and others, TLRs are the key systems of immune response regulation. In humans, TLRs consist of TLR1 to TLR10. They regulate cellular responses through engagement with TLR ligands, e.g., lipopolysaccharides (LPS) acts through TLR4 and dsRNA acts through TLR3, but there are certain common components between these two TLR pathways. dsRNA activates epithelial cells and dendritic cells in different directions, resulting in allergy-related Th2-skewing tendency in epithelial cells, and Th1-skewing tendency in dendritic cells. The Th2-skewing effect by stimulation of dsRNA on epithelial cells could be suppressed by the presence of LPS above some threshold. When LPS level decreases, the Th2-skewing effect increases. It may be via these interrelated networks and related factors that LPS modifies the allergic responses and provides a plausible mechanism of the hygiene hypothesis. Several hygiene hypothesis-related phenomena, seemingly conflicting, are also discussed in this review, along with their proposed mechanisms.

Diagnosis of vegetation recovery within herbaceous sub-systems in the West African Sahel Region

NASA Astrophysics Data System (ADS)

Anchang, J.; Hanan, N. P.; Prihodko, L.; Sathyachandran, S. K.; Ji, W.; Ross, C. W.

2017-12-01

The West African Sahel (WAS) region is an extensive water limited environment that features a delicate balance of herbaceous and woody vegetation sub systems. These play an important role in the cycling of carbon while also supporting the dominant agro-pastoral human activities in the region. Quantifying the temporal trends in vegetation with regard to these two systems is therefore very important in assessing resource sustainability and food security. In water limited areas, rainfall is a primary driver of vegetation productivity and past watershed scale studies in the WAS region have shown that increase in the slope of the productivity-to-rainfall relationship is indicative of increasing cover and density of herbaceous plants. Given the importance of grazing resources to the region, we perform a wall-to-wall pixel based analysis of changing short-term vegetation sensitivity to changing annual rainfall (hereafter referred to as dS) to examine temporal trends in herbaceous vegetation health. Results indicate that 43% of the Sahelian region has experienced changes (P < 0.05) in herbaceous vegetation (dS). Areas with significant increases in dS are well distributed across the region, but with major concentrations in North-Central Senegal, South Western and Central Mali and South Western Niger. Positive dS is indicative of herbaceous vegetation recovery, in response to changing management and rainfall conditions that promote long-term herbaceous community recovery following degradation during the 1970-1980s droughts.

Depressive symptoms in relation to overall survival in people with head and neck cancer: a longitudinal cohort study.

PubMed

Jansen, Femke; Verdonck-de Leeuw, Irma M; Cuijpers, Pim; Leemans, C René; Waterboer, Tim; Pawlita, Michael; Penfold, Chris; Thomas, Steven J; Waylen, Andrea; Ness, Andrew R

2018-06-21

To investigated the relation between pre-treatment depressive symptoms (DS) and the course of DS during the first year after cancer diagnosis, and overall survival among people with head and neck cancer (HNC). Data from the Head and Neck 5000 prospective clinical cohort study were used. DS were measured using the Hospital Anxiety and Depression Scale (HADS) pre-treatment, at 4 and 12 months follow-up. Also socio-demographic, clinical, lifestyle and mortality data were collected. The association between pre-treatment DS (HADS-depression>7) and course (never DS, recovered from DS, or persistent/recurrent/late DS at 12 months follow-up), and survival was investigated using Cox regression. Unadjusted and adjusted analyses were performed. In total, 384 of the 2,144 persons (18%) reported pre-treatment DS. Regarding DS course, 63% never had DS, 16% recovered, and 20% had persistent/recurrent/late DS. People with pre-treatment DS had a higher risk of earlier death than people without DS (Hazard Ratio (HR) =1.65; 95% confidence interval (CI) 1.33-2.05), but this decreased after correcting for socio-demographic, clinical, and lifestyle-related factors (HR=1.21; 95%CI 0.97-1.52). Regarding the course of DS, people with persistent/recurrent/late DS had a higher risk of earlier death (HR=2.04; 95%CI 1.36-3.05), while people who recovered had a comparable risk (HR=1.12; 95%CI 0.66-1.90) as the reference group who never experienced DS. After correcting for socio-demographic and clinical factors, people with persistent/recurrent/late DS still had a higher risk of earlier death (HR=1.66; 95%CI 1.09-2.53). Pre-treatment DS and persistent/recurrent/late DS were associated with worse survival among people with HNC. This article is protected by copyright. All rights reserved.

Activation of innate antiviral immune response via double-stranded RNA-dependent RLR receptor-mediated necroptosis

PubMed Central

Wang, Wei; Wang, Wei-Hua; Azadzoi, Kazem M.; Su, Ning; Dai, Peng; Sun, Jianbin; Wang, Qin; Liang, Ping; Zhang, Wentao; Lei, Xiaoying; Yan, Zhen; Yang, Jing-Hua

2016-01-01

Viruses induce double-stranded RNA (dsRNA) in the host cells. The mammalian system has developed dsRNA-dependent recognition receptors such as RLRs that recognize the long stretches of dsRNA as PAMPs to activate interferon-mediated antiviral pathways and apoptosis in severe infection. Here we report an efficient antiviral immune response through dsRNA-dependent RLR receptor-mediated necroptosis against infections from different classes of viruses. We demonstrated that virus-infected A549 cells were efficiently killed in the presence of a chimeric RLR receptor, dsCARE. It measurably suppressed the interferon antiviral pathway but promoted IL-1β production. Canonical cell death analysis by morphologic assessment, phosphatidylserine exposure, caspase cleavage and chemical inhibition excluded the involvement of apoptosis and consistently suggested RLR receptor-mediated necroptosis as the underlying mechanism of infected cell death. The necroptotic pathway was augmented by the formation of RIP1-RIP3 necrosome, recruitment of MLKL protein and the activation of cathepsin D. Contributing roles of RIP1 and RIP3 were confirmed by gene knockdown. Furthermore, the necroptosis inhibitor necrostatin-1 but not the pan-caspase inhibitor zVAD impeded dsCARE-dependent infected cell death. Our data provides compelling evidence that the chimeric RLR receptor shifts the common interferon antiviral responses of infected cells to necroptosis and leads to rapid death of the virus-infected cells. This mechanism could be targeted as an efficient antiviral strategy. PMID:26935990

Orbitrap mass spectrometry characterization of hybrid chondroitin/dermatan sulfate hexasaccharide domains expressed in brain.

PubMed

Robu, Adrian C; Popescu, Laurentiu; Munteanu, Cristian V A; Seidler, Daniela G; Zamfir, Alina D

2015-09-15

In the central nervous system, chondroitin/dermatan sulfate (CS/DS) glycosaminoglycans (GAGs) modulate neurotrophic effects and glial cell maturation during brain development. Previous reports revealed that GAG composition could be responsible for CS/DS activities in brain. In this work, for the structural characterization of DS- and CS-rich domains in hybrid GAG chains extracted from neural tissue, we have developed an advanced approach based on high-resolution mass spectrometry (MS) using nanoelectrospray ionization Orbitrap in the negative ion mode. Our high-resolution MS and multistage MS approach was developed and applied to hexasaccharides obtained from 4- and 14-week-old mouse brains by GAG digestion with chondroitin B and in parallel with AC I lyase. The expression of DS- and CS-rich domains in the two tissues was assessed comparatively. The analyses indicated an age-related structural variability of the CS/DS motifs. The older brain was found to contain more structures and a higher sulfation of DS-rich regions, whereas the younger brain was found to be characterized by a higher sulfation of CS-rich regions. By multistage MS using collision-induced dissociation, we also demonstrated the incidence in mouse brain of an atypical [4,5-Δ-GlcAGalNAc(IdoAGalNAc)2], presenting a bisulfated CS disaccharide formed by 3-O-sulfate-4,5-Δ-GlcA and 6-O-sulfate-GalNAc moieties. Copyright © 2015 Elsevier Inc. All rights reserved.

Natural versus human control on subsurface salt dissolution and development of thousands of sinkholes along the Dead Sea coast

NASA Astrophysics Data System (ADS)

Abelson, Meir; Yechieli, Yoseph; Baer, Gidon; Lapid, Gil; Behar, Nicole; Calvo, Ran; Rosensaft, Marcelo

2017-06-01

One of the most hazardous results of the human-induced Dead Sea (DS) shrinkage is the formation of more than 6000 sinkholes over the last 25 years. The DS shrinkage caused eastward retreat of underground brine replaced by fresh groundwater, which in turn dissolved a subsurface salt layer, to generate cavities and collapse sinkholes. The areal growth rate of sinkhole clusters is considered the most pertinent proxy for sinkholes development. Analysis of light detection and ranging, digital elevation models, and interferometric synthetic aperture radar allows translation of the areal growth rate to a salt dissolution rate of the salt layer, revealing two peaks in the history of the salt dissolution rate. These peaks cannot be attributed to the decline of the DS level. Instead, we show that they are related to long-term variations of precipitation in the groundwater source region, the Judea Mountains, and the delayed response of the aquifer system between the mountains and the DS rift. This response is documented by groundwater levels and salinity variations. We thus conclude that while the DS level decline is the major trigger for sinkholes formation, the rainfall variations more than 30 km to the west dominate their evolution rate. The influence of increasing rainfall in the Judea Mountains reaches the DS at a typical time lag of 4 years, and the resulting increase in the salt dissolution rate lags by a total time of 5-6 years.

Quantitative controls on location and architecture of carbonate depositional sequences: Upper miocene, cabo de gata region, SE Spain

USGS Publications Warehouse

Franseen, E.K.; Goldstein, R.H.; Farr, M.R.

1997-01-01

Sequence stratigraphy, pinning-point relative sea-level curves, and magnetostratigraphy provide the quantitative data necessary to understand how rates of sea-level change and different substrate paleoslopes are dominant controls on accumulation rate, carbonate depositional sequence location, and internal architecture. Five third-order (1-10 my) and fourth-order (0.1-1.0 my) upper Miocene carbonate depositional sequences (DS1A, DS1B, DS2, DS3, TCC) formed with superimposed higher-frequency sea-level cycles in an archipelago setting in SE Spain. Overall, our study indicates when areas of high substrate slope (> 15??) are in shallow water, independent of climate, the location and internal architecture of carbonate deposits are not directly linked to sea-level position but, instead, are controlled by location of gently sloping substrates and processes of bypass. In contrast, if carbonate sediments are generated where substrates of low slope ( 15.6 cm/ky to ??? 2 cm/ky and overall relative sea level rose at rates of 17-21.4 cm/ky. Higher frequency sea-level rates were about 111 to more than 260 cm/ky, producing onlapping, fining- (deepening-) upward cycles. Decreasing accumulation rates resulted from decreasing surface area for shallow-water sediment production, drowning of shallow-water substrates, and complex sediment dispersal related to the archipelago setting. Typical systems tract and parasequence development should not be expected in "bypass ramp" settings; facies of onlapping strata do not track base level and are likely to be significantly different compared to onlapping strata associated with coastal onlap. Basal and upper DS2 reef megabreccias (indicating the transition from cool to warmer climatic conditions) were eroded from steep upslope positions and redeposited downslope onto areas of gentle substrate during rapid sea-level falls (> 22.7 cm/ky) of short duration. Such rapid sea-level falls and presence of steep slopes are not conducive to formation of forced regressive systems tracts composed of down-stepping reef clinoforms. The DS3 reefal platform formed where shallow water coincided with gently sloping substrates created by earlier deposition. Slow progradation (0.39-1.45 km/my) is best explained by the lack of an extensive bank top, progressively falling sea level, and low productivity resulting from siliciclastic debris and excess nutrients shed from nearby volcanic islands. Although DS3 strata were deposited during a third-order relative sea-level cycle, a typical transgressive systems tract is not recognizable, indicating that the initial relative rise in sea level was too rapid (??? 19 cm/ky). Downstepping reefs, forming a forced regressive systems tract, were deposited during the relative sea-level fall at the end of DS3, indicating that relatively slow rates of fall (10 cm/ky or less) over favorable paleoslope conditions are conducive to generation of forced regressive systems tracts consisting of downstepping reef clinoforms. The TCC sequence consists of four shallow-water sedimentary cycles that were deposited during a 400 ky to 100 ky time span. Such shallow-water cycles, typical of many platforms, form only where shallow water intersects gently sloping substrates. The relative thicknesses of cycles (< 2 m to 15 m thick), magnitudes of relative sea-level fluctuations associated with each cycle (25-30 m), high rates of relative sea-level fluctuations (minimum of 25-120 cm/ky), and the widespread distribution of similar TCC cycles in the Mediterranean and elsewhere are supportive of a glacio-eustatic

Quantitative controls on location and architecture of carbonate depositional sequences: upper miocene, cabo de gata region, se Spain

USGS Publications Warehouse

Franseen, E.K.; Goldstein, R.H.; Farr, M.R.

1998-01-01

Sequence stratigraphy, pinning-point relative sea-level curves, and magnetostratigraphy provide the quantitative data necessary to understand how rates of sea-level change and different substrate paleoslopes are dominant controls on accumulation rate, carbonate depositional sequence location, and internal architecture. Five third-order (1-10 my) and fourth-order (0.1-1.0 my) upper Miocene carbonate depositional sequences (DS1A, DS1B, DS2, DS3, TCC) formed with superimposed higher-frequency sea-level cycles in an archipelago setting in SE Spain. Overall, our study indicates when areas of high substrate slope (> 15??) are in shallow water, independent of climate, the location and internal architecture of carbonate deposits are not directly linked to sea-level position but, instead, are controlled by location of gently sloping substrates and processes of bypass. In contrast, if carbonate sediments are generated where substrates of low slope ( 15.6 cm/ky to ??? 2 cm/ky and overall relative sea level rose at rates of 17-21.4 cm/ky. Higher frequency sea-level rates were about 111 to more than 260 cm/ky, producing onlapping, fining- (deepening-) upward cycles. Decreasing accumulation rates resulted from decreasing surface area for shallow-water sediment production, drowning of shallow-water substrates, and complex sediment dispersal related to the archipelago setting. Typical systems tract and parasequence development should not be expected in "bypass ramp" settings; facies of onlapping strata do not track base level and are likely to be significantly different compared to onlapping strata associated with coastal onlap. Basal and upper DS2 reef megabreccias (indicating the transition from cool to warmer climatic conditions) were eroded from steep upslope positions and redeposited downslope onto areas of gentle substrate during rapid sea-level falls (> 22.7 cm/ky) of short duration. Such rapid sea-level falls and presence of steep slopes are not conducive to formation of forced regressive systems tracts composed of downstepping reef clinoforms. The DS3 reefal platform formed where shallow water coincided with gently sloping substrates created by earlier deposition. Slow progradation (0.39-1.45 km/my) is best explained by the lack of an extensive bank top, progressively falling sea level, and low productivity resulting from siliciclastic debris and excess nutrients shed from nearby volcanic islands. Although DS3 strata were deposited during a third-order relative sea-level cycle, a typical transgresse??e systems tract is not recognizable, indicating that the initial relative rise in sea level was too rapid (??? 19 cm/ky). Downstepping reefs, forming a forced regressive systems tract, were deposited during the relative sea-level fall at the end of DS3, indicating that relatively slow rates of fall (10 cm/ky or less) over favorable paleoslope conditions are conducive to generation of forced regressive systems tracts consisting of downstepping reef clinoforms. The TCC sequence consists of four shallow -water sedimentary cycles that were deposited during a 400 ky to 100 ky time span. Such shallow-water cycles, typical of many platforms, form only where shallow water intersects gently sloping substrates. The relative thicknesses of cycles (< 2 m to 15 m thick), magnitudes of relative sea-level fluctuations associated with each cycle (25-30 m), high rates of relative sea-level fluctuations (minimum of 25-120 cm/ky), and the widespread distribution of similar TCC cycles in the Mediterranean and elsewhere are supportive of a glacio-eustati

Hiding the evidence: two strategies for innate immune evasion by hemorrhagic fever viruses.

PubMed

Hastie, Kathryn M; Bale, Shridhar; Kimberlin, Christopher R; Saphire, Erica Ollmann

2012-04-01

The innate immune system is one of the first lines of defense against invading pathogens. Pathogens have, in turn, evolved different strategies to counteract these responses. Recent studies have illuminated how the hemorrhagic fever viruses Ebola and Lassa fever prevent host sensing of double-stranded RNA (dsRNA), a key hallmark of viral infection. The ebolavirus protein VP35 adopts a unique bimodal configuration to mask key cellular recognition sites on dsRNA. Conversely, the Lassa fever virus nucleoprotein actually digests the dsRNA signature. Collectively, these structural and functional studies shed new light on the mechanisms of pathogenesis of these viruses and provide new targets for therapeutic intervention. Copyright © 2012. Published by Elsevier B.V.

Air Force Boom Event Analyzer Recorder (BEAR): System Description

DTIC Science & Technology

1989-08-01

8000008 ATTRY RAN START (OO87FDFO) 98 INDMBI IQU 87FDFOE KID OF BAT. RAN 53 (0087A030) 99 KIDDATA EQ 87A030H END OF VALID DATA (0087FEOO) 100 VABSTI 1QU...192 PORTC DS.B 1 PORT A COiD 008040 193 PODBD D.3 1 PORT B DATA 008041 194 PORN DS.B I PORT B COmmID 008042 195 W17IN DS.3 1 KETBOARD INPUT VALUE...RVO.L *EIDAT,DO GET KID 000482 223C 397 VDVI.L SOA5A51,Dl LOAD MAS 000488 30c1 398 1A*73 IO11.1 Dl,[AO)+ WRITE MASK 59 00048A DICO 399 CMI. DO,AO CHCK

An in situ method for real-time monitoring of soil gas diffusivity

NASA Astrophysics Data System (ADS)

Laemmel, Thomas; Maier, Martin; Schack-Kirchner, Helmer; Lang, Friederike

2016-04-01

Soil aeration is an important factor for the biogeochemistry of soils. Generally, gas exchange between soil and atmosphere is assumed to be governed by molecular diffusion and by this way fluxes can be calculated using by Fick's Law. The soil gas diffusion coefficient DS represents the proportional factor between the gas flux and the gas concentration gradient in the soil and reflects the ability of the soil to "transport passively" gas through the soil. One common way to determine DS is taking core samples in the field and measuring DS in the lab. Unfortunately this method is destructive and laborious and it can only reflect a small fraction of the whole soil. As a consequence, uncertainty about the resulting effective diffusivity on the profile scale, i.e. the real aeration status remains. We developed a method to measure and monitor DS in situ. The set-up consists of a custom made gas sampling device, the continuous injection of an inert tracer gas and inverse gas transport modelling in the soil. The gas sampling device has seven sampling depths (from 0 to -43 cm of depth) and can be easily installed into vertical holes drilled by an auger, which allows for fast installation of the system. Helium (He) as inert tracer gas was injected continuously at the lower end of the device. The resulting steady state distribution of He was used to deduce the DS depth distribution of the soil. For Finite Element Modeling of the gas-sampling-device/soil system the program COMSOL was used. We tested our new method both in the lab and in a field study and compared the results with a reference lab method using soil cores. DS profiles obtained by our in-situ method were consistent with DS profiles determined based on soil core analyses. Soil gas profiles could be measured with a temporal resolution of 30 minutes. During the field study, there was an important rain event and we could monitor the decrease in soil gas diffusivity in the top soil due to water infiltration. The effect of soil water infiltration deeper into the soil on soil gas diffusivity could be observed during the following hours. Our new DS determination device can be quickly and easily installed and allows for monitoring continuously soil gas transport over a long time. It allows following modifications of soil gas diffusivity due to rain events. In addition it enables the analysis of non-diffusive soil gas transport processes.

Confidence in the efficacy and safety of dietary supplements among United States active duty army personnel

PubMed Central

2012-01-01

Background United States Army Soldiers regularly use dietary supplements (DS) to promote general health, enhance muscle strength, and increase energy, but limited scientific evidence supports the use of many DS for these benefits. This study investigated factors associated with Soldiers’ confidence in the efficacy and safety of DS, and assessed Soldiers’ knowledge of federal DS regulatory requirements. Methods Between 2006 and 2007, 990 Soldiers were surveyed at 11 Army bases world-wide to assess their confidence in the effectiveness and safety of DS, knowledge of federal DS regulations, demographic characteristics, lifestyle-behaviors and DS use. Results A majority of Soldiers were at least somewhat confident that DS work as advertised (67%) and thought they are safe to consume (71%). Confidence in both attributes was higher among regular DS users than non-users. Among users, confidence in both attributes was positively associated with rank, self-rated diet quality and fitness level, education, and having never experienced an apparent DS-related adverse event. Fewer than half of Soldiers knew the government does not require manufacturers to demonstrate efficacy, and almost a third incorrectly believed there are effective pre-market federal safety requirements for DS. Conclusions Despite limited scientific evidence supporting the purported benefits and safety of many popular DS, most Soldiers were confident that DS are effective and safe. The positive associations between confidence and DS use should be considered when developing DS-related interventions or policies. Additionally, education to clarify Soldiers’ misperceptions about federal DS safety and efficacy regulations is warranted. PMID:23051046

MAI statistics estimation and analysis in a DS-CDMA system

NASA Astrophysics Data System (ADS)

Alami Hassani, A.; Zouak, M.; Mrabti, M.; Abdi, F.

2018-05-01

A primary limitation of Direct Sequence Code Division Multiple Access DS-CDMA link performance and system capacity is multiple access interference (MAI). To examine the performance of CDMA systems in the presence of MAI, i.e., in a multiuser environment, several works assumed that the interference can be approximated by a Gaussian random variable. In this paper, we first develop a new and simple approach to characterize the MAI in a multiuser system. In addition to statistically quantifying the MAI power, the paper also proposes a statistical model for both variance and mean of the MAI for synchronous and asynchronous CDMA transmission. We show that the MAI probability density function (PDF) is Gaussian for the equal-received-energy case and validate it by computer simulations.

Suppression of DS1 Phosphatidic Acid Phosphatase Confirms Resistance to Ralstonia solanacearum in Nicotiana benthamiana

PubMed Central

Nakano, Masahito; Nishihara, Masahiro; Yoshioka, Hirofumi; Takahashi, Hirotaka; Sawasaki, Tatsuya; Ohnishi, Kouhei; Hikichi, Yasufumi; Kiba, Akinori

2013-01-01

Nicotiana benthamiana is susceptible to Ralstonia solanacearum. To analyze molecular mechanisms for disease susceptibility, we screened a gene-silenced plant showing resistance to R. solanacearum, designated as DS1 (Disease suppression 1). The deduced amino acid sequence of DS1 cDNA encoded a phosphatidic acid phosphatase (PAP) 2. DS1 expression was induced by infection with a virulent strain of R. solanacearum in an hrp-gene-dependent manner. DS1 rescued growth defects of the temperature-sensitive ∆lpp1∆dpp1∆pah1 mutant yeast. Recombinant DS1 protein showed Mg2+-independent PAP activity. DS1 plants showed reduced PAP activity and increased phosphatidic acid (PA) content. After inoculation with R. solanacearum, DS1 plants showed accelerated cell death, over-accumulation of reactive oxygen species (ROS), and hyper-induction of PR-4 expression. In contrast, DS1-overexpressing tobacco plants showed reduced PA content, greater susceptibility to R. solanacearum, and reduced ROS production and PR-4 expression. The DS1 phenotype was partially compromised in the plants in which both DS1 and NbCoi1 or DS1 and NbrbohB were silenced. These results show that DS1 PAP may affect plant immune responses related to ROS and JA cascades via regulation of PA levels. Suppression of DS1 function or DS1 expression could rapidly activate plant defenses to achieve effective resistance against Ralstonia solanacearum. PMID:24073238

NASA Astrophysics Data System (ADS)

2018-05-01

The Seebeck coefficient has been used to investigate QCB in Cr alloys [8,9]. Plots of d S /d T (in the limit T → 2 K) as function of concentration for the (Cr97.8Si2.2)100-yMoy [8] and the (Cr84Re16)100-zVz [9] alloy systems depicted anomalies at the QCP. The possibility of QCB in the (Cr100-xAlx)95Mo5 alloy system is explored by analysing the S(T) data of Fig. 1 by performing a linear-least-squares fit through the 2 K < T < 6.5 K data points. The gradient was taken as dS / dT|T → 2K . Fig. 8 shows dS / dT|T → 2K for concentrations in the range 0.5 ≤ x ≤ 8.6. It increases rapidly to a maximum at x = 1.0, then decreases on further Al addition and displays a minimum just above x = 1.4. This is the concentration where magnetism is seen to disappear on the TN(x) magnetic phase diagram. dS / dT|T → 2K shows a second minimum just above x = 4.4, i.e. corresponding to the concentration where magnetism reappears on the TN(x) magnetic phase diagram (see Fig. 17). Similar minima were also observed at the QCP in the (Cr84Re16)100-zVz [9] and (Cr86Ru14)100-rVr [13] alloy systems. The relatively large error bars in Fig. 8 originate from the large errors in the fitting routine due to a significant scatter in the original Seebeck coefficient data at low temperatures. The solid line through the dS / dT|T → 2K data points is a guide to the eye, while the dotted vertical lines indicate the boundaries between the ISDW, P and CSDW phases. The minima observed in the dS / dT|T → 2K curve correlate to these boundaries.

Visual and Quantitative Assessment of Coronary Stenoses at Angiography Versus Fractional Flow Reserve: The Impact of Risk Factors.

PubMed

Adjedj, Julien; Xaplanteris, Panagiotis; Toth, Gabor; Ferrara, Angela; Pellicano, Mariano; Ciccarelli, Giovanni; Floré, Vincent; Barbato, Emanuele; De Bruyne, Bernard

2017-07-01

The correlation between angiographic assessment of coronary stenoses and fractional flow reserve (FFR) is weak. Whether and how risk factors impact the diagnostic accuracy of angiography is unknown. We sought to evaluate the diagnostic accuracy of angiography by visual estimate and by quantitative coronary angiography when compared with FFR and evaluate the influence of risk factors (RF) on this accuracy. In 1382 coronary stenoses (1104 patients), percent diameter stenosis by visual estimation (DS VE ) and by quantitative coronary angiography (DS QCA ) was compared with FFR. Patients were divided into 4 subgroups, according to the presence of RFs, and the relationship between DS VE , DS QCA , and FFR was analyzed. Overall, DS VE was significantly higher than DS QCA ( P <0.0001); nonetheless, when examined by strata of DS, DS VE was significantly smaller than DS QCA in mild stenoses, although the reverse held true for severe stenoses. Compared with FFR, a large scatter was observed for both DS VE and DS QCA . When using a dichotomous FFR value of 0.80, C statistic was significantly higher for DS VE than for DS QCA (0.712 versus 0.640, respectively; P <0.001). C statistics for DS VE decreased progressively as RFs accumulated (0.776 for ≤1 RF, 0.750 for 2 RFs, 0.713 for 3 RFs and 0.627 for ≥4 RFs; P =0.0053). In addition, in diabetics, the relationship between FFR and angiographic indices was particularly weak (C statistics: 0.524 for DS VE and 0.511 for DS QCA ). Overall, DS VE has a better diagnostic accuracy than DS QCA to predict the functional significance of coronary stenosis. The predictive accuracy of angiography is moderate in patients with ≤1 RFs, but weakens as RFs accumulate, especially in diabetics. © 2017 American Heart Association, Inc.

A novel label-free fluorescence strategy for methyltransferase activity assay based on dsDNA-templated copper nanoparticles coupled with an endonuclease-assisted signal transduction system.

PubMed

Lai, Q Q; Liu, M D; Gu, C C; Nie, H G; Xu, X J; Li, Z H; Yang, Z; Huang, S M

2016-02-21

Evaluating DNA methyltransferase (MTase) activity has received considerable attention due to its significance in the fields of early cancer clinical diagnostics and drug discovery. Herein, we proposed a novel label-free fluorescence method for MTase activity assay by coupling double-stranded DNA (dsDNA)-templated copper nanoparticles (CuNPs) with an endonuclease-assisted signal transduction system. In this strategy, dsDNA molecules were first methylated by DNA adenine methylation (Dam) MTase and then cleaved by the methylation-sensitive restriction endonuclease DpnI. The cleaved DNA fragments could not act as efficient templates for the formation of fluorescent CuNPs and thus no fluorescence signal was produced. Under optimized experimental conditions, the developed strategy exhibited a sensitive fluorescence response to Dam MTase activity. This strategy was also demonstrated to provide an excellent platform to the inhibitor screening for Dam MTase. These results demonstrated the great potential for the practical applications of the proposed strategy for Dam MTase activity assay.

Treatment Using the SpyGlass Digital System in a Patient with Hepatolithiasis after a Whipple Procedure.

PubMed

Harima, Hirofumi; Hamabe, Kouichi; Hisano, Fusako; Matsuzaki, Yuko; Itoh, Tadahiko; Sanuki, Kazutoshi; Sakaida, Isao

2018-05-23

An 89-year-old man was referred to our hospital for treatment of hepatolithiasis causing recurrent cholangitis. He had undergone a prior Whipple procedure. Computed tomography demonstrated left-sided hepatolithiasis. First, we conducted peroral direct cholangioscopy (PDCS) using an ultraslim endoscope. Although PDCS was successfully conducted, it was unsuccessful in removing all the stones. The stones located in the B2 segment were difficult to remove because the endoscope could not be inserted deeply into this segment due to the small size of the intrahepatic bile duct. Next, we substituted the endoscope with an upper gastrointestinal endoscope. After positioning the endoscope, the SpyGlass digital system (SPY-DS) was successfully inserted deep into the B2 segment. Upon visualizing the residual stones, we conducted SPY-DS-guided electrohydraulic lithotripsy. The stones were disintegrated and completely removed. In cases of PDCS failure, a treatment strategy using the SPY-DS can be considered for patients with hepatolithiasis after a Whipple procedure.

Nickel-63 production in copper samples exposed to the Hiroshima atomic bomb: estimation based on an excitation function obtained by neutron irradiation experiments.

PubMed

Takamiya, K; Imanaka, T; Ota, Y; Akamine, M; Shibata, S; Shibata, T; Ito, Y; Imamura, M; Uwamino, Y; Nogawa, N; Baba, M; Iwasaki, S; Matsuyama, S

2008-07-01

The upper and lower limits of the excitation function of the (63)Cu(n,p)(63)Ni reaction were experimentally determined, and the number of (63)Ni nuclei produced in copper samples exposed to atomic bomb neutrons in Hiroshima was estimated by using the experimental excitation functions and the neutron fluences given in the DS02 dosimetry system. The estimated number of (63)Ni nuclei was compared with that measured and with that calculated using the DS02 dosimetry system and the corresponding ENDF/B-VI cross section. In comparison with DS02, there is about a 60% maximum difference in (63)Ni production at the hypocenter when the experimental upper cross section values are used. The difference becomes smaller at greater distances from the hypocenter and decreases, for example, to less than 30 and 5% when using the upper and lower experimental cross sections at 1,000 m, respectively.

Comparing Charge Transport in Oligonucleotides: RNA:DNA Hybrids and DNA Duplexes.

PubMed

Li, Yuanhui; Artés, Juan M; Qi, Jianqing; Morelan, Ian A; Feldstein, Paul; Anantram, M P; Hihath, Joshua

2016-05-19

Understanding the electronic properties of oligonucleotide systems is important for applications in nanotechnology, biology, and sensing systems. Here the charge-transport properties of guanine-rich RNA:DNA hybrids are compared to double-stranded DNA (dsDNA) duplexes with identical sequences. The conductance of the RNA:DNA hybrids is ∼10 times higher than the equivalent dsDNA, and conformational differences are determined to be the primary reason for this difference. The conductance of the RNA:DNA hybrids is also found to decrease more rapidly than dsDNA when the length is increased. Ab initio electronic structure and Green's function-based density of states calculations demonstrate that these differences arise because the energy levels are more spatially distributed in the RNA:DNA hybrid but that the number of accessible hopping sites is smaller. These combination results indicate that a simple hopping model that treats each individual guanine as a hopping site is insufficient to explain both a higher conductance and β value for RNA:DNA hybrids, and larger delocalization lengths must be considered.

Cognitive Code-Division Channelization

DTIC Science & Technology

2011-04-01

22] G. N. Karystinos and D. A. Pados, “New bounds on the total squared correlation and optimum design of DS - CDMA binary signature sets,” IEEE Trans...Commun., vol. 51, pp. 48-51, Jan. 2003. [23] C. Ding, M. Golin, and T. Klve, “Meeting the Welch and Karystinos- Pados bounds on DS - CDMA binary...receiver pair coexisting with a primary code-division multiple-access ( CDMA ) system. Our objective is to find the optimum transmitting power and code

Self-Encoded Spread Spectrum Modulation for Robust Anti-Jamming Communication

DTIC Science & Technology

2009-06-30

experience in both theoretical and experimental aspects of RF and optical communications, multi-user CDMA systems, transmitter precoding and code...the performance of DS - and FH-SESS modulation in the presence of worst-case jamming, develop innovative SESS schemes that further exploit time and...Determine BER and AJ performance of the feedback and iterative detectors in DS -SESS under pulsed-noise and multi-tone jamming • Task 2: Develop a scheme

DS-MAC: differential service medium access control design for wireless medical information systems.

PubMed

Yuan, Xiaojing; Bagga, Sumegha; Shen, Jian; Balakrishnan, M; Benhaddou, D

2008-01-01

The integration of wireless networking technologies with medical information systems (telemedicine) have a significant impact on healthcare services provided to our society. Applications of telemedicine range from personalized medicine to affordable healthcare for underserved population. Though wireless technologies and medical informatics are individually progressing rapidly, wireless networking for healthcare systems is still at a very premature stage. In this paper we first present our open architecture for medical information systems that integrates both wired and wireless networked data acquisition systems. We then present the implementation at the physical layer and differential service MAC design that adapts channel provisioning based on the information criticality. Performance evaluation using analytical modeling and simulation shows that our DS-MAC provides differentiated services for emergency, warning, and normal traffic.

Thioredoxin system in obligate anaerobe Desulfovibrio desulfuricans: Identification and characterization of a novel thioredoxin 2.

PubMed

Sarin, Ritu; Sharma, Yagya D

2006-07-05

Metal corroding sulfate reducing bacteria have been poorly characterized at molecular level due to difficulties pertaining to isolation and handling of anaerobes. We report here for the first time the presence and characterization of thioredoxin 2 in an obligate anaerobic dissimilatory sulfate reducing bacterium Desulfovibrio desulfuricans. In silico analysis of the D. desulfuricans genome revealed the presence of thioredoxin 1 (dstrx1), thioredoxin 2 (dstrx2) and thioredoxin reductase (dstrxR) genes. These genes were found to be actively expressed by the bacteria under the anaerobic growth conditions. We have overexpressed the anaerobic thioredoxin genes in E. coli to produce functionally active recombinant proteins. Recombinant DsTrxR recognized both DsTrx1 and DsTrx2 as its substrate. Mutation studies revealed that the activity of DsTrx2 can be completely abolished with a single amino acid mutation (C69A) in the signature motif 'WCGPC'. Furthermore, the N-terminal domain of DsTrx2 containing two extra CXXC motifs was found to have a negative regulation on its biochemical activity. In conclusion, we have shown the presence of thioredoxin 2 for the first time in an obligate anaerobe which in this anaerobe may be required for its survival under either oxidative stress conditions or metal ion hemostasis.

Disrupted fornix integrity in children with chromosome 22q11.2 deletion syndrome

PubMed Central

Deng, Yi; Goodrich-Hunsaker, Naomi J.; Cabaral, Margarita; Amaral, David G.; Buonocore, Michael H.; Harvey, Danielle; Kalish, Kristopher; Carmichael, Owen; Schumann, Cynthia M.; Lee, Aaron; Dougherty, Robert F.; Perry, Lee M.; Wandell, Brian A.; Simon, Tony J.

2015-01-01

The fornix is the primary subcortical output fiber system of the hippocampal formation. In children with 22q11.2 deletion syndrome (22q11.2DS), hippocampal volume reduction has been commonly reported, but few studies as yet have evaluated the integrity of the fornix. Therefore, we investigated the fornix of 45 school-aged children with 22q11.2DS and 38 matched typically developing (TD) children. Probabilistic diffusion tensor imaging (DTI) tractography was used to reconstruct the body of fornix in each child's brain native space. Compared with children, significantly lower fractional anisotropy (FA) and higher radial diffusivity (RD) was observed bilaterally in the body of the fornix in children with 22q11.2DS. Irregularities were especially prominent in the posterior aspect of the fornix where it emerges from the hippocampus. Smaller volumes of hippocampal formations were also found in the 22q11.2DS group. The reduced hippocampal volumes were correlated with fornix lower FA and higher RD in the right hemisphere. Our findings provide neuroanatomical evidence of disrupted hippocampal connectivity in children with 22q11.2DS, which may help to further understand the biological basis for spatial impairments, affective regulation, and other factors related to the ultra-high risk for schizophrenia in this population. PMID:25748884

HNE-modified proteins in Down syndrome: Involvement in development of Alzheimer disease neuropathology.

PubMed

Barone, Eugenio; Head, Elizabeth; Butterfield, D Allan; Perluigi, Marzia

2017-10-01

Down syndrome (DS), trisomy of chromosome 21, is the most common genetic form of intellectual disability. The neuropathology of DS involves multiple molecular mechanisms, similar to AD, including the deposition of beta-amyloid (Aβ) into senile plaques and tau hyperphosphorylationg in neurofibrillary tangles. Interestingly, many genes encoded by chromosome 21, in addition to being primarily linked to amyloid-beta peptide (Aβ) pathology, are responsible for increased oxidative stress (OS) conditions that also result as a consequence of reduced antioxidant system efficiency. However, redox homeostasis is disturbed by overproduction of Aβ, which accumulates into plaques across the lifespan in DS as well as in AD, thus generating a vicious cycle that amplifies OS-induced intracellular changes. The present review describes the current literature that demonstrates the accumulation of oxidative damage in DS with a focus on the lipid peroxidation by-product, 4-hydroxy-2-nonenal (HNE). HNE reacts with proteins and can irreversibly impair their functions. We suggest that among different post-translational modifications, HNE-adducts on proteins accumulate in DS brain and play a crucial role in causing the impairment of glucose metabolism, neuronal trafficking, protein quality control and antioxidant response. We hypothesize that dysfunction of these specific pathways contribute to accelerated neurodegeneration associated with AD neuropathology. Copyright © 2017 Elsevier Inc. All rights reserved.

A systems biology approach to Down syndrome: identification of Notch/Wnt dysregulation in a model of stem cells aging.

PubMed

Cairney, C J; Sanguinetti, G; Ranghini, E; Chantry, A D; Nostro, M C; Bhattacharyya, A; Svendsen, C N; Keith, W N; Bellantuono, I

2009-04-01

Stem cells are central to the development and maintenance of many tissues. This is due to their capacity for extensive proliferation and differentiation into effector cells. More recently it has been shown that the proliferative and differentiative ability of stem cells decreases with age, suggesting that this may play a role in tissue aging. Down syndrome (DS), is associated with many of the signs of premature tissue aging including T-cell deficiency, increased incidence of early Alzheimer-type, Myelodysplastic-type disease and leukaemia. Previously we have shown that both hematopoietic (HSC) and neural stem cells (NSC) in patients affected by DS showed signs of accelerated aging. In this study we tested the hypothesis that changes in gene expression in HSC and NSC of patients affected by DS reflect changes occurring in stem cells with age. The profiles of genes expressed in HSC and NSC from DS patients highlight pathways associated with cellular aging including a downregulation of DNA repair genes and increases in proapoptotic genes, s-phase cell cycle genes, inflammation and angiogenesis genes. Interestingly, Notch signaling was identified as a potential hub, which when deregulated may drive stem cell aging. These data suggests that DS is a valuable model to study early events in stem cell aging.

Moving from Survival to Healthy Survival through Child Health Screening and Early Intervention Services Under Rashtriya Bal Swasthya Karyakram (RBSK).

PubMed

Singh, Arun K; Kumar, Rakesh; Mishra, C K; Khera, Ajay; Srivastava, Anubhav

2015-11-01

For negating the impact of early adversities on the development and ensuring a healthy, dynamic future for all children, Ministry of Health and Family Welfare in 2013 launched a programme for child health screening and early intervention services as Rashtriya Bal Swasthya Karyakram (RBSK) which aims to improve the quality of life with special focus on improving cognition and survival outcomes for "at risk" children. It has a systemic approach of prevention, early identification and management of 30 health conditions distributed under 4Ds: Defects at birth, Diseases, Deficiencies and Developmental delays including Disabilities spread over birth to 18 y of age in a holistic manner. There is a dedicated 4 member Mobile Health team for community screening and a dedicated 14 member team at District Early Intervention Center (DEIC) for comprehensive management. Existing health infrastructure and personnel are also integrated and utilized in this endeavor. Defects at birth are screened at Delivery points, home visits by accredited social health activist (ASHA), Anganwadi centers and at schools. Developmental delays are evaluated at DEIC through a multidisciplinary team with interdisciplinary approach. Five thousand four hundred eighteen dedicated Mobile Health teams have screened a total of 12.19 crore children till Dec.14. From April to Dec. 2014, 4.20 crore children were screened, of which birth to 6-y-old children were 2.13 crore while 2.07 crore were from 6 to 18 y. 17.7 lakh children were referred to tertiary centers and 6.2 lakh availed tertiary care. 50.7 lakhs were found positive for 4Ds; 1.35 lakhs were birth defects. RBSK is a step towards universal health care for free assured services.

Association of Burden of Atrial Fibrillation With Risk of Ischemic Stroke in Adults With Paroxysmal Atrial Fibrillation: The KP-RHYTHM Study.

PubMed

Go, Alan S; Reynolds, Kristi; Yang, Jingrong; Gupta, Nigel; Lenane, Judith; Sung, Sue Hee; Harrison, Teresa N; Liu, Taylor I; Solomon, Matthew D

2018-05-16

Atrial fibrillation is a potent risk factor for stroke, but whether the burden of atrial fibrillation in patients with paroxysmal atrial fibrillation independently influences the risk of thromboembolism remains controversial. To determine if the burden of atrial fibrillation characterized using noninvasive, continuous ambulatory monitoring is associated with the risk of ischemic stroke or arterial thromboembolism in adults with paroxysmal atrial fibrillation. This retrospective cohort study conducted from October 2011 and October 2016 at 2 large integrated health care delivery systems used an extended continuous cardiac monitoring system to identify adults who were found to have paroxysmal atrial fibrillation on 14-day continuous ambulatory electrocardiographic monitoring. The burden of atrial fibrillation was defined as the percentage of analyzable wear time in atrial fibrillation or flutter during the up to 14-day monitoring period. Ischemic stroke and other arterial thromboembolic events occurring while patients were not taking anticoagulation were identified through November 2016 using electronic medical records and were validated by manual review. We evaluated the association of the burden of atrial fibrillation with thromboembolism while not taking anticoagulation after adjusting for the Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA) or CHA2DS2-VASc stroke risk scores. Among 1965 adults with paroxysmal atrial fibrillation, the mean (SD) age was 69 (11.8) years, 880 (45%) were women, 496 (25%) were persons of color, the median ATRIA stroke risk score was 4 (interquartile range [IQR], 2-7), and the median CHA2DS2-VASc score was 3 (IQR, 1-4). The median burden of atrial fibrillation was 4.4% (IQR ,1.1%-17.23%). Patients with a higher burden of atrial fibrillation were less likely to be women or of Hispanic ethnicity, but had more prior cardioversion attempts compared with those who had a lower burden. After adjusting for either ATRIA or CHA2DS2-VASc stroke risk scores, the highest tertile of atrial fibrillation burden (≥11.4%) was associated with a more than 3-fold higher adjusted rate of thromboembolism while not taking anticoagulants (adjusted hazard ratios, 3.13 [95% CI, 1.50-6.56] and 3.16 [95% CI, 1.51-6.62], respectively) compared with the combined lower 2 tertiles of atrial fibrillation burden. Results were consistent across demographic and clinical subgroups. A greater burden of atrial fibrillation is associated with a higher risk of ischemic stroke independent of known stroke risk factors in adults with paroxysmal atrial fibrillation.

The type of adjuvant strongly influences the T-cell response during nanoparticle-based immunization

PubMed Central

Knuschke, Torben; Epple, Matthias; Westendorf, Astrid M

2014-01-01

Potent vaccines require the ability to effectively induce immune responses. Especially for the control of infectious diseases with intracellular pathogens, like viruses or bacteria, potent T-cell responses are indispensable. Several delivery systems such as nanoparticles have been considered to boost the immunogenicity of pathogen derived peptides or subunits for the induction of potent T-cell responses. Since they can be further functionalized with immunostimulants, like Toll-like receptor (TLR) agonists, they improve the response by enhanced activation of the innate immune system. Currently, TLR agonists like unmethylated CpG oligonucleotides and the synthetic dsRNA derivate polyriboinosinic acid-polyribocytidylic acid (poly[I:C]) are widely used as vaccine adjuvants. CpG and poly(I:C) trigger different TLRs and therefore show differential signal transduction. Recently, we established biodegradable calcium phosphate (CaP) nanoparticles as potent T cell inducing vaccination vehicles. In this commentary we discuss the role of CpG and poly(I:C) for the effective induction of virus-specific T cells during immunization with CaP nanoparticles. The presented results underline the importance of the right formulation of vaccines for specific immunization purpose. PMID:23982325

76 FR 27373 - 30-Day Notice of Proposed Information Collection: Medical Examination Forms for Immigrant or...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-11

...: Medical Examination Forms for Immigrant or Refugee Applicants ACTION: Notice of request for public comment... Examination for Immigrant or Refugee Applicant. OMB Control Number: 1405-0113. Type of Request: Revision of a.../VO). Form Number: DS-2053, DS-2054, DS-3030, DS-3024, DS-3025, DS-3026. Respondents: Immigrant visa...

75 FR 25911 - 30-Day Notice of Proposed Information Collection: Forms DS-2053, DS-2054; Medical Examination for...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-10

... DEPARTMENT OF STATE [Public Notice 6995] 30-Day Notice of Proposed Information Collection: Forms DS-2053, DS-2054; Medical Examination for Immigrant or Refugee Applicant; DS- 3030, Chest X-Ray and..., Medical Examination for Immigrant or Refugee Applicant (2007 Technical Instructions); and DS-3030, Chest X...

Luciferase reporter assay in Drosophila and mammalian tissue culture cells

PubMed Central

Yun, Chi

2014-01-01

Luciferase reporter gene assays are one of the most common methods for monitoring gene activity. Because of their sensitivity, dynamic range, and lack of endogenous activity, luciferase assays have been particularly useful for functional genomics in cell-based assays, such as RNAi screening. This unit describes delivery of two luciferase reporters with other nucleic acids (siRNA /dsRNA), measurement of the dual luciferase activities, and analysis of data generated. The systematic query of gene function (RNAi) combined with the advances in luminescent technology have made it possible to design powerful whole genome screens to address diverse and significant biological questions. PMID:24652620

Glycogen Phosphorylase and Glycogen Synthase: Gene Cloning and Expression Analysis Reveal Their Role in Trehalose Metabolism in the Brown Planthopper, Nilaparvata lugens Stål (Hemiptera: Delphacidae)

PubMed Central

Zhang, Lu; Wang, Huijuan; Chen, Jianyi; Shen, Qida; Wang, Shigui; Xu, Hongxing

2017-01-01

RNA interference has been used to study insects’ gene function and regulation. Glycogen synthase (GS) and glycogen phosphorylase (GP) are two key enzymes in carbohydrates’ conversion in insects. Glycogen content and GP and GS gene expression in several tissues and developmental stages of the Brown planthopper Nilaparvata lugens Stål (Hemiptera: Delphacidae) were analyzed in the present study, using quantitative reverse-transcription polymerase chain reaction to determine their response to double-stranded trehalases (dsTREs), trehalose-6-phosphate synthases (dsTPSs), and validamycin injection. The highest expression of both genes was detected in the wing bud, followed by leg and head tissues, and different expression patterns were shown across the developmental stages analyzed. Glycogen content significantly decreased 48 and 72 h after dsTPSs injection and 48 h after dsTREs injection. GP expression increased 48 h after dsTREs and dsTPSs injection and significantly decreased 72 h after dsTPSs, dsTRE1-1, and dsTRE1-2 injection. GS expression significantly decreased 48 h after dsTPS2 and dsTRE2 injection and 72 h after dsTRE1-1 and dsTRE1-2 injection. GP and GS expression and glycogen content significantly decreased 48 h after validamycin injection. The GP activity significantly decreased 48 h after validamycin injection, while GS activities of dsTPS1 and dsTRE2 injection groups were significantly higher than that of double-stranded GFP (dsGFP) 48 h after injection, respectively. Thus, glycogen is synthesized, released, and degraded across several insect tissues according to the need to maintain stable trehalose levels. PMID:28365765

Thermal transport properties, magnetic susceptibility and neutron diffraction studies of the (Cr100-xAlx)95Mo5 alloy system

NASA Astrophysics Data System (ADS)

Muchono, B.; Sheppard, C. J.; Venter, A. M.; Prinsloo, A. R. E.

2018-05-01

The Seebeck coefficient has been used to investigate QCB in Cr alloys [8,9]. Plots of d S /d T (in the limit T → 2 K) as function of concentration for the (Cr97.8Si2.2)100-yMoy [8] and the (Cr84Re16)100-zVz [9] alloy systems depicted anomalies at the QCP. The possibility of QCB in the (Cr100-xAlx)95Mo5 alloy system is explored by analysing the S(T) data of Fig. 1 by performing a linear-least-squares fit through the 2 K < T < 6.5 K data points. The gradient was taken as dS / dT|T → 2K . Fig. 8 shows dS / dT|T → 2K for concentrations in the range 0.5 ≤ x ≤ 8.6. It increases rapidly to a maximum at x = 1.0, then decreases on further Al addition and displays a minimum just above x = 1.4. This is the concentration where magnetism is seen to disappear on the TN(x) magnetic phase diagram. dS / dT|T → 2K shows a second minimum just above x = 4.4, i.e. corresponding to the concentration where magnetism reappears on the TN(x) magnetic phase diagram (see Fig. 17). Similar minima were also observed at the QCP in the (Cr84Re16)100-zVz [9] and (Cr86Ru14)100-rVr [13] alloy systems. The relatively large error bars in Fig. 8 originate from the large errors in the fitting routine due to a significant scatter in the original Seebeck coefficient data at low temperatures. The solid line through the dS / dT|T → 2K data points is a guide to the eye, while the dotted vertical lines indicate the boundaries between the ISDW, P and CSDW phases. The minima observed in the dS / dT|T → 2K curve correlate to these boundaries.

Anti-telomere antibodies in systemic lupus erythematosus (SLE): a comparison with five antinuclear antibody assays in 430 patients with SLE and other rheumatic diseases.

PubMed

Salonen, E M; Miettinen, A; Walle, T K; Koskenmies, S; Kere, J; Julkunen, H

2004-10-01

To investigate the prevalence and diagnostic significance of antibodies against telomeric DNA in systemic lupus erythematosus (SLE) and other autoimmune rheumatic diseases, and to make comparisons with five conventional anti-DNA or anti-nuclear antibody (ANA) assays. Antibodies to telomeres, which are highly repetitive sequences of DNA (TTAGGG/CCCTAA) at the end of eukaryotic chromosomes, were measured by an enzyme linked immunosorbent assay (ELISA) in 305 patients with SLE and 125 patients with other autoimmune rheumatic diseases (78 rheumatoid arthritis, 32 primary Sjögren's syndrome, eight mixed connective tissue disease, seven miscellaneous rheumatic diseases). Other assays used were two commercial ELISA assays for anti-dsDNA using calf thymus as antigen, Crithidialuciliae immunofluorescence, and radioimmunoassay (RIA) for anti-dsDNA and immunofluorescence using Hep-2 cells for ANA. The prevalence of anti-telomere in SLE was 60%, v 5% in rheumatoid arthritis and 18% in other autoimmune rheumatic diseases. Specificity of anti-telomere for SLE was 91%; positive and negative predictive values were 95% and 46%, respectively. For anti-dsDNA by two ELISA assays using calf thymus as antigen, sensitivities were 69% and 29% and specificities 66% and 96%, respectively. Other anti-dsDNA assays had low sensitivities (RIA 43%, Crithidia immunofluorescence 13%). The association of anti-telomere with a history of nephritis in patients with SLE was stronger (p = 0.005) than by any other assay (p = 0.006-0.999). The correlations between the different assays were good (p<0.001 for all comparisons). The new ELISA for anti-telomere antibodies using standardised human dsDNA as antigen is a sensitive and highly specific test for SLE.

Creation of an Open Framework for Point-of-Care Computer-Assisted Reporting and Decision Support Tools for Radiologists.

PubMed

Alkasab, Tarik K; Bizzo, Bernardo C; Berland, Lincoln L; Nair, Sujith; Pandharipande, Pari V; Harvey, H Benjamin

2017-09-01

Decreasing unnecessary variation in radiology reporting and producing guideline-concordant reports is fundamental to radiology's success in value-based payment models and good for patient care. In this article, we present an open authoring system for point-of-care clinical decision support tools integrated into the radiologist reporting environment referred to as the computer-assisted reporting and decision support (CAR/DS) framework. The CAR/DS authoring system, described herein, includes: (1) a definition format for representing radiology clinical guidelines as structured, machine-readable Extensible Markup Language documents and (2) a user-friendly reference implementation to test the fidelity of the created definition files with the clinical guideline. The proposed definition format and reference implementation will enable content creators to develop CAR/DS tools that voice recognition software (VRS) vendors can use to extend the commercial tools currently in use. In making the definition format and reference implementation software freely available, we hope to empower individual radiologists, expert groups such as the ACR, and VRS vendors to develop a robust ecosystem of CAR/DS tools that can further improve the quality and efficiency of the patient care that our field provides. We hope that this initial effort can serve as the basis for a community-owned open standard for guideline definition that the imaging informatics and VRS vendor communities will embrace and strengthen. To this end, the ACR Assist™ initiative is intended to make the College's clinical content, including the Incidental Findings Committee White Papers, available for decision support tool creation based upon the herein described CAR/DS framework. Copyright © 2017 American College of Radiology. Published by Elsevier Inc. All rights reserved.

A novel forward osmosis system in landfill leachate treatment for removing polycyclic aromatic hydrocarbons and for direct fertigation.

PubMed

Li, Jing; Niu, Aping; Lu, Chun-Jiao; Zhang, Jing-Hui; Junaid, Muhammad; Strauss, Phyllis R; Xiao, Ping; Wang, Xiao; Ren, Yi-Wei; Pei, De-Sheng

2017-02-01

Landfill leachate (LL) is harmful to aquatic environment because it contains high concentrations of dissolved organic matter, inorganic components, heavy metals, and other xenobiotics. Thus, the remediation of LL is crucial for environmental conservation. Here, a potential application of the forward osmosis (FO) filtration process with ammonium bicarbonate (NH 4 HCO 3 ) as a draw solution (DS) was investigated to remediate membrane bioreactor-treated LL (M-LL). After the leachate treatment, the toxicity and removal efficiencies of polycyclic aromatic hydrocarbons (PAHs) were evaluated using zebrafish and cultured human cells. The water recovery rate was improved using the current protocol up to 86.6% and 91.6% by both the pressure retarded osmosis (PRO) mode and the forward osmosis (FO) mode. Water flux increased with the increasing DS concentrations, but solution velocities decreased with the operation time. Toxicity tests revealed that the M-LL treated by NH 4 HCO 3 had no toxic effect on zebrafish and human cells. Moreover, green fluorescent protein (GFP) expression in the transgenic zebrafish Tg(cyp1a:gfp) induced by PAHs was very weak compared to the effects induced by untreated M-LL. Since the diluted DS met local safety requirements of liquid fertilizer, it could be directly applied as the liquid fertilizer for fertigation. In conclusion, this novel FO system using NH 4 HCO 3 as the DS provides a cheap and efficient protocol to effectively remove PAHs and other pollutants in LL, and the diluted DS can be directly applied to crops as a liquid fertilizer, indicating that this technique is effective and eco-friendly for the treatment of different types of LL. Copyright © 2016 Elsevier Ltd. All rights reserved.

Comparison of ethnicity, gender, age of onset and outcome in South Africans with systemic lupus erythematosus.

PubMed

Budhoo, A; Mody, G M; Dubula, T; Patel, N; Mody, P G

2017-04-01

Ethnicity, gender and age of onset are reported to influence the expression and outcome of systemic lupus erythematosus. We studied a multi-ethnic cohort of 408 South Africans (91.2% females) comprising 237 (58.1%) Indians, 137 (33.6%) African Blacks, 17 (4.2%) Mixed ethnicity and 17 (4.2%) Whites. The most common manifestations were arthritis (80.6%), photosensitivity (67.2%), oral ulcers (50.0%), malar rash (49.0%) and renal (39.2%). The common laboratory findings were positive anti-nuclear factor (96.8%), haematological (74.8%) and anti-dsDNA antibodies (45.3%). Serositis ( p = 0.002), nephritis ( p = 0.039), leucopaenia ( p = 0.001), haemolytic anaemia ( p = 0.026), anti-dsDNA antibodies ( p = 0.028) and anti-Sm antibodies ( p = 0.050) were more common in African Blacks compared to Indians. Males had increased prevalence of discoid rash ( p = 0.006) and anti-Sm antibodies ( p = 0.016). Discoid rash ( p = 0.018), renal involvement ( p < 0.001), psychosis ( p = 0.028), seizures ( p = 0.020), anti-dsDNA antibodies ( p = 0.009), leucopaenia ( p = 0.006), haemolytic anaemia ( p = 0.017) and thrombocytopaenia ( p = 0.023) were more common with early-onset systemic lupus erythematosus. On multivariate analysis, the independent predictors of death were renal involvement, anti-dsDNA antibodies and seizures. There were 53 (13%) deaths and the five- and 10-year survival was 90.8% and 85.7% respectively, with no differences related to ethnicity or age of onset. In conclusion, we report on the spectrum and outcome of systemic lupus erythematosus in a large South African multi-ethnic cohort.

Code-division multiple-access protocol for active RFID systems

NASA Astrophysics Data System (ADS)

Mazurek, Gustaw; Szabatin, Jerzy

2008-01-01

Most of the Radio Frequency Identification (RFID) systems operating in HF and UHF bands employ narrowband modulations (FSK or ASK) with Manchester coding. However, these simple transmission schemes are vulnerable to narrowband interference (NBI) generated by other radio systems working in the same frequency band, and also suffer from collision problem and need special anti-collision procedures. This becomes especially important when operating in a noisy, crowded industrial environment. In this paper we show the performance of RFID system with DS-CDMA transmission in comparison to a standard system with FSK modulation defined in ISO 18000-7. Our simulation results show that without any bandwidth expansion the immunity against NBI can be improved by 8 dB and the system capacity can be 7 times higher when using DS-CDMA transmission instead of FSK modulation with Manchester coding.

Study of Cabibbo suppressed decays of the Ds+ charmed-strange meson involving a KS0

NASA Astrophysics Data System (ADS)

Link, J. M.; Yager, P. M.; Anjos, J. C.; Bediaga, I.; Castromonte, C.; Machado, A. A.; Magnin, J.; Massafferri, A.; de Miranda, J. M.; Pepe, I. M.; Polycarpo, E.; Dos Reis, A. C.; Carrillo, S.; Casimiro, E.; Cuautle, E.; Sánchez-Hernández, A.; Uribe, C.; Vázquez, F.; Agostino, L.; Cinquini, L.; Cumalat, J. P.; Frisullo, V.; O'Reilly, B.; Segoni, I.; Stenson, K.; Tucker, R. S.; Butler, J. N.; Cheung, H. W. K.; Chiodini, G.; Gaines, I.; Garbincius, P. H.; Garren, L. A.; Gottschalk, E.; Kasper, P. H.; Kreymer, A. E.; Kutschke, R.; Wang, M.; Benussi, L.; Bianco, S.; Fabbri, F. L.; Zallo, A.; Reyes, M.; Cawlfield, C.; Kim, D. Y.; Rahimi, A.; Wiss, J.; Gardner, R.; Kryemadhi, A.; Chung, Y. S.; Kang, J. S.; Ko, B. R.; Kwak, J. W.; Lee, K. B.; Cho, K.; Park, H.; Alimonti, G.; Barberis, S.; Boschini, M.; Cerutti, A.; D'Angelo, P.; Dicorato, M.; Dini, P.; Edera, L.; Erba, S.; Inzani, P.; Leveraro, F.; Malvezzi, S.; Menasce, D.; Mezzadri, M.; Moroni, L.; Pedrini, D.; Pontoglio, C.; Prelz, F.; Rovere, M.; Sala, S.; Davenport, T. F.; Arena, V.; Boca, G.; Bonomi, G.; Gianini, G.; Liguori, G.; Lopes Pegna, D.; Merlo, M. M.; Pantea, D.; Ratti, S. P.; Riccardi, C.; Vitulo, P.; Göbel, C.; Otalora, J.; Hernandez, H.; Lopez, A. M.; Mendez, H.; Paris, A.; Quinones, J.; Ramirez, J. E.; Zhang, Y.; Wilson, J. R.; Handler, T.; Mitchell, R.; Engh, D.; Hosack, M.; Johns, W. E.; Luiggi, E.; Nehring, M.; Sheldon, P. D.; Vaandering, E. W.; Webster, M.; Sheaff, M.; Focus Collaboration

2008-02-01

We study the decay of Ds+ mesons into final states involving a KS0 and report the discovery of Cabibbo suppressed decay modes Ds+ →KS0π-π+π+ (179 ± 36 events) and Ds+ →KS0π+ (113 ± 26 events). The branching fraction ratios for the new modes are Γ (Ds+ →KS0π-π+π+)/Γ (Ds+ →KS0K-π+π+) = 0.18 ± 0.04 ± 0.05 and Γ (Ds+ →KS0π+)/Γ (Ds+ →KS0K+) = 0.104 ± 0.024 ± 0.014.

Study of Cabibbo suppressed decays of the Ds+ charmed-strange meson involving a KS0

NASA Astrophysics Data System (ADS)

FOCUS Collaboration; Link, J. M.; Yager, P. M.; Anjos, J. C.; Bediaga, I.; Castromonte, C.; Machado, A. A.; Magnin, J.; Massafferri, A.; de Miranda, J. M.; Pepe, I. M.; Polycarpo, E.; Dos Reis, A. C.; Carrillo, S.; Casimiro, E.; Cuautle, E.; Sánchez-Hernández, A.; Uribe, C.; Vázquez, F.; Agostino, L.; Cinquini, L.; Cumalat, J. P.; Frisullo, V.; O'Reilly, B.; Segoni, I.; Stenson, K.; Tucker, R. S.; Butler, J. N.; Cheung, H. W. K.; Chiodini, G.; Gaines, I.; Garbincius, P. H.; Garren, L. A.; Gottschalk, E.; Kasper, P. H.; Kreymer, A. E.; Kutschke, R.; Wang, M.; Benussi, L.; Bianco, S.; Fabbri, F. L.; Zallo, A.; Reyes, M.; Cawlfield, C.; Kim, D. Y.; Rahimi, A.; Wiss, J.; Gardner, R.; Kryemadhi, A.; Chung, Y. S.; Kang, J. S.; Ko, B. R.; Kwak, J. W.; Lee, K. B.; Cho, K.; Park, H.; Alimonti, G.; Barberis, S.; Boschini, M.; Cerutti, A.; D'Angelo, P.; Dicorato, M.; Dini, P.; Edera, L.; Erba, S.; Inzani, P.; Leveraro, F.; Malvezzi, S.; Menasce, D.; Mezzadri, M.; Moroni, L.; Pedrini, D.; Pontoglio, C.; Prelz, F.; Rovere, M.; Sala, S.; Davenport, T. F.; Arena, V.; Boca, G.; Bonomi, G.; Gianini, G.; Liguori, G.; Lopes Pegna, D.; Merlo, M. M.; Pantea, D.; Ratti, S. P.; Riccardi, C.; Vitulo, P.; Göbel, C.; Otalora, J.; Hernandez, H.; Lopez, A. M.; Mendez, H.; Paris, A.; Quinones, J.; Ramirez, J. E.; Zhang, Y.; Wilson, J. R.; Handler, T.; Mitchell, R.; Engh, D.; Hosack, M.; Johns, W. E.; Luiggi, E.; Nehring, M.; Sheldon, P. D.; Vaandering, E. W.; Webster, M.; Sheaff, M.

2008-02-01

We study the decay of Ds+ mesons into final states involving a KS0 and report the discovery of Cabibbo suppressed decay modes Ds+→KS0πππ (179±36 events) and Ds+→KS0π (113±26 events). The branching fraction ratios for the new modes are Γ(Ds+→KS0πππ)Γ(Ds+→KS0Kππ)=0.18±0.04±0.05 and Γ(Ds+→KS0π)Γ(Ds+→KS0K)=0.104±0.024±0.014.

KiDS-i-800: comparing weak gravitational lensing measurements from same-sky surveys

NASA Astrophysics Data System (ADS)

Amon, A.; Heymans, C.; Klaes, D.; Erben, T.; Blake, C.; Hildebrandt, H.; Hoekstra, H.; Kuijken, K.; Miller, L.; Morrison, C. B.; Choi, A.; de Jong, J. T. A.; Glazebrook, K.; Irisarri, N.; Joachimi, B.; Joudaki, S.; Kannawadi, A.; Lidman, C.; Napolitano, N.; Parkinson, D.; Schneider, P.; van Uitert, E.; Viola, M.; Wolf, C.

2018-07-01

We present a weak gravitational lensing analysis of 815 deg2 of i-band imaging from the Kilo-Degree Survey (KiDS-i-800). In contrast to the deep r-band observations, which take priority during excellent seeing conditions and form the primary KiDS data set (KiDS-r-450), the complementary yet shallower KiDS-i-800 spans a wide range of observing conditions. The overlapping KiDS-i-800 and KiDS-r-450 imaging therefore provides a unique opportunity to assess the robustness of weak lensing measurements. In our analysis we introduce two new `null' tests. The `nulled' two-point shear correlation function uses a matched catalogue to show that the calibrated KiDS-i-800 and KiDS-r-450 shear measurements agree at the level of 1 ± 4 per cent. We use five galaxy lens samples to determine a `nulled' galaxy-galaxy lensing signal from the full KiDS-i-800 and KiDS-r-450 surveys and find that the measurements agree to 7 ± 5 per cent when the KiDS-i-800 source redshift distribution is calibrated using either spectroscopic redshifts, or the 30-band photometric redshifts from the COSMOS survey.

KiDS-i-800: Comparing weak gravitational lensing measurements from same-sky surveys

NASA Astrophysics Data System (ADS)

Amon, A.; Heymans, C.; Klaes, D.; Erben, T.; Blake, C.; Hildebrandt, H.; Hoekstra, H.; Kuijken, K.; Miller, L.; Morrison, C. B.; Choi, A.; de Jong, J. T. A.; Glazebrook, K.; Irisarri, N.; Joachimi, B.; Joudaki, S.; Kannawadi, A.; Lidman, C.; Napolitano, N.; Parkinson, D.; Schneider, P.; van Uitert, E.; Viola, M.; Wolf, C.

2018-04-01

We present a weak gravitational lensing analysis of 815deg2 of i-band imaging from the Kilo-Degree Survey (KiDS-i-800). In contrast to the deep r-band observations, which take priority during excellent seeing conditions and form the primary KiDS dataset (KiDS-r-450), the complementary yet shallower KiDS-i-800 spans a wide range of observing conditions. The overlapping KiDS-i-800 and KiDS-r-450 imaging therefore provides a unique opportunity to assess the robustness of weak lensing measurements. In our analysis we introduce two new `null' tests. The `nulled' two-point shear correlation function uses a matched catalogue to show that the calibrated KiDS-i-800 and KiDS-r-450 shear measurements agree at the level of 1 ± 4%. We use five galaxy lens samples to determine a `nulled' galaxy-galaxy lensing signal from the full KiDS-i-800 and KiDS-r-450 surveys and find that the measurements agree to 7 ± 5% when the KiDS-i-800 source redshift distribution is calibrated using either spectroscopic redshifts, or the 30-band photometric redshifts from the COSMOS survey.

A novel in-situ method for real-time monitoring of gas transport in soil

NASA Astrophysics Data System (ADS)

Laemmel, Thomas; Maier, Martin; Schack-Kirchner, Helmer; Lang, Friederike

2017-04-01

Gas exchange between soil and atmosphere is important for the biogeochemistry of soils. Gas transport in soil is commonly assumed to be governed by molecular diffusion and is usually described by the soil gas diffusion coefficient DS characterizing the ability of the soil to "transport passively" gas through the soil. One way to determine DS is sampling soil cores in the field and measuring DS in the lab. Unfortunately this method is destructive and laborious. Moreover, a few previous field studies identified other gas transport processes in soil to significantly enhance the diffusive gas transport. However, until now, no method is available to measure gas transport in situ in the soil. We developed a novel method to monitor gas transport in soil in situ. The method includes a custom made gas sampling device, the continuous injection of an inert tracer gas and inverse gas transport modelling in the soil. The gas sampling device has several sampling depths and can be easily installed into a vertical hole drilled by an auger, which allows for fast installation of the system. Helium (He) as inert tracer gas was injected continuously at the lower end of the device. The resulting steady state distribution of He was used to deduce the depth profile of DS. Gas transport in the soil surrounding the gas-sampling-device/soil system was modeled using the Finite Element Modeling program COMSOL . We tested our new method both in the lab and during two short field studies and compared the results with a reference method using soil cores. DS profiles obtained by our in-situ method were consistent with DS profiles determined based on soil core analyses. During a longer monitoring field campaign, typical soil-moisture effects upon gas diffusivity such as an increase during a drying period or a decrease after rain could be observed consistently. Under windy conditions we additionally measured for the first time the direct enhancement of gas transport in soil due to wind-induced pressure-pumping which could increase the effective DS up to 30% in the topsoil. Our novel monitoring method can be quickly and easily installed and allows for monitoring continuously soil gas transport over a long time. It allows monitoring physical modifications of soil gas diffusivity due to rain events or evaporation but it also allows studying non-diffusive gas transport processes in the soil.

Autism spectrum disorder in Down syndrome: cluster analysis of Aberrant Behaviour Checklist data supports diagnosis.

PubMed

Ji, N Y; Capone, G T; Kaufmann, W E

2011-11-01

The diagnostic validity of autism spectrum disorder (ASD) based on Diagnostic and Statistical Manual of Mental Disorders (DSM) has been challenged in Down syndrome (DS), because of the high prevalence of cognitive impairments in this population. Therefore, we attempted to validate DSM-based diagnoses via an unbiased categorisation of participants with a DSM-independent behavioural instrument. Based on scores on the Aberrant Behaviour Checklist - Community, we performed sequential factor (four DS-relevant factors: Autism-Like Behaviour, Disruptive Behaviour, Hyperactivity, Self-Injury) and cluster analyses on a 293-participant paediatric DS clinic cohort. The four resulting clusters were compared with DSM-delineated groups: DS + ASD, DS + None (no DSM diagnosis), DS + DBD (disruptive behaviour disorder) and DS + SMD (stereotypic movement disorder), the latter two as comparison groups. Two clusters were identified with DS + ASD: Cluster 1 (35.1%) with higher disruptive behaviour and Cluster 4 (48.2%) with more severe autistic behaviour and higher percentage of late onset ASD. The majority of participants in DS + None (71.9%) and DS + DBD (87.5%) were classified into Cluster 2 and 3, respectively, while participants in DS + SMD were relatively evenly distributed throughout the four clusters. Our unbiased, DSM-independent analyses, using a rating scale specifically designed for individuals with severe intellectual disability, demonstrated that DSM-based criteria of ASD are applicable to DS individuals despite their cognitive impairments. Two DS + ASD clusters were identified and supported the existence of at least two subtypes of ASD in DS, which deserve further characterisation. Despite the prominence of stereotypic behaviour in DS, the SMD diagnosis was not identified by cluster analysis, suggesting that high-level stereotypy is distributed throughout DS. Further supporting DSM diagnoses, typically behaving DS participants were easily distinguished as a group from those with maladaptive behaviours. © 2011 The Authors. Journal of Intellectual Disability Research © 2011 Blackwell Publishing Ltd.

Visible light-sensitive APTES-bound ZnO nanowire toward a potent nanoinjector sensing biomolecules in a living cell

NASA Astrophysics Data System (ADS)

Lee, Jooran; Choi, Sunyoung; Bae, Seon Joo; Yoon, Seok Min; Choi, Joon Sig; Yoon, Minjoong

2013-10-01

Nanoscale cell injection techniques combined with nanoscopic photoluminescence (PL) spectroscopy have been important issues in high-resolution optical biosensing, gene and drug delivery and single-cell endoscopy for medical diagnostics and therapeutics. However, the current nanoinjectors remain limited for optical biosensing and communication at the subwavelength level, requiring an optical probe such as semiconductor quantum dots, separately. Here, we show that waveguided red emission is observed at the tip of a single visible light-sensitive APTES-modified ZnO nanowire (APTES-ZnO NW) and it exhibits great enhancement upon interaction with a complementary sequence-based double stranded (ds) DNA, whereas it is not significantly affected by non-complementary ds DNA. Further, the tip of a single APTES-ZnO NW can be inserted into the subcellular region of living HEK 293 cells without significant toxicity, and it can also detect the enhancement of the tip emission from subcellular regions with high spatial resolution. These results indicate that the single APTES-ZnO NW would be useful as a potent nanoinjector which can guide visible light into intracellular compartments of mammalian cells, and can also detect nanoscopic optical signal changes induced by interaction with the subcellular specific target biomolecules without separate optical probes.Nanoscale cell injection techniques combined with nanoscopic photoluminescence (PL) spectroscopy have been important issues in high-resolution optical biosensing, gene and drug delivery and single-cell endoscopy for medical diagnostics and therapeutics. However, the current nanoinjectors remain limited for optical biosensing and communication at the subwavelength level, requiring an optical probe such as semiconductor quantum dots, separately. Here, we show that waveguided red emission is observed at the tip of a single visible light-sensitive APTES-modified ZnO nanowire (APTES-ZnO NW) and it exhibits great enhancement upon interaction with a complementary sequence-based double stranded (ds) DNA, whereas it is not significantly affected by non-complementary ds DNA. Further, the tip of a single APTES-ZnO NW can be inserted into the subcellular region of living HEK 293 cells without significant toxicity, and it can also detect the enhancement of the tip emission from subcellular regions with high spatial resolution. These results indicate that the single APTES-ZnO NW would be useful as a potent nanoinjector which can guide visible light into intracellular compartments of mammalian cells, and can also detect nanoscopic optical signal changes induced by interaction with the subcellular specific target biomolecules without separate optical probes. Electronic supplementary information (ESI) available: Synthesis of APTES-modified ZnO nanowires, DNA functionalization and spectroscopic measurements with additional fluorescence image ad fluorescence decay times, cell culture, injection of a single nanowire into living cells, subcellular imaging and determination of cytotoxicity. See DOI: 10.1039/c3nr03042c

Needs and challenges of daily life for people with Down syndrome residing in the city of Rome, Italy.

PubMed

Bertoli, M; Biasini, G; Calignano, M T; Celani, G; De Grossi, G; Digilio, M C; Fermariello, C C; Loffredo, G; Luchino, F; Marchese, A; Mazotti, S; Menghi, B; Razzano, C; Tiano, C; Zambon Hobart, A; Zampino, G; Zuccalà, G

2011-08-01

Population-based surveys on the quality of life of people with Down syndrome (DS) are difficult to perform because of ethical and legal policies regarding privacy and confidential information, but they are essential for service planning. Little is known about the sample size and variability of quality of life of people with DS living in the city of Rome, which has a population of 2.7 million inhabitants. The aim of the present study is to explore the needs and challenges in health, social integration and daily life, of people with DS living in Rome. A cross-sectional, census-based survey was conducted in 2006. All family doctors (3016 in total) of the National Health Service were involved by the Statistical Bureau of the Municipality of Rome. As per the census, every resident citizen is registered with a family doctor and every person with disabilities is coded. Associations for Down Syndrome encouraged their members to participate in the research. Questionnaires were completed by families of people with DS, in accordance with privacy laws. An initial survey, conducted via a letter and a telephone contact with family doctors, identified 884 people with DS residing in the city of Rome. Data on the medical and social conditions of 518 people with DS, ranging in age from 0 to 64 years, were collected. Some 88% of these were living with their original family; 82.1% had one or more siblings, and 19.5% had lost one or both parents. A full 100% of children with DS were enrolled in the public school system. This ensures that they are fully occupied and entirely integrated in society. After secondary school there is a lack of opportunities. Thus, only 10% of adults were working with a regular contract. A mere 42.2% of people with DS aged 25-30 were involved in some form of regular activity (although not always on a daily basis). After the age of 30, the percentage of people demonstrating decline in function increased sharply, while disability-related support decreased. In other words, as people with DS age, daily life evolves increasingly around the home, with only occasional outdoor activities. The health, employment and social needs of the majority of people with DS in the city of Rome are not being met. The findings of this study underscore the urgent need for more comprehensive inclusion in society of adults with DS and for the provision of support services to create an enabling environment for inclusion. Because of the variability of performance among individuals with DS, there is a need to create more case-specific options in terms of work, living arrangements, social networking and medical services. Schooling and social inclusion in childhood alone do not guarantee a satisfactory quality of life in adulthood. It is argued herewith that policy of inclusion and support should extend over the entire lifetime of people with DS. © 2011 The Authors. Journal of Intellectual Disability Research © 2011 Blackwell Publishing Ltd.

Needs and challenges of daily life for people with Down syndrome residing in the city of Rome, Italy

PubMed Central

Bertoli, M; Biasini, G; Calignano, M T; Celani, G; De Grossi, G; Digilio, M C; Fermariello, C C; Loffredo, G; Luchino, F; Marchese, A; Mazotti, S; Menghi, B; Razzano, C; Tiano, C; Zambon Hobart, A; Zampino, G; Zuccalà, G

2011-01-01

Background Population-based surveys on the quality of life of people with Down syndrome (DS) are difficult to perform because of ethical and legal policies regarding privacy and confidential information, but they are essential for service planning. Little is known about the sample size and variability of quality of life of people with DS living in the city of Rome, which has a population of 2.7 million inhabitants. The aim of the present study is to explore the needs and challenges in health, social integration and daily life, of people with DS living in Rome. Methodology A cross-sectional, census-based survey was conducted in 2006. All family doctors (3016 in total) of the National Health Service were involved by the Statistical Bureau of the Municipality of Rome. As per the census, every resident citizen is registered with a family doctor and every person with disabilities is coded. Associations for Down Syndrome encouraged their members to participate in the research. Questionnaires were completed by families of people with DS, in accordance with privacy laws. Findings An initial survey, conducted via a letter and a telephone contact with family doctors, identified 884 people with DS residing in the city of Rome. Data on the medical and social conditions of 518 people with DS, ranging in age from 0 to 64 years, were collected. Some 88% of these were living with their original family; 82.1% had one or more siblings, and 19.5% had lost one or both parents. A full 100% of children with DS were enrolled in the public school system. This ensures that they are fully occupied and entirely integrated in society. After secondary school there is a lack of opportunities. Thus, only 10% of adults were working with a regular contract. A mere 42.2% of people with DS aged 25–30 were involved in some form of regular activity (although not always on a daily basis). After the age of 30, the percentage of people demonstrating decline in function increased sharply, while disability-related support decreased. In other words, as people with DS age, daily life evolves increasingly around the home, with only occasional outdoor activities. Conclusion The health, employment and social needs of the majority of people with DS in the city of Rome are not being met. The findings of this study underscore the urgent need for more comprehensive inclusion in society of adults with DS and for the provision of support services to create an enabling environment for inclusion. Because of the variability of performance among individuals with DS, there is a need to create more case-specific options in terms of work, living arrangements, social networking and medical services. Schooling and social inclusion in childhood alone do not guarantee a satisfactory quality of life in adulthood. It is argued herewith that policy of inclusion and support should extend over the entire lifetime of people with DS. PMID:21668802

First observation of the decay Ds+-->pn.

PubMed

Athar, S B; Patel, R; Yelton, J; Rubin, P; Eisenstein, B I; Karliner, I; Mehrabyan, S; Lowrey, N; Selen, M; White, E J; Wiss, J; Mitchell, R E; Shepherd, M R; Besson, D; Pedlar, T K; Cronin-Hennessy, D; Gao, K Y; Hietala, J; Kubota, Y; Klein, T; Lang, B W; Poling, R; Scott, A W; Zweber, P; Dobbs, S; Metreveli, Z; Seth, K K; Tomaradze, A; Libby, J; Powell, A; Wilkinson, G; Ecklund, K M; Love, W; Savinov, V; Lopez, A; Mendez, H; Ramirez, J; Ge, J Y; Miller, D H; Shipsey, I P J; Xin, B; Adams, G S; Anderson, M; Cummings, J P; Danko, I; Hu, D; Moziak, B; Napolitano, J; He, Q; Insler, J; Muramatsu, H; Park, C S; Thorndike, E H; Yang, F; Artuso, M; Blusk, S; Khalil, S; Li, J; Mountain, R; Nisar, S; Randrianarivony, K; Sultana, N; Skwarnicki, T; Stone, S; Wang, J C; Zhang, L M; Bonvicini, G; Cinabro, D; Dubrovin, M; Lincoln, A; Naik, P; Rademacker, J; Asner, D M; Edwards, K W; Reed, J; Briere, R A; Ferguson, T; Tatishvili, G; Vogel, H; Watkins, M E; Rosner, J L; Alexander, J P; Cassel, D G; Duboscq, J E; Ehrlich, R; Fields, L; Gibbons, L; Gray, R; Gray, S W; Hartill, D L; Heltsley, B K; Hertz, D; Hunt, J M; Kandaswamy, J; Kreinick, D L; Kuznetsov, V E; Ledoux, J; Mahlke-Krüger, H; Mohapatra, D; Onyisi, P U E; Patterson, J R; Peterson, D; Riley, D; Ryd, A; Sadoff, A J; Shi, X; Stroiney, S; Sun, W M; Wilksen, T

2008-05-09

Using e+e--->Ds*-Ds+ data collected near the peak Ds production energy, Ecm=4170 MeV, with the CLEO-c detector, we present the first observation of the decay Ds+-->pn. We measure a branching fraction B(Ds+-->pn)=(1.30+/-0.36(-0.16)+0.12)x10(-3). This is the first observation of a charmed meson decaying into a baryon-antibaryon final state.

An aligned porous electrospun fibrous membrane with controlled drug delivery - An efficient strategy to accelerate diabetic wound healing with improved angiogenesis.

PubMed

Ren, Xiaozhi; Han, Yiming; Wang, Jie; Jiang, Yuqi; Yi, Zhengfang; Xu, He; Ke, Qinfei

2018-04-01

A chronic wound in diabetic patients is usually characterized by poor angiogenesis and delayed wound closure. The exploration of efficient strategy to significantly improve angiogenesis in the diabetic wound bed and thereby accelerate wound healing is still a significant challenge. Herein, we reported a kind of aligned porous poly (l-lactic acid) (PlLA) electrospun fibrous membranes containing dimethyloxalylglycine (DMOG)-loaded mesoporous silica nanoparticles (DS) for diabetic wound healing. The PlLA electrospun fibers aligned in a single direction and there were ellipse-shaped nano-pores in situ generated onto the surface of fibers, while the DS were well distributed in the fibers and the DMOG as well as Si ion could be controlled released from the nanopores on the fibers. The in vitro results revealed that the aligned porous composite membranes (DS-PL) could stimulate the proliferation, migration and angiogenesis-related gene expression of human umbilical vein endothelial cells (HUVECs) compared with the pure PlLA membranes. The in vivo study further demonstrated that the prepared DS-PL membranes significantly improved neo-vascularization, re-epithelialization and collagen formation as well as inhibited inflammatory reaction in the diabetic wound bed, which eventually stimulated the healing of the diabetic wound. Collectively, these results suggest that the combination of hierarchical structures (nanopores on the aligned fibers) with the controllable released DMOG drugs as well as Si ions from the membranes, which could create a synergetic effect on the rapid stimulation of angiogenesis in the diabetic wound bed, is a potential novel therapeutic strategy for highly efficient diabetic wound healing. A chronic wound in diabetic patients is usually characterized by the poor angiogenesis and the delayed wound closure. The main innovation of this study is to design a new kind of skin tissue engineered scaffold, aligned porous poly (l-lactic acid) (PlLA) electrospun membranes containing dimethyloxalylglycine (DMOG)-loaded mesoporous silica nanoparticles (DS), which could significantly improve angiogenesis in the diabetic wound bed and thereby accelerate diabetic wound healing. The results revealed that the electrospun fibers with ellipse-shaped nano-pores on the surface were aligned in a single direction, while there were DS particles distributed in the fibers and the DMOG as well as Si ions could be controllably released from the nanopores on the fibers. The in vitro studies demonstrated that the hierarchical nanostructures (nanopores on the aligned fibers) and the controllable released chemical active agents (DMOG drugs and Si ions) from the DS-PL membranes could exert a synergistic effect on inducing the endothelial cell proliferation, migration and differentiation. Above all, the scaffolds distinctly induced the angiogenesis, collagen deposition and re-epithelialization as well as inhibited inflammation reaction in the wound sites, which eventually stimulated the healing of diabetic wounds in vivo. The significance of the current study is that the combination of the hierarchical aligned porous nanofibrous structure with DMOG-loaded MSNs incorporated in electrospun fibers may suggest a high-efficiency strategy for chronic wound healing. Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

DS2 Container and Weatherproofing Study

DTIC Science & Technology

1990-12-01

compatible with polyurethane based coating systems in general? Is it compatible with alkyd -based coatings? 10. How well do the labels placed on the...of the (older) alkyd enamel and (more recently) polyurethane camouflage coatings, leading eventually to seepage of the DS2. A shrink-wrap overpack...by John Wiley and Sons, Inc., Vol. 2, pp. 118- 119; Vol. 4, p. 3 and pp. 284-295; Vol. I, p. 133. 8. Fiber Composite Hybrid Materials, N.L. Hancox

An ion quencher operated lamp for multiplexed fluorescent bioassays.

PubMed

Qing, Taiping; Sun, Huanhuan; He, Xiaoxiao; Huang, Xiaoqin; He, Dinggeng; Bu, Hongchang; Qiao, Zhenzhen; Wang, Kemin

2018-02-01

A novel and adjustable lamp based on competitive interaction among dsDNA-SYBR Green I (SGI), ion quencher, and analyte was designed for bioanalysis. The "filament" and switch of the lamp could be customized by employing different dsDNA and ion quencher. The poly(AT/TA) dsDNA was successfully screened as the most effective filament of the lamp. Two common ions, Hg 2+ and Fe 3+ , were selected as the model switch, and the corresponding ligand molecules cysteine (Cys) and pyrophosphate ions (PPi) were selected as the targets. When the fluorescence-quenched dsDNA/SGI-ion complex was introduced into a target-containing system, ions could be bound by competitive molecules and separate from the complex, thereby lighting the lamp. However, no light was observed if the biomolecule could not snatch the metal ions from the complex. Under the optimal conditions, sensitive and selective detection of Cys and PPi was achieved by the lamp, with practical applications in fetal bovine serum and human urine. This ion quencher regulated lamp for fluorescent bioassays is simple in design, fast in operation, and is more convenient than other methods. Significantly, as many molecules could form stable complexes with metal ions selectively, this ion quencher operated lamp has potential for the detection of a wide spectrum of analytes. Graphical abstract A novel and adjustable lamp on the basis of competitive interaction among dsDNA-SYBR Green I, ions quencher and analyte was designed for bioanalysis. The filament and switch of lamp could be customized by employing different dsDNA and ions quencher.

Toxicological characterization of a novel wastewater treatment process using EDTA-Na2Zn as draw solution (DS) for the efficient treatment of MBR-treated landfill leachate.

PubMed

Niu, Aping; Ren, Yi-Wei; Yang, Li; Xie, Shao-Lin; Jia, Pan-Pan; Zhang, Jing-Hui; Wang, Xiao; Li, Jing; Pei, De-Sheng

2016-07-01

Landfill leachate has become an important source of environmental pollution in past decades, due to the increase of waste volume. Acute toxic and genotoxic hazards to organisms can be caused by landfill leachate. Thus, how to efficiently recover water from landfill leachate and effectively eliminate combined toxicity of landfill leachate are the most pressing issues in waste management. In this study, EDTA-Na2Zn as draw solution (DS) was used to remove the toxicity of membrane bioreactor-treated landfill leachate (MBR-treated landfill leachate) in forward osmosis (FO) process, and nanofiltration (NF) was designed for recovering the diluted DS. Zebrafish and human cells were used for toxicity assay after the novel wastewater treatment process using EDTA-Na2Zn as DS. Results showed that the water recovery rate of MBR-treated landfill leachate (M-LL) in FO membrane system could achieve 66.5% and 71.2% in the PRO and FO mode respectively, and the diluted DS could be efficiently recovered by NF. Toxicity tests performed by using zebrafish and human cells showed that M-LL treated by EDTA-Na2Zn had no toxicity effect on zebrafish larvae and human cells, but it had very slight effect on zebrafish embryos. In conclusion, all results indicated that EDTA-Na2Zn as DS can effectively eliminate toxicity of landfill leachate and this method is economical and eco-friendly for treatment of different types of landfill leachate. Copyright © 2016 Elsevier Ltd. All rights reserved.

Mass Balance of the West Antarctic Ice-Sheet from ICESat Measurements

NASA Technical Reports Server (NTRS)

Zwally, H. Jay; Li, Jun; Robins, John; Saba, Jack L.; Yi, Donghui

2011-01-01

Mass balance estimates for 2003-2008 are derived from ICESat laser altimetry and compared with estimates for 1992-2002 derived from ERS radar altimetry. The net mass balance of 3 drainage systems (Pine Island, Thwaites/Smith, and the coast of Marie Bryd) for 2003-2008 is a loss of 100 Gt/yr, which increased from a loss of 70 Gt/yr for the earlier period. The DS including the Bindschadler and MacAyeal ice streams draining into the Ross Ice Shelf has a mass gain of 11 Gt/yr for 2003-2008, compared to an earlier loss of 70 Gt/yr. The DS including the Whillans and Kamb ice streams has a mass gain of 12 Gt/yr, including a significant thickening on the upper part of the Kamb DS, compared to a earlier gain of 6 Gt/yr (includes interpolation for a large portion of the DS). The other two DS discharging into the Ronne Ice Shelf and the northern Ellsworth Coast have a mass gain of 39 Gt/yr, compared to a gain of 4 Gt/yr for the earlier period. Overall, the increased losses of 30 Gt/yr in the Pine Island, Thwaites/Smith, and the coast of Marie Bryd DSs are exceeded by increased gains of 59 Gt/yr in the other 4 DS. Overall, the mass loss from the West Antarctic ice sheet has decreased to 38 Gt/yr from the earlier loss of 67 Gt/yr, reducing the contribution to sea level rise to 0.11 mm/yr from 0.19 mm/yr

Intracellular oxidant activity, antioxidant enzyme defense system, and cell senescence in fibroblasts with trisomy 21.

PubMed

Rodríguez-Sureda, Víctor; Vilches, Ángel; Sánchez, Olga; Audí, Laura; Domínguez, Carmen

2015-01-01

Down's syndrome (DS) is characterized by a complex phenotype associated with chronic oxidative stress and mitochondrial dysfunction. Overexpression of genes on chromosome-21 is thought to underlie the pathogenesis of the major phenotypic features of DS, such as premature aging. Using cultured fibroblasts with trisomy 21 (T21F), this study aimed to ascertain whether an imbalance exists in activities, mRNA, and protein expression of the antioxidant enzymes SOD1, SOD2, glutathione-peroxidase, and catalase during the cell replication process in vitro. T21F had high SOD1 expression and activity which led to an interenzymatic imbalance in the antioxidant defense system, accentuated with replicative senescence. Intracellular ROS production and oxidized protein levels were significantly higher in T21F compared with control cells; furthermore, a significant decline in intracellular ATP content was detected in T21F. Cell senescence was found to appear prematurely in DS cells as shown by SA-β-Gal assay and p21 assessment, though not apoptosis, as neither p53 nor the proapoptotic proteins cytochrome c and caspase 9 were altered in T21F. These novel findings would point to a deleterious role of oxidatively modified molecules in early cell senescence of T21F, thereby linking replicative and stress-induced senescence in cultured cells to premature aging in DS.

Intracellular Oxidant Activity, Antioxidant Enzyme Defense System, and Cell Senescence in Fibroblasts with Trisomy 21

PubMed Central

Rodríguez-Sureda, Víctor; Vilches, Ángel; Sánchez, Olga; Audí, Laura; Domínguez, Carmen

2015-01-01

Down's syndrome (DS) is characterized by a complex phenotype associated with chronic oxidative stress and mitochondrial dysfunction. Overexpression of genes on chromosome-21 is thought to underlie the pathogenesis of the major phenotypic features of DS, such as premature aging. Using cultured fibroblasts with trisomy 21 (T21F), this study aimed to ascertain whether an imbalance exists in activities, mRNA, and protein expression of the antioxidant enzymes SOD1, SOD2, glutathione-peroxidase, and catalase during the cell replication process in vitro. T21F had high SOD1 expression and activity which led to an interenzymatic imbalance in the antioxidant defense system, accentuated with replicative senescence. Intracellular ROS production and oxidized protein levels were significantly higher in T21F compared with control cells; furthermore, a significant decline in intracellular ATP content was detected in T21F. Cell senescence was found to appear prematurely in DS cells as shown by SA-β-Gal assay and p21 assessment, though not apoptosis, as neither p53 nor the proapoptotic proteins cytochrome c and caspase 9 were altered in T21F. These novel findings would point to a deleterious role of oxidatively modified molecules in early cell senescence of T21F, thereby linking replicative and stress-induced senescence in cultured cells to premature aging in DS. PMID:25852816

Career development needs of vice chairs for education in departments of surgery.

PubMed

Sanfey, Hilary; Boehler, Margaret; Darosa, Debra; Dunnington, Gary L

2012-01-01

To identify the career development needs Vice Chair for Education in Surgery Departments (VCESDs). In all, 33 VCESDs were invited to complete an online survey to identify the scope of duties, scholarly activity, job satisfaction, and career development needs. A total of 29/33 (88%) VCESDs responded. Time constraints were the most frequent impediment for MDs vs. PhDs (p < 0.05). Dominant faculty development needs were conducting educational research (2.0 ± 0.78 for MDs, 1.33 ± 0.76 for PhDs), developing resident selection systems (1.68 ± 0.73), and mentorship programs (1.95 ± 0.77) for MDs, and developing teach the teacher programs (1 ± 0), and program performance evaluation systems (1.33 ± 0.76) for PhDs. The skills deemed to be of greatest importance were ability to communicate effectively (1.27 ± 0.55), resolve personnel conflicts (1.32 ± 0.57), and introduce change (1.41 ± 0.59). PhDs revealed a greater need to learn strategies for dealing with disruptive faculty (1.0 ± 0 vs 2.15 ± 0.87). This information will inform the future career development of VCESDs and will assist Department Chairs who wish to recruit and retain VCESDs. Copyright © 2012 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.

Two conformational states in D-shaped DNA: Effects of local denaturation

NASA Astrophysics Data System (ADS)

Lee, O.-Chul; Kim, Cheolhee; Kim, Jae-Yeol; Lee, Nam Ki; Sung, Wokyung

2016-06-01

The bending of double-stranded(ds) DNA on the nano-meter scale plays a key role in many cellular processes such as nucleosome packing, transcription-control, and viral-genome packing. In our recent study, a nanometer-sized dsDNA bent into a D shape was formed by hybridizing a circular single-stranded(ss) DNA and a complementary linear ssDNA. Our fluorescence resonance energy transfer (FRET) measurement of D-DNA revealed two types of conformational states: a less-bent state and a kinked state, which can transform into each other. To understand the origin of the two deformed states of D-DNA, here we study the presence of open base-pairs in the ds portion by using the breathing-DNA model to simulate the system. We provide strong evidence that the two states are due to the emergence of local denaturation, i.e., a bubble in the middle and two forks at ends of the dsDNA portion. We also study the system analytically and find that the free-energy landscape is bistable with two minima representative of the two states. The kink and fork sizes estimated by the analytical calculation are also in excellent agreement with the results of the simulation. Thus, this combined experimental-simulation-analytical study corroborates that highly bent D-DNA reduces bending stress via local denaturation.

Transcriptome profiling analysis reveals the role of latrophilin in controlling development, reproduction and insecticide susceptibility in Tribolium castaneum.

PubMed

Gao, Shanshan; Xiong, Wenfeng; Wei, Luting; Liu, Juanjuan; Liu, Xing; Xie, Jia; Song, Xiaowen; Bi, Jingxiu; Li, Bin

2018-06-01

Latrophilin of Tribolium castaneum (Tclph) has been reported to play crucial roles in growth, development and reproduction. However, the regulatory mechanism of Tclph associated with these physiology processes is unknown. Thus, the global transcriptome profiles between RNAi treated (ds-Tclph) and control larvae of T. castaneum were analyzed by RNA-sequencing. Totally, 274 differentially expressed genes (DEGs) were identified between the ds-Tclph and control samples. These DEGs were classified into 42 GO functional groups, including developmental process, reproduction and stress response. The results indicated that knockdown of Tclph disturbed the antioxidant activity process, and partially inhibited the serine protease (SP) and lipase signaling pathways to regulate the development and reproduction as well as the decreasing of the stress response in T. castaneum. Additionally, knockdown of Tclph suppressed IMD immunity pathways which likely modulated the effects of Tclph on stress response. Interestingly, CSPs, ESTs, CYPs, AOXs and BGs were significantly down-regulated in ds-Tclph larvae, implying that they cooperated with Tclph to reduce the activity of cellular metabolism system. FMOs was up-regulated in ds-Tclph insects suggested it may be involved in detoxifying alkaloid of insect metabolism system. These results implied that Tclph participated in phase 0, I and II cellular detoxification. Furthermore, RNAi against Tclph increased larval susceptibility to carbamates and organophosphates insecticides, supporting that Tclph was indeed involved into the insecticide susceptibility in T. castaneum.

Is irrigation with partial desalinated seawater a policy option for saving freshwater in the Kingdom of Saudi Arabia

NASA Astrophysics Data System (ADS)

Multsch, Sebastian; Alquwaizany, Abdulaziz S.; Lehnert, Karl-H.; Frede, Hans-Georg; Breuer, Lutz

2015-04-01

The agriculture sector consumes with 88 % a majority of the almost fossil water resources in the Kingdom of Saudi Arabia (KSA). Irrigation with saline water has been highlighted to be a promising technique to reduce fresh water consumption. Current desalination techniques, further developments, salt tolerant crop types and improved irrigation systems can potentially redesign future perspectives for irrigation agriculture, in particular by considering the growing desalination capacity in KSA (5 million m3 day-1 in 2003). Hence, we have analyzed the potential of using desalinated and partial desalinated seawater for growing crops in KSA by considering scenarios of salinity levels and desalination costs. The desalination process has been modelled with the ROSA© software considering a reverse osmosis (RO) plant. The spatial decision support system SPARE:WATER has been applied to assess the water footprint of crops (WFcrop). In order to maintain high crop yields, salts need to be washed out from the rooting zone, which requires the application of additional salt-free water. Therefore, high crop yields come along with additional water requirements and increased desalination effort and increased costs for proving high quality water. As an example, growing wheat with partial desalinated seawater from the Arabian Gulf with a RO plant has been investigated. Desalination reduces the salinity level from 76 dS m-1 to 0.5 dS m-1 considering two RO cycles, with cost of desalinized water in the range of 0.5 to 1.2 m-3. We acknowledge that cost only refer to desalination without considering others such as transport, water pumping or crop fertilization. The study shows that Boron is the most problematic salt component, because it is difficult to remove by RO and toxic in high concentrations for crops (wheat threshold of 0.5 to 1.0 mg l-1). The nationwide average WFcrop of wheat under surface irrigation is 2,628 m3 t-1 considering high water quality of 1 dS m-1 and 3,801 m3 t-1 at 12 dS m-1. Using sprinkler or drip irrigation systems the WFcrop decreases of about 20 % and 34 %, respectively. It can be shown that a salinity level larger than 9 dS m-1 increases leaching water requirement of wheat over proportional and that a salinity level of 9 dS m-1 reduces cost for irrigation water by about 11 % in comparison to the irrigation with nearly fresh water quality of 1 dS m-1. A trade-off analyses reveals that making desalinated seawater use profitable, cost need to be reduced below 0.2 m-3 for sprinkler and drip irrigation and even below 0.1 m-3 for widespread used surface irrigation systems. The authors gratefully acknowledge the support of the King Abdulaziz City for Science and Technology (KACST), Saudi Arabia, for funding the research Project No. 33-900 entitled 'Technology for desalinated seawater use in agriculture'.

Demographic, Lifestyle Factors, and Reasons for Use of Dietary Supplements by Air Force Personnel.

PubMed

Austin, Krista G; Price, Lori Lyn; McGraw, Susan M; Leahy, Guy; Lieberman, Harris R

2016-07-01

Dietary supplement (DS) use is common among U.S. Army personnel to purportedly improve health, provide energy, and increase strength. However, a comprehensive analysis of DS use among U.S. Air Force (USAF) personnel has not been conducted using the same survey instrument, which would permit direct comparisons to DS use by Army personnel. A standardized questionnaire was used to assess DS use, demographic factors, and reasons for use of DS by USAF personnel (N = 1750). Logistic regression models adjusted for age, sex, and rank were used to determine relationships among categories of DS (multivitamin and multimineral, individual vitamins and minerals, protein/amino acid supplements, combination products, herbal supplements, purported steroid analogs, and other) and demographic factors. Findings were compared to reports from other military services and civilian populations. DS were used by 68% of USAF personnel: 35% used 1-2 DS ≥ 1 time/wk, 13% 3-4 DS ≥ 1 time/wk, and 20% ≥ 5 DS ≥ 1 time/wk. There were 45% of personnel who used a multivitamin and mineral, 33% protein supplements, 22% individual vitamins/minerals, 22% combination products, and 7% herbals. Logistic regression demonstrated aerobic exercise duration and strength training were associated with increased DS use. Individuals who previously deployed were more likely to use DS. Like Army personnel, college students and athletes, USAF personnel use more DS than the general population and are more likely to use purported performance enhancing DS, such as protein supplements, and concurrently consume multiple DS. Austin KG, Price LL, McGraw SM, Leahy G, Lieberman HR. Demographic, lifestyle factors, and reasons for use of dietary supplements by Air Force personnel. Aerosp Med Hum Perform. 2016; 87(7):628-637.

Measurement of the Absolute Branching Fraction of Ds+→τ+ντ Decay

NASA Astrophysics Data System (ADS)

Ecklund, K. M.; Love, W.; Savinov, V.; Lopez, A.; Mendez, H.; Ramirez, J.; Ge, J. Y.; Miller, D. H.; Shipsey, I. P. J.; Xin, B.; Adams, G. S.; Anderson, M.; Cummings, J. P.; Danko, I.; Hu, D.; Moziak, B.; Napolitano, J.; He, Q.; Insler, J.; Muramatsu, H.; Park, C. S.; Thorndike, E. H.; Yang, F.; Artuso, M.; Blusk, S.; Khalil, S.; Li, J.; Mountain, R.; Nisar, S.; Randrianarivony, K.; Sultana, N.; Skwarnicki, T.; Stone, S.; Wang, J. C.; Zhang, L. M.; Bonvicini, G.; Cinabro, D.; Dubrovin, M.; Lincoln, A.; Rademacker, J.; Asner, D. M.; Edwards, K. W.; Naik, P.; Reed, J.; Briere, R. A.; Ferguson, T.; Tatishvili, G.; Vogel, H.; Watkins, M. E.; Rosner, J. L.; Alexander, J. P.; Cassel, D. G.; Duboscq, J. E.; Ehrlich, R.; Fields, L.; Gibbons, L.; Gray, R.; Gray, S. W.; Hartill, D. L.; Heltsley, B. K.; Hertz, D.; Jones, C. D.; Kandaswamy, J.; Kreinick, D. L.; Kuznetsov, V. E.; Mahlke-Krüger, H.; Mohapatra, D.; Onyisi, P. U. E.; Patterson, J. R.; Peterson, D.; Riley, D.; Ryd, A.; Sadoff, A. J.; Shi, X.; Stroiney, S.; Sun, W. M.; Wilksen, T.; Athar, S. B.; Patel, R.; Yelton, J.; Rubin, P.; Eisenstein, B. I.; Karliner, I.; Mehrabyan, S.; Lowrey, N.; Selen, M.; White, E. J.; Wiss, J.; Mitchell, R. E.; Shepherd, M. R.; Besson, D.; Pedlar, T. K.; Cronin-Hennessy, D.; Gao, K. Y.; Hietala, J.; Kubota, Y.; Klein, T.; Lang, B. W.; Poling, R.; Scott, A. W.; Zweber, P.; Dobbs, S.; Metreveli, Z.; Seth, K. K.; Tomaradze, A.; Libby, J.; Powell, A.; Wilkinson, G.

2008-04-01

Using a sample of tagged Ds+ decays collected near the Ds*±Ds∓ peak production energy in e+e- collisions with the CLEO-c detector, we study the leptonic decay Ds+→τ+ντ via the decay channel τ+→e+νeν¯τ. We measure B(Ds+→τ+ντ)=(6.17±0.71±0.34)%, where the first error is statistical and the second systematic. Combining this result with our measurements of Ds+→μ+νμ and Ds+→τ+ντ (via τ+→π+ν¯τ), we determine fDs=(274±10±5)MeV.

Deep Space 1: Testing New Technologies for Future Small Bodies Missions

NASA Technical Reports Server (NTRS)

Rayman, Marc D.

2001-01-01

Launched on October 24, 1998, Deep Space 1 (DS1) was the first mission of NASA's New Millennium Program, chartered to validate in space high-risk, new technologies important for future space science programs. The advanced technology payload that was tested on DS1 comprises solar electric propulsion, solar concentrator arrays, autonomous on-board navigation and other autonomous systems, several telecommunications and microelectronics devices, and two low-mass integrated science instrument packages. The mission met or exceeded all of its success criteria. The 12 technologies were rigorously exercised so that subsequent flight projects would not have to incur the cost and risk of being the fist users of these new capabilities. Examples of the benefits to future small body missions from DS1's technologies will be described.

Treatment of heavy metals by iron oxide coated and natural gravel media in Sustainable urban Drainage Systems.

PubMed

Norris, M J; Pulford, I D; Haynes, H; Dorea, C C; Phoenix, V R

2013-01-01

Sustainable urban Drainage Systems (SuDS) filter drains are simple, low-cost systems utilized as a first defence to treat road runoff by employing biogeochemical processes to reduce pollutants. However, the mechanisms involved in pollution attenuation are poorly understood. This work aims to develop a better understanding of these mechanisms to facilitate improved SuDS design. Since heavy metals are a large fraction of pollution in road runoff, this study aimed to enhance heavy metal removal of filter drain gravel with an iron oxide mineral amendment to increase surface area for heavy metal scavenging. Experiments showed that amendment-coated and uncoated (control) gravel removed similar quantities of heavy metals. Moreover, when normalized to surface area, iron oxide coated gravels (IOCGs) showed poorer metal removal capacities than uncoated gravel. Inspection of the uncoated microgabbro gravel indicated that clay particulates on the surface (a natural product of weathering of this material) augmented heavy metal removal, generating metal sequestration capacities that were competitive compared with IOCGs. Furthermore, when the weathered surface was scrubbed and removed, metal removal capacities were reduced by 20%. When compared with other lithologies, adsorption of heavy metals by microgabbro was 10-70% higher, indicating that both the lithology of the gravel, and the presence of a weathered surface, considerably influence its ability to immobilize heavy metals. These results contradict previous assumptions which suggest that gravel lithology is not a significant factor in SuDS design. Based upon these results, weathered microgabbro is suggested to be an ideal lithology for use in SuDS.

Temporary persistence of conduction block after prolonged kilohertz frequency alternating current on rat sciatic nerve

NASA Astrophysics Data System (ADS)

Bhadra, Narendra; Foldes, Emily; Vrabec, Tina; Kilgore, Kevin; Bhadra, Niloy

2018-02-01

Objective. Application of kilohertz frequency alternating current (KHFAC) waveforms can result in nerve conduction block that is induced in less than a second. Conduction recovers within seconds when KHFAC is applied for about 5-10 min. This study investigated the effect of repeated and prolonged application of KHFAC on rat sciatic nerve with bipolar platinum electrodes. Approach. Varying durations of KHFAC at signal amplitudes for conduction block with intervals of no stimulus were studied. Nerve conduction was monitored by recording peak Gastrocnemius muscle force utilizing stimulation electrodes proximal (PS) and distal (DS) to a blocking electrode. The PS signal traveled through the block zone on the nerve, while the DS went directly to the motor end-plate junction. The PS/DS force ratio provided a measure of conduction patency of the nerve in the block zone. Main results. Conduction recovery times were found to be significantly affected by the cumulative duration of KHFAC application. Peak stimulated muscle force returned to pre-block levels immediately after cessation of KHFAC delivery when it was applied for less than about 15 min. They fell significantly but recovered to near pre-block levels for cumulative stimulus of 50  ±  20 min, for the tested On/Off times and frequencies. Conduction recovered in two phases, an initial fast one (60-80% recovery), followed by a slower phase. No permanent conduction block was seen at the end of the observation period during any experiment. Significance. This carry-over block effect may be exploited to provide continuous conduction block in peripheral nerves without continuous application of KHFAC.

dsRNA binding properties of RDE-4 and TRBP reflect their distinct roles in RNAi

PubMed Central

Parker, Greg S.; Maity, Tuhin Subhra; Bass, Brenda L.

2008-01-01

SUMMARY dsRNA binding proteins (dsRBPs) facilitate Dicer functions in RNAi. C. elegans RDE-4 facilitates cleavage of long dsRNA to siRNA, while human TRBP functions downstream to pass siRNA to RISC. We show that these distinct in vivo roles are reflected in in vitro binding properties. RDE-4 preferentially binds long dsRNA, while TRBP binds siRNA with an affinity that is independent of dsRNA length. These properties are mechanistically based in the fact that RDE-4 binds cooperatively, via contributions from multiple domains, while TRBP binds non-cooperatively. Our studies offer a paradigm for how dsRBPs, which are not sequence-specific, discern dsRNA length. Additionally, analyses of the ability of RDE-4 deletion constructs and RDE-4/TRBP chimeras to reconstitute Dicer activity suggest RDE-4 promotes activity using its dsRBM2 to bind dsRNA, its linker region to interact with Dicer, and its C-terminus for Dicer activation. PMID:18948111

Comparison of Direct Sequence Spread Spectrum Rake Receiver with a Maximum Ratio Combining Multicarrier Spread Spectrum Receiver

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

Daryl Leon Wasden; Hussein Moradi; Behrouz Farhang-Broujeny

2014-06-01

This paper presents a theoretical analysis of the performance of a filter bank-based multicarrier spread spectrum (FB-MC-SS) system. We consider an FB-MC-SS setup where each data symbol is spread across multiple subcarriers, but there is no spreading in time. The results are then compared with those of the well-known direct sequence spread spectrum (DS-SS) system with a rake receiver for its best performance. We compare the two systems when the channel noise is white. We prove that as the processing gains of the two systems tend to infinity both approach the same performance. However, numerical simulations show that, in practice,more » where processing gain is limited, FB-MC-SS outperforms DS-SS.« less

Classical Affine W-Superalgebras via Generalized Drinfeld-Sokolov Reductions and Related Integrable Systems

NASA Astrophysics Data System (ADS)

Suh, Uhi Rinn

2018-02-01

The purpose of this article is to investigate relations between W-superalgebras and integrable super-Hamiltonian systems. To this end, we introduce the generalized Drinfel'd-Sokolov (D-S) reduction associated to a Lie superalgebra g and its even nilpotent element f, and we find a new definition of the classical affine W-superalgebra W(g,f,k) via the D-S reduction. This new construction allows us to find free generators of W(g,f,k), as a differential superalgebra, and two independent Lie brackets on W(g,f,k)/partial W(g,f,k). Moreover, we describe super-Hamiltonian systems with the Poisson vertex algebras theory. A W-superalgebra with certain properties can be understood as an underlying differential superalgebra of a series of integrable super-Hamiltonian systems.

Structural insights into RISC assembly facilitated by dsRNA-binding domains of human RNA helicase A (DHX9)

PubMed Central

Fu, Qinqin; Yuan, Y. Adam

2013-01-01

Intensive research interest has focused on small RNA-processing machinery and the RNA-induced silencing complex (RISC), key cellular machines in RNAi pathways. However, the structural mechanism regarding RISC assembly, the primary step linking small RNA processing and RNA-mediated gene silencing, is largely unknown. Human RNA helicase A (DHX9) was reported to function as an RISC-loading factor, and such function is mediated mainly by its dsRNA-binding domains (dsRBDs). Here, we report the crystal structures of human RNA helicase A (RHA) dsRBD1 and dsRBD2 domains in complex with dsRNAs, respectively. Structural analysis not only reveals higher siRNA duplex-binding affinity displayed by dsRBD1, but also identifies a crystallographic dsRBD1 pair of physiological significance in cooperatively recognizing dsRNAs. Structural observations are further validated by isothermal titration calorimetric (ITC) assay. Moreover, co-immunoprecipitation (co-IP) assay coupled with mutagenesis demonstrated that both dsRBDs are required for RISC association, and such association is mediated by dsRNA. Hence, our structural and functional efforts have revealed a potential working model for siRNA recognition by RHA tandem dsRBDs, and together they provide direct structural insights into RISC assembly facilitated by RHA. PMID:23361462

Structural insights into RISC assembly facilitated by dsRNA-binding domains of human RNA helicase A (DHX9).

PubMed

Fu, Qinqin; Yuan, Y Adam

2013-03-01

Intensive research interest has focused on small RNA-processing machinery and the RNA-induced silencing complex (RISC), key cellular machines in RNAi pathways. However, the structural mechanism regarding RISC assembly, the primary step linking small RNA processing and RNA-mediated gene silencing, is largely unknown. Human RNA helicase A (DHX9) was reported to function as an RISC-loading factor, and such function is mediated mainly by its dsRNA-binding domains (dsRBDs). Here, we report the crystal structures of human RNA helicase A (RHA) dsRBD1 and dsRBD2 domains in complex with dsRNAs, respectively. Structural analysis not only reveals higher siRNA duplex-binding affinity displayed by dsRBD1, but also identifies a crystallographic dsRBD1 pair of physiological significance in cooperatively recognizing dsRNAs. Structural observations are further validated by isothermal titration calorimetric (ITC) assay. Moreover, co-immunoprecipitation (co-IP) assay coupled with mutagenesis demonstrated that both dsRBDs are required for RISC association, and such association is mediated by dsRNA. Hence, our structural and functional efforts have revealed a potential working model for siRNA recognition by RHA tandem dsRBDs, and together they provide direct structural insights into RISC assembly facilitated by RHA.

Genetic Local Search for Optimum Multiuser Detection Problem in DS-CDMA Systems

NASA Astrophysics Data System (ADS)

Wang, Shaowei; Ji, Xiaoyong

Optimum multiuser detection (OMD) in direct-sequence code-division multiple access (DS-CDMA) systems is an NP-complete problem. In this paper, we present a genetic local search algorithm, which consists of an evolution strategy framework and a local improvement procedure. The evolution strategy searches the space of feasible, locally optimal solutions only. A fast iterated local search algorithm, which employs the proprietary characteristics of the OMD problem, produces local optima with great efficiency. Computer simulations show the bit error rate (BER) performance of the GLS outperforms other multiuser detectors in all cases discussed. The computation time is polynomial complexity in the number of users.

Personal notes [of D.S. Lewis, 7 September 1956 to 31 December 1959

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

Lewis, D.S.

1956-09-07

This report is a copy of the personal log of D.S. Lewis of the Irradiation Processing Dept. of Reactor Operations at Hanford and covers the period from 7 September 1956 through 31 December 1959. Data are presented on the following: (1) basic reactor operating data, including daily operating data, outage resumes, injuries and incidents, charging and tube replacement rates, panellit gage (flowmeter) trip failures, and thermocouple failures, and (2) basic reactor information on the water plant, electrical distribution, VSR`s, HCR`s, Ball 3X, Safety circuits, gas system, effluent system, process tube cross-section, and production scheduling.

Glycogen Phosphorylase and Glycogen Synthase: Gene Cloning and Expression Analysis Reveal Their Role in Trehalose Metabolism in the Brown Planthopper, Nilaparvata lugens Stål (Hemiptera: Delphacidae).

PubMed

Zhang, Lu; Wang, Huijuan; Chen, Jianyi; Shen, Qida; Wang, Shigui; Xu, Hongxing; Tang, Bin

2017-01-01

RNA interference has been used to study insects' gene function and regulation. Glycogen synthase (GS) and glycogen phosphorylase (GP) are two key enzymes in carbohydrates' conversion in insects. Glycogen content and GP and GS gene expression in several tissues and developmental stages of the Brown planthopper Nilaparvata lugens Stål (Hemiptera: Delphacidae) were analyzed in the present study, using quantitative reverse-transcription polymerase chain reaction to determine their response to double-stranded trehalases (dsTREs), trehalose-6-phosphate synthases (dsTPSs), and validamycin injection. The highest expression of both genes was detected in the wing bud, followed by leg and head tissues, and different expression patterns were shown across the developmental stages analyzed. Glycogen content significantly decreased 48 and 72 h after dsTPSs injection and 48 h after dsTREs injection. GP expression increased 48 h after dsTREs and dsTPSs injection and significantly decreased 72 h after dsTPSs, dsTRE1-1, and dsTRE1-2 injection. GS expression significantly decreased 48 h after dsTPS2 and dsTRE2 injection and 72 h after dsTRE1-1 and dsTRE1-2 injection. GP and GS expression and glycogen content significantly decreased 48 h after validamycin injection. The GP activity significantly decreased 48 h after validamycin injection, while GS activities of dsTPS1 and dsTRE2 injection groups were significantly higher than that of double-stranded GFP (dsGFP) 48 h after injection, respectively. Thus, glycogen is synthesized, released, and degraded across several insect tissues according to the need to maintain stable trehalose levels. © The Authors 2017. Published by Oxford University Press on behalf of Entomological Society of America.

A Novel Hybrid MADM Based Competence Set Expansions of a SOC Design Service Firm

NASA Astrophysics Data System (ADS)

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

As the IC (integrated circuit) industry migrates to the System-on-Chip (SOC) era, a novel business model, the SOC design service (DS), is emerging. However, how to expand a firm’s innovation competences while satisfying multiple objectives including highest quality, lowest cost, and fastest time to market as well as most revenues for economics of scale are always problems for a design service firm. Therefore, attempts to expand the innovation competences, and thus the competitiveness, of latecomers in the SOC DS industry have already become the most critical issue facing the top managers of SOC design service firms. In this paper, a novel multiple attribute decision making (MADM) analytic framework based on the concept of competence set expansion, as well as MADM methods consisting with DEMATEL, ANP and multiple objective decision making (MODM) will be proposed in order to define a path for expanding a late-coming SOC DS firm’s innovation capabilities. An empirical study on expanding innovation competence sets, of a late-coming Taiwanese DS firm then will be presented.

Insight into the effect of organic and inorganic draw solutes on the flux stability and sludge characteristics in the osmotic membrane bioreactor.

PubMed

Siddique, Muhammad Saboor; Khan, Sher Jamal; Shahzad, Muhammad Aamir; Nawaz, Muhammad Saqib; Hankins, Nicholas P

2018-02-01

In this study, chloride based (CaCl 2 and MgCl 2 ) and acetate based (NaOAc and MgOAc) salts in comparison with NaCl were investigated as draw solutions (DS) to evaluate their viability in the osmotic membrane bioreactor (OMBR). Membrane distillation was coupled with an OMBR setup to develop a hybrid OMBR-MD system, for the production of clean water and DS recovery. Results demonstrate that organic DS were able to mitigate the salinity buildup in the bioreactor as compared to inorganic salts. Prolonged filtration runs were observed with MgCl 2 and MgOAc in contrast with other draw solutes at the same molar concentration. Significant membrane fouling was observed with NaOAc while rapid flux decline due to increased salinity build-up was witnessed with NaCl and CaCl 2 . Improved characteristics of mixed liquor in terms of sludge filterability, particle size, and biomass growth along with the degradation of soluble microbial products (SMP) were found with organic DS. Copyright © 2017 Elsevier Ltd. All rights reserved.